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.

Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms such as bacteria. In addition to the manifestations of systemic inflammatory response syndrome and primary infection lesions， critical cases often have manifestations of organ hypoperfusion. The morbidity and mortality of sepsis have remained high in recent years， which seriously affect the quality of life of the patients. The pathogenesis of sepsis is complicated， in which uncontrollable inflammation is a key mechanism. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a key role in mediating inflammation in sepsis. The available therapies of sepsis mainly include resuscitation， anti-infection， vasoactive drugs， intensive insulin therapy， and organ support， which show limited effects of reducing the mortality. Therefore， finding new therapeutic drugs is a key problem to be solved in the clinical treatment of sepsis. In recent years， studies have shown that traditional Chinese medicine （TCM） can regulate the PI3K/Akt pathway via multiple pathways， multiple effects， and multiple targets to inhibit inflammation and curb the occurrence and development of sepsis， which has gradually become a hot spot in the prevention and treatment of sepsis. Moreover， studies have suggested that TCM has unique advantages in the treatment of sepsis. TCM can regulate the PI3K/Akt signaling pathway to inhibit inflammation， reduce oxidative stress， and control apoptosis in the prevention and treatment of sepsis. Despite the research progress， a systematic review remains to be performed regarding the TCM treatment of sepsis by regulating the PI3K/Akt signaling pathway. After reviewing relevant papers published in recent years， this study systematically summarizes the relationship between PI3K/Akt pathway and sepsis and the role of TCM in the treatment of sepsis， aiming to provide new ideas for the potential treatment of sepsis and the development of new drugs.

Objective:To systematically evaluate the application of patient-reported outcome measures (PROMs) in adult lung transplant recipients, and to explore their clinical value in assessing quality of life following transplantation.Methods:This study was a systematic review. Relevant studies published between January 2014 and July 2024 were searched in the PubMed and OVID Medline databases using keywords such as "lung transplantation" "quality of life" "HRQoL" "health indice" "patient-reported outcome measure" "questionnaire" "profile" "scale" "score" and "survey". Only English-language articles were included. Eligible studies were those that applied PROMs to assess quality of life in adult lung transplant recipients and were approved by ethics committees. Reviews, case reports, abstracts, and studies involving transplant candidates or recipients of lung-liver or lung-kidney combined transplantation were excluded. Data extracted included basic study information, study design, participant characteristics, and PROM usage. Frequently used PROMs and lung transplant-specific PROMs were summarized, and results with clearly reported time points were analyzed.Results:A total of 63 studies were included, comprising 54 (85.7%) observational studies and 9 (14.3%) interventional studies. The majority of studies originated from the United States (18 studies, 28.6%). A total of 55 different PROMs were identified, including 30 generic and 25 disease-specific instruments. The five most frequently used PROMs were the Short Form 36 (SF-36; 30 studies, 47.6%), the EuroQol 5 Dimension (EQ-5D; 12 studies, 19.0%), the St. George's Respiratory Questionnaire (SGRQ; 11 studies, 17.5%), the Hospital Anxiety and Depression Scale (HADS; 7 studies, 11.1%), and the modified Medical Research Council dyspnea scale (mMRC; 5 studies, 7.9%). Lung transplant-specific PROMs included the Lung Transplant Quality of Life questionnaire (LT-QOL), the Lung Transplant Valued Life Activities (LT-VLA) scale, and the Pulmonary-Specific Quality of Life Scale (PQLS), which were applied in only 6 studies (9.5%). Across studies, lung transplantation was associated with significant improvements in recipients' quality of life, sustained over a follow-up period of 3 to 60 months.Conclusions:A wide range of PROMs have been employed to assess health-related quality of life in lung transplant recipients; however, transplant-specific PROMs remain relatively scarce. PROMs provide valuable insights for reflecting and dynamically monitoring long-term quality of life, supplementing evidence for clinical decision-making, and optimizing post-transplant care strategies.

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Objective To study the inhibitory effect of secondary metabolites of Pseudomonas aeruginosa(PA)on Candida albicans(CA)and to explore some of the mechanisms.Methods PA and CA strains were i-solated from clinical specimens from the hospital.Then,PA strains with inhibitory effects on CA were screened through cross-line test and co-incubation test,and crude extracts of PA secondary metabolites were prepared,and were tested together with pyocyanin,phenazine-1-carboxylic acid,1-hydroxyphenazine,and 3-ox-ododecyl-l-homoserine lactone(3-oxo-HSL).The inhibitory effects of various PA secondary metabolites on CA were determined through minimum inhibitory concentration test,minimum bactericidal concentration test,time-sterilization curve measurement,and XTT method activity measurement test,and some mechanisms by which PA secondary metabolites inhibited CA were explored.Results The strongest inhibitory effect on CA was 1-hydroxyphenazine,and at a concentration of 6.250 μg/mL,the relative activity of CA decreased to 0.00%.Next were pyocyanin and PA crude extract,and the relative fungal activity of CA decreased to 0.00%at concentrations of 200 and 100 μg/mL.1-hydroxyphenazine,pyocyanin,3-oxo-HSL and PA crude extract all had inhibitory effects on the formation of CA hyphae.Reactive oxygen species(ROS)were generated in CA cells treated with 1-hydroxyphenazine,phenazine 1-carboxylic acid,pyocyanin,and PA crude extract,and the highest levels of ROS were induced by pyocyanin and 1-hydroxyphenazine.Conclusion Phenazine secondary metabolites 1-hydroxyphenazine and pyocyanin have significant inhibitory effects on the growth and activity of CA,and both induce the highest amount of ROS.The quorum-sensing signal molecule 3-oxo-HSL have no in-hibitory effect on CA growth,but have a significant inhibitory effect on the formation of fungal hyphae.

Objective:To systematically evaluate the application of patient-reported outcome measures (PROMs) in adult lung transplant recipients, and to explore their clinical value in assessing quality of life following transplantation.Methods:This study was a systematic review. Relevant studies published between January 2014 and July 2024 were searched in the PubMed and OVID Medline databases using keywords such as "lung transplantation" "quality of life" "HRQoL" "health indice" "patient-reported outcome measure" "questionnaire" "profile" "scale" "score" and "survey". Only English-language articles were included. Eligible studies were those that applied PROMs to assess quality of life in adult lung transplant recipients and were approved by ethics committees. Reviews, case reports, abstracts, and studies involving transplant candidates or recipients of lung-liver or lung-kidney combined transplantation were excluded. Data extracted included basic study information, study design, participant characteristics, and PROM usage. Frequently used PROMs and lung transplant-specific PROMs were summarized, and results with clearly reported time points were analyzed.Results:A total of 63 studies were included, comprising 54 (85.7%) observational studies and 9 (14.3%) interventional studies. The majority of studies originated from the United States (18 studies, 28.6%). A total of 55 different PROMs were identified, including 30 generic and 25 disease-specific instruments. The five most frequently used PROMs were the Short Form 36 (SF-36; 30 studies, 47.6%), the EuroQol 5 Dimension (EQ-5D; 12 studies, 19.0%), the St. George's Respiratory Questionnaire (SGRQ; 11 studies, 17.5%), the Hospital Anxiety and Depression Scale (HADS; 7 studies, 11.1%), and the modified Medical Research Council dyspnea scale (mMRC; 5 studies, 7.9%). Lung transplant-specific PROMs included the Lung Transplant Quality of Life questionnaire (LT-QOL), the Lung Transplant Valued Life Activities (LT-VLA) scale, and the Pulmonary-Specific Quality of Life Scale (PQLS), which were applied in only 6 studies (9.5%). Across studies, lung transplantation was associated with significant improvements in recipients' quality of life, sustained over a follow-up period of 3 to 60 months.Conclusions:A wide range of PROMs have been employed to assess health-related quality of life in lung transplant recipients; however, transplant-specific PROMs remain relatively scarce. PROMs provide valuable insights for reflecting and dynamically monitoring long-term quality of life, supplementing evidence for clinical decision-making, and optimizing post-transplant care strategies.

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.

ObjectiveTo explore the prevalence difference between northwest dryness syndrome and blood stasis syndrome of coronary heart disease （CAD） and their correlations with major adverse cardiovascular events （MACE）. MethodsThe medical records including general information and risk factors for vascular diseases （gender， age， smoking history， diabetes history， hypertension history， chronic kidney disease history and body mass index）， laboratory indicators （fasting blood glucose， triglyceride， high density lipoprotein cholesterol， etc.） of 499 CAD patients in the Department of Cardiology of the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University from November 1st， 2015 to September 30th，2020 were collected， and whether they suffered from northwest dryness syndrome or blood stasis syndrome was judged. The incidence of MACE was followed up for one year. The differences of cardiovascular risk factors between the northwest dryness syndrome and blood stasis syndrome of CAD were compared， and the correlation with MACE was analyzed. ResultsAmong the 499 CAD patients， there were 128 cases （25.65%） of simple blood stasis syndrome， 33 cases （6.61%） of simple northwest dryness syndrome， 209 cases （41.88%） of northwest dryness syndrome plus blood stasis syndrome， and 129 （25.85%） cases of not blood statis syndrom either northwest dryness syndrome. Univariate regression analysis showed that smoking history， diabetes history， fasting blood glucose abnormality， triglyceride abnormality， and high density lipoprotein cholesterol abnormality were positively correlated with northwest dryness syndrome in CAD patients （OR＞1， P＜0.05）， while smoking history， abnormal triglyceride and abnormal high density lipoprotein cholesterol were positively correlated with blood stasis syndrome in CAD patients （OR＞1， P＜0.05）. Multivariate regression analysis showed that the history of diabetes， abnormal triglyceride and abnormal high density lipoprotein cholesterol were positively correlated with northwest dryness syndrome of CAD （P＜0.05）. Smoking history， abnormal triglycerides and abnormal high density lipoprotein cholesterol were positively correlated with blood stasis syndrome （P＜0.05）. Association rule analysis showed that the confidence of CAD patients with northwest dryness syndrome complicated with blood stasis syndrome was 86.36%， and that of patients with blood stasis syndrome complicated with northwest dryness syndrome was 62.02%. Among the 499 patients， 96 had MACE in one year， accounting for 19.24% of the total. Logistics regression analysis showed that the correlation with incidence of MACE in CAD patients within one year from strong to weak was northwest dryness syndrome plus blood stasis syndrome ［OR = 5.113， 95%CI （3.118， 8.387）， P＜0.001）］， blood stasis syndrome［OR = 4.630， 95%CI （2.394， 8.955）， P＜0.001］， northwest dryness syndrome ［OR = 4.395， 95%CI （2.642， 7.309）， P＜0.001］. ConclusionBlood stasis syndrome is the main syndrome type of CAD in Xinjiang Uygur Autonomous Region. CAD patients with northwest dryness syndrome are more likely to have blood stasis syndrome， and most suffer from both northwest dryness syndrome and blood stasis syndrome simultaneously. There is the strongest correlation between northwest dryness syndrome plus blood stasis syndrome and 1-year occurrence of MACE in CAD.

Objective To construct c-Met CAR-T cells secreting PD-1 antibodies to reduce immune inhibitory effect of tumor cells and enhance the efficacy of CAR-T cell therapy against pancreatic cancer.Methods Kaplan-Meier Plotter,GEPIA,and Timer 2.0 bioinformatics databases were used to analyze c-Met expression in pancreatic cancer and its correlation with survival and immune infiltration status.In clinical samples of pancreatic cancer and pancreatic cancer Aspc-1 cells,c-Met and PD-L1 expressions were detected using immunohistochemistry or flow cytometry.Using gene editing technology,PD-1 secretory antibodies and HIS tags were linked to second-generation c-Met CAR molecules to construct PD-1/c-Met CAR plasmids,which were then packaged into lentiviruses for infection of activated T cells.The positive rate and cell subset distribution of CAR-T cells were analyzed with flow cytometry,and secretory PD-1 antibodies in cell supernatants were detected using Western blotting.The target cell killing efficiency and proliferative activity of the modified CAR-T cells were evaluated after activation,and cytokine secretion was analyzed using ELISA.Results The expression of c-Met was significantly higher in pancreatic cancer than in normal tissues,and its expression level was negatively correlated with the patients'survival and positively correlated with immune cell infiltration.The clinical samples of pancreatic cancer tissues expressed significantly higher levels of c-Met and PD-L1 than the adjacent tissues,and 90.7%and 57.7%of Aspc-1 cells were positive for c-Met and PD-L1,respectively.The constructed PD-1/c-Met CAR-T cells were capable of secreting PD-1 antibodies and showed a significantly higher killing efficiency against tumor cells than c-Met CAR-T cells at an effector-to-target ratio of 20:1,with also a higher proliferative activity after target cell stimulation and higher levels of IL-2 and TNF-α secretin.Conclusion PD-1/c-Met CAR-T cells have higher killing efficiency against pancreatic cancer cells with also higher proliferative activity than c-Met CAR-T cells.