Objective To investigate the causal relationship between gut microbiota and idiopathic pulmonary fibrosis (IPF). Methods Genome-wide association studies (GWAS) data of gut microbiota and IPF were obtained from MiBioGen and IEU OpenGWAS, respectively. Instrumental variables were screened by means of significance, linkage disequilibrium, weak instrumental variable screening, and removal of confounding factors (genetics, smoking, host characteristics). Inverse variance weighted (IVW) was used as the main Mendelian randomization (MR) analysis method, and the weighted median, simple mode, MR-Egger, and weighted mode were used to perform MR to reveal the causal effect of gut microbiota and IPF. The Cochrane's Q, leave-one-out, MR-Egger-intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and Steiger tests were used to analyze the heterogeneity, horizontal pleiotropy, outliers, and directionality, respectively. Results IVW analysis results showed that Actinobacteria [OR=1.773, 95%CI (1.323, 2.377), P<0.001], Erysipelatoclostridium [OR=2.077, 95%CI (1.107, 3.896), P=0.023], and Streptococcus [OR=1.35, 95%CI (1.100, 1.657), P=0.004] could increase the risk of IPF. Bifidobacterium [OR=0.668, 95%CI (0.620, 0.720), P<0.001], Ruminococcus [OR=0.434, 95%CI (0.222, 0.848), P=0.015], and Tyzzerella [OR=0.479, 95%CI (0.304, 0.755), P=0.001] could reduce the risk of IPF. No significant heterogeneity, horizontal pleiotropy, outliers, and reverse causality were found. Conclusion Actinobacteria, Erysipelatoclostridium and Streptococcus may increase the risk of IPF, while Bifidobacterium, Ruminococcus and Tyzzerella may reduce the risk of IPF. Regulation of the above gut microbiota may become a new direction in the study of the pathogenesis of IPF.

OBJECTIVE To explore the improvine mechanism of Yifei xuanfei jiangzhuo formula （YFXF） on vascular dementia （VAD） model rats based on the growth factor receptor-bound protein 2 （GRB2）/extracellular signal-regulated kinase （ERK）/cardiolipin synthase 1 （CRLS1） pathway. METHODS VAD rat model was established by permanent bilateral common carotid artery ligation. Forty-eight successfully modeled rats were randomly divided into the model group （normal saline）， donepezil hydrochloride group （positive control group， 0.2 g/kg）， and YFXF low- and high-dose groups （12.18 and 24.36 g/kg， calculated based on the total amount of crude drug）， respectively. In addition， a sham operation group （normal saline） was set up. There were 12 rats in each group. Daily intragastric administration of drug or normal saline was performed for 30 consecutive days. After the last administration， the spatial cognitive ability of the rats was evaluated， the pathological morphology of the hippocampus was observed， the contents of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） in serum were detected， the expression levels of GRB2/ERK/CRLS1 pathway-related proteins and the mRNA levels of GRB2， CRLS1， NADH dehydrogenase subunit 1（ND1）， Tafazzin （TAZ）， phospholipid scramblase 3（PLSCR3） and the ATP content in hippocampal tissue were measured. RESULTS Compared with the sham operation group， the escape latency of rats in the model group was significantly prolonged （ P ＜0.05）， and the number of crossing platform was significantly reduced （ P ＜0.05）， while the number of pyramidal cells and Nissl bodies in the hippocampus decreased sharply； the content of TNF-α in serum was significantly increased （ P ＜0.05）， and the content of IL-4 was significantly decreased （ P ＜0.05）； the expression levels of GRB2 and CRLS1 proteins， the phosphorylation level of ERK protein， the relative expression levels of GRB2， CRLS1，ND1， TAZ， and PLSCR3 mRNA， and the content of ATP in hippocampal tissue were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological changes in the hippocampal tissue of each administration group were alleviated， and the quantitative indicators were significantly restored （ P ＜0.05）. CONCLUSIONS YFXF may improve hippocampal neuron injury in VAD rats by activating the GRB2/ERK/CRLS1 pathway, maintaining cardiolipin homeostasis， and improving mitochondrial energy metabolism.

OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.

OBJECTIVES: Obtaining informed consent from research participants is an ethical and legal obligation for medical researchers in clinical studies. Electronic informed consent (eIC) is increasingly being adopted in clinical research worldwide. However, there is limited data on Chinese medical researchers' knowledge and attitudes toward eIC. This study aims to investigate their knowledge, attitudes, and influencing factors regarding eIC use in clinical research. METHODS: This cross-sectional study was conducted using stratified random sampling. From June to August 2022, medical researchers from 8 tertiary hospitals were surveyed via an online platform (Wenjuanxing). A self-developed eIC knowledge questionnaire and attitude scale were used to assess participants' understanding and perceptions of eIC. Univariate analysis was employed to explore factors influencing attitude scores and the correlation between knowledge and attitudes. A generalized linear model was used to analyze associations between demographic characteristics and attitude scores, including the frequency of difficulties in using smartphones or computers, preferred device for using eIC, and their interaction effects. Stratified analysis was further performed for significant interactions. RESULTS: A total of 399 valid questionnaires were collected. The mean accuracy rate on the eIC knowledge questionnaire was (94.88±15.50)%. Of the respondents, 74.9% had heard of eIC, and 84.5% preferred using mobile devices over computers to access eIC. The median attitude score was 3.41 (3.18, 3.76), indicating generally positive attitudes. Specifically, 81.7% found eIC more convenient than paper-based consent, 79.7% considered it more efficient, and 51.1% believed it could fully replace paper forms. However, 60.7% expressed concerns about data security and privacy, and 89.7% believed that relevant laws and regulations need improvement. Spearman correlation analysis showed a weak positive correlation between knowledge and attitude scores (r=0.171, P=0.001). Univariate analysis indicated that the frequency of difficulty using devices and preferred device for eIC were significantly associated with attitude scores (P<0.05). After adjusting for confounding factors, the generalized linear model demonstrated that participants who occasionally experienced had difficulty using devices had significantly lower attitude scores compared to those who never had difficulty (β=-0.040, 95% CI -0.071 to -0.009, P=0.012). Those who preferred using PCs had significantly lower attitude scores than those who preferred mobile devices (β=-0.066, 95% CI -0.108 to -0.023, P=0.002). Interaction analysis showed a significant interaction analysis showed a significant interaction between age and preferred device (P=0.011), particularly among participants aged ≥45-year (P<0.001). No other interactions were found to be significant (all P>0.05). CONCLUSIONS Medical researchers in China generally have a high level of knowledge and positive attitudes toward eIC, though concerns remain regarding data security and privacy. Future promotion of eIC in Chinese clinical research should be grounded in ethical considerations and address the specific needs of older users and mobile device users, while also enhancing researchers' competencies in using digital tools and eIC systems.
Humans ; Cross-Sectional Studies ; Informed Consent ; Surveys and Questionnaires ; Female ; Male ; Health Knowledge, Attitudes, Practice ; Adult ; Biomedical Research ; Research Personnel/psychology* ; Middle Aged ; China

Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer's disease (AD). The mitochondrial contact site and cristae organizing system (MICOS) plays a pivotal role in shaping the inner mitochondrial membrane, forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function. In the past decade, MICOS abnormalities have been extensively linked to AD pathogenesis. In particular, dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD, often in association with hallmark pathological features such as amyloid-β plaque accumulation, neurofibrillary tangle formation, and neuronal apoptosis. Furthermore, MICOS subunits interact with several etiologically relevant proteins, significantly influencing AD progression. The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD. Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment. In the present review, we introduce current understanding of MICOS structures and functions, highlight MICOS pathogenesis in AD, and summarize the available MICOS-targeting drugs potentially useful for AD.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

This review briefs the anti-hyperuricemia(HUA)mechanism of nutrition targeting the gut,such as the gut microbiota promoting the catabolism of purine and uric acid(UA),and increased its metabolites like uric acid.The review also summarizes the probiotics and prebiotics that have the effect of lowering uric acid targeting at the gut,providing reference and guidance for further research.In addition,this paper reviews the effects of various di-ets,such as the dietary approaches to stop hypertension(DASH)diet,the Mediterranean diet,and the low-purine diet,as well as the effects of individual foods including alcohol,coffee and tea,cherries,dairy products,fructose,and vitamin C on hyperuricemia and gout outcomes.

Objective To evaluate the application of modified chairside case-based learning(CBL)in the teaching of dental residents in the prosthodontic clinic.Methods Dental residents in Peking Union Medical College Hospital from September 2022 to September 2024 were enrolled.Traditional CBL was conducted in control group.Modified chairside CBL was conducted in test group.The scores of department rotation examination and questionnaire results were analyzed with t-test statistical analysis.Results The score of"patient reception"in test group was significantly higher than control group(P＜0.05).24 valid questionnaires were collected in two groups each.The rate of approval in test group was significantly higher than control group in the following items of questionnaire,including"reduce learning pressure or burden""improve the capacity of doctor-patient communication""improve the capacity of literature review""improve the capacity of group cooperation"(P＜0.05).Conclusions Modified chairside CBL has showed good teaching effects in improving the capacity of patient reception,doctor-patient communication,literature review,group cooperation,and meanwhile reduced learning pressure or burden.