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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina department of Orthopedic surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

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Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li department of Spine surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

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Digestive Surgical Emergencies in the General surgery department of the Reference Health Center in Commune I of the District of Bamako in Mali

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Surgical Science 2023年第10期14卷 646-657页

作者： Cheickna Tounkara Yacouba Fane Oumar Amadou Malle Siaka Diarra Modibo Sanogo Modibo Togola Bakary Keita Hamidou Samake Bakary Tientigui Dembele Alhassane Traore Adégné Pierre Togo Lassana Kante Zimogo Zié Sanogo Djibril Sangare department of General surgery and anesthesia-Resuscitation of the Reference Health Center of Commune I Bamako Mali Directorate of the Social Health Service of the Armed Forces of Mali Bamako Mali department of General surgery of CHU Gabriel TOURE Bamako Mali department of General surgery “A” of Point G Hospital Bamako Mali

Digestive surgical emergencies concern all patients admitted urgently and for whom a decision for surgical intervention may be necessary within 24 hours. They are on guard duty day and night. To carry out this work we have set ourselves the following objectives: Study digestive surgical emergencies in the general surgery department of the Cs ref CI of Bamako;Determine the frequency of digestive surgical emergencies;Describe the clinical and therapeutic aspects, and Analyze the results of treatment. From January 2016 to December 2016, the general surgery department of the Cs ref CI of Bamako carried out 200 digestive surgical emergencies whose files were usable;119 men and 81 women, a sex ratio of 1.5. The average age was 32.67 years;66% medical evacuation. Abdominal pain was the main reason for consultation. In the majority of cases, the physical examination made it possible to make the diagnosis. Faced with certain doubtful cases, we requested paraclinical examinations (ultrasound, ASP and the rhesus group). The main etiology was acute appendicitis with 59% of cases. The frequency of digestive surgical emergencies was 35.1% of all activities of the general surgery department of the Cs ref CI of Bamako. The postoperative course was complicated in 4% of cases. Surgical site infections were the most common postoperative complications, accounting for 3% of our patients. One death was noted, i.e. 0.5% of our sample. Acute peritonitis was the cause of death in 100% of cases.

关键词： Emergency Digestive surgery Post-Operative Complication

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Rapid sequence induction(RSI) in trauma patients: Insights from healthcare providers

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World Journal of Emergency Medicine 2019年第1期10卷 19-26页

作者： Bianca M.Wahlen Ayman El-Menyar Mohammad Asim Hassan Al-Thani department of anesthesia Hamad General Hospital Clinical Research Trauma & Vascular Surgery Hamad General Hospital Clinical Medicine Weill Cornell Medical College department of surgery Trauma Surgery Hamad General Hospital

BACKGROUND: We aimed to describe the current practice of emergency physicians and anaesthesiologists in the selection of drugs for rapid-sequence induction(RSI) among trauma ***: A prospective survey audit was conducted based on a self-administered questionnaire among two intubating specialties. The preferred type and dose of hypnotics, opioids, and muscle relaxants used for RSI in trauma patients were sought in the questionnaire. Data were compared for the use of induction agent, opioid use and muscle relaxant among stable and unstable trauma patients by the intubating ***: A total of 102 participants were included; 47 were anaesthetists and 55 were emergency physicians. Propofol(74.5%) and Etomidate(50.0%) were the most frequently used induction agents. Significantly higher proportion of anesthesiologist used Propofol whereas, Etomidate was commonly used by emergency physicians in stable patients(P=0.001). Emergency physicians preferred Etomidate(63.6%) and Ketamine(20.0%) in unstable patients. The two groups were comparable for opioid use for stable patients. In unstable patients, use of opioid differed significantly by intubating specialties. The relation between rocuronium and suxamethonium use did change among the anaesthetists. Emergency physicians used more suxamethonium(55.6% vs. 27.7%, P=0.01) in stable as well as unstable(43.4 % vs. 27.7%, P=0.08) ***: There is variability in the use of drugs for RSI in trauma patients amongst emergency physicians and anaesthesiologists. There is a need to develop an RSI protocol using standardized types and dose of these agents to deliver an effective airway management for trauma patients.

关键词： Rapid-sequence induction Trauma Emergency physicians Anaesthetists Drugs

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surgery of the Goiter in the ENT department of Chu Gabriel Toure: Problematic and Perspective

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International Journal of Otolaryngology and Head & Neck surgery 2019年第6期8卷 283-291页

作者： Kassim Diarra N’faly Konaté Youssouf Sidibé Tiguida Sissoko Fatogoma Issa Koné Boubacary Guindo Harouna Sanogo Bagayoko Drissa Kaloga Siaka Soumaoro Doumbia Kadidiatou Singare Samba Karim Timbo Mohamed Amadou Keita ENT and Head and Neck surgery department Gabriel Toure University Hospital Bamako Mali ENT and Head and Neck surgery department Mother-Child “Luxembourg” Hospital Bamako Mali ENT and Head and Neck surgery department Reference Health Kalanbancoro Bamako Mali anesthesia Resuscitation department Mother-Child “Luxembourg” Hospital Bamako Mali

Aims: To describe the diagnostic aspects, surgical indications and post-operative complications of thyroidectomies performed in our department. Materials and method: A descriptive retrospective study that took place in the ENT department and Cervicofacial surgery of Gabriel TOURE University Hospital of Bamako. We did a comprehensive sampling of all goiter cases from January 2013 to December 2018. Were included in the study, the records of patients of all ages and genders, admitted into the ward and scheduled for thyroidectomy (partial or total). The exclusion criteria were incomplete hospitalization records. There were a total of 139 files were retained. Results: In 60 months, 139 cases were collected out of 1720 patients hospitalized for surgery, representing a hospital prevalence of 8.08%. The average age was 46.89 years. (123 women and 16 men). The socio-professional categories were dominated by housewives (68.34%). The reported functional signs were tachycardia, asthenia and other signs of dysthyroidism in 59% as well as signs of compression in 24.46%. In 72 cases or 51.80%, the patients consulted between 2 and 10 years of disease progression. Twenty patients or 14.39% had a history of familial goiter and 2 patients had a history of thyroid surgery. On physical examination the swelling was antero-cervical in 56.83% of cases. In 96 cases or 69.06% the glandular diameter was between 5 and 9 cm. In 2 cases or 1.43% we noted cervical adenopathy in the jugulo-carotid chain. Ultrasound, TSHus and fT4 were performed first-line and systematically in all our patients. Ultrasound objectified an appearance of multinodular goiter in 106 cases or 76.26%. In 60.43% of cases the patients were TI classes RADS 3, they were TI RADS 4A in 16 cases or 11.51%. CT scans were performed in 3 patients or 2.15% to specify the loco-regional extension, to look for possible lymph node invasion, and to compress or dipping the goiter. Surgical indication was placed in front of a multinodular

关键词： Goiter Thyroidectomy Recurrent surgery

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Anastomotic stoma coated with chitosan film as a betamethasone dipropionate carrier for peripheral nerve regeneration

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Neural Regeneration Research 2018年第2期13卷 309-316页

作者： Ping Yao Peng Li Jun-jian Jiang Hong-ye Li department of Hand surgery Hangzhou Plastic Surgery Hospital department of anesthesia Affiliated Puai Hospital of Huazhong University of Science and Technology department of Hand surgery Huashan Hospital Fudan University department of Hand surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University

Scar hyperplasia at the suture site is an important reason for hindering the repair effect of peripheral nerve injury anastomosis. To address this issue, two repair methods are often used. Biological agents are used to block nerve sutures and the surrounding tissue to achieve phys- ical anti-adhesion effects. Another agent is glucocorticosteroid, which can prevent scar growth by inhibiting inflammation. However, the overall effect of promoting regeneration of the injured nerve is not satisfactory. In this regard, we envision that these two methods can be combined and lead to shared understanding for achieving improved nerve repair. In this study, the right tibial nerve was transected 1 cm above the knee to establish a rat tibial nerve injury model. The incision was directly sutured after nerve transection. The anastomotic stoma was coated with 0.5 × 0.5 cm^2 chitosan sheets with betamethasone dipropionate. At 12 weeks after injury, compared with the con- trol and poly （D, L-lactic acid） groups, chitosan-betamethasone dipropionate film slowly degraded with the shape of the membrane still intact. Further, scar hyperplasia and the degree of adhesion at anastomotic stoma were obviously reduced, while the regenerated nerve fiber structure was complete and arranged in a good order in model rats. Electrophysiological study showed enhanced compound muscle action potential. Our results confirm that chitosan-betamethasone dipropionate film can effectively prevent local scar hyperplasia after tibial nerve repair and promote nerve regeneration.

关键词： nerve regeneration chitosan betamethasone dipropionate scar nerve injury repair function restoration film drug release carrier neural regeneration

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Microglia lactylation in relation to central nervous system diseases

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Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui Yang Nan Mo Le Tong Jianhong Dong Ziwei Fan Mengxian Jia Juanqing Yue Ying Wang School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina department of Clinical Laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina College of Medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK department of Orthopedics(Spine surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina department of Pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina department of Clinical Research Center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system ***,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative *** has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of *** is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various *** review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting ***,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

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Major hepatectomy without blood transfusion:report of 51 cases

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Chinese Medical Journal 2004年第5期117卷 673-676页

作者：芮静安周立刘馥迪褚庆福王少斌陈曙光曲强魏学韩凯张宁赵海涛 department of General surgery department of surgery department of anesthesia

Background Blood transfusion has been found to be a devastating factor for outcomes of hepatectomy This study was to assess the value of major hepatectomy without blood transfusion Methods We retrospectively studied 51 patients who had undergone major hepatectomy without blood transfusion, including 29 patients with primary liver cancer, from August 1997 to December 2000 Sixty patients undergoing major hepatectomy with blood transfusion including 48 patients with primary liver cancer served as controls Hepatectomy was performed through normothermic interruption of the porta hepatis Intraoperative ultrasonography was performed to define tumor margins, and an ultrasound dissector was used to dissect liver parenchyma Results In the study group, the operative mortality and morbidity and 1-, 2-, and 3-year recurrence rates were 0%, 9 8%, 24 1%, 27 6% and 31 0%, respectively In the control group, they were 3 3%, 28 3%, 43 5%, 54 3% and 58 7%, respectively Significant differences were seen in morbidity and recurrence rates of patients with liver cancer between the two groups ( P <0 05) Conclusion Major hepatectomy without blood transfusion can reduce postoperative morbidity and recurrence rate of patients with liver cancer

关键词： hepatectomy blood transfusion primary liver cancer recurrence

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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2025年第1期68卷 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute department of Gastrointestinal Cancer Center Peking University Cancer Hospital & Institute department of Liver surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

关键词： extrachromosomal DNA cancer therapy tumor heterogeneity drug resistance tumor evolution

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Influencing factors and risk prediction model for emergence agitation after general anesthesia for primary liver cancer

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World Journal of Gastrointestinal surgery 2024年第7期16卷 2194-2201页

作者： Shu-Shu Song Li Lin Li Li Xiao-Dong Han department of anesthesia and surgery Wenzhou Central HospitalWenzhou 325099Zhejiang ProvinceChina

BACKGROUND General anesthesia is commonly used in the surgical management of gastrointestinal tumors;however,it can lead to emergence agitation(EA).EA is a common complication associated with general anesthesia,often characterized by behaviors,such as crying,struggling,and involuntary limb movements in *** treatment is delayed,there is a risk of incision cracking and bleeding,which can significantly affect surgical ***,having a proper understanding of the factors influencing the occurrence of EA and implementing early preventive measures may reduce the incidence of agitation during the recovery phase from general anesthesia,which is beneficial for improving patient *** To analyze influencing factors and develop a risk prediction model for EA occurrence following general anesthesia for primary liver *** Retrospective analysis of clinical data from 200 patients who underwent hepatoma resection under general anesthesia at Wenzhou Central Hospital(January 2020 to December 2023)was ***-surgery,the Richmond Agitation-Sedation Scale was used to evaluate EA presence,noting EA incidence after general *** were categorized by EA presence postoperatively,and the influencing factors were analyzed using logistic regression.A nomogram-based risk prediction model was constructed and evaluated for differentiation and fit using receiver operating characteristics and calibration *** EA occurred in 51(25.5%)*** analysis identified advanced age,American Society of Anesthesiologists(ASA)grade Ⅲ,indwelling catheter use,and postoperative pain as risk factors for EA(P<0.05).Conversely,postoperative analgesia was a protective factor against EA(P<0.05).The area under the curve of the nomogram was 0.972[95%confidence interval(CI):0.947-0.997]for the training set and 0.979(95%CI:0.951-1.000)for the test ***-Lemeshow test showed a good fit(χ^(2)=5.483,P=0.705),and calibration curves showed

关键词： Primary hepatocellular carcinoma resection General anesthesia Emergence agitation Risk factors Forecast Nomograph

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