BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

Focal choroidal excavation(FCE)is an elusive clinical sign characterized by a localized structural depression in the choroid. It has been increasingly recognized with the widespread use of optical coherence tomography(OCT), though its pathogenesis remains incompletely understood and may involve congenital developmental anomalies or acquired factors(such as inflammation or tumor compression). Studies indicate that FCE can occur independently or secondary to various chorioretinal diseases(e.g., central serous chorioretinopathy, choroidal osteoma, age-related macular degeneration, etc.). Clinically, it has also been observed that FCE may be associated with the development of choroidal neovascularization(CNV). Potential mechanisms linking FCE and CNV include: 1)mechanical traction-hypoxia-signaling pathway activation; 2)disruption of the retinal pigment epithelium(RPE)-Bruch's membrane-choroid complex barrier; 3)structural collapse induced by inflammatory scar contraction. Anti-vascular endothelial growth factor(VEGF)therapy is currently the mainstay of treatment for CNV secondary to FCE. By reviewing relevant domestic and international literature, this paper seeks to elucidate the possible pathological relationship between FCE and CNV, with the goal of facilitating early identification of high-risk patients and optimizing anti-VEGF treatment strategies. It also highlights the limitations of current research(such as sample heterogeneity and lack of histological validation of typing criteria), and suggests future directions, such as multicenter studies and molecular mechanism investigations, to support the development of personalized diagnostic and therapeutic approaches.

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

ObjectiveThe research focuses on developing modeling and evaluation methodologies for an animal model exhibiting spleen deficiency and dampness excess syndrome， with the aim of standardizing such animal models for future reference. MethodsBy conducting a literature search on animal models of spleen deficiency and dampness excess syndrome， relevant publications meeting inclusion and exclusion criteria will be identified based on publication date， data source， types of diseases involved， animal characteristics， modeling methods， modeling duration， macroscopic syndrome assessment indicators， macroscopic quantification indicators， laboratory testing parameters， intervention approaches， positive controls and application context. A database will be established to facilitate the extraction of this information for quantitative analysis， statistical evaluation， and visual representation. ResultsA total of 137 literature articles meeting the standards have been included in the research. The primary animal species used in animal models of spleen deficiency and dampness excess are SD rats. Modeling methods include single-factor， dual-factor composite， and triple-factor composite methods， with various models widely applied in validation of pharmacological effects and mechanistic explorations. Evaluation indices of animal models for spleen deficiency and dampness excess primarily consist of macroscopic syndrome evaluation indicators and macroscopic quantitative indicators. Laboratory testing indicators are mostly related to research areas such as fluid metabolism and gastrointestinal function. The most commonly studied herbal formulas currently include Shenling Baizhu San and Pingwei San， with natural recovery and the use of the western medicine metronidazole as the most frequently used positive controls. ConclusionThe application of animal models for spleen deficiency and dampness excess is gradually increasing， with various modeling methods already simulating the typical characteristics of this syndrome pattern. However， there are still many areas that are worth contemplating and improving. This study aims to provide reference and ideas for the standardization of symptom names in animal models of spleen deficiency and dampness excess， as well as for the improvement of model construction and evaluation systems.

Objective:To investigate the correlation between triglyceride-glucose-body mass index (TyG-BMI index) and the outcome of young patients with acute ischemic stroke (AIS).Methods:Consecutive young patients with first-ever AIS (aged 18-45 years) admitted to Pingyi County People's Hospital and Qingdao Municipal Hospital from January 2020 to December 2023 were included retrospectively. The demographic data, vascular risk factors, baseline blood pressure, baseline laboratory tests, classification of stroke etiology, baseline National Institutes of Health Stroke Scale (NIHSS) scores, and main treatment methods were collected. At 3 months after the onset of stroke, the modified Rankin Scale was used for outcome evaluation. A score of 0-2 was defined as good outcome and >2 were defined as poor outcome. Multivariate logistic regression analysis was used to identify independent factors associated with poor outcome in young patients with AIS. Results:A total of 253 young patients with AIS were enrolled, including 196 males (77.5%), aged 38.65±5.34 years; baseline NIHSS score 3.03±2.88. At 90 days after onset, 206 patients (81.4%) had good outcome, while 47 (18.6%) had poor outcome. The poor outcome group had significantly higher systolic blood pressure, triglycerides, fasting blood glucose, triglyceride glucose (TyG) index, body mass index (BMI), TyG-BMI index, and baseline NIHSS score than those of the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for gender, systolic blood pressure, baseline NIHSS score, and antiplatelet drug use, the TyG-BMI index was significantly independently associated with the poor outcome in young patients with AIS (odds ratio 1.039, 95% confidence interval 1.021-1.057; P<0.001). Conclusion:A higher baseline TyG-BMI index is independently associated with the poor outcome in young patients with AIS.

OBJECTIVE To investigate the characteristics of influenza A and influenza B viruses infections in the children aged between 0 and 14 years old after COVID-19 was downgraded to category B management of infectious diseases.METHODS From Jan.2023 to Feb.2024,a total of 2349 children aged between 0 and 14 years old who were treated in Beijing Hospital of Traditional Chinese Medicine,Capital Medical University due to influenza-like symptoms of infection and received nucleic acid testing for influenza A and influenza B viruses were recruited as the research subjects.The gender and age of the children as well as the seasons were observed by chi-square test.RESULTS Totally 2349 children were included in the study,and the total positive rate of influenza was 49.85％(1171/2349);the positive rate of influenza A virus was 36.36％(854/2349),the positive rate of influenza B virus was 13.92％(327/2349),and the positive rate of the mixed infections of influenza A virus and influenza B virus was 0.43％(10/2349).The positive rate of influenza A of the girls was the highest(44.17％)(x2=8.980,P=0.011)among the children aged less than 5 years old;the positive rate of influenza B of the boys was the highest(17.19％)(x2=8.378,P=0.015)among the children aged between 5 and 10 years old.There was significant difference in the positive rate of influenza A virus among the seasons in 2023 to 2024(x2=268.12,P＜0.001);the prevalence rate was 60.93％in spring,44.40％in autumn,22.01％in winter.There was significant difference in the positive rate of influenza B virus among the seasons in 2023 to 2024(x2=373.16,P＜0.001),and the preva-lence rate was 25.44％in winter.CONCLUSIONS The influenza viruses are prevalent in spring,autumn and winter from 2023 to 2024,and the influenza A is dominant.The positive rate of influenza viruses shows an upward trend among the children aged between 0 and 14 years old after the COVID-19 is downgraded to category B management of infectious diseases,with the peak of prevalence lagging behind.

OBJECTIVE To investigate the characteristics of influenza A and influenza B viruses infections in the children aged between 0 and 14 years old after COVID-19 was downgraded to category B management of infectious diseases.METHODS From Jan.2023 to Feb.2024,a total of 2349 children aged between 0 and 14 years old who were treated in Beijing Hospital of Traditional Chinese Medicine,Capital Medical University due to influenza-like symptoms of infection and received nucleic acid testing for influenza A and influenza B viruses were recruited as the research subjects.The gender and age of the children as well as the seasons were observed by chi-square test.RESULTS Totally 2349 children were included in the study,and the total positive rate of influenza was 49.85％(1171/2349);the positive rate of influenza A virus was 36.36％(854/2349),the positive rate of influenza B virus was 13.92％(327/2349),and the positive rate of the mixed infections of influenza A virus and influenza B virus was 0.43％(10/2349).The positive rate of influenza A of the girls was the highest(44.17％)(x2=8.980,P=0.011)among the children aged less than 5 years old;the positive rate of influenza B of the boys was the highest(17.19％)(x2=8.378,P=0.015)among the children aged between 5 and 10 years old.There was significant difference in the positive rate of influenza A virus among the seasons in 2023 to 2024(x2=268.12,P＜0.001);the prevalence rate was 60.93％in spring,44.40％in autumn,22.01％in winter.There was significant difference in the positive rate of influenza B virus among the seasons in 2023 to 2024(x2=373.16,P＜0.001),and the preva-lence rate was 25.44％in winter.CONCLUSIONS The influenza viruses are prevalent in spring,autumn and winter from 2023 to 2024,and the influenza A is dominant.The positive rate of influenza viruses shows an upward trend among the children aged between 0 and 14 years old after the COVID-19 is downgraded to category B management of infectious diseases,with the peak of prevalence lagging behind.

Objective To investigate the inhibitory effect and molecular mechanism of Huaier granule on the growth of sorafenib resistant hepatocellular carcinoma (HCC) cells. Methods The gradient concentration of Huaier granule was used to treat HCC cells, and the effect of Huaier granule on the proliferation, migration and invasion of sorafenib resistant HCC cells was analyzed. Bioinformatics methods were used to analyze the possible interaction between microRNA-31-5p (miR-31-5p) and sprouty-related proteins with an EVH1 domain 1 (SPRED1). The expression levels of miR-31-5p and SPRED1 in HCC cells were detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR); cell viability, proliferation, migration, invasion and apoptosis were detected by CCK-8, colony formation, scratch healing, Transwell and flow cytometry; RNA immunoprecipitation (RIP) assay and dual luciferase assay were used to verify the binding relationship between miR-31-5p and SPRED1. Results Huaier granule could significantly inhibit the proliferation, migration and invasion of sorafenib resistant HCC cells, and induce apoptosis. Bioinformatics analysis showed that miR-31-5p was highly expressed in HCC, and Huaier granule was able to down-regulate the expression of miR-31-5p, inhibit the proliferation and metastasis of sorafenib resistant HCC cells, and induce apoptosis; miR-31-5p showed a targeted inhibition effect on the expression of SPRED1. SPRED1 was down-regulated in HCC, and overexpression of SPRED1 was able to reverse the promoting effect of overexpression of miR-31-5p on proliferation and metastasis of sorafenib resistant HCC. Conclusion Huaier granule can inhibit sorafenib resistant HCC metastasis through the miR-31-5p/SPRED1 axis, indicating that Huaier granule has the potential to be used as a novel drug for HCC treatment.