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    2018 Year 24 Vol. 9 Issue

      OriginalPaper

    • Neil Kaplowitz
      2018, 24(9): 643-644. DOI: 10.1007/s11655-018-3004-4
      Abstract:Chinese medicine and herb medicine though used to treat liver diseases are an important cause of liver injury. Many phytochemicals have the potential to injure the liver, some in a dose-related fashion and more often in an idiosyncratic fashion, meaning occurrence is uncommon to rare in the population using these treatments. As is the case with pharmaceuticals, the phytochemicals are usually tolerated despite either no or mild transient subclinical injury but rarely in some susceptible patients cause moderate to severe liver injury which is likely mediated by the adaptive immune system.  
      Keywords:herb-induced liver injury;diagnosis and management;guideline;Chinese Medicine   
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      Published:2021-08-27
    • Xu-dong Tang,Bin Lu,Zhen-hua Li,Wei Wei,Li-na Meng,Bao-shuang Li,Zhi-peng Tang,Rui Gao,Feng-yun Wang,Fang Lu,Li-qun Bian,Ying-pan Zhao,Ping Wang,Yin-qiang Zhang
      2018, 24(9): 645-652. DOI: 10.1007/s11655-016-2596-9
      Abstract:To evaluate the efficacy and safety of Chinese medicine (CM) decoction Chang’an I Recipe (肠安 I 号方) in the treatment of irritable bowel syndrome with diarrhea (IBS-D). A multicenter, randomized, double-blind, placebo-controlled clinical trial was designed. Based on the order of inclusion, the IBS-D patients were randomly assigned to the treatment group or the placebo control group, administrated with Chang’an I Recipe or placebo, 150 mL/bag, 3 times daily, for 8 weeks. The primary indices of efficacy included the effective rates of IBS symptom severity score (IBS-SSS) and the differences in adequate relief (AR) responder; the secondary indexes of efficacy included the changes in scores of the IBS Quality of Life (IBS-QOL) and Hospital Anxiety and Depression (HAD) scales. The safety indices included adverse events and related laboratory tests. A total of 216 patients were included, with 109 in the treatment group and 107 in the control group, and finally 206 were included in the full analysis set (FAS), 191 were included in the per protocol set (PPS). In FAS, the total effective rate was 67.6% and 40.2% for the treatment and control groups, respectively, with 95% confidence interval (CI) for difference in the effective rates between the two groups of 14.4%–40.2%; while in PPS, the total effective rate was 71.3% and 41.2% for the treatment and control groups, respectively (95% CI 16.6%–43.4%). The consistent conclusions of FAS and PPS showed a better efficacy in the treatment group. Both FAS and PPS showed higher AR responder in the treatment group (FAS: 59.6% vs. 35.5%; PPS: 62.8% vs. 38.1%). As for IBS-QOL, the total score and scores in various dimensions of IBS-QOL were not significantly different between the two groups (P>0.05). Both anxiety and depression scales of HAD were not significantly different between the two groups (P>0.05). No adverse events or laboratory abnormalities were found to be obviously related to the tested drugs or clinically significant. Chang’an I Recipe was more effective than placebo in the treatment of IBS-D, with no obvious adverse reactions. (No.ChiCTR-TRC-09000328)  
      Keywords:irritable bowel syndrome with diarrhea;Chinese Medicine;Chang’an I Recipe;Placebo;randomized controlled trial   
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      Published:2021-08-27
    • Yong-an Ye,Xiao-ke Li,Da-qiao Zhou,Xiao-ling Chi,Qin Li,Li Wang,Bing-jiu Lu,De-wen Mao,Qi-kai Wu,Xian-bo Wang,Ming-xiang Zhang,Jing-dong Xue,Yong Li,Wei Lu,Jian-chun Guo,Feng Jiang,Xin-wei Zhang,Hong-bo Du,Xian-zhao Yang,Hui Guo,Da-nan Gan,Zhi-guo Li
      2018, 24(9): 653-660. DOI: 10.1007/s11655-018-3011-5
      Abstract:The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (调肝益脾颗粒, TGYP) or Tiaogan-Jianpi-Jiedu Granule (调肝健脾解毒颗粒, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as “a valuable endpoint”. We believe this trial could provide a reliable status for patients’ “journey” towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).  
      Keywords:chronic hepatitis B;Chinese Herbal Medicine;Tiaogan-Jianpi-Jiedu Granule;Tiaogan- Yipi Granule;protocol;randomized-controlled trial   
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      Published:2021-08-27
    • Li-rui Tang,Yan-yan Tao,Cheng-hai Liu,Hai-nan Wang
      2018, 24(9): 661-669. DOI: 10.1007/s11655-017-2773-5
      Abstract:To evaluate the preventive effect of salvianolate (Sal B) on glucose metabolism disorders of dimethylnitrosamine (DMN)-induced cirrhotic rats. Fifty-five Wistar rats were randomly divided into a control group (n=10) and a cirrhotic group (n=45) according to a random number table. Liver cirrhosis was induced by intraperitoneal administration of DMN. The cirrhotic rats were divided into model, Sal B and metformin groups (n=15), respectively. Rats in the model group were given saline, two treatment groups were given Sal B (50 mg/kg), metformin (150 mg/kg) respectively for 28 consecutive days, while rats in the control group were injected 0.9% saline with same volume of vehicle. Body weight was measured everyday. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp. Organ index, glucose tolerance test (OGTT), and fasting plasma glucose (FPG), fasting insulin (FINS), hepatic glycogen, hydroxyproline (HYP) and liver function were detected at the end of the treatment. Area under the curve (AUC) for OGTT was calculated. Liver and pancreas histology were determined by histopathological examination with hematoxylin and eosin staining (HE), Sirius Red staining and Masson’s trichrome staining, respectively. Hepatic expression of α-smooth muscle actin (α-SMA) and collagen (Col I) were evaluated by immunohistochemical staining. Compared with the model group, Sal B significantly increased body and liver weight, liver-body ratio, glucose infusion rate (GIR), FPG, FINS levels and hepatic glycogen at the end of administration (P<0.05 or P<0.01). Meanwhile, Sal B significantly decreased AUC for OGTT, spleen weight, spleen-body ratio, aminotransferase and HYP level (P<0.05 or P<0.01). Sal B was also effective in alleviating necrosis of liver tissue, suppressing fibrosis progression and inhibiting the expression of α-SMA and Col I in liver. Compared with the metformin group, Sal B had advantages in ameliorating FPG, hepatic glycogen, spleen weight, organ index, liver function and cirrhosis (P<0.05). Metformin increased insulin sensitivity more potently than Sal B (P<0.05). Sal B could improve glucose metabolism in cirrhotic rats by protecting hepatic glycogen reserve, increasing insulin sensitivity, and alleviating pancreatic morphology abnormalities. Sal B was clinically potential in preventing glucose metabolism anomalies accompanied with cirrhosis.  
      Keywords:salvianolate;fibrosis;cirrhosis;insulin resistance;glycogen;Metformin   
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      Published:2021-08-27
    • Jin-Woo Jung,Seung Hwan Jeon,Woong Jin Bae,Su Jin Kim,Mun Su Chung,Byung Il Yoon,Sae Woong Choi,U. Syn Ha,Sung Yeoun Hwang,Sae Woong Kim
      2018, 24(9): 670-675. DOI: 10.1007/s11655-017-2970-1
      Abstract:To investigate the anti-oxidative stress and preventive effect of modified Gongjin-dan (WSY-1075) in a detrusor underactivity rat model. Rats were randomly allocated to three groups: shamoperated (control), bladder outlet obstruction-induced detrusor underactivity (BOO-DU), and BOO-DU with WSY-1075 (WSY) groups. WSY-1075 was orally administrated to rats 200 mg daily for 2 weeks prior to the operation and 4 weeks after the operation. Bladder outlet obstruction was surgically induced in rats by ligation around the urethra avoiding total obstruction. Cystometrography was conducted on rats in each group for examination of bladders. Compared with the control group, bladder outlet obstruction led to a significant increase in oxidative stress with consequent changes to molecular composition, and decrease in maximal detrusor pressure (P<0.05). WSY-1075 treatment significantly suppressed oxidative stress and prevented degenerative and dysfunctional changes in bladder, as compared with BOO-DU group (P<0.05). WSY-1075 had beneficial effect on prevention of BOO-DU.  
      Keywords:detrusor underactivity;anti-oxidant;herbal   
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      Published:2021-08-27
    • Xiao-ming Wang,Wen-jie Xu,Liang-kui Xu,Shuai Song,Xue-feng Xing,Jia-bo Luo
      2018, 24(9): 676-682. DOI: 10.1007/s11655-017-2778-0
      Abstract:To investigate the antipyretic mechanism of Herba Ephedrae (Eph)-Ramulus Cinnamomi (RC) herb pair on yeast-induced pyrexia in rats. Totally 30 qualified male SD rats were randomly assigned to the normal control (NC) group, the pyrexia model (model) group, the Eph, RC and Eph-RC treatment groups by a random digital table, 6 rats in each group. Each rat received a 20% aqueous suspension of yeast (10 mL/kg) except the NC group. The 3 treatment groups were administered 8.1, 5.4 and 13.5 g/kg Eph, RC and Eph-RC respectively at 5 and 12 h after yeast injection, the NC group and the model groups were administered equal volume of distilled water. Rectal temperatures were measured at 0, 6, 8, 10, 12, 15, 18, 24 and 30 h and urine was collected prior to yeast injection and at 6, 10, 18, 24, 30, and 36 h after yeast injection. Then urine metabolomic profiling by gas chromatography tandem mass spectrometry, coupled with multivariate statistical analysis and pattern recognition techniques were used to explore the antipyretic effects of Eph-RC. Partial least squares discriminate analysis was used to analyze the metabolomics dataset including classification and regression in metabolomics plot profiling. Compared with the NC group, rectal temperatures were significantly higher in the model group (P<0.01), while 3 treatment groups decreased significantly compared with the model group (P<0.05 or P<0.01). Rectal temperatures of Eph-RC-treated rats started to go down at 6 h, and markedly decreased at 8, 12, 15, 18 and 24 h (P<0.05 or P<0.01), while those of the Eph and RC groups had decreased firstly at 8 h and were markedly lower at 12 h (P<0.05 or P<0.01). Seventeen potential biomarkers related to pyrexia were confirmed and identified, including pyruvic acid, L-phenylalanine, L-tyrosine, phenylacetic acid, hippuric acid, succinic acid, citrate and so on. Eight potential alterations of metabolic pathways including phenylalanine metabolism, citrate cycle, tryptophan metabolism, biosynthesis of valine, leucine and isoleucine, were identified in relation to the antipyretic effects of Eph-RC using MetPA software. The antipyretic effect of Eph-RC herb pair on yeast-induced pyrexia in rats involved correction of perturbed amino acid, fatty acid, and carbohydrate metabolism according to the metabolic pathway analysis with MetPA.  
      Keywords:Chinese Medicine;Herba Ephedrae;Ramulus Cinnamomi;herb pair;principal component analysis;partial least squares-discriminant analysis;biomarker   
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      Published:2021-08-27
    • Wen-ying Zeng,Yan Li,Zhi-lan Xu,Xiao-lei Xie,Feng-qin Xu,Na Rui
      2018, 24(9): 683-685. DOI: 10.1007/s11655-018-2978-2
        
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      Published:2021-08-27
    • Ling-xin Li,Kai Deng,Yun Qu
      2018, 24(9): 686-695. DOI: 10.1007/s11655-018-3005-3
      Abstract:To explore the effectiveness and safety of acupuncture in patients with post-stroke dysphagia by an update meta-analysis. Potentially eligible RCTs aimed to evaluate the effects of acupuncture vs. non-acupuncture treatments, such as rehabilitation training or routine medication on the swallowing difficulty after stroke were searched from PubMed, Cochrane Library, China National Knowledge Infrastructure, and other database from the earliest record to June 2016. Patient demographics, regimens for acupuncture, type of controls, methods of randomization, and measurements of the clinical symptoms of dysphagia were retrieved. The relative risk (RR) and 95% confidence interval (CI) of effective rate of dysphagia was calculated after intervention performed following admission. Subgroup analyses and a metaregression analysis were performed to describe the heterogeneity. Twenty-nine RCTs comprising 2,190 patients were included. The included studies had a medium quality grade based on the Consolidated Standards of Reporting Trials (CONSORT) and Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) checklist. Acupuncture therapy provided a higher effective rate compared with nonacupuncture treatments [RR=1.33, 95% confidence interval (CI), 1.25 to 1.43]. Subgroup and meta-regression analyses suggested that acupuncture intensity and measurement method were main sources of heterogeneity and resulted in a significant difference for pooled effect size. No severe adverse events were documented in these RCTs. Our meta-analysis provides a new evidence supporting the efficacy and safety of acupuncture in treatment to post-stroke dysphagia in short-term compared with rehabilitation or medication. More high-quality and large-scale research studies are needed.  
      Keywords:acupuncture;dysphagia;stroke;systematic review;meta-analysis;randomized controlled trials   
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      Published:2021-08-27
    • Jia-bo Wang,Yun Zhu,Zhao-fang Bai,Fu-sheng Wang,Xiu-hui Li,Xiao-he Xiao
      2018, 24(9): 696-706. DOI: 10.1007/s11655-018-3000-8
      Abstract:Herb-induced liver injury (HILI) is a type of adverse drug reactions related to using Chinese medicine (CM) or herbal medicine (HM), and is now a growing segment of drug-induced liver injury (DILI) worldwide. Owing to the complicated compositions and miscellaneous risk factors associated with the clinical usage of CM or HM, it is more challenging to diagnose and manage HILI than DILI. In the present guideline issued by the China Association of Chinese Medicine (CACM), the authors present an evidence chain-based workflow with 9 structured judgment criteria for diagnosing HILI. The 3 diagnostic ending points—suspected diagnosis, clinical diagnosis, and confirmed diagnosis—could be reached according to the length of the evidence chain acquired in the structured diagnostic workflow. Either identifying the species of CM or HM or excluding adulterations and toxin contaminants was strongly recommended to improve the level of evidence for a clinical diagnosis of HILI. In addition, the authors report that the improper use of CM, which violates the general law of CM theory, is one of the most important factors that contributes to HILI and should be avoided. By contrast, based on syndrome differentiation, some CM can also be used to treat HILI if used in accordance with the general law of CM theory. Therefore, 9 recommendations are put forward in this guideline.  
      Keywords:herb-induced liver injury;diagnosis;treatment;management;Chinese Medicine;guideline   
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      Published:2021-08-27
    • Tae-Hun Kim,Do-Hoon Kim,Seong Gyu Lee
      2018, 24(9): 707-712. DOI: 10.1007/s11655-017-2767-3
      Abstract:From the medical history of traditional Eastern Asian and Tibetan medicine, the origin and development of moxibustion seems to be closely related to Mongolia. To explore the current clinical practice of moxibustion in Mongolia, we visited a teaching hospital, the Traditional Medical Science, Technology and Production Corporation of Mongolia, in February 2014. Many types of moxibustion are found to be used, and various modalities and methods are practiced based on the principles of traditional Mongolian medicine. In particular, Mongolian drug moxibustion, which uses small butter-warmed bags packed with powdered aromatic herbs instead of moxa cones, is a unique moxibustion technique not found in other countries. In this paper, we introduce the clinical practice of moxibustion, specifically Mongolian drug moxibustion in Mongolia.  
      Keywords:traditional Mongolian medicine;moxibustion;Mongolian drug moxibustion   
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      Published:2021-08-27

      ReviewPaper

    • Jing-si Wang,Qiu-yun Zhang,Jin-lian Cheng,Lan-yu Chen,Nai-li Yao,Gui-zhi Sun,Yu-ling Chu
      2018, 24(9): 713-720. DOI: 10.1007/s11655-018-3007-1
      Abstract:Hepatic fibrosis is a common feature of almost all chronic liver diseases. Formation of new vessels (angiogenesis) is a process strictly related to the progressive fibrogenesis which leads to cirrhosis and liver cancer. This review mainly concerns the relationship between angiogenesis and hepatic fibrosis, by considering the mechanism of angiogenesis, cells in angiogenesis, anti-angiogenic and Chinese medicine therapies.  
      Keywords:angiogenesis;Hepatic Fibrosis;review;Chinese Medicine   
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      Published:2021-08-27
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