Based on the implementation of GMP, comprehensive improvement of quality control measures, and consideration of the 3Rs principle for experimental animals, Several years ago, WHO, the European Pharmacopoeia and the FDA gradually abolished the testing for abnormal toxicity of biological products, and the Chinese Pharmacopoeia 2025 Edition(Volume Ⅲ)also revised the testing for abnormal toxicity of biological products. In order to help users of the Chinese Pharmacopoeia(Volume Ⅲ) better understand and implement this pharmacopoeia, this article provides a detailed review of the changes in regulatory concepts for abnormal toxicity test in various countries and the process of gradually phasing out abnormal toxicity test, as well as the actual situation of China’s pharmaceutical industry. It also interprets the ideas and considerations for revising the Chinese Pharmacopoeia 2025 Edition(Volume Ⅲ) on abnormal toxicity test for biological products.

The lacrimal gland organoids are innovative in vitro cultured tissue model that mimics the lacrimal gland, retaining its original histological and molecular biological properties. This model can more accurately reproduce the physiological environment of the lacrimal gland, including its ductal system and tear film protein secretion. It offers a new platform for studying the physiopathological basis of the lacrimal gland, establishing disease models, conducting regenerative medicine applications, and performing drug screening. Currently, organoids technology is continuously evolving, with ongoing updates to the methods for in vitro culturing of the lacrimal gland. These advancements gradually address challenges related to cultivation complexity, cost, and time, demonstrating a wide range of application potential. In this paper, we summarize the latest progress in lacrimal gland organoids research both domestically and internationally, exploring the development of lacrimal gland organoids, 3D construction technologies, and their potential for clinical applications, in order to provide new insights for clinical research on lacrimal gland-related diseases and to promote broader application of lacrimal gland organoids in drug development and personalized diagnosis and treatment.

The lacrimal gland organoids are innovative in vitro cultured tissue model that mimics the lacrimal gland, retaining its original histological and molecular biological properties. This model can more accurately reproduce the physiological environment of the lacrimal gland, including its ductal system and tear film protein secretion. It offers a new platform for studying the physiopathological basis of the lacrimal gland, establishing disease models, conducting regenerative medicine applications, and performing drug screening. Currently, organoids technology is continuously evolving, with ongoing updates to the methods for in vitro culturing of the lacrimal gland. These advancements gradually address challenges related to cultivation complexity, cost, and time, demonstrating a wide range of application potential. In this paper, we summarize the latest progress in lacrimal gland organoids research both domestically and internationally, exploring the development of lacrimal gland organoids, 3D construction technologies, and their potential for clinical applications, in order to provide new insights for clinical research on lacrimal gland-related diseases and to promote broader application of lacrimal gland organoids in drug development and personalized diagnosis and treatment.

Objective To investigate the influencing factors of antibiotic-associated diarrhea(AAD)following congenital heart disease(CHD)surgery in pediatric patients,develop a nomogram-based predictive model,and validate its efficacy.Methods A retrospective analysis was conducted on the clinical data of pediatric patients who underwent CHD surgery in the Pediatric Intensive Care Unit(PICU)of a tertiary hospital in Guang-dong Province from July 2022 to July 2024.Patients were categorized into an AAD group and a non-AAD group.Univariate and multivariate logistic regression analyses were performed to identify risk factors for AAD occurrence following CHD surgery.A risk prediction model was developed,and a nomogram was constructed.The predictive performance of the model was evaluated using the Receiver Operating Characteristic(ROC)curve to calculate the area under the curve(AUC),the Hosmer-Lemeshow goodness-of-fit test,calibration curves,and clinical decision curve analysis.External validation of the model was conducted using data from patients in the Surgical Intensive Care Unit(SICU).Results The incidence of AAD following CHD surgery was 48.52%(229 out of 472 cases).Risk factors for AAD included the combined use of antibiotics,mechanical ventilation,elevated C-reactive protein levels,prolonged surgical duration,and extended antibiotic usage time(all with OR>1,P<0.05).Conversely,probiotic administration was identified as a protective factor(OR<1,P<0.05).The predictive model demon-strated excellent discrimination,as evidenced by the ROC curve areas:0.922(95%CI:0.894～0.951)in the modeling group,0.886(95%CI:0.838～0.915)in the internal validation group,and 0.862(95%CI:0.784～0.941)in the external validation group.Additionally,the model exhibited satisfactory calibration,as indicated by the Hosmer-Lemeshow test results:χ2=7.96,P=0.538 in the modeling group;χ2=4.24,P=0.895 in the inter-nal validation group;and χ2=9.923,P=0.270 in the external validation group.Furthermore,the model provided significant clinical utility.Conclusions Combined antibiotic use,duration of antibiotic therapy,mechanical ventilation,surgical duration,C-reactive protein(CRP)levels,and probiotic administration are key factors influ-encing the occurrence of AAD.The risk prediction model developed based on these variables demonstrates robust predictive performance and can serve as a valuable reference for the development and implementation of preventive and therapeutic strategies in clinical practice.

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.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

Objective To investigate the effects and mechanism of Dahuang Lingxian Prescription on bile duct reaction of cholestatic liver fibrosis rats caused by bile duct ligation.Methods A total of 40 SD rats were randomly divided into blank group,model group,ursodeoxycholic acid group and Dahuang Lingxian Prescription group,with 10 rats in each group.Except for the blank group,the remaining groups of rats underwent bile duct ligation surgery to establish a cholestatic liver fibrosis model.After surgery,the ursodeoxycholic acid group was given ursodeoxycholic acid solution by gavage,Dahuang Lingxian Prescription group was given Dahuang Lingxian Prescription solution by gavage,and the blank group and model group were given equal volume of normal saline by gavage,once a day for 3 consecutive weeks.The activities of serum AST,ALT,ALP,GGT and the contents of TBIL,TBA were tetected,the morphology of liver tissue was observed by HE staining,and the liver fibrosis was observed by Masson staining,immunohistochromic staining and Western blot were used to detect the expressions of CK19,CK7,EpCAM and SOX9 proteins.Results Compared with the blank group,the liver surface of the model group rats was rough,with a harder texture and obvious graininess,HE staining showed damage to the liver lobule structure,forming pseudo lobules,a large number of bile duct hyperplasia and inflammatory cell infiltration,and a significant increase in collagen fiber deposition(P<0.01);the activities of serum AST,ALT,ALP,GGT,as well as the contents of TBIL and TBA significantly increased(P<0.01);the positive expressions of CK19,CK7 and EpCAM in liver tissue significantly increased(P<0.01),and the protein expressions of CK19,CK7,EpCAM and SOX9 significantly increased(P<0.01).Compared with the model group,the appearance and texture of the liver of the rats in the ursodeoxycholic acid group and Dahuang Lingxian Prescription group were relatively softer,the lobular structure was less damaged,the inflammatory cells infiltration was less,the collagen fiber deposition was significantly reduced(P<0.01),the activities of serum AST,ALT,ALP,GGT,and the contents of TBIL and TBA were significantly decreased(P<0.01);the expressions of TBA and TBIL were significantly decreased(P<0.01),the positive expressions of CK19,CK7 and EpCAM significantly decreased(P<0.01),and the protein expression of CK19,CK7,EpCAM and SOX9 significantly decreased(P<0.01).Conclusion Dahuang Lingxian Prescription can inhibit the bile duct reaction associated with liver progenitor cells,decrease the expression of CK19,CK7,EpCAM and SOX9,and thus improve the cholestatic liver fibrosis of rats induced by bile duct ligation.

Driven by the"Big Health"concept,chronic disease management has gradually shifted from single-treatment approaches to comprehensive health maintenance.This paper analyzes the challenges in the development of community-based re-habilitation for chronic diseases in China,including workforce shortages,policy support gaps,funding constraints,and health ed-ucation deficiencies.Implementation pathways are proposed,such as strengthening rehabilitation teams,improving community re-habilitation management systems,diversifying funding sources,and promoting health education.Future directions include con-structing a multimodal collaborative"hospital-community-pharmacy"network,advancing integrated healthcare and prevention models,emphasizing scientific multi-morbidity management,and adopting AI-driven medical technologies.These strategies aim to optimize service models,enhance the overall effectiveness of community-based chronic disease rehabilitation,and support the implementation of the Healthy China initiative.

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.