Evaluation of individualized treatment of nonproliferative diabetic retinopathy: a multicenter, randomized, parallel-controlled study.

OBJECTIVE: To evaluate the differences in the efficacy of stationary treatment and individualized treatment for patients with nonproliferative diabetic retinopathy (NPDR). METHODS: This study was a randomized, controlled, multicenter clinical trial. Participants with NPDR were randomized into the stationary treatment group or the individualized treatment group. The stationary treatment group was given the basic treatment and Qiming granules, and the individualized treatment group was given the basic treatment, Qiming granules, and individualized Chinese herbal medicines over a 12-week period. The individualized therapeutic formula was also changed over time to adjust to the changes in the clinical presentation of the patient. We conducted observations of fundus retinal exudation and hemorrhage, visual acuity, Traditional Chinese Medicine symptom scores and other indicators. RESULTS: A total of 140 participants with NPDR were randomized into the stationary treatment group or the individualized treatment group, and 132 participants completed this study. Following the 12-week treatment, significant improvements in both primary and secondary outcomes were observed in the stationary and individualized treatment groups. No remarkable difference in the primary outcomes between the two groups was observed. However, there was a significant difference in the Traditional Chinese Medicine symptom scores (18 ± 7 vs 15 ± 6; P < 0.05). There were no severe adverse effects. CONCLUSION: Compared with stationary treatment, individualized treatment is more effective at relieving the Traditional Chinese Medicine symptoms and improving vision and fundus lesions at 12 weeks post treatment.

CTHRC1 mediates IL­1ß­induced apoptosis in chondrocytes via JNK1/2 signaling.

Osteoarthritis (OA), also known as degenerative joint disease or degenerative arthritis, is characterized by chondrocyte apoptosis. The aim of the present study was to investigate the effects of collagen triple helix repeat containing 1 (CTHRC1) and the c­Jun N­terminal kinase (JNK) 1/2 inhibitor SP600125 on rat chondrocytes cultured in vitro with interleukin (IL)­1ß. Chondrocytes were treated with different doses of IL­1ß and cell viability and CTHRC1 expression were assessed using Cell Counting Kit­8 and western blot assays, respectively. In separate experiments, chondrocytes were treated with CTHRC1­expressing constructs (pLVX­Puro­CTHRC1) and/or SP600125, or IL­1ß with either CTHRC1 short hairpin (sh)RNA constructs (shNRA­CTHRC1) or SP600125. The expression of CTHRC1, B­cell lymphoma (Bcl)­2, Bcl­2­associated X protein (Bax), cleaved caspase­3, poly ADP ribose polymerase (PARP)­1 and matrix metalloproteinase (MMP)­13 was measured using reverse transcription­quantitative polymerase chain reaction and western blotting assays. A Cell Counting Kit­8 assay was performed to examine cell viability. Annexin V/propidium iodide staining and flow cytometry assays were used to detect chondrocyte apoptosis. The expression of JNK1/2 and phosphorylated JNK1/2 was measured using western blotting. CTHRC1 was highly expressed in patients with OA compared with normal controls. IL­1ß treatment (5, 10 and 20 ng/ml) increased the protein expression of CTHRC1 in a dose­dependent manner and decreased the viability of chondrocytes in a time­dependent manner. pLVX­Puro­CTHRC1 mimics the effect of IL­1ß on chondrocyte apoptosis and JNK1/2 activity, and this is reversed by SP600125 treatment. However, transfection with shRNA­CTHRC1 or treatment with SP600125 inhibited IL­1ß­induced cell apoptosis and JNK1/2 activation. These results indicate that CTHRC1 downregulation may protect chondrocytes from IL­1ß­induced apoptosis by inactivating the JNK1/2 pathway.

Two sets of acupoint combination of similar functions engage shared neural representation: a functional magnetic resonance imaging study.

OBJECTIVE: To investigate whether the neural representations underlying alternating two acupoint combinations (ACs) are the same or not. METHODS: In this functional magnetic resonance imaging study, two sets of analgesia ACs were utilized, including Waiguan (TE5) and Qiuxu (GB40) for Group A, and Neiguan (PC6) and Taichong (LR3) for Group B, which are the most commonly adopted in clinical treatment. Each group had 20 healthy subjects. An experimental design was proposed, which consisted of a pre-needling resting phase, a needling phase and a post-needling resting phase. This paradigm optimally mimics the clinical protocol as well as focuses on both the stimulation and the resting periods. The results were subjected to general linear model analysis, conjunction analysis and the functional connectivity analysis. RESULTS: The rostral anterior cingulated cortex was engaged in the initiative period of the acupuncture effect in both groups, and it was chosen as the seed region for the functional connectivity analysis for the following resting period. The results showed that several shared brain regions were involved in both groups, in particular the insula, amygdala and hypothalamus. Moreover, significant differences were located at the posterior cingulated cortex as revealed by a two sample -test (P<0.05, corrected). Other regions showed no significant differences. This finding was further supported by the spatial correlation analysis that the two groups were significantly correlated (r =0.51, P<0.01). CONCLUSION: This preliminary research helps us understand the neurophysiological mechanisms of acupuncture when following clinical guidelines on ACs, as well as provides an important opportunity to develop better treatment strategies for reducing, or even preventing pain.

[Mild cognitive impairment disease treated with electroacupuncture: a multi-center randomized controlled trial].

OBJECTIVE: To verify the clinical efficacy on mild cognitive impairment (MCI) treated with electroacupuncture (EA) intervention based on the principle as "promoting the circulation of the Governor Vessel and regulating the marrow" and plan to provide the A-grade evidence of the evidence-based medicine for the clinical treatment of this disease with acupuncture and moxibustion. METHODS: The multi-center randomized controlled trial (RCT) was adopted. One hundred and ninety-two cases of MCI were randomized into an EA group and a nimodipine group, 96 cases in each one. In the EA group, EA was applied to Shenting (GV 24), Baihui (GV 20), Sishen cong (EX-HN 1) and Fengchi (GB 20), once every other day. In the nimodipine group, Nimodipine was pre scribed for oral administration. Four weeks constituted one course, the treatment of 8 weeks was required. The minimum mental state examination (MMSE) and the graphic recognition test (GRT) were applied before and in the 1st and 2nd session of treatment separately. The follow-up visit of MMSE scale was provided in the 1st, 3rd and 6th months after treatment separately. RESULTS: The total effective rate was 50.0% (47/94) in the EA group, which was superior to 34.4% (32/93) in the nimodipine group (P < 0.05). At the end of the 1st session treatment, the differences in MMSE total score and the cognitive, memory and speech dimensional scores were not significant statistically between two groups (all P > 0.05). At the end of the 2nd session treatment, the MMSE total score and the cognitive, memory, visual-space skill dimensional scores were improved in comparison before treatment (all P < 0.05). The results in the EA group were superior to those in the nimodipine group (all P < 0.05). But the difference in the speech dimensional score was not significant statistically between the two groups (P > 0.05). In the EA group, the GRT score was improved significantly after 2 sessions of treatment as compared with that before treatment (P < 0.01) and was superior to that in the nimodipine group (P < 0.05). In the 1st, 3rd and 6th month after treatment, the MMSE scale total scores were different significantly in statistics between the two groups (all P < 0.01). The long-term efficacy in the EA group was superior to that in the nimodipine group. CONCLUSION: Both of the EA therapy based on the principle as "promoting the circulation of the Governor Vessel and regulating the marrow" and the nimodipine program improve significantly the cognitive function of MCI patients. Compared with the nimodipine program, the EA therapy improves the comprehensive cognitive and the short-term memory abilities much more significantly and is especially advantageous at improving cognitive, memory and visual-space skill dimensions for MCI patients. In the half a year follow-up visit after the end of treatment, the long-term efficacy of EA is better than that of Nimodipine.

Adverse events associated with acupuncture: three multicentre randomized controlled trials of 1968 cases in China.

BACKGROUND: In order to evaluate the safety of acupuncture in China objectively, we investigated the adverse events associated with acupuncture based on three multicentre randomized controlled trials (RCTs) to assess the safety of acupuncture, identifying the common types of acupuncture adverse events, and analysing the related risk factors for their occurrence. METHODS: This observational study included patients who received acupuncture from three multicentre RCTs respectively for migraine, functional dyspepsia and Bell's palsy. The 1968 patients and their acupuncturists documented adverse events associated with acupuncture after treatment. We collected data about adverse events due to acupuncture treatment from their case report forms. We analysed the incidence and details of the adverse effects, and studied the risk factors for acupuncture adverse events with non-conditional logistic regression analysis. RESULTS: Among the 1968 patients, 74 patients (3.76%) suffered at least one adverse event throughout the treatment period. We did not observe the occurrence of serious adverse events. 73 patients with adverse events recovered within 2 weeks through effective treatment such as physiotherapy or self-treatment. A total of 3 patients withdrew because of adverse events. There were 9 types of adverse events related to acupuncture, including subcutaneous haematoma, bleeding, skin bruising and needle site pain. Subcutaneous haematoma and haemorrhage in the needling points were the most common adverse events. Age and gender were related to the occurrence of acupuncture adverse events. The older the patients were, the higher the risk of adverse events was. In addition, male patients had slightly higher risk of an adverse event than female patients. CONCLUSIONS: Acupuncture is a safe therapy with low risk of adverse events in clinical practice. The risk factors for adverse events (AEs) were related to the patients' gender and age and the local anatomical structure of the acupoints. AEs could be reduced and mitigated by improving the medical environment, ensuring a high technical level of the acupuncture practitioners and establishing a good relationship of mutual trust between doctor and patient. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00599586, NCT00599677, NCT00608660.

Effect on multifocal electroretinogram in persistently elevated intraocular pressure by erigeron breviscapus extract.

AIM: To observe the effect on multifocal electroretinogram (mfERG) in persistently elevated intraocular pressure (IOP) by erigeron breviscapus extract (also named Dengzhanhua in Chinese) in rat models. METHODS: The rat models with persistently elevated IOP were established by the method of Akira. Then, erigeron breviscapus extract was given for one month to observe the effect on mfERG in persistently elevated IOP in rats. RESULTS: As elevated IOP went on, the mfERG changes were mainly in weaken of reaction density with progressive development. After intervention of erigeron breviscapus extract, the total peak latency of P1 wave had recovered to some extent and the difference was significant when compared with control group (P<0.05); the total response density and P1 wave response density in second circle had risen noticeably, which had significant differences than those of control group (P<0.05). CONCLUSION: Erigeron breviscapus extract can improve the impaired visual function of persistently elevated IOP in rats, suggesting that this extract is the effective part of erigeron breviscapus for optic neuroprotection.

Improved quality monitoring of multi-center acupuncture clinical trials in China.

BACKGROUND: In 2007, the Chinese Science Division of the State Administration of Traditional Chinese Medicine(TCM) convened a special conference to discuss quality control for TCM clinical research. Control and assurance standards were established to guarantee the quality of clinical research. This paper provides practical guidelines for implementing strict and reproducible quality control for acupuncture randomized controlled trials (RCTs). METHODS: A standard quality control program (QCP) was established to monitor the quality of acupuncture trials. Case report forms were designed; qualified investigators, study personnel and data management personnel were trained. Monitors, who were directly appointed by the project leader, completed the quality control programs. They guaranteed data accuracy and prevented or detected protocol violations. Clinical centers and clinicians were audited, the randomization system of the centers was inspected, and the treatment processes were audited as well. In addition, the case report forms were reviewed for completeness and internal consistency, the eligibility and validity of the patients in the study was verified, and data was monitored for compliance and accuracy. RESULTS AND DISCUSSION: The monitors complete their reports and submit it to quality assurance and the sponsors. Recommendations and suggestions are made for improving performance. By holding regular meetings to discuss improvements in monitoring standards, the monitors can improve quality and efficiency. CONCLUSIONS: Supplementing and improving the existed guidelines for quality monitoring will ensure that large multi-centre acupuncture clinical trials will be considered as valid and scientifically stringent as pharmaceutical clinical trials. It will also develop academic excellence and further promote the international recognition of acupuncture.

[Quality monitoring in multi-central large sample acupuncture clinical trials].

OBJECTIVE: To ensure and enhance the quality of multi-central large sample clinical trials of acupunc ture and moxibustion. METHODS: Take the multi-central clinical trials supported by National Key Technology R &- D Program of "the 11th Five-year Plan" as an example to introduce the duty of monitors and simply describe the formulation of the monitoring plan, the monitoring procedure and contents of the monitoring plan and treatment of the commonly-seen problems. CONCLUSION: Quality monitoring work in multi-central large sample clinical trials of acupuncture and moxibustion is equally serious and scientific with clinical medical trials and it is an important way to guarantee the credible results.

[Experimental study of corpus cavernosal nerve evoked potential in diabetic rats].

OBJECTIVES: To observe the cavernosal nerve dysfunction of diabetic Sprague Dawley rats. METHODS: Thirty-five Sprague-Dawley rats were divided randomly into diabetes model group(n = 25) and normal group(n = 10). Diabetes model was established by administration of streptozotocin (63 mg/kg) in single intraperitoneal dosing. Giving single wave stimulus, corpus cavernosal nerve was measured for its latent period of reaction and myopotential. RESULTS: Compared with other groups, diabetic rats had longer reflection latent period(P < 0.01) and higher corpus cavernosum smooth muscle myopotential (P < 0.01). CONCLUSIONS: The results indicate that corpus cavernosal nerve dysfunction may play an important role in the erectile dysfunction of diabetic rats.