Volume 17, Issue 1

Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults with high metastasis rates. D-type cyclins (CCNDs) are central regulators of the cell division cycle and are among the most frequently deregulated therapeutic targets in human cancer. Recently, the E3 ligase adaptor, autophagy and beclin 1 regulator 1 (AMBRA1), was reported to regulate the stability of CCNDs, including CCND1, but its role in UVM has not been demonstrated. AMBRA1 is lowly expressed in UVM cells, and the ablation of AMBRA1 promotes the proliferation of 92.1 and OMM1 cells, whereas ectopically expressing AMBRA1 attenuates the proliferation of UVM cells. Further studies found that AMBRA1 promotes the ubiquitination and degradation of CCND1, and AMBRA1 regulates the proliferation of UVM cells in a CCND1-dependent manner. Thus, this study suggests that AMBRA1 serves as an important tumor suppressor by limiting UVM cell growth.

Papillary thyroid carcinoma (PTC) is the most frequent histological type of differentiated thyroid carcinoma. Long noncoding RNAs (lncRNAs) have been widely reported to play a key role in human malignancies, and PTC is included. This study aimed to find out the functions and mechanism of lncRNA LINC00475 in PTC. LINC00475 was upregulated in PTC cells and was mainly located in the cytoplasm according to reverse-transcription polymerase chain reaction analyses and subcellular fractionation assays. As shown by cell counting kit-8 assays, ethynyl deoxyuridine incorporation assays, wound healing assays, and transwell assays, LINC00475 knockdown suppressed cell viability, proliferation, migration, and invasion. Mechanistically, LINC00475 upregulated the expression of messenger RNA zinc finger CCHC-type containing 12 (ZCCHC12) by binding to miR-376c-3p. ZCCHC12 was a direct target gene of miR-376c-3p in PTC cells. The relationship between miR-376c-3p and LINC00475 (or ZCCHC12) in PTC cells was probed by luciferase reporter assays, RNA pulldown assays, and RNA immunoprecipitation assays. In addition, both mRNA and protein levels of ZCCHC12 were downregulated due to miR-376c-3p overexpression or LINC00475 silencing. ZCCHC12 overexpression partially reversed the suppressive effect of LINC00475 knockdown on malignant behaviors of PTC cells. In conclusion, LINC00475 promotes PTC cell proliferation, migration, and invasion by upregulating ZCCHC12 via the interaction with miR-376c-3p.

Objectives This study aimed to investigate the differences in complications between hepatitis B virus (HBV)-related and alcohol-related cirrhoses. Methods Medical records of patients with HBV-related and alcohol-related cirrhoses treated from January 2014 to January 2021 were, retrospectively, reviewed. The unadjusted rate and adjusted risk of cirrhotic complications between the two groups were assessed. Results The rates of hepatocellular carcinoma (HCC) and hypersplenism were higher in HBV-related cirrhosis (both P < 0.05), whereas the rates of hepatic encephalopathy (HE) and acute-on-chronic liver failure (ACLF) were higher in alcohol-related cirrhosis (both P < 0.05). After adjusting for potential confounders, HBV-related cirrhotic patients had higher risks of HCC (odds ratio [OR] = 34.06, 95% confidence interval [CI]: 4.61–251.77, P = 0.001) and hypersplenism (OR = 2.29, 95% CI: 1.18–4.42, P = 0.014), whereas alcohol-related cirrhotic patients had higher risks of HE (OR = 0.22, 95% CI: 0.06–0.73, P = 0.013) and ACLF (OR = 0.30, 95% CI: 0.14–0.73, P = 0.020). Conclusion Cirrhotic patients with different etiologies had different types of complications: HBV-related cirrhotic patients exhibited increased risks of HCC and hypersplenism and alcohol-related cirrhotic patients more readily developing HE and ACLF.

Gestational diabetes mellitus (GDM) can have adverse effects on pregnancy. GDM is associated with changes in the lipid profile of pregnant women. Finding out the early ways to diagnose GDM can prevent the adverse outcomes. This meta-analysis study aimed to determine the effect of GDM on lipid profile. PubMed, ProQuest, Web of Science, Scopus, Science Direct, Google Scholar, and ClinicalTrial were systematically searched for published articles relating to GDM until 2021 according to PRISMA guidelines. Newcastle Ottawa scale was used to assess the quality of the studies. Thirty-three studies with a sample size of 23,792 met the criteria for entering the meta-analysis. Pooled standardized mean difference (SMD) for total cholesterol (TC) and triglyceride (TG) was 0.23 mg/dL (95% CI: 0.11–0.34) and 1.14 mg/dL (95% CI: 0.91–1.38), respectively. The mean of TC and TG in people with GDM was higher than that in normal pregnant women. A similar pattern was observed for the very low-density lipoprotein (VLDL) and TG/high-density lipoprotein (HDL) ratio, with pooled SMD of 0.99 mg (95% CI: 0.71–1.27) and 0.65 mg (95% CI: 0.36–0.94), respectively. Pooled SMD for HDL was −0.35 mg/dL (95% CI: −0.54 to −0.16), women with GDM had a mean HDL lower than normal pregnant women. Although pooled SMD was higher for low-density lipoprotein (LDL) in the GDM group, this difference was not significant (0.14 [95% CI: −0.04 to 0.32]). Of all the lipid profiles, the largest difference between the GDM and control groups was observed in TG (SMD: 1.14). Elevated serum TG had the strongest effect on GDM. Higher levels of TC, LDL, VLDL, and TG/HDL ratio, and lower level of HDL were exhibited in GDM group. So, these markers can be considered as a reliable marker in the diagnosis of GDM.

Long noncoding RNA (lncRNA), specifically the upregulation of lncRNA NR2F1 antisense RNA 1 (NR2F1-AS1), has been involved in the progression of non-small cell lung cancer (NSCLC), but the mechanisms that underlie this remain unclear. In this study, the expression of NR2F1-AS1, miR-363-3p, and SOX4 was assessed in NSCLC cells. A loss-of-function assay was used to measure the tumorigenicity of NSCLC cells. The glycolysis and glutamine metabolism of NSCLC cells was also measured via extracellular acidification rate, consumption of glucose and glutamine, and production of lactate and ATP. The relationships among NR2F1-AS1, miR-363-3p, and SOX4 were detected via dual-luciferase reporter assay. HK-2, GLS1, and SOX4 levels were also analyzed. We found that both NSCLC tissues and cells had higher levels of NR2F1-AS1. Silencing of NR2F1-AS1 inhibited the tumorigenicity of cells in vitro and reduced the glycolysis and glutamine metabolism of NSCLC cells. Regarding its mechanism, NR2F1-AS1 positively regulated the SOX4 level by sponging miR-363-3p. Furthermore, miR-363-3p inhibition or SOX4 overexpression reversed the repressing role of sh-NR2F1-AS1 in the tumorigenicity of NSCLC cells. In summary, NR2F1-AS1 promotes the tumorigenicity of NSCLC cells by regulating miR-363-3p/SOX4.

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer associated with an unstable prognosis. Thus, there is an urgent demand for the identification of novel diagnostic and prognostic biomarkers as well as targeted drugs for LUAD. The present study aimed to identify potential new biomarkers associated with the pathogenesis and prognosis of LUAD. Three microarray datasets (GSE10072, GSE31210, and GSE40791) from the Gene Expression Omnibus database were integrated to identify the differentially expressed genes (DEGs) in normal and LUAD samples using the limma package. Bioinformatics tools were used to perform functional and signaling pathway enrichment analyses for the DEGs. The expression and prognostic values of the hub genes were further evaluated by Gene Expression Profiling Interactive Analysis and real-time quantitative polymerase chain reaction. Furthermore, we mined the “Connectivity Map” (CMap) to explore candidate small molecules that can reverse the tumoral of LUAD based on the DEGs. A total of 505 DEGs were identified, which included 337 downregulated and 168 upregulated genes. The PPI network was established with 1,860 interactions and 373 nodes. The most significant pathway and functional enrichment associated with the genes were cell adhesion and extracellular matrix-receptor interaction, respectively. Seven DEGs with high connectivity degrees (ZWINT, RRM2, NDC80, KIF4A, CEP55, CENPU, and CENPF) that were significantly associated with worse survival were chosen as hub genes. Lastly, top 20 most important small molecules which reverses the LUAD gene expressions were identified. The findings contribute to revealing the molecular mechanisms of the initiation and progression of LUAD and provide new insights for integrating multiple biomarkers in clinical practice.

Background Chronic urticaria is a common disease. Plasmapheresis is an alternative treatment that can be appropriate for patients who are resistant to treatment with 2nd generation antihistamines or for whom treatment with omalizumab is unsuitable. Objective To investigate the effect of plasmapheresis treatment in chronic urticaria. Methods A retrospective analysis was performed based on the data of 98 patients suffering from refractory chronic urticaria who received plasmapheresis as an alternative treatment in Vilnius University’s Hospital Santaros Clinics from 2000 to 2020. The efficiency of the treatment was evaluated by clinical judgment. Results 58.2% of the patients exhibited a complete or significant response; of these, 37.8% had temporary relief of symptoms and 20.4% achieved disease remission; 41.8% showed no response to the plasmapheresis. Men (34.8%) had a tendency to achieve disease remission more often than women (16%) ( p < 0.05). One patient did not finish the plasmapheresis treatment due to the symptoms’ exacerbation and treatment with omalizumab was initiated. Conclusion Plasmapheresis is a safe and effective alternative treatment when traditional treatment is unavailable or does not relieve symptoms completely. Our data showed that plasmapheresis was effective in more than half of our patients.

Gene expression profiling studies have shown the pathogenetic role of oncogenic pathways in extranodal natural killer/T-cell lymphoma (ENKL). In this study, we aimed to identify the microRNAs (miRNAs) playing potential roles in ENKL, and to evaluate the genes and biological pathways associated to them. Gene expression profiles of ENKL patients were acquired from the gene expression omnibus (GEO) database. Most differentially expressed (DE)-miRNAs were identified in ENKL patients using limma package. Gene targets of the DE-miRNAs were collected from online databases (miRDB, miRWalk, miRDIP, and TargetScan), and used in Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses on Database for annotation, visualization, and integrated discovery database, and then used in protein–protein interaction (PPI) analysis on STRING database. Hub genes of the PPI network were identified in cytoHubba, and were evaluated in Biological networks gene ontology. According to the series GSE31377 and GSE43958 from GEO database, four DE-miRNAs were screened out: hsa-miR-363-3p, hsa-miR-296-5p, hsa-miR-155-5p, and hsa-miR-221-3p. Totally 164 gene targets were collected from the online databases, and used in the GO and KEGG pathway analyses and PPI network analysis. Ten hub genes of the PPI network were identified: AURKA, TP53, CDK1, CDK2, CCNB1, PLK1, CUL1, ESR1, CDC20, and PIK3CA. Those hub genes, as well as their correlative pathways, may be of diagnostic or therapeutic potential for ENKL, but further clinical evidence is still expected.

Hepatocellular carcinoma (HCC) has a high incidence and poor prognosis and is the second most fatal cancer, and certain HCC patients also show high heterogeneity. This study developed a prognostic model for predicting clinical outcomes of HCC. RNA and microRNA (miRNA) sequencing data of HCC were obtained from the cancer genome atlas. RNA dysregulation between HCC tumors and adjacent normal liver tissues was examined by DESeq algorithms. Survival analysis was conducted to determine the basic prognostic indicators. We identified competing endogenous RNA (ceRNA) containing 15,364 pairs of mRNA–long noncoding RNA (lncRNA). An imbalanced ceRNA network comprising 8 miRNAs, 434 mRNAs, and 81 lncRNAs was developed using hypergeometric test. Functional analysis showed that these RNAs were closely associated with biosynthesis. Notably, 53 mRNAs showed a significant prognostic correlation. The least absolute shrinkage and selection operator’s feature selection detected four characteristic genes ( SAPCD2 , DKC1 , CHRNA5 , and UROD ), based on which a four-gene independent prognostic signature for HCC was constructed using Cox regression analysis. The four-gene signature could stratify samples in the training, test, and external validation sets ( p <0.01). Five-year survival area under ROC curve (AUC) in the training and validation sets was greater than 0.74. The current prognostic gene model exhibited a high stability and accuracy in predicting the overall survival (OS) of HCC patients.

Background/aims Uterine leiomyoma (ULM) is a kind of gene-involved benign tumor, which is located in the front of female reproductive tract. It is one of the most common reproductive tract tumors in women, which leads to abnormal menstruation, repeated pregnancy loss, and other serious gynecological diseases. Recently, microRNAs (miRNAs) have attracted much more attention in the process of exploring the molecular mechanisms of tumorigenesis. Furthermore, the deregulated miRNAs had been reported to play important roles in ULM pathology. Methods In this study, we assessed the expression level of microRNA-199a-5p (miR-199a-5p) in human ULM by quantitative polymerase chain reaction. After that cell counting kit 8, colony formation, 5-ethynyl-20-deoxyuridine, flow cytometry, and Western blot analyses were performed to investigate the effects of miR-199a-5p on ULM cell proliferation and apoptosis. Results We confirmed that miR-199a-5p was significantly downregulated in human ULM. The results of function analyses showed that miR-199a-5p inhibited cell proliferation and induced cell apoptosis in vitro . Bioinformatics tool showed oncogene MED12 was one of the target genes of miR-199a-5p, which mediated the effect of miR-199a-5p on the ULM. Conclusion Our results showed that miR-199a-5p functioned as an antitumor factor in human ULM cells. These findings broaden the current findings on the function of miR-199a-5p into the ULM pathogenesis, and miR-199a-5p may serve as a prognosis and therapeutic target for the ULM and its related diseases.

Background A large variety of factors can affect colorectal cancer (CRC) survival, including type 2 diabetes mellitus (T2DM) and paraneoplastic thrombocytosis. Although several common factors play a role in their development and platelets are damaged in both diseases, the combined relationship of the three conditions was never investigated previously. Methods A prospective, real-life observational cohort study was conducted with the inclusion of 108 CRC patients and 166 voluntary non-CRC subjects. Plasma interleukin-6 and thrombopoietin levels were measured. Results Study participants were divided into cohorts based on the presence of T2DM. Platelet count ( p < 0.0500) and interleukin-6 ( p < 0.0100) level were significantly higher in the CRC groups. Thrombopoietin level was higher in the T2DM, CRC, and CRC + T2DM groups ( p < 0.0500). Analysis of parameter changes over time and survival models revealed that neither platelet count, interleukin-6, nor thrombopoietin levels were affected by T2DM. Death of patients was associated with higher baseline platelet count ( p = 0.0042) and interleukin-6 level ( p < 0.0001). Conclusion Although the independent, disease-worsening effect of paraneoplastic thrombocytosis and T2DM is known, the coexistence of the two did not further impair the survival of CRC patients, suggesting that T2DM has no significant effect over paraneoplastic thrombocytosis.

Assisted oocyte activation (AOA) has been proposed as an effective technique to overcome the problem of impaired fertilization after intracytoplasmic sperm injection (ICSI) but the safety of AOA remains a concern. We aimed to investigate if AOA induces imprinting effects on embryos. We used 13 cleavage embryos, nine blastocysts, and eight placentas from 15 patients. The subjects were divided into six groups by tissue type and with or without AOA. The methylation levels of imprinted genes (H19, paternally expressed gene [PEG3] and small nuclear ribonucleoprotein polypeptide N [SNRPN]) were tested by pyrosequencing. We observed different methylation levels among cleavage embryos. The variability was much more remarkable between cleavage embryos than blastocysts and placenta tissues. The methylation levels were especially higher in SNRPN and lower in the H19 gene in AOA embryos than those without AOA. No significant difference was found either among blastocysts or among placenta tissues regardless of AOA. The methylation levels of the three genes in blastocysts were very similar to those in the placenta. Compared to conventional ICSI, AOA changed imprinting methylation rates at H19 and SNRPN in cleavage embryos but not in the blastocyst stage and placenta. We recommend that blastocyst transfer should be considered for patients undergoing AOA during in vitro fertilization.

Leptin and proprotein convertase subtilisin kexin 9 (PCSK9) play an important role in regulating blood lipid concentration. Recently, they have been found to show the ability to independently regulate the immune response. Vascular immune response has an important pathological function in the development of coronary heart disease (CHD) and thrombosis. The aim of this study was to explore the relationship between leptin, PCSK9, and vascular endothelial cell related inflammatory factors. First, detailed clinical information were collected and analyzed for 27 patients with stable CHD and corresponding 27 healthy controls. Second, using liquid-phase protein chip technology, leptin, PCSK9, and vascular-related inflammatory factors, such as E-selectin, vascular cell adhesion protein 1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), interferon-gamma (IFN-γ), and interleukin-17 (IL-17), were detected on the same platform. Finally, the correlation between leptin, PCSK9, and the inflammatory factors was analyzed. Through collecting clinical information of patients, it was suggested that there was a significant positive correlation between leptin and blood lipid level in CHD. Compared with healthy people, the levels of leptin, PCSK9, E-selectin, and ICAM-1 were significantly high in patients with CHD. There was a high positive correlation between leptin and E-selectin, ICAM-1, IFN-γ, and IL-17. Also, a high positive correlation between PCSK9 and E-selectin, IFN-γ, and IL-17 concentrations was observed. In general, leptin and PCSK9 may not only be able to regulate lipid metabolism, but may also be able to regulate inflammation in CHD.

As a significant chromosomal structural abnormality, chromosomal inversion is closely related to male infertility. For inversion carriers, the interchromosomal effect explains male infertility, but its specific mechanism remains unclear. Additionally, inversion carriers with different chromosomes have different clinical manifestations. Therefore, genetic counseling is difficult in clinical practice. Herein, four male carriers of pericentric inversion in chromosome 6 have been described. Two patients showed asthenospermia, one showed azoospermia, and the wife of the remaining patient had recurrent miscarriages. Through a literature search, the association between the breakpoint of pericentric inversion in chromosome 6 and male fertility problems are also discussed in this study. Overall, important genes related to asthenospermia in chromosome 6p21 were found, which may be related to the clinical phenotype. These results suggest that physicians should focus on the breakpoints of inversion in genetic counseling.

Background A dreaded complication of laparoscopic sleeve gastrectomy (LSG) is suture leak. The study aimed to assess the efficacy of the nebulized comonomer Glubran 2 ® ( N -butyl-cyanoacrylate + metacrylosysolfolane) applied to the LSG staple line. Methods A propensity-matched comparison analysis was conducted in 125 patients undergoing LSG between 2017 and 2019. Groups included those treated with Glubran ® (group 1, n = 70) and those without Glubran ® treatment (group 2, n = 55). Results There were differences in the mean body mass index (44.4 vs 43 kg/m 2 ; P < 0.05) between the groups. There was a non-significant increase in the operative time for group 1 compared with group 2 (97 ± 8 vs 93.8 ± 10.7 min; P = 0.07), with a greater amount of estimated blood loss (94.5 mL vs 87.8; P < 0.01). There were more severe complications in group 2 over group 1 cases (8 vs 0%; P < 0.05), although postoperative bleeding did not differ between the two groups (1.4 vs 5.4%). There were no postoperative leaks in group 1 patients, but there were two leaks in group 2 cases with an increased length of hospital stay in patients with a leak. Conclusion Glubran ® LSG support may reduce leak risk without increasing operating time.

The scoring of crescents (Cs) was recently added to the Oxford classification for IgA nephropathy (IgAN). Because of the short-term use of the C score in clinical practice, its validity and applicability need to be verified. We, retrospectively, analyzed the clinicopathological data of 144 primary IgAN patients diagnosed at our hospital from March 2017 to March 2019 and with complete ≥6-month follow-up data. We found that the C score was positively correlated with the Lee’s classification in the assessment of renal pathological changes and significantly correlated with increased proteinuria and decreased estimated glomerular filtration rate. Univariate Cox regression analysis showed an association of C formation with IgAN prognosis, and multivariate Cox regression indicated Cs as an independent prognosis factor. The optimal proportion of Cs for prognosis prediction by the receiver operating characteristic curve was 11%. Kaplan–Meier survival curve revealed a significantly decreased renal survival rate in patients with C proportions ≥11%. Further multivariate Cox regression analysis confirmed that the C proportion ≥11% is an independent risk factor for poor prognosis of IgAN patients. Our findings demonstrate that Cs are independently related to the prognosis of patients with IgAN, and the proportion of Cs ≥11% is an independent risk factor for poor outcomes.

The aim of this study is to reveal the potential value of dynamin3 (DNM3) in colorectal cancer (CRC) evaluation of clinical diagnosis and prognosis. A total of 100 tissue samples were collected from 50 patients with stages I–IV, CRC tissues ( n = 50) paired with non-cancerous adjacent colorectal tissues ( n = 50). The expression levels of DNM3 were detected in 50 cases of CRC tissues and 50 cases of non-cancerous adjacent colorectal tissues by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical method (IHC) was conducted to semi-quantify the expression of DNM3 protein. Results showed that the relative expression of DNM3 mRNA in CRC tissues was 0.634-fold of that in non-cancerous adjacent colorectal tissues. The positive rate of DNM3 protein in CRC tissues (42.0%) was much lower than that in non-cancerous adjacent colorectal tissues (66.0%; P < 0.05). The expression level of DNM3 protein in CRC tissues was dependent on tumor size, degree of histological differentiation, and clinical stage ( P < 0.05). The expression level of DNM3 mRNA in CRC tissues was significantly correlated with tumor size and pathology classification ( P < 0.05). The research shows that detecting the expression of DNM3 helps in analyzing the tumor size, degree of histological differentiation, and clinical stage. Expression of DNM3 may be associated with good outcome in CRC.

Epithelial ovarian cancer (EOC) is the leading cause of deaths due to cancer in women. Adipocytes have been suggested to play a key role in the stimulation of EOC growth. However, the mechanisms underlying the adipocyte-induced EOC proliferation remain undefined. Here, we provide the first evidence that adipocytes induce the activation of sphingosine kinase (SphK) 2 in EOC, which represents a novel pathway that mediates the adipocyte-induced EOC growth. SphK2 inhibition in EOC cells led to a remarkable inhibition of the adipocyte-induced cell proliferation. Moreover, the adipocyte-induced SphK2 activation in EOC cells was extracellular signal-regulated protein kinases (ERK) dependent. Furthermore, silencing SphK2 in EOC significantly inhibited the adipocyte-induced expression of phospho-ERK and c-Myc, two crucial players in EOC growth. Collectively, the current study unraveled a previously unrecognized role of SphK2 in the adipocyte-induced growth-promoting action in EOC, suggesting a novel target for EOC treatment.

The aim of this study was to investigate whether continuous renal replacement therapy (CRRT) influences the global end-diastolic volume index (GEDVI), cardiac index (CI), and extravascular lung water index (EVLWI) measured by Pulse Index Continuous Cardiac Output (PICCO) in febrile patients. Fifteen fever patients were included in this study. CI, GEDVI, EVLWI, heart rate (HR), and mean arterial pressure (MAP) were measured at five time-points: before CRRT (T0), immediately after CRRT started (T1), 15 min after CRRT started (T2), immediately after CRRT stopped (T3), and 15 min after CRRT stopped (T4). Results have shown that CI and GEDVI were decreased significantly in T1 (CI: 4.09 ± 0.72 vs 2.81 ± 0.58 L/min m 2 , P = 0.000 and GEDVI: 727.86 ± 63.47 vs 531.07 ± 66.63 mL/m 2 , P = 0.000). However, CI and GEDVI were significantly increased in T3 (CI: 4.09 ± 0.72 vs 7.23 ± 1.32 L/min m 2 , P = 0.000 and GEDVI 727.86 ± 63.47 vs 1339.17 ± 121.52 mL/m 2 , P = 0.000). There were no significant differences in T2 and T4. Among the five-time points, no measurement errors were observed with regards to HR, MAP, and EVLWI. Therefore, the data herein contained suggests that PICCO measurements should begin 15 min after the start or stop of CRRT.

In this study, we intended to figure out the biological significance of long non-coding RNAs (lncRNAs) solute carrier organic anion transporter family member 4A1 antisense RNA 1 (SLCO4A1-AS1) in pancreatic cancer (PC). Cell counting kit-8, colony formation, wound healing, transwell, and flow cytometry experiments were performed to reveal how SLCO4A1-AS1 influences PC cell proliferation, migration, invasion, and apoptosis. Thereafter, bioinformatics analysis, RNA immunoprecipitation assay, luciferase reporter assay, and RNA pull-down assay were applied for determining the binding sites and binding capacities between SLCO4A1-AS1 and miR-4673 or kinesin family member 21B (KIF21B) and miR-4673. The results depicted that SLCO4A1-AS1 was upregulated in PC, and SLCO4A1-AS1 knockdown suppressed PC cell growth, migration, invasion, and induced cell apoptosis. Furthermore, SLCO4A1-AS1 was verified to modulate the expression of KIF21B by binding with miR-4673. SLCO4A1-AS1 exerted an oncogenic function in PC. The overexpression of SLCO4A1-AS1 aggravated the malignant behaviors of PC via the upregulation of KIF21B by sponging miR-4673. Our findings revealed a novel molecular mechanism mediated by SLCO4A1-AS1, which might play a significant role in modulating the biological processes of PC.

Gastric cancer (GC) is one of the most common malignancies in digestive system. Accumulating evidence reveals the critical role of long noncoding RNAs (lncRNAs) in GC development. The study aimed to explore the functions and mechanism of lncRNA actin alpha 2, smooth muscle antisense RNA 1 (ACTA2-AS1) in GC. Reverse transcription-quantitative polymerase chain reaction analyses and subcellular fractionation assays showed that ACTA2-AS1 was lowly expressed in GC cells and was mainly distributed in the cytoplasm. Overexpressed ACTA2-AS1 inhibited GC cell viability, proliferation, migration, invasion, and epithelial-mesenchymal transition process, as suggested by cell counting kit-8 assays, colony formation assays, wound healing assays, Transwell assays and Western blot analyses. Mechanistically, ACTA2-AS1 served as a competing endogenous RNA (ceRNA) to bind with miR-378a-3p and thereby, antagonized the inhibitory effect of miR-378a-3p on the expression of messenger RNA phosphatidylinositol specific phospholipase C X domain containing 2 (PLCXD2). The binding capacity between miR-378a-3p and ACTA2-AS1 (or PLCXD2) was detected by RNA pulldown assays, luciferase reporter assays and RNA immunoprecipitation assays. Moreover, PLCXD2 knockdown rescued the inhibitory effect of ACTA2-AS1 overexpression on malignant behaviors of GC cells. Overall, ACTA2-AS1 inhibits malignant phenotypes of GC cells by acting as a ceRNA to target miR-378a-3p/PLCXD2 axis.

Background Circular RNAs (circRNAs) are associated with cisplatin resistance in gastric cancer (GC). This study aims to explore the role of circRNA AKT serine/threonine kinase 3 (circ_AKT3) in the resistance of GC to cisplatin. Methods 42 sensitive and 23 resistant GC patients were recruited for tissue collection. The cisplatin-resistant GC cells MKN-7/DDP and HGC-27/DDP were used for in vitro study. circ_AKT3, microRNA-206 (miR-206) and protein tyrosine phosphatase non-receptor type 14 (PTPN14) levels were detected via quantitative reverse transcription real-time PCR (qPCR) and Western blot. Cisplatin resistance was assessed by detecting P-glycoprotein (P-gp) level, half maximal inhibitory concentration (IC 50 ) of cisplatin and cell apoptosis. The target relationship between miR-206 and circ_AKT3 or PTPN14 was analyzed via dual-luciferase reporter and RNA pull-down assays. The role of circ_AKT3 in vivo was assessed using xenograft model. Results circ_AKT3 level was increased, but miR-206 was declined in cisplatin-resistant GC tissues and cells. circ_AKT3 knockdown or miR-206 overexpression decreased the level of P-gp and IC 50 of cisplatin and increased apoptosis of MKN-7/DDP and HGC-27/DDP cells. Additionally, circ_AKT3 targeted miR-206, and regulated cisplatin resistance by interacting with miR-206. PTPN14 was regulated by circ_AKT3 through miR-206 as a bridge. Also, circ_AKT3 knockdown decreased xenograft tumor growth. Conclusion circ_AKT3 knockdown suppressed cisplatin resistance using miR-206/PTPN14 axis in cisplatin-resistant GC cells.

Background Previous studies indicated that dysregulated expression of nicotinamide N -methyltransferase (NNMT) contributed to the tumor progression and predicted poor prognosis in various cancers. However, there was no exact conclusion on account of the contradictory results across studies. Methods The relevant studies up to December 7, 2020 were searched in PubMed, Web of Science, and Embase. The association between NNMT expression and prognostic outcomes was explored, including overall survival (OS), disease-free survival (DFS), and clinicopathological features. The bioinformatics database was used to validate the findings. Results Thirteen retrospective studies containing 2,591 patients with cancers were included in this analysis. High NNMT expression was significantly associated with shorter OS (hazard ratio [HR] = 2.01, 95% confidence interval [CI] = 1.42–2.86, and P < 0.01) and DFS (HR = 1.59, 95% CI = 1.23–2.05, and P < 0.01) compared to low NNMT expression in cancers. Compared to patients with low NNMT expression, patients with high NNMT expression tended to have worse tumor differentiation ( P = 0.03), earlier lymph node metastasis ( P = 0.01), earlier distant metastasis ( P = 0.02), and more advanced clinical stage ( P < 0.01). Conclusion High NNMT expression is an unfavorable factor of various cancers. NNMT is a promising indicator to predict the prognosis of various cancers and can serve as a potential therapeutic target in various cancers.

Glypican-2 (GPC2) has been reported to promote tumor progression through metabolic pathways. However, the role of GPC2 in colon adenocarcinoma (COAD) remains to be further investigated. This study was designed to evaluate the role of GPC2 in COAD. Based on patients with complete clinical information and GPC2 expression from the Cancer Genome Atlas-COAD database, we found that GPC2 mRNA was highly expressed in COAD tissues, which was associated with poor prognosis and tumornode-metastasis (TNM) stage. The predicted survival probability based on GPC2 mRNA expression and TNM stage was in good agreement with the observed survival probability. Furthermore, the genes coexpressed with GPC2 in COAD tissues were significantly enriched in basal cell carcinoma, Notch signaling pathway, and Hedgehog signaling pathway. After GPC2 was decreased through transfecting short hairpin RNA of GPC2 into HCT-8 and SW620 cells, cell cycle was arrested in G0/G1 phase, proliferation was decreased, apoptosis was increased, and migration and invasion were repressed. In conclusion, decreasing GPC2 significantly inhibited proliferation, migration, and invasion, and enhanced apoptosis, which implied that GPC2 can be considered a promising therapeutic target of COAD in the future.

Although cell-based or animal-based research evidence support the association of Holliday junction recognition protein (HJURP) with cancers, no pan-cancer investigation has been reported. The datasets of Gene Expression Omnibus database along with The Cancer Genome Atlas project were used to evaluate the expression of HJURP in various types of tumors. HJURP is overexpressed in a considerable number of cancers, and some changes in DNA methylation and genetic alterations are discovered in some types of tumors, such as kidney-related and adrenal gland-related tumors. Based on PrognoScan and gene expression profiling interactive analysis (GEPIA), the elevated expression of HJURP worsened the survival time of individuals with cancer. The biological general repository for interaction datasets (BioGRID) and The database for annotation, visualization and integrated discovery (DAVID) were used to establish the functional molecular network. It revealed that the cell cycle and p53 signaling pathway are the key molecular mechanisms that HJURP promotes carcinogenesis. The nomograms between HJURP and clinical pathological factors based on the Cox proportional hazards model showed a good prognostic performance in kidney carcinoma, hepatocellular carcinoma, and lung adenocarcinoma. Our first pan-cancer study provides a relatively profound insights into the oncogenic roles of HJURP across different tumors.

Background Radiotherapy-associated secondary cancer is an important issue for the treatment of breast cancer (BCa). This study aimed to investigate the molecular mechanism and genetic risk factors for radiation-associated secondary diseases in BCa. Methods The differentially expressed genes (DEGs) between preradiation and postradiation BCa samples in the GSE65505 dataset were obtained. The pathways related to the radiation-associated DEGs in the protein–protein interaction (PPI) network modules were identified. miRNAs targeted to the key genes in the PPI network were identified, and their association with BCa prognosis was analyzed. Results A total of 136 radiation-associated DEGs preradiation and postradiation BCa samples were screened out. The PPI network consisted of a significant module that consisted of 21 upregulated DEGs that were associated with “hsa04512: ECM–receptor interaction,” “hsa04151: PI3K-Akt signaling pathway,” and “hsa04115: p53 signaling pathway.” Sixteen DEGs, including three collagen genes collagen type I alpha 1 chain ( COL1A1 ), COL3A1 , and COL1A2 , were enriched in 17 radiation-associated pathways. The three genes were upregulated in BCa tissues compared with controls and were also elevated by radiation. They were targeted by hsa - miR - 29a / c , and the expression levels of hsa - miR - 29a / c were associated with a poor prognosis of BCa. Conclusions The upregulation of COL1A1 , COL3A1 , and COL1A2 might be genetic risk factors for radiation-associated secondary diseases in BCa.

The risk factors associated with metabolic syndrome (Met-S) including hypertension, hyperglycemia, central obesity, and dyslipidemia are preventable, particularly at their early stage. There are limited data available on the association between Met-S and preventable risk factors in young adults. We randomly selected 2,010 Saudis aged 18–30 years, who applied to be recruited in military colleges. All the procedures followed the guidelines of International Diabetes Federation. The results showed that out of 2,010 subjects, 4088 were affected with Met-S. The commonest risk factors were high blood sugar (63.6%), high systolic and diastolic blood pressures (63.3 and 37.3%), and high body mass index (57.5%). The prevalence of prediabetes and diabetes were 55.2 and 8.4%, respectively. Obesity, diabetes, hypertension, and hypertriglyceridemia were significantly associated with Met-S. The frequency of smoking was significantly linked with the development of Met-S. The prevalence of Met-S was found to be significantly higher in individuals with sedentary lifestyle. In conclusion, the results of this study clearly indicate that military recruits, who represent healthy young adults, are also prone to Met-S. The findings of this study will help in designing preventive measures as well as public awareness programs for controlling the high prevalence of Met-S in young adults.

Blood–brain barrier participates in the pathological process of ischemic stroke. MicroRNA-29c-5p was highly expressed in clinical samples from patients with ischemic stroke. In this study, oxygen-glucose deprivation (OGD) treatment of astrocytes enhanced the permeability of brain microvascular endothelial cells (BMECs), and the miR-29c-5p expression was elevated in clinical samples from patients with ischemic stroke. For the function of miR-29c-5p in ischemic stroke, the miR-29c-5p knockdown decreased the permeability and the tight junction protein (TJP) destruction of BMECs and ameliorated the inflammation induced by OGD-treated astrocytes. Mechanistically, miR-29c-5p interacted with lipoprotein receptor-related protein 6 (LRP6) and negatively regulated the LRP6 expression in astrocytes. Moreover, the rescue assays indicated that the interference with miR-29c-5p ameliorated the TJP destruction of BMECs and inflammation caused by OGD-treated astrocytes by increasing the LRP6 expression. Together, miR-29c-5p knockdown decreased the high permeability and the TJP destruction of BMECs and ameliorated the inflammation induced by OGD-treated astrocytes by elevating LRP6 expression.

Metabolic remodeling contributes to the pathological process of heart failure (HF). We explored the effects of cardiac contractility modulation (CCM) on myocardial metabolic remodeling in the rabbit model with HF. The HF in rabbit model was established by pressure uploading and then CCM was applied. We evaluated the cardiac structure and function by echocardiography, serum BNP level, and hematoxylin and eosin and Masson’s trichrome staining. We detected the accumulation of glycogen and lipid droplets in myocardial tissues by periodic acid-Schiff and Oil Red O staining. Then, we measured the contents of glucose, free fatty acid (FFA), lactic acid, pyruvate, and adenosine triphosphate (ATP) levels in myocardial tissues by corresponding kits and the expression levels of key factors related to myocardial substrate uptake and utilization by western blotting were analyzed. CCM significantly restored the cardiac structure and function in the rabbit model with HF. CCM therapy further decreased the accumulation of glycogen and lipid droplets. Furthermore, CCM reduced the contents of FFA, glucose, and lactic acid, and increased pyruvate and ATP levels in HF tissues. The protein expression levels related to myocardial substrate uptake and utilization were markedly improved with CCM treatment by further activating adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptor-α signaling pathways.

Chronic obstructive pulmonary disease (COPD) is mainly caused by cigarette smoking (CS), with oxidative stress being one key component during its pathogenesis. This study aimed to investigate the effects of quercitrin (QE) on cigarette smoke extract (CSE)-induced cell apoptosis and oxidative stress in human bronchial epithelial cells (HBECs) and its underlying mechanism. HBECs were treated with 2% CSE for 24 h to establish in vitro COPD cellular models. CCK-8 assay and flow cytometry analysis were performed to evaluate cell viability and apoptosis, respectively. Western blotting was applied to examine protein levels and ELISA kits were used to examine contents of the indicated oxidant/antioxidant markers. The results demonstrated that CSE promoted apoptosis and suppressed viability of HBECs and QE reversed these effects. CSE caused increase in T-AOC, superoxide dismutase, and glutathione (GSH) peroxidase contents and decrease in MDA, reactive oxygen species , and GSH contents in HBECs, which were rescued by QE treatment. The CSE-induced Nrf2 nuclear translocation and elevation of NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) expression were also reversed by QE in HBECs. The mitogen-activated protein kinase (MAPK) signaling was activated by CSE and further suppressed by QE in HBECs. Collectively, QE exerts a protective role in HBECs against cell apoptosis and oxidative damage via inactivation of the Nrf2/HO-1/NQO1 pathway and the MAPK/ERK pathway.

Purpose Smurf2, one of C2-WW-HECT domain E3 ubiquitin ligases, is closely related to the development and progression in different cancer types, including hepatocellular carcinoma (HCC). This study aims to illustrate the expression and molecular mechanism of Smurf2 in regulating the progression of HCC. Methods The expression of Smurf2 in human HCC and adjacent non-tumor liver specimens was detected using tissue microarray studies from 220 HCC patients who underwent curative resection. The relationships of Smurf2 and HCC progression and survival were analyzed using the chi-square test, Kaplan–Meier analysis, and Cox proportional hazards model. For Smurf2 was low expression in HCC cell lines, Smurf2 overexpression cell lines were established. The effect of Smurf2 on cell proliferation and migration was detected by Cell Counting Kit-8 and colony formation assay, and the epithelial–mesenchymal transition (EMT) markers and its transcription factors were tested by immunoblotting. The interaction and ubiquitination of Smad2 by Smurf2 were detected by co-immunoprecipitation and immunoprecipitation assay. Finally, the effect of Smurf2 on HCC was verified using the mouse lung metastasis model. Results Smurf2 was downregulated in HCC tissues compared to that of corresponding non-tumor liver specimens. The low expression of Smurf2 in HCC was significantly associated with macrovascular or microvascular tumor thrombus and the impairment of overall survival and disease-free survival. In vitro and in vivo analysis showed that Smurf2 overexpression decreased the EMT potential of HCC cells by promoting the ubiquitination of Smad2 via the proteasome-dependent degradation pathway. Conclusion The expression of Smurf2 was downregulated in HCC specimens and affected the survival of patients. Smurf2 inhibited the EMT of HCC by enhancing Smad2 ubiquitin-dependent proteasome degradation.

Acute lung injury (ALI) is a respiratory disorder characterized by acute respiratory failure. circRNA mus musculus (mmu)-circ_0001679 was reported overexpressed in septic mouse models of ALI. Here the function of circ_0001679 in sepsis-induced ALI was investigated. In vitro models and animal models with ALI were, respectively, established in mouse lung epithelial (MLE)-12 cells and C57BL/6 mice. Pulmonary specimens were harvested for examination of the pathological changes. The pulmonary permeability was examined by wet-dry weight (W/D) ratio and lung permeability index. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the bronchoalveolar lavage fluid (BALF), the lung tissues, and the supernatant of MLE-12 cells were measured by enzyme linked immunosorbent assay . Apoptosis was determined by flow cytometry. Bioinformatics analysis and luciferase reporter assay were used to assess the interactions between genes. We found that circ_0001679 was overexpressed in lipopolysaccharide (LPS)-stimulated MLE-12 cells. circ_0001679 knockdown suppressed apoptosis and proinflammatory cytokine production induced by LPS. Moreover, circ_0001679 bound to mmu-miR-338-3p and miR-338-3p targeted dual-specificity phosphatases 16 (DUSP16). DUSP16 overexpression reversed the effect of circ_0001679 knockdown in LPS-stimulated MLE-12 cells. Furthermore, circ_0001679 knockdown attenuated lung pathological changes, reduced pulmonary microvascular permeability, and suppressed inflammation in ALI mice. Overall, circ_0001679 knockdown inhibits sepsis-induced ALI progression through the miR-338-3p/DUSP16 axis.

The aim of the present study was to evaluate the usefulness of measuring whole blood coagulation with Sonoclot to predict return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiopulmonary arrest (OHCA). This was a prospective, observational clinical study on patients with OHCA who were transferred to our emergency department between August 2016 and July 2018. Patients were divided into two groups: patients with return of spontaneous circulation (ROSC[+] group) and those without (ROSC[−] group). We compared the activated clotting time (ACT), clot rate (CR), and platelet function (PF) as measured with Sonoclot, and the fibrinogen degradation products (FDP) level and D-dimer level between the two groups. We analyzed 87 patients: 37 in the ROSC(+) and 50 in the ROSC(−) groups. Regarding ACT, CR, PF, FDP, and D-dimer, we used receiver operating characteristic (ROC) curves to examine how well each factor predicts ROSC. The area under the ROC curve (AUC) of CR was higher than that of the FDP and D-dimer levels. Among patients with cardiogenic cardiac arrest, the AUC of CR was higher than the AUCs of other coagulation factors. In conclusion, viscoelastic blood coagulation measurements using Sonoclot may be useful for predicting ROSC in OHCA patients.

We aimed to screen the drug metabolism-related subgroups of pancreatic adenocarcinoma (PAAD) and to study the prognosis, clinical features, immune infiltration, and gene mutation differences of different subtypes in PAAD patients. All 181 cases of PAAD samples and clinical characteristics data were downloaded from The Cancer Genome Atlas (TCGA). After matching the drug metabolism-related genes downloaded from PMID 33202946 with the TCGA dataset, the drug metabolism-related genes were initially obtained. Besides, univariate Cox regression analysis was used to screen the drug metabolism genes related to the prognosis of PAAD. Moreover, the construction of the protein–protein interaction (PPI) network and gene ontology were performed. The four subgroups of PAAD obtained from unsupervised clustering analysis were systematically analyzed, including prognostic, GSVA, immune infiltration, and gene mutation analysis. A total of 83 drug metabolism genes related to the prognosis of PAAD were obtained and enriched in 16 pathways. The PPI network was composed of 248 relationship pairs. Four subgroups that can identify different subtypes of PPAD were obtained, and there were significant differences in survival and clinical characteristics, mutation types, and immune infiltration abundance between subgroups. A total of 17 different pathways among the four subgroups involved in cell cycle, response to stimulants such as drugs, and transmembrane transport. In this study, the four subgroups related to the drug metabolism of PAAD were comprehensively analyzed, and the important role of drug metabolism-related genes in the immune infiltration and prognosis of PAAD were emphasized.

Osteosarcoma (OS) is the most common type of primary malignant bone tumor. The early lung metastasis of osteosarcoma is one of the main factors of poor prognosis. Therefore, searching for new targets and new mechanisms of osteosarcoma metastasis is essential for the prevention and treatment of osteosarcoma. Our previous studies suggested that fatty acid synthase (FASN) was an oncogene and promoted osteosarcoma. In addition, it is reported that the expression of miR-195 was negatively correlated with osteosarcoma. Aberrant DNA methylation can reversely regulate the expression of miRNAs. However, whether miR-195 could target FASN in osteosarcoma and whether ectopic DNA methylation is the upstream regulatory mechanism of miR-195 in metastasis of osteosarcoma are not fully studied. The expressions were detected by qPCR and western blot, and methylation level was determined by methylation-specific PCR. Luciferase reporter assay, MTT, wound healing, and Transwell assay were used. We found that the expression of miR-195 was low in osteosarcoma. The methylation of miR-195 was high. miR-195 targeted and decreased the expression of FASN. In osteosarcoma, miR-195 inhibited cell proliferation, cell migration, and invasion. The methylation of miR-195 was related to decreased miR-195, it might promote osteosarcoma.

LIM domain only 3 (LMO3) interacts with transcription factors to regulate target genes involved in embryonic development. The oncogenic role of LMO3 in hepatocellular carcinoma, gastric cancer, and neuroblastoma has been reported recently. However, little is known about the biological function of LMO3 in papillary thyroid carcinoma (PTC). First, expression of LMO3 was dramatically enhanced in the PTC tissues and cell lines. Second, knockdown of LMO3 in PTC cells repressed cell proliferation and promoted cell apoptosis with downregulated Bcl-2 and upregulated cleaved caspase-3/PARP. In vitro cell migration and invasion of PTC were also retarded by siRNA-mediated silence of LMO3. Third, protein expression of LIM kinase (LIMK) 1-mediated phosphorylation of cofilin and nuclear translocation of β-catenin were reduced by the knockdown of LMO3. pcDNA-mediated overexpression of LIMK1 promoted cofilin phosphorylation and attenuated LMO3 silence-induced decrease of cofilin phosphorylation. Last, enhanced LIMK1 expression promoted PTC cell proliferation and metastasis and counteracted the suppressive effects of LMO3 silence on PTC cell proliferation and metastasis. In conclusion, LMO3 promoted PTC cell proliferation and metastasis by regulating LIMK1-mediated cofilin and the β-catenin pathway.

Many physiological and pathophysiological processes in cells or tissues are involved in mechanical stretch, which induces the gap junction gene expression and cytokine TGF beta changes. However, the underlying mechanisms of the gap junction gene expression remain unknown. Here, we showed that the mRNA and protein levels of Cx43 in human umbilical vein endothelial cells (HUVECs) were significantly increased after 24 h stretch stimulation, and TGF beta1 (not TGF beta2) expression was also upregulated. Administration of TGF beta1 into HUVECs without stretch also induced upregulation of Cx43 expression. However, SB431542, a specific inhibitor of the TGF beta1 receptor, blocked the Cx43 protein upregulation caused by TGF beta1. Further, the increase of Cx43 protein expression under the stretch condition was partially blocked by SB431542; it was also partially blocked by simultaneous administration of anti-TGF beta1 monoclonal neutralization antibody. Importantly, the upregulation of Cx43 induced by stretch was blocked by the administration of actin and microtubule inhibitors, while NEDD4, a key element in mediating Cx43 protein ubiquitination and degradation, was not changed under the stretch condition. In conclusion, upregulation of Cx43 expression under the 24 h stretch condition is mediated via TGF beta1 receptor signaling pathway, and it also involves the actin and microtubule cytoskeletal network.

We investigated menstrual irregularities after the first and second doses of the COVID-19 vaccine. Women answered a customised online questionnaire (ClinicalTrial.gov ID: NCT05083065) aimed to assess the vaccine type, the phase of the menstrual cycle during which the vaccine was administered, the occurrence of menstrual irregularities after the first and second doses, and how long this effect lasted. We excluded women with gynaecological and non-gynaecological diseases, undergoing hormonal and non-hormonal treatments, in perimenopause or menopause, as well as those who had irregular menstrual cycles in the last 12 months before vaccine administration. According to our data analysis, approximately 50–60% of reproductive-age women who received the first dose of the COVID-19 vaccine reported menstrual cycle irregularities, regardless of the type of administered vaccine. The occurrence of menstrual irregularities seems to be slightly higher (60–70%) after the second dose. Menstrual irregularities after both the first and second doses of the vaccine were found to self-resolve in approximately half the cases within two months. Based on these results, we suggest to consider these elements during the counselling of women who receive the COVID-19 vaccine, letting them know about the potential occurrence of temporary and self-limiting menstrual cycle irregularities in the subsequent month(s).

Little is known about the role of chronic gastritis on weight loss after laparoscopic sleeve gastrectomy (LSG). This study aims to investigate the relationship between histopathologic findings of gastric specimens, excess weight loss (% EWL), and excess BMI loss (% EBL) at 6 and 12 months follow up after LSG. We retrospectively reviewed the clinical records of 95 patients who had undergone LSG between January 2017 and December 2019. Based on the histopathological findings of gastric resection specimens, patients were divided into those with chronic gastritis (CG) and those without chronic gastritis (NoCG) and compared for their % EWL and % EBL at 6 and 12 months. The mean BMI was 44.74 kg/m 2 in the CG group and 44.14 kg/m 2 in the NoCG group. At 6 months follow up, the CG group had a mean % EWL of 45.7 and % EBL of 40.5, while NoCG had a mean % EWL of 51.1 and % EBL of 46.7. After 1-year follow-up, the CG group had a mean % EWL of 53.1 and a % EBL of 44.8, while the NoCG group had a % EWL of 54.1 and % EBL of 44. This observational study does not support the hypothesis that the occurrence of chronic gastritis can affect postoperative % EWL and % EBL.

Increased expression of membrane type 1-matrix metalloproteinase ( MT1-MMP / MMP14 ) is associated with the development of many cancers. MT1-MMP may promote the entry of yes-associated protein1 ( YAP1 ) into the nucleus by regulating the regulation of β1-integrin . The purpose of this study was to investigate the effects of MT1-MMP , β1-integrin and YAP1 on the prognosis of gliomas. The expression of proteins was detected by bioinformatics and immunohistochemistry. The relationship between three proteins and clinicopathological parameters was analyzed by the χ 2 test. Survival analysis was used to investigate the effects of three proteins on prognosis. The results showed that high expressions of MT1-MMP , β1-integrin and YAP1 were found in glioblastoma (GBM) compared with lower-grade glioma (LGG). There was a significantly positive correlation between MT1-MMP and β1-integrin ( r = 0.387), MT1-MMP and YAP1 ( r = 0.443), β1-integrin and YAP1 ( r = 0.348). Survival analysis showed that patients with overexpression of MT1-MMP , β1-integrin and YAP1 had a worse prognosis. YAP1 expression was the independent prognostic factor for progression-free survival (PFS). There was a statistical correlation between the expression of MT1-MMP and YAP1 and isocitrate dehydrogenase 1 ( IDHl ) mutation. Thus, this study suggested that MT1-MMP , β1-integrin and YAP1 , as tumor suppressors, are expected to be promising prognostic biomarkers and therapeutic targets for glioma patients.

When skin cells divide abnormally, it can cause a tumor or abnormal lymph fluid or blood. The masses appear benign and malignant, with the benign being limited to one area and not spreading, but some can spread throughout the body through the body’s lymphatic system. Skin cancer is easier to diagnose than other cancers because its symptoms can be seen with the naked eye. This makes us to provide an artificial intelligence-based methodology to diagnose this cancer with higher accuracy. This article proposes a new non-destructive testing method based on the AlexNet and Extreme Learning Machine network to provide better results of the diagnosis. The method is then optimized based on a new improved version of the Grasshopper optimization algorithm (GOA). Simulation of the proposed method is then compared with some different state-of-the-art methods and the results showed that the proposed method with 98% accuracy and 93% sensitivity has the highest efficiency.

Intrauterine adhesion (IUA) is the clinical manifestation of endometrial fibrosis. The dysregulation of microRNAs (miRNAs) has been confirmed to implicate in a diversity of human diseases, including IUA. Nevertheless, the specific function of miR-223-3p in IUA remains to be clarified. Reverse transcription quantitative polymerase chain reaction analysis displayed the downregulation of miR-223-3p in IUA tissues and endometrial epithelial cells (EECs). Results from wound healing assay, Transwell assay and western blotting showed that TGF-β facilitated the migration and invasion of EECs and induced epithelial-mesenchymal transition (EMT) process as well as extracellular matrix (ECM) deposition. Overexpression of miR-223-3p in EECs was shown to suppress the effects induced by TGF-β. Bioinformatics analysis and luciferase reporter assay revealed the binding relation between miR-223-3p and SP3. SP3 was highly expressed in IUA and its expression was inversely correlated with miR-223-3p expression in IUA tissue samples. Additionally, upregulation of SP3 reversed the influence of miR-223-3p on the phenotypes of EECs. In conclusion, miR-223-3p alleviates TGF-β-induced cell migration, invasion, EMT process and ECM deposition in EECs by targeting SP3.

Several studies reported that the expression of SIRT1 was associated with the clinical features of patients with esophageal squamous cell carcinoma (ESCC), but the function remains inconsistent. We conducted this study to illustrate the clinical value of SIRT1 expression in the early diagnosis and prediction of prognosis of ESCC. In this study, PubMed, Embase, and Web of Science were searched by two independent researchers and STATA14.0 software was used to conduct meta-analysis. The odds ratio with 95% confidence interval was used to estimate the pooled effect. Egger’s test and Begg’s funnel were used to assess publication bias. Sensitivity analysis was used to evaluate the reliability and stability of meta-analysis results. According to the inclusion and exclusion criteria, six studies were enrolled, including 811 cases of ESCC. Results of the meta-analysis indicated that SIRT1 was overexpressed in ESCC and the SIRT1 expression was closely related to the clinicopathological features of ESCC, such as tumor infiltration, tumor node metastasis (TNM) stage, and lymph node metastasis. In the survival analysis, high expression of SIRT1 represented a poor prognosis in ESCC patients. Our study demonstrated that SIRT1 was overexpressed in ESCC, and it might be a potential biomarker for progress of ESCC.

High circ_0020123 expression is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC) as previously reported. Whether circ_0020123 also plays an oncogenic role in lung adenocarcinoma (LUAD) is still unknown. Additionally, circ_0020123 is derived from part of exon (1312–3851) from its host gene PDZ domain-containing protein 8 (PDZD8). We hypothesized that circ_0020123 might affect malignant behaviors of LUAD cells by regulating PDZD8. Reverse transcription quantitative polymerase chain reaction revealed that PDZD8 was highly expressed in LUAD tissues and cells. PDZD8 knockdown suppressed LUAD cell proliferation and migration as shown by colony formation assays, Ethynyl deoxyuridine incorporation assays, Transwell assays, and wound healing assays. circ_0020123 was also found to be upregulated in LUAD tissues and cells. Moreover, circ_0020123 positively regulated PDZD8 expression in LUAD cells but exerted no significant effect on the transcriptional level of PDZD8. Mechanistically, circ_0020123 act as a competing endogenous RNA (ceRNA) to interact with miR-1283, thereby releasing the repression on PDZD8. Moreover, PDZD8 overexpression rescued the suppressive effect of circ_0020123 knockdown on LUAD cell proliferation and migration. In conclusion, circ_0020123 interacts with miR-1283 as a ceRNA to regulate PDZD8 expression, thus promoting the proliferation and migration of LUAD cells. The study might provide new biomarkers for future LUAD investigation.

MiRNAs play an important role in spermatogonial stem cells (SSCs). The purpose of this study was to investigate the basic function of miR-22-5p in cryptorchidism. The results of RT-PCR, western blot, and immunohistochemistry showed that miR-22-5p was increased while EZH2 decreased in the testicular tissues of patients with cryptorchidism. Overexpression of miR-22-5p inhibited the proliferation of SSCs, increased cell apoptosis rate, and reduced expression of SSC marker proteins (GDNF and DAZL); however, knockout of miR-22-5p has the opposite effect. The Luciferase reporter gene assays demonstrated that EZH2 is a direct target of miR-22-5p. Moreover, EZH2 overexpression could reverse the effect of miR-22-5p mimic on SSCs’ proliferation, apoptosis, and expression of SSC marker proteins. Our results demonstrated that miR-22-5p regulates SSCs’ self-renewal by targeting EZH2, which indicated that miR-22-5p may serve as a biological marker for the treatment of infertility caused by cryptorchidism.

Increasing evidence has verified the indispensable effect of microRNAs (miRNAs) in the biological processes of human diseases, including endometriosis. hsa-miR-340-5p was reported to display a low level in patients with endometriosis, but the detailed function of miR-340-5p in endometriosis is unclarified. RT-qPCR was used for the assessment of RNA levels of miR-340-5p and its downstream target genes in endometrial stromal cells (ESCs). Western blotting and Transwell assays revealed that upregulation of miR-340-5p suppressed the migration, invasiveness, and epithelial–mesenchymal transition (EMT) in ESCs. Bioinformatics tools were used to predict miR-340-5p downstream genes. Luciferase reporter assay displayed that miR-340-5p could bind to messenger RNA mitogen-activated protein kinase kinase kinase 2 (MAP3K2). MAP3K2 was targeted by miR-349-5p and could reverse the influence of miR-340-5p. miR-340-5p exerted its impact on the invasive characters of ESCs by inactivating the MAP3K2-mediated MAPK/ERK signaling. In conclusion, miR-340-5p restrains cell migration, invasiveness, and EMT in ESCs by targeting MAP3K2 and inactivating MAPK/ERK signaling.

Insufficient invasion of trophoblast cells is one of the important causes of preeclampsia (PE). Circular RNA (circRNA) has been proven to regulate the biological functions of trophoblast cells and mediate the progression of PE. The expression of circ_0085296, microRNA (miR)-942-5p, and thrombospondin 2 (THBS2) was detected by quantitative real-time PCR. In addition, the interaction between miR-942-5p and circ_0085296 or THBS2 was confirmed by dual-luciferase reporter assay and RIP assay. Our data showed that circ_0085296 was upregulated in the placental tissues of PE patients. Silenced circ_0085296 could enhance the proliferation, migration, invasion, and angiogenesis of HTR-8/SVneo cells. Besides, circ_0085296 was found to act as miR-942-5p sponge. Function analysis results suggested that miR-942-5p inhibitor reversed the positive regulation of circ_0085296 knockdown on the biological functions of HTR-8/SVneo cells. Moreover, THBS2 was a target of miR-942-5p, and its overexpression also reversed the promotion effect of miR-942-5p on the proliferation, migration, invasion, and angiogenesis of HTR-8/SVneo cells. Also, circ_0085296 was discovered to positively regulate THBS2 by sponging miR-942-5p. To sum up, our results revealed that circ_0085296 could inhibit trophoblast cells proliferation, migration, invasion, and angiogenesis by regulating miR-942-5p/THBS2, confirming that circ_0085296 might be a potential therapeutic target for PE.

Despite mechanical thrombectomy, the prognosis for many patients with anterior circulation ischemic stroke (ACIS) remains poor. This retrospective study reports consecutive mechanical thrombectomy procedures for ACIS at our hospital over 4 years. Hemodynamics were explored using transcranial Doppler ultrasound. The functional outcome was assessed using the modified Rankin scale. A total of 121 eligible cases were included: 61 (50.4%) exhibited good outcomes (modified Rankin scale score ≤2) by day 90. The logistic regression analysis showed that ipsilateral middle cerebral artery (iMCA) systolic blood flow (SBF) (OR = 0.983, 95% CI: 0.969–0.997, P = 0.014), preoperative National Institutes of Health Stroke Scale (NIHSS)score (OR = 1.160, 95% CI: 1.067–1.261, P < 0.001), intracranial hemorrhage after therapy (OR = 19.514, 95% CI: 4.364–87.265, P < 0.001), and Alberta Stroke Program Early Computed Tomography Score (OR = 0.639, 95% CI: 0.416–0.981, P = 0.040) were independently associated with prognosis. The iMCA SBF and preoperative NIHSS score were significantly predictive of a good outcome in the receiver operating characteristic analysis. In conclusion, elevated iMCA SBF might be a prognostic indicator of a good 90-day outcome following endovascular treatment in ACIS patients treated with mechanical thrombectomy, but large prospective studies are mandatory to validate the findings of our study.

Many breast cancer patients have both non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty pancreas disease (NAFPD). Consequently, we hypothesized that NAFPD and NAFLD were associated with breast cancer, and aimed to build a novel risk-stratification scoring system based on it. In this study, a total of 961 patients with breast cancer and 1,006 non-cancer patients were recruited. The clinical characteristics were collected and analyzed using logistic analysis. Risk factors were assessed by a risk rating system. Univariate analysis showed that body mass index, triglyceride, total cholesterol, NAFLD, NAFPD, low-density lipoprotein, and uric acid (UA) were significantly related to breast cancer. Among them, NAFLD, NAFPD, and UA were independent risk factors related to breast cancer identified by multivariate analysis. The risk assessment model was established based on these factors and demonstrated that the odds ratio sharply increased with the rising scores. Compared with the low-risk group, the odds ratio in the intermediate- and high-risk groups were 1.662 (1.380–2.001) and 3.185 (2.145–4.728), respectively. In conclusion, the risk-stratification scoring system combining NAFLD, NAFPD, and UA can accurately predict the occurrence of breast cancer.

The activation of signaling pathways induced by Toll-like receptor (TLR) has been demonstrated to play essential roles in multiple liver diseases. Toll-interacting protein (Tollip) acts as an endogenous negative modulator of TLR signaling and is implicated in various cardio-metabolic diseases. However, the effect of Tollip in hepatocellular carcinoma (HCC) remains elusive. In the current study, enhanced Tollip expression was observed in HCC cells and tissues examined by RT-PCR, western blot, and immunohistochemistry staining. Moreover, the co-immunofluorescence staining demonstrated that increased Tollip expression was primarily located in hepatocytes. Functionally, Tollip overexpression significantly increased proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cells, which ultimately accelerated tumorigenesis. Mechanistically, Tollip overexpression dramatically promoted the activation of PI3K/AKT signaling pathway in HCC cells which was attenuated by Tollip silencing. Importantly, the inhibition of PI3K/AKT axis can abolish the promoted effects of Tollip on proliferation and EMT of HCC cells. Our current study demonstrated that Tollip played an important role in the regulation of HCC development by engaging PI3K/AKT signaling pathway. These evidences suggested that the blockade of Tollip-PI3K/AKT axis was an ideal therapeutic treatment for management of HCC.

CircularRNAs (circRNAs) are collectively involved in periodontitis. The aim of this study was to explore the roles of circ_0062491 in osteogenic differentiation of PDLSCs and provide a novel method for periodontitis treatment. mRNA and protein expression levels were measured by qRT-PCR and western blotting. Alkaline phosphatase (ALP) and alizarin red S (ARS) staining were used to detect the activity of osteogenesis. Furthermore, the interactions between miR-142-5p and circ_0062491/ IGF1 were verified by a luciferase reporter assay. circ_0062491 was suppressed in PDL tissues of periodontitis patients and overexpressed in osteogenesis-induced PDLSCs. Upregulated circ_0062491 promoted osteogenic differentiation of PDLSCs. miR-142-5p was verified to be a target of circ_0062491, and the overexpression of miR-142-5p suppressed the osteogenic differentiation of PDLSCs induced by circ_0062491 Additionally, miR-142-5p targeted IGF1, and silenced IGF1 abrogated the effects of suppressed miR-142-5p on osteogenic differentiation of PDLSCs. In conclusion, circ_0062491 acted as a competing endogenous RNA to regulate osteogenic differentiation of PDLSCs via the miR-142-5p/ IGF1 axis. Graphical abstract

Human amniotic fluid collected during amniocentesis contains a heterogeneous population of differentiated and undifferentiated cells. Properties and number of these cells vary depending on the gestational age and the presence of potential fetal pathologies. The aim of this study was to analyze the effects of maternal, fetal, and environmental factors on the success rates of amniotic fluid stem cell cultures, the number of human amniotic fluid stem cells (hAFSC), their growth rates in primary cultures, and the number of cell passages. The study included 355 patients qualified for genetic amniocentesis at the Prenatal Genetic Unit, Department of Obstetrics, Gynecology and Oncologic Gynecology, Nicolaus Copernicus University Medical College in Bydgoszcz in 2011–2017. The mean age of the study participants was 34 ± 6.2 years, and mean gravidity amounted to 2.48 ± 1.4. Amniotic fluid sample volume turned out to be a highly significant ( p < 0.01) predictor of culture success, and the relationship was particularly evident in women older than 40 years. Another highly significant predictor of culture success was the presence of two cell populations in the sample ( p < 0.01). The likelihood of culture success correlated significantly ( p < 0.05) with the season of the year at the time of amniocentesis. The number of cell passages differed significantly depending on the maternal age ( p < 0.01). The number of passages also showed a highly significant relationship with the season of the year the sample was obtained ( p < 0.01). Younger maternal age was identified as a determinant of high passage number (≥3), and another highly significant determinant of high passage number was the presence of two cell populations in the amniotic fluid sample ( p < 0.01). Percentage of successfully established hAFSC cultures and the number of passages depended on amniotic fluid volume, the presence of two cell populations within the sample, and the season of the year. Individual characteristics of the donors, such as age and gravidity, did not exert a significant effect on the number of isolated hAFSCs and the rate of their growth. Patients’ place of residence, fetal karyotype, transportation time, and purity of the samples did not affect the success rates for primary cultures and the number of passages.

Long noncoding RNAs (lncRNAs) are key regulators of hepatic stellate cells (HSCs), yet the role of upregulated lncRNA-NONRATT013819.2 in activated HSCs remains uncertain. In this study, the effects of NONRATT013819.2 on proliferation, apoptosis, migration, and contraction of transforming growth factor (TGF)-β1-induced HSCs were investigated. The mechanisms of NONRATT013819.2 on the activated HSCs were explored by loss-of-function of NONRATT013819.2 and gain-of-function of the target gene. Here, TGF-β1 treatment resulted in a gradual increase in the expression of cytoskeleton markers (collagen, α-SMA, and TIMP1), NONRATT013819.2, miR24-3p, and lysyl oxidase (Lox) over time in HSCs. NONRATT013819.2 acted as a sponge of miR24-3p to competitively abolish the inhibition of the lox gene in HSCs. Silencing of NONRATT013819.2 suppressed the expression of cytoskeleton markers, proliferation, and the proportion of cells that entered the S-phase, and promoted apoptosis in TGF-β1-activated HSCs. These effects were reversed when lox overexpression was introduced simultaneously. Similarly, silencing of NONRATT013819.2 also blocked ECM reconstruction, while recused by lox overexpression in TGF-β1-activated HSCs. In conclusion, upregulation of NONRATT013819.2 promotes the myofibroblastic transition by competitively binding miR24-3p to release lox in HSCs. Therefore, targeted therapy of NONRATT013819.2 may have the potential for liver fibrosis.

Acute lung injury (ALI) is a devastating human malignancy characterized by excessively uncontrolled inflammation and lung endothelial dysfunction. Non-coding RNAs play essential roles in endothelial protections during the pathological processes of ALI. The precise functions and molecular mechanisms of the lncRNA-NORAD-mediated endothelial protection remain obscure. This study reports NORAD was significantly induced in human pulmonary microvascular endothelial cells (HPMECs) under lipopolysaccharide (LPS) treatment. Silencing NORAD effectively protected HPMECs against the LPS-induced cell dysfunction. In addition, RNA pull-down and luciferase assay validated that NORAD sponged miR-30c-5p, which showed reverse functions of NORAD in the LPS-induced cell injury of HPMECs. Furthermore, the glucose metabolism of HPMECs was significantly elevated under LPS stimulation which promoted the glucose consumption and extracellular acidification rate (ECAR) of HPMECs. Inhibiting NORAD or overexpressing miR-30c-5p suppressed glucose metabolism in HPMECs, leading to protective effects on HPMECs under LPS stimulation. The glycolysis key enzyme, lactate dehydrogenase-A (LDHA), was subsequently identified as a direct target of miR-30c-5p. Finally, recovery of miR-30c-5p in NORAD-overexpressing HPMECs effectively overrode the NORAD-promoted glycolysis and impaired endothelial dysfunction under LPS stimulation by targeting LDHA. Summarily, we demonstrated a NORAD-miR-30c-5p-LDHA-glycolysis axis in the LPS-induced HPMECs dysfunction in vitro and in vivo , contributing to the development of anti-ALI therapeutic approaches.

The present report investigates the impact of a Telemedicine Service (TMS) on the management of Idiopathic Pulmonary Fibrosis (IPF) during coronavirus disease of 2019 (COVID-19) outbreak in Italy. The TMS comprised 3 phone numbers, active 12 h per day, and an email address, monitored every 4 h by trained physicians; chat- and videoconference-services were also offered. At the end of the study period, our staff contacted all patients, to get information about the final outcome (i.e. composite hospitalisations/all causes of death). Outcomes were compared with a cohort of patients who attended our unit in the same period of the previous year (when no TMS was available). 189 patients participated in the present study. From 11th March to 4th May 2020, 61% of patients made at least one TMS access, mostly by emails (53%), followed by phone calls (33%). With regard to the primary outcome, TMS patients experienced a significant lower rate of events of the 182 patients of the no-TMS cohort ( p < 0.001). Specifically, a significant difference was observed for IPF hospitalisation ( p < 0.001) whereas no differences were observed with regard to deaths ( p = 0.64). TMS permits patients to be followed up even during COVID-19 lockdown, with an encouraging impact on outcomes.

This study aimed to investigate the possible influence of genetic and non-genetic factors on the incidence of clopidogrel adverse drug reactions (ADRs) in cardiology patients, including the most important CYP2C19 alleles, namely *2 and *17, as well as compliance, dose, drug interactions, and clinical factors. A total of 102 clopidogrel-treated adult Caucasian patients hospitalized at the Cardiology Department of the Clinical Center of Montenegro were enrolled in the study. Data on clinical outcomes of interest were obtained by intensive monitoring ADRs during hospitalization and one year after hospital discharge. Genotyping for CYP2C19 *2 and *17 was conducted using the real-time polymerase chain reaction method. ADRs were characterized using the Rawlins and Thompson classification and the World Health Organization criteria. Causality was assessed using the Naranjo probability scale. ADRs to clopidogrel were observed in 9 of 102 patients (8.8%). The observed frequencies of CYP2C19 *2 and *17 were 13.2 and 25.5%, respectively. Our study, which is the first to report the frequency of CYP2C19 polymorphism in the Montenegrin population, as well as to link the pharmacovigilance of clopidogrel with CYP2C19 gene variability, shows that the incidence of ADRs of clopidogrel in cardiac patients is high and depends on CYP2C19 polymorphisms, comedication/drug interactions, and gastrointestinal comorbidity.

This study aimed to assess the association between serum zinc level with some inflammatory and immunity factors and the duration of hospitalization and mortality rate in patients diagnosed with Covid-19. In this cross-sectional study, blood samples were taken from polymerase chain reaction (PCR) positive patients. New patients diagnosed with Covid-19, admitted to different public hospital wards, were considered eligible for entering the study. The study was done on 179 hospitalized patients diagnosed with Covid-19. Fourteen patients died during the hospitalization and the in-hospital mortality rate was 7.8%, with 9.1% (13 patients) of patients with serum zinc level less than 70 mcg/dL and 3.4% (1 patient) of patients with zinc levels more than 70 mcg/dL. Higher levels of zinc were significantly associated with a higher and lower level of interferon-gamma (IFN-γ) ( p -value = 0.035) and interleukin (IL)-6 ( p -value = 0.004), respectively. The level of serum zinc did not have a significant association with mortality even after adjusting for confounding factors. The relationship between zinc level and the duration of hospitalization was also not significant. In conclusion, serum zinc level had an association with IL-6 and IFN-γ level, but it did not have any significant association with hospital duration or mortality.

The purpose of this study was to investigate the relationship between night shift work and breast cancer (BC) incidence. A search was performed in PubMed, EBSCO, Web of Science, and Cochrane Library databases before June 2021. The exposure factor of this study is night shift work, the primary outcome is the risk of BC. A total of 33 observational studies composed of 4,331,782 participants were included. Night shift work increases the risk of BC in the female population (hazard ratio [HR] = 1.20, 95% confidence interval [Cl] = 1.10–1.31, p < 0.001), especially receptor-positive BC, including estrogen receptor (ER)+ BC (HR = 1.35, p < 0.001), progesterone receptor (PR)+ BC (HR = 1.30, p = 0.003), and human epidermal growth factor receptor 2 (HER2)+ BC (HR = 1.42, p < 0.001), but has no effect on HER2− BC (HR = 1.10, p = 0.515) and ER−/PR− BC (HR = 0.98, p = 0.827). The risk of BC was positively correlated with night shift working duration, frequency, and cumulative times. For women who start night work before menopause, night work will increase the incidence of BC (HR = 1.17, p = 0.020), but for women who start night work after menopause, night work does not affect BC (HR = 1.04, p = 0.293). Night work can increase the incidence of BC in the female population. The effect of long working hours, frequency, and the cumulative number of night shifts on BC is influenced by menopausal status.

Idiopathic achalasia is a primary esophageal motility disorder characterized by the absence of esophageal peristalsis and impaired relaxation of the lower esophageal sphincter (LES). However, the pathogenesis of idiopathic achalasia remains unclear. To further understand the pathogenesis, we conducted lncRNA and mRNA microarray analyses. LES specimens from 5 patients and 4 controls were used for microarray. Potential target genes with significantly changed lncRNA and mRNA were predicted using cis/trans-regulatory algorithms, followed by the Gene Ontology and KEGG pathway enrichment analysis to understand the biophysical effect. Finally, 7,133 significantly dysregulated mRNAs (3,136 increased and 3,997 decreased), along with 6,892 significantly dysregulated lncRNAs (4,900 increased and 1,992 decreased). Biophysical function analysis revealed that the cell adhesion molecule (CAM) pathway was a common pathway. The predicted lncRNA targets of NRXN1 (Down FC: 9.07), NTNG2 (UP FC: 2.75), CADM1 (Down FC: 2.26), NLGN1 (Down FC: 4.60), NEGR1 (Down FC: 2.335), CD22 (Down FC: 5.62), HLA-DQB1 (Down FC: 5.06), and HLA-DOA (Down FC: 2.31) were inputted in this pathway, which was mainly located in the synapse part of the neural system and immune system. Our study demonstrates the lncRNAs and corresponding mRNAs that may play important roles in idiopathic achalasia.

Spinal cord injury (SCI) is a devastating incident that induces neuronal loss and dysfunction. Notoginsenoside R1 (NGR1) has been reported to exhibit a neuroprotective role after SCI. In this study, the effect and molecular mechanisms of NGR1 in models of SCI were further investigated. Rat adrenal pheochromocytoma cell line (PC-12) were stimulated with lipopolysaccharide (LPS) to establish a cell model of SCI-like condition. The changes of proinflammatory cytokines and associated proteins were analyzed using enzyme linked immunosorbent assay (ELISA) and western blotting. A rat model of SCI was established. Nissl staining were used to observe the morphological characteristics of spinal cord tissues. reverse transcription-quantitative PCR (RT-qPCR) was used to measure the expression of miR-301a andKrüppel-like factor 7 (KLF7). Our results showed that NGR1 alleviated LPS-triggered apoptosis and inflammation in PC-12 cells. MiR-301a was upregulated in LPS-stimulated PC-12 cells and was downregulated by NGR1 treatment. MiR-301a overexpression reversed the effect of NGR1 in LPS-treated PC-12 cells. KLF7 was verified to be targeted by miR-301a. NGR1 activated Wnt/β-catenin signaling in LPS-treated PC-12 cells by inhibiting miR-301a and upregulating KLF7. Moreover, blocking wingless/integrated (Wnt)/β-catenin signaling eliminated the protective effect of NGR1 against SCI in vitro and in vivo . Overall, NGR1 could reduce inflammation and apoptosis and promote functional recovery of SCI rats by activating Wnt/β-catenin pathway.

In this study, we aim to investigate moscatilin in alleviating symptoms of autoimmune liver disease (ALD) in a concanavalin A (ConA)-induced liver injury mouse model and elucidate the underlying mechanisms. ALD mouse models were constructed by intravenous injection of ConA (20 mg/kg) and the serum level of alanine aminotransferase (ALT) was measured using an enzyme-linked immunosorbent assay. Moscatilin in various doses was administered for two days starting from a day before the ConA injection. We showed that moscatilin dose-dependently decreased ALT levels in liver tissue of ALD mouse models. Ifng and Tnfa also showed significant downregulation in liver tissues. Macrophages only showed significant Tnfa downregulation and CD4 + T cells only showed significant Ifng downregulation at high moscatilin doses. In vivo administration of moscatilin induced interleukin-37 upregulation in hepatic tissues. In vitro , moscatilin also induced IL-37 upregulation in hepatic stellate cell line JS-1 rather than immune cells represented by RAW264.7 and CTLL-2 cell lines, suggesting that the hepatic stellate cell is majorly responsive to moscatilin treatment in terms of interleukin (IL)-37 upregulation. Our data indicate that moscatilin could alleviate liver injury in ConA-induced ALD mouse models through anti-inflammatory activities, warranting further development of moscatilin as a new drug in treating ALD.

This study examined the potential mechanism of zoledronate on interleukin (IL)-1β-induced temporomandibular joint osteoarthritis (TMJOA) chondrocytes, using IL-1β-induced rabbit immortalized mandibular condylar chondrocytes cultured with zoledronate. Cell viability, apoptosis, mRNA, and protein expression of relevant genes involved in extracellular matrix (ECM) degradation, apoptosis, and Wnt/β-catenin signaling were examined. The involvement of the Wnt/β-catenin signaling was examined using Wnt/β-catenin inhibitor (2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-4-ol (XAV-939)) and activator lithium chloride (LiCl). Aggrecan and type II collagen were downregulated by zoledronate, especially with 100 nM for 48 h ( p < 0.01), consistently with the upregulation of A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) ( p < 0.001), matrix metalloprotease-9 (MMP-9) ( p < 0.01), caspase-3 ( p < 0.001) and downregulation of proliferating cell nuclear antigen (PCNA) ( p < 0.01). The apoptotic rate increased from 34.1% to 45.7% with 100 nM zoledronate for 48 h ( p < 0.01). The effects of zoledronate on ADAMTs4 ( p < 0.001), MMP-9 ( p < 0.001), caspase-3 ( p < 0.001), and PCNA ( p < 0.01) were reversed by XAV-939, while LiCl increased caspase-3 expression ( p < 0.01). In conclusion, zoledronate enhances IL-1β-induced ECM degradation and cell apoptosis in TMJOA chondrocytes. Wnt/β-catenin signaling might be involved in this process, but additional studies are necessary to determine the exact involvement of Wnt/β-catenin signaling in chondrocytes after zoledronate treatment.

Epithelial-mesenchymal transition (EMT) is critical in the development of coronary artery disease (CAD). However, landscapes of EMT-related genes have not been fully established in CAD. We identified the differentially expressed mRNAs and lncRNAs (DElncRNAs) from the Gene Expression Omnibus database. Pearson’s correlation analysis, the least absolute shrinkage and selection operator regression, and support vector machine reverse feature elimination algorithms were used to screen EMT-related lncRNAs. The cis–trans regulatory networks were constructed based on EMT-related lncRNAs. Quantitative real-time polymerase chain reaction was performed to validate the expression of EMT-related genes in a cohort of six patients with CAD and six healthy controls. We further estimated the infiltration of the immune cells in CAD patients with five algorithms, and the correlation between EMT-related genes and infiltrating immune cells was analyzed. We identified eight EMT-related lncRNAs in CAD. The area under curve value was greater than 0.95. The immune analysis revealed significant CD8 T cells, monocytes, and NK cells in CAD and found that EMT-related lncRNAs were correlated with these immune cell subsets. Moreover, SNAI2, an EMT-TF gene, was found in the trans-regulatory network of EMT-related lncRNAs. Further, we found SNAI2 as a biomarker for the diagnosis of CAD but it also had a close correlation with immune cell subsets in CAD. Eight EMT-related lncRNAs and SNAI2 have important significance in the diagnosis of CAD patients.

The objective of this study was to compare the clinical effectiveness of traditional vaginal surgery and transvaginal mesh (TVM) surgery on severe pelvic organ prolapse (POP). We performed a retrospective chart review study of 258 severe POP patients who underwent surgery between November 2010 and September 2016. One hundred forty patients underwent traditional vaginal surgery and 118 TVM surgery. The Pelvic Organ Prolapse Quantitation (POP-Q) staging was used for objective evaluation. The Pelvic Floor Distress Inventory-20 (PFDI-20), Pelvic Floor Disease Life Impact Questionnaire Simplified Version-7 (PFIQ-7), and Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire (PISQ-12) were used for subjective evaluation. Their complications were also recorded. All the data were collected in the outpatient department through the follow-up at 3 months, 1, 3, and 5 years after the operation. Forty patients in the traditional vaginal surgery group and 25 in the TVM group were lost to follow-up. There was no difference in the POP-Q score between the groups ( P = 0.346). The recurrence rate increased with follow-up time, reaching nearly 20% in the two groups by 5 years. The TVM group has higher PFDI-20 and PFIQ-7 scores and lower PISQ-12 scores than the traditional vaginal surgery group at six months, 1, 3, and 5 years, respectively ( P < 0.001). Mesh exposure has occurred in the TVM group. Both surgeries showed similar objective satisfaction and recurrence rate. However, traditional vaginal surgery has higher subjective satisfaction than TVM in our study and does not risk exposure to prosthetic material.

Splenic embolization is a minimally invasive alternative to splenectomy for the treatment of hypersplenism. This was a retrospective study of 101 patients with hypersplenism caused by cirrhosis who were treated with splenic embolization and for whom 6 months of follow-up data were available. Of these patients, 65 underwent partial splenic artery embolization (PSE), including 23 who underwent repeated PSE (RPSE). The incidence of abdominal pain was significantly higher in the PSE group than in the total splenic artery embolization (TSE) group ( P < 0.001), and its duration was also longer in the PSE group ( P = 0.003). Biochemical markers of liver function were compared before and after the operation; aminotransferase indices decreased (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), total bilirubin increased slightly, and albumin and prealbumin decreased after the operation (all P < 0.001). Platelet (PLT) counts began to increase at 1 week postoperatively, peaked at 1 month postoperatively, and then decreased gradually. There was no significant intergroup (PSE and TSE) difference at any time point (1 day, 1 week, 1 month, and 6 months postoperatively, P > 0.05). There was a significant intergroup (PSE and RPSE) difference in the mean postoperative change in PLT count ( P = 0.45). Splenic embolization can improve the inflammatory indicators of liver function. Performing PSE twice or more improves the PLT counts.

Non-small cell lung cancer (NSCLC) is a malignant tumor. Serum exosomal miR-27b is related to tumor diagnosis. We explored the roles of serum exosomal miR-27b in NSCLC. NSCLC patients were assigned to NSCLC-early/terminal groups, with healthy subjects as controls. miR-27b expression was assessed using reverse transcription-quantitative polymerase chain reaction, and its diagnostic efficiency was analyzed using the receiver operating characteristic curve. The correlation between serum exosomal miR-27b expression and tumor markers carcinoembryonic antigen 125 (CA125), carcinoembryonic antigen (CEA), and cytokeratin 19-soluble fragment (CYFRA21-1) was analyzed using the Pearson analysis. The downstream target genes were predicted. Epidermal growth factor receptor (EGFR) level was assessed using enzyme-linked immunosorbent assay. Correlations of miR-27b expression with serum EGFR level and CA125, CEA, and CYFRA21-1 levels were analyzed using the Pearson analysis. Serum exosomal miR-27b was diminished in NSCLC and was further decreased in the NSCLS-terminal group. The sensitivity of miR-27b < 0.8150 for NSCLC diagnosis was 76.64%, and the specificity was 83.33%. Serum exosomal miR-27b was negatively correlated with CA125, CEA, and CYFRA21-1. miR-27b targeted EGFR. Serum EGFR was raised in NSCLC and was further elevated in the NSCLS-terminal group. miR-27b expression was negatively correlated with EGFR level. EGFR level was positively correlated with CA125, CEA, and CYFRA21-1 levels. Collectively, low expression of miR-27b assisted NSCLC diagnosis, and miR-27b exerted effects on NSCLC through EGFR.

This study aims to explore the function and mechanism of exosomal circ_0000519 in non-small cell lung cancer (NSCLC) development. Expression of circ_0000519, microRNA (miR)-1258, and Ras homolog gene family V (RHOV) in serum samples of NSCLC patients or cell lines were examined via quantitative reverse transcription-polymerase chain reaction and Western blotting. The function of circ_0000519 was evaluated through 5-ethynyl-2′-deoxyuridine (EdU) staining, colony formation, transwell, Western blotting, xenograft, and immunohistochemistry analyses. The binding relationship was evaluated by a dual-luciferase reporter assay and RNA pull-down assay. Results showed that circ_0000519 abundance was enhanced in the serum samples of NSCLC patients and cells. circ_0000519 knockdown suppressed the cell growth by decreasing the colony-formation ability and Cyclin D1 expression and inhibited cell metastasis via reducing migration, invasion, and levels of Vimentin and matrix metalloproteinase 9 (MMP9). circ_0000519 overexpression promoted cell growth and metastasis. circ_0000519 was carried by exosomes and knockdown of exosomal circ_0000519 suppressed the cell growth and metastasis. miR-1258 was downregulated in NSCLC cells and targeted by circ_0000519. RHOV was targeted by miR-1258 and upregulated in the NSCLC cells. miR-1258 knockdown or RHOV overexpression attenuated the influence of exosomal circ_0000519 knockdown on cell growth and metastasis. Exosomal circ_0000519 knockdown decreased xenograft tumor growth. Collectively, the knockdown of exosomal circ_0000519 repressed the cell growth and metastasis in NSCLC through the miR-1258/RHOV axis, which provided a new insight into NSCLC development and treatment.

Our previous study has demonstrated that miR-455-5p was a tumor suppressor in colorectal cancer (CRC). This study aimed to investigate the role of miR-455-5p in 5-fluorouracil (5-Fu) in CRC. The expression of miR-455-5p, PIK3R1, and DEPDC1 was analyzed in HT-29 cells after treatment with different concentrations (0, 0.5, 2.5, and 12.5 μM) of 5-Fu. The effects of miR-455-5p on cell proliferation and apoptosis were analyzed by CCK-8 and flow cytometry. PIK3R1 and DEPDC1 were overexpressed to measure the mechanism of miR-455-5p on 5-Fu sensitivity. And the direct binding between miR-455-5p and DEPDC1 was detected by a dual-luciferase reporter assay. We found that miR-455-5p decreased, while PIK3R1 and DEPDC1 increased after 5-Fu treatment. miR-455-5p mimic significantly suppressed cell viability and elevated cell apoptosis in 5-Fu-treated HT-29 cells, whereas miR-455-5p inhibitor showed the opposite effects. Overexpression of PIK3R1 and DEPDC1 could attenuate the effects of miR-455-5p mimic on the viability and apoptosis of 5-Fu-treated cells. miR-455-5p could directly bind to DEPDC1 in HT-29 cells. In conclusion, miR-455-5p enhanced 5-Fu sensitivity by targeting PIK3R1 and DEPDC1 in CRC. This study provides a novel role of miR-455-5p in CRC and restoring miR-455-5p might be a therapeutic strategy to enhance chemosensitivity to 5-Fu.

The aim of this study is to determine whether the use of tranexamic acid (TXA) in patients with hip fracture reduces intraoperative and postoperative blood loss, and on the other hand, whether it increases thromboembolic risk. The study was performed on patients with hip fracture for a period of one year. Patients were divided into two groups (1:1): the first group receiving TXA and the second group receiving placebo. The amount of blood aspiration during the surgery was measured as well as drainage in the postoperative period of 24 h. The occurrence of deep vein thrombosis (DVT) was monitored before and after the surgery by ultrasound of the lower extremities. The amount of total blood loss was two times lower in patients who received TXA (291.8 ± 65.5 mL of blood vs 634.7 ± 150.5 mL of blood). Among the patients who developed DVT, one patient was from the group that did not receive TXA, and two patients were from the group that received TXA. The use of TXA in patients with hip fracture significantly reduces intraoperative and postoperative blood loss, without a significant thromboembolic risk.

The present study intends to clarify the hypothesis that isocitrate dehydrogenase 1 (IDH1) mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to ferroptosis through the in vitro and in vivo experiments. Cholangiocarcinoma RBE cell line was transfected with IDH1 R132C mutation plasmids and treated with erastin to induce ferroptosis, which were then microscopically photographed. Cell viability rate was calculated by trypan blue staining. The lipid ROS level was determined by using flow cytometer. The BALB/c nude mice were injected subcutaneously with IDH1 knockout (KO), WT, or R132C mutation cell line, followed by injecting erastin intraperitoneally. The tumor tissue was surgically separated for the measurement of tumor volume and weight. The results showed that IDH1 mutant RBE cell line are sensitive to erastin-induced ferroptosis, evidenced by the increased number of propidium iodide-positive cells, the decreased cell viability, and increased lipid ROS level. However, current targeted inhibitors of IDH1 mutation (AG120 and IDH305) reversed these effects caused by IDH1 mutation. The in vivo experiment showed that IDH1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to erastin-induced ferroptosis. This study indicated that IDH1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to erastin-induced ferroptosis.

This study investigated whether artemisinin (ART) exerts a neuroprotective effect against cerebral ischemia/reperfusion (I/R) injury. Hypoxia-glucose deprivation and reoxygenation (OGD/R) of SH-SY5Y cells were used as the I/R injury model in vitro . Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and lactate dehydrogenase (LDH) release was measured. Cell apoptosis and apoptosis-associated protein expression were determined via flow cytometry and western blotting, respectively. The levels of glutathione peroxidase, superoxide dismutase, catalase, and malondialdehyde were determined. The secretion of tumor necrosis factor-α and interleukin-1β was measured using ELISA. The activation of the nuclear factor kappa B (NF-κB) pathway was also determined. The indicated ART concentrations (0, 25, 50, 75, and 100 μM) had no significant effect on SH-SY5Y cell viability and LDH activity. ART promoted cell viability, reduced cell apoptosis, repressed cellular inflammation, and inhibited cellular oxidative stress and NF-κB signaling pathway in OGD/R-induced SH-SY5Y cells. In addition, all the protective effects of ART on OGD/R-induced SH-SY5Y cell injury were significantly reversed by an NF-κB agonist. In conclusion, ART protects neurons from OGD/R-induced damage in vitro by inhibiting the NF-κB signaling pathway. These results suggest that ART may be a potential agent for the treatment of cerebral I/R injury.

Homologous recombination deficiency (HRD) commonly occurs in breast cancer, which is the second cause of cancer death in women with a high rate of relapse and poor outcomes. Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Thus, we aim to develop a prognostic signature based on HRD expecting to help improve outcomes in TNBC. The Cancer Genome Atlas (TCGA)–TNBC cohort was divided into the training set and the testing set randomly. Sixteen genes were filtered from the prognostic HRD-associated genes to establish a prognostic model in the training set. Patients were divided into high-risk and low-risk groups based on the median value of the risk score. Prognosis analysis showed that the high-risk group was associated with a worse prognosis in the training set, the testing set, the entire TCGA–TNBC cohort, and the METABRIC–TNBC cohort. The time-dependent receiver operating characteristic curve showed that our model had very good accuracy in the prediction of 1–5-year overall survival in the TCGA–TNBC cohort. Besides, a comparison of the area under curve value and C -index between our model and four published models showed that our model had the best predictive efficiency compared to other models. Subsequently, a nomogram was established. Finally, our finding also indicated that our model was associated with immunoregulation in TNBC and had the potential to be the target for TNBC treatment. Therefore, our findings not only provided a new strategy in the personalized prognosis management of TNBC but also offered new insight into precision treatment in TNBC.

This study is intended to explore the mechanism that lidocaine ameliorates chronic constriction injury (CCI)-induced neuropathic pain (NP) related to the polarization of M1 and M2 microglia. CCI rats were established by surgery to induce NP. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats were determined. Microglial line HAPI cells were polarized into M1 or M2 cells using lipopolysaccharide (LPS) or interleukin (IL)-4, respectively. Immunofluorescence staining was performed to determine the Iba1/CD86- and Iba1/CD206-positive cells. Markers of M1 and M2 microglia were assessed using flow cytometry. Real-time polymerase chain reaction and enzyme-linked immunosorbent assay were performed to detect the level of mRNA and inflammatory factors. Lidocaine ameliorates CCI-induced NP, evidenced by the markedly increased values of MWT and TWL in NP rats. Lidocaine inhibited M1 microglia polarization but promoted M2 microglia polarization in a rat model of CCI-induced NP. Besides, in the in vitro experiment, lidocaine regulated M1/M2 polarization in LPS- or IL-4-treated HAPI microglia. Lidocaine ameliorates CCI-induced NP by regulating M1/M2 microglia polarization. This study investigated the biological role of lidocaine in regulating NP in rats, which may be helpful for revealing the pathogenic mechanisms of NP and provide a potential therapeutic factor.

This study aimed to determine whether microRNA-322-5p regulates seizure and seizure damage by targeting the TLR4/TRAF6/NF-κB-associated inflammatory signaling pathway. In a pilocarpine-induced epileptic rat model, the expressions of miR-322-5p, TLR4, NF-κB, TRAF6, IRF5, IL-1β, and GABA were assessed by a quantitative polymerase chain reaction and western blotting. Tunel detects hippocampal neuron apoptosis. The results showed that the expression of miR-322-5p significantly decreased in status epilepticus (SE) rats. The reduction of miR-322-5p was accompanied by increased levels of pro-inflammatory cytokines, an increased NF-κB expression, and reduced γ-aminobutyric acid (GABA) levels. Exogenous miR-322-5p reduced the expression of inflammatory molecules and increased the GABA levels in SE rats, and also reduced hippocampal neuronal cell apoptosis caused by epilepsy. In conclusion, the miR-322-5p significantly inhibited the TLR4/TRAF6/NF-κB-associated inflammation and reduced neuronal apoptosis, suggesting that its induction may be of potential interest for novel antiseizure medications.

The aim of this study was to verify the biological function of miR-1273h-5p in gastric cancer (GC) and its underlying mechanisms. The differential expression of microRNAs between GC and tumor-adjacent normal tissues was detected using microarrays, miR-1273h-5p, and chemokine (C-X-C motif) ligand 12 (CXCL12) mRNA, and protein levels were evaluated using polymerase chain reaction and Western blotting methods, cell proliferation, apoptosis, migration, and invasion were determined by CCK-8, flow cytometry, and transwell assay. Compared to tumor-adjacent normal tissue and gastric epithelial mucosa cell line cells, miR-1273h-5p was significantly downregulated in tissues and cells of GC. The overexpression of miR-1273h-5p could inhibit cell proliferation, migration, invasion, and promote cell apoptosis; in contrast, inhibition of miR-1273h-5p expression could reverse this process. Moreover, a significant upregulation of CXCL12 was observed when the miR-1273h-5p was downregulated in GC cells. Additionally, miR-1273h-5p significantly reduces tumor volume and weight. Thus, this study suggests that miR-1273h-5p regulates cell proliferation, migration, invasion, and apoptosis during GC progression by directly binding to CXCL12 mRNA 3′-untranslational regions, which may be a novel diagnostic and therapeutic target in GC.

Epidemiological and clinical characteristics of patients with COVID-19 have been reported in the last two years. A few studies reported clinical course of illness of median 22 days, including viral shedding of median 20 days, but there are several cases with a longer time of viral shedding. In this study, we included four cases with a longer illness course of more than 40 days who had been discharged or still in hospital by March 15, 2020. Demographic, clinical treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records. We described the epidemiological and clinical characteristics and the course of viral shedding. Two patients had comorbidity, one with hypertension and the other with diabetes. We found smoking was not an independent risk factor. D-dimer maybe related to the severity of illness but not to the course of the illness. Nucleic acid detection suggested that maybe more sampling sites represented more virus replication sites and longer course of illness. In this study we found some non-critical severe relatively young patients whose character was different from former studies described to provide a basis for reference to assess the risk of transmission and the isolation duration of patients.

Circular RNAs (circRNAs) serve as essential players in diverse human cancers, including retinoblastoma (RB). In this study, the function of circRNA Ring Finger Protein 20 (circRNF20) in RB progression was investigated. Quantitative real-time polymerase chain reaction, western blot assay or immunohistochemistry assay was performed to determine the expression of circRNF20, miR-132-3p and Paired Box 6 (PAX6). Dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay were utilized to verify the relationships among circRNF20, miR-132-3p and PAX6. In vivo experiment was done for circRNF20 function in tumor formation. It was found that ircRNF20 level was increased in RB tissues and linked to advanced tumor, nodes, metastases (TNM) stage and poor overall survival rate. Deficiency of circRNF20 suppressed cell proliferation, migration and invasion and induced apoptosis in vitro , as well as blocked tumor growth in vivo . circRNF20 directly targeted miR-132-3p and miR-132-3p overexpression inhibited RB cell progression. PAX6 was the target gene of miR-132-3p. Moreover, miR-132-3p inhibition or PAX6 overexpression reversed circRNF20 deficiency-mediated effects on RB cell malignant behaviors. In addition, exosomal circRNF20 was able to promote RB cell progression. Thus, we concluded that circRNF20 served as an oncogene in RB progression through the circRNF20/miR-132-3p/PAX6 pathway.

Both linezolid and vancomycin have good efficacy in the treatment of resistant Gram-positive bacterial infections. This systematic review and meta-analysis aimed to compare the efficacy and safety of linezolid vs vancomycin for the treatment of resistant Gram-positive bacterial infections in children under 12 years. Five randomly controlled trials involving 638 children that were treated with linezolid and vancomycin for resistant Gram-positive bacterial infections were searched from medical databases. Meta-analysis showed that linezolid and vancomycin had equivalent efficacies in clinical cure rates in the intent-to-treat population (95% confidence interval [CI] 0.88, 2.09) and microbiologically evaluable patients (95% CI: 0.46, 2.47). Linezolid and vancomycin also had equivalent pathogen eradication rates for Staphylococcus aureus (95% CI: 0.31, 4.81), methicillin-resistant S. aureus (95% CI: 0.36, 5.34), Enterococcus faecalis (95% CI: 0.32, 8.76), and coagulase-negative Staphylococci (95% CI: 0.43, 4.01). Vancomycin resulted in a higher incidence of alanine aminotransferase increase (95% CI: 0.37, 0.97), red man syndrome (95% CI: 0.01, 0.28), and rash (95% CI: 0.11, 0.73) than linezolid. Clinically, linezolid had a superior safety to vancomycin for resistant Gram-positive infections. Linezolid might be prescribed for the treatment of resistant Gram-positive bacterial infections in children under 12 years.

Diabetic nephropathy (DN) is one of the chronic microvascular diseases of diabetes. Studies revealed that inflammation is involved in the development of DN. However, its mechanisms are not fully clear. Here, we screened DN-related mRNAs by RNA sequencing in the renal tissues of db/db DN mice and normal control mice. The Swiss-Model, ZDOCK 3.0.2 and PyMOL 2.3.2 were applied for bioinformatics analysis. In total, we obtained 6,820 mRNAs that were dysexpressed in DN. Among them, Receptor for Activated C Kinase 1 (Rack1) was focused on for its high fold changes and high values of fragments per kilobase million (FPKM) in both two groups (FPKM >100). Moreover, Rack1 was highly expressed in DN in vivo and in vitro . Results displayed that the expressions of pro-inflammatory cytokines Mcp-1 and Tnf-α were increased when Rack1 was overexpressed in cells cultured with low glucose while the expressions of Mcp-1 and Tnf-α were decreased when Rack1 was silenced in cells cultured with high glucose. Furthermore, results showed that the established DN inflammatory factor nuclear factor NF-kappa-B (NF-κB) was regulated by Rack1 via the direct interaction between Rack1 and NF-κB subunits P50 and P65. In summary, this identified Rack1 could play an important role in the inflammation of DN via NF-κB, which can provide new insight for DN research.

Small nuclear RNAs (snRNAs) are rarely reported in cancer. This study is based on The Cancer Genome Atlas genome-wide data set to explore the prognostic value and molecular mechanism of snRNAs in gastric cancer (GC). Gene ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were used to explore the molecular mechanism of snRNAs. A total of 351 patients were included in the survival analysis, and 14 prognostic snRNAs were identified using multivariate survival analysis. We constructed a prognostic signature containing nine snRNAs, which can signally classify patients into high- and low-risk phenotypes (adjusted P < 0.0001, hazard ratio = 2.671, 95% confidence interval = 1.850–3.858). Combining the molecular mechanisms obtained by the three functional enrichment approaches, we concluded that this prognostic signature snRNAs participated in classical tumor-related signaling pathways, including Notch, PI3K, toll-like receptor, etc.; cell adhesion; cell cycle; cell proliferation; and other biological processes that affect the biological phenotype of cancer cells. We also found significant downregulation of the abundance of immune cell infiltrates and immune microenvironment scores for high-risk phenotypes of GC patients. In conclusion, this study has identified 14 prognostic snRNAs signally associated with GC overall survival and also constructed a novel prognostic signature containing nine prognostic snRNAs.

Pregnant women are more susceptible to smog pollution than the general population. This study focused on the association between smog and birth outcomes, considering both pregnant mothers and their offspring. In this retrospective study, conducted in Baoding between 2013 and 2016, we enrolled 842 participants. Birth outcomes were low birth weight (LBW), pregnancy-induced hypertension (PIH), gestational diabetes mellitus (GDM), and premature rupture of membranes (PROM). The overall prevalence of LBW, PIH, GDM, and PROM was 8.2%, 14.8%, 16.5%, and 12.1%, respectively. Compared with lower pollution level, higher pollution level of fine particulate matter (particulate matter with aerodynamics diameter <2.5 μm) (PM2.5), inhalable particle (particulate matter with aerodynamics diameter <10 μm) (PM10), and CO increased the risk of term with LBW. PM2.5, PM10, and NO 2 increased the risk of PIH during different trimesters, while PM10 increased the risk of PROM during trimester 3. In conclusion, smog significantly affects the risk of adverse birth outcomes by different exposure time windows.

Dysregulated microRNAs are closely related to the malignant progression of colorectal cancer (CRC). Although abnormal let-7i-3p expression has been reported in various human cancers, its biological role and potential mechanism in CRC remain unclear. Therefore, the purpose of this study was to investigate the expression and regulation of let-7i-3p in CRC. Here, we demonstrated that let-7i-3p expression was significantly downregulated in three CRC cell lines while CyclinD1 (CCND1) was upregulated compared with the normal colon epithelial FHC cells. Moreover, bioinformatics and luciferase reporter assays revealed that CCND1 was a direct functional target of let-7i-3p. In addition, let-7i-3p overexpression or CCND1 silencing inhibited cell cycle, proliferation, invasion, and migration and diminished the activation of p-ERK in HCT116 cells. However, exogenously expressing CCND1 alleviated these effects. Taken together, our findings may provide new insight into the pathogenesis of CRC and let-7i-3p/CCND1 might function as new therapeutic targets for CRC.

An important causative factor in osteoarthritis (OA) is the abnormal mechanical stress-induced bone remodeling of the subchondral bone. β2-adrenergic receptor (Adrb2) plays a major role in mechanical stresses that induce bone remodeling. The medial tibial plateau (MTP) and lateral tibial plateau (LTP) of patients with varus Knee osteoarthritis (KO) bear different mechanical stresses. The present study aimed to investigate the expression of Adrb2 in medial tibial plateau subchondral bone (MTPSB) and lateral tibial plateau subchondral bone (LTPSB) in patients with varus KO. A total of 30 tibial plateau samples from patients undergoing total knee arthroplasty for varus KO and MTPSB and LTPSB were studied. Statistical analysis was performed using paired sample t -tests. Safranin O-Fast Green staining and Micro-computed tomography showed significant differences in the bone structure between MTPSB and LTPSB. Tartrate-resistant acid phosphatase (TRAP)-positive cell density in MTPSB was higher than that in LTPSB. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction, and Western blot analysis revealed that compared to LTPSB, the levels of Adrb2, tyrosine hydroxylase (TH), and osteocalcin increased significantly in MTPSB. Double-labeling immunofluorescence showed Adrb2 was present in the majority of TRAP-positive multinuclear cells of the MTPSB. The expression of Adrb2 and TH was significantly higher in MTPSB than in LTPSB, confirming the involvement of these molecules in the development of OA.

Individuals with serious mental illness are more affected by emotional reactions, including suicidal behavior due to COVID‐19 and psychosocial consequences of pandemic. The current cross-sectional study aimed to explore the possible association of COVID-19 and suicidal behavior (suicide ideation and attempt) before and during pandemic-associated lockdown in Serbia. We retrospectively reviewed the clinical records of 104 adult psychiatric inpatients admitted at Psychiatric Clinic, University Clinic Center Niš, Serbia, after ending lockdown and compared the obtained results with 181 adult psychiatric inpatients admitted during the same period in 2019 and 2018. Suicide ideation were more frequent in 2020 comparing with 2019 and 2018 (25 vs 12.5%, vs 9.41%; p < 0.05). Around 28% of patients with suicide attempts were exposed daily to the information related to COVID-19 coming from social media, while this frequency was significantly lower, only 7.55% ( p < 0.1), among patients with no suicide ideation or attempts. Adjustment disorder was more frequent among patients with suicide attempts in comparison to the patients with suicide ideation (32 vs 11%), especially in patients without suicide ideation and attempts (32 vs 0%, p < 0.001). Of all studied patients with suicide attempts during 2020, 60% were not in the previous psychiatric treatment before admission.

Bacteria are the most common causative agents of ocular infections. Treatment with topical broad-spectrum antibiotics is recommended in severe cases. However, antibiotic resistance has become a major concern in recent years, although antibiotics are generally effective in treating ocular infections. Antibacterial compound screening is performed to identify alternative therapeutic options to antibiotics. The aim of this study was to assess the in vitro antimicrobial activity of an ophthalmic solution containing ozonated oil. Strains of bacterial species with a multidrug resistance profile, which are responsible for a large proportion of ocular infections, were isolated and selected from different biological samples. The bacterial isolates were cultured, and ozonated oil was used to evaluate the inhibition zones at different time points. The treatment exhibited antibacterial activity against all the tested species. The effect was lower against the strains of Pseudomonas aeruginosa and more evident against Staphylococcus and Streptococcus spp. Our results suggest that the administration of ozonated oil may be a candidate agent to treat some infections of the ocular surface with a potential role in antimicrobial prophylaxis.

Acute lung injury (ALI) is a severe respiratory disorder occurring in critical care medicine, with high rates of mortality and morbidity. This study aims to screen the potential biomarkers for ALI. Microarray data of lung tissues from lung-specific geranylgeranyl pyrophosphate synthase large subunit 1 knockout and wild-type mice treated with lipopolysaccharide were downloaded. Differentially expressed genes (DEGs) between ALI and wild-type mice were screened. Functional analysis and the protein–protein interaction (PPI) modules were analyzed. Finally, a miRNA-transcription factor (TF)-target regulation network was constructed. Totally, 421 DEGs between ALI and wild-type mice were identified. The upregulated DEGs were mainly enriched in the peroxisome proliferator-activated receptor signaling pathway, and fatty acid metabolic process, while downregulated DEGs were related to cytokine–cytokine receptor interaction and regulation of cytokine production. Cxcl5 , Cxcl9 , Ccr5 , and Cxcr4 were key nodes in the PPI network. In addition, three miRNAs (miR505, miR23A, and miR23B) and three TFs (PU1, CEBPA, and CEBPB) were key molecules in the miRNA-TF-target network. Nine genes including ADRA2A , P2RY12 , ADORA1 , CXCR1 , and CXCR4 were predicted as potential druggable genes. As a conclusion, ADRA2A , P2RY12 , ADORA1 , CXCL5 , CXCL9 , CXCR1 , and CXCR4 might be novel markers and potential druggable genes in ALI by regulating inflammatory response.

This study aimed to determine the relation of serum uric acid (UA) level with outcomes in adults with candidemia. Medical records of patients with candidemia treated from 2014 to 2017 were retrospectively reviewed. Patients were age- and sex-matched with healthy control subjects. The associations of UA and cystatin C (CysC) levels with diagnosis and prognosis of candidemia were determined. Sixty-four patients with candidemia (13 females and 51 males; mean age 48.5 years) and 64 matched control subjects were included. The median UA level of patients with candidemia was 255 μmol/L (range, 158–395 μmol/L), and of healthy controls was 398 μmol/L (range, 345–450 μmol/L) ( P < 0.001). The median CysC level of patients with candidemia was 1.07 mg/L (range, 0.89–1.59 mg/L), and of the healthy controls was 0.82 mg/L (range, 0.74–0.95 mg/L) ( P < 0.001). Patients with a favorable prognosis had significantly higher serum UA levels than those with a poor prognosis (181 μmol/L vs 344 μmol/L; P = 0.001). It was indicated that the estimated OR for UA was significantly > 1 ( P = 0.009), and the AUC was 0.734. In summary, a lower serum UA level is associated with a diagnosis of candidemia, and a poor outcome.

The tumor microenvironment is highly immunosuppressive. The genetically modified oncolytic vaccinia virus (OVV) is a promising vector for cancer immunotherapy. The aim of the present study was to assess the antitumor effects of human interleukin-2 (hIL2)-armed OVV in vitro . The hIL2 gene was inserted into a thymidine kinase and the viral growth factor double deleted oncolytic VV (VVDD) to generate recombinant hIL2-armed OVV (rVVDD-hIL2). Viral replication capacity in A549 cells was quantified by plaque titration on CV-1 cells. Production of hIL2 in cancer cells infected by rVVDD-hIL2 was measured by enzyme-linked immunosorbent assay. Finally, 3-(4,5-dimethylthiazol-2-yl)-5-(3-arboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay was performed to assess the antitumor effects of rVVDD-hIL2. The results showed that rVVDD-hIL2 viral particles expressed increasing levels of hIL2 in human and murine cancer cell lines with growing multiplicities of infection (MOIs). The insertion of the hIL2 gene did not impair the replication capacity of VV, and the rVVDD-hIL2 virus killed cancer cells efficaciously. The lytic effects of the recombinant oncolytic virus on tumor cells increased with the growing MOIs. In conclusion, these findings suggest that hIL2-armed VVDD effectively infects and lyses tumor cells, with high expression of hIL2.

The dysfunction and apoptosis of vascular endothelial cells are the initiating links in the formation of atherosclerosis. N6-methyladenosine (m6A) is an extremely extensive RNA methylation modification and its abnormality leads to the occurrence of various human diseases. In this study, we explored the effects of demethylase α -ketoglutarate-dependent dioxygenase ALKB homolog 5 (ALKBH5) on TNF-α-induced apoptosis of human umbilical vein endothelial cells (HUVECs). In TNF-α-treated HUVECs, the expression of ALKBH5 was significantly decreased. ALKBH5 overexpression promoted the proliferation and inhibited the apoptosis in TNF-α-treated HUVECs, suggesting that ALKBH5 had a protective effect on cell damage induced by TNF-α. Importantly, ALKBH5 promoted the expression of Bcl-2 in HUVECs. Bcl2 overexpression reduced the expression of Gadd45, Bax, and p21, which are transcriptionally activated by p53. But the expression of p53 has not been significantly affected, indicating that Bcl2 might regulate the apoptosis by inhibiting p53 downstream targets. In addition, ALKBH5 overexpression significantly increased the level of pri-miR-7 and decreased the level of miR-7. In conclusion, ALKBH5 attenuated the TNF-α-induced cell injury via promoting Bcl2 expression. Our research expands the understanding of the progression mechanism of atherosclerosis and provides a potential strategy for the protection of vascular endothelial injury.

Cardiovascular disease (CVD) makes our heart and blood vessels dysfunctional and often leads to death or physical paralysis. Therefore, early and automatic detection of CVD can save many human lives. Multiple investigations have been carried out to achieve this objective, but there is still room for improvement in performance and reliability. This study is yet another step in this direction. In this study, two reliable machine learning techniques, multi-layer perceptron (MLP), and K -nearest neighbour (K-NN) have been employed for CVD detection using publicly available University of California Irvine repository data. The performances of the models are optimally increased by removing outliers and attributes having null values. Experimental-based results demonstrate that a higher accuracy in detection of 82.47% and an area-under-the-curve value of 86.41% are obtained using the MLP model, unlike the K-NN model. Therefore, the proposed MLP model was recommended for automatic CVD detection. The proposed methodology can also be employed in detecting other diseases. In addition, the performance of the proposed model can be assessed via other standard data sets.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy among women of reproductive age associated with hyperandrogenism, oligo-amenorrhea, and infertility. Symptoms and their severity vary among the individuals. If the manifestation is mild, PCOS may remain undiagnosed. In more severe cases, it results in a spectrum of symptoms of metabolic syndrome, insulin resistance, and cardiovascular diseases. The diagnosis is established after a physical examination and evaluating the patient’s hormonal profile. In addition to these required methods, ultrasonographic assessment of the patient’s ovaries is another non-invasive, cheap, and time-saving tool, making the examination more profound and leading to the correct diagnosis. Specific ultrasonographic parameters are used to tell the healthy and polycystic ovaries apart: the ovarian volume (OV), ovarian follicle count, follicle distribution pattern, ovarian stromal echogenicity, and the resistance and pulsatility indices assessed using the Doppler function. This review evaluated the selected articles and ascertained the ultrasonographic parameters that accurately predict PCOS. This systematic review showed that the most valuable ultrasonographic parameters in diagnosing PCOS are the OV and follicle number per ovary.

Youth-onset non-small cell lung cancer (NSCLC) is a heterogeneous disease. It has a unique clinicopathology and special genetic background. In this study, three key genes, CDC20, CCNB2, and BUB1, have been identified in youth-onset NSCLC tumor tissues based on the TCGA and GEO cohorts. Functional enrichment analysis reveals that the “oocyte meiosis,” “cell cycle,” and the “P53 signaling pathway” are significantly enriched. Additionally, four survival genes, including AKAP12, CRIM1, FEN1, and SLC7A11, that affect the prognosis of youth-onset NSCLC patients are identified in this study. Finally, we construct a risk model to predict the overall survival of youth-onset NSCLC patients, the AUC of the risk model in 1, 3, and 5 years of overall survival is 0.808, 0.844, and 0.728. This study aims to provide a novel idea to explore the pathogenic genes of youth-onset NSCLC.

Autophagy participates in the regulation of pulmonary arterial hypertension (PAH). However, the role of autophagy-related genes (ARGs) in the pathogenesis of the PAH is still unclear. This study aimed to identify the ARGs in PAH via bioinformatics analysis. A microarray dataset (GSE113439) was downloaded from the Gene Expression Omnibus database to identify differentially expressed ARGs (DEARGs). Protein–protein interactions network, gene ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to screen hub genes and the underlying molecular mechanisms of PAH. Finally, the mRNA expression of the hub genes was validated using the GSE53408 dataset. Twenty-six DEARGs were identified, all of which were upregulated. Enrichment analyses revealed that these DEARGs were mainly enriched in the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, PI3K-Akt signaling pathway, response to hypoxia, response to nutrient levels, and autophagy. Among these hub genes, the mRNA expression levels of HSP90AA1, HIF1A, MET, IGF1, LRRK2, CLTC, DNM1L, MDM2, RICTOR, and ROCK2 were significantly upregulated in PAH patients than in healthy individuals. Ten hub DEARGs were identified and may participate in the pathogenesis of the PAH via the regulation of autophagy. The present study may provide novel therapeutic targets for PAH prevention and treatment and expand our understanding of PAH. Graphical abstract

The aim of this study is to investigate the protective effects of glaucocalyxin A (GLA) on airways in mouse models of asthma, concerning the inflammatory mediators, Th1/Th2 subgroup imbalance, and Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. Hematoxylin and eosin/periodic acid–Schiff staining was used to observe the pathological changes in lung tissues. Inflammatory cytokine contents in the bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay. Protein expression levels were detected with Western blot, immunohistochemistry, and immunofluorescence. In vivo studies showed that, in ovalbumin (OVA)-induced asthmatic mouse models, the GLA treatments reduced the airway hyperresponsiveness and the secretion of inflammatory cells, declined the proliferation of goblet cells, decreased the levels of IL-4, IL-5, and IL-13, and increased the contents of interferon-γ and IL-12. Moreover, GLA inhibited the protein expression levels of TLR4, MyD88, TRAF6, and NF-κB in OVA-induced asthmatic mouse models. Further in vitro studies showed that GLA inhibited the expression of NF-κB, p-IκBα, tumor necrosis factor-α, IL-6, and IL-1β and blocked the nuclear transfer of NF-κB in lipopolysaccharide-stimulated RAW264.7 macrophages. Conclusively, GLA can inhibit the inflammatory responses in OVA-induced asthmatic mice and inhibit the release of inflammatory factors in LPS-induced RAW264.7 macrophages, which may be related to the inhibition of TLR4/NF-κB signaling pathway.

Papillary thyroid cancer (PTC) is the most prevalent type of TC worldwide; however, its pathological process remains unclear at the molecular level. In the current study, we analyzed the microarray data of PTC tissues and non-neoplastic thyroid tissues, and confirmed miR-100-5p as a downregulated miRNA in PTC. Via bioinformatic approach, western blotting, and TOP/FOP-flash assay, miR-100-5p was observed to be involved in the inactivation of Wnt/β-catenin signaling in TPC-1 and KTC-1. Frizzled Class Receptor 8 (FZD8), the coupled receptor for canonical Wnt/β-catenin signaling, was verified to be targeted and inhibited by miR-100-5p in TPC-1 and KTC-1. In the function assay, miR-100-5p mimic repressed PTC cell proliferation and induced cell apoptosis of TPC-1 and KTC-1; meanwhile, transfection of full-length FZD8 attenuated the effect of miR-100-5p mimic. Moreover, in the collected samples, miR-100-5p was lowly expressed in PTC tissues compared with normal tissues, especially in those of advanced stage (Stage III/IV vs Stage I/II), while FZD8 was highly expressed in PTC tissues, which in PTC tissues was inversely correlated to miR-100-5p. Thus, we suggest that overexpression of miR-100-5p inhibits the development of PTC by targeting FZD8.

The function of small ubiquitin-like modifier (SUMO)-related genes in hepatocellular carcinoma (HCC) remains unclear. This study aimed to analyze the expression profile and prognostic relevance of SUMO-related genes using publicly available data. A set of bioinformatics tools and experiments were integrated to explore the mechanism of the genes of interest. The least absolute shrinkage and selection operator Cox regression analysis was used to construct a prognostic model. SUMO-2 and SUMO-activating enzyme subunit 1 (SAE1) were upregulated in HCC. The enrichment analysis indicated that SUMO-2 and SAE1 might regulate the cell cycle. The downregulation of SAE1 inhibited the proliferation of HCC cells, whereas the upregulation of the gene promoted cell proliferation. IGF2BP3 contributed to the upregulation of SAE1 in an N6-methyladenosine (m6A)-dependent way. Eventually, an SAE1-related risk score (SRRS) was developed and validated in HCC. SRRS could serve as an independent prognostic factor and predict the efficiency of transarterial chemoembolization in patients with HCC.

We evaluated the clinical impact, in daily clinical practice, of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) therapies in patients with type 2 diabetes. Data from 500 unselected consecutive patients were retrospectively analyzed. Only those with a full assessment at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment with SGLT2i or GLP1RA were included in the study ( n = 167). At baseline, patients had a high mean body weight (BW), abdominal circumference (AC), body mass index (BMI), and HOMA index. Despite normal C-peptide values, 39 patients were being treated with insulin (up to 120 IU/day). During therapy, a progressive improvement in BW, BMI, and AC was observed with both the molecules. Fasting glucose and glycated Hb decrease was already significant at T3 in all patients, while the HOMA index selectively improved with SGLT2i therapy. Renal function parameters remained stable regardless of the drug used. Finally, SGLT2i reduced serum uric acid and improved the lipid profile, while GLP1RA reduced serum levels of liver enzymes. Both the therapeutic regimens allowed a significant reduction or complete suspension of unnecessary insulin therapies. Our real life data confirm the results obtained from randomized clinical trials and should be taken as a warning against inappropriate use of insulin in patients with preserved β-cell function.

Osteoporosis is a major health concern worldwide. The present study aimed to identify effective biomarkers for osteoporosis detection. In osteoporosis, 559 differentially expressed genes (DEGs) were enriched in PI3K-Akt signaling pathway and Foxo signaling pathway. Weighted gene co-expression network analysis showed that green, pink, and tan modules were clinically significant modules, and that six genes (VEGFA, DDX5, SOD2, HNRNPD, EIF5B, and HSP90B1) were identified as “real” hub genes in the protein–protein interaction network, co-expression network, and 559 DEGs. The sensitivity and specificity of the support vector machine (SVM) for identifying patients with osteoporosis was 100%, with an area under curve of 1 in both training and validation datasets. Our results indicated that the current system using the SVM method could identify patients with osteoporosis.

This research aims to explore the role of Tanshinone IIA (Tan IIA) and microRNA (miR)-30b-5p in chemoresistance of colorectal cancer (CRC). The expression levels of miR-30b-5p and apoptosis and caspase activation inhibitor (AVEN) was detected by reverse transcription-quantitative polymerase chain reaction assay. The cell proliferation and apoptosis were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. The target relationship between miR-30b-5p and AVEN was confirmed by Dual-luciferase reporter assay. Transwell assay was performed to assess CRC cells’ metastasis. Western blot was carried out to measure the apoptosis-related protein. The results showed that miR-30b-5p was lowly expressed in oxaliplatin-resistance CRC cells SW480 (SW480/R) compared to SW480 cells. Overexpression of miR-30b-5p significantly suppressed the malignant biological behaviors of SW480/R cells and significantly promoted the sensitivity of SW480/R cells to oxaliplatin by down-regulated AVEN expression. Besides, Tan IIA treatment upregulated miR-30b-5p expression in SW480/R cells. Moreover, miR-30b-5p upregulation strengthened the promoting effect of Tan IIA on the sensitivity of SW480/R cells to oxaliplatin. In conclusion, Tan IIA and miR-30b-5p could reverse oxaliplatin resistance of CRC cells and may thus be potential treatment strategies for treating patients with CRC.

This study was conducted to investigate the effect of microRNA-212-5p (miR-212-5p) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) cells. Microarray datasets (EXP00394 and EXP00660) were downloaded from the dbDEMC database, and the differentially expressed microRNAs between high-grade and low-grade NPC were analyzed. miR-212-5p and methyltransferase like 3 (METTL3) expression levels in NPC tissues and cells were determined by the quantitative real-time polymerase chain reaction and Western blot. Besides, the relationship between miR-212-5p expression and clinicopathological characteristics of patients was analyzed by the Chi-square test. Cell counting kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU) assay, and flow cytometry were adopted to detect the effect of miR-212-5p on the cell proliferation and apoptosis. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis were performed to explore the potential biological functions and the signal pathways related to the target genes of miR-212-5p. Bioinformatics prediction and dual luciferase reporter gene assay were used to verify the relationship between miR-212-5p and METTL3 3′ untranslated region. Besides, western blot was adopted to detect the expression of METTL3. Gene set enrichment analysis was performed to analyze the downstream pathways in which METTL3 was enriched. It was found that miR-212-5p was downregulated in NPC tissues, and the low miR-212-5p expression was associated with lymph node metastasis and poor differentiation. miR-212-5p overexpression inhibited the growth and promoted apoptosis of NPC cells; miR-212-5p inhibition functioned oppositely. Mechanistically, miR-212-5p inhibited the proliferation and promoted apoptosis of NPC cells via suppressing METTL3 expression. miR-212-5p/METTL3 was associated with processes of RNA transport and cell cycle. In conclusion, miR-212-5p inhibits the progression of NPC by targeting METTL3.

Research has suggested a significant prognostic value of ST-T changes in various cardiovascular diseases and malignant tumors. However, their role in predicting prognosis in patients with peripheral T-cell lymphomas (PTCLs) remains unknown. Here, we investigated the prognostic potential of ST-T changes in all-cause mortality of PTCLs patients. In total, 131 patients with PTCLs between January 2015 and April 2020 were enrolled. Univariable and multivariable COX proportional hazards regression models were used to find the relationship between ST-T changes and all-cause mortality in these patients. A significant difference in all-cause mortality was found between patients with ST-T abnormalities and those without definite abnormalities in the ST-T segments ( P = 0.027). Multivariable Cox risk regression analysis indicated that patients with ST-T changes had greater all-cause mortality than patients with normal ST-T segments in the intermediate-high/high-risk groups ( P < 0.001). In addition, ST-T changes were markedly distinction in patients with hypoproteinemia than in those with no definite abnormalities in the ST-T segments ( P = 0.021). ST-T changes may serve as potential, simple, and effective prognostic factors for all-cause mortality in PTCLs patients, especially in the intermediate-high/high-risk and hypoproteinemia groups. Therefore, regular ECG monitoring is recommended to guide the clinical treatment of patients with PTCLs.

Collagen type XI alpha 1 (COL11A1) as an oncogene has been reported in several malignant tumors. Herein, we aimed to explore the function of COL11A1 and its upstream regulators in lung adenocarcinoma (LUAD). COL11A1 expression prognostic significance, gene ontology, Kyoto Encyclopedia of Genes and Genomes, and immune infiltration were explored in LUAD. In vitro experimental measurements were implemented to validate the function of COL11A1 and LINC00665 in LUAD cells. Our study demonstrated that LINC00665-2 and COL11A1 were significantly upregulated in LUAD tissues compared with nontumor tissues. COL11A1 was positively correlated with multiple immune cell enrichment, suggesting that COL11A1 may be a prospective therapeutic target to enhance the efficacy of immunotherapy in LUAD. A regulatory mechanism LINC00665-2/microRNAs (miRNAs)/COL11A1 axis was identified to facilitate the tumorigenesis of LUAD. si-LINC00665 transfection induced the inhibition of growth and migration, and apoptosis was reversed by the overexpression of COL11A1 in LUAD cells. In conclusion, LINC00665 as a competing endogenous RNA sponging multiple miRNAs to modulate COL11A1 expression in LUAD, suggesting that LINC00665/miRNAs/COL11A1 axis may contribute to the pathogenesis of LUAD.

This study aimed to provide additional information on the influence of perinatal factors on fecal (f)-calprotectin values in preterm infants. Calprotectin was determined from the first spontaneous stool (analyzed on the Alegria device by using the enzyme-linked immunosorbent assay [ELISA] method) obtained from neonates at a mean age of 3.41 ± 2.44 days of life. We analyzed 114 subjects who had a body weight of 1847.67 ± 418.6 g and were born at a gestational age of 32.6 ± 2.43 weeks, without intestinal and other congenital anomalies or any diseases other than those related to premature birth. The values of f-calprotectin are in a positive correlation with female subjects, intrauterine growth restriction, significant ductus arteriosus, enteral feeding intolerance, postnatal prolonged use of broad-spectrum antibiotics, and values ​​of bicarbonates (analyzed in a sample of capillary arterial blood). Measurement of f-calprotectin in the first 7 days after birth can help to early detect the intestinal distress or early staging of necrotizing enterocolitis in premature infants.

The purpose of this study was to investigate the effect of cystic areas of osteonecrosis of the femoral head (ONFH) on stress distribution and disease progression in the femoral head. A total of 85 patients (106 hips) diagnosed with Association Research Circulation Osseous stage II non-traumatic and non-surgical treatment were retrospectively analyzed. The presence of cystic areas and diameter of cystic areas were compared between the two groups. In addition, five spherical cystic areas of different diameters were constructed and the maximum stress was observed. There was a difference between the two groups in whether cystic areas appeared in the femoral head, with 49.1% in the collapse group showing cystic areas, which was significantly higher than that in the non-collapse group (18.4%) ( P < 0.05). In addition, the diameter of the cystic areas was significantly larger in the collapsed group than in the non-collapsed group ( P < 0.05). The maximum and mean von Mises stress value around the necrotic area and around the cystic area of the femoral head increased with the increase of the cystic diameter. Stress concentration areas can be generated around the cystic areas. The presence and increased diameter of the cystic areas accelerates the collapse of the ONFH femoral head.

Revision procedures and the resulting bone loss are a big challenge for orthopedic surgeons. Therefore, we checked what functional outcomes that 3D-printed cone augments can offer to patients with bone defects (Anderson Orthopedic Research Institute [AORI] classification type 2B and 3) in the knee and whether the use of cones can delay the necessity to use a megaprotheses. Data from 64 patients ( M = 22; W = 42) who underwent total knee arthroplasty (TKA) revision were included in the analysis. The Knee Society Clinical Rating System (KSS) and the range of motion in the knee joint were used for the functional assessment. The mean follow-up was 28 months (range: 18–44 months). The survival rate for aseptic loosening at follow-up was 100%. Infection occurred in two (3.1%) patients. The mean KSS score increased from 12.75 points preoperatively to 66.56 postoperatively ( p < 0.001). The mean range of motion in the knee changed from 61.15° preoperatively to 115.93° postoperatively ( p < 0.001). 3D-printed cone augments seem to be a good solution for patients requiring a TKA revision procedure. When used in patients with bone defects classified as 2B and 3 (AORI), they can be a good alternative, delaying the need for megaprotheses.

Acute myocardial infarction is one of the leading causes of morbidity worldwide, but the underlying mechanism responsible for myocardial ischemia–reperfusion (I/R) injury remains elusive. lncRNA plays roles in inflammatory response, cell apoptosis and regulation of myocardial ischemia. However, whether lncRNA HAGLR could regulate myocardial I/R injury and the molecular mechanism need to be further investigated. lncRNA has been shown to bind to miRNAs and compete with endogenous RNAs. miR-133a-3p has been shown to regulate cardiomyocyte apoptosis and ischemic myocardial injury. In this work, it has shown that knockdown of HAGLR could suppress inflammatory response and cell apoptosis induced by I/R and, thus, alleviate myocardial I/R injury. HAGLR promoted myocardial I/R injury by inhibiting miR-133a-3p to promote MAPK1 expression.

This study aimed to investigate whether ghrelin affected the autophagy and inflammatory response of intestinal intraepithelial lymphocytes (IELs) by regulating the NOD2/Beclin-1 pathway in an intestinal ischemia–reperfusion (I/R) injury model. Twenty hours after implementing the intestinal I/R injury rat model, the small intestine and both lungs were collected for histological analysis. The morphological changes in the intestinal mucosa epithelium and lung tissues were evaluated using hematoxylin-eosin staining. The activity of autophagic vacuoles and organ injury were evaluated using electron microscopy. The cytokine levels (IL-10 and TNF-α) in IEL cells and lung tissue were determined using enzyme-linked immunosorbent assay. RT-qPCR and western blot assays were conducted to check the NOD2, Beclin-1, and ATG16 levels. Ghrelin relieved the I/R-induced destruction of the intestinal mucosa epithelium and lung tissues. Moreover, ghrelin enhanced autophagy in the intestinal epithelium and lungs of I/R rats. In addition, the levels of autophagy-associated proteins (Beclin-1, ATG16, and NOD2) were higher in the ghrelin treatment group than in rats with I/R. Ghrelin reduced significantly the IL-10 and TNF-α levels. However, these changes were reversed by the NOD2 antagonist. In conclusion, ghrelin may relieve I/R-induced acute intestinal mucosal damage, autophagy disorder, and inflammatory response in IELs by regulating the NOD2/Beclin-1 pathway.

Up to 20% of patients after total knee arthroplasty (TKA) are not satisfied with the result. Several designs of new implants try to rebuild natural knee kinematics. We hypothesized that an innovative implant design leads to better results concerning femoral rollback compared to an established implant design. For this pilot study, 21 patients were examined during TKA, receiving either an innovative (ATTUNE TM Knee System (DePuy Inc.), n = 10) or an established (PFC TM (DePuy Inc.), n = 11) knee system. All patients underwent computer navigation. Knee kinematics was assessed after implantation. Outcome measure was anterior–posterior translation between femur and tibia. We were able to demonstrate a significantly higher femoral rollback in the innovative implant group ( p < 0.001). The mean rollback of the innovative system was 11.00 mm (95%-confidence interval [CI], 10.77–11.24), of the established system 8.12 mm (95%-CI, 7.84–8.42). This study revealed a significantly increased lateral as well as medial femoral rollback of knees with the innovative prosthesis design. Our intraoperative finding needs to be confirmed using fluoroscopic or radiographic three-dimensional matching under full-weight-bearing conditions after complete recovery from surgery.

The purpose of this study was to investigate the correlation between fibular head height and the incidence and severity of osteoarthritis associated with varus knee deformity. The fibular head height, joint line convergence angle (JLCA) and medial proximal tibial angle (MPTA) were measured in a three-dimensional model. Ordinal multivariate logistic regression was used to analyze the correlation between fibular head height and Kellgren–Lawrence (K–L) grade. Pearson correlation was used to analyze the correlation between fibular head height and K–L grade. A total of 232 patients (232 knees) were finally included in the study. There were significant differences in JLCA and hip–knee–ankle angle ( P < 0.05), and both JLCA and hip–knee–ankle angle increased with severe aggravation of K–L grade. Both fibular head height and MPTA decreased as the K–L grade was severely aggravated. There was a significant negative correlation between K–L grade and fibular head height ( r = −0.812, P < 0.001). Furthermore, there was a significant negative correlation between fibular head height and hip–knee–ankle angle ( r = −0.7905, P < 0.001). In addition to body mass index, fibular head height is a risk factor for the pathogenesis of osteoarthritis associated with varus knee deformity; the smaller the fibular head height, the more severe the degree of varus deformity.

This study aimed to investigate the role and mechanism of long non-coding RNA (lncRNA) WT1 antisense RNA (WT1-AS) in cerebral ischemic stroke. The Starbase database and dual-luciferase reporter gene assay were used to analyze the interaction between lncRNA WT1 antisense RNA (lncRNA WT1-AS) and microRNA-186-5p (miR-186-5p). Reverse transcription-quantitative PCR analysis was performed to determine lncRNA WT1-AS and miR-186-5p levels. An oxygen glucose deprivation (OGD)-induced SH-SY5Y cell injury model was established. Cell viability and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and flow cytometric assays, respectively. Caspase 3 activity was evaluated using a caspase 3 activity detection kit. The results showed that miR-186-5p is a direct target of the lncRNA WT1-AS. In addition, lncRNA WT1-AS levels were downregulated and miR-186-5p levels were upregulated in the blood samples of patients with ischemic stroke and OGD-induced SH-SY5Y cells. WT1-AS overexpression promoted OGD-induced cell viability and reduced the cell apoptosis and caspase 3 activity. However, these effects were reversed by miR-186-5p overexpression. Furthermore, the results demonstrated that the X-linked inhibitor of apoptosis (XIAP) was directly targeted by miR-186-5p. Similarly, transfection with the miR-186-5p inhibitor reduced OGD-induced neuronal damage by upregulating XIAP expression. In conclusion, lncRNA WT1-AS attenuates hypoxia/ischemia-induced neuronal injury in cerebral ischemic stroke through the miR-186-5p/XIAP axis.

Pulmonary embolism (PE) is a fatal condition particularly in critically ill patients. We determined the association among the cardiac troponin T (cTnT) level, acute physiologic and chronic health evaluation (APACHE III) scoring system, and in-hospital mortality in critically ill patients with acute PE. A total of 501 patients with PE were initially enrolled. According to the multivariable logistic regression model for in-hospital mortality, the odds ratio of the cTnT level and APACHE III score was 1.96 (95% confidence interval [CI] = 1.18–3.24, P = 0.008) and 1.03 (95% CI = 1.02–1.05, P < 0.001), respectively. The area under the curve (AUC) of cTnT and APACHE III score for in-hospital mortality was 0.630 (95% CI = 0.586–0.672, P = 0.03) and 0.740 (95% CI = 0.699–0.778, P = 0.02), respectively. The discriminatory cTnT and APACHE III threshold values for in-hospital mortality were 0.08 ng/L and 38 score, respectively; the sensitivities and specificities of cTnT were 46.48 and 83.10%, respectively, whereas those of the APACHE III score were 74.88 and 54.19%, respectively. The cTnT and APACHE III scores were combined in the logistic analysis model, and a regression equation was derived to calculate the in-hospital mortality. The AUC was found to increase to 0.788 (95% CI = 0.734–0.840, P = 0.025). The sensitivity and specificity increased to 84.5 and 71.4%, respectively. The cTnT and APACHE III scores exhibited a significant association with in-hospital mortality of critically ill patients with PE. In conclusion, these parameters in combination can significantly improve the in-hospital mortality prediction.

Long non-coding RNAs have been confirmed closely related to the metastasis and angiogenesis of breast cancer (BC). LINC01857 can promote the growth and metastasis of BC cells. The present work focused on exploring the role of LINC01857 in BC metastasis and angiogenesis and investigating the possible mechanisms. The results showed that LINC01857 and CENPQ were highly expressed in BC tissues and cells, while miR-2052 was contrarily expressed. In vitro study showed that low expression of linc01857 could inhibit the migration ability and vascularization of BC cells, and mir-2052 inhibitor partially restored the effect of si-LINC01857 on the migration ability and vascularization of BC cells. Likewise, inhibition of CENPQ can partially rescue the effects of miR-2052 inhibitor on the migration ability and vascularization of BC cells. In vivo studies showed that down-regulation of LINC01857 notably suppressed tumor growth and angiogenesis in nude mice. The miR-2052 inhibitor partially restored the effects of si-LINC01857. CENPQ suppression partially rescued the effects of the miR-2052 inhibitor. To conclude, LINC01857/miR-2052/CENPQ is the potential novel target for BC treatment.

We aimed to study the function and mechanism of endothelial cell-specific molecule 1 (ESM1) in endometrial cancer (EC). The binding relationship between SPI1 and ESM1 was predicted by bioinformatics analysis and verified by the dual-luciferase reporter assay. The expressions and effects of SPI1 and ESM1 were determined using quantitative real-time PCR, immunohistochemistry, Western blot, and functional experiments. ESM1 was highly expressed in EC and was associated with the poor prognosis of patients. ESM1 silencing suppressed the viability, proliferation, invasion, and angiogenesis of EC cells, down-regulated expressions of PCNA, N-cadherin, Vimentin, VEGFR-1, VEGFR2, and EGFR, but upregulated E-cadherin level, while ESM1 overexpression did oppositely. Moreover, SPI1 bound to ESM1. Overexpressed SPI1 promoted the expression of ESM1 and induced malignant phenotype (viability, proliferation, and invasion), which were countervailed by ESM1 silencing. Collectively, ESM1 induced by SPI1 promotes the malignant phenotype of EC.

Selenium-binding protein 1 (SELENBP1) is frequently dysregulated in various malignancies including colorectal cancer (CRC); however, its roles in progression of CRCs and the underlying mechanism remain to be elucidated. In this study, we compared the expression of SELENBP1 between CRCs and colorectal normal tissues (NTs), as well as between primary and metastatic CRCs; we determined the association between SELENBP1 expression and CRC patient prognoses; we conducted both in vitro and in vivo experiments to explore the functional roles of SELENBP1 in CRC progression; and we characterized the potential underlying mechanisms associated with SELENBP1 activities. We found that the expression of SELENBP1 was significantly and consistently decreased in CRCs than that in adjacent NTs, while significantly and frequently decreased in metastatic than primary CRCs. High expression of SELENBP1 was an independent predictor of favorable prognoses in CRC patients. Overexpression of SELENBP1 suppressed, while silencing of SELENBP1 promoted cell proliferation, migration and invasion, and in vivo tumorigenesis of CRC. Mechanically, SELENBP1 may suppress CRC progression by inhibiting the epithelial–mesenchymal transition.

It is not determined whether serum visfatin levels are related to the presence and severity of coronary artery disease (CAD) in non-diabetic subjects. In this study, a total of 65 consecutive non-diabetic participants who underwent coronary angiography were enrolled. Serum visfatin and fasting glucose, as well as the serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride, were measured in all participants before the procedure. The extent of coronary artery lesions was determined by Gensini score. Serum visfatin levels were significantly lower in patients with CAD compared to participants with normal coronary arteries. Inversely, the circulating levels of fasting glucose were found to be elevated in patients with CAD compared with the control subjects. Multivariable logistic regression analysis demonstrated that visfatin and impaired fasting glucose (IFG) were independently associated with the presence of CAD in non-diabetics. No significant relationship was found between serum visfatin and fasting glucose levels in IFG subjects. However, there was a negative association between visfatin concentrations and Gensini score in participants with IFG. Both circulating visfatin concentrations and IFG are independently associated with CAD in non-diabetics. Serum visfatin levels are negatively related to the angiographic severity of CAD in subjects with IFG.

This study aims to compare treatments and outcomes of mechanical complications of acute myocardial infarction (MI) during the Covid-19 and in the pre-Covid-19 era. Electronic databases have been searched for MI mechanical complications during the Covid-19 era and in the previous period from January 1998 to January 2020 (pre-Covid-19 era), until October 2021. To perform a quantitative analysis of non-comparative series, a meta-analysis of proportion has been conducted. Early mortality after surgical treatment was 15.0% while it was significantly higher after conservative treatment (62.4%) ( P = 0.026). Early mortality after surgical treatment was seemingly higher in the pre-Covid-19 era but the difference did not reach statistical significance (15.0% vs 38.9%; P = 0.13). Mortality in patients treated conservatively, or turned down for surgery, was lower during the Covid-19 pandemic (62.4% vs 97.7%; P = 0.001). The crude mean prevalence of the use rate of conservative or surgical treatment across the studies during Covid-19 and in the pre-Covid-19 era was comparable. The current increased incidence of MI mechanical complications might be a consequence of delayed presentation or restricted access to hospital facilities. Despite the general negative impact of Covid-19 on cardiac surgery volumes and outcomes and the apparent increase of the incidence of MI complications, the outcomes of their surgical and clinical treatment seem not to have been affected during the pandemic.

Neonatal stroke is a devastating condition that causes brain injury in babies and often leads to lifelong neurological impairment. Recent prospective population studies of neonatal stroke are lacking. Neonatal strokes are different from those in older children and adults. A better understanding of its aetiology, current management, and outcomes could reduce the burden of this rare condition. The study aims to explore the incidence and 2 year outcomes of neonatal stroke across an entire population in the UK and Republic of Ireland. This is an active national surveillance study using a purpose-built integrated case notification-data collection online platform. Over a 13 month period, with a potential 6 month extension, clinicians will notify neonatal stroke cases presenting in the first 90 days of life electronically via the online platform monthly. Clinicians will complete a primary questionnaire via the platform detailing clinical information, including neuroimaging, for analysis and classification. An outcome questionnaire will be sent at 2 years of age via the platform. Appropriate ethics and regulatory approvals have been received. The neonatal stroke study represents the first multinational population surveillance study delivered via a purpose-built integrated case notification-data collection online platform and data safe haven, overcoming the challenges of setting up the study.

To develop effective medicines, researchers must first understand the common and distinct mechanisms that drive oncogenic processes in human cancers. TWF1 and TWF2 belong to the actin-depolymerizing factor homology family. TWF1 has been identified as an important gene in lung, breast, and pancreatic cancer in recent investigations. TWF2’s role in cancer remains largely unknown, no comprehensive pan-cancer studies have been conducted. We utilized the The Cancer Genome Atlas and Gene Expression Omnibus datasets to investigate the role of TWF2 in different types of cancers. TWF2 transcription in cancers and the number of TWF2 mutations were examined as part of our study. We also examined the possible functional pathways involved in TWF2-mediated oncogenicity. Our pan-cancer analysis provided a complete overview of the oncogenic effects of TWF2 in a wide range of human malignancies.

Mean corpuscular hemoglobin (MCH) is a common blood routine test index. To explore the relationship between MCH and length of hospital stay in patients with acute pancreatitis (AP), we included 273 patients with AP without coronary heart disease, diabetes, hypertension and anemia in this study. All data were separated into three groups according to the length of hospital stay. Gender ( p = 0.017) and severity classification ( p < 0.001) were significantly correlated with length of hospital stay among three groups. Notably, MCH level was significant different among three groups ( p = 0.009). Thus, all data were separated into two groups according to MCH level, and significant increases in the length of hospital stay were observed between two groups ( p = 0.030). A positive correlation between length of hospital stay and MCH was observed ( r = 0.172, p = 0.004). Multiple linear regression analysis showed that MCH was independent correlated with the length of hospital stay, no matter whether severity classification of AP was included (beta = 0.248, p < 0.001; beta = 0.212, p < 0.001). Our results demonstrated that the length of hospital stay was correlated with MCH level in patients with AP, and MCH level at admission may predict the length of hospital stay independent of severity classification in AP. These results may provide a potential evaluation basis for the management of patients with AP.

Genetic variation in UDP-glucuronosyltransferase 1A1 gene (UGT1A1) is a lithogenic risk factor for gallstone formation. This study aimed to assess genotype and allele frequencies of common UGT1A1 variants in patients with gallstone and hepatitis B virus (HBV)-related hepatic failure. This study enrolled 113 healthy individuals (CTRL), 54 patients with HBV infection (HBV), 134 patients with gallstone-free hepatic failure and HBV infection, and 34 patients with gallstone-related hepatic failure and HBV infection (GRHF). Peripheral venous blood samples were collected for genomic DNA isolation. Polymerase chain reaction amplification was carried out for UGT1A1, followed by direct sequencing. Analysis for genotype and allele frequencies of UGT1A1 variants ( UGT1A1*6 , UGT1A1*27 , UGT1A1*28 , and UGT1A1*60 ) was performed. The allele distributions of the four groups did not deviate from Hardy–Weinberg equilibrium. Allele (A) and genotype (CA) frequency distributions of UGT1A1*27 were significantly different between GRHF and CTRL, or between GRHF and HBV. GRHF and CTRL exhibited significant differences in allele (A) and genotype (CA) frequency distributions of UGT1A1*28. Linkage disequilibrium analysis suggested that haplotype G-G-[TA]7-T may be associated with gallstone in HBV-related hepatic failure. Our data reveal that UGT1A1*27 and UGT1A1*28 variants are significantly observed in patients with GRHF compared to healthy individuals.

Hypertrophic scarring (HTS) is a common fibroproliferative disorder that typically follows thermal and other injuries involving the deep dermis. The underlying pathogenic mechanisms are regulated by transforming growth factor-β (TGF-β); however, the exact mechanisms in HTS have not been elucidated. We conducted this study to explore the cellular signaling mechanisms for expression of Sar1a, a coat protein complex II-associated small GTPase, in HTS fibroblasts (HTSF). We found that Sar1a was upregulated in HTSF as compared to that in normal fibroblasts. Furthermore, stimulation of TGF-β1 increased the expression of Sar1a in HTSF, and small interfering RNA for Sar1a suppressed procollagen-I (PC-I) secretion. Next we investigated the signaling mechanism from TGF-β1 to Sar1a expression and its association with PC-I secretion. In the presence of TGF-β-activated kinase 1 (TAK1), c-Jun N-terminal kinase, or p38 inhibitors, the effect of TGF-β1 on Sar1a expression and PC-I secretion significantly decreased; however, it had no effect on collagen-1A (Col-1A) expression. Further, the inhibitors of Smad3 or extracellular signal-regulated kinases inhibited TGF-β1-induced Col-1A expression but had no effect on PC-I secretion and Sar1a expression. Taken together, our results suggested that TGF-β1 induces Sar1a expression through TAK1 signaling and this signaling event regulates PC-I secretion in HTSF.

Multiple studies have indicated that long non-coding RNAs are aberrantly expressed in cancers and are pivotal in developing various tumors. No studies have investigated the expression and function of long non-coding antisense RNA PCNA-AS1 in esophageal squamous cell carcinoma (ESCC). In this study, the expression of PCNA-AS1 was identified by qRT–PCR. Cell function assays were used to explore the potential effect of PCNA-AS1 on ESCC progression. A prediction website was utilized to discover the relationships among PCNA-AS1, miR-2467-3p and proliferating cell nuclear antigen (PCNA). Dual luciferase reporter gene and RNA immunoprecipitation (RIP) assays were executed to verify the binding activity between PCNA-AS1, miR-2467-3p and PCNA. As a result, PCNA-AS1 was highly expressed in ESCC and was associated with patient prognosis. PCNA-AS1 overexpression strongly contributed to ESCC cell proliferation, invasion and migration. PCNA-AS1 and PCNA were positively correlated in ESCC. Bioinformatics analysis, RIP and luciferase reporter gene assays revealed that PCNA-AS1 could act as a competitive endogenous RNA to sponge miR-2467-3p, thus upregulating PCNA. In conclusion, the current outcome demonstrates that PCNA-AS1 may be a star molecule in the treatment of ESCC.

Acute myeloid leukemia (AML) is the most heterogeneous hematological disorder and blast cells need to fight against immune system. Natural killer (NK) cells can elicit fast anti-tumor responses in response to surface receptors of tumor cells. NK-cell activity is often impaired in the disease, and there is a risk of insufficient tumor suppression and progression. The aim of this study is to assess the dysfunction of NK cells in AML patients via focusing on two important pathways. We obtained single-cell RNA-sequencing data from NK cells obtained from healthy donors and AML patients. The data were used to perform a wide variety of approaches, including DESeq2 (version 3.9), limma (version 3.26.8) power differential expression analyses, hierarchical clustering, gene set enrichment, and pathway analysis. ATP6AP2, LNPEP, PREP, IGF2R, CTSA, and THOP1 genes were found to be related to the renin–angiotensin system (RAS) family, while DPP3, GLRA3, CRCP, CHRNA5, CHRNE, and CHRNB1 genes were associated with the neurotransmitter pathways. The determined genes are expressed within different patterns in the AML and healthy groups. The relevant molecular pathways and clusters of genes were identified, as well. The cross-talks of NK-cell dysfunction in relation to the RAS and neurotransmitters seem to be important in the genesis of AML.

Dexamethasone can be used to prevent nausea and vomiting after surgery, but there is concern that it may induced perineal irritation. The aim of this study was to investigate the attenuation effect of dilution and slow injection on dexamethasone-induced perineal irritation. In this prospective, randomized, double-blind study, a total of 400 patients were enrolled and allocated into four groups: Group I, receiving 2 mL dexamethasone (5 mg/mL), Group II, receiving 5 mL dexamethasone (2 mg/mL), Group III, receiving 10 mL dexamethasone (1 mg/mL), and Group IV receiving 20 mL dexamethasone (0.5 mg/mL). Dexamethasone was diluted with 5% glucose. The injection time of dexamethasone was less than 2 s in Group I, while it was 30 s in Groups II, III, and IV. The incidence, onset, duration, and severity of perineal irritation were recorded. The incidence of dexamethasone-induced perineal irritation was 49, 33, 17, and 15% in Groups I, II, III, and IV, respectively. Group IV had less severity than Group I in mild and moderate perineal irritation ( P < 0.008). The onset and duration of perineal irritation of Groups II, III, and IV were significantly improved compared to Group I ( P < 0.001). Dexamethasone-induced perineal irritation can be alleviated by dilution of dexamethasone to 0.5 mg/mL with 5% glucose combined with prolonged injection time of 30 s.

Vascular calcification is a prominent manifestation of advanced atherosclerosis. Tumor necrosis factor-receptor-associated factors (TRAFs) were reported to participate in atherosclerosis development. In this study, the role and mechanism of TRAF6 in vascular calcification were explored. To induce the vascular calcification, oxidized low-density lipoprotein (Ox-LDL) was applied to treat vascular smooth muscle cells (VSMCs). TRAF6 protein expression in VSMCs was assessed by western blotting. Osteogenic differentiation of VSMCs was assessed by alkaline phosphatase activity analysis. Mineral deposition in VSMCs was evaluated by von Kossa staining. VSMC proliferation, migration, apoptosis, inflammation, and reactive oxygen species (ROS) generation were detected using cell counting kit-8, Transwell, flow cytometry, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), and dichlorodihydrofluorescein diacetate staining, respectively. Luciferase reporter assay was utilized to identify the binding relationship between miR-146-5p and TRAF6 in VSMCs. We found that Ox-LDL administration induced the calcification of VSMCs and elevated the TRAF6 level. TRAF6 knockdown restrained VSMC calcification, proliferation, migration, inflammation, and ROS generation caused by Ox-LDL. Mechanically, TRAF6 was targeted by miR-146-5p in VSMCs. Furthermore, TRAF6 overexpression offset the inhibitory effects of miR-146-5p upregulation on vascular calcification in VSMCs under the Ox-LDL condition. Overall, miR-146-5p restrains the calcification of VSMCs by suppressing TRAF6.

The study was aimed to investigate the role and mechanism of long non-coding RNAs (lncRNA) myocardial infarction-associated transcript (MIAT) in prostate cancer. The relationships between lncRNA MIAT and miR-361-3p, miR-361-3p and cell cycle and apoptosis regulator 2 (CCAR2) were predicted by StarBase and TargetScan, and verified by dual-luciferase reporter assay and RNA pull-down assay. Quantitative real-time PCR assay was performed to detect the mRNA expression of lncRNA MIAT, miR-361-3p, CCAR2, Bax, and Bcl-2 in the prostate cancer tissues or cells. The protein levels of CCAR2, Bax, and Bcl-2 were detected by Western blot analysis. The cell viability and apoptosis were detected by MTT assay and Flow cytometry analysis, respectively. lncRNA MIAT was upregulated, while miR-361 was downregulated in the prostate cancer tissues and Du145 cells. lncRNA MIAT negatively regulated miR-361-3p expression in Du145 cells. Downregulating lncRNA MIAT decreased the cell viability, induced the cell apoptosis, increased Bax expression, and decreased Bcl-2 expression in Du145 cells, while the effects were reversed by downregulating miR-361-3p or CCAR2 upregulation. Moreover, CCAR2 upregulation reversed the effects of miR-361-3p upregulation on Du145 cell viability and apoptosis. In conclusion, lncRNA MIAT participated in prostate cancer by regulating cell proliferation and apoptosis via miR-361-3p/CCAR2 axis.

Lung cancer (LC) is a prevailing primary tumor in the lung. lncRNA non-coding RNA activated by DNA damage (NORAD) is a popular target in human cancers. This experiment is designed to probe the mechanism of lncRNA in LC progression. NORAD expression in normal lung epithelial cells and LC cells was examined and then silenced to assess its effect on LC cell proliferation, invasion, and migration. Subcellular localization of NORAD was analyzed through online databases and then corroborated by fractionation of nuclear and cytoplasmic RNA assay. The target binding relations between NORAD and miR-28-3p and between miR-28-3p and E2F2 were verified. Eventually, LC cells with NORAD silencing were transfected with miR-28-3p inhibitor or pcDNA3.1-E2F2 to measure LC cell proliferation, invasion, and migration. NORAD was overexpressed in LC cells and NORAD knockout led to suppressed LC cell proliferation, invasion, and migration. Besides, NORAD targeted miR-28-3p and miR-28-3p targeted E2F2 transcription. Inhibiting miR-28-3p or overexpressing E2F2 could both annul the inhibitory role of si-NORAD in LC cell proliferation, invasion, and migration. Generally, our findings demonstrated that NORAD competitively bound to miR-28-3p with E2F2, to promote LC cell progression.

Autoimmune liver diseases (AILDs) are life-threatening chronic liver diseases, mainly including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and AIH–PBC overlap syndrome (OS), which are difficult to distinguish clinically at early stages. This study aimed to establish model to achieve the purpose of the diagnosis of AIH/PBC OS in a noninvasive way. A total of 201 AILDs patients were included in this retrospective study who underwent liver biopsy during January 2011 to December 2020. Serological factors significantly associated with OS were determined by the univariate analysis. Two multivariate models based on these factors were constructed to predict the diagnosis of AIH/PBC OS using logistic regression and random forest analysis. The results showed that immunoglobulins G and M had significant importance in both models. In logistic regression model, anti-Sp100, anti-Ro-52, anti-SSA, or antinuclear antibody positivity were risk factors for OS. In random forest model, activated partial thromboplastin time and ɑ-fetoprotein level were important. To distinguish PBC and OS, the sensitivity and specificity of logistic regression model were 0.889 and 0.727, respectively, and the sensitivity and specificity of random forest model were 0.944 and 0.818, respectively. In conclusion, we established two predictive models for the diagnosis of AIH/PBC OS in a noninvasive method and they showed better performance than Paris criteria for the definition of AIH/PBC OS.

Long non-coding RNA FAM230B and microRNA (miR-1182) have been characterized as critical players in cancer biology, while their roles in colorectal cancer (CRC) are unclear. We predicted that they could interact with each other and therefore explored the interaction between them in CRC. CRC and paired non-tumor tissue samples were collected from 60 CRC patients, and the expression of FAM230B and miR-1182 (premature and mature) in these samples was analyzed with RT-qPCR. The direct interaction between FAM230B and premature miR-1182 was analyzed with RNA-RNA pull-down assay, and the subcellular location of FAM230B was detected with subcellular fractionation assay. The interaction between FAM230B and miR-1182 was explored with overexpression assay, and their roles in regulating CRC cell proliferation, viability, and colony formation were assessed by BrdU assay, MTT assay, and colony formation assay, respectively. We found that FAM230B and premature miR-1182 were highly upregulated in CRC, while mature miR-1182 was downregulated in CRC. FAM230B was detected in both nucleus and cytoplasm, and it directly interacted with miR-1182. FAM230B overexpression increased the expression levels of premature miR-1182 but decreased the expression levels of mature miR-1182 in CRC cells. FAM230B promoted CRC cell proliferation, increased cell viability, accelerated colony formation, and suppressed the role of miR-1182 in inhibiting CRC cell proliferation. In conclusion, FAM230B is upregulated in CRC and it suppresses the maturation of miR-1182 to promote tumor growth.

This study aimed to unveil the detailed role and new mechanism of circ-LIMK1 in lung adenocarcinoma. Real-time quantitative polymerase chain reaction was performed to analyze the expression of circ-LIMK1, miR-512-5p, and HMGA1. 3-(4,5)-Dimethylthiahiazo(- z-y1 )-3,5-di-phenytetrazoliumromide assay was employed to test the half maximal inhibitory concentration of cisplatin (DDP). Western blot was used to measure the expression of HMGA1, multidrug resistance protein 1, mitochondrial 37S ribosomal protein, and vascular endothelial growth factor A. Colony formation assay, flow cytometry, transwell assay, and tube formation assay were performed to analyze cell functions. Animal models were established to assay the role of circ-LIMK1 in vivo . The expression of circ-LIMK1 was up-regulated in DDP-resistant tumor tissues and cells. Knockdown of circ-LIMK1 reduced DDP resistance, impaired cancer cell growth, migration, invasion, and angiogenesis. circ-LIMK1 targeted miR-512-5p, and HMGA1 was targeted by miR-512-5p. MiR-512-5p absence could restore the repressive effects of circ-LIMK1 knockdown on lung adenocarcinoma cell phenotypes. Overexpression of HMGA1 could restore the inhibitory effects of miR-512-5p enrichment on lung adenocarcinoma cell malignant phenotypes. Knockdown of circ-LIMK1 could reduce growth of DDP-resistant tumors in vivo . Collectively, circ-LIMK1 regulated DDP resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant tumor with a poor prognosis. The dysregulation of long non-coding RNAs (lncRNAs) is closely related to the tumorigenesis and progression of ESCC. However, the effects of lncRNA small nucleolar RNA host gene 3 (lncRNA SNHG3) in ESCC are still unclear. Therefore, a series of experiments methods, such as quantitative real-time polymerase chain reaction, function gain/loss experiments, western blots, and animal xenograft tumor model, were employed to explore the biological function and molecular mechanism of SNHG3 in ESCC. As results, we first reported that SNHG3 was significantly up-regulated in ESCC tissues and cells. SNHG3 knockdown obviously inhibited cell proliferation, migration, invasion, and promoted apoptosis. Mechanism analysis revealed that SNHG3 sponged miR-151a-3p to regulate PFN2. Inhibition of miR-151a-3p and overexpression of PFN2 attenuated the positive effect of SNHG3 knockdown on suppressing tumor progression. Furthermore, the anti-tumor effects of SNHG3 knockdown were also observed in vivo . In summary, our results indicated that SNHG3 knockdown suppressed tumor development via the miR-151a-3p/PFN2 axis, and targeting SNHG3 may provide a new opportunity for ESCC patients.

A multicenter cross-sectional survey study involving four Italian University Hospitals was performed to test the hypothesis that negative affect and positive affect (affective dimensions) mediate the association between risk perception (perceived risk of infection and death; cognitive dimensions) and the feeling of work exhaustion (WE) among obstetrics healthcare providers (HCPs) during the Coronavirus Disease 2019 (COVID-19) pandemic. Totally, 570 obstetrics HCPs were invited to complete the 104-item IPSICO survey in May 2020. A theoretical model built on the tested hypothesis was investigated by structural equation modelling. The model explained 32.2% of the WE variance. Only negative affect mediated the association between cognitive dimensions and WE and also the association between WE and psychological well-being before the pandemic, experiences of stressful events, female gender, and dysfunctional coping. Non-mediated associations with WE were observed for work perceived as a duty, experience of stressful events, support received by colleagues, and the shift strategy. Only previous psychological well-being, support by colleagues, and shift strategies were inversely associated with WE. Based on study results, monitoring negative than positive affect appears superior in predicting WE, with practical implications for planning psychological interventions in HCPs at the individual, interpersonal, and organizational levels.

Invasion and metastasis of melanoma are a series of complicated biological events regulated by multiple factors. The coregulation of many molecules involved in the development and progression of melanoma contributes to invasion and migration. mGluR1 is a metabotropic glutamate receptor that is overexpressed in melanocytes and is sufficient to induce melanoma. In our study, we found that mGluR1 was obviously increased in melanoma. Furthermore, we found that miR-129-5p could directly target and regulate mGluR1 mRNA, which was significantly reduced in A375 cells. Overexpression of miR-129-5p inhibited cell migration, invasion and clonal formation. lncRNA-AC130710 directly targeted and suppressed miR-129-5p in A375 cells. Downregulation of lncRNA-AC130710 suppressed the levels of mGluR1 mRNA by promoting miR-129-5p expression and further inhibiting migration, invasion and colony formation in A375 cells, which was associated with the activation of the PKCα-MAPK signaling pathway. Taken together, our study showed that the lncRNA-AC130710/miR-129-5p/mGluR1 axis plays an important role in the invasion and metastasis of melanoma.

Papillary thyroid carcinoma (PTC) accounts for more than 80% of all thyroid carcinoma cases. Small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) has been indicated to be carcinogenic in several cancers; however, its function and mechanism in PTC are unclarified. Real time quantitative polymerase chain reaction and western blotting revealed the upregulation of SNRPB and downregulation of tumor protein p53 in PTC tissues compared with the normal tissues. Flow cytometry and western blotting displayed that SNRPB silencing induced cell cycle arrest at G1 phase and suppressed the expression levels of Cyclin family proteins in PTC cells. In vivo experiments suggested that SNRPB silencing inhibited PTC tumor growth in mice. Bioinformatics analysis revealed that the expression of SNRPB and cell cycle-associated genes in thyroid carcinoma tissues is positively correlated. Immunofluorescence staining and co-immunoprecipitation demonstrated that SNRPB directly interacted with p53 and suppressed its expression in PTC cells. In conclusion, SNRPB facilitates cell cycle progression in PTC by inhibiting p53 expression.

Type 1 diabetes mellitus is characterized with decreased microbial diversity. Gut microbiota is essential for the normal physiological functioning of many organs, especially the brain. Prebiotics are selectively fermentable oligosaccharides [xylooligosaccharides (XOS), galactooligosaccharides, etc.] that promote the growth and activity of gut microbes and influence the gut–brain axis. Aerobic exercise is a non-pharmacological approach for the control of diabetes and could improve cognitive functions. The potential beneficial effect of XOS and/or aerobic training on cognition, the lipid profile and oxidative stress markers of experimental rats were evaluated in this study. Male Wistar rats were randomly divided into three streptozotocin-induced diabetic groups and a control group. Some of the rats, either on a XOS treatment or a standard diet, underwent aerobic training. The results showed that the aerobic training independently lowered the total cholesterol levels compared to the sedentary diabetic rats ( p = 0.032), while XOS lowers the malondialdehyde levels in the trained diabetic rats ( p = 0.034). What is more the exercise, independently or in combination with XOS beneficially affected all parameters of the behavioral tests. We conclude that aerobic exercises alone or in a combination with the prebiotic XOS could ameliorate the dyslipidemia, oxidative stress, and cognitive abilities in experimental type 1 diabetic animals.

Serpin family A member 1 ( SERPINA1 ) is expressed abundantly in gliomas and can predict unfavorable prognosis of patients with glioma. Studies have shown that nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 ( NQO1 ) can promote the proliferation of glioblastoma multiforme cells and enhance the expression of SERPINA1 , but its effects on glioma cells remain unknown. In this study, we explored the functions of SERPINA1 in glioma tumorigenesis in vitro and then investigated whether NQO1 affects the protein expression of SERPINA1 and its mRNA level. The results showed that the translation of SERPINA1 was suppressed while its mRNA level had no significant changes under the condition of NQO1 silencing. Luciferase reporter assay and biotin pull-down assay further indicated that NQO1 bond with SERPINA1 3′ untranslated region. miR-1321 was also identified to target SERPINA1 , repressing its mRNA and protein levels . SERPINA1 and NQO1 promoted glioma cell proliferation and suppressed cell apoptosis. Moreover, SERPINA1 rescued the effects of sh-NQO1 in glioma cell malignant phenotypes. In conclusion, our findings showed that oncogene NQO1 and antioncogene miR-1321 bind to oncogene SERPINA1 to affect proliferation and apoptosis of glioma cells, which can bring new solution of antitumor treatments for glioma in the future.

Cleavage and polyadenylation specific factor 7 ( CPSF7 ) is an important participator in the cleavage and polyadenylation of pre-mRNAs. This study aims to uncover the function and underlying mechanism of CPSF7 in lung adenocarcinoma (LUAD). CPSF7 expression in LUAD cells was measured using real time-quantitative polymerase chain reaction and Western blotting. Our results showed that CPSF7 expression was upregulated in LUAD cell lines (A549, H1299, and HCC827). To explore the function of CPSF7 on LUAD, CPSF7 was silenced by the si- CPSF7 transfection and overexpressed by the oe- CPSF7 transfection in A549 cells. Cell proliferation was measured using cell counting kit-8 and colony formation assays. Cell migration and invasion were measured by wound healing and Transwell assays, respectively. Our data revealed that CPSF7 silencing inhibited the viability, colony formation, migration, and invasion of LUAD cells. On the contrary, CPSF7 overexpression enhanced the malignant characteristics of LUAD cells. Additionally, expression of AKT/mTOR pathway-related proteins was detected using Western blotting. CPSF7 silencing blocked the AKT/mTOR signaling pathway. The intervention of SC79 (an activator of the AKT/mTOR pathway) weakened the antitumor effects of CPSF7 silencing in LUAD cells. Silencing of CPSF7 inhibits the malignant characteristics of LUAD cells by blocking the AKT/mTOR signaling pathway.

Lumbar plexus block is often used as analgesia for adult hip surgery, but it is rarely used in pediatric patients. This study aimed to compare the efficacy and feasibility of ultrasound-guided lumbar plexus block versus transversus abdominis plane block for postoperative analgesia in children with hip dislocation. Eighty children undergoing unilateral hip dislocation surgeries at our hospital from October 2019 to February 2021 were randomized to the lumbar plexus block group (group L) and transversus abdominis plane block group (group T). Compared with group L, the regional block time in group T was lower (8.0 ± 2.5 vs 11.5 ± 2.3 min, P < 0.05), and the ultrasound image definition was better ( P < 0.05). There were no significant differences in mean blood pressure and heart rate within 24 h (all P > 0.05). Children’s Hospital of Eastern Ontario Pain Scale scores were lower in group L than in group T at 18–24 h only (all P < 0.05). The satisfying analgesia rate in group L was higher than in group T (87.5 vs 65%, P < 0.05). No regional block-related complications were found in both groups. Ultrasound-guided lumbar plexus block showed a longer postoperative analgesic effect in children with hip dislocation compared with transversus abdominis plane block.

Preterm infants face a significant risk of brain injury in the perinatal period, as well as potential long-term neurodevelopmental disabilities. However, preterm children with brain injury lack specific clinical manifestations in the early days. Therefore, timely and accurate diagnosis of brain injury is of vital importance. This study was to explore the diagnostic efficiency of myelin basic protein (MBP) and 8-oxo-deoxyguanosine (8-oxo-dG) serum levels in brain injury of premature infants. A total of 75 preterm infants with gestational age between 28 and 32 weeks and birth weight higher than 1,000 g were prospectively included. MBP serum levels were significantly higher in premature infants with white matter injury (WMI). 8-oxo-dG serum levels were significantly increased in both WMI and periventricular–intraventricular hemorrhages (PIVH). MBP and 8-oxo-dG were significantly correlated. The area under the curve was 0.811 [95% confidence interval (CI) 0.667–0.955; p = 0.002] in MBP and 0.729 (95% CI 0.562–0.897; p = 0.020) in 8-oxo-dG. Therefore, the results showed that high MBP levels indicated a possibility of WMI in the premature brain during the early postnatal period, while high 8-oxo-dG levels were closely related to both WMI and PIVH, thus suggesting that MBP and 8-oxo-dG could be used as potential neuro-markers of preterm brain injury.

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies that have a poor prognosis. Necroptosis has been demonstrated in recent years to be a form of inflammatory cell death occurring in multicellular organism, which plays complex roles in cancer. However, the expression of necroptosis-related miRNAs and genes in HNSCC and their correlations with prognosis remain unclear. In this study, R software was used to screen differentially expressed miRNAs downloaded from The Cancer Genome Atlas. A prognostic model containing six necroptosis-related miRNAs (miR-141-3p, miR-148a-3p, miR-331-3p, miR-543, miR-425-5p, and miR-7-5p) was generated, whose risk score was validated as an independent prognostic factor for HNSCC. Target genes of the key miRNAs were obtained from TargetScan, miRDB, and miRTarBase, and 193 genes in the intersection of the three databases were defined as consensus genes. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses indicated that the composition of the tumor microenvironment as well as specific pathways may be closely related to necroptosis in HNSCC. Nine key genes were also obtained by the MCODE and cytoHubba plug-ins of Cytoscape: PIK3CD, NRAS, PTK2, IRS2, IRS1, PARP1, KLF4, SMAD2, and DNMT1. A prognostic model formed by the key gene was also established, which can efficiently predict the overall survival of HNSCC patients. In conclusion, necroptosis-related miRNAs and genes play important roles in tumor development and metastasis and can be used to predict the prognosis of HNSCC.

This study aimed to evaluate the effects of delayed femoral vein ligation on the clinical outcomes of hip disarticulation. We retrospectively reviewed 20 patients with extremity tumors (10 bone tumors and 10 soft tissue sarcomas [STS]) who underwent hip disarticulation. Patients treated for hip disarticulation with synchronous femoral vein ligation ( n = 10, regular surgery group) and hip disarticulation with delayed femoral vein ligation ( n = 10, delayed ligation group), respectively, were enrolled in this study. The operative time and blood loss were used to evaluate the clinical outcomes. The delayed ligation group had significantly lower operative times than the regular surgery group ( P < 0.05). Total, hidden, and intraoperative blood loss were all significantly lower in the delayed ligation group than in the regular surgery group ( P < 0.05). However, there were no significant differences in postoperative blood loss. In conclusion, delayed femoral vein ligation could significantly reduce the operative time, hidden blood loss, and intraoperative blood loss in patients undergoing hip disarticulation.

ASAP3 is involved in a variety of biological activities, including cancer progression in humans. In adult glioma, we explore the effects of ASAP3  and NOTCH3 and their relationships on prognosis. The Oncomine, TIMER, and Gene Expression Profiling Interactive Analysis databases were used to investigate ASAP3 expression. Immunohistochemistry was used to assess the levels of ASAP3  and NOTCH3 expressions. The effects of ASAP3  and NOTCH3 on prognosis were assessed using survival analysis. The results revealed that the amount of ASAP3 mRNA in gliomas was much higher than in normal tissue ( P < 0.01). Glioma patients with high ASAP3 mRNA expression had a worse overall survival and progression-free survival. ASAP3 overexpression is directly associated with the NOTCH signaling system. Immunohistochemistry revealed that ASAP3  and NOTCH3 were overexpressed in glioblastomas (GBMs). ASAP3 expression was associated with age, recurrence, tumor resection, postoperative chemoradiotherapy, World Health Organization (WHO) grade, and Ki-67 expression. ASAP3  expression was related to the isocitrate dehydrogenase-1 mutation in low-grade glioma. Gender, local recurrence, tumor resection, postoperative radio-chemotherapy, WHO grade, recurrence, and ATRX expression were all associated with NOTCH3  expression.  ASAP3  was shown to be positively associated with NOTCH3 ( r = 0.337, P = 0.000). Therefore, ASAP3 and NOTCH3  as oncogene factors have the potential to be prognostic biomarkers and therapeutic targets in adult glioma.

This research aimed to analyze lifestyle-related factors which influence Helicobacter pylori ( Hp ) infection and outcomes in Chinese adults. A single-center, retrospective study was performed from January 2012 to December 2020. Self-administered questionnaires were used to collect relevant lifestyle information, and the 13 C-urea breath test was used to diagnose active Hp infection. A total of 18,211 subjects were enrolled in the study, of which 5,511 were females (30.26%). Subjects were studied longitudinally for up to five follow-up visits. At baseline, gastric Hp test was negative in 10,670 subjects (58.59%) and positive in 7,541 subjects (41.41%). Males exhibited a significantly higher Hp infection rate than females (38.56% vs 2.65%, respectively; χ 2 = 26.45, P < 0.001). Throughout the course of follow-up, Hp positive rates in the subjects decreased ( χ trend 2 {\chi }_{\text{trend}}^{2} = 666.04, P < 0.001). Among the subjects with baseline negative results, 3–6% changed from negative to positive during follow-up. In contrast, among those with baseline positive results, >70% remained positive, and 21–26% changed from positive to negative. However, only 22–27% of Hp -infected subjects received pharmacotherapy. The results indicate the prevalence of Hp infection is high in the Chinese population. That additional effort is required to prevent and control Hp infection.

Esophageal cancer (EC) is an extremely aggressive malignant tumor. Homeobox A10 (HOXA10) is highly expressed and plays an important role in a variety of tumors. However, the function of HOXA10 in EC remains unclear. In this study, HOXA10 was observed to highly express in EC tissues and cells. Interestingly, the CCK-8 assay, flow cytometry, and colony formation assay confirmed that overexpression of HOXA10 promoted proliferation and suppressed cell apoptosis in EC cells. More importantly, the western blot assay indicated that the phosphorylation levels of ERK and p38 were elevated in EC cells overexpressed HOXA10, indicating that overexpression of HOXA10 activated p38/ERK signaling pathway in EC cells. These findings concluded that HOXA10 aggravated EC progression via activating p38/ERK signaling pathway, providing a potential therapeutic target for EC.

This meta-analysis aimed to investigate the correlation between early-life antibiotic use and allergic rhinitis. PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases were searched for available studies. Eighteen studies covering 1,768,874 children were included. Early-life antibiotics were associated with an increased incidence of allergic rhinitis (effect size (ES) = 5.00, 95% confidence interval [CI]: 4.88–5.13; I 2 = 95.7%, P heterogeneity <0.001). In Asia, Europe, and the USA, the incidence of allergic rhinitis in the antibiotic group was higher than that in the no medication group (Asia: ES = 3.68, 95% CI: 3.38–4.01; Europe: ES = 3.20, 95% CI: 3.00–3.42; USA: ES = 3.68, 95% CI: 2.74–4.95). Compared with the no medication group, children who received antibiotics in the first 1 week of life (ES = 5.75, 95% CI: 2.18–15.18), first 1 year of life (ES = 3.37, 95% CI: 3.20–3.55; I 2 = 64.2%, P heterogeneity = 0.001), or first 3 years of life (ES = 5.21, 95% CI: 2.42–11.19) had a higher incidence of allergic rhinitis. No individual study influenced the estimates of the meta-analysis. The funnel plot showed moderate symmetry and low publication bias. In conclusion, the use of antibiotics in early life was associated with allergic rhinitis. Still, most included studies analyzed antibiotic exposure as a dichotomous variable, without information on the type and dosage of antibiotics.

The objective of this study was to assess the impact of marital status on tonsil squamous cell carcinomas (TSCCs) prognosis and to analyze whether the impact is correlated with gender, age, and race. We examined the clinicopathological variables using Chi-squared tests and evaluated the association between survival and different variables using the methods of Kaplan–Meier. Univariate and multivariate analyses were performed to determine the effects of each variable on survival. A total of 10,720 patients were analyzed. The rate of being married was higher among Asian or Caucasian, and this rate decreased with higher tumor stage. While both married male and female survivors benefit from their marital status, we found a differential in cancer-specific survival based on gender, with males benefitting more than females ( p < 0.05). The same results were found in overall survival. Subgroup analysis shows that the protective effect of marriage was consistent in all patients except for N3 groups (all, p < 0.05). While there are survival benefits for married patients with TSCCs, married/partnered males may benefit more than females. Age, race, and gender could affect the correlation between marital status and survival.

Cervical cancer is the fourth most common cancer and the fourth leading cause of cancer death in women. Human papillomavirus (HPV16) E6/E7 heterogenous expression in C33A cells increased the mRNA and protein levels of KIF2A, while siRNA deletion of endogenous E6/E7 reduced the mRNA and protein levels of KIF2A in SiHa cells. KIF2A promoted cell migration and invasion, and regulated the expression of epithelial–mesenchymal transition-related proteins in C33A and SiHa cells. The exogenous expression of E6/E7 in C33A cells increased the phosphorylation of Akt, ERK, and JNK. However, Akt (API-2) and ERK (PD98059) inhibitors had no effect on the increase in KIF2A expression induced by E6/E7, while JNK inhibitors (JNK-IN-8 and SP600125) blocked the increase in KIF2A expression induced by E6/E7. The exogenous expression of E6/E7 increased the levels of transcription factor c-Jun, which is the classic substrate of JNK. Knockdown of c-Jun reduced the increase in KIF2A expression induced by E6/E7. In summary, KIF2A plays a key role in the motility and metastasis of cervical cancer. HPV16 E6/E7 can increase the levels of transcription factor c-Jun by activating the JNK signal, thereby up-regulating the transcriptional expression of KIF2A.

Most patients with liver cancer were found late and lost the chance of surgery. Liquid biopsy can monitor the risk of tumor recurrence and metastasis, quickly evaluate the curative effect of tumor treatment, and is conducive to early screening and auxiliary diagnosis of high-risk groups. Amino acid (AA) profiling has been used to the diagnosis and the prognosis for cancers. However, little was known about the profiles of AA of liver cancer. In this study, we used tRNA in Cancer database to analyze the AA levels in liver cancer tissues. Blood samples of patients with liver cancer were collected and analyzed using the automatic AA analyzer. We found that valine, isoleucine, and leucine were decreased significantly both in the plasma and the tumor tissues of patients with liver cancer. However, upregulation of methionine was observed in tissues and plasma of patients with liver cancer. Interestingly, tyrosine, and phenylalanine were decreased in tumor tissue but increased in the plasma of patients with liver cancer. This is the first report provided an overview of AA profile in both plasma and tissue for patients with liver cancer. AA levels can be used as diagnostic and prognostic markers of patients with liver cancer.

We retrospectively analyzed the data from patients admitted to the intensive care unit (ICU) of the Hospital of L’Aquila during the first and second waves of pandemic to identify pain related to COVID-19. Pain was evaluated by using the Numerical Rating Scale, and the assessment for neuropathic disturbances of pain was performed with von Frey’s hair and Lindblom tests. Pain increased significantly during hospitalization (from 48% at hospital admission to 94.3% at ICU discharge). Female patients were affected by somatic pain in 32.8% of the cases and by somatic pain and pain with neuropathic features (NFs) in 23.5% of the cases, during the ICU stay. Somatic pain and pain with NFs affected more frequently patients with cardiological and respiratory comorbidities. Patients treated with continuous positive airway pressure via helmet had a higher frequency of somatic pain and pain with neuropathic disturbances (84 and 74%, respectively). The frequency of somatic pain and pain with neuropathic disturbances was lower in patients sedated with propofol combined with ketamine. Females have been associated with a higher risk of somatic pain and pain with NFs. Patients with cardiological and respiratory comorbidities undergoing noninvasive ventilation had higher levels of pain. As conclusion, ketamine may reduce the promotion or the worsening of pain in COVID-19 patients.

Pesticides, which adversely affect the critical metabolic processes of organisms, disrupt the physiological balance by specifically targeting enzymes and may lead to such consequences that may lead to death. It provides benefits in agricultural activities. The p53 protein antagonizes bcl-2, an anti-apoptotic protein character, and induces apoptosis by causing mitochondrial membrane permeability. This study aims to show the effect of acetamiprid, which is an insecticide from the neonicotinoid class, on bcl-2 and p53 immunoreactivity, which has an important place in the apoptotic mechanism in kidney tissue. A total of four groups including control and three experimental groups (the acetamiprid was administered 5, 10, and 15 mg kg −1 ) were formed in the study. After acetamiprid was administered via gavage for 14 days, the kidney tissues taken from the mice, which were sacrificed by cervical dislocation, were fixed in 10% formaldehyde solution for histological and immunohistochemical analyses, and as a result of routine tissue follow-up, the sections were blocked in paraffin and stained with haematoxylin–eosin and immunostaining. The histopathological examinations revealed that while the kidney tissue had a normal structure in the control group, degeneration in the distal and proximal tubules, glomerular degeneration, increase in the capsular area, glomerular atrophy, and haemorrhage were determined in the acetamiprid groups at increasing severity and frequency depending on the dose of the applied substance. In the kidney tissue, Bcl-2 and p53 immunoreactivity was observed in glomerular cells, sinusoidal epithelium, and proximal and distal tubule cells. The acetamiprid caused pathological changes in the kidneys in the dose range used. This effect also affects the expression of bcl-2 and p53 genes, which are biomarkers in the apoptotic mechanism. As acetamiprid accumulates in tissues, it increases the expression of p53 from cell death receptors, while suppressing the anti-apoptotic bcl-2 expression.

We conducted a systematic review and meta-analysis of all published data to determine the impact of estradiol pretreatment on reproductive outcomes and ovary stimulation characteristics for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment with gonadotropin-releasing hormone (GnRH) antagonist protocol. MEDLINE, EMBASE, Cochrane Library, Web of Science, and China National Knowledge Infrastructure were searched, and any randomized controlled trials associated with estradiol pretreatment in GnRH antagonist protocol were included. Seven studies (1,236 patients) were included in the present study. The pooled data from the meta-analysis demonstrated no significant difference in ongoing pregnancy rate (odds ratio (OR): 0.92 (95% CI: 0.69–1.21; P = 0.53) and live birth rate OR: 0.98 (95% CI: 0.74–1.30; P = 0.90) between patients with and those without estradiol pretreatment in GnRH antagonist protocol. Duration of gonadotropin exposure, gonadotropin consumption, and the number of cumulus–oocyte complexes were not significantly different between groups. Luteal estradiol pretreatment in IVF/ICSI cycles with GnRH antagonist protocol in normal ovary responding population does not affect the reproductive outcomes. It is an encouraging option to facilitate cycle scheduling in GnRH antagonist protocol, for luteal estradiol pretreatment does not increase the duration of gonadotropin exposure or gonadotropin consumption.

This study aimed to explore the effects of long non-coding RNAs LINC00689 (LINC00689) in human nucleus pulposus cells (NPCs). NPCs were isolated and their morphology was observed. The proliferation and apoptosis of NPCs, and the levels of LINC00689, miR-3127-5p, Bax, Bcl-2, Cleaved caspase-3, ATG5, ATG7, p62, and LC3Ⅱ/LC3I were detected. Interrelations of LINC00689, miR-3127-5p, and ATG7 were analyzed. LINC00689 was down-regulated yet miR-3127-5p was up-regulated in NPCs. LINC00689 could competitively bind with miR-3127-5p, and ATG7 was targeted by miR-3127-5p in NPCs. Overexpressed LINC00689 promoted proliferation yet inhibited apoptosis of NPCs, whereas LINC00689 silencing did the opposite. Overexpressed LINC00689 raised ATG7 level and LC3Ⅱ/LC3I value yet reduced that of p62 level, but the depletion of LINC00689 did the contrary. ATG7 silencing abolished the effects of overexpressed LINC00689 in NPCs, and likewise, up-regulation of miR-3127-5p overturned the effects of overexpressed LINC00689 in NPCs. Collectively, the up-regulation of LINC00689 inhibits the apoptosis of NPCs via miR-3127-5p/ATG7 axis-mediated autophagy.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19). We conducted a retrospective study of COVID-19 inpatients in Wuhan Pulmonary Hospital (Wuhan, China) from January 1 to February 29, 2020. The subjects were divided into four groups due to different treatment regimes. We used the Kaplan–Meier method to determine the cumulative rates of in-hospital death and the Cox proportional hazard model to calculate the risk factors and corresponding hazard ratios. A total of 185 patients were included in this study. The median age of the patients was 62 years, including 94 men and 91 women. Kaplan–Meier analysis demonstrated that mortality was higher in older patients, higher in men, and lower in the low-flow oxygen therapy group. Body mass index (BMI) had no influence on mortality, as well as high flow oxygen therapy, Lopinavir–ritonavir (LPV/r) therapy, and the interferon-alpha add LPV/r therapy. Cox proportional hazard regression confirmed that the low flow oxygen therapy was independent protective factor for in-hospital death after adjusting for age, gender, and BMI. In conclusion, the mortality was higher in older patients, higher in men, and lower in the low-flow oxygen therapy group. BMI had no influence on mortality, as well as high flow oxygen therapy, LPV/r therapy, and interferon-alpha add LPV/r therapy.

This study investigated the implication of monitoring hypertensive disorders in pregnancy (HDP) to prevent preeclampsia (PE) in pregnant women of advanced maternal age. Between January 2016 and April 2021, 262 consecutive pregnant women aged ≥40 years were recruited. Extensive monitoring of hypertensive disorders in pregnancy, including blood hypercoagulability screening and subsequent interventions, was performed in 129 pregnant women in our university hospital. The remaining 133 patients from other centres, who did not receive antenatal maternal pregnancy screening and preventive intervention during the same period, constituted the non-intervention group enabling comparison to mimic a trial. The incidences of hypertensive disorders, mild and severe PE, eclampsia, and chronic hypertension complicated by PE in the intervention group were significantly lower than in the non-intervention group (10.08 versus 20.30%, 8.52 versus 18.80%, 7.75 versus 21.05%, 0 versus 3.01%, and 3.86 versus 15.04%, respectively; P < 0.05). Premature birth, low birth weight, and foetal loss were significantly rarer in the intervention group than in the non-intervention group (6.98 versus 24.81%, 7.75 versus 21.80%, and 0.78 versus 14.29% respectively; P < 0.001). The comparison of MP with routine blood coagulation biochemical examination found that the MP detection system of Beijing Yes Medical Devices Co., Ltd., had similar sensitivity as thromboelastogram. Still, it was significantly better than the routine biochemical indicators ( P < 0.01). Based on MP parameters, early anticoagulant treatment with low-molecular-weight heparin or low-dose aspirin in pregnant women with hypercoagulability can effectively prevent the occurrence of PE and significantly improve the prognosis of both mothers and infants.

Nasopharyngeal carcinoma is one of the common malignant tumors that the pathogenesis has not yet been completely defined. SETD1A (histone lysine methyltransferase SET domain-containing 1A) is related to the occurrence of various cancers. However, the role of SETD1A in nasopharyngeal carcinoma remains unclear. The SETD1A overexpression vector, si-NC, si-SETD1A#1, and si-SETD1A#2 were transfected into nasopharyngeal carcinoma cells to overexpress or knockdown SETD1A expression. The assay of biofunction was used to explore the role of SETD1A in nasopharyngeal carcinoma cells. The assay of glucose uptake, lactate release, ATP level, western blot, cell proliferation, and cellular apoptosis analysis were performed to investigate the potential mechanism of SETD1A regulation in nasopharyngeal carcinoma. This study was the first to show that SETD1A was upregulated in nasopharyngeal carcinoma cells and the overexpression of SETD1A significantly promoted the cell proliferation and glycolysis and suppressed the cellular apoptosis. Moreover, SETD1A enhances aerobic glycolysis and cell biological function of nasopharyngeal carcinoma cells via PI3K/AKT signaling pathway. SETD1A induced PI3K/AKT activation and subsequently prevented cellular apoptosis. In conclusion, this study identified overexpressed SETD1A as a positive regulator of proliferation that induced nasopharyngeal carcinoma cells’ aerobic glycolysis via PI3K/AKT signaling activation in vitro. This study laid a strong foundation for unveiling the precise anticancer mechanism of SETD1A. The SETD1A may become a novel biomarker for further inhibitor design to obstruct the PI3K/AKT-dependent nasopharyngeal carcinoma progression.

Chronic cerebral hypoperfusion (CCH) is a frequent ischemic cerebrovascular disease that induces brain dysfunction. Shunaoxin pills (SNX) are traditional Chinese medicines (TCM), frequently used for the treatment of CCH. The purpose of this study was to develop an activity-based screening system to identify the active ingredients of SNX. We developed a model of CCH and revealed that SNX induces cerebrovascular dilatation and protects against CCH-induced nerve cell injury in rats. Using the transcriptome analysis, we found that Ca 2+ -related signaling pathways play a major role in the effect of SNX against CCH. We developed an activity-based screening system based on the ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry coupled with a dual-luciferase reporter calcium assay to identify the active components of SNX. As a result, SNX dilates cerebral blood vessels, increasing cerebral blood flow by modulating calcium-related signaling pathways and regulating calcium homeostasis. Two calcium antagonists, ligustilide and senkyunolide I, were identified as active ingredients in SNX. In conclusion, we developed a rapid screening method suitable for the discovery of active natural products in TCM by integrating genomics and target pathway-oriented spectroscopic analysis.

Ten–eleven translocation 3 (TET3) participates in tumorigenesis and malignant transformation by mediating DNA demethylation and specific gene activation in malignances. This study aims to elucidate its molecular function and regulatory mechanism in esophageal squamous cell carcinoma (ESCC). Stable ESCC cells that infected with TET3 overexpression (OE) and knockdown lentiviral vector had been established. The biological behaviors and molecular mechanism of TET3 were demonstrated by cell biology experiments in vitro and in vivo . Tissues from patients with ESCC were used to demonstrate the clinical value of TET3. Our findings revealed that TET3 is highly expressed in ESCC tissues and related to poor prognosis of patients with ESCC. OE of TET3 presented a significant effect on proliferation, metastatic potential, and spheroid formation of ESCC cells by activating the PI3K/AKT/GSK3β/β-catenin axis. Knockdown of TET3 could remarkably reverse these malignant phenotypes. Patients with ESCC with high TET3 expression resulted in a shorter overall survival (OS) and disease-free survival. Based on the multivariate analysis, TET3 could be an independent favorable factor for predicting OS and recurrence. The high expression of TET3 not only aggravates malignant behaviors in vitro and in vivo but also becomes a novel biomarker for clinical monitoring and individualized precision treatment for patients with ESCC.

Infertility is a major health concern worldwide. This retrospective study aimed to assess the predictive value of the morphokinetic parameters of temporary-arrest embryos for the pregnancy outcomes of women undergoing frozen embryo transfer (FET) cycles. In this study, we evaluated 244 FET cycles with 431 day-4 temporary-arrest embryos. They were categorized into two groups (pregnancy and non-pregnancy) according to the pregnancy outcomes of the women after embryo transfer on day 5, and their fundamental characteristics were compared. The morphokinetic parameters from the time-lapse monitoring system were assessed according to different pregnancy outcomes. The mean number of embryo blastomeres thawed on day 3 in the pregnancy group was 7.47, which was significantly higher than the number in the non-pregnancy group ( p < 0.01). Besides, embryos in the non-pregnancy group contained more embryo fragments and lower grades than those in the pregnancy group ( p < 0.001). Furthermore, morphokinetic parameters: tPNa, t2, t5, and t5_tPNf showed a statistical difference between the pregnancy and non-pregnancy groups ( p < 0.05). Receiver-operating characteristic analysis revealed that the time from pronuclear fading to the 5-cell stage (t5_PNF) predicted the clinical prognosis outcomes (area under the curve = 0.64; 95% confidence interval [CI], 0.58–0.70; p < 0.001). The morphokinetic parameter t5_PNF could be regarded as a potential implantation predictor in our study.

This study aimed to determine the role of long noncoding RNA (lncRNA) WT1 antisense RNA (WT1-AS) in the occurrence and progression of preeclampsia (PE) and to determine the underlying molecular mechanisms. The associations between WT1-AS and microRNA (miR)-186-5p, and miR-186-5p and cell adhesion molecule 2 (CADM2) were predicted using StarBase software and verified via dual-luciferase assays. To explore the role of the human chorionic trophoblast line HTR-8/SVneo, gene (WT1-AS/miR-186-5p) gain/loss of function experiments were performed. Qualitative reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to evaluate transfection efficiency. Cell proliferation, apoptosis, cell migration, and invasion were assessed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2- H -tetrazolium bromide (MTT), flow cytometry, and transwell analysis, respectively. Moreover, CADM2 protein expression was measured by western blotting. The results indicated that overexpression of WT1-AS inhibited cell viability, migration, and invasion, and induced apoptosis in HTR-8/SVneo cells. We observed that miR-186a-5p directly targeted WT1-AS, and miR-186a-5p knockdown reversed the effects of WT1-AS knockdown in HTR-8/SVneo cells. Binding sites were found between miR-186-5p and CADM2, and CADM2-overexpression reversed the influence of miR-186-5p mimic on HTR-8/SVneo cells. In summary, our findings demonstrated that lncRNA WT1-AS participates in PE by regulating the proliferation and invasion of placental trophoblasts, through the miR-186-5p/CADM2 axis.

Bronchiectasis is a common comorbidity in chronic obstructive pulmonary disease (COPD). There are limited data regarding the incidence of bronchiectasis in COPD. The purpose of the study was to use a nationwide database to evaluate the incidence of bronchiectasis in COPD in Taiwan. We used a cohort of 2,000,000 individuals followed from 2005 to 2018. Patients with COPD diagnosed between January 1, 2011, and December 31, 2017, were selected, and those with bronchiectasis before COPD were excluded. In total, 134,366 patients with COPD were enrolled, and propensity score matching was used to ensure homogeneity of baseline characteristics between the COPD and non-COPD groups. The incidence rate of bronchiectasis was higher in the COPD group than in the non-COPD group (87.83 vs 69.80 per 10,000 person-years). The adjusted hazard ratio (1.9; 95% confidence interval 1.75–2.05; P < 0.001) of bronchiectasis indicated that the risk of bronchiectasis was 1.9 times higher for patients with COPD than for patients without COPD. In the COPD group, the age-stratified incidence rates of bronchiectasis increased with age (55.01, 80.92, 101.52, and 105.23 for 40–49, 50–59, 60–69, and over 70 years, respectively). The incidence of bronchiectasis was higher in patients with COPD than in the general population, the risk of bronchiectasis increased with age in COPD, and post-tuberculosis status was an important risk factor for bronchiectasis.

Integrin subunit alpha 3 (ITGA3) expression correlates with the development and prognosis of human cancers. This study aimed to investigate the association of ITGA3 expression with pancreatic cancer (PCa) prognosis. The ITGA3 gene expression data were extracted from The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) cohort and 14 Gene Expression Omnibus microarray datasets. The differences in ITGA3 expression levels between tumor and non-tumor tissues were compared using the Mann–Whitney U test. Cox regression analysis and meta-analysis were performed to detect the association of ITGA3 expression with PCa prognosis. ITGA3 expression was higher in tumors than in controls. Tumors with advanced grades (3/4) had higher ITGA3 levels compared with early-grade tumors (1/2). The meta-analysis of the TCGA PAAD cohort and seven microarray datasets (GSE28735, GSE62452, GSE79668, GSE71729, GSE57495, GSE78229, and GSE21501) showed that ITGA3 was a prognostic biomarker in PCa (hazard ratio (HR) = 1.38, 95% confidence interval (CI) 1.26–1.51, p < 0.00001). Five ITGA3-related genes, including ITGB1 (HR = 1.6), ITGB5 (HR = 1.6), ITGB6 (HR = 1.6), LAMA3 (HR = 2.1), and CD9 (HR = 2.3), correlated with PCa prognosis significantly ( p < 0.05). Functional enrichment analysis showed that ITGA3 was related to “hsa04151: PI3K-Akt signaling pathway” and “hsa04510: Focal adhesion.” We concluded that high ITGA3 expression was a potential prognostic biomarker in PCa.

miR-21 has been confirmed to be overexpressed in neonatal rat lungs with hyperoxia-mediated bronchopulmonary dysplasia (BPD). The specific function of miR-21 in BPD is still unclear. We established the hyperoxia-induced BPD rat model in vivo and the hyperoxia-induced pulmonary microvascular endothelial cells (PMVECs) model in vitro . Transwell assay was utilized to detect the migratory capability of PMVECs. Tube formation assay was utilized to measure angiogenesis ability. ELISA was utilized to test nitric oxide (NO) production and the intracellular and extracellular Asymmetric Dimethylarginine (ADMA) concentration. Furthermore, the interaction between miR-21 and dimethylarginine dimethylaminohydrolase 1 (DDAH1) was evaluated using luciferase reporter assay. We found that miR-21 expression in PMVECs was increased by hyperoxia stimulation. Inhibition of miR-21 improved the migratory and angiogenic activities of PMVECs and overexpression of miR-21 exerted the opposite effects. Furthermore, knockdown of miR-21 increased NO production and decreased intracellular and extracellular ADMA concentration in hyperoxia-treated PMVECs. Next we proved that miR-21 could bind to DDAH1 and negatively regulate its expression. Rescues assays showed that DDAH1 knockdown reversed the effects of miR-21 depletion on hyperoxia-mediated PMVEC functions, NO production, and ADMA concentration. Importantly, miR-21 downregulation restored alveolarization and vascular density in BPD rats. This study demonstrates that inhibition of miR-21 improves pulmonary vascular responses in BPD by targeting the DDAH1/ADMA/NO pathway.

Considerable attention has been focused on the clinical features of coronavirus disease 2019 (COVID-19), but it is also important for clinicians to differentiate it from influenza virus infections. In the present study, the rate of coexisting disease was lower in the severe COVID-19 group than in the influenza A group ( p = 0.003). Radiologically, severe COVID-19 patients had fewer instances of pleural effusion ( p < 0.001). Clinically, severe COVID-19 patients had relatively better disease severity scores, less secondary bacterial infections, shorter times to beginning absorption on computed tomography, but longer durations of viral shedding from the time of admission ( p < 0.05). Although the more severe influenza A patients required noninvasive respiratory support, these two groups ultimately yielded comparable mortalities. Based on the multiple logistic regression analysis, severe COVID-19 infection was associated with a lower risk of severe acute respiratory distress syndrome [odds ratio (OR) 1.016, 95% [confidence interval (CI)] 1.001–1.032, p = 0.041] and a better pneumonia severity index (OR 0.945, 95% [CI] 0.905−0.986, p = 0.009); however, these patients exhibited longer durations of viral shedding (OR 1.192, 95% [CI] 1.047−1.357, p = 0.008) than patients with severe influenza A infection. In conclusion, the conditions of severe influenza A patients appeared to be more critical than that of severe COVID-19 patients. However, relatively lower mortalities of these two severe cases are expected in the context of sufficient medical supplies.

We investigated the function of lncRNA zinc finger antisense 1 (ZFAS1) in intervertebral disc degeneration (IDD) progression in vitro and in vivo . Nucleus pulposus (NP) tissues were obtained from 20 patients with IDD. IL-1β was used to stimulate primary NP cells to establish the IDD models in vitro . Gene expression was determined by RT-qPCR. 5-Ethynyl-2′-deoxyuridine and flow cytometry were performed to determine cell proliferation and apoptosis, and western blotting was conducted to measure the apoptosis- and extracellular matrix (ECM)-related protein expression. Luciferase reporter assay was used to examine the interactions between the genes. We also investigated the effect of ZFAS1 in a mouse model of IDD induced by needle punctures. Our results showed that ZFAS1 expression was elevated in degenerative NP tissues and IL-1β-treated NP cells. ZFAS1 knockdown inhibited NP cell apoptosis and ECM degradation induced by IL-1β. Mechanically, ZFAS1 sponged miR-4711-5p and adaptor-associated kinase 1 (AAK1) was targeted by miR-4711-5p. Furthermore, AAK1 overexpression partially eliminated the impact of ZFAS1 depletion on NP cell proliferation, apoptosis, and ECM degradation. More importantly, the results of the in vivo studies confirmed the effect of silencing ZFAS1 on alleviating the symptoms of IDD mice. Overall, silencing ZFAS1 inhibits IDD progression by reducing NP cell apoptosis and ECM degradation through the miR-4711-5p/AAK1 axis.

N , N -Dimethylformamide (DMF) is widely used in chemical industries because of its excellent solvent properties. Poisoning accidents caused by DMF have been frequently reported, particularly hepatotoxicity; however, the hepatic pathological changes have rarely been described. This study aimed to summarise the pathological characteristics of the hepatotoxicity associated with DMF in clinical cases and to verify in animal models. Liver pathologies of two patients with liver failure due to DMF were retrospectively analysed. Thirty-six rats were categorised into the DMF group (intraperitoneally injected with 4 g/kg DMF once a week), carbon tetrachloride (CCl 4 ) group (intraperitoneally injected with 0.5 g/kg CCl 4 twice a week) and control group (intraperitoneally injected with normal saline once a week). The general condition and changes in hepatic pathology at 48 h and 8 weeks were observed. Liver tissues of patients exhibited multiple unevenly distributed inflammatory and fibrotic lesions. The DMF-induced liver injury animal model was successfully established. Inflammation and fibrosis were heterogeneously observed throughout the liver in the DMF group, contrast to entirely homogeneous lesions in the CCl 4 group. Specific hepatic pathological findings (heterogeneous lesions) caused by DMF detected for the first time in humans and animal model, may be significant in the clinical diagnosis of DMF poisoning.

The oncogenic role of lncRNA ELFN1-AS1 has been described in different cancers, including colon cancer (CC). However, how ELFN1-AS1 regulates CC malignancy remains unclear. In this study, ELFN1-AS1, AURKB, and miR-4270 expression levels in CC cells and tissues were determined using RT-qPCR and western blotting. CCK-8 and wound healing assays were also performed to analyze alterations in CC cell proliferation and migration. The expression of apoptosis-related proteins (Bax and Bcl-2) was determined via western blot analysis. RNA immunoprecipitation (RIP) assays coupled with luciferase reporter assays were employed to verify the relationship between miR-4270, ELFN1-AS1, and AURKB. An in vivo assay was performed using xenograft tumors in mice to detect the change of tumor growth. It was found that AURKB and ELFN1-AS1 expression was upregulated, whereas miR-4270 was downregulated in CC cells and tissues. ELFN1-AS1 silencing exhibited anti-proliferative, anti-migratory, and pro-apoptotic effects in CC cells. The tumor-suppressive effect of ELFN1-AS1 silencing was verified using in vivo assays. MiR-4270 was predicted to be a target of ELFN1-AS1 and AURKB as a target of miR-4270. Their interactions were further elucidated using luciferase reporter and RNA RIP assays. More importantly, treatment with a miR-4270 inhibitor not only rescued the tumor-suppressing effect of ELFN1-AS1 silencing but also abrogated the tumor suppressor functions of AURKB silencing in CC cells. Taken together, the ELFN1-AS1/miR-4270/AURKB axis facilitates CC tumorigenesis; therefore, targeting this axis might be a promising intervention in preventing CC progression.

The long noncoding RNA DARS-AS1 was aberrantly expressed and participated in several human cancer progressions, whereas whether DARS-AS1 is involved in human gastric cancer remains unclear. This study aimed to investigate the influence of DARS-AS1 on gastric cancer progression and explore the potential regulatory network of DARS-AS1/miR-330-3p/NAT10. The expression levels of DARS-AS1, miR-330-3p, and NAT10 were measured by quantitative real-time polymerase chain reaction. The CCK-8 assay and Transwell assay were used to determine the cell viability, migration, and invasion capacities, respectively. The target association between miR-330-3p and DARS-AS1 or NAT10 was confirmed using a luciferase reporter assay. In result, DARS-AS1 levels were elevated in tumor tissues and associated with shorter overall survival in patients with gastric cancer. Knockdown of DARS-AS1 could hamper cell viability, migration, and invasion in gastric cancer cells. DARS-AS1 acts as a competitive endogenous RNA to regulate the NAT10 expression by sponging miR-330-3p in gastric cancer cells. In conclusion, DARS-AS1 was elevated in gastric cancer, and DARS-AS1/miR-330-3p/NAT10 signaling offered some new horizons for predicting prognosis and a novel therapeutic method for the treatment of gastric cancer.

Previous studies have shown that some anesthesia drugs can inhibit tumor growth and metastasis. As a clinical anesthetic drug, dezocine has been reported to play an important role in immune function. However, the effects of dezocine on ovarian cancer cell growth and metastasis are not fully understood. In this study, we found that dezocine dose-dependently inhibited the viability of ES-2 and SKOV3 cells. Dezocine suppressed the migration and invasion abilities of ovarian cancer cells, and promoted apoptosis. Moreover, the Akt/mTOR signaling pathway was also inhibited by dezocine. Furthermore, mechanism study showed that dezocine could significantly inhibit the expression of CRABP2, and CRABP2 overexpression reversed the inhibitory effects of dezocine on ovarian cancer cell proliferation and migration. In conclusion, dezocine has significant anti-tumor effects on the growth and metastatic potential of ovarian cancer cells, and CRABP2 functions as a downstream effector of dezocine.

Preeclampsia (PE) is a common pregnancy-specific syndrome with an incidence of 4.6% in all pregnant women. Numerous studies have uncovered the functions and mechanisms of microsomal glutathione transferase 1 (MGST1) in different diseases and cellular processes, but whether MGST1 plays a role in PE remains unclear. Our study aimed to investigate the regulatory role of MGST1 in PE progression. In this study, the HTR8/SVneo cells were incubated with CoCl 2 (250 µM) to mimic hypoxia in trophoblasts. Real-time quantitative polymerase chain reaction revealed that MGST1 was dramatically reduced in the placenta of PE patients. The proliferation of HTR8/SVneo cells was assessed via the Cell Counting Kit-8 and colony formation assays, and the results showed that MGST1 upregulation increased the cell viability of HTR8/SVneo cells. In addition, wound healing and Transwell assays unveiled that the elevation of MGST1 enhanced trophoblast cell migration and invasion. Moreover, the upregulation of MGST1 alleviated the hypoxia-induced oxidative stress in trophoblast cell. Mechanically, we found that MGST1 regulated PE progression by activating the phosphoinositide-3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway. In conclusion, MGST1 alleviated the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promoted cell proliferation, migration, and invasion via the activation of the PI3K/AKT/mTOR pathway in PE. These results suggested that MGST1 can be a potential target for the prevention and treatment of PE.

The aim of this study was to investigate the effect of Bifidobacterium lactis Probio-M8 on glucolipid metabolism and gut microbiota (GM) composition in type 2 diabetes mellitus (T2DM) mice. The glucolipid metabolic profiles were analyzed. The 16S rRNA gene sequencing was employed to investigate GM. The levels of farnesyl X receptor (FXR) and cytochrome p450 7A1 (CYP7A1) were detected by quantitative polymerase chain reaction and western blot assays. The total bile acids (TBAs), ceramide (CE), glucagon-like peptide-1 (GLP-1), and fibroblast growth factor (FGF)-15 were also detected. The morphological features of liver and pancreas were also analyzed. Compared with the model group, Probio-M8 restored body weight, food intake and water intake, as well as improved hyperglycemia symptoms, serum glucolipid parameters, and the composition of intestinal microbes in T2DM diabetic mice. Moreover, the reduced level of FXR and the increased level of CYP7A1 in T2DM mice were reversed by Probio-M8 treatment. The increased levels of TBA and CE and the reduced levels of GLP-1 and FGF-15 in T2DM mice were altered after Probio-M8 stimulation. Besides, the altered morphology of liver and ileum in T2DM mice was alleviated by Probio-M8 treatment. Taken together, we suggested that the symptoms of T2DM could be ameliorated by Probio-M8 in T2DM mice.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancers. However, circ_DENND1B has not been studied yet. GSE100186 dataset was used for the level analysis of circ_DENND1B. The quantitative real-time PCR was used to verify the expression of circ_DENND1B, microRNA-122-5p (miR-122-5p) and tissue inhibitor of metalloproteinases-2 (TIMP2) in ccRCC tissues and cells. Cell proliferation, migration, invasion and apoptosis were detected by colony formation assay, thymidine analog 5-ethynyl-2′-deoxyuridine assay, 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide, transwell and flow cytometry. The binding of miR-122-5p to circ_DENND1B/TIMP2 was investigated by dual-luciferase reporter assay. Finally, the role of circ_DENND1B in ccRCC was detected by tumorigenesis experiment in mice. circ_DENND1B was downregulated in ccRCC and circ_DENND1B overexpression suppressed the malignant behaviors of ccRCC cells. circ_DENND1B acted as a sponge of miR-122-5p. miR-122-5p upregulation reversed the effects of circ_DENND1B on cell proliferation, migration, invasion and apoptosis. TIMP2 was a target of miR-122-5p. Overexpression of circ_DENND1B regulated TIMP2 level by inhibiting miR-122-5p expression in ccRCC cells. circ_DENND1B overexpression inhibited the tumor growth of ccRCC in vivo . circ_DENND1B inhibited ccRCC cell progression by promoting TIMP2 expression by sponging miR-122-5p, suggesting that circ_DENND1B might be an effective therapeutic target for ccRCC.

Melanoma is a rare, fatal type of skin tumor. Although EPH receptor A3 (EphA3) is deregulated in melanoma, its detailed role remained uncharacterized. Using real time quantitative PCR analysis and western blotting, EphA3 was identified to be upregulated in melanoma tissues and cells, while miR-3666 showed an opposite expression trend. Cell counting kit-8, scratch wound, and in vivo assays proved that EphA3 silence inhibited the melanoma cell proliferation and migration and retarded tumor growth in vivo . Furthermore, western blotting results displayed that EphA3 silence resulted in a low expression of p38-MAPK and p-ERK1/2. Mechanically, miR-3666 was proved to target EphA3 3′UTR by the luciferase reporter assay. Furthermore, miR-3666 mimic compromised the driven melanoma cell proliferation and migration by EphA3 overexpression. In addition, induction of ERK1/2 and p38 MAPK pathways offset the positive effect of EphA3 overexpression on melanoma cells. In conclusion, miR-3666 downregulated EphA3 expression and retarded melanoma malignancy via inactivating ERK1/2 and p38 MAPK pathways. Hence, miR-3666/EphA3 axis may represent a druggable target against melanoma progression.

Immune-related cardiotoxicities are uncommon but potentially fatal. The study aims to evaluate the value of pacemakers and methylprednisolone pulse therapy (MPPT) to patients with immune-related myocarditis concomitant with complete heart block (CHB). We first reviewed medical records of three patients with immune-related myocarditis concomitant with CHB. For the pooled analysis, we searched related cases with immune-related myocarditis in the PubMed database and screened the patients. Clinical characteristics, management, and outcomes were summarized. Our three patients developed immune-related myocarditis concomitant with CHB about 2 weeks after receiving pembrolizumab, and were successfully treated with pacemaker implantation and high-dose steroids (two received MPPT). In the pooled analysis, 21 cases were eligible with an overall fatality rate of 52%. Patients with pacemakers had a fatality rate of 38%, significantly lower than patients without them (38% vs 100%; p = 0.035), particularly the MPPT subgroup (25% vs 100%; p = 0.019). All five patients without pacemakers expired. Among patients with pacemakers, MPPT patients tended to have an inferior rate compared with non-MPPT patients. Timely pacemaker implantation played a crucial role in improving the outcomes of patients with immune-related myocarditis concomitant with CHB. Patients receiving MPPT appeared to have a better prognosis. Additionally, multidisciplinary consultation should be recommended for better management.

As a common complication of diabetes, diabetic pain neuropathy (DPN) is caused by neuron intrinsic and extrinsic factors. Neuron intrinsic factors include neuronal apoptosis and oxidative stress, while extrinsic factors are associated with glial activation. The present study was performed to reveal the functions of miR-130a-3p in apoptosis and oxidative stress of the high glucose (HG)-stimulated primary neurons as well as in the activation of microglial and astrocytes. Primary neurons, microglial, and astrocytes were isolated from newborn mice. Apoptosis was assessed by flow cytometry analysis and western blotting. Reactive oxygen species and glutathione levels were assessed to determine the oxidative stress. Markers of glial cells were detected by immunofluorescence staining. The results revealed that miR-130a-3p deficiency alleviated apoptosis and oxidative stress of HG-stimulated neurons as well as suppressed microglial and astrocyte activation. Moreover, sphingosine-1-phosphate receptor 1 (S1PR1) was found as a target downstream of miR-130a-3p. S1PR1 knockdown partially rescued the inhibitory effects of silenced miR-130a-3p on neuronal injury and glial activation. In conclusion, miR-130a-3p targets S1PR1 to activate the microglial and astrocytes and to promote apoptosis and oxidative stress of the HG-stimulated primary neurons. These findings may provide a novel insight into DPN treatment.

Introduction Chronic pain and breakthrough cancer pain (BTcP) have a high prevalence in all cancer types and cancer stages, combined with a significant physical, psychological, and economic burden. Despite efforts to improve appropriate management of cancer pain, a poor assessment and guilty undertreatment are still reported in many countries. The purpose of this expert opinion paper is to contribute to reduce and clarify these issues with a multidisciplinary perspective in order to share virtuous paths of care. Methods Common questions about cancer pain assessment and treatment were submitted to a multidisciplinary pool of Italian clinicians and the results were subsequently discussed and compared with the findings of the published literature. Conclusion Despite a dedicated law in Italy and effective treatments available, a low percentage of specialists assess pain and BTcP, defining the intensity with validated tools. Moreover, in accordance with the findings of the literature in many countries, the undertreatment of cancer pain is still prevalent. A multidisciplinary approach, more training programs for clinicians, personalised therapy drug formulations, and virtuous care pathways will be essential to improve cancer pain management.

Several causative factors are associated with hearing loss (HL) and brain disorders. However, there are many unidentified disease modifiers in these conditions. Our study summarised the most common brain disorders associated with HL and highlighted mechanisms of pathologies. We searched the literature for published articles on HL and brain disorders. Alzheimer’s disease/dementia, Parkinson’s disease, cognitive impairment, autism spectrum disorder, ataxia, epilepsy, stroke, and hypoxic-ischaemic encephalopathy majorly co-interact with HL. The estimated incidence rate was 113 per 10,000 person-years. Genetic, epigenetic, early life/neonatal stress, hypoxia, inflammation, nitric oxide infiltration, endoplasmic reticulum stress, and excess glutamate were the distinguished modifiers identified. Various mechanisms like adhesion molecules, transport proteins, hair cell apoptosis, and neurodegeneration have been implicated in these conditions and are serving as potential targets for therapies. To improve the quality of life of patients, these understandings will improve clinical diagnoses and management of HL and brain disorders.

Accumulated evidence suggest that the adverse outcome of severe coronavirus disease 2019 (COVID-19) is closely related to prothrombotic microvascular pathology with a high risk of venous thromboembolism. Furthermore, the first observational studies indicated that adjunct therapy with low-molecular weight heparin (LMWH) was associated with lower mortality in this cohort of patients. However, the timing of starting LMWH and the dose remain controversial in COVID-19 patients. Considering the above, the aim of this study was to reveal the rationale for using LMWH in the therapy of symptomatic COVID-19 patients based on experimental and clinical studies on LMWH in inflammatory settings with special consideration given to randomized trials.

Amyotrophic lateral sclerosis (ALS) is a fatal, multisystem neurodegenerative disease that causes the death of motoneurons (MNs) progressively and eventually leads to paralysis. In contrast, delayed onset muscle soreness (DOMS) is defined as delayed onset soreness, muscle stiffness, loss of force-generating capacity, reduced joint range of motion, and decreased proprioceptive function. Sensory deficits and impaired proprioception are common symptoms of both ALS and DOMS, as impairment at the proprioceptive sensory terminals in the muscle spindle is theorized to occur in both. The important clinical distinction is that extraocular muscles (EOM) are relatively spared in ALS, in contrast to limb skeletal muscles; however, the blink reflex goes through a gradual impairment in a later stage of disease progression. Noteworthy is, that, the stretch of EOM induces the blink reflex. The current authors suggest that the impairment of proprioceptive sensory nerve terminals in the EOM muscle spindles are partially responsible for lower blink reflex, beyond central origin, and implies the critical role of Piezo2 ion channels and Wnt-PIP2 signaling in this pathomechanism. The proposed microinjury of Piezo2 on muscle spindle proprioceptive terminals could provide an explanation for the painless dying-back noncontact injury mechanism theory of ALS.

Interleukin-35 (IL-35) is a lately observed cytokine and is part of the IL-12 cytokine family. IL-35 includes two subunits, p35 and Epstein-Barr virus-induced gene 3, and activates subsequent signaling pathways by binding to receptors to mediate signal transduction, thereby modulating the immunoregulatory functions of T cells, B cells, macrophages, and other immune cell types. Although there is currently limited research on the roles of IL-35 in human autoimmunity, many studies have demonstrated that IL-35 may mediate immunosuppression. Therefore, it plays an essential role in some autoimmune dermatoses, including systemic lupus erythematosus, psoriasis, systemic sclerosis, and dermatomyositis. We will introduce the structure and biological characteristics of IL-35 and summarize its effects on the occurrence and development of autoimmune dermatoses in this article. It is suggested that IL-35 is a possible target for therapy in the aforementioned diseases.

Primary sclerosing cholangitis (PSC) is a cholangiopathy caused by genetic and microenvironmental changes, such as bile homeostasis disorders and microbiota dysbiosis. Therapeutic options are limited, and proven surveillance strategies are currently lacking. Clinically, PSC presents as alternating strictures and dilatations of biliary ducts, resulting in the typical “beaded” appearance seen on cholangiography. The pathogenesis of PSC is still unclear, but cholangiocytes play an essential role in disease development, wherein a reactive phenotype is caused by the secretion of neuroendocrine factors. The liver–gut axis is implicated in the pathogenesis of PSC owing to the dysbiosis of microbiota, but the underlying mechanism is still poorly understood. Alterations in cholangiocyte responses and related signalling pathways during PSC progression were elucidated by recent research, providing novel therapeutic targets. In this review, we summarise the currently known underlying mechanisms of PSC pathogenesis caused by the dysbiosis of microbiota and newly reported information regarding cholangiocytes in PSC. We also summarise recently reported in vitro and in vivo models for studying the pathogenesis of PSC.

Although ketamine is primarily used for induction and maintenance of general anesthesia, it also presents sedative, amnestic, anesthetics, analgesic, antihyperalgesia, neuroprotective, anti-inflammatory, immunomodulant, and antidepressant effects. Its unique pharmacodynamics and pharmacokinetic properties allow the use of ketamine in various clinical settings including sedation, ambulatory anesthesia, and intensive care practices. It has also adopted to manage acute and chronic pain management. Clinically, ketamine produces dissociative sedation, analgesia, and amnesia while maintaining laryngeal reflexes, with respiratory and cardiovascular stability. Notably, it does not cause respiratory depression, maintaining both the hypercapnic reflex and the residual functional capacity with a moderate bronchodilation effect. In the pediatric population, ketamine can be administered through practically all routes, making it an advantageous drug for the sedation required setting such as placement of difficult vascular access and in uncooperative and oppositional children. Consequently, ketamine is indicated in prehospital induction of anesthesia, induction of anesthesia in potentially hemodynamic unstable patients, and in patients at risk of bronchospasm. Even more, ketamine does not increase intracranial pressure, and it can be safely used also in patients with traumatic brain injuries. This article is aimed to provide a brief and practical summary of the role of ketamine in the pediatric field.

Congenital adrenal hyperplasia (CAH) is a genetic disorder characterized by an impairment of steroid synthesis due to an altered production of 21-hydroxylase enzyme. Corticoid hormones are involved in the development and functioning of many organs. The aim of the present study was to review the international literature to collect data regarding oral manifestations of CAH. A review of the literature describing oral features of patients affected by CAH was performed using electronic databases (PubMed and Scopus). The data about number of patients, form of CAH, and oral findings were extracted and analyzed. Seven studies were included in the final analysis. The principal findings reported regarded an advanced dental development observed in patients with CAH. One paper reported amelogenesis imperfecta and periodontal issues. The dentist could be the first specialist involved in the CAH syndrome diagnosis, identifying the characteristic features described above, especially for the classical simple virilizing and non-classical form.

Migraine is a highly prevalent disorder with an enormous burden on societies. Different types of medications are used for controlling both acute attacks and prevention. This article reviews some non-pharmacological recommendations aiming to manage migraine disorder better and prevent headache attacks. Different triggers of migraine headache attacks, including environmental factors, sleep pattern changes, diet, physical activity, stress and anxiety, some medications, and hormonal changes, are discussed. It is advised that they be identified and managed. Patients should learn the skills to cope with the trigger factors that are difficult to avoid. In addition, weight control, management of migraine comorbidities, lifestyle modification, behavioural treatment and biofeedback, patient education, using headache diaries, and improving patients’ knowledge about the disease are recommended to be parts of migraine management. In addition, using neuromodulation techniques, dietary supplements such as riboflavin, coenzyme Q10 and magnesium, and acupuncture can be helpful. Non-pharmacological approaches should be considered in migraine management. Furthermore, the combination of pharmacological and non-pharmacological approaches is more effective than using each separately.

Various studies suggest that the atherogenic index of plasma (AIP) is associated with the risk of coronary artery disease (CAD) in different clinical scenarios. This review aimed to synthesize evidence of the association between AIP values and CAD. A literature search was carried out on four databases, namely, PubMed, Scopus, Web of Science, and Ovid-Medline. A handsearch was performed on preprint repositories (MedRxiv and Research Square). The effect measurements were expressed as odds ratios (OR) with their corresponding 95% confidence intervals (CI). For the quantitative synthesis, we employed a random-effects model. We analyzed 14 articles (with 40,902 participants) from seven different countries. The quantitative analysis revealed that an increase in one unit of AIP was associated with higher odds of developing CAD (OR 2.11; 95% CI 1.65–2.69; P < 0.001; I 2 = 98%). We conducted subgroup analyses of Chinese (OR 1.89; 95% CI 1.40–2.56; P < 0.001) and non-Chinese studies (OR 2.51; 95% CI 1.42–4.42; P < 0.001). The sensitivity analysis by risk of bias continued to demonstrate an association, and the heterogeneity remained unchanged (OR 1.75; 95% CI 1.33–2.31; P < 0.001; I 2 = 98%). Higher AIP values were associated with higher odds of developing CAD.

Thioredoxins (TRXs) are a class of ubiquitous and multifunctional protein. Mammal cells present three isoforms: a cytosolic and extracellular called thioredoxin 1 (TRX1), a mitochondrial (TRX2), and one specific in spermatozoids (TRX3). Besides, a truncated form called TRX80 exists, which results from the post-translational cleavage performed on TRX1. TRXs’ main function is to maintain the reduction–oxidation homeostasis of the cell, reducing the proteins through a thiol-disulfide exchange that depends on two cysteines located in the active site of the protein (Cys32-X-X-Cys35 in humans). In addition, TRX1 performs S-nitrosylation, a post-translational modification of proteins that depends on cysteines of its C-terminal region (Cys62, Cys69, and Cys73 in human TRX1). These modifications allow the TRXs to modulate the protein function and participate in regulating diverse cellular processes, such as oxidative stress, transcription, signaling cascades, apoptosis, inflammation, and immunologic response. This points out the crucial relevance of TRXs for cell function, signaling it as a strategic target for the treatment of many diseases and its possible use as a therapeutic factor.

In this study, a treatment method was assessed for the prevention and treatment of postpartum bleeding after combined surgery in patients having late pregnancy with the complication of acute Stanford type A aortic dissection. The clinical records of ten patients receiving treatment at the Second Xiangya Hospital of Central South University between March 2012 and March 2021 were retrospectively analysed. All patients were diagnosed with acute Stanford type A aortic dissection according to computed tomography angiography of the thoracic and abdominal aorta. Aortic valve function was assessed using two-dimensional echocardiography. All patients experienced uterine-incision delivery under systemic anaesthesia. During the operation, intrauterine Bakri balloon tamponade and cervical cerclage were performed. Postpartum bleeding was effectively controlled for all patients. The extracorporeal circulation time was 230–295 min, the postpartum 24 h bleeding volume was 500–870 mL, the volume of physiological saline injected into the balloon was 290–515 mL, and the intrauterine balloon compression time was 28–51 h. No postpartum bleeding occurred. A 42-days follow-up showed no late postpartum bleeding, poor uterine incision healing, or puerperal infection, and no uterine removal was performed. Intrauterine Bakri balloon tamponade plus cervical cerclage can effectively prevent intra- and postoperative postpartum bleeding in pregnant patients with aortic dissection.

Clinical treatment is challenging for elderly patients with lung cancer who cannot tolerate chemotherapy, do not have cancer driver genes, and have low expression of PD-L1. Since these patients are usually excluded from clinical studies, evidence-based medicine supporting the use of immunotherapy is lacking. Considering the potentially limited clinical benefits and high associated risk of hyperprogressive disease, determining an appropriate treatment is an urgent clinical challenge. We report a 71 year-old male patient diagnosed with advanced lung adenocarcinoma lacking key driving genes ( EGFR , ALK , and ROS-1 ), and low expression of PD-L1 on tumor cells (10–15%). The tumor tissue showed a low level of microsatellite instability, low tumor mutational burden, and no DNA mismatch repair deficiency on whole-exome sequencing (WES). However, a high blood tumor mutational burden was detected. After considering the biomarkers of therapeutic effect and ruling out the risk of hyperprogressive disease, pembrolizumab 200 mg was administered every 3 weeks for a year (17 cycles). The disease remained stable for >39 months, and adverse effects were mild and well-tolerated. Therefore, a comprehensive biomarker evaluation, especially in elderly patients lacking driving genes, is essential. Liquid biopsy technology and WES may be useful for overcoming the limitations of tissue biopsy.

Bilateral medial medullary infarction (BMMI) is an extremely rare type of cerebrovascular accident often resulting in poor functional consequences. “Heart appearance” on diffusion-weighted imaging (DWI) of magnetic resonance imaging (MRI) is the unique presentation of BMMI. In this article, we present an acute ischemic stroke patient whose brain MRI showed the atypical “heart appearance” sign, manifested unusual bilateral central facial paralysis concurrently. For an early diagnosis of BMMI, it is essential to recognize the characteristic clinical and MRI findings of this rare type of stroke. Abnormal small dot or linear DWI signal at the midline of the brainstem should not be ignored at the early stage of stroke.

Malignant hyperthermia (MH) is an autosomal dominant genetic condition of the skeletal muscle triggered by inhaled general anesthetic agents or succinylcholine and associated with a hypermetabolic state and skeletal muscle rigidity. Tachycardia, increased carbon dioxide production, hypercarbia, hyperthermia, acidosis, hyperkalemia, cardiac arrhythmias, muscle rigidity, and rhabdomyolysis are common symptoms of MH. As the progression of the syndrome could be rapid or less evident, even experienced physicians have difficulty in diagnosing MH, which can lead to delays in treatment and increased mortality. We report a rare case of a 36-year-old man, who underwent open reduction and internal fixation of the left clavicle after inhaled anesthetics. The patient developed dyspnea, hypotension, unremitting hyperthermia, tachycardia, and elevated serum myoglobin, and finally died of pyemia and disseminated intravascular coagulation. We reviewed the process of disease development, summarized the steps of diagnosis, and improved genetic testing. Exome sequencing revealed a new mutation c.8519G>A (p.arg2840 GLN) in the RYR1 gene that could be associated with MH. The gene mutation was also found in his daughter’s genetic test. This case emphasized the importance of the awareness of MH and its atypical clinical symptoms. The presence of dyspnea, hypotension, unremitting hyperthermia, tachycardia, and raised myoglobin in serum might further strengthen the clinical diagnosis of suspected MH.

A 42-year-old man with four months of retrosternal pain and two months of skin rashes and proximal muscle weakness was diagnosed with dermatomyositis (DM) based on muscle enzyme analysis and needle electromyography. Chest computed tomography (CT) showed scattered inflammation nodules in both lungs’ upper lobes with negative sputum smear for lung cancer and pulmonary tuberculosis (TB). A good clinical response to oral prednisone was obtained, except for the retrosternal pain in the preceding two months. Urgent CT pulmonary angiography ruled out pulmonary thromboembolism but revealed squamous cell lung cancer with metastases in the sternum and mediastinal lymph nodes. In retrospect, we found osteolytic destruction consistent with sternal metastasis on CT taken at the initial treatment of DM, which was missed by radiologists. Simultaneously, the man was diagnosed with pulmonary TB based on rapid mycobacterial TB detection. This case report indicates the radiologic errors and highlights the importance of a thorough search for underlying lung cancer and pulmonary TB in patients with DM, especially in countries with a high TB burden.

Uterine inversion is a rare disease that is particularly uncommon among non-puerperal women. Herein we reported the only case of uterine inversion known to us that was caused by the endometrial thickening and changes in the polypoid lesion in early puberty. The patient was admitted to our hospital because of massive vaginal bleeding, abdominal pain, and a protruding mass from the vagina. We obtained the patient history by collecting the results of various examinations (including magnetic resonance imaging and color Doppler ultrasound), accurate diagnosis was performed, and a reasonable treatment protocol was developed. She was subjected to laparoscopic uterine-sparing surgery to preserve her fertility. Uterine inversion is a rare disease, and early diagnosis and selection of appropriate treatment options are essential for patients with fertility requirements.

Splenic artery aneurysm (SAA) is a rare condition; however, it is one of the most common intra-abdominal aneurysm. In the emergency department (ED), due to an uncommon cause of shock and syncope in SAA, it poses great diagnostic challenge for emergency physicians. Here we reported a case of spontaneous rupturing of SAA. A 47-year-old man presented to the ED for syncope and shock. As he had unstable hemodynamic, we gave him fluid resuscitation and point-of-care ultrasound (POCUS), free intraperitoneal fluid was identified on ultrasound, then hemorrhagic ascites was identified by a diagnostic abdominal paracentesis. The rare but life-threatening diagnosis of spontaneous rupturing of SAA was confirmed by contrast-enhanced Computed Tomography and surgery. Spontaneous SAA rupturing is a rare fatal condition which needs immediate diagnosis and management to achieve a favorable outcome. Though there are no risk factors, emergency physicians should consider SAA in the differential diagnosis of sudden collapse. Also, as an emergency physician, it is very important to be a master of first aid skills such as POCUS and treat patients according to the process.

For the last 2 years, one of the most frequent causes of respiratory failure is coronavirus disease 2019 (COVID-19). The symptoms are not specific. Imaging diagnostics, especially high-resolution computed tomography, is a diagnostic method widely used in the diagnosis of this disease. It is important to emphasize that not only SARS-CoV-2 infection may manifest as interstitial pneumonia. Other diseases such as other viral, fungal, atypical bacterial pneumonia, autoimmune process, and even cancer can also manifest as ground-glass opacities or consolidations in the imaging of the lungs. In this case report, we described a patient who manifested many symptoms that seemed to be COVID-19. However, all performed antigen and polymerase chain reaction tests were negative. The diagnostics must have been extended. Microbiological and mycological blood cultures and sputum cultures were performed. Blood cultures were negative but in sputum, Candida albicans and Candida glabrata were identified. Targeted therapy with fluconazole was implemented with a satisfactory result. The patient was discharged from the hospital in a good general condition with no complaints.

Pulmonary Aspergillus infection may have a variety of manifestations depending on the patients’ immunity status and pre-existing lung conditions. Radiographically, aspergilloma, which is usually associated with noninvasive Aspergillus fumigatus conidia, may feature a characteristic mass in a cavity commonly located in the upper lobes of the lung. It is typically encountered upon pre-existing lung damage. Here we report Aspergillus growing in a pulmonary metastatic cavity in a 47-year-old male worker with a history of tongue cancer after a radical operation with neck dissection and concurrent chemotherapy in 2014. Chest radiography and computed tomography showed a cavitary lesion with a ball-in-hole lesion in the right upper lobe (RUL) and two cystic lesions within the bilateral upper lung field. Endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) from the RUL anterior segmental bronchus (RB3) revealed the presence of Aspergillus conidia and squamous cell carcinoma. Wedge resection of the cystic lesion within the left upper lobe confirmed the diagnosis of metastatic squamous cell carcinoma. This is a rare case of aspergillosis within cavities of pulmonary metastases in a patient who was diagnosed with tongue squamous cell carcinoma. The conclusive distinction between neoplasm and fungal infection is difficult to achieve by radiography, and a pathological biopsy by EBUS-TBB is necessary to aid diagnosis. Clinicians should be aware of such an atypical presentation of metastases coexisting with Aspergillus infection.

Paragangliomas are rare neuroendocrine tumors that originate in the chromaffin cells of the adrenal medulla or lymph nodes. Paragangliomas manifest in rare cases as catecholamine crisis, leading to heart failure, intracranial hemorrhage, renal failure, arrhythmias, pulmonary edema, or multisystem failure. Takotsubo cardiomyopathy is also called apical ballooning syndrome or stress cardiomyopathy. Left ventricular dysfunction with apical hyperkinesis and basilar and midventricular akinesis in the absence of coronary artery disease is highly suggestive of a variant of stress cardiomyopathy (inverted takotsubo cardiomyopathy). Herein, we report the case of a 69-year-old man with an unknown retroperitoneal paraganglioma who suffered from cardiogenic shock due to inverted takotsubo cardiomyopathy. He was treated with venoarterial extracorporeal membrane pulmonary oxygenation (ECMO) in combination with an intra-aortic balloon pump. After the restoration of cardiac function, a successful transition to curative retroperitoneal paraganglioma resection was performed. We conclude that ECMO is a valuable option for undiagnosed endocrine emergencies, helping to restore cardiac function and allowing sufficient time for further accurate diagnosis and specific treatment.

Lymphoma relapse is very common in clinical work, but lineage switch at relapse is rare. Although some cases have reported acute lymphocytic leukemia (ALL) switch to acute myeloid leukemia (AML) or myeloid sarcoma upon relapse, phenotype switch seldom occurs in other types of lymphoma. Here we report six cases with lineage switch from lymphoma to myeloid neoplasms. In our cohort, three cases were mantle cell lymphoma (MCL), and the other three cases were T-cell lymphoblastic lymphoma (T-LBL), B-cell lymphoblastic lymphoma (B-LBL), and diffuse large B-cell lymphoma (DLBCL) at the initial diagnosis. When linage switch occurred, most cases were AML M5 phenotypes, and only one case was myelodysplastic syndrome (MDS) phenotype. 11q23/mixed-lineage leukemia (MLL) rearrangement was negative in all cases. Although intensive therapy and stem cell transplantation have been applied in most cases, the poor outcome cannot be reversed. Therefore, we found that lineage switch could occur not only from ALL to AML or vice versa , but also from MCL or DLBCL to AML. Moreover, the incidence of MLL rearrangement in lineage switch is lower in adult hematologic malignancies as compared with pediatric patients.

Tracheal extubation is a risky phase of anaesthesia. Most complications that occur when an endotracheal tube is removed are of minor nature, but those that require critical action can end in serious complications or even death. Patient – A 55-year-old woman was admitted for elective transabdominal hysterectomy and adnexal procedures. Anaesthesia – Standard monitoring. For induction, we used fentanyl, propofol, and rocuronium. The maintenance phase of anaesthesia was without complications. After extubation, the patient presented with severe trismus and mask ventilation was unsuccessful (cannot ventilate) – It was not until 200 mg of succinylcholine was administered that the masseter muscle spasm subsided. Extubation is a process that must always be planned. A routine approach and lack of a contingency plan is responsible for a number of complications related to the period of patient awakening and associated with the removal of the endotracheal tube. Trismus, in response to extubation, is a phenomenon not described in the literature in non-high risk patients.

Pubovesical fistula (PVF) is a rare complication of radical treatments for prostate cancer (PCa), especially when a multimodal approach is performed. We present a case of PVF with extensive communication between the bladder and the pubic bones, and lymph node metastases of PCa treated by cystectomy and salvage lymphadenectomy. We describe a case of a 65-year old male patient who, after radical prostatectomy and adjuvant radiation therapy, suffered from suprapubic and perineal pain, ambulation difficulties and recurrent urinary tract infections. Cystoscopy, cystography and contrast-enhanced magnetic resonance imaging diagnosed a PVF. Choline positron emission tomography/computed tomography scan demonstrated PCa lymph node metastases. After the failure of conservative treatment, open radical cystectomy with ureterocutaneostomy diversion and salvage lymphadenectomy were performed with resolution of symptoms. At 3-month follow-up, the pelvic and perineal pain was completely regressed and 1-year later the patient was still asymptomatic. This clinical case shows efficacy and safety of combined salvage lymphadenectomy and cystectomy with urinary diversion for the treatment of late PCa node metastasis and PVF.

The coronavirus 2019 (COVID-19) disease is now responsible for one of the most challenging and concerning pandemics. Since December 2020, the world has had access to COVID-19 prophylaxis; thus, we encounter adverse events from vaccination more often due to the vast vaccination range. We present two case reports of difficult-to-treat skin vasculitis due to COVID-19 vaccination that were successfully treated in a tertiary-level university hospital. When encountering systemic treatment, resistant skin vasculitis plasmapheresis could be a choice of treatment.

Fistulas arising between ureters and iliac arteries (UAF) are rare pathological events and frequently require emergency treatment, as they are associated with massive haematuria and haemorrhagic shock. The medical history plays a key role in the diagnostic and therapeutic process, as it allows to include UAF among the differential diagnoses of gross haematuria. The emergency treatments of fistulas arising between the urinary system and the vascular system include the open repairing surgery or the endovascular grafting, the latter generally better tolerated by patients suffering from multiple comorbidities or not eligible for traditional surgery. Nephrostomy or ureteral stent can be used to drain the affected upper urinary tract temporarily or permanently. Herein, we reported two cases of oncological patients affected by UAF and treated successfully by endovascular procedures. Furthermore, we performed a narrative review of the literature concerning UAF and its diagnostic and therapeutic management. Although our study did not allow us to state definitive conclusion about the diagnostic and therapeutic management of UAF due to small sample size, our findings support previous experiences in favour of the treatment of fistulas with an endovascular approach.

Although the incidence of multiple primary malignancies (MPMs) is increasing, synchronous triple primary malignant tumours with prostate, bladder and lung is rarely reported. Gene mutation is thought to be a reason for MPMs, and severe cardiovascular diseases may interrupt the cancer treatment. Here we reported a 64-year-old male patient with synchronous triple primary malignant tumours of the bladder urothelial carcinoma, prostate adenocarcinoma, and non-small cell lung cancer (NSCLC) with mutations in TP53 and MEK1, all the three malignancies were diagnosed within 10 days. Although being interrupted by severe cardiovascular diseases (including myocardial infarction, venous thrombosis, and aneurism of the aortic root), he was successfully treated with radical cystoprostatectomy, chemotherapy plus pembrolizumab (a PD-1 antibody), and radiotherapy of the lung lesion, followed by maintenance monotherapy of pembrolizumab, overall survival was more than 26 months. In conclusion, a patient of synchronous triple primary malignant tumours with prostate, bladder, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases was treated successfully, which may suggest that comprehensive treatment, especially radical treatment such as operation and radiation, is very important for MPMs.

Mucinous cystic neoplasms (MCN) are rare premalignant neoplasms of the pancreas typically found as single lesions in the pancreatic body and tail of women in the fifth and sixth decade of life, constituting 2–5% of pancreatic neoplasms. We present a 50-year-old female patient with a large tail mass of the pancreatic body (size of 15 cm × 12 cm) with elevated tumor indicators. Computed tomography and magnetic resonance imaging revealed a large cystic lesion with septa and wall nodules. During the operation, the tumor capsule wall adhered to the left half colon and mesentery and could not be detached. Splenectomy and left hemicolectomy were performed. The postoperative pathological examination of the specimens confirmed a premalignant pancreatic mucous cystic tumor with moderate heterocytosis. The preoperative diagnosis of pancreatic MCN and MCN with invasive carcinoma is discussed, considering the characteristics of this case. Age, tumor size, texture, tumor marker elevation, and cystic wall condition are important characteristics of malignant MCN. Nevertheless, it is still very difficult to determine accurately whether an MCN is malignant or not before an actual pathological examination of the resected specimen.