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 investigate the impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer (GBC).Methods:The multi-center real-world study was conducted. The clinicopathological data of 629 patients with GBC, who were admitted to 14 medical centers including The First Affiliated Hospital of Army Medical University from the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, from April 2020 to April 2024 were collected. There were 225 males and 404 females, aged (64±10)years. Patients underwent open curative-intent resection for GBC. Observation indicators: (1)surgery, postoperative complica-tions and adverse outcomes; (2) analysis of risk factors affecting postoperative adverse outcomes in patients and population attributable fraction (PAF). Missing data in predictor variables were addressed using multiple imputation with chained equations, while cases with missing outcome variables were addressed using the "multiple imputation then deletion (MID)" strategy. The severity of multicollinearity among independent variables was assessed using the variance inflation factor (VIF) test. Multivariable possion regression models with log link and robust error variance were construc-ted incorporating restricted cubic splines (3 knots) to address nonlinear relationships in continuous variables, calculating adjusted relative risk ( RR) with corresponding 95% confidence interval ( CI). Adjusted PAF was calculated for each imputed dataset using the AF package of R software, with subsequent pooling performed according to Rubin's rules. Results:(1) Surgery, postoperative complications and adverse outcomes. All 629 patients underwent curative-intent resection for GBC, of which 143 cases had postoperative complications, including 68 cases of intra-abdominal ascites, 39 cases of pulmonary infection, 21 cases of bile leakage, 12 cases of intra-abdominal hemorrhage, 11 cases of liver failure, 10 cases of pan-creatic fistula, 10 cases of wound infection, 10 cases of gastroparesis, 7 cases of cholangitis, 7 cases of sepsis. The same patient could have more than one kind of complication. Of 629 patients, there were 19 cases of postoperative 90-day death and 11 cases of missing data, 42 cases with post-operative 90-day reoperation and 7 cases with missing data, 44 cases with postoperative 90-day readmission and 3 cases with missing data, 155 cases with prolonged postoperative hospital stay and 3 cases with missing data. (2) Analysis of risk factors affecting the postoperative adverse outcomes in patients and PAF. Results of multivariate analysis showed that pulmonary infection and liver failure were independent risk factors for postoperative 90-day mortality ( RR=3.74, 12.15, 95% CI as 1.18-11.83, 1.98-74.48, P<0.05). Pulmonary infection demons-trated the highest PAF as 4.61% (95% CI as 3.94%-5.28%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, and intra-abdominal hemorrhage were independent risk factors for post-operative 90-day reoperation ( RR=4.80, 3.62, 3.46, 4.99, 95% CI as 2.49-9.26, 1.42-9.21, 1.34-8.92, 1.55-16.06, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 8.65% (95% CI as 8.22%-9.08%, P<0.05). Intra-abdominal ascites, bile leakage, and liver failure were independent risk factors for postoperative 90-day readmission ( RR=6.20, 3.33, 14.33, 95% CI as 3.21-11.95, 1.33-8.35, 3.72-55.28, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 9.11% (95% CI as 8.85%-9.37%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, liver failure, and wound infection were independent risk factors for prolonged postoperative hospital stay ( RR=2.29, 2.21, 2.26, 2.14, 3.35, 95% CI as 1.63-3.23, 1.41-3.46, 1.32-3.86, 1.11-4.13, 1.70-6.60, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 6.03% (95% CI as 5.71%-6.35%, P<0.05). Conclusion:Pulmonary infection is the most significant risk factor for postoperative 90-day mortality after curative-intent resection for GBC, while intra-abdominal ascites is the most significant risk factor for postoperative 90-day reoperation, postoperative 90-day readmission, and prolonged postoperative hospital stay.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective:To assess the safety of a novel domestically developed direct visualization system of peroral cholangiopancreatoscopy for the exploration of biliary tract.Methods:Clinical data from 384 patients with biliary tract diseases who underwent endoscopic retrograde cholangiopancreatography (ERCP) at the Endoscopy Center of Shanghai Xuhui District Central Hospital from November 2017 to December 2022 were retrospectively analyzed. Patients were categorized into 2 groups based on the type of cholangioscope: the novel cholangiopancreatoscopy system group ( n=159) and the SpyGlass group ( n=225). In the novel cholangiopancreatoscopy system group, the new direct visualization system of China-made peroral cholangiopancreatoscopy was used for bile duct exploration, while the SpyGlass group utilized the SpyGlass system for bile duct inspection. Propensity score matching (PSM) was used as a nearest-neighbor method with a caliper of 0.01 to minimize confounding factors, resulting in a balanced sample of 122 patients in each group after matching. The primary outcome was the incidence of short-term complications, with secondary outcomes including technical success rates and post-treatment outcomes. Results:After PSM, there were no significant differences in baseline characteristics between the two groups ( P>0.05). Regarding short-term postoperative complications, pancreatitis occurred in 1.6% (2/122) of patients in the novel cholangiopancreatoscopy system group and 7.4% (9/122) in the SpyGlass group. The new system significantly reduced the incidence of post-procedure pancreatitis ( χ2=4.665, P=0.031). The cholecystitis was absent in the novel cholangiopancreatoscopy system group, while it occurred in 0.8% (1/122) cases in the SpyGlass group, with no significant difference between the two groups after the procedure ( P=1.000). Regarding technical success rate, the novel system group achieved a rate of 99.2% (121/122), while the SpyGlass group achieved 97.5% (119/122) ( P=0.622). A slightly higher success rate was observed in the novel system group.There were 81 cases of postoperative biliary drainage in the novel cholangiopancreatoscopy system group and 74 cases in the SpyGlass group. Conclusion:The novel direct visualization system of peroral cholangiopancreatoscopy is safer than SpyGlass in the exploration of biliary system diseases. Endoscopists are encouraged to choose the appropriate cholangioscopy system based on individual patient characteristics for the direct visualization, diagnosis, and treatment of biliary diseases.

Objective:To explore the causal relationship between 1 400 blood metabolites and hyperthyroidism or hypothyroidism by using Mendelian randomization(MR) approach.Methods:This study employed a bi-directional Mendelian randomization analysis and sourced data of blood metabolites related to hyperthyroidism and hypothyroidism from the genome-wide association study(GWAS) database. R software and TwoSampleMR software package were used for analysis. The inverse variance weighting method(IVW) was used as the main method, and MR-Egger regression, weighted median method, simple mode and weighted mode were used as supplementary methods to analyze the causal relationship between blood metabolites and hyperthyroidism and hypothyroidism. The false-positive rate was corrected by false discovery rate(FDR, FDR<0.2) to control for false positives; Meta-analysis of different sample pools was performed for overall assessment. Results:The analysis found three blood metabolites significantly linked to hypothyroidism: pregnenediol disulfate(IVW: OR=1.068, 95% CI 1.032-1.106, P<0.001), 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE(IVW: OR=0.891, 95% CI 0.840-0.944, P<0.001), and linoleic-arachidonic glycerin(IVW: OR =0.923, 95% CI 0.885-0.963, P<0.001). Glutamine was also noted(IVW: OR=0.998, 95% CI 0.997-0.999, P<0.001). Reverse MR showed no significant correlation between hyperthyroidism and the four metabolites(IVW: P>0.05). Validation from FinnGen Biospecimen Library and UKB Biospecimen Library confirmed these findings. Conclusions:Among 1 400 blood metabolites, pregnenediol disulfate showed a positive correlation with hypothyroidism. In contrast, 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE and linoleic-arachidonic glycerin exhibited negative correlations with hypothyroidism, while glutamine showed a negative correlation with hyperthyroidism. This study offers insights into the pathogenesis, early screening, and treatment of hyperthyroidism and hypothyroidism.

Objective:To analyze the three-dimensional radiographic characteristics of solid variant of odontogenic keratocyst(SOKC)using multi-slice spiral tomography(MSCT).Methods:Clinical records,histopathological reports and MSCT images of 8 patients were retrospectively acquired,radiographic features,including lesion site,size,borders,jaw expansion,internal structures and relationship with surrounding tissues were analyzed.Results:8 cases(4 males and 4 females)aged 37-65 years were included.Among them,4 lesions were located in the maxilla and the other 4 in mandible.Clinically,the lesions manifested as an enlargement of the affected area in the jaw bone,with pain present in 6 cases.On MSCT scans,all lesions showed evident jaw expansion.The boundaries of the lesions were clear in 3 cases,and unclear in 5 cases.4 cases exhibited multilocular radiolucent lesions,while the other 4 cases showed mixed radiolucent/opaque lesions resembling fibro-osseous lesion.The maxilla lesions involved the palate,na-sal cavity,maxillary sinus and orbital floor.All mandible SOKCs were recurrent and infectious,with involvement of the surrounding soft tissue.Conclusion:SOKC exhibits imaging characteristics that differentiate from conventional odontogenic keratocysts.Radio-graphically,it presents as a benign or low-grade malignant solid jaw mass.

With the rising prevalence of chronic diseases and an aging population,China's traditional segmented health-care delivery model is increasingly inadequate for meeting the growing demand for long-term,systematic health management.In response,the"Physician-Pharmacist Co-management"model has emerged,aiming to enhance the quality and continuity of care through close collaboration between physicians and pharmacists.This paper starts from the concept and origin of"Physician-Phar-macist Co-management"model,focusing on its China-specific advantages shaped by national healthcare policies and clinical real-ities.Unlike the internationally recognized Collaborative Drug Therapy Management(CDTM)model,the Chinese approach re-flects local healthcare structures and needs.Using obstructive pulmonary disease(COPD)as a case study,we examine the mod-el's application and value in managing chronic respiratory diseases.Data indicate that,after the implementation of"physician-pharmacist co-management"model in COPD patients,the CAT score decreased by approximately 24％,the annual rate of acute exacerbation-related hospitalizations declined by about 72％,and the proportion of patients with regular pulmonary rehabilitation exercise habits increased by roughly 3.3-fold.Additionally,the percentage of patients without adverse reactions rose from 47.37％to 64.41％,and the vaccination rate increased by about 2.7-fold.These findings demonstrate the model's significant advantages in improving clinical outcomes,enhancing patient adherence,and reducing healthcare costs.Despite benefits,howev-er,the"Physician-Pharmacist Co-management"model in China faces several challenges,including limited public awareness,gaps in pharmacist training,and insufficient policy support.To address these challenges,this study recommends strengthening public education,establishing comprehensive evaluation systems for pharmaceutical professionals,and improving incentive mech-anisms.Overall,the findings suggest that the"Physician-Pharmacist Co-management"model holds considerable promise for im-proving the quality of chronic disease management,enhancing patient adherence,and optimizing healthcare resource utilization in China.

Objective:To explore the position and length of anchor placement during the repair of anterior talofibular ligament (ATFL) in adolescents with unclosed epiphyseal plates by measuring the relevant data in three-dimensional CT.Methods:A total of 100 three-dimensional CT images of adolescent patients with unclosed epiphyseal plates were collected from the database of the Radiology Center of Renhe Hospital Affiliated to China Three Gorges University from January 1, 2017 to January 1, 2024. There were 69 males and 31 females, aged 12.38±0.90 years (range, 11-14 years), 47 on the left side and 53 on the right side, with a height of 155.72±5.84 cm (range, 145-175 cm), a weight of 48.02±5.93 kg (range, 40-72 kg), and a body mass index (BMI) of 19.77±1.61 kg/m 2 (range, 17.69-24.91 kg/m 2). The built-in measurement tool of the picture archiving and communication system (PACS) was used to measure the angle (α) between the direction of the nail placement and the longitudinal axis of the fibula, the distance between the nail placement point and the posterior edge of the fibula ( d), and the height from the nail placement point to the level of the fibula tip ( h) to evaluate the position and length of the anchor placement. Results:In adolescent patients, α was 47.50°±3.28° (range, 40.00°-56.00°), d was 17.12±1.80 mm (range, 11.70-21.90 mm), and h was 5.21±1.17 mm (range, 3.40-7.90 mm). The α, d and h of male patients were 47.48°±3.13° (range, 42.00°-56.00°), 17.49±1.54 mm (range, 14.45-21.90 mm) and 5.25±1.07 mm (range, 3.70-7.90 mm), respectively. Those of female patients were 47.55°±3.66° (range, 40.00°-53.00°), 16.30±2.07 mm (range, 11.65-20.30 mm) and 5.07±1.56 mm (range, 3.40-7.00 mm), respectively. There was a significant difference in d between male and female patients ( t=3.193, P=0.002), but there was no significant difference in α and h ( t=0.098, P=0.922; t=0.296, P=0.770). Conclusions:The safe range of anchor placement during ATFL anatomical repair in adolescents with unclosed epiphyseal plates is about 3.40-7.90 mm above the tip of fibula and 56°-90° with the longitudinal axis of fibula. Male patients with unclosed epiphyseal plates should choose anchors with a length of 14 mm and shorter, while females should choose anchors with a length of 10.8 mm.

Objective To explore the effect of young plasma intraperitoneal injection on the fertility and ovarian function of aging mice and analyze its potential molecular mechanism.Methods Fifty-four-week-old female C57BL/6 mice and 8-week-old male C57BL/6 mice were selected.Among them,the female mice were randomly divided into three groups:the young plasma group,the aging plasma group and the normal saline group.The young plasma group and the aging plasma group received intraperitoneal injection of plasma from young(25-29 years old)and elderly(45-49 years old)female donors,respectively.Each injection was 500 μL,administered every other day for 2 weeks.The saline group received an equal volume of saline.After the last injection,mating experiments were conducted to evaluate fertility.Ovarian histopathological changes were observed by HE staining.Oocytes and fertilized eggs were collected after superovulation and cultured in vitro to assess oocyte quality and embryo developmental potential.Transcriptomic analysis of ovarian tissue was performed,followed by KEGG and GO enrichment analysis.Results Compared with the normal saline group and the aging plasma group,the number of offspring increased in the young plasma group,which reflected higher extrusion rate of first polar body(PB1),decreased fragmentation rate of oocytes and increased conversion rate of two-cell embryos and increased formation rate of blastocysts.There were no significant differences in these indicators between the aging plasma group and the normal saline group.Transcriptomic sequencing revealed that the differentially expressed genes in ovarian tissue of the young plasma group were mainly involved in steroid biosynthesis and metabolic pathways.Among them,the expression level of steroid sulfatase protein was significantly upregulated.Conclusion Systemic infusion of young plasma enhances the reproductive potential of aging ovaries in elderly mice.The sulfated steroid metabolites in plasma may be key substances in restoring ovarian function and delaying the process of ovarian aging.

Background and Aims:Perihilar cholangiocarcinoma(pCCA)is associated with poor prognosis.Radical resection remains the mainstay of treatment;however,high recurrence rates and limited overall survival(OS)after surgery.Metabolic syndrome(MetS)has been linked to unfavorable outcomes in various malignancies,but its impact on postoperative outcomes in pCCA is unclear.This study aimed to evaluate the influence of MetS on perioperative and long-term outcomes in patients undergoing radical resection for pCCA.Methods:A retrospective analysis was conducted on 223 patients who underwent radical resection for pCCA at the First Affiliated Hospital of Army Medical University between January 2018 and December 2023.Patients were categorized into a MetS group(n=50)and a non-MetS group(n=173)according to diagnostic criteria.Perioperative complications,overall survival(OS),and recurrence-free survival(RFS)were compared between groups.Prognostic factors were identified using multivariate analysis.Results:No significant differences were observed between the two groups regarding median hospital stay,overall complications,or severe complications(all P＞0.05).The 1-,3-,and 5-year OS rates in the MetS group were 62.3％,22.3％,and 0,respectively,compared with 78.2％,39.5％,and 22.0％in the non-MetS group.Corresponding RFS rates were 46.2％,16.9％,and 0 in the MetS group vs.63.8％,29.6％,and 18.8％in the non-MetS group.Median OS and RFS were significantly shorter in the MetS group than in the non-MetS group(15.0 vs.27.0 months;12.0 vs.21.0 months;P=0.021 and P=0.037,respectively).Multivariate analysis identified MetS and major vascular invasion as independent predictors of OS,while MetS,jaundice,R0 resection,and major vascular invasion were independent predictors of RFS(all P＜0.05).Conclusion:MetS is significantly associated with worse long-term survival and higher recurrence risk after radical resection for pCCA.Incorporating MetS into preoperative assessment and postoperative management strategies may help improve patient outcomes.