OBJECTIVE To study the pharmacokinetic characteristics of antidepressant active components from Jiaotai pills in healthy subjects. METHODS Eight healthy subjects （3 males and 5 females） were recruited and given a single oral dose of 8.55 g of Jiaotai pills. Venous blood samples were collected before administration （0 h） and at intervals from 0.25 to 36.0 hours post- administration. After treating the plasma samples with protein precipitation， the blood concentrations of the antidepressant active ingredients （coptisine， berberine， magnoflorine， and palmatine） in Jiaotai pills were determined using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. DAS 2.0 software was employed to calculate the pharmacokinetic parameters of healthy subjects [half-life （t1/2）， peak concentration （cmax）， time to peak concentration （tmax）， area under the concentration-time curve （AUC）， and mean residence time （MRT）] using a non-compartmental model. RESULTS After healthy subjects took Jiaotai pills， the drug-time curve of the four antidepressant active ingredients conforms to a two-compartment model and tmax values were similar， with all reaching peak blood concentrations within 2.00 to 4.00 hours post-administration. However， the t1/2 and MRT of coptisine and berberine were significantly longer than that of magnoflorine and palmatine. There were also significant differences in the AUC and cmax among the four antidepressant active ingredients， with magnoflorine exhibiting markedly higher AUC0-t and cmax compared to the other three components. CONCLUSIONS In this study，LC-MS/MS is used to analyze the pharmacokinetic characteristics of the antidepressant active ingredients from Jiaotai pills in healthy subjects， can provide valuable references for the clinical application of Jiaotai pills.

Objective To explore the application value of dual-phase dual-energy CT (DECT) perfusion imaging in preoperative lung function assessment of lung cancer patients. Methods Data were collected from patients with stageⅠA non-small cell lung cancer who underwent surgical treatment in the Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, from November 2022 to June 2024. All patients underwent DECT perfusion imaging and pulmonary function testing (PFT) before surgery. PFT observation indicators included ventilation function indicators such as forced expiratory volume in one second (FEV1), forced vital capacity (FVC), 1-second rate (FEV1/FVC), maximal voluntary ventilation (MVV), and diffusion function indicators such as diffusing capacity for carbon monoxide (DLCO) and DLCO per liter of alveolar volume (DLCO/VA). The software eXamine was used to obtain quantitative parameters of DECT perfusion imaging, including volume parameters and perfusion parameters of both lungs and each lung lobe. The correlation between the volume parameters and perfusion parameters of both lungs and the ventilation and diffusion function indicators of the patients, as well as the differences in quantitative parameters of each lung lobe, was analyzed. Results The end-inspiration lung volume and biphasic volume difference were strongly positively correlated with FEV1 and FVC (r=0.636, r=0.682, r=0.614, r=0.624, P<0.001) and moderately positively correlated with MVV and DLCO (r=0.499, r=0.514, r=0.549, r=0.447, P<0.001); the end-expiration lung volume was weakly negatively correlated with DLCO/VA (r=−0.295, P=0.026); the volume ratio was positively correlated with FEV1, FVC, MVV, and MVV% (r=0.424, r=0.399, r=0.415, r=0.310, P<0.05); the end-inspiration iodine content was weakly positively correlated with DLCO/VA% (rs=0.292, P=0.030); the end-expiration iodine content was weakly positively correlated with FEV1, FVC, MVV, DLCO%, and DLCO/VA (r=0.307, r=0.299, r=0.295, r=0.366, r=0.320, P<0.05) and moderately positively correlated with DLCO (r=0.439, P<0.001); the end-inspiration iodine concentration was negatively correlated with FEV1, FVC, MVV, and MVV% (rs=−0.407, rs=−0.426, rs=−0.352, rs=−0.277, P＜0.05); the end-expiratory phase iodine concentration was moderately positively correlated with DLCO/VA (r=0.403, P=0.002); both the iodine concentration difference and the iodine concentration ratio were moderately positively correlated with FEV1, FEV1%, FVC, MVV, MVV% (P<0.05). The lung volume and iodine concentration ratio values were both highest in the left upper lung lobe and lowest in the right middle lung lobe; the differences in lung volume, lung volume ratio, intrapulmonary iodine content, and intrapulmonary iodine concentration were all highest in the lower lobes of both lungs and lowest in the middle lobe of the right lung. Conclusion Dual-phase DECT perfusion imaging can accurately assess overall lung function and quantify regional lung function.

BACKGROUND: Endoscopic sphincterotomy (EST) is widely used to treat common bile duct stones (CBDS); however, long-term studies have revealed the increasing incidence of recurrent CBDS after EST. Loss of sphincter of Oddi function after EST was the main cause of recurrent CBDS. Reparation of the sphincter of Oddi is therefore crucial. This study aims to investigate the effectiveness and safety of endoclip papilloplasty (ECPP) for repairing the sphincter of Oddi and elucidate its mechanism. METHODS: Eight healthy Bama minipigs were randomly divided into the EST group and the ECPP group at a 1:1 ratio, and bile samples were collected before endoscopy and 6 months later. All minipigs underwent transabdominal biliary ultrasonography for the diagnosis of cholelithiasis 6 months after endoscopy. The biliary microbiota composition and alpha and beta diversity were analyzed by 16S ribosomal RNA gene sequencing. Differential metabolites were analyzed by bile acid metabolomics to explore the predictive indicators of cholelithiasis. RESULTS: Three minipigs were diagnosed with cholelithiasis in the EST group, while none in the ECPP group showed cholelithiasis. The biliary Firmicutes/Bacteroidota (F/B) ratio was increased after EST and decreased after ECPP. The Chao1 and observed species index significantly decreased 6 months after EST ( P  = 0.017 and 0.018, respectively); however, the biliary α-diversity was similar before and 6 months after ECPP. The β-diversity significantly differed in the EST group before and 6 months after EST, as well as in the ECPP group before and 6 months after ECPP (analysis of similarities [ANOSIM]: R  = 0.917, P  = 0.040; R  = 0.740, P  = 0.035; respectively). Glycolithocholic acid (GLCA) and taurolithocholic acid (TLCA) accumulated in bile 6 months after EST. CONCLUSIONS ECPP has less impact on the biliary microenvironment than EST and prevents duodenobiliary reflux by repairing the sphincter of Oddi. The bile levels of GLCA and TLCA may be used to predict the risk of cholelithiasis.
Animals ; Swine, Miniature ; Swine ; Cholelithiasis/prevention & control* ; Sphincterotomy, Endoscopic/methods* ; Sphincter of Oddi/surgery* ; Female ; Male

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.

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 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.

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.

Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.

Objective:A retrospective study was conducted to investigate the safety of Percutaneous Endoscopic Gastrostomy(PEG)in elderly patients with Amyotrophic Lateral Sclerosis(ALS)and to identify the factors influencing major complications.The aim is to establish a more robust foundation for optimizing both the procedure and its timing, thereby enhancing the evidence base for refining the surgical approach.Methods:We retrospectively collected clinical data from elderly ALS patients(≥60 years old)who underwent PEG at Peking University Third Hospital between January 2006 and January 2024.This dataset includes information on general health conditions, the progression of ALS, comorbidities, surgical details, and related complications.Additionally, we analyzed the postoperative complications experienced by the included patients, focusing specifically on the risk factors associated with aspiration pneumonia.Results:A total of 140 patients were included in the study, with a mean age of 68.2±5.9 years.Among these, 69 were male(49.3%)with a mean age of 68.4±6.5 years, and 71 were female(50.7%)with a mean age of 67.7±6.0 years.Successful outcomes were observed in 139 cases(99.3%).One case was not completed due to respiratory arrest caused by intraoperative aspiration.Postoperative complications occurred in 36 cases(25.7%), which included 9 cases of wound infection(6.4%), 1 case of abdominal infection(0.7%), 21 cases of aspiration pneumonia(15.0%), 1 case of local fistula leakage(0.7%), 2 cases of transient fever(1.4%), and 2 cases of death during hospitalization(1.4%).Both univariate and multivariate analyses indicated that an onset duration of ≤1 year( P=0.020)and a half-sitting position( P=0.022)significantly influenced the occurrence of aspiration pneumonia, acting as protective factors( β<0, OR<1). Conclusions:PEG is a safe method for providing enteral nutrition to elderly patients with ALS.While most complications associated with the procedure are mild and can be managed, Aspiration pneumonia remains a common and serious complication.However, early surgical intervention and the use of a semi-seated position during the procedure can help reduce the incidence of aspiration pneumonia.

Objective:To compare the clinical efficacy and effects on cognitive function of magnetic seizure therapy (MST) and modified electroconvulsive therapy (MECT) in the treatment of major depressive episode (MDE).Methods:From January 1, 2019 to December 31, 2021, 40 patients who met the MDE diagnostic criteria in the fifth edition of the Diagnostic Statistical Manual of Mental Disorders (DSM-5) were selected in Shanghai Mental Health Center. Participants were randomly assigned to MECT therapy group (20 patients) and MST therapy group (20 patients) using the random number table method. Both groups received MECT or MST while using serotonin reuptake inhibitors (SSRIs), 3 times a week for 4 weeks. The 17-items Hamilton Depression Rating Scale (HAMD 17) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were performed before and after treatment. HAMD 17 reduction rate and effective rate were the main assessment indicators, while RBANS total score and factor scores were considered as the secondary assessment indicators. T-test was used to compare the reduction rate of HAMD 17 between the two groups, and corrected Chi-square test or Fisher′s exact probability method was used to compare the effective rate of treatment between the two groups. HAMD 17 scores and RBANS scores before and after treatment were compared using two-factor repeated measure ANOVA. Results:There were no significant differences in baseline HAMD 17 scores and RBANS scores between 2 groups( t=0.29, P=0.773; t=0.67, P=0.509). The treatment effective rate in the MECT group was 90% (18/20), and the average reduction rate of HAMD 17 was 67.9%. Meanwhile, the effective rate of MST group was 75% (15/20), and the average reduction rate of HAMD 17 was 60.9%. There was no significant difference in the reduction rate and effective rate of HAMD 17 between the two groups ( t=0.69, P=0.493; χ2=0.16, P=0.693). The total scores and factor scores of RBANS after treatment were lower than those before treatment, with statistical significance(total scores: F=19.29, P<0.001;immediate memory score: F=6.22, P=0.020; language function score: F=9.13, P=0.006;attention score: F=5.23, P=0.031;delayed memory score: F=35.90, P<0.001). There was no significant difference in the total scores and factor scores of RBANS before and after treatment in MST group(total scores: F=0.49, P=0.490;immediate memory score: F=2.25, P=0.147;language function score: F=1.22, P=0.280;attention score: F=0.23, P=0.640;delayed memory score: F=0.02, P=0.887). Conclusions:The efficacy of MST treatment and MECT treatment in treating MDE patients seems to be comparable. MDE patients receiving MST had less impact on cognitive function compared to those treated with MECT.