Lin-Peng Wang

Factors contributing to therapeutic effects evaluated in acupuncture clinical trials

Acupuncture treatment has been widely used for many conditions, while results of the increasing numbers of randomized trials and systematic reviews remain controversial. Acupuncture is a complex intervention of both specific and non-specific factors associated with therapeutic benefit. Apart from needle insertion, issues such as needling sensation, psychological factors, acupoint specificity, acupuncture manipulation, and needle duration also have relevant influences on the therapeutic effects of acupuncture. Taking these factors into consideration would have considerable implications for the design and interpretation of clinical trials.

Immediate Analgesia Effect of Single Point Acupuncture in Primary Dysmenorrhea: A Randomized Controlled Trial

BACKGROUND Acupuncture is often used for primary dysmenorrhea. OBJECTIVE To assess the efficacy of a single point of acupuncture in the management of primary dysmenorrhea compared with sham acupuncture and no acupuncture. METHODOLOGY Patients with primary dysmenorrhea were randomly assigned to acupoint group (n=50), unrelated acupoint group (n=50), nonacupoint group (n=46), or no acupuncture group (n=48). Acupuncture and sham acupuncture were administered once-daily for 3 days with electro-acupuncture at Sanyinjiao (SP6) that was specifically designed to treat primary dysmenorrhea, or an unrelated acupoint (Xuanzhong, GB39), or nonacupoint location. The primary outcome was pain intensity as measured by a 100-mm visual analog scale (VAS) at baseline; 5, 10, 30, and 60 minutes following the start of the first intervention. Cox retrospective symptom scale (RSS), verbal rating scale (VRS), pain total time, and proportion of participants using analgesics were also recorded during three menstrual cycles. RESULTS The primary comparison of VAS scores demonstrated that patients receiving acupuncture (-15.56 mm, 95% CI -22.16 to -8.95, P<0.001), unrelated acupoint (-18.14 mm, 95% CI -24.81 to -11.47, P<0.001), and nonacupoint (-10.96 mm, 95% CI -17.62 to -4.30, P=0.001) treatment presented significant improvements compared with no acupuncture group. There were no significant differences among the four groups with respect to secondary outcomes. CONCLUSION Acupuncture was better than no acupuncture for relieving the pain of dysmenorrhea following a single point of acupuncture, but no differences were detected between acupoint acupuncture and unrelated acupoint acupuncture, acupoint acupuncture and nonacupoint acupuncture.

Acupuncture Effect and Central Autonomic Regulation

Acupuncture is a therapeutic technique and part of traditional Chinese medicine (TCM). Acupuncture has clinical efficacy on various autonomic nerve-related disorders, such as cardiovascular diseases, epilepsy, anxiety and nervousness, circadian rhythm disorders, polycystic ovary syndrome (PCOS) and subfertility. An increasing number of studies have demonstrated that acupuncture can control autonomic nerve system (ANS) functions including blood pressure, pupil size, skin conductance, skin temperature, muscle sympathetic nerve activities, heart rate and/or pulse rate, and heart rate variability. Emerging evidence indicates that acupuncture treatment not only activates distinct brain regions in different kinds of diseases caused by imbalance between the sympathetic and parasympathetic activities, but also modulates adaptive neurotransmitter in related brain regions to alleviate autonomic response. This review focused on the central mechanism of acupuncture in modulating various autonomic responses, which might provide neurobiological foundations for acupuncture effects.

Acupuncture for Chronic Severe Functional Constipation: A Randomized Trial

Chronic constipation affects approximately 16% of the worlds population (1), 17.1% of persons in Europe (2), 12% to 19% of those in North America (3), and 10.8% of those in Asia (1). Patients with severe chronic constipation have complete spontaneous bowel movements (CSBMs) no more than twice per week, with hard stools, frequent straining, and the sensation of incomplete evacuation (4). Most chronic constipation is functional and is associated with decreased quality of life (5). Laxatives produce only temporary relief, and constipation tends to reoccur after discontinuing medication (6, 7). Nearly half of patients are dissatisfied with their traditional therapies, such as laxatives (8). Other treatment options may include prokinetic agents. In a trial, 1 to 2 mg of prucalopride (an agonist for 5-hydroxytryptamine receptor 4) per day was reported to normalize BMs in 37.9% of patients with severe chronic constipation (9). However, the adverse cardiac effects induced by some prokinetic agents cannot be ignored (10), and their long-term effects remain unknown. A systematic review supports the use of acupuncture for chronic constipation (11), and our previous study indicates that electroacupuncture (EA) might have some sustained effects (12). However, the evidence for the therapeutic effects of acupuncture is limited because many randomized, controlled trials have had small sample sizes or other methodological limitations (11). Our goal was to determine the efficacy of EA for the treatment of chronic severe functional constipation (CSFC) over an 8-week treatment period and evaluate the maintenance of effects throughout the 12-week follow-up. We hypothesized that EA would be superior to sham EA (SA) at both end points. Methods Design Overview We conducted a multicenter, randomized, parallel, sham-controlled trial at 15 sites in China. The study duration per patient was 22 weeks: 2 weeks before randomization (baseline assessment); 8 weeks of treatment; and 12 weeks of follow-up without treatment. Researchers screened candidates for study participation, and experienced physicians at digestive or anorectal departments made diagnoses. Participants Participants were included if they met the diagnosis of functional constipation based on the Rome III diagnostic criteria for functional gastrointestinal disorders (13), had CSFC with 2 or fewer mean weekly CSBMs for more than 3 months, were aged between 18 and 75 years, had not taken constipation medication for a minimum of 2 weeks before enrollment except for rescue medicine (glycerol or sorbitol anal enema), had not received acupuncture for constipation, and had not participated in any other trial in the previous 3 months. The exclusion criteria were constipation caused by irritable bowel syndrome or drugs or that was secondary to endocrine, metabolic, neurologic, or postoperative diseases; severe cardiovascular, hepatic, or renal diseases; cognitive dysfunction, aphasia, mental disorders, or illness that could affect patient cooperation; pregnant or lactating women; abdominal aortic aneurysm or hepatosplenomegaly; blood coagulation disorders or regular anticoagulant use, including warfarin or heparin (an exception was antiplatelet treatment using aspirin or clopidogrel); and cardiac pacemaker implantation. Candidates signed informed consent. After the 2-week baseline assessment, eligible participants were randomly assigned and received their first treatment on the same day. The study was performed according to common guidelines for clinical trials (Declaration of Helsinki and International Conference on Harmonisation Good Clinical Practice E6 guidance). The study protocol (14) adhered to the Standards for Reporting Interventions in Clinical Trials of Acupuncture guidelines and was approved by the ethics committees of each responsible site. Randomization and Blinding Participants were allocated to the EA or SA group using stratified block randomization. The randomization sequences were generated by using PROC PLAN in SAS, version 9.4 (SAS Institute), with the study site as the stratification factor and the block length as 4. Acupuncturists obtained each patients random number and assignment through the central randomization system (Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences). All participants were treated separately to prevent communication. Except for acupuncturists, all relevant parties were blinded to the intervention (EA vs. SA) groups. Participants were informed that they had an equal chance of allocation to the EA or SA group before study participation. To test the success of blinding, we randomly selected 140 participants (70 from each group, with 9 to 10 participants at each site) for the blinding assessment; the acupuncturists asked them to guess whether they received EA or SA after treatments in weeks 4 and 8. Intervention Study interventions were developed by the consensus of acupuncture experts and per the results of our pilot study (Cai Y, Wu J, Liu Z. Electroacupuncture versus sham electroacupuncture for chronic severe functional constipation: a randomized controlled pilot study. 2012. Unpublished data.). Fifteen acupuncturists with 2 to 3 years of experience at the 15 sites administered the EA and SA treatments. All acupuncturists had at least a 5-year undergraduate education and were registered practitioners of traditional Chinese medicine. All research assistants and acupuncturists received a 2-day training session before study initiation. Both treatments consisted of 28 sessions, each for 30 minutes, and were administered over 8 weeks (5 sessions in each of the first 2 weeks, and 3 sessions in each of the remaining 6 weeks). Disposable needles (Huatuo) and the SDZ-V EA apparatus (Suzhou Medical Appliance) were used. Participants in the EA group received EA at the bilateral acupoints of Tianshu (ST25), Fujie (SP14), and Shangjuxu (ST37) (15). When participants were supine, 0.3050mm or 0.3575mm needles were inserted approximately 30 to 70 mm into ST25 and SP14 slowly and vertically, without manipulation, until they pierced the muscle layer of the abdominal wall. Paired alligator clips from the EA apparatus were attached transversely to the needle holders at bilateral ST25 and SP14. The EA stimulation lasted for 30 minutes with a dilatational wave of 10/50 Hz and a current intensity of 0.1 to 1 mA depending on the participants comfort level (preferably with skin around the acupoints shivering mildly without pain). In addition, 0.3040mm needles were inserted vertically about 30 mm into ST37 and 3 small, equal manipulations of twirling, lifting, and thrusting (once every 10 minutes) were performed to reach acupuncture de qia soreness, heaviness, and distension sensation when needling (16). Participants in the SA group received shallow needling at bilateral sham ST25, sham SP14, and sham ST37 (nonacupoints that were located at different physical locations than ST25, SP14, and ST37 for EA) (Supplement). Specifically, 0.3025mm needles were inserted vertically about 3 to 5 mm into nonacupoints without manipulation. Similar to EA, paired alligator clips from the specially constructed EA apparatus were attached to the needle holders of sham ST25 and sham SP14. When switched on, the EA apparatus in the SA group had the same working power indicator and sound without actual current output. Supplement. Data Supplement In both groups, participants without BMs for 3 or more consecutive days were allowed to use 110-mL glycerol or 40- to 60-mL sorbitol anal enema as rescue medicine with documentation in the stool diary. Outcomes and Follow-up Participants completed a stool diary during the 22-week study period and the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL) (17) at baseline and weeks 4 and 8. The main components of the stool diary included BMs, SBMs, CSBMs, stool consistency, straining, and medication use. Participants documented their stool consistency according to the Bristol Stool Form Scale (18) (scored from 1 to 7 for stool types 1 to 7, respectively). Straining was rated with scores of 0, 1, 2, and 3 indicating not difficult; a little difficult, need some straining to defecate; difficult, need straining to defecate; and very difficult, need hard straining to defecate, respectively. An SBM was defined as a BM that occurred without use of any medication or other methods to assist defecation in the previous 24 hours (4). A BM was not considered as an SBM when it occurred within 24 hours after the use of any assisted method for defecation. The PAC-QOL allowed participants to score the effects of constipation on physical discomfort, psychosocial discomfort, worriedness and concerns, and satisfaction in their daily lives. Higher scores indicate greater impairment or dissatisfaction. The primary outcome was the change from baseline in mean CSBMs per week, calculated as the total number of CSBMs divided by the number of weeks in the assessment period, during weeks 1 to 8. Secondary outcomes included the changes from baseline in mean CSBMs per week during weeks 9 to 20, mean SBMs per week during weeks 1 to 8, mean scores for stool consistency and straining of SBMs during weeks 1 to 8, and health-related quality of life via PAC-QOL score at weeks 4 and 8; the proportion of participants with 3 or more mean CSBMs per week (4); the proportion of participants using rescue medicine and other defecation measures; and the mean weekly frequency of using rescue medicine and other defecation aids during weeks 1 to 4, 1 to 8, and 9 to 20. We also assessed the CSBMs per week and their change from baseline during treatment and follow-up (not prespecified). Adverse events (AEs) were appropriately assessed, managed, and categorized by the acupuncturists and related clinical specialists within 24 hours. Severe AEs had to be reported to the principal investigator and the independent data and safety monitoring

Anatomical localization of isocitrate dehydrogenase 1 mutation: a voxel-based radiographic study of 146 low-grade gliomas

A brain tumors location is associated with the genetic profile of its tumor precursor cells. Mutations in isocitrate dehydrogenase 1 (IDH1) are an early event in tumor development and play a critical role in gliomagenesis. This study was conducted to specify the anatomical characteristics of IDH1 mutation in low‐grade gliomas and to further explore the origin of gliomas with IDH1 mutation. The impact of IDH1 mutation on disease prognosis was also evaluated.

Efficacy of Acupuncture for Primary Insomnia: A Randomized Controlled Clinical Trial

Objectives. To investigate the six-week influence of acupuncture on sleep quality and daytime functioning in primary insomnia. Methods. The study was a double-dummy, single-blinded, randomized, placebo-controlled clinical trial. A total of 180 patients with primary insomnia were randomly assigned to 3 groups: verum group underwent verum acupuncture plus placebo; estazolam group underwent estazolam plus sham acupuncture; sham group underwent sham acupuncture plus placebo. The outcome was measured by Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and the 36-item short-form health survey (SF-36). Results. The three groups showed significant improvement compared with the pretreatment baseline. Compared with the other two groups, the verum group reported improved sleep quality (SQ) and vitality (VT), decreased daytime dysfunction (DD) and sleepiness (ESS score). The differences were kept from the treatment period to the end of the trial. Discussion. Verum acupuncture appeared to be more effective in increasing sleep quality and daytime functioning than sham acupuncture and estazolam. Trial Registration. The trial is registeded with ClinicalTrials.gov ISRCTN12585433.

Efficacy of Acupuncture for Acute Migraine Attack: A Multicenter Single Blinded, Randomized Controlled Trial

OBJECTIVE We aim to investigate the efficacy of acupuncture for acute migraine attacks comparing with sham acupuncture. DESIGN The study was designed as a multicenter, single-blinded, randomized controlled clinical trial. SETTING AND PATIENTS From March 2007 to February 2009, 150 patients were randomly allocated to verum or sham acupuncture group in a ratio of 1:1. INTERVENTIONS Every patient received a verum or sham acupuncture treatment when having a migraine attack and, medications were allowed if the pain failed to be relieved two hours after the acupuncture. OUTCOME MEASURES The primary outcome was visual analog scale (VAS) scores for pain, ranging from 0 (no pain) to 10 (worst pain ever). RESULTS The mean VAS scores 24 hours after treatment decreased from 5.7 ± 1.4 to 3.3 ± 2.5 in the verum acupuncture group, and from 5.4 ± 1.3 to 4.7 ± 2.4 in the sham acupuncture group. Significant differences existed between the two groups (P = 0.001). CONCLUSIONS This trial suggested that verum acupuncture group was superior to sham acupuncture group on relieving pain and reducing the usage of acute medication.

Effect of acupuncture on Deqi traits and pain intensity in primary dysmenorrhea: analysis of data from a larger randomized controlled trial

BackgroundDeqi is a central concept in traditional Chinese acupuncture. We performed a secondary analysis on data from a larger randomized controlled trial (RCT) in order to assess the effect of acupuncture on deqi traits and pain intensity in primary dysmenorrhea.MethodsA total of 60 primary dysmenorrhea patients were enrolled and randomly assigned to one of three treatment groups. Acupuncture was given at SP6, GB39 or nonacupoint. Subjective pain was measured by a 100-mm visual analogue scale (VAS) before and after acupuncture. The Massachusetts General Hospital acupuncture sensation scales (MASS) with minor modification was used to rate deqi sensations during acupuncture.ResultsThe results showed that VAS scores of pain after acupuncture were significantly decreased comparing to before acupuncture treatment in all three groups (P = 0.000). However, no significant differences were found among three groups at the beginning or end of acupuncture treatment (P = 0.928, P = 0.419).ConclusionsThere was no statistical difference among three groups in terms of intensity of deqi feeling. The types of sensation were similar across the groups with only minor differences among them.Trial registrationTrial registration number: Controlled-Trials.com ISRCTN24863192.

Biomarkers of Oxidative Stress in Vascular Dementia Patients

OBJECTIVE Little is known about the role of oxidative stress in the pathogenesis of vascular dementia (VaD). The aim of this study was to investigate the biomarkers of oxidative stress in urine, as reflected by 8-hydroxydeoxyguanosine (8-OHdG), 8-isoprostaglandin F(2a) (8-isoPGF(2a)) and nitrotyrosine (NT) levels, in a group of well characterized VaD patients and in two control groups of Vascular Not Demented (VaND) patients and health y subjects. METHODS Ninety-six subjects from the Tianjin municipality in China were recruited. Forty-six patients were in the VaD group, 24 patients with VaND and 26 persons with no signs of cognitive disorder were employed as control groups. Urinary 8-OHdG and 8-isoPGF(2a) was performed using enzyme-linked immunosorbent assay (ELISA), and urinary NT levels were measured by chemiluminescence detection. RESULTS Significantly higher urinary 8-OHdG levels were detected in VaD patients compared to VaND patients and healthy control subjects. In contrast, urinary 8-isoPGF(2a) levels were significantly lower in VaD patients compared with two control groups. For NT levels, no statistically significant differences were observed among the three groups. CONCLUSION Increased urinary 8-OHdG level was a potential marker of oxidative stress in VaD patients. Furthermore, it is also important to take into account potential confounders in order to improve the identification of changes in the status of oxidative stress as related to VaD.

Acupuncture improves locomotor function by enhancing GABA receptor expression in transient focal cerebral ischemia rats.

Stroke is the major cause of long-term disability among adults. Recent studies have found that GABAergic inhibitory neurotransmission plays a vital role in ameliorate locomotor damage after ischemic injury. Acupuncture has been widely used to improve locomotor function. However, the underlying mechanisms remain unclear. The present study is designed to investigate whether GABA and GABA receptors are involved in the mechanism underlying acupuncture treatment in rats with middle cerebral artery occlusion (MCAO). One week after acupuncture at JiaJi acupoint, the locomotor function and infarct volumes were tested. Then level of GABA and the expressions of GABAAγ2 and GABABR2 were assessed by high-performance liquid chromatography, immunofluorescence and immunohistochemistry, respectively. Compared with normal group, GABAAγ2 and GABABR2 expressions were decreased in striatum and spinal cord of the MCAO group. After acupuncture, the expressions of the two receptors were increased, but levels of GABA and trafficking protein, kinesin binding 1 (TRAK1), which plays a role in the intracellular transport of GABA receptors, were unchanged. The present study suggests that acupuncture could reverse locomotor function by modulating the expressions of GABA receptors in MCAO rats.