Volume 18, Issue 1

Most patients with metastatic breast cancer or gastric cancer who are treated with trastuzumab, an anti-HER2 monoclonal antibody, become refractory to the drug within a year after the initiation of treatment. Although the combination of trastuzumab with pertuzumab produced synergetic effects in the treatment of HER2-overexpressing cancers, not all patients with HER2 overexpression benefited from the trastuzumab plus pertuzumab combination. To improve the clinical benefits of trastuzumab, we systemically investigated the combination of inetetamab (Cipterbin), an analog of trastuzumab, with a variety of small molecules, including tyrosine kinase inhibitors (TKIs) and chemotherapeutic agents in vivo . We showed that pan-TKIs-induced synergistic antitumor effects with inetetamab in the treatment of these two types of cancers and that adding chemotherapeutic agents to the existing TKI plus anti-HER2 monoclonal antibody combination strategies induced additional inhibitory effects, suggesting that such combination strategies may be choices for the treatment of these two tumors. Thus, combination therapies targeting distinct and broad pathways that are essential for tumor growth and survival can be effective for treating metastatic breast cancers and gastric cancers.

This network meta-analysis (NMA) aims to investigate the efficacy and safety of different pharmacological treatments for idiopathic membranous nephropathy (IMN). Thirty-four relevant studies were extracted from PubMed, Embase, Cochrane database, and MEDLINE. Treatment with tacrolimus (TAC), cyclophosphamide (CTX), mycophenolate mofetil, chlorambucil (CHL), cyclosporin A (CSA), steroids, rituximab (RTX), and conservative therapy were compared. Outcomes were measured using remission rate and incidence of side effects. Summary estimates were expressed as the odds ratio (OR) and 95% confidence intervals (CIs). The quality of findings was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. In the direct meta-analysis for comparison of complete remission (CR) rate, the curative effect of RTX is inferior to CTX (OR 0.37; CI 0.18, 0.75). In the NMA of CR rate, the results showed that the curative effects of CTX, CHL, and TAC were significantly higher than those of the control group. The efficacy of RTX is not inferior to the CTX (OR 0.81; CI 0.32, 2.01), and the level of evidence was moderate; CSA was not as effective as RTX, and the difference was statistically significant with moderate evidence (OR 2.98, CI 1.00, 8.91). In summary, we recommend CTX and RTX as the first-line drug for IMN treatment.

Little is known about the genetic background of pigmented paravenous retinochoroidal atrophy (PPRCA) due to rarity of patients. In this study, we identified two pathogenic variants in RPGRIP1 in a 2-year-old boy with PPRCA screened by whole-exome sequencing (WES). The patient presented to our department with photophobia for 17 months, and then he underwent fundus photography and fluorescein fundus angiography. Genomic DNA was extracted from peripheral blood of the proband and the parents. Trio-WES strategy was utilized to identify the causal variants from the proband and the parents, followed by validation based on Sanger sequencing. The patient was finally diagnosed with PPRCA after differential diagnosis. Two heterozygous pathogenic variants were detected by WES according to the American college of medical genetics and genomics guidelines, including NM_020366.4: c.2592T > G: p.Y864* and NM_020366.4: c.154C > T: p.R52* in RPGRIP1 located in exon 17 and exon 3, leading to termination codon, respectively. This is the first study reporting pathogenic variants within RPGRIP1 as causal for PPRCA.

Phytoestrogens and cold negatively influence male fertility. However, the combined effects of these two factors on male reproduction remain unknown. Herein, we studied the changes of sperm parameters and identify potential biomarkers involved in testis of rats, which were intervened by phytoestrogens combined with cold stress. Male Sprague–Dawley rats were randomly divided into control and model groups. The rats in the model group were fed an estrogen diet and placed in a climate chamber [10 ± 2°C; humidity of 75 ± 5%] for 12 h/daily. When compared with the control group after 24 weeks, the rats in the model group showed increased food intake, urine and stool outputs, and higher estradiol and follicle-stimulating hormone levels. However, lower sperm concentration, motility, and viability, and reduced testosterone levels were detected. The epithelial cells of the seminiferous tubules and epididymal ducts presented morphological abnormalities. Proteomic analysis showed that 24 testicular proteins were upregulated and 15 were downregulated. The identified proteins were involved in reticulophagy and stress response. Our findings suggest that the phytoestrogens combined with cold stress had negative effects on the reproductive function of male rats and provide the basis for the establishment of “course simulation” type of oligospermia animal model.

Warfarin is an anticoagulant commonly used as an oral drug in preventing and treating thromboembolic diseases. The international normalized ratio (INR) is a clinical monitoring anticoagulation intensity index that adjusts the dose based on important references. In particular, INR value must be strictly monitored when warfarin is used for anticoagulation therapy in infected patients. Herein, we report a 54-year-old female patient diagnosed with pulmonary embolism and venous thrombosis of the lower limbs. After the warfarin administration, the INR was always substandard. The patient did not take other warfarin-interacting drugs or foods during the hospital stay. Metagenome next-generation sequencing suggested a bloodstream infection caused by Escherichia coli , which was further confirmed by blood culture. After meropenem administration for anti-infective treatment, the INR value rose rapidly to a standard level. Considering the lack of relevant reports, this case is the first report of potential interaction between E. coli and warfarin. Further, in patients with thromboembolic diseases complicated by infection, antibiotics should be chosen reasonably with close monitoring of the INR to avoid the interaction of warfarin and antibiotics and to ensure the effectiveness and safety of warfarin treatment.

The increase in the level of neutrophils following subclinical Cushing’s disease is an uncommon clinical phenomenon that is characterized by insignificant biochemical or clinical evidence of hypercortisolism. In this study, we reported a 37-year-old female patient who presented with palpitations and fatigue, and showed increased neutrophils that were unaffected by anti-infection therapy. The patient was suspected of having a urinary tract infection because of occasionally with urinary frequency, urgency, increased procalcitonin, leukocytosis, and an increased proportion of neutrophils. The ineffectiveness of anti-infection therapy ruled out the possibility of urinary tract infection. Further examination of the bone marrow excluded the possibility of blood disease. However, the levels of blood cortisol and adrenocorticotropic hormone (ACTH) increased, and a magnetic resonance imaging examination revealed lesions in the sphenoidal sinus and sella area of the sphenoidal bone, which confirmed the relationship between increased glucocorticoids and increased neutrophils. This was further confirmed by follow-up surgery and pathological examination, which revealed silent corticotropin adenomas, which are characterized by the lack of biochemical or clinical evidence of hypercortisolism with positive immunostaining for ACTH.

Chronic periodontitis is an inflammatory disease characterized by inflammation of the soft tissues of the gums. To combat this disease, more effective drugs are still needed to identify and develop. Isoimperatorin is a kind of a natural compound, which has anti-inflammatory, analgesic, antitumor, antivirus, and other pharmacological effects. However, its possible effects on the progression of chronic periodontitis are still unclear. In this study, we used human periodontal membrane fibroblasts (hPDLCs), human bone marrow-derived macrophages, and found that isoimperatorin reduced hPDLCs viability. In addition, isoimperatorin alleviated the oxidative stress of periodontal membrane cells. Isoimperatorin reduced proinflammatory factor secretion and receptor activator for nuclear factor-κB ligand–induced osteoclast differentiation in periodontal membrane cells. Further, isoimperatorin inhibited the activation of ERK1/2 and nuclear factor-κB pathways. We, therefore, thought isoimperatorin could serve as a promising drug for the treatment of this disease.

Osteoarthritis (OA) is the most common joint disease affecting approximately 10% of men and 18% of women older than 60. Its pathogenesis is still not fully understood; however, emerging evidence has suggested that chronic low-grade inflammation is associated with OA progression. The pathological features of OA are articular cartilage degeneration in the focal area, including new bone formation at the edge of the joint, subchondral bone changes, and synovitis. Conventional drug therapy aims to prevent further cartilage loss and joint dysfunction. However, the ideal treatment for the pathogenesis of OA remains to be defined. Macrophages are the most common immune cells in inflamed synovial tissues. In OA, synovial macrophages undergo proliferation and activation, thereby releasing pro-inflammatory cytokines, including interleukin-1 and tumor necrosis factor-α, among others. The review article discusses (1) the role of synovial macrophages in the pathogenesis of OA; (2) the progress of immunoregulation of synovial macrophages in the treatment of OA; (3) novel therapeutic targets for preventing the progress of OA or promoting cartilage repair and regeneration.

Joubert syndrome (JBTS) is a class of heterogeneous ciliopathy genetically associated with CPLANE1 mutations. The characteristics of clinical phenotypes and CPLANE1 variants were analyzed in a 2-month-old patient. A 2-month-old patient with JBTS was diagnosed after clinical evaluation including family history, physical examination, cerebral MRI, ultrasonography imaging, VEGG, ocular fundus examination, and comprehensive blood and urine testing. Whole exome sequencing (WES) was performed to detect CPLANE1 variants, and Sanger sequencing was used to confirm the variants. This JBTS patient presented with oculomotor apraxia, dysregulation of breathing pattern, and ataxia. MRI revealed poor continuity of cerebelli, batwing appearance, and molar tooth sign. This patient was noted with abnormal hematology, dysregulation of hepatic function, thyroid function, immunity, and renal function, and encephalopathy. CPLANE1 (c.8948dupT (p.P2984Tfs*7) and c.247G > T (p.G83X)) variants were noticed in the patient as a pathogenic variant and caused autosomal recessive inheritance. The JBTS patient with mutations in CPLANE1 (c.8948dupT (p.P2984Tfs*7) and c.247G > T (p.G83X)) developed JBTS phenotypes. The novel CPLANE1 c.8948dupT (p.P2984Tfs*7) variant will assist clinicians and geneticists in reaching a precise diagnosis for JBTS.

The morbidity and mortality of BCR-ABL -negative myeloproliferative neoplasia (MPN) patients is highly dependent on thrombosis that may be affected by antiphospholipid antibodies (aPLA) and lupus anticoagulant. Our aim was to evaluate the association of the aPLA together with platelet receptor glycoprotein (GP) Ia/IIa c.807C>T CT/TT genotypes and thrombotic complications in patients with MPNs. The study included 108 patients with BCR-ABL -negative MPN with data of previous thrombosis. Two different screening and one confirmatory test for the lupus anticoagulant were performed. Thrombotic complications were present in 59 (54.6%) subjects. aPLA were more frequently found in MPN patients with thrombosis vs no thrombosis (25.4 and 6.1%; p = 0.007). MPN patients with arterial thrombosis were more frequently positive for aPLA vs no arterial thrombosis (38.8 and 11.9%; p = 0.001). aPLA were more frequently found in patients with cerebrovascular events vs other arterial thrombotic complications or no thrombosis, respectively (39.3, 6.1, and 12.9%; p < 0.001). MPN patients with thrombosis were more frequently positive with aPLA and had platelet receptor GP Ia/IIa c.807C>T CT/TT genotypes compared to MPN patients without thrombosis (18.6 and 2.0%; p = 0.006). aPLA alone or with coexistence with platelet receptor GP Ia/IIa c.807C>T CT/TT polymorphism could be associated with thrombotic complications in patients with MPN.

This study investigated the effect of combined thymosin α1 and vitamin C (Tα1 + VitC) on the immunological responses of septic rats. Five groups were designed. The septic model was established by the cecal ligation puncture (CLP) method. The sham group did not undergo CLP, the model group was given normal saline solution, the Tα1 group was given Tα1 (200 µg/kg), the VitC group was given VitC (200 mg/kg), and the Tα1 + VitC group was given Tα1 + VitC. Specimens for immunological analyses were collected at 6, 12, 24, and 48 h posttreatment in each group except for the sham group (only at 48 h). CD4 + CD25 + T cells in the peripheral blood and dendritic cell (DC) proportions in the spleen were analyzed by flow cytometry. Tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), transforming growth factor-β (TGF-ß1), and nuclear factor kappa-B (NF-κB) were measured by ELISA. CD4 + CD25 + T cells and OX62 + DCs levels significantly increased in the model group and decreased in the Tα1 and/or VitC treatment groups. Similarly, the levels of TNF-α, IL-6, TGF-ß1, and NF-κB significantly increased in the model group and decreased in the Tα1, VitC, and Tα1 + VitC groups, indicating that combined Tα1 and VitC therapy may help regulate the immunological state of patients with sepsis, thereby improving prognosis.

Few studies focused on the roles of high glucose combined with high lipid in placental development or fetal growth. This study was designed to investigate the roles of high glucose combined with high lipid in mitochondrial dysfunction of JEG-3 cells. We determined the cellular proliferation and apoptosis, superoxide dismutase (SOD) activity, concentration of malondialdehyde (MDA), and lactic acid dehydrogenase in control group, high glucose group, high lipid group, and high glucose and high lipid group, together with the mitochondrial dysfunction, Nrf2, HO-1, SMAC, and cytochrome C (Cyt- C ) expression. Significant decrease of SOD and significant elevation of MDA was seen in high glucose and high lipid group compared with the other three groups. There was significant decrease in mitochondrial SMAC and Cyt- C in high glucose group, high lipid group, and high glucose and high lipid group compared with those of control group. Nrf2 and HO-1 protein expression in high glucose combined with high lipid group showed significant decrease compared with that of high lipid group or high glucose group. We speculated that combination of high glucose and high lipid induced oxidative stress in JEG-3 cells, and Nrf2/ARE pathway may be related to this process.

Glioblastoma (GBM) is a malignant brain tumor. The purpose of this study is to estimate the potential effects and underlying mechanisms of a ubiquitin-specific protease 8 (USP8) small-molecule inhibitor on the phenotypic characteristics of GBM cells. The growth, migration, invasion, and stemness of GBM LN229 and T98G cells were evaluated by conducting cell proliferation, colony formation, wound healing, transwell, Ki-67 staining, spheroid formation, and ionizing radiation assays, and the results collectively showed the suppressive effects of USP8 inhibition on GBM cells. Furthermore, transcriptomic profiling of GBM cells treated with the USP8 inhibitor deubiquitinase (DUB)-IN-1 revealed significantly altered mRNA expression induced by pharmacological USP8 inhibition, from which we confirmed downregulated Aurora kinase A (AURKA) protein levels using immunoblotting assays. Our findings indicated that the proliferation, invasion, and stemness of LN229 and T98G cells were markedly suppressed by USP8 inhibition. Pharmacological USP8 suppression elicits multiple tumor-inhibitory effects, likely through dysregulating various mRNA expression events, including that of the key cell cycle regulator and oncogenic protein AURKA. Therefore, our observations corroborate the GBM-supportive roles of USP8 and suggest pharmacological USP8 inhibition is a viable therapeutic approach to target GBM. The purpose of this study was to investigate the effect and mechanism of action of the USP8 inhibitor DUB-IN-1 on GBM.

This study aimed to explore the effects of tissue inhibitor of metalloproteinases‐1 (TIMP‐1) on levocarnitine (LC)-mediated regulation of angiotensin II (AngII)-induced myocardial fibrosis (MF) and its underlying mechanisms. H9C2 cells were treated with AngII for 24 h to induce fibrosis. The cells were then treated with LC or transfected with TIMP‐1-OE plasmid/si‑TIMP‐1. Cell apoptosis, viability, migration, and related gene expression were analyzed. AngII treatment significantly upregulated Axl , α-SMA , and MMP3 expression ( P < 0.05) and downregulated STAT4 and TIMP1 expression ( P < 0.05) relative to the control levels. After transfection, cells with TIMP-1 overexpression/knockdown were successfully established. Compared with that of the control, AngII significantly inhibited cell viability and cell migration while promoting cell apoptosis ( P < 0.05). LC and TIMP-1-OE transfection further suppressed cell viability and migration induced by Ang II and upregulated apoptosis, whereas si-TIMP-1 had the opposite effect. Furthermore, LC and TIMP-1-OE transfection downregulated Axl, AT1R, α-SMA, collagen III, Bcl-2 , and MMP3 expression caused by AngII and upregulated caspase 3, p53, and STAT4 expression, whereas si-TIMP-1 had the opposite effect. TIMP-1 is therefore a potential therapeutic target for delaying MF progression.

The age-related decline in T-cell function among elderly individuals remains unclear. We thus investigated the interrelationship between T-cell subsets and age to identify the changes in T-cell phenotypes and develop an age prediction model for the elderly population. A total of 127 individuals aged >60 years were divided into three groups (youngest-old group, 61–70 years, n = 34; middle-old group, 71–80 years, n = 53; and oldest-old group, ≥ 81 years, n = 40). The percentage of CD8+CD28− cells ( P = 0.001) was highest in the oldest-old group and then followed by the middle-old group, while the youngest-old group was the lowest. Both females and males demonstrated significant decreases in the absolute counts of CD4+CD45RA+ cells ( P = 0.020; P = 0.002) and CD8+CD28+ cells ( P = 0.015; P = 0.005) with age. Multivariate linear regression showed that the percentage of CD8+CD28− cells ( P < 0.001) was an independent predictor of aging after adjusting for sex, body mass index, hospitalization duration, smoking, drinking, chronic medical illness, and medications at admission. In conclusion, our results suggest that aging in elderly individuals is accompanied by a decrease in the counts of T-cell subpopulations. CD8+CD28− cells may be potential targets for elderly individuals in antiaging-related immunosenescence.

Bilateral renal clear cell carcinoma (BRCC) is a rare type of renal cell carcinoma (RCC) that accounts for only 1–5% of RCC cases and has a poor clinical prognosis. The origin, tumor microenvironment, cellular molecular features, and intra-tumoral heterogeneity of BRCC are still unclear. We downloaded BRCC single-cell transcriptome sequencing data from the gene expression omnibus database biochip GSE171306, containing 3,575 cells from left-sided clear cell renal cell carcinoma (ccRCC) and 3,568 cells from right-sided ccRCC, and used a series of R packages for data quality control (QC) and subsequent analysis of BRCC single-cell transcriptome data, including the use of the R packages Seurat and scCancer for cell QC, identification of major cell types, and cell annotation; R package scran for calculation of cell cycle scores; R package infercnv for malignancy scoring of tumor cells; R package ReactomeGSA for functional enrichment analysis; R package Monocle 2 for the analysis of cell differentiation trajectories; and R package CellphoneDB for the analysis of intercellular interactions. In this study, by analyzing the high-quality single-cell transcriptome data of BRCC, we identified 18 cell types and found that left- and right-sided ccRCC were approximately the same in terms of cell type and the number of each cell but differed significantly in terms of tumor cell malignancy score, tumor microenvironment, and cell stemness score. In the cell differentiation trajectory analysis of BRCC, we found that endothelial cells and macrophages play an extremely important role in its tumor progression. Further cell communication analysis was performed, and we found that it may signal through ligand–receptors, such as vascular endothelial growth factor–vascular endothelial growth factor receptor1 (VEGF–VEGFR1), MIF–(CD74-CXCR4), and growth arrest-specific protein 6–AXL, to influence the development of BRCC. The analysis of single-cell transcriptomic data of human BRCC suggests that left- and right-sided ccRCC may be of the same tumor origin, but the left-sided ccRCC is more malignant and has a better immune response.

Iron metabolism is considered to play the principal role in sepsis, but the key iron metabolism-related genetic signatures are unclear. In this study, we analyzed and identified the genetic signatures related to the iron-metabolism in sepsis by using a bioinformatics analysis of four transcriptomic datasets from the GEO database. A total of 21 differentially expressed iron metabolism-related signatures were identified including 9 transporters, 8 enzymes, and 4 regulatory factors. Among them, lipocalin 2 was found to have the highest diagnostic value as its expression showed significant differences in all the comparisons including sepsis vs healthy controls, sepsis vs non-sepsis diseases, and mild forms vs severe forms of sepsis. Besides, the cytochrome P450 gene CYP1B1 also showed diagnostic values for sepsis from the non-sepsis diseases. The CYP4V2, LTF, and GCLM showed diagnostic values for distinguishing the severe forms from mild forms of sepsis. Our analysis identified 21 sepsis-associated iron metabolism-related genetic signatures, which may represent diagnostic and therapeutic biomarkers of sepsis, and will improve our understanding of the molecular mechanism underlying the occurrence of sepsis.

Obesity is a main risk factor for diabetes and cardiovascular disorders and is closely linked to preadipocyte differentiation or adipogenesis. Peroxisome proliferator-activated receptor γ (PPARγ) is an indispensable transcription factor in adipogenesis. A newly identified long noncoding RNA, Acart , exerts a protective effect against cardiomyocyte injury by transactivating PPARγ signaling. However, the function of Acart in preadipocyte differentiation is unclear. To investigate the function of Acart in adipogenesis, a well-established preadipocyte, the 3T3-L1 cell line, was induced to differentiate, and Acart level was assessed during differentiation using quantitative real-time PCR. The biological role of Acart in adipogenesis was analyzed by assessing lipid droplet accumulation, PPARγ and CCAAT/enhancer-binding protein α (C/EBPα) expression, and 3T3-L1 cell proliferation and apoptosis after Acart silencing. We found that Acart level was promptly increased during preadipocyte differentiation in vitro . Acart was also significantly upregulated in obese mouse-derived subcutaneous, perirenal, and epididymal fat tissues compared with nonobese mouse-derived adipose tissues. Functionally, Acart depletion inhibited preadipocyte differentiation, as evidenced by a significant decrease in lipid accumulation and PPARγ and C/EBPα expression levels. Acart silencing also inhibited 3T3-L1 cell proliferation, whereas Acart overexpression accelerated 3T3-L1 cell proliferation and decreased cell apoptosis. Taken together, the current results reveal a novel function of Acart in regulating preadipocyte proliferation and differentiation.

Primary malignant melanoma of the parotid gland (PGMM) is extremely rare, with a poor prognosis. Surgery is the main treatment option followed by adjuvant treatments such as radiotherapy, but which adjuvant treatment to be optimal is still controversial. In this case, a 63-year-old male PGMM patient was first misdiagnosed as a “myoepithelial tumor” and then treated with surgery, postoperative immunotherapy (sintilimab), chemotherapy, and radiotherapy successfully. The progression free survival was more than 19 months without signs of metastasis or recurrence to date. To our best knowledge, this is the first report of postoperative immunotherapy combined with chemotherapy and radiotherapy for PGMM. Our case indicated that combination therapy including surgery, adjuvant immunotherapy (sintilimab) combined with chemotherapy and radiotherapy may be a potential treatment option for PGMM, which needs further research.

Radiotherapy is an essential postoperative treatment for grade II gliomas. However, comparative dosimetric studies of different radiotherapy plans for grade II gliomas are still lacking. Therefore, we conducted this case series analysis to compare the dosimetric differences among helical tomotherapy (TOMO), volumetric modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT) for grade II gliomas. To achieve that, seven diagnosed postoperative patients with grade II gliomas were analyzed by computed tomography and then planned with TOMO, VMAT, and IMRT. The plan target volume (PTV) prescribed dose was 50 Gy (daily fraction of 2.0 Gy, 5 days/week). The expected treatment efficiency was measured by monitor units (MUs) scoring. Treatment plans of the patients were compared in the quality of target volumes dosage coverage, the efficiency of dosage delivery, and the dosage exposure of normal adjacent organs at risk (OAR). Differences in each method were measured by utilizing the Nonparametric ANOVA. The study shows that TOMO achieved a significantly higher PTV-D 98% (doses received by 98% of the PTV volume) than VMAT and IMRT (50.30 ± 0.13 vs 49.21 ± 0.19, p = 0.006; 50.30 ± 0.13 vs 49.78 ± 0.18, p = 0.014), while there was no difference in PTV-D 2% (doses received by 2% of the PTV volume). IMRT achieved a conformity index (CI) preferably, and TOMO generated a favorable homogeneity index (HI) ( p < 0.05 for both). The MUs were fewer for VMAT than IMRT and TOMO (294 ± 19, 572 ± 24, 317 ± 97, respectively). IMRT achieved better protection for the lens and brain stems. Our case series study indicated that TOMO, VMAT, and IMRT achieved a comparatively good target dosimetric coverage, and most OARs were protected well. IMRT is not inferior to TOMO and VMAT and is still very suitable for treating most grade II glioma patients.

Acute lung injury (ALI) followed with severe inflammation and oxidative stress. Anti-inflammatory and antioxidant are the properties of aquaporin 1 (AQP1) and aquaporin 5 (AQP5). The goal of this study was to see if soy isoflavone can diminish lipopolysaccharide (LPS)-induced ALI and the underling mechanism. LPS-induced ALI was given to Sprague–Dawley rats 14 days following oophorectomy. One hour before the LPS challenge, estradiol (1 mg/kg) was administered subcutaneously as positive control and soy isoflavone was intragastric administration for 14 days prior to LPS challenge with different doses. Six hours after LPS challenge, the pulmonary edema, pathophysiology, inflammation, and the oxidative stress in lung tissues of rats were discovered. We found that soy isoflavone can reduce pulmonary edema and the lung pathology in a dose-dependent manner. Furthermore, tumor necrosis factor-alpha, interleukin-1β, and interleukin-6 were decreased in rats treated with soy isoflavone. Meanwhile, soy isoflavone reduced pulmonary oxidative stress by decreasing malondialdehyde levels, while increasing superoxide dismutase levels in lung tissues in a dose-dependent manner. Mechanically, we found that the mRNA and protein level of AQP1 and AOP5 were increased in lung tissues of rats treated with soy isoflavone compared the LPS-treated rats. Thus, soy isoflavone alleviates LPS-induced ALI through inducing AQP1 and AQP5. Graphical abstract

The present study reports a patient case with a 17α-hydroxylase deficiency accompanied by triple X syndrome. A 17α-hydroxylase deficiency leads to a very low 17α-hydroxylated steroid synthesis as well as a non-feedback increase in the adrenocorticotropic hormone level. Meanwhile, the progesterone level increases the 17α-hydroxyprogesterone level and decreases the dehydroepiandrosterone sulfate level. The patient is characterized by intractable hypokalemia, high urinary potassium, hyperaldosteronemia, hyporeninemia, hypocortisolemia, hypertension, gonadal and secondary sexual dysplasia, a decreased estrogen level, primary amenorrhea, and infertility. The imaging findings indicate a presence of multiple bilateral adrenal gland adenomas, and the sequencing indicates a missense CYP17A1-E7 gene pathogenic variant. The karyotype is a 47, XXX [3]/46, XX [47] low-level chimeric karyotype. The patient’s parents are cousins. To our knowledge, this patient is the first case diagnosed with congenital adrenal hyperplasia caused by hydroxylase deficiency and triple X syndrome. The uniqueness of this case is that this patient has two very rare genetic diseases, probably due to the marriage of close relatives.

Currently, there is no consensus on whether maintenance dialysis increases cancer risk in patients with end-stage renal disease (ESRD). Therefore, this study was to systematically evaluate the risk of cancer among ESRD patients undergoing maintenance dialysis. Related studies on the impact of maintenance dialysis on cancer risk were retrieved from PubMed, Embase, Cochrane Library, and other databases from their respective inceptions to 19 February 2021. ESRD patients receiving maintenance dialysis were classified into cancer including non-melanoma skin cancer (NMSC) and cancer excluding NMSC. Standardized incidence ratio (SIR) with its 95% confidence interval (95% CI) was calculated to assess cancer risk. Fourteen studies were included in the meta-analysis. The risk of cancer in patients undergoing maintenance dialysis (with or without NMSC) was significantly higher than controls both in cancer including NMSC (SIR = 1.38, 95% CI: 1.27–1.49, P < 0.001) and cancer excluding NMSC (SIR = 1.34, 95% CI: 1.23–1.47, P < 0.001). Subgroup results identified the higher risk of cancer incidence in both men and women receiving maintenance dialysis. Meanwhile, elevated excess risks were observed among patients with younger age and shorter follow-up time ( P < 0.001). Meanwhile, the combined SIR of bladder, cervix, colorectum, kidney, liver, thyroid, tongue, and other cancers were all increased ( P < 0.05). ESRD patients undergoing dialysis has higher risk of cancer.

Poor outcomes in advanced gastric cancer necessitate alternative therapeutic strategies. 6-Phosphogluconate dehydrogenase (6-PGDH), an enzyme that catalyzes the decarboxylation step in the oxidative pentose phosphate pathway, has been identified as a promising therapeutic target in many cancers. In this study, we systematically investigated the expression and function of 6-PGDH in gastric cancer. We found that 6-PGDH expression and activity were aberrantly elevated in gastric cancer tissues compared to their adjacent normal tissues. 6-PGDH knockdown using two independent shRNAs resulted in minimal 6-PGDH levels and activity, decreased growth, and enhanced gastric cancer cell sensitivity to 5-flurorouracil. However, 6-PGDH knockdown did not affect the cancer cells. Mechanistic studies showed that 6-PGDH inhibition disrupted lipid biosynthesis and redox homeostasis in gastric cancer, inhibited growth, and induced apoptosis. Notably, the in vitro findings were validated using an in vivo gastric cancer xenograft mouse model. This study established that 6-PGDH is broadly elevated in gastric cancer patients and that 6-PGDH inhibition can sensitize gastric cancer cells in response to chemotherapy.

Given the miR-33’s mechanistic relationships with multiple etiological factors in the pathogenesis of atherosclerosis (AS), we investigated the therapeutic potentials of dual-targeted microbubbles (HA-PANBs) in foam cell-specific release of anti-miR-33 (ANM33) oligonucleotides, resulting in the early prevention of AS progression and severity. The intracellular localization, loading optimization, and therapeutic effects of HA-PANBs were examined in detail in a co-cultured cell model of phagocytosis. Compared with non-targeting nanobubbles (NBs) and single-targeted microbubbles as controls, HA-PANBs efficiently delivered the ANM33 specifically to foam cells via sustained release, exhibiting its clinical value in mediating RNA silencing. Moreover, when used at a dose of 12 µg/mL HA-PANBs per 10 7 cells for 48 h, a higher release rate and drug efficacy were observed. Therefore, HA-PANBs, effectively targeting early AS foam cells, may represent a novel and optimal gene therapy approach for AS management.

Angiosarcoma is a rare subtype of soft tissue sarcoma with identifiable vascular differentiation. It can occur at any age and develop throughout the body, but it is most commonly found in skin, soft, and breast tissues. Primary retroperitoneal angiosarcoma is rarely reported in the relevant literature. This article reports a case of primary retroperitoneal angiosarcoma in a middle-aged man, with the relevant literature reviewed in detail. A 46-year-old male had experienced left waist pain for 2 months. An ultrasonic examination revealed a mass in the left retroperitoneum, and left retroperitoneal lesions were confirmed via computed tomography (CT) and magnetic resonance imaging (MRI). The tumor was removed surgically, and the CT scan revealed local tumor recurrence after 1 month when the first adjuvant therapy was performed. The patient died of a massive hemorrhage from a ruptured tumor. Angiosarcoma has high malignancy and a poor prognosis. Its early diagnosis and treatment significantly impact the long-term survival rate of patients.

This study set out to determine the key metabolite changes underlying the pathophysiology of severe preeclampsia (PE) using metabolic analysis. We collected sera from 10 patients with severe PE and from 10 healthy pregnant women of the same trimester and analyzed them using liquid chromatography mass spectrometry. A total of 3,138 differential metabolites were screened, resulting in the identification of 124 differential metabolites. Kyoto encyclopedia of genes and genomes pathway analysis revealed that they were mainly enriched in the following metabolic pathways: central carbon metabolism in cancer; protein digestion and absorption; aminoacyl-transfer RNA biosynthesis; mineral absorption; alanine, aspartate, and glutamate metabolism; and prostate cancer. After analysis of 124 differential metabolites, 2-hydroxybutyric acid was found to be the most critical differential metabolite, and its use allowed the differentiation of women with severe PE from healthy pregnant women. In summary, our analysis revealed that 2-hydroxybutyric acid is a potential key metabolite for distinguishing severe PE from healthy controls and is also a marker for the early diagnosis of severe PE, thus allowing early intervention.

Malignant pleural effusion (MPE) is a serious complication of advanced tumor, with relatively high morbidity and mortality rates, and can severely affect the quality of life and survival of patients. The mechanisms of MPE development are not well defined, but much research has been conducted to gain a deeper understanding of this process. In recent decades, although great progress has been made in the management of MPE, the diagnosis and treatment of MPE are still major challenges for clinicians. In this article, we provide a review of the research advances in the mechanisms of MPE development, diagnosis and treatment approaches. We aim to offer clinicians an overview of the latest evidence on the management of MPE, which should be individualized to provide comprehensive interventions for patients in accordance with their wishes, health status, prognosis and other factors.

Microbial safety has become a research hotspot with the development of manned space technology. Escherichia coli is a conditional pathogen that can cause infectious diseases. Therefore, it is necessary to study the influence of the space environment on E. coli . Phenotypic experiments including growth curves, morphology, and environmental resistance experiment were used to study the phenotypic changes of E. coli after exposure to the space environment for 12 days carried by the “SJ-10” satellite. Tandem mass tag was used to assess the proteome change of E. coli. We found that the survival rate of E. coli in the spaceflight group was decreased when cultivated in acidic and high-salt environments. Proteomic analysis identified 72 downregulated proteins involved in chemotaxis, intracellular pH elevation, glycolate catabolic process, and glutamate metabolic process in the spaceflight group. Meanwhile, only one protein mtr that was involved in the uptake of tryptophan in E. coli was upregulated in the spaceflight group. Our research showed that proteomics results can explain phenotypic results, which demonstrated the successful application of proteomics in mechanism research. Our data provide a comprehensive resource for understanding the effect of the space environment on E. coli .

Advances in brain imaging have led to a higher incidence of brain metastases (BM) being diagnosed. Stereotactic radiotherapy (SRS), systemic immunotherapy, and targeted drug therapy are commonly used for treating BM. In this study, we summarized the differences in overall survival (OS) between several treatments alone and in combination. We carried out a systematic literature search on Pubmed, EMBASE, and Cochrane Library. Differences in OS associated with Immune checkpoint inhibitors (ICI) alone versus targeted therapy alone and SRS + ICI or ICI alone were evaluated. This analysis was conducted on 11 studies involving 4,154 patients. The comprehensive results of fixed effect model showed that the OS of SRS + ICI group was longer than that of the ICI group (hazard ratio, 1.72; 95% CI: 1.41–2.11; P = 0.22; I 2 = 30%). The combined fixed-effect model showed that the OS time of ICI was longer than that of targeted therapy (hazard ratio, 2.09; 95% CI: 1.37–3.20; P = 0.21; I 2 = 35%). The study had a low risk of bias. In conclusion, our analysis confirmed that immunotherapy alone showed a higher OS benefit in BM patients than targeted therapy alone. The total survival time of patients with SRS combined with ICI was higher than that of patients with single ICI.

The P2RY1 receptor is known to cause cancer by activating the ERK signal pathway, and its DNA methylation status and corresponding regulatory mechanism remain unknown. This study used the DNA methylation chip to profile the genome-wide DNA methylation level in gastric cancer tissues. The proliferation and apoptosis of the SGC7901 gastric cancer cell line were determined after treatment with a selective P2RY1 receptor agonist, MRS2365. The promoter region of P2RY1 was found to be highly methylated with four hypermethylated sites (|Δ β value| > 0.2) in diffuse gastric cancer and was validated by bioinformatics analysis in the TCGA database. Also, immunohistochemical staining data obtained from the HPA database demonstrated the downregulated expression of proteins encoded by P2RY1 in stomach cancer tissue. The analysis of MRS2365-treated cells by annexin V/propidium iodide staining and caspase-3 activity assays indicated the induction of apoptosis in SGC7901 cells. The P2RY1 receptor activation in human SGC7901 gastric cancer cells via the MRS2365 agonist induced apoptosis and reduced cell growth. High DNA methylation in the promoter region of P2RY1 might have contributed to the reduced expression of P2RY1’s mRNA, which was likely responsible for the “aggressive” nature of the diffuse gastric cancer.

This retrospective case–control study examined the association between the rs2071559 (-604T/C) single nucleotide polymorphism (SNP) in the vascular endothelial growth factor receptor ( VEGFR ) -2 gene and the risk of diabetic retinopathy (DR) in Northern Han Chinese. This study included patients diagnosed with diabetes mellitus (DM) in Shijiazhuang between 07/2014 and 07/2016. The healthy controls were unrelated individuals who received routine physical examinations. The diabetic patients were grouped as DM (diabetes but no fundus examination abnormalities), proliferative DR (PDR), and non-proliferative DR (NPDR). Finally, 438 patients were included: 114 controls and 123, 105, and 96 patients in the DM, NPDR, and PDR groups, respectively. In the multivariable analyses and all genetic models, the VEGFR-2 rs2071559 SNP was not associated with DR (among all diabetic patients) or with PDR (among the patients with DR) after adjustment for age, sex, duration of DM, blood glucose, systolic blood pressure, diastolic blood pressure, and body mass index (all P > 0.05). In conclusion, the VEGFR-2 - 604T/C rs2071559 SNP is not associated with DR or PDR in the Han Chinese population of Shijiazhuang (China).

This study was devoted to demonstrating the role of IL-31 and IL-34 in the diagnosis and treatment of chronic periodontitis (CP). From the results, we found that the IL-31 and IL-34 levels were significantly increased in GCF and serum of CP patients compared with healthy controls or obese patients. Meanwhile, the area under the curve results further verified the diagnostic potential of IL-31 and IL-34 in terms of discriminating CP from obese patients at the GCF and serum levels. Finally, after 1 year of continuous treatment, we found that IL-31 and IL-34 levels were decreased in CP, suggesting their potential as biomarkers in CP treatment response. Monitoring GCF and serum levels of IL-31 and IL-34 contributed to CP detection and treatment response.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that exhibits aggressive tumor phenotypes, including rapid metastasis and tumor recurrence. Integrins belong to the family of transmembrane glycoproteins involved in regulating cell adhesion, proliferation, and differentiation through cell–cell and cell–extracellular matrix interactions. Aberrant β1 integrin signaling has been implicated in cancer invasion and metastasis processes. The present work aimed to investigate the role of β1 integrin in TNBC cancer progression using a mouse 4T1 cell line as a model system. We have sorted a subset of tumor-initiating cells (TICs) from the 4T1 cell line based on CD133 positivity by flow cytometry. RT-PCR and protein analysis studies showed the transcriptional upregulation of β1 integrin and its downstream target focal adhesion kinase in 4T1-TICs compared to parental 4T1 cells. In addition, the expression of β1 receptors in TICs is significantly higher than in parental population cells. Furthermore, in vitro cellular assays revealed that CD133 + TICs have higher clonogenic ability, invasion, and sphere formation potential. These findings suggest that β1 integrin has a potential role in TNBC invasion and metastasis. Hence, β1 integrin could be a possible factor for future targeted cancer therapies.

Whether metagenomic next-generation sequencing (mNGS) could benefit patients with suspected severe central nervous system (CNS) infection in terms of diagnosis and antibiotic treatment remains unknown. We retrospectively analyzed 79 patients with suspected CNS infection and undertook mNGS. The value of mNGS was investigated in terms of identification of pathogen and guidance for the adjustment of antibiotic treatment. The relationship between the time of initiating mNGS since onset and the Glasgow Outcome Scale (GOS) score after 90-day follow-up were analyzed. Fifty out of 79 cases with suspicious severe CNS infection were finally diagnosed. Despite previous routine laboratory tests, mNGS further promoted the accurate identification of pathogens in 23 cases (47.9%). The sensitivity, specificity, and accuracy of mNGS test in this study were 84.0, 79.3, and 82.3%, respectively. Furthermore, mNGS facilitated the adjustment of empirical antibiotic treatments in 38 cases (48.1%). The time of taking mNGS since onset had an insignificant weak positive correlation with GOS after 90-day follow-up ( r = −0.73, P = 0.08). mNGS facilitated the accurate identification of pathogens in suspicious severe CNS infections and promoted the accurate antibiotic therapy even empirical antibiotics were administrated. It should be taken as early as possible to improve the clinical outcome of patients with suspicious severe CNS infection.

Chemotherapy for advanced non-small-cell lung cancer (NSCLC) remains the first treatment choice. Angiogenesis inhibitors are effective for lung cancer treatment. This study explored whether chemotherapy combined with angiogenesis inhibitors could achieve better efficacy in NSCLC. The zebrafish A549 xenograft model was used to investigate the combined effect of apatinib and chemotherapeutic agents in NSCLC. Apatinib combined with pemetrexed demonstrated the highest antitumor effect compared with apatinib combined with gemcitabine or paclitaxel in vitro . In the zebrafish A549 xenograft model, apatinib and pemetrexed, alone or in combination, showed significant inhibition of tumor growth. Co-treatment with apatinib and pemetrexed demonstrated the best antitumor effects, suggesting that the combination of apatinib and pemetrexed might be a promising alternative therapy for patients with lung cancer. Apatinib combined with pemetrexed had enhanced antitumor effects compared with either one alone in the zebrafish model of NSCLC.

Primary thyroid adenoid cystic carcinoma (PTACC) is an extremely rare type of mucin-secreting adenocarcinoma. Currently, it is difficult to diagnose, and it lacks standard treatment protocols. We report the case of a 53-year-old female patient with PTACC who underwent additional intensity-modulated radiotherapy 1 month after surgical treatment with an uneventful course. No invasion or distant metastasis was detected at the 7-month follow-up after radiotherapy, and the prognosis was favorable. In this case, herein, we have summarized the diagnostic features of the disease and proposed that postoperative adjuvant radiotherapy can significantly improve the patient’s prognosis. Finally, we further confirmed the important role of radiotherapy in PTACC by reviewing relevant literature, which may provide clinicians with valuable treatment experience.

In the early stage, our research group cloned Echinococcus granulosus -specific antigen, EgG1Y162, from protoscolex and adult worms of E. granulosus . In order to enhance the immunogenicity of the vaccine, we prepared a recombinant vaccine by tandemly linking EgG1Y162, splicing the protein and linker at the gene level. This approach is expected to improve the immunogenicity of the vaccine by enhancing the molecular weight of the protein and increasing the antigenic epitopes. Bioinformatics was used to predict the physicochemical properties, transmembrane domain, protein structure, and T-/B-cell antigenic epitope of different recombinant proteins, EgG1Y162-linker-EgG1Y162. Finally, the linker sequence, “GGGGSGGG,” which had the least influence on the migration of recombinant protein T/B epitope and can fold normally in series with EgG1Y162, was selected to design the recombinant vaccine. The plasmid was produced using genetic engineering techniques, and the recombinant protein, EGG1Y162-GGGGSGGG-EgG1Y162, was induced to be expressed and purified. EgG1Y162-GGGGSGGG-EgG1Y162 was identified to be correctly expressed with 100% specificity. Compared with EgG1Y162, EgG1Y162-GGGGSGGG-EgG1Y162 was more likely to promote dendritic cell maturation. EgG1Y162-GGGGSGGG-EgG1Y162 was speculated to have the potential to improve antigen immunogenicity by increasing the molecular weight and antigenic epitope.

Losartan has become a hot spot in the treatment of non-alcoholic fatty liver disease (NAFLD) among angiotensin receptor blocker drugs. We sought to conduct a systematic examination and meta-analysis to examine the effects of losartan on patients with NAFLD. We searched for potentially randomized controlled trials in PubMed, Embase, China National Knowledge Infrastructure, Wanfang, and the Cochrane database up to October 09, 2022. We used the Cochrane risk of bias tool to evaluate the study quality. Analysis of subgroups, sensitivity analysis, and publishing bias were explored. The quality of the included studies was moderate to high. Six trials involving 408 patients were included. The meta-analysis demonstrated that aspartate transaminase was significantly affected by losartan therapy (mean difference [MD] = −5.34, 95% confidence interval [CI] [−6.54, −4.13], Z = 8.70, P < 0.01). The meta-analysis subgroup showed that losartan 50 mg once daily could lower the level of alanine aminotransferase (MD = −18.92, 95% CI [−21.18, −16.66], Z = 16.41, P < 0.01). There was no statistically significant difference in serum total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein.

N6-methyladenosine (m 6 A) is a representative of RNA methylation modification, which plays a critical role in the epigenetic modification process of regulating human diseases. As a key protein for m 6 A, methyltransferase 3 (METTL3) had been identified to be associated with a variety of diseases. The publications related to METTL3 were searched in the Web of Science Core Collection from the earliest mention to July 1st, 2022. Being screened by the retrieval strategy, a total of 1,738 articles related to METTL3 were retrieved. Much of our work focused on collecting the data of annual publication outputs, high-yielding countries/regions/authors, keywords, citations, and journals frequently published for qualitative and quantitative analysis. We found that diseases with high correlations to METTL3 not only included various known cancers but also obesity and atherosclerosis. In addition to m 6 A-related enzyme molecules, the most frequent key molecules were MYC proto-oncogene (C-MYC), Enhancer of zeste homolog 2 (EZH2), and Phosphatase and tensin homolog deleted on chromosome 10 (PTEN). METTL3 and methyltransferase 14 (METTL14) may function through opposite regulatory pathways in the same disease. “Leukemia,” “Liver Cancer,” and “Glioblastoma” were speculated to be potential hotspots in METTL3 related study. The number of publications had significantly surged year by year, demonstrating the growing importance of the research on epigenetic modification in the pathology of various diseases.

Unit variance (UV) scaling, mean centering (CTR) scaling, and Pareto (Par) scaling are three commonly used algorithms in the preprocessing of metabolomics data. Based on our NMR-based metabolomics studies, we found that the clustering identification performances of these three scaling methods were dramatically different as tested by the spectra data of 48 young athletes’ urine samples, spleen tissue (from mice), serum (from mice), and cell (from Staphylococcus aureus ) samples. Our data suggested that for the extraction of clustering information, UV scaling could serve as a robust approach for NMR metabolomics data for the identification of clustering analysis even with the existence of technical errors. However, for the purpose of discriminative metabolite identification, UV scaling, CTR scaling, and Par scaling could equally extract discriminative metabolites efficiently based on the coefficient values. Based on the data presented in this study, we propose an optimal working pipeline for the selection of scaling algorithms in NMR-based metabolomics analysis, which has the potential to serve as guidance for junior researchers working in the NMR-based metabolomics research field.

The PI3K/AKT/mTOR (phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin) pathway can be initiated by PROK1 (prokineticin 1), but its effect and mechanism of action in pancreatic carcinoma (PC) are not fully understood. In this study, we elucidated the roles of PROK1 and its related molecules in PC in vivo . PANC-1 cells with PROK1 knockdown were injected into BALB/c nude mice. The growth and weight of the tumor were monitored and measured, which was followed by TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling), immunohistochemical staining, and hematoxylin and eosin staining. The key proteins related to proliferation, apoptosis, and the PI3K/AKT/mTOR pathway were determined by Western blotting. We also used public databases to identify the molecules related to PROK1. The reduction of PROK1 inhibited angiopoiesis and promoted apoptosis in vivo . PCNA-1, cyclin D1, and Bcl-2 decreased considerably, while Bax and cleaved caspase-3 increased significantly after PROK1 inhibition. The PI3K/AKT/mTOR signal inhibition was also closely associated with PROK1 knockdown. The possible related molecules of PROK1, such as von Willebrand factor, were screened and considered to be involved in the aberrant activation of PI3K/AKT. In conclusion, PROK1 knockdown significantly prevented tumor growth and promoted apoptosis of human PC cells in vivo , where the PI3K/AKT/mTOR pathway was probably inhibited. Therefore, PROK1, along with its related molecules, might be important targets for PC therapy.

The cytoskeleton plays an important role in epilepsy; however, the mechanism is unknown. Therefore, this study aimed to reveal the mechanism of cytoskeletal proteins in epilepsy by investigating the expression of cytoskeletal proteins and synaptophysin (SYP) in mice at 0, 3, 6, and 24 h, 3 days, and 7 days in a kainic acid (KA)-induced epileptic model. Our results demonstrated that the expression of F-actin decreased significantly between 3 and 6 h, 6 and 24 h, and 24 h and 3 days ( P < 0.05). Meanwhile, the expression of the neurofilament light chain, neurofilament medium chain, and neurofilament heavy chain subunits was significantly decreased ( P < 0.001) at 3 h after the KA injection compared to the KA 0 h group, followed by an elevation at 6 h and a further decrease at 24 h compared to at 6 h. SYP expression was significantly decreased between 0 and 3 h as well as between 3 and 6 h ( P < 0.05). At 24 h, the level was increased compared to at 6 h and continued to increase at 3 days after the KA injection. Thus, we propose that cytoskeletal proteins may be involved in the pathogenesis of epilepsy.

We investigated the effect of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) on lymphocytes and white blood cells of patients with malignant tumors. After PEG-rhG-CSF treatment, the count of lymphocytes increased in 66 cases, remained unchanged in 2 cases, and decreased in 20 cases. The difference in lymphocyte count before and after treatment was statistically significant ( P < 0.001). White blood cell changes were positively correlated with lymphocyte changes ( r = 0.36, P = 0.001). In the subgroup with increased white blood cells ( n = 80), there were 62 cases with increased lymphocytes, 1 case with unchanged lymphocytes, and 17 cases with decreased lymphocytes after PEG-rhG-CSF treatment. There was significant difference in the count of lymphocytes and white blood cells ( P < 0.001). In the subgroup with 6 mg of PEG-rhG-CSF ( n = 66) and the subgroup with 3 mg of PEG-rhG-CSF ( n = 22), the changes of white blood cell and lymphocyte counts before and after treatment were statistically significant ( P < 0.001). The two were positively correlated in the 6 mg PEG-rhG-CSF subgroup, with correlation coefficient r = 0.34 ( P = 0.002). PEG-rhG-CSF can increase the count of lymphocytes and white blood cells in patients with malignant tumors, and the increase of lymphocytes is positively correlated with the increase of white blood cells.

Chlamydia psittaci ( C. psittaci ) pneumonia is a zoonotic infectious disease caused by C. psittaci , which is often underdiagnosed. The application of metagenomic next-generation sequencing (mNGS) provides an unbiased method for the detection of unknown pathogens. A 46-year-old man received empirical treatment with piperacillin-tazobactam and moxifloxacin after an initial diagnosis of prostatitis and pneumonia. However, he experienced recurrent symptoms and a cough, and a chest computed tomography (CT) showed aggravated pulmonary inflammation. Upon further questioning, the patient recalled a history of contact with pigeons, and a bronchoscope alveolar lavage fluid analysis with mNGS suggested C. psittaci infection. Following treatment with doxycycline, the patient’s symptoms were rapidly alleviated, and chest CT showed pulmonary lesions absorption. The patient was followed up for 1 month without any discomfort. This case highlights that initial manifestations of C. psittaci pneumonia may present with atypical symptoms such as prostatitis. Furthermore, mNGS can be a useful tool for the detection of rare or unknown pathogens such as C. psittaci .

Postoperative cognitive dysfunction (POCD) is a common complication of cognitive decline after surgery and anesthesia. Sevoflurane, as a commonly used anesthetic, was found to cause POCD. Nudix Hydrolase 21 (NUDT21), a conserved splicing factor, has been reported to exert important functions in multiple diseases’ progression. In this study, the effect of NUDT21 on sevoflurane-induced POCD was elucidated. Results showed that NUDT21 was down-regulated in the hippocampal tissue of sevoflurane-induced rats. Morris water maze test results revealed that overexpression of NUDT21 improved sevoflurane-induced cognitive impairment. In addition, TUNEL assay results indicated that enhanced NUDT21 alleviated sevoflurane-induced apoptosis of hippocampal neurons. Furthermore, overexpression of NUDT21 suppressed the sevoflurane-induced LIMK2 expression. Taken together, NUDT21 alleviates sevoflurane-induced neurological damage in rats by down-regulating LIMK2, providing a novel target for the prevention of sevoflurane-induced POCD.

The relationship between interleukin ( IL )-10 and IL-6 gene polymorphisms and squamous cell carcinoma (SCC) has been demonstrated but with inconsistent conclusions. The aim of this study was to evaluate the potential associations of IL gene polymorphisms and the SCC risk. PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biomedical Database, WanFang, and China Science and Technology Journal Database databases were searched for articles reporting the correlations of IL-10 and IL-6 gene polymorphisms with the SCC risk. Odds ratio and 95% confidence interval were calculated using Stata Version 11.2. Meta-regression, sensitivity, and publication bias were analyzed. False-positive reporting probability and Bayesian measure of the false-discovery probability were used to explore the credibility of the calculation. Twenty-three articles were included. The IL-10 rs1800872 polymorphism showed a significant correlation with the SCC risk in the overall analysis. Studies pooled by ethnicity revealed that the IL-10 rs1800872 polymorphism reduced the SCC risk in the Caucasian population. The results of this study suggest that the IL-10 rs1800872 polymorphism may confer a genetic susceptibility to SCC, particularly oral SCC, in Caucasians. However, the IL-10 rs1800896 or IL-6 rs1800795 polymorphism was not significantly associated with the SCC risk.

This study examined exosomal hepatitis B virus (HBV)-DNA levels in chronic HBV infection (CHB). Patients were grouped according to the European Association for the Study of the Liver classification (1: HBV-DNA-positive CHB, normal alanine aminotransferase [ALT]; 2: HBV-DNA-positive CHB, elevated ALT; 3: HBV-DNA-negative HBeAb-positive CHB, normal ALT; 4: HBV-DNA-positive HBeAg-negative HBeAb-positive CHB, elevated ALT; 5: HBV-DNA-negative, HBcAb-positive; 6: HBV-negative, normal ALT). Exosomes were isolated, comparative analysis of exosomes and serum HBV-DNA. The HBV-DNA content was lower in exosomes than in serum for groups 1, 2, and 4 (all P < 0.05). In the groups negative for serum HBV-DNA (groups 3 and 5), the exosomal HBV-DNA levels were higher than the serum HBV-DNA levels (all P < 0.05). The exosomal and serum HBV-DNA levels were correlated in groups 2 ( R 2 = 0.84) and 4 ( R 2 = 0.98). The exosomal HBV-DNA levels were correlated with total bilirubin ( R 2 = 0.94), direct bilirubin ( R 2 = 0.82), and indirect bilirubin ( R 2 = 0.81) in group 5 (all P < 0.05). In patients with CHB and negative for serum HBV-DNA, exosomal HBV-DNA was detectable and could be used to monitor the treatment effects. Exosomal HBV-DNA could be used in patients with a high suspicion of HBV infection but negative for serum HBV-DNA.

To investigate the mechanism of shear stress on endothelial cell dysfunction for providing a theoretical basis for the reduction of arteriovenous fistula dysfunction. The in vitro parallel plate flow chamber was used to form different forces and shear stress to mimic the hemodynamic changes in human umbilical vein endothelial cells, and the expression and distribution of krüppel-like factor 2 (KLF2), caveolin-1 (Cav-1), p-extracellular regulated protein kinase (p-ERK), and endothelial nitric oxide synthase (eNOS) were detected by immunofluorescence and real-time quantitative polymerase chain reaction. With the prolongation of the shear stress action time, the expression of KLF2 and eNOS increased gradually, while the expression of Cav-1 and p-ERK decreased gradually. In addition, after cells were exposed to oscillatory shear stress (OSS) and low shear stress, the expression of KLF2, Cav-1, and eNOS decreased and the expression of p-ERK increased. The expression of KLF2 increased gradually with the prolongation of action time, but it was still obviously lower than that of high shear stress. Following the block of Cav-1 expression by methyl β-cyclodextrin, eNOS expression decreased, and KLF2 and p-ERK expression increased. OSS may lead to endothelial cell dysfunction by Cav-1-mediated KLF2/eNOS/ERK signaling pathway.

This study examined the effects of the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count after pulmonary infection. Sprague‒Dawley rats were subjected to tracheal injection of lipopolysaccharide (LPS) to establish animal models of pulmonary infection. By inhibiting the PI3K/AKT pathway or inhibiting/inducing mitochondrial autophagy in macrophages, the severity of the pulmonary infection and the leukocyte count were altered. The PI3K/AKT inhibition group did not show a significant difference in leukocyte counts compared with the infection model group. Mitochondrial autophagy induction alleviated the pulmonary inflammatory response. The infection model group had significantly higher levels of LC3B, Beclin1, and p-mTOR than the control group. The AKT2 inhibitor group exhibited significantly increased levels of LC3B and Beclin1 compared with the control group ( P < 0.05), and the Beclin1 level was significantly higher than that in the infection model group ( P < 0.05). Compared with the infection model group, the mitochondrial autophagy inhibitor group exhibited significantly decreased levels of p-AKT2 and p-mTOR, whereas the levels of these proteins were significantly increased in the mitochondrial autophagy inducer group ( P < 0.05). PI3K/AKT inhibition promoted mitochondrial autophagy in macrophages. Mitochondrial autophagy induction activated the downstream gene mTOR of the PI3K/AKT pathway, alleviated pulmonary inflammatory reactions, and decreased leukocyte counts.

The aim of this study was to systematically evaluate the correlation between the rs231775 locus polymorphism in the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene and genetic susceptibility to Graves’ disease (GD) in children. Some studies found that the CTLA-4 gene polymorphism was associated with GD in children. The data up to February 2022 were retrieved from the databases. Stata 15.0 software was used for meta-analysis. A total of seven studies were included in our research. The results of the meta-analysis showed that the rs231775 locus polymorphism in the CTLA-4 gene in general and Asian populations was correlated with children’s susceptibility to GD (A vs G: OR = 0.75, 95% CI (0.660–0.86); GG vs AA: OR = 1.34, 95% CI (1.04–1.73); AG vs AA: OR = 1.32, 95% CI (1.02–1.10); AG + GG vs AA: OR = 3.81, 95% CI (2.17–6.70); GG vs AA + AG: OR = 1.23, 95% CI (1.05–1.45)). In summary, the rs231775 locus polymorphism in the CLTA-4 gene may be a risk factor for GD in Asian children. The G allele may be a susceptibility factor, while the allele A may be a protective factor against GD in Asian children. In the future, more large-scale studies may be needed to verify our results.

Deficiency of phosphate (Pi) is one of the main growth-limiting factors for crops. Generally, phosphate transporters play a key role in the uptake of P in the crops. However, current knowledge regarding the molecular mechanism underlying Pi transport is still limited. In this study, a phosphate transporter (PT) gene, designated HvPT6 , was isolated from a cDNA library constructed from hulless barley “Kunlun 14.” The promoter of HvPT6 showed a large number of elements related to plant hormones. The expression pattern also indicated that HvPT 6 was highly induced by low phosphorus, drought, abscisic acid, methyl jasmonate and gibberellin. Phylogenetic tree analysis revealed that HvPT6 belongs to the same subfamily of the major facilitator superfamily as OsPT6 from Oryza sativa . Subcellular localization of HvPT6:GFP using transient expression of Agrobacterium tumefaciens showed the green fluorescent protein signal in the membrane and nucleus of the Nicotiana benthamiana leaves. Overexpressing HvPT6 led to a longer and higher lateral root length and dry matter yield in the transgenic Arabidopsis lines under low Pi conditions, indicating that HvPT6 improves plant tolerance under Pi-deficient conditions. This study will lay a molecular basis for phosphate absorption mechanism in barley and breeding barley with high-efficient phosphate uptake.

Diabetic nephropathy is a microvascular complication of diabetes mellitus, threatening the health of millions of people. Herein, we explored a blood glucose independent function of coptisine on diabetic nephropathy. A diabetic rat model was established by intraperitoneal administration of streptozotocin (65 mg/kg). Coptisine treatment (50 mg/kg/day) retarded body weight loss and reduced blood glucose. On the other hand, coptisine treatment also decreased kidney weight and the levels of urinary albumin, serum creatinine, and blood urea nitrogen, indicating an improvement of renal function. Treatment with coptisine also mitigated renal fibrosis, with alleviative collagen deposition. Likewise, in vitro study showed that coptisine treatment decreased apoptosis and fibrosis markers in HK-2 cells treated with high glucose. Furthermore, after coptisine treatment, the activation of NOD-like receptor pyrin domain containing protein 3 (NRLP3) inflammasome was repressed, with decreased levels of NLRP3, cleaved caspase-1, interleukin (IL)-1β, and IL-18, indicating that the repression of NRLP3 inflammasome contributed to the effect of coptisine on diabetic nephropathy. In conclusion, this study revealed that coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome. It is indicated that coptisine may have the potential to be used in the diabetic nephropathy treatment.

To explore the serum levels of IL-39, CXCL14, and IL-19 in patients with tuberculosis (TB) along with their clinical significances and their concentration changes in macrophages after Bacille Calmette-Guérin vaccine ( BCG ) or Mycobacterium tuberculosis ( M. tb ) H37Rv stimulation in vitro . The serum levels of IL-39, CXCL14, and IL-19 of 38 TB patients, and 20 healthy staff members were measured by enzyme-linked immunosorbent assay. Moreover, the levels of IL-19, CXCL14, and IL-39 in cultured THP-1 macrophages were detected at 12, 24, and 48 h after stimulation with BCG or M. tb H37Rv strains. It was found the serum level of IL-39 was significantly reduced and CXCL14 was remarkably elevated in TB patients. In vitro , at 48 h after stimulation, IL-39 level of cultured THP-1 macrophages in the H37Rv group was significantly lower than that in the BCG and control groups, and the CXCL14 level of cultured THP-1 macrophages in the H37Rv stimulation group was remarkably higher than that in the control group. Therefore, IL-39 and CXCL14 may be involved the pathogenesis of TB, and serum IL-39 and CXCL14 could potentially serve as a new biomarker of TB.

This study introduced whole-exome sequencing (WES) in prenatal diagnosis of fetal bowel dilatation to improve the detection outcome when karyotype analysis and copy number variation sequencing (CNV-seq) were uninformative in detecting pathogenic variants. The work reviewed 28 cases diagnosed with fetal bowel dilatation and analyzed the results of karyotype analysis, CNV-seq, and WES. Among the 28 cases, the detection rate in cases with low risk of aneuploidy was 11.54% (3/26), which is lower than 100% (2/2) in cases with high risk of aneuploidy. Ten low-risk aneuploidy cases with isolated fetal bowel dilatation had normal genetic testing results, while the remaining 16 cases with other ultrasound abnormalities were detected for genetic variants at a rate of 18.75% (3/16). The detection rate of gene variation was 3.85% (1/26) by CNV-seq and 7.69% (2/26) by WES. This study suggested that WES could reveal more genetic risk in prenatal diagnosis of fetal bowel dilatation and has value in prenatal diagnosis to reduce birth defects.

Infective endocarditis (IE) caused by Gemella morbillorum is rare. Consequently, little is known about the natural course of endocarditis caused by this pathogen. This report describes the case of a 37-year-old male patient with G. morbillorum endocarditis. The patient was hospitalized for a fever of unknown origin. He complained of intermittent fever of unknown origin for 2 months. He had also undergone root canal therapy for pulpitis a month ago. After admission, the infectious pathogen G. morbillorum was identified using metagenomic next-generation sequence technology. The anaerobic blood culture bottle showed only Gram-positive cocci. Transthoracic echocardiography showed 10 mm vegetation on the aorta, which met the IE diagnostic Duke’s criteria, and the patient was diagnosed with G. morbillorum IE. Because no bacterial colonies were formed on the culture, the drug sensitivity test could not be conducted. Ceftriaxone anti-infective drugs are based on careful consideration of the literature and patient. Six days after antibiotic treatment in our department, the patient was discharged from the hospital in stable condition and had no adverse reactions at 1 week of follow-up. To help clinicians better understand the disease of G. morbillorum IE, we also reviewed and discussed the relevant cases published after 2010 when presenting the report.

Thymomas and thymic carcinomas are rare and primary tumors of the mediastinum which is derived from the thymic epithelium. Thymomas are the most common primary anterior mediastinal tumor, while ectopic thymomas are rarer. Mutational profiles of ectopic thymomas may help expand our understanding of the occurrence and treatment options of these tumors. In this report, we sought to elucidate the mutational profiles of two ectopic thymoma nodules to gain deeper understanding of the molecular genetic information of this rare tumor and to provide guidance treatment options. We presented a case of 62-year-old male patient with a postoperative pathological diagnosis of type A mediastinal thymoma and ectopic pulmonary thymoma. After mediastinal lesion resection and thoracoscopic lung wedge resection, the mediastinal thymoma was completely removed, and the patient recovered from the surgery and no recurrence was found by examination until now. Whole exome sequencing was performed on both mediastinal thymoma and ectopic pulmonary thymoma tissue samples of the patient and clonal evolution analysis were further conducted to analyze the genetic characteristics. We identified eight gene mutations that were co-mutated in both lesions. Consistent with a previous exome sequencing analysis of thymic epithelial tumor, HRAS was also observed in both mediastinal lesion and lung lesion tissues. We also evaluated the intratumor heterogeneity of non-silent mutations. The results showed that the mediastinal lesion tissue has higher degree of heterogeneity and the lung lesion tissue has relatively low amount of variant heterogeneity in the detected variants. Through pathology and genomics sequencing detection, we initially revealed the genetic differences between mediastinal thymoma and ectopic thymoma, and clonal evolution analysis showed that these two lesions originated from multi-ancestral regions. Graphical abstract This result revealed genetic differences between type A ectopic pulmonary thymoma and mediastinal thymoma with high tumor heterogeneity.

The latest surveillance from the Centers for Disease Control and Prevention shows that the annual incidence of V. vulnificus infection is increasing. Unfortunately, in less well-known high-risk groups, this infection is usually excluded from differential diagnosis. Transmitted through wound exposure or ingestion, the mortality rate of foodborne diseases of V. vulnificus is the highest of all V. vulnificus . V. vulnificus is as lethal early diagnosis as Ebola and bubonic plague, so timely treatment is imperative. Sepsis caused by V. vulnificus infection mainly exists in the United States and is rarely reported in Southeast Asia. We report a 78-year-old man who went to the local hospital and complained of swelling in his right hand with severe pain. He ate raw salmon 2 days ago and denied other recognized seafood stab or trauma history and other seafood contact history. He was in septic shock at the time of treatment, so we immediately transferred to the emergency intensive care unit and tested for metagenomic next-generation sequencing (mNGS). The diagnosis was confirmed the second day after admission, and eventually he was cured and discharged from the hospital only after medical treatment, thus avoiding the risk of surgical debridement or even amputation. mNGS is helpful for early clinical diagnosis and effective early intervention for etiology, so that patients can get a good prognosis.

Pulmonary atresia (PA) is a severe cyanotic congenital heart disease. Although some genetic mutations have been described to be associated with PA, the knowledge of pathogenesis is insufficient. The aim of this research was to use whole-exome sequencing (WES) to determine novel rare genetic variants in PA patients. We performed WES in 33 patients (27 patient–parent trios and 6 single probands) and 300 healthy control individuals. By applying an enhanced analytical framework to incorporate de novo and case–control rare variation, we identified 176 risk genes (100 de novo variants and 87 rare variants). Protein‒protein interaction (PPI) analysis and Genotype-Tissue Expression analysis revealed that 35 putative candidate genes had PPIs with known PA genes with high expression in the human heart. Expression quantitative trait loci analysis revealed that 27 genes that were identified as novel PA genes that could be affected by the surrounding single nucleotide polymorphism were screened. Furthermore, we screened rare damaging variants with a threshold of minor allele frequency at 0.5% in the ExAC_EAS and GnomAD_exome_EAS databases, and the deleteriousness was predicted by bioinformatics tools. For the first time, 18 rare variants in 11 new candidate genes have been identified that may play a role in the pathogenesis of PA. Our research provides new insights into the pathogenesis of PA and helps to identify the critical genes for PA.

We investigated the influence of DNA fragmentation index (DFI) on in vitro fertilization (IVF), embryo transfer (ET), and intracytoplasmic sperm injection (ICSI). We analyzed the semen parameters of 61 cycles in infertile couples undergoing IVF-ET and ICSI and determined DFI by sperm chromatin dispersion testing. Based on DFI, the patients were differentiated into a control group (DFI < 25%, n = 35) and a test group (DFI ≥ 25%, n = 26). Flow cytometry and immunofluorescence were used to investigate the extent of sperm reactive oxygen species (ROS) and apoptosis. We also investigated the effect of DFI on pregnancy outcomes of IVF-ET/ICSI. DFI was negatively related to sperm motility and positively correlated with ROS and apoptosis ( P < 0.05). Abnormally elevated DFI reduced the rate of transplantable, high-quality embryos, implantation, clinical pregnancy, delivery, and live birth after IVF-ET, and increased the chance of early abortion per transfer cycle ( P < 0.05). However, there was no significant correlation between DFI and fertilization rate, cleavage rate, transplantable rate, high-quality embryo rate, implantation rate, clinical pregnancy rate, early abortion rate, delivery rate and live birth rate when assisted by ICSI ( P > 0.05). Sperm DNA integrity is crucial for fertilization and the development of healthy offspring. ROS may increase the level of DFI by inducing apoptosis in sperm.

We report here the clinical diagnosis and treatment and genetic mutations of an infant with You-Hoover-Fong syndrome (YHFS). The relevant literature review was conducted. A female infant aged 17 months was admitted to Nanhai Affiliated Maternity and Children’s Hospital of Guangzhou University of Chinese Medicine due to “global development delay complicated with postnatal growth retardation for more than 1 year.” The infant was diagnosed with YHFS due to the onset of extremely severe mental retardation, microcephaly, abnormal hearing, severe protein–energy malnutrition, congenital cataract, cleft palate (I°), congenital atrial septal defect, brain atrophy, hydrocephalus, and brain hypoplasia. The whole exon sequencing revealed two compound heterozygous mutations, including a likely pathogenic TELO2 variant, c.2245A > T (p.K749X) from her mother and an uncertain variant, c.2299C > T (p.R767C) from her father, validated by Sanger sequencing. After bilateral cataract surgery, the infant obtained better visual acuity and showed more responses and interactions with her parents. Diagnosis and treatment of this case prompt that these TELO2 variants have not been reported, deepening the understanding of the molecular and genetic mechanism of YHFS in clinical practice.

Cell-free circulating tumor DNA (ctDNA) is synthesized by tumor cells, including metastatic tumors, and circulates in the bloodstream. Evidence suggests that ctDNA is a potential predictive and prognostic biomarker for colorectal cancer (CRC), but its predictive efficacy in detecting CRC liver metastasis (CLM) remains unclear. Additionally, its utility in the clinical setting needs further investigation. We conducted a meta-analysis to determine the utility of ctDNA as a biomarker for predicting the prognosis of CLM and investigate the relationship between CLM and ctDNA positivity. A literature search was performed in electronic databases to identify relevant studies published up to March 19, 2022. We retrieved data on overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) for both ctDNA-positive and ctDNA-negative colorectal liver metastasis (CLM) patients from the selected articles. Hazard ratios (HRs) were also calculated for these survival outcomes analysis was also performed. The stability of the combined meta-analysis was verified by sensitivity analysis and publication bias evaluation. Ten trials were included, and 615 patients were evaluated. In patients with CLM, pooled HRs revealed a substantial link between ctDNA positivity and RFS/DFS. Subgroup analysis revealed that ctDNA had a prospective detection value. Sensitivity analysis and publication bias evaluation indicated stable results. Although the results on pooled HR for OS suggested that ctDNA-positive patients had a shorter survival time, their pooled HRs had a relatively evident heterogeneity, and sensitivity analysis and publication bias evaluation indicated that pooled HRs were extremely unstable. In conclusion, our results demonstrate that ctDNA appears to be a prognostic biomarker for resectable CLM patients.

Primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri is a fatal infection with a mortality rate of more than 95%, despite advances in antimicrobial chemotherapy and supportive care. Initial manifestations of PAM are indistinguishable from bacterial meningitis. Prompt diagnosis and antifungal treatment may help decline the overall mortality. Here we present a case of a 38-year-old man transferred to our hospital due to mild headache, which deteriorated quickly. Severe increased intracranial pressure was found. The cerebrospinal fluid (CSF) was yellowish with significantly increased leukocyte and protein. Smear and culture were negative. The patient was first diagnosed with pyogenic meningoencephalitis. However, the symptoms deteriorated. Metagenomic next-generation sequencing (mNGS) of CSF was applied and finally confirmed N. fowleri as the protist pathogen within 24 h. However, due to the time cost of sampling and transportation (2 days), the diagnosis came too late, and the patient passed away 1 day before. In summary, mNGS is a rapid and accurate diagnostic method for clinical practices, especially for rare central nervous system infections. It should be used as quickly as possible for acute infections, such as PAM. All aspects of patient interrogation and prompt identification should be paramount to ensure appropriate treatment and decline the overall mortality.

The Dolichol kinase (DOLK) gene encodes the polytopic DOLK protein associated with the endoplasmic reticulum (ER) N-glycosylation pathway catalyzing the final step in the biosynthesis of dolichol phosphate. Dolichol phosphate is an oligosaccharide carrier required for N-glycosylation of DOLK protein, with its deficiency leading to a severe hypo glycosylation phenotype in humans which can cause congenital disorders of glycosylation and death in early infancy. The aim of the present study is to identify the phylogenetic relationship between human and ortholog species based on their conserved sequences in DOLK gene. Sequence alignment of DOLK was carried out in this study and the evolutionarily conserved regulatory sequences were identified using bioinformatics. Promoter sequence of human DOLK was compared with orthologous sequences from different organisms. Conserved non-coding sequences (CNS) and motifs in promoter regions were found by analyzing upstream promoter sequences of Homo sapiens DOLK and its orthologous genes in other organisms. Conserved sequences were predicted in the promoter regions in CNS1 and CNS2. Conserved protein sequences were also identified by alignment of the orthologous sequences. Organisms with similar gene sequences are assumed to be closely related and the ER N-glycosylation pathway is conserved in them.

This study aims to determine the ultrastructural changes in collagen fibrils in rabbit conjunctiva after conjunctival crosslinking using riboflavin and ultraviolet A (UVA) light at an irradiation intensity of 45 mW/cm 2 . Conjunctival crosslinking may increase conjunctival stiffness. The supertemporal quadrants of the right eyes of 24 adult rabbits were treated with a topical riboflavin solution (0.25%) before irradiation with UVA light at 45 mW/cm 2 for 4 min. After 3 weeks, the collagen fibrils in fibril bundles were examined by electron microscopy. Immunohistochemical staining was used to detect the expression levels of collagen I and collagen III in the rabbits’ conjunctiva. The diameter of the collagen fibrils in the fibril bundles varied slightly, ranging from 30 to 60 nm in the conjunctival stroma of the control group. In the treatment group, the diameter of collagen fibrils ranged from 60 to 90 nm. The thickest collagen fibrils were observed in the treatment group (up to 90 nm in diameter). In contrast, those in the conjunctival stroma of the control group were considerably smaller (up to 60 nm in diameter). However, thicknesses of collagen fibrils displayed a unimodal distribution. Both collagen I and collagen III increased after treatment with riboflavin and UVA light irradiation at 45 mW/cm 2 . The data indicate that in rabbits, conjunctival crosslinking with riboflavin and UVA light at 45 mW/cm 2 for 4 min is safe and does not induce ultrastructural alterations of the conjunctival cells. The conjunctival crosslinking with riboflavin and UVA light at 45 mW/cm 2 can increase the diameter of collagen fibrils, but the average densities of collagen I and collagen III have no statistical significance.

Gastric carcinoma is a frequent malignant tumor worldwide. NM23 plays an important role in pathological processes, including in the occurrence and development of tumors. The purpose of this study is to examine the effect of NM23 transfection of human gastric carcinoma cells (BGC-823) on growth and metastases of BGC-823 abdominal cancer xenografts in nude mice. BGC-823 cells were transfected with an adenovirus vector for NM23 (NM23-OE), transfected with an empty vector (NC), or were not transfected (Ctrl). Eighteen female BALB/c-nu mice were randomly divided into three groups (six per group) according to the type of BGC-823 cells administered by intraperitoneal injection. After 2 weeks, necropsies of mice were performed, abdominal circumferences were measured, and abdominal cavities were searched by ultrasound. In order to observe the xenografts in nude mice, there were gross macroscopic observations and microscopic observations. In addition, immunohistochemical analysis and western blot of NM23 were also performed. Green fluorescence in the NM23-OE and NC cells indicated successful transfection. The multiplicity of infection is 80%. A comparison of the three groups of mice indicated the NM23-OE group had positive conditions (abdominal circumferences: 81.83 ± 2.40 mm), but the other groups had negative conditions and enlarged abdomens (NC: 90.83 ± 2.32 mm; Ctrl: 92.67 ± 2.07 mm). Ultrasound observations confirmed large tumors in the NC and Ctrl groups, but did not find in the NM23-OE group. There were no obvious ascites in the NM23-OE group, but the cytological examination of ascites exfoliation in NC and Ctrl groups indicated that there were large and deep-stained gastric carcinoma cells. Tumor expression of NM23 was greater in the NM23-OE group than in the NC and Ctrl groups (both p < 0.05). In conclusion, transfection of BCG-823 cells with NM23 rather than an empty vector (NC) or no vector (Ctrl) led to reduced growth and metastases of abdominal cancer xenografts in nude mice.

The treatment of preeclampsia is delivering women and extracting the placenta, but the Chinese Society of Obstetrics and Gynecology guidelines do not recommend the delivery of babies without severe features. The objectives of the study were to compare the effectiveness and safety of nifedipine and phytosterol in combination with nicardipine for the management of severe preeclampsia. Women (19–32 years; gestation age ≥ 30 weeks) with the complication of severe preeclampsia have received 10 mg of oral nifedipine (pregnant women received 10 mg of oralnifedipine, n = 112) or 1 mg/h intravenous nicardipine (pregnant women received 1 mg/h intravenous nicardipine (ND cohort), n = 115) or oral 10 mg nifedipine and 500 mg phytosterol (pregnant women received oral 10 mg nifedipine and 500 mg phytosterol (np cohort), n = 111) until 150/100 mmHg blood pressure was achieved. The time required to achieve the desired blood pressure control was 13 minutes shorter in the NP cohort compared to the NF ( p < 0.0001, t = 11.605), and 3 minutes shorter compared to the ND ( p < 0.0001, t = 2.79) cohorts. Stillbirths were reported in 14 (13%), 28 (24%), and 10 (9%) infants, and 13 (12%), 26 (23%), and 10 (9%) infants died from the NF, ND, and NP cohorts, respectively. The undesirable tocolytic effect was reported in 17 (15%) women of the ND cohort. Phytosterol with nifedipine has a synergistic or additive effect on the management of preeclampsia with fewer adverse outcomes.

Retiform hemangioendothelioma (RH) is a type of low-grade malignant angiosarcoma. It commonly involves the skin and subcutaneous tissue of the lower extremities, but a few cases have been reported in the gut. However, hepatic RH has not been previously reported. This report presents the case of RH of the liver in a 61-year-old woman who was admitted to the hospital having presented with liver space–occupying lesions of 2 months evolution. The patient underwent an abdominal ultrasound examination, which indicated a hemangioma, but abdominal computed tomography diagnosed a liver abscess. In order to determine the nature of the lesion, an ultrasound-guided liver biopsy was performed, after which a pathological diagnosis confirmed the presence of RH in the liver. The patient underwent ultrasound-guided microwave ablation three times and has been followed up for 8 years with no tumor recurrence or metastasis. Surgical excision is still the first choice for the treatment of hepatic RH. As shown in this case, however, for patients who refuse to undergo surgery or have surgical contraindications, ultrasound-guided microwave ablation is an alternative treatment option. The report of this case expands the scope of liver tumors to a certain extent and provides a reference for clinical diagnosis and treatment.

Curcumin is the most abundant derivative of turmeric rhizome. Although studies have proved that curcumin could inhibit the growth of tumors, its specific molecular mechanism has not yet been fully elucidated. This study aims to systematically elaborate the mechanisms of curcumin against hepatocellular carcinoma. The anti-tumor effect of curcumin was determined by the cell viability test. Flow cytometry was applied to examine the cell cycle and the apoptosis of cancer cells, and the cancer cell migration was detected by wound healing experiments. The expressions of signal transducers and activators of transcription 3 (STAT3), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) in cancer cells were examined by immunostaining and analyzed by the Image J analysis system. After treatment with curcumin, the apoptosis ratio of HepG2 cells increased significantly ( P < 0.05). The proliferation of cancer cells was arrested at the S-phase cell cycle, and the migration of cancer cells was inhibited by the increasing concentration of curcumin, together with the decreasing expressions of STAT3, VEGF, and HIF-1α signaling pathways. The results indicate that curcumin could effectively inhibit the growth and migration of hepatocarcinoma cells by inducing cancer cell apoptosis, blocking the cancer cell cycle in the S phase, and reducing the expression of STAT3, VEGF, and HIF-1α signaling pathways.

Waldenström macroglobulinemia (WM) rarely leads to pulmonary embolism. Due to its low incidence, the underlying pathophysiology, prognosis, and optimal treatment remain largely unexplored and uninvestigated. In this study, a patient with a double-clonal WM, a rare subtype, presented with pulmonary embolism. The patient had a small number of plasma cells without morphological abnormalities, and an effective therapeutic response was observed. Nonetheless, the clinical prognosis requires a long-term follow-up.

Intestinal duplication is a rare congenital malformation that can occur in any segment of the digestive tract. It is most commonly found in the ileum of infants and is rarely reported in adults, especially in the colon. Diagnosing intestinal duplication can be extremely challenging due to its diverse clinical manifestations and complex anatomical structure. Surgical intervention is currently considered the mainstay of treatment. In this report, we presented a case of giant duplication of the transverse colon in an adult.

Ectopic thyroid tissue is a rare condition manifested as the appearance of thyroid tissue outside the thyroid gland. Here, we report a case of ectopic thyroid tissue in the breast. A 48-year-old Chinese woman who was diagnosed with breast cancer received modified radical mastectomy. A thyroid tissue was found on subsequent pathological examination. The ectopic thyroid tissue was confirmed by immunohistochemistry staining of thyroid biomarkers, including thyroglobulin, thyroid transcription factor-1, and thyroid peroxidase. Currently, abnormal thyroid anlage descent is the main theory to explain ectopic thyroid tissue, especially lingual thyroid. However, it is far-fetched to explain the pathogenesis of ectopic thyroid tissues existed in organs or tissues far from thyroid such as iris, cardiac, pulmonary, duodenal, adrenal, and vertebral. Here, we reviewed the previous cases of ectopic thyroid tissue in breast and proposed a “entoderm migration” theory to explain distant ectopic thyroid tissues based on embryonic development perspective.

Pancreatic cancer (PAAD) is usually found when it is already in its advanced stage, which has limited options available for treatment and poor overall survival. The SDR16C5 gene is necessary for embryonic and adult tissue differentiation, development, and apoptosis, and it also participates in immune response and regulates energy metabolism. However, the role of SDR16C5 in PAAD remains unclear. In this study, we find that SDR16C5 was highly expressed in multiple tumors including PAAD. Furthermore, higher expression of SDR16C5 was significantly associated with poorer survival. We also find that the knockdown of SDR16C5 can inhibit PAAD cell proliferation and promote cell apoptosis by repressing Bcl-2, cleaved caspase 3, and cleaved caspase 9 protein expression. Moreover, silencing SDR16C5 inhibits the migration of PANC-1 and SW1990 cells by interrupting epithelial–mesenchymal transition. KEGG pathway analysis and immunofluorescence staining indicate that SDR16C5 is associated with immunity and may also participate in the development of PAAD through the IL-17 signaling pathway. Collectively, our findings provide evidence that SDR16C5 is overexpressed in PAAD patients and promotes its proliferation, migration, invasion, and apoptosis-inhibition of PAAD cells. Thus, SDR16C5 may be a potential prognostic and therapeutic target. Graphical abstract

Breast cancer is one of the most common malignancies in women. However, cases of vaginal metastases of breast cancer are rarely reported in China and abroad. The main clinical symptom of vaginal metastases of breast cancer is vaginal bleeding. This article aims to provide a reference for the diagnosis and clinical management of vaginal metastases from breast cancer. This article describes in detail the management of a 50-year-old woman with vaginal metastases from breast cancer, who was admitted to the hospital with persistent vaginal bleeding without apparent causes. Persistent vaginal bleeding was found after two and a half years when her breast cancer surgery was performed. After comprehensive evaluation, vaginal mass resection was performed. Postoperative histopathology confirmed that the vaginal mass was breast cancer metastasis. The patient was treated with local radiotherapy and three cycles of eribulin and bevacizumab after the vaginal mass was removed. A reexamination of computed tomography showed that the chest wall metastases were less extensive than before. Orbital metastases were also reduced in size, which was revealed by the physical examination. The patient had since failed to return to hospital on time for a regular treatment due to personal reasons. After 9 months of follow-up, the patient died of multiple metastases. The diagnosis of vaginal masses is based on pathological examination, and systemic treatment should be the mainstay when extensive metastases are presented.

The present study aimed to screen the best time window for the transplantation of bone marrow mesenchymal stem cells (MSCs) after acute myocardial infarction (MI) through targeted ultrasound microbubbles loaded with SDF-1α antibody. Thirty-six MI miniswine were randomly divided into six experimental groups according to the duration after infarction (1 day, 3 days, 1 week, 2 weeks, 3 weeks, and 4 weeks after infarction). MSCs were labeled with BrdU and then injected through the coronary artery in the stem cell transplantation group to detect the number of transplanted MSCs at different time points after MI. Three miniswine were randomly selected as the control group (sham operation: open chest without ligation of the coronary artery). All SDF-1α groups and control groups were injected with a targeted microbubble ultrasound contrast agent. The values of the myocardial perfusion parameters ( A , β , and A × β ) were determined. A T , β T , and ( A × β ) T varied with time and peaked 1 week after MI ( P < 0.05). The number of transplanted stem cells in the myocardium through coronary injection of MSCs at 1 week was the greatest and consistent with the changing tendency of A T , β T , and ( A × β ) T ( r = 0.658, 0.778, 0.777, P < 0.05). β T ( X ), ( A × β ) T ( X ), and the number of transplanted stem cells was used to establish the regression equation as follows: Y = 36.11 + 17.601 X ; Y = 50.023 + 3.348 X ( R 2 = 0.605, 0.604, P < 0.05). The best time window for transplanting stem cells was 1 week after MI. The myocardial perfusion parameters of the SDF-1α targeted contrast agent can be used to predict the number of transplanted stem cells in the myocardial tissue.

Malignant melanoma (MM) is characterized by rapid growth, frequent metastasis, and high mortality. Targeted therapy for MM is still a research hotspot due to the increasing understanding of the hippo pathway. The aim of this study is to investigate the role of transcriptional coactivator with PDZ-binding motif (TAZ) in MM tumorigenesis. Based on the database analysis, we found that the median mRNA expression of TAZ (5.4) was found to be similar to that of YAP (5.5) in 473 human melanoma specimens. However, in 63 MM cell lines, the median expression of TAZ (10.8) was expressed at a higher level than that of YAP (9.5), which was then validated in A375. TAZ down-regulation by siRNA decreased the migration (72%) and invasion (74%) abilities of A375. Furthermore, the down-regulation of TAZ inhibited the proliferation of A375 without affecting apoptosis. We subsequently blocked hippo signaling with verteporfin and found that verteporfin application decreased the number of migrating (63%) and invading (69%) cells, respectively. We further found that Cyr61 declined following TAZ down-regulation. Moreover, TAZ negatively correlates with melanoma patient’s overall survival. Our data proved that TAZ contributed to MM metastasis, which might be a potential therapeutic target in the future.

Gitelman syndrome (GS) is an autosomal recessive renal tubal disease characterized by hypomagnesemia, hypokalemia, and hypocalciuria. The disease is caused by defects in the SLC12A3 gene, which encodes the thiazide diuretic-sensitive sodium chloride cotransporter (NCCT). In this study, a 20-year-old female patient with recurrent hypokalemia was tested for a hypokalemia-related panel using Next Generation Sequencing. Pedigree analysis was performed on her parents (non-consanguineous) and sister using Sanger sequencing. The results revealed that the patient carried compound heterozygous variants of the SLC12A3 gene: c.179C > T (p.T60M) and c.1001G > A (p.R334Q). Furthermore, her asymptomatic 6-year-old sister also carried both mutations. While the p.T60M mutation had been reported previously, the p.R334Q mutation was novel, and amino acid position 334 was identified as a mutation hotspot. Our findings provide an accurate molecular diagnosis that is essential for the diagnosis, counseling, and management of not only the symptomatic patient but also her asymptomatic sister. This study contributes to our understanding of the GS, which has a prevalence of approximately 1 in 40,000 and a heterozygous mutation carrier rate of 1% in Caucasians. Specifically, we observed a compound heterozygous mutation of the SLC12A3 gene in a 20-year-old female patient presenting with clinical symptoms consistent with GS.

Maternal nutrition is pivotal for offspring’s growth and development. Insufficient or unbalanced nutrition may cause osteoporosis and other diseases. Protein and calcium are essential dietary nutrients for offspring’s growth. However, the optimal contents of protein and calcium in maternal diet remain unclear. In the present study, we set four different protein and calcium content-pregnancy nutrition groups, including normal full-nutrient (Normal), low protein and low calcium (Pro−; Ca−), high protein and low calcium (Pro+; Ca−), and high protein and high calcium groups (Pro+; Ca+), to evaluate the weight gain of maternal mice as well as the weight, bone metabolism, and bone mineral density of offspring mice. When the vaginal plug is found, the female mouse will be kept in a single cage and fed with corresponding feed until delivery. The findings demonstrate that Pro−; Ca− diet affects the growth and development of offspring mice after birth. In addition, a low-calcium diet inhibits the growth of embryonic mice. Collectively, the present work further confirms the importance of protein and calcium in the maternal diet and deeply suggests their respective roles in different development stages. Graphical abstract

Wheat pests and diseases are one of the main factors affecting wheat yield. According to the characteristics of four common pests and diseases, an identification method based on improved convolution neural network is proposed. VGGNet16 is selected as the basic network model, but the problem of small dataset size is common in specific fields such as smart agriculture, which limits the research and application of artificial intelligence methods based on deep learning technology in the field. Data expansion and transfer learning technology are introduced to improve the training mode, and then attention mechanism is introduced for further improvement. The experimental results show that the transfer learning scheme of fine-tuning source model is better than that of freezing source model, and the VGGNet16 based on fine-tuning all layers has the best recognition effect, with an accuracy of 96.02%. The CBAM-VGGNet16 and NLCBAM-VGGNet16 models are designed and implemented. The experimental results show that the recognition accuracy of the test set of CBAM-VGGNet16 and NLCBAM-VGGNet16 is higher than that of VGGNet16. The recognition accuracy of CBAM-VGGNet16 and NLCBAM-VGGNet16 is 96.60 and 97.57%, respectively, achieving high precision recognition of common pests and diseases of winter wheat.

Prosthetic valve endocarditis is a serious complication after heart valve replacement, accounting for about 20–30% of infective endocarditis (IE). Aspergillosis infection accounts for 25–30% of fungal endocarditis, and the mortality rate is 42–68%. Aspergillus IE often has negative blood cultures and lacks fever, which makes diagnosis difficult and delays antifungal therapy. Our study reported a case of IE in a patient with Aspergillus infection after aortic valve replacement. Ultra-multiplex polymerase chain reaction was used to identify Aspergillus infection and guide treatment. The purpose of this study was to enhance the understanding of the management of patients with endocarditis infected by fungi after valve replacement regarding the early detection, timely intervention, and treatment of the fungal infection to reduce the risk of death and improve the long-term survival of patients.

Since the outbreak of the novel coronavirus nearly 3 years ago, the world’s public health has been under constant threat. At the same time, people’s travel and social interaction have also been greatly affected. The study focused on the potential host targets of SARS-CoV-2, CD13, and PIKfyve, which may be involved in viral infection and the viral/cell membrane fusion stage of SARS-CoV-2 in humans. In this study, electronic virtual high-throughput screening for CD13 and PIKfyve was conducted using Food and Drug Administration-approved compounds in ZINC database. The results showed that dihydroergotamine, Saquinavir, Olysio, Raltegravir, and Ecteinascidin had inhibitory effects on CD13. Dihydroergotamine, Sitagliptin, Olysio, Grazoprevir, and Saquinavir could inhibit PIKfyve. After 50 ns of molecular dynamics simulation, seven compounds showed stability at the active site of the target protein. Hydrogen bonds and van der Waals forces were formed with target proteins. At the same time, the seven compounds showed good binding free energy after binding to the target proteins, providing potential drug candidates for the treatment and prevention of SARS-CoV-2 and SARS-CoV-2 variants. Graphical abstract

Immune checkpoint inhibitors (ICIs) are widely used to treat a variety of cancers and common infectious diseases with high efficacy. During the coronavirus disease 2019 (COVID-19) pandemic, studies suggested that COVID-19 patients may benefit from ICI immunotherapy. However, clinical studies on the safety and efficacy of ICI in COVID-19 patients are still being conducted. Currently, it is not clear whether cancer patients undergoing ICI immunotherapy should adjust their treatment strategy after infection with SARS-CoV-2 and whether ICI can reduce the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, reports of patients with different types of tumors infected with SARS-CoV-2 under ICI immunotherapy were classified and sorted, including lung cancer, melanoma, squamous cell carcinoma of the head and neck, and hematologic malignances. The safety and efficacy of ICI in antitumor and anti-SARS-CoV-2 therapies were compared and further discussed to provide more reference materials for the application of ICI treatment. In a word, COVID-19 has changed the ICI treatment strategy for cancer patients indeed, and ICI treatment may be a “double-edged sword” for cancer patients complicated with COVID-19.

The value of CT-guided puncture with methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses was explored. A total of 113 patients with 146 nodules and masses were treated with methylene blue mixed with autologous blood for preoperative localization and thoracoscopic surgery in the Department of Thoracic Surgery, the First Affiliated Hospital of Fujian Medical University between October 2021 and October 2022. The localization effect, complications, and pathological conditions were observed. The localization success rate was 98.63% (144/146). The localization failed nodules and masses could still be located by looking for needle eyes and reading films. The whole group successfully completed thoracoscopic surgery. The average interval of operation after puncture was 22.16 ± 6.22 h. There was a small amount of suspicious hemothorax after puncture. There was no pneumothorax after puncture in the whole group. There were no hemoptysis, irritating dry cough, and other reactions. The overall complication rate was 2.65%, and no special treatment was given. It is safe and effective to use methylene blue mixed with autologous blood for CT-guided preoperative puncture and localization of small pulmonary nodules and masses.

We aimed to characterize the stomach adenocarcinoma (STAD) microbiota and its clinical value using an integrated analysis of the microbiome and transcriptome. Microbiome and transcriptome data were downloaded from the Cancer Microbiome Atlas and the Cancer Genome Atlas databases. We identified nine differentially abundant microbial genera, including Helicobacter , Mycobacterium , and Streptococcus , which clustered patients into three subtypes with different survival rates. In total, 74 prognostic genes were screened from 925 feature genes of the subtypes, among which five genes were identified for prognostic model construction, including NTN5 , MPV17L , MPLKIP , SIGLEC5 , and SPAG16 . The prognostic model could stratify patients into different risk groups. The high-risk group was associated with poor overall survival. A nomogram established using the prognostic risk score could accurately predict the 1, 3, and 5 year overall survival probabilities. The high-risk group had a higher proportion of histological grade 3 and recurrence samples. Immune infiltration analysis showed that samples in the high-risk group had a higher abundance of infiltrating neutrophils. The Notch signaling pathway activity showed a significant difference between the high- and low-risk groups. In conclusion, a prognostic model based on five feature genes of microbial subtypes could predict the overall survival for patients with STAD.

Abnormal mitochondrial function resulting in inadequate energy supply leads to sarcopenia and IR, suggesting that maintaining mitochondrial homeostasis by regulating mitophagy may be a promising strategy for sarcopenia IR therapy. Herein, we constructed sarcopenia mice model, which was treated with berberine and/or SIRT1/mitophagy inhibitors, and the activity of SIRT1/mitophagy signaling pathway was identified. Then, muscle tissue, blood biochemical index, inflammatory factors, GTT, and ITT were detected. We found that berberine treatment increased the body weight and alleviated d -galactose-induced weight loss in mice. SIRT1/mitophagy inhibitors suppressed the effects of berberine in the treatment of sarcopenia. The effect of berberine on the increase of muscle tissue, improving metabolic disorders, reducing the expression of inflammatory factors, and suppressing sarcopenia insulin resistance (IR) were reversed by SIRT1/mitophagy inhibitors. Our study establishes proof-of-concept to distinct the effect of berberine in sarcopenia IR, and provides strong evidence to support the hypothesis that berberine-induced SIRT1 triggers mitochondrial autophagy pathway and suppresses IR in sarcopenia.

One of the most severe side effects of systemic lupus erythematosus (SLE) is lupus nephritis (LN). To search for potential therapeutic targets in SLE is crucial for the progression of SLE. In this study, we selected C57BL/6J mice as controls and MRL/lpr mice as an LN model and obtained dual specificity phosphatase 2 (DUSP2)-overexpressed mice by injecting AAV-DUSP2 plasmid into the tail vein. Then, proteinuria, urea nitrogen, dsDNA and TNF-α, IL-6, and IL-1β levels were measured in each group of mice. In addition, renal histopathological damage was assessed by hematoxylin–eosin. Finally, STAT3 phosphorylation levels were detected by Western blot assay. The results showed that DUSP2 could reduce proteinuria, urea nitrogen, dsDNA and TNF-α, IL-6, and IL-1β levels and improve renal tissue injury in mice with LN. Mechanistically, DUSP2 inhibited STAT3 phosphorylation. These results demonstrated that DUSP2 played a role in ameliorating LN, which provided potential targets for LN research. Graphical abstract

A lung abscess is a necrotizing infection caused by microbiomes that lead to the loss of healthy lung tissue. The routine culture is a waste of time and yields false-negative results, and clinicians could only choose empiric therapy or use broad‐spectrum antibiotics, which could significantly contribute to the problem of resistance or aggravate the condition. We report three patients with a routine-culture-negative lung abscess. The presenting symptoms included fever, cough, dyspnea, and chest pain, and a computed tomography scan revealed a lesion in the lungs. The bronchoalveolar lavage fluid and pleural fluid were tested for pathogens using metagenome next-generation sequencing (mNGS), and the results revealed Fusobacterium nucleatum and Streptococcus spp. ( S. constellatus , S. intermedius ) as the most represented microbial pathogens. Our data demonstrated that mNGS could be a promising alternative diagnostic tool for pathogen detection, and the pathogen lists indicate that it will be important to focus on the Streptococcus genus rather than the dominant Streptococcus spp. in terms of co-infection of pathogen determined by shotgun mNGS. Graphical abstract The aim of this article was to employ shotgun mNGS for pathogen diagnosis in three patients with lung abscesses. The pleural fluid or bronchoalveolar lavage fluid from patients was sent to traditional culture and the shotgun mNGS test. Laboratory culture tested negative and shotgun mNGS analysis revealed a co-infection caused by Fusobacterium nucleatum and Streptococcus spp. After standard treatment of co-infection, patients gradually improved and were discharged. This figure is drawn by Figdraw.

The aim of this study is to investigate certain genetic features of intrahepatic cholangiocarcinoma (ICCA). A total of 12 eligible ICCA patients were enrolled, and tumor tissues from the patients were subjected to next-generation sequencing of a multi-genes panel. Tumor mutation burden (TMB), mutated genes, copy number variants (CNVs), and pathway enrichment analysis were performed. The median TMB was 2.76 Mutation/Mb (range, 0–36.62 Mutation/Mb) in ICCA patients. The top two most commonly mutated genes in ICCA were KRAS (33%) and TP53 (25%). The co-mutations of KRAS and TP53 were 16.7% (2/12) in ICCA patients. Notably, patient P6 with the highest TMB did not have KRAS and TP53 mutations. Additionally, TP53 and/or KRAS alterations were significantly associated with poor progression-free survival than those with wild type (1.4 months vs 18 months). DNA damage repair and homologs recombinant repair deficiencies were significantly associated with high TMB in ICCA cases. In conclusion, we found that certain genetic mutations of TP53 and KRAS could predict poor prognosis in ICCA patients.

Granulomatous polyangiitis (GPA) is a rare systemic autoimmune vasculitis disease that is highly correlated with anti-neutrophil cytoplasmic antibodies (ANCAs). It was formerly called as “Wegener’s granulomatosis.” The clinical manifestations are diverse, mainly involving the upper respiratory tract, lungs, and kidneys, and this disease can involve the brain parenchyma as an isolated solid mass. Only one case has been reported thus far. To provide further information on this rare case, we report a case of GPA involving the fourth ventricle and review the relevant literature. A 32-year-old Chinese female developed fever, cough, and shortness of breath for 20 days. An 80 mm × 80 mm skin ulcer was seen on the right lower limb. CT showed multiple large patches of increased density in both lungs. The patient’s serological ANCA was positive. Later, the patient developed dizziness and headache. Magnetic resonance imaging of the head showed a mass of approximately 21 mm × 24 mm in the fourth ventricle. The patient had a craniotomy for mass resection, and macroscopically, the mass was gray–red and measured 25 mm × 20 mm × 20 mm, was soft, had local hemorrhage and necrosis, and had no capsule. The main microscopic features included necrotizing granulomatous vasculitis, the patient’s immunohistochemistry was positive for CD68 and negative for glial fibrillary acidic protein, and the acid-fast staining and hexaamine silver staining were negative. Combined with the clinical history, serology, and imaging, the pathological diagnosis was GPA in the fourth ventricle. The patient was switched to rituximab combined with steroid therapy because she did not tolerate cyclophosphamide. After 5 months of follow-up, the patient’s lung lesions and skin ulcers had completely improved, but the brain lesions had further progressed. When a patient has multiple system diseases, abnormal clinical manifestations, and positive serological ANCAs, a diagnosis of GPA should be carefully considered, and biopsies of easy-to-access sites should be performed. If the patient’s histopathological manifestations include vasculitis, granuloma, and necrosis, a diagnosis of GPA is more likely. If a patient subsequently develops an intraventricular mass, the clinicians should consider a diagnosis of GPA, which can rarely involve the cerebral ventricle to avoid an unnecessary biopsy or surgical treatment of intracranial lesions. When a patient is intolerant to the traditional treatment drug cyclophosphamide and needs to be switched to rituximab, the treatment effect of intracerebral lesions is not ideal; therefore, the treatment of lesions involving GPA in the ventricle is worthy of further exploration.

Child mortality, particularly among infants below 5 years, is a significant community well-being concern worldwide. The health sector’s top priority in emerging states is to minimize children’s death and enhance infant health. Despite a substantial decrease in worldwide deaths of children below 5 years, it remains a significant community well-being concern. Children under five years of age died at 37 per 1,000 live birth globally in 2020. However, in underdeveloped countries such as Pakistan and Ethiopia, the fatality rate of children per 1,000 live birth is 65.2 and 48.7, respectively, making it challenging to reduce. Predictive analytics approaches have become well-known for predicting future trends based on previous data and extracting meaningful patterns and connections between parameters in the healthcare industry. As a result, the objective of this study was to use data mining techniques to categorize and highlight the important causes of infant death. Datasets from the Pakistan Demographic Health Survey and the Ethiopian Demographic Health Survey revealed key characteristics in terms of factors that influence child mortality. A total of 12,654 and 12,869 records from both datasets were examined using the Bayesian network, tree (J-48), rule induction (PART), random forest, and multi-level perceptron techniques. On both datasets, various techniques were evaluated with the aforementioned classifiers. The best average accuracy of 97.8% was achieved by the best model, which forecasts the frequency of child deaths. This model can therefore estimate the mortality rates of children under five years in Ethiopia and Pakistan. Therefore, an online model to forecast child death based on our research is urgently needed and will be a useful intervention in healthcare.

Metaplastic matrix-producing breast carcinoma is a type of metaplastic breast carcinoma (MBC), which is a rare malignancy, accounting for 0.2–1% of breast carcinomas. A 52-year-old female visited a hospital because of a palpable painless mass in the right breast and was diagnosed with Breast Imaging Reporting and Data System (BI-RADS) category 4A via ultrasound (US) with a suspected positive lymph node at the right axillary region. Excision of the breast mass was performed and histopathologically confirmed that it was MBC with osseous differentiation. No distant metastasis was revealed before a modified radical mastectomy; however, metastasis to a lymph node of the right axillary region was observed (1/22). She received six cycles of TEC scheme chemotherapy (docetaxel, epirubicin, and cyclophosphamide, 21 days) and 5 weeks of radiotherapy (48 Gy/25 f/5 days a week), but without any follow-up examinations since radiotherapy. Twenty-four months after surgery, distant metastases to lungs and liver were confirmed and died 3 months later. This case provides valuable information for clinicians on MBC and suggests that further examination or biopsy should be performed to US BI-RADS 4A masses before surgery. In addition, regular postoperative follow-up plays important roles in detecting metastases early and improving prognosis. Graphical abstract

Protein Z (PZ), a vitamin-K-dependent anticoagulant glycoprotein, is reported to be highly expressed in various malignant tissues and correlated with a poor prognosis in patients with lung cancer. This study aimed to investigate the pathological activity of PZ on lung cancer cell migration, invasion, and metastasis. PZ was assessed by Western blot in three non-small-cell lung cancer cell lines (A549, H1299, and H1975). Meanwhile,western blot was used to detect the expression of EMT pathway-related proteins (Slug, Vimentin, and N-cadherin) in the A549 cells knocked down with siRNA. The cellular proliferation, migration, and invasion were detected by Cell Counting Kit (CCK)-8, wound healing, and Transwell assays in the A549 cells. The results showed that PZ expression was higher in A549, H1299, and H1975 cells, according to Western blot. CCK-8, wound healing, and Transwell assays showed that knockdown of PZ significantly decreased cellular proliferation, migration, and invasion, as well as the protein levels of Slug, Vimentin, and N-cadherin in the A549 cells. In conclusion, the pro-metastasis activity of PZ may modulate the epithelial–mesenchymal transition pathway in lung cancer A549 cells. Graphical abstract Epithelial–mesenchymal transition (EMT)-related proteins (Slug, vimentin, and N-cadherin) are downregulated by Protein Z silencing, which significantly prohibits cellular proliferation and EMT activity (decrease of cellular migration and invasion) in non-small-cell lung cancer cells.

Acute kidney injury is a fatal disease characterized by a rapid deterioration of kidney function. Capsaicin ( trans -8-methyl- N -vanillyl-6-nonenamide) is a natural product extracted from Capsicum . The aim of this study was to explore the protective effect of capsaicin on inflammation, apoptosis, and mitochondrial dysfunction in an in vitro model of acute kidney injury. Lipopolysaccharide (LPS)-induced acute kidney injury model was established in HK-2 cells to investigate the protective effect of capsaicin. Cell viability was assessed using CCK-8 assay, and protein expression was detected using western blot and immunofluorescence assay. Intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential were analyzed by flow cytometry. Cell apoptosis was detected by propidium iodide staining. The results showed that capsaicin ameliorated LPS-induced cytotoxicity in vitro and attenuated the release of interleukin (IL)-1β and IL-18. Intriguingly, genipin abolished the protective effect of capsaicin. Molecularly, capsaicin activated transient receptor potential cation channel subfamily V member 1 –mitochondrial uncoupling protein 2 axis and inhibited caspase-1-mediated pyroptosis. In addition, capsaicin alleviated LPS-induced ROS production and mitochondrial membrane potential disruption and inhibited apoptosis. These findings suggest that capsaicin shows a protective effect in in vitro acute kidney injury model. Graphical abstract

Inhibition of Toll-like receptor 4 (TLR4)-mediated inflammatory pathways exerts a critical effect on neuronal death; therefore, it is a possible new therapeutic approach for traumatic brain injury (TBI). Resatorvid (TAK-242) is a novel small-molecule compound widely used to inhibit TLR4-mediated pathways, but the protective mechanism of TAK-242 in TBI remains unclear. Herein, we analyzed the neuroprotective effects of TAK-242 in rats after TBI. The rat model of brain injury was established using a modified Free-fall device, and the rats were injected with TAK-242 (0.5 mg/kg) through the caudal vein before TBI. The rats were allocated into four groups: a sham group, a TBI group, a TBI + vehicle group, and a TBI + TAK-242 group. The brain tissue was extracted for histology and determination of the expression of autophagy-related proteins and inflammatory mediators. TAK-242 pretreatment significantly reduced the damage to hippocampal neurons. Neuronal autophagy increased after brain injury, whereas TAK-242 significantly reduced autophagy marker protein LC3-II in the hippocampus. In addition, TAK-242 pretreatment significantly downregulated NF-κB p65, TNF-α, and IL-1β in the hippocampus. In conclusion, TAK-242 significantly reduced hippocampal neuronal damage by inhibiting autophagy and neuroinflammatory activity, possibly via the NF-κB signaling pathway. Graphical abstract

Ewing’s sarcoma (ES) is an aggressive cancer in young adults. Primary ES occurring in the chest with pleural effusion is even rarer. We report the case of a 15-year-old girl who presented with intermittent chest pain occurring for more than 2 months and cough and wheezing for 10 days. Radiological imaging showed a large soft tissue mass with multiple small vessel shadows near the left mediastinum and bloody pleural effusion in the left thorax. ES was diagnosed by positive immunostaining for CD99, FLI-1, and NKX2 combined with fluorescence in situ hybridization detection of the EWSR1 gene arrangement. With chemotherapy, lung computed tomography revealed that the tumor had become much smaller, and the fluid was absorbed. We report a case of extraskeletal Ewing’s sarcoma (EES) in the mediastinum with pleural effusion, which is unusual and challenging. EES is a highly malignant tumor with a poor prognosis. Early diagnosis and treatment can improve the survival rate of patients. Graphic abstract the timeline of the treatment

Gut microbiota are closely related to health, and the β2-adrenergic receptor ( ADRB2 ) gene is associated with gastrointestinal diseases. However, little is known about the relationship between ADRB2 gene polymorphisms and intestinal microbiota. In the present study, we aimed to explore the relationship between ADRB2 gene polymorphisms and gut microbiota in Chinese Han adolescents. Data analysis showed that the relative abundance, PICRUSt function prediction, and Chao1 and ACE indices of gut microbiota were significantly different between males and females ( P < 0.05). The rs1042711 was positively associated with the relative abundance of Actinobacteria, Coriobacteriia, Bifidobacteriales, Erysipelotrichi, and Erysipelotrichales. The rs12654778 was negatively associated with Bacilli, Lactobacillales, Bacteroidaceae, and Bacteroides . rs1042713 was positively associated with Lactobacillales and Bifidobacteriales. The rs1042717 was positively associated with Bifidobacteriales and negatively associated with Veillonellaceae. The rs1042719 was negatively associated with Erysipelotrichi and Erysipelotrichales and positively associated with Erysipelotrichi, Erysipelotrichales, Bifidobacteriales, and Ruminococcaceae in females. The rs1801704 was positively associated with Erysipelotrichi, Erysipelotrichales, Bifidobacteriales, Actinobacteria, Coriobacteriia, and Bifidobacteriales. The rs2053044 was positively associated with Ruminococcaceae, Dialister , Firmicutes, Clostridia, Clostridiales, Bifidobacteriales, and Faecalibacterium and negatively associated with Bacilli, Lactobacillales, Lachnospiraceae, and Porphyromonadaceae ( P < 0.05). These results suggested that the relative abundance, diversity, and PICRUSt function predictions of male and female gut microbiomes differ significantly and that ADRB2 gene polymorphisms were associated with gut microbiome abundance in Chinese Han adolescents. Graphical abstract Gut microbiota are closely related to health, and the β2-adrenergic receptor gene ( ADRB2 ) is associated with gastrointestinal diseases. In the present study, we aimed to explore the relationship between ADRB2 gene polymorphisms and gut microbiota in Chinese Han adolescents. The relative abundance, diversity, and PICRUSt function predictions of male and female gut microbiomes differ significantly and that ADRB2 gene polymorphisms were associated with gut microbiome abundance in Chinese Han adolescents.

Articular cartilage degeneration caused by chondrocyte damage is the primary pathological mechanism of osteoarthritis (OA). Oxidative stress is correlated with chondrocyte injury by potentiating ferroptosis, a newly identified form of cell death. Given the effects of Tanshinone IIA (Tan IIA) on alleviating oxidative stress, we further explored whether Tan IIA inhibited chondrocyte death and cartilage degeneration by decreasing ferroptosis. ATDC5 chondrocytes were treated with lipopolysaccharides (LPS) and Tan IIA, and cell viability was assessed using cell counting kit-8 (CCK-8) assays. Matrix metalloproteinase-13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS5), and type II collagen (Col II) levels were measured using quantitative real-time polymerase chain reaction (qRT‒PCR), western blotting, and immunofluorescence (IF) analysis. We demonstrated that Tan IIA treatment prominently increased ATDC5 cell viability and decreased cell apoptosis in the presence of LPS-induced stress. MMP13 and ADAMTS5 expression was increased, and Col II expression was decreased in ATDC5 cells after LPS stimulation, whereas these changes were reversed by Tan IIA. Mechanistically, Tan IIA inhibited LPS-induced ferroptosis in ATDC5 cells, as indicated by decreased levels of iron, reactive oxygen species, and malondialdehyde and increased GSH levels. Importantly, a ferroptosis agonist partially abrogated the effect of Tan IIA on alleviating chondrocyte damage and death. Taken together, these results suggest that Tan IIA ameliorates chondrocyte apoptosis and cartilage degeneration by inhibiting ferroptosis and may be a potential therapeutic agent for OA. Graphical abstract

Inflammatory cytokine storms (CS) in COVID-19 patients are associated with elevated levels of 13 specific cytokines, potentially impacting male fertility by causing testicular cell damage and disrupting the immune microenvironment. Some patients present with scrotal discomfort and orchitis. However, few studies have explored cytokine expression in testicular cells and their role in cell-to-cell communication. In this study, we integrated single-cell sequencing data sets of testicular cells, annotating 20 cell clusters using marker genes and the Human Cell Landscape database. We constructed cell pseudo-chronological trajectories, hub genes, and analyzed the cytokine interaction network between sperm cells using CellChat. Our findings identified 12 types of testicular cells, with four cytokines (IL8, CCL2, CCL3, and TNF) potentially involved in immune processes. Pseudo-chronological trajectory analysis indicated IL8 and CCL3's essential roles in testicular macrophages and endothelial cell development, affecting the immune microenvironment. We determined eight key cytokines (IL1, IL2, IL4, IL6, CCL, CSF3, TNF, and IFN-II) functions in cell interaction networks. Network analysis of exogenous cytokines directly acting on testicular cells showed IL2 potentially affecting all testicular cells, suggesting a vital role in cell communication. This research offers valuable insights into CSs effects on testicular cells and their potential impact on male fertility during COVID-19 infection.

This study aimed to investigate the effect of periostin (PN) on the expression of receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), microtubule-associated protein1 light chain 3B (LC3B), and Beclin1 in mouse alveolar bone specimens and cultured osteoblasts in vitro , to preliminarily explore the role of PN and autophagy in remodeling bone metabolism during tooth eruption. Mice at 5 days of age were injected with 75 ng/mL recombinant PN protein under the periosteum for 3 consecutive days according to the standard of 1 mL/100 g/day. Then, their mandibles were removed, and the expression of bone metabolic and autophagy factors was detected by immunohistochemistry. Mouse osteoblast-like cells cultured in vitro were treated with recombinant PN at a concentration of 75 ng/mL. The changes in the aforementioned indicators were compared again by immunofluorescence and western blotting 72 h after dosing. The results of the mouse samples showed that the protein expression of RANKL, LC3B, and Beclin1 decreased, accompanied by the decrease in RANKL/OPG ratio. However, OPG protein expression increased in the dosing group. Immunofluorescence and western blotting results of osteoblasts cultured in vitro showed that the protein expression of RANKL, LC3B, Beclin1, and the RANKL/OPG ratio in the experimental group decreased, but OPG expression increased. PN may regulate alveolar bone metabolism during tooth eruption by inhibiting the RANKL/OPG ratio and autophagy, which will provide a new research perspective for further exploration of the mechanisms during tooth eruption. Graphical Abstract

The aim of this study was to investigate the role of ferroptosis in diabetic nephropathy (DN) and the mechanism of its regulatory genes. HK-2 cells were cultured with high glucose and mice were intraperitoneally injected with streptozotocin to establish DN models. GSE111154 was analyzed to identify the abnormal expression of genes associated with DN. Cell injury was evaluated through CCK-8 assay and 4′,6-diamidino-2-phenylindole/phenylindole double staining. The levels of iron, glutathione, malondialdehyde, urinary albumin, and urinary creatinine were determined by ELISA. Furthermore, western blot and RT-qPCR were used to detect protein and mRNA levels, respectively. Our data showed that heterochromatin protein 1 is an abnormally elevated gene related to DN and is further elevated by ferroptosis activators. Inhibition of HP1 significantly inhibited ferroptosis but promoted cell viability. In addition, nuclear factor erythroid2-related factor2 (NRF2) was decreased in DN cell model, but increased under the action of ferroptosis activators. NRF2 silencing reversed the protective effects of HP1 inhibition on HK-2 cells. Additionally, HP1 silencing also alleviated kidney damage in DN mice. Collectively, these findings suggest that inhibiting HP1 inhibits ferroptosis via NRF2 pathway, thereby protecting renal tubular epithelial cells from damage. Graphical abstract

This study aims to investigate the influence of topical estrogen management in postmenopausal patients who had undergone CO 2 laser ablation for vaginal squamous intraepithelial lesions (SILs). The clinical data of 211 postmenopausal women with vaginal SILs were reviewed. Patients were divided into two groups by 2-month different management: Group 1 (intervention group): patients were treated with estrogen cream 0.5 g every other day and Group 2 (control group): no topical agent was used for the treatment of patients. In low-grade squamous intraepithelial lesions (LSILs), the response rates for patients in the intervention group and the control group were 49.1% (27/55) and 54.2% (16/48), respectively; human papillomavirus (HPV) status turned negative in 12 (12/38, 31.6%) patients of the intervention group and in 15 (15/35, 42.9%) patients of the control group. In high-grade squamous intraepithelial lesions (HSILs), the response rates for patients in the intervention group and the control group were 72.4% (42/58) and 78.0% (39/50), respectively, nearly 1.5 times higher than those of the LSIL patients; 22 (22/54, 40.7%) patients of the intervention groups and 12 (12/46, 26.1%) patients of the control group cleared the HPV infection. In postmenopausal patients, local use of estrogen cream improves the recognition of lesions and is conducive to precision medicine.

The aim of this study is to explore a novel classification and investigate the clinical significance of hepatocellular carcinoma (HCC) cells. We analyzed integrated single-cell RNA sequencing and bulk RNA-seq data obtained from HCC samples. Cell trajectory analysis divided HCC cells into three subgroups with different differentiation states: state 1 was closely related to phosphoric ester hydrolase activity, state 2 was involved in eukaryotic initiation factor 4E binding, translation regulator activity and ribosome, and state 3 was associated with oxidoreductase activity and metabolism. Three molecular classes based on HCC differentiation-related genes (HDRGs) from HCC samples were identified, which revealed immune checkpoint gene expression and overall survival (OS) of HCC patients. Moreover, a prognostic risk scoring (RS) model was generated based on eight HDRGs, and the results showed that the OS of the high-risk group was worse than that of the low-risk group. Further, potential therapeutic drugs were screened out based on eight prognostic RS-HDRGs. This study highlights the importance of HCC cell differentiation in immunotherapy, clinical prognosis, and potential molecular-targeted drugs for HCC patients, and proposes a direction for the development of individualized treatments for HCC.

This meta-analysis investigated the effect of physical exercise (PE) on the levels of oxidative biomarkers in randomized controlled trials (RCTs) involving healthy subjects. We searched five databases for articles until May 1, 2023. A random-effect meta-analysis, subgroup analysis, meta-regressions as well as trim and fill method were conducted using STATA 11.0, involving ten articles. According to the results of the meta-analysis, PE had no significant effect on superoxide dismutase (SOD), glutathione peroxidase, and catalase levels. PE induced significant increase in total antioxidant status (standardized mean difference [SMD] 1.53, 95% CI 0.73–2.32), and PE could significantly reduce the level of malondialdehyde (MDA) (SMD −1.11, 95% CI −2.15 to −0.06). Sensitivity analyses and subgroup analyses showed that male participants, body mass index (BMI) <25, exercise duration between 1 and 12 weeks, resistance exercise or multicomponent exercise, and exercise of low or moderate intensity were associated with a significant PE-induced decrease in MDA concentrations. Meta-regression analysis identified the age of the participants as a confounder of the effect of PE on SOD levels. The older age of the subjects was associated in a gradient fashion with incident SOD levels. Further RCTs are required to investigate the optimal PE protocol for people of different ages and BMI as well as the effect of PE on oxidative stress.

Lysosome dysfunction has been shown to play an important role in cancer progression. However, few research studies have reported the role of lysosomes in head and neck squamous cell carcinoma (HNSCC) progression. Lysosome-related genes (LRGs) were collected from the Molecular Signatures Database. Differentially expressed lysosome-related genes (DELRGs) were identified from the TCGA-HNSCC dataset. The least absolute shrinkage and selection operator and multivariate Cox regression analysis were used to identify the prognostic genes. The prognostic values and expression of hub DELRGs were further validated by GEO datasets. Estimation of STromal and Immune cells in MAlignant Tumors using Expression data and the single-sample gene set enrichment analysis were applied to evaluate the correlation between cathepsin G (CTSG) and immune infiltrates. Twenty-two DELRGs were identified. Among them, CTSG was an independent prognostic biomarker for HNSCC patients. Gene set enrichment analysis indicated that the potential mechanism of CTSG in regulating HNSCC was associated with the immune- and inflammation-related pathways. CTSG expression was highly correlated with immune cell infiltration. Finally, two potential compounds (CH and MAN) targeting CTSG protein were identified, and their reliability was validated through molecular docking analysis. CTSG was associated with immune infiltration and had prognostic value in HNSCC patients, which may be a potential biomarker for predicting the outcome of immunotherapy. Graphical Abstract

Most laboratory tests to detect the presence of anti-SARS-CoV-2 antibodies use enzyme-linked immunosorbent assays (ELISA) or chemiluminescence immunoassays (CLIA); however, equipment for these immunoassays is unavailable in many areas of low- and middle-income countries. Rapid lateral flow immunoassay (LFIA) tests are an equipment-free option, but their high price may make them less suitable for conducting seroprevalence surveys. Here, we describe a simple dual antigen ELISA dot-blot test to detect anti-SARS-CoV-2 IgG antibodies with high sensitivity (94–98%) and specificity (92–100%), compared to commercially available ELISA and CLIA options. Additionally, this ELISA dot-blot test can be completed in one hour using minimal laboratory equipment. Importantly, this immunoassay is significantly more affordable than most LFIA tests available on the global market. The dot-blot strips may be stored for up to 7 days under freezing conditions. This ELISA dot-blot test is a cost-effective option for conducting seroprevalence screenings in areas lacking ELISA or CLIA facilities, compared to LFIA tests.

The pathogenesis of Parkinson’s disease (PD) remains unclear. Among the pathological manifestations is the progressive degeneration of the nigrostriatal dopaminergic pathway, leading to massive loss of neurons in the substantia nigra pars compacta and dopamine (DA) depletion. Therefore, the current drug treatment is primarily based on DA supplementation and delaying the progression of the disease. However, as patients’ symptoms continue to worsen, the drug effect will gradually decrease or even disappear, thereby further aggravating clinical symptoms. Gas signaling molecules, such as hydrogen sulfide (H 2 S), nitric oxide (NO), carbon monoxide (CO), and hydrogen (H 2 ), exhibit pleiotropic biological functions and play crucial roles in physiological and pathological effects. In common neurodegenerative diseases including Alzheimer’s disease and PD, gas signal molecules can prevent or delay disease occurrence via the primary mechanisms of antioxidation, anti-inflammatory response, and antiapoptosis. This article reviews the therapeutic progress of gas signaling molecules in PD models and discusses the possibility of their clinical applications.

The aim of this study was to investigate the effects of adiponectin (APN) on the proliferation and phenotypic transformation of human skin fibroblasts (HSFs) induced by TGF-β1. Primary fibroblast cultures were collected from prepuce surgery, and the cell viability and proliferative activity of HSFs were detected by Cell Counting Kit-8 and EdU assays. In addition, cell migration was detected by Transwell assay. The protein levels of related genes in HSF were detected by Western blotting. The results showed that the proliferation and migration abilities of HSF in the TGF-β1 group were significantly improved, and the relative protein expression levels of PCNA, α-SMA, and Collagen I in the TGF-β1 group were greatly increased. Furthermore, TGF-β1 stimulated the phosphorylation of p38 in HSF, while APN pretreatment significantly inhibited the TGF-β1-induced phosphorylation of p38. Additionally, blocking the p38 MAPK signaling pathway relieved the injury in the HSF induced by TGF-β1 and enhanced the therapeutic effect of APN in the TGF-β1-treated HSF. In conclusion, APN inhibits TGF-β1-induced HSF proliferation and myofibroblast phenotypic transformation by activating the p38 MAPK signaling pathway. APN is expected to become a potential target for preventing and treating skin fibrosis and pathological scars. Graphical abstract

Bladder urothelial carcinoma (BLCA) is the most common malignant tumor of the urinary tract with a high lethality rate, and its immunotherapy resistance and tumor recurrence have become a major challenge in its clinical treatment. G Protein-Coupled Receptors (GPRs) are the largest family of receptors on the cell membrane surface, involved in multiple signaling pathways, and are excellent targets for oncology drug action. The transcriptome profile, single cell transcriptome profile, and clinical data of BLCA were extracted and integrated from TCGA and GEO databases, respectively. The GPR-related genes were obtained from GSEA-MSigDB database. The GPR-related gene signatures of 15 genes were constructed by using the methods of least absolute shrinkage and selection operator regression, multifactor Cox model. At the same time, tumor microenvironment (TME)-score signatures were constructed based on the immune microenvironment of BLCA, and GPR-TME-score signature was further constructed. The stability of this model was verified by using the external dataset GSE160693. We constructed risk groups by combining BLCA patient prognostic information, and with the help of BLCA scRNA transcriptome profiling, we explored differences in prognosis, immune scores, cell–cell interactions, tumor mutational burden, immune checkpoints, and response to immunotherapy in each risk group. We found that the GPR-TME-score signature was an independent prognostic factor for BLCA patients. the TME-score was a protective factor for the prognosis of BLCA patients. Among BLCA patients, GPR-high + TME-low risk group had the worst prognosis, while GPR-high + TME-high risk group had the best prognosis, and the latter had better immune score and immunotherapy response. The above differences in immune response among the subgroups may be related to the higher immune cell infiltration in the GPR-high + TME-high group. GPR-related gene signatures and TME are closely related to BLCA prognosis and immunotherapy, and GPR-related gene signature can be a useful tool to assess BLCA prognosis and immunotherapy response.

This study aimed to investigate whether α-fetoprotein (AFP) could affect the malignant behavior of AFP-producing gastric cancer (AFP-GC) and to explore the relationship between AFP and mesenchymal–epithelial transition factor (c-Met) in AFP-GC. In this study, 23 patients with AFP-GC (AFP[+]) and 18 patients with common gastric cancer (AFP[−]) were evaluated for the c-Met expression using immunohistochemical analysis. The AFP-GC cell line, GCIY, was used. The AFP endoribonuclease-prepared small interfering RNA (siRNA) and eukaryotic AFP overexpression vector were used to increase/knockdown the expression of AFP. Afterward, the c-Met expression was evaluated by polymerase chain reaction and western blot. The proliferation, migration, and invasion of GCIY cells were estimated before and after the AFP overexpression/knockdown. The c-Met expression in both groups was the same ( p > 0.05), and AFP[+] group had a higher positive incidence of the c-Met expression than the AFP[−] group ( p < 0.01). Furthermore, the c-Met expression frequency was decreased by AFP knockdown and increased by AFP overexpression ( p < 0.01). The cell counting kit-8 cell proliferation assay, cell invasion, and migration assays confirmed that the AFP could affect the malignant biological behavior of AFP-GC. These findings suggest that AFP contributes to the malignant biological properties of AFP-GC and the high expression of c-Met in AFP-GC.

CXCR4 and CXCR7 have been revealed to be receptors of CXCL12. This research was designed to probe the expression of chemokine CXCL12 and its receptors CXCR4 and CXCR7 in placental tissues of patients with placenta previa and the effect of CXCL12/CXCR4/CXCR7 axis on the biological functions of human trophoblast cells. CXCL12, CXCR4, and CXCR7 expression in placental tissue from patients with placenta previa and healthy puerperae was detected. CXCL12, CXCR4, and CXCR7 expression in human trophoblast cell lines (HTR8/SVneo cells) was assessed after suppression or overexpression of CXCL12, CXCR4, and CXCR7. The cell proliferative, invasive, and migratory capacities were also evaluated in HTR8/SVneo cells after suppression or overexpression of CXCL12, CXCR4, and CXCR7. CXCL12, CXCR4, and CXCR7 expression was elevated in placental tissues from patients with placenta previa. Downregulation of CXCL12, CXCR4, and CXCR7 could lead to decreased mRNA levels of CXCL12, CXCR4, and CXCR7 in HTR-8/SVneo cells, which was accompanied by diminished cell proliferative, migratory, and invasive capabilities. Overexpression of CXCL12, CXCR4, and CXCR7 genes presented an opposite tendency. CXCL12, CXCR4, and CXCR7 are highly expressed in placental tissues of patients with placenta previa and induce the biological activities of HTR8/SVneo cells.

High thyroid stimulating hormone (TSH) levels may stimulate papillary thyroid cancer (PTC) cell proliferation; however, the relationship between TSH levels and PTC risk remains controversial. We aim to ascertain the association through a meta-analysis. Literature searches were conducted in PubMed, Embase, and Web of Science databases. After literature screening, the methodological quality was assessed using the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality methods. Cochran’s Q and I 2 tests were used to evaluate heterogeneity in the meta-analysis. Egger’s test was applied to assess publication bias. A total of 12 eligible studies were included in this meta-analysis; all were of moderate and high methodological quality. The pooled results suggested that increased TSH levels were significantly associated with PTC risk; however, the included studies were significantly heterogeneous. Stratification analysis indicated that the heterogeneity might be from the area or type of control. Although significant publication bias existed among the studies, the trim-and-fill method and sensitivity analysis revealed that the combined results were stable and robust. TSH levels are significantly associated with the PTC risk; however, more high-quality studies in large sample sizes are recommended to verify the extrapolation of these findings. Graphical abstract

The diagnosis of sepsis still lacks a practical and reliable gold standard. The purpose of this study was to confirm the effect of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) combined with soluble suppression of tumorigenicity 2 (sST2) in the diagnosis of sepsis through the correlation between sTREM-1, sST2, and sequential organ failure assessment (SOFA) scores. Baseline data of 91 patients with sepsis in the intensive care unit were collected, sTREM-1 and sST2 were detected, and the correlation between markers and SOFA score was analyzed. Besides, the prognostic value of baseline and postadmission indicators for sepsis was analyzed with death as the outcome. The results showed that the expressions of sST2 and sTREM-1 in death group and survival group were higher than those in the survival group ( p < 0.05). Correlation analysis showed that sST2, sTREM-1, and the joint diagnosis model had a high correlation with SOFA score ( p < 0.05), but poor correlation with Acute Physiology and Chronic Health Evaluation Ⅱ score ( p > 0.05). Among them, joint diagnosis model has the highest correlation. Receiver operating characteristic curve analysis showed that combined diagnosis had higher area under curve values. sTREM-1/sST2 can be better used in the diagnosis of sepsis than the single biomarker detection, and the combination of the above two biomarkers has potential application value in the detection and prognosis prediction of sepsis. Graphical abstract

We aimed to investigate the potential diagnostic value of five serum neuroactive substances in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with depression. A total of 103 patients with AECOPD were enrolled between August 2020 and August 2021. All patients were assessed using a self-rating depression scale and divided into AECOPD with or without depression groups. Baseline data and serum neuroactive substance levels were compared between the two groups. Logistic regression was used to identify the risk factors. The diagnostic performance of neuroactive substances was evaluated using receiver operating characteristic (ROC) curves. Patients with AECOPD complicated with depression exhibited higher partial pressure of CO 2 values and higher chronic obstructive pulmonary disease assessment test (CAT) scores. An elevated proportion of patients with more than two acute exacerbations (AEs) in the previous year was observed in this patient group (all P < 0.001). The CAT score and number of AEs during the previous year were identified as independent risk factors for AECOPD complicated with depression. No significant differences were observed in the levels of aspartic acid and glutamate between the two groups ( P > 0.05). Serum γ-aminobutyric acid (GABA) and glycine (Gly) levels were decreased. In contrast, serum nitric oxide (NO) levels were increased in the AECOPD complicated with the depression group ( P < 0.05). Serum GABA and Gly levels exhibited a negative correlation, and NO levels positively correlated with the number of AEs in the previous year and the CAT score. The area under the ROC curve values for GABA, Gly, and NO were 0.755, 0.695, and 0.724, respectively. Serum GABA exhibited a sensitivity of 85.1% and a specificity of 58.9%, below the cut-off value of 4855.98 nmol/L. Serum GABA, Gly, and NO may represent potential biomarkers for AECOPD complicated with depression. Graphical abstract

The process of aging is marked by a gradual deterioration in the physiological functions and functional reserves of various tissues and organs, leading to an increased susceptibility to diseases and even death. Aging manifests in a tissue- and organ-specific manner, and is characterized by varying rates and direct and indirect interactions among different tissues and organs. Cardiovascular disease (CVD) is the leading cause of death globally, with older adults (aged >70 years) accounting for approximately two-thirds of CVD-related deaths. The prevalence of CVD increases exponentially with an individual’s age. Aging is a critical independent risk factor for the development of CVD. AMP-activated protein kinase (AMPK) activation exerts cardioprotective effects in the heart and restores cellular metabolic functions by modulating gene expression and regulating protein levels through its interaction with multiple target proteins. Additionally, AMPK enhances mitochondrial function and cellular energy status by facilitating the utilization of energy substrates. This review focuses on the role of AMPK in the process of cardiac aging and maintaining normal metabolic levels and redox homeostasis in the heart, particularly in the presence of oxidative stress and the invasion of inflammatory factors.

To investigate the specific role of TRIM29 in colon cancer progression, bioinformatic analysis was performed on TRIM29. Colon cancer tissues were collected and colon cancer cells were cultured for further experiments. Cell viability and proliferation were determined using CCK-8, colony formation, and EDU staining assays. The mRNA and protein levels of TRIM29 and KRT5 were determined using quantitative real-time PCR and western blotting, respectively. The interaction between TRIM29 and KRT5 was detected using a co-immunoprecipitation (CO-IP) assay. Cycloheximide treatment was performed to analyse the stability of KRT5. TRIM29 was upregulated in colon cancer tissues and cells. TRIM29 knockdown decreased the cell viability and proliferation and ubiquitination levels of KRT5 and enhanced the protein stability and expression of KRT5. The CO-IP assay confirmed that TRIM29 and KRT5 binded to each other. KRT5 knockdown neutralises the inhibitory effect of sh-TRIM29 on colon cancer cell growth and TRIM29 knockdown prevented the proliferation of colon cancer cells by decreasing ubiquitination of KRT5, which enhanced the protein stability and expression of KRT5 in cancer cells. Thus, targeting TRIM29-mediated ubiquitination levels of KRT5 might be a new direction for colon cancer therapy. Graphical abstract

Liver steatosis is the most widespread chronic liver condition. Its global incidence is rising swiftly and is currently estimated to be 24%. Liver steatosis is strongly related with numerous metabolic syndrome characteristics, like obesity, insulin resistance, hyperlipidemia, and hypertension. The gastrointestinal tract contains about 100 trillion commensal organisms and more than 7,000 distinct bacterial strains. Fat deposition in the liver without secondary causes is known as liver steatosis. Dysregulation of the gut flora is one of the factors connected to the onset of fatty liver disease. Dietary choices may alter constitution of the microbiome and cause gut microbiome dysbiosis, particularly due to the intake of food high in fructose sugars, animal products, and saturated fats. Various gut bacteria cause nutrient metabolism in multiple ways, setting off different inflammatory cascades that encourage liver disease and pathways that help fat build up in the liver. Due to their relatively stable nature, genetic factors may not be responsible for the constant increase in liver steatosis incidence. Genetic factors set the stage for liver steatosis pathogenesis. This review will offer an overview of our present knowledge of the roles played by gut microbiota in regulating the development of liver steatosis, potential side effects, and potential treatment targets.

Small cell lung cancer (SCLC) rarely metastasizes to the ovary, and is difficult to diagnose given its overlapping clinical features and histological characteristics with primary ovarian cancer. Since therapies for SCLC and primary ovarian cancer differ, it is important to determine the original site of ovarian lesions. This report describes the differential diagnosis of metastatic from primary ovarian cancer. A 46-year-old Chinese woman with a history of SCLC, confirmed by transbronchial lung biopsy in August 2018, presented with abdominal distension in December 2018. Ultrasound examination and whole abdomen computed tomography showed one mass in each ovary. A provisional diagnosis of ovarian tumor was given. A palliative total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed; and three postoperative courses of chemotherapies. The patient died from multiple organ failure in May 2019. Metastatic ovarian cancer from SCLC was determined based on characteristic histological and immunohistochemical staining.

Sepsis is a syndrome caused by an imbalance in the inflammatory response of the body caused by an infection that leads to organ dysfunction, with the kidney being one of the most commonly affected organs. Sepsis-related acute kidney injury (SAKI) is strongly linked to increased mortality and poor clinical outcomes. Early diagnosis and treatment can significantly reduce patient mortality. On the other hand, the pathogenesis of SAKI is not fully understood, and early diagnosis of SAKI is a clinical challenge. Therefore, the current review describes biomarkers of acute kidney injury in sepsis and discusses the various pathogenic mechanisms involved in the progression of acute kidney injury in sepsis to develop new clinical treatment avenues.

Patients with sepsis face high mortality rates and a bleak prognosis, prompting the need for advanced therapeutic interventions. A male patient diagnosed with moderately low-differentiated squamous cell carcinoma received diverse treatments, including radiotherapy, chemotherapy, immunotherapy, and targeted therapy to inhibit angiogenesis. Subsequently, he developed sepsis after comprehensive treatment, and conventional antibiotic combinations proved ineffective in combating the infection. As an experimental approach, allogeneic natural killer (NK) cell infusion was administered. Following the NK cell infusion, the patient regained consciousness, and laboratory analyses showed reduced infection-related markers, suppressed serum inflammatory cytokines, and elevated anti-tumor cytokines. However, the therapeutic effect only lasted 2–3 days. In vitro investigations demonstrated that the allogeneic NK cell product reduced interleukin-6 levels in the patient’s serum. Moreover, subsequent co-cultivation of the NK cell product with the patient’s serum resulted in a decrease in the proportion of cytotoxic subpopulations of NK cells and a downregulation of the expression of NK-mediated killing molecules. In conclusion, adoptive transfusion of allogeneic NK cells may improve sepsis symptoms in patients with tumor-related sepsis. In vitro co-culture tests hold promise in providing predictive biomarkers for treatment effectiveness. Graphical abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disorder. Its pathogenesis is complicated but highly related to aberrant Th17 overactivation. Uncontrolled Th17 cell expansion and activation in populations and associated activities contribute to the progression of RA. Although clinical RA remedies are available, not all RA patients respond to these treatments, and adverse effects are always a concerning issue during treatment. To expand the repertoire of possible anti-RA remedies, we chose the phytochemical compound erianin, isolated from Dendrobium sp., and evaluated its antiarthritic effect in vitro and in vivo . We found that erianin efficiently controlled the differentiation and activation of Th17 cell development from primary CD4 T cells, limiting IL-17A cytokine production and RORγT transcript generation. In line with molecular docking models, the essential signaling pathway for Th17 polarization, the JAK/STAT3 pathway, was inhibited upon erianin treatment, with dose-dependent inhibition of phosphorylation shown by western blotting. More importantly, erianin treatment reduced arthritic manifestations and proinflammatory cytokine levels in collagen-induced arthritis (CIA) mice, as well as protecting the joint histological microstructure. Overall, erianin revealed a promising inhibitory effect on Th17 overactivation and decreased disability in CIA mice. Therefore, erianin could be further developed as a candidate RA remedy.

Clear cell renal cell carcinoma (ccRCC) is a major pathological type of kidney cancer with a poor prognosis due to a lack of biomarkers for early diagnosis and prognosis prediction of ccRCC. In this study, we investigated the aberrant expression of Acyl-coenzyme A oxidase 1 (ACOX1) in ccRCC and evaluated its potential in diagnosis and prognosis. ACOX1 is the first rate-limiting enzyme in the peroxidation β-oxidation pathway and is involved in the regulation of fatty acid oxidative catabolism. The mRNA and protein levels of ACOX1 were significantly downregulated in ccRCC, and its downregulation was closely associated with the tumor-node-metastasis stage of patients. The ROC curves showed that ACOX1 possesses a high diagnostic value for ccRCC. The OS analysis suggested that lower expression of ACOX1 was closely related to the worse outcome of patients. In addition, gene set enrichment analysis suggested that expression of ACOX1 was positively correlated with CDH1, CDH2, CDKL2, and EPCAM, while negatively correlated with MMP9 and VIM, which strongly indicated that ACOX1 may inhibit the invasion and migration of ccRCC by reversing epithelial-mesenchymal transition. Furthermore, we screened out that miR-16-5p is upregulated at the mRNA transcript level in ccRCC and negatively correlated with ACOX1. In conclusion, our results showed that ACOX1 is abnormally low expressed in ccRCC, suggesting that it could serve as a diagnostic and prognostic biomarker for ccRCC. Overexpression of miR-16-5p may be responsible for the inactivation of ACOX1.

Periodontal ligament stem cells (PDLSCs) have multidirectional differentiation potential and self-renewal abilities and are important seed cells for the regenerative repair of periodontal tissues. In recent years, many studies have identified multiple signalling pathways involved in regulating the osteogenic differentiation of PDLSCs in an inflammatory environment. In this article, we review the osteogenic differentiation of PDLSCs in an inflammatory environment in terms of signalling pathways and provide new ideas for the regenerative treatment of periodontal tissues. Graphical Abstract PDLSCs possess multidirectional differentiation potential and self-renewal ability. In the inflammatory environment, signalling pathways, such as Wnt/β-catenin, Wnt/Ca 2+ , Wnt/PCP, NF-κB, MAPK, BMPs, and PI3K/AKT, are involved in regulating the osteogenic differentiation of PDLSCs. In addition, multiple signalling pathways that interact with microRNAs play crucial roles in the osteogenic differentiation of PDLSCs.

Liver failure is a common clinical syndrome of severe liver diseases, which belongs to one of the critical medical conditions. Immune response plays a leading role in the pathogenesis of liver failure. Lactic acid as a target for the treatment and prediction of liver failure has not attracted enough attention. Since the emergence of the concept of “histone lactation,” lactic acid has shown great promise in immune response and escape. Therefore, targeted lactic acid may be a reliable agent to solve immune and energy metabolism disorders in liver failure. Based on the relationship between lactic acid and immune response, the cross-talk between lactic acid metabolism, its compounds, and immune regulation and its significance in the diagnosis and treatment of liver failure were expounded in this article to provide new ideas for understanding and treating liver failure.

The aim of this study was to investigate the clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma. Histopathology, immunohistochemistry, and human epidermal growth factor receptor 2 (HER2) gene testing were conducted for seven cases of gastric pleomorphic giant cell carcinoma. In histomorphological terms, all seven cases involved pleomorphic giant cell carcinoma, accounting for more than 10% of the entire tumor, with pleomorphic spindle cells and giant cells mixed with various histomorphological structures of adenocarcinoma with high, intermediate, and low differentiation. There was large heterogeneity in the HER2 protein expression and HER2 gene amplification in the gastric pleomorphic giant cell carcinoma, and both levels of HER2 were focal in three cases, accounting for 42.9% (3/7). The mismatch repair gene proteins MLH1, MSH2, PMS2, and MSH6 were positive. Routine immunohistochemical markers, i.e., pan-cytokeratin, epithelial membrane antigen, villin, caudal-type homeobox 2, E-cadherin, and p53, were positive in the gastric pleomorphic giant cell carcinoma, while vimentin, calponin, smooth muscle actin, nestin, S-100, cluster of differentiation (CD) 99, desmin, and CD34 were focally expressed in both the spindle and the giant cells, with Ki-67-positive cells accounting for 70–80%. Gastric pleomorphic giant cell carcinoma presents multiple histomorphological features and is easily confused with various tumors. Clarifying the histopathological features of this type of tumor is important for differential diagnosis and precise treatment.

Currently, there are no cases of targeted, individualized repeated transcranial magnetic stimulation (rTMS) treatment based on event-related potential (ERPs) results showing the activation of functional brain regions. The identification and treatment of mild cognitive impairment after traumatic brain injury are challenging. rTMS has shown unique advantages in previous studies, with positive effects on noninvasive modulation and neuroplasticity after brain injury. The selection of the rTMS parameters and targets remains controversial. ERPs indicate the cortical activity involved in cognitive processing in patients. Therefore, this study proposes that ERPs can be used as biomarkers of cognitive recovery. The results of this study will guide the development of rTMS protocols for patient treatment. To help clinicians better apply rTMS and ERPs in combination, we conducted a relevant literature review and discussion, detailing the therapeutic mechanisms of the combination of ERPs and rTMS. This will facilitate the precise assessment and personalized treatment of such patients, improve the abnormal processing patterns of patients, and promote their return to life and society. Graphical abstract

The extracellular matrix (ECM) has been strongly correlated with cancer progression in various tumor types. However, the specific mechanisms underlying ECM-associated tumor behaviors remain unclear. In this study, we found an enriched distribution of fibrin in tumor tissues obtained from high-grade non-small cell lung cancer (NSCLC) patients. For further investigation, we established an in vitro 3D culture system using fibrin gel and found that NSCLC cells grown in this system exhibited increased stemness and tumorigenesis. Mechanistically, we demonstrated that fibrin facilitated the activation of the phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling pathway through integrin β1. Furthermore, we found that blocking integrin β1 signals enhanced the tumor suppressive effects of chemotherapy, providing a novel approach for clinical therapy for NSCLC. Graphical abstract

Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases and is considered as the most common type of cancer. DLX4 was originally identified as a β-globin gene suppressor in red blood cells, which plays critical roles in several types of cancers. However, the role and related mechanism of DLX4 in NSCLC are still unclear. The study aimed to uncover the expression of DLX4 in human NSCLC cells and tissues, reveal its possible role in NSCLC, and investigate the underlying mechanisms. Immunoblot and TCGA database were used to detect the expression of DLX4 in human NSCLC cells and tissues. CCK-8, colony formation, and FCM assays were conducted to detect the effects of DLX4 on the viability and cell cycle of NCI-H2170 and A549 cells. Immunoblot assays were further performed to investigate the possible mechanism underlying DLX4 affecting the growth of NSCLC. We revealed that knockdown of DLX4 inhibited NSCLC cell proliferation. We further revealed that DLX4 knockdown induced the NSCLC cell cycle arrest. Our results further showed that downregulation of DLX4 suppressed YB-1 expression, which further suppressed CKS2 expression, thereby suppressing tumor growth of NSCLC. In conclusion, DLX4 has the potential to serve as a promising drug for NSCLC treatment.

An increasing number of studies show that vascular endothelial growth factor is an important regulator of hair growth, and involves in processes of hair follicle development by vascularization. Recently, VEGF receptor-2 (VEGFR-2) has been detected in epithelial cells of hair follicles, indicating that it may have a direct role in the biological activity of hair follicles. To explore how VEGFR-2 regulates hair follicle development, we investigated the co-expression pattern of VEGFR-2 with β-catenin, Bax, Bcl-2, involucrin, AE13 (hair cortex cytokeratin), keratin 16, keratin 14, and Laminin 5 by immunofluorescence double staining in anagen hair follicles of normal human scalp skin. The results of double staining immunofluorescence showed a strong overlapping and similar expression pattern for VEGFR-2 with β-catenin and Bcl-2, and revealing associated expression pattern with involucrin, AE13, keratin 14, keratin 16, and Laminin 5. These results elucidated that VEGFR-2 activation may participate in hair follicle differentiation, proliferation, and apoptosis in vivo . Graphical abstract

Tendon is a connective tissue that produces movement by transmitting the force produced by muscle contraction to the bones. Most tendinopathy is caused by prolonged overloading of the tendon, leading to degenerative disease of the tendon. When overloaded, the oxygen demand of tenocytes increases, and the tendon structure is special and lacks blood supply, which makes it easier to form an oxygen-deficient environment in tenocytes. The production of reactive oxygen species due to hypoxia causes elevation of inflammatory markers in the tendon, including PGE2, IL-1β, and TNF-α. In the process of tendon healing, inflammation is also a necessary stage. The inflammatory environment formed by cytokines and various immune cells play an important role in the clearance of necrotic material, the proliferation of tenocytes, and the production of collagen fibers. However, excessive inflammation can lead to tendon adhesions and hinder tendon healing. Some important and diverse biological functions of the body originate from intercellular signal transduction, among which cytokine mediation is an important way of signal transduction. In particular, NF-κB, NLRP3, p38/MAPK, and signal transducer and activator of transcription 3, four common signaling pathways in tendinopathy inflammatory response, play a crucial role in the regulation and transcription of inflammatory factors. Therefore, summarizing the specific mechanisms of inflammatory signaling pathways in tendinopathy is of great significance for an in-depth understanding of the inflammatory response process and exploring how to inhibit the harmful part of the inflammatory response and promote the beneficial part to improve the healing effect of the tendon.

In the human immunodeficiency virus (HIV)-infected population, especially HIV with concomitant tuberculosis (TB) or Hodgkin’s lymphoma (HL), numerous risk factors have been reported in recent years. Among them, the decreased CD4 + T cell count was recognized as the common risk factor. We report a case of a patient with HIV and TB and HL co-occurrence, in which patient’s CD4 + T cell count was inconsistent with disease. A 58-year-old male presented with fever and shortness of breath that persisted for 2 months. The patient had a 4-year history of HIV infection and underwent antiretroviral therapy (ART) effectively. After blood test, computed tomography, bone biopsy, and lymphoma biopsy, the patient was diagnosed with skeletal TB and HL, underwent TB treatment and received ART, and underwent four cycles of chemotherapy. CD4 + T cell count was not decreased before diagnosed with TB/HL and increased in this case after the fourth cycle of chemotherapy. We collected and analyzed CD4 + T cell counts in our case and reviewed relevant literature. It is suggested that CD4 + T cell count may be insufficient to predict the risk of HIV-related disease, especially lymphoproliferative disorders.

The clinical characteristics and diagnosis of ten cases with severe Chlamydia psittaci pneumonia were analyzed. Ten patients had high fever, cough, or diarrhea, and all had a history of contact with birds or poultry. The white blood cell count of the patients was normal or slightly increased. The percentage of neutrophils ( N %) and C reactive protein of the patients were significantly increased. Chest computer tomography showed patchy consolidation of both lungs, with one-sided lung lobes prominent, and bronchial inflation signs. All the patients were admitted to the intensive care unit due to respiratory failure. Nine patients needed ventilator-assisted ventilation therapy, and one patient needed high-flow oxygen therapy. All patients had sepsis, and five patients developed septic shock. The patients were diagnosed with severe C. psittaci pneumonia by clinical manifestations and contact history. After timely adjustment of tetracycline-based treatment, eight patients recovered and were discharged, and two patients died of septic shock and respiratory failure. Patients with poultry contact should be cautious toward C. psittaci pneumonia. A better method for the detection of C. psittaci is metagenomic next-generation sequencing. Its examination can shorten the diagnosis time. In a later stage, large-sample research is needed to guide clinical diagnosis and treatment.

Pulmonary arterial hypertension (PAH) is a rapidly progressing cardiopulmonary disease. It is characterized by increased pulmonary artery pressure and vascular resistance. The most notable histopathological characteristic is vascular remodeling. The changes in the basement membrane (BM) are believed to be related to vascular remodeling. It is crucial to identify potential biomarkers associated with the BM in PAH, to guide its treatment. The microarray datasets GSE117261 and GSE113439 were downloaded from the Gene Expression Omnibus. Two data sets were examined to identify genes associated with the BM by analyzing gene expression changes. Next, we analyzed the relevant genes in the Kyoto Encyclopedia of Genes and Genomes using Gene Ontology and Disease Ontology annotationand conducted pathway enrichment analysis. We conducted a protein–protein interaction network analysis on the genes related to BMs and used the cell cytoHubba plug-in to identify the hub genes. Furthermore, we conducted an immune infiltration analysis and implemented a histogram model. Finally, we predicted and analyzed potential therapeutic drugs for PAH and set up a miRNA network of genetic markers. Six candidate genes related to BMs, namely Integrin Subunit Alpha V, Integrin Subunit Alpha 4, ITGA2, ITGA9, Thrombospondin 1, and Collagen Type IV Alpha 3 Chain, were identified as potential modulators of the immune process in PAH. Furthermore, ginsenoside Rh1 was found to significantly impact drug targeting based on its interactions with the six BM-related genes identified earlier. A novel biomarker related to the BM, which plays a crucial role in the development of PAH, has been identified.

5,10-methylenetetrahydrofolate reductase (MTHFR) mutations play a significant role in various types of cancers, serving as crucial regulators of folate levels in this process. Several studies have examined the effects of smoking and drinking on MTHFR-related cancers, yielding inconsistent results. Therefore, the objective of this study was to evaluate the magnitude of the effects of gene-smoking or gene-drinking interactions on cancer development. We conducted a comprehensive literature search in PubMed, Web of Science, CNKI, and Wan Fang databases up until May 10th, 2022, to identify relevant articles that met our inclusion criteria. The extracted data from these studies were used to calculate the overall odds ratio (OR) and corresponding 95% confidence interval (95% CI) using either a fixed-effect or random-effect model in Stata version 11.2. Stratified analyses were performed based on ethnicity, control group origin, and cancer classification to assess the risk of cancers associated with gene-smoking or gene-drinking interactions. Sensitivity analyses were conducted to investigate potential sources of heterogeneity, and publication bias was assessed using the Begg’s test and Egger’s test. Additionally, regression analysis was employed to explore the influence of relevant variables on heterogeneity. To evaluate the statistical correlations, analytical methods such as the false-positive report probability and the Bayesian false discovery probability were applied to assess the reliability of the findings. In our meta-analysis, a total of 47 articles were included, comprising 13,701 cases and 21,995 controls for the C677T polymorphism and 5,149 cases and 8,450 controls for the A1298C polymorphism. The results indicated a significant association between C677T polymorphism and cancer risks when combined with smoking (CT + TT vs CC, OR [95% CI] = 1.225 [1.009–1.487], p = 0.041). Stratified analysis further revealed a significant increase in liver cancer risk for individuals with the C677T when combined with smoking (liver cancer: CT + TT vs CC, OR [95% CI] = 1.564 [1.014–2.413], p = 0.043), particularly among Asian smokers (CT + TT vs CC, OR [95% CI] = 1.292 [1.007–1.658], p = 0.044). Regarding the A1298C polymorphism, an elevated risk of cancer was observed in mixed populations alone (CC + AC vs AA, OR [95% CI] = 1.609 [1.087–2.381], p = 0.018), as well as when combined with smoking (CC + AC vs AA, OR [95% CI] = 1.531 [1.127–2.080], p = 0.006). In non-drinkers, C677T polymorphism was found to be associated with esophageal cancer risk (C677T: CT + TT vs CC, OR [95% CI] = 1.544 [1.011–2.359], p = 0.044) and colon cancer risk (CC + AC vs AA, OR [95% CI] = 1.877 [1.166–3.054], p = 0.010), but there was no clear link between this polymorphism and cancer risk among drinkers. The association between the C677T polymorphism and cancer risk among smokers was found to be significant, suggesting that the combination of tobacco and the C677T polymorphism may enhance the carcinogenic process, particularly in liver cancer. However, no similar relationship was observed for the A1298C polymorphism. Interestingly, significantly increased cancer risk was observed in individuals with C677T genetic variants who were nondrinkers, but not among drinkers. These findings highlight the potential role of the C677T polymorphism in modifying cancer risk in specific contexts, such as smoking and alcohol consumption.

It is essential to revisit the global biodiversity, search for ethnopharmacologically relevant plants, and unveil their untapped potential to overcome the complications associated while treating infections triggered by multiple antibiotic-resistant Staphylococcus aureus . Catharanthus roseus (L.) G. Don of the Apocynaceae family is a medicinal plant used for remedial purposes against infectious diseases from ancient times. In this study, we intended to evaluate the mechanism by which the ethanolic extract of C . roseus root (EECRR) causes the reversal of ampicillin resistance in S. aureus . To achieve this goal, we have stained EECRR-treated S. aureus with acridine orange, analysed DNA damage by comet assay, and studied the alteration of plasmid band pattern and expression of penicillin-binding protein 2a (PBP2a) protein. Experiments revealed better S. aureus killing efficiency of EECRR at its minimum inhibitory concentration (MIC) doses due to DNA damage and reducing plasmid band intensities along with a decline in the expression of PBP2a in EECRR-treated cells at half-MIC dose. EECRR proved to be an efficient growth inhibitor of S. aureus that reduces the expression of PBP2a. Therefore, EECRR can also render ampicillin-resistant S. aureus susceptible to the antibiotic. Graphical abstract

The presented case report describes an incredibly rare instance of an intramedullary bronchial cyst located in the thoracic spinal canal on the dorsal side of the spinal cord, which was observed in a patient with chronic myelogenous leukemia. A 29-year-old man presented with back pain for half a month, along with numbness and pain below the chest and ribs for 1 week. Hypersensitivity was present in the inferior plane of the long xiphoid process in the nervous system. Magnetic resonance imaging (MRI) showed intramedullary cystic lesions in the vertebral body plane of the third to the fourth thoracic vertebra. There was no recurrence during the 6-month postoperative follow-up period. The histopathological findings were consistent with bronchogenic cysts. Cystic lesions were eliminated through the posterior median approach. After the cyst ruptured during surgery, gel liquid was seen, and the majority of the cyst walls were removed. One week after the surgery, the hypersensitivity fully subsided. Six months following surgery, an updated MRI revealed no recurrence. Intramedullary bronchogenic cysts on the dorsal side of the thoracic spine are extremely uncommon. Diagnosis requires histopathological evidence, and it is challenging to diagnose before surgery. Prompt surgical resection is recommended in case of positive diagnosis.

This study aimed to determine the role of bacterial lipoprotein (BLP) in autophagy and apoptosis. Western blot was used to examine autophagy biomarkers in mouse bone marrow-derived macrophages (BMDMs) after infection with Salmonella typhimurium ( S. typhimurium ) and Staphylococcus aureus ( S. aureus ) and BLP stimulation. In BMDMs, enhanced protein expression of LC3-II was observed after S. typhimurium or S. aureus infection ( P < 0.05) and BLP stimulation ( P < 0.05). Autophagy inhibition by chloroquine resulted in increased levels of LC3-Ⅱ and p62 protein ( P < 0.05). Persistently upregulated expressions of Atg3 and Atg7 were observed following BLP stimulation ( P < 0.05), and knockdown of Atg3 or Atg7 significantly attenuated BLP-enhanced protein expression of LC3-Ⅱ in BMDMs. Furthermore, we found that the autophagy inhibitor 3-methyladenine prevented BLP- and infection-induced macrophage apoptosis. BLP is not only required for autophagy and apoptosis activation in macrophages but also for regulating the balance between autophagy and apoptosis. Graphical abstract BLP as a bacteria component is an important factor in autophagy activation and induces apoptosis. BLP-induced macrophage apoptosis was suppressed by inhibiting autophagy.

Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and high mortality rates. It remains a prevailing clinical need to distinguish whether the patient can benefit from therapy, such as chemotherapy. By integrating single-cell and global transcriptome data, we have for the first time identified TCL1A+ B cell functions that are prognostically relevant in TNBC. This finding broadens the perspective of traditional tumor-infiltrating lymphocytes in predicting survival, especially the potential value of B cells in TNBC. Single-cell RNA-seq data from five TNBC patients were collected to identify the association between immune cell populations and clinical outcomes. Functional analysis was according to gene set enrichment analysis using pathways from MsigDB. Subsequently, the gene signature of TCL1A+ B cells based on differential expression genes of TCL1A+ B cells versus other immune cells was used to explore the correlation with tumor microenvironment (TME) and construct a prognostic signature using a non-parametric and unsupervised method. We identified TCL1A+ B cells as a cluster of B cells associated with clinical outcomes in TNBC. Functional analysis demonstrated its function in B cell activation and regulation of immune response. The highly enriched TCL1A+ B cell population was found to be associated with a thermal TME with anti-tumor effects. A high abundance of TCL1A+ B cell population is positively correlated with a favorable therapeutic outcome, as indicated by longer overall survival. The present study suggests that TCL1A+ B cells play a key role in the treatment and prognostic prediction of TNBC, although further studies are needed to validate our findings. Moreover, the integration of transcriptome data at various resolutions provides a viable approach for the discovery of novel prognostic markers.

The aim of this study was to analyze the role of Ezrin in esophageal squamous cell carcinoma (ESCC) and investigate potential therapeutic targets for ESCC by interfering with Ezrin expression. Bioinformatics analysis revealed that Ezrin expression differed significantly among patients with different clinical stage ESCC. Moreover, there was a significant correlation between Ezrin and yes-associated protein/connective tissue growth factor (YAP 1 /CTGF) levels in esophageal cancer. Sixty paraffin-embedded ESCC tissue samples were examined and Ezrin and YAP 1 /CTGF levels were determined using immunohistochemistry. The positive expression rates of Ezrin and YAP 1 /CTGF were significantly lower in adjacent tissues than in ESCC tissues. Furthermore, knockdown of Ezrin expression inhibited colony formation and reduced cell migration and invasion. Compared with control ESCC cells, protein expression levels of YAP 1 and CTGF were significantly downregulated in cells with Ezrin knocked down. We conclude that Ezrin may be involved in ESCC progression through the Hippo signaling pathway.

Plaque vulnerability has been the subject of several recent studies aimed at reducing the risk of stroke and carotid artery stenosis. Atherosclerotic plaque development is a complex process involving inflammation mediated by macrophages. Plaques become more vulnerable when the equilibrium between macrophage recruitment and clearance is disturbed. Lipoperoxides, which are affected by iron levels in cells, are responsible for the cell death seen in ferroptosis. Ferroptosis results from lipoperoxide-induced mitochondrial membrane toxicity. Atherosclerosis in ApoE(−/−) mice is reduced when ferroptosis is inhibited and iron intake is limited. Single-cell sequencing revealed that a ferroptosis-related gene was substantially expressed in atherosclerosis-modeled macrophages. Since ferroptosis can be regulated, it offers hope as a non-invasive method of treating carotid plaque. In this study, we discuss the role of ferroptosis in atherosclerotic plaque vulnerability, including its mechanism, regulation, and potential future research directions.

Crohn’s disease (CD) is a recurrent, chronic inflammatory condition of the gastrointestinal tract which is a clinical subtype of inflammatory bowel disease for which timely and non-invasive diagnosis in children remains a challenge. A novel predictive risk signature for pediatric CD diagnosis was constructed from bioinformatics analysis of six mRNAs, adenomatosis polyposis downregulated 1 (APCDD1), complement component 1r, mitogen-activated protein kinase kinase kinase kinase 5 (MAP3K5), lysophosphatidylcholine acyltransferase 1, sphingomyelin synthase 1 and transmembrane protein 184B, and validated using samples. Statistical evaluation was performed by support vector machine learning, weighted gene co-expression network analysis, differentially expressed genes and pathological assessment. Hematoxylin–eosin staining and immunohistochemistry results showed that APCDD1 was highly expressed in pediatric CD tissues. Evaluation by decision curve analysis and area under the curve indicated good predictive efficacy. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis confirmed the involvement of immune and cytokine signaling pathways. A predictive risk signature for pediatric CD is presented which represents a non-invasive supplementary tool for pediatric CD diagnosis. Graphical abstract

Membrane proteins are the targets for most drugs and play essential roles in many life activities in organisms. In recent years, unnatural amino acids (UAAs) encoded by genetic code expansion (GCE) technology have been widely used, which endow proteins with different biochemical properties. A class of photosensitive UAAs has been widely used to study protein structure and function. Combined with photochemical control with high temporal and spatial resolution, these UAAs have shown broad applicability to solve the problems of natural ion channels and receptor biology. This review will focus on several application examples of light-controlled methods to integrate GCE technology to study membrane protein function in recent years. We will summarize the typical research methods utilizing some photosensitive UAAs to provide common strategies and further new ideas for studying protein function and advancing biological processes.

Hexokinase 2 (HK2) has been associated with carcinogenic growth in numerous kinds of malignancies as essential regulators during the processing of glucose. This study aimed to explore the effects of HK2 on diffuse large B-cell lymphoma (DLBCL) cells via the ERK1/2 signaling. Expressions of HK2 and ERK1/2 were examined in DLBCL cell lines using quantitative reverse transcription polymerase chain reaction and western blotting. HK2 and ERK1/2 were attenuated through HK2 small-interfering RNA (siRNA) and ERK inhibitor FR180204, respectively, in U2932 and SU-DHL-4 cells. Cell Counting Kit-8, clone formation, transwell, and flow cytometry assays were used in evaluating the effects of HK2 and ERK1/2 on cell proliferation, migration, and apoptosis. Moreover, a xenograft model was created to assess the roles of HK2 in vivo . HK2 and ERK1/2 were evidently up-regulated in DLBCL cell lines. HK2 knockdown and FR180204 markedly suppressed the proliferation and clonogenesis of U2932 and SU-DHL-4 cells and promoted cell apoptosis in vitro . We also found that HK2 silencing suppressed tumor growth in vivo . Notably, HK2 knockdown inactivated the ERK1/2 signaling pathway both in vitro and in vivo . These data indicate that inhibition of HK2 may suppress the proliferation, migration, and invasion of DLBCL cells, partly via inhibiting the ERK1/2 signaling pathway.

Osteoarthritis (OA) is a painful joint disease that is common among the middle-aged and elderly populations, with an increasing prevalence. Therapeutic options for OA are limited, and the pathogenic mechanism of OA remains unclear. The roles of cytokines and signaling pathways in the development of OA is a current research hot spot. Interleukin (IL)-17 is a pleiotropic inflammatory cytokine produced mainly by T helper 17 cells that has established roles in host defense, tissue repair, lymphoid tissue metabolism, tumor progression, and pathological processes of immune diseases, and studies in recent years have identified an important role for IL-17 in the progression of OA. This narrative review focuses on the mechanisms by which IL-17 contributes to articular cartilage degeneration and synovial inflammation in OA and discusses how IL-17 and the IL-17 signaling pathway affect the pathological process of OA. Additionally, therapeutic targets that have been proposed in recent years based on IL-17 and its pathway in OA are summarized as well as recent advances in the study of IL-17 pathway inhibitors and the potential challenges of their use for OA treatment.

Circadian cycle is a fundamental characteristic of life formed in the long-term evolution of organisms and plays an important role in maintaining the proliferation, migration, and activation of immune cells. Studies have shown that circadian rhythm disorders affect the occurrence and development of neuroinflammation by inducing glial cell activation and peripheral immune responses. In this article, we briefly described the research progress of neuroinflammation and circadian rhythm in recent years and explored the effects and possible mechanism of circadian rhythmicity on microglia, astrocytes, and peripheral immune function.

The interaction between intestinal microecological dysregulation, altered inflammatory factors, and cirrhosis is unclear. The aim of this systematic review and meta-analysis was to synthesize the results of previous studies to assess the efficacy of probiotics in the treatment of cirrhosis and their effect on inflammatory factors, as well as to explore the relationship between gut microecological dysregulation and liver disease to gain a deeper understanding of this interaction. Up to December 2022, eligible studies were identified by searching the following databases: National Knowledge Infrastructure (CNKI), Wanfang Data, Web of Science, PubMed, Embase, Medline, and the Cochrane Library. Statistical analysis was performed using software RevMan Version 5.4. A total of 33 eligible randomized controlled trials were included in the study, and data on probiotic strains, duration of intervention, measures in the control group, and outcomes were extracted and evaluated. Compared to the control group, the experimental group had significant improvements in overall efficacy. The results of the meta-analysis revealed that probiotic use significantly decreased biochemical parameters for liver function, including aspartate transaminase, alanine aminotransferase, and total bilirubin. Similar result was obtained in interleukin-6, tumor necrosis factor-α, and endotoxin. However, probiotic intervention did not significantly affect interleukin-2 and interleukin-10. The current meta-analysis illustrates that probiotic supplementation reduces inflammatory markers and biochemical parameters for liver function in patients with cirrhosis, suggesting that probiotic management may be a novel treatment for cirrhosis. Furthermore, the interaction of the gut microbiota, associated metabolites, and inflammation factors with cirrhosis may provide a promising therapeutic target for the pharmacological and clinical treatment of cirrhosis.

Meningiomas are extra-axial neoplasms that originate from the arachnoid cap cells located on the inner surface of the meninges. Approximately 36% of central nervous system tumors are meningiomas. Based on earlier findings to be benign in most cases, they are categorized as slow-growing tumors that form gradually over time. Meningiomas are usually asymptomatic and discovered inadvertently. They rarely present with immediate clinical symptoms or abrupt hemorrhagic strokes. However, tumor hemorrhage can be fatal in high-grade meningiomas, particularly those with vascularization. We describe a 58-year-old man who was hospitalized after experiencing an unexpectedly acute headache. The right cerebellar hemisphere and vermis cerebellar hemorrhage were detected on computed tomography (CT), and the cerebellar hemorrhage was explained by a diagnosis of hypertension. When additional analysis of the patient’s chest CT indicated lung mass lesions, we assumed that the lung cancer had spread to the brain. However, the pathological outcomes of a guided definite pulmonary aspiration biopsy, in conjunction with resection of the cerebellar tumor, suggested a subtentorial meningioma with ruptured hemorrhage and pulmonary meningioma metastasis. The patient was transferred to a hospital closer to home for ongoing follow-up and, after 2 months, he had recovered well.

Speckle type BTB/POZ protein (SPOP) may have cancer promoting or inhibiting effects. At present, the role of SPOP in hepatocellular carcinoma (HCC) has rarely been studied. In this study, to investigate the effects of SPOP in HCC and elucidate the underlying molecular mechanisms of its relationship with genes, differentially expressed genes (DEGs) were classified through RNA sequencing. The gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes functional pathway analysis were used to further predict the function of DEGs after the overexpression of SPOP. The biological function of SPOP-regulated alternative splicing events in cells is comprehensively assessed. The Cancer Genome Atlas database and Gene Expression Omnibus dataset were performed to evaluate the correlation between SPOP and HCC progression. Due to SPOP overexpression, 56 DEGs in the HCC related pathway were further identified. The results showed that SPOP overexpression facilitated the cell proliferation and changed the gene expression profiles of human normal hepatocytes. SPOP-regulated alternative splicing events were involved in pathways associated with cellular processes, metabolism, environmental information procession, organismal systems, and so on. In conclusion, SPOP may potentially exhibit tumor-promoting effects, necessitating further investigations to unveil its molecular mechanisms comprehensively.

Gastric cancer (GC) is the 5th most common cancer and the 3rd leading cause of cancer-related death worldwide. It is of great significance to study the underlying molecular mechanism of GC, and targeting glycolysis is a good strategy to treat GC. SET domain containing 5 (SETD5) contains a catalytic methyltransferase SET domain, which is known as a lysine methyltransferase that affects the progression of multiple cancers. However, its possible role in GC was still unclear. Here, we revealed that SETD5 was highly expressed in GC and was associated with a poor prognosis. Further through the in vitro experiments, we revealed that the downregulation of SETD5 inhibited the proliferation and migration of GC cells. Knockdown of SETD5 inhibited glucose consumption and glycolysis. Further studies have shown that SETD5 knockdown restrained the Akt signaling pathway. Therefore, we thought that SETD5 could act as a GC target.

Intravenous immunoglobulin (IVIG) resistance leads to serious complications in Kawasaki disease (KD) with no effective treatment. This study aimed to investigate the effects of pentraxin 3 (PTX3) on human coronary artery endothelial cells (HCAECs). PTX3 levels were measured using quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay, and western blotting. Cell viability was detected using the MTT assay. Biological functions were analyzed using CCK-8, EdU, flow cytometry, TUNEL, and qRT-PCR. The levels of factors of the NF-κB pathway were examined using western blotting. The results demonstrated that PTX3 expression was highest in patients and HCAECs with IVIG-resistance. Knockdown of PTX3 promoted proliferation and suppressed apoptosis and inflammation of IVIG-resistant HCAECs, whereas PTX3 overexpression produced the opposite results. Moreover, PTX3 activated the NF-κB pathway in IVIG-resistant HCAECs. A rescue study showed that PTX3 modulated biological behaviors by regulating the NF-κB pathway. Overall, our findings demonstrate that PTX3 promotes IVIG resistance-induced endothelial injury by activating the NF-κB pathway, suggesting that PTX3 may become a novel therapeutic target for patients with IVIG-resistant KD. Graphical abstract

Ectopic thyroid is a rare malformation induced by a migration defect in the developing gland during embryogenesis. In 90% of cases, the ectopic thyroid is located in the lingual region, whereas it is extremely rare in the abdominal cavity, particularly in the pancreas. A 50-year-old female patient presented to the Taizhou First People’s Hospital with a complaint of recurrent mid-lower abdominal pain and diarrhea for approximately a month. The abdominal computed tomography scan revealed a space-occupying lesion with abundant blood supply in the head of the pancreas during the consultation. This led to the suspicion of a neuroendocrine tumor. The doctor considered that this lesion in the head of the pancreas could be responsible for the patient’s incontinence. A laparoscopic pancreaticoduodenectomy was performed after relevant tests were undertaken and contraindications were ruled out. The patient was diagnosed with ectopic thyroid of the pancreas through postoperative pathology. Ectopic thyroid can be considered in middle-aged and elderly women who present with a mass with abundant blood supply and an unknown diagnosis. Subsequent treatments should be decided after fine-needle aspiration cytology.

There is growing evidence that higher body mass index (BMI) is associated with lower survival in breast cancer patients. The aim of this study was to investigate whether there is an association between body mass index (BMI) at breast cancer diagnosis and breast cancer prognosis and whether this association is dependent on menopausal status and tumor subtype in a less developed population in northern China. We collected 1,225 patients with primary invasive cancer in stage I-IIIC for retrospective analysis from October 2010 to December 2020. We used Kaplan–Meier and Cox regression analyses and estimated the relationship between baseline BMI and breast cancer-specific survival (BCSS). Next, we further evaluated whether the effect of BMI on breast cancer prognosis differed by menopausal status and tumor subtype. We found that death rate and prognosis were worse for patients with BMI ≥ 24, more than four positive lymph nodes, and triple negative status. Interestingly, BMI played a different prognostic role depending on tumor subtype and menopausal status. For premenopausal women, patients with BMI ≥ 24 had significantly lower BCSS compared to those with BMI < 24 in human epidermal growth factor receptor 2 (HER2) overexpression (HR: 4.305, p = 0.004) and triple negative subtypes (HR: 1.775, p = 0.048). By contrast, there was no association between BMI ≥ 24 and higher death regardless of tumor subtype in post-menopausal patients ( p > 0.05). BMI influences breast cancer outcome depending on tumor subtype and menopause. BMI ≥ 24 might be a risk factor for BCSS, particularly in premenopausal women with HER2 overexpression or triple negative subtype. In contrast, BMI ≥ 24 was not associated with higher death regardless of tumor subtype in post-menopausal patients.

Malignant melanoma (MM) frequently occurs in the skin or mucosa, whereas malignant melanoma of unknown primary (MUP) is diagnosed in patients with lymph nodes or visceral organs as the site of origin, where it is challenging to detect the primary lesion by comprehensive examination. MUP is possibly related to the spontaneous regression of the primary lesion. In addition, primary hepatic melanoma (PHM) usually refers to the primary MM occurring in the liver, with no typical primary lesions and no manifestations of tumor metastasis. A 61-year-old male patient with liver as the site of origin was diagnosed with MM by Melan-A, HMB-45, and S-100 immunohistochemistry staining of liver biopsy tissue. Based on a comprehensive examination, no basis was found for melanoma in sites such as the skin, mucosa, five sense organs, brain, digestive tract, respiratory tract, or genitalia, and the patient was subsequently diagnosed with MUP. MMs require a comprehensive inspection, beginning with the liver, to search for the primary lesion; if the primary lesion is not found, the possibility of PHM or MUP should be considered.

In this case report, a 53-year-old woman was diagnosed with severe NE after receiving chemotherapy for breast cancer. The patient with breast cancer was treated with a single cycle of docetaxel (140 mg) + epirubicin (130 mg) + cyclophosphamide (0.9 g) chemotherapy. However, the woman presented with symptoms of fatigue and diarrhea 5 days later accompanied with severe neutropenia according to the routine blood test. The computed tomography examination displayed the thickening and swelling of the colorectal wall. After the diagnosis of NE, the woman received antibiotics and supportive treatment, but her symptoms were not improved. The Chinese herbal medicine (CHM) diagnostic pattern was then designed for the patient. The patient was administered with two CHM decoctions. One decoction contained 24 kinds of herbal materials, and the other one was called pure ginseng decoction. These two decoctions were administered to the patient 2 or 3 times per day to tonify the spleen, nourish Qi and blood, and remove phlegm and damp heat symptoms. After the CHM treatment lasting for 10 days, the symptoms of the patient were improved, and she was discharged. In conclusion, CHM treatment played an indispensable role in curing the woman with chemotherapy-induced NE.

Klotho is a recently discovered protein that has positive effects on all systems of the body, for example, regulating calcium and phosphorus metabolism, protecting nerves, delaying aging and so on. Fibroblast growth factors (FGFs) are a group of polypeptides that function throughout the body by binding with cell surface FGF receptors (FGFRs). Endocrine FGFs require Klotho as a co-receptor for FGFRs. There is increasing evidence that Klotho participates in calcium and phosphorus regulation and metabolic regulation via the FGF–Klotho axis. Moreover, soluble Klotho can function as a separate hormone to regulate homeostasis on various ion channels and carrier channels on the cell surface. This review mainly explains the molecular basis of the membrane signaling mechanism of Klotho.

The purpose of this study was to determine the effect of amiodarone (Ami) on hERG-T618I currents in HEK293 cells. A transient transfection method was used to transfer hERG-T618I and hERG wild-type (WT) channel plasmids into HEK293 cells. An extracellular local perfusion method was used for administration. Currents were recorded using the whole-cell patch clamp technique. Ami (10 μM) had a greater retarding effect on the hERG-T618I channel than WT ( P < 0.05). The half-inhibitory concentration for the mutant was approximately 1.82 times that of WT ( P < 0.05). The WT current inhibition fraction against Ami was significantly greater than T618I in the same cell ( P < 0.05). The STEP current of the mutant channel was larger than the WT channel, but the characteristic of inward rectification did not appear. Ami reduced the STEP current of the mutant channel, and the steady-state activation curve indicated that channel activation decreased ( P > 0.05). Ami restored partial inactivation of the mutant channel. Ami effectively reduced the current in the phase 2 plateau ( P < 0.05), but the phase 3 current did not exhibit the characteristics of a WT current. Ami inhibited hERG-T618I currents on HEK293 cells, but the effect was weaker than WT. Graphical abstract Ami (10 μM) had a greater retarding effect on the hERG-T618I channel than WT ( P < 0.05). The half-inhibitory concentration for the mutant (4.56 μM) was approximately 1.82 times that of WT (2.51 μM).

Listeria monocytogenes ( LM ) infections of the central nervous system are deadly and have vague symptoms. Traditional cerebro spinal fluid culture has a low positive rate, and because antibiotic use is common following therapy, it is more challenging to assess the response from pathogen content. In this case, a 66-year-old man who had a fever, a headache, and vomit was admitted to the hospital. He had diabetes, decline in thyroid function, and a history of pituitary tumor removal surgery. His initial treatment with ribavirin, ceftriaxone antibiotic, and moxifloxacin did not go well. Using two etiological tests (culture and metagenomic next-generation sequencing [mNGS]), his cerebrospinal fluid tested positively for LM . Ampicillin-sulbactam and meropenem were used as treatments once LM meningitis was identified. After treatment, his cerebrospinal fluid was assessed once more. Culture: negative; targeted next-generation sequencing (tNGS): positive and shows changes in the copy number of the LM . After 44 days of treatment, the patient finally stopped taking antibiotics, and the prognosis was good. Our study showed that mNGS and tNGS, as novel approaches for pathogen detection, are capable of identifying pathogens quickly, sensitively, and accurately, especially when there are few infections present (such as after antibiotic treatment). The two methods can be a powerful assistance for helping clinicians to choose the best course of action.

This study aimed to compare the new bone formation, the process of remodeling, and the viability of bone grafts, using a combination of platelet-rich plasma (PRP) and Marburg bone graft versus bone grafts without any additional elements. For this study, 48 rabbits (with 24 rabbits in each group) were used. Bone defects were made in the femur, and the bone graft used was the human femoral head prepared according to the Marburg Bone Bank. Rabbits were divided into the following groups: heat-treated bone graft (HTBG group) and HTBG with PRP (HTBG + PRP group). After 14, 30, and 60 days post-surgery, the assessment of the results involved X-ray, histopathological, and histomorphometric analyses. The greater new bone formation was detected in the HTBG + PRP group on the 14 and 30 day ( p < 0.001). Furthermore, the group using bone grafts with PRP demonstrated notably enhanced remodeling, characterized by stronger bone integration, more significant graft remineralization, and a circular pattern of newly formed bone. The PRP–bone graft complex improves bone tissue repair in the bone defect in the initial stages of bone regeneration. PRP has been identified to enhance the remodeling process and amplify the osteoconductive and osteoinductive capabilities of HTBGs.

This study aimed to evaluate the clinical utility of small breast epithelial mucin (SBEM) as a prognostic biomarker in an independent patient cohort. The paraffin-embedded tissues and clinicopathological data of 105 patients with breast cancer were collected, and the expression of SBEM in breast cancer samples was detected by immunohistochemical staining. The correlations between clinicopathological variables and the expression of SBEM were analyzed, and its significance as a prognostic indicator for breast cancer patients was determined. Immunohistochemical staining revealed that SBEM was expressed mostly in the cytomembrane and cytoplasm, with markedly increased SBEM expression (≥4 points on staining intensity) observed in 34 of 105 breast cancer tissues (32.4%). Elevated expression of SBEM was found to be significantly associated with larger tumor size ( P = 0.002), more frequent lymph node metastasis ( P = 0.029), advanced tumor node metastasis stage ( P = 0.005), reduced expression of the progesterone receptor (PR) ( P = 0.002), and a higher Ki-67 index ( P = 0.006). Survival analysis indicated that patients with elevated SBEM expression had worse overall survival (OS) (5-year OS rate: 50.5 vs 93.9% for high and low SBEM expression, respectively, P < 0.001) and disease-free survival (DFS) (5-year DFS rate: 52.8 vs 81.7% for high and low SBEM expression, respectively, P = 0.001) rates than those with low expression of SBEM. Univariate and multivariate Cox analyses demonstrated that elevated expression of SBEM (hazard ratio [HR] = 1.994, 95% confidence interval [CI]: 1.008–3.945, P = 0.047), tumor size (HR = 2.318, 95% CI: 1.071–5.017, P = 0.033), and PR status (HR = 0.195, 95% CI: 0.055–0.694, P = 0.012) were independent predictors of OS in breast cancer patients. Elevated expression of SBEM was associated with both aggressive tumor characteristics and poor survival, indicating its potential as a useful prognostic biomarker for breast cancer patients.

Non-adherent culture is critical for the transdifferentiation of stem cells from mesoderm to neuroectoderm. Sphere culture has been reported to directly induce the adipose tissue cells to neural stem cells. Here we aimed to evaluate continuous non-adherent culture on the transdifferentiation potential of human adipose-derived stem cells (ASCs) into retinal lineage. Human ASCs were induced into retinal lineage by the treatment of noggin, dickkopf-related protein 1, and IGF-1 (NDI) under adherent and non-adherent culture. The NDI induction treatment with the adherent culture for 21 days promoted robust expression of retinal markers in the induced ASCs as compared to those without NDI induction on the adherent culture. With continuous non-adherent culture for 21 days, human ASCs could highly express retinal marker genes even without NDI induction treatment as compared to those on the adherent culture. The combination of continuous non-adherent culture with the NDI induction did not show a significant upregulation of the retinal marker expression as compared to either NDI induction with the adherent culture or continuous non-adherent culture without NDI induction treatment. In summary, both non-adherent culture and NDI induction medium could independently promote the transdifferentiation of human ASCs into retinal lineage. Yet, their combination did not produce an enhancement effect.

Oxidative stress is closely linked to tumor initiation and development, conferring a survival advantage to cancer cells. Therefore, understanding cancer cells’ antioxidant molecular mechanisms is crucial to cancer therapy. In this study, we discovered that H 2 O 2 -induced oxidative stress increased Nrf3 expression in colon cancer cells. Overexpression of Nrf3 decreased H 2 O 2 -mediated cytotoxicity and apoptosis. Furthermore, Nrf3 reduced reactive oxygen species levels and malondialdehyde concentrations after H 2 O 2 treatment. Mechanistically, H 2 O 2 -mediated cell apoptosis involves multiple signaling proteins, including Akt, bcl-2, JNK, and p38. An increase in Nrf3 expression in colon cancer cells treated with H 2 O 2 partly reversed Akt/Bcl-2 inhibition, whereas it decreased activation of p38 and JNK. In addition, we found that increasing Nrf3 decreased stress-associated chemical-induced cell death, resulting in drug resistance. According to these results, Nrf3 is critical for drug resistance and oxidant adaptation.

Necrolytic migratory erythema (NME) is usually associated with paraneoplastic syndrome caused by functional pancreatic neuroendocrine tumor (PNET). Accurate diagnosis and effective treatment of NET-related NME is challenging due to its rarity and lack of typical clinical symptoms and specific pathological manifestations. Here we report a rare case of PNET with NME as the initial manifestation. 68Ga-DOTA-TATE PET/MR was used to detect the primary pancreatic and metastatic liver tumors. Finally, the patient was diagnosed as PNET via liver biopsy. After four cycles of standard capecitabine plus temozolomide chemotherapy combined with long-acting octreotide, the patient’s skin lesions on both lower extremities improved only slightly, while tumors remained stable and unchanged in size. Then the patient was treated with surufatinib. Two months later, the skin lesions healed completely, and tumors responded significantly. This rare case suggests that surufatinib may be a promising therapy for patients with PNET-associated NME.

Albumin and prealbumin serve as vital markers reflecting hepatic synthesis activity and overall body nutrient status. Hypoproteinemia can result from various etiological factors, with reduced blood inflow into the liver due to portal vein thrombosis being one such cause. However, literature addressing this specific association remains limited. This report presents an atypical case of malnutrition involving a patient who experienced prolonged hypoproteinemia attributable to a gradual decline in hepatic blood perfusion caused by progressive portal thrombosis and cavernous transformation of the portal vein (CTPV). The case encompasses an in-depth analysis of the factors contributing to undernutrition, the etiology and diagnosis of hypoproteinemia, and its clinical implications. Vigilance for the presence of hypoproteinemia is essential in the management of patients afflicted by progressive portal vein thrombosis complicated by CTPV. Timely and effective interventions aimed at rectifying hypoproteinemia can significantly enhance clinical outcomes. Moreover, reduced hepatic blood flow should be considered a plausible underlying cause in cases of unexplained hypoproteinemia, warranting thorough evaluation. This case underscores the importance of recognizing the intricate interplay between hepatic vascular pathology and protein homeostasis in clinical practice.

We investigated the effects of collagen type I alpha 1 (COL1A1) on tumor-associated fibroblast activation and matrix remodeling in the tumor microenvironment of breast cancer. Cells were divided into the blank control, negative control, and siRNA-COL1A1 groups, or HKF control, HKF + exosomes (EXO), HKF + siRNA negative control-EXO, and HKF + siRNA-COL1A1-EXO co-culture groups. Western blot and quantitative real-time PCR detected gene expressions. COL Ⅰ, COL Ⅲ, and TGF-β1 were detected by enzyme-linked immunosorbent assay. We found that compared with blank and negative control groups, COL1A1 expression and the secretion of exosomes by breast cancer cells were inhibited in the siRNA-COL1A1 group. Compared with the HKF control group, the COL Ⅰ, COL Ⅲ, TGF-β1, α-SMA, and fibroblast activation protein (FAP) were increased, while the E-cadherin and CAV-1 were decreased in the HKF + EXO, HKF + siRNA negative control-EXO, and HKF + siRNA-COL1A1-EXO co-culture groups. Compared with HKF + EXO and HKF + siRNA negative control-EXO co-culture groups, the COL Ⅰ, COL Ⅲ, TGF-β1, α-SMA, and FAP were decreased, and the E-cadherin and CAV-1 were increased in the HKF + siRNA-COL1A1-EXO co-culture group. Collectively, COL1A1 down-regulation may inhibit exosome secretion possibly via inhibiting COL Ⅰ and upregulating CAV-1, thereby inhibiting tumor-associated fibroblast activation and matrix remodeling in the tumor microenvironment. Graphical abstract

Liver fibrosis is a type of chronic pathological liver damage involving liver tissue hypoxia and abnormal extracellular matrix deposits. Hepatic stellate cells (HSCs) activation is critical for liver fibrosis. Currently, inhibiting HSCs activation or inducing HSCs ferroptosis is considered an effective strategy for the treatment of liver fibrosis. Sarcoma protein kinase (Src) is an important member of the tyrosine protein kinase family. Hypoxia causes Src phosphorylation at tyrosine 416 (Tyr 416), and inhibiting Src activation can alleviate liver fibrosis. There is currently little research on the relationship between Src activation and ferroptosis in liver fibrosis. 1-(1,1-Dimethylethyl)-1-(4-methylphenyl)-1 H -pyrazolo[3,4-d]pyrimidin-4-amine (PP1) is an inhibitor of Src activation at Tyr 416. Therefore, in this study we treated HSC-T6 cells with PP1 under normoxic and hypoxic culture conditions; moreover, PP1 was also used to treat a carbon tetrachloride-induced mouse liver fibrosis model. We explored whether inhibiting Src activation could alleviate liver fibrosis by promoting HSCs ferroptosis in vitro and in vivo . In vitro experiments showed that inhibiting Src activation in HSC-T6 cells significantly reduced hypoxia-inducible factor-1α (HIF-1α) expression and HSC-T6 cells activation, and ferroptosis was significantly increased. In vivo experiments revealed that inhibiting Src activation in fibrotic livers reduced HIF-1α expression; meanwhile, ferroptosis was promoted, and liver fibrosis was alleviated. Therefore, inhibiting Src activation, which increases HSCs ferroptosis, can alleviate liver fibrosis.

Chronic obstructive pulmonary disease (COPD) and asthma are common airway diseases, and there are similarities and differences between them. Serum eosinophil (EOS) has potential application value in the diagnosis, treatment, and prognosis of COPD and asthma. However, the clinical application value of serum EOS in these two diseases is controversial. In this work, recent research progress on the application of serum EOS in COPD and asthma was analyzed, and the potential application of serum EOS in the two diseases was expounded from several aspects, including the correlation between the pathogenesis of COPD and asthma and EOS, as well as the correlation between the diagnosis, treatment, and prognosis of the two diseases and serum EOS. The results revealed that serum EOS was important in the pathogenesis, diagnosis, treatment, and prognosis of COPD and asthma and exhibited a potential clinical application value. However, further study was needed to evaluate the threshold, which provided guidance for the clinical diagnosis and treatment of COPD and asthma.

Coexisting or mixed type of colorectal tumors has been rarely reported. This study was designed to investigate clinicopathological characteristics of co-existing or mixed colorectal adenocarcinoma and highly differentiated neuroendocrine tumor (NET-G1). To do that, clinicopathological characteristics of five cases of co-existing or mixed colorectal adenocarcinoma and NET-G1 admitted to our institution between 2017 and 2021 were retrospectively analyzed and literature review was conducted. Four patients were male and one female, aged 62–75 years old. Among them, four cases were diagnosed with rectal cancer and one case of colon cancer. Gross examination found that one patient was diagnosed with multiple colon polyps including three malignant polyps, and the remaining four cases of ulcerous masses. The tumors infiltrated into the muscle layer in two cases, and three cases with tumors infiltrating into surrounding adipose tissues. Microscopic examination revealed one patient developed poorly differentiated adenocarcinoma and four cases of moderately differentiated adenocarcinoma. Four patients had adenocarcinoma and NET-G1 in colon, and one case of adenocarcinoma in colon and NET-G1 in appendix. To conclude, co-existing or mixed colorectal tumors are extremely rare in clinical settings. Clinicopathological characteristics of five cases of co-existing or mixed adenocarcinoma and NET-G1 are diverse and adenocarcinoma is more aggressive in most affected patients.

The use of menopausal hormone therapy (MHT) has declined due to concerns about its potential side effects. However, its pivotal role in managing postmenopausal osteoporosis is gaining increased recognition. In this article, we explore how MHT assists postmenopausal women in maintaining bone health and preventing fractures. Recent research indicates that MHT significantly reduces the risk of fractures in women. This benefit is evident regardless of a woman’s bone mineral density or their use of progestogens. However, there is limited evidence suggesting that the skeletal benefits continue once the treatment is discontinued. Possible complications of MHT include heart attacks, clots, strokes, dementia, and breast cancer. The most suitable candidates for MHT are women who have recently entered menopause, are experiencing menopausal symptoms, and are below 60 years of age with a minimal baseline risk of adverse events. The treatment is available to those who meet these criteria. For women undergoing premature menopause, MHT can be considered as a means to protect bone health, especially if initiated before menopause or if accelerated bone loss is documented soon after menopause. Such decisions should be made after evaluating individual risk factors and benefits.

The detection of colorectal cancer (CRC) lymph node (LN) metastases significantly influences treatment choices, yet identifying them in samples is time-consuming and error-prone. To enhance efficiency, we have established a LN metastasis detection method utilizing triple-parameter flow cytometry (tFCM) and have conducted a comparative assessment of its accuracy and cost-effectiveness in contrast to conventional pathological examinations. This technique utilized biomarkers cytokeratin 20 (CK20), epithelial cell adhesion molecules (EpCAM), and Pan-CK. tFCM’s sensitivity was validated by analyzing known cell line concentrations (SW480 and SW620) in peripheral blood mononuclear cells (PBMCs), with CK20, EpCAM, and Pan-CK showing significant expression in CRC cell lines but not in PBMCs. A strong linear correlation was observed in the mixed leukocyte environment ( R 2 = 0.9988). Subsequently, tFCM and pathological sections were employed to analyze LNs from CRC patients, enabling comparison of detection accuracy. Within the 36 LNs studied, tFCM successfully identified tumor cells with varying metastasis degrees, including micro-metastasis and isolated tumor cell clusters. Notably, relying solely on pathological sections led to a potential 25% misdiagnosis rate for LNs. In contrast, tFCM effectively minimized this risk. In summary, compared to traditional pathological sections, tFCM is a more advantageous method for detecting nodal metastasis in CRC patients, offering a more precise prognosis for these patients. Graphical abstract

With the development and progress of society, people’s average life expectancy has increased, and relevant literature reports that the number of postmenopausal women in China continues to increase. With lifespans extended, the transition period and post-menopause period have become the longest essential period in every woman’s life. The life quality of women troubled by perimenopausal syndrome has been significantly reduced, which also places a burden on families and society. It is well known that hormone replacement therapy plays a vital role in improving women’s menopause-related symptoms and is the most effective medical measure. With research ongoing into the treatment of menopausal symptoms in different patients, dose size, treatment duration, and medication regimens for hormones are still hot topics of discussion. This article reviews the definition, clinical diagnosis, staging, clinical manifestations, and treatment of menopause and explores the current diagnosis and treatment scenarios of perimenopausal syndrome.

According to Mendel’s law of genetic separation, there must be a certain blood relationship between members of the same family, and two individuals with blood relations must have the following three situations, that is, there are two homologous genes (I denotes), one homologous gene (T denotes), and no homologous genes (O denotes), which is the ITO index for calculating the blood relationship between two individuals. The AGGU Expressmarker 22 kit, ABI 3500 genetic analyzer, and GeneMapper ID-X v1.5 software were used to statistically analyze the ITO index of the gene locus of 5 kinds of samples, 28 pairs of monozygotic twins (MT), 4,000 pairs of parent–offspring (PO), 392 pairs of full sibling (FS), 138 pairs of half-siblings (HS) (including grandchildren, uncles, and nephews) and 3,500 pairs of unrelated individuals (UI). Observing the median distribution of ITO index found that from MT, PO, FS, HS to UI, the more distant the kinship, the smaller the ITO index. Full sibling index (FSI)/half-sibling index (HSI) ≥ 1 can be used as the FS discriminant standard, FSI/HSI < 1 can be used as the HS discriminant standard. According to the distance of kinship, from the direction of MT, PO, FS, HS, and UI, the proportion of the maximum ITO index of the same type of sample in the true kinship index item showed a decreasing trend. ITO index is an important statistical means to identify the kinship between two individuals, according to which the ITO index can accurately determine the kinship between individuals, which has high application value. MT index is not 0 to identify relatives as MT, PO index is an important indicator to distinguish between relatives as PO and FS. The critical values of ITO index discriminant values for UI and HS need to be further studied.

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems and organs, with pulmonary involvement known to be associated with disease prognosis and mortality. Acute lupus pneumonitis (ALP) resembling miliary tuberculosis (TB) is rare. Here, we present a case of ALP mimicking miliary TB and review the literature. A 19-year-old male student was referred to our hospital with fever. Although the patient met the diagnostic criteria for SLE, diffuse miliary nodules in both lungs were observed on a chest computed tomography scan. A series of tests, including pathological testing of bronchoscopy brushes, T-lymphocyte culture + interferon assay (A + B), tuberculin test, detection of mycobacterium TB DNA, and acid-fast bacilli smear in bronchoalveolar lavage fluid, were unable to confirm the presence of TB infection. We considered the patient to have ALP. After beginning ALP therapy, his symptoms disappeared, and the imaging and hematological results returned to normal. Miliary TB and ALP have similar clinical manifestations and imaging changes, which make diagnosis difficult. This case highlights the need to ensure accurate diagnosis and treatment to improve prognosis.

Evidence has proved that intracranial aneurysm (IA) formation and rupture might be closely related to inflammatory response and oxidative stress. Our objective was to evaluate the potential of CD36 and glutathione (GSH) as biomarkers for IA. In this study, the enzyme-linked immunosorbent assay was used to measure the plasma levels of CD36 and GSH in 30 IA patients and 30 healthy controls. Then, correlation analysis, receiver operating characteristic (ROC) curve, and logistic regression analysis were performed. The results showed that the plasma level of CD36 in IA patients was significantly higher than that in the control group ( P < 0.0001), and plasma GSH was significantly lower compared with that in the control group ( P < 0.0001). ROC analysis showed that CD36 and GSH had high sensitivity (90.0 and 96.6%) and specificity (96.6 and 86.6%) for IA diagnosis. The combined sensitivity and specificity achieved were 100 and 100%, respectively. The plasma levels of CD36 and GSH did not show a significant correlation with age, the Glasgow Coma Scale, Hunter–Hess score, aneurysm size, aneurysm height, aneurysm neck, and aspect ratio. The AUC of the logistic regression model based on CD36 and GSH was 0.505. Our results suggested that the combination of plasma CD36 and GSH could serve as potential biomarkers for IA rupture.

This study aimed to investigate effects of pulmonary fractalkine (FKN/CX3CL1) on angiogenesis and tube formation. Tube forming capability of pulmonary vascular endothelial cells (PVECs) was evaluated. CCK-8 assay was used to evaluate proliferation of PVECs. RT-PCR assay was used to determine angiogenesis specific biomarkers. Western blot was applied to identify CX3CR1, Akt, phosphorylated Akt (p-Akt), Erk1/2, phosphorylated Erk1/2 (p-Erk1/2), vascular endothelial growth factor A (VEGFA), and inducible nitric oxide synthase (iNOS) expression. VEGF-A and platelet-derived growth factor (PDGF) levels were examined using ELISA. FKN was safe and triggered tube formation in PVECs. FKN significantly enhanced VEGF-A, PDGF, and iNOS gene transcription compared to the Control group ( p < 0.05). CX3CR1 interfering (LV5-CX3CR1 shRNA) remarkably reduced CX3CR1 expression compared to those in LV5 blank group ( p < 0.05). Ratios of p-Akt/Akt and p-Erk/Erk were significantly decreased in CX3CR1 shRNA-treated PVECs administered Akt inhibitor (or Erk inhibitor) and 10 ng/mL FKN compared to CX3CR1 shRNA-treated PVECs administered 10 ng/mL FKN ( p < 0.05). FKN increased VEGF-A and iNOS expression through activating Akt/Erk pathway. FKN promoted VEGF-A/iNOS expression and triggered p-Akt/Akt and p-Erk/Erk pathway through modulating CX3CR1. FKN-treated macrophages enhanced activation of Akt/Erk pathway. FKN-treated macrophages enhanced PDGF and VEGF-1 expression in PVECs. FKN modulated pulmonary angiogenesis and tube formation through modulating CX3CR1 and growth factors and activating p-Akt/Akt and p-Erk/Erk signaling pathway.

Graphical abstract Abstract The main focus of this study was to compare the predictive value of coagulation, fibrinolysis, thromboelastography, stress response, and immune function in predicting the incidence of deep venous thrombosis (DVT) in lung cancer (LC) patients undergoing thoracoscopic LC resection vs thoracotomy LC resection. To do that, a prospective, single-center, case-control study involving 460 LC patients was conducted. The risk indicators affecting patients with DVT after LC resection in the testing cohort were determined using logistic regression and receiver operator characteristic (ROC) analyses. One validation cohort was used to assess the risk prediction models. DVT incidence was higher in the thoracoscopic group (18.7%) than in the thoracotomy group (11.2%) in the testing cohort ( χ 2 = 4.116, P = 0.042). The final model to predict the incidence of DVT after thoracoscopic LC excision (1 day after surgery) was as follows: Logit( P ) = 9.378 – 0.061( R -value) – 0.109( K value) + 0.374(α angle) + 0.403(MA) + 0.298(FIB) + 0.406(D-D) + 0.190(MDA) − 0.097(CD4 + /CD8 + ). For thoracotomy LC resection, the final model (3 days after operation) was: Logit( P ) = –2.463 − 0.026( R -value) − 0.143( K value) + 0.402(α angle) + 0.198(D-D) + 0.237(MDA) + 0.409(SOD). In the validation cohort, this risk prediction model continued to demonstrate good predictive performance. As a result, the predictive accuracy of postoperative DVT in patients who underwent thoracoscopic LC resection and thoracotomy LC resection was improved by risk prediction models.

Essential tremor (ET) is a common neurological disorder with a difficult clinical diagnosis, primarily due to the lack of relevant biomarkers. The current study aims to identify possible biomarkers for ET by screening miRNAs using machine learning algorithms. In this investigation, public datasets and our own datasets were used to examine the ET disorder. The ET datasets originated from public sources. To generate our own dataset, high-throughput sequencing analyses were performed on ET and control samples from the First People’s Hospital of Yunnan Province. Functional enrichment analysis was employed to identify the potential function of differentially expressed genes (DEGs). Using datasets from the Gene Expression Omnibus database, Lasso regression analysis and support vector machine recursive feature elimination were used to screen potential diagnostic genes for ET. To identify the genes responsible for the final diagnosis, area under the curves (AUCs) of the receiver operating characteristic was examined. Finally, an ssGSEA representing an ET immune landscape was created. The sample exhibited expression profiles that corresponded with six genes in the public database. Three diagnostic genes were discovered with AUCs >0.7 that can distinguish ET from normal data: APOE, SENP6, and ZNF148. Single-gene GSEA indicated that these diagnostic genes were closely associated with the cholinergic, GABAergic, and dopaminergic synapse networks. The immune microenvironment of ET was also affected by these diagnostic genes. According to the findings, these three DEGs ( APOE , SENP6 , and ZNF148 ) may successfully differentiate between samples from ET patients and normal controls, serving as a helpful diagnostic tool. This effort provided a theoretical foundation for elucidating the pathogenesis of ET and raised hopes of overcoming the diagnostic difficulty of ET clinically. Graphical abstract

In this study, magnetic resonance imaging (MRI) based on a deep learning algorithm was used to evaluate the clinical effect of the small-incision approach in treating proximal tibial fractures. Super-resolution reconstruction (SRR) algorithm was used to reconstruct MRI images for analysis and comparison. The research objects were 40 patients with proximal tibial fractures. According to the random number method, patients were divided into a small-incision approach group (22 cases) and an ordinary approach group (18 cases). The peak signal-to-noise ratio (PSNR) and the structural similarity index (SSIM) of the MRI images before and after the reconstruction of the two groups were analyzed. The operative time, intraoperative blood loss, complete weight-bearing time, complete healing time, knee range of motion, and knee function of the two treatments were compared. The results showed that after SRR, the PSNR and SSIM of MRI images were 35.28 and 0.826 dB, respectively, so the MRI image display effect was better. The operation time in the small-incision approach group was 84.93 min, which was significantly shorter than that in the common approach group, and the intraoperative blood loss was 219.95 mL, which was significantly shorter than that in the common approach group ( P < 0.05). The complete weight-bearing time and complete healing time in the small-incision approach group were 14.75 and 16.79 weeks, respectively, which were significantly shorter than those in the ordinary approach group ( P < 0.05). The half-year knee range of motion and 1-year knee range of motion in the small-incision approach group were 118.27° and 128.72°, respectively, which were significantly higher than those in the conventional approach group ( P < 0.05). After 6 months of treatment, the rate of good treatment was 86.36% in the small-incision approach group and 77.78% in the ordinary approach group. After 1 year of treatment, the rate of excellent and good treatment was 90.91% in the small-incision approach group and 83.33% in the ordinary approach group. The rate of good treatment for half a year and 1 year in the small incision group was significantly higher than that in the common approach group ( P < 0.05). In conclusion, MRI image based on deep learning algorithm has a high resolution, good display effect, and high application value. The small-incision approach can be applied to the treatment of proximal tibial fractures, which showed good therapeutic effects and a high positive clinical application value.

With the popularization and application of artificial intelligence and medical image big data in the field of medical image, the universality of modes and the rapid development of deep learning have endowed multi-mode fusion technology with great development potential. Technologies of 5G and artificial intelligence have rapidly promoted the innovation of online hospitals. To assist doctors in the remote diagnosis of cancer lesions, this article proposes a cancer localization and recognition model based on magnetic resonance images. We combine a convolution neural network with Transformer to achieve local features and global context information, which can suppress the interference of noise and background regions in magnetic resonance imaging. We design a module combining convolutional neural networks and Transformer architecture, which interactively fuses the extracted features to increase the cancer localization accuracy of magnetic resonance imaging (MRI) images. We extract tumor regions and perform feature fusion to further improve the interactive ability of features and achieve cancer recognition. Our model can achieve an accuracy of 88.65%, which means our model can locate cancer regions in MRI images and effectively identify them. Furthermore, our model can be embedded into the online hospital system by 5G technology to provide technical support for the construction of network hospitals.

Arthritis is a musculoskeletal disorder. Millions of people have arthritis, making it one of the most common joint disorders. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the most common types of arthritis among the many different types available. Pain, stiffness, and inflammation are among the early signs of arthritis, which can progress to severe immobility at a later stage if left untreated. Although arthritis cannot be cured at any point in time, it can be managed if diagnosed and treated correctly. Clinical diagnostic and medical imaging methods are currently used to evaluate OA and RA, both debilitating conditions. This review is focused on deep learning approaches used by taking medical imaging (X-rays and magnetic resonance imaging) as input for the detection of RA.

In developing countries, child health and restraining under-five child mortality are one of the fundamental concerns. UNICEF adopted sustainable development goal 3 (SDG3) to reduce the under-five child mortality rate globally to 25 deaths per 1,000 live births. The under-five mortality rate is 69 deaths per 1,000 live child-births in Pakistan as reported by the Demographic and Health Survey (2018). Predictive analytics has the power to transform the healthcare industry, personalizing care for every individual. Pakistan Demographic Health Survey (2017–2018), the publicly available dataset, is used in this study and multiple imputation methods are adopted for the treatment of missing values. The information gain, a feature selection method, ranked the information-rich features and examine their impact on child mortality prediction. The synthetic minority over-sampling method (SMOTE) balanced the training dataset, and four supervised machine learning classifiers have been used, namely the decision tree classifier, random forest classifier, naive Bayes classifier, and extreme gradient boosting classifier. For comparative analysis, accuracy, precision, recall, and F 1-score have been used. Eventually, a predictive analytics framework is built that predicts whether the child is alive or dead. The number under-five children in a household, preceding birth interval, family members, mother age, age of mother at first birth, antenatal care visits, breastfeeding, child size at birth, and place of delivery were found to be critical risk factors for child mortality. The random forest classifier performed efficiently and predicted under-five child mortality with accuracy (93.8%), precision (0.964), recall (0.971), and F 1-score (0.967). The findings could greatly assist child health intervention programs in decision-making.

This study explored the predictive value of the monocyte-to-lymphocyte ratio (MLR) and platelet–lymphocyte ratio (PLR) in patients with acute-on-chronic liver failure (ACLF). A retrospective analysis was carried out on 40 patients with ACLF from January 2018 and August 2019 in our hospital. The patient’s clinical information during hospitalization was collected, and their survivals were followed for 3 months. MLR and PLR values of patients were compared, and the correlation between liver function indicators and prognosis was analyzed. We observed that MLR levels in the survival and death groups were 0.521 (0.311, 0.827) and 0.741 (0.442, 1.121), respectively. MLR levels were markedly enhanced in the death group compared to the survival group ( P = 0.021). The receiver operating characteristic curve (ROC) exhibited that the area under the ROC curve and 95% confidence interval for the survival group was 0.641 (0.528–0.757). Survival analysis demonstrated that the 3-month survival of the high MLR group was markedly lower than that of the low MLR group ( P = 0.001). Multivariate regression exposed that MLR and PLR were independent prognostic factors for ACLF. MLR and PLR could be prospective prognosticative markers of ACLF.

The purpose of this study is to investigate the efficacy of bilateral upper-limb training (BULT) in helping people with upper-limb impairments due to stroke or brain illness regain their previous level of function. Patients recuperating from a stroke or cerebral disease were given the option of undergoing BULT or conventional training to enhance their upper-limb function. Participants were randomly allocated to one of the several different fitness programs. Results from the action research arm test, Box and block test, Wolf motor function test, Fugal–Meyer evaluation, and any other tests administered were taken into account. Some researchers have found that exercising with BULT for just 30 min per day for 6 weeks yields significant results. There were a total of 1,411 individuals from 10 randomized controlled trials included in this meta-analysis. Meta-analysis findings revealed that biofeedback treatment outperformed conventional rehabilitation therapy in reducing lower leg muscular strain, complete spasm scale score, electromyography score, and inactive ankle joint range of motion. An analysis of the literature found that BULT improved limb use in people who had suffered a stroke and hemiplegia but it did not provide any additional benefit over unilateral training.

The expression status of proinflammatory cytokines in high-altitude pulmonary arterial hypertension (PAH) has been well studied. However, the changes in interleukin (IL)-8 and tumor necrosis factor α (TNF-α) during the reversible changes in pulmonary vascular remodeling (PVR) in PAH after detaching from a hypobaric hypoxic environment have not been elucidated. This investigation elucidated a high-altitude PAH rat model. Then, PAH rats in the high-altitude group were maintained in the high-altitude area, and rats in the low-altitude group returned to the low-altitude area. After 0, 10, 20, and 30 days of PAH modeling, right ventricular systolic pressure (RVSP) and the mean pulmonary arterial pressure (mPAP) were assessed. Right ventricular (RV) hypertrophy was reflected by the ratio of RV/[left ventricle + interventricular septum (S)]. Pathological changes in PVR were accessed by hematoxylin-eosin staining, and medial wall thickness (WT%) and medial wall area (WA%) were measured. TNF-α and IL-8 levels in pulmonary artery tissues and blood were measured with Western blot assay and enzyme-linked immunosorbent assay, respectively. Our results showed that PAH rats exhibited a substantial increase in RVSP and mPAP, RV hypertrophy, PVR, and enhanced generation of TNF-α and IL-8. Then, we found that these pathological changes were gradually aggravated and TNF-α and IL-8 levels were increased in rats in the high-altitude group after 10, 20, and 30 days of PAH modeling. In contrast, the mPAP was decreased and PVR was alleviated in rats in the low-altitude group, accompanying with reduced TNF-α and IL-8 production. In conclusion, our study demonstrated that the generation of TNF-α and IL-8 was also reversible during the reversible changes in PVR after detaching from a hypobaric hypoxic environment. Thus, proinflammatory cytokine TNF-α and IL-8 levels are positively correlated with PVR severity.

In accordance with the inability of various hair artefacts subjected to dermoscopic medical images, undergoing illumination challenges that include chest-Xray featuring conditions of imaging acquisi-tion situations built with clinical segmentation. The study proposed a novel deep-convolutional neural network (CNN)-integrated methodology for applying medical image segmentation upon chest-Xray and dermoscopic clinical images. The study develops a novel technique of segmenting medical images merged with CNNs with an architectural comparison that incorporates neural networks of U-net and fully convolutional networks (FCN) schemas with loss functions associated with Jaccard distance and Binary-cross entropy under optimised stochastic gradient descent + Nesterov practices. Digital image over clinical approach significantly built the diagnosis and determination of the best treatment for a patient’s condition. Even though medical digital images are subjected to varied components clarified with the effect of noise, quality, disturbance, and precision depending on the enhanced version of images segmented with the optimised process. Ultimately, the threshold technique has been employed for the output reached under the pre- and post-processing stages to contrast the image technically being developed. The data source applied is well-known in PH 2 Database for Melanoma lesion segmentation and chest X-ray images since it has variations in hair artefacts and illumination. Experiment outcomes outperform other U-net and FCN architectures of CNNs. The predictions produced from the model on test images were post-processed using the threshold technique to remove the blurry boundaries around the predicted lesions. Experimental results proved that the present model has better efficiency than the existing one, such as U-net and FCN, based on the image segmented in terms of sensitivity = 0.9913, accuracy = 0.9883, and dice coefficient = 0.0246.

In patients with sepsis-induced coagulopathy (SIC), the Chinese DIC scoring system (CDSS) of the Chinese Society of Thrombosis and Hemostasis score, the Japanese Association for Acute Medicine (JAAM) score, the International Society of Thrombosis and Hemostasis (ISTH), and the Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA Guidelines (CRUSADE) score were compared for their predictive significance (SIC). From August 2021 through August 2022, 92 SIC patients hospitalized in our hospital’s Department of Critical Care Medicine served as study participants. Groups of patients were created with a bad prognosis ( n = 35) and a favorable prognosis ( n = 57) 14 days following admission. Electronic medical records were used to compile patient information such as demographics (gender, age, and body mass index), medical history (hypertension, diabetes, chronic obstructive pulmonary disease, and chronic kidney disease), treatment (mechanical ventilation, APACHE II score at admission), and outcomes (results). All patients’ JAAM, CDSS, ISTH, and CRUSADE scores were recorded. The APACHE II scores of the group with a poor prognosis were noticeably ( p < 0.05) higher upon admission than those of the group with a favorable prognosis. The poor prognosis group had higher JAAM, ISTH, CDSS, and CRUSADE scores than the good prognosis group (all p < 0.05). Partial coagulation indicators in fibrinogen, D-dimer, activated partial thromboplastin time, and prothrombin time were positively linked with JAAM, ISTH, CDSS, and CRUSADE (all p < 0.05). At admission, the JAAM, ISTH, CDSS, CRUSADE, and APACHE II scores were independently linked with SIC patients’ prognosis (all p < 0.05) in a multivariate logistic regression analysis. According to receiver operating characteristic analysis, the area under the curve for predicting the prognosis of SIC patients using the JAAM, ISTH, CDSS, and CRUSADE4 scores was 0.896, 0.870, 0.852, and 0.737, respectively, with 95% CI being 0.840–0.952, 0.805–0.936, 0.783–0.922 and 0.629–0.845, respectively (all p < 0.05). The prognosis of SIC patients may be predicted in part by their JAAM, ISTH, CDSS, and CRUSADE4 scores, with the CDSS score being the most accurate. This research provides important recommendations for improving the care of patients with SIC.

With the continuous development of the pharmaceutical industry, people have always paid attention to the safety and effectiveness of drugs, including innovative drugs and generic drugs. For pharmaceutical companies as manufacturers, drug development is a very lengthy process that requires high costs, millions of man-hours, thousands of trials, and the mobilization of hundreds of researchers. Therefore, efforts need to be made to develop drugs with high safety and effectiveness. Drug research and development plays an important role today. Based on this, this article applied computer molecular simulation embedded technology and artificial intelligence technology to drug research and development. First, the problems faced in the research and development of anti-inflammatory disease-dependent tumor drugs were introduced, and then the applications of computer molecular simulation embedded technology and artificial intelligence technology in drug research and development were analyzed. Subsequently, the application of artificial intelligence in drug research and development teaching was analyzed, and a teaching system based on computer molecular simulation embedded technology and artificial intelligence was designed. Finally, the application effects of computer molecular simulation embedded technology and artificial intelligence technology were analyzed, and a feasible conclusion was drawn. The use of computer molecular simulation embedded technology and artificial intelligence technology can greatly improve the efficiency of drug research and development, and the research and development safety of imatinib mesylate has been improved by 7%. On the other hand, it can improve students’ learning interest and stimulate their learning interest, and students’ drug research and development capabilities have been improved. Drug research and development for inflammatory-dependent tumors has good application prospects.

Liver disease is an important disease that seriously threatens human health. It accounts for the highest proportion in various malignant tumors, and its incidence rate and mortality are on the rise, seriously affecting human health. Modern imaging has developed rapidly, but the application of image segmentation in liver tumor surgery is still rare. The application of image processing technology represented by artificial intelligence (AI) in surgery can greatly improve the efficiency of surgery, reduce surgical complications, and reduce the cost of surgery. Hepatocellular carcinoma is the most common malignant tumor in the world, and its mortality is second only to lung cancer. The resection rate of liver cancer surgery is high, and it is a multidisciplinary surgery, so it is necessary to explore the possibility of effective switching between different disciplines. Resection of hepatobiliary and pancreatic tumors is one of the most challenging and lethal surgical procedures. The operation requires a high level of doctors’ experience and understanding of anatomical structures. The surgical segmentation is slow and there may be obvious complications. Therefore, the surgical system needs to make full use of the relevant functions of AI technology and computer vision analysis software, and combine the processing strategy based on image processing algorithm and computer vision analysis model. Intelligent optimization algorithm, also known as modern heuristic algorithm, is an algorithm with global optimization performance, strong universality, and suitable for parallel processing. This algorithm generally has a strict theoretical basis, rather than relying solely on expert experience. In theory, the optimal solution or approximate optimal solution can be found in a certain time. This work studies the hepatobiliary surgery through intelligent image segmentation technology, and analyzes them through intelligent optimization algorithm. The research results showed that when other conditions were the same, there were three patients who had adverse reactions in hepatobiliary surgery through intelligent image segmentation technology, accounting for 10%. The number of patients with adverse reactions in hepatobiliary surgery by conventional methods was nine, accounting for 30%, which was significantly higher than the former, indicating a positive relationship between intelligent image segmentation technology and hepatobiliary surgery.

Neonatal hypoxic ischemic encephalopathy is a common disease, which is caused by fetal hypoxia, asphyxia, and other reasons. It may cause sequelae of the nervous system and even death in children. Computer tomography examination can clarify the scope and location of the disease and provide the basis for clinical treatment and prognosis. Relevant personnel analyzed the symptoms of ischemic hypoxia and found that ischemia and hypoxia were the main causes of encephalopathy. Neonatal ischemia and hypoxia are easy to cause serious damage. At present, with the development of medicine, the function of the human brain is the most important issue in natural science. The law of neural activity and the role of molecular cells, organs, and systems have fundamental construction significance for the prevention and treatment of nerve and mental diseases. By analyzing the value of the diagnosis of neonatal hypoxic-ischemic encephalopathy in the analysis of experimental data, by setting the newborns in the controlled group and the trial group as experimental subjects, this paper analyzed the situation of newborns in terms of body temperature, body weight, and respiratory rate, and used Apgar score to score these standards. It was found that the score of the controlled group was 7 and above, and the score of the trial group was below 7. It was found that the Apgar scoring method was more simple. Then, the newborns were analyzed by cord blood gas analysis. It was found that most of the data in the control group were between 7.8 and 8.4, and the data in the trial group were between 5.8 and 7.1. The umbilical blood gas analysis score of the experimental group was lower than that of the control group. By comparing the satisfaction of cord blood gas analysis and the Apgar score, it was found that the satisfaction of cord blood gas analysis was 24.06% higher than that of the Apgar score.