OBJECTIVE To assess the bleeding risk signals associated with the concomitant use of direct oral anticoagulants （DOACs） and triazole antifungals， and to provide pharmacovigilance evidence for the safety evaluation and monitoring of combined clinical use. METHODS Adverse event reports involving the concomitant use of DOACs and triazole antifungals were extracted from the US FDA Adverse Event Reporting System （FAERS） from the first quarter of 2004 to the third quarter of 2025. Nine bleeding-related preferred terms （PTs） were selected. The Ω shrinkage measure， additive model， multiplicative model， and combined risk ratio method were employed to detect drug-drug interaction signals. The strength of positive signals was further analyzed based on the Ω shrinkage measure. RESULTS A total of 790 adverse event reports involving the concomitant use of DOACs and triazole antifungals were included， among which 229 reports involved nine bleeding-related PTs. A total of 13 signals were consistently identified as posit ive by all four methods. These signals involved six drug combinations： apixaban-fluconazole， apixaban-posaconazole， rivaroxaban-itraconazole， dabigatran etexilate-fluconazole， apixaban-voriconazole， and dabigatran etexilate-itraconazole. The Ω shrinkage measure showed that the apixaban-posaconazole combination exhibited stronger signals for bleeding （ Ω ＝2.73， Ω 025 ＝2.05） and hemoptysis （ Ω ＝2.17， Ω 025 ＝0.83）； the apixaban-fluconazole combination exhibited stronger signals for hematoma （ Ω ＝2.30， Ω 025 ＝1.47） and hematuria （ Ω ＝1.71， Ω 025 ＝0.74）； the rivaroxaban-itraconazole combination exhibited stronger signals for epistaxis （ Ω ＝2.01， Ω 025 ＝0.90） and hematoma （ Ω ＝1.93， Ω 025 ＝0.42）； no positive Ω signals were observed for intracranial hemorrhage or upper gastrointestinal hemorrhage. CONCLUSION S This study suggests that the concomitant use of DOACs and triazole antifungals may increase the risk of bleeding-related events， with differences in signal strength and signal distribution across various drug combinations. In clinical practice， particular attention should be paid to the concomitant use of apixaban or rivaroxaban with strong cytochrome P450 3A4 or P-glycoprotein inhibitors such as posaconazole and itraconazole. For other DOAC-triazole antifungal combinations， close monitoring for bleeding-related manifestations and timely adjustment of anticoagulation or antifungal regimens are also warranted.

OBJECTIVE To investigate the clinical characteristics of drug-induced liver injury （DILI） induced by glucagon- like peptide-1 receptor agonists （GLP-1RAs）， and to provide a reference for safe clinical medication. METHODS Using search terms such as “GLP-1”“GLP-1RAs”“semaglutide” “drug-induced liver injury”， relevant studies from PubMed， Embase， the Cochrane Library， CNKI， Wanfang Data and VIP were retrieved. Descriptive analysis was performed on cases of DILI induced by GLP-1RAs. RESULTS A total of 11 studies， comprising 11 patients， were included. Among them， 4 were male （36.4%） and 7 were female （63.6%）. Patient ages ranged from 17 to 64 years； 5 patients （45.5%） were between 50 and 65 years old. Six patients were treated for diabetes， and five for weight loss. Ten patients had underlying diseases. The shortest time to the onset of DILI was 5 days after medication， while the longest was approximately 180 days. The DILIs induced by GLP-1RAs were mainly hepatocellular injury type （6 cases）； severity levels included severe （3 cases）， moderate （6 cases）， and mild （2 cases）. Gastrointestinal symptoms and jaundice were the most common clinical manifestations. The association between DILI and GLP- 1RAs was assessed as “probable” in 10 cases and “possible” in 1 case. All 11 patients improved after drug discontinuation and （or） corresponding treatment. CONCLUSIONS DILI induced by GLP-1RAs is relatively concentrated in patients aged 50-65， with a higher incidence in females. The risk may be further increased in patients with underlying diseases. Clinical use of these agents should enhance pharmaceutical care， including identification of high-risk populations and patient education （especially symptom recognition）. When relevant symptoms appear， the drug should be discontinued immediately， with liver-protective therapy initiated when necessary， to ensure patient safety of drug use.

Objective To explore the efficacy and mechanism of the aqueous extract of Sauropus spatulifolius in treating constipation based on network pharmacology analysis and experiments.Meth-ods Network pharmacology analysis was conducted using an online platform to investigate the molec-ular mechanism of Sauropus spatulifolius in treating constipation.Loperamide-induced mouse consti-pation models and intestinal epithelial cell(IEC)injury models were constructed.Therapeutic effects were evaluated using indicators such as the time to the first black stool,fecal water content,and gas-trointestinal transit rate.Annexin V-FITC staining was used to assess apoptosis,JC-1 staining was used to detect mitochondrial membrane potential,chemiluminescence was used to measure adenosine triphosphate(ATP)levels,and western blotting was used to detect the expression of relevant proteins.Results Network pharmacology analysis revealed that 29 active components in Sauropus spatulifolius targeted 19 genes associated with constipation,with AKT1 identified as one of the key genes.Exper-imental results demonstrated that the aqueous extract of Sauropus spatulifolius effectively alleviated loperamide-induced constipation symptoms in mice,including weight loss,reduced intestinal motili-ty,prolonged defecation time,and decreased fecal water content.Additionally,the aqueous extract of Sauropus spatulifolius inhibited IEC-6 cell apoptosis,restored mitochondrial membrane potential,and maintained intracellular ATP levels.The therapeutic mechanism involved downregulating the ex-pression of Bel-2-associated X protein(Bax),cytochrome C,Cleaved-Caspase3,and aquaporin 3(AQP3),as well as enhancing protein kinase B(Akt)phosphorylation.Conclusion The aque-ous extract of Sauropus spatulifolius effectively ameliorates constipation symptoms in mouse models,and its mechanism may be related to improving intestinal cell energy metabolism,inhibiting IEC ap-optosis,and reducing AQP3 expression,suggesting that Sauropus spatulifolius could serve as a po-tential drug for the clinical treatment of constipation.

Objective To investigate the preventive effect of low molecular weight heparin combined with nursing intervention on thrombosis after cesarean section. Methods A total of 100 parturient with cesarean section were randomly divided into observation group and control group, with 50 cases in each group. The observation group was given low molecular weight heparin as a nursing measure to prevent thrombosis on the basis of comprehensive nursing. The risk of thrombosis, nursing satisfaction degree and incidence of complications were compared between the two groups, and the effect and safety of low molecular weight heparin combined with nursing intervention in preventing thrombosis after cesarean section were evaluated. Results The positive rate of Homan sign, the number of cases with significantly increased lower limb circumference, the number of cases with elevated D-dimer level, the number of cases with persistent pain and swelling, and the number of cases with abnormal skin temperature and color changes in the observation group were all significantly lower has a certain effect in preventing thrombosis after cesarean section and is relatively safe, which can improve nursing satisfaction degree and postoperative recovery quality of parturient.

Bladder cancer is one of the most common malignancy in the urinary system over the world. Urine cytology and cystoscopy are important tools for bladder cancer diagnosis and recurrence monitoring. However, due to the limited sensitivity and invasive procedure, there is an urgent need to develop new non-invasive and highly sensitive liquid biopsy approaches. Urine biopsy is a research focus in the field and has great potential. This review focused on protein-based urine markers (including NMP22, BTA and UroVysion etc.) and DNA or RNA-based urine markers (including cfDNA, AssureMDx and Xpert BC Monitor etc.), which were used for bladder cancer diagnosis and recurrence monitoring, and summarized the sensitivity and specificity of each biomarker as well as their characteristics in the diagnosis and recurrence surveillance of bladder cancer. This study provides theoretical and empirical support for further optimization and application of these biomarkers in clinical practice.

Objective:To analyze the clinical and radiological features of patients with resected pancreatic serous cystic neoplasm (SCN).Methods:A retrospective analysis was conducted on the clinical and radiological data of 172 patients with pancreatic SCN who underwent surgical resection and were pathological confirmed at Peking Union Medical College Hospital from September 2014 to April 2022. These patients were categorized into two cohorts including 2014—2018 cohort ( n=84) and 2019—2022 ( n=88) for comparative analysis based on the operation time. Results:The radiological diagnostic accuracy for SCN was found to be notably low at 11.6%(20/172), which was mostly misdiagnosed as mucinous cystic neoplasms (86/172, 50.0%) and intraductal papillary mucinous neoplasms (35/172, 20.3%). No statistically significant variance was observed on the misdiagnosis rate between the two cohorts. There was a substantial increase of the number of lesions located in pancreatic body and tail (76.1% vs 53.6%, P=0.004) and a marked decrease in the number of those located in pancreatic head and neck (22.7% vs 39.3%, P=0.019) in 2019-2022 cohort, compared to the 2014-2018 cohort. Furthermore, there was a significant reduction in the occurrence of SCN calcification and peri-lesional venous alterations (22.8% vs 45.1%, P=0.006; 25.0% vs 46.4%, P=0.003), a decrease in the presence of fibrous scarring within SCN (31.8% vs 45.2%, P=0.070), and an increase in cases with dilatation of the upstream main pancreatic duct (28.2% vs 16.3%, P=0.065). The clinical characteristics and the rate of postoperative complications did not significantly differ between the two cohorts. Complication rates after pancreatoduodenectomy were significantly higher than those following distal pancreatectomy (46.4% vs 22.9%, P=0.010). The presence of clinical symptoms was significantly linked to the size of SCN and the expansion of the main pancreatic duct (45.4% vs 29.3%, P=0.032; 64.9% vs 31.2%, P<0.001). Conclusions:The accuracy of preoperative radiological diagnosis for SCN is still low, with a noted increase in the proportion of SCN exhibiting atypical radiological features in recent years. The frequency of postoperative complications is relatively high and does not have an obvious decreased trend.

ABSTRACT OBJECTIVE To investigate the current situation of pediatric pharmacist-managed clinic in China, and to provide reference for pediatric pharmacist-managed clinic construction and improvement. METHODS Domestic Children's hospitals, Women's & Children's Hospital, and general hospitals with pediatric unit were selected as the survey objects, questionnaires were distributed through the Wenjuanxing Application, and SPSS 26.0 was used to describe the data. The development of pediatric pharmacist-managed clinic, the qualification of visiting pharmacists, the situation of post training and training needs were analyzed. RESULTS A total of 101 valid questionnaires were collected. Pediatric pharmacist-managed clinics had been set up in 55(54.5%) hospitals, of which 35 were independent pharmacists' clinics, and most had well medical document and patient management processes. However, about 70% of hospitals did not charge registration fees, and more than half of hospitals had fewer than 5 patient-visits per day. 85.5% of the hospitals were visited by clinical pharmacists, and about half of them were senior clinical pharmacists with more than 10 years of working experience. But only 3.6% of visiting pharmacists had the right of specific prescription. In 101 hospitals relevant post training for pharmacists had been carried out in 36 hospitals, of which 25 hospitals had set up pharmacist-managed clinic. In addition to pharmaceutical expertise, more than 50% of pharmacists had a strong demand for the improvement of physician-patient communication and problem-solving ability, and 30%-40% of the demand was focused on the collection of medication history, psychological counseling ability, and case-based learning in the pharmacist-managed clinic. CONCLUSION At present, the domestic pediatric pharmacist-managed clinic shows a vigorous development trend, however, there are insufficient registration fees, visits, and post training. Appropriate service methods of pediatric pharmacist-managed clinic should be actively explored, and a pediatric specialized training system for should be well constructed to improve the competency.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.

Objective:To evaluate the feasibility of Full-stack Smart Pelvic Floor Ultrasound (FSPFU) software in the acquisition and measurement of the minimal levator hiatus (LH).Methods:Transperineal pelvic floor ultrasonography was performed in 119 women of 6-month postpartum from Nov.2020 to Jan.2021 of Shenzhen Second People′s Hospital. Mid-sagittal plane of pelvic floor was set as the initial plane, and the three-dimensional volume data was acquired. The dataset was stored in the machine. The offline volume data was manually adjusted to obtain the minimal LH images and measured by four physicians (two junior physicians as the D1 group and two senior physicians as the D2 group). For comparison, the results were also obtained using the fully automated method—the FSPFU software by a junior physician (the D3 group). The obtained parameters of minimal LH included area, circumference, anterioposterior diameter, transverse diameter, left and right levator-urethral gap distance. Analysis time was recorded for each group. The contours of minimal LH were outlined by three groups and the overlapping rate was calculated. The quality of the resulted images was evaluated and scored by another two senior physicians(A and B) independently.Results:The D3 group had a significant shorter analysis time compared with the other two groups, and the D1 group took a longer time than the D2 group, regardless of the cystocele severity (D1: 82.97 s, D2: 62.51 s, D3: 2.71 s, all P<0.05). The intergroup agreements and correlations of the minimum LH area were good (all ICC>0.85, rs>0.70, P<0.001) and the outlined contours were largely overlapped (>92%). There was no significant difference in image quality among the three groups(all P>0.05). Conclusions:FSPFU software can automatically obtain and measure the minimum LH in an efficient and accurate way, which can improve the effectiveness of the present pelvic floor examination. FSPFU software can be an useful tool in the diagnosis of pelvic floor dysfunctional diseases.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.