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 compare the biological characteristics of human induced pluripotent stem cell-derived platelet exosomes (hiPSC-Plt-Exos) with those of conventional apheresis platelet exosomes (Plt-Exos), specifically focusing on their differential abilities to enhance the proliferation and migration of human umbilical cord mesenchymal stem cells (hUC-MSCs). Methods: Exosomes were isolated from hiPSC-derived Plt and apheresis Plt concentrate using size exclusion chromatography. These exosomes were then characterized through nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. Co-culture experiments into hUC-MSCs were conducted with hiPSC-Plt-Exos and apheresis Plt-Exos, respectively. Their effects on the proliferation and migration of hUC-MSCs were assessed via cell proliferation assays and scratch tests. Results: hiPSC-Plt-Exos and apheresis Plt-Exos exhibited comparable particle sizes, morphological features (such as the characteristic cup-shaped structure), and surface markers (including CD9 and HSP70). Notably, hiPSC-Plt-Exos demonstrated a significantly greater ability to enhance the proliferation and migration of hUC-MSCs compared to apheresis Plt-Exos (P<0.05). These differences provide critical comparative data for their application in various clinical contexts. Conclusion: This study establishes a theoretical foundation for developing precise therapeutic strategies based on hiPSC-Plt-Exos. Furthermore, it underscores the necessity of selecting the appropriate type of exosomes according to the specific disease microenvironment to achieve optimal therapeutic outcomes.

ObjectiveTo investigate the influence of platelet-albumin-bilirubin （PALBI） score on the textbook outcome （TO） of patients with hepatocellular carcinoma （HCC） after hepatectomy， as well as the association of different PALBI scores before surgery with the achievement of TO after hepatectomy in HCC patients. MethodsA retrospective analysis was performed for the data of HCC patients who underwent hepatectomy in West China Hospital of Sichuan University and Ziyang Central Hospital from January 2013 to January 2022. TO was defined as no serious complication within 30 days after surgery， no death within 90 days， no rehospitalization within 30 days after discharge， no blood transfusion in the perioperative period， RO resection， and no prolongation of hospital stay. The chi-square test was used for comparison of categorical data between two groups. The univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for the achievement of TO after hepatectomy in HCC patients. The Kaplan-Meier method was used to plot the survival curves of HCC patients， and the Log-rank test was used for comparison. ResultsA total of 3 599 patients were included in this study， among whom 2 369 （65.8%） achieved TO. The multivariate Logistic regression analysis showed that PALBI grade （PALBI grade 2： odds ratio ［OR］=1.562， 95% confidence interval ［CI］： 1.308‍ ‍—‍ ‍1.864， P<0.001； PALBI grade 3： OR=2.216， 95%CI： 1.463‍ ‍—‍ ‍3.359， P<0.001） was an independent risk factor for achievement of TO after surgery in HCC patients. The proportion of patients achieving TO decreased with the increase in PALBI grade. Among the patients with PALBI grade 1， 2 or 3， the patients achieving TO accounted for 70.2%， 54.2%， and 38.4%， respectively （χ²=106.295， P<0.001）. The incidence rate of serious complications within 30 days， the mortality rate of patients within 90 days after hepatectomy， readmission rate within 30 days after discharge， perioperative blood transfusion rate， and the rate of prolonged hospital stay all increased with the increase in PALBI grade （all P<0.05）. For the patients achieving TO， the 1-， 3-， and 5-year relapse-free survival rates were 79.5%， 60.6%， and 51.5%， respectively， and the overall survival rates were 92.1%， 80.0%， and 71.1%， respectively； for those who did not achieve TO， the 1-， 3-， and 5-year relapse-free survival rates were 68.5%， 52.7%， and 46.2%， respectively， and the overall survival rates were 83.3%， 66.0%， and 57.1%， respectively. The patients who achieved TO had significantly better relapse-free survival rate and overall survival rate than those who did not achieve TO （χ²=18.936 and 79.371， both P<0.001）. ConclusionPreoperative PALBI grade can affect the achievement of TO after hepatectomy in HCC patients， and it is more difficult for patients with a higher PALBI grade to achieve TO. Preoperative PALBI score can be used to early identify the patients with a high risk of postoperative complications， provide early intervention， and enhance perioperative management， thereby improving the perioperative safety and long-term prognosis of HCC patients after hepatectomy.

Thalamocortical circuitry has a substantial impact on emotion and cognition.Previous studies have demonstrated alterations in thalamocortical functional connectivity(FC),characterized by region-dependent hypo-or hyper-connectivity,among individuals with major depressive disorder(MDD).However,the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear.Hence,we analyzed dynamic FC(dFC)between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls(HCs)to investigate time-varying changes in thalamocortical FC in patients with MDD.Moreover,dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time.Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated.We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks,compared with the HCs.In addition,MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration.The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort.Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms.Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients.The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.

Objective:To establish and verify a simple clinical prediction model for obstructive sleep apnea syndrome(OSAS)in children.Methods:The clinical data of 95 children aged 2-12 years underwent polysomnography(PSG)were screened.The subjects with OAHI≤1 were included into non-OSAS group(n=22)and those with OAHI＞1 into OSAS group(n=73).Gender,age,body mass index(BMI),night pulse minimum oxygen saturation(SpO2),tonsil grading and adenoid grading of the 2 groups were compared and analyzed.Binary Logistic regression analysis was used to statistically analyze the data and establish a clinical prediction model for OSAS in children.Results:There was significant difference in age,BMI,SpO2,tonsil grading and adenoid grading between the 2 groups(P＜0.05),there was no significant gender difference(P＞0.05).The model equation was as follows:X=2.366-0.769(age-continuous variable)+0.248(BMI-continuous variable)-3.413(SPO2-continuous variable)+2.104(tonsil grade Ⅲ-Ⅳ"yes").The result of internally validated Hosmer-Lemeshow test was P=0.612(P＞0.05),AUC was 0.821(0.713-0.929,P＜0.01),sensi-tivity was 83.3％,specificity was 76.4％.The accuracy of external validation was 73.8％,the AUC was 0.805(0.664-0.943,P＜0.01),the sensitivity was 84.6％and the specificity was 75％.Conclusion:The predictive model may have good predictive efficacy for 2-12 years old children with OSAS,and may assist clinicians in diagnosing children with OSAS.

AIM: To compare the effects of night-wearing orthokeratology lenses and frame glasses on the treatment of juvenile myopia, and provide reference for the selection of myopia treatment methods in adolescents.METHODS: A prospective study was conducted on 106 adolescent myopia patients who received treatment in our hospital from June to November 2020. According to the wishes of patients, they were divided into two groups with 53 cases in each group. The control group was given regular frame glasses after optometry, while the observation group was given night-wearing orthokeratology lenses. The uncorrected visual acuity(LogMAR), refractive index(spherical equivalent and cylindrical lens power), and ocular biological parameters(axial length, central corneal thickness, anterior chamber depth and lens thickness)were compared between the two groups.RESULTS: The uncorrected visual acuity(LogMAR)of the observation group was lower than that of the control group at 1a after treatment(0.51±0.12 vs. 0.73±0.15), and the spherical equivalent(-0.23±0.05 vs. -5.32±1.35D)and cylindrical lens power(-1.53±0.22 vs. -1.97±0.35DC)were smaller than those of the control group(P<0.001). The axial length of the eyes in the two groups increased at 1a after treatment and the axial length in the control group was longer(25.53±0.84 vs. 25.95±0.83 mm); the lens thickness of the observation group was increased compared with that before treatment(3.39±0.19 vs. 3.31±0.15 mm; P<0.05). After 1a treatment, the accommodative amplitude(14.29±1.37 vs. 12.90±1.07D), accommodative facility(11.05±2.09 vs. 7.59±1.82cpm), and total staining rate of corneal epithelium in the observation group were higher than those in the control group(15.1% vs. 1.9%), and the accommodative lag was lower than that in the control group(0.55±0.11 vs. 0.97±0.30D; P<0.05). There were no significant differences in corneal cell density(3197.23±249.66 vs. 3207.41±258.14 cells/mm2), corneal endothelial cell area(309.27±28.04 vs. 312.62±24.95mm2)and the incidence of complications between the two groups before and after treatment(5.7% vs. 9.4%; P>0.05).CONCLUSION: Night-wearing orthokeratology lenses can improve uncorrected visual acuity in adolescent patients with myopia, reduce the spherical equivalent and cylindrical lens power, and improve the accommodation-related parameters, but has no significant effect on the corneal function.

【Objective】 To analyze the data of clinical blood transfusion quality control supervision in Shanghai, so as to provide reference for the improvement of clinical blood transfusion quality management in hospitals at all levels. 【Methods】 The data of clinical blood transfusion quality control supervision in hospitals at all levels from 2016 to 2021 were retrospectively analyzed to obtain the characteristics and indicators in the quality management. 【Results】 The overall level of clinical blood transfusion quality management in Shanghai steadily improved from 2016 to 2021 (F=3.82, P<0.01), and the management level of different hospitals varied significantly (F=9.00, P<0.01). In 2021, the full compliance rates of housing facilities, instruments and equipment, diagnostic reports and medical record writing among the third-level indicators of clinical blood transfusion quality management in hospitals at all levels were as follows: 86.49%(32/37), 100% (37/37)and 43.24%(16/37) for tertiary comprehensive hospitals; 61.11%(11/18), 88.89%(16/18) and 50.00% (9/18)for tertiary specialized hospitals; 60.87%(14/23), 78.26%(18/23)and 47.83%(11/23) for secondary comprehensive hospitals, ; 60.00%(9/15), 66.67%(10/15), 40.00%(6/15) for secondary specialized hospitals; 52.38%(11/21), 38.10%(8/21), 42.86%(9/21) for private hospitals. 【Conclusion】 The characteristics of clinical blood transfusion quality management in hospitals at all levels in Shanghai differed significantly, with different strengths and weaknesses. Hospitals should improve blood transfusion management in terms of housing facilities, personnel management, system process as well as diagnostic reports and medical record writing, in order to enhance the clinical blood transfusion quality management.

Objective:To explore the association between the frequency of using smoking cessation application (APP) and the effect of smoking cessation in smoking cessation clinic.Methods:A clinical trial with a non-randomized controlled design was conducted in the smoking cessation clinic of China-Japan Friendship Hospital from July 2019 to June 2021. Participants were given a comprehensive smoking cessation intervention of mobile APP combined with bupropion. The primary outcome measures were carbon monoxide validated sustained abstinence at 9-12 weeks.Results:A total of 187 participants were included in the final analysis. After 12-week intervention, the sustained abstinence at 9-12 weeks was 42.2%. For the frequency of APP use, 20.9% (39/187) of the participants used it≥6 days per week, 62.0% (116/187) used it 2-5 days per week, and 17.1% (32/187) used it≤1 day per week. Multivariate analysis showed that smoking cessation rate was associated with smoking duration, cigarettes smoked per day and frequency of APP use. Participants with higher frequency of APP use had a higher likelihood of quitting smoking ( OR=4.95, 95% CI: 1.32-18.63). Conclusion:The increased frequency of mobile smoking cessation APP use is associated with higher probability of quitting smoking in smoking cessation clinic.

Immune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non-small-cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD-1) and its ligand (PD-L1), have remarkable antitumor efficacy and have been approved as a standard first- or second-line treatment in non-oncogene-addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long-term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early-phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.

Immune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non-small-cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD-1) and its ligand (PD-L1), have remarkable antitumor efficacy and have been approved as a standard first- or second-line treatment in non-oncogene-addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long-term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early-phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.