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    2018 Year 24 Vol. 3 Issue

      OriginalPaper

    • Yao-long Chen,Chen Zhao,Li Zhang,Bo Li,Chuan-hong Wu,Wei Mu,Jia-ying Wang,Ke-hu Yang,You-ping Li,Chiehfeng Chen,Yong-yan Wang,Chen Wang,Zhao-xiang Bian,Hong-cai Shang
      2018, 24(3): 163-170. DOI: 10.1007/s11655-017-2795-2
      Abstract:How to test the treatments of Chinese medicine (CM) and make them more widely accepted by practitioners of Western medicine and the international healthcare community is a major concern for practitioners and researchers of CM. For centuries, various approaches have been used to identify and measure the efficacy and safety of CM. However, the high-quality evidence related to CM that produced in China is still rare. Over the recent years, evidence-based medicine (EBM) has been increasingly applied to CM, strengthening its theoretical basis. This paper reviews the past and present state of CM, analyzes the status quo, challenges and opportunities of basic research, clinical trials, systematic reviews, clinical practice guidelines and clinical pathways and evidence-based education developed or conducted in China, pointing out how EBM can help to make CM more widely used and recognized worldwide.  
      Keywords:evidence-based medicine;Chinese Medicine;randomized controlled trial;systematic review;clinical practice guidelines   
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      Published:2021-08-27
    • Tong Zhang,Yu-fei Yang,Bin He,Dan-hui Yi,Jie Hao,Da Zhang
      2018, 24(3): 171-177. DOI: 10.1007/s11655-017-2962-2
      Abstract:To verify the efficacy and safety of Quxie Capsule (祛邪胶囊) in patients with metastatic colorectal cancer (mCRC). The present study was a randomized, double-blind, placebo-controlled trial. Sixty patients with mCRC were randomized into two groups at a 1:1 ratio by sealed envelope. The treatment group received conventional therapy combined with Quxie Capsule for 3 months. The control group was treated with conventional therapy combined with placebo for 3 months. Main outcome measures were overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed according to age, right or left-sided disease, and second-line therapy to determine the differences in PFS and OS between the two groups. Patients were followed up every 3 months until Dec 31st 2016. The median OS was 23 months in the treatment group [95% confidence interval (CI): 15–not calculated] vs. 14 months in the control group (95% CI: 11–22, P=0.060). The OS of the treatment group tended to be longer than that of the control group (P>0.05). In the subgroups of patients <65 years old, left-sided colon, and 2nd-line therapy, the treatment group showed a significant survival benefit compared with the control group (P=0.006, 0.038, 0.013, respectively). There were no significant differences between the two groups in PFS (P>0.05). Safety analysis showed no severe hematological toxicity or liver and renal function injury in the treatment group. Quxie Capsule showed good safety and efficacy, and could prolong the OS of patients with mCRC. (Registration No. ChiCTR-IOR-16009733)  
      Keywords:Chinese Medicine;Quxie Capsule;metastatic colorectal cancer;randomized controlled trial   
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      Published:2021-08-27
    • Meng Li,Miao-miao Wang,Xiu-wei Guo,Chao-yong Wu,Dao-rui Li,Xing Zhang,Pei-tong Zhang
      2018, 24(3): 178-184. DOI: 10.1007/s11655-017-2971-1
      Abstract:To assess the efficacy of Chinese medicine (CM) on patients with pancreatic cancer (PC) in a retrospective population-based study. Between January 1, 2013, and August 30, 2016, according to whether received Western medicine treatment, the patients were included into either integrative medicine (IM) group or CM group. All enrolled patients were orally administrated with Gexia Zhuyu Decoction (膈下逐瘀汤) or Liujun Ermu Decoction (六君二母汤) by syndrome differentiation, twice a day, last for at least 2 months. The primary end point was overall survival (OS). A total of 174 patients with PC were enrolled in this study. In stage I/II, the median OS was 20.5 months in the IM group [95% confidence interval (CI), 12.499 to 28.501] and 11.17 months in the CM group (95% CI, 5.160 to 17.180, P=0.015). The 1- and 2-year survival rates for the two groups were 47.0%, 40.0% and 21.0%, 21.0%, respectively. In stage III/IV, median OS was 13.53 months (95% CI, 8.665 to 18.395) in the IM group versus 6.4 months (95% CI, 0.00 to 15.682) in the CM group, respectively (P=0.32). The 1- and 2-year survival rate for the IM and CM groups were 27.0%, 7.0% and 20.0%, 2.0%, respectively. Intervention of CM contributes to the different survival benefits for PC in different stages. Multimodality treatment might be a promising strategy for PC patients in early stage. While, in advanced stage, CM might be an alternative candidate for PC patients.  
      Keywords:survival benefifit;Chinese Medicine;Integrative Medicine;Pancreatic Cancer;treatment selection   
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      Published:2021-08-27
    • Jing Zhou,Dong Yang,Shu-hong Zhou,Jin-ping Wang,Yue-shu Liu,Shu-lan Wang
      2018, 24(3): 185-192. DOI: 10.1007/s11655-017-2954-2
      Abstract:To examine the efficacy and safety of bathing therapy with Taohong Siwu Decoction (桃红四物汤, TSD) in the treatment of early-stage, mild-moderate diffuse cutaneous systemic sclerosis (dcSSc). This randomized, placebo-controlled trial enrolled 148 men and women (18–60 years) with dcSSc (disease duration 12 months) and baseline modified Rodnan skin score (MRSS) 10. Patients were randomized into a TSD group (71 cases bathing with TSD plus oral prednisone) or control group (71 cases bathing with placebo plus oral prednisone). Bathing (40 °C, 30 min) of the upper and lower limbs was carried out once daily for 12 consecutive weeks. The primary outcome measure was MRSS; secondary outcomes were Raynaud’s phenomenon (RP) score, quality of life (QOL), physician visual analogue scale (VAS), patient VAS, percent predicted diffusing capacity for carbon monoxide (DLCO), percent predicted forced vital capacity (FVC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level and overall treatment effect. The final analysis included 135 patients (control group, 68 cases; TSD group, 67 cases). Primary and secondary outcome measures after 2 weeks of treatment showed no improvement (versus baseline) in both groups, with no differences between groups. At 12 weeks, QOL, physician VAS, patient VAS, ESR and CRP were improved in both groups, but MRSS and RP score were improved only in the TSD group (all P<0.05). MRSS, RP score, QOL, physician VAS, patient VAS, ESR and CRP differed significantly between groups (all P<0.05). Meanwhile, the overall treatment effect was significantly higher in the TSD group than in the control group (P<0.05). Adverse events in the two groups were similar (P>0.05). Bathing with TSD plus oral prednisone achieves better outcomes than oral prednisone alone in patients with dcSSc and is not associated with serious adverse events.  
      Keywords:Chinese Medicine;bathing therapy;systemic sclerosis;treatment efficacy;adverse effects   
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      Published:2021-08-27
    • Gui-xin He,Jun Xie,Hao Jiang,Wei Tan,Biao Xu
      2018, 24(3): 193-199. DOI: 10.1007/s11655-017-2955-1
      Abstract:To evaluate the effect of treatment with Qishen Yiqi Dripping Pills (芪参益气滴丸, QSYQ) on myocardial injury and myocardial microvascular function in patients undergoing elective percutaneous coronary intervention (PCI). Eighty patients undergoing elective PCI were randomly assigned to QSYQ and control groups. The QSYQ group received QSYQ at a dosage of 0.5 g 3 times daily (3–7 days before PCI and then daily for 1 month) and regular medication, which comprised of aspirin, clopidogrel, statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in the absence of contradiction. The control group received only the regular medication. The index of microcirculatory resistance (IMR) was measured at maximal hyperemia after PCI. The fractional flow reserve was measured before and after the procedure. Troponin I levels were obtained at baseline and 20–24 h after the procedure. Pre-PCI troponin I levels between the two groups were similar (0.028±0.05 vs. 0.022±0.04 ng/mL, P=0.55). However, post- PCI troponin I levels in the QSYQ group were significantly lower than that in the control group (0.11±0.02 vs. 0.16±0.09 ng/mL, P<0.01). IMR values were significantly lower in the QSYQ group as compared to the control group (16.5±6.1 vs. 31.2±16.0, P<0.01). Multivariate analysis identified QSYQ treatment as the only independent protective factor against IMR >32 (odds ratio=0.29, 95% confidence interval: 0.11–0.74, P=0.01). The present study demonstrated the benefit of QSYQ in reducing myocardial injury and preserving microvascular function during elective PCI.  
      Keywords:Myocardial Injury;microvascular impairment;Percutaneous Coronary Intervention;Chinese Medicine;herbs   
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      Published:2021-08-27
    • Xin Sun,Yan-na Zhao,Song Qian,Rui-lan Gao,Li-ming Yin,Li-pei Wang,Beng-hock Chong,Su-zhan Zhang
      2018, 24(3): 200-206. DOI: 10.1007/s11655-017-2754-8
      Abstract:To investigate the potential efficacy of panaxadiol saponins component (PDS-C), a biologically active fraction isolated from total ginsenosides, to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide (CTX). Mice with myelosuppression induced by CTX were treated with PDS-C at a low- (20 mg/kg), moderate- (40 mg/kg), or high-dose (80 mg/kg) for 7 consecutive days. The level of peripheral white blood cell (WBC), neutrophil (NEU) and platelet (PLT) were measured, the histopathology and colony formation were observed, the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot. In response to PDS-C therapy, the peripheral WBC, NEU and PLT counts of CTX-induced myelosuppressed mice were significantly increased in a dose-dependent manner. Similarly, bone marrow histopathology examination showed reversal of CTX-induced myelosuppression with increase in overall bone marrow cellularity and the number of hematopoietic cells (P<0.01). PDS-C also promoted proliferation of granulocytic and megakaryocyte progenitor cells in CTX-treated mice, as evidenced by significantly increase in colony formation units-granulocytes/monocytes and -megakaryocytes (P<0.01). The enhancement of hematopoiesis by PDS-C appears to be mediated by an intracellular signaling pathway, this was evidenced by the up-regulation of phosphorylated mitogen-activated protein kinase (p-MEK) and extracellular signal-regulated kinases (p-ERK), and receptor tyrosine kinase (C-kit) and globin transcription factor 1 (GATA-1) in hematopoietic cells of CTX-treated mice (P<0.05). PDS-C possesses hematopoietic growth factor-like activities that promote proliferation and also possibly differentiation of hematopoietic progenitor cells in myelosuppressed mice, probably mediated by a mechanism involving MEK and ERK protein kinases, and C-kit and GATA-1 transcription factors. PDS-C may potentially be a novel treatment of myelosuppression and pancytopenia caused by chemotherapy.  
      Keywords:panaxadiol saponins component;Ginsenosides;chemotherapy-induced myelosuppression;mitogen-activated protein kinase;extracellular signal-regulated kinase;receptor tyrosine kinase;globin transcription factor 1;Chinese Medicine   
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      Published:2021-08-27
    • Jing Lin,Qiao-yan Cai,Wen Xu,Jiu-mao Lin,Jun Peng
      2018, 24(3): 207-212. DOI: 10.1007/s11655-016-2459-4
      Abstract:To study the chemical composition, anticancer, anti-neuroinflflammatory, and antioxidant activities of the essential oil of Patrinia scabiosaefolia (EO-PS). Patrinia scabiosaefolia was analyzed by gas chromatography-mass spectrometry. Eight human carcinoma cell lines, including SGC-7901, AGS, HepG2, HT-29, HCT-8, 5-FU/HCT-8, HeLa, and MDA-MB-231, were assessed by methylthiazolyldiphenyltetrazolium bromide (MTT) assay. Anti-neuroinflflammatory activity was assessed by production of interleukin (IL)-1β and IL-6 induced by lipopolysaccharide in BV-2 cells (microglia from mice). The antioxidant activity was evaluated with a 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay. Forty-four components, representing 83.919% of the total oil, were identifified in the EO-PS. The major constituents were caryophyllene oxide (12.802%), caryophyllene (6.909%), α-caryophyllene (2.927%), β-damascenone (3.435%), calarene (5.621%), and phenol (3.044%). The MTT assay showed that the EO-PS exhibited significant dose-dependent growth inhibition in the 50–200 μg/mL dilution range. The EO-PS exhibited a dose-dependent scavenging activity against the DPPH radical, with an half of maximal inhibitory concentration 1.455 mg/mL. The EO-PS possesses a wide range of antitumor, anti-neuroinflflammatory and antioxidant activities, suggesting that it may be a good candidate for further investigations of new bioactive substances.  
      Keywords:Patrinia scabiosaefolia;essential oil;anti-neuroinflflammatory;anticancer;antioxidant;caryophyllene oxide   
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      Published:2021-08-27
    • Yu Zhang,li Hou,Xin-yi Chen
      2018, 24(3): 213-217. DOI: 10.1007/s11655-017-2963-1
      Abstract:To investigate the effects of Compound Zhebei Granule (复方浙贝颗粒, CZG) combined with doxorubicin hydrochloride (adriamycin, ADM) on specific surface antigens in mice with KG-1a transplanted cells. A subcutaneous tumor xenograft model was established by injection of the acute myeloid leukemia cell line KG-1a into the axillary flfl anks of BALB/c-nude mice. Twenty-four tumor bearing mice were divided into 4 groups according to a random number table, including normal saline control group, ADM group, high-dose CZG group, and mid-dose CZG group, with 6 mice in each group. Drug administration occurred on the 14th day after cell inoculation, and normal saline control group mice were gavaged with normal saline at 0.2 mL/10 g every other day. ADM group mice were intraperitoneally injected with ADM 1 mg/kg [conversion of adults, 40 mg/(m2•d)] every other day. High- and mid-dose CZG groups mice were gavaged with CZG at the dose of 8 and 4 g/kg respectively every other day and intraperitoneally injected with ADM (1 mg/kg) every other day. The administration period lasted for 10 days. The tumor xenografts were made into mononuclear cell suspensions after dissection, and the expressions of specific surface antigens, including CD34+CD38-, CD34+CD38-CD123+, CD34+CD38-CD96+ and CD34+CD38-CD33+, in KG-1a cell line tumor xenografts were detected by flfl ow cytometry. Compared with the control and ADM groups, expression of CD34+CD38- in the two CZG groups was significantly lower (P<0.05). Compared with the control group, expression of CD34+CD38-CD123+ in the two CZG groups decreased (P<0.05). The high-dose CZG group showed more obvious outcomes compared with the ADM group (P<0.05). Compared with the control and ADM groups, the expression of CD34+CD38-CD96+ and CD34+CD38-CD33+ in the two CZG groups decreased (P<0.05). CZG combined with doxorubicin could reduce the expression of CD34+CD38-, CD34+CD38-CD123+, CD34+CD38-CD96+ and CD34+CD38-CD33+ in KG-1a cell line tumor xenografts, which shows that CZG could target leukemia stem cells and play a role in chemosensitization.  
      Keywords:acute myeloid leukemia;Chinese Medicine;doxorubicin;adriamycin   
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      Published:2021-08-27
    • Jing Liu,Si-nai Li,Lu Liu,Kun Zhou,Yan Li,Xiao-yun Cui,Jie Wan,Jin-jin Lu,Yan-chao Huang,Xu-sheng Wang,Qian Lin
      2018, 24(3): 218-226. DOI: 10.1007/s11655-017-2753-9
      Abstract:To exam the effect and safety of conventional acupuncture (CA) on cardiac arrhythmia. Nine medical databases were searched until February 2016 for randomized controlled trials. Heterogeneity was measured by Cochran Q test. Meta-analysis was conducted if I2 was less than 85% and the characteristics of included trials were similar. Nine qualified studies involving 638 patients were included. Only 1 study had definitely low risk of bias, while 7 trials were rated as unclear and 1 as high. Meta-analysis of CA alone did not have a significant benefit on response rate compared to amiodarone in patients with atrial fibrillation (Af) and atrial flutter (AF) [relative risk (RR): 1.09; 95% confidence interval (CI): 0.79–1.49; P=0.61; I2=61%, P=0.11]. However, 1 study with higher methodological quality detected a lower recurrence rate of Af in CA alone as compared with sham acupuncture plus no treatment, and benefits on ventricular rate and time of conversion to normal sinus rhythm were found in CA alone group by 1 study, as well as the response rate in CA plus deslanoside group by another study. Meta-analysis of CA plus anti-arrhythmia drug (AAD) was associated with a significant benefit on the response rate when compared with AAD alone in ventricular premature beat (VPB) patients (RR, 1.19, 95% CI: 1.05–1.34; P=0.005; I2=13%, P=0.32), and an improvement in quality-of-life score (QOLS) of VPB also showed in 1 individual study. Besides, a lower heart rate was detected in the CA alone group by 1 individual study when compared with no treatment in sinus tachycardia patients (MD–21.84 [–27.21,–16.47]) and lower adverse events of CA alone were reported than amiodarone. CA may be a useful and safe alternative or additive approach to AADs for cardiac arrhythmia, especially in VPB and Af patients, which mainly based on a pooled estimate and result from 1 study with higher methodological quality. However, we could not reach a robust conclusion due to low quality of overall evidence.  
      Keywords:acupuncture;cardiac arrhythmia;systematic review   
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      Published:2021-08-27
    • Xiu-wei Guo,Nai-dong Hu,Gui-zhi Sun,Meng Li,Pei-tong Zhang
      2018, 24(3): 227-231. DOI: 10.1007/s11655-017-2951-5
      Abstract:To assist decision-makers interpret and choose among conflfl icting meta-analyses, as well as to offer treatment recommendations based on current best evidence by performing a systematic review of overlapping meta-analyses regarding Shenyi Capsule (参一胶囊, SC) plus chemotherapy versus chemotherapy of non-small cell lung cancer (NSCLC). A literature search was conducted to select systematic reviews comparing SC plus chemotherapy with chemotherapy for NSCLC. Meta-analyses only composed of randomized controlled trials (RCTs) met the inclusion criteria. Two authors individually estimated the quality of meta-analysis and extracted data. The Jadad decision algorithm was applied to guarantee which meta-analysis provided the best original evidence. A total of 5 meta-analyses were included. All the studies composed of RCTs or quasi-RCTs and were regarded as level-II evidence. The scores of the Assessment of Multiple Systematic Reviews ranged from 3 to 6 (median 4). A high-quality meta-analysis with more RCTs was chosen, which suggested that SC plus chemotherapy could increase incidence of short-term efficacy, improve the quality of life and survival rate in comparison to chemotherapy. However, there was no statistically significant difference between SC plus chemotherapy and chemotherapy regarding chemotherapy-induced side effect, such as liver and kidney function obstacle, leukopenia, hemoglobin decrement and gastrointestinal adverse reaction. Based on the best available evidence, treatment effect of SC plus chemotherapy was better than chemotherapy and did not increase side effects. Therefore, SC plus chemotherapy may be superior to chemotherapy for treating NSCLC. However, due to some limitations, SC plus chemotherapy should be cautiously considered, and further high-quality meta-analyses are needed.  
      Keywords:non-small cell lung cancer;Shenyi Capsule;Chinese Medicine;chemotherapy;integrative treatment;systematic review;meta-analysis   
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      Published:2021-08-27
    • Liu Long-tao
      2018, 24(3): 232-236. DOI: 10.1007/s11655-018-2981-6
        
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      Published:2021-08-27
    • Yun-long Li,Qiao-xing Li,Rui-jiang Liu,Xiang-qian Shen
      2018, 24(3): 237-240. DOI: 10.1007/s11655-015-2154-x
      Abstract:Amarogentin is an efficacious Chinese herbal medicine and a component of the bitter apricot kernel. It is commonly used as an expectorant and supplementary anti-cancer drug. β-Glucosidase is an enzyme that hydrolyzes the glycosidic bond between aryl and saccharide groups to release glucose. Upon their interaction, β-glucosidase catalyzes amarogentin to produce considerable amounts of hydrocyanic acid, which inhibits cytochrome C oxidase, the terminal enzyme in the mitochondrial respiration chain, and suspends adenosine triphosphate synthesis, resulting in cell death. Hydrocyanic acid is a cell-cycle-stage-nonspecific agent that kills cancer cells. Thus, β-glucosidase can be coupled with a tumor-specific monoclonal antibody. β-Glucosidase can combine with cancer-cell-surface antigens and specifically convert amarogentin to an active drug that acts on cancer cells and the surrounding antibodies to achieve a killing effect. β-Glucosidase is injected intravenously and recognizes cancer-cell-surface antigens with the help of an antibody. The prodrug amarogentin is infused after β-glucosidase has reached the target position. Coupling of cell membrane peptides with β-glucosidase allows the enzyme to penetrate capillary endothelial cells and clear extracellular deep solid tumors to kill the cells therein. The Chinese medicine amarogentin and β-glucosidase will become an important treatment for various tumors when an appropriate monoclonal antibody is developed.  
      Keywords:amarogentin;β-glucosidase;antibody enzymatic prodrug;targeting therapy;Chinese Medicine   
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