Volume 18, Issue 1

Inflammatory responses play a critical role in the progress of neurodegenerative disorders. MSC-Exos is considered to have an anti-inflammatory effect on the treatment strategy for brain injury. However, the therapeutic effect and possible mechanism of Exosomal miR-210 on microglia polarization-induced neuroinflammation and neurite outgrowth have not been reported. MSC-Exos were isolated by ultracentrifugation, identified by Nanosight NS300, transmission electron microscopy, and western bolt. In vitro , to explore the protective mechanism of MSC-Exos against neuroinflammation, the microglial BV2 cell was exposed to lipopolysaccharide to assess inflammatory changes. The intake of 1,1’-dioctadecyl-3,3,3’,3’-tetramethylindocarbocyanine perchlorate (Dil)-MSC-Exos into microglia was observed by fluorescence microscopy. The results showed that Exosomal miR-210 treatment significantly inhibited the production of nitric oxide and pro-inflammatory cytokines. Exosomal miR-210 treatment also increased the number of M2 microglia cells and inhibited M1 microglia polarization. In addition, western blot demonstrated that Exosomal miR-210 reduced neuronal apoptosis. Thus, Exosomal miR-210 attenuated neuronal inflammation and promoted neurite outgrowth. Exosomal miR-210 from MSCs attenuated neuronal inflammation and contributed to neurogenesis possibly by inhibiting microglial M1 polarization.

Our object was to examine how the pre- and post-pandemic COVID-19 impacted the care of acute ST-segment elevation myocardial infarction (STEMI) patients in county hospitals. Using January 20, 2020, as the time point for the control of a unique coronavirus pneumonia epidemic in Jieshou, 272 acute STEMI patients were separated into pre-epidemic (group A, n = 130) and epidemic (group B, n = 142). There were no significant differences between the two groups in terms of mode of arrival, symptom onset-to-first medical contact time, door-to-needle time, door-to-balloon time, maximum hypersensitive cardiac troponin I levels, and in-hospital adverse events ( P > 0.05). Emergency percutaneous coronary intervention (PCI) was much less common in group B (57.7%) compared to group A (72.3%) ( P = 0.012), and the proportion of reperfusion treatment with thrombolysis was 30.3% in group B compared to 13.1% in group A ( P < 0.001). Logistic regression analysis showed that age ≥76 years, admission NT-proBNP levels ≥3,018 pg/ml, and combined cardiogenic shock were independent risk factors for death. Compared with thrombolytic therapy, emergency PCI treatment further reduced the risk of death in STEMI. In conclusion, the county hospitals treated more acute STEMI with thrombolysis during the COVID-19 outbreak.

This study aims to explore the role and mechanism of circ-IARS in non-small-cell lung cancer (NSCLC) progression. Expression of circ-IARS, microRNA (miR)-1252-5p, and hepatoma-derived growth factor (HDGF) was measured by real-time quantitative PCR and western blotting. The interactions among circ-IARS, miR-1252-5p, and HDGF were determined by dual-luciferase reporter assay and RNA immunoprecipitation. Cell behaviors were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2′-deoxyuridine (EdU) assay, flow cytometry, scratch wound assay, and transwell assay, and validated in in vivo xenograft model. Exosomes were isolated using commercial kit, and the expression and functions of exosomal circ-IARS (exo-circ-IARS) were analyzed as described above. Results showed that the expression of circ-IARS was upregulated in NSCLC cells, NSCLC tissues, and serum exosomes from NSCLC patients. circ-IARS exhaustion antagonized cell proliferation, cell cycle progression, migration, and invasion and promoted apoptosis in NSCLC. Molecularly, circ-IARS could sponge miR-1252-5p to modulate the expression of the downstream gene HDGF. In addition, miR-1252-5p downregulation attenuated circ-IARS exhaustion-mediated effects in H1299 and A549 cells. MiR-1252-5p mimic-induced effects were relieved by increasing HDGF expression in H1299 and A549 cells. Exo-circ-IARS promoted H460 cell proliferation, migration, and invasion and inhibited cell apoptosis. Silencing circ-IARS retarded tumor growth of NSCLC cells in vivo . Thus, circ-IARS, secreted by exosomes, was a novel oncogene in NSCLC and regulated the malignant development of NSCLC cells via circ-IARS/miR-1252-5p/HDGF competing endogenous RNA regulatory axis.

Circular RNAs have been reported to be widely involved in cancer cell tumorigenesis and drug resistance; here, the aim of this study was to investigate whether circRNA Integrin Subunit Alpha 7 (ITGA7) (circ_ITGA7) was associated with the tumor growth and radiosensitivity of colorectal cancer (CRC). We found that circ_ITGA7 expression was lower in CRC tissues and cells than those in the normal tissues and cell lines according to quantitative real-time polymerase chain reaction. As shown by cell counting kit-8 assay, flow cytometry, colony formation assay, and xenograft experiment, ectopic overexpression of circ_ITGA7 remarkably restrained CRC tumor growth and enhanced radiosensitivity in vitro and in vivo . Mechanistically, circ_ITGA7 could target microRNA (miR)-766 to prevent the degradation of its target gene mothers against decapentaplegic homolog 4 (SMAD4), the binding between miR-766 and circ_ITGA7 or SMAD4 was first verified by dual-luciferase activity assay. Additionally, miR-766 up-regulation reversed the inhibitory effects of circ_ITGA7 on CRC growth and radiosensitivity. Besides that, inhibition of miR-766 reduced CRC cell growth and sensitized cells to radiotherapy, and these effects mediated by miR-766 inhibitor were rescued by the silencing of SMAD4. In all, circ_ITGA7 suppressed CRC growth and enhanced radiosensitivity by up-regulating SMAD4 through sequestering miR-766, providing an insight for the further development of CRC treatment.

Pancreatic cancer (PC) is an aggressive malignant disease. Pancreatic ductal adenocarcinoma (PDAC) is a main type of PDAC. The inhibition of aerobic glycolysis in PC cells is one of the approaches to treat PDAC. WD repeat protein 79 (WDR79) acts as a scaffold protein and is involved in several physiological processes. Since WDR79 affects the progression of several types of cancers, whereas its role in PDAC remains unclear. This study was aimed to investigate the role of WDR79 in the progression of PDAC and clarify the mechanism. We found that WDR79 was highly expressed in PDAC cells. Knockdown of WDR79 inhibited the growth as well as the motility of PDAC cells, while overexpression of WDR79 contributed to the growth and motility. The ablation of WDR79 restrained aerobic glycolysis of PDAC cells. Mechanically, we found that WDR79 depletion increased SIRT4 expression by suppressing UHRF1 expression, which counteracted the function of WDR79 in PDAC. We thought that WDR79 could serve as a target for treating PDAC.

Recent studies have reported that collagen type V alpha 2 ( COL5A2 ) is a hub gene and associated with the prognosis of gastric cancer (GC) patients, playing an important role in GC. In this study, we aim to fathom out the biological roles of COL5A2 and its relevant mechanism in GC. Oncomine, gene expression profiling interactive analysis, and UALCAN were used to explore the effects of COL5A2 on GC. Cell counting kit-8 assay, colony formation assay, and transwell assay were conducted to investigate the biological behaviors of GC cell lines AGS and SGC-7901. Quantitative reverse transcription polymerase chain reaction and western blot were performed to determine gene and protein expressions. COL5A2 expression was up-regulated and negatively correlated with survival percentage of GC patients. COL5A2 expression was notably elevated in high stage and high grade of GC. Down-regulation of COL5A2 inhibited proliferation, migration, and invasion of AGS and SGC-7901 cells. COL5A2 induced epithelial–mesenchymal transition (EMT) by promoting the expressions of mesenchymal markers (SNAI1, SNAI2, TWIST, VIM, and MMP2), thereby facilitating the malignant phenotypes of GC. COL5A2 plays an oncogenic role in GC and has potential to predict the progression and prognosis of GC patients.

This study investigated the function of telomerase RNA component (TERC) in spinal cord injury (SCI). SCI models were established in rats via laminectomy and PC-12 cells were treated with lipopolysaccharide (LPS). TERC and miR-34a-5p expressions in cells and rat spinal cords were detected by quantitative reverse transcription polymerase chain reaction, followed by overexpression/knockdown of TERC/miR-34a-5p. Spinal cord histopathological changes were examined via hematoxylin–eosin staining. miR-34a-5p′ relation with TERC and XBP-1 was predicted by TargetScan and checked by dual-luciferase reporter/RNA immunoprecipitation assays. Cell biological behaviors were assessed by Cell counting kit-8, wound healing, Transwell, and flow cytometry assays. XBP-1 and inflammation/apoptosis-related protein expressions were analyzed by western blot. TERC was upregulated and miR-34a-5p was low-expressed in SCI tissues and LPS-induced PC-12 cells. TERC-knockdown alleviated histopathological abnormalities yet upregulated miR-34a-5p in SCI tissues. In LPS-induced PC-12 cells, TERC knockdown promoted cell viability, migration, invasion, and inhibited apoptosis, while TERC overexpression ran oppositely. TERC knockdown downregulated the XBP-1, IL-6, TNF-α, Bax, p-p38/t-p38, and cleaved caspase-9/-3, but upregulated Bcl-2 and p-Akt/t-Akt. TERC targeted miR-34a-5p, which further targeted XBP-1. miR-34a-5p downregulation exerted effects opposite to and offset TERC knockdown-induced effects. TERC knockdown facilitated the regeneration of neuron tissues yet inhibited inflammation in SCI through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis.

The object was to enhance the bioactivity of pure polyether-ether-ketone (PEEK) by incorporating nano-TiO 2 (n-TiO 2 ) and investigate its potential mechanism. PEEK/n-TiO 2 composite was manufactured using a 3D PEEK printer and characterized by scanning electron microscopy (SEM), 3D profiler, energy-dispersive spectroscopy, and Fourier-transform infrared (FT-IR) analyses. Cytocompatibility was tested using SEM, fluorescence, and cell counting kit-8 assays. Osteogenic differentiation was evaluated by osteogenic gene and mineralized nodule levels. The expression of the candidate miRNAs were detected in composite group, and its role in osteogenic differentiation was studied. As a results the 3D-printed PEEK/n-TiO 2 composite ( Φ = 25 mm, H = 2 mm) was successfully fabricated, and the TiO 2 nanoparticles were well distributed and retained the nanoscale size of the powder. The Ra value of the composite surface was 2.69 ± 0.29, and Ti accounted for 22.29 ± 12.09% (in weight), and FT-IR analysis confirmed the characteristic peaks of TiO 2 . The cells in the composite group possessed better proliferation and osteogenic differentiation abilities than those in the PEEK group. miR-154-5p expression was decreased in the composite group, and the inhibition of miR-154-5p significantly enhanced the proliferation and osteogenic differentiation abilities. In conclusion, 3D-printed PEEK/n-TiO 2 composite enhanced cytocompatibility and osteogenic induction ability by downregulating miR-154-5p, which provides a promising solution for improving the osteointegration of PEEK.

Propofol, an intravenous anesthetic agent, exerts an anti-tumor peculiarity in multifarious tumors. Circular RNA hsa_circ_0000735 (circ_0000735) is involved in non-small cell lung cancer (NSCLC) progression. The purpose of this study is to investigate whether propofol can curb NSCLC progression via regulating circ_0000735 expression. Cell viability, proliferation, apoptosis, and invasion were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, 5-ethynyl-2′-deoxyuridine, flow cytometry, and transwell assays. Evaluation of protein levels was performed using western blotting or immunohistochemistry. Detection of circ_0000735 in tissue samples and cells was carried out using a real-time quantitative polymerase chain reaction. The molecular mechanisms associated with circ_0000735 were predicted by bioinformatics analysis and verified by dual-luciferase reporter assays. The relationship between propofol and circ_0000735 in vivo was verified by xenograft models. The results showed that circ_0000735 was overexpressed in NSCLC samples and cells. Propofol treatment overtly decreased circ_0000735 expression in NSCLC cells and repressed NSCLC cell viability, proliferation, invasion, and facilitated NSCLC cell apoptosis, but these effects mediated by propofol were counteracted by circ_0000735 overexpression. Circ_0000735 functioned as a miR-153-3p sponge and regulated integrin-β1 (ITGB1) expression via adsorbing miR-153-3p. ITGB1 overexpression reversed circ_0000735 silencing-mediated effects on NSCLC cell viability, proliferation, invasion, and apoptosis. In conclusion, propofol restrained NSCLC growth by downregulating circ_0000735, which functioned as a miR-153-3p sponge and regulated ITGB1 expression via adsorbing miR-153-3p. This study provides evidence to support that propofol curbs NSCLC progression by regulating circRNA expression.

Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) has been reported to be a vital modulator in tumorigenesis of gastric cancer (GC). However, the detailed regulatory mechanism of PVT1 in GC remains largely unclear. In this work, the expressions of PVT1 and microRNA-16 (miR-16) were detected by quantitative real-time PCR (qRT-PCR) in GC tissues and cell lines. GC cell lines NCI-N87 and MKN45 cell lines were chosen for the following assays. After PVT1 was overexpressed or depleted, CCK-8 and Transwell assays were performed to examine the cell viability and invasive capacity. Cell cycle was analyzed by flow cytometry. The expression of cyclin D1 (CCND1) at mRNA and protein levels was measured by qRT-PCR and western blot. The competitive endogenous RNA molecular mechanism among PVT1, miR-16 and CCND1 was verified by bioinformatics analysis, luciferase-reporter gene assay and RNA immunoprecipitation assay. In the present study, it was revealed that PVT1 expression was remarkably evaluated in GC tissues and cell lines than that in the corresponding control group. PVT1 positively regulated the proliferation, migration and cell cycle progression of GC cells. Besides, miR-16 was identified as a target of PVT1, and CCND1 was identified as a target of miR-16. The depletion of PVT1 promoted the expression of miR-16 and suppressed CCND1 expression. Moreover, either miR-16 inhibitor or CCND1 overexpression plasmid could reverse the promoting effects of PVT1 on the malignant biological behaviors of GC cells. In conclusion, PVT1 promoted CCND1 expression by negatively regulating miR-16 expression to enhance the viability, invasion and cell cycle progression of GC cells.

The dysregulated expression of circRNA in gastric cancer (GC) induces paclitaxel (Tax) resistance of cancer cells, which in turn affects disease progression and prognosis. Here, we sought to investigate the role and mechanism of circ_002136 in Tax-resistant GC. In this study, we found the enriched circ_002136 level and the declined miR-16-5p level in Tax-resistant GC tissues and cells. Biologically, knockdown of circ_002136 elevated the Tax sensitivity of Tax-resistant GC cells, inhibited the cell motility properties, and simultaneously drove the apoptosis. Mechanically, circ_002136 promoted the HMGA1-mediated cellular Tax resistance and cell invasion by sponging miR-16-5p. Furthermore, circ_002136 silencing impeded the growth of Tax-resistant GC tumors in vivo . Overall, our study revealed a novel signaling pathway that could be used for future clinical applications, namely the circ_002136/miR-16-5p/HMGA1 axis to regulate the Tax resistance of GC cells.

The purpose of this study was to evaluate the short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer patients. PUBMED, EMBASE, and the Cochrane Library were searched from inception to Apr 15, 2021. Short-term surgical outcomes were compared between the simultaneous gastrectomy plus cholecystectomy group and the gastrectomy only group. Five retrospective studies with 3,315 patients and 1 randomized controlled trial with 130 patients were included. There was no significant difference in age, sex, surgical methods, or reconstruction. In terms of short-term outcomes, no significance was found in postoperative complications (odds ratio, OR = 1.08, I 2 = 24%, 95% CI = 0.78–1.50, P = 0.65), postoperative biliary complications (OR = 0.98, I 2 = 0%, 95% CI = 0.43–2.25, P = 0.96), mortality (OR = 1.28, I 2 = 0%, 95% CI = 0.49–3.37, P = 0.61), and postoperative hospital stay (MD = −0.10, I 2 = 0%, 95% CI = −0.73–0.54, P = 0.77) between the two groups. Simultaneous gastrectomy plus cholecystectomy in gastric cancer patients is safe and does not increase the short-term outcomes.

Oral squamous cell carcinoma (OSCC) is a common tumor in the world. Despite the rapid development of medical care, OSCC is also accompanied by high incidence and mortality every year. Therefore, it is still necessary to continuously develop new methods or find new targets to treat OSCC. Previous research showed that scavenger receptor class A member 5 (SCARA5) was one of the potential biomarkers of OSCC, and its expression is significantly low in OSCC. This study aimed to explore the role and related molecular mechanisms of SCARA5 in OSCC. In this study, we found that the SCARA5 expression was lower in CAL-27 and SCC-9 cells than that in human normal oral epithelial keratinocytes. SCARA5 overexpression significantly inhibited cell proliferation and induced apoptosis of CAL-27 and SCC-9 cells. In addition, SCARA5 repressed OSCC cell epithelial–mesenchymal transformation (EMT), evidenced by increased E-cadherin expression and reduced N-cadherin expression. Finally, we found that SCARA5 could suppress STAT3, PI3K, and AKT phosphorylation. Therefore, SCARA5 was related to STAT3 and PI3K/AKT signaling pathways in OSCC. In conclusion, SCARA5 inhibited the proliferation and EMT and induced the apoptosis of OSCC cells through the inhibition of STAT3 and PI3K/AKT signaling pathways, thereby exerting a tumor suppressor effect.

This study investigated the molecular mechanisms underlying the involvement of the Notch signaling pathway and autophagy in the development of pulmonary fibrosis in pigeon breeder’s lung (PBL). Rats were divided into control (Ctrl), PBL model (M), M + D (Notch signaling inhibition), M + W (autophagy inhibition), and M + R (autophagy induction) groups. Lyophilized protein powder from pigeon shedding materials was used as an allergen to construct a fibrotic PBL rat model. The mechanism by which Notch signaling regulated autophagy in the pulmonary fibrosis of PBL was investigated by inhibiting the Notch pathway and interfering with autophagy. Pulmonary interstitial fibrosis was significantly greater in the M group and the M + W group than in the M + D and M + R groups. The expression of α-smooth muscle actin was significantly higher in the M, M + D, and M + W groups than in the Ctrl group ( P < 0.05). The expression of the cell autophagy markers Beclin1 and LC3 was lower in the M, M + D, and M + W groups than in the Ctrl group ( P < 0.05), whereas Beclin1 and LC3 expressions were higher in the M + D and M + R groups than in the M group. The levels of reactive oxygen species in serum and lung tissues were higher in the M, M + D, M + W, and M + R groups than in the Ctrl group ( P < 0.05). The Notch signaling pathway is involved in the pathological process of pulmonary fibrosis in the rat model of PBL by regulating autophagy.

lncRNA TPT1-AS1 plays an oncogenic role in ovarian and cervical cancers. However, its involvement in the pathological progress of esophageal squamous-cell carcinomas (ESCCs) is unclear. lncRNA TPT1-AS1 was mainly localized in the cytoplasm of ESCC cells and interacted with miR-26a. In ESCC tissues, lncRNA TPT1-AS1 level was obviously increased, while miR-26a level was decreased. Interestingly, lncRNA TPT1-AS1 level was not significantly correlated with miR-26a level but was positively correlated with HMGA1 mRNA, a target of miR-26a. In ESCC cell lines KYSE510 and KYSE-30, lncRNA TPT1-AS1 overexpression enhanced HMGA1 expression, while it had no effect on miR-26a expression. Cell migration and proliferation assays indicated that lncRNA TPT1-AS1 and HMGA1 overexpression promoted ESCC cell migration and invasion, while their effects were alleviated by miR-26a overexpression. The migration and invasion of ESCC cells were suppressed by lncRNA TPT1-AS1 knockdown. In conclusion, lncRNA TPT1-AS1 plays an oncogenic role in ESCC and might function by upregulating HMGA1 via sponging miR-26a.

Gastric cancer (GC) is a common cancer worldwide with high mortality. Sirtuin 1 (SIRT1) and apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) are abnormally expressed in GC cells and related to p53, which is involved in ferroptosis. Thus, we explore the mechanism via which SIRT1, APE1, and p53 impact ferroptosis in GC cells. Specifically, GC cells were transfected with small-interfering RNA for SIRT1 (SiSIRT1) or small-interfering RNA for APE1 (SiAPE1) or with short-hairpin RNA for p53, and the cell viability, Fe 2+ , malondialdehyde (MDA), and glutathione (GSH) contents were detected by cell counting kit-8 assay and enzyme-linked immunosorbent assay. Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were conducted to quantify SIRT1, APE1, p53, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) levels in GC cells. Silencing of SIRT1 decreased viability, GSH content, and expressions of GPX4 and SLC7A11, while increased Fe 2+ , MDA content, and p53 expression in GC cells. Such aforementioned effects were reversed by APE1 overexpression. Also, SiAPE1 generated the same effects as SiSIRT1 on the above aspects, which was offset by p53 silencing. In short, SIRT1/APE1 promotes the growth of GC cells by targeting p53 to inhibit ferroptosis.

The functional recovery following spinal cord injury (SCI) remains a challenge clinically. Among the proteins interacted with the glycoprotein non-metastatic melanoma B (GPNMB) , epidermal growth factor receptor (EGFR) during activation is able to promote the proliferation of neural stem cells (NSCs) in the spinal cord. We investigated the roles of GPNMB and EGFR in regulating the survival and differentiation of the NSCs. By overexpression and short-hairpin RNA-mediated knockdown of GPNMB in the NSCs, GPNMB promoted cell viability and differentiation by increasing the expressions of βIII tubulin and CNPase (2′,3′-cyclic nucleotide 3-phosphodiesterase). Using co-immunoprecipitation, we found that EGFR interacted with GPNMB . Furthermore, EGFR had a similar effect as GPNMB on promoting cell viability and differentiation. Overexpression of EGFR reversed the decrease in viability and differentiation caused by the knockdown of GPNMB , and vice versa . Last but not least, we tested the effect of GPNMB and EGFR on several intracellular pathways and found that GPNMB/EGFR modulated the phosphorylated (p)-c-Jun N-terminal kinase (JNK)1/2/JNK1/2 ratio and the p-nuclear factor κB (NF-κB p65)/NF-κB p65 ratio. In sum, our findings demonstrate the interaction between GPNMB and EGFR that regulates cell bioprocesses, with the hope to provide a new strategy of SCI therapy.

More clinical evidence is needed regarding the relative priority of treatments for brain metastases (BMs) from EGFR/ALK-negative/unselected non-small cell lung cancer (NSCLC). PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov databases were searched. Overall survival (OS), central nervous system progression-free survival (CNS-PFS), and objective response rate (ORR) were selected for Bayesian network meta-analyses. We included 25 eligible randomized control trials (RCTs) involving 3,054 patients, investigating nine kinds of treatments for newly diagnosed BMs and seven kinds of treatments for previously treated BMs. For newly diagnosed BMs, adding chemotherapy, EGFR-TKIs, and other innovative systemic agents (temozolomide, nitroglycerin, endostar, enzastaurin, and veliparib) to radiotherapy did not significantly prolong OS than radiotherapy alone; whereas radiotherapy + nitroglycerin showed significantly better CNS-PFS and ORR. Surgery could significantly prolong OS (hazard ratios [HR]: 0.52, 95% credible intervals: 0.41–0.67) and CNS-PFS (HR: 0.32, 95% confidence interval: 0.18–0.59) compared with radiotherapy alone. For previously treated BMs, pembrolizumab + chemotherapy, nivolumab + ipilimumab, and cemiplimab significantly prolonged OS than chemotherapy alone. Pembrolizumab + chemotherapy also showed better CNS-PFS and ORR than chemotherapy. In summary, immune checkpoint inhibitor (ICI)-based therapies, especially ICI-combined therapies, showed promising efficacies for previously treated BMs from EGFR/ALK-negative/unselected NSCLC. The value of surgery should also be emphasized. The result should be further confirmed by RCTs.

Type I collagen carboxyl-terminal peptide β (β-CTX) increases in osteoporosis. The study aimed to explore the relationship between serum β-CTX and the risk of osteoporosis as well as sarcopenia in Chinese elderly inpatients. Around 228 patients whose age >65 years were recruited in this cross-sectional study. Dual-energy X-ray scanning was used to access skeletal muscle and bone mass. Serum concentration of β-CTX as well as the prevalence of osteoporosis were significantly higher in low skeletal muscle index (SMI) group than that in the normal SMI group ( P < 0.05). Serum β-CTX levels negatively correlated with SMI and bone mass ( P < 0.05). Total muscle mass, appendicular skeletal muscle mass, SMI, total bone mass, and bone mass at various sites including the limbs, spine, and pelvis decreased significantly, and the prevalence of low SMI increased with the increase of the quartiles of β-CTX. Higher serum β-CTX had an increased risk of low SMI and osteoporosis ( P < 0.05). Summarily, with increasing serum β-CTX levels, both muscle and bone mass decreased in Chinese elderly inpatients. Serum β-CTX was positively associated with the risk of not only osteoporosis but also skeletal muscle loss.

Non-small cell lung cancer (NSCLC) accounts for 80% of total lung cancers, which are the main killer of cancer-related death worldwide. Circular RNA (circRNA) has been found to modulate NSCLC development. However, the role of circ_0000376 in NSCLC development has been underreported. The present work showed that circ_0000376 and 3-phos-phoinositide-dependent protein kinase-1 (PDPK1) expression were dramatically increased, but miR-545-3p was decreased in NSCLC tissues and cells. circ_0000376 expression was closely associated with lymph node metastasis, tumor-node-metastasis stage, and tumor size of NSCLC patients. circ_0000376 knockdown repressed NSCLC cell proliferation, migration, invasion, and glutaminolysis but induced cell apoptosis. Additionally, miR-545-3p bound to circ_0000376, and circ_0000376 regulated cell phenotypes by associating with miR-545-3p. MiR-545-3p also participated in NSCLC cell proliferation, migration, invasion, apoptosis, and glutaminolysis by targeting PDPK1. Further, circ_0000376 absence repressed tumor formation in vivo . Collectively, circ_0000376 regulated NSCLC cell tumor properties by the miR-545-3p/PDPK1 axis, suggesting that circ_0000376 could be employed as a therapeutic target for NSCLC.

To evaluate the effect of delivery in a vertical birth chair (VBC) and traditional delivery table (DT) supported by women’s movement during labor on the labor process, fetal outcome, maternal hormone levels, birth comfort, and satisfaction. This randomized controlled trial was conducted with 1:1:1 allocation. Group 1: in the VBC in upright position, Group 2: on the DT in supine position, these groups supported by freedom of movement, control group: on the DT in supine position, labor in bed. The duration of second stage of labor was not different between the groups ( p = 0.246). The occurrence of instrumental birth, episiotomy, and perineal laceration was also not different among the groups ( p = 0.772, p = 0.953, and p = 0.124). The use of uterotonic was observed in control group ( p = 0.001). 1 and 5 APGAR scores of newborns were not different in all groups ( p = 0.121, p = 0.268). The lowest pain score was observed in Group 1 ( p = 0.001). Birth comfort and satisfaction were higher in Group 1 ( p = 0.001 and p = 0.001). Decreased postpartum prolactin levels and increased postpartum oxytocin levels were observed in the control and Group 1 ( p = 0.004, p = 0.006). Freedom of movement during labor and delivery using VBC in upright position can play birth-promoting and supporting role. There were no negative effects on the fetal outcome.

Emerging evidence has demonstrated that ubiquitin conjugating enzyme E2 J1 (UBE2J1) exerts pivotal function in many cancers. UBE2J1 was reported to be dysregulated in endometrial cancer (EC). This study was designed to further investigate the regulatory character and mechanism of UBE2J1 in EC. Bioinformatic tools and databases were used to analyze gene expression pattern and gene expression correlation in EC tissues, and the prognosis of EC patients. Gene expression was evaluated by reverse-transcription quantitative polymerase chain reaction. Western blot was used for protein level detection. In vitro cell apoptosis was detected by flow cytometry analyses and TUNEL assays. In vivo cell apoptosis was evaluated by detecting Bax and Bcl-2 expression in tumor tissues via immunohistochemical and western blot analyses. In this study, UBE2J1 knockdown promoted cell apoptosis in EC cells and in mouse models of EC. PI3K and AKT expression is positively correlated with UBE2J1 level and is related to poor prognosis of EC patients. UBE2J1 knockdown repressed the PI3K/AKT pathway both in vitro and in vivo . UBE2J1 downregulation decreased MDM2 expression, but increased p53 expression. MDM2 overexpression reverses the promotion of UBE2J1 knockdown on cell apoptosis in EC. Overall, UBE2J1 knockdown induces cell apoptosis in EC by inactivating the PI3K/AKT signaling and suppressing the MDM2/p53 signaling.

The main purpose of our research was to further clarify the effectiveness and potential pathophysiological principles of metabolic resuscitation therapy in critically ill patients with sepsis and septic shock. We found that metabolic resuscitation therapy is beneficial for patients with sepsis and septic shock, shortening the length of intensive care unit (ICU) stay, reducing the duration of vasopressor use, and reducing the ICU mortality rate of patients with sepsis and septic shock, but it does not reduce the hospital mortality rate.

Decreased locomotor activity and altered urinary frequency are induced by bilateral common iliac vein ligation in rats. As a carotenoid, lycopene has a strong anti-oxidative function. This research investigated the function of lycopene in the pelvic venous congestion (PC) rat model and the underlying molecular mechanism. Lycopene and olive oil were administered intragastrically on a daily basis for 4 weeks after successful modeling. Locomotor activity, voiding behavior, and continuous cystometry were analyzed. The levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), nitrate and nitrite (NO x ), and creatinine in the urine were measured. Gene expression in the bladder wall was analyzed by quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot. Locomotor activity, single voided volume, the interval between the bladder contractions, and urinary NO x /cre ratio were all decreased in rats with PC, while the frequency of urination, urinary 8-OHdG/cre ratio, inflammatory responses, and nuclear factor-κB (NF-κB) signal activity were all increased. Lycopene treatment increased locomotor activity, decreased frequency of urination, elevated urinary NO x level, and decreased urinary 8-OHdG level in the PC rat model. Lycopene also inhibited PC-enhanced pro-inflammatory mediator expression and NF‐κB signaling pathway activity. In conclusion, lycopene treatment ameliorates PC-induced phenotypes and shows an anti-inflammatory effect in the PC rat model.

Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) promotes the maintenance of established patterns of DNA methylation in mammalian cells. Extensive methylation of connexin26 (COX26) during hearing impairment has been demonstrated. The present study aims to determine whether UHRF1 can induce the methylation of COX26 in cochlea damaged by intermittent hypoxia (IH). After the establishment of the cochlear injury model through IH treatment or isolation of the cochlea containing Corti’s organ, pathological changes were observed via HE staining. Expressions of COX26 and UHRF1 were detected by quantitative reverse-transcription polymerase chain reaction and Western blot. The effect of COX26 methylation levels was analyzed by methylation-specific PCR (MSP). Phalloidin/immunofluorescence staining was used to observe structural changes. The binding relationship between UHRF1 and COX26 was verified by chromatin immunoprecipitation. IH caused cochlear damage, accompanied by increased methylation of COX26 and expression of UHRF1 in the cochlea of neonatal rats. CoCl 2 treatment caused the loss of cochlear hair cells, downregulation and hypermethylation of COX26, abnormal upregulation of UHRF1, and disordered expressions of apoptosis-related proteins. UHRF1 in cochlear hair cells binds to COX26, and its knockdown upregulated COX26 level. Overexpressed COX26 partially alleviated the CoCl 2 -caused cell damage. UHRF1 induces COX26 methylation and aggravates the cochlear damage caused by IH.

Long intergenic noncoding RNA 00511 (LINC00511) predicts poor prognosis in various malignancies and functions as an oncogene in distinct malignant tumors. The role of LINC00511 in melanoma progression was assessed. In our research, expression of LINC00511 in melanoma cells was detected by quantitative reverse transcription PCR. Colony formation and CCK8 assays were used to detect cell proliferation. Cell metastasis was evaluated by transwell and wound healing assays. Downstream target of LINC00511 was investigated by luciferase activity assay. As a results, LINC00511 was elevated in melanoma cells and tissues. Loss of LINC00511 decreased cell viability, reduced proliferation, invasion, and migration of melanoma. miR-610 was target of LINC00511, and miR-610 binds to 3′UTR of nucleobindin-2 (NUCB2). Inhibition of miR-610 attenuated LINC00511 deficiency-induced decrease of NUCB2 in melanoma cells. Loss of miR-610 weakened LINC00511 deficiency-induced decrease of cell viability, proliferation, invasion, and migration of melanoma. In conclusion, silence of LINC00511 reduced cell proliferation and metastasis of melanoma through down-regulation of miR-610-mediated NUCB2.

Vitamin D is a fat-soluble vitamin with multiple functions. However, the metabolism of people with different vitamin D concentrations is still unclear. Herein, we collected clinical data and analysed the serum metabolome of people with 25-hydroxyvitamin D (25[OH]D) ≥40 ng/mL (A), 30 ng/mL ≤25(OH)D <40 ng/mL (B) and 25(OH)D <30 ng/mL (C) by the ultra-high-performance liquid chromatography-tandem mass spectrometry method. We found that haemoglobin A1c, fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance and thioredoxin interaction protein were enhanced, while HOMA-β was reduced with the decrease of 25(OH)D concentration. In addition, people in the C group were diagnosed with prediabetes or diabetes. Metabolomics analysis showed that seven, thirty-four and nine differential metabolites were identified in the groups B vs A, C vs A and C vs B, respectively. Metabolites associated with cholesterol metabolism and bile acid biosynthesis, such as 7-ketolithocholic acid, 12-ketolithocholic acid, apocholic acid, N -arachidene glycine and d -mannose 6-phosphate, were significantly upregulated in the C group compared with the A or B groups. In conclusion, the disorder of vitamin D metabolism may be related to cholesterol metabolism and bile acid biosynthesis. This study provided a basis for exploring the possible mechanism leading to abnormal vitamin D metabolism.

Hashimoto’s thyroiditis (HT) is an autoimmune illness caused by a combination of genetic, epigenetic, and environmental factors. The pathogenesis of HT is not fully elucidated, especially in epigenetics. The epigenetic regulator Jumonji domain-containing protein D3 (JMJD3) has been extensively investigated in immunological disorders. This study has been performed to explore the roles and potential mechanisms of JMJD3 in HT. Thyroid samples from patients and healthy subjects were collected. We first analyzed the expression of JMJD3 and chemokines in the thyroid gland using real-time PCR and immunohistochemistry. In vitro , the apoptosis effect of the JMJD3-specific inhibitor GSK-J4 on the thyroid epithelial cell line Nthy-ori 3-1 was evaluated using FITC Annexin V Detection kit. Reverse transcription-polymerase chain reaction and Western blotting were applied to examine the inhibitory effect of GSK-J4 on the inflammation of thyrocytes. In the thyroid tissue of HT patients, JMJD3 messenger RNA and protein levels were substantially greater than in controls ( P < 0.05). Chemokines C–X–C motif chemokine ligand 10 (CXCL10) and C–C motif chemokine ligand 2 (CCL2) were elevated in HT patients, and thyroid cells with stimulation of tumor necrosis factor α (TNF-α). GSK-J4 could suppress TNF-α-induced synthesis of chemokines CXCL10 and CCL2 and prohibit thyrocyte apoptosis. Our results shed light on the potential role of JMJD3 in HT and indicate that JMJD3 may become a novel therapeutic target in HT treatment and prevention.

Previous studies have indicated that the development of preeclampsia (PE) involves the regulation of circular RNA (circRNA). However, the role of hsa_circ_0014736 (circ_0014736) in PE remains unknown. Thus, the study proposes to reveal the function of circ_0014736 in the pathogenesis of PE and the underlying mechanism. The results showed that circ_0014736 and GPR4 expression were significantly upregulated, while miR-942-5p expression was downregulated in PE placenta tissues when compared with normal placenta tissues. circ_0014736 knockdown promoted the proliferation, migration, and invasion of placenta trophoblast cells (HTR-8/SVneo) and inhibited apoptosis; however, circ_0014736 overexpression had the opposite effects. circ_0014736 functioned as a sponge for miR-942-5p and regulated HTR-8/SVneo cell processes by interacting with miR-942-5p. Additionally, GPR4, a target gene of miR-942-5p, was involved in miR-942-5p-mediated actions in HTR-8/SVneo cells. Moreover, circ_0014736 stimulated GPR4 production through miR-942-5p. Collectively, circ_0014736 inhibited HTR-8/SVneo cell proliferation, migration, and invasion and induced cell apoptosis through the miR-942-5p/GPR4 axis, providing a possible target for the treatment of PE.

In recent years, off-label use of sirolimus (SIR) has been gaining attention in the clinical practice. However, since it is critical to achieve and maintain therapeutic blood levels of SIR during treatment, the regular monitoring of this drug in individual patients must be implemented, especially in off-label indications of this drug. In this article, a fast, simple, and reliable analytical method for determining SIR levels in whole blood samples is proposed. Sample preparation based on dispersive liquid–liquid microextraction (DLLME) followed by liquid chromatography-mass spectrometry (LC-MS/MS) was fully optimized toward the analysis of SIR and proposed as a fast, simple, and reliable analytical method for determining the pharmacokinetic profile of SIR in whole-blood samples. In addition, the practical applicability of the proposed DLLME-LC-MS/MS method was evaluated by analyzing the pharmacokinetic profile of SIR in whole blood samples obtained from two pediatric patients suffering from lymphatic anomalies, receiving this drug as off-label clinical indication. The proposed methodology can be successfully applied in routine clinical practice for the fast and precise assessment of SIR levels in biological samples, thus allowing SIR dosages to be adjusted in real time during pharmacotherapy. Moreover, the measured SIR levels in the patients indicate the need for monitoring between doses to ensure the optimal pharmacotherapy of patients. Graphical abstract

This study aimed to explore the effects of osteogenic growth peptide C-terminal pentapeptide (G36G), and its analog G48A on bone modeling in rats with ovariectomy-induced osteoporosis. Ovariectomized rats were administered PBS (OVX group), risedronate (RISE group), G36G combined with risedronate (36GRI group), G36G (G36G group), or G48A (G48A group). The sham-operation rats (SHAM group) were administered PBS. Serum osteocalcin and IGF-2 levels in the SHAM, OVX, G36G, G48A, and RISE groups were observably lower than the 36GRI group ( P < 0.01) and the bone mineral density of the entire femur, distal metaphysis, and lumbar L1–L4 in the 36GRI group were notably increased ( P < 0.05). The bending energy of the 36GRI group was prominently higher than the other groups ( P < 0.05). Other features measured in the study that provided significant outcomes was the ratio of femora ash weight/dry weigh, parameters of trabecular bone volume (TBV)/total tissue volume, TBV/sponge bone volume, mean trabecular plate thickness, mean trabecular plate space, bone surface, parameters of sfract(s) and sfract(d), tetracycline-labeled, and osteoid surfaces. Bone loss in ovariectomized rats may be partially inhibited by G36G and G48A. A combination treatment with G36G and risedronate may be an effective intervention for osteoporosis.

This study aimed to explore the prognostic and predictive value of autophagy-related lncRNAs in papillary thyroid carcinoma (PTC). The expression data of autophagy-related genes and lncRNAs of the PTC patients were obtained from TCGA database. Autophagy-related-differentially expressed lncRNAs (DElncs) were identified and used to establish the lncRNAs signature predicting patients’ progression-free interval (PFI) in the training cohort. Its performance was assessed in the training cohort, validation cohort, and entire cohort. Effects of the signature on I-131 therapy were also explored. We identified 199 autophagy-related-DElncs and constructed a novel six-lncRNAs signature was constructed based on these lncRNAs. This signature had a good predictive performance and was superior to TNM stages and previous clinical risk scores. I-131 therapy was found to be associated with favorable prognosis in patients with high-risk scores but not those with low-risk scores. Gene set enrichment analysis suggested that a series of hallmark gene sets were enriched in the high-risk subgroup. Single-cell RNA sequencing analysis suggested that the lncRNAs were mainly expressed in thyroid cells but not stromal cells. In conclusion, our study constructed a well-performed six-lncRNAs signature to predict PFI and I-131 therapy benefits in PTC.

Locally advanced breast cancer patients have a poor prognosis; however, the relationship between potential targets and the response to treatment is still unclear. The gene expression profiles of breast cancer patients with stages from IIB to IIIC were downloaded from The Cancer Genome Atlas. We applied weighted gene co-expression network analysis and differentially expressed gene analysis to identify the primary genes involved in treatment response. The disease-free survival between low- and high-expression groups was analyzed using Kaplan–Meier analysis. Gene set enrichment analysis was applied to identify hub genes-related pathways. Additionally, the CIBERSORT algorithm was employed to evaluate the correlation between the hub gene expression and immune cell types. A total of 16 genes were identified to be related to radiotherapy response, and low expression of SVOPL, EDAR, GSTA1, and ABCA13 was associated with poor overall survival and progression-free survival in breast cancer cases. Correlation analysis revealed that the four genes negatively related to some specific immune cell types. The four genes were downregulated in H group compared with the L group. Four hub genes associated with the immune cell infiltration of breast cancer were identified; these genes might be used as a promising biomarker to test the treatment in breast cancer patients.

Our purpose was to devise a radiomics model using preoperative computed tomography angiography (CTA) images to differentiate new from old emboli of acute lower limb arterial embolism. 57 patients (95 regions of interest; training set: n = 57; internal validation set: n = 38) with femoral popliteal acute lower limb arterial embolism confirmed by pathology and with preoperative CTA images were retrospectively analyzed. We selected the best prediction model according to the model performance tested by area under the curve (AUC) analysis across 1,000 iterations of prediction from three most common machine learning methods: support vector machine, feed-forward neural network (FNN), and random forest, through several steps of feature selection. Then, the selected best model was also validated in an external validation dataset ( n = 24). The established radiomics signature had good predictive efficacy. FNN exhibited the best model performance on the training and validation groups: its AUC value was 0.960 (95% CI, 0.899–1). The accuracy of this model was 89.5%, and its sensitivity and specificity were 0.938 and 0.864, respectively. The AUC of external validation dataset was 0.793. Our radiomics model based on preoperative CTA images is valuable. The radiomics approach of preoperative CTA to differentiate new emboli from old is feasible.

Long noncoding RNAs (lncRNAs) mediate important epigenetic regulation in a wide range of biological processes. However, the effect of all dysregulated lncRNAs in myocardial infarction (MI) is not clear. Whole transcriptome sequencing analysis was used to characterize the dynamic changes in lncRNA and mRNA expression. A gene network was constructed, and genes were classified into different modules using WGCNA. In addition, for all dysregulated lncRNAs, gene ontology analysis and cis -regulatory analysis were applied. The results demonstrated that a large number of the differentially co-expressed genes were primarily linked to the immune system process, inflammatory response, and innate immune response. The functional pathway analysis of the MEblue module included immune system process and apoptosis, and MEbrown included the T-cell receptor signal pathway by WGCNA. In addition, through cis -acting analysis of lncRNA regulation, the cis -regulated mRNAs were mainly enriched in immune system processes, innate immune responses, and VEGF signal pathways. We found that lncRNA regulation of mRNAs plays an important role in immune and inflammatory pathways. Our study provides a foundation to further understand the role and potential mechanism of dysregulated lncRNAs in the regulation of MI, in which many of them could be potential targets for MI.

Previous studies suggest that baclofen may be useful in the treatment of intractable hiccup caused by chemotherapy. This study was aimed to assess the possible efficacy and safety of baclofen. In total, 65 patients with intractable hiccup caused by chemotherapy were screened. 45 patients with intractable hiccup caused by chemotherapy were finally recruited. Participants in the trial received 10 mg baclofen three times daily for 3 days. The primary outcome measure was cessation of hiccups. Secondary outcome measures included efficacy and adverse events. All 45 patients completed the study. Among them, 41 cases were cured (91.11%, 41/45), 4 cases were relieved (8.89%, 4/45), and the overall effective rate was 100% (45/45). Furthermore, the median remission time was 2(1, 9) times, the median cure time was 2(1, 9) times, the remission rate of one-time was 13.33% (6/45), the remission rate of two-time was 53.33% (24/45), and 2 cases (4.44%, 2/45) relapsed after drug withdrawal. No serious adverse events were documented. Only 1 case (2.22%) had grade 2 fatigue and 2 cases (4.44%) had grade 1 sleepiness. Baclofen is safe and effective in the treatment of intractable hiccup caused by chemotherapy of malignant tumor.

Lung cancer is one of the malignant tumors, and genetic background is a risk factor in lung cancer that cannot be neglected. In this study, we aimed to find out the effect of MRPS30-DT and NINJ2 variants on lung cancer risk. In this study, the seven selected single-nucleotide polymorphisms (SNPs) of MRPS30-DT and NINJ2 were genotyped in 509 lung cancer patients and 501 healthy controls based on the Agena MassARRAY platform. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis to evaluate association between gene polymorphisms and lung cancer risk. False-positive report probability was also used to assess false-positive results. Furthermore, the interaction between SNPs was analyzed by multifactor dimensionality reduction to predict lung cancer risk. We identified the genotype TA of rs16901963 (T < A) in MRPS30-DT as a protective factor against lung cancer, while rs16901963-TT was significantly associated with an increased risk of lung cancer. We also revealed that the effect of MRPS30-DT and NINJ2 variants on the risk of lung cancer was dependent on age, gender, smoking, and drinking status. In conclusion, this study first proved that MRPS30-DT and NINJ2 variants played important roles in affecting the susceptibility to lung cancer.

The efficacy of immune checkpoint inhibitors (ICIs) on KRAS-mutant advanced non-small cell lung cancer (NSCLC) remains controversial. This retrospective study compared the effects of ICIs treatment and chemotherapy on the prognosis of patients with KRAS-mutant advanced NSCLC and different mutant subtypes in the real world. The study included 95 patients with KRAS-mutant advanced NSCLC. Patients treated with first-line ICIs plus platinum-containing chemotherapy had better progression-free survival (PFS) (7.4 vs 4.5 months, P = 0.035) and overall survival (OS) (24.1 vs 13.2 months, P = 0.007) than those receiving platinum-containing chemotherapy alone, and second-line ICI monotherapy was associated with better PFS (4.8 vs 3.0 months, P = 0.043) and OS (18.0 vs 13.8 months, P = 0.013) than chemotherapy monotherapy. There was no significant difference in PFS (5.267 vs 6.734 months, P = 0.969) and OS (19.933 vs 20.933 months, P = 0.808) between patients with KRAS-mutant and KRAS-wild-type NSCLC treated with ICIs or between KRAS G12C and KRAS non-G12C patients (PFS: 8.1 vs 4.8 months, P = 0.307; OS: 21.3 vs 21.8 months, P = 0.434). In summary, patients with advanced NSCLC with KRAS mutations can benefit from ICIs, but no difference between KRAS mutant subtypes was observed.

Pyroptosis is a recently identified form of programmed cell death; however, its role in lung adenocarcinoma (LUAD) remains unclear. Therefore, we set out to explore the prognostic potential of pyroptosis-related genes in LUAD. The pyroptosis-related risk score (PRRS) was developed by least absolute shrinkage and selection operator Cox regression and multivariate Cox regression. We found that PRRS was an independent prognostic factor for LUAD. LUAD patients in the high-PRRS group showed a significantly shorter overall survival (OS) and enriched in cell proliferation-related pathways. Then pathway enrichment analyses, mutation profile, tumor microenvironment, and drug sensitivity analysis were further studied in PRRS stratified LUAD patients. Tumor purity (TP) analyses revealed that L-PRRS LUAD patients had a lower TP, and patients in L-TP + L-PRRS subgroup had the most prolonged OS. Mutation analyses suggested that the L-PRRS LUAD patients had a lower tumor mutation burden (TMB), and patients in H-TMB + L-PRRS subgroup had the most prolonged OS. Drug sensitivity analyses showed that PRRS was significantly negatively correlated with the sensitivity of cisplatin, besarotene, etc., while it was significantly positively correlated with the sensitivity of kin001-135. Eventually, a nomogram was constructed based on PRRS and clinical characters of LUAD. Overall, the pyroptosis-related signature is helpful for prognostic prediction and in guiding treatment for LUAD patients.

Patients with non-small-cell lung cancer (NSCLC) have a low survival rate. Long non-coding RNA (LncRNA) LANCL1 antisense RNA 1 (LANCL1-AS1) was indicated to be downregulated in NSCLC; however, its detailed function in NSCLC is unanswered. Real-time quantitative polymerase chain reaction revealed the downregulation of LANCL1-AS1 in NSCLC cell lines and subcellular fractionation assay showed that LANCL1-AS1 was mainly located in the cytoplasm of NSCLC cells. Cell counting kit-8, Transwell, and tube formation assays displayed that overexpression of LANCL1-AS1 suppressed NSCLC cell proliferation, migration, invasiveness, and angiogenesis in vitro . Animal experiments validated the tumor-suppressive role of LANCL1-AS1 in tumor-bearing mice. Mechanistically, LANCL1-AS1 upregulated glia maturation factor gamma (GMFG) expression by competitively binding to miR-3680-3p. GMFG knockdown reversed LANCL1-AS1 overexpression-mediated inhibitory impact on NSCLC malignant behaviors. Collectively, LANCL1-AS1 upregulation inhibits the progression of NSCLC by modulating the miR-3680-3p/GMFG axis.

Neuroblastoma (NB) is a common childhood cancer. Circular RNA RAN binding protein 17 (circRANBP17) has been identified to participate in diverse tumor progression. This study aims to explore the function and mechanism of circRANBP17 in NB. The levels of circRANBP17, miR-27b-3p and KDM1A in NB tissues and cells were measured by qRT-PCR. Mouse model assay was performed to investigate the effect of circRANBP17 knockdown on tumor formation in vivo . The levels of circRANBP17 and KDM1A were significantly up-regulated, and the level of miR-27b-3p was strikingly down-regulated in NB tissues and cells (SK-N-SH and SK-N-AS). Functional studies indicated that miR-27b-3p inhibitor mitigated the inhibitory effects on cell proliferation, migration, invasion and the promoting effect on cell apoptosis in SK-N-SH and SK-N-AS cells induced by circRANBP17 knockdown. Also, miR-27b-3p regulated NB cell malignancy by targeting KDM1A. Further studies revealed that miR-27b-3p inhibitor reversed the low expression of KDM1A induced by circRANBP17 knockdown. In support, circRANBP17 knockdown led to inhibition of tumor formation in vivo . In conclusion, circRANBP17 modulated KDM1A to promote cell proliferation, migration, invasion and restrain cell apoptosis in NB by sponging miR-27b-3p, and the new regulatory network may provide a theoretical basis for the further study of NB.

Osteoarthritis (OA) is a type of common degenerative joint disorder, in which adipose mesenchymal stem cells (ADSCs) and the secreted exosomes play an important role. The purpose of this study was to investigate the role and mechanism of exosomes derived from ADSCs (ADSC-exos) in OA. The gradient of IL-1β concentration was designed to construct the articular chondrocyte model of arthritic mice. The expression of miR-93-5p and ADAMTS9 in articular chondrocytes was detected by reverse transcription quantitative polymerase chain reaction. Dual luciferase reporter gene assay was performed to verify the interaction between them. Monodansylcadaverine staining was used to visualize the autophagosome formation and cell apoptosis was analyzed by flow cytometry. ADSC-exos were authenticated by transmission electron microscope and western blot assay. miR-93-5p was found to be downregulated in IL-1β-treated articular chondrocytes compared with OA cartilage while ADAMTS9 was upregulated, which was identified as a direct target gene of miR-93-5p. Silencing of ADAMTS9 attenuated the effects of miR-93-5p. Exosomal miR-93-5p can reduce the release of inflammatory factors in mouse arthritis cell models. This study first described the mechanism under that ADSC-exos inhibited inflammation and alleviated OA through the innovative targets miR-93-5p/ADAMTS9 signal axis. This provided a new method for the treatment of OA. Graphical abstract

Most of advanced hypopharyngeal squamous cell carcinoma (HSCC) are resistant to chemotherapy, and there is still lack of effective treatment for HSCC now. The present study aimed to investigate whether downregulation of RNA-binding motif protein 17 (RBM17) could enhance cisplatin sensitivity and inhibit cell invasion in HSCC and the underlying mechanism. We observed that RBM17 was upregulated in tumor tissues and associated with poor progression. Treatment of FaDu cells with cisplatin increased RBM17 expression in mRNA levels. Downregulation of RBM17 enhanced cisplatin-mediated inhibition of FaDu cells. In addition, downregulation of RBM17 effectively suppressed tumor cell migration and invasion through the reversion of epithelial–mesenchymal transition. Moreover, downregulation of RBM17 could significantly slow tumor growth in FaDu xenograft tumor model. Liquid chromatography–mass spectrometry/mass spectrometry detection and independent PRM analysis showed that 21 differentially expressed proteins were associated with the downregulation of RBM17. Taken together, our study implied that downregulation of RBM17 could serve as a novel approach to enhance cisplatin sensitivity in HSCC.

Laryngeal squamous cell carcinoma (LSCC) is an aggressive and lethal malignant neoplasm with extremely poor prognoses. Accumulating evidence has indicated that preferentially expressed antigen in melanoma (PRAME) is correlated with several kinds of cancers. However, there is little direct evidence to substantiate the biological function of PRAME in LSCC. The purpose of the current study is to explore the oncogenic role of PRAME in LSCC. PRAME expression was analyzed in 57 pairs of LSCC tumor tissue samples through quantitative real-time PCR, and the correlation between PRAME and clinicopathological features was analyzed. The result indicated that PRAME was overexpressed in the LSCC patients and correlated with the TNM staging and lymphatic metastasis. The biological functions and molecular mechanism of PRAME in LSCC progression were investigated through in vitro and in vivo assays. Functional studies confirmed that PRAME facilitated the proliferation, invasion, migration, and epithelial–mesenchymal transition of LSCC cells, and PRAME also promoted tumor growth in vivo . HDAC5 was identified as an upstream regulator that can affect the expression of PRAME. Moreover, PRAME played the role at least partially by activating PI3K/AKT/mTOR pathways. The above findings elucidate that PRAME may be a valuable oncogene target, contributing to the diagnosis and therapy of LSCC.

Sleep can affect nonalcoholic fatty liver disease (NAFLD). We investigated the association between sleep duration, sleep quality, and NAFLD. From January to December 2018, 1,073 patients (age: 37.94 ± 10.88, Body Mass Index (BMI): 22.85 ± 3.27) were enrolled. Pittsburgh Sleep Quality Index Questionnaire and Munich Chronotype Questionnaire were used to assess sleep duration, quality, and habits. Ultrasonography was used to diagnose NAFLD. Multivariate logistic regression models were used to calculate the odds ratio (OR) and 95% confidence interval (CI) of the risk of NAFLD by different types of sleep duration and sleep quality. No significant differences in sleep time, sleep quality, and sleep habits between the NAFLD and the non-NAFLD groups were observed ( P > 0.05). There was no correlation between sleep duration and NAFLD in the whole cohort. After adjusting for age, exercise, fasting plasma glucose, and BMI, the group with long sleep duration showed a decreased risk of NAFLD in men (OR = 0.01, 95% CI: 0.001–0.27, P = 0.032). However, in all four adjusted models, no correlation between sleep duration, quality, and NAFLD was found in women. In conclusion, sleep duration was significantly and negatively associated with NAFLD in men but not women. Prospective studies are required to confirm this association.

This article focuses on deciphering the effect of myostatin (MSTN) on podocyte apoptosis in membranous nephropathy (MN) and fathoming out its underlying mechanism. Rats received the intravenous injection of cationized-bovine serum albumin to induce MN in vivo , while angiotensin II (Ang II) was exposed to AB8/13 cells to induce MN model in vitro . The mRNA expression of MSTN was detected by qRT-PCR. The effects of MSTN silencing on MN model rats and cells were assessed by cell counting kit-8 assay, flow cytometry, hematoxylin and eosin staining, and TUNEL assay. The expressions of proteins related to apoptosis and Smad3/protein kinase A (PKA)/NADPH oxidase 4 (NOX4) signaling pathway were examined by western blot. As a result, MSTN was highly expressed in MN cell and rat models. Besides, knockdown of MSTN elevated the MN cell viability and dwindled apoptosis rate, as well as attenuated kidney injury in MN rats. Meanwhile, MSTN silencing lessened the expressions of phosphorylated (p)-Smad3 and Nox4, while boosting the p-PKA expression in MN rats and cells. Additionally, Smad3 overexpression reversed the above effects of MSTN silencing on Ang II-induced podocytes. In conclusion, MSTN knockdown restrains the podocyte apoptosis through regulating Smad3/PKA/NOX4 signaling pathway. Graphical abstract

Colorectal cancer (CRC) is a common malignant gastrointestinal tumor. Long noncoding RNAs (lncRNAs) are revealed to be critically involved in CRC progression, providing new direction for exploring the pathogenesis of CRC. This study aimed to explore the biological functions and regulatory mechanisms of lncRNA AC125257.1 in CRC. Western blotting and reverse-transcription quantitative polymerase chain reaction were used for the measurement of gene expression. Cell counting kit-8 assay and flow cytometry analysis were used to explore the effects of AC125257.1 on CRC cell viability and apoptosis. RNA pull-down and immunoprecipitation assays were performed for validating the binding between AC125257.1 and its potential downstream microRNA. Results showed that lncRNA AC125257.1 expression was upregulated in CRC cells and tumor tissues. AC125257.1 enhanced cell viability and suppressed apoptosis of CRC cells. Moreover, the knockdown of AC125257.1 suppressed CRC progression in vitro and inhibited tumor growth in vivo . miR-133a-3p was revealed to bind with AC125257.1 in CRC cells. CASC5 was proved to be targeted by miR-133a-3p. Moreover, rescue assays indicated that the knockdown of AC125257.1 suppressed the pathogenic overexpression of CASC5. To conclude, AC125257.1 aggravates CRC development via miR-873-5p/CASC5 axis. Our findings might suggest a novel perspective that AC125257.1 may become the target for CRC treatment.

The objective of this cross-sectional study was to investigate health management, well-being, and pandemic-related perspectives of chronic disease patients in the context of stringent measures, and associated correlates. A self-report survey was administered during the Omicron wave lockdown in Shanghai, China. Items from the Somatic Symptom Scale (SSS) and Symptom Checklist-90 were administered, as well as pandemic-related items. Overall, 1,775 patients (mostly married females with hypertension) were recruited through a community family physician group. Mean SSS scores were 36.1 ± 10.5/80, with 41.5% scoring in the elevated range (i.e., >36). In an adjusted model, being female, diagnosis of coronary artery disease and arrhythmia, perceived impact of pandemic on life, health condition, change to exercise routine, tolerance of control measures, as well as perception of future and control measures were significantly associated with greater distress. One-quarter perceived the pandemic had a permanent impact on their life, and 44.1% perceived at least a minor impact. One-third discontinued exercise due to the pandemic. While 47.6% stocked up on their medications before the lockdown, their supply was only enough for two weeks; 17.5% of participants discontinued use. Chief among their fears were inability to access healthcare (83.2%), and what they stated they most needed to manage their condition was medication access (65.6%). Since 2020 when we assessed a similar cohort, distress and perceived impact of the pandemic have worsened. Greater access to cardiac rehabilitation in China could address these issues.

Lung cancer is rare in young people, but the incidence and mortality are on the rise. We retrospectively analyzed the data of young patients aged ≤45 years diagnosed as lung cancer in our hospital from 2014 to 2021. The purpose was to explore the clinicopathological characteristics of young patients, and the risk factors affecting overall survival (OS) time. The results showed that the young patients were mainly female, had no smoking history, asymptomatic at initial diagnosis, with a high proportion of adenocarcinoma and stage I–II. We divided all patients into two groups according to age and found that the proportion of stage I–II in 18–35 years group was significantly higher than that in 36–45 years group ( P = 0.021). The main manifestation of tumor was ground glass opacity (GGO) in 18–35 years group, while most showed non-GGO in 36–45 years group ( P = 0.003). The proportion of minimally invasive adenocarcinoma was higher in 18–35 years group, while the invasive adenocarcinoma was higher in 36–45 years group ( P = 0.004). Univariate analysis showed that asymptomatic, stage I–II, surgery, women, with few or no metastatic organs had longer OS. Multivariate analysis showed that the independent factors affecting the OS of young patients were tumor stage and more metastatic organs.

Acute myeloid leukemia (AML) is classified into favorable-risk, intermediate-risk, and poor-risk subtypes. This study aimed to compare the serum proteomic signatures of the three AML subtypes and identify prognostic biomarkers for AML. Serum samples from patients with favorable-risk ( n = 14), intermediate-risk ( n = 19), and poor-risk AMLs ( n = 18) were used for the analysis of tandem mass tag (TMT) labeling-based quantitative proteomics. Comparative analysis was performed to identify differentially expressed proteins (DEPs) between groups. Prognostic proteins were screened using binary logistics regression analysis. TMT-MS/MS proteomics analysis identified 138 DEPs. Fumarate hydratase (FH), isocitrate dehydrogenase 2 (IDH2), and enolase 1 (ENO1) were significantly upregulated in poor-risk patients compared with favorable-risk patients. ELISA assay confirmed that patients with poor-risk AMLs had higher levels of IDH2, ENO1, and FH compared with intermediate-risk AML patients. Logistics analysis identified that proteins 3-hydroxyacyl-CoA dehydrogenase type-2 (HADH, odds ratio (OR) = 1.035, p = 0.010), glutamine synthetase (GLUL, OR = 1.022, p = 0.039), and lactotransferrin (LTF, OR = 1.1224, p = 0.016) were associated with poor prognosis, and proteins ENO1 (OR = 1.154, p = 0.053), FH (OR = 1.043, p = 0.059), and IDH2 (OR = 3.350, p = 0.055) were associated with AML prognosis. This study showed that AML patients had elevated levels of FH, IDH2, ENO1, LTF, and GLUL proteins and might be at high risk of poor prognosis.

Radiation-related teeth damage is a common complication in nasopharyngeal carcinoma (NPC) patients undergoing radiotherapy (RT) that seriously affects their oral health-related quality of life (OHRQoL). However, few studies have focused on protecting teeth function. This study aimed to calculate dental dose limits based on OHRQoL. Analysis was performed on 96 NPC patients who received RT (all received routine pre-radiotherapy dental interventions in our department). Based on the General Oral Health Assessment Index (GOHAI), OHRQoL was assigned into poor (<46) and good condition groups (≥46). The binary logistic regression analysis model was used for single-factor and multivariate analyses to identify the independent factors affecting OHRQoL. The cut-off value of dose received by teeth was obtained by drawing a receiver operating characteristic curve. NPC patients experienced a decline in OHRQoL following RT ( P < 0.05). Univariate analysis of GOHAI revealed that the average dose of maxillary anterior teeth, the average dose received by the oral cavity, tumor volume (GTVnx), and liking of the sweet food all affected GOHAI ( P < 0.05). Multivariate analysis indicated that the average dose of maxillary anterior teeth and liking sweet food were independent factors that influenced the OHRQoL of NPC patients with RT. When the average dose received by maxillary anterior teeth is greater than 28.78 Gy, and there is a tendency in sweet food, the OHRQoL will deteriorate. NPC patients who received RT had a better OHRQoL if the average dose to maxillary anterior teeth was limited to less than 28.78 Gy and the intake of high-sugar foods was reduced.

GRIN2A is associated with epilepsy (EP); however, its regulatory mechanism involving upstream miRNA (miR-30b-5p) has been overlooked. In this study, we aimed to identify the regulatory mechanism of the miR-30b-5p/GRIN2A axis in EP. Hippocampal neurons isolated from mice were incubated in magnesium-free medium for 48 h to establish an in vitro EP model. An in vivo model of EP was constructed by the intraperitoneal injection of atropine into mice. Nissl staining and hematoxylin and eosin staining were used to evaluate pathological injuries in the hippocampal CA1 regions of mice. The CCK8 assay confirmed that miR-30b-5p overexpression restored the suppressed proliferative capacity of hippocampal neurons exposed to magnesium-free conditions. Caspase-3 activity assay revealed that miR-30b-5p overexpression abrogated the increased apoptosis of hippocampal neurons under magnesium-free conditions. In an in vivo model of EP, miR-30b-5p overexpression reversed pathological injuries in the hippocampal CA1 regions of mice and abrogated the increased apoptosis in the EP mouse model. Luciferase assays and western blotting confirmed that miR-30b-5p targeted GRIN2A, thereby inhibiting GRIN2A expression. Overall, miR-30b-5p can protect against cell proliferation and attenuate apoptosis in hippocampal neurons under magnesium-free conditions by targeting GRIN2A.

Our pre-investigation has revealed that long non-coding RNA (LncRNA) AL137789.1 has the potential to predict the survival of patients with pancreatic carcinoma (PCa). Accordingly, the mechanism underlying the implication of AL137789.1 in PCa is covered in the current study. The non-tumor and paired tumor tissues were collected. Kaplan–Meier curve was employed to estimate the survival of PCa patients with high or low expression of AL137789.1. The proliferation, migration, invasion, and cell cycle of PCa cells were determined, and the cytotoxicity of CD8 + T cells was evaluated as well. Levels of AL137789.1, E-cadherin, N-cadherin, and Vimentin were quantified. According to the experimental results, AL137789.1 was highly expressed in PCa and related to a poor prognosis of patients. Overexpressed AL137789.1 enhanced the proliferation, migration, and invasion of PCa cells, increased the cell population at G2/M and S phases yet decreased that in G0/G1 phase, and diminished the cytotoxicity of CD8 + T cells. Also, overexpressed AL137789.1 elevated levels of N-cadherin and Vimentin, while lessening E-cadherin levels. However, the silencing of AL137789.1 produced contrary effects. Collectively, lncRNA AL137789.1 plays a tumor-promotive role in PCa by enhancing the progression and immune escape.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common developmental defect that significantly affects the morphology and function of the stomatognathic system in children. The etiology of these birth defects is multifactorial, and single nucleotide polymorphisms (SNPs) in IRF6 and FGF1 have been associated with NSCL/P. This study aimed to evaluate whether SNPs in IRF6 , namely rs2013162, rs642961, rs2235373, and rs34010 in FGF1 , are associated with NSCL/P occurrence in the Polish population. The study included 627 participants: 209 children with NSCL/P and 418 healthy controls. DNA was isolated from saliva in the study group and from umbilical cord blood in controls. Genotyping of polymorphisms was performed using quantitative PCR. There was no statistically significant association of IRF6 gene variants with NSCL/P occurrence, although for rs2013162, AA genotype, odds ratio (OR) = 1.16 and for AC genotype, OR = 0.83; for rs642961, AA genotype, OR = 0.84 and for AG genotype, OR = 1.41; and for rs2235373, AA genotype, OR = 0.79 and for AG, OR = 0.85. In the instance of rs34010 polymorphism in FGF1 , the presence of the AA genotype was statistically significant in reducing the risk of NSCL/P (OR = 0.31, p = 0.001). Genetic variation in FGF1 is an important risk marker of NSCL/P in the Polish population, which cannot be stated for the polymorphisms in the IRF6 gene.

The sideroflexin (SFXN) family is a group of mitochondrial membrane proteins. Although the function of the SFXN family in mitochondria has been widely recognized, the expression levels, role, and prognostic value of this family in breast cancer (BC) have not been clearly articulated and systematically analysed. In our research, SFXN1 and SFXN2 were significantly upregulated in BC versus normal samples based on Gene Expression Profiling Interactive Analysis 2 and the Human Protein Atlas databases. We found that high SFXN1 expression was significantly related to poor prognosis in BC patients and that high SFXN2 expression was significantly associated with good prognosis in BC patients. Gene Ontology analysis of the SFXN family was performed based on the STRING database to explore the potential functions of this family, including biological processes, cellular components, and molecular functions. Based on the MethSurv database, we found that two SFXN1 CpG sites (5′-UTR-S_Shelf-cg06573254 and TSS200-Island-cg17647431), two SFXN2 CpG sites (3′-UTR-Open_Sea-cg04774043 and Body-Open_Sea-cg18994254), one SFXN3 CpG site (Body-S_Shelf-cg17858697), and nine SFXN5 CpG sites (1stExon;5′-UTR-Island-cg03856450, Body-Open_Sea-cg04016113, Body-Open_Sea-cg04197631, Body-Open_Sea-cg07558704, Body-Open_Sea-cg08383863, Body-Open_Sea-cg10040131, Body-Open_Sea-cg10588340, Body-Open_Sea-cg17046766, and Body-Open_Sea-cg22830638) were significantly related to the prognosis of BC patients. According to the ENCORI database, four negative regulatory miRNAs for SFXN1 (hsa-miR-22-3p, hsa-miR-140-5p, hsa-miR-532-5p, and hsa-miR-582-3p) and four negative regulatory miRNAs for SFXN2 (hsa-miR-9-5p, hsa-miR-34a-5p, hsa-miR-532-5p, and hsa-miR-885-5p) were related to poor prognosis for BC patients. This study suggests that SFXN1 and SFXN2 are valuable biomarkers and treatment targets for patients with BC.

Bronchoscopy has been widely used for the therapy of lung cancer. This study aimed to evaluate the therapeutic efficacy and adverse reactions of bronchoscopic intratumoral injection of endostar and cisplatin in patients with lung squamous cell carcinoma (LSCC). A total of 40 LSCC patients who underwent conventional chemoradiotherapy were included in this study, and 20 of them received a bronchoscopic injection of endostar and cisplatin as an additive therapeutic modality (treatment group). The clinical response rate, progression-free survival (PFS), and adverse reactions of the patients were compared and analyzed. The treatment group had better short- and long-term therapeutic efficacy compared to the control group, but no significant differences were observed between the two therapeutic regimens in adverse reactions. Elderly and advanced LSCC patients had worse therapeutic efficacy and a high probability of adverse reactions after the therapy. Collectively, our analysis data demonstrated that the bronchoscopic intratumoral injection of endostar and cisplatin had improved therapeutic efficacy, and the cardiovascular adverse reactions were within the controllable range in the treatment of LSCC in clinical practices.

Myocardial infarction–associated transcript (MIAT) is a long noncoding RNA that plays a critical role in a variety of diseases. Accordingly, this study probed into the possible interaction mechanism between MIAT and miR-378a-5p in breast cancer. Concretely, MIAT and miR-378a-5p expressions in breast cancer tissues and cells were measured. After transfection with siMIAT and miR-378a-5p inhibitor, the viability and proliferation of breast cancer cells were examined by cell counting kit-8 and colony formation assays. The expressions of apoptosis-related proteins were detected. According to the results, MIAT was highly expressed in breast cancer tissues and cells. MIAT silencing could decrease Bcl-2 expression, viability, and proliferation of breast cancer cells and increase the expressions of cleaved caspase-3 and Bax. MIAT and miR-378a-5p could directly bind to each other, and MIAT silencing promoted the expression of miR-378a-5p. miR-378a-5p expression was low in breast cancer tissues. The miR-378a-5p inhibitor enhanced the viability and proliferation of breast cancer cells and partially reversed the effects of MIAT silencing on the breast cancer cells. In conclusion, MIAT silencing inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p, indicating the potential of MIAT as a new target for the treatment of breast cancer.

Insulin-like-growth factor-1 (IGF-1) is the ligand for insulin-like growth factor-1 receptor (IGF-1R), and the roles of IGF-1/IGF-1R in diabetic nephropathy (DN) are well-characterized previously. However, the biological functions of AG1024 (an IGF-1R inhibitor) in DN remain unknown. This study investigates the roles and related mechanisms of AG-1024 in DN. The experimental DN was established via intraperitoneal injection of streptozotocin, and STZ-induced diabetic rats were treated with AG1024 (20 mg/kg/day) for 8 weeks. The 24 h proteinuria, blood glucose level, serum creatinine, and blood urea nitrogen were measured for biochemical analyses. The increase in 24 h proteinuria, blood glucose level, serum creatinine, and blood urea of DN rats were conspicuously abated by AG1024. After biochemical analyses, the renal tissue specimens were collected, and as revealed by hematoxylin and eosin staining and Masson staining, AG-1024 mitigated typical renal damage and interstitial fibrosis in DN rats. Then, the anti-inflammatory effect of AG-1024 was assessed by western blotting and ELISA. Mechanistically, AG-1024 upregulated SOCS1 and SOCS3 expression and decreased phosphorylated JAK2, STAT1, and STAT3, as shown by western blotting. Collectively, AG-1024 (an IGF-1R inhibitor) ameliorates renal injury in experimental DN by attenuating renal inflammation and fibrosis via the SOCS/JAK2/STAT pathway.

KIAA1199, a major glycosaminoglycan component of the extracellular matrix, was reported to induce a fibrosis-like process. However, the relationship between KIAA1199 and liver fibrosis remains unclear. The liver fibrosis mouse model was established with carbon tetrachloride (CCl 4 ). Here, we found that KIAA1199 was upregulated in CCl 4 -induced liver fibrosis. The expression of KIAA1199 was also increased in TGF-β-stimulated LX-2 cells. To clarify the impact of KIAA1199 in hepatic stellate cells (HSCs), we downregulated the expression of KIAA1199 in LX-2 cells by RNA interference. Cell proliferation, apoptosis, and migration were determined by CCK-8, flow cytometry, and transwell assay. We found that KIAA1199 knockdown reduced the expression of fibrosis markers α-SMA and COL1A1. Depletion of KIAA1199 inhibited cell proliferation by downregulating cyclin B1 and cyclin D1 and promoted cell apoptosis by upregulating Bax and downregulating Bcl-2. Moreover, KIAA1199 knockdown decreased matrix metalloproteinase-2 (MMP-2) and MMP-9 expression to inhibit the migration ability of LX-2 cells. Silencing KIAA1199 also suppressed the epithelial–mesenchymal transition phenomenon. Collectively, our study revealed that KIAA1199 knockdown alleviated the activation, proliferation, and migration of HSCs, while promoting apoptosis of HSCs, which suggests that KIAA1199 may be a potential regulator of liver fibrosis.

Diabetes mellitus (DM) increases the destruction of periodontal tissue and impairs osteogenesis differentiation. Exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analogue, can be used for treating DM and promotes bone regeneration. The aim of this study was to explore the effect and mechanism of Ex-4 on improving the osteogenesis of periodontal ligament stem cells (PDLSCs) in a high glucose environment. Alkaline phosphatase staining and alizarin red staining were used to detect the osteogenic differentiation of PDLSCs. The results showed that 10 nM Ex-4 could reduce the osteogenesis inhibition of PDLSCs induced by high glucose. RT-PCR and western blot results showed that Ex-4 increased the osteogenesis-related gene expression of ALP, Runx2, and Osx, and upregulated the phosphorylation of P38, JNK, and ERK1/2; the peak effect was observed in the range 0.5–1.0 h. Mitogen-activated protein kinase (MAPK) inhibitors PD98059, SB203580, and SP600125 blocked the effects of Ex-4 on MAPK activation and decreased the expression of ALP, Runx2, and Osx in PDLSCs. Moreover, after Ex-4 treatment, the total β-catenin, p-GSK3β, LEF, and Runx2 protein levels increased under normal or high glucose environments. In conclusion, our results indicated that Ex-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of PDLSCs in a high glucose environment.

Considering the role of glycolysis inhibition as a novel therapeutic strategy for cancer, including breast cancer (BC), we wondered whether glycolysis could affect BC progression by regulating transmembrane O -mannosyltransferase-targeting cadherins 3 (TMTC3). Following the intervention, lactic acid production in BC cells was monitored, and viability, proliferation, and apoptosis assays were performed. The expressions of TMTC3 and endoplasmic reticulum (ER) stress- and apoptosis-related factors Caspase-12, C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X (Bax) were quantified. TMTC3 was lowly expressed in BC tissue and cell. The promotion of glycolysis via glucose represses TMTC3 expression and apoptosis yet enhances lactic acid production and growth of BC cell, along with promoted levels of Caspase-12, CHOP, GRP78, and Bcl-2 yet repressed level of Bax, while the contrary results were evidenced after 2-deoxyglycouse intervention. Overexpressed TMTC3 additionally abrogated the effects of glycolysis on increasing the viability and proliferation yet inhibiting the apoptosis of BC cells, with the increased expressions of Caspase-12, CHOP, and GRP78, and Bcl-2 yet decreased level of Bax. Collectively, inhibiting glycolysis restrained the growth and attenuated the ER stress of BC cell by regulating TMTC3.

This study aimed to evaluate the significance of EMX2OS in lung adenocarcinoma (LUAD) prognosis and development and its potential molecular mechanism. Paired tissue samples were collected from 117 LUAD patients. The EMX2OS expression level was detected by PCR and correlated with patients’ clinicopathological features by a series of statistical analyses. The function of EMX2OS in cell proliferation and metastasis was evaluated by CCK8 and Transwell assay. In mechanism, the interaction between EMX2OS and miR-653-5p was assessed by the dual-luciferase reporter assay, and the regulatory effect of miR-653-5p on EMX2OS tumor suppressor role was also estimated. Significant downregulation of EMX2OS and its negative correlation with miR-653-5p was observed in LUAD tissues. A significant relationship was revealed in EMX2OS with TNM stage, lymph node metastasis, and differentiation of LUAD patients, and associated with the poor prognosis of patients. EMX2OS suppressed the proliferation and metastasis of LUAD cells and negatively regulated the expression of miR-653-5p. The overexpression of miR-653-5p could reverse the inhibitory effect of EMX2OS on LUAD cells. In conclusion, EMX2OS served as a biomarker in LUAD that indicated patients’ prognosis and regulated cellular processes via regulating miR-653-5p.

Since tectorigenin has been reported to possess anti-inflammation, redox balance restoration, and anti-apoptosis properties, we determine to unravel whether tectorigenin has potential in alleviating spinal cord injury (SCI). Herein, PC12 cells were induced by lipopolysaccharide (LPS) to establish in vitro SCI models. The cell viability and apoptosis were detected through cell counting kit-8 and flow cytometry assays. The caspase-3/8/9 content was measured by colorimetric method. Western blot was conducted to quantify the expressions of cleaved caspse-3/8/9, IGFBP6, TLR4, IκBα, p-IκBα, RELA proto-oncogene, p65, and p-p65. Enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction were carried out to quantitate expressions of IGFBP6, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). SwissTargetPrediction and GSE21497 database were utilized to predict the potential therapeutic targets of tectorigenin. Comparison of IGFBP6 expression in SCI tissues and normal tissues was analyzed by GEO2R. Our study found that LPS induced the declined cell viability, elevated cell apoptosis, upregulation of caspase-3/8/9, cleaved caspase-3/8/9, IL-1β, IL-6, TNF-α, IGFBP6, and TLR4, and the activation of IκBα and p65 in PC12 cells. Tectorigenin reversed the above effects of LPS. IGFBP6 was predicted to be the potential therapeutic target of tectorigenin and was overexpressed in SCI tissues. Notably, IGFBP6 overexpression offset the effects of tectorigenin on PC12 cells. In conclusion, tectorigenin could alleviate the LPS-induced apoptosis, inflammation, and activation of NF-κB signaling in SCI cell models via inhibiting IGFBP6.

In this study, we determined the diagnostic performance of adding ultrasound (US) with/without fine‐needle aspiration cytology (FNAC) to computed tomography (CT)/magnetic resonance imaging (MRI) in evaluating neck lymphadenopathy (LAP) in patients with head and neck cancer treated with irradiation. We included 269 patients who had neck LAP after radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) resulting from cancers of the head and neck region between October 2008 and September 2018. The diagnostic methods consisted of the following: 1) CT/MRI alone, 2) CT/MRI combined with a post-RT US predictive model, and 3) CT/MRI combined with US + FNAC. We compared their diagnostic performance using receiver operating characteristic (ROC) curves. In total, 141 (52%) malignant and 128 (48%) benign LAPs were observed. Regarding the diagnostic accuracy, the area under the ROC curves was highest for the combined CT/MRI and US + FNAC (0.965), followed by the combined CT/MRI and post-RT US predictive model (0.906) and CT/MRI alone (0.836). Our data suggest that the addition of a US examination to CT/MRI resulted in higher diagnostic performance than CT/MRI alone in terms of diagnosing recurrent or persistent nodal disease during the evaluation of LAP in patients with irradiation-treated head and neck cancer.

Hepatic fibrosis (HF) is a precursor of liver cirrhosis, and activated hepatic stellate cells are an important driver of fibrosis. F-box and WD repeat domain containing 7 (FBXW7) expression level is down-regulated in HF, but the underlying mechanism is yet to be elucidated. The interaction between FBXW7 and delta-like ligand 1 (DLL1) was predicted. LX-2 cells were subjected to transfection of FBXW7/DLL1 silencing or overexpression plasmid. The expressions of FBXW7 and DLL1 in HF in vitro were measured by quantitative reverse transcription polymerase chain reaction and western blot. The LX-2 cell cycle, viability, proliferation, and ubiquitination were determined by flow cytometry, cell counting kit-8, colony formation, and ubiquitination assays, respectively. FBXW7 overexpression suppressed the cell viability and proliferation, facilitated cell cycle arrest, and down-regulated α-smooth muscle actin (α-SMA), Collagen I, and DLL1 protein levels, but FBXW7 silencing did the opposite. DLL1 was bound to and ubiquitin-dependently degraded by FBXW7 overexpression. DLL1 overexpression promoted the cell viability and proliferation, accelerated cell cycle, and up-regulated the levels of α-SMA, Collagen I, NOTCH2, NOTCH3, and HES1, but these trends were reversed by FBXW7 overexpression. To sum up, FBXW7 overexpression suppresses the progression of HF in vitro by ubiquitin-dependently degrading DLL1.

Radiotherapy resistance is a challenge for colorectal cancer (CRC) treatment. Circular RNAs (circRNAs) play vital roles in the occurrence and development of CRC. This study aimed to investigate the role of circ_0005615 in regulating the radiosensitivity of CRC. The levels of circ_0005615, microRNA-665 (miR-665), and notch receptor 1 (NOTCH1) were detected by quantitative real-time PCR or western blot. The radiosensitivity of CRC cells was assessed by colony formation assay. Cell viability, apoptosis, and colony formation were assessed by Cell Counting Kit-8 assay, flow cytometry, and colony formation assay. Cell migration and invasion were confirmed by transwell assay and scratch assay. The binding relationship between miR-665 and circ_0005615 or NOTCH1 was verified by dual-luciferase reporter assay. Xenograft assay was used to test the effect of circ_0005615 on radiosensitivity in vivo . circ_0005615 and NOTCH1 were up-regulated, and miR-665 was down-regulated in CRC tissues and cells. Radiation decreased circ_0005615 and NOTCH1 levels and increased miR-665 level. Knockdown of circ_0005615 enhanced radiosensitivity of CRC cells. Moreover, circ_0005615 sponged miR-665 to regulate the radioresistance of CRC cells. Besides, miR-665 targeted NOTCH1 to mediate the radiosensitivity of CRC cells. Furthermore, circ_0005615 depletion increased CRC radiosensitivity in vivo . circ_0005615 silencing elevated radiosensitivity of CRC by regulating miR-665/NOTCH1 axis.

Long noncoding RNAs (lncRNAs) are known to participate in the pathological process of cardiac hypertrophy. This study aimed to investigate the function of the lncRNA, myosin heavy-chain associated RNA transcript ( Mhrt ), in cardiac hypertrophy and its possible mechanism of action. Adult mouse cardiomyocytes were treated with angiotensin II (Ang II) and transfected with Mhrt ; cardiac hypertrophy was evaluated by estimating atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy-chain levels, and cell surface area by reverse transcription-quantitative polymerase chain reaction, western blotting, and immunofluorescence staining. The interaction between the Mhrt /Wnt family member 7B (WNT7B) and miR-765 was assessed using a luciferase reporter assay. Rescue experiments were performed by analyzing the role of the miR-765/WNT7B pathway underlying the function of Mhrt . The results indicated that Ang II induced hypertrophy of cardiomyocytes; however, overexpression of Mhrt alleviated the Ang II-induced cardiac hypertrophy. Mhrt acted as a sponge for miR-765 to regulate the expression of WNT7B. Rescue experiments revealed that the inhibitory effect of Mhrt on myocardial hypertrophy was abolished by miR-765. Additionally, the knockdown of WNT7B reversed the suppression of myocardial hypertrophy induced by downregulating miR-765. Taken together, Mhrt alleviated cardiac hypertrophy by targeting the miR-765/WNT7B axis.

Atrial fibrosis is involved in the progression of atrial fibrillation (AF). miR-499-5p is the most downregulated microRNA in arrhythmogenic cardiomyopathy hearts. Sry-related high-mobility-group box 6 (SOX6) is associated with apoptosis, inflammatory responses, and fibrosis. This study investigated the mechanism of miR-499-5p in ameliorating AF rats by regulating SOX6. AF rat models were established by injecting Ach–CaCl 2 mixture, and the rats were treated with Lv-miR-499-5p/oe-SOX6/si-SOX6 before modeling. AF duration was recorded using electrocardiogram. miR-499-5p and SOX6 expression levels in the myocardium were determined by reverse transcription-quantitative polymerase chain reaction. The binding of miR-499-5p and SOX6 was validated. The atrial fibrosis degree and cardiomyocyte apoptosis were assessed using the Masson and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining methods. Levels of SOX6, atrial fibrosis markers (collage I/α-SMA/TGFβ1), cell cycle-related proteins (p21/CDC25/Cyclin B1), and cell senescence markers (SA-β-gal/γ-H2AX) were measured using Western blotting and immunohistochemistry. miR-499-5p was downregulated and SOX6 was upregulated in AF rats. miR-499-5p overexpression shortened the AF duration, alleviated atrial fibrosis, and decreased collage I/α-SMA/TGFβ1. miR-499-5p targeted SOX6 to ameliorate atrial fibrosis. AF rats exhibited increased p21/CDC25/Cyclin B1/SA-β-gal/γ-H2AX levels and raised cardiomyocyte apoptosis. SOX6 silencing downregulated p21 and alleviated cardiomyocyte cycle arrest, cell senescence, and apoptosis in AF rats. Shortly, miR-499-5p suppresses atrial fibrosis and cardiomyocyte senescence by targeting SOX6 and downregulating p21, thus mitigating AF in rats. Graphical abstract

Cholesterol stimulates inflammation and affects the normal function of islet tissues. However, the precise mechanism underlying the effects of cholesterol on islet cells requires clarification. In this study, we explored the role of cholesterol in glucose utilization in pancreatic cells. Beta-TC-6 cells and mice were treated with cholesterol. We used glucose detection kits to identify the glucose content in the cell culture supernatant and mouse serum and an enzyme-linked immunosorbent assay was used to detect insulin levels in the serum. Glucose-6-phosphatase catalytic subunit 2 (G6PC2), 78 kDa glucose-regulated protein (GRP78), 94 kDa glucose-regulated protein (GRP94), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), caspase-1 (casp1), and interleukin-1β (IL-1β) expression levels were detected using immunofluorescence, immunohistochemistry, western blotting, and reverse transcription-quantitative polymerase chain reaction. Hematoxylin–eosin staining was used to detect the histological alterations in pancreatic tissues. Cholesterol decreased beta-TC-6 cell glucose utilization; enhanced pancreatic tissue pathological alterations; increased glucose and insulin levels in mouse serum; increased G6PC2, GRP78, GRP94, and NLRP3 expression levels; and elevated casp1 and pro-IL-1β cleavage. Cholesterol can attenuate glucose utilization efficiency in beta-TC-6 cells and mice, which may be related to endoplasmic reticulum stress and inflammation.

Circular RNAs have been demonstrated to act as vital participants in various diseases, including preeclampsia (PE). This study aimed to research the effects of circ_0004904 on PE. The contents of circ_0004904, microRNA-19b-3p (miR-19b-3p) and arrestin domain containing 3 (ARRDC3) were quantified by quantitative real-time PCR and western blot. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 5-ethynyl-2′-deoxyuridine assays were enforced to assess cell proliferation. The transwell assay and flow cytometry were applied to detect the cell migration, invasion, and apoptosis. The liaison between miR-19b-3p and circ_0004904 or ARRDC3 was demonstrated by dual-luciferase reporter assay. Thereafter, circ_0004904 and ARRDC3 were augmented, and miR-19b-3p was restrained in PE. Circ_0004904 silencing contributed to cell proliferation, migration, and invasion, but restrained cell apoptosis in trophoblast cells. Further, miR-19b-3p was a target of circ_0004904, and miR-19b-3p could target ARRDC3. Additionally, circ_0004904 accelerated PE evolution via changing ARRDC3 level by binding to miR-19b-3p. In all, circ_0004904 encouraged PE progress via miR-19b-3p/ARRDC3 axis.

Liver cancer is a prevalent malignant tumor with high mortality worldwide, making it urgent to explore new targets for liver cancer therapy. N-terminal EF-hand calcium binding protein 3 (NECAB3) is a new recognized regulator of cancer, while its role in liver cancer remained elusive. Thus, the study clarified the action of NECAB3 on liver cancer development and explored the detailed mechanism. We found that NECAB3 was enhanced in liver cancer. Knockdown of NECAB3 restrained liver cancer cell migration and invasion. Besides, knockdown of NECAB3 suppressed the activation of the hypoxia-inducible factor 1-alpha (HIF-1α)/Ras like without CAAX 1 (RIT1) pathway. Furthermore, NECAB3 regulated liver cancer migration and invasion through modulating RIT1 expression. Moreover, downregulation of NECAB3 suppressed liver cancer tumor growth in vivo . In conclusion, NECAB3 was upregulated in liver cancer. Knockdown of NECAB3 suppressed aggressive phenotype of liver cancer via modulating the HIF-1α/RIT1 axis, providing a possible target for liver cancer therapy.

Framingham risk score (FRS), systematic coronary risk evaluation (SCORE), the 10-year atherosclerotic cardiovascular disease risk algorithm (ASCVD), and their modified risk scores are the most common cardiovascular risk scores. The aim of this case–control study was to evaluate the performance of cardiovascular risk scores in detecting carotid subclinical atherosclerosis (SCA) in patients with idiopathic inflammatory myopathies (IIMs). A total of 123 IIMs patients (71.5% female, mean age 50 ± 14 years) and 123 age- and gender-matched healthy controls were included in this study. Carotid SCA was more prevalent in IIMs patients compared with controls (77.2 vs 50.4%, P < 0.001). Moreover, patients with carotid SCA+ had older age, and all risk scores were significantly higher in IIMs patients with SCA+ compared to subjects with SCA− (all P < 0.001). According to FRS, SCORE, and ASCVD risk scores, 77.9, 96.8, and 66.7% patients with SCA+ were classified as low risk category, respectively. The modified scores also demonstrated a modest improvement in sensitivity. Notably, by adopting the optimal cutoff values, these risk scores had good discrimination on patients with SCA+, with area under curves of 0.802–0.893. In conclusion, all cardiovascular risk scores had a poor performance in identifying IIMs patients at high cardiovascular risk.

Ovarian cancer is one of the major gynaecological malignancies and a leading cause of cancer-related deaths worldwide. Dysregulation of miR-2053 has been reported in numerous types of cancer; however, its function in ovarian cancer remains largely unknown. In our study, the roles of miR-2053 during the development of ovarian cancer were investigated. miR-2053 expression was examined in ovarian cancer specimens and cells. Furthermore, the detailed functions and downstream targets of miR-2053 were identified. Briefly, the levels of miR-2053 were assessed in ovarian cancer tissues and paired non-cancerous samples, as well as in ovarian cancer cells using reverse transcription-quantitative polymerase chain reaction. The proliferation of cells was determined by cell counting kit-8 kit, and the levels of PCNA were also examined using immunostaining. Cell migration and invasion were evaluated using Transwell assay, and E-cad expression was assessed by immunostaining. In addition, cell apoptosis was determined by flow cytometry, and the expression of cleaved caspase-3 was examined using western blotting. The results revealed the downregulation of miR-2053 in ovarian cancer tissues and cells. Moreover, miR-2053 mimics suppressed the proliferation, migration, and invasion of ovarian cancer cells, while cell apoptosis was promoted. In addition, SOX4 was a putative downstream molecule of miR-2053 in ovarian cancer. Furthermore, SOX4 is involved in miR-2053-regulated growth and metastasis of ovarian cancer cells. In summary, miR-2053 and its novel target SOX4 could serve essential roles during tumour development of ovarian cancer, more importantly, miR-2053/SOX4 axis may be novel candidate for targeted therapy for patients with ovarian cancer.

The chemokine, C-X-C motif chemokine ligand 12 (CXCL12) and its G-protein-coupled receptor (GPCR) and C-X-C chemokine receptor type 4 (CXCR4), are closely associated with promoting hepatocellular carcinoma (HCC) chemotaxis and metastasis. The binding of CXCL12 and CXCR4 depends on the heterotrimeric Gi proteins to regulate actin polymerisation and mobility in HCC. Although the role of GPCR/Gi signalling in carcinogenesis migration has been intensively studied, the detailed mechanism remains largely unknown. In this study, a small interfering RNA technique was used to knock down the Nucleophosmin 1 (NPM1) gene expression. Through the chemotaxis and invasion assays, wound healing, proliferation, filamentous-actin, immunofluorescence, immunohistochemical assays, and co-immunoprecipitation assays, we investigated the specific biological role and underlying mechanisms of the NPM1 in HCC. Additionally, dimethyl fumarate (DMF), a fumaric acid ester, was used to inhibit the HCC cell chemokines and metastasis by regulating ELMO1 and NPM1. Therefore, this study reported that NPM1 gene expression was upregulated in the HCC tissues and cell lines. The NPM1 knockdown significantly inhibited the proliferation, migration, and chemotaxis of the HepG2 cells in vitro. Further mechanistic studies suggested that the NPM1 interacts with ELMO1 and the CXCL12/CXCR4 pathway activates NPM1-dependent regulation of the ELMO1 localisation. Furthermore, the DMF significantly inhibited tumour metastasis induced by the NPM1/ELMO1 signalling pathway, as observed in in vitro cell functional experiments. These data suggested that as a potentially novel therapeutic approach, the simultaneous targeting of NPM1 and ELMO1 could effectively be used to treat HCC.

Sepsis is one of the most fatal inflammatory diseases with multiple organ failure caused by pathological infection. α-Hederin, a monodesmosidic triterpenoid saponin, has many biological activities including anti-inflammation. This study aimed to investigate the effect of α-Hederin on lung and liver injuries in septic mice. Mice underwent cecal ligation and puncture-induced sepsis were intraperitoneally injected with 0.3 or 3 mg/kg α-Hederin. α-Hederin treatment dose-dependently attenuated the lung and liver injuries in septic mice. Correspondingly, α-Hederin significantly decreased malondialdehyde production, increased the levels of superoxide dismutase and glutathione in lung tissues, reduced serum alanine aminotransferase and aspartate aminotransferase activities, and suppressed the levels of TNF-α and IL-6 in both tissues and in the serum. Moreover, α-Hederin augmented CD206 level and inhibited the productions of CD86 and iNOS in lung and liver tissues of septic mice. Importantly, p-p65/p65 was suppressed, whereas IκB was elevated by α-Hederin. In conclusion, α-Hederin could improve the lung and liver injuries in mice with sepsis by regulating macrophage M1/M2 polarization and inhibiting the activation of NF-κB signaling pathway.

No consensus has been reached on the dysbiosis signs of microbiota in patients with urinary tract infections (UTIs). This meta-analysis aimed to verify the relationship between microbiota levels and UTIs. PubMed, Web of Science, and Embase databases were retrieved for related articles published from inception until October 20, 2021. The standardized mean difference (SMD) and its related 95% confidence intervals (CIs) of the microbiota diversity and abundance were pooled under a random-effects model. Twelve studies were included in this meta-analysis. The pooled analysis revealed that the microbiota diversity was lower in patients with UTIs than in healthy individuals (SMD = −0.655, 95% CI = −1.290, −0.021, I 2 = 81.0%, P = 0.043). The abundance of specific bacteria was higher in UTI subjects compared with healthy control individuals (SMD = 0.41, 95% CI = 0.07–0.74, P = 0.017), especially in North America patients with UTIs. Similar results were also found in studies with the total sample size being greater than 30. Importantly, Escherichia coli levels were increased in patients with UTI, whereas Lactobacillus levels decreased. E. coli and Lactobacilli have huge prospects as potential microbiota markers in the treatment of UTIs.

Patients with castration-resistant prostate cancer (CRPC) often develop drug resistance after treatment with enzalutamide. The goal of our study was to identify the key genes related to enzalutamide resistance in CRPC and to provide new gene targets for future research on improving the efficacy of enzalutamide. Differential expression genes (DEGs) associated with enzalutamide were obtained from the GSE151083 and GSE150807 datasets. We used R software, the DAVID database, protein–protein interaction networks, the Cytoscape program, and Gene Set Cancer Analysis for data analysis. The effect of RAD51 knockdown on prostate cancer (PCa) cell lines was demonstrated using Cell Counting Kit-8, clone formation, and transwell migration experiments. Six hub genes with prognostic values were screened ( RAD51 , BLM , DTL , RFC2 , APOE , and EXO1 ), which were significantly associated with immune cell infiltration in PCa. High RAD51 , BLM , EXO1 , and RFC2 expression was associated with androgen receptor signaling pathway activation. Except for APOE , high expression of hub genes showed a significant negative correlation with the IC50 of Navitoclax and NPK76-II-72-1. RAD51 knockdown inhibited the proliferation and migration of PC3 and DU145 cell lines and promoted apoptosis. Additionally, 22Rv1 cell proliferation was more significantly inhibited with RAD51 knockdown than without RAD51 knockdown under enzalutamide treatment. Overall, six key genes associated with enzalutamide resistance were screened ( RAD51 , BLM , DTL , RFC2 , APOE, and EXO1 ), which are potential therapeutic targets for enzalutamide-resistant PCa in the future.

This prospective cohort study aimed to characterise the impact of oxaliplatin-based chemotherapy and its neurotoxic side effects (i.e., chemotherapy-induced neuropathy) on functional fall-risk and falls. Twenty chemotherapy-naïve participants (mean age, 59 years; 16 males) were consecutively included. A multimodal fall risk assessment was performed at four time points within 6 months. Polyneuropathy was assessed using the Neurologic Disability Scale; the fall risk was assessed by functional tests (Tinetti Test, Chair-Rising Test, and Timed up and Go Test). Patient-reported outcomes comprised the Hospitality Anxiety and Depression Scale (HADS), the Falls Efficacy Scale – International (FES-I) to assess the fear of falling, and the Physical Activity for the Elderly (PASE) questionnaire. Three falls occurred during the study. All fallen participants had a high fall risk-index (≥4 more risk factors) compared to only 30% of the non-fallen participants ( p = 0.03) and suffered more frequently from pre-existing mild polyneuropathy ( p = 0.049). Study discontinuation ( n = 12) was associated with a higher rate of polypharmacy ( p = 0.045), anxiety (HADS-A, p = 0.03), and specific fear of falling (FES-I, p = 0.025). In contrast, study completers ( n = 8) reported an improvement in physical activity (PASE) ( p = 0.018). In summary, pre-existing fall-risk factors impacted more falls than chemotherapy. A fall risk index offers a time-efficient screening option in an outpatient oncological setting.

According to the World Health Organization, midwife-led care is the most appropriate and cost-effective type of perinatal care. As the Covid-19 pandemic with its drastic changes and challenges for the health systems and the medical staff made large adjustments to the healthcare delivery system, midwife-led care became an even more important supportive tool in maintaining unnecessary interventions. This retrospective cohort study aims to compare the outcomes of midwife-led care and team-led care in low-risk births between the Covid-19 pandemic and non-Covid-19 pandemic period. The total studied population was 1,185 singleton births and consisted of 727 births during the non-Covid-19 period and 458 births from the Covid-19 period. The study revealed the safety of low-risk birth care during the first wave of the Covid-19 pandemic in both groups. The maternal and perinatal outcomes remained stable without an increased rate of unsuccessful vaginal births and newborn asphyxia; moreover, birth care of low-risk women provided by midwives preserved autonomy, integrity, and resistance to responding to a disaster. The aforementioned results exhibit that high-quality, safe supervision by midwives in low-risk births can be provided even in high-stress circumstances.

Liver cirrhosis affects the structures and physiological functions of the intestine. Our previous study revealed that liver injury inhibited 25-hydroxylation of vitamin D (25(OH)-VD). The aim of this study was to investigate the roles and mechanisms of vitamin D in liver cirrhosis-induced intestinal injury. The rat liver cirrhosis model was established through the administration of carbon tetrachloride (CCl 4 ) for 8 weeks. Hematoxylin–eosin staining was performed to unveil the intestinal injury induced by liver cirrhosis. Enzyme-linked immunosorbent and reverse transcription PCR (RT-PCR) analysis were used to determine the levels of 25(OH)-VD, vitamin D receptor, Cytochrome P450 24A1 (CYP24A1), and α-defensin 5 (DEFA5) in rat and human serum of liver cirrhosis. Furthermore, liver cirrhosis rats were treated with low-dose (500 IU/kg) and high-dose (2,000 IU/kg) vitamin D intraperitoneally. The expression levels of TLR4/MyD88/NF-κB signaling pathway were evaluated by RT-PCR and Western blot. In conclusion, we determined the deficiency of vitamin D and down-regulation of DEFA5 and intestinal damage induced by liver cirrhosis. Moreover, vitamin D effectively inhibited liver cirrhosis-induced intestinal inflammation and oxidative stress through the TLR4/MyD88/NF-κB pathway. Vitamin D might be a promising therapeutic strategy for future treatment of liver-induced intestinal injury.

The aim of this study is to investigate the prognostic immune-related factors in breast cancer (BC) metastasis. The gene expression chip GSE159956 was downloaded from the gene expression omnibus database. Differentially expressed genes (DEGs) were selected using GEO2R online tools based on lymph node and metastasis status. The intersected survival-associated DEGs were screened from the Kaplan–Meier curve. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) annotation analyses were performed to determine the survival-associated DEGs. Immune-related prognostic factors were screened based on immune infiltration. The screened prognostic factors were verified by the Cancer Genome Atlas (TCGA) database and single-sample gene set enrichment analysis (ssGSEA). As a result, twenty-eight upregulated and three downregulated genes were generated by the survival analysis. The enriched GO and KEGG pathways were mostly correlated with “regulation of cellular amino acid metabolic process,” “proteasome complex,” “endopeptidase activity,” and “proteasome.” Six of 19 (17 upregulated and 2 downregulated) immune-related prognostic factors were verified by the TCGA database. Four immune-related factors were obtained after ssGSEA, and three significant immune-related factors were selected after univariate and multivariate analyses. Based on the risk score receiver operating characteristic, the three immune-related prognosis factors could be potential biomarkers of BC metastasis. In conclusion, APPL1, RPS6KB2, and GALK1 may play a pivotal role as potential biomarkers for prediction of BC metastasis.

Immunogenic cell death (ICD), a unique form of cancer cell death, has therapeutic potential in anti-tumour immunotherapy. The aim of this study is to explore the predictive potential of ICD in the prognosis and immunotherapy outcomes of glioblastoma multiforme (GBM). RNA sequencing data and clinical information were downloaded from three databases. Unsupervised consistency clustering analysis was used to identify ICD-related clusters and gene clusters. Additionally, the ICD scores were determined using principal component analysis and the Boruta algorithm via dimensionality reduction techniques. Subsequently, three ICD-related clusters and three gene clusters with different prognoses were identified, with differences in specific tumour immune infiltration-related lymphocytes in these clusters. Moreover, the ICD score was well differentiated among patients with GBM, and the ICD score was considered an independent prognostic factor for patients with GBM. Furthermore, two datasets were used for the external validation of ICD scores as predictors of prognosis and immunotherapy outcomes. The validation analysis suggested that patients with high ICD scores had a worse prognosis. Additionally, a higher proportion of patients with high ICD scores were non-responsive to immunotherapy. Thus, the ICD score has the potential as a biomarker to predict the prognosis and immunotherapy outcomes of patients with GBM.

Circ_0038467 and miR-203 exert important functions in lipopolysaccharide (LPS)-induced inflammation, which contributes to osteoarthritis (OA). Our preliminary deep sequencing analysis revealed altered expression of Circ_0038467 and miR-203 in OA and a close correlation between them. This study was therefore to explore crosstalk between them in OA. The expression of Circ_0038467, mature miR-203, and miR-203 precursor in OA patients and controls was determined using RT-qPCR. An overexpression assay was performed to explore the role of Circ_0038467 in regulating the expression of mature miR-203 and miR-203 precursor. Cell apoptosis was analyzed by cell apoptosis assay. Circ_0038467 was upregulated in OA and positively correlated with mature miR-203 but not that of miR-203 precursor. In chondrocytes, increased expression levels of both Circ_0038467 and miR-203 were observed after LPS treatment. In chondrocytes, overexpression of Circ_0038467 increased the expression levels of mature miR-203 but not that of miR-203 precursor. Overexpression of Circ_0038467 and miR-203 increased cell apoptosis. Then, the miR-203 inhibitor reversed the effects of overexpression of Circ_0038467 on cell apoptosis. Interestingly, Circ_0038467 was detected in both the cytoplasm and nucleus. Circ_0038467 directly interacted with the precursor miR-203. Therefore, Circ_0038467 is highly expressed in OA and it may promote the production of mature miR-203 to increase apoptosis of chondrocytes induced by LPS.

Fine-needle aspiration cytology (FNAC) is commonly used to obtain a pre-surgical pathological diagnosis in many organs, but its cost-effectiveness in lymphadenopathy has not been studied yet. We calculated the cost and diagnostic accuracy of a diagnostic algorithm that uses FNAC as a first-line procedure and compared it to a purely surgical approach in 545 consecutive lymphadenopathies. In 74% of the cases, FNAC alone can obtain a sufficiently detailed diagnosis, avoiding the surgical biopsy. In doing so, the average cost of diagnosis is cut to less than one-third, the patient avoids an invasive procedure and the diagnosis is reached earlier. In conclusion, the systematic use of lymph node-FNAC in the initial assessment of lymphadenopathy is clinically and economically advantageous as it avoids surgical biopsies in cases where cytology can suffice.

Non-small-cell lung cancer (NSCLC) is a dominating type of lung cancer with high morbidity and mortality. Midazolam has been reported to promote cell apoptosis in NSCLC, but the molecular mechanism of midazolam remains to be further explored. In the current work, cell viability, proliferation, migration, and apoptosis rates of NSCLC cells treated with midazolam were measured using cell counting kit-8 assay, 5-ethynyl-2′-deoxyuridine (EdU) and colony formation assays, transwell, and flow cytometry assay, respectively, to evaluate the malignant behaviors. Western blot was applied to access EGFR/MEK/ERK pathway-related protein levels. The results demonstrated midazolam significantly declined the viability of NSCLC cells. Furthermore, midazolam restrained cell proliferation and migration and contributed to cell apoptosis in NSCLC. Midazolam exerted suppressive function to EGFR pathway during NSCLC development. Moreover, the activation of EGFR/MEK/ERK pathway abrogated the effects of midazolam on NSCLC cell proliferation, apoptosis, and migration. Taken together, midazolam exhibited anti-tumor effects hallmarked by EGFR pathway inhibition, providing a novel insight into the treatment of NSCLC.

To explore the pharmacological mechanism of naringin (NRG) in renal fibrosis (RF) based on network pharmacology combined with molecular docking and experimental validation. We used databases to screen for the targets of NRG and RF. The “drug-disease network” was established using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of targets were performed using Metascape, and molecular docking was performed using Schrödinger. We established an RF model in both mice and cells to validate the results of network pharmacology. After screening the database, we identified 222 common targets of NRG and RF and established a target network. Molecular docking showed that the target AKT had a good interaction with NRG. We found that the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway was enriched by multiple targets and served as a target for experimental validation through GO and KEGG. The results revealed that NRG ameliorated renal dysfunction, reduced the release of inflammatory cytokines, decreased the expression of α-SMA, collagen I, and Fn, and recovered the expression of E-cad by inhibiting the PI3K/AKT signaling pathway. Our study used pharmacological analysis to predict the targets and mechanisms of NRG against RF. Furthermore, experiments proved that NRG inhibited RF effectively by targeting the PI3K/AKT signaling pathway.

Laryngeal squamous cell carcinoma (LSCC) is a common malignancy among men in the anatomical position of head and neck. Hoarseness, pharyngalgia, and dyspnea are common symptoms. LSCC is a complex polygenic carcinoma that is caused by many factors involving polygenic alteration, environmental pollution, tobacco, and human papillomavirus. Classical protein tyrosine phosphatase nonreceptor type 12 (PTPN12) has been extensively studied to decipher its mechanism as a tumor suppressor gene in various human carcinomas; however, there is no comprehensive elucidation of the PTPN12 expression and its regulatory mechanisms in LSCC. As such, we expect to provide new insights for finding new biomarkers and effective therapeutic targets in LSCC. Immunohistochemical staining, western blot (WB), and quantitative real-time RT-PCR (qRT-PCR) were used for the messenger RNA (mRNA) and protein expression analyses of PTPN12, respectively. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H -tetrazolium, clone formation, transwell migration, and transwell invasion assays were used to assess the proliferation, migration, and invasion ability of LSCC cells. Online prediction and design software tools (http://www.targetscan.org/ and http://www.microRNA.org) were used to predict associated miRNA. Studying the targeted regulatory relationship between miR-146b-3p and PTPN12 was based on dual luciferase reporter gene analysis. qRT-PCR was used to assess miR-146b-3p expression in LSCC. miR-146b-3p inhibitor and mimic were transfected, followed by qRT-PCR and WB assays to detect the expression of PTPN12. The gain and loss functional experiments were used to investigate the effects of miR-146b-3p transfection on the proliferation, migration, and invasion of tumor cells. Online bioinformatics prediction software (https://cn.string-db.org/ and https://www.genecards.org/) was used to determine potential downstream target genes of PTPN12. qRT-PCR and WB analyses were used to assess the mRNA and protein expression levels of target genes. Our study showed significantly decreased mRNA and protein expression levels of PTPN12 in LSCC compared with the adjacent normal tissues. The lower PTPN12 mRNA expression was correlated with pathological differentiation, and lower PTPN12 protein expression was correlated with the TNM stage in LSCC tissues. The subsequent in vitro functional analyses showed the inhibitory effect of PTPN12 over-expression on the proliferation, migration, and invasiveness abilities of LSCC cell line. Using online prediction and design software, miR-146b-3p was searched to target PTPN12. The miR-146b-3p was expressed at a high level in LSCC tissues and cell lines. Luciferase reporter assay exhibited that miR-146b-3p inhibited the luciferase activity of PTPN12 markedly. The functional analyses showed the tumor-promoting role of miR-146b-3p on the proliferation, migration, and invasiveness abilities of LSCC cell. Furthermore, co-transfection of cells with miR-146b-3p and PTPN12 significantly restored the inhibitory effect of PTPN12 on LSCC cell growth, migration, and invasiveness. This phenomenon unveiled that miR-146b-3p regulated the proliferation, migration, and invasion of LSCC cells by targeting PTPN12. EGFR and ERBB2 were selected as the downstream-regulation target genes. Up-regulation of PTPN12 significantly suppressed EGFR expression. Accordingly, the miR-146b-3p mimic significantly up-regulated the EGFR expression. However, up-regulation of PTPN12 and miR-146b-3p mimic suppressed ERBB2 protein expression but induced its gene expression. Down-regulation of PTPN12 is associated with up-regulation of miR-146b-3p in LSCC. Moreover, PTPN12 serves as a tumor suppressor gene through regulating the proliferation, migration, and invasion of LSCC cells. miR-146b-3p/PTPN12 axis is expected to be a novel therapeutic target in LSCC.

The miR-141-3p has been reported to participate in regulating autophagy and tumor-stroma interactions in ovarian cancer (OC). We aim to investigate whether miR-141-3p accelerates the progression of OC and its effect on macrophage 2 polarization by targeting the Kelch-like ECH-associated protein1-Nuclear factor E2-related factor2 (Keap1-Nrf2) pathway. SKOV3 and A2780 cells were transfected with miR-141-3p inhibitor and negative control to confirm the regulation of miR-141-3p on OC development. Moreover, the growth of tumors in xenograft nude mice treated by cells transfected with miR-141-3p inhibitor was established to further testify the role of miR-141-3p in OC. The expression of miR-141-3p was higher in OC tissue compared with non-cancerous tissue. Downregulation of miR-141-3p inhibited the proliferation, migration, and invasion of ovarian cells. Furthermore, miR-141-3p inhibition also suppressed M2-like macrophage polarization and in vivo OC progression. Inhibition of miR-141-3p significantly enhanced the expression of Keap1, the target gene of miR-141-3p, and thus downregulated Nrf2, while activation of Nrf2 reversed the reduction in M2 polarization by miR-141-3p inhibitor. Collectively, miR-141-3p contributes to tumor progression, migration, and M2 polarization of OC by activating the Keap1-Nrf2 pathway. Inhibition of miR-141-3p attenuates the malignant biological behavior of ovarian cells by inactivating the Keap1-Nrf2 pathway.

In view of the association between long noncoding RNA OIP5-AS1 and osteoarthritis (OA) pathology, the corresponding potential mechanism is worthy of exploration. Primary chondrocytes were identified by morphological observation and immunohistochemical staining of collagen II. The association between OIP5-AS1 and miR-338-3p was analyzed by StarBase and dual-luciferase reporter assay. After the expression of OIP5-AS1 or miR-338-3p in interleukin (IL)-1β-stimulated primary chondrocytes and CHON-001 cells was manipulated, cell viability, proliferation, apoptosis rate, apoptosis-related protein (cleaved caspase-9, Bax) expressions, extracellular matrix (ECM) (matrix metalloproteinase (MMP)-3, MMP-13, aggrecan, and collagen II), PI3K/AKT pathway, and mRNA expressions of inflammatory factors (IL-6 and IL-8), OIP5-AS1, and miR-338-3p were determined by cell counting kit-8, EdU, flow cytometry, Western blot, and quantitative reverse transcription-polymerase chain reaction. As a result, the expression of OIP5-AS1 was downregulated in IL-1β-activated chondrocytes, while miR-338-3p was overexpressed. OIP5-AS1 overexpression reversed the effects of IL-1β on viability, proliferation, apoptosis, ECM degradation, and inflammation in chondrocytes. However, OIP5-AS1 knockdown exhibited opposite effects. Interestingly, the effects of OIP5-AS1 overexpression were partially offset by miR-338-3p overexpression. Furthermore, OIP5-AS1 overexpression blocked the PI3K/AKT pathway by modulating miR-338-3p expression. In sum, OIP5-AS1 promotes viability and proliferation, and inhibits apoptosis and ECM degradation in IL-1β-activated chondrocytes by targeting miR-338-3p through blocking the PI3K/AKT pathway, indicating an attractive strategy for OA treatment.

Long non-coding RNAs (lncRNAs) play a key role in cancer progression, including non-small-cell lung cancer (NSCLC). LncRNA long intergenic non-protein-coding RNA 00607 (LINC00607) was previously discovered to be downregulated in lung adenocarcinoma tissues. Nevertheless, the potential role of LINC00607 in NSCLC is still unclear. The expression of LINC00607, miR-1289, and ephrin A5 (EFNA5) in NSCLC tissues and cells was tested by reverse transcription quantitative polymerase chain reaction. Cell viability, proliferation, migration, and invasion were measured by 3-(4,5-dimethylthiazole-2-y1)-2,5-diphenyl tetrazolium bromide, colony formation, wound healing, and Transwell assays. The relationship among LINC00607, miR-1289, and EFNA5 in NSCLC cells was verified by the luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation assay. In this study, LINC00607 was downregulated in NSCLC, and its low level is associated with poor prognosis of NSCLC patients. Furthermore, LINC00607 overexpression repressed NSCLC cell viability, proliferation, migration, and invasion. LINC00607 bound with miR-1289 in NSCLC. EFNA5 was a downstream target of miR-1289. EFNA5 overexpression also inhibited NSCLC cell viability, proliferation, migration, and invasion. EFNA5 knockdown antagonized the influence of LINC00607 overexpression on NSCLC cell phenotypes. Overall, LINC00607 serves as a tumor suppressor gene in NSCLC through binding with miR-1289 and modulating the level of EFNA5.

The study of subjective well-being (SWB) is important as it is related to the reduction of morbidity and mortality, with the maintenance of functionality and autonomy in the elderly population. The impact of the formative intervention on the SWB of informal caregivers (ICGs) during the pandemic crisis of COVID-19 was analyzed. This study is a quasi-experimental single-group, longitudinal study with a sample of 31 ICGs and their dependents. A form was used for data collection, and data processing was performed using IBM SPSS (Statistical Package for the Social Sciences), using descriptive statistics and inferential statistics. Of the total sample, the majority were female (90.3%). The difference between the mean of positive affection and negative affection at Moment 1 (M1) was –0.0581 ± 0.71590 and 0.04645 ± 0.53326 at Moment 2 (M2). The mean rank ordering of the difference between the two types of affection differed significantly between M2 and M1 (Wilcoxon: p < 0.000), with that of M2 being higher than M1 (16.93 > 2.50). The formative intervention, within the scope of community nursing, had a significant impact on increasing the SWB of the ICG in this sample. This study may contribute to improving the SWB of ICG and their dependents.

Mitochondrial dysfunction and oxidative stress are considered to be two main drivers of diabetic myocardial ischemia-reperfusion injury (DM + MIRI). Nuclear factor-erythroid 2-related factor 2 (Nrf2) and Dynamin-related protein 1 (Drp1) play central roles in maintaining mitochondrial homeostasis and regulating oxidative stress, but the effects of the Nrf2-Drp1 pathway on DM-MIRI have not been reported. The aim of this study is to investigate the role of the Nrf2-Drp1 pathway in DM + MIRI rats. A rat model of DM + MIRI and H9c2 cardiomyocyte injury were constructed. The therapeutic effect of Nrf2 was assessed by detecting myocardial infarct size, mitochondrial structure, levels of myocardial injury markers and oxidative stress, apoptosis, and Drp1 expression. The results showed that DM + MIRI rats had increased myocardial infarct size and Drp1 expression in myocardial tissue, accompanied by increased mitochondrial fission and oxidative stress. Interestingly, Nrf2 agonist dimethyl fumarate (DMF) could significantly improve cardiac function, mitochondrial fission, and decrease oxidative stress levels and Drp1 expression after ischemia. However, these effects of DMF would be largely counteracted by the Nrf2 inhibitor ML385. Additionally, Nrf2 overexpression significantly suppressed Drp1 expression, apoptosis, and oxidative stress levels in H9c2 cells. Nrf2 attenuates myocardial ischemia-reperfusion injury in DM rats by reducing Drp1-mediated mitochondrial fission and oxidative stress.

Unfolded protein response (UPR) plays an important role in the pathogenesis of many liver diseases. BMI1 has a liver protection effect, but whether it participates in the regulation of hepatocyte death through UPR is not well defined. Herein, the endoplasmic reticulum stress model was established by inducing hepatocyte line (MIHA) with tunicamycin (TM, 5 µg/ml). Cell counting kit-8 assay and flow cytometry were used to evaluate the viability and apoptosis of hepatocytes. The expression levels of BMI1, KAT2B, and proteins related to UPR (p-eIF2α, eIF2α, ATF4, and ATF6), NF-κB (p65 and p-p65), apoptosis (cleaved caspase-3, bcl-2, and bax) and necroptosis (p-MLKL and MLKL) were determined by Western blot. The relationship between KAT2B and BMI1 was determined by co-immunoprecipitation and ubiquitination assay. The results showed that TM not only promoted UPR, apoptosis, and necroptosis in hepatocytes but also upregulated the expression levels of BMI1 and KAT2B and activated NF-κB pathway. BAY-117082 reversed the effects of TM on viability, apoptosis, NF-κB pathway, and BMI1 but strengthened the effects of TM on KAT2B/MLKL-mediated necroptosis. BMI1 promoted the ubiquitination of KAT2B, and BMI1 overexpression reversed the effects of TM on viability, apoptosis, and KAT2B/MLKL-mediated necroptosis. In summary, overexpression of BMI1 promotes the ubiquitination of KAT2B to block the MLKL-mediated necroptosis of hepatocytes.

The objective of this study was to offer new approach for selection of persons with asymptomatic bladder cancer (BC) and highly risky persons for the BC occurrence. Also, it is a part of the BC screening protocol (study is ongoing). Study populations were 100 newly diagnosed (diagnosis maximum 1-year old) males with BC and 100 matched (by sex and age ±5 years) controls (not oncology patients from the same hospital). A hospital based, matched case–control study was done. Statistical analysis comprised of four steps: t -test, univariate logistic regression, multivariate logistic regression, and scoring. The fifth step comprised of two changes, deleting one variable and addition of another variable. Six variables were statistically significant: Caucasian men over 45 years age, tobacco smoking over 40 pack-years, occupational and/or environmental exposure to the proved BC carcinogens over 20 years, macrohematuria, difficulty urinating, BC in relatives up to fourth degree of kinships, and they were used for an easy and fast selection of the individuals with high risk for BC occurrence and BC asymptomatic patients (optimal selection at the population level). The final results showed highly significant probability ( p < 0.001), with area under ROC curve of 0.913, negative predictive values of 89.7% (95% CI 10.3–100%), and a specificity of 78%. Positive predictive value was 80.5% (95% CI 19.5–100%) and a sensitivity of 91%. It is possible to recruit asymptomatic BC patients (primary prevention) by using this model, as well as persons with high risk for BC occurrence (primordial prevention). This study is the first part of the BC screening protocol and the second part of the BC screening protocol study is ongoing (urine analysis).

The aim of this study was to verify the effects of circular RNA nuclear factor of activated T-cells, cytoplasmic 3 (circNFATC3), in oral squamous cell carcinoma (OSCC) development. The levels of circNFATC3, microRNA-520h (miR-520h), and lactate dehydrogenase A (LDHA) were measured by qRT-PCR and western blot analysis. The cellular functions were assessed by using commercial kits, MTT assay, EdU assay, flow cytometry analysis, and transwell assay. The interactions between miR-520h and circNFATC3 or LDHA were confirmed by dual-luciferase reporter assay. Finally, the mice test was enforced to evaluate the character of circNFATC3. We observed that the contents of circNFATC3 and LDHA were upregulated and miR-520h levels were downregulated in OSCC tissues compared with those in paracancerous tissues. For functional analysis, circNFATC3 knockdown repressed the cell glycolysis metabolism, cell proliferation, migration, and invasion, although it improved cell apoptosis in OSCC cells. LDHA could regulate the development of OSCC. circNFATC3 acted as a miR-520h sponge to modulate LDHA expression. In addition, the absence of circNFATC3 subdued tumor growth in vivo . In conclusion, circNFATC3 promoted the advancement of OSCC by adjusting the miR-520h/LDHA axis.

Ventilation in the prone position (PP) has been used for decades in patients with acute respiratory distress syndrome (ARDS) and is associated with a reduction in mortality rate. Its application has been extended to patients with SARS-Cov-2 pneumonia and is recommended by the main international organizations. The objective is to evaluate the effects of PP on the outcomes of patients with SARS-Cov-2 pneumonia admitted to a multipurpose intensive care unit. This is a quantitative, quasi-experimental, single-group, longitudinal and retrospective study. Data were collected based on clinical records. Data were processed using SPSS (version 26.0). PP significantly increased oxygenation in patients with SARS-Cov-2 pneumonia, with a mean increase of 21.27% between the PaO 2 /FiO 2 ratio before and after the PP. However, its effectiveness was inversely proportional to the number of cycles performed and the timing of orotracheal intubation. PP improves oxygenation in patients with SARS-Cov-2 pneumonia. However, multiple PP sessions are not beneficial, as this procedure is no longer effective after the fourth cycle. This study thus contributes to better management in the approach of critically ill patients with SARS-Cov-2 pneumonia.

The objective was to explore the efficacy of Tongdu Tuina manipulation in the treatment of primary single-symptom enuresis in children. A total of 102 children aged 5–16 with primary single-symptom enuresis were included in this study and randomly assigned to the Tuina group, the medication group and the control group, with 34 children in each group. The Tongdu Tuina group included manipulation of the Guanyuan, Qihai, Zhongji, Mingmen, kidney, Baihui, Sishencong and bladder acupoints, five times a week, the medication group was treated with 0.1 mg desmopressin acetate every night, and in the control group, the patients were given foods with high water content and underwent water deprivation 2 h before bedtime every night. The intervention time of each group was 1 month. The participants were followed up on Day 1 following treatment, as well as half a month, 1 month and 3 months after the implementation of the intervention measures, and the effective rate, the incidence of enuresis per week and the recurrence rate were calculated. As a result baseline demographic characteristics were comparable among 102 patients. Overall, 32 patients in the Tongdu Tuina group, 30 patients in the medication group and 34 patients in the control group completed the intervention. After half a month of treatment, there was no significant difference in the therapeutic efficacy among the three groups ( P = 0.158), but each treatment could effectively reduce the frequency of weekly enuresis. The frequency of weekly enuresis in the Tongdu Tuina group was 3.8 ± 1.1 times, while that in the medication group was 4.0 ± 2.0 times. The frequency of weekly enuresis in the control group was 4.7 ± 1.8 times, and the difference was statistically significant ( P = 0.016). After 1 month of treatment, the effective rates of the Tongdu Tuina group and the medication group were significantly increased (87.5% vs 83.33%, P < 0.0001), which was not the case with the control group. The frequency of enuresis was 1.9 ± 2.1 times per week in the Tongdu Tuina group, 2.4 ± 1.8 times per week in the medication group and 4.0 ± 0.9 times per week in the control group after 1 month of treatment. The difference between the three groups was statistically significant ( P = 0.021), and there was a difference between the Tongdu Tuina group and the medication group ( P < 0.0001). There was no significant difference between recurrence rate and the incidence of adverse events ( P = 0.837, P = 0.856). In conclusion, both Tuina manipulation and desmopressin treatment can effectively improve children’s primary single-symptom enuresis with safety. However, Tongdu Tuina therapy may be superior to desmopressin treatment.

Dihydroartemisinin (DHA) has been found to inhibit the expression of von Willebrand factor (VWF), a marker of endothelial cell injury, but its mechanism in cerebral ischemia/reperfusion (I/R) injury remains obscure. In this study, I/R model was constructed through middle cerebral artery occlusion (MCAO) in rats, followed by DHA administration. The effect of DHA on rat cerebral I/R injury was investigated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin staining, TUNEL staining, and Western blot. Brain microvascular endothelial cells (BMVECs) isolated from newborn rats were exposed to oxygen–glucose deprivation/reoxygenation (OGD/R), and then treated with DHA. The results showed that MCAO treatment induced infarction, nerve cell apoptosis, and brain tissue impairment in rats, which was mitigated by DHA. OGD/R inhibited viability and accelerated apoptosis of BMVECs, which was alleviated by DHA. I/R procedures or OGD/R up-regulated expressions of VWF, ATG7, Beclin1, and LC3-II/LC3-I ratio, while down-regulating Occludin, Claudin-5, ZO-1, P62, SIRT1, and FOXO1 expressions in vivo and in vitro ; however, these effects of I/R procedures or OGD/R were offset by DHA. VWF overexpression reversed the above effects of DHA on OGD/R-induced BMVECs. In summary, DHA ameliorates cerebral I/R injury in rats by reducing VWF level and activating autophagy-mediated SIRT1/FOXO1 signaling pathway.

Circular RNA (circRNA) is involved in the pathogenesis of atherosclerosis (AS). The present work analyzed the RNA expression of circ_0113656, microRNA-188-3p (miR-188-3p), and insulin-like growth factor 2 (IGF2) by quantitative real-time polymerase chain reaction. The protein expression of proliferating cell nuclear antigen (PCNA), matrix metalloprotein 2 (MMP2), and IGF2 was detected by Western blotting. Cell viability, proliferation, invasion, and migration were analyzed using the cell counting kit-8, 5-ethynyl-2′-deoxyuridine, transwell invasion, and wound-healing assays, respectively. The interactions among circ_0113656, miR-188-3p, and IGF2 were identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. The results showed that circ_0113656 and IGF2 expression were significantly upregulated, while miR-188-3p was downregulated in the blood of AS patients and oxidized low-density lipoprotein (ox-LDL)-treated HVSMCs in comparison with controls. The ox-LDL treatment induced HVSMC proliferation, migration, and invasion accompanied by increases in PCNA and MMP2 expression; however, these effects were attenuated after circ_0113656 knockdown. Circ_0113656 acted as a miR-188-3p sponge and it regulated ox-LDL-induced HVSMC disorders by binding to miR-188-3p. Besides, the regulation of miR-188-3p in ox-LDL-induced HVSMC injury involved IGF2. Further, the depletion of circ_0113656 inhibited IGF2 expression by interacting with miR-188-3p. Thus, the circ_0113656/miR-188-3p/IGF2 axis may mediate ox-LDL-induced HVSMC disorders in AS, providing a new therapeutic strategy for AS.

It is predictable that the renin–angiotensin–aldosterone and kinin–kallikrein systems are dysregulated in COVID-19 (COV) patients because SARS-CoV-2 requires ACE2 to cause an infection. This study aimed to assess the serum levels of des-arg(9)-bradykinin (DABK) and angiotensin 1–7 (ang-(1–7)) in patients with COV who had the above-mentioned cardiovascular disease risk factors. In a cross-sectional study, 69 COV patients were selected among patients referred to the main referral center for these patients, in Kerman, Iran, and 73 matched control (non-COV) individuals among individuals who participated in the KERCARD cohort study. Serum levels of DABK and ang-(1–7) were measured by ELISA in the groups of CTL (healthy), HTN, DM, OB, COV, COV + HTN, COV + DM, and COV + OB. Ang-(1–7) levels were lower in the COV + HTN group compared to the HTN group. DABK levels were higher in the COV, HTN, and OB groups and in DM + COV subjects compared to their corresponding control group. The levels of ang-(1–7) and DABK were related to HTN and OB, respectively. According to the findings, we can infer that an increase in DABK production in those with the cardiovascular disease risk factors of diabetes, obesity, and hypertension or a decrease in ang-(1–7) in those with hypertension may contribute to the adverse outcomes of SARS-CoV-2 infection.

The aim of this study was to evaluate the effect of maternal age and body mass index (BMI) on induction of labor with oral misoprostol for premature rupture of membrane (PROM) at term. We have conducted retrospective cross-sectional study, including only term (37 weeks or more of gestation) PROM in healthy nulliparous women with a negative vaginal-rectal swab for group B streptococcus, a single cephalic fetus with normal birthweight, and uneventful pregnancy that were induced after 24 h from PROM. Ninety-one patients were included. According to the multivariate logistic regression, age and BMI odds ratio (OR) for induction success were 0.795 and 0.857, respectively. The study population was divided into two groups based on age (<35 and ≥35 years) and obesity (BMI <30 and ≥30). Older women reported a higher induction failure rate ( p < 0.001); longer time to cervical dilation of 6 cm ( p = 0.03) and delivery ( p < 0.001). Obese women reported a higher induction failure rate ( p = 0.01); number of misoprostol doses ( p = 0.03), longer time of induction ( p = 0.03) to cervical dilatation of 6 cm ( p < 0.001), and delivery ( p < 0.001); and higher cesarean section ( p = 0.012) and episiotomy rate ( p = 0.007). In conclusion, maternal age and BMI are two of the main factors that influence oral misoprostol efficacy and affect the failure of induction rate in term PROM.

Corona virus disease 2019 (COVID-19) is prone to induce multiple organ damage. The kidney is one of the target organs of SARS-CoV-2, which is susceptible to inducing acute kidney injury (AKI). Huanglian Jiedu Decoction (HLJDD) is one of the recommended prescriptions for COVID-19 with severe complications. We used network pharmacology and molecular docking to explore the therapeutic and protective effects of HLJDD on COVID-19-associated AKI. Potential targets related to “HLJDD,” “COVID-19,” and “Acute Kidney Injury/Acute Renal Failure” were identified from several databases. A protein–protein interaction (PPI) network was constructed and screened the core targets according to the degree value. The target genes were then enriched using gene ontology and Kyoto Encyclopedia of Genes and Genomes. The bioactive components were docked with the core targets. A total of 65 active compounds, 85 common targets for diseases and drugs were obtained; PPI network analysis showed that the core protein mainly involved JUN, RELA, and AKT1; functional analysis showed that these target genes were mainly involved in lipid and atherosclerosis signaling pathway and IL-17 signal pathway. The results of molecular docking showed that JUN, RELA, and AKT1 had good binding activity with the effective chemical components of HLJDD. In conclusion, HLJDD can be used as a potential therapeutic drug for COVID-19-associated AKI.

Diagnosis of central precocious puberty (CPP) in girls remains a huge challenge. The current study was to measure the serum expression of methyl-DNA bind protein 3 (MBD3) in CPP girls and assess its diagnostic efficacy. To begin with, we enrolled 109 CPP girls and 74 healthy pre-puberty girls. Then, MBD3 expression in their serum samples was measured via reverse transcription-quantitative polymerase chain reaction, and its diagnostic efficacy on CPP was assessed via the receiver operating characteristic (ROC) curve, followed by correlation analysis between serum MBD3 and patient age, gender, bone age, weight, height, body mass index, basal luteinizing hormone (LH), peak LH, basal follicle-stimulating hormone (FSH), peak FSH, and ovarian size using bivariate correlations method. Finally, independent predictors of MBD3 expression were confirmed using multivariate linear regression analysis. MBD3 was highly expressed in sera of CPP patients. The area under the ROC curve of MBD3 diagnosing CCP was 0.9309, with 1.475 cut-off value (92.66% sensitivity and 86.49% specificity). MBD3 expression positively correlated with basal LH, peak LH, basal FSH, and ovarian size, among which basal LH was considered the strongest independent predictor of MBD3, followed by basal FSH and peak LH. In summary, serum MBD3 could act as a biomarker in aiding CPP diagnosis.

Clinical presentation of central nervous system (CNS) infections caused by varicella-zoster virus (VZV) is highly sophisticated, making identification challenging. We retrospectively reported 18 cases of VZV neurologic disease confirmed by metagenomic next-generation sequencing (mNGS). The detection rate of mNGS was higher than that of PCR assay (100 vs 66.7%, p < 0.05) and serum IgM antibody (100 vs 68.8%, p < 0.05) measurement. Of the 18 cases, five patients were diagnosed with acute meningitis, three with acute meningitis combined with facial neuritis, three with acute meningitis combined with polycranial neuritis, and the remaining seven with various clinical diagnoses. Typical clinical symptoms included headache (15), fever (9), and rash (11). Cranial or spinal MRI showed abnormalities in 12 patients, and 17 patients had obvious neurological symptoms. The predominant genotype of VZV in this study was genotype J (100%, 10/10). All patients were treated with acyclovir/penciclovir and dexamethasone, 16 recovered and 2 died. Our study highlights the good performance of mNGS in diagnosing CNS infection caused by VZV. It could provide additional diagnostic evidence in patients with diverse clinical spectrum and variable manifestations.

Fistula in ano is a common anorectal disease in adults. Currently, surgery remains the definitive therapeutic approach, but in some cases, it can lead to serious complications as faecal or gas incontinence. Therefore, sphincter sparing treatments should be considered for complex fistulas. One of the sphincteric preserving treatment is the filling with a dermal extract commonly called “collagen glue” as Salvecoll-E ® gel. This is a multicentric, prospective, observational study on the use of Salvecoll-E ® gel in treatment of complex anal fistulas. We treated 70 patients from May 2016 to May 2017. In the first phase, we debrided the fistula tract using a loose seton kept for 4–6 weeks. In the second phase, the seton was removed and the fistula tract was filled with Salvecoll-E ® gel. In this article, we report results at 36 months of follow-up. Fifty patients (71.4%) had completely healed fistula within 36 months of follow-up. Twenty-eight patients (28.2%) had recurrences. Among these failures, 65% were within 6 months. All low transphincteric fistulas healed. Recurrences occurred only in median and high transphincteric fistulas. No patient had a worsening of continence status measured with Cleveland Clinic Florida Incontinence Severity score. Salvecoll-E ® gel is a recent finding among sphincter-sparing treatments. In this study, we demonstrate that it is a safe option in the treatment of complex fistulas. Final results are satisfactory and in line with the best results published in literature among mini-invasive treatments.

Study has demonstrated the abnormal expression and role of lncRNA CASC15 in diabetes patients with chronic renal failure. However, its role in diabetes nephropathy (DN) is still unclear. This study aimed to investigate the potential mechanism and role of lncRNA CASC15 in DN. The relationship between miR-424 and CASC15/SP-A was predicted by Starbase software and verified by luciferase reporter assay. HK-2 cells were treated with 25 mM glucose (HG) for 24 h to establish DN cell model. MTT and flow cytometry analysis were carried out to test cell proliferation and apoptosis. Epithelial-to-mesenchymal transition (EMT) markers were analyzed by RT-qPCR and western blot assay. We proved that CASC15 could interact with miR-424, and SP-A was a target of miR-424. HG-treatment significantly enhanced lncRNA CASC15 level and decreased miR-424 level in HK-2 cells. LncRNA CASC15-siRNA significantly improved cell viability, repressed apoptosis, promoted E-cadherin expression, and inhibited N-cadherin expression in HG-treated HK-2 cells, and these effects were reversed by miR-424 inhibitor. SP-A was highly expressed in HG-treated HK-2 cells. The biological effects of miR-424 mimic on HG-treated HK-2 cells were reversed by SP-A-plasmid. In conclusion, lncRNA CASC15 inhibition relieved HG-induced HK-2 cell injury and EMT through miR-424/SP-A axis.

This research aimed to evaluate the eradication efficacy, safety, and gastrointestinal symptom relief rates of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy in primary eradication patients in Yangzhou, China. It also investigated the possible factors influencing the success of different H elicobacter pylori eradication regimens. A single-center, prospective, open-label, randomized controlled study was performed from December 2020 and October 2021, in which 255 patients with H. pylori infection were assigned in a 1:1:1 ratio to the three different groups. Our results showed that high-dose dual therapy (91.0%, 71/78) and resistance gene-based triple therapy (94.9%, 75/79) achieved eradication rates and compliance equivalent to those of empirical bismuth quadruple therapy (85.3%, 64/75) in the per-protocol analysis, while high-dose dual therapy had lower rates of adverse events (11.5%, 9/78, P < 0.05), fewer side effects, and greater safety. Most patients’ gastrointestinal discomfort symptoms improved after eradication of H. pylori . Poor compliance ( P < 0.05) and antibiotic resistance ( P < 0.05) were risk factors for the efficacy of H. pylori eradication. Therefore, the appropriate regimen can be individualized for eradication therapy in clinical practice according to the patient’s resistance and tolerance to the drug.

Heart failure (HF) is a major global cause of morbidity and mortality. This study aimed to elucidate the role of secreted protein acidic and rich in cysteine-related modular calcium-binding protein 2 (SMOC2) in HF development and its underlying mechanism. Using a rat HF model, SMOC2 expression was examined and then knocked down via transfection to assess its impact on cardiac function and damage. The study also evaluated the effects of SMOC2 knockdown on autophagy-related molecules and the transforming growth factor beta 1 (TGF-β1)/SMAD family member 3 (Smad3) signaling pathway. Intraperitoneal injection of the TGF-β agonist (SRI-011381) into the HF rat model was performed to explore the SMOC2-TGF-β1/Smad3 pathway relationship. SMOC2 expression was elevated in HF rats, while its downregulation improved cardiac function and damage. SMOC2 knockdown reversed alterations in the LC3-II/I ratio, Beclin-1, and p62 levels in HF rats. Through transmission electron microscope, we observed that SMOC2 knockdown restored autophagosome levels. Furthermore, SMOC2 downregulation inhibited the TGF-β1/Smad3 signaling pathway, which was counteracted by SRI-011381. In conclusion, SMOC2 knockdown inhibits HF development by modulating TGF-β1/Smad3 signaling-mediated autophagy, suggesting its potential as a therapeutic target for HF.

This cohort study investigated the impact of chronic diseases on fall risk in middle-aged and older individuals, offering insights for fall prevention strategies. Analysing data from 4,670 participants aged 40+ years, we used a Cox proportional risk model to assess chronic disease types, numbers, and interactions with other factors on fall injury risk across age groups. Results showed that middle-aged adults with respiratory diseases had a 26% increased fall risk (hazard ratio [HR] = 1.26, 95% confidence interval [CI]: 1.05–1.48), and a linear dose–response relationship was observed between chronic disease number and fall risk ( p < 0.001). The study also examined interaction effects of chronic diseases with gender, disability, and fall injury history. Female middle-aged and older adults with chronic diseases had a 67% higher fall risk than their male counterparts without chronic diseases (HR = 1.67, 95% CI: 1.36–1.88). In conclusion, chronically ill middle-aged and older adults have a higher fall risk, with high-risk groups including women, those with chronic diseases, and individuals with fall injury history. Fall prevention efforts should target middle-aged adults as well.

Circular RNA (circRNA) THBS1 has been shown to exist as an oncogene in non-small-cell lung cancer, but its role in cervical cancer is still unclear. Our experiment aimed to uncover the functions and specific mechanism of circRNA THBS1 in cervical cancer cells. Levels of circRNA THBS1 and miR-543 in cervical cancer tissues and cell lines were assessed by RT-qPCR. starBase and dual luciferase reporter gene assay were applied for investigating the correlation between miR-543 and circRNA THBS1/HMGB2. Cell proliferation and apoptosis were evaluated by MTT and flow cytometry, respectively. Furthermore, the levels of HMGB2, E-cadherin, and N-cadherin in HeLa cells were determined by RT-qPCR and western blot analysis. Our data revealed that circRNA THBS1 was significantly upregulated and miR-543 was low expressed in cervical cancer tissues and cell lines. circRNA THBS1 interacted with miR-543 and negatively regulated miR-543 expression in HeLa cells. Silencing of circRNA THBS1 remarkably suppressed HeLa cells’ viability, accelerated cells’ apoptosis, and inhibited the EMT of HeLa cells, while these changes were reversed by miR-543 inhibitor. Moreover, miR-543 affected HeLa cells by targeting HMGB2. In conclusion, circRNA THBS1 silencing inhibited the malignant biological behaviors of cervical cancer cells via the regulation of miR-543/HMGB2 axis.

Circular RNA has been reported to play a key role in neuroblastoma (NB); however, the role of circ_0000285 in NB remains unclear. The aim of this study was to elucidate the role of circ_0000285 in NB. We studied the expression patterns of miR-582-3p and circ_0000285 in NB tissues and cells using real-time quantitative polymerase chain reaction. The expression of proteins associated with apoptosis (Bax and Bcl-2) and the proteins associated with Wnt/β-catenin (Wnt, p-Gsk-3β, Gsk-3β, β-catenin, and C-myc) were quantified by western blotting. In vivo animal models were prepared for the functional verification of circ_0000285 on tumor growth. The potential binding of circ_0000285 to miR-582-3p was ascertained using dual-luciferase reporter and RNA-binding protein immunoprecipitation experiments. Noticeable upregulation of circ_0000285 expression was observed in NB tumor samples and cell lines. In vivo and in vitro experiments indicated that the absence of circ_0000285 repressed NB cell proliferation and migration, provoked apoptosis, and impaired the activity of Wnt/β-catenin signaling. miR-582-3p is targeted by circ_0000285 and is poorly expressed in NB cells. The additional repression of miR-582-3p in NB cells after circ_0000285 silencing largely recovered circ_0000285 silencing-suppressed NB cell proliferation and migration and enhanced apoptosis. The absence of miR-582-3p restored Wnt/β-catenin signaling activity impaired by the knockdown of circ_0000285. circ_0000285 functions as an miR-582-3p sponge to strengthen Wnt/β-catenin signaling activity, thus exacerbating NB development. Graphical abstract

The goal of this study was to demonstrate the functions and specific mechanism of long non-coding RNA (lncRNA) GNAS-AS1 in lung adenocarcinoma. Levels of lncRNA GNAS-AS1, microRNA (miR)-433-3p, and Rab3A were assessed by quantitative real-time PCR (qRT-PCR). The target-binding sites of lncRNA GNAS-AS1, miR-433-3p, and Rab3A were predicted and confirmed by bioinformatics tool (StarBase) and a dual-luciferase reporter system. Cell proliferation and apoptosis were checked using MTT and flow cytometry, respectively. Additionally, the levels of apoptosis-related and epithelial–mesenchymal transition (EMT)-associated genes in A549 cells were analyzed by qRT-PCR and western blot. We found that lncRNA GNAS-AS1 was upregulated, miR-433-3p was low-expressed, and Rab3A was overexpressed in lung adenocarcinoma tissues and cell lines. LncRNA GNAS-AS1 interacted with miR-433-3p and negatively regulated miR-433-3p levels. Rab3A was a direct target of miR-433-3p. Downregulation of lncRNA GNAS-AS1 remarkably suppressed cell proliferation, promoted cell apoptosis, decreased B-cell lymphoma-2 (Bcl-2) expression, enhanced the Bcl-2-Associated X (Bax) level, promoted E-cadherin expression, and reduced N-cadherin and Rab3A levels. However, the miR-433-3p inhibitor reversed all these findings. Similarly, the inhibitory effects of miR-433-3p mimic on A549 cells were reversed by the Rab3A-plasmid. In conclusion, lncRNA GNAS-AS1 downregulation suppressed lung adenocarcinoma cell proliferation and EMT through the miR-433-3p/Rab3A axis.

UCA1 is predicted to bind to miR-132, which is a key player in the proliferation of vascular smooth muscle cells (VSMCs). This research studied the role of lncRNA UCA1 in atherosclerosis. The binding of UCA1 to miR-132 was proved by dual luciferase activity assay and RNA immunoprecipitation. UCA1 and miR-132 failed to affect each other’s expression in VSMCs. UCA1 was upregulated and miR-132 was decreased in atherosclerosis plasma. However, they are not closely correlated across atherosclerosis and control plasma sample. Interestingly, UCA1 suppressed the role of miR-132 in downregulating Lrrfip1 expression and promoting VSMC proliferation. Therefore, UCA1 is downregulated in atherosclerosis and may regulate miR-132/Lrrfip1 axis to promote VSMC proliferation.

Full spectrum flow cytometry brings a breakthrough for minimal residual disease (MRD) detection in acute myeloid leukemia (AML). We aimed to explore the role of a new panel in MRD detection. We established a 24-color full-spectrum flow cytometry panel. A tube of 24-color antibodies included CD45, CD117, CD34, HLA-DR, CD15, CD64, CD14, CD11c, CD11b, CD13, CD33, CD371, CD7, CD56, CD19, CD4, CD2, CD123, CD200, CD38, CD96, CD71, CD36, and CD9. We discovered that when a tube meets 26 parameters (24 colors), these markers were not only limited to the observation of MRD in AML, but also could be used for fine clustering of bone marrow cells. Mast cells, basophils, myeloid dendritic cells, and plasmacoid dendritic cells were more clearly observed. In addition, immune checkpoint CD96 had the higher expression in CD117+ myeloid naive cells and CD56dimNK cells, while had the lower expression in CD56briNK cells in AML-MRD samples than in normal bone marrow samples. CD200 expression was remarkably enhanced in CD117+ myeloid naive cells, CD4+ T cells, T cells, activated T cells, CD56dimNK cells, and CD56briNK cells in AML-MRD samples. Our results can be used as important basis for auxiliary diagnosis, prognosis judgment, treatment guidance, and immune regulation in AML.

Irreversible cardiomyopathy was caused by the therapeutic of anthracyclines in the chemotherapy of cancers. The cell apoptosis and autophagy were induced by anthracyclines in AC16 cells. MiR-223-3p ascends in anthracycline-treated AC16, but the expression of nuclear factor I-A (NFIA) was specifically down-regulated. However, the underlying molecular mechanism between NFIA and miR-223-3p is unclear now in AC16 cells. In our research, NFIA expression was dampened in AC16 cells by miR-223-3p mimics. Additionally, miR-223-3p knockdown hindered the apoptosis and autophagy in anthracycline-treated AC16. Furthermore, NFIA was predicted and verified as a miR-223-3p’s downstream target and rescued the functions of miR-223-3p. These findings illustrated that miR-223-3p advances anthracycline-stimulated cardiomyocyte damage progression by targeting NFIA, implying the promising therapeutic function of miR-223-3p on cardiomyocyte damage in cancer patients.

Two independent experiments were performed with three groups each (sepsis control, sepsis, and sepsis with apoE23 treatment) to investigate the anti-inflammatory effect of apolipoprotein 23 (apoE23) in a mouse model of sepsis induced by S. typhimurium . Survival rates; plasma level variations in tumor necrosis factor (TNF)-α, interleukin (IL)-6, and lipopolysaccharide (LPS); S. typhimurium colony-forming units in the spleen tissue; and mRNA and protein expression levels of low-density lipoprotein receptor (LDLR), LDLR-related protein (LRP), syndecan-1, and scavenger receptor B1 were evaluated in the livers of mice from the three groups. Results found that the survival rate of septic mice treated with apoE23 was 100% within 48 h, while it was only 40% in septic mice without apoE23 treatment ( P < 0.001). The plasma LPS, TNF-α, and IL-6 levels and the S. typhimurium load in mice in the apoE23-treated group were significantly lower than those in septic mice ( P < 0.05). Moreover, apoE23 restored the downregulated expression of LDLR and LRP in the liver tissue of septic mice. So apoE23 exhibits an anti-inflammatory effect in the mouse model of S. typhimurium -induced sepsis. Further studies are required to understand the mechanisms underlying the anti-inflammatory effects of apoE23.

We investigated the somatic mutations and key driving factors of cervical cancer by whole exome sequencing . We found 22,183 somatic single nucleotide variations (SNVs) in 52 paired samples. Somatic SNVs in cervical cancer were significantly higher than those in high-grade intraepithelial lesion and low-grade squamous intraepithelial lesion groups ( P < 0.05). C → T/G accounted for 44.12% of base substitution. Copy number variation (false discovery rate < 0.05) was found in 57 chromosome regions. The three regions with significant differences between cervical cancer and non-cervical cancer groups were 1q21.1, 3q26.33, and 13q33.1, covering genes related to tumor proliferation, differentiation, and apoptosis. The frequency of human papillomavirus (HPV) insertion/integration and the number of “ tCw ” mutations in the cervical cancer group were significantly higher than those in the non-cervical cancer group ( P < 0.05). The total number of mutations was positively correlated with the number of “ tCw ” mutations ( R 2 = 0.7967). HPV insertion/integration (OR = 2.302, CI = 1.523–3.589, P = 0.0005), APOBEC enrichment (OR = 17.875, CI = 2.117–150.937, P = 0.001), and HLA-B*39 in HLA-I (OR = 6.435, CI = 0.823–48.919, P = 0.0042) were risk factors for cervical cancer, while HLA-DQB1*05 in HLA-II was a protective factor (OR = 0.426, CI = 0.197–0.910, P = 0.032). Conclusively, HPV insertion/integration, APOBEC mutagenesis, and HLA polymorphisms are high-risk factors for cervical cancer and may be causes of genome instability and somatic mutations. This study provides experimental data for revealing the molecular mechanism of cervical cancer.

Nasopharyngeal carcinoma (NPC) is one of the most ordinary malignant tumors. Current research has suggested that circular RNAs play an important role in tumor genesis and progression. The purpose of this study is to explore the function and underlying mechanisms of circ_0028007 in NPC. The levels of circ_0028007, miR-1179, and Squalene epoxidase (SQLE) were detected by quantitative real-time polymerase chain reaction. Cell proliferation was detected by colony formation assay and thymidine analog 5-ethynyl-2′-deoxyuridine assay. Cell apoptosis was detected by flow cytometry. Relevant kits detected caspase-3, glucose, and lactate levels. Western blot assay was used to detect the related protein content. Dual-luciferase reporter assay and RNA pull-down assay were used to examine the target relationship between miR-1179 and circ_0028007 or SQLE. circ_0028007 and SQLE were highly expressed in NPC, while miR-1179 was lowly expressed. circ_0028007 silencing inhibited NPC cell proliferation and promoted apoptosis. However, the effect of circ_0028007 down-regulation on NPC cells was partially restored by co-transfection with miR-1179 inhibitor. Overexpression of SQLE partially restored the cell proliferation inhibited by circ_0028007 knockdown. circ_0028007 could regulate NPC progression via the miR-1179/SQLE axis. Therefore, circ_0028007 might be a new therapeutic target for NPC.

Laparoendoscopic single-site surgery (LESS) has become a novel minimally invasive approach applied as an option to perform hysterectomy. The aim of the study was to evaluate the influence of LESS hysterectomy on the sexual function in women with benign gynecologic indications. From October 2016 to May 2021, a total of 486 premenopausal, sexually active women were eligible. Female sexual function index (FSFI) was used to assess sexual function preoperatively and 6, 12 months postoperatively. Total FSFI score ≤26.55 indicated female sexual dysfunction (FSD). Compared with pre-operation, each subdomain and total FSFI scores increased at 6 (all p < 0.05) and 12 months (all p < 0.001). Prevalence of FSD decreased at 6 (30 vs 39.9%, p = 0.002) and 12 months (27 vs 39.9%, p < 0.001). In patients with preoperative FSD, each subdomain and total FSFI scores improved at 6 and 12 months (all p < 0.001), while decreased at 6 months ( p < 0.001) and had no significant difference at 12 months ( p = 0.54) in patients without preoperative FSD. These results suggest that LESS hysterectomy has a significant positive effect on the sexual function in women with benign gynecologic diseases, especially those with preoperative FSD.

Roxadustat (FG-4592) is a specific hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor. We investigated the effects of FG-4592 pretreatment on survival and second choke vessels of multi-territory perforator flaps in rats. In total, 72 rats were divided into two groups ( n = 36 each): the experimental (FG-4592) group and the control group. FG-4592 was administered orally as a single dose of 60 mg/kg every other day; the first drug solution was administered to the animals 7 days before the surgical procedure. On postoperative day 7, the surviving flap area was calculated. At 12 h post-surgery, in the second choke zone in the flaps, macrovascular hinges were compared by angiography and imaging, and microvascular changes were assessed by histology. Laser Doppler imaging was used to evaluate flap perfusion at the second choke zone at 12 h and 7 days after surgery. At 7 days after surgery, the flap survival area and perfusion were significantly greater in rats given FG-4592 compared with controls. At 12 h after surgery, the diameter of macrovascular and microvascular vessels, nitric oxide content, perfusion, and the protein levels of HIF-1α and inducible nitric oxide synthase were also significantly greater in FG-4592-treated rats than controls. In conclusion, pretreatment with roxadustat may improve initial flap survival and dilate the second choke zone vessels in a multi-territory perforator flap.

Heroin can cause damage to many human organs, possibly leading to different types of arrhythmias and abnormal electrophysiological function of the heart muscle and the steady state of calcium-ion channels. We explored cardiomyocytes treated with heroin and the effect on calcium-ion channels. Transcriptomics and metabolomics were used to screen for differential genes and metabolite alterations after heroin administration to jointly analyze the effect of heroin on calcium channels in cardiomyocytes. Cardiomyocytes from primary neonatal rats were cultured in vitro and were treated with different concentrations of heroin to observe the changes in morphology and spontaneous beat frequency and rhythm by a patch clamp technique. Transcriptomic studies selected a total of 1,432 differentially expressed genes, 941 upregulated and 491 downregulated genes in rat cardiomyocytes from the control and drug intervention groups. Gene Ontology functional enrichment showed that 1,432 differential genes selected by the two groups were mainly involved in the regulation of the multicellular organismal process, response to external stimulus, myofibril, inflammatory response, muscle system process, cardiac muscle contraction, etc. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that these genes were mainly concentrated in cardiac muscle contraction, osteoclast differentiation, adrenergic signaling in cardiomyocytes, dilated cardiomyopathy, hypertrophic cardiomyopathy, and other important pathways. Metabolomic testing further suggested that cardiomyocyte metabolism was severely affected after heroin intervention. After the treatment with heroin, the L-type calcium channel current I – V curve was up-shifted, the peak value was significantly lower than that of the control group, action potential duration 90 was significantly increased in the action potential, resting potential negative value was lowered, and action potential amplitude was significantly decreased in cardiomyocytes. In this study, heroin could cause morphological changes in primary cardiomyocytes of neonatal rats and electrophysiological function. Heroin can cause myocardial contraction and calcium channel abnormalities, damage the myocardium, and change the action potential and L-type calcium channel.

The aim of this study was to explore risk factors of recurrent bacterial vaginosis (RBV) among women of reproductive age. This cross-sectional study was carried out in real-world conditions. Women with RBV were selected, and simultaneously uncomplicated bacterial vaginosis (UBV) and those who underwent routine gynecological examination and had normal vaginal microflora were also recruited as the control. Totally, 316 participants were enrolled. Univariate analysis showed that unemployment, desserts, and wiping were related to UBV, while there was no definite relationship between education, high body mass index, smoking, sedentary lifestyle, and RBV or UBV. History of human papillomavirus infection, contraceptive methods, age at first sexual intercourse, and not cleaning vulva during sexual activity were connected with UBV, while the history of other vaginitis and number of sexual partners in the previous year were related to both RBV and UBV. Multivariate logistic regression analysis revealed that lower educational level increased the risk of suffering RBV. Interestingly, no smoking was a protective factor. Moreover, the absence of other vaginitis and an exclusive sexual partner could also weaken the risk of incurring RBV. These various adverse factors alter endocrine function and vaginal immunity, further leading to the recurrence of BV. It is necessary to take corresponding measures to avoid risk factors and to help lessening the prevalence of RBV among women of reproductive age.

Alkbh5 is one of the primary demethylases responsible for reversing N6-methyladenosine (m 6 A) modifications on mRNAs, and it plays a crucial role in many physiological and pathological processes. Previous studies have shown that Alkbh5 is required for maintaining the function of leukemia stem cells but is dispensable for normal hematopoiesis. In this study, we found that Alkbh5 deletion led to a moderate increase in the number of multiple progenitor cell populations while compromising the long-term self-renewal capacity of hematopoietic stem cells (HSCs). Here, we used RNA-seq and m 6 A-seq strategies to explore the underlying molecular mechanism. At the molecular level, Alkbh5 may regulate hematopoiesis by reducing m 6 A modification of Cebpa and maintaining gene expression levels. Overall, our study unveiled an essential role for Alkbh5 in regulating HSC homeostasis and provides a reference for future research in this area.

Coronavirus disease 2019 (COVID-19) caused a progress in research to find a solution to this pandemic. Also, various advances in pharmacotherapy against COVID-19 have emerged. Regarding antiviral therapy, casirivimab and imdevimab are antibodies combination against COVID-19. Standard antiviral therapy against COVID-19 includes remdesivir and favipiravir. The objectives were to compare progression and multi-organ function of hospitalized COVID-19 patients between these three antiviral groups. 265 COVID-19 hospitalized patients were included in this study and were divided into 3 groups (1:2:2), respectively, Group (A): casirivimab and imdevimab, group (B): remdesivir, and group (C): favipiravir. The design of the study is a single blind non-randomized controlled trial. This study is a phase IV clinical trial (post-marketing study). The duration of the study was about 6 months after receiving the ethical approval. Casirivimab and imdevimab achieved less case progression as presented by lower World Health Organization scale ( P < 0.05 in comparing group A with B and C) and better multi-organ functions as presented by lower Sequential Organ Function Assessment score ( P < 0.05 in comparing group A with B and C) than remdesivir and favipiravir. From all these results, it is concluded that Group A (casirivimab and imdevimab) produces better outcomes than B (remdesivir) and C (favipiravir) intervention groups.

This study aimed to assess the correlation among the peak intensity (PI) values of quantitative parameters, microvessel density (MVD), microvessel maturity, and International Society of Urological Pathology (ISUP) grades in biopsy specimens from prostate cancer (PCa) patients. The study population included PCa patients who underwent targeted and systematic biopsy, without radiation or chemohormonal therapy before biopsy. Contrast-enhanced transrectal ultrasonography (CE-TRUS) was performed in all patients before biopsy. Contrast-enhancement patterns and PI values of quantitative parameters were observed. Tumor tissue samples were immunostained for CD31 expression. MVD, microvessel maturity, and ISUP grades were determined in prostate biopsy specimens. Based on the contrast enhancement patterns of prostate lesions, 16 patients were assigned to a low-enhancement group and 45 to a high-enhancement group. The number of mature vessels, MVD, mature vessel index, and ISUP grades were all higher in the high-enhancement group than in the low-enhancement group (all P < 0.05). The immature vessel index was lower in the high-enhancement group than in the low-enhancement group ( P < 0.05). The PI value was positively correlated with the number of mature vessels ( r = 0.372). In conclusion, enhancement patterns on CE-TRUS can reflect microvessel maturity in PCa. The PI value was positively correlated with the number of mature vessels.

Alpha cypermethrin (α-CYP) is an insecticide, a member of the group of synthetic pyrethroid pesticides. This study aims to assess the histopathological and biochemical subacute effects of α-CYP on the renal tissues of 48 male Spraque–Dawley adult rats. In this study, the rats were divided into six groups: control, α-CYP (10 mg kg −1 ), α-CYP (20 mg kg −1 ), caffeic acid phenethyl ester (CAPE) (10 µmol kg −1 ), α-CYP + CAPE (10 mg kg −1 ), and α-CYP + CAPE (20 mg kg −1 ) groups. The percentage of weight gain was found to be dose-dependent on α-CYP in all groups. As a result of exposure, the normal histological structure of renal tissue was also observed in the control and CAPE groups, while glomerular atrophy and haemorrhage, enlargement of Bowman capsule, glomerular lobulation, and degeneration in distal and proximal tubules were noted in the α-CYP-treated groups with an increased frequency and severity in parallel with the dose increase. Although the severity and intensity of lesions decreased in the α-CYP + CAPE groups, they were statistically insignificant ( p > 0.05). A decrease in the antioxidant parameter levels and an increase in oxidant parameters were observed in parallel with the negative effects of the antioxidant system in the α-CYP-treated groups. The groups exposed to CAPE in combination with α-CYP exhibited a therapeutic trend towards normalization in biochemical parameters due to the antioxidant character of CAPE. However, considering the statistical difference between the groups treated with α-CYP alone and CAPE alone, it was observed that the therapeutic features of those chemicals were not robust.

Norepinephrine (NE) has a certain effect on the improvement of renal function. However, whether NE can alleviate cyclosporin A (CsA)-induced nephrotoxicity needs further study. The effect of CsA (1.25, 2.5, 5, and 10 μM) on the human renal epithelial cell vitality, lactate dehydrogenase (LDH) activity, apoptosis, and secreted frizzled-related protein 1 (SFRP1) level was examined by cell counting kit-8, enzyme-linked immunosorbent assay, flow cytometer, and western blot. The effect of NE on the LDH activity, apoptosis, and SFRP1 level of human renal epithelial cells induced by CsA was examined again. After silencing of SFRP1 in human renal epithelial cells, the SFRP1 level, cell vitality, and apoptosis were examined again. CsA (1.25, 2.5, 5, and 10 μM) attenuated the cell vitality and SFRP1 level but enhanced the LDH activity and apoptosis in human renal epithelial cells, while the above effects were reversed by NE. Moreover, SFRP1 silencing reversed the regulation of NE on the SFRP1 level, cell vitality, and apoptosis in human renal epithelial cells induced by CsA. In conclusion, NE relieved CsA-induced nephrotoxicity via enhancing the expression of SFRP1. Graphical abstract

Lymphocyte apoptosis is a latent factor for immunosuppression in sepsis. Forkhead box protein P3 (FOXP3) can interact with RUNX family transcription factor 1 (RUNX1) in regulatory T cells. Our research was to probe whether RUNX1/FOXP3 axis affects immunosuppression in the process of sepsis by modulating T and B lymphocyte apoptosis. We constructed sepsis model in mice and mouse CD4 + T and CD19 + B lymphocytes. RUNX1 and FOXP3 expressions and apoptosis in cells were assessed by western blot, quantitative real-time PCR, and flow cytometer. Inflammation of serum and pathological damage was assessed by ELISA and H&E staining. Relationship between RUNX1 and FOXP3 was assessed by co-immunoprecipitation. The findings showed that RUNX1 ameliorated the survival rate, pathological damage, and decreased inflammation-related factors, and inhibited apoptosis of CD4 + T and CD19 + B cells in cecal ligation and puncture mice. Furthermore, RUNX1 up-regulated the viability and down-regulated apoptotic rate with the changed expressions of apoptosis-related molecules in lipopolysaccharide (LPS)-mediated CD4 + T and CD19 + B cells. Additionally, FOXP3 interacted with RUNX1, and its silencing decreased RUNX1 expression and reversed the inhibitory effect of RUNX1 on apoptosis of LPS-mediated CD4 + T and CD19 + B cells. In summary, the RUNX1/FOXP3 axis alleviated immunosuppression in sepsis progression by weakening T and B lymphocyte apoptosis.

Bladder cancer is a common malignant tumor. FOXP1 has been found to be abnormally expressed in tumors such as renal cell carcinoma and endometrial cancer. Here, this investigated the biological roles of Foxp1 in the occurrence and development of bladder cancer. Patients with bladder cancer were obtained from China-Japan Friendship Hospital. Bladder cancer cell lines (5637, UMUC3, J82, and T24 cell) were used in this experiment. Foxp1 mRNA and protein expression levels in patients with bladder cancer were increased, compared with paracancerous tissue (normal). OS and DFS of Foxp1 low expression in patients with bladder cancer were higher than those of Foxp1 high expression. Foxp1 promoted bladder cancer cell growth in vitro model. Foxp1 increased the Warburg effect of bladder cancer. Foxp1 suppressed β-adrenoceptor (β-AR) expression in vitro model. ChIP-seq showed that Foxp1 binding site (E1, TTATTTAT) was detected at −2,251 bp upstream of the β-AR promoter. β-AR Reduced the effects of Foxp1 on cell growth in vitro model. β-AR reduced the effects of Foxp1 on the Warburg effect in vitro model by STAT3 activity. Taken together, our findings reveal that Foxp1 promoted the occurrence and development of bladder cancer through the Warburg effect by the activation of STAT3 activity and repressing β-AR transcription, and which might serve as an important clue for its targeting and treatment of bladder cancer.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging global epidemic. The intention of this study was to explore the risk model and validation of CRKP infection in patients with cerebrovascular disease in the intensive care unit (ICU). The data of patients with cerebrovascular disease and Klebsiella pneumoniae infection were retrospectively collected. The patients were divided into the CRKP group and the carbapenem-susceptible Klebsiella pneumoniae (CSKP) group. There were significant differences ( P < 0.05) between the CRKP group and the CSKP group for many variables. Multivariate binary logistic regression analysis showed that the number of types of antibiotics used, history of glucocorticoid use, and duration of mechanical ventilation before the occurrence of infectious bacteria are the independent risk factors for CRKP infection in patients with cerebrovascular disease in the ICU, and a nomogram risk model was constructed accordingly. The area under the ROC curve of the risk model was 0.868 (95% CI: 0.803–0.934).

Currently, the effect and molecular mechanism of calycosin, the main active ingredient of Qinshi Simiao San, which can alleviate chronic prostatitis (CP), on CP remain unclear. This study aimed to elucidate the potential mechanism of action of calycosin in CP in a rat CP model. The prostate tissue morphology was evaluated based on hematoxylin–eosin staining. Enzyme-linked immunosorbent assay was conducted to evaluate inflammatory cytokine and immune factor levels (secretory immunoglobulin A [SIgA]; immunoglobulin G [IgG]) in prostate tissues and serum. Additionally, representative biomarkers of oxidative stress, including malondialdehyde, superoxide dismutase, and catalase were detected using detection kits, and reactive oxygen species release was evaluated using immunofluorescence staining. Furthermore, the p38 mitogen-activated protein kinase (p38MAPK)/NF-kappaB (NF-κB) signaling pathway was analyzed by western blotting. The results showed that calycosin substantially ameliorated the pathological damage to prostate tissues of the CP rats. Moreover, calycosin significantly downregulated interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha, IgG, and SIgA levels. Furthermore, we found that calycosin considerably suppressed oxidative stress and inhibited the activation of the p38MAPK/NF-κB signaling pathway in rats with CP. In summary, our findings revealed that calycosin protects against CP in rats by inhibiting the p38MAPK/NF-κB pathway.

Phosphodiesterase 4D interacting protein ( PDE4DIP ) interacts with cAMP-specific phosphodiesterase 4D and its abnormal expression promotes the development of hematological malignancies, breast cancer, and pineal cell carcinoma. However, there is currently no systematic pan-cancer analysis of the association between PDE4DIP and various cancers. Thus, this study aimed to elucidate the potential functions of PDE4DIP in various cancers. Based on the multiple public databases and online websites, we conducted comprehensive analyses for PDE4DIP in various cancers, including differential expression, prognosis, genetic variation, DNA methylation, and immunity. We thoroughly analyzed the specific role of PDE4DIP in acute myeloid leukemia (LAML). The results indicated that there were differences in PDE4DIP expression in cancers, and in kidney chromophobe, LAML, pheochromocytoma and paraganglioma, thymoma, and uveal melanoma, PDE4DIP had potential prognostic value. PDE4DIP expression was also correlated with genetic variation, DNA methylation, immune cell infiltration, and immune-related genes in cancers. Functional enrichment analysis showed that PDE4DIP was mainly related to immune-related pathways in cancers, and in LAML, PDE4DIP was mainly related to immunoglobulin complexes, T-cell receptor complexes, and immune response regulatory signaling pathways. Our study systematically revealed for the first time the potential prognostic and immunotherapeutic value of PDE4DIP in various cancers, including LAML.

It is of urgent need to understand the safety and effectiveness of novel coronavirus (COVID-19)-inactivated vaccine in patients with hyperlipidemia (HLD). However, data on the safety and immune response of SARS-CoV-2-inactivated vaccine in HLD patients are limited. In this prospective study, 105 patients with HLD and 74 healthy controls (HCs) were selected. Within 16–168 days after inoculation-inactivated vaccine, the anti-receptor-binding domain (RBD) IgG and SARS-CoV-2 neutralizing antibodies (NAbs) were evaluated, respectively. Flow cytometry was performed to evaluate RBD-specific B cells and memory B cells. There was no significant difference between HLD patients and HCs in adverse events (AEs) within 7 days after vaccination, and no serious AEs occurred. The seropositivity rates and titers of two Abs (anti-RBD IgG and CoV-2 NAbs) were lower in HLD patients than in HCs (all, p < 0.05). HLD showed significantly lower frequencies of RBD-specific B cells than HCs ( p = 0.040). However, in high cholesterol, high triglyceride, mixed (MiX), and lipid control (HC) subgroups, there was no significant difference in the seropositivity rates and titers of the both Abs. Through mixed factor analysis shows that days between the second dose and sample collection/antibody measurement were associated with the lower anti-RBD IgG antibody levels. In conclusion, inactivated COVID-19 vaccine is safe and well tolerated for HLD patients, but the humoral immune may be limited.

The aim of our study is to disclose the role and underlying molecular mechanisms of circular RNA ubiquitin protein ligase E3 component n -recognin 4 (circ-UBR4) in atherosclerosis (AS). Our data showed that circ-UBR4 expression was upregulated in AS patients and oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) compared with healthy volunteer and untreated VSMCs. In addition, ox-LDL stimulated proliferation, migration, and inflammation but decreased apoptosis in VSMCs, which were overturned by the inhibition of circ-UBR4. miR-515-5p was sponged by circ-UBR4, and its inhibitor reversed the inhibitory effect of circ-UBR4 knockdown on proliferation, migration, and inflammation in ox-LDL-induced VSMCs. Insulin-like growth factor2 (IGF2) was a functional target of miR-515-5p, and overexpression of IGF2 reversed the suppressive effect of miR-515-5p on ox-LDL-stimulated VSMCs proliferation, migration, and inflammation. Collectively, circ-UBR4 knockdown decreased proliferation, migration, and inflammation but stimulated apoptosis in ox-LDL-induced VSMCs by targeting the miR-515-5p/IGF2 axis.

To understand the clinical characteristics of omicron in COVID-19 Rehabilitation Clinic after the current shift of dynamic zeroing policy, we consecutively collected the patients’ data who visited in COVID-19 Rehabilitation Clinic of a Grade-A tertiary hospital in Hangzhou, Zhejiang Province, from January 3 to January 10, 2023, analyzed related data and then compared the pneumonia between elderly and non-elderly groups. The results showed that 95.68% of the patients in COVID-19 Rehabilitation Clinic had symptoms, 70.10% had a dry cough, 12.36% had abnormal complete blood count or C-reactive protein, 19.35% had electrolyte disorder, and 2% had abnormal troponin or creatine kinase-MB. 40.45% of patients had abnormal lung CT findings, among them 86.49% of elderly patients had abnormal lung CT findings, and the utilization rate of glucocorticoids in COVID-19 Rehabilitation Clinic was only 5.98%, although people are all susceptible to getting the COVID-19 infection, the elderly are more prone to getting pneumonia, and the glucocorticoids utilization rate is relatively insufficient. It is needed to be stressed that Chinese medical staff should pay more attention to the elderly patients who are vulnerable to getting pneumonia during this period.

Ulcerative colitis (UC) is an inflammatory bowel disease and associated with metabolic imbalance. Luteolin (LUT) reportedly exhibits anti-inflammatory activity. However, its regulatory effects on metabolites remain indistinct. Here, the effects of LUT on immune response and oxidative stress in UC were determined. Serum metabolomics profiles of UC rats treated with LUT were obtained utilizing liquid chromatography-mass spectrometry. The results revealed that LUT treatment alleviated colon tissue injury, colon shortening, weight loss, and inflammatory response in UC rats. Additionally, the levels of superoxide dismutase and total antioxidant capacity were elevated, but malondialdehyde content was reduced in serum of UC rats, while these changes were abrogated by LUT. Metabolomics analysis unveiled that l -malic acid, creatinine, l -glutamine, and l -lactic acid levels were remarkably decreased, while dimethyl sulfone, 5-methylcytosine, cysteine-S-sulfate, and jasmonic acid levels were notably increased after LUT treatment. Furthermore, differential metabolites primarily participated in d -glutamine and d -glutamate metabolism, glutathione metabolism, and citrate cycle pathways. In summary, these results demonstrated that LUT improved immune response, alleviated oxidative stress, and altered metabolites in UC rats. This study lays the root for further exploring the mechanism of LUT in the treatment of UC.

Calcific aortic valve disease (CAVD) is an important cause of disease burden among aging populations. Excessive active endoplasmic reticulum stress (ERS) was demonstrated to promote CAVD. The expression level of miR-199a-5p in patients with CAVD was reported to be downregulated. In this article, we aimed to investigate the function and mechanism of miR-199a-5p in CAVD. The expression level of miR-199a-5p and ERS markers was identified in calcific aortic valve samples and osteogenic induction by real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry, and western blotting (WB). Alizarin red staining, RT-qPCR, and WB were used for the verification of the function of miR-199a-5p. The dual luciferase reporter assay and rescue experiment were conducted to illuminate the mechanism of miR-199a-5p. In our study, the expression level of miR-199a-5p was significantly decreased in calcified aortic valves and valve interstitial cells’ (VICs) osteogenic induction model, accompanying with the upregulation of ERS markers. Overexpression of miR-199a-5p suppressed the osteogenic differentiation of VICs, while downregulation of miR-199a-5p promoted this function. 78 kDa glucose-regulated protein (GRP78) and activating transcription factor 6 (ATF6), both of which were pivotal modulators in ERS, were potential targets of miR-199a-5p. miR-199a-5p directly targeted GRP78 and ATF6 to modulate osteoblastic differentiation of VICs. miR-199a-5p inhibits osteogenic differentiation of VICs by regulating ERS via targeting GRP78 and ATF6.

To observe the effect of iliac fascia space block combined with esketamine intravenous general anesthesia in proximal femoral nail antirotation (PFNA) of the elderly. Eighty elderly patients who underwent PFNA were randomly divided into experimental group and control group. In the experimental group, iliac fascial block combined with esketamine and propofol intravenous general anesthesia was used to keep spontaneous breathing. The control group used iliac fascia block combined with remifentanil and propofol intravenous general anesthesia to maintain spontaneous breathing. Record important indexes such as heart rate (HR), mean arterial pressure (MAP), pulse oxygen saturation (SpO 2 ), visual analogue score (VAS) scores, etc. at different moment during the operation. Trial data showed that there were significant differences in HR, MAP, and SpO 2 between the two groups at the beginning of operation, and there was no significant difference in VAS scores between the two groups at each moment after surgery, and there were significant differences in the number of vasopressor applications, length of hospital stay, and QoR-15 scores between the two groups, and there were significant differences in the incidence of total adverse reactions and the incidence of hypotension. The trial indicated that patients in the experimental group have more stable hemodynamics and lower stress response, which is conducive to rapid recovery after surgery.

Although elevated blood ketone body levels reduce major adverse cardiac and cerebrovascular events (MACCEs) risk in chronic heart failure, their relationship with acute myocardial infarction remains unknown. We investigated this relationship in patients with acute myocardial infarction. This single-institution retrospective observational study analyzed data from 114 patients with acute myocardial infarction at Nihon University Hospital from May 1, 2018, to November 1, 2022. The cut-off value of acetoacetate for the incidence of in-hospital MACCE was determined by drawing a receiver operating characteristic curve (ROC) and defining patients with acetoacetate above and below the optimal cut-off point value as ROC and low-acetoacetate (LA) groups, respectively. Propensity score matching was performed between the LA and high-acetoacetate (HA) groups. Sex, peak creatine kinase, lactate, and blood glucose were defined as confounding factors between in-hospital MACCEs and acetoacetate, and 1:1 propensity score matching between the LA and HA groups was used, resulting in 40 patients from both groups enrolled in the analysis. There was a significantly lower incidence of in-hospital MACCEs in the HA group (LA group: 9 [22%] vs HA group: 1 [3%], P = 0.014). In conclusion, in acute myocardial infarction, elevated blood acetoacetate levels reduce the risk of MACCE.

We aimed to evaluate the effects of postpartum progesterone on obstetric anal sphincter injury (OASI) healing in female rats using an experimental OASI model. Twenty-eight female rats were divided into four groups after birth: sham-30, sham-90, progesterone (P4)-30, and P4-90. Moreover, OASI model was established in all groups. Subsequently, except for the sham groups, medroxyprogesterone acetate (0.15 mg) was intramuscularly injected into the P4 groups. After 30 and 90 days, the rats were euthanized under general anesthesia after recording the data. The anal sphincter region was collected for histopathological examination. Progesterone and thiol/disulfide homeostasis studies were performed on blood samples. No significant differences were observed between the groups regarding the external anal sphincter (EAS), internal anal sphincter (IAS), or connective tissue thickness ( p = 0.714, p = 0.135, and p = 0.314, respectively). No statistically significant differences in the total thiol, native thiol, disulfide, and progesterone levels were found between the groups ( p = 0.917, p = 0.503, p = 0.361, and p = 0.294, respectively). The endometrial thickness was lower in the P4 groups than in the sham groups ( p = 0.031). Postpartum progesterone administration did not affect IAS and EAS or connective tissue thickness or disrupt the thiol–disulfide balance. However, this administration led to endometrial thinning.

Copper can be toxic at very high intracellular concentrations and can inhibit prostate cancer (PCa) progression. Recently, a study reported the mechanism of cuproptosis and the potentially associated genes. However, the function of these cuproptosis-related genes in PCa remains unknown. Based on the RNA sequence and clinical data from public databases, we analyzed the clinical value of cuproptosis-related genes in PCa. DLD , DLAT , PDHA1 , and CDKN2A were expressed differently between normal and PCa tissues. The FDX1 , LIAS , DLAT , GLS , and CDKN2A genes can affect PCa progression, while PDHA1 and CDKN2A influence the patients’ disease-free survival (DFS) status. The expression of LIAS , LIPT1 , DLAT , and PDHB did not alter upon the incidence of PCa in Chinese patients. A constructed regression model showed that FDX1 , PDHA1 , MTF1 , and CDKN2A can be risk factors leading to PCa in both Western and Chinese patients with PCa. The lasso regression model reflected that these genes can affect the patients’ DFS status. Additionally, the cuproptosis-related genes were associated with immune cell infiltration. We also verified the high expression of PDHA1 and CDKN2A , in clinical samples. In conclusion, we identified a novel cuproptosis-related gene signature for predicting the development of PCa.

Adverse cardiovascular events are associated with vascular calcification (VC) process, where vascular smooth muscle cells (VSMCs) differentiate into osteoblastic phenotype and deposit hydroxyapatite crystals. Microtubule-associated protein kinesin family member 2C (KIF2C) expression is decreased obviously in VSMC during calcification induction. Accordingly, we investigate the role and potential mechanism of KIF2C on VSMC calcification. The effects of β-glycerophosphate (β-GP)/KIF2C/lumican (LUM) on calcification, calcium content, alkaline phosphatase (ALP) activity, calcification-related markers, Tubulin, the ratio of polymerized (Po) to free (Fr) tubulin, as well as levels of LUM, apolipoprotein B (APOB), and KIF2C were assessed by Alizarin red S staining, calcium assay kit, ALP assay kit, Western blot, immunofluorescence, and quantitative real-time PCR. The interplay between LUM and APOB was estimated using co-immunoprecipitation and immunofluorescence. As a result, β-GP promoted calcification of human VMSCs (HVMSCs) and repressed KIF2C expression. KIF2C overexpression reversed the effect of β-GP on HVSMCs. LUM silencing attenuated β-GP-induced promotion on HVSMC calcification and increased KIF2C expression by interacting with APOB. Collectively, LUM silencing can alleviate β-GP-induced VSMC calcification through mitigating the repression of APOB on KIF2C expression.

Hepatocellular carcinoma (HCC) is a frequently diagnosed malignancy with a high mortality rate. Cisplatin (CDDP) is a widely applied anti-cancer drug. However, a large population of liver cancer patients developed CDDP resistance. The polypyrimidine tract binding protein (PTBP1) is an RNA-binding protein involving in progressions of diverse cancers. Here we report PTBP1 was significantly upregulated in liver tumors and cell lines. Silencing PTBP1 effectively sensitized HCC cells to CDDP. From the established CDDP-resistant HCC cell line (HepG2 CDDP Res), we observed that CDDP-resistant cells were more sensitive to CDDP under low glutamine supply compared with that in HCC parental cells. CDDP-resistant HCC cells displayed elevated glutamine metabolism rate. Consistently, PTBP1 promotes glutamine uptake and the glutamine metabolism key enzyme, glutaminase (GLS) expression. Bioinformatics analysis predicted that the 3′-UTR of GLS mRNA contained PTBP1 binding motifs which were further validated by RNA immunoprecipitation and RNA pull-down assays. PTBP1 associated with GLS 3′-UTR to stabilize GLS mRNA in HCC cells. Finally, we demonstrated that the PTBP1-promoted CDDP resistance of HCC cells was through modulating the GLS–glutamine metabolism axis. Summarily, our findings uncovered a PTBP1-mediated CDDP resistance pathway in HCC, suggesting that PTBP1 is a promisingly therapeutic target to overcome chemoresistance of HCC.

To investigate whether there is an influence on the results of lumbar spine bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) under three different hip flexion angles (90°, 45°, 0° of hip flexion). We collected a total of 60 outpatients, including 44 females (56.4 ± 5.7 years) and 16 males (50.2 ± 13.7 years). The DXA results of the lumbar spine were scanned and analyzed in three different positions with hip flexion of 90°, 45°, and 0°. We found that there was no significant difference in the area of interest, bone mineral content, BMD, and vertebral body height of the lumbar vertebral body measured by DXA in three hip flexion positions of 90°, 45°, and 0°; Pearson’s correlation analysis showed that lumbar BMD in hip flexion 90° was correlated with it in hip flexion 45° ( r = 0.998, P ＜0.01) and in hip flexion 0° ( r = 0.996, P ＜0.01) respectively. There was no statistically significant difference in the diagnosis of BMD between 90° and 45° hip flexion ( P = 0.903), which was the same as 90° and 0° hip flexion ( P = 0.822). Therefore, we conclude that different hip flexion angles can be used in lumbar BMD detection by DXA, which is beneficial to patients who have difficulty in hip flexion, especially for elderly patients with osteoporosis.

We aimed to investigate the clinical efficacy of blood purification technology based on cytokine adsorption in the treatment of sepsis. Sixty patients with sepsis were randomly divided into control ( n = 30) and experimental ( n = 30) groups. Both groups were given routine treatment and continuous venovenous hemofiltration, and on this basis, the experimental group received acrylonitrile/sodium methacrylate (AN69ST) blood purification. The levels of C-reactive protein, procalcitonin, white blood cell count, albumin, platelets, total bilirubin, creatinine, lactic acid, and APACE II score, as well as secretion of inflammatory factors interleukin (IL)-6 and tumor necrosis factor (TNF-α) were compared. The hospitalization time, mechanical ventilation (MV) time, drug use time, and mortality were analyzed. After treatment, the secretion levels of IL-6 and TNF-α were decreased, and other indicators were significantly improved compared with those before treatment ( P < 0.05), especially in the experimental group ( P < 0.05). The hospitalization time, MV time, and drug use time in the experimental group were significantly lower than those of the control group ( P < 0.05), and the mortality was lower than that in the control group ( P < 0.05). In conclusion, blood purification technology based on cytokine adsorption can significantly improve various indicators of sepsis patients, reduce hospitalization time, reduce mortality, and improve the prognosis.

The objective was to examine the pooled effects of antibiotic–probiotic combinations by examining the cure rate and recurrence rate for bacterial vaginosis (BV). A systematic literature search was conducted from electronic databases. All parallel randomized controlled trials (RCTs) that focused on the effects of antibiotics combined with intravaginal probiotics were included. Cure rate and recurrence rate were the primary and secondary outcomes to be analyzed. Meta-analysis was conducted following the Cochrane handbook for Systematic Reviews of Interventions. As a result, of 923 studies identified, 11 articles involving 1,493 BV patients met the inclusion criteria and nine were available for meta-analysis. A meta-analysis of two studies evaluated the recurrence rate 12–16 weeks after treatment. Results showed a statistically significant difference favoring the antibiotics plus probiotics group vs the antibiotics plus placebo group (relative risk 0.62, 95% confidence interval [CI]: 0.45–0.85). The narrative review in one study indicated that the cure rate was higher in the antibiotics plus probiotics group, giving a significant HR ratio of 0.73 (95% CI 0.54–0.98) ( p = 0.042). In conclusion, vaginal application of Lactobacillus in combination with antibiotics for the treatment of BV could be a promising method for both reducing the recurrence rate and relieving symptoms of BV.

The aim of this study is to explore the prognostic value of vascular invasion (VI) in hepatocellular carcinoma (HCC) by searching for competing endogenous RNAs (ceRNA) network and constructing a new prognostic model for HCC. The differentially expressed genes (DEGs) between HCC and normal tissues were identified from GEO and TCGA. StarBase and miRanda prediction tools were applied to construct a circRNA-miRNA-mRNA network. The DEGs between HCC with and without VI were also identified. Then, the hub genes were screened to build a prognostic risk score model through the method of least absolute shrinkage and selection operator. The prognostic ability of the model was assessed using the Kaplan−Meier method and Cox regression analysis. In result, there were 221 up-regulated and 47 down-regulated differentially expressed circRNAs (DEcircRNAs) in HCC compared with normal tissue. A circRNA-related ceRNA network was established, containing 11 DEcircRNAs, 12 DEmiRNAs, and 161 DEmRNAs. Meanwhile, another DEG analysis revealed 625 up-regulated and 123 down-regulated DEGs between HCC with and without VI, and then a protein–protein interaction (PPI) network was built based on 122 VI-related DEGs. From the intersection of DEGs within the PPI and ceRNA networks, we obtained seven hub genes to build a novel prognostic risk score model. HCC patients with high-risk scores had shorter survival time and presented more advanced T/N/M stages as well as VI occurrence. In conclusion a novel prognostic model based on seven VI-associated DEGs within a circRNA-related ceRNA network was constructed in this study, with great ability to predict the outcome of HCC patients.

Combined cancer immunotherapy and targeted therapy have proven to be effective against various cancers and therefore have recently become the focus of cancer research. Signal transducer and activator of transcription 3 (STAT3) is a member of the STAT protein family of transcription factors. Several studies have shown that STAT3 can affect the prognosis of cancer patients by regulating immune microenvironment (IME). Therefore, STAT3 may have high research value for the development of combined immunotherapy/targeted therapy approaches for the treatment of cancer patients. We found differences in STAT3 expression between tumor and normal tissues. Kaplan−Meier survival and Cox regression analyses showed that high expression of STAT3 is associated with poor prognosis in low-grade glioma (LGG) patients. The results of the analysis of the area under the curve of the receiver operating characteristic curve further suggested that the expression of STAT3 is an effective way to evaluate the prognosis of patients with glioma. The results of the IME analysis revealed that the immune and matrix scores of LGGs were positively correlated with the expression of STAT3 ( P < 0.05). The results of immune cell infiltration analysis showed that STAT3 was positively correlated with resting dendritic cells, eosinophils, neutrophils, M0 macrophages, M1 macrophages, CD4 memory resting T cells, and CD8 T cells in LGG patients, but negatively correlated with activated mast cells and M2 macrophages ( P < 0.05). Our gene set enrichment analysis identified 384 enriched pathways. According to the enrichment scores, the top ten most significantly upregulated pathways were related to immune response. The top ten most significantly downregulated pathways were related to cell signal transduction and the regulation of cell survival, proliferation, and metabolism. Genetic alteration analysis showed that missense mutations in STAT3 account for the majority of mutations, and STAT3 mutations mostly occur in the Src homology domain. In conclusion overexpression of STAT3 can promote the development and growth of tumors by regulating IME, which is significantly related to the poor prognosis of cancer patients. Therefore, targeted inhibition of STAT3 expression may have high research value for the development of combined immunotherapy/targeted therapy approaches for the treatment of cancer patients.

Bladder urothelial carcinoma (BLCA) is one of the most common cancer-related deaths in the world, along with high mortality. Due to the difficult detection of early symptoms, the treatment for this disease is still dissatisfactory. Thus, the current research hotspot is beginning to focus on the immune microenvironment in this disease, aiming to provide guidance for diagnosis and treatment. In this study, the single-cell RNA sequencing data downloaded from the gene expression omnibus database was used to classify the immune cells of BLCA. And the final seven T-cell-related cell clustering genes associated with BLCA prognosis ( HSPA2 , A2M , JUN , PDGFRB , GBP2 , LGALS1 , and GAS6 ) were screened out, and then used for constructing the prognostic model against BLCA based on the Cox and LASSO regression analysis. Satisfactorily, the model could efficiently evaluate the overall survival of BLCA and had the potential to be applied for the clinic treatment. Moreover, we also revealed that the difference in immune infiltration levels and gene mutation might account for the diverse prognosis in BLCA patients. In a word, our findings provided a novel insight for designing efficient immunotherapies for BLCA.

The aim of this study was to explore the changes in pH and pepsin concentrations in oral lavage fluid of rabbit reflux model. A total of 18 New Zealand rabbits were randomly divided into two groups. The lower esophageal sphincters (LESs) of the rabbits in the experimental group (EG) were dilated by balloon after the LESs were localized by manometry. The pH levels of the throat and the lower esophagus were monitored 1 week before and 2 weeks after inflation. Oral lavage fluid was collected 1 week before, and 2 and 8 weeks after inflation. The pH monitoring showed that the percentage of reflux time, the number of reflux events, and the longest time of reflux after the dilation (AE) in the EG were significantly higher than before the dilation ( P < 0.01). The pepsin concentrations at 2 and 8 weeks AE in the EG were significantly higher than that before and that in the control group ( P < 0.05). Based on receiver operating characteristic curve analysis, the best diagnostic threshold value was 30.3 ng/ml. The reflux model constructed by balloon inflation of the LES in rabbits is characterized by a decrease in throat pH and an increase in salivary pepsin concentration.

This study aimed to explore the role and mechanism of felodipine in lung cancer therapy. Murine subcutaneous lung squamous cancer (LUSC) models constructed by KLN-205 cells were utilized to assess the effect of felodipine monotherapy and in combination with the programmed cell death protein 1 antibody (PD1ab) and cytotoxic T lymphocyte-associated antigen-4 (CTLA4ab). Immunohistochemistry analysis was subsequently applied to detect the number of CD8+ T cells and Ki67+ cells. Lastly, a series of in vitro and in vivo experiments were performed to evaluate the effects of felodipine on human LUSC cells and explore the preliminary mechanism underlying felodipine inhibition. The results revealed that felodipine monotherapy exerted a significant inhibitory effect on LUSC growth and synergistic antitumoral activity with PD1ab and CTLA4ab. Meanwhile, immunohistochemistry analysis displayed that felodipine promoted CD8+ T-cell infiltration and downregulated Ki67 expression in tumor cells. Moreover, in vitro and in vivo experiments utilizing human LUSC cells determined that felodipine impaired the proliferative and migratory abilities of cancer cells. In addition, TCGA data analysis uncovered that nuclear factor of activated T cell (NFAT1) expression was positively correlated with overall survival and disease-free survival. Finally, the cell counting kit-8 assay signaled that felodipine might suppress tumor growth by modulating NFAT1.

Recent studies revealed that endoplasmic reticulum (ER) stress played an emerging role of in valve calcification. Tanshinone IIA (TanIIA) has been a research hotspot in cardiovascular diseases. Previously we found that sodium TanIIA dampened the pathological phenotype transition of valvular interstitial cells (VICs) by affecting ER stress published in Chinese Journal. Here, we test the hypothesis that TanIIA attenuates the pro-osteogenic effects of oxidized low-density lipoprotein (oxLDL) in VICs by reducing induction of ER stress. Patients’ aortic valve (AV) was collected, and porcine VICs were cultured for in vitro model. ER stress markers were tested in human leaflets by immunostaining. Immunoblotting were used to test the osteoblastic factors such as Runx2, osteocalcin, and ER stress markers GRP78, CHOP, XBP1, etc. Alkakine phosphate (ALP) activity assay were used to test the activity of ALP kinase. Pro-inflammatory gene expression was detected by polymerase chain reaction. As a result, ER stress markers were elevated in patients’ calcified AVs. OxLDL induced osteogenesis and inflammation via promoting ER stress. TanIIA attenuated oxLDL induced ER stress. TanIIA also inhibited theosteoblastic factors and inflammatory cytokine expressions in VICs. In conclusion, our data provide evidence that TanIIA exerts anti-inflammation and anti-osteogenic effects in VICs by attenuating ER stress, and ER stress acts as an important regulator in oxLDL induced VICs’ phenotype transition.

Non-small cell lung cancer (NSCLC) is one of the most lethal malignant tumors. It has been shown that the general anesthetic agents, propofol and astragaloside IV (AS-IV) both exert antitumor effects in NSCLC. However, the effects of the combination of propofol with AS-IV in NSCLC remain unclear. Cell counting kit-8, and EdU and Transwell assays were performed to evaluate NSCLC cell viability, proliferation, and migration. Cell apoptosis and autophagy were observed by flow cytometric analysis and TUNEL and LC3 staining, respectively. AS-IV notably enhanced the anti-proliferative, pro-apoptotic, and anti-migratory properties of propofol in NSCLC cells. Moreover, AS-IV remarkably facilitated the anti-autophagy effect of propofol in NSCLC cells by downregulating LC3, Beclin 1, and ATG5. Significantly, the pro-apoptotic ability of the AS-IV/propofol combination in NSCLC cells was further enhanced by the autophagy inhibitor 3-MA, suggesting that autophagy plays a tumor-promoting role in NSCLC cells. Collectively, AS-IV could facilitate the antitumor abilities of propofol in NSCLC cells by inhibiting autophagy. These findings may be beneficial for future studies on the use of AS-IV and propofol for the treatment of NSCLC.

Acquired resistance to chemotherapeutic drugs in gallbladder cancer (GBC) results in therapy failure. This study is aimed to establish oxaliplatin (OXA)-resistant GBC cell lines and uncover their gene expression profiles. First, two OXA-resistant GBC cell lines (GBC-SD/OXA and SGC996/OXA) were established by gradually increasing the drug concentration, and the resistance index was 4–5. The two resistant cell lines showed slower proliferation and higher stemness, colony formation, and migration abilities. Epithelial mesenchymal transformation and increased levels of P-glycoprotein were also detected. Next RNA-sequence analysis identified 4,675 dysregulated genes (DGs) in resistant cells, and most of the 12 randomly selected DGs were verified to be consistent with the sequence results. Kyoto Encyclopedia of Genes and Genomes analysis indicated that several DGs were involved in resistance- and phenotype-related pathways, of which the activations of PD-L1 and ERK1/2 were both verified in resistant cell lines. In conclusion, this study is the first to report the gene expression profile of OXA-resistant GBC cells and provides a useful database for target development.

Cognitive impairment in multiple sclerosis (MS) can adversely impact participation in employment, activities of daily living, and wider society. It affects 40–70% of people living with MS (pwMS). There are few effective treatments for cognitive impairment in people with MS. Neuromodulation with intermittent theta-burst stimulation (iTBS) has potential for treating cognitive impairment in pwMS. This single-centre mixed-methods feasibility randomised controlled trial (NCT04931953) will assess feasibility, acceptability, and tolerability of procedures used for applying iTBS for improving cognitive performance in pwMS. Participants will be randomised into three intervention groups with varying lengths of iTBS treatment (from 1 to 4 weeks) and a sham-control group. Quantitative data will be collected at three time points (baseline, end of intervention, and 8-week follow-up). End of the intervention semi-structured interviews will explore the views and experiences of the participants receiving the intervention, analysed using framework analysis. Quantitative and qualitative data will be synthesised to explore the impact of the iTBS intervention. Ethical approval has been received from the Health Research Authority (21/LO/0506) and recruitment started in June 2022. The results will inform the design of an RCT of the efficacy of iTBS as a therapeutic intervention for cognitive impairment in pwMS.

Epigenetic alteration is a key feature that contributes to the progression of bladder cancer (BC) and long non-coding RNAs serve crucial role in the epigenetic modulation. This study was designed to explore the epigenetic regulation of LINC00592 in BC. LINC00592 expression in BC was examined. Then, LINC00592 was silenced in BC cell followed by cell behavior analyses using CCK-8, transwell, western blot, or flow cytometry. Potential downstream target of LINC00592 was explored using RNA pull-down assay and methylation of WIF1 was determined using methylated-specific PCR. In addition, WIF1 or/and LINC00592 were silenced in BC cells followed by cell behavior analyses to explore the regulation between them. Upregulation of LINC00592 was significantly detected in BC tissues and cells. In BC cells silencing LINC00592 suppressed the proliferation, migration, and epithelial-mesenchymal transitions (EMT), but enhanced apoptosis. Moreover, LINC00592 recruited DNMT1, DNMT3A, and DNMT3B to enhance WIF1 promoter methylation. In addition, WIF1 overexpression suppressed the proliferation, migration, as well as EMT, but enhanced apoptosis. Silencing WIF1 significantly attenuated the role of silencing LINC00592 in suppressing the proliferative, migratory, and EMT ability of BC cells, and increasing the apoptosis. LINC00592 promoted the growth and metastasis of BC via enhancing the promoter methylation of WIF1 and decreasing WIF1 transcription.

Critical illness may disrupt nutritional, protective, immune, and endocrine functions of the gastrointestinal tract, leading to a state of gastrointestinal dysmotility. We aimed to identify factors associated with the occurrence of gastrointestinal dysmotility in critically ill patients. A cross-sectional retrospective study was conducted, using patient files as a source of data. The study included 185 critically ill patients treated in the intensive care unit of the University Clinical Center, Kragujevac, Serbia, from January 1, 2016, to January 1, 2022. Significant risk factors associated with some form of gastrointestinal dysmotility were acute kidney injury (with paralytic ileus, nausea, vomiting, and constipation), recent abdominal surgery (with ileus, nausea, vomiting, and constipation), mechanical ventilation (with ileus, and nausea), age (with ileus and constipation), and use of certain medication such as opioids (with ileus, gastro-esophageal reflux, nausea, vomiting, and constipation), antidepressants (with ileus, nausea, and vomiting), and antidiabetics (with ileus). On the other hand, Charlson comorbidity index had divergent effects, depending on the form of gastrointestinal dysmotility: it increased the risk of gastro-esophageal reflux but protected against ileus, nausea, and vomiting. In clonclusion, recognition of factors associated with gastrointestinal dysmotility should initiate preventative measures and, thus, accelerate the recovery of critically ill.

Can the spinal cord stimulation (SCS) regulate the autonomic nerves through the endothelin-1 (ET-1) and nerve growth factor (NGF)/p75NTR pathways and thus inhibit the occurrence of atrial fibrillation (AF)? In our research, 16 beagles were randomly divided into a rapid atrial pacing (RAP) group ( n = 8) and a RAP + SCS group ( n = 8), and the effective refractory period (ERP), ERP dispersion, AF induction rate, and AF vulnerability window (WOV) at baseline, 6 h of RAP, 6 h of RAP + SCS were measured. The atrial tissue was then taken for immunohistochemical analysis to determine the localization of ET-1, NGF, p75NTR, NF-kB p65, and other genes. Our results showed that SCS attenuated the shortening of ERP in all parts caused by RAP, and after 6 h of SCS, the probability of AF in dogs was reduced compared with that in the RAP group. Moreover, the expression of ET-1, NGF, and p75NTR in the atrial tissues of dogs in the RAP + SCS group was significantly increased, but the expression of NF-kB p65 was reduced. In conclusion, SCS promotes the positive remodeling of cardiac autonomic nerves by weakening NFκB p65-dependent pathways to interfere with the ET-1 and NGF/p75NTR pathways to resist the original negative remodeling and inhibit the occurrence of AF.

Small-cell lung cancer (SCLC) has a poor prognosis and can be diagnosed with systemic metastases. Nevertheless, the molecular mechanisms underlying the development of SCLC are unclear, requiring further investigation. The current research aims to identify relevant biomarkers and available drugs to treat SCLC. The bioinformatics analysis comprised three Gene Expression Omnibus datasets (including GSE2149507, GSE6044, and GSE30219). Using the limma R package, we discovered differentially expressed genes (DEGs) in the current work. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were made by adopting the DAVID website. The DEG protein–protein interaction network was built based on the Search Tool for the Retrieval of Interacting Genes/Proteins website and visualized using the CytoHubba plugin in Cytoscape, aiming to screen the top ten hub genes. Quantitative real-time polymerase chain reaction was adopted for verifying the level of the top ten hub genes. Finally, the potential drugs were screened and identified using the QuartataWeb database. Totally 195 upregulated and 167 downregulated DEGs were determined. The ten hub genes were NCAPG, BUB1B, TOP2A, CCNA2, NUSAP1, UBE2C, AURKB, RRM2, CDK1, and KIF11. Ten FDA-approved drugs were screened. Finally, two genes and related drugs screened could be the prospective drug targets for SCLC treatment.

Chronic obstructive pulmonary disease (COPD) is commonly caused by smoking. FUN14 domain-containing protein 1 (FUNDC1) plays a fundamental role in mitochondrial autophagy and apoptosis in cigarette smoke extract (CSE)-treated BEAS-2B cells. The present study investigated the mechanism of action of FUNDC1 in mitochondrial dysfunction and apoptosis in CSE-treated BEAS-2B cells. The interaction between ubiquitin-specific peptidase 19 (USP19) and FUNDC1 was analyzed using co-immunoprecipitation. Effects of USP19 knockdown and/or FUNDC1 overexpression on the survival, apoptosis, mitochondrial membrane potential, and oxygen consumption rate (OCR) of BEAS-2B cells treated with 15% CSE were determined. In BEAS-2B cells, CSE inhibited cell survival, promoted apoptosis, increased the expression of USP19 and FUNDC1, increased the ratio of LC3 II to LC3 I (LC3 II/I), and decreased mitochondrial membrane potential and TOM20 levels. In CSE-treated BEAS-2B cells, USP19 knockdown reduced FUNDC1 and LC3 II/I, increased the levels of TOM20, improved cell survival, mitochondrial membrane potential, and OCR, and inhibited apoptosis. USP19 deubiquitinates FUNDC1. FUNDC1 overexpression inhibited the effect of USP19 knockdown in CSE-treated BEAS-2B cells. Overall, decreasing USP19 expression alleviates CSE-induced mitochondrial dysfunction in BEAS-2B cells by downregulating FUNDC1, providing novel insights into the molecular mechanism of FUNDC1 regulation in COPD.

Some changes appeared in women’s menstrual cycle after receiving the coronavirus disease 2019 (COVID-19) vaccine, but the information about the pattern and characteristics of these symptoms was unclear. This study was conducted to estimate the prevalence of menstruation change and evaluate the association between COVID-19 vaccination and the occurrence of such disturbance. An online web-based survey was conducted during March–April 2022 that targeted 729 COVID-19 vaccinated women aged between 18 and 45 years in the Jazan region of Kingdom of Saudi Arabia. The tool collected demographic information, psychological data, and COVID-19 post-vaccination side effects. The overall prevalence of menstrual change among the women was 60.9% (95% CI 57.3–64.4). 66.3% and 64.1% of women, respectively, in the age group of 25–34 and 35–45 years were more affected. Most of the detected abnormalities were related to delayed menstruation and changes in pain intensity. Menstrual disturbances that occur after immunization are transient and have no long-term implications. Menstrual disorders are prevalent before vaccination, but there is a considerable increase following vaccination. Because there is no apparent cause for these post-vaccine disturbances, and their effects are difficult to anticipate, it is preferable to warn those concerned and encourage them to learn more about the biological changes causing these problems.

Accumulating evidence shows that Schwann cells’ (SCs) death caused by high glucose (HG) is involved in the pathological process of diabetic peripheral neuropathy (DPN). Ferroptosis is a novel form of regulatory cell death driven by iron-dependent lipid peroxidation. However, it is not clear whether ferroptosis is involved in the death process of SCs induced by HG. The expression of ferroptosis-related indicators in the serum of DPN patients was detected by ELISA. Subsequently, using cell counting kit‑8, western blot, real-time PCR, and Ki-67 staining, we investigated the effects of HG on the ferroptosis of SCs and initially explored the underlying mechanism. The results showed that the serum levels of glutathione peroxidase 4 (GPX4) and glutathione in patients with DPN decreased, while malondialdehyde levels increased significantly. Then, we observed that erastin and HG induced ferroptosis in SCs, resulting in the decrease in cell activity and the expression level of GPX4 and SLC7A11, which could be effectively reversed by the ferroptosis inhibitor Fer-1. Mechanistically, HG induced ferroptosis in SCs by inhibiting the NRF2 signaling pathway. Our results showed that ferroptosis was involved in the death process of SCs induced by HG. Inhibition of ferroptosis in SCs might create a new avenue for the treatment of DPN.

This study aimed to investigate the effect of aquaporin-4 (AQP4) on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts. A model of diffuse ischemic brain injury was established, and adenovirus was injected stereotactically through the lateral ventricle of mice. The water content of the brain tissue was measured. The co-expression of glial fibrillary acidic protein (GFAP) and AQP4 and the aggregation of p-tau and neuronal marker were detected through immunofluorescence double staining. The expression of phosphorylated microtubule-associated protein tau (p-tau, Ser202/Thr205, Thr205, Ser396, Ser404), interleukin(IL)-6, IL-1β, tumor necrosis factor (TNF)-a, growth associated protein43 (GAP43), GFAP, and ionized calcium-binding adapter molecule 1 (Iba1) was detected through Western blot. It was found that the brain water content in the model group was increased and decreased after the AQP4 interference. Compared with the sham group, the expression of GFAP, p-tau, IL-1β, TNF-a, Iba1, and p-tau was increased in the model group ( p < 0.05). Compared with the model group, the expression of p-tau, IL-6, IL-1β, TNF-a, GFAP, and Iba1 was decreased after AQP4 interference ( p < 0.05). It is indicated that AQP4 positively regulates neurodegeneration and persistent neuroinflammation caused by tau protein aggregation after cerebral microinfarcts.

Ubiquitin-conjugating enzyme E2 C (UBE2C) plays a carcinogenic role in gastric cancer (GC); yet, its role in cisplatin (DDP) resistance in GC is enigmatic. This study sought to probe into the impact of UBE2C on DDP resistance in GC and its concrete molecular mechanism in GC progression. Bioinformatics analysis was used to analyze differentially expressed mRNAs and predict upstream regulatory molecules in GC. Real-time quantitative reverse transcriptase polymerase chain reaction and western blot were used to detect the expression of UBE2C and MYB proto-oncogene like 2 (MYBL2). Dual luciferase and chromatin immunoprecipitation (ChIP) assays were used to verify the binding relationship. Cell counting kit-8 was used to detect cell viability and calculate IC 50 values. Flow cytometry was used to detect the cell cycle. Comet assay was used to detect DNA damage. Western blot was used to detect the expression of DNA loss-related proteins (γ-H2AX, ATM/p-ATM). The knockdown of highly expressed UBE2C in GC cell lines could reduce cell viability, induce G2/M arrest, induce apoptosis, and promote DNA damage and DDP sensitivity. Bioinformatics analysis predicted that the substantially upregulated MYBL2 was an upstream transcription factor in UBE2C. The binding relationship between the UBE2C promoter region and MYBL2 was verified by dual luciferase and ChIP. Overexpression of UBE2C in the rescue experiment was found to reverse the inhibited GC progression and promoted DDP sensitivity brought by the knockdown of MYBL2. In conclusion, the MYBL2/UBE2C regulatory axis may be a potential way to overcome DDP resistance in GC.

The purpose of this study was to examine the characteristics of proximal and distal gastroesophageal reflux in patients with gastroesophageal reflux disorder and analyze their clinical symptoms. A total of 67 patients with typical esophageal symptoms were selected for this study. All participants completed the reflux disease questionnaire and a questionnaire survey of extraesophageal symptoms. Diagnosis was made using a 24-h impedance-pH detection and proton pump inhibitor. The results showed that the proximal reflux group had a higher number of acid reflux episodes compared to the distal reflux group ( P < 0.05). Similarly, the proximal reflux group also had a higher number of gas reflux episodes compared to the distal reflux group ( P < 0.05). On the other hand, the distal reflux group had a higher number of mixed reflux episodes compared to the proximal reflux group ( P < 0.05). These differences were statistically significant. This study revealed that acid reflux and gas reflux were more predominant in the proximal reflux group, while mixed reflux was more predominant in the distal reflux group.

This study attempted to identify exosomal circular RNAs (circRNAs) as diagnostic and prognostic biomarkers for patients with ST-segment elevation myocardial infarction (STEMI). The differentially expressed exosomal circRNAs (DEECs) were screened from microarray dataset (GSE160717 and GSE197137) and RNA-Seq dataset (GSE208194), and the expression levels of DEECs in patients with STEMI were validated using reverse transcription and quantitative real-time PCR. The diagnostic value of DEECs was assessed using receiver operating characteristic curves. The major adverse cardiovascular event (MACE)-free 1-year survival rate was evaluated using the Kaplan–Meier method, and the factors affecting prognosis were determined using Cox regression model analysis. Results showed that four DEECs were screened including exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, and exo-circ-0055440, and only upregulated exo-circ-0020887 and exo-circ-0009590 expression was validated in patients with STEMI. The exo-circ-0020887 and exo-circ-0009590 expression was positively correlated with hs-CRP, LDL-C, cTnI, and CK-MB. The exo-circ-0020887 and exo-circ-0009590 showed good diagnostic efficacy to distinguish STEMI patients from healthy controls (area under the curves: 0.85 and 0.80). STEMI patients with high levels of exo-circ-0020887 and exo-circ-0009590 had lower MACE-free 1-year survival rate, and exo-circ-0020887 and exo-circ-0009590 expression was independent risk factors for adverse prognosis. In summary, upregulation of plasma exo-circ-0020887 and exo-circ-0009590 might act as potential biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in patients with STEMI.

Endometriosis (EM) is a prevalent estrogen-dependent disorder that adversely affects the life quality of many reproductive-age women. Previous evidence has suggested the significant role of miR-429 in EM; however, its molecular mechanisms underlying EM pathogenesis are unclarified. Human endometrial stromal cells (HESCs) were identified using immunofluorescence staining and flow cytometry. A mouse EM model was established by endometrial auto-transplantation. RNA and protein expression of molecules was examined using real-time quantitative polymerase chain reaction and western blotting, respectively. In vitro functional experiments showed that inhibiting miR-429 restrained HESC proliferation, migration, and invasiveness. Luciferase reporter assay confirmed that miR-429 targeted hypoxia-inducible factor 1 subunit alpha inhibitor (HIF1AN) in HESCs. HIF1AN silencing offset the negative regulation of miR-429 inhibition on the HIF1A/vascular endothelial growth factor (VEGF) signaling pathway. In vivo experiments showed that depletion of miR-429 attenuated ectopic lesion development in the mouse EM model. Collectively, suppressing miR-429 hinders the invasive behaviors of HESCs and EM progression in mice by targeting HIF1AN and regulating the HIF1A/VEGF signaling pathway.

Through bibliometric analysis, we aim to comprehensively understand the research dynamics in this field, reveal key scientific research achievements and breakthrough discoveries, and provide valuable reference and guidance for future research directions. Utilizing the Web of Science, we retrieved the literature pertaining to ultrasonics-guided regional anesthesiology (1994–2022). CiteSpace and VOSviewer were used for bibliometric and knowledge mapping analysis. Our examination encompassed publication trends, authorship patterns, institutional contributions, frequently occurring keywords, keyword clustering, and emerging terminology trends. Of the 570 papers reviewed, there was a rising trend in publications each year. The main keywords in regional anesthesia were ultrasound guidance, nerve, analgesia, and pain score. Key research areas were regional anesthesia, ultrasound guidance, approach, pain score, and plane block. The U.S. led in research. Stanford University, University of Toronto, and Cork University Hospital were central institutions. Chan V was the top author with 24 articles, while Marhofer P was the most cited at 150 times. Regional anesthesia and pain medicine were the predominant journal in both publications and citations. In conclusion, research in this field consistently grew yearly, and visualization showcased trends in ultrasound-guided regional anesthesia. These visuals provided key bibliometric insights, helping researchers further explore and understand this domain.

The stress response molecule nuclear protein‑1 (NUPR1) is essential for the growth of multiple types of human malignant tumor cells. However, the significance of NUPR1 in lung cancer is still not entirely elucidated. Therefore, this study is aimed to explore the function and underlying mechanisms of NUPR1 in lung cancer. NUPR1 mRNA and protein levels in lung cancer cell lines (A549 or H1299 cells) were silenced through siRNA transfection and western blot observed its successful infection efficiency. Then, using tube formation and wound healing experiments, the effects of si-NUPR1 on angiogenesis and migration of human umbilical vein endothelial cells (HUVEC) were examined, respectively, which indicated inhibitory effects on the angiogenesis and migration of HUVEC. Vascular endothelial growth factor A (VEGFA), a vital molecule in angiogenesis, was detected by PCR and western blot assays, manifesting NUPR1 knockdown represses VEGFA expression. Furthermore, the knockdown of NUPR1 may reduce angiogenesis by lowering VEGFA expression through inositol-requiring enzyme 1 (IRE1)/X box binding protein 1 (XBP1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 A (eIF2α)/recombinant activating transcription factor 4 (ATF4) signaling pathways in A549 or H1299 cells. In conclusion, these findings demonstrated that NUPR1 knockdown inhibits angiogenesis in A549 and H1299 cells through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways, indicating that NUPR1 could represent a novel lung cancer therapeutic target.

This is a retrospective study of patients admitted to Jackson Hospital, Montgomery, Alabama, with a diagnosis of COVID-19 from January 1, 2021, to February 15, 2022. The independent variables used in the models were patient sex, age, race, BMI category, daily D-dimer categories, categories of anticoagulation doses, bleeding episodes, and vaccination status. The three different categories of anticoagulation doses were considered for the purpose of the study which were Enoxaparin 40 mg daily vs Enoxaparin 80 mg daily vs Enoxaparin 1 mg/kg or equivalent daily. The study reviewed a total of 100 hospitalized patients. Intermediate-dose anticoagulation was found to be the optimal dose as only 14% patients died compared to a 36 and 50% death rate among those treated with low-dose and high-dose anticoagulation, respectively. The multivariate linear regression model predicting patient oxygen requirements revealed D-dimer and bleeding status to be statistically significant predictors with a p value of <0.01. For the patients who had a D-dimer value ≥2 µg/mL, the oxygenation requirement was predicted to be 31 L higher than those with a D-dimer <2 µg/mL (99% CI; p < 0.01). When mean D-dimer and corresponding oxygen requirements were calculated per hospitalization days category, the D-dimer levels and oxygen requirements were noted to follow the same trends indicating that both values tended to increase and decrease simultaneously. The study concludes daily D-dimer trends can predict COVID-19 patient survival or daily oxygen requirements indicating that D-dimer can be the miracle molecule for COVID-19 prognosis.

Intracranial aneurysm (IA) is a type of cerebrovascular disease that mainly occurs in the circle of Willis. Abnormalities in RNA methylation at the N6-methyladenosine (m6A) site have been associated with numerous types of human diseases. WTAP recruits the m6A methyltransferase complexes to the mRNA targets, and its expression is positively correlated with m6A methylation levels. This research aimed to explore the potential mechanisms of m6A methylation in IA. A selective arterial ligation method was used to establish an IA rat model; thereafter, the m6A methylation level and m6A methylation-related genes were determined in blood and circle of Willis samples using a commercial kit and real-time quantitative PCR, respectively. Subsequently, rat brain microvascular endothelial cells (rBMVECs) were treated with TNF-α, and the expression of m6A methylation-related genes within the cells were assessed. Lastly, the effects of WTAP on TNF-α-induced rBMVECs were further investigated through in vitro experiments. In result, the m6A RNA methylation level evidently declined in the blood and circle of Willis’ samples of the IA rats, as compared to the corresponding samples from the control rats ( P < 0.05). Compared to the results in the control rats/cells, WTAP expression was significantly downregulated, whereas ALKBH1 expression was evidently upregulated in the blood and circle of Willis samples of the TNF-α-induced rBMVECs of IA rats. Consequently, TNF-α-induced rBMVECs and rBMVECs with WTAP overexpression were successfully established. TNF-α inhibited the viability of the rBMVECs, promoted apoptosis, and significantly upregulated cleaved-caspase3 and downregulated WTAP expression. In contrast, WTAP overexpression significantly reversed these changes caused by TNF-α ( P < 0.05). In conclusion, WTAP overexpression may modulate the growth of TNF-α-induced rBMVECs by enhancing WTAP expression and its m6A methylation.

The aim of this study was to evaluate the efficacy of endoscopic polypectomy as a therapeutic treatment for malignant alteration of colorectal polyps. In a 5-year research, 89 patients were included, who were tested and treated at the University Clinical Center Kragujevac, Kragujevac, Serbia, with the confirmed presence of malignant alteration polyps of the colon by colonoscopy, which were removed using the method of endoscopic polypectomy and confirmed by the histopathological examination of the entire polyp. After that, the same group of patients was monitored endoscopically within a certain period, controlling polypectomy locations and the occurrence of a possible remnant of the polyp, in the period of up to 2 years of polypectomy. We observed that, with an increasing size of polyps, there is also an increase in the percentage of the complexity of endoscopic resection and the appearance of remnant with histological characteristics of the invasive cancer. The highest percentage of incomplete endoscopic resection and the appearance of remnant with histological characteristics of the invasive cancer were shown at malignant altered polyps in the field of tubulovillous adenoma. Eighteen patients in total underwent the surgical intervention. In conclusion, our data support the high efficacy of endoscopic polypectomy for the removal of the altered malignant polyp.

We elucidated the effect of S100A4 on airway remodeling by regulating airway inflammation and epithelial–mesenchymal transition (EMT) in mouse models of asthma. Asthmatic mouse models were established by sensitization and challenged with ovalbumin (OVA). Anti-S100A4 antibody or control IgG antibody was administered daily before the OVA challenge. After the last challenge, airway inflammation and airway hyperresponsiveness were measured; lung tissues and bronchoalveolar lavage fluid (BALF) were harvested. Lung tissue sections were stained and evaluated for pathological changes. Levels of inflammatory cytokines were measured using ELISA. Levels of S100A4 and EMT markers were determined via western blotting analysis. Human bronchial epithelial cells were stimulated with 100 mg/mL house dust mites (HDMs) to evaluate the effect of S100A4 downregulation on EMT in vitro . S100A4 was increased in lung tissues and BALF from asthmatic mice. The asthmatic mice presented airway hyperresponsiveness, airway inflammation, and airway remodeling. After anti-S100A4 antibody administration, pathophysiological signs, including airway hyperresponsiveness and increased infiltration of inflammatory cells, were attenuated. Additionally, anti-S100A4 administration downregulated vimentin and α-SMA expression and upregulated E-cadherin expression in OVA-challenged mice. S100A4 downregulation also inhibited EMT process in HDM-stimulated 16HBE cells. Anti-S100A4 antibody administration alters airway remodeling by preventing EMT in mouse models of asthma.

Predicting MYC and BCL2 double-expressor lymphoma prognosis using the system immune-inflammatory index (SII) and prognostic nutritional index (PNI) (DEL). From January 2015 to December 2021, 281 diffuse large B-cell lymphoma (DLBCL) wax blocks were used to make tissue chips. Screening double expressor lymphoma (DEL) instances involved immunocytochemistry and fluorescence in situ hybridization. Academic analysis used clinicopathological characteristics and follow-up data. SII, PNI, and DEL prognosis were correlated using univariate and multivariate cox regression analysis. The median age of 78 DEL patients is 60 (range: 43–74). SII and PNI cut-off values of 603.5, 3.07, and 144 predict PFS and OS well. Lower SII is associated with longer PFS (HR for SII = 0.34, 95% CI 0.15–0.76, P = 0.006; HR for NLR = 0.46, 95% CI 0.22–0.99, P = 0.048; HR for PLR = 0.39, 95% CI 0.17–0.94, P = 0.025; LMR = 0.39, 95%, CI 0.17–0.94, P = 0.025) and OS (HR for SII = 0.16, 95% CI 0.05–0.51, P = 0.005; HR for PNI = 0.20, 95% CI 0.06–0.62, P = 0.002). SII and PNI are promising predictors for twofold expressor DLBCL. Combining these increase prediction accuracy.

Identifying and appropriately managing urinary tract infections (UTIs) among chronic kidney disease (CKD) patients are essential to reduce further disease complications and economic burden. Hence, this study aims to determine the prevalence of UTIs among CKD patients and study the antibiogram of the bacterial isolates. Four hundred eighty-two clean catch midstream urine samples were collected from CKD patients during the study period. The samples were cultured, and bacteria were isolated using standard microbiological techniques. Antibiotic susceptibility testing was performed by the Kirby–Bauer disc diffusion method following the Clinical and Laboratory Standards Institute guidelines. Of the 482 CKD patients, 15.8% were culture positive, and the majority was elderly aged group population. Most bacterial isolates were Escherichia coli 50%, followed by Pseudomonas aeruginosa 15.80%, Enterococcus species 15.80%, and Klebsiella pneumoniae 11.84%. The majority of bacteria were found to be resistant to beta-lactam antibiotics, ampicillin (94.67%), ceftriaxone (89.04%), cefotaxime (87.5%), and ceftazidime (84.0%), while polymyxin, colistin, vancomycin, meropenem, and imipenem were the most sensitive antibiotics. In our study, higher levels of antibiotic resistance were observed among urinary isolates. Therefore, our findings suggest clinicians to choose better antibiotic options to treat UTIs among CKD patients.

Uterine cervical intraepithelial abnormalities and cancer development may also depend upon biological problems that arise as a result of complex molecular disturbances within the vaginal space, in addition to the widely known causative effect of human papillomavirus (HPV) infection. Chronic oxidative stress is a consequence of oxygen reduction in the vaginal space. Reactive oxygen species (ROS) and free radicals are yet unrecognizable causative agents and are probably very important factors for cervical intraepithelial neoplasia (CIN) and cancer development. The intermediate compounds of oxygen reduction on these metabolic pathways are superoxide anion ( O 2 ˙ − {\text{O}}_{2}^{ \textdotaccent -} ), hydrogen peroxide (H 2 O 2 ), hydroxide ions (OH − ), and hydroxyl radical (HO˙). Considering these points, the aim of this work was to summarize how these compounds can damage all molecules, including DNA, of vulnerable metaplastic cervical epithelium. Finally, in some women with a poor immune defense system, ROS alone or accompanied by a high-risk HPV type may promote all levels of CIN and cancer development.

Lower-grade glioma (LGG), a prevalent malignant tumor in the central nervous system, requires accurate prediction and treatment to prevent aggressive progression. We aimed to explore the role of disulfidptosis-related genes (DRGs) in LGG, a recently discovered form of programmed cell death characterized by abnormal disulfide accumulation. Leveraging public databases, we analyzed 532 LGG tumor tissues (The Cancer Genome Atlas), 1,157 normal samples (Genotype-Tissue Expression), and 21 LGG tumor samples with 8 paired normal samples (GSE16011). Our research uncovered intricate relationships between DRGs and crucial aspects of LGG, including gene expression, immune response, mutation, drug sensitivity, and functional enrichment. Notably, we identified significant heterogeneity among disulfidptosis sub-clusters and elucidated specific differential gene expression in LGG, with myeloid cell leukemia-1 (MCL1) as a key candidate. Machine learning techniques validated the relevance of MCL1, considering its expression patterns, prognostic value, diagnostic potential, and impact on immune infiltration. Our study offers opportunities and challenges to unravel potential mechanisms underlying LGG prognosis, paving the way for personalized cancer care and innovative immunotherapeutic strategies. By shedding light on DRGs, particularly MCL1, we enhance understanding and management of LGG.

Contemporary understanding of the dynamic anatomy of pelvic floor support has led us to new conservative surgery for uterine prolapse (UP). In this study, we comprehensively evaluate the safety and feasibility of a new technique for uterine-preserving pelvic organ prolapse surgery: laparoscopic rectus abdominis hysteropexy for uterine prolapse (LRAHUP). A retrospective study was conducted between 2006 and 2016. Sixty-five women diagnosed with advanced prolapsed uterus were eligible and grouped into traditional vaginal surgery (TVS, n = 30) group and new laparoscopic surgery (NLS, n = 35) group. Evaluated items of 65 cases included surgery-related parameters and postoperative outcomes. Surgical safety evaluating indicators, including operation time, blood loss, postoperative hospitalized day, and operation complications, also showed great significant difference between two groups ( P < 0.05). The subjective index of post-operative Pelvic Floor Distress Inventory-short form 20 scores and some objective anatomic outcomes all showed great difference between pre- and post-operation ( P < 0.05). Although the TVL showed no difference between pre- and post-operation in the same group, the TVL displayed a remarkable elongation. And a remarkable tendency was a higher cumulative recurrence ratio in the TVS group and a shorter follow-up period in the NLS group. LRAHUP may be a good procedure to manage women with advanced prolapsed uterus.

The aim of this retrospective cohort study is to understand if and how much the preventive self-isolation approach might have been a valid model to avoid care-related infection, not only from COVID-19 but also from other non-viral infectious diseases. From March to May 2020, the healthcare and management staff of the Villa Santa Maria long-term care facilities, located in the village of Montenero di Bisaccia (Campobasso, Molise, Italy), decided to carry out a preventive self-isolation plan to safeguard the residents from SARS-CoV-2. The impact on other infectious diseases was evaluated by analyzing the antibiotic therapies prescription trend among the inpatients. Our data showed that although self-isolation protected residents and caregivers from SARS-CoV-2, it can also be associated with mobility reduction, leading to an increase in bedridden pathologies, namely, pressure ulcers and pressure sores. The simultaneous isolation of residents and caregivers in the same location significantly reduced any outside influence as a cause of possible infections.

This study was conducted to investigate the effects of anti-gravity treadmill (AGT) training, which provides visual feedback and Biorescue training on proprioception, muscle strength, balance, and gait, in stroke patients. A total of 45 people diagnosed with post-stroke were included as study subjects; they were randomized to an AGT training group provided with visual feedback (Group A), a Biorescue training group provided with visual feedback (Group B), and an AGT/Biorescue group that subsequently received AGT training and Biorescue training (Group C). A muscle strength-measuring device was used to evaluate muscle strength. Timed Up and Go and Bug Balance Scale assessment sheets were used to evaluate balance ability. Dartfish software was used to evaluate gait ability. The results of the study showed that Groups A and C had a significant increase in muscle strength compared with Group B; in terms of balance and gait abilities, Group C showed a significant increase in balance ability and gait speed and a significant change in knee joint angle compared with Groups A and B. In conclusion, this study suggests that including a method that applies multiple therapeutic interventions is desirable in the rehabilitation of stroke patients to improve their independence.

Chronic prostatitis (CP) is one of the diseases that reduce the quality of life (QoL) of young men. To date, there is no consensus on the management of these patients. It is essential to continue research into the treatment of CP, despite the use of various therapies, including low-energy extracorporeal shockwave therapy (ESWT). The main objective of this study is to observe and record the clinical symptomatology of patients during a 48-week follow-up period after ESWT treatment. Between 2019 and 2021, 28 patients with type IIIB CP/chronic pelvic pain syndrome were enrolled. Patients underwent ESWT once weekly for 4 weeks (3,000 individual sessions, maximum total energy flux density 0.25 mJ/mm 2 , frequency 3 Hz). Participants were assessed at 0, 4, 12, 24, 36 and 48 weeks post-treatment using the visual analogue scale (VAS), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and International Index of Erectile Function (IIEF)-5. The mean age of patients was 47.1 ± 13.7 years (range 28–4 years). The positive effect of LI-ESWT was reflected in improvements in VAS, NIH-CPSI, and IIEF-5 scores. Regression of patients’ symptoms was observed as early as 4 weeks after treatment. The greatest progress was achieved at week 24. In addition, a slight worsening was observed at week 36 and 48, with stable progress. The treatment significantly improved the QoL of the patients, with the most significant improvement in the VAS score. In conclusion, this treatment approach is safe, most effective in the first 6 months. Thereafter, the efficacy of the treatment diminishes, but is sustained over a longer period.

This meta-analysis aimed to evaluate the diagnostic accuracy of touch imprint cytology (TIC) for sentinel lymph node (SLN) metastases of patients with clinical node-negative early breast cancer. The PubMed, Web of Science, Embase, and the Cochrane Library databases were meticulously searched to retrieve literature published from January 2005 to September 2022 by two independent reviewers. The meta-analysis was performed using STATA16.0, Meta-Disc 1.4, and RevMan 5.4.9. According to the inclusion criteria, 4,073 patients from 13 studies were included in this meta-analysis. The pooled sensitivity and specificity of TIC for detecting SLN metastases were 0.77 (95% CI 0.66–0.85) and 0.99 (95% CI 0.97–1.00), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 76.15 (95% CI 29.16–198.84) and 0.23 (95% CI 0.15–0.36), respectively. The pooled diagnostic odds ratio was 326.82 (95% CI 132.76–804.56) and the area under the sROC curve was 0.97 (95% CI 0.95–0.98), respectively. This meta-analysis revealed that TIC with high sensitivity and specificity is a feasibility and accuracy diagnosis technique for intraoperative detection of SLN metastases in breast cancer.

The study aimed to analyze the mortality and leading causes of death associated with Sjögren’s syndrome (SS) in the United States (US) between 1999 and 2020 using a multicause approach. We analyzed mortality based on SS as the cause-of-death. Using mortality rates, number of deaths, and historical trends, we examined sex, age of death, comparisons of SS- and polymyalgia rheumatica-related deaths (multiple cause-of-death) in the last 20 years, changes in the ranking of causes of death when SS was the underlying cause-of-death (UCD) in the first and last 5 years of the last 20 years, and the number of deaths and standardized mortality (per 100,000 people) when SS combined with interstitial lung disease (ILD) or tumor was the multiple cause-of-death. An SS-standardized mortality trend chart and a trend line were created. In 22 years, the total number of SS-related deaths in the US was 7,817, including 7,016 women. When SS was the UCD and non-UCD, the standardized ratios of female-to-male deaths (per 100,000 people) were approximately 4.6–13:1 and 6.8–19.6:1, respectively. SS-related deaths were more common in people aged >60 years and concentrated in patients aged 60–79. In cases where SS and polymyalgia rheumatica were the multiple cause-of-death, the number of deaths and age-standardized mortality of SS and polymyalgia rheumatica increased, although lower in SS than in polymyalgia rheumatica. Regarding SS as the UCD, heart disease ranks first. Concerning the number of deaths and standardized mortality in the first (1999–2003) and second (2016–2020) 5 years, when SS-ILD and SS combined with tumors were the multiple causes of death, the number increased in the second 5 years compared to that in the first 5 years. When SS combined with COVID-19 was the multiple cause-of-death, 73 deaths occurred, comprising 64 females and 9 males. Death predominance was observed among women and patients aged 60–79 years with SS. Although the SS-standardized mortality rate was low, an increasing trend was observed. When SS was the primary cause-of-death, heart disease remained primarily involved, followed by malignant neoplasms. The number of patients with SS-ILD and SS combined with tumors in the past 22 years and the standardized mortality rate after 5 years increased compared with those of the previous 5 years. Concurrent SS and COVID-19 may be related to the increased SS deaths.

As a high metastatic tumor, patients having hepatocellular carcinoma (HCC) show poor prognosis. The carcinogenic roles of circMMP11 are generally described in the development of other cancers. However, there is a lack of studies on its involvement in HCC. Therefore, we investigated the potential role and molecular mechanisms of CircMMP11 in the development of HCC in vitro , providing preliminary evidence for the clinical treatment of HCC. First, we examined the expression of CircMMP11 in HCC tissues and cell lines in both clinical and in vitro experiments. We then used a loss-of-function assay to determine CircMMP11’s regulatory role on the malignant characteristics of HCC cells. The results showed that high expression of CircMMP11 in HCC was associated with patient overall survival. Serum CircMMP11 had good diagnostic efficacy in distinguishing HCC patients from the control group. In vitro , inhibiting CircMMP11 suppressed the malignant characteristics of human HCC cell lines by directly sequestering miR-361-3p, which further affected the downstream gene HMGB1 expression. In addition, we knocked down CircMMP11 and found that its deletion inhibited the malignant characteristics of HCC cells through the miR-361-3p/HMGB1 axis.

We discuss the clinical characteristics and prognostic significance of adult individuals with PTPN11 mutations who have developed acute myeloid leukemia (AML) (none acute promyelocytic leukemia). Next generation sequencing and Sanger sequencing were used to detect 51 gene mutations, and multiplex-PCR was used to detect 41 fusion genes from 232 de novo adult AML patients retrospectively. About 7.76% patients harbored PTPN11 mutations, 20 PTPN11 alterations were identified, all of which were missense mutations in the N-SH2 ( n = 16) and PTP ( n = 4) domains located in exon 3. Patients with PTPN11 mut had significantly higher platelet counts and hemoglobin levels ( p < 0.001), which were mainly detected in M5 ( n = 12, 66.67%, p < 0.001) subtype. Patients with MLL-AF6 positive showed a higher frequency of PTPN11 mut ( p = 0.018) in the 118 AML cases. PTPN11 mut were accompanied by other mutations, which were NPM1 (44.44%), DNMT3A (38.89%), FLT3 (38.89%), and NRAS (17.2%). PTPN11 mut had a negative impact on the complete remission rate in M5 subtype patients ( p < 0.001). However, no statistically significant effect on overall survival (OS) with PTPN11 mut patients in the whole cohort and age group ( p > 0.05) was observed. Further analysis revealed no significant difference in OS among NPM1 mut / PTPN11 mut , NPM1 mut / PTPN11 wt , DNMT3A mut / PTPN11 mut , and DNMT3A mut / PTPN11 wt patients ( p > 0.05). Multivariate analysis showed the proportion of bone marrow blasts ≥65.4% was a factor significantly affecting OS in PTPN11 mut patients ( p = 0.043).

The molecular mechanisms of epigenetic regulation in gastric cancer development are not yet well established. In this study, we demonstrated that KMT2A was highly expressed in gastric cancer and associated with poor outcomes of patients and revealed that KMT2A was significantly associated with stemness and increased nuclear β-catenin in gastric cancer. Mechanistically, KMT2A activated the translocation of β-catenin into the nucleus of gastric cancer cells, and then, β-catenin served as a coactivator of KLF11, which promoted the expression of specific gastric cancer stemness-related molecules, including SOX2 and FOXM1. Together, KMT2A is an important epigenetic regulator of gastric cancer stemness, which provides a novel insight to the potential application of targeting against KMT2A in treating gastric cancer.

A prospective observational study (ClinicalTrial ID: NCT05771415) was conducted to compare placental oxygenation in low-risk, uncomplicated term pregnancies measured by near-infrared spectroscopy (NIRS) in relation to the placental maturity grade determined by ultrasound assessment according to the Grannum scale. We included 34 pregnancies divided into two groups according to placental maturation. For each pregnancy, measurements were taken at the site above the central part of the placenta (test) and at the site outside of the placenta on the lower abdomen (control). Student’s t -test was used to compare tissue oxygenation index (TOI) values among the study groups. The normality of distribution was proven by the Kolmogorov‒Smirnov test. In women with low placental maturity grade, the mean TOI value above the placenta was 70.38 ± 3.72, which was lower than the respective value in women with high placental maturity grade (77.99 ± 3.71; p < 0.001). The TOI values above the placenta and the control site were significantly different in both groups (70.38 ± 3.72 vs 67.83 ± 3.21 and 77.99 ± 3.71 vs 69.41 ± 3.93; p < 0.001). The results offer a new perspective on placental function based on specific non-invasive real-time oxygenation measurements. Unfortunately, and because of technical limitations, NIRS cannot yet be implemented as a routine clinical tool.

To determine whether ultrasound (US) features of breast cancer are associated with Breast Imaging and Reporting Data System molecular subtype, histologic grade, and hormone receptor status as well as to assess the predictive value of these features. Retrospective analysis of the medical records of 220 consecutive patients with invasive breast cancer was reviewed according to the PIK3CA -mutated molecular tumor subtype. US findings of all patients were analyzed. Breast tumors harboring a PIK3CA -mutation were large and exhibited liquefied necrosis and posterior echo attenuation in the nodule. Moreover, such tumors were lobulated and calcified. The aspect ratio of the PIK3CA -mutant was more likely >1. The average nodule elasticity (7.479 ± 0.993 m/s) was measured using US shear wave elastography. Microcalcification was easier to detect inside the nodule using a fluorescence technique. Measurement of the nodule blood flow spectrum showed that the internal blood flow resistance index of nodules was lower than that of other types of breast cancer. The sonographic features of PIK3CA -mutated breast cancers were strongly associated with extensive and liquefied necrosis. The ability to predict molecular subtypes, particularly using US to detect the triple-negative subtype, may play an important role in early management and treatment.

Immunotherapy is a promising treatment for advanced colorectal cancers (CRCs). However, immunotherapy resistance remains a common problem. Immunogenic cell death (ICD), a form of regulated cell death, induces adaptive immunity, thereby enhancing anti-tumor immunity. Research increasingly suggests that inducing ICD is a promising avenue for cancer immunotherapy and identifying ICD-related biomarkers for CRCs would create a new direction for targeted therapies. Thus, this study used bioinformatics to address these questions and create a prognostic signature, aiming to improve individualized CRC treatment. We identified two ICD -related molecular subtypes of CRCs. The high subtype showed pronounced immune cell infiltration, high immune activity, and high expression of human leukocyte antigen and immune checkpoints genes. Subsequently, we constructed and validated a prognostic signature comprising six genes ( CD1A , TSLP , CD36 , TIMP1 , MC1R , and NRG1 ) using random survival forest analyses. Further analysis using this prediction model indicated that patients with CRCs in the low-risk group exhibited favorable clinical outcomes and better immunotherapy responses than those in the high-risk group. Our findings provide novel insights into determining the prognosis and design of personalized immunotherapeutic strategies for patients with CRCs. Graphical abstract