Objective To explore the mechanism of matrine in the treatment of uveal melanoma by network pharmacology,and the related results were verified by molecular docking and cell experiments.Methods The potential targets of matrine were obtained from Swiss Target Prediction,SuperPred and TCMSP databases.The targets related to uveal melanoma were obtained from GeneCards,OMIM,CTD and DrugBank databases.Protein-protein interaction(PPI)network was established to screen core targets.Gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)signal pathway analysis were carried out for potential targets.The interaction between matrine and core targets was evaluated by molecular docking technique.The effects of different concentrations of matrine(0.25 g/L,0.50 g/L,1.00 g/L,2.00 g/L)on the proliferation of uveal melanoma cells were evaluated based on CCK-8 method.Western blot was used to verify the regulatory effects of different concentrations of matrine(0.25 g/L,0.50 g/L,1.00 g/L,2.00 g/L)on PI3K-Akt signaling pathway.Results A total of 208 potential targets of matrine were identified,and 5 453 targets related to uveal melanoma were obtained.The topological analysis of PPI network revealed 8 core targets,namely interleukin-6(IL-6),tumor necrosis factor(TNF),myelocytomatosis proteins(MYC),signal transducer and activator of transcription 3(STAT3),caspase-3(CASP3),heat shock protein 90AB1(HSP90AB1),mammalian target of rapamycin(mTOR),and matrix metalloproteinase 9(MMP9).GO enrichment analysis showed that biological processes(BP)mainly included inflammatory response,protein phosphorylation and response to exogenous stimuli;cell components(CC)mainly included plasma membrane,cell surface and cytoplasm;molecular function(MF)mainly included the same protein binding,ATP binding and kinase activity.The enrichment analysis of KEGG pathway showed that the effect of matrine was mediated by viral carcinogenesis,cancer pathway,TNF signaling pathway and PI3K-Akt signaling pathway.Molecular docking showed that matrine had good binding ability with the selected core targets.The results of cell experiments showed that matrine at concentrations of 0.50 g/L,1.00 g/L and 2.00 g/L could inhibit the proliferation of MuM2B cells,and the cell survival rate gradually decreased with the increase of concentration.Matrine at concentrations of 0.50 g/L,1.00 g/L and 2.00 g/L could down-regulate the protein expression levels of p-PI3K and p-Akt,and the protein expression levels of p-PI3K and p-Akt gradually decreased with the increase of concentration.Conclusion Matrine acts on tar-gets such as IL-6,TNF,MYC,STAT3,CASP3,HSP90AB1,mTOR,MMP9,and exerts therapeutic effects on uveal melanoma by viral carcinogenesis,cancer pathway,TNF signaling pathway and PI3K-Akt signaling pathway,etc.

Aim To explore the mechanism of rhein in the treatment of IgA nephropathy in rats by impro-ving spleen immune function based on mTORC1 path-way.Methods Thirty-two SD rats were randomly di-vided into control group,model group(IgAN),rhein group(RH)and rapamycin group.The deposition of IgA in mesangial region and pathological changes of spleen and kidney were observed,and the ratio of Th/Ts in spleen was determined by immunohistochemical method.The protein expressions of p-mTOR,p-p70S6k,TGF-β1 and TNF-α in spleen were detected by Western blot.Results Compared with the control group,IgAN group significantly increased urinary sludge red blood cell count,24 hour urinary total pro-tein,serum creatinine,blood urea nitrogen,serum IgA,Th/Ts,p-mtor,p-P70S6K and spleen TNF-αprotein expression levels(P＜0.01),and spleen TGF-β1 protein expression(P＜0.05).IgA deposi-tion in mesangial area of the kidney increased signifi-cantly,and pathological changes were observed in spleen and kidney.Compared with IgAN group,urine sludge red blood cell count,serum IgA,Th/Ts,p-mTOR,p-P70S6K and TNF-α protein expression lev-els in RH and RAPA groups were significantly reduced(P＜0.01).24 hour urinary total protein,blood urea nitrogen,serum creatinine and spleen TGF-β1 protein decreased(P＜0.05),the deposition of IgA in the mesangial region of the kidney decreased,and the pathological changes of spleen and kidney were allevia-ted.There was no significant difference between RH group and RAPA group.Conclusions RH can allevi-ate IgA nephropathy by inhibiting the activity of m-TORC1 pathway in the spleen of IgA nephropathy rats,thereby inhibiting the differentiation of splenic lympho-cytes and reducing the secretion of IgA.

Objective:To develop and validate machine learning models for predicting the cumulative live birth rate (CLBR) following in vitro fertilization (IVF) and to analyze key predictive features using SHAP values. Methods:This retrospective study included data from patients who underwent IVF-embryo transfer at the Department of Reproductive Medicine, Baoding Maternal and Child Health Hospital, between January 2017 and December 2022. Patients were categorized into two groups based on live birth outcome: the live birth group ( n=1 036) and the non-live birth group ( n=756). The dataset was randomly divided into a training set and a validation set in a ratio of 7∶3. Five algorithms were utilized for model development: logistic regression, random forest, extreme gradient boosting (XGBoost), support vector machine, and neural networks. Model performance was assessed using the area under the receiver operating characteristic (AUC) curve, F1 score, and calibration curves. Clinical decision curve analysis (DCA) was employed to evaluate the clinical utility of the models. SHAP values were used to interpret feature importance in the XGBoost model and enhance its explainability. Results:The XGBoost model demonstrated the best performance in predicting CLBR,with accuracy of 72.44%, AUC of 0.775, and F1 score of 0.654, accuracy and F1 score outperforming logistic regression (accuracy was 70.02%, F1 score was 0.585), random forest (accuracy was 71.69%, F1 score was 0.606), support vector machine (accuracy was 70.20%, F1 score was 0.607), and neural network (accuracy was 68.72%, F1 score was 0.560). The calibration curve of XGBoost closely aligned with the diagonal line, indicating that the predicted probabilities were very close to the actual outcomes, demonstrating good calibration. DCA indicated that the XGBoost model provided higher net benefits across a wide range of clinical decision thresholds. SHAP value analysis identified number of previous IVF failures, antral follicle count, anti-Müllerian hormone level, percentage of normal sperm morphology, and sperm DNA fragmentation index as key predictors of CLBR.Conclusion:The XGBoost model exhibits excellent predictive performance and calibration for CLBR, with SHAP values providing important insights into feature importance. This model has the potential to support the development of personalized treatment strategies in clinical practice. However, its generalizability needs to be validated using external datasets to ensure its applicability to diverse populations.

Objective To explore the association between nocturnal blood pressure decline rate and chronic heart failure(CHF).Methods In this study,a total of 711 individuals who underwent 24-h ambulatory blood pressure monitoring were divided into control group(n=433)and CHF group(n=278).The characteristics of the study population and nocturnal blood pressure decline rate were compared between CHF group and control group.Restricted spline analysis was utilized to examine the linear or non-linear association between nocturnal blood pressure decline rate and the prevalence of CHF.The relationship between nocturnal blood pressure decline rate and CHF was further investigated based on multivariable Logistic regression model.Results Nocturnal systolic blood pressure decline rate was significantly different in CHF group and control group[(3.3±7.1)mmHg vs.(5.0+6.7)mmHg,P=0.001].No significant difference in nocturnal diastolic blood pressure was found between the two groups[(5.7±7.6)mmHg vs.(6.8±7.2)mmHg,P=0.061].Restricted spline analysis showed a significant linear association between nocturnal systolic blood pressure decline rate and CHF risk.After adjusting for age,sex,smoking,body mass index,24-hour systolic blood pressure,24-hour diastolic blood pressure,type 2 diabetes mellitus and hyperlipidemia,multivariate Logistic regression analysis revealed that nocturnal systolic blood pressure decline rate was negatively associated with the prevalence of CHF(OR=0.97,95％CI:0.95-0.99;P=0.010).However,no significant association was found between nocturnal diastolic blood pressure decline rate and CHF risk.Conclusion Nocturnal systolic blood pressure decline rate is associated with the prevalence of CHF.Individuals with decreased nocturnal systolic blood pressure decline have a significantly increased risk of CHF.

Objective:Invasive pulmonary mucormycosis(PM)is a rare but highly lethal opportunistic infection.COVID-19 associated mucormycosis(CAM)is difficult to diagnose,often leading to misdiagnosis or missed diagnosis,and has poor treatment outcomes.This study reports a case of successfully treated CAM and explores optimized diagnostic and therapeutic strategies.Methods:A retrospective analysis of the diagnosis and treatment process in a 50-year-old female patient with COVID-19 associated with diabetic ketoacidosis(DKA)and invasive pulmonary mucormycosis was conducted.Combined with a literature review,the therapeutic efficacy of local bronchoscopic instillation in conjunction with systemic treatment using liposomal Amphotericin B(L-AmB)was specifically evaluated.Results:The patient was rapidly diagnosed with Rhizopus microsporus infection through metagenomic next-generation sequencing(mNGS).She subsequently received antifungal treatment with intravenous L-AmB combined with local bronchoscopic instillation.After treatment,the patient was significantly improved,with imaging studies showing gradual absorption of the lesions.Follow-up at six months revealed no recurrence.A literature review suggests that early diagnosis and multimodal therapy are key to improving survival rates in patients with CAM.Conclusion:mNGS can significantly improve the early diagnosis rate of CAM.The combination of local and systemic treatment with L-AmB is valuable in improving prognosis.Early diagnosis,multimodal antifungal therapy,and individualized management are key to increasing the survival rate of patients with CAM.

Objective To explore the mechanism of matrine in the treatment of uveal melanoma by network pharmacology,and the related results were verified by molecular docking and cell experiments.Methods The potential targets of matrine were obtained from Swiss Target Prediction,SuperPred and TCMSP databases.The targets related to uveal melanoma were obtained from GeneCards,OMIM,CTD and DrugBank databases.Protein-protein interaction(PPI)network was established to screen core targets.Gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)signal pathway analysis were carried out for potential targets.The interaction between matrine and core targets was evaluated by molecular docking technique.The effects of different concentrations of matrine(0.25 g/L,0.50 g/L,1.00 g/L,2.00 g/L)on the proliferation of uveal melanoma cells were evaluated based on CCK-8 method.Western blot was used to verify the regulatory effects of different concentrations of matrine(0.25 g/L,0.50 g/L,1.00 g/L,2.00 g/L)on PI3K-Akt signaling pathway.Results A total of 208 potential targets of matrine were identified,and 5 453 targets related to uveal melanoma were obtained.The topological analysis of PPI network revealed 8 core targets,namely interleukin-6(IL-6),tumor necrosis factor(TNF),myelocytomatosis proteins(MYC),signal transducer and activator of transcription 3(STAT3),caspase-3(CASP3),heat shock protein 90AB1(HSP90AB1),mammalian target of rapamycin(mTOR),and matrix metalloproteinase 9(MMP9).GO enrichment analysis showed that biological processes(BP)mainly included inflammatory response,protein phosphorylation and response to exogenous stimuli;cell components(CC)mainly included plasma membrane,cell surface and cytoplasm;molecular function(MF)mainly included the same protein binding,ATP binding and kinase activity.The enrichment analysis of KEGG pathway showed that the effect of matrine was mediated by viral carcinogenesis,cancer pathway,TNF signaling pathway and PI3K-Akt signaling pathway.Molecular docking showed that matrine had good binding ability with the selected core targets.The results of cell experiments showed that matrine at concentrations of 0.50 g/L,1.00 g/L and 2.00 g/L could inhibit the proliferation of MuM2B cells,and the cell survival rate gradually decreased with the increase of concentration.Matrine at concentrations of 0.50 g/L,1.00 g/L and 2.00 g/L could down-regulate the protein expression levels of p-PI3K and p-Akt,and the protein expression levels of p-PI3K and p-Akt gradually decreased with the increase of concentration.Conclusion Matrine acts on tar-gets such as IL-6,TNF,MYC,STAT3,CASP3,HSP90AB1,mTOR,MMP9,and exerts therapeutic effects on uveal melanoma by viral carcinogenesis,cancer pathway,TNF signaling pathway and PI3K-Akt signaling pathway,etc.

Liver diseases have a high prevalence rate worldwide with relatively poor long-term clinical outcomes and have become one of the leading causes of disease burden and death around the world,which poses significant challenges to public health.Eosinophils(Eos)are a class of highly conserved multifunctional immune cells that play critical effector roles in allergic diseases.In recent years,an increasing amount of evidence has shown that Eos plays an important role in the pathogenesis of liver diseases,exerting a protective or harmful effect in different liver diseases,which has become a research hotspot in this field.This article elaborates on the role and potential mechanism of action of Eos in liver diseases,in order to provide a new perspective for in-depth research on the pathogenesis of liver diseases and lay the foundation for developing therapeutic strategies targeting Eos.

Objective:To investigate the detection rates of and risk factors for psycho-cardiological diseases in civil aviation aircrews.Methods:A total of 134 civil aviation aircrews with cardiovascular diseases detected during annual physical examinations at the Aviation Health Center of China Southern Airlines Co., Ltd. in 2023 were selected. Psychological evaluation was conducted using the Patient Health Questionnaire-9 for depression screening and the Generalized Anxiety Disorder-7 for anxiety screening. The results of psychological assessments were compared across civil aviation aircrews with cardiovascular diseases and of different types. Multiple Logistic regression analysis was used to identify risk factors to psycho-cardiological diseases.Results:Among the 134 aircrews with cardiovascular diseases, 30 were found to suffer from depression, 71 from anxiety, and 9 from both. The detection rate of psycho-cardiological diseases was 68.66% (92/134) and significantly different between crews who were different in age ( P=0.013), flying hours ( χ2=9.68, P=0.035), jobs ( χ2=16.33, P=0.008), and exercise habits ( χ2=11.35, P=0.042). No significant differences were observed in detection rates between genders or between those with a family history of disease and those without (both P>0.05). Multivariate Logistic regression analysis showed that ages 40-49 (compared to ages <30, OR=2.450, 95% CI: 1.324-4.563), flying hours of 10 000-20 000 h (compared to <5 000 h, OR=2.865, 95% CI: 1.452-5.683), pilots (compared to flight attendants, OR=3.123, 95% CI: 1.671-5.832), and inactivity (compared to regular physical activity, OR=2.156, 95% CI: 1.179-3.924) were risk factors for psycho-cardiological diseases. Conclusions:The detection rate of psycho-cardiological diseases is notably high among civil aviation aircrews, with a number of risk factors.

Objective To explore the association between nocturnal blood pressure decline rate and chronic heart failure(CHF).Methods In this study,a total of 711 individuals who underwent 24-h ambulatory blood pressure monitoring were divided into control group(n=433)and CHF group(n=278).The characteristics of the study population and nocturnal blood pressure decline rate were compared between CHF group and control group.Restricted spline analysis was utilized to examine the linear or non-linear association between nocturnal blood pressure decline rate and the prevalence of CHF.The relationship between nocturnal blood pressure decline rate and CHF was further investigated based on multivariable Logistic regression model.Results Nocturnal systolic blood pressure decline rate was significantly different in CHF group and control group[(3.3±7.1)mmHg vs.(5.0+6.7)mmHg,P=0.001].No significant difference in nocturnal diastolic blood pressure was found between the two groups[(5.7±7.6)mmHg vs.(6.8±7.2)mmHg,P=0.061].Restricted spline analysis showed a significant linear association between nocturnal systolic blood pressure decline rate and CHF risk.After adjusting for age,sex,smoking,body mass index,24-hour systolic blood pressure,24-hour diastolic blood pressure,type 2 diabetes mellitus and hyperlipidemia,multivariate Logistic regression analysis revealed that nocturnal systolic blood pressure decline rate was negatively associated with the prevalence of CHF(OR=0.97,95％CI:0.95-0.99;P=0.010).However,no significant association was found between nocturnal diastolic blood pressure decline rate and CHF risk.Conclusion Nocturnal systolic blood pressure decline rate is associated with the prevalence of CHF.Individuals with decreased nocturnal systolic blood pressure decline have a significantly increased risk of CHF.

Objective:Invasive pulmonary mucormycosis(PM)is a rare but highly lethal opportunistic infection.COVID-19 associated mucormycosis(CAM)is difficult to diagnose,often leading to misdiagnosis or missed diagnosis,and has poor treatment outcomes.This study reports a case of successfully treated CAM and explores optimized diagnostic and therapeutic strategies.Methods:A retrospective analysis of the diagnosis and treatment process in a 50-year-old female patient with COVID-19 associated with diabetic ketoacidosis(DKA)and invasive pulmonary mucormycosis was conducted.Combined with a literature review,the therapeutic efficacy of local bronchoscopic instillation in conjunction with systemic treatment using liposomal Amphotericin B(L-AmB)was specifically evaluated.Results:The patient was rapidly diagnosed with Rhizopus microsporus infection through metagenomic next-generation sequencing(mNGS).She subsequently received antifungal treatment with intravenous L-AmB combined with local bronchoscopic instillation.After treatment,the patient was significantly improved,with imaging studies showing gradual absorption of the lesions.Follow-up at six months revealed no recurrence.A literature review suggests that early diagnosis and multimodal therapy are key to improving survival rates in patients with CAM.Conclusion:mNGS can significantly improve the early diagnosis rate of CAM.The combination of local and systemic treatment with L-AmB is valuable in improving prognosis.Early diagnosis,multimodal antifungal therapy,and individualized management are key to increasing the survival rate of patients with CAM.