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author:("Lao, mixing")
2.  Imaging Neurodegenerative Diseases: Mechanisms and Interventions 
BioMed Research International  2014;2014:419317.
doi:10.1155/2014/419317
PMCID: PMC4283430  PMID: 25587534
4.  DAMGO in the central amygdala alleviates the affective dimension of pain in a rat model of inflammatory hyperalgesia 
Neuroscience  2013;252:10.1016/j.neuroscience.2013.08.030.
Pain has sensory-discriminative and emotional-affective dimensions. Recent studies show that the affective component can be assessed with a conditioned place avoidance (CPA) test. We hypothesized that systemic morphine before a post-conditioning test would more potently attenuate the affective aspect compared to the sensory component and that DAMGO, a μ-selective opioid receptor agonist, injected into the central nucleus of the amygdala (CeA) would reduce established CPA. A rat model of inflammatory pain, produced by a complete Freund adjuvant (CFA) injection into the hind paw, was combined with a CPA test. Three experiments were performed on adult male Sprague-Dawley rats. Systemic morphine (0.5 or 1.0 mg/kg) in Experiment 1, intrathecal (i.t.) morphine (2.5 μg/rat) in Experiment 2, and intra-CeA DAMGO (7.7-15.4 ng/0.4μl) in Experiment 3 were given to CFA-injected rats (n=6-8/group) prior to a post-conditioning test. Saline-injected rats were used as control. Time spent in a pain-paired compartment was recorded twice, before conditioning and after a post-conditioning test. Paw withdrawal latency (PWL) to a noxious thermal stimulus was measured before experiment at day −1 and after the post-conditioning test; hyperalgesia was defined as a decrease in PWL. The data showed that CFA-injected rats had significantly negative CPA compared to those of saline-injected rats (P<0.05). Low dosage systemic morphine significantly (P<0.05) reduced CFA-induced CPA but had no effect on PWL. I.t. morphine did not inhibit the display of CPA but significantly increased PWL, suppressing hyperalgesia (P<0.05). Intra-CeA DAMGO significantly inhibited the display of CPA compared to saline (P<0.05) but had no effect on PWL. The data demonstrates that morphine attenuates the affective component more powerfully than it does the sensory and suggests that the sensory and the emotional-affective dimensions are underpinned by different mechanisms.
doi:10.1016/j.neuroscience.2013.08.030
PMCID: PMC3864641  PMID: 23994597
Conditioned place avoidance; pain; opioid; amygdala; spinal cord; hyperalgesia
5.  The effects of acupuncture on rates of clinical pregnancy among women undergoing in vitro fertilization: a systematic review and meta-analysis 
Human Reproduction Update  2013;19(6):696-713.
BACKGROUND
Recent systematic reviews of adjuvant acupuncture for IVF have pooled heterogeneous trials, without examining variables that might explain the heterogeneity. The aims of our meta-analysis were to quantify the overall pooled effects of adjuvant acupuncture on IVF clinical pregnancy success rates, and evaluate whether study design-, treatment- and population-related factors influence effect estimates.
METHODS
We included randomized controlled trials that compared needle acupuncture administered within 1 day of embryo transfer, versus sham acupuncture or no adjuvant treatment. Our primary outcome was clinical pregnancy rates. We obtained from all investigators additional methodological details and outcome data not included in their original publications. We analysed sham-controlled and no adjuvant treatment-controlled trials separately, but since there were no large or significant differences between these two subsets, we pooled all trials for subgroup analyses. We prespecified 11 subgroup variables (5 clinical and 6 methodological) to investigate sources of heterogeneity, using single covariate meta-regressions.
RESULTS
Sixteen trials (4021 participants) were included in the meta-analyses. There was no statistically significant difference between acupuncture and controls when combining all trials [risk ratio (RR) 1.12, 95% confidence interval (CI), 0.96–1.31; I2 = 68%; 16 trials; 4021 participants], or when restricting to sham-controlled (RR 1.02, 0.83–1.26; I2 = 66%; 7 trials; 2044 participants) or no adjuvant treatment-controlled trials (RR 1.22, 0.97–1.52; I2 = 67%; 9 trials; 1977 participants). The type of control used did not significantly explain the statistical heterogeneity (interaction P = 0.27). Baseline pregnancy rate, measured as the observed rate of clinical pregnancy in the control group of each trial, was a statistically significant effect modifier (interaction P < 0.001), and this covariate explained most of the heterogeneity of the effects of adjuvant acupuncture across all trials (adjusted R2 = 93%; I2 residual = 9%). Trials with lower control group rates of clinical pregnancy showed larger effects of adjuvant acupuncture (RR 1.53, 1.28–1.84; 7 trials; 1732 participants) than trials with higher control group rates of clinical pregnancy (RR 0.90, 0.80–1.01; 9 trials; 2289 participants). The asymmetric funnel plot showed a tendency for the intervention effects to be more beneficial in smaller trials.
CONCLUSIONS
We found no pooled benefit of adjuvant acupuncture for IVF. The subgroup finding of a benefit in trials with lower, but not higher, baseline pregnancy rates (the only statistically significant subgroup finding in our earlier review) has been confirmed in this update, and was not explained by any confounding variables evaluated. However, this baseline pregnancy rate subgroup finding among published trials requires further confirmation and exploration in additional studies because of the multiple subgroup tests conducted, the risk of unidentified confounders, the multiple different factors that determine baseline rates, and the possibility of publication bias.
doi:10.1093/humupd/dmt026
PMCID: PMC3796945  PMID: 23814102
acupuncture; assisted conception; complementary medicine; in vitro fertilization; systematic review
7.  Acupuncture Induces Time-Dependent Remodelling Brain Network on the Stable Somatosensory First-Ever Stroke Patients: Combining Diffusion Tensor and Functional MR Imaging 
Different treatment interventions induce distinct remodelling of network architecture of entire motor system. Acupuncture has been proved to be of a promising efficacy in motor recovery. However, it is still unclear whether the reorganization of motor-related brain network underlying acupuncture is related with time since stroke and severity of deficit at baseline. The aim of study was to characterize the relation between motor-related brain organization following acupuncture and white matter microstructural changes at an interval of two weeks. We demonstrated that acupuncture induced differential reorganization of motor-related network for stroke patients as time-lapse since stroke. At the baseline, acupuncture can induce the increased functional connectivity between the left primary motor cortex (M1) and the right M1, premotor cortex, supplementary motor area (SMA), thalamus, and cerebellum. After two-week recovery, the increased functional connectivity of the left M1 was more widely distributed and primarily located in the insula, cerebellum, basal ganglia, and SMA. Furthermore, a significant negative relation existed between the FA value in the left M1 at the baseline scanning and node centrality of this region following acupuncture for both baseline and two-week recovery. Our findings may shed a new insight on understanding the reorganization of motor-related theory underlying motor impairments after brain lesions in stroke patients.
doi:10.1155/2014/740480
PMCID: PMC4101930  PMID: 25101136
8.  Effectiveness of moxibustion treatment as adjunctive therapy in osteoarthritis of the knee: a randomized, double-blinded, placebo-controlled clinical trial 
Arthritis Research & Therapy  2014;16(3):R133.
Introduction
Our objective was to compare the effectiveness and safety of traditional Chinese moxibustion to that of sham moxibustion in patients with chronic knee osteoarthritis (KOA) pain.
Methods
We conducted a randomized placebo-controlled trial involving 110 patients with KOA who met the inclusion criteria. These patients randomly received either active moxibustion (n = 55) or sham moxibustion control (n = 55) at acupoints Dubi (ST 35), extra-point Neixiyan (EX-LE 4), and an Ashi (tender) point three times a week for 6 weeks. Effects were evaluated with Western Ontario and McMaster Universities’ Osteoarthritis Index (WOMAC VA 3.1) criteria at the end of the course of treatment and 3, 12, and 24 weeks after the initial treatment.
Results
The WOMAC pain scores showed greater improvement in the active treatment group than in control at weeks 3 (P = 0.012), 6 (P <0.001), 12 (P = 0.002), and 24 (P = 0.002) as did WOMAC physical function scores of the active treatment group at week 3 (P = 0.002), 6 (P = 0.015), and 12 (P <0.001) but not 24 (P = 0.058). Patients and practitioners were blinded successfully, and no significant adverse effects were found during the trial.
Conclusions
A 6-week course of moxibustion seems to relieve pain effectively and improve function in patients with KOA for up to 18 weeks after the end of treatment. Moxibustion treatment appears to be safe, and the usefulness of the novel moxa device was validated.
Trial registration
Current controlled trial: ISRCTN68475405. Registered 4 April 2014.
doi:10.1186/ar4590
PMCID: PMC4095686  PMID: 24962039
9.  Preliminary Study on Pain Reduction of Monosodium Iodoacetate-Induced Knee Osteoarthritis in Rats by Carbon Dioxide Laser Moxibustion 
In order to study the effects of CO2 laser moxibustion on the pain and inflammatory cytokine expression in the spinal dorsal horn of rats with monosodium iodoacetate- (MIA-) induced knee osteoarthritis (KOA), we designed an experiment by randomly assigning 8 SD rats into 3 groups, namely, a CO2 laser moxibustion group, a sham treatment group, and a blank control group. The treatment group received a laser moxibustion on acupoint Dubi (ST 35; 5 min/treatment, 1 treatment/day) for 8 days, and after treatment, the rats exhibited significantly increased interhindpaw differences compared with their preinduction values. Meanwhile, cytokine microarray analysis showed that one cytokine (TIMP-1) was significantly upregulated and two cytokines (Agrin and MMP-8) were significantly downregulated in treatment group. The present study suggested that CO2 laser moxibustion created certain pain reduction in the rats with MIA-induced KOA and significantly inhibited the expression of most inflammatory cytokines in the ipsilateral spinal dorsal horn.
doi:10.1155/2014/754304
PMCID: PMC4074960  PMID: 25013448
10.  Effectiveness guidance document (EGD) for Chinese medicine trials: a consensus document 
Trials  2014;15:169.
Background
There is a need for more Comparative Effectiveness Research (CER) on Chinese medicine (CM) to inform clinical and policy decision-making. This document aims to provide consensus advice for the design of CER trials on CM for researchers. It broadly aims to ensure more adequate design and optimal use of resources in generating evidence for CM to inform stakeholder decision-making.
Methods
The Effectiveness Guidance Document (EGD) development was based on multiple consensus procedures (survey, written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders, including patients, clinicians, researchers and payers were involved in creating this document.
Results
Recommendations were developed for “using available data” and “future clinical studies”. The recommendations for future trials focus on randomized trials and cover the following areas: designing CER studies, treatments, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication.
Conclusion
The present EGD provides the first systematic methodological guidance for future CER trials on CM and can be applied to single or multi-component treatments. While CONSORT statements provide guidelines for reporting studies, EGDs provide recommendations for the design of future studies and can contribute to a more strategic use of limited research resources, as well as greater consistency in trial design.
doi:10.1186/1745-6215-15-169
PMCID: PMC4045891  PMID: 24885146
Comparative effectiveness research; Effectiveness guidance document; Chinese medicine research
12.  Effectiveness Study of Moxibustion on Pain Relief in Primary Dysmenorrhea: Study Protocol of a Randomized Controlled Trial 
Dysmenorrhea is a prevalent problem in menstruating women. As a nonpharmacologic and free of relevant side effects intervention, moxibustion is considered as a safe treatment and has long been recommended for dysmenorrhea in China. However, the exact effects of moxibustion in PD have not been fully understood. Therefore we designed this random clinical trial aiming to (1) investigate whether moxibustion is safe and effective for pain relief in primary dysmenorrhea when compared to conventional pain-killers and (2) assess the acceptability and side effects associated with moxibustion. The results of this trial will contribute to a better understanding of the different effects of moxibustion in pain relief in primary dysmenorrhea when compared to conventional pharmacologic pain treatment.
doi:10.1155/2014/434978
PMCID: PMC3996889  PMID: 24803947
13.  Acupuncture for Essential Hypertension: A Meta-Analysis of Randomized Sham-Controlled Clinical Trials 
Background. Acupuncture is frequently advocated as an adjunct treatment for essential hypertension. The aim of this review was to assess its adjunct effectiveness in treating hypertension. Methods. We searched PubMed, the Cochrane Library, EMBASE, and the Chinese databases Sino-Med, CNKI, WanFang, and VIP through November, 2012, for eligible randomized controlled trials that compared acupuncture with sham acupuncture. Outcome measures were changes in diastolic (DBP) and systolic blood pressure (SBP). Results. A total of 4 randomized controlled trials were included. We found no evidence of an improvement with the fact that acupuncture relative to sham acupuncture in SBP change (n = 386; mean difference = −3.80 mmHg, 95% CI = −10.03–2.44 mmHg; I2 = 99%), and an insignificant improvement in DBP change (n = 386; mean difference = −2.82 mmHg, 95% CI = −5.22–(−0.43) mmHg; I2 = 97%). In subgroup analyses, acupuncture significantly improved both SBP and DBP in patients taking antihypertensive medications. Only minor acupuncture-related adverse events were reported. Conclusions. Our results are consistent with acupuncture significantly lowers blood pressure in patients taking antihypertensive medications. We did not find that acupuncture without antihypertensive medications significantly improves blood pressure in those hypertensive patients.
doi:10.1155/2014/279478
PMCID: PMC3960742  PMID: 24723957
15.  Spinal interleukin-17 promotes thermal hyperalgesia and NMDA NR1 phosphorylation in an inflammatory pain rat model 
Pain  2012;154(2):294-305.
It is known that interleukin-17 (IL-17) is associated with autoimmune disorders and that peripheral IL-17 plays a role in arthritis and neuropathic pain. The present study investigated the possibility of spinal cell expression of IL-17 during inflammatory pain and possible IL-17 involvement in such pain. Hyperalgesia was induced by injecting complete Freund’s adjuvant (CFA, 0.08 ml, 40 μg Mycobacterium tuberculosis) into one hind paw of the rat. Paw withdrawal latency (PWL) was tested before (−48 h) and 2 and 24 h after CFA to assess hyperalgesia. IL-17 antibody (0.2–2 μg/rat) was given intrathecally (i.t.) 24 h before CFA to block the action of basal IL-17 and 2 h prior to each of two PWL tests to block CFA-induced IL-17. I.t. recombinant IL-17 (10–400 ng/rat) was administered to naive rats to determine its effects on PWL and phosphorylated-NR1 (p-NR1). P-NR1 modulates N-methyl-D-aspartate receptor (NMDAR) activity to facilitate pain. Spinal cords were removed for IL-17 immunostaining, double immunostaining of IL-17/cell markers and IL-17 receptor A (IL-17RA)/NR1, for western blot of IL-17, p-NR1, IL-17RA, and GFAP, for in situ IL-17RA hybridization, and for real time PCR of IL-17RA. The data shows that 1) IL-17 is up-regulated in activated and non-activated astrocytes, 2) IL-17RA is localized in NR1-immunoreactive neurons and up-regulated, and 3) IL-17 antibody at 2 μg/rat significantly increased PWL (P<0.05) and decreased p-NR1 and IL-17RA compared to control in CFA- and IL-17-injected rats. The results suggest that spinal IL-17 is produced by astrocytes and enhances p-NR1 to facilitate pain.
doi:10.1016/j.pain.2012.10.022
PMCID: PMC3563420  PMID: 23246025
Interleukin-17; spinal cord; glial cells; hyperalgesia; inflammation; pain
16.  Personalized Medicine and Opioid Analgesic Prescribing for Chronic Pain: Opportunities and Challenges 
Use of opioid analgesics for pain management has increased dramatically over the past decade, with corresponding increases in negative sequelae including overdose and death. There is currently no well-validated objective means of accurately identifying patients likely to experience good analgesia with low side effects and abuse risk prior to initiating opioid therapy. This paper discusses the concept of data-based personalized prescribing of opioid analgesics as a means to achieve this goal. Strengths, weaknesses, and potential synergism of traditional randomized placebo-controlled trial (RCT) and practice-based evidence (PBE) methodologies as means to acquire the clinical data necessary to develop validated personalized analgesic prescribing algorithms are overviewed. Several predictive factors that might be incorporated into such algorithms are briefly discussed, including genetic factors, differences in brain structure and function, differences in neurotransmitter pathways, and patient phenotypic variables such as negative affect, sex, and pain sensitivity. Currently available research is insufficient to inform development of quantitative analgesic prescribing algorithms. However, responder subtype analyses made practical by the large numbers of chronic pain patients in proposed collaborative PBE pain registries, in conjunction with follow-up validation RCTs, may eventually permit development of clinically useful analgesic prescribing algorithms.
Perspective
Current research is insufficient to base opioid analgesic prescribing on patient characteristics. Collaborative PBE studies in large, diverse pain patient samples in conjunction with follow-up RCTs may permit development of quantitative analgesic prescribing algorithms which could optimize opioid analgesic effectiveness, and mitigate risks of opioid-related abuse and mortality.
doi:10.1016/j.jpain.2012.10.016
PMCID: PMC3564046  PMID: 23374939
Opioid analgesics; chronic pain; personalized medicine; side effects; opioid abuse
18.  Topical treatment with Tong-Luo-San-Jie Gel alleviates bone cancer pain in rats 
Journal of ethnopharmacology  2012;143(3):905-913.
Ethnopharmacological relevance
The herbal analgesic gel Tong-Luo-San-Jie (TLSJ) and its modifications are used in traditional Chinese medicine to manage cancer pain. However, its mechanisms are still unknown.
Aim of the study
To investigate the effects and mechanisms of TLSJ gel on bone cancer pain in a rat model.
Materials and Methods
A bone cancer pain rat model was established by inoculating Walker 256 rat carcinoma cells directly into the right tibial medullary cavity of Sprague-Dawley rats (150–170 g); Phosphate buffered saline (PBS) tibial inoculation was used as control. Cancer-bearing rats were treated twice a day with external TLSJ gel (0.5 g/cm2/day) or inert gel control for 21 days (n=10/group). Behavioral tests such as mechanical threshold and paw withdrawal latency (PWL) were carried out. Osteoclastic activities were determined and carboxyterminal pyridinoline cross-linked type I collagen telopeptides (ICTP) and bone-specific alkaline phosphatase (BAP) concentrations were detected with ELISA after treatment. Adverse effects were monitored, and biochemical and histological tests were performed in naïve rats treated with local TLSJ gel for six weeks.
Results
TLSJ treatment significantly restored bone cancer-induced decrease of PWL and mechanical threshold compared to inert gel. It also decreased the level of blood serum ICTP and BAP and inhibited osteoclast activities. No adverse effects or abnormal biochemical and histological changes were detected after TLSJ treatment.
Conclusion
The present study shows that TLSJ significantly inhibits bone cancer-induced thermal and mechanical sensitization. It suggests that the gel may be useful in managing cancer pain and that it may act by inhibiting osteoclastic activity.
doi:10.1016/j.jep.2012.08.026
PMCID: PMC3498764  PMID: 22960543
Chinese herbs; bone cancer pain; Tong-Luo-San-Jie (TLSJ) gel; type I collagen carboxy- terminal telopeptide; bone-specific alkaline phosphatase; osteoclast
19.  Patterns of Traditional Chinese Medicine Diagnosis in Thermal Laser Acupuncture Treatment of Knee Osteoarthritis 
Knee osteoarthritis (OA) manifests with pain, joint stiffness, and limited function. In traditional Chinese medicine, knee OA is differentiated into three patterns: yang deficiency and cold coagulation, kidney deficiency, and blood stasis. The objective of this study was to determine whether yang deficiency cold coagulation patients respond better to thermal laser acupuncture treatment than do non-yang deficient patients. Fifty-two patients with OA were allocated to group A (yang deficient, n = 26) or B (non-yang deficient, n = 26). All patients received a 20-min thermal laser acupuncture treatment at acupoint Dubi (ST 35) three times a week for two weeks and twice a week for another four weeks. Outcome assessments were performed immediately after the first treatment, and at weeks 2, 6, and 10. Group A function scores were significantly better than those of Group B at weeks 2 (P = 0.049), 6 (P = 0.046), and 10 (P = 0.042), but no significant differences were found between the two groups in pain and stiffness scores at any time point. No significant adverse effect was observed. The combined 10.6 μm–650 nm laser treatment might be most beneficial to yang deficiency cold coagulation knee OA patients, particularly in improving function.
doi:10.1155/2013/870305
PMCID: PMC3771475  PMID: 24069060
20.  Preclinical safety evaluation of the aqueous acetone extract of Chinese herbal formula Modified Huo Luo Xiao Ling Dan 
Objective
To investigate the safety of oral administration of Modified Huo Luo Xiao Ling Dan (HLXLD), a compound traditional Chinese herbal medicine.
Methods
The toxicological information of HLXLD and its individual constituent herbs was searched in cintcm or TCMlars (www.cintcm.com), PubMed (MEDLINE), Chinese Herbal Medicine (1999) and WHO Monographs on Selected Medicinal Plants (Vol. I—III). Single-dose acute toxicity was assessed by using the highest possible dosage. Motor function test was used to determine whether the herbal formula might cause motor impairment. Nine-day HLXLD repeat-dose sub-chronic toxicity/adverse effects, and 42-day chronic toxicity/adverse effects in rats were also assessed.
Results
The literature searches showed that HLXLD and its eleven ingredient herbs had no side/adverse effects listed in the traditional Chinese medicine literature. Under the dosages proposed in the formula, the HLXLD formula had no side/adverse effects according to MEDLINE, Chinese Herbal Medicine and WHO Monographs on Selected Medicinal Plants. The studies in rats showed: (1) in single-dose acute toxicity assessment, the maximal feasible single oral dose, 9.20 g/kg HLXLD, showed no significant effect on clinical signs, or body weight and mortality over a 14-day period in rats; (2) during motor function test, nine-day repeat-dose of daily HLXLD treatment at 4.60 g/kg did not cause motor impairment; (3) in nine-day HLXLD repeat-dose sub-chronic toxicity/adverse effects assessment, there were no noticeable abnormal behavioral changes or obvious adverse reactions and signs in complete Freund's adjuvant inflamed rats (highest observed dosage: 4.60 g/kg), and no noticeable adverse effects were observed during, or 14 days after nine-day treatment at 4.60 g/kg in non-inflamed rats; (4) during 42-day chronic toxicity/adverse effects assessments, no noticeable abnormal behavioral changes, no obvious adverse reactions and signs were observed in normal rats administered with HLXLD at a dose of 2.30 g/kg and the values of serum biochemistry and histopathology were in normal range.
Conclusion
Both existing information and animal data support that Modified HLXLD is a safe herbal product for clinical application.
PMCID: PMC3739922  PMID: 20456842
Chinese herb formula; Modified Huo Luo Xiao Ling Dan; Safety; Literature investigation; Acute toxicity tests; Motor function; Sub-acute toxicity; Chronic toxicity tests; Rats
21.  Acupuncture for treatment of irritable bowel syndrome 
Background
Irritable bowel syndrome (IBS) is a common, costly, and difficult to treat disorder that impairs health-related quality of life and work productivity. Evidence-based treatment guidelines have been unable to provide guidance on the effects of acupuncture for IBS because the only previous systematic review included only small, heterogeneous and methodologically unsound trials.
Objectives
The primary objectives were to assess the efficacy and safety of acupuncture for treating IBS.
Search methods
MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Cumulative Index to Nursing and Allied Health, and the Chinese databases Sino-Med, CNKI, and VIP were searched through November 2011.
Selection criteria
Randomized controlled trials (RCTs) that compared acupuncture with sham acupuncture, other active treatments, or no (specific) treatment, and RCTs that evaluated acupuncture as an adjuvant to another treatment, in adults with IBS were included.
Data collection and analysis
Two authors independently assessed the risk of bias and extracted data. We extracted data for the outcomes overall IBS symptom severity and health-related quality of life. For dichotomous data (e.g. the IBS Adequate Relief Question), we calculated a pooled relative risk (RR) and 95% confidence interval (CI) for substantial improvement in symptom severity after treatment. For continuous data (e.g. the IBS Severity Scoring System), we calculated the standardized mean difference (SMD) and 95% CI in post-treatment scores between groups.
Main results
Seventeen RCTs (1806 participants) were included. Five RCTs compared acupuncture versus sham acupuncture. The risk of bias in these studies was low.We found no evidence of an improvement with acupuncture relative to sham (placebo) acupuncture for symptom severity (SMD-0.11, 95%CI −0.35 to 0.13; 4 RCTs; 281 patients) or quality of life (SMD = −0.03, 95%CI −0.27 to 0.22; 3 RCTs; 253 patients). Sensitivity analyses based on study quality did not change the results. A GRADE analysis indicated that the overall quality of the evidence for the primary outcomes in the sham controlled trials was moderate due to sparse data. The risk of bias in the four Chinese language comparative effectiveness trials that compared acupuncture with drug treatment was high due to lack of blinding. The risk of bias in the other studies that did not use a sham control was high due to lack of blinding or inadequate methods used for randomization and allocation concealment or both. Acupuncture was significantly more effective than pharmacological therapy and no specific treatment. Eighty-four per cent of patients in the acupuncture group had improvement in symptom severity compared to 63% of patients in the pharmacological treatment group (RR 1.28, 95% CI 1.12 to 1.45; 5 studies, 449 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to a high risk of bias (no blinding) and sparse data. Sixty-three per cent of patients in the acupuncture group had improvement in symptom severity compared to 34% of patients in the no specific therapy group (RR 2.11, 95% CI 1.18 to 3.79; 2 studies, 181 patients). There was no statistically significant difference between acupuncture and Bifidobacterium (RR 1.07, 95% CI 0.90 to 1.27; 2 studies; 181 patients) or between acupuncture and psychotherapy (RR 1.05, 95% CI 0.87 to 1.26; 1 study; 100 patients). Acupuncture as an adjuvant to another Chinese medicine treatment was significantly better than the other treatment alone. Ninety-three per cent of patients in the adjuvant acupuncture group improved compared to 79% of patients who received Chinese medicine alone (RR 1.17, 95% CI 1.02 to 1.33; 4 studies; 466 patients). There was one adverse event (i.e. acupuncture syncope) associated with acupuncture in the 9 trials that reported this outcome, although relatively small sample sizes limit the usefulness of these safety data.
Authors’ conclusions
Sham-controlled RCTs have found no benefits of acupuncture relative to a credible sham acupuncture control for IBS symptom severity or IBS-related quality of life. In comparative effectiveness Chinese trials, patients reported greater benefits from acupuncture than from two antispasmodic drugs (pinaverium bromide and trimebutine maleate), both of which have been shown to provide a modest benefit for IBS. Future trials may help clarify whether or not these reportedly greater benefits of acupuncture relative to pharmacological therapies are due entirely to patients’ preferences for acupuncture or greater expectations of improvement on acupuncture relative to drug therapy.
doi:10.1002/14651858.CD005111.pub3
PMCID: PMC3718572  PMID: 22592702
*Acupuncture Therapy; Irritable Bowel Syndrome [*therapy]; Randomized Controlled Trials as Topic; Humans
22.  Characterizing Acupuncture De Qi in Mild Cognitive Impairment: Relations with Small-World Efficiency of Functional Brain Networks 
As an intermediate state between normal aging and dementia, mild cognitive impairment (MCI) became a hot topic and early treatments can improve disease prognosis. Acupuncture is shown to have possible effect in improving its cognitive defect. However, the underlying neural mechanism of acupuncture and relations between De Qi and different needling depths are still elusive. The present study aimed to explore how acupuncture can exert effect on the reorganization of MCI and to what extent needling depths, associating with De Qi sensations, can influence the acupuncture effects for MCI treatment. Our results presented that MCI patients exhibited losses of small-world attributes indicated by longer characteristic path lengths and larger clustering coefficients, compared with healthy controls. In addition, acupuncture with deep needling can induce much stronger and a wide range of De Qi sensations both in intensity and prevalence. Acupuncture with deep needling showed modulatory effect to compensate the losses of small-world attributes existed in MCI patients while acupuncture with superficial needling did not. Furthermore, acupuncture with deep needling enhanced the nodal centrality primarily in the abnormal regions of MCI including the hippocampus, postcentral cortex as well as anterior cingulate cortex. This study provides evidence to understand neural mechanism underlying acupuncture and the key role of De Qi for MCI treatment.
doi:10.1155/2013/304804
PMCID: PMC3725922  PMID: 23935659
23.  The efficacy and safety study of electro-acupuncture for severe chronic functional constipation: study protocol for a multicenter, randomized, controlled trial 
Trials  2013;14:176.
Background
Previous research has shown that electro-acupuncture (EA) may be effective for functional constipation. We report a protocol for a randomized controlled trial using EA to confirm the efficacy and safety for severe chronic functional constipation.
Methods/design
This is a randomized, controlled trial. A total of 1,034 patients will be randomly allocated into the EA group (n=517) and the sham EA group (n=517). The EA group receives needling at ST25, SP14 and ST37 and the sham EA group receives needling at sham ST25, SP14 and ST37. The primary outcome measure is the changed number of weekly average complete spontaneous bowel movements(CSBMs) during 8 weeks of treatment, compared with baseline. The secondary outcome measures are: 1) the proportion of participants having three or more CSBMs on average per week; 2) the changed number of weekly average CSBMs during weeks 9 to 20; 3) the changed number of weekly average spontaneous bowel movements during 8 weeks of treatment; 4) stool consistency; 5) degree of difficulty in defecation; 6) patient assessment of constipation quality of life questionnaire (PAC-QOL); 7) incidence of adverse events; and 8) usage of medicine for constipation.
Discussion
This trial will evaluate the efficacy and safety of EA for severe chronic functional constipation.
Trial registration
Protocol Registration System of ClinicalTrial.gov, NCT01726504
doi:10.1186/1745-6215-14-176
PMCID: PMC3706209  PMID: 23768191
Chronic functional constipation; Electro-acupuncture; Multicenter RCT; Efficacy; Safety
24.  Acupuncture for irritable bowel syndrome: systematic review and meta-analysis 
Objective
Evidence-based treatment guidelines have been unable to provide evidence-based guidance on the effects of acupuncture for irritable bowel syndrome (IBS) because the only previous systematic review included only small, heterogeneous and methodologically unsound trials. We conducted a new systematic review and meta-analysis of randomized controlled trials (RCTs) to estimate the effects of acupuncture for treating IBS.
Methods
MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, Cumulative Index to Nursing and Allied Health, and the Chinese databases Sino-Med, CNKI, and VIP were searched through November 2011. Eligible RCTs compared acupuncture with sham acupuncture, other active treatments, or no (specific) treatment, and evaluated acupuncture as an adjuvant to another treatment. Our outcomes were overall IBS symptom severity and health-related quality of life. Dichotomous data were pooled to provide a relative risk (RR) of substantial improvement after treatment, and continuous data were pooled to provide a standardized mean difference (SMD) in post-treatment scores between groups.
Results
Seventeen RCTs (N=1806) were included. We found no evidence of an improvement with acupuncture relative to sham acupuncture on symptom severity (SMD = −0.11, 95% confidence interval: −0.35 to 0.13; 4 RCTs) or quality of life (SMD = −0.03, −0.27 to 0.22; 3 RCTs). Because of the homogeneity of the results of the sham-controlled trials, results were unaffected by restriction to the 4 sham-controlled RCTs that used adequate randomization, blinding, and had few withdrawals/drop-outs. Among RCTs that did not use a placebo control, acupuncture was more effective than pharmacological therapy (RR of symptom improvement=1.28, 1.12 to 1.45; 5 RCTs) and no (specific) treatment (RR = 2.11, 1.18 to 3.79; 2 RCTs). There was no difference between acupuncture and Bifidobacterium (RR = 1.07, 0.90 to 1.27; 2 RCTs) or between acupuncture and psychotherapy (RR=1.05, 0.87 to 1.26; 1 RCT). Acupuncture as an adjuvant to another Chinese medicine treatment was statistically significantly better than the other treatment alone, in trials with a high risk of bias (RR = 1.17, 1.02 to 1.33; 4 RCTs).
Conclusions
Sham-controlled RCTs have found no benefits of acupuncture relative to a credible sham acupuncture control on IBS symptom severity or IBS-related quality of life. In comparative effectiveness Chinese trials, patients reported greater benefits from acupuncture than from pharmacological therapies. Future trials may help clarify whether or not these reportedly greater benefits of acupuncture relative to pharmacological therapies are due entirely to patients’ preferences for acupuncture or patients’ greater expectations of improvement on acupuncture relative to drugs.
doi:10.1038/ajg.2012.66
PMCID: PMC3671917  PMID: 22488079
25.  Acupuncture De Qi in Stable Somatosensory Stroke Patients: Relations with Effective Brain Network for Motor Recovery 
Acupuncture has been widely used for treating stroke and De Qi may play an important role. In spite of its acceptance, the neural mechanism underlying acupuncture for motor recovery is still elusive. Particularly, by what extent De Qi sensations can reliably predict the therapeutical acupuncture effect on the mediating recovery from stroke is urgent to investigate. Nine stroke patients were assessed by De Qi, neurological examination, and scanned with acupuncture stimuli across two time points at an interval of two weeks. And we adopted multivariate Granger causality analysis to explore the interregional influences within motor executive brain network during post-acupuncture resting state. Our findings indicated that acupuncture at GB34 can enhance the recovery of stroke mainly by strengthening causal influences between the ipsilesional and contralesional motor cortex. Moreover, centrality of some motor-related regions correlated with clinical variables and thus served as a predictor of stroke recovery. Along the same line, the centrality of these motor-related regions has also high relations with the De Qi sensation. Our findings suggest that De Qi having relatively stable reliability may be essential and used as a predictor to the therapeutic effectiveness of acupuncture for stroke recovery.
doi:10.1155/2013/197238
PMCID: PMC3684124  PMID: 23818921

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