ObjectiveTo elucidate the underlying mechanism through which Zhuluan decoction suppresses excessive autophagy in human ovarian granulosa cells （KGN） and ameliorates premature ovarian insufficiency （POI） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsThe optimal concentration of cyclophosphamide for inducing a POI model in KGN cells was identified via the cell counting kit-8 （CCK-8） assay. Subsequently， the impacts of varying concentrations of Zhuluan decoction-containing serum on the viability of the KGN cell model were assessed. After the optimal drug concentration was determined， KGN cells were categorized into the following groups： blank control （20% blank serum）， model （20% blank serum + 5 μmol·L^-1 cyclophosphamide）， Zhuluan decoction-containing serum （20% Zhuluan decoction-containing serum + 5 μmol·L^-1 cyclophosphamide）， autophagy inhibitor （20% blank serum + 5 μmol·L^-1 cyclophosphamide + 20 μmol·L^-1 chloroquine phosphate）， autophagy inhibitor + Zhuluan decoction-containing serum （20% Zhuluan decoction-containing serum + 5 μmol·L^-1 cyclophosphamide + 20 μmol·L^-1 chloroquine phosphate）， and estradiol valerate （20% estradiol valerate-containing serum + 5 μmol·L^-1 cyclophosphamide）. Following 48 hours of incubation， flow cytometry was utilized to measure the apoptosis rate of KGN cells in each group. Western blotting was employed to quantify the protein levels of PI3K， phosphorylated （p）-Akt， Akt， p-mTOR， and mTOR， along with the expression levels of autophagy-related proteins such as Beclin1， autophagy-related 5 homolog （ATG5）， and microtubule-associated protein 1 light chain 3 （LC3）， in each group. Additionally， monodansylcadaverine （MDC） staining was performed to evaluate the extent of autophagy in each group. ResultsIncubation of KGN cells with 5 μmol·L^-1 cyclophosphamide for 48 h successfully established a POI model， marked by a significant inhibition of KGN cell proliferation. Notably， the inhibitory effect of cyclophosphamide on KGN cell proliferation exhibited a positive correlation with its concentration. Zhuluan decoction-containing serum at 20% and 30% promoted cell proliferation and mitigated the inhibitory effect of cyclophosphamide on KGN cell proliferation， with comparable therapeutic efficacy observed at both concentrations. Compared with the blank control group， the model group displayed an elevated apoptosis rate （P<0.01）， reduced protein levels of PI3K， p-Akt， and p-mTOR （P<0.01）， increased protein levels of Beclin1， LC3， and ATG5 （P<0.01）， no significant alterations in the protein levels of Akt and mTOR， and an enhanced MDC autophagy fluorescence intensity （P<0.01）. In comparison to that the model group， the apoptosis rates in the blank control group， model group， Zhuluan decoction-containing serum group， autophagy inhibitor group， autophagy inhibitor + Zhuluan decoction-containing serum group， and estradiol valerate group all reduced （P<0.05， P<0.01）， with the most pronounced reduction observed in the autophagy inhibitor + Zhuluan decoction-containing serum group. The protein levels of PI3K， p-Akt， and p-mTOR were higher in other groups than in the model group （P<0.05， P<0.01）， being the highest in the autophagy inhibitor + Zhuluan decoctio-containing serum group （P<0.01）. The protein levels of Beclin1 and ATG5 were lower in other groups than in the model group （P<0.05， P<0.01）. The expression level of LC3 declined in the Zhuluan decoction-containing serum group and the estradiol valerate group （P<0.05， P<0.01）， while it decreased without statistical significance in the autophagy inhibitor group and the autophagy inhibitor + Zhuluan decoction-containing serum group. ConclusionZhuluan decoction may activate the PI3K/Akt/mTOR pathway to inhibit excessive autophagy and counteract the detrimental effects of cyclophosphamide on the KGN cell model， thus managing POI.

ObjectiveTo elucidate the underlying mechanism through which Zhuluan decoction suppresses excessive autophagy in human ovarian granulosa cells （KGN） and ameliorates premature ovarian insufficiency （POI） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsThe optimal concentration of cyclophosphamide for inducing a POI model in KGN cells was identified via the cell counting kit-8 （CCK-8） assay. Subsequently， the impacts of varying concentrations of Zhuluan decoction-containing serum on the viability of the KGN cell model were assessed. After the optimal drug concentration was determined， KGN cells were categorized into the following groups： blank control （20% blank serum）， model （20% blank serum + 5 μmol·L^-1 cyclophosphamide）， Zhuluan decoction-containing serum （20% Zhuluan decoction-containing serum + 5 μmol·L^-1 cyclophosphamide）， autophagy inhibitor （20% blank serum + 5 μmol·L^-1 cyclophosphamide + 20 μmol·L^-1 chloroquine phosphate）， autophagy inhibitor + Zhuluan decoction-containing serum （20% Zhuluan decoction-containing serum + 5 μmol·L^-1 cyclophosphamide + 20 μmol·L^-1 chloroquine phosphate）， and estradiol valerate （20% estradiol valerate-containing serum + 5 μmol·L^-1 cyclophosphamide）. Following 48 hours of incubation， flow cytometry was utilized to measure the apoptosis rate of KGN cells in each group. Western blotting was employed to quantify the protein levels of PI3K， phosphorylated （p）-Akt， Akt， p-mTOR， and mTOR， along with the expression levels of autophagy-related proteins such as Beclin1， autophagy-related 5 homolog （ATG5）， and microtubule-associated protein 1 light chain 3 （LC3）， in each group. Additionally， monodansylcadaverine （MDC） staining was performed to evaluate the extent of autophagy in each group. ResultsIncubation of KGN cells with 5 μmol·L^-1 cyclophosphamide for 48 h successfully established a POI model， marked by a significant inhibition of KGN cell proliferation. Notably， the inhibitory effect of cyclophosphamide on KGN cell proliferation exhibited a positive correlation with its concentration. Zhuluan decoction-containing serum at 20% and 30% promoted cell proliferation and mitigated the inhibitory effect of cyclophosphamide on KGN cell proliferation， with comparable therapeutic efficacy observed at both concentrations. Compared with the blank control group， the model group displayed an elevated apoptosis rate （P<0.01）， reduced protein levels of PI3K， p-Akt， and p-mTOR （P<0.01）， increased protein levels of Beclin1， LC3， and ATG5 （P<0.01）， no significant alterations in the protein levels of Akt and mTOR， and an enhanced MDC autophagy fluorescence intensity （P<0.01）. In comparison to that the model group， the apoptosis rates in the blank control group， model group， Zhuluan decoction-containing serum group， autophagy inhibitor group， autophagy inhibitor + Zhuluan decoction-containing serum group， and estradiol valerate group all reduced （P<0.05， P<0.01）， with the most pronounced reduction observed in the autophagy inhibitor + Zhuluan decoction-containing serum group. The protein levels of PI3K， p-Akt， and p-mTOR were higher in other groups than in the model group （P<0.05， P<0.01）， being the highest in the autophagy inhibitor + Zhuluan decoctio-containing serum group （P<0.01）. The protein levels of Beclin1 and ATG5 were lower in other groups than in the model group （P<0.05， P<0.01）. The expression level of LC3 declined in the Zhuluan decoction-containing serum group and the estradiol valerate group （P<0.05， P<0.01）， while it decreased without statistical significance in the autophagy inhibitor group and the autophagy inhibitor + Zhuluan decoction-containing serum group. ConclusionZhuluan decoction may activate the PI3K/Akt/mTOR pathway to inhibit excessive autophagy and counteract the detrimental effects of cyclophosphamide on the KGN cell model， thus managing POI.

Objective To explore an artificial intelligence (AI)-based method for automated hand hygiene monitoring and to compare the effectiveness of three algorithms (UniFormerV2, TDN, C3D) in recognizing hand hygiene steps in surgical settings, thereby aiding hospital infection control. Methods From April to October 2024, we non-invasively collected 641 video recordings of healthcare staff performing hand hygiene at four-bay scrub sinks in two tertiary hospitals using overhead HD cameras. The dataset was annotated by five trained experts for model training and validation. Results Following training on 385 samples, internal validation (n=119) showed the C3D model achieved 81% accuracy, 87% recall, and an 83% F1-score. The TDN model achieved 93%, 91%, and 92% for the same metrics. The UniFormerV2 model outperformed both, with an accuracy, recall, and F1-score of 93%—an improvement of over 10 percentage points compared to traditional CNNs (TDN, C3D). It also achieved an 84% accuracy in external validation, demonstrating strong generalization. Conclusion The UniFormerV2 model is more accurate than CNN-based models for hand hygiene step recognition and shows robust performance in external validation. It presents a viable tool for healthcare facilities to enhance hand hygiene management, ultimately improving medical quality and patient safety.

OBJECTIVE To systematically evaluate the efficacy and safety of 6 kinds of GLP-1RAs in the treatment of type 2 diabetes mellitus （T2DM） patients with overweight or obesity， and to provide evidence-based reference for clinical practice. METHODS A comprehensive search was conducted in PubMed， Embase， Web of Science， the Cochrane Library， CNKI， VIP， Wanfang Data， and CBM from the inception to December 1， 2025. Randomized controlled trials （RCTs） were screened according to inclusion and exclusion criteria. Data extraction and risk of bias assessment were performed on the included studies. Network meta-analysis was conducted using Stata 17.0 software. RESULTS A total of 29 eligible RCTs were included， involving 7 404 patients. Six GLP-1RAs were evaluated： semaglutide， liraglutide， exenatide， dulaglutide， polyethylene glycol loxenatide， and beinaglutide. In terms of glycemic control， semaglutide had the highest probability of ranking first in reducing glycated hemoglobin （HbA1c） and fasting plasma glucose levels， followed by polyethylene glycol loxenatide. In terms of weight management， semaglutide showed the highest probability of ranking first， followed by liraglutide and exenatide. Regarding safety， dulaglutide had the highest probability of ranking first in reducing the incidence of gastrointestinal adverse events； none of the GLP-1RAs significantly increased the risk of severe hypoglycemia. Subgroup analysis revealed that liraglutide 1.8 mg， qd and exenatide extend-release 2.0 mg， qw demonstrated superior efficacy in reducing HbA1c and body weight compared with other doses/dosage forms of the same agents. CONCLUSIONS For T2DM patients with overweight or obesity， semaglutide offers the greatest benefits in glycemic control and weight reduction， while dulaglutide demonstrates superior gastrointestinal tolerability. Liraglutide 1.8 mg， qd and exenatide extend-release 2.0 mg， qw show relatively better overall efficacy in glycemic control and weight reduction among the same agents.

The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."

In recent years,significant progress has been made in the radiological diagnosis,molecular profiling,and systemic therapy of cholangiocarcinoma(CCA).Nevertheless,there are still many challenges in early identification,precise classification,and effective management.Given the marked heterogeneity between CCA subtypes and the recent research advances,the European Association for the Study of the Liver has developed evidence-based management recommendations for extrahepatic CCA,covering both perihilar and distal subtypes.This guideline particularly emphasizes the need for precise classification systems,the integration of emerging molecular studies,and practical diagnostic and therapeutic strategies reflecting real-world clinical scenarios.

Objective:To assess the long-term risk of relapse in patients with Crohn's disease (CD) who discontinued infliximab (IFX) monoclonal antibody and to identify risk factors associated with relapse.Methods:A single-center retrospective observational study was conducted from February 2006 to October 2016. The study included CD patients who were treated with scheduled IFX infusions at the First Affiliated Hospital of Sun Yat-sen University and assessed in corticosteroid-free clinical remission at the time of withdrawal were included. The primary outcome was clinical relapse. We evaluated the risk of relapse using Kaplan-Meier method. Factors associated with time to relapse was identified using the multiple Cox proportional hazards regression analysis.Results:We included 97 eligible patients, and 75 (77.3%) experienced a relapse after a median follow-up time of 124 months. Among them, 45 patients (46.4%) relapsed within 3 years after IFX withdrawal. The 1-, 2-, 3-, 5-, and 10-year relapse-free survival were 79.4%, 59.8%, 52.6%, 42.0% and 22.6%, respectively. Risk factors for relapse included age ≤ 16 ( HR = 2.62, 95% CI: 1.30-5.31; P = 0.007) and failure to achieve biological remission (CRP > 3 mg/L, HR = 2.37, 95% CI: 1.29-4.36; P = 0.006) at drug withdrawal. Induction with biologics or systemic steroids were both effective (89%-100% relieved) in relapsers. Conclusions:Nearly half of CD patients relapsed within 3 years after discontinuation of IFX treatment. Early age of discontinuation and failure to achieve serum biological remission at the time of discontinuation are independent predictors of clinical relapse.

Objective:To investigate the effectiveness and safety of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer who progressed after first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi).Methods:Clinical pathological data and prognostic information were retrospectively collected from 30 ovarian cancer patients who underwent SCS between January 2018 and June 2024. The Kaplan-Meier method was used to analyze the second progression-free survival (PFS2) time and 3-year overall survival (OS) rate.Results:(1) Primary treatment: the median age at diagnosis was 51.3 years. A total of 40% (12/30) patients underwent primary debulking surgery with an expectation of achieving no gross residual disease (R0), while 60% (18/30) received neoadjuvant chemotherapy and interval debulking surgery. Optimal cytoreduction was achieved in 93% (28/30) of patients. BRCA1/2 gene testing was performed in 29 patients (testing rate 97%, 29/30), identifying 11 BRCA-mutated (37%, 11/30) and 18 BRCA wild-type (60%, 18/30) patients. The median duration of PARPi maintenance therapy among the 30 patients was 11.9 months; patients with BRCA gene mutations had a median duration of 19.2 months, while those with BRCA wild-type had a median duration of 10.1 months. (2) Secondary surgery: pathologically confirmed recurrence patterns, single lesion in 9 patients (30%, 9/30), oligo-lesion (2 lesions) in 3 patients (10%, 3/30), and multi-lesion (≥3 lesions) in 18 patients (60%, 18/30). Among the 30 patients, optimal cytoreduction was achieved in 97% (29/30) of SCS patients, with suboptimal cytoreduction in 1 patient (3%, 1/30). Adjuvant chemotherapy included platinum+paclitaxel in 24 (80%, 24/30) patients and platinum+liposomal doxorubicin in 6 (20%, 6/30) patients. PARPi re-treatment was administered to 17 patients (57%, 17/30) after chemotherapy. (3) Efficacy and safety: as of the follow-up cutoff in June 2024, the median follow-up time was 28.0 months. A total of 19 (63%, 19/30) patients experienced the next recurrence. The median PFS2 time after SCS was 18.5 months. Recurrence occurred in 7 BRCA-mutated and 12 BRCA gene wild-type patients. Median PFS2 time was significantly longer in BRCA-mutated patients compared to BRCA wild-type patients (25.7 vs 14.1 months; P=0.028). Three deaths occurred during follow-up, resulting in a 3-year OS rate of 90%. Among the 30 patients, postoperative complications occurred in 4 patients (13%, 4/30). One patient developed a ureteral fistula on 7 days post-SCS requiring ureteral stenting, and one patient was transferred to the intensive care unit on 1 day post-SCS due to hypovolemic shock. No deaths occurred within 30 days after SCS. Conclusion:For platinum-sensitive recurrent ovarian cancer patients progressed after first-line PARPi maintenance therapy who are anticipated to achieve R0 resection, SCS represents a safe and effective second-line treatment option.

Objective:To explore the protective effect and mechanism of Rougan Tongluo Decoction on ischemic stroke induced motor disorder rats based on NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Gasdermin D(GSDMD)/Cysteinyl aspartate specific proteinase 1(Caspase-1)pathway.Methods:Establishing a rat model of ischemic stroke with motor disorders using the modified suture method.The rats were randomly divided into model control group,Rougan Tongluo Decoction low,medium and high dose groups and butylphthalide soft capsule group,with 10 rats in each group,Another 10 rats were selected as sham surgery group.After 28 days of administration,the neurological function of rats in each group was evaluated by the Zea-Longa scoring method;The forelimb grasping force of rats in each group was detected by grip tester;The coordination ability of rats was evaluated by rat-mouse rotarod instrument;The expression of NLRP3,GSDMD,Caspase-1 protein and Interleukin-1β(IL-1β)was detected by immunohistochemistry.Results:The NLRP3,Caspase-1,GSDMD protein and IL-1β expression Zea-Longa score in the cerebral cortex of the model control group were significantly higher than those in sham surgery group,the forelimb grasping force was lower than that in sham surgery group,and the latency period for turning the baton was shorter than that in sham surgery group(P＜0.05).The Zeba-Longa score,NLRP3,Caspase-1,GSDMD protein and IL-1 β expression in the cerebral cortex the butylphthalide soft capsule group,low dose,medium dose,high dose Rougan Tongluo decoction group were lower than those in model control group,the forelimb grasping force was higher than that in model control group,and the latency period for turning the baton was longer than that in model control group(P＜0.05).Conclusion:Rougan Tongluo Decoction may alleviate inflammatory response by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to improve neurological function and motor ability in ischemic stroke induced motor disorder rats.

Objective To explore the differences in coronary-based and lesion-based fat attenuation index(FAI)in patients with coronary artery disease(CAD)across different risk stratifications,and to compare the diagnostic efficiency of coronary-based and lesion-based FAI in stable CAD patients with myocardial ischemia.Methods The patients with CAD,who underwent preoperative coronary CT angiography(CCTA)and invasive coronary angiography(ICA)with coronary fractional flow reserve(FFR)measurement between Apr 2019 and Oct 2022 in Zhongshan Hospital,Fudan University,were retrospectively collected.There were 57 cases of acute coronary syndrome(ACS)patients and 206 cases of stable CAD patients included following inclusion criteria.The coronary-based and lesion-based FAI were measured,and the differences in these indices were recorded and analyzed among ACS patients,ischemic and non-ischemic groups of stable CAD patients(FFR=0.8 as the threshold).ROC curves were utilized to assess the diagnostic efficiency of coronary-based and lesion-based FAI for myocardial ischemia in stable CAD patients.Results The coronary-based FAI and lesion-based FAI in ACS patients were significantly higher than those in stable CAD patients[coronary-based FAI:(-72.40±6.83)HU vs.(-76.82±9.01)HU,P<0.001;lesion-based FAI:(-65.65±4.79)HU vs.(-77.48±8.64)HU,P<0.001].Among stable CAD patients,the lesion-based FAI in the ischemic group was significantly higher than that in the non-ischemic group[(-69.28±5.65)HU vs.(-80.10±7.75)HU,P<0.001].The diagnostic efficiency of lesion-based FAI for predicting myocardial ischemia in stable CAD patients was superior to coronary-based FAI(AUC:0.892 vs.0.525,Z=9.803,P<0.001).Conclusion Coronary-based and lesion-based FAI tended to be higher in ACS patients than in stable CAD patients,suggesting a potential for stratifying CAD patients with different risks.Lesion-based FAI showed some promise in evaluating myocardial ischemia among stable CAD patients.