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Enhancement of anti-PD-L1 antibody plus anlotinib efficacy due to downregulation of PD-L1 in the micro-conduit endothelium within the tumor: a randomized double-blind trial

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Cancer Biology & Medicine 2024年第10期 951-962页

作者： Cuicui Zhang Tianqing Chu Qiming Wang Ying Cheng Yongxiang Zhang Ruili Wang Leilei Ma Chaonan Qian Baohui Han Kai Li department of thoracic Oncology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer department of Respiratory Medicine Shanghai Chest Hospital Shanghai Jiaotong University department of Internal Medicine Affiliated Cancer Hospital of Zhengzhou University Henan Cancer Hospital department of thoracic Medical Oncology Jilin Cancer Hospital department of Respiratory & Critical Care Medicine Tianjin Chest Hospital Panovue Biotechnology (Beijing) Co. Ltd Medical Affairs department Chia-Tai Tian Qing Pharmaceutical Co.Ltd. department of Radiation Oncology Guangzhou Concord Cancer Center

Objective: the possible enhancing effect of anlotinib on programmed death receptor ligand（PD-L1） antibody and the efficacypredicting power of PD-L1 in micro-conduit endothelium, including lymphatic endothelial cells（LECs） and blood endothelial cells（BECs）, were determined to identify patients who would benefit from this ***: PD-L1 positivity in LECs, BECs, and tumor cells（TCs） was assessed using paraffin sections with multicolor immunofluorescence in an investigator's brochure clinical trial of TQB2450（PD-L1 antibody） alone or in combination with anlotinib in patients with non-small cell lung cancer. Progression-free survival（PFS） with different levels of PD-L1 expression was compared between the two ***: Among 75 patients, the median PFS（m PFS） was longer in patients who received TQB2450 with anlotinib [10 and 12 mg（161 and 194 days, respectively）] than patients receiving TQB2450 alone（61 days） [hazard ratio（HR）10 mg= 0.390（95% confidence interval {CI}, 0.201±0.756）, P = 0.005; HR12 mg= 0.397（0.208±0.756）, P = 0.005]. the results were similar among 58 patients with high PD-L1 expression in LECs and TCs [159 and 209 vs. 82 days, HR10 mg= 0.445（0.210±0.939）, P = 0.034; HR12 mg= 0.369（0.174±0.784）, P = 0.009], and 53 patients with high PD-L1 expression in BECs and TCs [161 and 209 vs. 41 days, HR10 mg= 0.340（0.156±0.742）, P = 0.007; HR12 mg= 0.340（0.159±0.727）, P = 0.005]. No differences were detected in the m PFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 ***: Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs. Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs, which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.

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Mediating Role of Glucose-Lipid Metabolism in the Association between the Increased Risk of Coronary Heart Disease and Exposure to Organophosphate Esters,Phthalates,and Polycyclic Aromatic Hydrocarbons

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Environment & Health 2024年第3期2卷 170-179页

作者： Duo Zhang Xiang Liu Jiazichao Tu Qinru Xiao Linjiang Han Jinfeng Fu Junye Bian Ruyue Zhang Jimei Chen Yijia Shao Shaoyou Lu School of Public Health(Shenzhen) Sun Yatsen UniversityShenzhen 518107China department of Cardiac Surgery Guangdong Cardiovascular InstituteGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China

there is a lack of human evidence concerning the cardiovascular effects of combined exposure to endocrine *** case-control study sought to investigate coronary heart disease(CHD)associations with exposure to organophosphate flame retardants(OFRs),phthalates(PAEs),and polycyclic aromatic hydrocarbons(PAHs)among 148 adults with coronary-angiography-diagnosed CHD and 320 healthy adults from southern *** mediating role of glucose-lipid metabolism was also *** kernel machine regression suggested that when exposure status was fixed to the 75th percentile with the median value as the reference,exposure to OFRs,PAEs,and PAHs was associated with an 84%(95%CI:36%−134%),132%(12%−252%),and 214%(89%−331%)increased risk of developing CHD,*** quantile sum regression indicated urinary bis(2-butoxyethyl)phosphate(BBOEP),dibutyl phosphate(DBP),monoisononyl phthalate(miNP),and metabolites of phenanthrene may be major contributors to the overall effect of *** further analyses on identified chemical risk factors,mediation analyses suggested exposure to phenanthrene may increase the risk of CHD via elevating total cholesterol and blood glucose,while exposure to DiNP mainly associates with serum ***,we observed a slight mediation effect of oxidative DNA damage between urinary BBOEP and risk of *** results provide potential direction for further experimental *** evidence is needed to clarify the causation of the results.

关键词： Cardiovascular disease Flame retardants Plasticizers Combined exposure analysis Oxidative stress

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Molecular adsorbent recirculating system in dealing with maternal Amanita poisoning during the second pregnancy trimester: a case report

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Hepatobiliary & Pancreatic Diseases International 2004年第1期3卷 152-154页

作者： BangFu Wu MinMin Wang department of Gastroenterology Guangzhou 12th Municipal People's Hospital China.

BACKGROUND:A 27-year-old woman in her 20th week of pregnancy was hospitalized because of food poisoning caused by Amanita phalloides.;MEthODS:Previously extracorporeal purification treatments with 2 times of hemodialysis plus hemoperfusion and a high volume therapeutic plasma exchange (PE) in addition to intensive medication during the first 8 days failed to improve hepatic encephalopathy (HE) and liver function but developed deep coma with severe blood chemistry and signs of threatened abortion.;RESULTS:Treatments with intermittent molecular adsorbent recirculating system (MARS) for 3 times resulted in an immediate improvement of liver function and clinical symptoms including HE and threatened abortion until her fully recovery. When the life-threatening maternal illness was cured gestation went on until premature birth at the 36th week of pregnancy, and the infant underwent an undisturbed development.;CONCLUSIONS:MARS method appears to be an optimal therapy for patients with acute liver failure secondary to cytoxic mushroom poisoning during pregnancy.

关键词： molecular adsorbent recirculating system Amanita mushroom poisoning pregnancy

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Cancer immunotherapy with envelopedself-amplifying mRNA CARG-2020 thatmodulates IL-12,IL-17 and PD-L1 pathways toprevent tumor recurrence

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Acta Pharmaceutica Sinica B 2024年第1期14卷 335-349页

作者： Ju Chen Bhaskara Reddy Madina Elham Ahmadi Timur Olegovich Yarovinsky Marie Marthe Krady Eileen Victoria Meehan Isabella China Wang Xiaoyang Ye Elise Pitmon Xian-Yong Ma Bijan Almassian Valerian Nakaar Kepeng Wang department of Immunology School of MedicineUniversity of Connecticut Health CenterFarmingtonCT 06030USA CaroGen Corporation FarmingtonCT 06030USA the Eighth Clinical Medical College of guangzhou University of Chinese Medicine Foshan Hospital of Traditional Chinese MedicineFoshan 528000China the Loomis Chaffee School WindsorCT 06095USA

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for ***,we describe the application of virus-like vesicles(VLV)for delivery of three immunomodulators alone and in combination,as a promising approach for cancer *** vectors were designed to deliver single chain interleukin(IL)-12,shorthairpin RNA(shRNA)targeting programmed death ligand 1(PD-L1),and a dominant-negative form of IL-17 receptor A(dn-IL17RA)as a single payload or as a combination *** delivery of the VLV vector expressing IL-12 alone,as well as the trivalent vector(designated CARG-2020)eradicated large established ***,only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice,indicating a benefit of the combined *** abscopal effects of CARG-2020 on the non-injected contralateral tumors,as well as protection from the tumor cell re-challenge,suggest immune-mediated mechanism of protection and establishment of immunological ***,CARG-2020 potently activates th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting *** ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

关键词： Virus-like vesicles Oncolytic virus IL-12 IL-17 PD-L1 T cell exhaustion Combination therapy Cancer immunotherapy

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Ivosidenib in Chinese patients with relapsed or refractory isocitrate dehydrogenase 1 mutated acute myeloid leukemia:a registry study

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Blood Science 2024年第3期6卷 33-41页

作者： Mingyuan Sun Qingsong Yin Yang Liang Chunkang Chang Jing Zheng Jian Li Chunyan Ji Huiying Qiu Junmin Li Yuping Gong Sheng Luo Yan Zhang Rumei Chen Zhenwei Shen Zenglian Yue Siyuan Wang Qingmei Shi Jason Yang Jie Jin Jianxiang Wang State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseaseInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjinChina department of Hematology Henan Cancer HospitalZhengzhouChina department of Hematologic Oncology State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouChina department of Hematology Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong UniversityShanghaiChina department of Hematology Fujian Medical University Union HospitalFuzhouChina department of Hematology Peking Union Medical College HospitalBeijingChina department of Hematology Qilu Hospital of Shandong UniversityJinanChina department of Hematology The First Affiliated Hospital of Soochow UniversitySuzhouChina department of Hematology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina department of Hematology West China Hospital of Sichuan UniversityChengduChina department of Hematology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina CStone Pharmaceuticals(Suzhou)Co.Ltd. SuzhouChina department of Hematology The First Affiliated HospitalZhejiang UniversitySchool of MedicineHangzhouChina

Ivosidenib,an isocitrate dehydrogenase 1(IDH1)inhibitor,has demonstrated clinical benefits in a pivotal study(AG120-C-001)in patients with IDH1-mutated(mIDH1)acute myeloid leukemia(AML).A registry study(CS3010-101:NCT04176393)was conducted to assess the pharmacokinetic(PK)characteristics,safety,and efficacy of ivosidenib in Chinese patients with relapsed or refractory(R/R)mIDH1 *** received ivosidenib 500 mg once daily for 28-day cycles until disease *** subjects underwent intensive PK/progressive disease(PD)*** subjects had the clinical response assessed at screening,every 28 days through month 12,and then every 56 *** November 12,2019,and April 2,2021,30 patients were enrolled;26(86.7%)had de novo AML and 18(60.0%)were transfusion-dependent at *** single and repeated doses of ivosidenib,median time to maximum plasma concentration(T_(max))was 4.0 and 2.0 hours,*** inter-individual variability of pharmacokinetic exposure was moderate to high(coefficient of variation[CV],25%–53%).No obvious accumulation was observed after repeated doses at cycle 2 day *** the clinical response,the CR+CRh rate was 36.7%(95%confidence interval[CI]:19.9%–56.1%),the median duration of CR+CRh was 19.7 months(95%CI:2.9 months–not reached[NR]),and median duration of response(DoR)was 14.3 months(95%CI:6.4 months–NR).Consistent clinical benefits and safety of ivosidenib were consistently observed at the final data cutoff with median follow-up time 26.0 months,as compared with primary data cutoff,and the data from Chinese R/R mIDH1 AML patients were also consistent with results from pivotal study.

关键词： China IDH1 mutation Ivosidenib Relapsed or refractory acute myeloid leukemia

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Appraising the causal effects of circulating micronutrients on liver cirrhosis:Evidence from large-scale Mendelian randomization analysis

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Portal Hypertension & Cirrhosis 2024年第3期3卷 160-170页

作者： Junlong Lin Jialin Chen Zhichao Li Baifeng Qian Yunpeng Hua department of Liver Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongChina

Aims:Observational research has identified links between micronutrient levels and chronic liver ***,the lack of randomized controlled experiments has impeded the ability to establish a cause-and-effect connection regarding micronutrients and cirrhosis of the *** Mendelian randomization(MR)analysis aimed to examine the causal impact of micronutrients on liver ***:We selected genetic instrumental variables related to 12 micronutrients from genome-wide studies on individuals of European descent,covering an array of over 9,851,867 single nucleotide polymorphisms and 460,351 *** from patients with cirrhosis in the FinnGen database(https://***/fi)were used.A two-sample MR approach was employed to establish genetically causal *** analyses used random effects and inverse variance weighted(IVW)methods,with additional sensitivity analyses for ***–Egger intercept analysis and Cochran's Q test assessed horizontal pleiotropy and ***,multivariable Mendelian randomization(MVMR)was conducted to address potential confounding ***:IVW and weighted median methods showed that most micronutrients included were not significantly associated with a genetic susceptibility to liver ***,MR analysis demonstrated a significant association between circulating vitamin D levels and a reduced risk of liver cirrhosis(odds ratio IVW=0.53,ptheMR–Egger intercept showed no evidence of horizontal pleiotropy(p=0.178),whereas Cochran's Q test found no heterogeneity(p=0.799).Furthermore,MVMR analysis confirmed vitamin D was identified as a factor that independently mitigates the risk of liver ***:this research constitutes the most comprehensive MR investigation in this field,providing evidence supporting a protective link between circulating vitamin D levels and cirrhosis *** suggests that maintaining sufficient vitamin D could be a cost-effecti

关键词： liver cirrhosis Mendelian randomization micronutrient vitamin D

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Telitacicept as a novel treatment for refractory lupus nephritis complicated by podocytic infolding glomerulopathy

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Rheumatology & Autoimmunity 2024年第3期4卷 186-188页

作者： Lu Zhou Haoguang Li Rongwei Zhang Qifeng Jiang Xinwang Duan department of Rheumatology and Immunology The Second Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchangChina department of Pathology Guangzhou Huayin Medical Laboratory CenterGuangzhouChina

To the Editor,Lupus nephritis(LN),a renal symptom of systemic lupus erythematosus(SLE),frequently causes severe organ damage in SLE patients.1 there is no consensus on the definition of refractory LN,which has been suggested to occur when remission is not achieved after 3–12 months of combined glucocorticoids and immunosuppressive therapy.2 Podocytic infolding glomerulopathy(PIG),a rare type of glomerular morphological alteration,is primarily characterized by the presence of microspheres,microtubular structures,or a combination of the two,which are associated with podocyte infolding into the glomerular basement membrane(GBM).3,4 the exact pathogenesis of PIG remains unclear,but it may be associated with autoimmune diseases like SLE and Sjögren's *** occurrence of refractory LN complicated by PIG is rare and poses significant challenges in ***,we endeavor to provide the patient with benefits by employing a novel treatment,Telitacicept,which has demonstrated the potential to achieve complete renal remission in such cases.

关键词： nephritis lupus Lupus

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Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study

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World Journal of Hepatology 2024年第5期16卷 809-821页

作者： Yuan-Yao Zhang Sen Luo Hai Li Shu-Ning Sun Xian-Bo Wang Xin Zheng Yan Huang Bei-Ling Li Yan-Hang Gao Zhi-Ping Qian Feng Liu Xiao-Bo Lu Jun-Ping Liu Hao-Tang Ren Yu-Bao Zheng Hua-Dong Yan Guo-Hong Deng Liang Qiao Yan Zhang Wen-Yi Gu Xiao-Mei Xiang Yi Zhou Yi-Xin Hou Qun Zhang Yan Xiong Cong-Cong Zou Jun Chen Ze-Bing Huang Xiu-Hua Jiang Ting-Ting Qi Yuan-Yuan Chen Na Gao Chun-Yan Liu Wei Yuan Xue Mei Jing Li Tao Li Rong-Jiong Zheng Xin-Yi Zhou Jun Zhao Zhong-Ji Meng department of Infectious Disease Institute of Biomedical ResearchRegulatory Mechanism and Targeted Therapy for Liver Cancer Shiyan Key LaboratoryHubei provincial Clinical Research Center for Precise Diagnosis and Treatment of Liver CancerTaihe HospitalHubei University of MedicineShiyan 442000Hubei ProvinceChina department of Gastroenterology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200120China department of Infectious Diseases Southwest HospitalThe Third Military Medical University(Army Medical University)Chongqing 400000China Center of Integrative Medicine Beijing Ditan HospitalCapital Medical UniversityBeijing 100020China department of Infectious Diseases Institute of Infection and ImmunologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430020Hubei ProvinceChina department of Infectious Diseases Hunan Key Laboratory of Viral HepatitisXiangya HospitalCentral South UniversityChangsha 110051Hunan ProvinceChina Hepatology Unit Department of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina department of Hepatology The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina department of Liver Intensive Care Unit Shanghai Public Health Clinical CentreFudan UniversityShanghai 200093China Tianjin Institute of Hepatology Nankai University Second People's HospitalTianjin 300192China Infectious Disease Center The First Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830054Xinjiang Uygur Autonomous RegionChina department of Infectious Diseases and Hepatology The Second Hospital of Shandong UniversityJinan 250000Shandong ProvinceChina State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseaseThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina department of Infectious Diseases The Thir

BACKGROUND Acute-on-chronic liver disease(AoCLD)accounts for the majority of patients hospitalized in the department of Hepatology or Infectious *** To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of *** Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure(ACLF)study cohort were included in this *** clinical characteristics and outcomes,and the 90-d survival rate associated with each clinical type of AoCLD were analyzed,using the Kaplan-Meier method and the log-rank *** A total of 3375 patients with AoCLD were enrolled,including 1679(49.7%)patients with liver cirrhosis acute decompensation(LC-AD),850(25.2%)patients with ACLF,577(17.1%)patients with chronic hepatitis acute exacer-bation(CHAE),and 269(8.0%)patients with liver cirrhosis active phase(LC-A).the most common cause of chronic liver disease(CLD)was HBV infection(71.4%).the most common precipitants of AoCLD was bacterial infection(22.8%).the 90-d mortality rates of each clinical subtype of AoCLD were 43.4%(232/535)for type-C ACLF,36.0%(36/100)for type-B ACLF,27.0%(58/215)for type-A ACLF,9.0%(151/1679)for LC-AD,3.0%(8/269)for LC-A,and 1.2%(7/577)for *** HBV infection is the main cause of CLD,and bacterial infection is the main precipitant of *** most common clinical type of AoCLD is *** diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

关键词： Acute-on-chronic liver disease Acute-on-chronic liver failure Liver cirrhosis Clinical features Prognosis

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血液透析期间香蕉摄入量对患者血清钾水平的影响:一项膳食管理的随机对照试验

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International Journal of Nursing Sciences 2024年第2期11卷 197-204页

作者：全梓林李彩霞赵立艳崔冬梅刘双信尹燕唐奇曾德汉宋利符霞 the department of Nephrology The Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina the department of Nursing The Eighth Affiliated HospitalSun Yat-Sen UniversityShenzhenChina

目的评估血液透析期间香蕉摄入量对维持性血液透析患者(maintenance hemodialysis,MHD)血清钾水平的影响。方法本研究为单中心、随机对照临床试验,于2021年9月15日至12月15日选取中国南方地区1所三级甲等医院的126例MHD患者,并将其随机... 详细信息

目的评估血液透析期间香蕉摄入量对维持性血液透析患者(maintenance hemodialysis,MHD)血清钾水平的影响。方法本研究为单中心、随机对照临床试验,于2021年9月15日至12月15日选取中国南方地区1所三级甲等医院的126例MHD患者,并将其随机分为干预组(n=64)和对照组(n=62)。干预组患者在血液透析期间摄入约250克香蕉,而对照组患者在血液透析期间不摄入任何食物。在血液透析前通过病例信息收集患者人口学信息和血液透析相关参数,通过采集患者透析前血液样品来评估实验室指标(如血常规、生化指标、炎症指标、肝功能、肾功能等)。在血液透析2 h和4 h、下次血液透析前分别测量两组患者的血清钾和血糖水平,并记录透析中相关并发症。采用重复测量方程分析对两组患者血清钾和血糖指标进行比较。结果最终122例MHD患者完成研究(干预组和对照组各61例)。结果显示,两组患者血清钾水平在组别和时间上不存在交互作用(P>0.05),而干预组患者血清钾水平在血液透析2 h(3.9±0.5比3.6±0.3)mmol/L和血液透析4 h(3.5±0.4比3.3±0.3)mmol/L均高于对照组(P0.05)。干预组患者在血液透析期间心律失常(8.2%比29.5%,P=0.003)和低钾血症的发生率(52.5%比80.3%,P=0.002)均低于对照组。结论血液透析开始时摄入约250 g香蕉不会引起高钾血症,可有效降低低钾血症和心律失常的发生率,并防止血液透析过程中血清钾水平下降过快。建议医务人员应与营养学家进一步合作,为MHD患者制订适用的膳食管理计划。

关键词：血糖水果血液透析护理钾血清

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X-irradiation for inhibiting glial scar formation in injured spinal cord

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Neural Regeneration Research 2013年第17期8卷 1582-1589页

作者： Guangzhi Ning Renhui Chen Yulin Li Qiang Wu Qiuli Wu Yan Li Shiqing Feng department of orthopedics Tanjin Medical University General Hospital department of orthopedics Tianjin 4th Central Hospital

X-irradiation has a beneficial effect in treating spinal cord injury. We supposed that X-irradiation could improve the microenvironment at the site of a spinal cord injury and inhibit glial scar formation. thus, this study was designed to observe the effects of 8 Gy X-irradiation on the injury site at 6 hours and 2, 4, 7, and 14 days post injury, in terms of improvement in the microenvironment and hind limb motor function. Immunohistochemistry showed that the expression of macrophage marker ED-1 and the area with glial scar formation were reduced. In addition, the Basso, Beattie and Bresnahan score was higher at 7 days post injury relative to the other time points post injury. Results indicated that X-irradiation at a dose of 8 Gy can inhibit glial scar formation and alleviate the inflammatory reaction, thereby repairing spinal cord injury. X-irradiation at 7 days post spinal cord injury may be the best time window.

关键词： neural regeneration spinal cord glial scar X-irradiation functional recovery astrocytes grants-supported paper neuroregeneration

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