Chemotherapy-induced peripheral neuropathy

化疗引起的周围神经病变
  • 文章类型: Journal Article
    化疗引起的周围神经病变(CIPN)不仅影响化疗的耐受性,但也会导致癌症患者难以忍受和延长的神经性疼痛。目前,度洛西汀是唯一用于治疗PN的药物。然而,该药物的临床应用仍面临若干挑战.因此,我们专注于中药(TCM),以寻找有效和安全的替代药物。黄芪桂枝五物汤(HGWD)是临床上用于治疗神经痛已有数千年的传统中药。本研究旨在探讨HGWD对顺铂诱导的PC12细胞神经损伤的保护作用,并阐明其可能的作用机制。
    从大鼠模型制备含HGWD的血清和空白血清。通过细胞计数试剂盒-8(CCK-8)测定评估HGWD对顺铂(10μmol/L)诱导的PC12细胞损伤的保护作用。使用RNA-seq分析HGWD保护的PC12细胞中的RNA表达,随后,使用基因本体论(GO)和基因集富集分析(GSEA)进一步分析差异表达基因(DEGs)。
    CCK-8结果表明,用含HGWD的血清预处理PC12细胞(5%,10%,15%)显著增加细胞活力至10μmol/L顺铂诱导的细胞死亡。RNA-seq分析显示CIPN组843个DEGs,HGWD组249个。这项研究的GSEA结果表明,HGWD可能通过增强轴突引导来治疗PN。
    这项研究为使用HGWD治疗CIPN提供了有价值的证据,部分通过改进轴突导向途径来实现。
    UNASSIGNED: Chemotherapy-induced peripheral neuropathy not only affects the tolerability of chemotherapy, but also causes intolerable and prolonged neuropathic pain in cancer patients. Currently, duloxetine is the only drug used to treat chemotherapy-induced peripheral neuropathy. However, the clinical use of this drug still faces several challenges. Therefore, we focused on traditional Chinese medicine to find an effective and safe alternative medicine. Huangqi Guizhi Wuwu Decoction is a traditional Chinese medicine that has been clinically used for treating nerve pain for thousands of years. This study aimed to investigate the neuroprotective effect of Huangqi Guizhi Wuwu Decoction on cisplatin-induced nerve injury in PC12 cells and to elucidate its potential mechanism of action.
    UNASSIGNED: Huangqi Guizhi Wuwu Decoction-containing serum and blank serum were prepared from a rat model. The protective effects of Huangqi Guizhi Wuwu Decoction on cisplatin (10 µmol/L)-induced PC12 cell injury were assessed by a Cell Counting Kit-8 assay. RNA expression in Huangqi Guizhi Wuwu Decoction-protected PC12 cells was analyzed using RNA-seq, and subsequently, differentially expressed genes were further analyzed using Gene Ontology and Gene Set Enrichment Analysis.
    UNASSIGNED: The Cell Counting Kit-8 results showed that pretreatment of PC12 cells with Huangqi Guizhi Wuwu Decoction-containing serum (5%, 10%, 15%) significantly increased cells\' viability to 10 µmol/L cisplatin-induced cell death. RNA-seq analysis revealed 843 differentially expressed genes in the chemotherapy-induced peripheral neuropathy group and 249 in the Huangqi Guizhi Wuwu Decoction group. The gene set enrichment analysis results in this study suggest that Huangqi Guizhi Wuwu Decoction may treat chemotherapy-induced peripheral neuropathy by enhancing axon guidance.
    UNASSIGNED: This study provides valuable evidence for using Huangqi Guizhi Wuwu Decoction in treating chemotherapy-induced peripheral neuropathy, partially achieved by improving axon guidance pathways.
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  • 文章类型: Published Erratum
    [这修正了文章DOI:10.3389/freur.2023.1252259。].
    [This corrects the article DOI: 10.3389/fneur.2023.1252259.].
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  • 文章类型: Journal Article
    化疗引起的周围神经病变(CIPN)仍然缺乏有效的治疗药物。本研究旨在系统评价黄芪桂枝五物汤(HGWD)单独或联合阳性药物对CIPN防治的效果。
    PubMed,Embase,WebofScience,科克伦,中国国家知识基础设施(CNKI),万方数据,在中国科学技术杂志(VIP)和中国生物医学(CBM)数据库中搜索HGWD用于CIPN预防和治疗的随机对照试验(RCT)。搜索时间从数据库建立到2023年10月17日不等。Cochrane偏差风险评估工具用于质量评估,ReviewManager5.3和STATA12.0用于荟萃分析,和GRADEprofiler用于证据水平评估。
    共32个RCT,涉及1987名患者。荟萃分析结果显示:1.就总CIPN发生率而言,HGWD组低于空白对照组。HGWD和HGWD阳性药物组的发生率均低于单药阳性药物组。2.就严重CIPN的发生率而言,HGWD组低于空白对照组和阳性药物组。HGWD+阳性药物组与阳性药物组之间无统计学差别。敏感性分析显示,HGWD组的严重发生率低于阳性药物组3。HGWD没有增加化疗相关不良事件的数量。
    HGWD可以安全有效地预防CIPN,减少症状,提高生活质量,减少化疗药物对感觉神经传导的影响。然而,需要更多高质量的RCT来比较HGWD与阳性对照药物预防严重CIPN的疗效.
    UNASSIGNED: Chemotherapy-induced peripheral neuropathy (CIPN) still lacks efficient therapeutic drugs. This study aimed to systematically evaluate the effects of Huangqi Guizhi Wuwu Decoction (HGWD) alone or combined with positive drugs on CIPN prevention and treatment.
    UNASSIGNED: The PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure (CNKI), Wan Fang Data, China Science and Technology Journal (VIP) and Chinese Biomedical (CBM) databases were searched for randomized controlled trials (RCTs) of HGWD for CIPN prevention and treatment. The search time ranged from database establishment to October 17, 2023. The Cochrane risk-of-bias assessment tool was used for quality assessment, Review Manager 5.3 and STATA 12.0 were used for meta-analysis, and GRADEprofiler was used for evidence level assessment.
    UNASSIGNED: A total of 32 RCTs involving 1987 patients were included. The meta-analysis results revealed the following: 1. In terms of the total CIPN incidence, that in the HGWD group was lower than that in the blank control group. The incidence in both the HGWD and HGWD+positive drug groups was lower than that in the monotherapy-positive drug group. 2. In terms of the incidence of severe CIPN, that in the HGWD group was lower than that in the blank control and positive drug groups. There was no statistically significant difference between the HGWD+positive drug and positive drug groups. Sensitivity analysis revealed that the results of severe incidence in the HGWD group was lower than that in the positive drug group were unstable 3. HGWD did not increase the number of chemotherapy-related adverse events.
    UNASSIGNED: HGWD can safely and effectively prevent CIPN, reduce symptoms, improve quality of life and reduce the impact of chemotherapy drugs on sensory nerve conduction. However, more high-quality RCTs are needed to compare the efficacy of HGWD with that of positive control drugs in preventing severe CIPN.
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  • 文章类型: Journal Article
    紫杉醇(PTX)是一种微管稳定剂,破坏微管解聚和再聚合的正常循环,导致细胞周期停滞和癌细胞死亡。它通常用作各种恶性肿瘤的一线化疗药物,比如乳腺癌,非小细胞肺癌,和卵巢癌。然而,PTX化疗与常见和严重的副作用有关,包括化疗引起的周围神经病变(CIPN)。随着癌症治疗的进步和生存率的提高,CIPN对患者生活质量的影响越来越显著。迄今为止,CIPN没有有效的治疗策略。Surtuin3(SIRT3)是位于线粒体上的烟酰胺腺嘌呤二核苷酸(NAD)依赖性蛋白质脱乙酰酶。它将乙酰化底物蛋白的赖氨酸侧链的乙酰基转移到NAD,产生脱乙酰蛋白质来调节线粒体能量代谢过程。SIRT3已被发现在各种疾病中发挥重要作用,包括衰老,神经退行性疾病,癌症,心脏病,代谢性疾病,等。然而,SIRT3在CIPN中的作用仍然未知。这项研究首次发现激活SIRT3有助于改善紫杉醇诱导的CIPN。烟酰胺核苷(NR)可通过激活SIRT3-MnSOD2和SIRT3-Nrf2通路保护背根神经节(DRG)线粒体免受紫杉醇引起的氧化损伤。此外,NR可以加强紫杉醇的抗癌活性。一起,我们的研究为CIPN的治疗提供了新的策略和候选药物。
    Paclitaxel (PTX) is a microtubule stabilizer that disrupts the normal cycle of microtubule depolymerization and repolymerization, leading to cell cycle arrest and cancer cell death. It is commonly used as a first-line chemotherapeutics for various malignancies, such as breast cancer, non-small cell lung cancer, and ovarian cancer. However, PTX chemotherapy is associated with common and serious side effects, including chemotherapy-induced peripheral neuropathy (CIPN). As cancer treatment advances and survival rates increase, the impact of CIPN on patients\' quality of life has become more significant. To date, there is no effective treatment strategy for CIPN. Surtuin3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+) dependent protein deacetylase located on mitochondria. It transfers the acetyl group of the lysine side chain of acetylated substrate proteins to NAD+, producing deacetylated proteins to regulate mitochondrial energy metabolic processes. SIRT3 has been found to play an important role in various diseases, including aging, neurodegenerative diseases, cancer, heart disease, metabolic diseases, etc. However, the role of SIRT3 in CIPN is still unknown. This study found for the first time that activating SIRT3 helps to improve paclitaxel-induced CIPN. Nicotinamide riboside (NR) can protect dorsal root ganglion (DRG) mitochondria against oxidative damage caused by paclitaxel through activating SIRT3-MnSOD2 and SIRT3-Nrf2 pathway. Moreover, NR can enhance the anticancer activity of paclitaxel. Together, our research provides new strategy and candidate drug for the treatment of CIPN.
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  • 文章类型: Journal Article
    化疗引起的周围神经病变(CIPN)是各种化疗药物引起的最常见的脱靶不良反应,如顺铂,奥沙利铂,紫杉醇,长春新碱和硼替佐米.CIPN的特征是主要传入感觉轴突纤维的大量损失,导致患者的感觉障碍。估计有19-85%的患者在化疗过程中发生CIPN。缺乏预防措施,治疗方案有限,往往需要减量甚至提前终止挽救生命的化疗,影响治疗效果和患者生存。在这篇评论中,我们总结了目前对CIPN发病机制的认识。化学治疗剂诱导的一个突出变化涉及神经元细胞骨架结构的破坏和轴突运输动力学,这在很大程度上受外周神经元微管稳定性干扰的影响。由于我们周围神经系统的血液神经屏障无效,暴露于某些化学治疗剂会导致周围神经线粒体肿胀,导致线粒体通透性转换孔的开放和细胞色素c的释放,导致初级传入感觉纤维的变性。CIPN患者的伤害性信号传导和疼痛传递加剧通常与神经元兴奋性增加有关,这主要是由于背根神经节神经元中各种离子通道的表达升高。CIPN的另一个重要促成因素是由免疫细胞浸润增加和炎性细胞因子产生引起的神经炎症。在中枢神经系统中,化疗剂还在脊髓背角和前扣带回皮质中诱导神经元过度兴奋,导致引起CIPN的中枢敏化发展。新出现的证据表明,肠道微生物群(生态失调)的组成和多样性的变化可能对CIPN的发展和进展产生直接影响。总的来说,所有这些方面都有助于CIPN的发病机制。RNA测序的最新进展为计算机药物筛选提供了坚实的平台,能够鉴定新的治疗剂或重新调整现有药物以缓解CIPN。对提高接受化疗的癌症患者的生活质量并改善其整体治疗结果抱有巨大的承诺。
    Chemotherapy-induced peripheral neuropathy (CIPN) is the most common off-target adverse effects caused by various chemotherapeutic agents, such as cisplatin, oxaliplatin, paclitaxel, vincristine and bortezomib. CIPN is characterized by a substantial loss of primary afferent sensory axonal fibers leading to sensory disturbances in patients. An estimated of 19-85% of patients developed CIPN during the course of chemotherapy. The lack of preventive measures and limited treatment options often require a dose reduction or even early termination of life-saving chemotherapy, impacting treatment efficacy and patient survival. In this Review, we summarized the current understanding on the pathogenesis of CIPN. One prominent change induced by chemotherapeutic agents involves the disruption of neuronal cytoskeletal architecture and axonal transport dynamics largely influenced by the interference of microtubule stability in peripheral neurons. Due to an ineffective blood-nerve barrier in our peripheral nervous system, exposure to some chemotherapeutic agents causes mitochondrial swelling in peripheral nerves, which lead to the opening of mitochondrial permeability transition pore and cytochrome c release resulting in degeneration of primary afferent sensory fibers. The exacerbated nociceptive signaling and pain transmission in CIPN patients is often linked the increased neuronal excitability largely due to the elevated expression of various ion channels in the dorsal root ganglion neurons. Another important contributing factor of CIPN is the neuroinflammation caused by an increased infiltration of immune cells and production of inflammatory cytokines. In the central nervous system, chemotherapeutic agents also induce neuronal hyperexcitability in the spinal dorsal horn and anterior cingulate cortex leading to the development of central sensitization that causes CIPN. Emerging evidence suggests that the change in the composition and diversity of gut microbiota (dysbiosis) could have direct impact on the development and progression of CIPN. Collectively, all these aspects contribute to the pathogenesis of CIPN. Recent advances in RNA-sequencing offer solid platform for in silico drug screening which enable the identification of novel therapeutic agents or repurpose existing drugs to alleviate CIPN, holding immense promises for enhancing the quality of life for cancer patients who undergo chemotherapy and improve their overall treatment outcomes.
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  • 文章类型: Journal Article
    针对乳腺癌患者化疗引起的周围神经病变(CIPN)症状,构建个性化的多学科神经毒性管理程序,并评估其应用效果。
    对我院2022年1月至2024年1月收治的133例乳腺癌化疗患者的临床资料进行回顾性分析。根据收到的护理方案,患者分为对照组(n=66)和干预组(n=67).对照组给予常规护理干预,而干预组在对照组干预的基础上接受个性化护理干预。化疗期间实施护理方案。比较两组化疗前及化疗后3个月的神经病变程度,癌症相关的疲劳,消极的情绪状态,和症状管理知识,态度,和实践(KAP)。
    干预组的神经病变严重程度(FACT/GOG-Ntx)明显降低,癌症相关性疲劳(CFS),化疗后负性情绪(PHQ-9、GAD-7)评分与对照组比较(P<0.05)。此外,干预组的症状管理知识得分较高,信仰,行为(P<0.05)。
    个性化的多学科神经毒性管理计划显著改善了神经病变的严重程度,减少癌症相关的疲劳和负面情绪,加强症状管理知识,态度,以及接受化疗的乳腺癌患者的实践。
    UNASSIGNED: To construct a personalized multidisciplinary neurotoxicity management program for chemotherapy-induced peripheral neuropathy (CIPN) symptoms in breast cancer patients and evaluate its application effects.
    UNASSIGNED: A retrospective analysis was conducted on clinical data of 133 breast cancer chemotherapy patients admitted to our hospital from January 2022 to January 2024. Based on the nursing protocols received, patients were divided into a control group (n = 66) and an intervention group (n = 67). The control group received conventional nursing interventions, while the intervention group received personalized nursing interventions in addition to the control group interventions. The nursing programs were carried out during chemotherapy. A comparison was made between the two groups before chemotherapy and 3 months after chemotherapy in terms of the degree of neuropathy, cancer-related fatigue, negative emotional status, and symptom management knowledge, attitudes, and practices (KAP).
    UNASSIGNED: The intervention group showed significantly lower neuropathy severity (FACT/GOG-Ntx), cancer-related fatigue (CFS), and negative emotions (PHQ-9, GAD-7) scores after chemotherapy compared to the control group (p < 0.05). Additionally, the intervention group exhibited higher scores for symptom management knowledge, beliefs, and behaviors (p < 0.05).
    UNASSIGNED: Personalized multidisciplinary neurotoxicity management program significantly improved neuropathy severity, reduced cancer-related fatigue and negative emotions, and enhanced symptom management knowledge, attitudes, and practices among breast cancer patients undergoing chemotherapy.
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  • 文章类型: Journal Article
    目的:本文旨在为癌症患者化疗引起的周围神经病变(CIPN)的综合医疗护理提供基于证据的最有效策略总结。
    方法:遵循“6S”模型,有关CIPN管理的相关证据收集自国内和国际知名的循证资源网站和数据库.对纳入的文章进行了方法学质量评价,并使用澳大利亚JBI循证医疗保健中心的文献评估标准(2016年版)提取证据。
    结果:本研究共纳入60篇文章,包括2条准则,5份专家共识声明,和53个系统审查。这些文章的发现在7个维度上进行了总结,包括危险因素筛查,评估,诊断,预防,治疗,管理,和健康教育,从而鉴定出42份相关证据。
    结论:本研究为癌症患者的CIPN管理提供了一个全面的循证建议。为从事临床实践的医疗保健专业人员提供指导。然而,在执行这些建议时,至关重要的是要考虑患者的个人临床情况,preferences,和专家判断,确保在现实世界的临床设置的可行性和适用性。
    OBJECTIVE: This paper aims to provide an evidence-based summary of the most effective strategies for comprehensive healthcare of chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients.
    METHODS: Following the \"6S\" model, relevant evidence on CIPN management was collected from reputable evidence-based resource websites and databases nationally and internationally. The included articles were evaluated for methodological quality, and evidence was extracted using the Australian JBI Evidence-based Health Care Center\'s literature evaluation standard (2016 edition).
    RESULTS: A total of 60 articles were included in this study, comprising 2 guidelines, 5 expert consensus statements, and 53 systematic reviews. The findings of these articles were summarized across 7 dimensions, including risk factor screening, assessment, diagnosis, prevention, treatment, management, and health education, resulting in the identification of 42 relevant pieces of evidence.
    CONCLUSIONS: This study provides a comprehensive synthesis of evidence-based recommendations for managing CIPN in cancer patients, offering guidance for healthcare professionals engaged in clinical practice. However, when implementing these recommendations, it is crucial to consider the individual patient\'s clinical circumstances, preferences, and expert judgment, ensuring feasibility and applicability in real-world clinical settings.
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  • 文章类型: Published Erratum
    [这修正了文章DOI:10.3389/freur.2023.1252259。].
    [This corrects the article DOI: 10.3389/fneur.2023.1252259.].
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  • 文章类型: Journal Article
    背景:化疗引起的周围神经病变(CIPN)降低了整体生活质量并导致化疗中断。熊果酸,一种天然的三萜类化合物,存在于果皮和许多草药和香料中,可以作为过氧化物酶体增殖物激活受体γ(PPARγ)激动剂,并已被广泛用作具有广泛药理活性的草药,包括抗癌,抗炎和神经保护作用。
    方法:我们使用表型药物筛选方法在体外和体内鉴定熊果酸作为潜在的神经保护药物,并进行了额外的生化实验以鉴定其作用机制。
    结果:我们的研究表明熊果酸降低了紫杉醇诱导的神经毒性和细胞凋亡,导致CIPN的改进。此外,我们探讨了熊果酸对CIPN的潜在作用机制。因此,熊果酸抑制CHOP(C/EBP同源蛋白)表达,表明内质网(ER)应激抑制,并调节CHOP相关的凋亡调节因子(Bcl2家族)逆转紫杉醇诱导的细胞凋亡。此外,我们发现熊果酸对紫杉醇诱导的周围神经病变的治疗作用是PPARγ依赖性的。
    结论:综合来看,本研究提示熊果酸有潜力作为一种新的PPARγ激动剂靶向内质网应激相关的凋亡途径,以改善紫杉醇诱导的外周神经性疼痛和神经损伤,为CIPN提供新的临床治疗方法。
    BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) reduces the overall quality of life and leads to interruption of chemotherapy. Ursolic acid, a triterpenoid naturally which presents in fruit peels and in many herbs and spices, can function as a peroxisome proliferator-activated receptor γ (PPARγ) agonist, and has been widely used as an herbal medicine with a wide spectrum of pharmacological activities, including anti-cancer, anti-inflammatory and neuroprotective effect.
    METHODS: We used a phenotypic drug screening approach to identify ursolic acid as a potential neuroprotective drug in vitro and in vivo and carried out additional biochemical experiments to identify its mechanism of action.
    RESULTS: Our study demonstrated that ursolic acid reduced neurotoxicity and cell apoptosis induced by pacilitaxel, resulting in an improvement of CIPN. Moreover, we explored the potential mechanisms of ursolic acid on CIPN. As a result, ursolic acid inhibited CHOP (C/EBP Homologous Protein) expression, indicating the endoplasmic reticulum (ER) stress suppression, and regulating CHOP related apoptosis regulator (the Bcl2 family) to reverse pacilitaxel induced apoptosis. Moreover, we showed that the therapeutic effect of ursolic acid on the pacilitaxel-induced peripheral neuropathy is PPARγ dependent.
    CONCLUSIONS: Taken together, the present study suggests ursolic acid has potential as a new PPARγ agonist targeting ER stress-related apoptotic pathways to ameliorate pacilitaxel-induced peripheral neuropathic pain and nerve injury, providing new clinical therapeutic method for CIPN.
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  • 文章类型: Systematic Review
    超过一半的癌症患者会出现严重的化疗引起的周围神经病变(CIPN),导致生活质量低下,对功能的负面影响,以及治疗依从性方面的挑战。最近的研究表明,运动疗法对减轻CIPN症状有积极影响,还可以改善生活质量。balance,和活动水平。这项荟萃分析的目的是评估运动疗法对CIPN疗效的影响。
    Embase的计算机搜索,WebofScience,CNKI,万方数据,VIP,从数据库创建到2022年11月,CIPN运动疗法RCT的CBM,不受语言限制。使用CochraneHandbook5.3偏倚风险评估工具评估纳入研究的质量。采用Revman5.3软件对纳入研究进行质量评价。研究结果的异质性通过I2检验,连续变量以加权平均差或标准平均差表示,置信区间设定为95%。Stata15.0用于进行荟萃分析。
    共纳入15项RCT,共1,124例患者。Meta分析显示试验组在总症状评分(SMD:-0.62;95%Cl:-0.99,-0.24)方面优于对照组,麻木,刺痛,生活质量评分(总分,物理,函数),疼痛,balance,和神经毒性功能评估(FACT/GOG-NTX)问卷(p<0.05)。
    每周治疗的持续时间和频率都不同,这可能会对结果产生一些影响。
    运动疗法可以通过改善症状评分(总症状评分,麻木,刺痛),生活质量评分(总分,物理功能),疼痛,balance,和FACT/GOG-NTX问卷。它还需要更多高质量的完善和验证,多中心,未来的大样本RCT。
    https://www.crd.约克。AC.uk/prospro/display_record.php?ID=CRD42022373131,标识符:CRD42022373131。
    More than half of cancer patients develop severe chemotherapy-induced peripheral neuropathy (CIPN), resulting in low quality of life, negative effects on function, and challenges in treatment compliance. Most recent studies have shown that exercise therapy has a positive impact on reducing CIPN symptoms and can also improve quality of life, balance, and activity levels. The aim of this meta-analysis was to evaluate the effect of exercise therapy on the efficacy of CIPN.
    Computerized search of Embase, Web of Science, CNKI, Wan Fang Data, VIP, CBM for RCTs on exercise therapy for CIPN from database creation to November 2022, without language restriction. The Cochrane Handbook 5.3 risk of bias assessment tool was used to evaluate the quality of the included studies. Then Revman 5.3 software was used to evaluate the quality of the included studies. The heterogeneity of the research results is tested by I2, continuous variables were presented as weighted mean difference or standard mean difference, and confidence intervals were set at 95%. Stata15.0 was utilized to conduct a meta-analysis.
    A total of 15 RCTs with 1,124 patients were included. Meta-analysis showed that the test group was superior to the control group in terms of total symptom score (SMD: -0.62; 95% Cl: -0.99, -0.24), numbness, tingling, quality of life score (total score, physical, function), pain, balance, and neurotoxicity function assessment (FACT/GOG-NTX) questionnaire (p < 0.05).
    The duration and frequency of treatment are different every week, which may have some impact on the results.
    Exercise therapy can be effective in treating CIPN by improving symptom score (total symptom score, numbness, tingling), quality of life score (total score, physical function), pain, balance, and FACT/GOG-NTX questionnaires. It still needs to be refined and validated by more high-quality, multicenter, large-sample RCTs in the future.
    https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373131, identifier: CRD42022373131.
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