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Efficacy of Wen-Luo-Tong on peripheral neuropathy Induced by Chemotherapy or Target Therapy: A Randomized, Double-Blinded, Placebo-Controlled Trial

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Chinese Journal of Integrative Medicine 2022年第7期28卷 579-585页

作者： DENG Bo JIA Li-qun WAN Dong-gui WANG Bao-yi CHENG Zhi-qiang DENG Chao Center of Science and Technology China-Japan Friendship HospitalBeijing 100029China Integrative Oncology Department of Chinese Medicine and Western Medicine China-Japan Friendship HospitalBeijing 100029China

Objective: To evaluate the efficacy of Wen-Luo-Tong Granules(WLT) local administration in the treatment of patients with peripheral neuropathy(PN) induced by chemotherapy or target therapy. Methods: This study is a randomized, double-blinded, and placebo-controlled trial. Seventy-eight patients with PN induced by chemotherapy or target therapy were enrolled from China-Japan Friendship Hospital between July 2019 and January 2020. They were randomly assigned to WLT(39 cases) and control groups(39 cases) using a block randomization method. The WLT group received WLT(hand and foot bath) plus oral Mecobalamin for 1 week, while the control group received placebo plus oral Mecobalamin. The primary endpoint was PN grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events(NCI-CTCAE). The secondary endpoints included quantitative touch-detection threshold, neuropathy symptoms, Quality of Life QuestionnaireChemotherapy Induced peripheral neuropathy(QLQ-CIPN20), and Quality of Life Questionnaire-Core30(QLQ-C30). Results: After treatment, the PN grade in the WLT group was significantly lower than that in the control group(1.00±0.29 vs. 1.75±0.68, Pneuropathy symptom score, QLQ-CIPN 20(sensory scale, motor scale, autonomic scale, and sum score), and QLQ-C30(physical functioning, role functioning, emotional functioning, and global health) in the WLT group significantly improved after treatment(P<0.01 or P<0.05). Conclusion: WLT local administration was significantly effective in the treatment of patients with PN induced by chemotherapy or target therapy.(Trial registration No. ChiCTR1900023862)

关键词： peripheral neuropathy chemotherapy target therapy Chinese medicine Wen-Luo-Tong randomized controlled trial

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A genetic variant study of bortezomib-induced peripheral neuropathy in Chinese multiple myeloma patients

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Oncology Research 2024年第5期32卷 955-963页

作者： YAN ZHANG HEYANG ZHANG JING WANG XIN WEI YI QU FENG XU LIJUN ZHANG Department of Hematology The First Affiliated Hospital of China Medical UniversityShenyang110001China

Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response varies among individuals.Genetic factor may play an important role in BIPN.Methods:A nextgeneration sequencing(NGS)panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy.mRNA expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR(RT-qPCR).Serum homocysteine(Hcy)levels were detected in 40 samples by chemiluminescent microparticle immunoassay(CMIA).Results:Compared with the non-BIPN group(n=89),a total of 8 significantly associated single nucleotide polymorphisms(SNPs)were identified in the BIPN group(n=115):MTHFR(rs1801131,rs1801133,rs17421511),EPHX1(rs1051740),MME(rs2016848),ALDH1A1(rs6151031),HTR7(rs1935349)and CYP2A6(rs8192720).The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment(NP group)was lower than that of newly diagnosed patients without peripheral neuritis after treatment(NnP group)(1.70±0.77 vs.2.81±0.97,p=0.009).Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group(11.66±1.79μmol/L vs.8.52±3.29μmol/L,p=0.016)and healthy controls(11.66±1.79μmol/L vs.8.55±2.13μmol/L,p≤0.001).Conclusion:CYP2A6,EPHX1,MTHFR,ALDH1A1,HTR7,MME and BIPN are linked in Chinese MM patients.BIPN is more likely to occur in patients with lower MTHFR mRNA expression,which might result in higher serum Hcy levels.

关键词： Multiple Myeloma peripheral neuropathy Bortezomib Bortezomib-induced peripheral neuropathy Next-generation sequencing MTHFR Serum Hcy

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A ＂Triple Trouble＂ Case of Facioscapulohumeral Muscular Dystrophy Accompanied by peripheral neuropathy and Myoclonic Epilepsy

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Chinese Medical Journal 2018年第18期131卷 2164-2171页

作者： Xiao-Dan Lin Jun-Jie He Feng Lin Hai-Zhu Chen Liu-Qing Xu Wei Hu Nai-Qing Cai Min-Ting Lin Ning Wang Zhi-Qiang Wang Guo-Rong Xu Department of Neurology and Institute of Neurology First Affiliated Hospital Fujian Medical University Fuzhou Fujian 350005 China Fujian Key Laboratory of Molecular Neurology Fuzhou Fujian 350005 China

Background： Facioscapulohumeral muscular dystrophy （FSHD） is characterized by asymmetric muscular deficit of facial, shoulder-girdle muscles, and descending to lower limb muscles, but it exists in several extramuscular manifestations or overlapping syndromes. Herein, we report a ＂complex disease plus＂ patient with FSHD1, accompanied by peripheral neuropathy and myoclonic epilepsy. Methods： Standard clinical assessments, particular auxiliary examination, histological analysis, and molecular analysis were performed through the new Comprehensive Clinical Evaluation Form, pulsed-field gel electrophoresis-based Southern blot, Multiplex Ligation-dependent Probe Amplification （MLPA）, whole exome sequencing （WES）, and targeted methylation sequencing. Results： The patient presented with mild facial weakness, humeral poly-hill sign, scapular winging, peroneal weakness, drop foot, pes cavus, and myoclonic epilepsy. Furthermore, electrophysiology revealed severely demyelinated and axonal injury. The muscle and nerve biopsy revealed broadly fiber Type II grouping atrophy and myelinated nerve fibers that significantly decreased with thin myelinated fibers and onion bulbs changes. Generalized sharp and sharp-slow wave complexes on electroencephalography support the diagnosis toward myoclonic epilepsy. In addition, molecular testing demonstrated a co-segregated 20-kb 4q35-EcoRI fragment and permissive allele A, which corresponded with D4Z4 hypomethylation status in the family. Both the patient＇s mother and brother only presented the typical FSHD but lacked overlapping syndromes. However, no mutations for hereditary peripheral neuropathy and myoclonic epilepsy were discovered by MLPA and WES. Conclusions： The present study described a ＂tripe trouble＂ with FSHD, peripheral neuropathy, and myoclonic epilepsy, adding the spectrum of overlapping syndromes and contributing to the credible diagnosis of atypical phenotype. It would provide a direct clue on medical care and genetic counseling.

关键词： Facioscapulohumeral Muscular Dystrophy Myoclonic Epilepsy Overlapping Syndromes peripheral neuropathy TripleTrouble

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HLA class Ⅱ alleles and risk for peripheral neuropathy in type 2 diabetes patients

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Neural Regeneration Research 2016年第11期11卷 1839-1844页

作者： Ahmad Marzban Javad Kiani Mehrdad Hajilooi Hamzeh Rezaei Zohreh Kahramfar Ghasem Solgi Division of Endocrinology Department of Internal MedicineSchool of MedicineHamadan University of Medical Sciences Department of Immunology School of MedicineHamadan University of Medical Sciences Psoriasis Research Center Department of DermatologyFarshchian HospitalHamadan University of Medical Sciences

The potential impact of human leukocyte antigen （HLA） genotype variations on development of diabetic peripheral neuropathy （DPN） is not well determined. This study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes （T2D） patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index （BMI） and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers （PCR-SSP） method. T2D patients with DPN showed higher frequencies of HLA-DRB1＊10 and DRB1＊12 alleles compared to control group （P = 0.04）. HLA-DQB1＊02 allele and HLA-DRB1＊07-DQB1＊02 haplotype were associated with a decreased risk for developing DPN in T2D patients （P = 0.02 and P = 0.05 respectively）. Also, patients with severe neuropathy showed higher frequencies of DRB1＊07 （P = 0.003） and DQB1＊02 （P = 0.02） alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB 1 and DQB 1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our findings implicate a possible protective role of HLA-DQB1＊02 allele and HLA-DRB1＊07-DQB1＊02 haplotype against development of peripheral neuropathy in T2D patients. Therefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.

关键词： nerve regeneration HLA-DRB1 HLA-DQB1 alleles genotypes haplotypes peripheral neuropathy type 2 diabetes neural regeneration

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High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis

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Neural Regeneration Research 2015年第5期10卷 814-818页

作者： Hong-xia Xue Wen-yi Fu Hua-dong Cui Li-li Yang Ning Zhang Li-juan Zhao Department of Rheumatology and Immunology Shengjing Hospital of China Medical University Department of Rheumatology and Immunology the First Affiliated Hospital of China Medical University

Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among an- kylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treat- ments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the 〈 6 months medication and 〉 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclu- sion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

关键词： nerve regeneration peripheral nerve injury thalidomide ankylosing spondflitis adversereactions peripheral neuropathy prospective study treatment dose treatment time age sex neuralregeneration

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Myelin protein zero and its antibody in serum as biomarkers of n-hexane-induced peripheral neuropathy and neurotoxicity effects

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Chinese Medical Journal 2014年第8期127卷 1536-1540页

作者： Jia Xiaowei Liu Qingjun Zhang Yanshu Dai Yufei Duan Huawei Bin Ping Niu Yong Liu Jie Zhong Liuzhen Guo Jisheng Liu Xiaofeng Zheng Yuxin Key Laboratory of Chemical Safety and Health National Institute for Occupational Health and Poison Control Chinese Center for Disease Control and Prevention Beijing 100050 China DSM Regulatory Affairs Depart-ment DSM (China) Ltd. Beijing 100000 China College of Public Health Hebei United University Tangshan Hebei 063009 China Suzhou Fifth People's Hospital Suzhou Jiangsu 215007 China Xixiang Health Inspection of Bao'an Distract Shenzhen Guangzhou Guangdong 500000 China

Background Chronic exposure to n-hexane can lead to peripheral neuropathy that no effective treatment regimen could be applied presently. This study investigated whether myelin protein zero （P0） protein and its antibody could be used to distinguish n-hexane intoxication and protect workers from peripheral neuropathy. Methods We compared P0 protein and its antibody among three levels of n-hexane-exposed groups, which included 18 patients with n-hexane-induced peripheral neuropathy as case group, 120 n-hexane-exposed workers as n-hexane- exposed control group, and 147 non-hexane-exposed participants used as control group. ELISA method was applied to detect P0 protein and its antibody. Results P0 protein in serum was significantly higher in the case group and n-hexane-exposed control group in comparison with the control group （P〈0.01）. Compared with the n-hexane-exposed control group, the case group also had significant increase of P0 protein （P〈0.01）. After 6 months therapy, P0 protein was observed to decrease significantly in the case group （P〈0.01）. The P0 antibody in serum was significantly higher in the n-hexane-exposed control group than in the control group （P〈0.01）, but not significantly different between cases and controls. Conclusions P0 antibodies in serum may be a short-term effect biomarker for n-hexane exposure. P0 protein in serum may be an early effective biomarker for peripheral nerve neuropathy and its biological limit value needs investigation in the future study.

关键词： n-hexane marker peripheral neuropathy myelin protein zero

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Effect of tumor necrosis factor inhibitors on rheumatoid arthritis-induced peripheral neuropathy A cohort study

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Neural Regeneration Research 2012年第11期7卷 862-866页

作者： Naizhi Wang Yingying Guo Lili Yang Wenyi Fu Yanbing Xu Linxin Hou Shuai Zhao Ning Zhang Department of Rheumatism Shengjing Hospital China Medical University Shenyang 110004 Liaoning Province China

In this historical cohort study, 236 patients with primary rheumatoid arthritis were treated with the tumor necrosis factor inhibitors, etanercept or infliximab （n = 80）, or by conventional methods （n = 156）. Results revealed that 11 patients developed varying types of peripheral neuropathy at 1-2 years post-treatment （mean 16 months）. The incidence of peripheral neuropathy in the tumor necrosis factor inhibitors treatment group was 8.8% （7/80）, which was significantly higher than the conventional treatment group （2.6%; 4/156）. The relative risk of developing peripheral neuropathy in the tumor necrosis factor inhibitors treatment group was 3.41 （95% confidence interval： 1.03 11.31）. Comparison of the tumor necrosis factor inhibitors revealed that etanercept and infliximab had no significant difference in terms of inducing peripheral neuropathy. Experimental findings indicate that tumor necrosis factor inhibitors may increase the risk of peripheral neuropathy.

关键词： tumor necrosis factor inhibitors adverse reactions peripheral neuropathy rheumatoid arthritis cohort study risk factors

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Efficacy of combining traditional Chinese medicine fumigation with Western medicine for diabetic peripheral neuropathy:A systematic review and meta-analysis

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International Journal of Nursing Sciences 2015年第3期2卷 295-303页

作者： Lei Zhang Xu Tian Yue Ma Ying-Hui Jin Fan-Jie Meng Graduate College Tianjin University of Traditional Chinese MedicineTianjin 300193China Department of Nursing Shijiazhuang College of MedicineShijiazhuang 050061China School of Nursing Tianjin University of Traditional Chinese MedicineTianjin 300193China Department of Teachers'Development and Evaluation Tianjin University of Traditional Chinese MedicineTianjin 300193China

Objective:A systematic review and meta-analysis was conducted to evaluate the effectiveness of supplementing Western medicine with Traditional Chinese medicine(TCM)fumigation in patients with diabetic peripheral neuropathy.Methods:The China Biomedical Literature,Chinese full-text periodical,China National Knowledge Infrastructure,WanFang,PubMed,EMbase,and Cochrane Library databases were searched for relevant randomized controlled trials published from inception through May 2015.The methodological quality of eligible studies was evaluated using the Cochrane Risk Bias Assessment tool,and summarized effects were calculated using Reviewer Manager 5.1 software.Subgroup analysis was conducted based on the duration of intervention.Results:The initial search identified 312 relevant studies,of which 40 randomized controlled trials involving 3497 patients were eligible for analysis.The results indicated that TCM fumigation significantly improved the curative effects[risk ratio(RR)=1.34,95%CI(confidence interval):1.29e1.39],common peroneal motor nerve conduction velocity[standard mean difference(SMD)=2.93,95%CI:2.26e3.61],common peroneal sensory nerve conduction velocity(SMD=2.23,95%CI:1.46e3.01),and plasma viscosity(SMD=1.02,95%CI:1.35e0.69)compared to Western medicine alone(all p<0.01).A subgroup analysis indicated that the curative effects were significant after 15 days(RR=1.31,95%CI:1.21e1.42),30 days(RR=1.33,95%CI:1.26e1.40),and 60 days(RR=1.50,95%CI:1.32e1.71)of combined treatment(all p<0.01).

关键词： Fumigation Diabetic peripheral neuropathy Traditional Chinese medic

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Lysosomal dysfunction in Schwann cells is involved in bortezomib-induced peripheral neuropathy

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中国药理学与毒理学杂志 2021年第9期35卷 683-684页

作者： WU Zhan-xun YAN Wen-ping CHEN Zhong WU Jia-ying ZHANG Xiang-nan Institute of Pharmacology&Toxicology Col-lege of Pharmaceutical SciencesKey Laboratory of Medical Neurobiology of the Ministry of Health of ChinaZhejiang UniversityHangzhou 310058China Department of Pharmacy the First Affili-ated HospitalSchool of MedicineZhejiang Univer-sityHangzhou 310003China

OBJECTIVE The proteasome inhibitor bortezomib(BTZ)is a first-line anti-multi⁃ple myeloma drug.BTZ-induced peripheral neu⁃ropathy(BIPN)is a main adverse effect that char⁃acterized by neuropathic pain.There is still no strategy to prevent or treat BIPN,attributed to the unidentified mechanisms underlying BIPN.Previous studies suggested that BTZ impairs Schwann cells and thus leads to axonal demye⁃lination,whereas it remained not fully understood how BTZ cause Schwann cell death.It was observed that BTZ upregulates the autophagy marker LC3-Ⅱprotein in Schwann cells.However,it remains unclear whether BTZ causes autopha⁃gy-lysosome dysfunction in Schwann cells.METHODS The male C57BL/6 mice were intra⁃venous injection of BTZ(1 mg·kg-1 per day,twice weekly for a total of 4 weeks).The paw withdraw⁃al latency was tested by the Von Frey test and Hargreaves test to reflect the neuropathic pain.The conduction velocity and the action potential amplitude of the tail nerve were tested by neuro⁃physiological assessment to reflect peripheral nerve function.The histomorphology of the sciat⁃ic nerves was detected by immunofluorescence and transmission electron microscopy to reflect the demyelination and axonal degeneration.The RSC96 cells,the Schwann cell-like immortal cells,were cultured and exposed to BTZ.The lysosomal function was determined by Lyso⁃Tracker and DQ-BSA staining.Autophagy-relat⁃ed proteins,including p62 and LC3,and lysosom⁃al hydrolase cathepsin B were determined by Western blotting.RESULTS①BTZ induced mechano-allodynia,neurological conduction abnormalities of the tail nerve,demyelination and axonal degeneration of the sciatic nerves.②BTZ caused lysosomal dysfunction,resulting in the blockade of autophagy flux in Schwann cells and sciatic nerves.③The lysosomal activator Torin1 reversed lysosomal dysfunction caused by BTZ in Schwann cells.④Torin1 improved BTZ-induced mechano-allodynia and demyelination of sciatic nerves.CONCLUSION BTZ led to lyso⁃somal dysfunction in Schwann cells and contrib⁃uted to BIPN.Lysosomal

关键词： bortezomib peripheral neuropathy sciatic nerves demyelination Schwann cells lysosome

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Sixty-one Patients with Diabetic peripheral neuropathy Treated by Tongluo Yangyin Recipe (通络养阴方)

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Chinese Journal of Integrative Medicine 2007年第3期13卷 190-194页

作者：徐文刚 Hospital of Integrative Chinese and Western Medicine

Objective： To observe the therapeutic effect of Tongluo Yangyin Recipe （通络养阴方, TLYYR） in patients with diabetic peripheral neuropathy （DPN）. Methods： Ninety-nine patients with diabetes mellitus type 2 were assigned, according to the order of their visit, to two groups： 61 in the treated group and 38 in the control group. They were given the same information about diabetes mellitus and treated with the same therapy： strict diet control and Western drugs for hypoglycemia. In addition, the treated group received one dose （200 mL） of TLYYR in water decoction every day in two portions, while the control group had vitamin B1 100 mg and vitamin B12 250 μ g administered daily via intramuscular injection. The course for all patients was 28 days. Results： The treated group experienced a therapeutic effect superior to that of the control group, with the difference between the total effective rates and the markedly effective rates （P〈0.05, P〈0.01）. The blood levels of total cholesterol （TC） and triglyceride （TG） fell, the hemorrheological manner improved, the transmission velocity of the median nerve and common peroneal nerve significantly increased in the treated group after treatment （P〈0.05）, although the treatment showed no significant influence on blood glucose level （P〉0.05）. Conclusion： TLYYR could promote blood microcirculation, improve nutritional metabolism of peripheral nerve, and thus accelerating DPN repair.

关键词： diabetes mellitus peripheral neuropathy Tongluo Yangyin Recipe nourishing yin to moisten dryness activating blood circulation to relief pain

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