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Global, regional, and national burden of nonmalignant digestive diseases, 1990-2023: a systematic analysis from the GBD study 2023. 全球、地区和国家非恶性消化疾病负担,1990-2023:来自GBD研究2023的系统分析
IF 10.1 2区 医学 Q1 SURGERY Pub Date : 2026-02-12 DOI: 10.1097/JS9.0000000000004481
Fan Jiang, Xueting Li, Youbo Chen, Lei Zhang, Lei Wang, Yue Liu, Zheyi Han, Yanjie Cao, Shoubin Ning

Background: This study assesses the global burden of 21 digestive diseases using data from the Global Burden of Disease (GBD) 2023 study.

Methods: We analyzed prevalence, incidence, deaths, and disability-adjusted life years (DALYs) by calculating age-standardized rates (ASRs), examining temporal trends, and evaluating associated risk factors.

Results: In 2023, the global age-standardized DALY rate (ASDR) for digestive diseases was 1017.15 (95% uncertainty interval [UI] [905.18, 1124.33] per 100,000, with an age-standardized mortality rate (ASMR) of 27.18 [24.26, 30.06]. Cirrhosis and other chronic liver diseases followed, with an ASDR of 487.22 [430.22, 548.90] and an ASMR of 14.27 [12.73, 15.97]. Gastroesophageal reflux disease (GERD) was the only cause that presented upward trends in total percent change (TPC). The highest incidence of digestive diseases was observed in the United States Virgin Islands (9304.43 in 2023), while Egypt recorded the highest burden of cirrhosis (1389.31 in 2023). ASDR peaked among infants (<1 year) and older adults (≥95 years). Males aged 30-94 years carried a disproportionately high burden of cirrhosis, indicating an urgent need for age- and sex-specific interventions. For the ASDR of overall digestive diseases, metabolic risks-primarily high body mass index (BMI)-demonstrated notable regional variation. Middle and high-middle Socio-demographic Index (SDI) regions aligned with the global average (approximately 34 per 100,000), while low and low-middle SDI regions remained significantly lower (around 16 per 100,000).

Conclusion: The declining trend in alcohol-related digestive diseases contrasts sharply with the rising burden of conditions driven by metabolic risks, such as NAFLD and GERD. Targeted interventions are urgently needed to address the high burden of common gastrointestinal disorders in high-risk regions and aging populations, as well as cirrhosis among middle-aged and younger men.

背景:本研究使用全球疾病负担(GBD) 2023研究的数据评估21种消化系统疾病的全球负担。方法:我们通过计算年龄标准化率(asr)、检查时间趋势和评估相关危险因素来分析患病率、发病率、死亡率和残疾调整生命年(DALYs)。结果:2023年,消化道疾病的全球年龄标准化DALY率(ASDR)为1017.15 / 10万(95%不确定区间[UI][905.18, 114.33]),年龄标准化死亡率(ASMR)为27.18[24.26,30.06]。其次是肝硬化及其他慢性肝病,ASDR为487.22 [430.22,548.90],ASMR为14.27[12.73,15.97]。胃食管反流病(GERD)是唯一在总百分比变化(TPC)中呈现上升趋势的原因。美属维尔京群岛的消化系统疾病发病率最高(2023年为9304.43),而埃及的肝硬化发病率最高(2023年为1389.31)。结论:酒精相关消化系统疾病的下降趋势与代谢风险(如NAFLD和GERD)导致的疾病负担上升形成鲜明对比。迫切需要有针对性的干预措施来解决高危地区和老龄化人群常见胃肠道疾病的高负担,以及中年和年轻男性的肝硬化。
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引用次数: 0
Development and validation of prediction model for early allograft dysfunction following liver transplantation based on systematic review and meta-analysis. 基于系统回顾和荟萃分析的肝移植术后早期同种异体移植物功能障碍预测模型的建立和验证。
IF 10.1 2区 医学 Q1 SURGERY Pub Date : 2026-02-12 DOI: 10.1097/JS9.0000000000004394
Zhihong Zheng, Shuman Kuang, Zipei Wang, Lijin Zhao, Haitao Zhao

Background: Early allograft dysfunction (EAD) is a common complication following liver transplantation. Early identification of high-risk recipients is crucial to improving postoperative outcomes.

Methods: A predictive model for EAD was developed based on a meta-analysis of 22 cohort studies involving 17 582 liver transplantation (LT) donor-recipient pairs. Risk factors and their odds ratios were extracted, and only those statistically significant in the pooled analysis were included in the model. The validation cohort, consisting of both deceased donor liver transplantation and living donor liver transplantation recipients from China, used a manually set cutoff value of 22.5. Risk of bias was assessed using the Newcastle-Ottawa Scale.

Results: Significant risk factors included donor after circulatory death, donor age, donor body mass index, cholestatic liver disease, cold ischemia time, intraoperative fresh frozen plasma, and intraoperative red blood cell transfusion. The final model achieved a mean area under the receiver operating characteristic curve of 0.744 in external validation.

Conclusion: This prediction model reliably estimates the risk of EAD in adult LT recipients and may serve as a practical clinical tool. Cholestatic liver disease may play a role in the development of EAD, and further studies are warranted to validate this association.

背景:早期同种异体移植物功能障碍(EAD)是肝移植术后常见的并发症。早期识别高危受者对改善术后预后至关重要。方法:基于涉及17582对肝移植供体-受体的22项队列研究的荟萃分析,建立EAD的预测模型。提取危险因素及其比值比,仅纳入合并分析中有统计学意义的因素。验证队列包括来自中国的已故供肝移植和活体供肝移植受者,使用人工设置的临界值22.5。偏倚风险采用纽卡斯尔-渥太华量表进行评估。结果:循环死亡后供者、供者年龄、供者体重指数、胆汁淤积性肝病、冷缺血时间、术中新鲜冷冻血浆、术中红细胞输注是供者的重要危险因素。经外部验证,最终模型在受试者工作特征曲线下的平均面积为0.744。结论:该预测模型可靠地估计了成人肝移植受者EAD的风险,可作为实用的临床工具。胆汁淤积性肝病可能在EAD的发展中起作用,需要进一步的研究来证实这种关联。
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引用次数: 0
Surgical approaches for complex hepatic and perihepatic tumors: a single-center experience with ante situm and ex situ techniques. 复杂肝脏和肝周肿瘤的手术入路:原位前和非原位技术的单中心经验。
IF 10.1 2区 医学 Q1 SURGERY Pub Date : 2026-02-12 DOI: 10.1097/JS9.0000000000004935
Ammar Khan, Bjarte Fosby, Sheraz Yaqub, Svein Dueland, Pål-Dag Line

Background: Ante situm and ex situ liver surgery may offer potential treatment options for patients with locally advanced hepatic and perihepatic tumors deemed unresectable by conventional techniques. However, the complexity of the procedures and historically high morbidity and mortality rates have limited their widespread adoption. This study aims to evaluate perioperative morbidity, mortality, and long-term survival outcomes following ante situm and ex situ liver surgery.

Materials and methods: This single-center cohort study examines a consecutive series of patients who underwent ante situm and ex situ liver surgery at Oslo University Hospital between 2001 and 2023.

Results: A total of 35 patients underwent surgery during the study period, including 19 primary cancers and 9 colorectal liver metastases. Seven patients had benign conditions, including giant hemangiomas (n = 3), hepatic venous occlusive syndrome (n = 3), and alveolar echinococcosis (n = 1). The overall 90-day mortality rate was 5.7%. Patients with benign conditions demonstrated 100% survival at 5 years. Among patients with primary tumors, survival rates at 1, 3, and 5 years were 84.2, 67.4, and 49.4%, respectively. In contrast, the survival rates for patients with metastatic cancer were 50.0% at 1 year, 37.5% at 3 years, and 0% at 5 years.

Conclusion: In carefully selected patients, ante situm and ex situ liver surgery provide a viable option for technically unresectable liver tumors, with manageable perioperative risks and encouraging long-term outcomes, especially for benign and primary malignancies.

背景:原位和移位肝手术可能为传统技术认为不能切除的局部晚期肝脏和肝周肿瘤患者提供潜在的治疗选择。然而,手术的复杂性和历史上较高的发病率和死亡率限制了它们的广泛采用。本研究旨在评估原位和非原位肝手术的围手术期发病率、死亡率和长期生存结果。材料和方法:这项单中心队列研究调查了2001年至2023年间在奥斯陆大学医院接受原位前和非原位肝手术的连续患者。结果:研究期间共有35例患者接受手术治疗,其中原发癌19例,结直肠肝转移9例。7例患者有良性情况,包括巨大血管瘤(n = 3)、肝静脉闭塞综合征(n = 3)和肺泡包虫病(n = 1)。90天总死亡率为5.7%。良性疾病患者5年生存率为100%。原发肿瘤患者的1年、3年和5年生存率分别为84.2%、67.4和49.4%。相比之下,转移性癌症患者的1年生存率为50.0%,3年生存率为37.5%,5年生存率为0%。结论:在精心挑选的患者中,原位和移位肝手术为技术上不可切除的肝肿瘤提供了可行的选择,围手术期风险可控,长期预后良好,特别是对于良性和原发性恶性肿瘤。
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引用次数: 0
Severe abdominal adverse events following open abdomen: a multicenter retrospective observational study. 开腹后严重腹部不良事件:一项多中心回顾性观察研究。
IF 10.1 2区 医学 Q1 SURGERY Pub Date : 2026-02-12 DOI: 10.1097/JS9.0000000000004951
Ryo Yamamoto, Masayuki Shimizu, Hiroharu Shinozaki, Kazuhiko Sekine, Tomohiro Kurihara, Junichi Sasaki

Background: Open abdomen (OA) is a surgical strategy used for conditions such as intra-abdominal organ injury, abdominal compartment syndrome, and abdominal sepsis. However, some patients experience severe abdominal adverse events after OA, which can lead to prolonged hospital stays and the failure of primary fascial closure. This study aimed to identify practical predictors of severe abdominal adverse events in patients treated with OA.

Methods: This post hoc analysis used data from the nationwide, multicenter retrospective OPTITAC study, which included adult patients (≥18 years) who had undergone laparotomy requiring OA between 2010 and 2022 across 12 hospitals. Severe abdominal adverse events after OA included anastomotic leakage, enteroatmospheric fistula, pancreatic and biliary fistula, and abdominal fascia dehiscence after closure. Predictive factors from preoperative, intraoperative, and postoperative phases were analyzed using generalized estimating equations to account for institutional and regional differences in the management of patients with OA.

Results: Of the 302 patients included in this study, 74 (24.5%) experienced severe abdominal adverse events after OA. Higher body mass index (BMI) and receiving <2 l fluid resuscitation within 6 hours before laparotomy were associated with an increased incidence of severe abdominal adverse events [odds ratios (ORs): 1.06 (1.01-1.18) and 2.39 (1.60-3.57), respectively). In contrast, greater preoperative fluid volume was associated with a decreased incidence of severe abdominal adverse events [OR: 0.73 (0.59-0.91) per 1 l increase]. In addition, a fluid balance <2 l within 24 hours after surgery was associated with abdominal adverse events in patients with nonelevated postoperative serum lactate levels.

Conclusions: Low preoperative fluid volume and high BMI were associated with an increased incidence of severe abdominal adverse events in patients undergoing OA. These findings underscore the importance of fluid resuscitation before surgery in patients undergoing OA.

背景:开腹手术(OA)是一种用于腹腔内器官损伤、腹腔隔室综合征和腹腔脓毒症等疾病的手术策略。然而,一些患者在OA后会出现严重的腹部不良事件,这可能导致住院时间延长和初级筋膜闭合失败。本研究旨在确定OA患者严重腹部不良事件的实际预测因素。方法:本事后分析使用了来自全国多中心回顾性OPTITAC研究的数据,该研究包括2010年至2022年间12家医院接受剖腹手术需要OA的成年患者(≥18岁)。OA术后严重的腹部不良事件包括吻合口漏、肠瘘、胰瘘、胆道瘘、缝合后腹筋膜开裂。术前、术中和术后各阶段的预测因素使用广义估计方程进行分析,以解释OA患者管理的机构和地区差异。结果:在本研究纳入的302例患者中,74例(24.5%)在OA后出现严重的腹部不良事件。结论:术前低液量和高BMI与OA患者严重腹部不良事件发生率增加相关。这些发现强调了OA患者术前液体复苏的重要性。
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引用次数: 0
Phosphatidylcholine modulates trabecular meshwork resilience to glaucomatous injury via regulation of TGFBR3 signaling. 磷脂酰胆碱通过调节TGFBR3信号通路调节小梁网对青光眼损伤的恢复力。
IF 10.1 2区 医学 Q1 SURGERY Pub Date : 2026-02-10 DOI: 10.1097/JS9.0000000000004321
Yuening Shen, Tingting Liu, Chen Tan, Yadan Quan, Jianguo Sun, Xinghuai Sun

Introduction: Glaucoma is a main cause of irreversible blindness, which is mainly characterized by increased intraocular pressure (IOP) and degeneration of retinal ganglion cells. Current therapies primarily act by reducing aqueous humor production or enhancing its outflow to lower IOP. However, because glaucoma is a chronic disease requiring lifelong management, many patients experience reduced efficacy or develop tolerance to available medications over time. Consequently, there is an urgent need for novel pharmacological strategies that provide sustained IOP control. Dysfunction in human trabecular meshwork cells (HTMCs), which are crucial for the drainage of aqueous humor, significantly contributes to rising IOP. Phosphatidylcholine (PC) species have been recognized as potential therapeutic agents, but their causal relevance and mechanisms in glaucoma remain unclear.

Methods: We initially applied bidirectional Mendelian randomization (MR) analysis based on genome-wide associations of 648,214 individuals from European and East Asian ancestry to investigate the causal associations between 179 lipid species and glaucoma. We then explored the causal effects of PC(18:2/20:4) using HTMCs under hydrostatic pressure. The RNA sequencing, western blotting, immunofluorescence, proteomics, and flow cytometry were applied to explore the molecular mechanisms.

Results: MR results revealed that PC(18:2/20:4) functions as a protective factor for glaucoma (odds ratio = 0.89; 95% confidence interval = 0.82-0.96; P = 0.004) and no evidence for reverse causation was observed. In HTMCs, PC(18:2/20:4) could reduce the ROS production, inhibit apoptosis and fibrosis (Bax, Caspase-3, TGF-β2/3, MYOC), and recover the mitochondrial membrane potential. Transcriptomic and proteomic level data both demonstrated the activation of AMPK pathway and autophagy-related genes. Mechanistically, PC(18:2/20:4) activated AMPK via TGFBR3-dependent mechanism and inhibited mTOR. Meanwhile, blocking TGFBR3 reversed the beneficial effects.

Conclusion: This integrative study demonstrated that PC(18:2/20:4) is a causal and relevant lipid modulator in pathogenesis of glaucoma. PC(18:2/20:4) protects HTMCs from pressure-induced oxidative stress, fibrosis, and apoptosis by activating the TGFBR3-AMPK/mTOR pathway. Our findings provide experimental basis for further development of lipid-based therapy to preserve HTMCs in glaucoma.

青光眼是不可逆性失明的主要原因,主要表现为眼压升高和视网膜神经节细胞变性。目前的治疗主要是通过减少房水的产生或增加房水的流出来降低IOP。然而,由于青光眼是一种需要终身治疗的慢性疾病,随着时间的推移,许多患者的疗效下降或对现有药物产生耐受性。因此,迫切需要新的药理学策略来提供持续的IOP控制。人类小梁网细胞(HTMCs)的功能障碍是房水引流的关键,是IOP升高的重要原因。磷脂酰胆碱(PC)已被认为是潜在的治疗药物,但其在青光眼中的因果关系和机制尚不清楚。方法:我们首先采用双向孟德尔随机化(MR)分析,基于648,214名来自欧洲和东亚血统的个体的全基因组关联,研究179种脂质与青光眼之间的因果关系。然后,我们在静水压力下使用htmc来探索PC(18:2/20:4)的因果效应。应用RNA测序、western blotting、免疫荧光、蛋白质组学、流式细胞术等方法探讨其分子机制。结果:MR结果显示PC(18:2/20:4)是青光眼的保护因素(优势比= 0.89,95%可信区间= 0.82-0.96,P = 0.004),无反向因果关系。在htmc中,PC(18:2/20:4)可减少ROS的产生,抑制细胞凋亡和纤维化(Bax、Caspase-3、TGF-β2/3、MYOC),恢复线粒体膜电位。转录组学和蛋白质组学水平的数据均显示AMPK通路和自噬相关基因的激活。在机制上,PC(18:2/20:4)通过tgfbr3依赖机制激活AMPK,抑制mTOR。同时,阻断TGFBR3逆转了有益效果。结论:本综合研究证实PC(18:2/20:4)在青光眼发病机制中具有重要的脂质调节作用。PC(18:2/20:4)通过激活TGFBR3-AMPK/mTOR通路,保护htmc免受压力诱导的氧化应激、纤维化和凋亡。我们的研究结果为进一步发展以脂质为基础的治疗来保护青光眼htmc提供了实验基础。
{"title":"Phosphatidylcholine modulates trabecular meshwork resilience to glaucomatous injury via regulation of TGFBR3 signaling.","authors":"Yuening Shen, Tingting Liu, Chen Tan, Yadan Quan, Jianguo Sun, Xinghuai Sun","doi":"10.1097/JS9.0000000000004321","DOIUrl":"https://doi.org/10.1097/JS9.0000000000004321","url":null,"abstract":"<p><strong>Introduction: </strong>Glaucoma is a main cause of irreversible blindness, which is mainly characterized by increased intraocular pressure (IOP) and degeneration of retinal ganglion cells. Current therapies primarily act by reducing aqueous humor production or enhancing its outflow to lower IOP. However, because glaucoma is a chronic disease requiring lifelong management, many patients experience reduced efficacy or develop tolerance to available medications over time. Consequently, there is an urgent need for novel pharmacological strategies that provide sustained IOP control. Dysfunction in human trabecular meshwork cells (HTMCs), which are crucial for the drainage of aqueous humor, significantly contributes to rising IOP. Phosphatidylcholine (PC) species have been recognized as potential therapeutic agents, but their causal relevance and mechanisms in glaucoma remain unclear.</p><p><strong>Methods: </strong>We initially applied bidirectional Mendelian randomization (MR) analysis based on genome-wide associations of 648,214 individuals from European and East Asian ancestry to investigate the causal associations between 179 lipid species and glaucoma. We then explored the causal effects of PC(18:2/20:4) using HTMCs under hydrostatic pressure. The RNA sequencing, western blotting, immunofluorescence, proteomics, and flow cytometry were applied to explore the molecular mechanisms.</p><p><strong>Results: </strong>MR results revealed that PC(18:2/20:4) functions as a protective factor for glaucoma (odds ratio = 0.89; 95% confidence interval = 0.82-0.96; P = 0.004) and no evidence for reverse causation was observed. In HTMCs, PC(18:2/20:4) could reduce the ROS production, inhibit apoptosis and fibrosis (Bax, Caspase-3, TGF-β2/3, MYOC), and recover the mitochondrial membrane potential. Transcriptomic and proteomic level data both demonstrated the activation of AMPK pathway and autophagy-related genes. Mechanistically, PC(18:2/20:4) activated AMPK via TGFBR3-dependent mechanism and inhibited mTOR. Meanwhile, blocking TGFBR3 reversed the beneficial effects.</p><p><strong>Conclusion: </strong>This integrative study demonstrated that PC(18:2/20:4) is a causal and relevant lipid modulator in pathogenesis of glaucoma. PC(18:2/20:4) protects HTMCs from pressure-induced oxidative stress, fibrosis, and apoptosis by activating the TGFBR3-AMPK/mTOR pathway. Our findings provide experimental basis for further development of lipid-based therapy to preserve HTMCs in glaucoma.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multi-target modulation of the homologous recombination pathway by resveratrol promotes DNA damage repair in POI: integrated network pharmacology, molecular dynamics simulation, and experimental validation. 白藜芦醇多靶点调控同源重组通路促进POI DNA损伤修复:综合网络药理学、分子动力学模拟和实验验证
IF 10.1 2区 医学 Q1 SURGERY Pub Date : 2026-02-05 DOI: 10.1097/JS9.0000000000004655
Zhaoyang Yu, Weilong Peng, Mujun Li, Feiwen Li, Tao Zhang, Yingqi Nong, Chang Liu, Wenjuan Liu, Hongfan Ding, Xiaoyin Lv, Jiao Wang, Xiqian Zhang, Fenghua Liu, Huimei Wu

Background: Premature ovarian insufficiency (POI) is characterized by gonadotropin elevation, estrogen deficiency, and follicular loss. Resveratrol (RSV), a natural polyphenol with antioxidant and anti-aging properties, shows therapeutic promise for POI, but its molecular targets and mechanisms remain unclear.

Methods: Network pharmacology analysis was used to identify overlapping targets of RSV and POI, followed by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, protein-protein interaction (PPI) network construction, and hub gene screening. Molecular docking and dynamics simulations were performed to characterize the affinity and binding stability. In vivo, a cyclophosphamide-induced POI rat model was established to evaluate the protective effects of RSV on ovarian morphology and hormone levels. In vitro, a 4-hydroperoxycyclophosphamide-induced granulosa cell model was used to assess DNA damage and homologous recombination (HR) activity through TUNEL staining, Western blotting, and nuclear foci analysis, with RAD51 inhibition applied to verify pathway dependence.

Results: About 609 overlapping genes between RSV- and POI-related targets were identified. GO and KEGG enrichment analyses revealed significant involvement in reproductive system development, DNA repair complex, and cellular senescence. PPI and topological analysis identified three core genes - ATM, BRCA1, and RAD51 - significantly enriched in the HR pathway. Molecular docking and dynamic simulations indicate that RSV has a strong affinity and stable binding mode with these three targets. In vivo, RSV ameliorated cyclophosphamide-induced ovarian injury, increasing serum anti-Müllerian hormone levels and secondary follicle counts. Mechanistically, in the POI cell model, RSV upregulated RAD51 and downregulated γH2AX expression, thereby promoting HR pathway activation and DNA double-strand break repair. The protective effect of RSV was abolished by the RAD51 inhibitor RI-1. Immunofluorescence foci analysis further verified that RSV enhanced the recruitment of RAD51 to DNA damage sites and reduced nuclear γH2AX accumulation.

Conclusion: This study provides structural and experimental evidence for the target selection, structural optimization, and molecular mechanism of RSV in the treatment of POI.

背景:卵巢功能不全(POI)以促性腺激素升高、雌激素缺乏和卵泡丧失为特征。白藜芦醇(Resveratrol, RSV)是一种具有抗氧化和抗衰老特性的天然多酚,具有治疗POI的前景,但其分子靶点和机制尚不清楚。方法:采用网络药理学分析方法鉴定RSV和POI的重叠靶点,然后进行基因本体(GO)/京都基因与基因组百科全书(KEGG)富集、蛋白-蛋白相互作用(PPI)网络构建和枢纽基因筛选。通过分子对接和动力学模拟来表征其亲和力和结合稳定性。在体内,建立环磷酰胺诱导的POI大鼠模型,研究RSV对卵巢形态和激素水平的保护作用。在体外,采用4-氢过氧环磷酰胺诱导的颗粒细胞模型,通过TUNEL染色、Western blotting和核病灶分析来评估DNA损伤和同源重组(homologous recombination, HR)活性,并应用RAD51抑制来验证途径依赖性。结果:共鉴定出609个RSV与poi相关靶点的重叠基因。GO和KEGG富集分析揭示了生殖系统发育、DNA修复复合体和细胞衰老的显著参与。PPI和拓扑分析确定了三个核心基因- ATM, BRCA1和RAD51 -在HR通路中显著富集。分子对接和动力学模拟表明,RSV与这三个靶点具有较强的亲和力和稳定的结合模式。在体内,RSV改善了环磷酰胺诱导的卵巢损伤,增加了血清抗勒氏杆菌激素水平和次级卵泡计数。机制上,在POI细胞模型中,RSV上调RAD51,下调γ - h2ax表达,从而促进HR通路激活和DNA双链断裂修复。RSV的保护作用被RAD51抑制剂RI-1所消除。免疫荧光病灶分析进一步证实RSV增强了RAD51在DNA损伤位点的募集,减少了核γ - h2ax的积累。结论:本研究为RSV治疗POI的靶点选择、结构优化及分子机制提供了结构和实验依据。
{"title":"Multi-target modulation of the homologous recombination pathway by resveratrol promotes DNA damage repair in POI: integrated network pharmacology, molecular dynamics simulation, and experimental validation.","authors":"Zhaoyang Yu, Weilong Peng, Mujun Li, Feiwen Li, Tao Zhang, Yingqi Nong, Chang Liu, Wenjuan Liu, Hongfan Ding, Xiaoyin Lv, Jiao Wang, Xiqian Zhang, Fenghua Liu, Huimei Wu","doi":"10.1097/JS9.0000000000004655","DOIUrl":"https://doi.org/10.1097/JS9.0000000000004655","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) is characterized by gonadotropin elevation, estrogen deficiency, and follicular loss. Resveratrol (RSV), a natural polyphenol with antioxidant and anti-aging properties, shows therapeutic promise for POI, but its molecular targets and mechanisms remain unclear.</p><p><strong>Methods: </strong>Network pharmacology analysis was used to identify overlapping targets of RSV and POI, followed by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, protein-protein interaction (PPI) network construction, and hub gene screening. Molecular docking and dynamics simulations were performed to characterize the affinity and binding stability. In vivo, a cyclophosphamide-induced POI rat model was established to evaluate the protective effects of RSV on ovarian morphology and hormone levels. In vitro, a 4-hydroperoxycyclophosphamide-induced granulosa cell model was used to assess DNA damage and homologous recombination (HR) activity through TUNEL staining, Western blotting, and nuclear foci analysis, with RAD51 inhibition applied to verify pathway dependence.</p><p><strong>Results: </strong>About 609 overlapping genes between RSV- and POI-related targets were identified. GO and KEGG enrichment analyses revealed significant involvement in reproductive system development, DNA repair complex, and cellular senescence. PPI and topological analysis identified three core genes - ATM, BRCA1, and RAD51 - significantly enriched in the HR pathway. Molecular docking and dynamic simulations indicate that RSV has a strong affinity and stable binding mode with these three targets. In vivo, RSV ameliorated cyclophosphamide-induced ovarian injury, increasing serum anti-Müllerian hormone levels and secondary follicle counts. Mechanistically, in the POI cell model, RSV upregulated RAD51 and downregulated γH2AX expression, thereby promoting HR pathway activation and DNA double-strand break repair. The protective effect of RSV was abolished by the RAD51 inhibitor RI-1. Immunofluorescence foci analysis further verified that RSV enhanced the recruitment of RAD51 to DNA damage sites and reduced nuclear γH2AX accumulation.</p><p><strong>Conclusion: </strong>This study provides structural and experimental evidence for the target selection, structural optimization, and molecular mechanism of RSV in the treatment of POI.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Commentary on "Health-related quality-of-life, complications, and mortality rates after geriatric acetabular fracture". 对“老年髋臼骨折后与健康有关的生活质量、并发症和死亡率”的评论。
IF 10.1 2区 医学 Q1 SURGERY Pub Date : 2026-02-05 DOI: 10.1097/JS9.0000000000004668
Chengan Yang, Aihu Liu, Wenhai Zhao
{"title":"Commentary on \"Health-related quality-of-life, complications, and mortality rates after geriatric acetabular fracture\".","authors":"Chengan Yang, Aihu Liu, Wenhai Zhao","doi":"10.1097/JS9.0000000000004668","DOIUrl":"https://doi.org/10.1097/JS9.0000000000004668","url":null,"abstract":"","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Estimating the global macroeconomic impact of colorectal cancer: evidence from Global Burden of Disease 2021 and Value of a Statistical Life Year framework. 估计结直肠癌的全球宏观经济影响:来自2021年全球疾病负担的证据和统计生命年框架的价值。
IF 10.1 2区 医学 Q1 SURGERY Pub Date : 2026-02-05 DOI: 10.1097/JS9.0000000000004687
Wenwen Lv, Shihan Wang, Lei Duan, Yejun Wu, Xia Tian, Zhongxun Dong, Shuhua Xu, Bingshun Wang

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related death globally. However, its macroeconomic burden remains underexplored.

Methods: Using Global Burden of Disease (GBD) 2021 data, we quantified the economic welfare loss due to CRC across 204 countries using the Value of a Statistical Life Year (VSLY) approach. The Valuation of a Statistical Life (VSL) was derived by adjusting the U.S. benchmark ($11.8 million) based on per capita gross domestic product (GDP) and income elasticity (base case: 1.0). VSLY was calculated by dividing VSL by half the national life expectancy. Country-specific Value of Lost Welfare (VLW) was estimated and expressed as a percentage of GDP (VLW/GDP). Aggregated analyses were performed by sociodemographic index (SDI) and GBD regions. Sensitivity analyses used alternative elasticity values (0.55, 1.5) and applied a 3% discount rate.

Findings: In 2021, global CRC-related VLW was estimated at $3.49 trillion (95% uncertainty interval [UI]: $3.02-$3.96 trillion), equivalent to 2.28% (95% UI: 1.97%-2.58%) of global GDP. VLW/GDP ratios were highest in high-SDI regions (2.81%) and the Central Europe, Eastern Europe, and Central Asia super-region (3.48%). At the national level, VLW ranged from <$500 million in small island states to >$0.6 trillion in China and the U.S. Discounting increased VLW estimates by 35%-67%.

Conclusions: CRC imposes a substantial and inequitable economic burden, particularly in economically developed and aging societies. Incorporating VSLY into cancer burden assessments underscores the urgency of investing in prevention, early detection, and surgical capacity strengthening, especially in middle-income and resource-limited settings.

Graphical abstract:

背景:结直肠癌(CRC)是全球第三大最常诊断的癌症,也是癌症相关死亡的第二大原因。然而,其宏观经济负担仍未得到充分探讨。方法:使用全球疾病负担(GBD) 2021数据,我们使用统计生命年价值(VSLY)方法量化了204个国家结直肠癌造成的经济福利损失。统计寿命的估值(VSL)是根据人均国内生产总值(GDP)和收入弹性(基本情况:1.0)调整美国基准(1180万美元)得出的。VSLY的计算方法是将VSL除以国民预期寿命的一半。具体国家的福利损失价值(VLW)被估计并表示为国内生产总值的百分比(VLW/GDP)。按社会人口指数(SDI)和GBD地区进行汇总分析。敏感性分析采用替代弹性值(0.55,1.5),并采用3%的贴现率。研究结果:2021年,全球与crc相关的VLW估计为3.49万亿美元(95%不确定区间[UI]: 3.02- 3.96万亿美元),相当于全球GDP的2.28% (95% UI: 1.97%-2.58%)。VLW/GDP比率最高的是高sdi地区(2.81%)和中欧、东欧和中亚超级地区(3.48%)。从国家层面来看,中国和美国的VLW规模在0.6万亿美元之间。折扣使VLW的估值提高了35%-67%。结论:CRC造成了巨大且不公平的经济负担,特别是在经济发达和老龄化社会。将VSLY纳入癌症负担评估强调了投资于预防、早期发现和加强手术能力的紧迫性,特别是在中等收入和资源有限的环境中。图形化的简介:
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引用次数: 0
Comment on "Global, regional, and national burden of appendicitis among children and adolescents from 1990 to 2021 and projection to 2040: a cross-sectional study". 对“1990年至2021年全球、区域和国家儿童和青少年阑尾炎负担及2040年预测:一项横断面研究”的评论。
IF 10.1 2区 医学 Q1 SURGERY Pub Date : 2026-02-04 DOI: 10.1097/JS9.0000000000004854
Yamei Wu
{"title":"Comment on \"Global, regional, and national burden of appendicitis among children and adolescents from 1990 to 2021 and projection to 2040: a cross-sectional study\".","authors":"Yamei Wu","doi":"10.1097/JS9.0000000000004854","DOIUrl":"https://doi.org/10.1097/JS9.0000000000004854","url":null,"abstract":"","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
HER2-targeted molecular probes for cancer imaging: construction, optimization, and clinical applications. 靶向her2的肿瘤成像分子探针:构建、优化及临床应用
IF 10.1 2区 医学 Q1 SURGERY Pub Date : 2026-02-04 DOI: 10.1097/JS9.0000000000004829
Xinyu Guo, Wenjiao Min, Zhengyu Li

The expression of human epidermal growth factor receptor 2 (HER2) is a critical biomarker for guiding precision therapy in HER2-positive cancers. However, conventional diagnostic approaches are invasive and fail to resolve the spatiotemporal heterogeneity of HER2 expression. Molecular imaging using HER2-targeted probes provides a noninvasive alternative, enabling quantitative assessment of HER2 status at the whole-body level. This capability supports critical clinical needs including early molecular subtyping, sensitive detection of metastases, and dynamic monitoring of treatment response. This review focuses on the rational design and engineering strategies of emerging HER2-targeted probes, highlighting key advances in probe architecture and functional optimization. We systematically evaluate how optimization strategies improve imaging contrast, metabolic stability, and targeting specificity. Despite considerable preclinical progress, the widespread clinical translation of these probes remains challenged by issues in scalable manufacturing, reproducible quality control, and regulatory validation. Addressing these application barriers represents a critical objective for future research to fully realize the potential of HER2-targeted molecular imaging in precision oncology.

人表皮生长因子受体2 (HER2)的表达是指导HER2阳性癌症精准治疗的关键生物标志物。然而,传统的诊断方法是侵入性的,无法解决HER2表达的时空异质性。使用HER2靶向探针进行分子成像提供了一种无创替代方法,可以在全身水平上定量评估HER2状态。这种能力支持关键的临床需求,包括早期分子分型、转移的敏感检测和治疗反应的动态监测。本文综述了新兴her2靶向探针的合理设计和工程策略,重点介绍了探针结构和功能优化方面的关键进展。我们系统地评估优化策略如何提高成像对比度、代谢稳定性和靶向特异性。尽管取得了相当大的临床前进展,但这些探针的广泛临床转化仍然受到可扩展制造、可重复质量控制和监管验证等问题的挑战。解决这些应用障碍是未来研究的关键目标,以充分发挥her2靶向分子成像在精确肿瘤学中的潜力。
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International journal of surgery
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