Rheumatoid arthritis(RA)is an autoimmune disease characterized by synovitis,synovial cell proliferation,neo-vascularization,and bone and cartilage destruction.Its pathogenesis is complex and has not yet been fully elucidated.A variety of cells,cytokines and signaling pathways are involved in the pathogenesis of RA.Hypoxia-inducing factor(HIF)and oxygen-sensing signaling pathway(PHD-HIF-VHL)are closely related to the occurrence and development of RA,and play an important role in syno-vial cell proliferation,inflammatory response and cartilage destruction.In this study,the research progress of oxygen sensing signaling pathway in RA was described from the aspects of the mechanism of oxygen sensing signaling pathway and its involvement in the patho-genesis of RA,in order to provide ideas and theoretical basis for the research of anti-RA drugs by targeting important molecules of oxy-gen sensing signaling pathway.

ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

Depressive disorders are common mental illnesses characterized by significant and persistent low mood, with features such as high prevalence, high disability rate, and high suicide rate. The microbiota-gut-brain axis may be one of the potential mechanisms underlying depressive disorders. Gut microbiota metabolites, as important mediators of MGBA signaling, play roles in depressive disorders through multiple pathways. These include short-chain fatty acids, which can regulate the transmission of the vagus nerve, inflammatory responses, and 5-hydroxytryptamine synthesis; secondary bile acids, which can activate farnesoid X receptor and Takeda G protein-compled receptor 5; and choline, which can regulate DNA methylation and trimethylamine N-oxide production. This article reviews the literature on the potential mechanisms of action of gut microbiota metabolites, such as short-chain fatty acids, secondary bile acids, and choline, in depressive disorders. The literature was retrieved from CNKI, PubMed, and Web of Science databases from 2010 to 2025. It aims to provide a theoretical basis for the prevention and treatment of depressive disorders.

BACKGROUND: Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients. METHODS: A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to evaluat associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyze relationships between these changes and functional improvements. RESULTS: A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs . 82.5%, odds ratio [OR] = 2.98, P  = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P  >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P  <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes ( P  <0.05). CONCLUSION: Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials. TRAIL REGISTRATION ClinicalTrials.gov , NCT05990894.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Anticoagulants/therapeutic use* ; C-Reactive Protein/metabolism* ; Interleukin-6/metabolism* ; Intracranial Thrombosis/drug therapy* ; Prospective Studies ; Steroids/therapeutic use* ; Venous Thrombosis/drug therapy*

Objective To investigate the loci in the STRtyper-21G kit that are prone to tolerance mismatches when compared with the GlobalFilerTM kit and the PowerPlex? 21 kit,and to analyze the underlying causes.Methods A total of 5,870 database comparison reports involving STRtyper-21G profiles and other autosomal STR kits were examined for identity alignment.Samples showing mismatched loci were re-tested using the STRtyper-21G,GlobalFilerTM,and PowerPlex? 21 kits.For loci with mismatches,primers were redesigned and sequencing was performed.Results Eight mismatched samples(8/5 870)were identified,involving the loci D18S51,D8S1179,and D2S1338.Sequencing revealed that the allele dropout at D18S51 was due to a G→A mutation at the 79th base upstream of the core sequence;at D8S1179,a C→A mutation at the 4th base upstream;and at D2S1338,a C→T mutation at the 22nd base downstream.Conclusion All mismatches were attributable to mutations in primer binding regions.These findings provide reference for interpreting mismatch results in the STRtyper-21G database.When mismatches occur at these loci and the profiles are homozygous,exclusion conclusions should be made with caution.

Rheumatoid arthritis(RA)is an autoimmune disease characterized by synovitis,synovial cell proliferation,neo-vascularization,and bone and cartilage destruction.Its pathogenesis is complex and has not yet been fully elucidated.A variety of cells,cytokines and signaling pathways are involved in the pathogenesis of RA.Hypoxia-inducing factor(HIF)and oxygen-sensing signaling pathway(PHD-HIF-VHL)are closely related to the occurrence and development of RA,and play an important role in syno-vial cell proliferation,inflammatory response and cartilage destruction.In this study,the research progress of oxygen sensing signaling pathway in RA was described from the aspects of the mechanism of oxygen sensing signaling pathway and its involvement in the patho-genesis of RA,in order to provide ideas and theoretical basis for the research of anti-RA drugs by targeting important molecules of oxy-gen sensing signaling pathway.

Objective To observe the value of hypoperfusion intensity ratio(HIR)of CT perfusion(CTP)for predicting infarct core progression and prognosis of acute ischemic stroke(AIS).Methods Totally 271 AIS patients were retrospectively enrolled and divided into rapid progression group(group A,n=92)and slow progression group(group B,n=179)according to infarction growth rate(IGR).Clinical data,CTP parameters,treatment strategies and patients' outcome were compared between groups.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the efficacy of HIR for predicting rapid progression in infarct core of AIS.The mediating relationships among HIR,IGR and modified Rankin scale(mRS)90 days after treatment were analyzed.Results Significant differences of National Institute of Health stroke scale(NIHSS)score,Alberta stroke program early CT score(ASPECTS),also of interval time between onset and CTP,infarct core volume,hypoperfusion volume,HIR,whether intravenous thrombolysis and mRS score 90 days after treatments were found between groups(all P＜0.05).The AUC of HIR for predicting infarct core progression of AIS was 0.856,with sensitivity and specificity was 73.91％and 81.56％,respectively,when the optimal cutoff value was 0.42.IGR was a complete mediating variable between HIR and mRS score 90 days after treatment.Conclusion HIR of CTP could be used to effectively predict infarct core progression of AIS,which completely affected prognosis through mediating variable IGR.

Objective To observe the value of hypoperfusion intensity ratio(HIR)of CT perfusion(CTP)for predicting infarct core progression and prognosis of acute ischemic stroke(AIS).Methods Totally 271 AIS patients were retrospectively enrolled and divided into rapid progression group(group A,n=92)and slow progression group(group B,n=179)according to infarction growth rate(IGR).Clinical data,CTP parameters,treatment strategies and patients' outcome were compared between groups.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the efficacy of HIR for predicting rapid progression in infarct core of AIS.The mediating relationships among HIR,IGR and modified Rankin scale(mRS)90 days after treatment were analyzed.Results Significant differences of National Institute of Health stroke scale(NIHSS)score,Alberta stroke program early CT score(ASPECTS),also of interval time between onset and CTP,infarct core volume,hypoperfusion volume,HIR,whether intravenous thrombolysis and mRS score 90 days after treatments were found between groups(all P＜0.05).The AUC of HIR for predicting infarct core progression of AIS was 0.856,with sensitivity and specificity was 73.91％and 81.56％,respectively,when the optimal cutoff value was 0.42.IGR was a complete mediating variable between HIR and mRS score 90 days after treatment.Conclusion HIR of CTP could be used to effectively predict infarct core progression of AIS,which completely affected prognosis through mediating variable IGR.

Objective To investigate the loci in the STRtyper-21G kit that are prone to tolerance mismatches when compared with the GlobalFilerTM kit and the PowerPlex? 21 kit,and to analyze the underlying causes.Methods A total of 5,870 database comparison reports involving STRtyper-21G profiles and other autosomal STR kits were examined for identity alignment.Samples showing mismatched loci were re-tested using the STRtyper-21G,GlobalFilerTM,and PowerPlex? 21 kits.For loci with mismatches,primers were redesigned and sequencing was performed.Results Eight mismatched samples(8/5 870)were identified,involving the loci D18S51,D8S1179,and D2S1338.Sequencing revealed that the allele dropout at D18S51 was due to a G→A mutation at the 79th base upstream of the core sequence;at D8S1179,a C→A mutation at the 4th base upstream;and at D2S1338,a C→T mutation at the 22nd base downstream.Conclusion All mismatches were attributable to mutations in primer binding regions.These findings provide reference for interpreting mismatch results in the STRtyper-21G database.When mismatches occur at these loci and the profiles are homozygous,exclusion conclusions should be made with caution.

Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.