Objective To construct a dynamic prediction model for JC polyomavirus (JCV) reactivation after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 128 recipients who met the inclusion criteria and received kidney transplantation in Nanfang Hospital, Southern Medical University, from June 2021 to December 2024. Dynamic Cox regression and dynamic restricted mean survival time (RMST) regression based on the landmark method were adopted to establish the dynamic prediction models, and Monte Carlo cross-validation was used to evaluate model performance. Results The dynamic models could predict the incidence and onset time of JCV reactivation within the subsequent 3 months according to covariates at each landmark time point from the 1st to the 6th month after transplantation. Remuzzi score, body mass index and warm ischemia time were independent risk factors for JCV reactivation, while a history of urinary BK polyomavirus reactivation served as a protective factor. The median values of the area under the curve, C-index and Brier score of the dynamic Cox model were 0.873, 0.851 and 0.065 respectively, and the C-index of the dynamic RMST model was 0.829, all of which were superior to those of the static model. Conclusions The landmark-based dynamic models exhibit excellent predictive performance, which may integrate baseline data and post-transplant follow-up information to realize dynamic assessment of the risk and time window of JCV reactivation, thereby providing evidence for optimizing post-operative monitoring and individualized intervention strategies.

ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

Von Hippel-Lindau syndrome is a type of neoplastic disease that can involve multiple organs and systems, and it can be manifested as pheochromocytoma in the adrenal gland. We recently admitted a patient with a complicated bilateral adrenal pheochromocytomas associated with VHL in a child. After multidisciplinary diagnosis and treatment, detailed perioperative treatment and monitoring, the patient recovered well after surgery. This article aims to increase the experience of diagnosis and treatment of VHL-pheochromocytoma in children by sharing this rare case.

Objective To explore the mechanism by which the early growth response protein 1(EGR1)/AMP-activated protein kinase(AMPK)/nuclear factor erythroid 2-related factor 2(Nrf2)pathway improves Neuro-2a cell injury via Mendelian randomization(MR),bioinformatics and in vitro models of ischemic stroke(IS).Methods The blood proteins associated with genetic susceptibility to IS were identified based on MR analysis.Then,the GSE22255 dataset was comprehensively analyzed,including GSEA,immunoinfiltration and differential expression analysis.The transcription factors closely related to the occurrence and development of IS were identified after joint analysis with MR results,and the biological functions of key genes were further verified by in vitro experiments.Results A total of 712 proteins related to IS susceptibility were identified by MR analysis.A total of 2357 differentially expressed genes were identified from the GSE22255 dataset,and 75 intersection genes and 34 transcription factors were identified after combined analysis with MR results.In vitro experiments showed that knockdown of EGR1 expression could significantly inhibit oxygen-glucose deprivation/reperfusion(OGD/R)-induced Neuro-2a cell damage,and the mechanism might be related to the up-regulation of p-AMPK and Nrf2 protein expression.Conclusion This study integrates MR analysis,transcriptomics and in vitro experiments to reveal the potential role of 75 IS susceptibility genes and transcription factor EGR1 in the pathogenesis of IS,which provides theoretical basis for the development of therapeutic drugs for IS.

Von Hippel-Lindau syndrome is a type of neoplastic disease that can involve multiple organs and systems, and it can be manifested as pheochromocytoma in the adrenal gland. We recently admitted a patient with a complicated bilateral adrenal pheochromocytomas associated with VHL in a child. After multidisciplinary diagnosis and treatment, detailed perioperative treatment and monitoring, the patient recovered well after surgery. This article aims to increase the experience of diagnosis and treatment of VHL-pheochromocytoma in children by sharing this rare case.

Objective:To investigate the learning curves of gastroscopy and colonoscopy for surgeons.Methods:Clinical data of ordinary digestive endoscopy performed by gastrointestinal surgeons in Peking University People's Hospital from March, 2022 to March, 2024 were collected retrospectively. Learning curves were plotted according to the number of examinations and learning time, and the cumulative sum control chart method was used to determine the number of cases required to achieve proficiency in endoscopic examination.Results:Six gastrointestinal surgeons (sequentially) received training in gastroscopy and colonoscopy. All surgeons were male physicians with a doctoral degree and the professional title of attending physician. The average age was (33.0 ±1.9) years, and the average job tenure was (4.0±1.8) years. The median time required for proficiency in gastroscopy was 31 weeks, with a median number of cases of 624. Similarly, the median time required for proficiency in colonoscopy was also 31 weeks but with a median number of cases of 470.Conclusions:Surgeons need at least 31 weeks of independent operation to become proficient in endoscopic examination and more than 600 cases to be proficient in gastroscopy. Surgeons with gastroscopy experience also need 31 weeks of independent operation but at least 450 cases to become proficient in colonoscopy.

Objective To explore the mechanism by which the early growth response protein 1(EGR1)/AMP-activated protein kinase(AMPK)/nuclear factor erythroid 2-related factor 2(Nrf2)pathway improves Neuro-2a cell injury via Mendelian randomization(MR),bioinformatics and in vitro models of ischemic stroke(IS).Methods The blood proteins associated with genetic susceptibility to IS were identified based on MR analysis.Then,the GSE22255 dataset was comprehensively analyzed,including GSEA,immunoinfiltration and differential expression analysis.The transcription factors closely related to the occurrence and development of IS were identified after joint analysis with MR results,and the biological functions of key genes were further verified by in vitro experiments.Results A total of 712 proteins related to IS susceptibility were identified by MR analysis.A total of 2357 differentially expressed genes were identified from the GSE22255 dataset,and 75 intersection genes and 34 transcription factors were identified after combined analysis with MR results.In vitro experiments showed that knockdown of EGR1 expression could significantly inhibit oxygen-glucose deprivation/reperfusion(OGD/R)-induced Neuro-2a cell damage,and the mechanism might be related to the up-regulation of p-AMPK and Nrf2 protein expression.Conclusion This study integrates MR analysis,transcriptomics and in vitro experiments to reveal the potential role of 75 IS susceptibility genes and transcription factor EGR1 in the pathogenesis of IS,which provides theoretical basis for the development of therapeutic drugs for IS.

Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.

Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.