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   Table of Contents - Current issue
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January-March 2022
Volume 8 | Issue 1
Page Nos. 1-167

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REVIEW ARTICLES  

Forsythosides as essential components of Forsythia-based traditional chinese medicines used to treat inflammatory diseases and COVID-19 p. 1
Christian Bailly
DOI:10.4103/wjtcm.WJTCM_36_21  
The dried fruits of the plant Forsythia suspensa (Forsythia Fructus: Lianqiao in Chinese) are used in many herbal preparations to treat various diseases or the associated symptoms. Forsythia extracts contain phenylethanoid glycosides (PhGs) such as the forsythosides (Fst A-to-P). The leading products, Fst-A,-B and-F (arenarioside), can be found also in >90 other plants inventoried here. The pharmacological properties of Fst are reviewed, with emphasis on their anticancer, antiviral, and antibacterial activities, which essentially derive from their anti-inflammatory and antioxidant effects. Fst-B functions as a potential binder of the repressor protein Kelch-like ECH-association protein 1 (Keap 1), thus promoting the nuclear translocation of the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) implicated in the subsequent activation of the production of antioxidant enzymes and repression of the oxidative stress. The regulation of the Nrf2/Heme oxygenase-1 pathway is the central piece of the multifaceted mechanism of action of Fst-A/B. Their prominent antioxidant and anti-inflammatory effects support the use of these compounds in different inflammation-related diseases and conditions, from sepsis to neuroprotection and many other pathologies discussed here. In addition, these properties contribute to the antiviral action of the compounds. Fst-A/B displays activities against the influenza A virus and different Fst-containing traditional Chinese medicinal (TCMs) have revealed beneficial effects to combat the current COVID-19 pandemic. The mechanisms whereby Fst-A/B could inhibit viral multiplication are discussed. PhGs likely contribute to the anti-COVID-19 activities reported with several TCM such as Shuang-Huang-Lian oral liquid, Lianhua-Qingwen capsules, and others. This review highlights the pharmacological profile of Fst and illustrates health benefits associated with the use of Forsythia Fructus.
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A review of the pharmacology, application, ethnopharmacology, phytochemistry, quality control, processing, toxicology, and pharmacokinetics of Paridis Rhizoma p. 21
Song-Tao Liu, Huan Yu, A-Jiao Hou, Wen-Jing Man, Jia-Xu Zhang, Song Wang, Xue-Jiao Wang, Sen-Wang Zheng, Xiao-Lin Su, Liu Yang
DOI:10.4103/wjtcm.wjtcm_4_21  
Paridis Rhizoma (PR) is also known as the flower with seven leaves and one branch, PR with golden thread, etc. It tastes bitter, numb, and slightly cold and has little poison. It is often used for the treatment of external skin infection, sore throat, snake bite, fall pain, frightening convulsion, and other diseases. PR has analgesic, sedative, anti-inflammatory, hemostatic, antitumor, antibacterial, antiviral, and renal and liver protective effects; inhibition of angiogenesis; immune regulation; and antioxidant and cardiovascular effects, and antifertility and anti-early pregnancy sperm killing effects. Steroidal saponins, β-ecdysone, polysaccharides, microelements, flavonoid glycosides, and amino acids were isolated from PR. In this paper, its pharmacology, application, ethnopharmacology, phytochemistry, quality control, toxicology, and pharmacokinetics were reviewed. This information suggests that we should focus on the development of new drugs related to PR, including specific ingredients, so as to make PR play a greater therapeutic potential. At the same time, attention should be paid to the rational use of PR resources to avoid excessive using, resulting in resource shortage. Therefore, we can carry out the research on the substitutes of PR, a large-scale planting of (Paridis Rhizoma) PR, and develop the same genus of PR and other resources. So far, great progress has been made in pharmacology and phytochemistry, especially in antitumor research, and many traditional uses have been confirmed and clarified by modern pharmacological research. However, there are few studies on the mechanism of its pharmacological action and few studies on processing. To develop new drugs in the future, more studies and experiments are still needed to prove the effect of PR and explore more new effects.
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Recent advances of traditional chinese medicine in the regulation of myocardial mitochondrial function p. 50
Shi-Yao Wan, Jin-Gui Hu, Yu Zhang, Bo-Yang Yu, Jun-Ping Kou, Fang Li
DOI:10.4103/wjtcm.wjtcm_78_20  
Cardiovascular disease is a crucial disease threatening human health, and its mortality rate ranks first among Chinese residents. Myocardial mitochondrial dysfunction is the main cause of various heart diseases such as myocardial infarction, myocarditis, hypertrophic cardiomyopathy, and heart failure. In recent years, many studies have confirmed that traditional Chinese medicine (TCM) can be used to improve myocardial mitochondrial function and treat heart disease. The purpose of this review was to analyze the regulatory mechanism of myocardial mitochondrial function by summarizing the effect of TCM on cardiovascular disease.
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Engineered production of bioactive natural products from medicinal plants p. 59
Ozkan Fidan, Jie Ren, Jixun Zhan
DOI:10.4103/wjtcm.wjtcm_66_21  
Plant natural products have been particularly important due to their use in food, cosmetic, and pharmaceutical industries. In particular, Traditional Chinese Medicine provides a precious potential for the discovery of bioactive natural products and development of novel modern medicines. However, the existing production methods for plant natural products such as chemical synthesis and plant extraction does not meet the current demand. Due to their environmental and economic concerns, engineered production of valuable natural products in microbial hosts has become an attractive alternative platform. This review covers the recent advances in the engineered production of plant natural products in microorganisms. A special focus was placed on the biotechnological production of plant-derived terpenoids, flavonoids, and alkaloids. Some successful examples of engineered production of plant natural products (or their precursors) such as artemisinin, paclitaxel, naringenin, quercetin, berberine, and noscapine are summarized. This clearly indicates that the engineered production method is a promising approach with various advantages over current methods.
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ORIGINAL ARTICLES Top

Integrated miRNA and mRNA analysis identified potential mechanisms and targets of qianggan extracts in preventing nonalcoholic steatohepatitis p. 77
Jie Huang, Meng Li, Wen-Jun Zhoua, Ze-Min Yao, Guang Ji, Li Zhang, Ming-Zhe Zhu
DOI:10.4103/wjtcm.wjtcm_48_21  
Objective: Qianggan (QG) extract is a patented traditional Chinese medicine that has been widely used for the clinical treatment of nonalcoholic steatohepatitis (NASH). However, its mechanism remains unclear. Methods: The efficacy of QG was evaluated in mice with methionine-and-choline-deficient diet-induced NASH by measuring serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels and by H and E staining of liver sections. Microarray and bioinformatics analyses were performed to obtain hepatic microRNA (miRNA) and mRNA expression profiles and to mine potential mechanisms and therapeutic targets. Furthermore, representative miRNA and mRNA expression levels were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: QG extract significantly improved NASH. Twelve differentially expressed miRNAs and 1124 differentially changed mRNAs were identified as potential targets of QG extract. Integrated analysis detected 976 miRNA–mRNA regulatory pairs, and networks including 11 miRNAs and 427 mRNAs were constructed by Cytoscape. Hub nodes including miR-7050-5p, miR-212-3p, Bcl2l11, and Kras were filtered out. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that 427 mRNAs were enriched in pathways including apoptotic process, immune response, FoxO signaling pathway, and natural killer cell-mediated cytotoxicity. We also constructed a protein–protein interaction network with 254 nodes, and identified hub genes including Kras, Fasl, and Ncam1. Finally, the results of qRT-PCR were in good accordance with microarray data. Conclusion: This study identified important hub miRNAs and mRNAs involved in the mechanism of QG extract and which might provide potential therapeutic targets for patients with NASH.
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Interim analysis report of kuanxiong aerosol in improving angina and quality of life after percutaneous coronary intervention p. 87
Luo-Qi Lin, Bing-Xin Wu, Miao-Yang Lin, Qiu-Xiong Chen, Dan-Ping Xu
DOI:10.4103/wjtcm.wjtcm_26_21  
Objective: The objective is to observe the effect of Kuanxiong aerosol (KXA) on angina and the quality of life of patients after percutaneous coronary intervention (PCI). Materials and Methods: Six hundred patients with angina after PCI (AAP) were randomly assigned to an experimental group and a control group (n = 300 in each group) and received basic treatment with KXA or basic treatment (respectively) for 8 weeks. The Seattle Angina Questionnaire (SAQ) and visual analog scale (VAS) scores of the two groups during the screening period and five follow-up periods were compared. Results: A total of 179 patients were included in this interim report, including 85 in the experimental group and 94 in the control group. Among the five-dimensional scores of the SAQ, the improvement in the angina frequency and quality of life scores in the experimental group was better than those in the control group after treatment (P < 0.01), and the difference in scores of the remaining dimensions was not statistically significant (P > 0.01). The difference in VAS scores between the two groups was not statistically significant (P > 0.01). No obvious adverse reactions were observed between the two groups. Conclusions: KXA can reduce the frequency of AAP and improve patients' quality of life.
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Pharmacokinetic comparison of four major bio-active components of naoxintong capsule in normal and acute blood stasis rats using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry p. 92
Wei-Xia Li, Shu-Qi Zhang, Man-Man Li, Hui Zhang, Xiao-Yan Wang, Lu Niu, Jin-Fa Tang, Xue-Lin Li
DOI:10.4103/wjtcm.wjtcm_53_21  
Objective: To compare the pharmacokinetic differences of the main components of Naoxintong capsule (NXTC) in normal and acute blood stasis rats. Materials and Methods: Rats were subcutaneously injected with adrenaline hydrochloride twice; during the two subcutaneous injections, the rats were placed in ice water for 4 min to reproduce the model rat of acute blood stasis. The normal and acute blood stasis rats were administrated a 5.04 g/kg dose of NXTC suspension. Then, blood samples were collected from the posterior retinal venous plexus at different time points. Plasma concentrations of four major bio-active components including caffeic acid, ferulic acid, formononetin, and tanshinone IIA in NXTC were measured using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry. Phoenix WinNonlin v6.2 software was used to calculate the pharmacokinetic parameters. Results: Compared with the normal rats, the acute blood stasis rats showed a significant decrease in Cmax of ferulic acid and formononetin, AUCall of caffeic acid and ferulic acid, and AUCINF_obs of ferulic acid. Conversely, an increase in the Vz_F_obs and MRTlast of ferulic acid and caffeic acid was observed. These findings demonstrate that the absorption of the four NXTC components was weakened in the acute blood stasis rats and that the elimination time was prolonged. Conclusions: The significant difference in some parameters of the four NXTC components between the normal and acute blood stasis rats might be caused by an increase in blood viscosity and the subsequent slowing down of blood flow in the acute blood stasis rats. The pharmacokinetic study conducted in pathological state can provide important information and scientific basis for further rational clinical application of NXTC.
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Network pharmacology-based study of the anti-oxidative mechanism of san miao wan in treatment of arthritis p. 100
Xue-Qin Hao, Yan-Qi Kou, Xiao-Juan Xie, Jiao-Wang , Jing-Bo Lv, Jie Su, Ke-Xin Liu, Gao-Feng Liang
DOI:10.4103/wjtcm.wjtcm_46_21  
San Miao Wan (SMW) is a traditional Chinese medicine (composed of Cortex phellodendri, Rhizoma atractylodes, and Radix cyathulae) widely used in China to treat arthritis; however, its underlying mechanism remains unknown. We established the target gene library of SMW and performed gene ontology enrichment analysis of related target genes. The component-target protein-protein interaction (PPI) network of SMW and the disease-target PPI network of arthritis were merged to form a core PPI network. Finally, the anti-oxidative effect of SMW for treating arthritis was evaluated in a rat arthritis model induced by sodium urate. The results showed that R. atractylodes contained four active components with 68 target proteins, R. cyathulae contained two active components and 139 target proteins, and C. phellodendri contained eight active components and 275 target proteins. The target genes of R. cyathulae were highly related to the synthesis and metabolism of reactive oxygen species, while target genes of R. atractylodes and C. phellodendri were highly related to the circulatory system. The component-target PPI network of SMW and the disease-target PPI network of arthritis predominantly overlapped. In vivo, SMW effectively reduced knee swelling induced by sodium urate, decreased serum malondialdehyde levels, and increased serum superoxide dismutase levels. In conclusion, the therapeutic effects of SMW in arthritis are associated with its anti-oxidative properties.
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Herbal medicine teng-long-bu-zhong-tang inhibits the growth of human RKO colorectal cancer by regulating apoptosis, senescence, and angiogenesis p. 110
Meng-Meng Wei, Shuang-Shuang Wang, Jia-Lu Zheng, Lei Chen, Xiao Peng, Jin-Fang Chen, Hong-Mei An, Bing Hu
DOI:10.4103/wjtcm.wjtcm_42_21  
Background: Teng-Long-Bu-Zhong-Tang (TLBZT) is a traditional Chinese herbal medicine used to treat colorectal cancer (CRC). In the present study, we observed the anti-cancer effects of TLBZT on human RKO CRC. Materials and Methods: Mice were subcutaneously transplanted with RKO cells, divided into control, 5-Fu-administered, TLBZT-administered, and TLBZT and 5-Fu combination-administered groups, and treated with 5-Fluorouracil (5-Fu) and/or TLBZT. Apoptosis was detected by TdT-mediated dUTP nick-end labeling assay. The activity of caspase-3,-8, and-9 was detected using specific commercial kits. Cell senescence was assessed using senescence β-galactosidase staining. Protein expression was evaluated by immunohistochemistry. Results: TLBZT inhibited RKO CRC tumor growth, enhanced the anti-cancer effects of 5-Fu, induced apoptosis, and activated caspase-3,-8, and-9. TLBZT induced cell senescence accompanied by the downregulation of cyclin E1 and cyclin-dependent kinase 2 expressions. TLBZT also inhibited angiogenesis and the expression of hypoxia-inducible factor 1 subunit alpha and vascular endothelial growth factor-A. Conclusions: TLBZT inhibited RKO CRC tumor growth and enhanced the anti-cancer effects of 5-Fu, and it could be associated with apoptosis and cell senescence induction, and angiogenesis inhibition.
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Quercetin-3-O-β-D-glucuronide inhibits mitochondria pathway-mediated platelet apoptosis via the phosphatidylinositol-3-kinase/AKT pathway in immunological bone marrow failure p. 115
Le-Min Xia, Ai-Ping Zhang, Qin Zheng, Jie Ding, Zhe Jin, Hai Yu, Wan-Hui Wong, He-Ping Yu
DOI:10.4103/wjtcm.wjtcm_44_21  
Objective: Quercetin-3-O-β-D-glucuronide (QG) can alleviate immunological bone marrow failure (BMF) by increasing platelet counts. However, the principal mechanism is less known. This study aimed at deciphering the possible underlying mechanism of QG that is indicated in thrombocytopenic purpura. Methods: In vitro and in vivo experiments were carried out for investigating the mechanism behind QG-facilitated inhibition of mitochondrial pathway-mediated excessive apoptosis of platelets through the phosphatidylinositol-3-kinase (PI3K)/AKT pathway. Results: Our results revealed that QG, the main effective ingredient of Herba Sarcandrae, increases the number of platelets and decreases the expression of Bax, Bad, Bid, and caspase-9 in immunological BMF, indicating the inhibition of mitochondrial pathway-mediated apoptosis. Moreover, we found that the protein and mRNA expressions, as well as the phosphorylated levels of PI3K and AKT, were increased significantly by QG, suggesting the activation of the PI3K/AKT pathway. Furthermore, the inhibition of the PI3K/AKT pathway by LY294002 antagonizes the effects of QG on platelet counts and mitochondrial pathway-mediated apoptosis. Conclusion: We demonstrate that QG inhibits the mitochondria pathway-mediated platelet apoptosis via the PI3K/AKT pathway in immunological BMF. This study thus sheds light on exploring the possible regulatory mechanism of traditional Chinese medicine in the treatment of thrombocytopenia induced by BMF.
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Effect of salivary antimicrobial factors on microbial composition of tongue coating in patients with coronary heart disease with phlegm-stasis syndrome p. 123
Juan Ye, Ke-Lei Su, Yue-Hua Xu, Yang Yang, Qian Zhou, Wei Gao, Xue-Ting Cai, Qing-Yu Wei, Meng Cao, Peng Cao
DOI:10.4103/wjtcm.wjtcm_34_21  
Objective: Phlegm-stasis syndrome is one of the most common traditional Chinese medicine (TCM) syndromes and found in 59% of patients with coronary heart disease (CHD) in routine TCM clinical practice in China. One of the diagnostic criteria of phlegm-stasis syndrome is its characteristic white-greasy and thin tongue coating. We have previously reported that different types of tongue coating have different microbiome characteristics that can be used as diagnostic markers. However, the microbial characteristics of tongue coating of CHD patients with phlegm-stasis syndrome, including coating feature and underlying reason of formation, have rarely been reported. Herein, we examined the characteristic microbiome of tongue coating, and discussed the cause of tongue coating formation via salivary proteins in patients with phlegm-stasis syndrome. Methods: We examined white-greasy and thin tongue coatings obtained from 10 patients with CHD having phlegm-stasis syndrome (n = 10), and compared with those of patients with almost no coating – patients with Qi-Yin deficiency syndrome (n = 10) – and healthy controls (n = 10). 16S rRNA sequencing of tongue coating microbiome and isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative analysis of salivary proteins were used to detect tongue coating and salivary protein separately. Salivary levels of sIgA, lysozyme, and amylase were detected by ELISA. Results: We identified Candidatus_Saccharimonas and Candidate_division_TM7_norank as the prominent members of tongue coating in patients with CHD having phlegm-stasis syndrome. Salivary proteins involved in biological processes, pentose phosphate pathway, and complement and coagulation cascades were among the differentially expressed proteins identified in patients with CHD having phlegm-stasis syndrome on iTRAQ analysis. Moreover, the formation of microbiota in tongue coating was associated with salivary sIgA, lysozyme, and saliva flow rate. Conclusions: We explored the characteristics of microbial composition of tongue coating patients with CHD having phlegm-stasis syndrome and identified correlations between salivary proteins and microbiome formation, providing a theoretical and mechanistic basis for tongue coating formation.
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Mechanism exploration of the classical traditional chinese medicine formula huoluo xiaoling pill in clinical treatment and the traditional chinese medicine theory “treating different diseases with the same method”: A network pharmacology study and molecular docking verification p. 131
Yu-Xin Hu, Zhi-Qing Zhang, Qin-Jie Zhou, Jun-Ya Liao, Xin-Lou Chai
DOI:10.4103/wjtcm.wjtcm_58_21  
Objective: To analyze the possible mechanism of the Huoluo Xiaoling Pill in the treatment of three diseases, hyperglycemia, hyperlipidemia, and metabolic syndrome, and to provide ideas for learning the mechanism of “Treating different diseases with the same method” in Traditional Chinese Medicine (TCM) theory. Materials and Methods: The Traditional Chinese Medicine System Pharmacology Database and UniProt databases were used to screen the main ingredients and targets of the Huoluo Xiaoling Pill. The GeneCards database was used to screen the targets of the diseases, and Cytoscape 3.7.2 was used to construct a “Drug-Components-Targets-Disease” network to determine the core components. The STRING database was used to construct the protein-protein-interaction network, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomics enrichment analyses were carried out on the Metascape database. AutoDock 1.5.6 was used for molecular docking. Results: A total of 118 active components and 208 targets were screened in the Huoluo Xiaoling Pill. Quercetin, tanshinone IIA, luteolin, and ellagic acid were potential core components of Huoluo Xiaoling Pill treating the three diseases, and interleukin 6, Tumor necrosis factor, and vascular endothelial growth factor were potential key targets. Co-occurring GO biological processes involved responses to the molecules of bacterial origin, and the AGE-RAGE signaling, fluid shear stress, and atherosclerosis pathways were the co-occurring pathways. Molecular docking revealed good docking conditions between screened targets and components. Conclusion: This study predicted the mechanism of the Huoluo Xiaoling Pill in treating the three diseases. At the same time, the co-occurring targets and pathways between the three diseases provided a material basis for the TCM theory, “Treating different diseases with the same method.”
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Ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry based bile and urine metabonomics study on the ameliorative effects of Curcuma wenyujin rhizoma on acute blood stasis in rats p. 141
Min Hao, Meng-Ting Zhao, Huang-Jin Tong, De Ji, Lin Li, Lian-Lin Su, Wei Gu, Chun-Qin Mao, Tu-Lin Lu
DOI:10.4103/wjtcm.wjtcm_55_21  
Background: Curcuma wenyujin rhizome (CWR) is a commonly used Chinese herbal medicine for treating blood stasis in China for 1000 of years. However, the underlying mechanism of CWR remains unclear. Aims and Objectives: The purpose of this study is to clarify the bioactive mechanism of CWR in treating blood stasis. Materials and Methods: In this study, pharmacological indexes, including hemorheology and four blood coagulation indexes were tested. Bile and urine metabolomics were engaged by UPLC-Q/TOF-MS. Multivariate statistical analysis were used to screen out differential endogenous metabolites. Results: The results indicated that CWR significantly ameliorated the hemorheology and coagulation functions of acute blood stasis (ABS) model rats. Moreover, 27 endogenous metabolites between the CWR group and the ABS group were screened, and the levels were all improved to certain degrees by CWR preadministration. Metabonomics results indicated that ABS was mainly related to linoleic acid metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism, pentose and glucuronate intercereasonversions, steroid hormone biosynthesis, and primary bile acid biosynthesis. Conclusion: In a word, the metabolomics method is consistent with the holistic view of traditional Chinese medicine (TCM) that can be a powerful means to illustrate the biological activity mechanism of CWR in treating blood stasis and to offer research demonstration for further study on the effector mechanism of TCM.
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Therapeutics of integrative medicine ameliorate immunological disorders of the nervous system: A meta-analysis p. 153
Jin-Yun Ma, Jennifer Cruz, Jason Jin, Xiao-Yan Peng, Ai-Ming Zhang, Xiao-Dong Cheng
DOI:10.4103/wjtcm.wjtcm_57_21  
Objective: The objective of the study is to evaluate the therapeutic efficacy of integrative medicine in the treatment of immunological disorders of the nervous system. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were adopted to conduct this study, which included randomized controlled trials with a confirmed diagnosis of multiple sclerosis (MS), myasthenia gravis (MG), and Guillain–Barre syndrome (GBS), all of which were treated with integrative medicine. The effective rate, recurrent frequency, and disease score were used as the markers of outcome variables for the meta-analysis. Results: A total of 48 randomized control trials were included. The effective rates of treatment with integrative medicine were noticeably higher than those with Western medicine alone for the three diseases. The recurrence frequency for MS and the recurrence rate for MG treated with integrative medicine were reduced more than those with Western medicine alone. The Extended Disability Status Scale, acetylcholine receptor antibody, and Hughes scores for MS, MG, and GBS, respectively, treated with integrative medicine were significantly lower than those with Western medicine alone. The risks of bias in the literature evaluation showed that the quality of the included studies was not high. Conclusions: Compared to treatment with Western medicine alone, integrative medicine might ameliorate immunological disorders of the nervous system.
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