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.

[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

Stroke is the leading cause of death and disability among adults in China， and its common complications include digestive system abnormalities， cognitive impairment， depression， stroke-associated pneumonia， and hemiplegia. The combination of traditional Chinese and Western medicine has great potential in treating post-stroke complications. Xinglou Chengqitang （XLCQT） is a representative prescription of alleviating the disease in the upper part by treating the lower part. It has definite therapeutic effect and high safety. Clinically， XLCQT is often used to treat stroke and its complications. However， the quantity and quality of clinical trials of XLCQT in treating post-stroke complications need to be improved. Additionally， since the basic research is weak， the material basis and multi-target mechanism for the efficacy of this prescription are unknown. This article reviews XLCQT in terms of the pharmacodynamic basis， medicinal properties， safety evaluation， and progress in clinical research and mechanisms in treating post-stroke complications. This article summarizes 22 key active ingredients of XLCQT in treating acute stroke complicated with syndrome of phlegm heat and fu-organ excess. Among these key active ingredients， resveratrol， kaempferol， luteolin， chrysoeriol， apigenin， （+）-catechin， and adenosine have good pharmacokinetic properties and high bioavailability. The mechanisms of XLCQT in treating post-stroke complications are complex， including inflammatory response， brain-gut axis， hypothalamic-pituitary-adrenal （HPA） axis， intestinal flora， neurotrophic factors， autophagy， oxidative stress， and free radical damage. This review helps to deeply understand the pharmacodynamic basis and mechanisms of XLCQT in treating post-stroke complications and provides a theoretical basis for the clinical application of XLCQT against post-stroke complications and the development of drugs.

[摘 要] 目的：探究环状RNA（circRNA）调控舌鳞状细胞癌（TSCC）顺铂（CDDP）耐药的机制。方法：本研究以TSCC化疗敏感CAL27细胞与耐药CAL27-res细胞为研究对象，RT-qPCR检测两种细胞内hsa_circ_0034762的表达量差异，流式细胞术检测细胞凋亡率，Western blotting检测自噬相关蛋白p62及LC3-Ⅱ/LC3-Ⅰ比值，透射电镜观察自噬小体的数量，双萤光素酶报告实验检测hsa_circ_0034762与miR-17-3p的结合关系，荧光原位杂交实验检测二者在细胞中的共定位，敲低hsa_circ_0034762联合抑制miR-17-3p进行功能回复实验。结果：相比亲本化疗敏感细胞，TSCC耐药细胞CAL27-res自噬水平显著提升，表现为自噬小体数量增加、LC3-Ⅱ/LC3-Ⅰ比值升高及p62蛋白表达降低。hsa_circ_0034762在TSCC耐药组织及CAL27-res细胞中高表达。敲低hsa_circ_0034762后，CAL27-res细胞凋亡率升高，自噬小体数量减少，p62蛋白表达增加，LC3-Ⅱ/LC3-Ⅰ比值降低（均P < 0.05）。双萤光素酶报告实验与荧光原位杂交实验发现hsa_circ_0034762与miR-17-3p存在靶向结合作用。抑制miR-17-3p可部分逆转hsa_circ_0034762敲低所致的促凋亡及抑制自噬效应。结论：hsa_circ_0034762在TSCC耐药细胞及组织中高表达。敲低hsa_circ_0034762可能通过miR-17-3p抑制细胞自噬并促进细胞凋亡，从而降低TSCC细胞的化疗耐药性。

BackgroundObstructive sleep apnea （OSA） represents a prevalent sleep disordered breathing condition characterized by complex pathophysiology. The arousal threshold （ArTH）， a core non-anatomical contributor to OSA pathogenesis， is intimately tied to the disease severity and clinical phenotypes. To date， research regarding factors associated with ArTH has yielded inconsistent findings， and ArTH profiles and disparities across populations with different genetic backgrounds are not fully elucidated. ObjectiveTo explore the differences of ArTH in OSA patients with different genetic backgrounds and analyze the key factors affecting ArTH， thereby providing evidence for understanding OSA pathophysiology and formulating targeted treatment regimens. MethodsA total of 285 patients who met the diagnostic criteria for OSA， as defined by the Multidisciplinary Diagnosis and Treatment Guidelines for Adult Obstructive Sleep Apnea， were retrospectively enrolled in this study. All participants underwent overnight polysomnography （PSG） at the Sleep Medicine Center of Inner Mongolia Mental Health Center from December 2022 to May 2024. Based on the study design， the cohort was stratified into two distinct genetic background subgroups （group A and group B）. Demographic and clinical characteristics， the Epworth Sleepiness Scale （ESS） score， and overnight PSG data were collected. The apnea hypopnea index （AHI）， the lowest pulse oxygen saturation （LSpO₂）， and fraction of hypopneas （F_Hypopneas） were utilized as surrogate indicators to estimate ArTH in OSA patients. The influencing factors of low ArTH were tested by binary Logistic regression analysis. ResultsAmong the 285 OSA patients， there were 227 cases （79.65%） in group A and 58 cases （20.35%） in group B. Comparisons between the two genetic background subgroups revealed no statistically significant differences in the proportion of low ArTH， ESS score， PSG parameters， and the three markers for low ArTH （AHI<30 events/h， LSpO₂>82.5%， F_Hypopneas>58.3%） （P>0.05）. Binary Logistic regression analysis identified sex （OR=2.421， 95% CI： 1.070–5.478）， BMI （OR=0.847， 95% CI： 0.770–0.932）， N1 sleep duration （OR=0.974， 95% CI： 0.963–0.985）， and hypertension （OR=0.348， 95% CI： 0.143–0.848） as independent factors associated with low ArTH in the total cohort. Stratified analysis by genetic backgrounds revealed that sex（OR=3.799， 95% CI： 1.389–10.392）， BMI（OR=0.819， 95% CI：0.723–0.929）， and N1 sleep duration（OR=0.973， 95% CI： 0.961–0.986） were independent factors of low ArTH in group A. In contrast， only N1 sleep duration （OR=0.951， 95% CI： 0.911–0.993） remained a significant factor in group B. ConclusionArthur may have conservative characteristics in patients with OSA with different genetic backgrounds， but the pathophysiological mechanism of OSA may have population heterogeneity. ［Funded by Inner Mongolia Autonomous Region Natural Science Fundation Project （number， 2024QN08050）； Intra-institutional Scientific Research Project of Inner Mongolia Mental Health Center （number， 2022QNWN0010）］

Objective To develop a symptom and function assessment scale for patients after Nuss procedure for pectus excavatum and to test its reliability and validity. Methods Following the principles and procedures of patient-reported outcome (PRO) scale development stipulated by the U.S. Food and Drug Administration, an initial draft was formed through literature analysis, qualitative interviews, and Delphi expert consultation. The preliminary draft was used to conduct a pre-survey on patients who underwent Nuss procedure for pectus excavatum at Guangdong Provincial People's Hospital, and the reliability and validity of the scale were tested. Results A preliminary PRO-based symptom and function scale was constructed, covering two domains: symptoms and impact on daily functions. The symptom dimension included six items: chest tightness, palpitations, pain, shortness of breath, foreign body sensation of the steel plate, and distress; while the impact on daily functions included four items: difficulty in getting out of bed or lying down, raising arms, bending over, and standing or sitting for a long time. A total of 73 patients who underwent Nuss procedure for pectus excavatum were included in the questionnaire survey, with 70 valid questionnaires collected, including 64 males and 6 females, with 56 patients aged 12-17 years and 14 patients ≥18 years. Through exploratory factor analysis, two common factors were extracted, with a cumulative variance contribution rate of 70%. The Cronbach’s α coefficient of the scale was 0.917. Conclusion The scale developed in this study has good reliability and validity, high reliability and stability, and can be used as an evaluation tool for the recovery status of patients after Nuss procedure for pectus excavatum.

Objective To investigate the correlation between gut microbiota characteristics and immunotherapy efficacy in patients with advanced microsatellite stable (MSS) advanced gastrointestinal tumors. Methods Thirty patients with advanced MSS gastrointestinal tumors, including fourteen cases of gastric cancer and sixteen cases of colorectal cancer, who were admitted from November 1, 2022, to July 31, 2025 were enrolled. All patients underwent gut microbiota testing and received corresponding interventions on the basis of the results, followed by treatment with antiangiogenic agents combined with immunotherapy. Some patients additionally received probiotics or fecal microbiota transplantation. The primary endpoints were disease control rate (DCR) and objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression analyses were used to assess potential prognostic factors. Results Among the thirty patients, no complete response was observed. Two cases of partial response (PR), twelve cases of stable disease, and sixteen cases of progressive disease were recorded. The ORR was 6.7%, and the DCR was 46.7%. The median PFS was 6.4 months, and the median OS was 8.3 months. Both PR patients were classified as having a medium risk of gut microbiota dysbiosis and exhibited a Bacteroides-dominated enterotype. Multivariate analysis indicated that tumor type, liver metastasis, and bone metastasis were potential prognostic factors for PFS and OS. Conclusion Patients with a medium risk of gut dysbiosis may exhibit a relatively favorable response to immunotherapy, suggesting that gut microbiota status could serve as a potential biomarker for predicting treatment efficacy in advanced MSS gastrointestinal tumors.

Objective Jejunal interposition is an important option for restoring gastrointestinal continuity in patients with complex esophageal cancer in whom the stomach is unavailable for reconstruction due to previous gastrectomy, tumor involvement, failed gastric conduit, or other constraints. Although the jejunum offers a caliber similar to the esophagus, a rich blood supply, and preserved peristaltic function, anatomical variations in mesenteric length and vascular arcades render long-segment and high-level reconstruction susceptible to excessive tension, mesenteric torsion, venous congestion, and inadequate distal perfusion. This consensus aims to provide standardized recommendations for the application of jejunal interposition in this specific patient population. Methods This consensus was developed in accordance with the WHO Handbook for Guideline Development and Chinese national guideline development standards, with reference to the Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREE Ⅱ), Reporting Items for Practice Guidelines in Healthcare (RIGHT), and Scientific, Transparent and Applicable Rankings (STAR) checklists. The project was registered on the international practice guidelines registry platform (PREPARE-2026CN1384). The working group systematically searched Chinese and English evidence addressing 12 clinical questions. Evidence was graded using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 system, with structured appraisal of risk of bias, inconsistency, indirectness, and imprecision. Recommendations were formulated through two rounds of Delphi surveys and a face-to-face consensus meeting, with an agreement threshold of ≥75%. Results The consensus generated 12 recommendations covering indications, selection between jejunum and colon, preoperative assessment, surgical approach and reconstruction route, pedicled jejunal interposition (PJI), supercharged pedicled jejunal interposition (SPJ), indocyanine green (ICG) perfusion assessment, perioperative nutrition, management of anastomotic leakage, long-term follow-up, and special treatment scenarios. Given that the available direct evidence is predominantly derived from single-center retrospective cohorts and case series, recommendations extrapolated from general esophagectomy or other gastrointestinal surgical evidence are deliberately phrased with caution. Conclusion Jejunal interposition is a safe and effective approach for digestive tract reconstruction in patients with complex esophageal cancer in whom the stomach is unavailable. This consensus emphasizes that clinical decision-making should be individualized based on the patient's prior treatment history, reconstruction height, vascular anatomy, technical availability, and institutional experience in the Chinese context.

Colchicine, a classic anti-inflammatory agent, has been long used for the prevention and treatment of gouty arthritis and familial Mediterranean fever. Given the pivotal role of inflammation in the development and progression of cardiovascular diseases, the clinical value of colchicine in the secondary prevention of cardiovascular diseases has attracted significant attention. Diabetes mellitus （DM） leads to severe and irreversible vascular complications, and cardiovascular diseases are the leading cause of death in patients with DM. However, existing research indicated heterogeneity in the therapeutic efficacy of colchicine among patients with cardiovascular diseases and those with diabetes complicated by cardiovascular conditions. The heterogeneity manifests as differences in efficacy across various disease stages, patient baseline characteristics, specific cardiovascular event types, endpoint definitions, and treatment regimens. The current domestic and international research findings on colchicine in relation to cardiovascular events—both in patients with CVD and in those with diabetes—were reviewed, with the aim of elucidating the underlying causes of this efficacy heterogeneity and providing evidence-based guidance for identifying patients likely to benefit and optimizing individualized treatment strategies in clinical practice.

Neurodegenerative diseases (NDs), particularly Alzheimer’s disease (AD) and Parkinson’s disease (PD), and cardiovascular diseases (CVDs), including heart failure (HF) and coronary artery disease (CAD), are major chronic disorders associated with population aging. Their frequent coexistence in clinical practice suggests that they may not progress independently, but may instead be linked through bidirectional pathological communication within the brain-heart axis. Epidemiological evidence underscores this clinical burden: systematic reviews and meta-analyses have reported pooled relative risks for dementia of approximately 1.27 among individuals with a history of CAD and 1.60 among those with HF, while the pooled prevalence of cognitive impairment and dementia in patients with HF has been estimated at approximately 41.42% and 19.79%, respectively. This review synthesizes current evidence on the mechanistic links, disease-state manifestations, biomarkers, and potential therapeutic strategies involved in the comorbidity between NDs and CVDs from the perspective of the brain-heart axis. The brain and heart communicate through autonomic, neuroendocrine, neuroimmune, vascular, and humoral pathways. Sympathetic activation, parasympathetic withdrawal, vagal dysfunction, cerebral hypoperfusion, endothelial injury, blood-brain barrier (BBB) alterations, peripheral immune activation, and circulating inflammatory mediators may jointly contribute to cross-organ pathological signaling. Oxidative stress and inflammatory response are not specific to the brain-heart axis; rather, they may act as candidate amplifying processes within this network. Mitochondrial dysfunction and NADPH oxidase activation can increase the generation of reactive oxygen species and reactive nitrogen species, which may activate nuclear factor-κB, the NLRP3 inflammasome, and mitogen-activated protein kinase/c-Jun N-terminal kinase signaling. These pathways can promote the release of interleukin-1β, interleukin-6, tumor necrosis factor‑α, and other inflammatory mediators, which may in turn aggravate mitochondrial injury, endothelial dysfunction, immune cell activation, and further oxidant generation. Cytokines, chemokines, oxidized lipids, mitochondrial DNA, damage-associated molecular patterns, and extracellular vesicles may transmit these signals between the cardiovascular and central nervous systems, whereas autonomic reflexes provide an additional route for bidirectional amplification. Distinct disease states illustrate different manifestations of this network. The association between AD and CVDs may involve vascular risk factors, impaired amyloid-β clearance, abnormal cholesterol homeostasis, cerebral microvascular injury, neuroinflammation, and endothelial dysfunction. HF-related cognitive impairment may be linked to reduced cardiac output, recurrent cerebral hypoperfusion, hypoxia-related signaling, BBB dysfunction, circulating inflammation, and impaired autonomic feedback. In PD, cardiovascular autonomic dysfunction and abnormalities in heart rate and blood pressure regulation may interact with vascular injury, reduced cerebral perfusion, inflammation, and oxidative stress. However, the relationship between PD and CAD remains heterogeneous and may be modified by age, ethnicity, medication use, metabolic factors, and coexisting diseases. Biomarker evaluation should therefore move beyond isolated indicators. Traditional markers, including malondialdehyde, superoxide dismutase, glutathione, C-reactive protein, and interleukin-6, reflect systemic oxidative or inflammatory burden but lack sufficient specificity to distinguish primary neurodegeneration, cardiovascular injury, or a comorbid state involving both. Greater clinical value may be obtained from cross-system panels that combine oxidative stress and inflammatory markers with cardiac stress or injury biomarkers, such as N-terminal pro-B-type natriuretic peptide; glial or neuronal biomarkers, such as glial fibrillary acidic protein and neurofilament light chain; BBB- or endothelial injury-related biomarkers; and omics-derived candidates, including microRNAs, long non-coding RNAs, DNA methylation signatures, metabolites, and proteins. Multi-omics integration and artificial intelligence-assisted analysis may support risk stratification, disease monitoring, and prediction of treatment response. However, these approaches require standardized analytical platforms, validation in independent cohorts, and careful distinction between associative findings and causal mechanisms. Potential interventions include antioxidant, anti-inflammatory, mitochondria-targeted, and multi-target combination strategies, together with emerging approaches such as nanodelivery, CRISPR/Cas9- or CRISPR/dCas9-based regulation, mesenchymal stem cell-mediated mitochondrial transfer, and ergothioneine supplementation. Nevertheless, most available evidence is indirect, preclinical, or derived from other disease indications, and no single drug or technology can currently be regarded as specific to brain-heart axis comorbidity. The clinical relevance of these strategies will depend on whether they can be matched to dominant pathological phenotypes and improve both neurological and cardiovascular outcomes. Overall, comorbidity between NDs and CVDs is more appropriately understood as a heterogeneous cross-organ regulatory network than as a disorder driven by a single pathway. Future research should prioritize multicenter longitudinal cohorts, standardized clinical phenotyping, validation of cross-system biomarker panels, and mechanism-guided interventions in clearly defined patient subgroups, with integrated assessment of cognitive function, cardiovascular events, quality of life, long-term safety, and treatment response.