OBJECTIVE To explore and predict the quality markers （Q-markers） of Compound xiebai capsules for the treatment of chronic obstructive pulmonary disease （COPD） by constituents analysis combined with network pharmacology and molecular docking studies， and to establish the quality standard of Compound xiebai capsules. METHODS UHPLC-TOF-MS was used for qualitative analysis of Compound xiebai capsules， and the candidate Q-markers of Compound xiebai capsules were screened by combining network pharmacology and molecular docking technology. Further， HPLC was applied to establish the fingerprints of 15 batches of Compound xiebai capsules and to conduct quantitative analysis of the main components. RESULTS A total of 51 components were identified from Compound xiebai capsules. Among them， 15 components， namely oxyberberine， methylworenine， coptisine， tetrahydroberberine， epiberberine， berberine， magnoflorine， gandensin， cucurbitacin D， hydroxygenkwan， jatrorrhizine， columbamine， quercetin， cucurbitacin R， and palmatine， were determined as the candidate Q-markers for Compound xiebai capsules in the treatment of COPD. A total of 13 common peaks were calibrated in the fingerprints of 15 batches of Compound xiebai capsules for COPD treatment， with similarity values ranging from 0.976 to 0.999 compared to the reference fingerprint. Seven components were identified among these peaks， namely peak 5 （magnoflorine）， peak 8 （jatrorrhizine）， peak 9 （epiberberine）， peak 10 （columbamine）， peak 11 （coptisine）， peak 12 （palmatine）， and peak 13 （berberine）. Their respective contents were （0.267±0.048）， （0.453±0.084）， （0.572±0.160）， （0.392±0.074）， （1.076±0.273）， （1.477±0.271）， and （6.664±1.249） mg/g （ n ＝3）. CONCLUSIONS This study predicted 15 candidate Q-markers of Compound xiebai capsules in the treatment of COPD and established the fingerprint along with a quantitative determination method for seven major components.

Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective To investigate the effect of withaferin A on aquaporin 4(AQP4)expression and brain edema in rats with traumatic brain injury(TBI).Methods A TBI rat model was established using the modified free-fall Feeney method,following which the rats were divided into model group and low-dose,medium-dose and high-dose withaferin A groups.Another sham operation group was set up,with 15 rats in each group.Withaferin A was administered once a day by intraperitoneal injection for seven consecutive days.The neurological function of the rats was evaluated using the neurological severity score(NSS),the brain water content was measured using the dry-wet spe-cific gravity method,the blood brain barrier permeability was measured using the Evans Blue method,and the histopathological changes of the cerebral cortex were observed by HE staining.Further,the apoptosis level of the hippocampal cells was observed by TUNEL staining and the expression levels of AQP4 mRNA in the cerebral cortex was detected by real-time quantitative PCR.The expression levels of rhe AQP4 protein in the cerebral cortex,and that of Bax,Bcl-2 and cleaved caspase-3 proteins in the hippocampus were detected by Western blotting.Results Medium and high doses of disolanesin A significantly improved the histopathological changes in the cerebral cortex and decreased the neurological impairment,brain water content and blood brain barrier permeability scores in TBI rats.Simultaneously,A QP4 mRNA and protein expression levels in the cerebral cortex,and Bax and cleaved caspase-3 protein expression and apoptosis levels in the hippocampal tissues of TBI rats decreased;however,Bcl-2 protein expression levels increased.Conclusion Withaferin A can reduce brain edema after TBI and improve neurological function.The mechanism may be related to the inhibition of AQP4 expression.

Objective To investigate the effect of withaferin A on aquaporin 4(AQP4)expression and brain edema in rats with traumatic brain injury(TBI).Methods A TBI rat model was established using the modified free-fall Feeney method,following which the rats were divided into model group and low-dose,medium-dose and high-dose withaferin A groups.Another sham operation group was set up,with 15 rats in each group.Withaferin A was administered once a day by intraperitoneal injection for seven consecutive days.The neurological function of the rats was evaluated using the neurological severity score(NSS),the brain water content was measured using the dry-wet spe-cific gravity method,the blood brain barrier permeability was measured using the Evans Blue method,and the histopathological changes of the cerebral cortex were observed by HE staining.Further,the apoptosis level of the hippocampal cells was observed by TUNEL staining and the expression levels of AQP4 mRNA in the cerebral cortex was detected by real-time quantitative PCR.The expression levels of rhe AQP4 protein in the cerebral cortex,and that of Bax,Bcl-2 and cleaved caspase-3 proteins in the hippocampus were detected by Western blotting.Results Medium and high doses of disolanesin A significantly improved the histopathological changes in the cerebral cortex and decreased the neurological impairment,brain water content and blood brain barrier permeability scores in TBI rats.Simultaneously,A QP4 mRNA and protein expression levels in the cerebral cortex,and Bax and cleaved caspase-3 protein expression and apoptosis levels in the hippocampal tissues of TBI rats decreased;however,Bcl-2 protein expression levels increased.Conclusion Withaferin A can reduce brain edema after TBI and improve neurological function.The mechanism may be related to the inhibition of AQP4 expression.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of ileocecal valve lipoma.Methods:A retrospective cohort study was performed on data of ileocecal lipoma patients who underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2013 to June 2023. According to the lesion location, the patients were divided into ileocecal valve group and cecum group. The operation time, operation speed, en bloc resection rate, complications, and follow-up outcomes between the two groups were compared.Results:A total of 59 patients with ileocecal lipoma were enrolled, including 31 patients in the ileocecal valve group and 28 patients in the cecum group.There were no significant differences in gender, age, specimen size, or lesion size between the two groups ( P>0.05). Lipomas in both the ileocecal valve group and the cecum group were successfully resected by ESD. The en bloc resection rates were 100.0% (31/31) and 92.9% (26/28) respectively, and the difference was not statistically significant ( χ2=0.033, P=0.133). Median operative duration significantly differed between the two groups ( ileocecal valve group 26 min VS cecum group 20 min, Z=-0.136, P=0.027), as did resection speed (ileocecal valve group 0.14 cm2/min VS cecum group 0.24 cm2/min, Z=-0.223, P=0.022). Adverse events included one postoperative fever in the ileocecal valve group and one delayed bleeding in the cecum group. During the median follow-up of 38 months (7-106 months), there was no case of residual tumor or recurrence. Conclusion:Despite technical challenges in ESD of ileocecal valve lipoma, it is still a safe, feasible and effective treatment method.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

Objective To evaluate the value of modified percutaneous endoscopic gastrostomy(PEG)for patients with amyotrophic lateral sclerosis(ALS)and dysphagia.Methods From January 2018 to December 2023,47 patients with ALS were treated with modified PEG in our hospital.The surgery was performed under local anesthesia.The patients were placed in a semi-seated position,and the surgeon performed surgery with an ultra-fine endoscope through oral entrance to the stomach.Results The modified PEG were successfully completed in all the 47 cases.The operation time was5-20 min[mean,(10.3±1.7)min].The postoperative hospitalization lasted for2-8 d(mean,2.8 d).Postoperative complications occurred in6 cases(12.8%),including aspiration pneumonia in4 cases(8.5%)and incision infection in2 cases(4.3%).The body mass index was17.06±0.89 before PEG and 18.15±0.81 at 3 months after PEG,with significant difference(t=-10.373,P=0.000).Conclusion For ALS patients with dysphagia,modified PEG is feasible,which significantly improves nutritional status of patients.

Objective To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective To evaluate the value of modified percutaneous endoscopic gastrostomy(PEG)for patients with amyotrophic lateral sclerosis(ALS)and dysphagia.Methods From January 2018 to December 2023,47 patients with ALS were treated with modified PEG in our hospital.The surgery was performed under local anesthesia.The patients were placed in a semi-seated position,and the surgeon performed surgery with an ultra-fine endoscope through oral entrance to the stomach.Results The modified PEG were successfully completed in all the 47 cases.The operation time was5-20 min[mean,(10.3±1.7)min].The postoperative hospitalization lasted for2-8 d(mean,2.8 d).Postoperative complications occurred in6 cases(12.8%),including aspiration pneumonia in4 cases(8.5%)and incision infection in2 cases(4.3%).The body mass index was17.06±0.89 before PEG and 18.15±0.81 at 3 months after PEG,with significant difference(t=-10.373,P=0.000).Conclusion For ALS patients with dysphagia,modified PEG is feasible,which significantly improves nutritional status of patients.