Latest Issue
      2021 Year 27 Vol. 7 Issue

        Regulation and Guideline

      • Jun LIU,Nian WANG,Hai-xia DANG,Bing-wei CHEN,Li ZHANG,Chong ZOU,Cheng-liang ZHONG,Ju-kai HUANG,Qiong LIU,Ya-nan YU,Meng JIANG,Wei-xiong LIANG,Qi-guang CHEN,Yong-yan WANG,Chun-ti SHEN,Zhong WANG,Zhong WANG
        2021, 27(7): 483-489. DOI: 10.1007/s11655-020-3439-2
        Abstract：Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.  
        Keywords：data monitoring committee;Chinese Medicine Data Monitoring Committee;clinical trial;community standard;Chinese medicine   
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        Published：2021-09-01

        Original Article

      • Xian-ge HUANG,Li-hua ZHU,Lei ZHOU,Wei-jie XU,Yi-lin YAO,Zhi-yi ZHOU,He-gen LI
        2021, 27(7): 490-495. DOI: 10.1007/s11655-020-3428-5
        Abstract：Objective:To investigate the effects of multidisciplinary and comprehensive Chinese medicine (CM) treatments on progression-free survival (PFS) and median survival time (MST) in patients with advanced nonsmall cell lung cancer (NSCLC) and identify factors that influence progression and prognosis.Methods:Clinical data of 855 patients with advanced NSCLC who received multidisciplinary and comprehensive CM treatments at Longhua Hospital from January 2009 to December 2018 were retrospectively analyzed. Univariate analysis was performed by the Kaplan-Meier method and log-rank sequential inspection. Multivariate analysis of significant variables from the univariate analysis was performed with Cox regression modeling. Key factors correlated to progression and prognosis were screened out, and a Cox proportional hazard model was established to calculate the prognostic index.Results:The PFS and MST of 855 advanced NSCLC patients were 9.0 and 26.0 months, respectively. The 1-, 2-, 3-, and 5-year survival rates were 79.2%, 54%, 36.2%, and 17.1%, respectively. Gender, pathologic type, and clinical stage were independent prognostic risk factors; surgical history, radiotherapy, treatment course of Chinese patent medicine, intravenous drip of Chinese herbal preparation, duration of oral administration of Chinese herbal decoction (CHD), and intervention measures were independent prognostic protective factors. Gender was an independent risk factor for progression, while operation history and oral CHD administration duration were independent protective factors (all P<0.05). Women with stage Ⅲb–Ⅲc lung adenocarcinoma had the best outcomes.Conclusions:Female patients have lower progression risk and better prognoses than male patients, younger patients have higher progression risk but better long-term prognoses than the elderlys, and patients with lower performance status scores are at lower risk for progression and have better prognoses. Comprehensive CM treatments could significantly reduce progression risk, improve prognosis, and prolong survival time for patients with advanced NSCLC. This treatment mode offers additional advantages over supportive care alone.  
        Keywords：advanced non-small cell lung cancer;prognostic factor;progression factor;survival analysis;Chinese medicine   
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        Published：2021-09-01
      • Shao-quan XIONG,Yu CHEN,Li-juan WANG,Pan-pan LYU,Wan LIAO,Cui WANG,Jian-long KE,Xi ZHU,Jin-yang WANG,Xian-ying SHEN,Guang-ping LI,Li-zhu LIN
        2021, 27(7): 502-508. DOI: 10.1007/s11655-019-3184-6
        Abstract：Objective:To study the use of Chinese medicine (CM) in cancer patients in southern China.Methods:A total of 1,950 cancer patients finished questionnaires in four provinces in southern China. The survey included socio-demographic and clinical characteristics of participants, dosage forms, efficacy, and side effects.Results:The study results showed that cancer patients with higher education (>12 years) were more likely to accept the treatment of Chinese herbs. There were 54.61% (1,065 cases) of patients chose Chinese herbs for the initial treatment and 14.46% (282 cases) chose Chinese herbs as monotherapy. Most patients (54.51%, 1,063 cases) continuously used CM for more than 6 months, and a few of them (212 cases) used CM for up to 3 years. All kinds of dosage forms of CM had been used, including CM decoction, CM patent prescription and CM injection. Concerning the efficacy in the view of patients, 40.31% (786 cases) believed that it would be effective to take Chinese herbs before they starting the anti-cancer treatment, and the percentage increased to 81.08% after 1-month CM treatment. The effect of Chinese herbs was mainly demonstrated by symptom relief and improvement of quality of life, and 8.31% (162 cases) of patients experienced control of tumor growth and decreased tumor markers. Furthermore, only 14.31% (279 cases) participants reported that they experienced side effects during CM treatment.Conclusion:This large scale investigation reflects the current situation of domestic CM usage objectively and comprehensively, which might provide new ways for cancer treatment.  
        Keywords：Chinese medicine;herbs;cancer;South China;efficacy;side and toxic effect   
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        Published：2021-09-01
      • Zheng-xin LI,Zhi-min ZHAO,Ping LIU,Qing-shan ZHENG,Cheng-hai LIU
        2021, 27(7): 509-513. DOI: 10.1007/s11655-020-3257-6
        Abstract：Background:Antiviral therapy can lead to regression of fibrosis in chronic hepatitis B (CHB), but it has a limited effect on cirrhosis. Chinese medicines (CMs), particularly Fuzheng Huayu Tablet (扶正化 瘀片, FZHY), have an antifibrotic effect in patients with CHB.Objective:To observe the safety and efficacy of adjunctive FZHY in patients with hepatitis B virus (HBV) cirrhosis, this study was designed as a randomized, placebo-controlled, double-blind, parallel assignment, multicenter trial at 20 centers in China. The total 700 naive patients will be enrolled with compensate cirrhosis due to HBV, and randomly assigned into 2 groups, receiving entecavir (0.5 mg, daily) and FZHY placebo (1.6 g, 3 times a day), or entecavir (0.5 mg, daily ) and FZHY (1.6 g, 3 times a day), respectively. The primary endpoint was histological improvement at week 48. The secondary outcome is the decline values of liver fibrosis using the noninvasive methods from baseline to week 48 in each arm of the study. Adverse events such as stomach upset, headache, fatigue, dizziness, nausea will be strictly recorded.Discussion:Through this study, we hope to generate a solid evidence for the therapeutic strategy of HBV cirrhosis with a combination of anti-viral such as ETV and anti-fibrotic herbal product such as FZHY. Protocol version: Version 1.3, Date: 2014.12.4. Trial registration number: NCT02241590.  
        Keywords：chronic hepatitis B;liver fibrosis;Fuzheng Huayu Tablet;randomized multicenter trial;trial protocol   
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        Published：2021-09-01
      • Lei GAO,Cai-xia HAO,Gan-lin ZHANG,Ke-xin CAO,Ming-wei YU,Qi-wei LI,Xue-man MA,Guo-wang YANG,Xiao-min WANG
        2021, 27(7): 514-519. DOI: 10.1007/s11655-020-3191-7
        Abstract：Objective:To study the effect and mechanism of Huayu Wan (化瘀丸, HYW) in combination of chemotherapy of tumor treatment.Methods:HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the efficacy of doxorubicin was studied.Results:HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P<0.01). Furthermore, HYW improved drug delivery of doxorubicin to tumor tissues, and this activity was associated with HYW-induced microvascular proliferation (P<0.01).Conclusions:HYW can promote microangiogenesis and increase blood supply in tumor tissues, which in turn may increase the risk of metastasis. At the same time, HYW increases drug delivery and improves the efficacy of chemotherapy drugs through vascular proliferation. Therefore, rational judgment must be exercised when considering applying HYW to an antitumor regimen.  
        Keywords：Huayu Wan;Chinese medicine;fluorescent doxorubicin;drug delivery   
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        Published：2021-09-01
      • Jing-kang WANG,Bao-sheng ZHAO,Min WANG,Chen-yue LIU,Ya-qi LI,Quan-tao MA,Peng-fei LI,Tie-shan WANG,Chun-guo WANG,Yong-ming ZHOU
        2021, 27(7): 520-526. DOI: 10.1007/s11655-020-3433-8
        Abstract：Objective:To investigate the effects of matrine on antigen presentation of dendritic cells (DCs), and to explore the pharmacological mechanism of matrine on anti-tumor effect.Methods:Different concentrations (0, 1, 2, 4, 8 and 16 μg/mL) of matrine were co-cultured with DCs, the harvested DCs were co-cultured with antigens of Lewis lung cancer (LLC) cells, and then DCs and T cells were co-cultured to produce DCs-activated killer (DAK) cells, which have significant tumor-killing activity. The expression of cytokines, mRNA and protein of toll-like receptors (TLRs) in DCs were detected by enzyme linked immunosobent assay, polymerase chain reaction and Western blot, respectively. And the killing effect of DAK were measured by MTT assay.Results:Matrine significantly increased the mRNA expression of TLR7, TLR8, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF-6) and IκB kinase (IKK), as well as the protein expression of TLR7 and TLR8, and up-regulated the levels of interleukin-12 (IL-12), IL-6 and tumor necrosis factor-α (TNF-α), meanwhile, it also increased the expressions of MHC-Ⅱ, CD54, CD80 and CD86 in DCs. DCs-activated effector T cells had significant tumor-killing activity. When the concentration of matrine was more than 4 μg/mL, all indices had significant difference (P<0.01 or P<0.05).Conclusion:Matrine plays an anti-tumor role by regulating TLRs signal transduction pathway, promoting the secretion of inflammatory cytokines and enhancing immune function.  
        Keywords：matrine;Chinese medicine;dendritic cells;tumors;toll-like receptors;inflammatory cytokines   
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        Published：2021-09-01
      • Yu DING,Hou-yong ZHU,Li-zong ZHANG,Bei-bei GAO,Liang ZHOU,Jin-yu HUANG
        2021, 27(7): 527-533. DOI: 10.1007/s11655-019-3176-6
        Abstract：Objective:To investigate the protective effects of Shexiang Tongxin Dropping Pill (麝香通心滴丸, STDP) following sodium laurate-induced coronary microembolization (CME) in rats.Methods:Forty rats were divided into 4 groups: the control (sham) group, CME group, low-dose STDP pretreatment group (20 mg•kg-1•d-1), and high-dose STDP pretreatment group (40 mg•kg-1•d-1). The rats were intragastric administrated with STDP 2 weeks before operation. Moreover, the histopathological alterations were observed using optical microscopy and transmission electron microscopy. Antioxidant biomarkers were analyzed by enzyme-linked immunosorbent assay. Mitochondrial functions including the mitochondrial permeability transition pore (mPTP) mtDNA copy number were determined and proteins of AKT/GSK3β were analyzed by Western blot.Results:The rats in the CME group showed a significant increase in the fibrinogen-like protein 2 expression level and mitochondrial dysfunction and a decrease in the expression level of antioxidant biomarkers (superoxide dismutase and catalase, P<0.01 for all). In contrast, the rats in the low- and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi (P<0.05); moreover, STDP restored the antioxidant-related protein activities and mitochondrial function, inhibited mPTP opening, decreased AKT-Ser473 phosphorylation, and increased GSK3β-Ser9 phosphorylation (P<0.05 or P<0.01).Conclusion:STDP may be useful for treatment of CME, possibly via regulation of mPTP opening and AKT/GSK3β phosphorylation.  
        Keywords：Shexiang Tongxin Dropping Pill;Chinese medicine;coronary microembolization;mitochondrial permeability transition pore;Akt;GSK3β   
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        Published：2021-09-01
      • Bo ZHANG,Hong-sheng CHANG,Kai-li HU,Xue YU,Li-na LI,Xiang-qing XU
        2021, 27(7): 534-541. DOI: 10.1007/s11655-019-3051-5
        Abstract：Objective:To study the antidepressant-like effect and action mechanism of geniposide and eleutheroside B combination treatment on the lipopolysaccharide (LPS)-induced depression mice model.Methods:Depression mice model was established by lipopolysaccharide (LPS) injection. Totally 48 mice were randomly divided into 6 groups (8 rats per group) according to a random number table, including normal, model, fluoxetine (20 mg/kg), geniposide (100 mg/kg) + eleutheroside B (100 mg/kg), geniposide + eleutheroside B + WAY 100635 (0.03 mg/kg), geniposide + eleutheroside B+ N-methyl-D-aspartic acid receptor (NMDA, 75 mg/kg) groups, respectively. After continuous administration for 10 days, autonomic activity tests after 30 min of administration were performed on the 10th day. On the 11th day, except for the normal group, the mice in the other groups were intraperitoneally injected with LPS (1 mg/kg), and the behavioral tests were performed 4 h later. Enzyme linked immunosorbent assay was used to detect tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) levels in mice serum. The mRNA expression of indoleamine 2,3-dioxygenase (IDO) and nuclear transcription factor (NF-κB) were detected by real-time quantitative polymerase chain reaction. Western-blot analysis was used to detect IDO and NF-κB protein expressions in hippocampus tissue.Results:Compared with the normal group, a single administration of LPS increased the immobility time in the forced swimming test (FST) and tail suspension test (TST, P<0.01), without affecting autonomous activity. Compared with the model group, fluoxetine and geniposide + eleutheroside B administration significantly improved the immobility time of depressed mice in the FST and TST, decreased serum IL-1β content, inhibited the expression levels of NF-κB gene and protein in hippocampus tissues (P<0.05 or P<0.01). Compared with the model group, geniposide + eleutheroside B treatment significantly reduced serum TNF-α content and inhibited IDO mRNA and protein expressions in hippocampus (P<0.05 or P<0.01). In addition, NMDA partly prevented the inhibition of IDO mRNA expression by geniposide + eleutheroside B; NMDA and WAY-100635 also partly prevented the reduction of IL-1β content induced by geniposide + eleutheroside B treatment (P<0.05 or P<0.01).Conclusions:The combination of geniposide and eleutheroside B showed a certain antidepression-like effect. Its main mechanism of action may be contributed to inhibiting the activation of NF-κB, decreasing the proinflammatory cytokines such as TNF-α, IL-1β, and inhibiting in the neuroinflammatory reaction. Additionally, it also affects tryptophan metabolism, reduces the expression of a key enzyme of tryptophan metabolism, IDO. And this antidepressant-like effect may be mediated by 5-hydroxytryptamine and glutamate systems.  
        Keywords：geniposide;eleutheroside B;antidepressant effect;mechanism;5-hydroxytryptamine;glutamate   
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        Published：2021-09-01
      • Hong-xing YANG,Peng WANG,Ning-ning WANG,Shao-dan LI,Ming-hui YANG
        2021, 27(7): 542-550. DOI: 10.1007/s11655-019-3166-8
        Abstract：Objective:To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (通心络胶囊, TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI).Methods:Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group, MIRI group, low- and high-dose TXL (0.5 and 1 g•kg-1•d-1, respectively) groups, atorvastatin (ATV) group (7.2 g•kg-1•d-1), chloroquine (CQ) group (10 g•kg-1•d-1), and highdose TXL + CQ group. After pharmacological administration for 7 days, rats underwent left anterior descending artery ligation surgery to establish the MIRI models with 50 min ischemia followed by 4 h reperfusion. Blood was taken for cardiac troponin I (cTnI) detection and hearts were harvested for infarct staining and apoptosis detection. The autophagy or mitophagy proteins and ubiquitinated proteins were detected by Western blotting.Results:Compared with the sham group, the MIRI group exhibited a larger infarcted area (27.13%±0.01%, P<0.01), a higher apoptotic index (34.33%±2.03% vs.1.81%±0.03%, P<0.01), and higher cTnI expression (14.18±1.01 vs. 7.96±0.32, P<0.01). The mitochondrial integrity was damaged in the MIRI group, while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58 vs. 4.33±1.15, P<0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (P<0.05). The ubiquitin response was significantly downregulated in the high-dose TXL group relative to the MIRI group (P<0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL.Conclusions:TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.  
        Keywords：Chinese medicine;mitophagy;ischemia-reperfusion injury;Parkin;ubiquitin   
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        Published：2021-09-01

        Clinical Experience

      • Xiao-qing XU,Wen-qi DENG,Da-yang WANG,Meng LI,Dong-lei KOU,Pei-tong ZHANG
        2021, 27(7): 496-501. DOI: 10.1007/s11655-020-3197-1
        Abstract：Objective:To evaluate the effect of Chinese medicine (CM) treatment on survival time and quality of life (QOL) in patients with small cell lung cancer (SCLC).Methods:This was an exploratory and prospective clinical observation. Patients diagnosed with SCLC receiving CM treatment were included and followed up every 3 months. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and QOL.Results:A total of 136 patients including 65 limited-stage SCLC (LS-SCLC) patients and 71 extensivestage SCLC (ES-SCLC) patients were analyzed. The median OS of ES-SCLC patients was 17.27 months, and the median OS of LS-SCLC was 40.07 months. The survival time was 16.27 months for SCLC patients with brain metastasis, 9.83 months for liver metastasis, 13.43 months for bone metastasis, and 18.13 months for lung metastasis. Advanced age, pleural fluid, liver and brain metastasis were risk factors, while longer CM treatment duration was a protective factor. QOL assessment indicated that after 6 months of CM treatment, scores increased in function domains and decreased in symptom domains.Conclusion:CM treatment might help prolong OS of SCLC patients. Moreover, CM treatment brought the trend of symptom amelioration and QOL improvement. These results provide preliminary evidence for applying CM in SCLC multi-disciplinary treatment.  
        Keywords：small cell lung cancer;Chinese medicine;survival time;follow-up;quality of life   
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        Published：2021-09-01

        Review

      • Lee Ga-Young,Lee Jin-Seok,Son Chang-Gue,Lee Nam-Hun
        2021, 27(7): 551-560. DOI: 10.1007/s11655-020-3425-8
        Abstract：Colorectal cancer (CRC) is one of the most prevalent and lethal cancer types around the world. Most of the CRC patients are treated with chemotherapeutic drugs alone or combined. However, up to 90% of metastatic cancer patients experience the failure of treatment mostly because of the acquired drug resistance, which can be led to multidrug resistance (MDR). In this study, we reviewed the recent literature which studied potential CRC MDR reversal agents among herbal medicines (HMs). Among abundant HMs, 6 single herbs, Andrographis paniculata, Salvia miltiorrhiza, Hedyotis diffusa, Sophora flavescens, Curcuma longa, Bufo gargarizans, and 2 formulae, Pien Tze Huang and Zhi Zhen Fang, were found to overcome CRC MDR by two or more different mechanisms, which could be a promising candidate in the development of new drugs for adjuvant CRC chemotherapy.  
        Keywords：colorectal cancer;drug resistance;herbal medicine   
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        Published：2021-09-01
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