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.

To summarise the clinical experience of Professor TONG Xiaolin in treating prediabetes combined with overweight or obesity using the method of relieving depression and reducing turbidity. It is believed that prediabetes belongs to the category of "spleen-heat syndrome" in traditional Chinese medicine， and its core pathogenesis is center fullness with internal heat， while obesity is the initiating factor for exacerbating center fullness and internal heat， therefore， it is of great significance to reduce the risk of diabetes by interrupting the transformation between overweight， obesity and glucose metabolism abnormality. It is proposed that the main pathogenesis of prediabetes combined with overweight or obesity is qi depression and turbidity obstruction in middle jiao， with qi depression as the root and turbidity obstruction as the cause， forming a treatment idea with the method of relieving depression and reducing turbidity as the core. In clinic， Dahuang Huanglian Xiexin Decoction （大黄黄连泻心汤） is used as the basic prescription， with a primary focus on directing the turbid downward， supplemented by regulating qi， which embodies the concept of "promoting movement through descent， then figuring out the root of spleen-heat syndrome. Furthermore， the treatment is flexibly modified based on the patient's deficiency-excess syndrome to ensure individualized therapy.

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.

Syndrome differentiation and treatment is an integral part of the traditional Chinese medicine （TCM） diagnostic and therapeutic system， whose development exhibits distinct stages. This paper systematically reviews the evolutionary trajectory of syndrome differentiation and treatment， from symptom-based treatment in Inner Canon of Yellow Emperor （《黄帝内经》）， to ZHANG Zhongjing's establishment of the disease-pulse-syndrome-treatment framework， through its application and development in the Ming and Qing dynasties， and finally to its recognition as a fundamental characteristic of TCM in modern times. However， the overemphasis on syndrome differentiation and treatment， coupled with a diminished focus on disease concepts， has led to its gradual alienation as the primary diagnostic and therapeutic model. The alienation mainly manifests as a tendency to prioritize syndrome over disease， resulting in the overgeneralization and limited application of the concept， and causing a lack of specificity in practice. This paper emphasizes that a correct understanding of syndrome differentiation and treatment is a necessary premise for the deve-lopment and improvement of the TCM diagnostic and therapeutic system. By integrating modern medical diagnosis to clarify disease targets and applying TCM thinking to extract common patterns of diseases， precise alignment between syndrome differentiation and treatment and modern clinical demands can be achieved， providing a reference for addressing the contemporary challenges of syndrome differentiation and treatment.

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.

The aim of this study is to determine the effects of Inonotus obliquus polysaccharides on the main organs and hormones of male mice infected with Neosporidium.The animal model of neosporidiosis in BALB/c mice was established.After intragastric administration,the pathological changes of brain,liver and spleen were observed by histopathology,the worm load in brain,liver and spleen was detected by qPCR,and the levels of FSH,LH and T4 in serum of male mice were detected by ELISA.The results showed that compared with the blank control group,granular spherical lesions could be seen in the brain tissue of mice in the model group,with patchy necrosis of hepatocytes,splenic hemorrhage,red pulp hyperemia and a large number of red blood cell infil-tration.Inonotus obliquus polysaccharides can improve the injury of brain,liver,spleen and other organs and tissues.The worm load in the brain of the Inonotus obliquus polysaccharide group was significantly lower than that of the model group on the 14th day and 21st day(P＜0.01),and that of the liver and spleen on the 21st day was significantly lower than that of the model group(P＜0.01).The level of FSH in the model group and Inonotus obliquus polysaccharide group was signif-icantly lower than that in the blank control group(P＜0.05 or P＜0.01),while that in the Inono-tus obliquus polysaccharide group was significantly higher than that in the model group(P＜0.05 or P＜0.01).The level of LH in the model group was significantly higher than that in the blank control group(P＜0.01),while that in the Inonotus obliquus polysaccharide group was significant-ly higher than that in the blank control group on the 7th day and 42nd day(P＜0.05).There was significant difference in T4 level between the model group and the blank group(P＜0.05 or P＜0.01),while the Inonotus obliquus polysaccharide group was similar to the blank control group on the 21st and 35th day(P＞0.05).Inonotus obliquus polysaccharides can improve the damage of Neosporidium on brain,liver and spleen of male rats,reduce the insect load in brain,liver and spleen,regulate the levels of FSH,LH and T4 hormones,and maintain the stability of reproductive system.

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.

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.