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   Table of Contents - Current issue
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January-March 2020
Volume 6 | Issue 1
Page Nos. 1-120

Online since Friday, March 13, 2020

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REVIEW ARTICLES  

Academician kai-xian chen talks about the development of traditional chinese medicine and global medicine p. 1
Kai-Xian Chen
DOI:10.4103/wjtcm.wjtcm_30_19  
Following the spirit of Central Committee about the Opinions on Promoting the Inheritance, Innovation, and Development of Traditional Chinese Medicine, Academician Chen Kai-Xian, from Shanghai University of Traditional Chinese Medicine, made a wonderful report on the development of traditional Chinese medicine (TCM) and global medicine. The report deeply elaborated on five aspects: the characteristics and advantages of TCM, the challenges faced by contemporary medicine, the status and role of TCM in the contemporary era, the inheritance and innovation of TCM, and the cooperation and development of “Belt and Road.”
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Aristolochic acid-induced genotoxicity and toxicogenomic changes in rodents Highly accessed article p. 12
Xi-Lin Li, Xiao-Qing Guo, Hai-Rong Wang, Tao Chen, Nan Mei
DOI:10.4103/wjtcm.wjtcm_33_19  
Aristolochic acid (AA) is a group of structurally related nitrophenanthrene carboxylic acids found in many plants that are widely used by many cultures as traditional herbal medicines. AA is a causative agent for Chinese herbs nephropathy, a term replaced later by AA nephropathy. Evidence indicates that AA is nephrotoxic, genotoxic, and carcinogenic in humans; and it also induces tumors in the forestomach, kidney, renal pelvis, urinary bladder, and lung of rats and mice. Therefore, plants containing AA have been classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer. In our laboratories, we have conducted a series of genotoxicity and toxicogenomic studies in the rats exposed to AA of 0.1–10 mg/kg for 12 weeks. Our results demonstrated that AA treatments induced DNA adducts and mutations in the kidney, liver, and spleen of rats, as well as significant alteration of gene expression in both its target and nontarget tissues. AA treatments altered mutagenesis- or carcinogenesis-related microRNA expression in rat kidney and resulted in significant changes in protein expression profiling. We also applied benchmark dose (BMD) modeling to the 3-month AA-induced genotoxicity data. The obtained BMDL10(the lower 95% confidence interval of the BMD10that is a 10% increase over the background level) for AA-induced mutations in the kidney of rats was about 7 μg/kg body weight per day. This review constitutes an overview of our investigations on AA-induced genotoxicity and toxicogenomic changes including gene expression, microRNA expression, and proteomics; and presents updated information focused on AA-induced genotoxicity in rodents.
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Nanocarriers to enhance solubility, bioavailability, and efficacy of artemisinins p. 26
Anna Rita Bilia, Maria Camilla Bergonzi, Joelle C Boulos, Thomas Efferth
DOI:10.4103/wjtcm.wjtcm_2_20  
The therapeutic potential of artemisinin (ART) and its derivatives (ARTs) is not limited to malaria but has been recently expanded to other infections with protozoans, trematodes, or viruses as well as to cancer. Due to their limited poor water and oil solubility, rapid degradation by the liver, and short half-life, they have a low bioavailability after oral administration. Consequently, there is a pressing necessity to formulate new ART preparations to raise its bioavailability and efficacy. Nanosized drug delivery systems represent important tools in modern medicine with wide clinical applications, because of their potential modulation of pharmacokinetic and biodistribution. This review focuses on polymer-based systems, lipid-based systems, and inorganic nanoparticles loaded with ARTs. The overall goal of this field of research is to enhance their solubility and stability to improve bioavailability at much lower doses and to increase long-term safety. In addition, the opportunity to reach highly specific site-targeted delivery by these nanocarriers confers a high medicinal value. Remarkably, most of the reported nanoparticulate drug delivery systems are biologically inactive or marginally immunogenic, generating no antigenic or pyrogenic reactions but only partial intrinsic toxicity. As clinical studies in human patients are available so far, there is a pressing need to translate preclinical results on ART-based nanosystems into clinical settings.
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International clinical practice guideline of chinese medicine: Chronic obstructive pulmonary disease p. 39
Jian-Sheng Li
DOI:10.4103/wjtcm.wjtcm_9_20  
Chronic obstructive pulmonary disease (COPD) is a major chronic disease that seriously endangers public health. Some remarkable results have shown that Chinese medicine has an obvious clinical effect in preventing and treating COPD. To further promote the normative use of Chinese medicine to better guide the clinical diagnosis and treatment of COPD, the World Federation of Chinese Medicine Societies developed a panel to establish the guidelines by systematically evaluating, based on the revision and transformation of Guidelines for Chinese Medicine Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease released by the China Association of Chinese Medicine in 2019 (Standard No: T/CACM 1319-2019), the latest clinical research evidence at home and abroad, formatting the International Clinical Practice Guideline of Chinese Medicine—Chronic Obstructive Pulmonary Disease, and publishing in both Chinese and English. The guidelines consist of 12 parts: preface, introduction, scope, normative references, terms and definitions, disease diagnosis and staging, severity assessment, etiology and pathogenesis, syndrome differentiation and treatment, other treatment, prevention and care, and appendix. They also standardize the contents of traditional Chinese medicine (TCM) etiology and pathogenesis, syndrome differentiation and treatment, and prevention and care of COPD. These guidelines are applicable to clinical respiratory physicians of TCM and integrated traditional Chinese and western medicine. The release of these guidelines will help improve the effect and level of Chinese medicine for COPD.
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Network Meta-analysis of Four Chinese Patent Medicines Combined with Angiotensin Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Early Diabetic Nephropathy Treatment p. 51
Jing Zhang, Jing Li, Jia-Qin Huang
DOI:10.4103/wjtcm.wjtcm_41_19  
The objective of the study is to systematically evaluate the efficacy of four Chinese patent medicines in combination with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in the treatment of early diabetic nephropathy (DN). Retrospectively, previously published randomized controlled trials (RCTs) of four different Chinese patent medicines combined with ACEI or ARB in the treatment of patients with early DN were searched overall from databases. The data were analyzed by R, Generate Mixed Treatment Comparisons and STATA softwares. A total of 78 RCTs were finally included. Network meta-analysis showed that the total effective rate of the Jinshuibao capsule-ACEI/ARB combination group and Huangkui capsule-ACEI/ARB combination groups were better than the others; Jinshuibao capsule-ACEI/ARB combination group reduced the 24-h urinary protein excretion (24-h UTP), urine microalbumin excretion rate (UAER), serum creatinine (Scr), and glycosylated hemoglobin (HbAlc) values. The Huangkui capsule-ACEI/ARB combination demonstrated a better reduction of (blood urea nitrogen [BUN]). Reduced incidences of adverse effects were only observed on treatment with Bailing capsule-ACEI/ARB combination. In early DN, combination of Jinshuibao capsule-ACEI/ARB provided the highest effective rate; moreover, it could reduce the 24-h values of UTP, UAER, Scr, and HbAlc; Huangkuai capsule-ACI/ARB combination group showed a good effect on reducing BUN. Bailing capsule-ACEI/ARB combination group had reduced the incidences of adverse reactions.
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Recent advances in the study of ancient books on traditional chinese medicine p. 61
Li Gao, Chun-Hua Jia, Wei Wang
DOI:10.4103/wjtcm.wjtcm_3_20  
The ancient books on traditional Chinese medicine (TCM) are the source of knowledge for TCM physicians. Therapeutic principles and therapeutic methods for healing many diseases are recorded in these ancient TCM books, providing a huge number of references for modern TCM physicians on conducting diagnosis and administering treatment for different diseases. The ancient TCM books can be dated back thousands of years, and this vast knowledge is recorded in different medical books in the form of text. However, it is difficult to systematically assimilate much information in ancient TCM books. At present, many researchers are applying advanced analytical techniques to analyze the text data in the ancient TCM books. Advanced techniques that have been applied include database construction, cognitive linguistic analysis, fuzzy logic, data mining, and artificial intelligence (AI) technology. There are different characteristics in these advanced analytical techniques. In this study, we comprehensively review recent advances in these techniques applied to the study of ancient TCM books. Furthermore, as AI technology is increasingly utilized in the medical field as well as in the study of ancient TCM books, we also review the application of AI technology to the study of ancient TCM books.
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ORIGINAL ARTICLES Top

Text mining and analysis of treatise on febrile diseases based on natural language processing p. 67
Kai Zhao, Na Shi, Zhen Sa, Hua-Xing Wang, Chun-Hua Lu, Xiao-Ying Xu
DOI:10.4103/wjtcm.wjtcm_28_19  
Objective: With using natural language processing (NLP) technology to analyze and process the text of “Treatise on Febrile Diseases (TFDs)” for the sake of finding important information, this paper attempts to apply NLP in the field of text mining of traditional Chinese medicine (TCM) literature. Materials and Methods: Based on the Python language, the experiment invoked the NLP toolkit such as Jieba, nltk, gensim, and sklearn library, and combined with Excel and Word software. The text of “TFDs” was sequentially cleaned, segmented, and moved the stopped words, and then implementing word frequency statistics and analysis, keyword extraction, named entity recognition (NER) and other operations, finally calculating text similarity. Results: Jieba can accurately identify the herbal name in “TFDs.” Word frequency statistics based on the word segmentation found that “warm therapy” is an important treatment of “TFDs.” Guizhi decoction is the main prescription, and five core decoctions are identified. Keyword extraction based on the term “frequency-inverse document frequency” algorithm is ideal. The accuracy of NER in “TFDs” is about 86%; latent semantic indexing model calculating the similarity, “Understanding of Synopsis of Golden Chamber (SGC)” is much more similar with “SGC” than with “TFDs.” The results meet expectation. Conclusions: It lays a research foundation for applying NLP to the field of text mining of unstructured TCM literature. With the combination of deep learning technology, NLP as an important branch of artificial intelligence will have broader application prospective in the field of text mining in TCM literature and construction of TCM knowledge graph as well as TCM knowledge services.
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A systematic review and meta-analysis of randomized controlled trials on treating ulcerative colitis by the integration method of heat-clearing, damp-excreting, spleen-strengthening, and stasis-removing of traditional chinese medicine with western medicine p. 74
Zi-Jun Jia, Zhen-Huan Yanga, Cai-Xia Jia, Kun-Min Xiao, Yi-Qun Niu, Jie Chen, Shao-Jie Duan, Shu-Kun Yao, Yan Li
DOI:10.4103/wjtcm.wjtcm_1_20  
Objective: The objective of this study was to systematically evaluate the clinical efficacy of the integration method of heat-clearing, dampness-excreting, spleen-strengthening, and stasis-removing from traditional Chinese medicine (TCM) combined with Western medicine for the treatment of ulcerative colitis (UC). Materials and Methods: The databases China National Knowledge Infrastructure, China Biology Medicine disc (CBMdisc), WANFANG, VIP, and PubMed were searched for randomized controlled trials investigating the integration of the TCM methods of clearing heat, draining dampness, invigorating the spleen, and removing stasis, combined with Western medicine to treat UC from January 2009 to March 2019. Two reviewers independently conducted literature searches, screenings, data extractions, and literature bias evaluations. A meta-analysis was conducted using RevMan 5.3 and Stata 13.0 software. Results: In total, 15 studies involving 1289 patients were included. The results of the meta-analysis showed that the total effective rate of treatment in the experimental groups was higher than that of the control groups (relative risk [RR] = 1.27, 95% confidence interval [CI]: 1.21, 1.35, Z = 8.74,P < 0.00001). In the subgroup analysis, the total effective rate of oral TCM combined with Western medicine was higher than that of the control groups (RR = 1.24, 95% CI: 1.15, 1.33, Z = 5.88,P < 0.00001). The total effective rate of oral TCM with enemas combined with Western medicine was higher than that of the control group (RR = 1.30, 95% CI: 1.12, 1.50, Z = 3.52,P= 0.0004). The comparison between Western medicine alone and oral TCM combined with enteroscopy and Western medicine showed that the effective rate of enteroscopy (RR = 1.18, 95% CI: 1.05, 1.33, Z = 2.86,P= 0.004) and the symptom scores before and after treatment all improved more in the combined treatment groups than in those of the Western medicine group alone, with statistically significant differences (RR = −4.23, 95% CI: −4.93, −3.53, Z = 11.84,P < 0.00001). Conclusion: The integration of the TCM methods of heat clearing, dampness excreting, spleen strengthening, and stasis removing combined with Western medicine can significantly improve the cure rate of UC, and is an effective method to treat UC.
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Study on medication rules of modern chinese herbal medicine in the treatment of non-small cell lung cancer based on data mining p. 83
Li-Ting Liu, Cui-Yun Zhao, Tong Wu, Zi-Yang Yu, Yuan Sun, Jie Li
DOI:10.4103/wjtcm.wjtcm_36_19  
Objective: Based on data mining technology, we attempted to explore the medication rules of modern traditional Chinese medicine (TCM) compounds in non-small cell lung cancer (NSCLC) treatment, to provide a reference for clinical drug use. Methods: From 2010 to 2017, TCM compounds used for NSCLC treatment were collected from the Beijing 301 Hospital. The modern TCM compounds utilized in the treatment of NSCLC were established in the prescription database. Excel, SPSS 22, and SPSS Modeler14.2 software were utilized for the frequency analysis, factor analysis, cluster analysis, and association analysis. Then, the quantitative and qualitative analyses of the regularity of TCM compound medications were performed, and the possible mechanism was discussed. Results: The treatment of NSCLC using Chinese herbal compounds involved 231 prescriptions, 389 types of Chinese herbs, and 135 types of high-frequency Chinese herbs. Of these, Fritillaria cirrhosa, stir-baked fried Scutellariae, raw Os Draconis, Poria cocos (Schw.) Wolf, and Scutellaria barbata were the top five frequently prescribed Chinese herbs. Among the 39 types of drugs, heat-clearing and detoxifying drugs and qi-tonifying drugs were the leading. Cold, warm, flat, slightly cold, sweet, bitter, and pungent of four properties and five tastes and the meridians of lung, spleen, and stomach were most commonly selected. Factor analysis extracted 12 common factors, and the cumulative contribution rate was 65.595%, which mainly contained tonifying qi and blood; tonifying yin, clearing away heat, and eliminating stagnation; tonifying the spleen, regulating qi, and eliminating phlegm. Forty drug groups were obtained by cluster analysis; a total of 63 association rules were obtained by association analysis. The pairs of Poria cocos → dried tangerine peel and fried Atractylodes macrocephala → dried tangerine peel were commonly used in NSCLC, while the three most frequent herb groups were raw Astragalus → fried A. macrocephala and Poria cocos; raw-medicated leaven → fried A. macrocephala and Poria cocos; and dried tangerine peel → fried A. macrocephala and Poria cocos. Conclusion: Lung cancer is mainly caused by qi stagnation, phlegm obstruction, phlegm, and blood stasis. Based on the principle of strengthening the body and dispelling pathogens, clinical treatment of NSCLC involves clearing heat and detoxifying, tonifying the spleen, regulating qi, eliminating phlegm to dispel pathogens, and tonifying qi and blood to strengthen the body.
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Effects of dachaihu decoction and its “prescription elements” on intestinal flora of nonalcoholic fatty liver disease model rats p. 97
Yan Sun, Min Wang, Shu-Jing Zhang, Yu-Shan Gao, Lin Chen, Meng-Yao Wu, Xin-Lei Zhang, Lu Zhou, Hui-Min Yuan, Feng-Jie Zheng, Jian Cui, Yu-Hang Li
DOI:10.4103/wjtcm.wjtcm_38_19  
Objective: The study objective was to observe the effect of Dachaihu decoction and its “prescription elements” on intestinal flora of model rats with nonalcoholic fatty liver disease (NAFLD). Materials and Methods: Healthy male Sprague-Dawley rats were randomly divided into the following seven groups (n = 105): normal, model, pioglitazone hydrochloride (PH), Shuganlidan, Jianpihuatan, Tongfuxiezhuo, and dachaihu decoction (DD). 16SrRNA high-throughput IIlumina sequencing platform was used for sequencing, and bioinformatics analysis of rat intestinal flora was done. Results: Compared with the normal group, rats in the model, PH, Shuganlidan, Jianpihuatan, Tongfuxiezhuo, and DD groups showed significant differences in the intestinal microflora structure. The microorganisms that play an important role in the normal group are Ruminococcaceae, Oscillospira, Lactobacillales, Lactobacillaceae, Lactobacillus, bacilli, Ruminococcus, TM7, Spirochaetes, Clostridium, Elusimicrobia, Elusimicrobiaceae, Elusimicrobiales, Lactobacillus helveticus, Lactobacillus reuteri, Elusimicrobium, RF39, and Christensenellaceae; in the model group are Ruminococcus gnavus; in the PH group are Prevotella, Paraprevotellaceae, and Blautia; in the Jianpihuatan group are Bacteroidetes, Bacteroidia, Bacteroidales, Roseburia, Rikenellaceae, and Stridium methylpentosum; in the TongfuXiezhuo group are Bacteroidaceae, Bacteroides, Porphyromonadaceae, Parabacteroide, 4C0d_2, Cyanobacteria, YS2, Parabacteroides distasonis, Bacteroides uniformis, Verrucomicrobiaceae, Verrucomicrobiae, Verrucomicrobiales, Akkermansia, Akkermansia muciniphila, Coprobacillus, Parabacteroides gordonii, Blautia producta, and Ruminococcus torques; and in the DD group are Erysipelotrichales, Erysipelotrichi, and Erysipelothrichaceae. Conclusion: The Tongfuxiezhuo prescription elements of the DD significantly improved the intestinal flora of rats with NAFLD, improving the relative abundance of beneficial bacteria in the intestinal flora of NAFLD rats such as Bacteroides, Sartre genus, Vibrio pseudobutyrate bacteria, and Akkermansia muciniphila. This subsequently improved the glucose and lipid metabolism in NAFLD rats, reducing fat deposition in the liver, inhibiting intestinal inflammatory reaction, and maintaining the integrity of intestinal mucosal barrier. The action target is the intestinal axis of “intestinal–hepatic axis.”
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Free and hidden fumonisins in hordei fructus germinatus and their transfer to the decoction p. 106
Ling Hu, Hai-Qiang Zhu, Mei-Lin Ni, Jian Yang, Chuan-Zhi Kang, Lan-Ping Guo
DOI:10.4103/wjtcm.wjtcm_5_20  
Objective: This study aimed to determine the free and hidden fumonisins in Hordei Fructus Germinatus samples and to investigate the transfer rates of these mycotoxins from Hordei Fructus Germinatus to its decoction. Materials and Methods: The contamination levels of free and hidden fumonisins in a total of 60 Hordei Fructus Germinatus samples were analyzed using high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The decoction procedure was simulated with a highly contaminated Hordei Fructus Germinatus sample, and fumonisins in the resulting decoction preparation were determined by LC-MS/MS. Results: Among all the samples, 8.3% were contaminated with free fumonisins (FB1 and/or FB2) and 13.3% were contaminated with total fumonisins (free + hidden, measured as hydrolyzed fumonisins, i.e., HFB1 and/or HFB2). The concentrations of FB1and HFB1reached up to 83 and 95 μg/kg, respectively, whereas FB2and HFB2were detected only in traces. The transfer rates of free and total fumonisins from Hordei Fructus Germinatus to the decoction were 71.8% and 83.3% for FB1and FB2, respectively. In comparison, much lower transfer rates were found for total fumonisins, i.e., 38.2% and 24.7% for HFB1and HFB2, respectively. Conclusion: The incidence and contamination levels of free and hidden fumonisins in Hordei Fructus Germinatus samples were generally low. Regarding decoction preparation, the transfer rates of free fumonisins into the decoction were high, whereas a large part of hidden fumonisins were retained in Hordei Fructus Germinatus rather than migrating into water.
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Investigation on the mode of action of the traditional chinese medical prescription-yiqihuoxue formula, an effective extravasation treatment for cerebral vascular microemboli in ApoE-/- mice p. 112
Chao Jiang, Ting Wang, Zhong-Ju Xu, Xu Chao, Pierre Duez
DOI:10.4103/wjtcm.wjtcm_8_20  
Objective: The objective of this study was to investigate the mechanisms underlying anti-embolism and extravasational effects of traditional Chinese medical prescription YiqiHuoxue (YQHX) formula in ApoE-/-mice with cerebral vascular microemboli. Materials and Methods: An ApoE-/-mice model with microemboli was developed by infusing fluorescently labeled heterologous fibrin-rich microparticles into the internal carotid artery of ApoE-/-gene knockout male mice through the common carotid artery. Before microemboli injection, the animals were randomly divided into four groups of 10 animals, treated daily for 6 weeks by intragastric administration: The ApoE-/-control group (physiological saline, 0.2 mL/10 g/d), YQHX group (0.2 ml/10 g/d), clopidogrel group (3 mg/kg/d), and atorvastatin group (3 mg/kg/d); a further group was constituted of normal male C57BL/6J mice (with the same genetic background as ApoE-/-mice; normal control group; no treatment; microemboli injection). The mice in each microemboli group were divided into three subgroups, the 2-h, 24-h, and 72-h subgroups, corresponding to the time after microemboli injection. Two hours (or 24 h or 72 h) after microemboli injection, the changes in aortic intima and brain tissue were analyzed by histopathology, the amounts of fluorescent emboli being measured by fluorescence microscopy image analysis. Comparison points included the microemboli induced loss of aorta functions and pathological changes, atherosclerotic plaque, brain ultrastructure and functions, and embolus extravasation. Results: Loss of aorta functions and adverse pathological changes, atherosclerotic plaque, serious damage in brain ultrastructure and functions, and reduced thrombus elimination were obviously serious in microemboli injected ApoE-/-mice. These symptoms were significantly relieved by the YQHX pretreatment: (i) the ratio of thrombus accumulation was increased with a significant decrease in thrombus extravasation in ApoE-/-mice, while YQHX induced an increased thrombus extravasation; (ii) the degree of aortic intimal thickening and brain tissue structural disorders were significantly increased in ApoE-/-mice, but overtly inhibited in the YQHX group; (iii) YQHX restored cell viability and homeostasis in the brain; (iv) YQHX regulated the expression of pro- and anti-inflammatory cytokines in the aorta; and (v) YQHX reduced cortical nerve nuclei pyknosis, edema, liquefaction, and necrosis induced by brain hypoxia, especially in the 24 h and 72 h groups. Conclusions: These findings indicate that the protective effects of YQHX on the brain against microemboli-induced injury may be attributed to the activation of extravasation mechanisms, which are involved in the cerebrovascular injury pathway and constitutively important in the progression of ischemic stroke.
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