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Advances in immunotherapy for hepatitis B virus associated hepatocellular carcinoma patients

World Journal of Hepatology 2024年第10期16卷 1158-1168页

作者： Wei-Hua Cao Ya-Qin Zhang Xin-Xin Li Zi-Yu Zhang Ming-Hui Li Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityPeking University Ditan Teaching HospitalBeijing 100015China

Hepatitis B virus(HBV)infection plays an important role in the occurrence and development of hepatocellular carcinoma(HCC),and the rate of HBV infection in liver cancer patients in China is as high as 92.05%.Due to long-term exposure to chronic antigens from the gut,the liver needs to maintain a certain level of immune tolerance,both to avoid severe inflammation caused by non-pathogenic antigens and to maintain the possibility of rapid and violent responses to infection and ***,HBV infection interacts with the tumor microenvironment(TME)through a highly complex and intertwined signaling pathway,which results in a special TME in *** to changes in the TME,tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through cytotoxic T-lymphocy-associated protein-4(CTLA-4)and programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1).Interferons,as a class of immune factors with strong biological activity,can improve the TME of HBV-HCC through various *** recent years,the systematic treatment of HCC has gradually come out of the *** addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs,immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of *** present,immunotherapy based on PD-1/L1 inhibitors has gradually become a new direction of systematic treatment for HCC,and the disease charac-teristics of patients included in global clinical studies are different from those of Chinese ***,whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide *** review aims to elucidate the advances of immuno-therapy for HBV related HCC patients with regard to:(1)Immunotherapy based on interferons;(2)Immunotherapy based on PD-1/L1 inhibitors;(3)Immunotherapy based on CTLA4 inhibitors;(4)Adoptive cell transfer;(5)Combination immunotherapy str

关键词： Hepatitis B virus Hepatocellular carcinoma Immune checkpoint inhibitors Peginterferon alpha Systematic treatment

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Retinal nerve fiber layer defects and chronic kidney disease:the Kailuan Eye Study

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International Journal of Ophthalmology(English edition) 2024年第9期17卷 1696-1706页

作者： Qian-Qian Wan Jin-Qiong Zhou Li-Jian Fang Ya-Xing Wang Ye-Nan Wang Qian Wang Yan-Ni Yan Xuan Yang Shou-Ling Wu Shuo-Hua Chen Jost B Jonas Wen-Bin Wei Beijing Tongren Eye Center Beijing Key Laboratory of Intraocular Tumor Diagnosis and TreatmentBeijing Ophthalmology&Visual Sciences Key LabMedical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information TechnologyBeijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Ophthalmology the Second Hospital of Anhui Medical UniversityHefei 230000Anhui ProvinceChina Department of Ophthalmology Beijing Liangxiang HospitalCapital Medical UniversityBeijing 102400China Beijing Institute of Ophthalmology Beijing Key Laboratory of Ophthalmology and Visual SciencesBeijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Ophthalmology Xuanwu HospitalCapital Medical UniversityBeijing 100730China Department of Cardiology Kailuan General HospitalTangshan 063000Hebei ProvinceChina health Care Center Kailuan GroupTangshan 063000Hebei ProvinceChina Department of Ophthalmology Medical Faculty Mannheim of the Ruprecht-Karls-University of HeidelbergHeidelberg 69117Germany

AIM:To investigate whether retinal nerve fiber layer defects(RNFLDs)is a potential risk factor for chronic kidney disease(CKD)in Chinese ***:The Kailuan Eye Study was a populationbased study that included 14440 *** participants underwent detailed assessments,RNFLDs were diagnosed using color fundus ***:Overall,12507 participants[8533 males(68.23%)]had complete systemic examination data and at least one evaluable fundus *** were found in 621 participants[5.0%;95%confidence interval(CI):4.6%-5.34%],and 70 cases of multiple RNFLDs were found(11.27%).After adjusting multiple factors,RNFLDs was significantly associated with CKD severity,the ORs of CKD stage 3,stage 4 and stage 5 were 1.698,4.167,and 9.512,*** RNFLDs were also associated with CKD severity after adjusting multiple factors,the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 ***,2294 participants had CKD(18.34%,95%CI:17.68%-18.99%).After adjusting for other factors,CKD presence was significantly correlated with the presence of ***:The strongest risk factors for RNFLDs are CKD and ***,RNFLDs can be an ocular feature in patients with *** can help detect systemic diseases,and assessment for RNFLDs should be considered in CKD patients.

关键词： chronic kidney disease retinal nerve fiber layer defects Kailuan Eye Study fundus examination

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The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes:findings from a prospective,nationwide,and multicenter registry

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Journal of Geriatric Cardiology 2024年第5期21卷 523-533页

作者： Rui FU Ying-Xuan ZHU Kong-Yong CUI Jin-Gang YANG Hai-Yan XU Dong YIN Wei-Hua SONG Hong-Jian WANG Cheng-Gang ZHU Lei FENG Wei WU Kai-HongCHEN Yan-Yan ZHAO Ye LU Ke-Fei DOU Yue-Jin YANG on behalf of the CAMI Registry Investigators Cardiometabolic Medicine Center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Medical research&Biometrics Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Coronary Heart Disease Center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Cardiology Guangzhou Traditional Chinese Medical College First Affiliated HospitalGuangdong ProvinceChina Department of Cardiology Longyan Hospital First HospitalFujian ProvinceChina 不详

OBJECTIVES To evaluate the predictive value of fasting plasma glucose(FPG)for in-hospital mortality in patients with acute myocardial infarction(AMI)with different glucose metabolism *** We selected 5,308 participants with AMI from the prospective,nationwide,multicenter CAMI registry,of which 2,081 were diabetic and 3,227 were *** were divided into high FPG and low FPG groups according to the optim-al cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts,*** primary endpoint was in-hospital *** Overall,94 diabetic patients(4.5%)and 131 nondiabetic patients(4.1%)died during hospitalization,and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L,*** with individuals who had low FPG,those with high FPG were significantly associated with higher in-hospital mortality in diabet-ic cohort(10.1%vs.2.8%;odds ratio[OR]=3.862,95%confidence interval[CI]:2.542-5.869)and nondiabetic cohort(7.4%vs.1.7%;HR=4.542,95%CI:3.041-6.782).After adjusting the potential confounders,this significant association was not ***-more,FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic *** FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic *** This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mor-tality in AMI patients with and without *** might be useful to stratify patients with AMI.

关键词： patients fasting infarction

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Degradable magnesium alloy suture promotes fibrocartilaginous interface regeneration in a rat rotator cuff transosseous repair model

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Journal of Magnesium and Alloys 2024年第1期12卷 384-393页

作者： Baoxiang Zhang Wen Zhang Fei Zhang Chao Ning Mingyang An Ke Yang Lili Tan Qiang Zhang Department of Sports Medicine Chinese PLA General HospitalBeijing 100853China Shi-changxu Innovation Center for Advanced Materials Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Materials Science and Engineering University of Science and Technology of ChinaShenyang 110016China Medical School of PLA Beijing 100853China Institute of Orthopedics Chinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Lab of Musculoskeletal Trauma&War Injuries of Chinese PLABeijing 100853China

Despite transosseous rotator cuff tear repair using sutures is widely accepted for tendon-bone fixation,the fibrocartilaginous enthesis regeneration is still hardly achieved with the traditional *** the present work,degradable magnesium(Mg)alloy wire was applied to suture supraspinatus tendon in a rat acute rotator cuff tear model with Vicryl Plus 4±0 absorbable suture as *** shoulder joint humerus-supraspinatus tendon complex specimens were retrieved at 4,8,and 12 weeks after *** Mg alloy suture groups showed better biomechanical properties in terms of ultimate load to *** observation showed that hyperplastic response of the scar tissue at the tendon-bone interface is progressively alleviated over time in the both Mg alloy suture and Vicryl suture *** the histological analysis,for Mg alloy suture groups,chondrocytes appear to proliferate at 4 weeks postoperatively,and the tendon-bone interface showed an orderly structural transition zone at 8 weeks *** collagenous fiber tended to be aligned and the tendon-bone interlocking structures apparently formed,where transitional structure from unmineralized fibrocartilage to mineralized fibrocartilage was closer to the native fibrocartilaginous *** vivo degradation of the magnesium alloy wire was completed within 12 *** results indicated that Mg alloy wire was promising as degradable suture with the potential to promotes fibrocartilaginous interface regeneration in rotator cuff repair.

关键词： Rotator cuff repair Mg alloy wire Tendon-bone healing Fibrocartilaginous interface

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D-scheduler:A scheduler in time-triggered distributed system through decoupling dependencies between tasks and messages

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Science China(Technological Sciences) 2024年第1期67卷 183-196页

作者： YANG TingTing ZHANG YuQi YUE FengLai WUNIRI QiQiGe TONG Chao School of Computer Science&Engineering Beihang UniversityBeijing 100191China State Key Laboratory of Virtual Reality Technology and Systems Beihang UniversityBeijing 100191China National Innovation Center of Intelligent and Connected Vehicles Beijing 100176China

Time-triggered architecture,as a mainstream design of the distributed real-time system,has been successfully applied in the aerospace,automotive and mechanical ***,time-triggered scheduling is a challenging NP-hard *** are few studies that could quickly solve the scheduling problem of large distributed time-triggered *** solve this problem,a communication affinity parameter is defined in this paper to describe the degree of bias of the shaper task towards sending or receiving *** on this,an innovative task-message decoupling model named D-scheduler is built to reduce the computation complexity of the scheduling problem in large-scale ***,we provide mathematical proof that our model is a convex optimization that is easy to solve with existing computational *** experiments substantiate the efficacy of the *** dramatically reduces the scheduling complexity of large-scale real-time systems with a small loss of solving space compared to the federal scheduler.

关键词： time-triggered architecture time-triggered scheduling communication affinity parameter task-message decoupling model

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Advances in functional MRI research in bipolar disorder:from the perspective of mood states

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General Psychiatry 2024年第1期37卷 33-43页

作者： Yankun Wu Yun-Ai Su Linlin Zhu Jitao Li Tianmei Si Department of Clinical Psychopharmacology Peking University Sixth HospitalPeking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)BeijingChina Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratoryof Mental Health(Peking University)National Clinical Research Centerfor Mental Disorders(Peking University Sixth Hospital)BeijingChina

Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and *** breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar ***,the pathophysiology underlying mood instability,mood switching and the development of extreme mood states is less well *** reviewpresents a comprehensive overviewof current evidence from functional MRI studies from the perspective of mood *** first summarise the disrupted brain activation patterns and functional connectivity that have been reported in bipolar disorder,irrespective of the mood *** next focus on research that solely included patients in a single mood state for a better understanding of the pathophysiology of bipolar disorder and research comparing patients with different mood states to dissect mood state-related ***,we briefly summarise current theoretical models and conclude this review by proposing potential avenues for future research.A comprehensive understanding of the pathophysiology with consideration of mood states could not only deepen our understanding of how acute mood episodes develop at a neurophysiological level but could also facilitate the identification of biological targets for personalised treatment and the development of new interventions for bipolar disorder.

关键词： anatomy bipolar functional

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Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues

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Protein & Cell 2024年第8期15卷 594-611页

作者： Jian Wu Chaoye Wang Shuhui Sun Tianmin Ren Lijie Pan Hongyi Liu Simeng Hou Shen Wu Xuejing Yan Jingxue Zhang Xiaofang Zhao Weihai Liu Sirui Zhu Shuwen Wei Chi Zhang Xu Jia Qi Zhang Ziyu Yu Yehong Zhuo Qi Zhao Chenlong Yang Ningli Wang Beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing Key Laboratory of Ophthalmology and Visual SciencesBeijing 100730China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou 510060China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Department of Neurosurgery Peking University Third HospitalCenter for Precision Neurosurgery and Oncology of Peking University Health Science CenterBeijing 100191China Spencer Center for Vision research Byers Eye InstituteSchool of MedicineStanford UniversityPalo AltoCA 94304USA

The progressive degradation in the trabecular meshwork(TM)is related to age-related ocular diseases like primary open-angle ***,the molecular basis and biological significance of the aging process in TM have not been fully ***,we established a dynamic single-cell transcriptomic landscape of aged macaque TM,wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM ***,we divided TM cells into 13 clusters and performed an in-depth analysis on cluster O,which had the highest aging score and the most significant changes in cell proportions between the two ***,we found that the APOE gene was an important differentially expressed gene in cluster O during the aging process,highlighting the close relationship between cell migration and extracellular matrix regulation,and TM *** work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components,thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal *** work provides valuable insights for future clinical diagnosis and treatment of glaucoma.

关键词： single-cell transcriptomic atlas macaque trabecular meshwork ocular outflow tissue aging

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More common RNAemia in the early stage of severe SARS-CoV-2 BF.7.14 infections in pediatric patients

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Biosafety and health 2024年第1期6卷 5-11页

作者： Yu Sun Runan Zhu Yang Pan Ri De Shuang Liu Liping Jia Bing Lv Xiaoyun Li Dongmei Chen Yao Yao Dong Qu Daitao Zhang Linqing Zhao Laboratory of Virology Bejing Key Laboratory of Etiology of Viral Diseases in ChildrenCapital Institute of PediatricsBejing 100020China Institute for Infectious Disease and Endemic Disease Control Bejing Center for Disease Control and Prevention Beijing 100013China Department of Intensive Care Unit Affiliated Children's Hospital of Capital Institute of PediatricsBeijing 100020China

The risk factors of severe infections in children during the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)outbreak in Beijing remain ***‐CoV‐2‐positive children admitted to the intensive care unit(ICU)with collected plasma specimens were enrolled and screened for common pathogens using capillary electrophoresis‐based multiplex PCR from December 12,2022,to January 24,*** SARS‐CoV‐2 subvariants were identified using next‐generation *** was positive for two(positive;P),one(suspicious;S),or no(negative;N)SARS‐CoV‐2 genes were classified as plasmatic RNA‐positive(RNAemia;P+S)or without RNAemia(N).Clinical and laboratory data of the enrolled cases were then collected and *** 34 enrolled children included 26 males and 24 younger than three *** were negative for other respiratory ***.7.14(18/29)was the predominant *** loads in respiratory specimens,hours from symptom onset to the first respiratory specimen collection(time‐variable),with comorbidities and BF.7.14 and BA.5.2 distributions were significantly different in P vs.N and RNAemia *** RNAemia *** most cases,the T lymphocyte ratios decreased,while the cytokine level and the B lymphocyte ratio *** time variables were 2.22±2.05 and 4.00±2.49 days in BF.7.14 and BA.5.2 infections,*** conclusion,SARS‐CoV‐2 was more likely to cause severe infections among males aged≤3 years old with comorbidities during the SARS‐CoV‐2 outbreak in Beijing,while RNAemia is more common in children at the early stage of severe BF.7.14 infections,and most had high cytokine levels and B‐cell activation.

关键词： Severe SARS‐CoV‐2 infection Pediatric patients Risk factor RNAemia BF.7.14

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Icariin plus curcumol enhances autophagy through the mTOR pathway and promotes cathepsin B-mediated pyroptosis of prostate cancer cells

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Asian Pacific Journal of Tropical Biomedicine 2024年第2期14卷 55-64页

作者： Xu-Yun Wang Wen-Jing Xu Bo-Nan Li Tian-Song Sun Wen Sheng Department of Andrology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing100010China Department of Dermatology The First Affiliated Hospital of Hunan University of Chinese MedicineChangsha410021China School of Integrated Chinese and Western Medicine Hunan University of Chinese MedicineChangsha410208China Andrology Laboratory Hunan University of Chinese MedicineChangsha410208China School of Rehabilitation Medicine and health Care Hunan University of MedicineHuaihua418000China School of Traditional Chinese Medicine Hunan University of MedicineHuaihua418000China

Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying ***:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and *** expression was analyzed using monodansylcadaverine *** and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR *** damage was examined using the lactate dehydrogenase ***,cathepsin B and NLRP3 were detected by ***:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of *** levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus *** changes were reversed upon overexpression of ***,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol *** cathepsin B reversed the regulatory effects of icariin plus ***:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin *** findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.

关键词： Icariin Curcumol Autophagy mTOR Cathepsin B Pyroptosis Prostate cancer

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Phase I clinical trial of intracerebral injection of lentiviral-ABCD1 for the treatment of cerebral adrenoleukodystrophy

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Science Bulletin 2024年第16期69卷 2596-2603页

作者： Qiu-Hong Wang Jing Wanga Zhi-Pei Ling Zhi-Qiang Cui Jie Gong Rui Zhang Shi-Jun Li Yang-Yang Wang Rui Yang De-Hui Huang Wen He Jing Gao Chen Feng Pei-Li Hu Li-Ying Liu Lung-Ji Chang Li-Ping Zou Senior Department of Pediatrics Chinese PLA General HospitalBeijing 100853China Medical School of Chinese PLA Beijing 100853China Department of Neurosurgery Hainan Hospital of PLA General HospitalSanya 572013China Department of Neurosurgery The First Medical Center of Chinese PLA General HospitalBeijing 100853China Chengdu Women’s and Children’s Central Hospital School of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 611731China School of Medicine University of Electronic Science and Technology of ChinaChengdu 610054China Beijing Meikang Biotechnology Co. LTD.Beijing 100085China Department of Radiology The First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Neurology The First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Pediatrics Xuanwu HospitalCapital Medical UniversityBeijing 100053China Shenzhen Geno-Immune Medical Institute Shenzhen 518057China Beijing Institute for Brain Disorders Center for Brain Disorders research Capital Medical UniversityBeijing 100069China

This was a single-arm,multicenter,open-label phase I *** vectors(LV)carrying the ABCD1 gene(LV-ABCD1)was directly injected into the brain of patients with childhood cerebral adrenoleukodystrophy(CCALD),and multi-site injection was *** injection dose increased from 200 to 1600 lL(vector titer:1×10^(9) transduction units per mL(TU/mL)),and the average dose per kilogram body weight ranges from 8 to 63.6 lL/*** primary endpoint was safety,dose-exploration and immunogenicity and the secondary endpoint was initial evaluation of efficacy and the expression of ABCD1 protein.A total of 7 patients participated in this phase I study and were followed for 1 *** injectionrelated serious adverse event or death *** adverse events associated with the injection were irritability(71%,5/7)and fever(37.2-38.5℃,57%,4/7).Adverse events were mild and selflimited,or resolved within 3 d of symptomatic *** maximal tolerable dose is 1600 *** 5 cases(83.3%,5/6),no lentivirus associated antibodies were *** overall survival at 1-year was 100%.The ABCD1 protein expression was detected in neutrophils,monocytes and *** study suggests that the intracerebral injection of LV-ABCD1 for CCALD is safe and can achieve successful LV transduction in vivo;even the maximal dose did not increase the risk of adverse ***,the direct LV-ABCD1 injection displayed low *** addition,the effectiveness of intracerebral LV-ABCD1 injection has been preliminarily demonstrated while further investigation is *** study has been registered in the Chinese Clinical Trial Registry(https://***/,registration number:ChiCTR1900026649).

关键词： Adrenoleukodystrophy Lentiviral vectors ABCD1 Intracerebral injection

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