ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

OBJECTIVE The emergence of evolving variants of Coronavirus disease 2019(COVID-19)has fostered the need for change of newer and adaptive treatments for these infections.During the COVID-19 pandemic and persists,traditional Chinese medicine(TCM)herbs exhibit significant bioactivity and therapeutic effect.This study is aimed to evaluate the efficacy of four TCM preparations on 28-day mortality risk of patients and changes of the laboratory indicators.METHODS The retrospective cohort study included patients with COVID-19 who were admitted to the Jiangsu Province Hospital of Chinese Medicine from December 15,2022 to January 15,2023,and those died within 48 hours of admission or cannot be tracked for outcomes were excluded.The pri-mary outcome was survival status in 28 days(death or survival)starting from the day of admission.The second outcomes were labora-tory indicators,including absolute lymphocyte count,lactate dehydrogenase,creatinine,and blood urea nitrogen.Binary logistic re-gressions were used to estimate the effect of TCM preparations on the primary and secondary outcomes in main analysis.Meanwhile,heterogeneity and robustness of results from main analysis were assessed by subgroup analyses and multiple sensitivity analyses.RESULTS 1 816 eligible patients were included in analysis dataset,including 573 patients received standard care(control group)and 1 243 patients received TCM preparations(hospital preparation group).The 28-day mortality rate of hospital preparation group was lower than that of control group(4.75%vs.14.83%),and the difference was statistically significant(χ2=54.666,P<0.001).The risk of 28-day mortality was 0.535 times lower in the hospital preparation group as compared with the control group(OR=0.46,95%CI:0.305-0.708,P<0.001)showed by multivariable binary logistic regressions.Subgroup analyses showed that taking TCM preparations reduced the 28-day mortality risk.Sensitivity analyses demonstrated that the results of the main analysis for primary outcomes were robust.For secondary outcomes,the risk of abnormal absolute lymphocyte counts at discharge in the hospital prepara-tion group decreased by 0.284 times(OR=0.703,95%CI:0.515-0.961,P=0.027).CONCLUSION Compared with standard of care,taking four hospital preparations including Kanggan Heji,Feining Heji,Qishen Gubiao Keli,and Qianghuo Qushi Qingwen Heji decreased risk of 28-day mortality among hospitalized COVID-19 patients.TCM therapy achieves adequate therapeutic effects in COVID-19.

Rapid developments in biotechnology have led researchers to seek new method to improve the efficiency and accuracy of biomedical research and drug development,promoting interdisciplinary integration.Recent advancements in artificial intelligence(AI)technologies have brought unprecedented opportunities to this field.The integration of various AI models allows researchers to better utilize multi-omics data,identify disease phenotypes,interpret animal behavior,assess treatment effects,improve experimental designs,reduce the use of experimental animals,enhance animal facility management,and improve animal welfare.This article reviews the advancements in AI biomedical research over the past decade and discusses its contributions to disease phenotype identification,the selection and design of experimental animal models,animal behavior analysis,and animal facility management.It also points out the challenges related to data standardization,AI model selection and interpretability,the extrapolation process from AI models to animal experiments and clinical practice,as well as ethical considerations in using AI in sensitive areas involving human genetics and personalized medicine.This review aims to help researchers and practitioners in relevant fields understand the current state and opportunities of AI development,thus providing support for its broader application.

Environmental pollutants generated by industrialization,characterized by microplastics,are increasingly impairing male fertility in the form of"environmental hidden toxins".Although the concept of environmental toxicity has been proposed for a long time,its practical application remains limited.Therefore,this study innovatively introduces and elaborates on the concept of"environmental hidden toxins",highlighting its pathogenic characteristics,including latency,turbidity,consumptive nature,concurrent nature,and transmutation.Environmental hidden toxin can be classified into five categories based on the properties:stagnation toxins,scorching toxins,turbid toxins,desiccating toxins,and latent toxins.The core pathogenesis of environmental hidden toxins-induced male infertility involves three stages:firstly,invading the lungs and spleen,leading to the gradual depletion of healthy qi;secondly,forming toxin-stasis complexes that obstruct the spermatic pathway;and lastly,penetrating deeply into the seminal chamber,directly damaging the genuine essence.The treatment principle emphasizes"strengthening the foundation and clearing the source,"advocating dual strategies of detoxification and strengthening vital qi.This includes enhancing clarity and lowering turbidity,fortifying the earth to generate metal to replenish healthy qi;resolving stasis,unblocking collaterals,and dispelling toxins to eliminate pathogenic factors;and nourishing the kidneys,replenishing essence,and expelling toxins to preserve the genuine essence.All the above approaches form a holistic traditional Chinese medicine(TCM)strategy that treating both manifestation and root cause of disease.The study provides theoretical foundations and offers novel clinical insights into TCM interventions for male infertility caused by environmental pollutants.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Objective:To evaluate the diagnostic value of native T1 mapping in differentiating Oxford classification (MEST-C) scores in patients with IgA nephropathy.Methods:In this prospective study, patients who underwent both T1 mapping and renal biopsy at the First Medical Center of the Chinese PLA General Hospital between April 2023 and October 2024 were consecutively enrolled. Two radiologists, blinded to clinical and pathological information, measured renal T1 mapping parameters, including cortical T1 (cT1), medullary T1 (mT1), the corticomedullary difference (ΔT1), and the corticomedullary ratio (T1 ratio). Clinical and renal biopsy data based on the Oxford classification from patients with IgA nephropathy were collected. The Oxford classification includes five indicators: Mesangial hypercellularity (M), Endocapillary hypercellularity (E), Segmental glomerulosclerosis or adhesion (S), Tubular atrophy/interstitial fibrosis (T), and Cellular or fibrocellular crescents (C). Spearman correlation analysis was applied to evaluate the associations between MEST-C scores and T1 parameters. The diagnostic performance of T1 parameters for discriminating among scores of the Oxford classification was analyzed using the receiver operating characteristic (ROC) curve.Results:A total of 124 patients with IgA nephropathy were included in this study [66 males, 58 females; age 19-70 years, 39 (30, 51) years]. Except for the E indicator, M, S, T, and C were significantly correlated with renal T1 values ( ρ=0.177-0.414, all P<0.05). cT1 showed the best diagnostic efficacy for the S score, with an area under the curve (AUC) of 0.798, a sensitivity of 68.7%, and a specificity of 88.0%. The best T1 parameter for differentiating the T score was the T1 ratio, with an AUC of 0.687, a sensitivity of 57.9%, and a specificity of 79.1%. Conclusion:Native T1 mapping can be used for the non-invasive assessment of the S and T scores in the Oxford classification of patients with IgA nephropathy.

Objective:To evaluate the efficacy of preoperative prediction of regional lymph node (RLN) metastasis in renal cell carcinoma (RCC) using a machine learning model based on habitat imaging radiomics from renal MRI.Methods:This cross-sectional study retrospectively analyzed 220 patients with RCC who underwent nephrectomy and RLN dissection at four medical centers of Chinese PLA General Hospital from January 2010 to August 2023. The cohort included 65 patients with RLN metastasis and 155 without. A stratified random sampling method was used to divide 175 patients from the first medical center into a training set ( n=140) and an internal test set ( n=35) in an 8∶2 ratio, while 45 patients from the third, fourth, and fifth medical centers constituted the external test set. The primary RCC lesions were categorized into 15 habitat subregions based on corticomedullary-phase enhancement and T 2WI signal intensity on MRI, and the volume fractions of different subregions were analyzed. In the training cohort, radiomics features derived from the habitat subregions were used to construct a radiomics model employing various machine learning algorithms, including extremely random trees (ET), gradient boosting decision trees (GBDT), random forest (RF), and support vector machine (SVM). The optimal model was selected and combined with RLN short-axis diameter to develop a combined model. The efficacy of each model in predicting RLN metastasis was evaluated using the receiver operating characteristic (ROC) curve. Results:The volume fraction of hyper-enhanced hyper-intense regions in the non-metastatic group was significantly higher than that in the metastatic group (0.05±0.09 vs. 0.02±0.03; t=3.00, P=0.003). Among the machine learning models constructed using 15 optimal habitat radiomics features, the SVM model demonstrated the best performance, with area under the ROC curve (AUC) values of 0.85 (95% CI 0.72-0.98) in the internal test set and 0.82 (95% CI 0.67-0.98) in the external test set, surpassing those of the ET, GBDT, and RF models. The combined model, integrating the SVM model with RLN short-axis diameter, achieved AUC values of 0.94 (95% CI 0.85-1.00) in the internal test set and 0.89 (95% CI 0.78-1.00) in the external test set, with RLN short-axis diameter contributing AUC values of 0.81 (95% CI 0.66-0.96) and 0.81 (95% CI 0.68-0.94), respectively. The diagnostic sensitivity of the combined model was 91.7% in the internal test set and 85.7% in the external test set, with specificities of 78.3% and 67.7%, respectively. Conclusion:The combined model based on MRI habitat imaging radiomics and RLN short-axis diameter demonstrates excellent preoperative assessment capability for RLN metastasis in RCC.

Objectives:To investigate the clinical characteristics of patients with idiopathic pulmonary arterial hypertension(IPAH)with cardiovascular comorbidities.Methods:A total of 150 patients with IPAH admitted to Fuwai Hospital,Chinese Academy of Medical Sciences from October 2014 to June 2024 were enrolled in this retrospective study.The clinical variables,cardiac structure and hemodynamic characteristics were analyzed and compared between IPAH patients with or without cardiovascular comorbidities.Results:The mean age of the 150 patients was(35.9±12.5)years,73.3%of whom were female.There were 88(58.7%)IPAH patients with cardiovascular comorbidities.Compared to those without cardiovascular comorbidities(n=62),patients with cardiovascular comorbidities were older([38.9±12.3]years vs.[31.7±11.9]years,P=0.001),and N-terminal pro-B-type natriuretic peptide level was higher(1 469.0[656.8,2 615.8]pg/ml vs.923.5[304.4,1 958.8]pg/ml,P=0.006).The hemodynamic examination indicated that patients with cardiovascular comorbidities were featured with higher mean right atrial pressure(6.0[3.3,9.0]mmHg[1 mmHg=0.133 kPa]vs.4.0[3.0,6.3]mmHg,P=0.006),but lower mixed venous oxygen saturation([67.0±7.0]%vs.[70.3±6.9]%,P=0.010)and cardiac index(2.4[1.9,2.9]L/[min·m2]vs.2.8[2.3,3.8]L/[min·m2],P=0.013).Among IPAH patients with cardiovascular comorbidities,compared to patients with 1 comorbidity,patients with≥2 comorbidities were older(51.0[40.0,63.3]years vs.35.0[29.3,43.8]years,P<0.001),left atrial anteroposterior diameter([35.6±4.8]mm vs.[30.4±4.4]mm,P<0.001)and left end-diastolic anteroposterior diameter([40.8±7.5]mm vs.[35.8±5.5]mm,P=0.006)were larger.In patients with cardiovascular comorbidities,hypertension was the most common comorbidity(48.9%).Conclusions:Patients with IPAH and cardiovascular comorbidities exhibit aging characteristics.A series of cardiovascular comorbidities,including hypertension,significantly impact the clinical features,cardiac structural parameters,and hemodynamic status of IPAH.The assessment and management of comorbidities in IPAH patients should be prioritized in the future clinical practice.

Objective To evaluate the relationship between systemic inflammation makers and bone mineral density(BMD)in male patients with type 2 diabetes(T2DM).Methods A total of 261 male patients with T2DM were selected and divided into three groups based on diagnostic criteria:the normal bone mass group(96 cases),the reduced bone mass group(111 cases)and the osteoporosis group(54 cases).Differences in systemic inflammation markers and bone metabolic markers were compared between the three groups.Multivariate ordered Logistic regression analysis was used to investigate factors influencing the progression from normal bone mass to osteoporosis in male patients with T2DM.Receiver operating characteristic(ROC)curves were used to evaluate the predictive value of inflammatory markers for osteoporosis in male patients with T2DM.Correlation analysis was conducted to investigate the correlation between inflammatory markers and BMD and bone turnover markers(BTM)in male patients with T2DM.Results Platelet count(PLT),platelet-to-lymphocyte ratio(PLR),systemic inflammatory index(SII)and neutrophil-to-lymphocyte ratio(NLR)were significantly higher in the osteoporosis group than those in the normal bone mass group(P＜0.05).Multivariate ordered Logistic regression analysis showed that PLR and SII were risk factors for the progression from normal bone mass to osteoporosis in male patients with T2DM(P＜0.05).The area under the ROC curve of PLR was 0.590,and the cut-off value was 96.67.The area under the curve of SII was 0.613,with a cut-off value of 307.9,and the area under the combined curve of the above two indicators was 0.612.In patients with osteoporosis and osteopenia,SII,PLR and PLT were negatively correlated with L1-4 BMD and left hip BMD(P＜0.05).SII was also negatively correlated with left femoral neck BMD(P＜0.05).Conclusion Inflammatory markers PLR and SII have predictive values for the progression from normal bone mass to bone loss and osteoporosis in male patients with T2DM.