BackgroundMedical treatment has been the mainstay of chronic rhinitis management. Meanwhile, innovative minimally invasive nasal surgery has shown promising results. The therapeutic outcomes of these surgical interventions compared with medical treatment in chronic rhinitis have not been discussed previously.ObjectiveThis study aimed to evaluate the efficacy of radiofrequency ablation of the inferior turbinate of the intraturbinate segment of the posterior nasal nerve (RAPN) in comparison with intranasal corticosteroid spray (INCS) plus oral antihistamines for the treatment of chronic rhinitis.MethodsA retrospective cohort study was conducted on patients with chronic rhinitis who had an inadequate response to medication. Inclusion criteria included a 24-h Reflective Total Nasal Symptom Score (rTNSS) ≥4 and a rhinorrhea score ≥1. Patients with prior nasal surgeries, caudal septal deviation, or acute/chronic rhinosinusitis were excluded. The primary endpoint was the change in 24-h rTNSS and Nasal Obstruction Symptom Evaluation (NOSE) scores at the 3-month follow-up.ResultsA total of 64 patients were included: 44 received RAPN, and 20 received INCS. Baseline rTNSS was 7.3 ± 2.1 for RAPN and 6.9 ± 2.3 for INCS (p = .497). Both groups showed significant improvement in rTNSS and NOSE scores at 1 and 3 months (p < .001). However, the RAPN group demonstrated significantly greater improvement than the INCS group at 1 to 3 months of follow-up (p = .001). Subscore analysis revealed that rhinorrhea (at 1 and 3 months) and sneezing (at 1 month) did not differ significantly between groups. One case of postoperative anterior epistaxis was noted in the RAPN group.ConclusionsBoth INCS and RAPN are highly effective in alleviating chronic rhinitis symptoms. Although RAPN does not establish definitive superiority over medical therapy across all neurogenic domains, it provides comparable, sustained symptom control with the distinct advantage of drug-free maintenance, offering a valuable therapeutic alternative.
Time in the OR is expensive and hands-on training is often scarce for surgical trainees in pediatric urology. Antireflux surgeries are complex procedures consisting of several key steps and training of these is crucial to reduce the learning curve, however, only a few simulation models exist for training surgical procedures in pediatric urology. Our aim was to develop and evaluate a simple, low-budget and easily reproducible training model to simulate common antireflux procedures. A four main component model was developed to simulate the key steps of the procedures for easily accessible at home training. It consists of three commercially available balloons and a piece of synthetic undercast padding. A detailed description of the assembly of the training model as well as the crucial key steps of the procedures were provided. A 5-point Likert scale including 23 items was used to assess the model in regards to anatomical realism, usefulness as a training tool as well as overall reactions to the model. The survey was evaluated within workshops for trainees and final year students. In total, 81 surveys were answered with a 98.5% completion rate of all answered items. The model scored an overall mean value of 4.3 points (median value 4.6) and was reported to be quickly and easily assembled to represent realistic anatomical dimensions. It was evaluated as a useful training tool to improve surgical skills for at home training. Evaluators stated that simulation with the model helped to feel safer in the operating room with a mean of seven simulation procedures with the model. We present a low budget, disposable training model for ureteral reimplantation to train the most important component steps outside the clinical setting. This model demonstrated promising potential for internalizing the different steps of the procedure as well as improving skills in surgical training outside the operating room.
The data of eight patients with end-stage heart failure who experienced in-hospital sudden cardiac arrest and received cardiopulmonary resuscitation (CPR), followed by extracorporeal membrane oxygenation (ECMO) combined with delayed left ventricular assist device (LVAD) implantation in Fujian Medical University Union Hospital from January 2022 to June 2025 were retrospectively reviewed. Among them, there were seven males and one female, with a median age of 56 (50, 63) years. The etiologies included ischemic cardiomyopathy (five cases), dilated cardiomyopathy (two cases) and low cardiac output syndrome after severe valvular heart disease surgery (one case). All patients were stabilized by ECMO rescue before LVAD implantation, with an ECMO support time of 9.5 (6.5, 12.0) days. All surgeries were performed under general anesthesia with cardiopulmonary bypass. Postoperatively, six cases discharged smoothly, two cases died in hospital, and one case developed cerebral infarction which recovered after interventional thrombectomy. For discharged patients, follow-up was conducted at 1, 3, 6 and 12 months, the mechanical pump functioned normally, and cardiac function was significantly improved. The study suggests that ECMO can stabilize the condition of these high-risk patients, and bridging to LVAD can relieve the pressure on the donor heart and improve prognosis. 回顾性纳入2022年1月至2025年6月福建医科大学附属协和医院8例心源性猝死心肺复苏后接受体外膜肺氧合(ECMO)并桥接左心室辅助装置(LVAD)植入治疗的终末期心力衰竭患者。其中男7例,女1例,年龄56(50,63)岁,包括缺血性心肌病5例、扩张型心肌病2例及重症瓣膜病术后低心排血量综合征1例。所有患者经ECMO抢救稳定后行LVAD植入,ECMO支持时间9.5(6.5,12.0)d,手术均在全身麻醉体外循环下进行,术后6例顺利出院,2例院内死亡,1例并发脑梗死经治疗后恢复。患者出院后1、3、6、12个月随访,机械泵运转正常,心功能明显改善。研究结果提示,ECMO可稳定此类高危患者病情,桥接LVAD能缓解供心压力并改善预后。.
Cataract surgery in patients with chronic anterior uveitis may be associated with increased risk for complications and poor outcomes. This study analyses visual outcome, uveitis course and complications after cataract surgery with intraocular lens (IOL) implantation in adolescents and adults with juvenile idiopathic arthritis (JIA)-associated or antinuclear antibodies (ANA)-positive uveitis. Data before and at 6 weeks, 1 and 2 years after surgery were retrospectively analysed according to Standardization of Uveitis Nomenclature (SUN) standards. Surgery was performed with small incisions, phacoemulsification and IOL implantation. Surgical technique was adapted to pre-existing uveitis-related morphological abnormalities. Predictors of visual outcome and vision-threatening complications at 2-year follow-up (FU) were analysed. 93 surgeries of 83 patients (84% female; mean age 24.8±16.2 years) with JIA-associated (84%) or ANA-positive (16%) anterior uveitis were analysed. Preoperative treatment included topical steroids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; 72.0%) or biological (b) DMARDs (65.6%). Besides cataract, uveitis-related complications (eg, fibrotic lens membrane, posterior synechiae and pupil contraction) were present in 95.7% before surgery. Best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (logMAR) improved from 1.57±1.32 preoperatively to 0.42±0.83 at 2 years (p<0.001). Postoperative complications included posterior synechiae formation (30%), giant-cell deposits (35.7%), posterior capsule opacification (51.9%) and macular oedema (12.7%). Significant preoperative predictors of poor visual outcome included poor BCVA and high laser flare (LF) values, and those of postoperative ocular complications also included poor BCVA and a lack of systemic anti-inflammatory drug use (each, p<0.05). Beneficial outcomes can be achieved following cataract surgery with IOL implantation in adolescents and adults with JIA-associated or ANA-positive anterior uveitis. Important prerequisites include preoperative inactivity, appropriate surgical technique and sustained long-term uveitis inactivity with the use of DMARDs.
Postoperative mortality commonly follows complications that are not prevented, recognised or managed effectively. Ward-based nursing care is central to surveillance, escalation and rescue, but population-level evidence using shift-level staffing data is limited. This national population-based cohort study examined the association between surgical ward nurse staffing and postoperative outcomes. Adults aged 18 years or older undergoing inpatient surgery under general or neuraxial anaesthesia in public hospitals in Aotearoa New Zealand between 2022 and 2024 were included. Prospectively recorded TrendCare staffing data were linked to administrative health datasets. The exposure was shift-level staffing variance, defined as the difference between required and available nursing care hours on surgical wards in the treating hospital during admission. The primary outcome was 90-day postoperative mortality. Secondary outcomes were postoperative complications and failure to rescue. The cohort included 202 428 patients undergoing 223 415 surgical admissions. Within 90 days, 6296 admissions resulted in death (2.8%). Complications occurred in 41 722 admissions (18.7%), with failure to rescue in 15.1%. Of 281 147 surgical ward shifts, 122 186 (43.5%) were understaffed. After adjustment, each one-nurse reduction in staffing per shift was associated with higher odds of mortality (aOR: 1.13, 95% CI: 1.07-1.18), complications (aOR: 1.07, 95% CI: 1.05-1.10) and failure to rescue (aOR: 1.07, 95% CI: 1.00-1.14). Modelling estimated that correcting observed staffing deficits was associated with 182 fewer deaths annually. Lower surgical ward nurse staffing was associated with increased postoperative mortality, complications and failure to rescue. Nurse staffing is a modifiable system factor associated with postoperative safety and should be prioritised to improve surgical outcomes.
Achieving tension-free repair of large and massive rotator cuff tears remains challenging. Although muscle advancement techniques have been proposed, their biomechanical effects remain unclear. This study evaluated the effects of stepwise supraspinatus (SSP) and infraspinatus (ISP) muscle advancement on tendon-footprint distance in a porcine ex vivo model. Twelve shoulders from seven porcine specimens were prepared by detaching the SSP and ISP tendons from the footprint, followed by a standardized resection of 15 mm of the tendon stump. The tendon-footprint distance was measured under a 20 N load. Four conditions were tested: control, SSP alone, SSP + upper ISP, and SSP + entire ISP. Data were analyzed using the Friedman test with post hoc Wilcoxon signed-rank tests and Bonferroni correction. The median (interquartile range) distances were 23.0 (18.8-26.3) mm in the control, 19.0 (15.0-24.0) mm with SSP alone, 16.5 (9.8-18.3) mm with SSP + upper ISP, and 0.5 (0.0-4.0) mm with SSP + entire ISP. Significant differences were observed among conditions (P < 0.001). SSP + entire ISP showed significantly smaller distances than all other conditions (P = 0.015). SSP + upper ISP also showed smaller distances than control (P = 0.032) and SSP alone (P = 0.036), whereas no difference was found between control and SSP alone (P = 0.132). Stepwise muscle advancement progressively reduces the tendon-footprint distance, with SSP+entire ISP providing the greatest effect. ISP advancement may be critical for tension-free repair.
We aimed to evaluate the risks and outcomes of coronary artery bypass grafting in patients aged ≥80 years in Australia. We conducted a retrospective cohort study of 96,849 patients who underwent isolated coronary artery bypass surgery between 1 January 2001 and 31 December 2022, using data from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons cardiac surgery database. Patients were stratified into octogenarians and non-octogenarians. Primary outcomes included operative mortality (30-day or in-hospital death) and long-term survival. Kaplan-Meier estimates were used to analyse survival, logistic regression to identify predictors of early mortality, and Cox proportional hazards to identify predictors of late mortality. Survival in the octogenarian cohort was compared with an age- and sex-matched Australian population. Operative mortality was 2.8% in octogenarians vs 1.0% in non-octogenarians. The median follow-up was 3.4 years, with Kaplan-Meier estimated survival rates of 93%, 72%, 37% and 14% at 1, 5, 10, and 15 years. Median survival was 8.0 years in octogenarians, compared to 6.7 years in an age- and sex-matched general Australian population. The standardised mortality ratio was 0.78 (95% confidence interval 0.75-0.82; p<0.001). Although octogenarians undergoing coronary artery bypass have a higher operative risk than younger patients, mortality rates are lower than previously reported. Surgery in this population may be associated with favourable long-term survival compared to the general population. These findings support careful patient selection and shared decision-making when considering surgical revascularisation in the elderly.
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Objective: To evaluate the predictive value of the admission creatinine-to-albumin ratio (CAR) for 30-day all-cause mortality and in-hospital adverse events in patients with type B aortic dissection (TBAD) undergoing thoracic endovascular aortic repair (TEVAR). Methods: This retrospective cohort study analyzed clinical data from 968 consecutive TBAD patients undergoing TEVAR at Guangdong Provincial People's Hospital from January 2010 to January 2024. Admission serum creatinine and albumin levels within 24 hours were used to calculate CAR. The optimal cut-off value of CAR was identified via maximally selected rank statistics for predicting 30-day all-cause mortality. Patients were stratified into high-CAR (≥the cut-off value of CAR) and low-CAR (<the cut-off value of CAR) groups. The primary endpoint was 30-day all-cause mortality. The secondary endpoints were in-hospital adverse events with particular focus on new-onset dialysis. Analyses included Kaplan-Meier survival, multivariable Cox and logistic regression, restricted cubic spline (RCS) analysis. Subgroup analyses were performed by age (<65 vs.≥65 years), sex, clinical phase of TBAD (acute, subacute, chronic), TBAD type (complicated vs. uncomplicated), DeBakey classification, and maximum aortic diameter. Sensitivity analyses were conducted by excluding patients with stage Ⅳ to V chronic kidney disease or cirrhosis. Results: A total of 968 patients were included, with an age of (55.2±11.4) years, and 835 (86.3%) were male. CAR predicted 30-day mortality with an area under the curve of 0.714. The optimal cut-off value was 3.00, yielding a low-CAR group (n=621) and a high-CAR group (n=347). The 30-day mortality was 4.6% (16/347) in the high-CAR group versus 1.1% (7/621) in the low-CAR group (P<0.01). Kaplan-Meier survival analysis yielded consistent results (Plog-rank<0.01). RCS analysis indicated a non-linear association between CAR and 30-day mortality risk (non-linearity P=0.03). The multivariable Cox regression analysis showed that CAR was an independent risk factor for 30 d all-cause mortality (HR=1.10, 95%CI 1.03-1.17). In-hospital adverse events were more frequent in the high-CAR group than in the low-CAR group (15.9% (55/347) vs. 5.6% (35/621), P<0.01), and logistic regression confirmed CAR as an independent predictor (OR=1.10, 95%CI 1.05-1.17). Notably, new-onset dialysis showed the most pronounced intergroup difference among all individual adverse events (5.8% (20/347) vs. 0.6% (4/621), P<0.01) and multivariable logistic regression further confirmed CAR as an independent predictor of new-onset dialysis (OR=1.09, 95%CI 1.02-1.16). Subgroup analyses demonstrated consistent predictive performance for 30-day mortality and in-hospital adverse events across major clinical subgroups (all interaction P>0.05). For new-onset dialysis, the effect of CAR was significantly stronger in complicated TBAD than in uncomplicated TBAD (interaction P=0.02). Results held after excluding patients with Ⅳ-Ⅴ time renal disease or cirrhosis. Conclusions: Admission CAR≥3.00 independently predicts 30-day mortality and in-hospital adverse events in TBAD patients following TEVAR, with a non-linear dose-response relationship. Among all endpoints, CAR demonstrates the strongest predictive value for postoperative severe renal deterioration (new-onset dialysis), an effect that appears amplified in complicated TBAD. 目的: 评估入院24 h内肌酐与白蛋白比值(CAR)对接受胸主动脉腔内修复术(TEVAR)的B型主动脉夹层患者术后30 d全因死亡及院内不良事件的预测价值。 方法: 本研究为回顾性队列研究。纳入2010年1月至2024年1月于广东省人民医院接受TEVAR治疗的B型主动脉夹层患者。采集入院24 h内血清肌酐与白蛋白并计算CAR。以最大选择秩统计量确定CAR预测30 d全因死亡的截断值,据此将患者分为高CAR组(≥截断值)与低CAR组。主要终点为术后30 d全因死亡,次要终点为术后院内不良事件(重点关注新发透析)。采用受试者工作特征曲线、Kaplan-Meier生存曲线、限制性立方样条分析CAR对术后30 d全因死亡的评估效能及二者的剂量-反应关系,使用多因素Cox比例风险回归模型分析CAR对患者术后30 d死亡的影响,logistic回归分析探讨CAR对院内不良事件和新发透析事件的影响。并按年龄(<65岁与≥65岁)、性别、临床分期(急性期、亚急性期、慢性期)、B型主动脉夹层类型(复杂型与非复杂型)、DeBakey分型及主动脉最大直径进行亚组分析,通过剔除慢性肾脏病Ⅳ~Ⅴ期及肝硬化患者进行敏感性分析。 结果: 共纳入968例患者,年龄(55.2±11.4)岁,男性835例(86.3%)。CAR预测术后30 d死亡的曲线下面积为0.714。CAR的截断值为3.00。低CAR组621例,高CAR组347例。高CAR组术后30 d全因死亡率高于低CAR组[4.6%(16/347)比1.1%(7/621),P<0.01],Kaplan-Meier生存分析结果与之一致(Plog-rank<0.01)。限制性立方样条分析提示CAR与术后30 d全因死亡风险呈非线性关联(非线性P=0.03)。高CAR组院内不良事件发生率高于低CAR组[15.9%(55/347)比5.6%(35/621),P<0.01],各单项事件中两组在新发透析发生率方面差异明显[5.8%(20/347)比0.6%(4/621),P<0.01]。多因素Cox比例风险回归分析结果显示,CAR是术后30 d全因死亡的独立危险因素(HR=1.10,95%CI 1.03~1.17);多因素logistic回归分析结果显示,CAR是院内不良事件(OR=1.10,95%CI 1.05~1.17)及新发透析(OR=1.09,95%CI 1.02~1.16)的独立危险因素。亚组分析显示CAR对术后30 d全因死亡及院内不良事件的预测效能在各亚组中保持一致(P交互均>0.05);对于新发透析,CAR在复杂型亚组中的预测效应值高于非复杂型亚组(P交互=0.02)。排除Ⅳ~Ⅴ期肾病及肝硬化患者后结果稳健。 结论: 入院CAR≥3.00可独立预测B型主动脉夹层患者TEVAR术后30 d死亡及院内不良事件风险增加,且该关联呈非线性剂量-反应关系。CAR对术后严重肾功能恶化(新发透析)的预判价值在所有终点中最为突出,且该效应在复杂型B型主动脉夹层患者中可能进一步增强。.
Cancer pain in pancreatic ductal adenocarcinoma (PDAC) is characterized by complex mechanisms, severe, and often difficult-to-control. Pain not only represents a major source of suffering for PDAC patients but can also promote tumor progression through intricate neuro-immune crosstalk networks. The traditional three-step analgesic ladder is often insufficient for managing PDAC pain. In recent years, the earlier application of minimally invasive interventional techniques, the adoption of multi-disciplinary team, and the integration of smart healthcare tools are driving PDAC pain management toward more precise approaches. Exploration of the tumor-neuro-immune interaction network offers novel insights for driving personalized analgesia. This article systematically reviews the latest advances in analgesic approaches for PDAC, with an emphasis on optimizing existing therapies, defining the role of minimally invasive interventions, and outlining future research directions for precision analgesia. 胰腺导管腺癌(PDAC)疼痛机制复杂、程度剧烈且难以控制。疼痛不仅是PDAC患者的主要痛苦来源,还可通过复杂的神经-免疫交互网络促进肿瘤进展。传统的三阶梯镇痛模式难以充分应对PDAC疼痛。近年来,微创介入技术的前移、多学科诊疗模式的引入以及智慧医疗工具的整合,正推动PDAC疼痛管理向更精准的方向发展。同时肿瘤-神经-免疫交互网络的机制探索,为驱动个体化镇痛提供了新思路。该文系统梳理PDAC镇痛策略的最新进展,着重讨论现有疗法的优化、微创介入的定位及未来精准镇痛的研究方向。.
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Traumatic brain injury (TBI) is a major cause of morbidity and mortality, and cognitive impairment can be devastating among survivors. The objective was to assess an association between gabapentin and cognitive impairment after TBI. This retrospective cohort study used the multinational TriNetX Research Network (>150 million patients). Adults (≥18 years) with a first TBI and Glasgow Coma Scale (GCS) score recorded on the day of injury were included. Patients with known cognitive impairment or gabapentin exposure were excluded. The cohort (n = 49,925) was stratified into mild (GCS 13-15; n = 34,376), moderate (9-12; n = 4035), and severe (3-8; n = 12,845) TBI. The risk of cognitive impairment and mortality were assessed using Cox proportional hazard models adjusted for known predictors. Secondary analyses examined levetiracetam use (as seizure prophylaxis) and long-term medical and functional outcomes. Among 49,925 included patients w, 3.5% received gabapentin on the day of TBI. After adjustment, gabapentin was associated with a 22% lower risk of cognitive impairment in mild TBI (HR = 0.78; 95% CI, 0.62-0.98; P = .03) and a 46% lower risk of mortality in severe TBI (HR = 0.54; 95% CI, 0.40-0.72; P < .001). Levetiracetam showed no protective association with cognition. Long-term follow-up associated gabapentin use with lower mortality but higher rates of psychiatric/sleep diagnoses, reduced mobility, atrial fibrillation, and pulmonary embolism. Although causality cannot be inferred, these findings suggest gabapentin warrant prospective investigation as a candidate neuroprotective therapy.
To examine the scientific production, publication trends, conceptual structure, and thematic evolution of nursing-related literature on spinal surgery. Descriptive bibliometric study. Bibliographic data were retrieved from the Web of Science Core Collection, Scopus, and PubMed on May 22, 2026. No language or publication-year restrictions were applied. The search strategy was based on two concept clusters: spinal surgery and nursing. After duplicate removal, eligibility screening, data cleaning, and bibliographic standardization, analyses were performed using Bibliometrix/Biblioshiny and VOSviewer. Publication trends, citation indicators, productive sources, authors, institutions, countries, keyword co-occurrence, thematic mapping, and trend topics were analyzed. A total of 266 publications published between 1951 and 2026 were included. These publications appeared in 96 sources and involved 786 authors. The annual growth rate was 2.63%, with the highest output recorded in 2023 (n = 19). The United States led in publication output and citation impact. The literature was primarily structured around spinal fusion, nursing, lumbar vertebrae, spinal surgery, scoliosis, patient outcomes, pain, and postoperative care. Nursing assessment, patient education, and the perioperative period emerged as motor themes, while postoperative care, enhanced recovery after surgery, and nursing care represented recent trends. The spinal surgery nursing literature has evolved toward a patient-centered, outcome-focused, perioperative, and multidisciplinary orientation. Strengthening evidence-based perioperative assessment, patient education, pain management, postoperative monitoring, complication prevention, discharge planning, and continuity of care may improve recovery, patient safety, functional outcomes, and care coordination.
Objective: To investigate the expression profile of Centromere Protein N (CENPN) in invasive breast cancer (BRCA), evaluate its prognostic significance, and assess its involvement in immune regulation. Methods: The expression, prognostic value, and correlation with tumor immunogenicity of CENPN in BRCA tissues were analyzed based on The Cancer Genome Atlas (TCGA) database. Verification was conducted using cancerous and adjacent normal tissues from BRCA patients who underwent surgical treatment at Yantai Mountain Hospital between January 2022 and April 2023. CENPN expression in various immune cells in the blood was examined using the Human Protein Atlas (HPA) database. Genetic alterations of CENPN in breast cancer tissues were analyzed via the cBioPortal database. CENPN-related genes were screened using the GEPIA 2.0 database, and the interaction network between CENPN and similar genes was visualized with the STRING database. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were employed to explore the potential biological functions of CENPN. The correlation between CENPN expression and immune cell infiltration, as well as immune cell markers in BRCA tissues, was assessed using the TIMER 2.0 database. The effect of CENPN on the proliferation ability of breast cancer MCF-7 cells was detected by the CCK-8 assay, and its impact on the migration ability of MCF-7 cells was evaluated by a wound healing assay. Results: Analysis of TCGA database data revealed that CENPN expression was significantly higher in BRCA tissues compared to adjacent normal tissues (P<0.05). Validation in our institutional cohort demonstrated a significantly higher positivity rate for CENPN in the 17 breast cancer tissues (82.4%) than in the paired paracancerous tissues (5.9%, P<0.001). According to the HPA database, elevated CENPN expression was observed in T-reg cells, naïve B cells, and myeloid dendritic cells. Kaplan-Meier survival analysis indicated that patients with high CENPN expression had poorer overall survival (HR=1.39, P<0.001), recurrence-free survival (HR=1.31, P<0.001), post-progression survival (HR=1.28, P=0.036), and distant metastasis-free survival (HR=1.6, P<0.001). Correlation analysis revealed a negative association between CENPN expression and tumor mutational burden in BRCA patients (r=-0.196, P<0.001). Furthermore, CENPN expression was positively correlated with 5 out of 20 common immune checkpoint genes and negatively correlated with the remaining 15, suggesting its potential for predicting immunotherapy response. Analysis via the cBioPortal database showed that invasive lobular breast carcinoma had the highest CENPN alteration frequency, with amplification being the most common alteration in BRCA. Invasive mixed mucinous breast carcinoma exhibited the highest mutation frequency, and a key missense mutation (K329N) was identified as a potential driver in BRCA.GO enrichment analysis demonstrated that CENPN-related genes were primarily involved in cell cycle, DNA metabolic processes, cell division, nuclear lumen, chromosomes, nucleoplasm, and functions related to ATP, nucleotide, and small molecule binding. KEGG pathway analysis indicated significant enrichment in DNA replication, cellular senescence, mismatch repair, homologous recombination, p53 signaling pathway, and FOXO signaling pathway. Correlation analysis using the TIMER 2.0 database established associations between CENPN expression and the infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in BRCA. Positive correlations were also found with markers for CD8+ T cells, B cells, T cells, and T-cell exhaustion.CCK-8 assay and wound healing experiments confirmed that CENPN knockdown significantly suppressed malignant phenotypes, including proliferation and migration, in MCF-7 cells. Additionally, CENPN knockdown was found to enhance the chemosensitivity of MCF-7 cells to the anti-tumor agents 5-fluorouracil and gemcitabine. Conclusion: CENPN serves as a potential prognostic biomarker and a novel target for immunotherapy in BRCA. 目的: 探讨着丝粒蛋白N(CENPN)在浸润性乳腺癌(BRCA)中的表达特征、预后价值及在免疫调控中的作用。 方法: 基于癌症基因组图谱(TCGA)数据库分析BRCA组织中CENPN的表达、预后价值及与BRCA肿瘤免疫原性的相关性,利用2022年1月至2023年4月在烟台市烟台山医院行手术治疗的17例BRCA患者的癌组织及癌旁正常组织进行验证。基于人类蛋白质图谱(HPA)数据库分析CENPN在血液各种免疫细胞中的表达。通过cBioPortal数据库分析乳腺癌组织中的CENPN基因变异情况。通过基因表达谱数据动态分析2.0数据库筛选CENPN相关基因,并通过相互作用基因/蛋白检索工具网站可视化CENPN与相关基因的相互作用网络,采用基因本体论(GO)富集分析、京都基因和基因组百科全书(KEGG)分析以及基因集富集分析探索CENPN可能的生物学功能。利用肿瘤免疫浸润估算资源(TIMER)数据库2.0评估CENPN表达与BRCA组织中免疫细胞浸润及免疫细胞标志物之间的相关性。采用CCK-8法检测CENPN对乳腺癌MCF-7细胞增殖能力的影响,采用划痕实验评估CENPN对MCF-7细胞迁移能力的影响。 结果: TCGA数据库资料显示,BRCA组织中CENPN的表达高于癌旁正常组织(P<0.05)。自有的17例乳腺癌组织CENPN阳性率为82.4%,显著高于癌旁组织(5.9%,P<0.001)。HPA数据库资料显示,CENPN在T-reg细胞、初始B细胞以及髓样树突状细胞中表达增强。Kaplan-Meier生存分析显示,CENPN高表达患者的总生存期(HR=1.39,P<0.001)、无复发生存期(HR=1.31,P<0.001)、进展后生存期(HR=1.28,P=0.036)和无远处转移生存期(HR=1.6,P<0.001)较差。相关性分析显示,CENPN表达与BRCA患者的肿瘤突变负荷呈负相关(r=-0.196,P<0.001),与20个常见的免疫检查点基因中的5个呈正相关,15个呈负相关,具有预测免疫治疗有效性的潜力。cBioPortal数据库分析显示,乳腺浸润性小叶癌中CENPN变异发生率最高,BRCA中CENPN的扩增频率最高,乳腺浸润性混合性黏液癌中突变频率最高,CENPN区错义突变点位位于K329N,其可能是BRCA的推定驱动因素。GO功能富集分析显示,CENPN相关基因主要与细胞周期、DNA代谢过程、细胞分裂、核腔、染色体、核浆、三磷酸腺苷结合、核苷酸结合以及小分子结合等功能有关。KEGG通路富集分析显示,CENPN相关基因主要富集在DNA复制、细胞衰老、错配修复、同源重组、p53及叉头框蛋白O等信号通路中。通过TIMER 2.0数据库的相关分析显示,CENPN表达与BRCA中的B细胞、CD4+ T细胞、CD8+ T细胞、巨噬细胞、中性粒细胞及树突状细胞之间存在相关性,且与CD8+ T细胞标志物、B细胞标志物、T细胞标志物和T细胞衰竭标志物呈正相关。CCK-8法和划痕实验结果显示,敲降CENPN能够显著抑制MCF-7细胞的增殖和迁移等恶性特征,且能够进一步增强MCF-7细胞对抗肿瘤药物5-氟尿嘧啶和吉西他滨的化疗敏感性。 结论: CENPN可作为预测乳BRCA预后的潜在生物标志物,也是BRCA免疫治疗的潜在靶点。.
Objective: To develop and validate a risk scoring system for post-percutaneous coronary intervention (PCI) gastrointestinal bleeding in East Asian patients with acute coronary syndrome (ACS) based on the Fine-Gray model. Methods: This post-hoc analysis was performed on the BleeMACS international multicenter registry study. Patients with ACS undergoing PCI from 15 hospitals across 10 countries between November 2003 and June 2014 were enrolled and stratified into the East Asian group (China and Japan) and the non-East Asian group (other countries). The Fine-Gray model was used to screen predictors and construct an integer-based risk scoring system, with LASSO competing-risk regression for sensitivity analysis. The primary endpoint was gastrointestinal bleeding within 1 year after discharge, with death treated as a competing risk event. Bootstrap resampling was applied for internal validation. Calibration performance was assessed using calibration slope, intercept, and expected-to-observed (E/O) risk ratio. Risk stratification was performed using the Aalen-Johansen cumulative incidence function curve and Gray's test. The temporal distribution of bleeding events was analyzed, and subgroup analyses were conducted according to sex, diabetes mellitus, chronic kidney disease, and dual antiplatelet therapy (DAPT) status. Results: A total of 15 401 ACS patients were enrolled, with an age of (63.6±12.7) years and 3 592 females (23.32%). There were 2 332 patients in the East Asian group and 13 069 in the non-East Asian group. The final model incorporated seven predictors: admission hemoglobin (subdistribution hazard ratio (SHR)=0.82, 95%CI 0.74-0.90), age (SHR=1.02, 95%CI 1.01-1.04), hypertension (SHR=1.57, 95%CI 1.10-2.25), history of heart failure (SHR=1.97, 95%CI 1.08-3.57), peptic ulcer (SHR=3.25, 95%CI 1.41-7.52), proton-pump inhibitor use (SHR=1.54, 95%CI 1.12-2.12), and bleeding history (SHR=1.65, 95%CI 0.98-2.78). The bootstrap-corrected C-index was 0.693 (95%CI 0.652-0.738), with a calibration slope of 0.969 and an E/O ratio of 0.99, indicating favorable overall calibration performance. Risk stratification showed that the bleeding risk in the high-risk group was 3.93 times that in the low-risk group in the overall cohort. For the East Asian group, Gray's test P=0.116, with no significant difference among risk strata. The trend of bleeding risk was consistent with that of the overall cohort, and the ratio of cumulative bleeding risk between the high-and low-risk subgroups was 2.72 in the East Asian group. During the 1-year follow-up, 160 cases of post-PCI gastrointestinal bleeding occurred. The cumulative incidence was higher in East Asian patients than in non-East Asian patients (34 cases (1.46%) vs. 126 cases (0.96%)), with a higher proportion of late bleeding events (181-365 days) (14 cases (41.2%) vs. 41 cases (32.5%)). Subgroup analyses demonstrated stable risk stratification and good calibration performance across clinical subgroups. Conclusions: The gastrointestinal bleeding risk scoring system established in this study exhibits acceptable discrimination and excellent calibration, with stable performance in East Asian populations and various clinical subgroups. East Asian ACS patients have a higher incidence of post-PCI gastrointestinal bleeding with persistent late risk, indicating the need for prolonged monitoring and individualized antithrombotic therapy strategies. 目的: 基于Fine-Gray模型开发并验证适用于东亚急性冠脉综合征(ACS)患者经皮冠状动脉介入治疗(PCI)术后消化道出血的风险评分系统。 方法: 本研究为BleeMACS国际多中心注册研究的事后分析,纳入2003年11月至2014年6月来自10个国家15家医院接受PCI的ACS患者。按地域分为东亚组(中国和日本)与非东亚组(其余国家)。采用Fine-Gray模型筛选预测因子并构建整数风险评分系统,以LASSO竞争风险回归进行敏感性分析。主要终点事件为出院后1年消化道出血,死亡作为竞争风险事件。采用Bootstrap重抽样进行内部验证,通过校准斜率、截距及期望风险与观察风险比值评估校准性能;采用Aalen-Johansen累积发生函数曲线及Gray检验进行风险分层;同时分析出血事件时间分布并按性别、糖尿病、慢性肾脏病、是否接受双联抗血小板治疗开展亚组分析。 结果: 共纳入15 401例ACS患者,年龄(63.6±12.7)岁,女性3 592例(23.32%)。东亚组2 332例,非东亚组13 069例。最终模型纳入7个预测因子:入院血红蛋白[亚分布风险比(SHR)=0.82,95%CI 0.74~0.90]、年龄(SHR=1.02,95%CI 1.01~1.04)、高血压(SHR=1.57,95%CI 1.10~2.25)、心力衰竭病史(SHR=1.97,95%CI 1.08~3.57)、消化道溃疡(SHR=3.25,95%CI 1.41~7.52)、质子泵抑制剂应用(SHR=1.54,95%CI 1.12~2.12)和出血史(SHR=1.65,95%CI 0.98~2.78)。Bootstrap重抽样校正后C指数为0.693(95%CI 0.652~0.738),模型校准斜率0.969、期望风险与观察风险比值0.99,模型整体校准性能优异。风险分层显示,总体队列中高风险组与低风险组的1年累积出血发生率之比为3.93;东亚组Gray检验P=0.116,风险分层组间差异无统计学意义,但风险趋势与总体队列一致,东亚组高、低风险亚组的累积出血风险比为2.72。随访1年期间,共发生160例PCI术后消化道出血事件,东亚组事件累积发生率高于非东亚组[34例(1.46%)比126例(0.96%)],且后期(181~365 d)出血事件占比更高[14例(41.2%)比41例(32.5%)]。亚组分析显示模型在各临床亚组中风险分层稳定、校准性能良好。 结论: 本研究构建的消化道出血风险评分系统具有中等水平的区分度与优异的校准性能,在东亚人群及各临床亚组中均表现稳定。东亚ACS患者PCI术后消化道出血发生率较高且风险持续至后期,提示需延长监测并实施个体化抗栓治疗策略。.
Currently, anesthesia-based sleep therapy is experiencing a role expansion from short-term intervention for perioperative sleep disturbances to long-term treatment of chronic refractory insomnia. Integrating evidence-based data and clinical practice, this article systematically reviews the clinical application of anesthetic agents and techniques in perioperative sleep management and the treatment of chronic refractory insomnia. Rational perioperative use of anesthetic agents such as dexmedetomidine, esketamine, and propofol, together with anesthetic techniques like stellate ganglion block, can ameliorate perioperative sleep disturbances. In the domain of chronic insomnia, anesthesia-induced sleep balance therapy, patient-controlled sleep, and multimodal sleep promotion encompassing innovative anesthesia-based sleep therapy provide novel therapeutic avenues for refractory insomnia. However, current anesthesia-based sleep therapy is confronted with challenges, including low-quality evidence, high dependence on in-hospital medical resources, and underdeveloped professional standards and regulatory frameworks. Future efforts should focus on improving the evidence system, promoting clinical standardization, and advancing systematic framework construction, thereby facilitating the high-quality development of the innovative anesthesia-based sleep therapy within the field of sleep medicine. 当前,麻醉睡眠治疗正经历从围手术期睡眠紊乱短期干预向难治性失眠长期治疗的角色拓展。该文结合循证证据及临床实践,系统梳理麻醉药物及技术在围手术期睡眠管理和慢性难治性失眠治疗中的临床应用。围手术期合理应用右美托咪定、艾司氯胺酮、丙泊酚等药物及星状神经节阻滞等技术,可改善围手术期睡眠障碍。在慢性失眠领域,麻醉诱导睡眠平衡术、患者自控睡眠及涵盖麻醉睡眠创新疗法在内的多模式睡眠策略为难治性失眠提供了新的干预路径。然而,目前麻醉睡眠治疗存在循证证据等级低、院内医疗资源依赖性高、行业规范与监管体系不健全等挑战。未来需深化证据体系、加强临床规范化及推进体系化建设,以推动麻醉睡眠创新治疗在睡眠医学领域的高质量发展。.
Joint luxation is a common occurrence in veterinary medicine. Prompt and accurate assessment of a luxation is essential for restoring normal joint function. A proper orthopedic examination, along with orthogonal radiographs, is the first step in correctly diagnosing and determining treatment options. Treatment choices include conservative management, surgical stabilization, or a combination of both. The appropriate treatment depends on the patient's evaluation, the specific joint affected, and the extent of the damage.
Structural variants (SVs) are increasingly recognized as key contributors to adaptive evolution, yet they remain underexplored compared with single-nucleotide variation. To understand how large-scale genomic changes shape repeated evolution, we leveraged multiple levels of sequence data across the powerful evolutionary model system of the Mexican tetra fish (Astyanax mexicanus). We constructed one of the first pangenome graphs from a naturally evolving vertebrate, enabling comprehensive discovery of SVs among 120 fish from 11 populations. We discover substantial amounts of structural variation and explore the roles of genomic biases and selection in shaping the distribution of these variants. More than 2400 high-confidence cave-specific deletions are enriched in biological pathways involved in vision, metabolism, and behavior and cluster nonrandomly in quantitative trait loci linked to cavefish traits. Additionally, 67 genes harbor unique deletions between independent cavefish lineages. These reused genes show evidence of population-specific selection (99% contain selective sweeps compared with 8%-15% in genes lacking SVs), indicating that deletions likely rose in frequency through repeated positive selection rather than drift. Together, these results reveal that recurrent deletion events have repeatedly contributed to the evolution of cave-adapted phenotypes and highlight deletions as underexplored contributors of adaptive evolution in extreme environments.
腹主动脉瘤是一种常见的真性动脉瘤。近年来,腹主动脉瘤的发病率和死亡率明显增加,目前治疗方法主要为预防性手术。大量研究显示腹主动脉瘤患者体内铁水平明显升高,铁代谢异常在腹主动脉瘤的发生和发展过程中发挥重要作用。该文主要对铁代谢及其在腹主动脉瘤发病机制中的作用进行综述,以期为腹主动脉瘤的预防和治疗提供新的视角。.