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/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.

ObjectiveIdentification and analysis, animal regression test, and drug susceptibility study were conducted on a pathogenic strain causing diarrhea in cynomolgus monkeys, aiming to provide a practical basis for the clinical treatment of Citrobacter freundii. MethodsFresh fecal samples were collected from nine diarrheal cynomolgus monkeys and streaked on Salmonella-Shigella (SS) medium, LB medium, and Columbia blood agar medium, and incubated at 37 ℃ for 24 h. Subsequently, the isolated strain was identified by colony morphology observation, Gram staining, biochemical tests and 16S rRNA gene sequencing, and PCR was used to detect its major virulence genes. After propagation, the isolate was intragastrically administered to healthy cynomolgus monkeys and C57BL/6 mice for animal regression tests to evaluate its pathogenicity. Finally, the disk-diffusion method was used to detect the antimicrobial susceptibility of the isolate. ResultsA single bacterial strain, designated MF071743, was isolated from 9 fecal samples collected from diarrheal cynomolgus monkeys. The isolate formed pink, smooth, round colonies on SS medium; translucent, smooth, moist, shiny colonies with neat edges on LB medium; and smooth, moist, off-white colonies on Columbia blood agar medium. Gram staining revealed that the isolate was a Gram-negative, spore-free short bacillus. Biochemical tests showed that the isolate was positive for motility test, mannitol test, hydrogen sulfide test, methyl red test, citrate utilization test, gas production from glucose test, raffinose test, sorbitol test, and D-xylose test, but negative for phenylalanine test, gluconate test, indole test, Voges Proskauer (VP) test, urease test, lysine test, ornithine test, and adonitol test. The results of 16S rRNA gene sequencing showed that the gene sequence similarity between strain MF071743 and Citrobacter freundii was 99.0%. PCR results showed that this strain carries genes encoding the urease accessory proteins UreD, UreE, and UreF. Animal intragastric administration assays demonstrated that the strain caused loose stools in cynomolgus monkeys, and all C57BL/6 mice died within 72 h. Drug susceptibility test results indicated that the isolate was sensitive to 16 antibiotics, including ceftriaxone, amikacin, gentamicin, ceftazidime, and levofloxacin, while it exhibited resistance to 5 antibiotics, including ampicillin, cefazolin, vancomycin, erythromycin, and cephalexin. ConclusionA strain of Citrobacter freundii with certain drug resistance was isolated from the feces of diarrheal cynomolgus monkeys. The results of this study provide a reference for the diagnosis and treatment of gastrointestinal diseases in captive laboratory monkeys.

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 explore the effects of piperacillin/tazobactam combined with acetylcysteine solution on severe pneumonia after cerebral infarction,and to analyze its impact on cardiopulmonary and neurological function.METHODS A total of 86 patients with severe pneumonia after cerebral infarction admitted to Yulin Xingyuan Hos-pital from Jan.2022 to Jun.2024 were selected and divided into a control group and a study group using the ran-dom number table method(single blind),with 43 cases in each group.The control group was treated with intrave-nous drip of piperacillin/tazobactam,while the study group received additional inhalation of acetylcysteine solution based on the control group's treatment.The levels of inflammatory factors[C-reactive protein(CRP),interleukin-6(IL-6)and procalcitonin(PCT)],lung function indicators[forced vital capacity(FVC),peak expiratory flow rate(PEF),forced expiratory volume in one second(FEV1)and mean maximal expiratory flow rate(MMEF)],cardiac function indicators[left ventricular ejection fraction(LVEF),cardiac output(CO),cardiac index(CI)and stroke volume(SV)],NIH Stroke Scale(NIHSS)score,clinical efficacy,and the occurrence of adverse reactions were compared before and after treatment.RESULTS Compared with the control group,the study group had low levels of CRP,IL-6,PCT and NIHSS scores after treatment(P<0.05),and high levels of FVC,PEF,FEV1,MMEF,LVEF,CO,CI,and SV after treatment(P<0.05).The overall response rate in the study group was 95.35%,higher than 81.40%in the control group(χ2=4.074,P=0.044).There was no statistically significant difference in the incidence of adverse reactions between the control group and the study group during treatments(χ2=0.179,P=0.672).CONCLUSION Piperacillin/tazobactam combined with inhaled acetylcysteine solution for the treatment of severe pneumonia after cerebral infarction can improve clinical efficacy,reduce levels of inflamma-tory factors,and enhance cardiopulmonary and neurological functions in patients,which has a high safety profile.

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 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 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.