Bone marrow mesenchymal stem cell transplantation downregulates plasma level and the microglia expression of transforming growth factor ß1 in the acute phase of cerebral cortex ischemia.

BACKGROUND: Both bone marrow mesenchymal stem cell (BM-MSC) and transforming growth factor-ß1 (TGF-ß1) have a strong anti-inflammatory capacity in stroke. But their relationship has not been well addressed. In this study, we investigated how intravenous BM-MSC transplantation in rats effected the expression of TGF-ß1 48 h post cerebral ischemia, and we analyzed the main cells that produce TGF-ß1. METHODS: We used a distal middle cerebral artery occlusion (dMCAO) model in twenty Sprague-Dawley (SD) rats. The rats were randomly divided into two groups: the ischemic control group and the postischemic BM-MSC transplantation group. One hour after the dMCAO model was established, the rats were injected in the tail vein with either 1 ml saline or 1 × 106 BM-MSCs suspended in 1 ml saline. ELISAs were used to detect TGF-ß1 content in the brain infarct core area, striatum and the plasma at 48 h after cerebral infarction. Immunofluorescent staining of brain tissue sections for TGF-ß1, Iba-1, CD68 and NeuN was performed to determine the number and the proportion of double stained cells and to detect possible TGF-ß1 producing cells in the brain tissue. RESULTS: Forty-eight hours after ischemia, the TGF-ß1 content in the infarcted area of the BM-MSC transplantation group (23.94 ± 4.48 pg/ml) was significantly lower than it was in the ischemic control group (34.18 ± 4.32 pg/ml) (F = 13.534, P = 0.006). The TGF-ß1 content in the rat plasma in the BM-MSC transplantation group (75.91 ± 12.53 pg/ml) was significantly lower than it was in the ischemic control group (131.18 ± 16.07 pg/ml) (F = 36.779, P = 0.0002), suggesting that after transplantation of BM-MSCs, TGF-ß1 levels in the plasma decreased, but there was no significant change in the striatum area. Immunofluorescence staining showed that the total number of nucleated cells (1037.67 ± 222.16 cells/mm2) in the infarcted area after transplantation was significantly higher than that in the ischemic control group (391.67 ± 69.50 cells/mm2) (F = 92.421, P < 0.01); the number of TGF-ß1+ cells after transplantation (35.00 ± 13.66 cells/mm2) was significantly reduced in comparison to that in the ischemic control group (72.33 ± 32.08 cells/mm2) (F = 37.680, P < 0.01). The number of TGF-ß1+/Iba-1+ microglia cells in the transplantation group (3.67 ± 3.17 cells/mm2) was significantly reduced in comparison to that of the ischemic control group (13.67 ± 5.52 cells/mm2) (F = 29.641, P < 0.01). The proportion of TGF-ß1+/Iba-1+ microglia cells out of all Iba-1+ microglia cells after transplantation (4.38 ± 3.18%) was significantly decreased compared with that in the ischemic control group (12.81 ± 4.86%) (F = 28.125, P < 0.01). CONCLUSIONS: Iba-1+ microglia is one of the main cell types that express TGF-ß1. Intravenous transplantation of BM-MSCs does not cooperate with TGF-ß1+ cells in immune-regulation, but reduces the TGF-ß1 content in the infarcted area and in the plasma at 48 h after cerebral infarction.

Oral Chinese herbal medicine for kidney nourishment in Alzheimer's disease: a systematic review of the effect on MMSE index measures and safety.

OBJECTIVE: To evaluate the effectiveness and safety of the Chinese herbal medicine for kidney nourishment (CHMK) assessed with the Mini-Mental Status Examination (MMSE) index objective outcome measures in individuals with Alzheimer's disease. METHODS: Searches were conducted in 7 medical databases from their inceptions until July 19, 2014 for randomized controlled trials (RCTs) that compared the oral administration of CHMK plus conventional pharmacotherapy with the same conventional pharmacotherapy alone with MMSE index measures as outcomes. Relevant resources were also manually retrieved. Two reviewers screened the citations of the reports, assessed the risk of bias and extracted data independently. Data analysis was carried out with Cochrane Collaboration's RevMan5.2.6 software and evidence quality grading evaluation of the systematic review was conducted with Grades of Recommendations Assessment Development and Evaluation (GRADE) profiler software. RESULTS: A total of 20 studies involving 1682 participants were included in the meta-analysis. There were 15 trials that compared CHMK with conventional pharmacotherapy and 5 trials that compared CHMK plus conventional pharmacotherapy with conventional pharmacotherapy alone. The main meta-analysis results showed relative benefits in effective rates in five studies (odds ratio [OR] 2.74, 95% confidence interval [CI] 1.55-4.85) and cure rate/clinical-control rates in five studies (OR 1.91, 95% CI 1.27-2.88) in favor of the CHMK plus conventional pharmacotherapy group. As for CHMK compared with conventional pharmacotherapy, no significant differences were noted in the effective rate (OR 1.09, 95% CI 0.82-1.46; cure rate (OR 1.06, 95% CI 0.81-1.38) and detailed sub-group of MMSE scores from the onset time to 4 weeks (weighted mean difference [WMD] 0.31, 95% confidence interval [CI] -0.81 to 1.42, 8 weeks WMD 1.12, 95% CI -0.54 to 2.78, 12 weeks (WMD 0.43, 95% CI -1.62 to 2.48, or 24 weeks WMD 1.92, 95% CI -1.60 to 5.44) follow-up and the overall effect (WMD 0.79, 95% CI -0.11 to 1.69). Moreover, weaknesses in methodological quality were identified in most studies according to Cochrane Risk of Bias tool assessment, while the quality level of GRADE classification indicated "very low". The incidence of adverse events with CHMK (0.87%) was lower than in the conventional pharmacotherapy group (4.08%), which revealed use of CHMK was relatively safer than conventional pharmacotherapy alone. CONCLUSION: The effectiveness and safety of oral administration of CHMK cannot be currently determined because of publication bias and the low quality level of the included trials. Further studies on a larger scale and with more rigorous designs are required to define the role of CHMK in the treatment of AD.

[Application exploration of comparative effectiveness research in clinical efficacy optimization of abdominal acupuncture].

The concepts and characteristics of comparative effectiveness research (CER) are analyzed to explore its scientific research methodology in clinical efficacy optimization of abdominal acupuncture. The designs of CER focus on patients, which emphasize assessment of comprehensive efficacy in real medical environment instead of simple efficacy in randomized controlled trial (RCT). Its research strategy involves four categories and three subject, covering acquiring, saving and management, comparison and application of clinical evidence, which has practical application value in comprehensive comparison of advantages and efficacy rules of different acupuncture therapies and acupoint prescriptions. By establishing clinical registration system, oversized-sample data could be acquired from different centers to effectively overcome insufficient sample-induced sampling error. It has important value in system summary and optimization of clinical efficacy of abdominal acupuncture. The CER fully illustrates clinical reality of acupuncture-moxibustion and provides strong support of scientific data for optimization of curative effect. It embodies prescription standardization, manipulation normalization and methodization of syndrome differentiation in clinic of abdominal acupuncture, which is expected to achieve evidence-based optimization of treatment prescription and technique in abdominal acupuncture.

Deqi sensation in placebo acupuncture: a crossover study on chinese medicine students.

Objective. To evaluate the similarity of deqi sensation of real and noninvasive placebo acupuncture in healthy people with knowledge of Chinese medicine. Methods. In a crossover design, volunteers recruited from Chinese medicine college students were randomized to two groups to receive two phases of intervention with a one-week washout interval. In Group A, the participants were firstly treated by real acupuncture and then by sham needle, and the treatment sequence was reversed in Group B. VAS for pain intensity and deqi sensation was evaluated as outcomes. Results. Sixty-three volunteers were recruited and 60 were included and finished the study. In Group A, VAS was higher in Phase I than in Phase II (P = 0.017). Only treatment methods were selected as factor to VAS difference (P = 0.046) in ANOVA test. More positive deqi was reported in Group A in Phase I when treated by real acupuncture (P = 0.039), but the difference was not significant in Phase II (P = 0.301). Conclusion. The noninvasive placebo acupuncture device can effetely simulate the deqi sensation as real acupuncture, but it is less likely to evoke the active effect of deqi in real practice. This trial is registered with Chinese Clinical Trial Registry: ChiCTR-ORC-09000505.

Effects of acupuncture treatment on depression insomnia: a study protocol of a multicenter randomized controlled trial.

BACKGROUND: More than 70% of patients with depression who see their doctors experience insomnia. Insomnia treatment is a very important link for depression treatment. Furthermore, antidepression treatment is also important for depression insomnia. In acupuncture, LU-7 (Lie Que) and KID-6 (Zhao Hai), which are two of the eight confluence points in meridian theory, are used as main points. An embedded needle technique is used, alternately, at two groups of points to consolidate the treatment effect. These two groups of points are BL-15 (Xin Shu) with BL-23 (Shen Shu) and BL-19 (Dan Shu) with N-HN-54 (An Mian). The effectiveness of these optimized acupuncture formulas is well proven in the practice by our senior acupuncturists in Guangdong Provincial Hospital of TCM. This study has been designed to examine whether this set of optimized clinical formulas is able to increase the clinical efficacy of depression insomnia treatment. METHODS/DESIGN: In this randomized controlled multicenter trial, all the eligible participants are diagnosed with depression insomnia. All participants are randomly assigned to one of two groups in a ratio of 1:1 and receive either conventional acupuncture treatment or optimized acupuncture treatment. Patients are evaluated using the Pittsburgh Sleep Quality Index(PSQI)and the Hamilton rating scale(HAMD) for depression. The use of antidepression and hypnotics drugs is also considered. Results are obtained at the start of treatment, 1 and 2 months after treatment has begun, and at the end of treatment. The entire duration of the study will be approximately 36 months. DISCUSSION: A high quality of trial methodologies is utilized in the study, and the results may provide better evidence for the effectiveness of acupuncture as a treatment for depression insomnia. The optimized acupuncture formula has potential benefits in increasing the efficacy of treating depression insomnia. TRIAL REGISTRATION: The trial was registered in Chinese Clinical Trial Register (ChiCR-TRC-00000481) on 12 August 2009.

[Chronic neck pain of cervical spondylosis treated with acupuncture and moxibustion in terms of the heart and kidney theory: a randomized controlled trial].

OBJECTIVE: To evaluate the clinical efficacy of acupuncture and moxibustion on chronic neck pain of cervical spondylosis in terms of the heart and kidney theory. METHODS: One hundred and eleven cases were randomized into a heart-kidney acupuncture group (55 cases) and a conventional acupuncture group (56 cases). In the heart-kidney acupuncture group, acupuncture was applied to Bailao (EX-HN 15), Shenmen (HT 7) and Wangu (SI 4). Afterwards, the direct moxibustion was applied to Dazhui (GV 14), Xinshu (BL 15) and Shenshu (BL 23). After moxibustion, the intradermal needling therapy was provided at Bailao (EX-HN 15), Xinshu (BL 15) and Shenshu (BL 23). In the conventional acupuncture group, acupuncture was applied to Bailao (EX-HN 15) and Zhongzhu (TE 3) at first. Afterwards, the direct moxibustion was done at Dazhui (GV 14), Bailao (EX-HN 15) and Jianzhongshu (SI 15). After moxibustion, the interdermal needling therapy was provided at Bailao (EX-HN 15) and Jianzhongshu (SI 15). The northwick park pain questionnaire (NPQ) was adopted as the main efficacy index for the evaluation. RESULTS: After the intervention and during the follow-up visit period, NPQ scores were all reduced remarkably as compared with those before the intervention for the patients in two groups (all P < 0.001), but the differences were not statistically significant in groups (all P > 0.05). By the age stratification analysis for the patients in two groups, the program in terms of the heart and kidney theory achieved the superior efficacy for the patients over 45 years old as compared with those in the conventional acupuncture group (P < 0.05, P < 0.01). By the stratification analysis of the sick duration, the program in terms of the heart and kidney theory achieved the superior efficacy for the patients with over 7 years sick duration as compared with those in the conventional acupuncture group (P < 0.05, P < 0.01). CONCLUSION: The acupuncture and moxibustion therapeutic program in terms of the heart and kidney theory achieves the superior efficacy on chronic pain of cervical spondylosis for the patients over 45 years old and with over 7 years sick duration. It is one of the optimized programs for the treatment of this disease.

The optimized acupuncture treatment for neck pain caused by cervical spondylosis: a study protocol of a multicentre randomized controlled trial.

BACKGROUND: Neck pain is one of the chief symptoms of cervical spondylosis (CS). Acupuncture is a well-accepted and widely used complementary therapy for the management of neck pain caused by CS. In this paper, we present a randomized controlled trial protocol evaluating the use of acupuncture for CS neck pain, comparing the effects of the optimized acupuncture therapy in real practice compared with sham and shallow acupuncture. METHODS/DESIGN: This trial uses a multicentre, parallel-group, randomized, sham acupuncture and shallow acupuncture, controlled single-blind design. Nine hospitals are involved as trial centres. 945 patients who meet inclusion criteria are randomly assigned to receive optimized acupuncture therapy, sham acupuncture or shallow acupuncture by a computerized central randomization system. The interventions past for 4 weeks with eight to ten treatments in total. The group allocations and interventions are concealed to patients and statisticians. The Northwick Park Neck Pain Questionnaire (NPQ) is used as the primary outcome measure, and the McGill Pain Questionnaire (MPQ) and The Short Form (36) Health Survey (SF-36) are applied as secondary outcome measures. The evaluation is performed at baseline, at the end of the intervention, and at the end of the first month and the third month during follow-up. The statistical analyses will include baseline data comparison and repeated measures of analysis of variance (ANOVA) for primary and secondary outcomes of group and time differences. Adverse events (AEs) will be reported if they occur. DISCUSSION: This trial is a multicentre randomized control trial (RCT) on the efficacy of acupuncture for CS neck pain and has a large sample size and central randomization in China. It will strictly follow the CONSORT statement and STRICTA extension guideline to report high-quality study results. By setting the control groups as sham and shallow acupuncture, this study attempts to reveal the effects of real acupuncture versus placebo or non-classic acupuncture treatment and evaluate whether classic Chinese medical acupuncture is effective on CS neck pain. This study will provide evidence for the effects of acupuncture on CS neck pain. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-00000184.

Meta analysis of the curative effect of acupuncture on post-stroke depression.

OBJECTIVE: To systematically evaluate the curative effect of acupuncture on post-stroke depression (PSD). METHODS: The internet was used to retrieve the Wanfang Medical Data System, Chinese Periodical Net, the Weipu Information Resources System, PubMed and the Cochrane Library Database. Relevant articles, up to September 2010, were manually retrieved. These papers included studies that had performed random and semi-random control trials for the use of acupuncture to treat PSD. Fifteen random control tests involving 1096 patients were included in this study and individual cases, interventional measures and curative effects were extracted from this research. Grade methodological quality evaluation and meta-analysis were performed on these studies. RESULTS: Comparison between the acupuncture group and the Western medicine group for the curative rate on PSD revealed an OR of 1.48, 95% CI = [1.11 1.97] and P = 0.008. Comparison of obviously effective rate shows that OR = 1.39, 95% CI = [1.08 1.80] and P = 0.01. Comparison of effective rate shows that OR = 0.83, 95% CI = [0.631.09] and P = 0.18. CONCLUSION: Comparison between the acupuncture group and Western medicine group in treating PSD revealed that there is a statistical difference in curative rate and remarkably effective rate, but no difference in effective rate.

Principles of ethics review on traditional medicine and the practice of institute review board in China.

As one of the significant parts of medical science research in China, the research on Chinese medicine (CM) reflects the essence of healthcare tradition in the country both theoretically and clinically, and embodies the values of Chinese culture. Therefore, in the practice of ethics review on CM research protocols, besides abiding by the contemporary prevalent international principles and guidelines on bioethics, which emphasizes the scientific and bioethical value of the study, we should also stress the CM theoretical background and relevant clinical experience in the framework of Chinese culture and values. In this paper, we went over the traits of CM clinical research and the experience from the practice of ethics review by the institution review board for bioethics, and then attempted to summarize the key points for the bioethics review to CM researches in China, so as to serve as reference for the bioethics review to traditional and alternative medicine researches.

A preliminary study on the medical expenditure of Chinese medicine and integrative medicine treatment for influenza A (H1N1) in the fever clinics.

OBJECTIVE: To analyze the effectiveness of Chinese medicine and integrated Chinese and Western medicine for influenza A (H1N1) in the fever clinics and its relevant expenditure. METHODS: A prospective survey on the clinical epidemic observation and follow-up was conducted from July 2009 to October 2009 with a self-developed questionnaire whose contents including the clinical data of the confirmed 149 H1N1 cases and their relevant therapeutic expenditure. The patients were assigned to the Chinese medicine group (22 cases treated by Chinese medicine alone) and integrative medicine group (124 cases treated by both Chinese medicine and Western medicine). The data were processed with descriptive analysis, t test and χ (2), and sum-rank test. RESULTS: The proportion of clinical recovery of Chinese medicine group (81.8%) was higher than that of integrative medicine group (54.8%) with statistical significance (P=0.02). The average fever durations in both groups were 3.5 to 4 days, showing no significant difference (P=0.86). In the comparisons of average cost of Chinese herbs, drugs, therapies, and total cost, those of the Chinese medicine group were lower than those in the integrative group (P=0.01, P=0.00, P=0.00, P=0.00). CONCLUSIONS: The H1N1 patients in the fever clinic who received Chinese medicine treatment had a higher clinical recovery proportion than those who received integrated Chinese and Western medicine treatment with lower medical cost. However, due to small sample size of the Chinese medicine group in the study, the conclusion needs further confirmation by studies with large sample size.

Preventive treatment of traditional Chinese medicine as antistress and antiaging strategy.

Premedical intervention before diseases is one of the principal practices in traditional Chinese medicine (TCM) for tackling health problems and diseases. This paper explains the preventive treatment principle in TCM regarding the subhealth condition following stress-induced pathophysiological situations, mainly oxidative and glycation stresses, in the framework of metabonomics and cell biology. Scientific interpretations for various preventive treatments in TCM present the idea that disease prevention should surpass medical intervention in humans. Antistress biology is proposed for the first time as a preclinical practice or strategy for antiaging.

[Logistic regression analysis on therapeutic effect of acupuncture on neck pain caused by cervical spondylosis and factors influencing therapeutic effect].

OBJECTIVE: To explore the main factors influencing the therapeutic effect of acupuncture on neck pain caused by cervical spondylosis, so as to provide references for further increasing the therapeutic effect of acupuncture. METHODS: One hundred and six cases were randomly divided into an observation group and a control group, 53 cases in each group. The observation group was treated with routine acupuncture at Dazhui (GV 14), Jingbailao (Ex-HN 15) and Jianzhongshu (SI 15); and the control group was treated with sham acupuncture at 1 cm lateral to Bailao (Ex-HN 15) and Jianzhongshu (SI 15). The needles were retained for 20 min in the two groups and infrared radiation was used for adjuvant treatment in this period. Northwick Park Neck Pain Questionnaire (NPQ) was used to assess the patients' quality of life before and after the treatment. The potential influential factors were analyzed by Logistic regression. RESULTS: The effective rate was 75.5% in the observation group and 52.8% in the control group with a significant difference between the two groups (P<0.05). The Logistic regression analysis indicated that the therapeutic effect in the observation group was superior to the control group (OR = 2.670), and both the attack frequency and duration of the neck pain will influence the therapeutic effect (OR = 1.055 and OR = 2.446). CONCLUSION: Acupuncture has a better therapeutic effect on neck pain caused by cervical spondylosis, and patient's clinical history about attack frequency and duration of neck pain are factors influencing clinical therapeutic effect.

Analysis on the effect of acupuncture in treating cervical spondylosis with different syndrome types.

OBJECTIVE: To observe the clinical effect of acupuncture in treating cervical spondylosis with different syndrome types. METHODS: One hundred and seventeen patients were randomized into the treated group: (59 cases), treated with normal acupuncture, and the control group (58 cases), treated with sham acupuncture, operated once every other day, 9 times in total (in 18 days) as one therapeutic course, and a succeeding 3-month follow-up study was carried out after terminating the therapy. The efficacy of treatment was evaluated with the Northwick Park Neck Pain Questionnaire (NPQ) and Visual Analogue Scale (VAS), and the scores gained in patients with different syndrome types were analyzed with a general linear model. RESULTS: The NPQ and VAS: scores showed a linear decreasing tendency in both groups at the time of ending treatment and the 1st month of follow-up, but showed a secondary curve increasing tendency in the 3rd month of follow-up. Multivariate analysis showed the difference was of statistical significance (P<0.05). However, the analysis through lead-in of syndrome type as an individual influencing factor showed that syndrome type exerts a significant influence on VAS score (P<0.05), but has insignificant influence on the NPQ score (P>0.05). CONCLUSION: Acupuncture shows: good immediate effect in treating cervical spondylosis, but its long-term effect is not satisfactory. The difference in syndrome type may have some impact on the effects of acupuncture in alleviating pain, but exerts no evident influence on the comprehensive effect.