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Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei Chen Shiming Yang Senior department of Otolaryngology Head and Neck surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina department of Otorhinolaryngology Head and Neck surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina department of Otolaryngology Head and Neck surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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Prognostic relevance of number and ratio of metastatic lymph nodes in resected carcinoma of the ampulla of Vater

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Chinese Journal of Cancer Research 2013年第6期25卷 735-742页

作者： Jianguo Zhou Qian Zhang Peng Li Yi Shan Dongbing Zhao Jianqiang Cai department of abdominal surgery Cancer HospitalChinese Academy of Medical Sciences & Peking Union Medical College department of General surgery Aerospace Central Hospital

Objectives： To explore the prognostic relevance of the number and ratio of metastatic lymph nodes in resected Carcinoma of the ampulla of Vater （CAV）. Methods： The clinical data of 155 patients who underwent pancreaticoduodenectomy （PD） for cancer of the ampulla of Vater between January 1990 and December 2010 were retrospectively analyzed. Kaplan- Meier method was used in survival analysis and Log rank method in comparison. Multivariate analysis was performed using Cox proportional hazards model. Results： Among these 155 patients, the in-hospital mortality rate was 4.5%, lymph node positive disease was 21.3%, and the 5-year survival rate was 51.6%. Patients with a lymph node ratio （LNR）〉20% were more likely to have tumor differentiation, depth of duodenal involvement, depth of pancreatic invasion, T-stage and TNM-Stage. The number of the metastatic lymph nodes is important prognostic factors of the CAV. Univariate analysis showed that the factors associated with the prognosis included tumor size （P=0.036）, tumor differentiation （P=0.019）, LNR （P=0.032）, mtmber of metastatic lymph nodes （P=0.024）, lymph node metastasis （P=0.03）, depth of pancreatic invasion （P=0.001）, T-stage （P=0.002）, TNM stage （P=0.001）, elevated CA 19-9 （P=0.000）, and jaundice （P=0.021）. Multivariate analysis showed that the factors associated with the prognosis were the number of metastatic lymph nodes （P=0.032; RR： 1.283; 95% CI： 1.022-1.611）, tumor size （P=0.043; RR： 1.736; 95% CI： 1.017-2.963）, and elevated CA 19-9 （P=0.003; RR： 3.247; 95% CI： 1.504-7.010）. Conclusions： LNR is a useful factor for predicting the prognosis of the radical treatment for CAV,, whereas the number of metastatic lymph nodes is the most important factor. Further research on the locations, number, and LNR will be clinically meaningful to improve survival in patients with CAV.

关键词： Ampulla of vater lymph nodes metastasis carcinoma prognosis

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Pathophysiology and prevention of postoperative peritoneal adhesions

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World Journal of Gastroenterology 2011年第41期17卷 4545-4553页

作者： Willy Arung Michel Meurisse Olivier Detry department of General surgery Cliniques Universitaires de LubumbashiUniversity of Lubumbashi department of abdominal surgery and Transplantation CHU de LiègeUniversity of Liege

Peritoneal adhesions represent an important clinical challenge in gastrointestinal surgery. Peritoneal adhesions are a consequence of peritoneal irritation by infection or surgical trauma, and may be considered as the pathological part of healing following any peritoneal injury, particularly due to abdominal surgery. The balance between fi brin deposition and degradation is critical in determining normal peritoneal healing or adhesion formation. Postoperative peritoneal adhesions are a major cause of morbidity resulting in multiple complications, many of which may manifest several years after the initial surgical procedure. In addition to acute small bowel obstruction, peritoneal adhesions may cause pelvic or abdominal pain, and infertility. In this paper, the authors reviewed the epidemiology, pathogenesis and various prevention strategies of adhesion formation, using Medline and PubMed search. Several preventive agents against postoperative peri-toneal adhesions have been investigated. Their role aims in activating fi brinolysis, hampering coagulation, diminishing the inflammatory response, inhibiting col-lagen synthesis or creating a barrier between adjacentwound surfaces. Their results are encouraging but most of them are contradictory and achieved mostly in animal model. Until additional fi ndings from future clinical researches, only a meticulous surgery can be recommended to reduce unnecessary morbidity and mortality rates from these untoward effects of surgery. In the current state of knowledge, pre-clinical or clini-cal studies are still necessary to evaluate the effective-ness of the several proposed prevention strategies of postoperative peritoneal adhesions.

关键词： abdominal surgery Laparoscopy Complica-tion Occlusion abdominal pain

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Simultaneous hepatic resection benefits patients with synchronous colorectal cancer liver metastases

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Chinese Journal of Cancer Research 2016年第5期28卷 528-535页

作者： Yuan Li Xinyu Bi Jianjun Zhao Zhen Huang Jianguo Zhou Zhiyu Li Yefan Zhang Hong Zhao Jianqiang Cai department of abdominal surgery Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College

Objective： The safety of the simultaneous resection of synchronous colorectal cancer liver metastases （SCRLM） is still being debated. However, this simultaneous operative approach is more commonly adopted at present than in the past. Therefore, we compared simultaneous hepatic resection with delayed hepatic resection in this ***： All patients with SCRLM diagnosed before initial treatment between January 2009 and September 2013 were retrospectively included in our study. Short-term and long-term outcomes were compared in patients who underwent simultaneous colorectal and hepatic resection and those treated by delayed ***： Among the 73 patients diagnosed with SCRLM, simultaneous coloreetal and hepatic resection was performed in 60 patients （82.2%）, while delayed hepatic resection was performed in 13 patients （17.8%）. The mortality rate was zero. The postoperative complication rate after delayed resection was higher than, but not significantly different from, that after simultaneous resection （46% vs. 23%, P=0.166）. The duration of operating time （240 vs. 420 min, P〈0.05） and postoperative hospital stay time （11 vs. 18 days, P〈0.05） were shorter in the simultaneous resection group. After the initial treatments were given, the 1-, 2-, and 3-year survival rates in the simultaneous resection group were 77%, 59%, and 53%, respectively, whereas those in the delayed resection group were 67%, 42%, and 10%, respectively. The 5-year survival rate in the simultaneous resection group was 23%; overall survival differed significantly between the two groups （P=0.037）. Median disease-free survival （DFS） times were 19.1 months in the simultaneous resection group and 8.8 months in the delayed resection group. DFS differed significantly between the two groups. Coenclusions： Simultaneous colorectal and hepatic resection is safe and exhibits advantages in the longtime survival of patients.

关键词： Colorectal cancer synchronous liver metastases simultaneous resection survival

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abdominal Trauma Management: About 62 Cases at the department of General surgery of Hôpital SominéDOLO de Mopti, Mali

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Surgical Science 2021年第6期12卷 204-210页

作者： Djibril Traoré Bréhima Traoré Fodé Mory Keita Dramane Cissé Modibo Coulibaly Mory Koné Abdoul Karim Djimdé Kiffery Ibrahim Korotimi Mallé Abdoulaye Traoré Oumar Guindo Mathias Diassana Pierre M. Coulibaly Bakary T. Dembélé Pierre A. Togo department of General surgery H&ocirc pital Sominé DOLO de Mopti Mopti Mali department of surgery Polyclinique des armées Kati Mali department of Biomedical Laboratory H&ocirc pital Sominé DOLO de Mopti Mopti Mali department of Anesthesia and Resuscitation H&ocirc pital Sominé DOLO de Mopti Mopti Mali department of Public Health H&ocirc pital Sominé DOLO de Mopti Mopti Mali department of Gynecology and Obstetrics H&ocirc pital Sominé DOLO de Mopti Mopti Mali department of General surgery CHU Gabriel Touré Bamako Mali

We undertook a prospective and descriptive observational study on abdominal trauma from February 1, 2016 to August 31, 2017. The aim of this work was to identify the typology and management of abdominal trauma cases in our surgery department. Overall, abdominal trauma represented 3.54% (62/1751) of all surgeries during the study period. Among the 62 cases, men accounted for 59 and women for 3. The sex ratio was 19.67. The mean age was 24 ± 15 years. Road accidents were the most represented with 43.5% of cases. The couple of signs, hypovolemic shock and abdominal pain and decrease on blood pressure were the prominent clinical symptoms with 100.0%, and 50.0% of cases, respectively. abdominal ultrasound and abdominal x-ray without contrast were performed in 67.0% and 18.0% of cases, respectively. abdominal trauma was divided into two entities: contusion 68% and wounds 32%. Medical treatment was sufficient in 23.00% of cases. Laparotomy as a surgical approach was performed in 77.0% of cases. Local hemostasis plus drainage (27.08%), splenectomy (25.00%), suture (14.58%), hemostasis by tamponade (8.33%) and colostomy (2.08%) were undertaken as surgical procedures when it came to deal with contusions. Debridement of wounds plus suture and hemostasis by tamponade was performed in 18.73% and 4.16 cases, respectively. The most observed lesions were those of the spleen with 27.42% and those of the small bowel with 24.19%. The postoperative follow-up was straightforward in 83.33% of cases. The overall mortality was 4.17%.

关键词： Trauma-Abdomen-Emergency-Hôpital Sominé DOLO de Mopti

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期68卷 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang department of Oncology The Fifth Medical Center of Chinese PLA General Hospital department of Thoracic surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteraction<0.001).Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNSCLCs（P=0.040） and sqNSCLCs（P=0.014）,*** the POPLAR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio（HR）=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del（HR=1.05,P=0.64）.Conversely,sqNSCLCs without LRP1B-del benefited more from atezolizumab（HR=0.60,P=0.002） than those with LRP1B-del（HR=1.30,P=0.31）.Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

关键词： non-squamous NSCLC squamous NSCLC LRP1B deleterious mutations predictive biomarker immune checkpoint inhibitor

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Inhibitory effect of modified citrus pectin on liver metastases in a mouse colon cancer model

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World Journal of Gastroenterology 2008年第48期14卷 7386-7391页

作者： Hai-Ying Liu Zhi-Liang Huang Guo-Hua Yang Wei-Qun Lu Nan-Rong Yu department of abdominal surgery Affiliated Tumor Hospital of Guangzhou Medical College Guangzhou 510095 Guangdong Province China

AIM: To discuss the expression of glactin-3 in liver metastasis of colon cancer and its inhibition by modi- fied citrus pectin (MCP) in mice. METHODS: Seventy-five Balb/c mice were randomly di- vided into negative control group (n = 15), positive con- trol group (n = 15), low MCP concentration group (n = 15), middle MCP concentration group (n = 15) and high MCP concentration group (n = 15). CT26 colon cancer cells were injected into the subcapsule of mouse spleen in positive control group, low, middle and high MCP concentrations groups, except in negative control, to set up a colon cancer liver metastasis model. The concen- tration of MCP in drinking water was 0.0%, 0.0%, 1.0%, 2.5% and 5.0% (wt/vol), respectively. Liver metastasis of colon cancer was observed after 3 wk. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of galectin-3 in serum. Expression of ga- lectin-3 in liver metastasis was detected by immunohis- tochemistry. RESULTS: Except for the negative group, the percent- age of liver metastasis in the other 4 groups was 100%, 80%, 73.3% and 60%, respectively. The number of liver metastases in high MCP concentration group was significantly less than that in positive control group (P = 0.008). Except for the negative group, the median volume of implanted spleen tumor in the other 4 groups was 1.51 cm3, 0.93 cm3, 0.77 cm3 and 0.70 cm3, respec- tively. The volume of implanted tumor in middle and high MCP concentration groups was significantly smaller than that in positive control group (P = 0.019; P = 0.003). The concentration of serum galectin-3 in positive control and MCP treatment groups was significantly higher than that in the negative control group. However, there was no significant difference between them. Except for the negative control group, the expression of galectin-3 in liver metastases of the other 4 groups showed no sig- nificant difference. CONCLUSION: Expression of galetin-3 increases sig- nificantly in liver meta

关键词： Pectin Colonic neoplasms Metastasis Liver Mice

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Nanoparticles for the treatment of spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1665-1680页

作者： Qiwei Yang Di Lu Jiuping Wu Fuming Liang Huayi Wang Junjie Yang Ganggang Zhang Chen Wang Yanlian Yang Ling Zhu Xinzhi Sun department of Orthopedic surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina University of Chinese Academy of Sciences BeijingChina department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

关键词： antioxidants axon regeneration biocompatible materials drug carriers nanoparticles nerve regeneration neuroinflammatory diseases neuroprotection spinal cord injury stem cells

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Current status and perspectives in split liver transplantation

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World Journal of Gastroenterology 2015年第39期21卷 11003-11015页

作者： Andrea Lauterio Stefano Di Sandro Giacomo Concone Riccardo De Carlis Alessandro Giacomoni Luciano De Carlis Transplant Center Department of General Surgery and Abdominal Transplantation Niguarda Cà Granda Hospital department of General surgery University of Pavia Medical School

Growing experience with the liver splitting technique and favorable results equivalent to those of whole liver transplant have led to wider application of split liver transplantation(SLT) for adult and pediatric recipients in the last decade. Conversely, SLT for two adult recipients remains a challenging surgical procedure and outcomes have yet to improve. Differences in organ shortages together with religious and ethical issues related to cadaveric organ donation have had an impact on the worldwide distribution of SLT. Despite technical refinements and a better understanding of the complex liver anatomy, SLT remains a technically and logistically demanding surgical procedure. This article reviews the surgical and clinical advances in this field of liver transplantation focusing on the role of SLT and the issues that may lead a further expansion of this complex surgical procedure.

关键词： Liver transplantation Split liver Segmental liver

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Octogenarian liver grafts:Is their use for transplant currently justified?

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World Journal of Gastroenterology 2017年第17期23卷 3099-3110页

作者： Carlos Jiménez-Romero Felix Cambra Oscar Caso Alejandro Manrique Jorge Calvo Alejandro Marcacuzco Paula Rioja David Lora Iago Justo HPB surgery and abdominal Organ Transplantation Unit University Hospital“Doce de Octubre” department of surgery Facultad de Medicina

AIMTo analyse the impact of octogenarian donors in liver *** present a retrospective single-center study, performed between November 1996 and March 2015, that comprises a sample of 153 liver transplants. Recipients were divided into two groups according to liver donor age: recipients of donors ≤ 65 years (group A; n = 102), and recipients of donors ≥ 80 years (group B; n = 51). A comparative analysis between the groups was performed. Quantitative variables were expressed as mean values and SD, and qualitative variables as percentages. Differences in properties between qualitative variables were assessed by χ2 test. Comparison of quantitative variables was made by t-test. Graft and patient survivals were estimated using the Kaplan-Meier ***, 3 and 5-year overall patient survival was 87.3%, 84% and 75.2%, respectively, in recipients of younger grafts vs 88.2%, 84.1% and 66.4%, respectively, in recipients of octogenarian grafts (P = 0.748). One, 3 and 5-year overall graft survival was 84.3%, 83.1% and 74.2%, respectively, in recipients of younger grafts vs 84.3%, 79.4% and 64.2%, respectively, in recipients of octogenarian grafts (P = 0.524). After excluding the patients with hepatitis C virus cirrhosis (16 in group A and 10 in group B), the 1, 3 and 5-year patient (P = 0.657) and graft (P = 0.419) survivals were practically the same in both groups. Multivariate Cox regression analysis demonstrated that overall patient survival was adversely affected by cerebrovascular donor death, hepatocarcinoma, and recipient preoperative bilirubin, and overall graft survival was adversely influenced by cerebrovascular donor death, and recipient preoperative *** standard criteria for utilization of octogenarian liver grafts are: normal gross appearance and consistency, normal or almost normal liver tests, hemodynamic stability with use of < 10 μg/kg per minute of vasopressors before procurement, intensive care unit s

关键词： Older liver Donor age Marginal liver Liver transplant Aging liver

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