ObjectiveTo investigate the application of the novel inflammatory factor adsorption column CA280 combined with low-dose plasma exchange （LPE） in patients with acute-on-chronic liver failure （ACLF）. MethodsA prospective cohort study was designed， and a total of 93 ACLF patients who were admitted to The Ninth Hospital of Nanchang from June 2023 to January 2025 were enrolled and randomly divided into DPMAS+LPE group with 50 patients and CA280+LPE group with 43 patients. In addition to comprehensive medical treatment， the patients in the DPMAS+LPE group received DPMAS and LPE treatment， and those in the CA280+LPE group received CA280 and LPE treatment. The two groups were observed in terms of routine blood test results， liver function parameters， renal function markers， electrolytes， coagulation function parameters， cytokines， adverse events， and 28-day prognosis before surgery （baseline）， during surgery （DPMAS or CA280）， and after surgery （after sequential LPE treatment）. The paired t-test was used for comparison of normally distributed continuous data before and after treatment within each group， and the independent-samples t test was used for comparison between groups； the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment within each group， and the Mann-Whitney U test was used for comparison between groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups， and the Spearman test was used for correlation analysis. ResultsAfter CA280 treatment， the ACLF patients had significant reductions in the levels of cytokines （IL-6， IL-8， IL-10， TNF-α， and IFN-γ）， liver function parameters （ALT， AST， ALP， TBil， DBil， Alb， and glutathione reductase）， and the renal function marker urea nitrogen （all P<0.05）， and in terms of coagulation function parameters， there were significant increases in prothrombin time， activated partial thromboplastin time （APTT）， thrombin time， and international normalized ratio （INR） and significant reductions in prothrombin activity （PTA） and fibrinogen （FIB） （all P<0.05）. Compared with the DPMAS+LPE group， the CA280+LPE group showed better improvements in the serum cytokines IL-8 （Z=-2.63， P=0.009）， IL-10 （Z=-3.94， P<0.001）， and TNF-α （Z=-1.53， P=0.023）， and the two artificial liver support systems had a similar effect in improving liver function （ALT， AST， GGT， GR， TBil， and DBil） （all P >0.05）， but the CA280+LPE group showed a significantly greater reduction in Alb （Z=-2.08， P=0.037）. CA280+LPE was more effective in reducing uric acid （Z=-2.97， P=0.003）. Compared with DPMAS+LPE， CA280+LPE treatment resulted in a significant reduction in INR （Z=-4.01， P<0.001）， a significant increase in APTT （Z=-2.53， P=0.011）， and significant greater increases in PTA （Z=-6.28， P<0.001） and FIB （Z=-3.93， P<0.001）. There were no significant differences in the incidence rates of adverse reactions and the rate of improvement at discharge between the two groups （all P>0.05）. The Spearman correlation analysis showed that IL-6 was significantly correlated with WBC （r=0.22， P=0.042）， TBil （r=0.29， P=0.005）， and FIB （r=-0.33， P=0.003）； IL-8 was positively correlated with APTT （r=0.37， P<0.001） and INR （r=0.25， P=0.013）； TNF-α was significantly correlated with WBC （r=0.40， P<0.001） and TBil （r=0.34， P<0.001）. ConclusionCompared with DPMAS， CA280 combined with LPE can effectively clear proinflammatory cytokines and improve liver function in ACLF patients， but it has a certain impact on Alb and coagulation function. This regimen provides a new option for the individualized treatment of ACLF and can improve the short-term prognosis of patients， but further studies are needed to verify its long-term efficacy.

This paper interprets the disease name related to bi （痹） disease in traditional Chinese medicine （TCM） from the perspective of micropathological phenotypes in knee osteoarthritis （KOA）. By systematically reviewing classical TCM literature on the pathogenesis and clinical features of different subtypes such as damp-retention bi， bone bi， and tendon bi， and integrating these with current research on pathological subtypes of KOA including the synovitis type， cartilage-meniscus type， and subchondral bone type， the study explores the correlation between traditional disease terms and modern micropathological phenotypes. The author proposes subtype classifications of damp-retention bi corresponding to synovial inflammation， bone bi related to abnormal subchondral bone remodeling， and tendon bi representing cartilage and meniscus degeneration. This approach provides a microscopic biological explanation for TCM syndrome differentiation and offers new perspectives for advancing integrative diagnostic and therapeutic strategies in both Chinese and western medicine.

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.

Objective:To compare the efficacy of 68Ga-Pentixafor PET/CT in guiding surgical treatment of primary aldosteronism (PA) with that of adrenal venous sampling (AVS), and to explore its value in the diagnosis and management of PA. Methods:A total of 83 patients (62 males, 21 females, age (48.5±10.4) years) who received unilateral adrenal PA based on 68Ga-Pentixafor PET/CT or AVS results at the Department of Urological Surgery of Peking Union Medical College Hospital from January 1, 2021 to May 31, 2023 were retrospectively enrolled. Clinical data of patients were collected and the postoperative benefit rates guided by the two examination methods were compared according to the international multi-center PA surgical outcome standard. Quantitative indexes in 68Ga-Pentixafor PET/CT (SUV max, ratio of lesion SUV max to normal-adrenal-tissue SUV mean (LAR), ratio of lesion SUV max to normal-liver SUV mean (LLR), and ratio of lesion SUV max to contralateral SUV max (LCR)) were obtained for comparative analysis in patients with different surgical outcomes. Mann-Whitney U test, χ2 test or Fisher′s exact test were used to analyze the data. Results:Among 83 patients, 35 underwent AVS-guided surgery and 48 underwent 68Ga-Pentixafor PET/CT-guided surgery, with no significant difference of surgical benefit rates (85.7%(30/35) vs 85.4%(41/48); χ2=0.01, P=0.970). There was no significant difference of surgical benefit rates between 2 methods in such subgroups: <35 years (2/3 vs 7/8), ≥35 years (87.5%(28/32) vs 85.0%(34/40)), males (85.2%(23/27) vs 88.6%(31/35), females (7/8 vs 10/13), patients with unilateral lesions indicated by CT results (13/15 vs 83.9%(26/31)), patients with bilateral lesions indicated by CT results (85.0%(17/20) vs 15/17) (all χ2<0.01, all P>0.05). In PET/CT group, the LCR of patients who benefited from surgery ( n=41) was higher than that of patients who did not benefit ( n=7; 3.19(2.24, 4.90) vs 1.89(1.59, 2.88); Z=-2.09, P=0.036), and other quantitative indicators also tended to be higher. Conclusions:The positive results of 68Ga-Pentixafor PET/CT and AVS have the same clinical value in guiding PA patients to receive unilateral adrenal surgery. 68Ga-Pentixafor PET/CT is expected to become a non-invasive examination method to guide the treatment decisions in PA patients.

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.

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.

Urothelial carcinoma (UC), including bladder urothelial carcinoma and upper tract urothelial carcinoma (UTUC), is the most common malignant tumor in the urinary system. Traditional cell line models fall short in simulating its tumor microenvironment and in vivo behavior. Patient-derived organoid (PDO) models offer a new way to overcome these shortcomings. This paper reviews the construction techniques of PDO models in UC, their biological simulation capabilities, and their applications in preclinical research. It also analyzes the technical limitations of these models. PDO models can retain the histological, genomic, and transcriptomic features of the parent tumor and accurately simulate the tumor microenvironment and biological behavior. They have been widely used in bladder cancer research, providing a precise platform for drug screening, personalized treatment, and immunotherapy evaluation. However, their use in UTUC research is still in its infancy. In the future, through technological optimization, PDO models are expected to enhance their value in UC research, advancing precision medicine research and clinical translation.