Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Mesenchymal stem cells(MSCs)are multipotent stromal cells that possess the capacity for self-renewal and differentiation into multiple cell lineages.Due to the ease of procurement,robust expansion in vitro,the multipotency,they are recognized as a vital source of stem cells in the field of regenerative medicine.MSCs can be isolated from various tissues,including bone marrow,adipose tissue,and umbilical cord.Research indicates that Human umbilical cord mesenchymal stem cells(hUCMSCs)play an effective role in wound healing and tissue regeneration,and can be utilized for the repair of skin wounds.They are also considered to be the most promising seed cells for skin tissue engineering.This review aims to provide an overview of the biological characteristics of hUCMSCs,the mechanisms in promoting skin wound healing,and their clinical applications.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To explore the characteristics of brain functional connectivity changes associated with repetitive transcranial magnetic stimulation (rTMS) in adolescents with anhedonia symptoms, and to develop a predictive model of treatment efficacy based on baseline functional connectivity.Methods:A total of 88 adolescents (aged 13-18 years) with major depressive disorder and comorbid anhedonia, diagnosed according to the Diagnostic And Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), were enrolled in a randomized, double-blind, block-design trial. Participants received either active rTMS ( n=44) or sham stimulation ( n=44) for 15 consecutive days with individualized targeting. Resting-state functional magnetic resonance imaging (fMRI) data and clinical assessments were collected before and after the intervention. Brain regions were parcellated using the Brainnetome Atlas to construct whole-brain functional connectivity matrices. Linear mixed-effects models were used to identify functional connections showing significant group×time interaction effects. The percentage change in Snaith-Hamilton Pleasure Scale (SHAPS) scores (ΔSHAPS) served as the dependent variable in multiple regression analyses to examine the explanatory power of connectivity changes for treatment response. A connectome-based predictive modeling (CPM) approach was employed to predict individual treatment responses based on baseline functional connectivity with permutation testing used to validate model robustness. Results:Thirty-one functional connections showing significant group×time interaction ( F=6.67-15.69, all P<0.01) were identified between the active and sham stimulation groups, primarily involving the subcortical network (SCN), dorsal attention network (DAN), limbic network (LN), and default mode network (DMN). Changes in these connections accounted for 53% of the variance in ΔSHAPS (adjusted R2=0.53, F=4.574, P=0.001). The CPM model based on baseline connectivity showed strong predictive performance (10-fold cross-validation: r=0.65, R2=0.40, MAE=0.095, permutation P<0.001; leave-one-out cross-validation: r=0.74, R2=0.52, MAE=0.013, permutation P<0.001). Among the 59 predictive features, those originating from the LN contributed most substantially, particularly cross-network connections with the DMN and SCN. Correlation analyses revealed widespread associations between baseline predictive features and rTMS-induced connectivity changes, including significant negative correlations between baseline LN-DMN connectivity and post-treatment changes in DAN and subcortical connectivity. Conclusion:rTMS significantly alleviates anhedonia symptoms in adolescents with depression and induces widespread reconfiguration of functional connectivity across multiple brain networks. The CPM model based on baseline connectivity features effectively predicts rTMS treatment efficacy for anhedonia, providing new insights for individualized treatment strategies in adolescent depression.

Atherosclerosis is the most common cause of ischemic stroke. Antiplatelet aggregation is considered as the effective treatment for atherosclerotic ischemic stroke. Ticagrelor is a novel P2Y12 receptor antagonist, which has the advantages as rapid onset, strong effect, no need for liver metabolism activation and reversible platelet inhibition. Studies have confirmed that ticagrelor has a better therapeutic effect on ischemic stroke patients who are resistant to clopidogrel; especially in dual antiplatelet therapy, patients used ticagrelor have lower stroke risk and severe hemorrhage risk does not increase in these patients. This article reviews the recent advances in mechanism of ticagrelor and its application in acute ischemic stroke, with the aim of providing references for clinical application of ticagrelor.

Objective To investigate the labeling of dialysis-related information in the instructions of drugs for systemic use in patients with end-stage renal disease undergoing hemodialysis,and to provide reference for further standardization and im-provement of drug instructions.Methods Collected the information on pharmacokinetics and drug dose adjustment in hemodi-alysis patients with end-stage renal disease from the instructions of chemicals and biologics used systemically in XuanWu hospital's formulary from January to March 2023.Classified and compared the labeling rates of the corresponding information of the originally developed drugs and generic drugs,imported drugs and domestic drugs;Drugs eliminated by non-renal route,or with mo-lecular weight≥5 000,or binding rate of plasma protein ≥ 60％,or drug distribution volume＞360L were classified as"non-dialysis group",and other drugs were classified as"dialysis group",compared the labeling rate of corresponding information of drugs in"dialysis group"and"non-dialysis group";and compared the labeling rate and content with relevant information in Lexicomp and Micromedex.Results Among the 930 drug instructions,the labeling rates of drug dialysis clearance,drug adjustment,and ex-plicit drug adjustment plan were 16.67％,25.16％,and 24.52％.There was no significant difference in the labeling rate of dialysis-related information between original and generic drugs,and imported and domestic drugs.There was a significant difference in the labeling rate of dialysis-related information between the"dialyzable group"and the"non-dialyzable group"(P＜0.01).The differ-ence in the labeling rate of dialysis related information between the investigated drug instructions and the corresponding drugs in Lexicomp or Micromedex was statistically significant(P＜0.01).Conclusion Attention should be paid to the lack of informa-tion and unclear labeling of hemodialysis patients with end-stage renal disease in the drug instructions by relevant departments.

Objective:The aim of this study was to assess the frailty status of patients with heart failure undergoing CRT-D and then explore the predictive value of frailty for all-cause mortality and heart failure-related readmissions in these patients.Methods:We retrospectively included 374 patients with chronic heart failure who underwent CRT-D treatment at the First Affiliated Hospital of Xinjiang Medical University between June 2020 and June 2024. Based on the Tilburg Debilitation Assessment Scale, 175 patients (46.8%) were classified as frail while 199 (53.2%) were classified as non-frail. The baseline data between the two groups was compared using Cox regression analysis and Kaplan-Meier curves were used for survival analysis. P-values of <0.05 indicated statistically significant differences. Results:A total of 374 patients aged 25-93 (68±11) years were enrolled in this study, 101 (27.0%) of which were female. Among these, 175 (46.8%) were categorized as frail, and 199 (53.2%) were classified as non-frail. Over a median follow-up time of 23 (5, 45) months, 35 (9.4%) patients experienced all-cause mortality, with 30 (17.1%) deaths occurring in the frail group and 5 (2.5%) in the non-frail group; meanwhile, readmission events due to heart failure occurred in a total of 174 (46.5%) patients, including 122 (70.1%) in the frail group, and 52 (29.9%) in the non-frail group. Cox analysis showed that frailty was a significant determinant of all-cause mortality ( HR=21.25, 95% CI 3.99-113.30, P<0.001) and readmission among heart failure patients receiving CRT-D ( HR=2.52, 95% CI 1.73-3.68, P<0.001). Log-rank tests showed that the survival rate of patients in the frail group was significantly lower than that of patients in the non-frail group ( HR=7.22, 95% CI 2.80-18.60, P<0.001) and the risk of readmission events due to heart failure was significantly higher among patients in the frail group than among those in the non-frail group ( HR=2.75, 95% CI 1.98-3.81, P<0.001). Conclusions:Frailty is an independent predictor of postoperative all-cause mortality and the occurrence of heart failure-related readmissions in patients with heart failure treated receiving CRT-D.

Objective To investigate the labeling of dialysis-related information in the instructions of drugs for systemic use in patients with end-stage renal disease undergoing hemodialysis,and to provide reference for further standardization and im-provement of drug instructions.Methods Collected the information on pharmacokinetics and drug dose adjustment in hemodi-alysis patients with end-stage renal disease from the instructions of chemicals and biologics used systemically in XuanWu hospital's formulary from January to March 2023.Classified and compared the labeling rates of the corresponding information of the originally developed drugs and generic drugs,imported drugs and domestic drugs;Drugs eliminated by non-renal route,or with mo-lecular weight≥5 000,or binding rate of plasma protein ≥ 60％,or drug distribution volume＞360L were classified as"non-dialysis group",and other drugs were classified as"dialysis group",compared the labeling rate of corresponding information of drugs in"dialysis group"and"non-dialysis group";and compared the labeling rate and content with relevant information in Lexicomp and Micromedex.Results Among the 930 drug instructions,the labeling rates of drug dialysis clearance,drug adjustment,and ex-plicit drug adjustment plan were 16.67％,25.16％,and 24.52％.There was no significant difference in the labeling rate of dialysis-related information between original and generic drugs,and imported and domestic drugs.There was a significant difference in the labeling rate of dialysis-related information between the"dialyzable group"and the"non-dialyzable group"(P＜0.01).The differ-ence in the labeling rate of dialysis related information between the investigated drug instructions and the corresponding drugs in Lexicomp or Micromedex was statistically significant(P＜0.01).Conclusion Attention should be paid to the lack of informa-tion and unclear labeling of hemodialysis patients with end-stage renal disease in the drug instructions by relevant departments.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Objective: To establish a progressive research strategy for “colonic components analysis - efficacy verification and mechanism exploration - gut microbiota”, screen pharmacodynamic substances, and investigate their mechanism via gut microbiota. Methods: The pharmacodynamics of Gegen Qinlian decoction (GQD) were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis (UC). Ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC. To analyze the structure and function of characteristic genera of GQD and its active components, 16S rRNA sequencing was performed. Results: We identified 67 prototypic and 14 metabolic components of GQD in the UC colon. The primary prototype components are flavonoids and alkaloids, including puerarin (PUE), baicalin (BAI), and berberine (BER). The metabolism was predominantly sulfonation. Efficacy verification showed that the main active components, puerarin, baicalin, and berberine, had good therapeutic effects on UC. The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota. The abundance of gut microbiota involved in the metabolism of the prototype components was influenced by the corresponding components. The function prediction results showed that PUE was the most comparable to GQD, with 24 consistent pathways. BAI and BER showed comparable gut microbiota regulation pathways. Characteristic pathways of BER include glucometabolic processes. Conclusion This study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components. This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC, as well as changes in the structure and function of the gut microbiota, clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.