Meta-analysis of Traditional Chinese Medicine in treating functional

Transcription

1 Online Submissions: J Tradit hin Med 202 December 5; 32(): info@journaltcm.com ISSN JTM. All rights reserved. EVIDENE-BASED STUDY Meta-analysis of Traditional hinese Medicine in treating functional dyspepsia of liver-stomach disharmony syndrome huijie Wang, Mingjin Zhu, Wei Xia, Wei Jiang, Yan Li aa huijie Wang, Wei Jiang, Yan Li, Department of Gastroenterology, The Affiliated Hospital of Liaoning University of Traditional hinese Medicine, Shenyang 0032, hina Mingjin Zhu, Wei Xia, Liaoning University of Traditional hinese Medicine, Shenyang 0032, hina Supported by Shenyang Municipal Program for Science and Technology 20 (F ) orrespondence to: Prof. huijiewang, Department of Gastroenterology, The Affiliated Hospital of Liaoning University of Traditional hinese Medicine,. 33, Beiling dajie St. Huanggu District, Shenyang 0032, hina. zhumj63@63.com Telephone: or Accepted: July, 202 Abstract OBJETIVE: To systematically assess the clinical effectiveness of traditional hinese medicine (TM) in the treatment of functional dyspepsia (FD) of liver-stomach disharmony syndrome by meta-analysis. METHODS: Random controlled trials (RTs) were retrieved from databases, including Pubmed, hina national knowledge infrastructure, Wanfang Data, VIP Information, and the ochrane Library. Trials were selected according to inclusion criteria. The effects of traditional hinese medicine (TM) versus prokinetic agents in the treatment of functional dyspepsia (FD) of liver-stomach disharmony syndrome were compared by meta-analysis. RevMan was used for data analysis. The effective rate was assessed by odds ratios (ORs), and 95% confidence intervals (Is) were calculated. The cure rate was analyzed by the Peto OR. Simple statistical analysis was chosen to assess the frequency of prescribed hinese herbs in treating this syndrome. RESULTS: Thirteen trials were included, involving 53 patients, and these were of poor methodological quality. Twelve studies mentioned the effective rate and cure rate. TM therapy showed a better clinical effect rate compared with that with prokinetic agents [OR: 3.2, 95% I (2.27,.5)]. The TM group also had a better cure rate than that in the group of prokinetic agents [Peto OR: 2.26, 95% I (.6, 3.8)]. With regard to the frequency of hinese herbs used in these 3 trials, Baishao (Radix Paeoniae), haihu (Radix Bupleuri), and Gancao (Radix Glycyrrhizae) were mostly prescribed, followed by Xiangfu (Rhizoma yperi), Zhishi (Fructus Aurantii Immaturus), Zhiqiao (Fructus Aurantii), Foshou (itrus medica var.sarcodactylis), and henpi (Pericarpium itri Reticulatae). serious adverse effects were reported. ONLUSION: TM therapy shows a superior effective rate and cure rate compared with those in prokinetic agents in the treatment of FD of liver-stomach disharmony syndrome. However, further strictly designed RTs are required because of the poor quality of included trials. 202 JTM. All rights reserved. Key words: Dyspepsia; Liver-stomach disharmony; Meta-analysis; Traditional hinese medicine INTRODUTION Functional dyspepsia (FD) is defined as the presence of gastrointestinal symptoms, such as epigastric pain, epigastric burning, postprandial fullness, and early satiation, nausea or vomiting in the absence of any organic, JTM www. journaltcm. com 55 December 5, 202 volume 32 Issue

2 Wang J et al. Meta-analysis of TM in treating FD of liver-stomach disharmony syndrome systemic, or metabolic disease. The pathophysiology of FD has been widely investigated, but is still not well identified. 2 FD is frequently encountered in clinical practice. FD was found to affect up to 23.5% of the population in a study in Guangzhou, hina. 3 A large population-based study in Europe showed that 20.6% of patients had suffered from epigastric symptoms during the preceding 2-month period. Although there is no specific remedy for FD, it is believed that improvement of living habits and psychological management are beneficial to these patients. 5 Routine therapies commonly used are eradication of Helicobacter pylori, dopaminergic receptor blockers, sucralfate, and bismuth subsalicylate, or even antidepressants. Some patients may be symptom-free for years, while some continue to be symptomatic without the help of medicine. TM also plays an important role in improving the symptoms of FD in the hinese mainland. In TM, FD is considered as nearly equivalent to the TM term "stuffiness and fullness", 6 which is divided into different syndromes according to different clinical symptoms and signs. The basic syndromes include liver-stomach disharmony syndrome, fluid and food retention syndrome, dampness-heat of spleen and stomach syndrome, cold and heat in complexity syndrome, and spleen-stomach weakness syndrome. 7 The syndrome of liver-stomach disharmony and spleenstomach weakness syndrome are predominant among those FD outpatients. 8 Epidemiology shows some relation between the occurrence of dyspepsia and recent events in a patient's life, as well as psychosocial factors. 9 Additionally, 5.2% of inpatients with FD have mood disturbances, 3 implying that emotional instability might be the cause of some symptoms of FD. In the theory of TM, emotional instability is closely related to disorder of liver-qi, which leads to the syndrome of liver-stomach disharmony. To determine whether TM offers advantages over routine Western Medicine in treating FD with liver-stomach disharmony syndrome, we undertook a systematic review and meta-analysis of all relevant randomized controlled trials (RTs). METHODS Search strategy We identified studies by searching the following databases: Pubmed, hina national knowledge infrastructure Data-base (99 to May 202), Wanfang Data (989 to May 202), VIP Information (989 to May 202), and the ochrane Library. Search terms were "functional dyspepsia", "liver-stomach disharmony" and "disharmony between the liver and stomach", and "random control", "clinical trial", and "TM". Studies published in English and hinese were considered, and only data available in the full text were reviewed. Inclusion and exclusion criteria Studies were eligible for inclusion in the meta-analysis if they met all of the following criteria: ) the study was designed as an RT; 2) patients included in the study were diagnosed with FD according to Rome III, 0 and the TM syndrome must be liver-stomach disharmony; 6 3) TM versus prokinetic agents was investigated; ) criteria for successful treatment were clearly stated and treatment success was measured including the symptom scores; and 5) the treatment course lasted for 2 weeks or more. Trials were excluded for the following reasons: ) studies were not RTs; 2) the experimental group contained both TM and prokinetic agents; and 3) repeatedly published studies. Data extraction To avoid bias in the data extraction process, two reviewers (Mingjin Zhu and Wei Xia) independently abstracted and compared the results. All data were checked for internal consistency, and disagreements were resolved by discussion between the two reviewers and by seeking the opinion of a senior reviewer (huijie Wang) if necessary. Details abstracted from the studies, including the name of the first author, year of publication, number and mean age of the participants, male-female ratio, and adverse reactions were listed. When more than one published article described a single study, we extracted data from the study providing the most detailed information. Assessment of methodological quality Included RTs were strictly evaluated according to the methods of evaluating risk of bias as described in the ochrane Handbook.2.2 for Systematic Reviews of Interventions (version 200). The quality of trials was assessed by examining: randomization, the allocation concealment, baseline characteristics, blinding, withdrawals/dropouts, and selective reporting of outcomes, which were ranked by A (low risk of bias), B (moderate risk of bias), and (high risk of bias). We also used the modified Jadad scoring system for quality assessment. Data analysis Review Manager provided by the ochrane ollaboration was used to analyze collected data. Odds ratios (ORs) were used for dichotomous data, with 95% confidence intervals (Is). The hi-squared test for homogeneity was carried out to determine whether the distribution of results was compatible with the assumption that differences between trials were due to chance variation alone. Heterogeneity was presented as significant when I 2 was over 50% or P<0., and a random effect model was used for the meta-analysis. If I 2 was less than 50% and P>0., there was significant heterogeneity, and a fixed effect model was used. A funnel plot was carried out to assess publication bias. 2 JTM www. journaltcm. com 56 December 5, 202 volume 32 Issue

3 Wang J et al. Meta-analysis of TM in treating FD of liver-stomach disharmony syndrome Sensitivity analysis To evaluate the effect of methodological characteristics of RTs on the results of this meta-analysis, sensitivity analysis was used to reanalyze the data by changing inclusion criteria or using different statistical methods. If the sensitivity analysis was close to the results, this strengthened the level of confidence. RESULTS In this review, 53 articles were retrieved from the five above-mentioned electronic databases. Thirty-eight articles were excluded by reading the headlines and abstract, because they were not controlled trials (n=5), they were not randomized (n=7), the experimental group was TM combined with other drugs (n=0), both groups were TM therapies (n=), they contained other TM syndromes (n=0), or were duplicated articles (n=2). The rest of the 5 articles were carefully reviewed. Two articles described the same studies, and therefore, we chose the detailed study. The other excluded article showed different data between the abstract and the content. Therefore, a total of 3 studies involving 53 patients were included in the systematic review All 3 studies included were of a parallel design, single center, and had a positive control group. Trials were only performed in hina and were written in hinese. The characteristics of included trials are shown in Tables and 2. Methodological quality of included trials All trails were of poor methodological quality and at high risk of bias. Only one trial 2 barely met the quality grade B and with a modified Jadad score of 2 points, while the rest were grade with a modified Jadad score of point. All studies were described as randomized, but only four trials,6,8,25 presented specific methods of allocation sequence. An RT with high quality and low bias should have blinding and allocation concealment strictly designed and conducted. However, none of the trials mentioned blinding and allocation concealment. Dropouts were sometimes inevitable when conducting clinical trials, and intention-to-treat should be taken into consideration, but the identified studies failed to provide any data on dropouts. Only two studies 2,2 mentioned adverse effects, while others failed to provide any specific information about adverse effects. Effective rate meta-analysis The 3 studies compared TM interventions with prokinetic agents, and 2 studies 3-2 reported total effective rates: the group using TM therapy varied from 83.3% to 93.33%, while the group of prokinetic agents varied from 56.7% to 82.2% [OR: 3.2, 95%I (2.27,.5)]. There was no heterogeneity among trials (χ 2 =3.3, P=0.99>0., I 2 =0% ), and therefore, the M-H fixed-effect model was used. The tests for overall effect showed that TM therapy was better than prokinetic agents, and there was a statistical significance in effective rate (P<0.00) between the TM group and prokinetic agents (Figure ). One study 25 only compared single symptoms separately. The bias of those 2 trials was that a funnel plot was used to assess publication bias (Figure 2). The funnel-shape was slightly asymmetrical, indicating that there might be publication bias in those studies. ure rate meta-analysis Nine studies 3,6-8,20-2 described the cure rate. The Peto fixed effects model is the more appropriate model for rare events. 26 The cure rate is a small probability event, and therefore, we used the Peto OR to reduce bias. The incorporated data showed that TM therapy outweighed the prokinetic agents in curing FD (Peto OR: 2.26, 95%I=[.6, 3.8]), and there was no heterogeneity (χ 2 =3.5, P=0.92; I²=0%). Subgroup analyses Herbal therapy versus domperidone alone with weeks' course: Eight studies 3,,6,7,20,2,23,2 compared hinese herbs alone with domperidone alone in a -week course. There was a significantly higher effective rate in herbal therapy than domperidone alone [663 patients OR: 2.99, 95% I (.93,.63)], and there was no significant heterogeneity (χ 2 =2.98, P= 0.89, I²=0%). Herb therapy versus mosapride: Two studies 8,9 compared hinese herbs with mosapride. The merged analysis showed that hinese herbal medicine achieved a higher response rate than mosapride [OR: 3.98, 95% I (.50, 0.5)], and there was no significant heterogeneity (χ 2 =2.78, P=0.92, I²=0%) (Figure 3). Sensitivity analyses We renewed the analysis according to methodological quality (with specific random method or follow-up). Five,6,8,2,25 of the studies with a relatively higher quality were selected, and their merged data showed that there was a significant difference between TM therapy and the control groups [OR: 3.37, 95% I (.72, 6.62]), and there was no significant heterogeneity in this analysis (χ 2 =2.8, P=0.90, I² =0% ). This result agrees with the whole analysis. The selective ratio for single hinese herbs in the identified studies The hinese herbs were chosen by the researchers according to the principle of TM treatment in treating liver-stomach disharmony syndrome, namely dispersing the depressed liver-qi and regulating the stomach. To clearly understand hinese herbal medicine, we performed a simple statistical analysis on the frequency of hinese herbs used in these 3 trials. The distribution of these herbs is shown in Figure. Baishao (Radix Paeoniae), haihu (Radix Bupleuri), and Gancao (Radix JTM www. journaltcm. com 57 December 5, 202 volume 32 Issue

4 Wang J et al. Meta-analysis of TM in treating FD of liver-stomach disharmony syndrome Table 2 General process of each included trials Reference Pang J Wang HF 200 Zou YJ Yang XJ hen W Zhou YX hen Y Zhang ZL Tan HL Li JS Li D Li YH Dang JN TM group Ganweishu capsule, 3 capsules tid po haihu shugan powder haihu shugan decoction Hewei xiaoyao decoction Jiawei sini powder Xingqi tongjiang pill, pills tid po and Jupi porridge Liqi hewei oral liquid, 0ml tid po Jiangqi hezhong decoction Shuwei decoction Jianpi shugan decoction Shuhe decotion Modified Sini powder Shugan jianpi formula and acupuncture Intervention ontrol group Domperidone, 0 mg tid po Domperidone, 0 mg tid po Polyzyme tablets, 3 tablets tid po + Domperidone, 0 mg tid po Domperidone, 0 mg tid p Domperidone, 0 mg tid po Mosapride, 5 mg tid po Mosapride itrate, 5 mg tid po Domperidone, 0 mg tid po Domperidone, 0 mg tid po Domperidone, 0 mg tid po Domperidone, 0 mg tid po Domperidone, 0 mg tid po Domperidone, 0 mg tid po Trial period (weeks) 2 Outcome measures and gastric fluid emptying rate, HAMA a score and HAMD score, EGG a, MOT a, GAS a, gastric emptying rate (barium strips), FDDQL a Effective rate (%) TM Group ontrol group tes: a HAMA: Hamilton anxiety scale; HAMD: Hamilton depression scale; EGG: electrogastrogram; MOT: motilin; GAS: gastrin; FDDQL: the functional digestive diseases quality of life questionnaire. Powder and decoction were cooked and taken in a hinese traditional way. Table haracteristics of the studies included in the meta-analysis Male Female Mean age Reference n TM ontrol TM ontrol group group group group Pang J :26 2: Wang HF : Zou YJ :29 9: Yang XJ :9 2: hen W :33 27: Zhou YX hen Y :8 2: Zhang ZL :3 : Tan HL :3 8: Li JS :35 55: Li D :7 2: Li YH :29 8: Dang JN :26 7: te: TM: Traditional hinese Medicine; ITT: intention-to-treat Methods of random process Random digits table Random digits table Random design Drawing lots Blinding Allocation concealment M-Jadad score 2 ITT Follow up Yes Quality grade B ity at basel ine Adverse effect JTM www. journaltcm. com 58 December 5, 202 volume 32 Issue

5 Wang J et al. Meta-analysis of TM in treating FD of liver-stomach disharmony syndrome Figure omparison of the effective rate between the TM group and prokinetic agents SE (log[or]) OR Figure 2 Funnel plot of the effective rate between the TM group and prokinetic agents Figure 3 Subgroup analysis of the effective rate JTM www. journaltcm. com 59 December 5, 202 volume 32 Issue

6 Wang J et al. Meta-analysis of TM in treating FD of liver-stomach disharmony syndrome.2.0 Radix Paeoniae Alba Radix Bupleuri 0.8 Radix Glycyrrhizae Proportion Rhizoma yperi a Rhizoma Atractylodis Macrocephalae b c d hinese herb Figure Frequency of single hinese herbs chosen in the 3 included trials a Zhishi (Fructus Aurantii Immaturus), Zhiqiao (Fructus Aurantii), Foshou (itrus medica var.sarcodactylis), and henpi (Pericarpium itri Reticulatae). b haunxiong (Ligusticum chuanxiong Hort.), huanlianzi (Fructus Toosendan), and Banxia (Rhizoma Pinelliae). c Yujin (Radix urcumae), Sugeng (aulis Perillae), Shenqu (Massa Medicata Fermentata), Shanzha (Fructus rataegi), Muxiang (Radix Aucklandiae), and Houpo (Magnolia officinalis Rehd. et Wils). d Sharen (Fructus Amomi), Maiya (Fructus Hordei Germinatus), Jineijin (Endothelium orneum Gigeriae galli), Huanglian (optis chinensis Franch), Fuling (Poria), Danggui (Radix Angelicae Sinensis), henxiang (Aquilariae Lignum Resinatum), and Baihe (Lilium brownii var. viridulum). Glycyrrhizae) were mostly used, and the dosages were 9-5 g, 9-5 g, and 6-0 g, respectively. DISUSSION Herbal medications provide symptom relief in FD, and the evidence grade is moderate. 27 They have a long history of use in the treatment of dyspeptic complaints. Their mechanisms of action are not completely understood. However, findings suggest that herbal medications might modulate the activity of the smooth musculature of the digestive tract. 28 The results of our meta-analysis of data from 3 trials suggest that TM has higher effective and cure rates in treating FD of liver-stomach disharmony syndrome than routine prokinetic agents (domperidone or mosapride). However, all identified studies were of poor quality. study adopted blinding, concealment, and all the trials were conducted from single centers, which all influenced the reliability of this systematic review. There was no specific adverse effects mentioned in the TM group, and only one study mentioned that domperidone had an adverse effect of epigastric discomfort and morepassing flatuses. Although some traditional hinese herbal medicines were reported to be toxic, 29 herbal medicine still plays an important role in treating chronic diseases in hina with fewer adverse effects reported. Figure shows the frequency of chosen herbs in treating FD with liver-stomach disharmony syndrome. The frequently-used herbs (>6/3) were Baishao (Radix Paeoniae), haihu (Radix Bupleuri), Gancao (Radix Glycyrrhizae), Xiangfu (Rhizoma yperi), Baizhu (Rhizoma Atractylodis Macrocephalae), Zhishi (Fructus Aurantii Immaturus), Zhiqiao (Fructus Aurantii), Foshou (itrus Medica var. Sarcodactylis), and henpi (Pericarpium itri Reticulatae), of which the major effects are soothing the liver and regulating Qi. In addition, these herbs constitute the majority of a famous traditional hinese prescription called haihu Shugan Powder (Bupleurm Powder for Dispersing Depressed Liver-Qi), which relieves depression of the liver-qi, and promotes the circulation of Qi and relieves pain. 30 This treatment aims to treat the syndrome of stagnation of Qi due to depression of the liver, focusing on the manifestations of stagnation of Qi and pain on the liver meridian area. This review indirectly reveals that there is close connection between the syndrome of stagnation of Qi due to depression and the syndrome of liver-stomach disharmony. The syndrome of stagnation of Qi due to depression can lead to the syndrome of liver-stomach disharmony according to the five-element theory of TM. In other words, this is called "wood restricting earth". Therefore, dispersing the depressed liver-qi and regulating Qi for harmonizing the stomach JTM www. journaltcm. com 520 December 5, 202 volume 32 Issue

7 Wang J et al. Meta-analysis of TM in treating FD of liver-stomach disharmony syndrome is a reasonable treatment for this syndrome. Limitations of this systematic review The main limitation of our review is in the low methodological quality. The reason for this may be because all of the studies were conducted in hina and the research might have specialized in TM but lacked the standard operation of RTs. Most of the authors did not know the correct method for generating a randomization sequence, while a few of them knew it, but did not follow it properly. 3 Some authors refuse to publish negative results, which also causes bias. Every study regarded symptom scores as a leading indicator of therapeutic effect. Although a symptom score scale was scientifically designed, it was still subjective and the scores might easily have been affected by the patients and researchers to some extent. Only three studies used an objective observation indicator (gastric fluid emptying rate, electrogastrogram, motilin, gastrin and gastric emptying rate of barium strips). An objective criterion is more persuasive. Direction for future clinical research Further exploration of trial design and standards for reporting trial results is required, and more high-quality controlled trials are required for assessing the effects of TM compared with other drugs and placebo. All RTs should refer to the ONSORT (onsolidated Standards of Reporting Trials) for TM. 32 The preferred research should be multicenter, and blinding, concealment, and intention-to-treat are recommended to raise the quality of RTs. For scientific research, the main outcome measures should be carefully considered to make the research more objective and conceivable. REFERENES Zhu W, Wang JY. Functional gastrointestinal disorders. In hen HZ. Practice of internal medicine. 3th ed. Beijing: People's Medical Publishing House, 2009: Rita B, Braden K. Functional dyspepsia. Ther Adv Gastroenterol 200; 3(3): Li YY, Nie YQ, Sha WH, Su H. The link between psychosocial factors and functional dyspepsia: an epidemiological study. hin Med J (Engl) 2002; 5(7): Piessevaux H, De Winter B, Louis E, et al. Dyspeptic symptoms in the general population: a factor and cluster analysis of symptom groupings. Neurogastroenterol Motil 2009; 2(): Bennett EJ, Piesse, Palmer K, Badcock A, Tennant, Kellow JE. Functional gastrointestinal disorders: psychological, social, and somatic features. Gut 998; 2(3): Zhang SS, Wang HB, Li QG. TM standard in diagnosis and treatment of functional dyspepsia (draft). Zhong Guo Zhongxiyi Jiehe Xiao Hua Za Zhi 2002; 0 (). 7 Zheng XY. Guiding principle of clinical research on new drugs of hinese medicine in the treament of stuffiness and fullness. In: Guiding principle of clinical research on new drugs of hinese medicine (trial implementation). Edited by: Yu XH. Bejing: hin Med Sci Press, 2002: Liu SL, Mei GQ, Zhao YQ, Sun JQ, Wan XG, Zhang ML. Study on law of clinical syndrome differentiation in TM for functional dyspepsia. Zhong Guo Yi Yao Xue Bao 200; 9(8): Stanghellini V. Relationship between upper gastrointestinal symptoms and lifestyle, psychosocial factors and comorbidity in the general population: results from the Domestic/Inter-national Gastroenterology Surveillance Study (DIGEST). Scand J Gastroenterol Suppl 999; 23: Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology 2006; 30(5): Bañares R, Albillos A, Rincón D, et al. Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding: a meta-analysis. Hepatology 2002; 35(3): Egger M, Davey Smith G, Schneider M, Minder. Bias in meta-analysis detected by a simple, graphical test. BMJ 997; 35(709): Pang J, Feng WJ. Efficacy observation of Ganweishu capsule in the treatment of functional dyspepsia of liver-stomach disharmony syndrome. Shanxi Zhong Yi 2009; 25(): 3-. Wang HF, Zhang J, Wang JQ. linical observation of Modified haihu shugan powder in the treatment of functional dyspepsia. Beijing Zhong Yi Yao 200; 29(0): Zou YJ, Lv HY, hen SH. linical observation of Modified haihu shugan decoction in the treatment of functional dyspepsia of liver-stomach disharmony syndrome. Guangxi Zhong Yi Yao 2007; 30(): Yang XJ. Hewei xiaoyao decoction in treating 5 cases of functional dyspepsia of liver-stomach disharmony syndrome. Zhong Yi Yao Dao Bao 2009; 5(3): hen W, Duan YP. Modified Sini powder in treating functional dyspepsia. Zhejiang Zhong Xi Yi Jie He Za Zhi 2005; 5(9): Zhou YX. linical observation of Xingqi tongjiang pill combined with Jupi porridge in treating functional dyspepsia. Hubei Zhong Yi Za Zhi 202; 3(3): hen Y, Zhou XH, Wu J, et al. Efficacy observation of Liqi hewei oral liquid in treating 30 cases of functional dyspepsia of liver-stomach disharmony syndrome. Jilin Zhong Yi Yao 200; 2(2): Zhang ZL, Wu J, Shen SW. Jiangqi hezhong decoction in treating 30 cases of functional dyspepsia of liver-stomach disharmony syndrome. Fujian Zhong Yi Yao 2008; 39(): Tan HL, Wang XJ. linical observation of Shuwei decoction in treating 30 cases of functional dyspepsia of liver-stomach disharmony syndrome. Zhong Guo Shi Yan Fang Ji Xue Za Zhi 2009; 5(9): Li JS. Efficacy observation of Jianpi shugan decoction in treating 96 cases of functional dyspepsia. Xin Zhong Yi 2008; 0(6): JTM www. journaltcm. com 52 December 5, 202 volume 32 Issue

8 Wang J et al. Meta-analysis of TM in treating FD of liver-stomach disharmony syndrome 23 Li D, Gu ZJ. Shuhe decoction in treating 30 cases of functional dyspepsia of liver-stomach disharmony syndrome. Anhui Zhong Yi Xue Yuan Xue Bao 20; 30(5): Li YH. Modified Sini powder in treating 50 cases of functional dyspepsia of liver-stomach disharmony syndrome. Shandong Zhong Yi Za Zhi 2009; 28(): Dang JN, Gao P. linical observation of combination of acupuncture and medicine in treating functional dyspepsia. Shangxi Zhong Yi 2009; 25(2): Peto SD, Yoon KL. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta analysis. BMJ 2000; 32(7270): Miwa H, Ghoshal U, Gonlachanvit S, et al. Asian consensus report on functional dyspepsia. J Neurogastroenterol Motil 202; 8(2): Melzer J, Rösch W, Reichling J, Brignoli R, Saller R. Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast). Aliment Pharmacol Ther 200; 20(-2): osyns JP. Aristolochic acid and 'hinese herbs nephropathy': a review of the evidence to date. Drug Saf 2003; 26 (): Li J, Deng ZJ, Lian JW. Formula of Traditional hinese Medicine. Beijing: hina Press of Traditional hinese Medicine 2006; Wu TX, Li YP, Bian ZX, Liu GJ, Moher D. Randomized trials published in some hinese journals: how many are randomized? Trials 2009; 0: Wu TX, Li YP, Bian ZX, et al. onsolidated standards for reporting trials of Traditional hinese Medicine (ON- SORT for TM) (For Solicitation of omments). hin J Evid-based Med 2007; 7(9): JTM www. journaltcm. com 522 December 5, 202 volume 32 Issue