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Article ; Online: Wen-Shen-Tong-Luo-Zhi-Tong Decoction regulates bone-fat balance in osteoporosis by adipocyte-derived exosomes.

Wang, Lining / Pan, Yalan / Liu, Mengmig / Sun, Jie / Yun, Li / Tu, Pengcheng / Wu, Chengjie / Yu, Ziceng / Han, Zhitao / Li, Muzhe / Guo, Yang / Ma, Yong

Pharmaceutical biology

2023 Volume 61, Issue 1, Page(s) 568–580

Abstract: Context: Wen-Shen-Tong-Luo-Zhi-Tong (WSTLZT) Decoction is a Chinese prescription ...

Abstract	Context: Wen-Shen-Tong-Luo-Zhi-Tong (WSTLZT) Decoction is a Chinese prescription with antiosteoporosis effects, especially in patients with abnormal lipid metabolism. Objective: To explore the effect and mechanism of WSTLZT on osteoporosis (OP) through adipocyte-derived exosomes. Materials and methods: Adipocyte-derived exosomes with or without WSTLZT treated were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blotting (WB). Co-culture experiments for bone marrow mesenchymal stem cells (BMSCs) and exosomes were performed to examine the uptake and effect of exosome in osteogenesis and adipogenic differentiation of BMSC. MicroRNA profiles, luciferase and IP were used for exploring specific mechanisms of exosome on BMSC. Results: ALP, Alizarin red and Oil red staining showed that WSTLZT-induced exosomes from adipocyte can regulate osteoblastic and adipogenic differentiation of BMSC. MicroRNA profiles observed that WSTLZT treatment resulted in 87 differentially expressed miRNAs ( Conclusions: WSTLZT can exert anti-OP effect through SPRY2 via the MAKP signalling by miR-122-5p carried by adipocyte-derived exosomes.
MeSH term(s)	Mice ; Animals ; Exosomes/genetics ; Exosomes/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Cell Differentiation ; Adipogenesis ; Osteogenesis ; Adipocytes
Chemical Substances	MicroRNAs
Language	English
Publishing date	2023-03-31
Publishing country	England
Document type	Journal Article
ZDB-ID	1440131-9
ISSN	1744-5116 ; 1388-0209
ISSN (online)	1744-5116
ISSN	1388-0209
DOI	10.1080/13880209.2023.2190773
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Article ; Online: The Chinese medicine Xin-tong-tai granule protects atherosclerosis by regulating oxidative stress through NOX/ROS/NF-κB signal pathway.

Wei, Jia-Ming / Yuan, Hui / Liu, Cheng-Xin / Wang, Zi-Yan / Shi, Min / Guo, Zhi-Hua / Li, Ya

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 165, Page(s) 115200

Abstract: Background: Xin-tong-tai Granule (XTTG), a traditional Chinese medicine, has been used to treat ...

Abstract	Background: Xin-tong-tai Granule (XTTG), a traditional Chinese medicine, has been used to treat atherosclerosis (AS), but its mechanism is poorly understood. Intriguingly, oxidative stress has been recognized as vital factors in the treatment of atherosclerosis. Purpose: This study aims to explore the potential mechanism of XTTG for treating AS. Methods: An in-vivo model of AS was established by feeding ApoE Results: XTTG improved blood lipid levels and pathological aortic changes of ApoE Conclusion: XTTG can inhibit NOX/ROS/NF-κB signaling pathway, reduce damages caused by oxidative stress, and exert anti-AS effects.
MeSH term(s)	Animals ; Humans ; Mice ; Apolipoproteins E/genetics ; Apolipoproteins E/metabolism ; Atherosclerosis/drug therapy ; Atherosclerosis/prevention & control ; Atherosclerosis/genetics ; Lipoproteins, LDL/pharmacology ; NF-kappa B/metabolism ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Superoxide Dismutase/metabolism ; Drugs, Chinese Herbal/pharmacology
Chemical Substances	Apolipoproteins E ; Lipoproteins, LDL ; NF-kappa B ; Reactive Oxygen Species ; Superoxide Dismutase (EC 1.15.1.1) ; Drugs, Chinese Herbal
Language	English
Publishing date	2023-07-26
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.115200
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Article ; Online: Clinical Effect of Yiqi Naoluo Tong Decoction in the Treatment of Cerebral Infarction

Hou Yujin / Jie Xiaosu / Guo Xin / Zhang Yingying / Shi Hua / Lou Yuanjun

E3S Web of Conferences, Vol 218, p

2020 Volume 03011

Abstract: Objective: To apply Yiqi Naoluo Tong Decoction for clinical treatment of patients ... The conventional treatment methods were combined with Yiqi Naoluo Tong Decoction and single conventional treatment ... significant and statistically meaningful. Conclusion: The addition of Yiqi Naoluo Tong Decoction ...

Abstract	Objective: To apply Yiqi Naoluo Tong Decoction for clinical treatment of patients with cerebral infarction, and analyze the therapeutic effect of this method. Methods: 150 cases of cerebral infarction patients who were treated in our hospital were set as the research objects and divided into two groups. The conventional treatment methods were combined with Yiqi Naoluo Tong Decoction and single conventional treatment. Results: After treatment, the improvement of the test group of patients was better than that of the control group, and compared with the control group, the comparison result showed that P<0.05, the difference was significant and statistically meaningful. Conclusion: The addition of Yiqi Naoluo Tong Decoction in the clinical treatment of patients with cerebral infarction can improve the patients’ neurological deficits, quality of life, limb motor function and ability of daily living. This shows that this medicine has a higher clinical application value.
Keywords	Environmental sciences ; GE1-350
Subject code	610 ; 616
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	EDP Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Huang-Pu-Tong-Qiao Formula Ameliorates the Hippocampus Apoptosis in Diabetic Cognitive Dysfunction Mice by Activating CREB/BDNF/TrkB Signaling Pathway.

Ye, Shu / Xie, Dao-Jun / Zhou, Peng / Gao, Hua-Wu / Zhang, Meng-Ting / Chen, Da-Bao / Qin, Yun-Peng / Lei, Xin / Li, Xin-Quan / Liu, Juan / Cheng, Ya-Xun / Yao, Yong-Chuan / Cai, Biao / Shen, Guo-Ming

Evidence-based complementary and alternative medicine : eCAM

2021 Volume 2021, Page(s) 5514175

Abstract: Background: Huang-Pu-Tong-Qiao formula (HPTQ), a traditional Chinese medicine (TCM) formula used ...

Abstract	Background: Huang-Pu-Tong-Qiao formula (HPTQ), a traditional Chinese medicine (TCM) formula used to improve cognitive impairment. However, the underlying neuroprotective mechanism of HPTQ treated for diabetic cognitive dysfunction (DCD) remains unclear. The purpose of this study was to investigate the neuroprotective mechanism of HPTQ in DCD mice based on molecular docking. Methods: To investigate the neuroprotective effect of HPTQ in DCD, the Morris water maze (MWM), novel object recognition (NOR) test was used to detect the learning and memory changes of mice; hematoxylin-eosin (HE) staining was used to investigate the damage of hippocampal neurons; the western blot (WB) was used to examine the level of brain-derived neurotrophic factor (BDNF) of hippocampus. To investigate the neuroprotective mechanism of HPTQ in DCD, molecular docking was used to predict the possible target proteins of different active components in HPTQ and then the WB was used to verify the expression of key target proteins in the hippocampus of mice. Results: HPTQ improved the learning and memory ability, hippocampal neuron damage, and the level of BDNF in the hippocampus of the DCD model treated with HFD/STZ for 12 weeks. Besides, the results of molecular docking showed that the main chemical components of HPTQ could be well combined with the targets of Bcl-2-associated X (Bax) and B-cell lymphoma2 (Bcl-2) and caspase-3. The levels of Bax/Bcl-2 protein ratio and caspase-3 increased in the DCD model while the HPTQ inhibited it. In addition, HPTQ restored DCD-induced decline of p-CREB, BDNF, TrkB, and p-Akt in the hippocampus. Conclusions: These data indicated that HPTQ ameliorates the hippocampus apoptosis in diabetic cognitive dysfunction mice by activating CREB/BDNF/TrkB signaling pathway.
Language	English
Publishing date	2021-06-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2171158-6
ISSN	1741-4288 ; 1741-427X
ISSN (online)	1741-4288
ISSN	1741-427X
DOI	10.1155/2021/5514175
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Article ; Online: The anaphylactoid constituents in Xue-Sai-Tong injection.

Xiang, Zheng / Qiao, Tie / Xiao, Hang / Kang, Ting-Guo / Dou, Deqiang / Li, Haibo / Kuang, Haixue

Planta medica

2013 Volume 79, Issue 12, Page(s) 1043–1050

Abstract: Xue-Sai-Tong injection, a traditional Chinese medicine with total saponins of Sanqi ginseng ... reaction induced by Xue-Sai-Tong injection was one of the main adverse drug reactions which has occurred ... from the degranulation of mast cells and RBL-2H3 cells stimulated by Xue-Sai-Tong injection was explored. Mediators ...

Abstract	Xue-Sai-Tong injection, a traditional Chinese medicine with total saponins of Sanqi ginseng as active ingredients, has been used for more than 500 years to treat coronary artery disease in China. Anaphylactoid reaction induced by Xue-Sai-Tong injection was one of the main adverse drug reactions which has occurred frequently in recent years. It is of importance to elucidate its anaphylactoid constituents. The in vivo anaphyalctoid tests indicated that the anaphylactoid mediators could be used as indexes to evaluate the anaphylactoid action. Further, the in vitro model based on determining the mediators release from the degranulation of mast cells and RBL-2H3 cells stimulated by Xue-Sai-Tong injection was explored. Mediators released from mast cells and RBL-2H3 cells caused by Xue-Sai-Tong injection were determined by comparison of the methods of fluorospectrophotometry, ELISA, and spectrophotometry, respectively, revealing that the histamine release induced by the Xue-Sai-Tong injection could not be assayed accurately by the method of fluorospectrophotometry because of the interference of saponins and unknown components in the injection. The rat peritoneal mast cell was also not an optimal cell model for determining histamine and β-hexosaminidase release due to the higher spontaneous release ratio during the cell collection. Thus, ELISA determination of the histamine release from RBL-2H3 cells is a suitable in vitro model to assay the anaphylactoid reaction of Xue-Sai-Tong injection. Previously, abnormal hemolysis in some batches of Xue-Sai-Tong injection was observed in the course of their HD₅₀ (half hemolytic dosage) determination. This study further found that injections which exhibited an abnormal hemolysis phenomenon also caused a higher release of the anaphylactoid mediators from RBL-2H3 cells, indicating the HD₅₀ could be an auxiliary index to evaluate anaphylactoid action of the herbal injection indirectly. Research for anaphylactoid components in Xue-Sai-Tong injection indicated that proteins with over 10 KDa of molecular weight, but not ginsenosides, could be the main constituents inducing the release of anaphylactoid mediators from RBL-2H3 cells. An HPLC method for protein determination in the Xue-Sai-Tong injection was established subsequently, and the content of proteins with molecular weights of over 10 KDa in the injections showed an obviously positive correlation with the histamine release induced by the injections. In addition, taking ginsenoside-Rd coupled with BSA as an example, the hapten property of ginsenosides was studied and the ratio of ginsenoside-Rd to BSA was determined to be 8:1 by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the ginsenoside-BSA conjugate showed a stronger action to stimulate histamine release from the RBL-2H3 cells.
MeSH term(s)	Anaphylaxis/chemically induced ; Animals ; Cell Line, Tumor ; China ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/administration & dosage ; Drugs, Chinese Herbal/adverse effects ; Drugs, Chinese Herbal/isolation & purification ; Ginsenosides/adverse effects ; Ginsenosides/chemistry ; Ginsenosides/isolation & purification ; Guinea Pigs ; Histamine/metabolism ; Histamine Release/drug effects ; Male ; Mast Cells/drug effects ; Mast Cells/metabolism ; Medicine, Chinese Traditional ; Panax notoginseng/chemistry ; Plant Proteins/analysis ; Plant Proteins/metabolism ; Rats ; Rats, Wistar ; Saponins/adverse effects ; Saponins/chemistry ; Saponins/isolation & purification ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; beta-N-Acetylhexosaminidases/drug effects ; beta-N-Acetylhexosaminidases/metabolism
Chemical Substances	Drugs, Chinese Herbal ; Ginsenosides ; Plant Proteins ; Saponins ; sanqi ; Histamine (820484N8I3) ; beta-N-Acetylhexosaminidases (EC 3.2.1.52)
Language	English
Publishing date	2013-08
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	123545-x
ISSN	1439-0221 ; 0032-0943
ISSN (online)	1439-0221
ISSN	0032-0943
DOI	10.1055/s-0032-1328746
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Huo Xue Tong Luo capsule, a vasoactive herbal formula prevents progression of asymptomatic osteonecrosis of femoral head: A prospective study.

Wei, Qiu-Shi / Hong, Guo-Ju / Yuan, Ying-Jia / Chen, Zhen-Qiu / Zhang, Qing-Wen / He, Wei

Journal of orthopaedic translation

2018 Volume 18, Page(s) 65–73

Abstract: ... of a specific vasoactive herbal formula, Huo Xue Tong Luo capsule (HXTL capsule), for the treatment of patients ...

Abstract	Background/objective: A prospective cohort study aimed to evaluate the clinical efficacy of a specific vasoactive herbal formula, Huo Xue Tong Luo capsule (HXTL capsule), for the treatment of patients with asymptomatic osteonecrosis of femoral head (ONFH). Methods: We evaluated a clinical trial of 55 patients (59 hips) with asymptomatic ONFH (no joint collapse) evaluated by Steinberg staging system and necrosis range classification criteria. Then, they were given HXTL capsule under specific protocol. Among them, 39 males and 16 females with an average age of 36.4 ± 10.1 years were followed up for an average of 4.38 years during treatment. The aggravation of clinical and imaging results was assessed by initial pain and joint collapse. The clinical and imaging outcomes of these patients were compared with those of a historical control group from the literature under critical inclusion criteria. Results: At the latest follow-up, initial pain occurred in five of 59 (8.5%) hips of patients taking HXTL capsule compared with 31 of 81 (38.3%) controls ( Conclusion: As an agent formulated by vasoactive herbals, HXTL capsule with specific protocol is an effective medicine for relieving hip pain and preventing joint collapse in patients with asymptomatic ONFH. The translational potential of this article: The translation potential of this prospective cohort study is that the initially officially approved clinical indication for HXTL capsule for treatment of ONFH is due to its possible effect of revascularization on angiogenesis of necrosis. It is has been now proven to be effective for a new clinical application.
Language	English
Publishing date	2018-12-21
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2747531-1
ISSN	2214-031X
ISSN	2214-031X
DOI	10.1016/j.jot.2018.11.002
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Article ; Online: Huang-Pu-Tong-Qiao Formula Ameliorates the Hippocampus Apoptosis in Diabetic Cognitive Dysfunction Mice by Activating CREB/BDNF/TrkB Signaling Pathway

Shu Ye / Dao-Jun Xie / Peng Zhou / Hua-Wu Gao / Meng-Ting Zhang / Da-Bao Chen / Yun-Peng Qin / Xin Lei / Xin-Quan Li / Juan Liu / Ya-Xun Cheng / Yong-Chuan Yao / Biao Cai / Guo-Ming Shen

Evidence-Based Complementary and Alternative Medicine, Vol

2021 Volume 2021

Abstract: Background. Huang-Pu-Tong-Qiao formula (HPTQ), a traditional Chinese medicine (TCM) formula used ...

Abstract	Background. Huang-Pu-Tong-Qiao formula (HPTQ), a traditional Chinese medicine (TCM) formula used to improve cognitive impairment. However, the underlying neuroprotective mechanism of HPTQ treated for diabetic cognitive dysfunction (DCD) remains unclear. The purpose of this study was to investigate the neuroprotective mechanism of HPTQ in DCD mice based on molecular docking. Methods. To investigate the neuroprotective effect of HPTQ in DCD, the Morris water maze (MWM), novel object recognition (NOR) test was used to detect the learning and memory changes of mice; hematoxylin-eosin (HE) staining was used to investigate the damage of hippocampal neurons; the western blot (WB) was used to examine the level of brain-derived neurotrophic factor (BDNF) of hippocampus. To investigate the neuroprotective mechanism of HPTQ in DCD, molecular docking was used to predict the possible target proteins of different active components in HPTQ and then the WB was used to verify the expression of key target proteins in the hippocampus of mice. Results. HPTQ improved the learning and memory ability, hippocampal neuron damage, and the level of BDNF in the hippocampus of the DCD model treated with HFD/STZ for 12 weeks. Besides, the results of molecular docking showed that the main chemical components of HPTQ could be well combined with the targets of Bcl-2-associated X (Bax) and B-cell lymphoma2 (Bcl-2) and caspase-3. The levels of Bax/Bcl-2 protein ratio and caspase-3 increased in the DCD model while the HPTQ inhibited it. In addition, HPTQ restored DCD-induced decline of p-CREB, BDNF, TrkB, and p-Akt in the hippocampus. Conclusions. These data indicated that HPTQ ameliorates the hippocampus apoptosis in diabetic cognitive dysfunction mice by activating CREB/BDNF/TrkB signaling pathway.
Keywords	Other systems of medicine ; RZ201-999
Subject code	616
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Shi's Yi-Qi Bu-Shen Tong-Luo decoction combined with manipulation in the management of wrist stiffness after distal radius fracture: Study protocol clinical trial (SPIRIT Compliant).

Wu, Hai-Yang / Wang, Yi-Ru / Gui, Jing / Wen, Guo-Wei / Tang, Zhen-Yin / Liu, Ping / Wu, Jun-Hao

Medicine

2020 Volume 99, Issue 9, Page(s) e19308

Abstract: ... rehabilitation after distal radius fracture. Shi's Yi-Qi Bu-Shen Tong-Luo decoction (BTD) combined with wrist ...

Abstract	Introduction: Wrist stiffness is a common sequela of distal radial fractures. Manipulation is generally used and effective, but problems exist, such as intense pain, swelling during the process of manipulation and long treatment period. Therefore, a combinative therapeutic strategy is necessary to benefit rehabilitation after distal radius fracture. Shi's Yi-Qi Bu-Shen Tong-Luo decoction (BTD) combined with wrist manipulation has been used in the Shanghai Ninth People's Hospital Huangpu Branch in last few decades. BTD has potential therapeutic effects on rehabilitation after distal radius fracture, which should be evaluated by rigorous clinical trial. Methods/design: A randomized, double-blind, placebo-controlled clinical trial will be conducted to determine the efficiency of BTD in relief of wrist stiffness and pain and function rehabilitation. A total of 80 wrist stiffness patients with or without pain and edema will be enrolled, and treated with wrist manipulation plus BTD or placebo for 4 weeks. The primary outcome measure is the Cooney wrist score. The second outcome measures include pain numerical rating scale, patient rated wrist evaluation, 36-item short form health survey questionnaire, and side effects. Discussion: Although BTD has shown effects on rehabilitation after distal radius fracture in the Shanghai Ninth People's Hospital Huangpu Branch for decades, the universality of this efficacy needs evaluated. The results of this trial will provide a convincing evidence. Trial registration: ChiCTR2000029260, January 19, 2020.
MeSH term(s)	Adult ; China ; Drugs, Chinese Herbal/standards ; Drugs, Chinese Herbal/therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Physical Therapy Modalities/standards ; Physical Therapy Modalities/statistics & numerical data ; Radius Fractures/complications ; Radius Fractures/therapy ; Surveys and Questionnaires ; Treatment Outcome ; Wrist Joint/abnormalities ; Wrist Joint/physiology
Chemical Substances	Drugs, Chinese Herbal ; yi-qi-bu-shen
Language	English
Publishing date	2020-02-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000019308
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Book: Zhongguo zhen jiu jiao liu tong jian

Guo, Yi

2012

Author's details	fen juan zhu bian Guo Yi
MeSH term(s)	Acupuncture/education ; Acupuncture/history ; International Cooperation
Language	Chinese
Size	18, 3, 362 pages :, illustrations, portraits
Edition	Di 1 ban.
Document type	Book
ISBN	9787560545998 ; 7560545998
Database	Catalogue of the US National Library of Medicine (NLM)

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Article ; Online: Traditional Chinese medicine (Shun-Qi-Tong-Xie Granule) for irritable bowel syndrome: study protocol for a randomised controlled trial.

Wang, Xiao-xiang / Luo, Rui-jie / She, Bin / Chen, Yan / Guo, Jia

Trials

2014 Volume 15, Page(s) 273

Abstract: ... complementary therapies in China. We designed this study to evaluate the efficacy and safety of Shun-Qi-Tong-Xie Granule ...

Abstract	Background: Irritable bowel syndrome (IBS) is a common gastrointestinal functional disorder with no effective therapy. Traditional Chinese medicine (TCM) is one of the most common complementary therapies in China. We designed this study to evaluate the efficacy and safety of Shun-Qi-Tong-Xie Granule (SQTX Granule), a TCM treatment, in patients with IBS with diarrhea (IBS-D). Methods/design: A randomised, double-blinded, placebo-controlled, multi-centre, superiority clinical trial to evaluate the efficacy and safety of SQTX Granule is proposed. Eligible patients (Rome III) with IBD-S will be randomly assigned into SQTX Granule group and the placebo group. Patients will receive a 28-day treatment and a 2-month follow-up. The primary outcome measures include the scores of IBS-quality of life (IBS-QOL) rating scale and IBS-symptom severity scale (IBS-SSS) rating scale. The secondary outcome measures include the improvement of symptom scores, and the duration of abdominal pain and diarrhea. Discussion: According to TCM theory, SQTX Granule has a regulating effect on abdominal pain, diarrhea and the syndrome of liver-spleen disharmony, which is similar to the symptoms of IBS-D. This study will provide objective evidence to evaluate the efficiency and safety of SQTX Granule in IBS-D treatment. Trial registration: ChiCTR-TRC-14004241. Date of registration: 9 February 2014.
MeSH term(s)	Abdominal Pain/drug therapy ; Abdominal Pain/etiology ; Administration, Oral ; Clinical Protocols ; Diarrhea/drug therapy ; Diarrhea/etiology ; Double-Blind Method ; Drugs, Chinese Herbal/administration & dosage ; Drugs, Chinese Herbal/adverse effects ; Drugs, Chinese Herbal/therapeutic use ; Humans ; Irritable Bowel Syndrome/complications ; Irritable Bowel Syndrome/diagnosis ; Irritable Bowel Syndrome/drug therapy ; Medicine, Chinese Traditional ; Phytotherapy ; Plants, Medicinal ; Quality of Life ; Research Design ; Time Factors ; Treatment Outcome
Chemical Substances	Drugs, Chinese Herbal ; shun-qi-tong-xie
Language	English
Publishing date	2014-07-07
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2040523-6
ISSN	1745-6215 ; 1468-6694 ; 1468-6708
ISSN (online)	1745-6215 ; 1468-6694
ISSN	1468-6708
DOI	10.1186/1745-6215-15-273
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