OBJECTIVE To investigate the causal relationships between gut microbiota， blood metabolites and antidepressant treatment response from a genetic perspective， and to assess the potential mediating role of blood metabolites. METHODS This study utilized a two-sample Mendelian randomization （MR） design. Exposure data were derived from four large-scale gut microbiome genome-wide association study （GWAS） datasets and two blood metabolite GWAS datasets. The inverse variance weighted method was used as the primary method to evaluate the causal relationships between gut microbiota， blood metabolites and antidepressant effects. The robustness， heterogeneity and horizontal pleiotropy of the results were evaluated through various sensitivity analyses. Additionally， the false discovery rate （FDR） was applied to correct type Ⅰ errors caused by multiple hypothesis testing. Finally， MR mediation analysis was conducted to test the potential mediating effect of blood metabolites. RESULTS The s_ Bilophila was negatively associated with the effectiveness of antidepressant treatment （ P ＝8.030×10 －5 ， then P ＝0.033 after FDR correction）， and the f_Bacteroidales was positively associated with the effectiveness of antidepressant treatment （ P ＝3.275×10 －4 ， then P ＝0.034 after FDR correction）. Over a hundred blood metabolites were also screened out as being associated with antidepressant response， but after FDR correction， no significant causal relationship was observed. The P value of the mediation effect proportion of blood metabolites in the “gut microbiota-blood metabolites-antidepressant efficacy” pathway was greater than 0.05. CONCLUSIONS The s_ Bilophila may represent a risk factor for antidepressant effects， whereas the f_Bacteroidales may serve as a protective factor for antidepressant effects. The correlation between blood metabolites and antidepressant efficacy is not strong， and no genetic evidence is found to support that the investigated blood metabolites play a key mediating role between the gut microbiota and antidepressant response.

Serotonin-selective reuptake inhibitors （SSRIs）， as widely used antidepressants in clinical practice， exhibit significant individual differences in antidepressant efficacy. Gut microbiota plays an important role in the development and progression of depression， and the use of SSRIs exerts a significant impact on the gut microbiota of patients with depression. Based on this， this article reviews the research progress on the interactions between the antidepressant effects of SSRIs and gut microbiota. It has been found that SSRIs can influence the diversity， abundance， and function of the gut microbiota directly or indirectly. Conversely， the composition of the gut microbiota and differences in its functional metabolic pathways， and other factors， can in turn affect the antidepressant effects of SSRIs. Therefore， in clinical practice， gut microbiota diversity can be utilized as a predictive indicator for the antidepressant effects of SSRIs. Probiotics can be employed as an adjunct therapy alongside SSRIs， and dietary adjustments， as well as fecal microbiota transplantation， can be used to enhance the therapeutic efficacy of SSRIs. In the future， large-scale， multicenter clinical studies should be conducted， enrolling a broadly representative cohort of patients with depression， to uncover the true association between the antidepressant effects of SSRIs and gut microbiota， thereby opening up more effective avenues for the comprehensive treatment of depression.

The occurrence and development of a variety of retinal diseases are related to inflammatory responses,and various inflammatory cells play an important role in retinal damage,which can lead to vision impairment,vision loss,and blindness.Microglia are resident immune cells in the retina,distributed in the inner layer of the retina.They mainly maintain the normal homeostasis of the retina,regulate the apoptosis of neurons,and play an immune surveillance role in the retina.Under inflammatory stimulation,microglia in the retina are activated,secrete a variety of inflammatory factors,engulf neurons and photoreceptors,and destroy the blood-retinal barrier,aggravating retinal damage.This article reviews the physiological function of microglia and the changes in microglia under the inflammatory effects of various retinal diseases.It also discusses how to inhibit microglia from damaging the retina and promote microglia to control retinal inflammation,thereby providing a basis for the clinical treatment of various retinal diseases.

Objective:To explore the effect of health status on the elder care choice,providing empirical evidence to optimize care provision and deepen the understanding of family risk-coping mechanisms.Method:Multinomial Logit model was used to examine the effects of health stock and health changes on the elder care choice,followed by an income heterogeneity analysis.Results:The impact of health status on the choice of elder care arrangements exhibited clear pathway differentiation and group heterogeneity.In the long-term effect,poor baseline cognitive ability was a key factor driving the elderly to turn to their children for elderly care,with each one-point decrease in the MMSE score increasing this probability by an average of 0.5 percentage points.In the short-term effect,an acute deterioration in either physical function(ΔADL)or cognitive ability(ΔMMSE)significantly increased the likelihood of transitioning to living with children,with the probabilities increasing by an average of 1.7 and 0.3 percentage points,respectively.In contrast,transitioning to institutional care—in both the long and short term—was driven solely by the deterioration of physical function,increasing the probability by 0.4 and 0.3 percentage points,respectively.The heterogeneity analysis further revealed that these clear decision pathways hold primarily for the high-income group,while the elder care choice of the low-income group was less sensitive to health indicators.Conclusion:The elder care choice is not solely determined by health risks but is a social process where health status and family economic resources are closely intertwined,ultimately manifesting as a divergence between the"strategic choices"of high-income groups and the"constrained reactions"of low-income groups.

The occurrence and development of a variety of retinal diseases are related to inflammatory responses,and various inflammatory cells play an important role in retinal damage,which can lead to vision impairment,vision loss,and blindness.Microglia are resident immune cells in the retina,distributed in the inner layer of the retina.They mainly maintain the normal homeostasis of the retina,regulate the apoptosis of neurons,and play an immune surveillance role in the retina.Under inflammatory stimulation,microglia in the retina are activated,secrete a variety of inflammatory factors,engulf neurons and photoreceptors,and destroy the blood-retinal barrier,aggravating retinal damage.This article reviews the physiological function of microglia and the changes in microglia under the inflammatory effects of various retinal diseases.It also discusses how to inhibit microglia from damaging the retina and promote microglia to control retinal inflammation,thereby providing a basis for the clinical treatment of various retinal diseases.

Objective:To explore the effect of health status on the elder care choice,providing empirical evidence to optimize care provision and deepen the understanding of family risk-coping mechanisms.Method:Multinomial Logit model was used to examine the effects of health stock and health changes on the elder care choice,followed by an income heterogeneity analysis.Results:The impact of health status on the choice of elder care arrangements exhibited clear pathway differentiation and group heterogeneity.In the long-term effect,poor baseline cognitive ability was a key factor driving the elderly to turn to their children for elderly care,with each one-point decrease in the MMSE score increasing this probability by an average of 0.5 percentage points.In the short-term effect,an acute deterioration in either physical function(ΔADL)or cognitive ability(ΔMMSE)significantly increased the likelihood of transitioning to living with children,with the probabilities increasing by an average of 1.7 and 0.3 percentage points,respectively.In contrast,transitioning to institutional care—in both the long and short term—was driven solely by the deterioration of physical function,increasing the probability by 0.4 and 0.3 percentage points,respectively.The heterogeneity analysis further revealed that these clear decision pathways hold primarily for the high-income group,while the elder care choice of the low-income group was less sensitive to health indicators.Conclusion:The elder care choice is not solely determined by health risks but is a social process where health status and family economic resources are closely intertwined,ultimately manifesting as a divergence between the"strategic choices"of high-income groups and the"constrained reactions"of low-income groups.

Objective:To establish an in vivo infection model of West Nile virus (WNV) pseudovirus and evaluate the neutralizing activity of antibody WNV-XH1.Methods:A stable cell line that can package the WNV pseudovirus was established in the early stage to prepare the pseudovirus supernatant. The supernatant was concentrated and infected BHK21 cells to detect the titer of the pseudovirus. After intraperitoneal injection of the pseudovirus into C57BL/J mice, bioluminescence imaging was performed to observe the infection status of the pseudovirus in the mice. After simultaneous infection, blood was collected and ELISA was used to detect NS1 levels in mouse serum. The in vivo functional activity of antibody WNV-XH1 was evaluated using the established mouse infection model.Results:Fluorescence was detected in C57BL/J mice infected with WNV pseudovirus, and the NS1 levels in the peripheral blood serum of mice infected with pseudovirus were significantly higher than those of non infected mice (1.453±0.09vs0.305±0.018). After intravenous administration of WNV-XH1 antibody before the attack, the fluorescence signal in the mice decreased and the serum NS1 level decreased (0.384±0.015).Conclusions:A successful in vivo infection model of WNV pseudovirus was established, and it was confirmed that the antibody WNV-XH1 had a protective effect against WNV pseudovirus infection in vivo.

Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.

OBJECTIVE To design the implementation path around the key links of the management in the clinical comprehensive evaluation of drug in China， and to provide suggestions for optimizing and perfecting the management in the clinical comprehensive evaluation of drug. METHODS Based on the relevant experience of drug evaluation management in typical countries regions at home and abroad， the discussion was performed and the management mechanism was designed from seven aspects， such as funding source， selection of topics， staff management， information management， data management， evaluation process and quality assessment. RESULTS & CONCLUSIONS In terms of funding sources， the financial department can provide funding guarantees or other alternative forms such as performance evaluations to encourage all parties to undertake the clinical comprehensive evaluation of drug projects. In terms of the selection of topics， a “top-down” or “bottom-up” selection mode can be determined according to the project’s nature and actual situation， and a selection process of “forming alternatives-setting up theme selection list-demonstrating and publishing theme selection list” can be formed. In terms of staff management， the specialty of team members should be specified， and the expert team should be established to provide clinical comprehensive evaluation of drug. In terms of information management， the national/provincial basic informational platform should be established， and the registration system should be established. In terms of data management， a regional health data-sharing platform should be formed and the “application-checking-utilization” mechanism should be conducted. In terms of the evaluation process， the evaluation procedures that concern on project implementation plan demonstration system and project closing review system should be constructed. In terms of quality assessment， quality assessment and reward and punishment mechanism for project completion，that consider the quality of management first while focusing on the technical quality， can be established. The management mechanism based on the standardized implementation of the seven key links will standardize the development of clinical comprehensive evaluation of drugs in China to some extent， and help improve the quality of clinical comprehensive evaluation projects for drugs.

Diabetes mellitus (DM) is a major metabolic disease endangering global health, with diabetic nephropathy (DN) as a primary complication lacking curative therapy. Sporoderm-broken spores of Ganoderma lucidum (GLP), an herbal medicine, has been used for the treatment of metabolic disorders. In this study, DN was induced in Sprague-Dawley rats using streptozotocin (STZ) and a high-fat diet (HFD), and the protective mechanisms of GLP were investigated through transcriptomic, metabolomic, and network pharmacology (NP) analyses. Our results demonstrated that GLP intervention ameliorated renal damage and inflammation levels in DN rats. Integrative metabolomic and transcriptomic analysis revealed that GLP treatment modulated glucose and cellular energy metabolisms by regulating relevant genes. GLP significantly suppressed the inflammations by impacting glucose and energy metabolism-related gene expression (Igfbp1 and Angptl4) and enhanced metabolic biomarkers of 4-Aminocatechol. In addition, NP analysis further indicated that GLP may efficiently alleviate DN via immune-related pathways. In conclusion, this study provides supportive evidence of the anti-inflammatory effects of GLP supplements, highlighting their potential for promising clinical applications in treating DN.