Pub Date : 2026-02-12DOI: 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.
{"title":"Global, regional, and national burden of nonmalignant digestive diseases, 1990-2023: a systematic analysis from the GBD study 2023.","authors":"Fan Jiang, Xueting Li, Youbo Chen, Lei Zhang, Lei Wang, Yue Liu, Zheyi Han, Yanjie Cao, Shoubin Ning","doi":"10.1097/JS9.0000000000004481","DOIUrl":"https://doi.org/10.1097/JS9.0000000000004481","url":null,"abstract":"<p><strong>Background: </strong>This study assesses the global burden of 21 digestive diseases using data from the Global Burden of Disease (GBD) 2023 study.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165455","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}
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.
{"title":"Development and validation of prediction model for early allograft dysfunction following liver transplantation based on systematic review and meta-analysis.","authors":"Zhihong Zheng, Shuman Kuang, Zipei Wang, Lijin Zhao, Haitao Zhao","doi":"10.1097/JS9.0000000000004394","DOIUrl":"https://doi.org/10.1097/JS9.0000000000004394","url":null,"abstract":"<p><strong>Background: </strong>Early allograft dysfunction (EAD) is a common complication following liver transplantation. Early identification of high-risk recipients is crucial to improving postoperative outcomes.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165362","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}
Pub Date : 2026-02-12DOI: 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.
{"title":"Surgical approaches for complex hepatic and perihepatic tumors: a single-center experience with ante situm and ex situ techniques.","authors":"Ammar Khan, Bjarte Fosby, Sheraz Yaqub, Svein Dueland, Pål-Dag Line","doi":"10.1097/JS9.0000000000004935","DOIUrl":"https://doi.org/10.1097/JS9.0000000000004935","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165195","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}
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.
{"title":"Severe abdominal adverse events following open abdomen: a multicenter retrospective observational study.","authors":"Ryo Yamamoto, Masayuki Shimizu, Hiroharu Shinozaki, Kazuhiko Sekine, Tomohiro Kurihara, Junichi Sasaki","doi":"10.1097/JS9.0000000000004951","DOIUrl":"https://doi.org/10.1097/JS9.0000000000004951","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14401,"journal":{"name":"International journal of surgery","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165258","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}
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.
{"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}
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.
{"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}
Pub Date : 2026-02-05DOI: 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.
{"title":"Estimating the global macroeconomic impact of colorectal cancer: evidence from Global Burden of Disease 2021 and Value of a Statistical Life Year framework.","authors":"Wenwen Lv, Shihan Wang, Lei Duan, Yejun Wu, Xia Tian, Zhongxun Dong, Shuhua Xu, Bingshun Wang","doi":"10.1097/JS9.0000000000004687","DOIUrl":"https://doi.org/10.1097/JS9.0000000000004687","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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%.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Graphical abstract: </strong></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":"146149752","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}
Pub Date : 2026-02-04DOI: 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}
Pub Date : 2026-02-04DOI: 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.
{"title":"HER2-targeted molecular probes for cancer imaging: construction, optimization, and clinical applications.","authors":"Xinyu Guo, Wenjiao Min, Zhengyu Li","doi":"10.1097/JS9.0000000000004829","DOIUrl":"https://doi.org/10.1097/JS9.0000000000004829","url":null,"abstract":"<p><p>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.</p>","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":"146149745","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}