Acupuncture for Opioid Dependence Patients Receiving Methadone Maintenance Treatment: A Network Meta-Analysis.

Objectives: Opioid dependence has been a threat to public health for hundreds of years. With the increasing number of studies on acupuncture-related therapies for opioid dependence patients receiving methadone maintenance treatment (MMT), its effect of acupuncture therapy in treating MMT patients remains controversial. Therefore, we conducted a multiple-treatments meta-analysis, and incorporated both direct and indirect comparisons, in order to discover the most effective treatment for opioid dependence patients receiving MMT. Methods: Five English databases and three Chinese databases were searched from its inception to August 20, 2020, in order to compare the effects of acupuncture-related therapies and MMT, which was summarized as Western medicine (WM) in the following texts. The quality of studies was assessed according to Cochrane's risk of bias tool 5.1.0, and a pair-wise meta-analysis, cumulative meta-analysis, and the network meta-analysis was performed using the R software (Version 3.6.1) and STATA (Version 14.0). The primary outcome was the effective rate, which was calculated by the ratio of detoxifying patients to the total. The secondary outcome was the Modified Himmelsbach Opiate Withdrawal Scale (MHOWS). Results: A total of 20 trials were included, which consisted of comparisons among WM, traditional Chinese medicine (TCM), and the four types of acupuncture, namely, manual acupuncture (MA), electro-acupuncture (EA), auricular acupuncture (AA), and transcutaneous electrical acupoint stimulation (TEAS). Though none of the trials were at low risk of bias. In the pair-wise meta-analysis, no statistically significant differences were observed in terms of the effective rate. Furthermore, MA was more efficacious than WM, EA, and TEAS in MHOWS, with mean differences (MDs) of (-8.59, 95% CI: -15.96 to -1.23, P < 0.01), (-6.15, 95% CI: -9.45 to -2.85, P < 0.05), and (-10.44, 95% CI: -16.11 to -4.77, P < 0.05), respectively. In the network meta-analysis, MA was more effective than WM (RR: 1.40, 95% CI: 1.05 to 1.99) on the effective rate, and (MD: -5.74, 95% CI: -11.60 to -0.10) on MHOWS. TEAS was more effective than WM (MD: -15.34, 95% CI: -27.34 to -3.46) on MHOWS. Synthetically, MA had the highest probability to rank first in treating opioid dependence. Conclusions: The existing evidence shows that acupuncture related-therapies may effectively be used for treating patients receiving MMT, and that manual acupuncture may be the best choice for opioid dependence among all kinds of acupuncture-related therapies. Nevertheless, reducing the relapse and promoting the recovery of opioid dependence need more efforts from not only the medical industry but also government support, security system, and educational popularization. To strengthen the assurance of acupuncture-related therapies in the treatment of opioid dependence, we expected that clinical trials with high quality would be conducted, to provide more confident evidence.

Acupuncture for amnestic mild cognitive impairment: A pilot multicenter, randomized, parallel controlled trial.

INTRODUCTION: Patients with amnesic mild cognitive impairment (aMCI) are more likely to develop Alzheimer disease than corresponding age normal population. Because Alzheimer disease is irreversible, early intervention for aMCI patients seems important and urgent. We have designed a pilot multicenter, randomized, parallel controlled trial to assess the efficacy and safety of acupuncture on aMCI, explore the feasibility of acupuncture in the treatment of aMCI, so as to provide a reference for large-sample clinical trials in the next stage. METHOD: We designed a pilot multicenter, randomized, parallel controlled trial. This trial aims to test the feasibility of carrying out a large-sample clinical trial. In this trial, 50 eligible patients with aMCI will be included and allocated to acupuncture group (n = 25) or sham acupuncture group (n = 25) at random. Subjects will accept treatment 2 times a week for 12 weeks continuously, with a total of 24 treatment sessions. We will select 6 acupoints (GV20, GV14, bilateral BL18, bilateral BL23). For the clinical outcomes, the primary outcome is Montreal cognitive assessment, which will be assessed from baseline to the end of this trial. And the secondary outcomes are Mini-mental State Examination, Delayed Story Recall, Clinical Dementia Rating scale, Global Deterioration Scale, Activity of Daily Life, Alzheimer Disease Assessment Scale-Cognitive Section, brain magnetic resonance imaging, brain functional magnetic resonance imaging, and event-related potential P300, which will be assessed before and after treatment. In addition, we will assess the safety outcomes from baseline to the end of this trial and feasibility outcome after treatment. We will evaluate neuropsychological assessment scale (Montreal cognitive assessment, Mini-mental State Examination, Alzheimer Disease Assessment Scale-Cognitive Section) at 3 months and 6 months after treatment. DISCUSSION: This pilot trial aims to explore the feasibility of the trial, verify essential information of its efficacy and safety. This pilot study will provide a preliminary basis for carrying out a larger clinical trial of acupuncture on aMCI in near future.

Clinical and Economic Evaluation of Acupuncture for Opioid-Dependent Patients Receiving Methadone Maintenance Treatment: The Integrative Clinical Trial and Evidence-Based Data.

Objective: From the health care and societal perspectives, this study aimed to evaluate the clinical and economic effects of acupuncture as an adjunctive therapy for patients receiving methadone maintenance treatment (MMT). Methods: We conducted a parallel-arm RCT in China in 2019. Patients were included who met the diagnostic criteria and receive MMT for more than 30 days. Patients were randomly assigned to the exposed group (acupuncture plus MMT) or control group (MMT) at a 1:1 ratio. Daily methadone dosage, drug cravings using the VAS score, and insomnia using the Pittsburgh Sleep Quality Index (PSQI) were chosen as the effectiveness indexes, and the quality-adjusted life years (QALYs) was chosen as the utility index. Results: Overall, 123 patients were included. The exposed group was significantly (P < 0.05) better than the control group in the improvement of daily methadone dosage (17.68 vs. 1.07), VAS (38.27 vs. 2.64), and PSQI (2.18 vs. 0.30). The QALY was 0.0784 (95%CI: 0.0761-0.0808) for the exposed group and 0.0762 (95%CI: 0.0738-0.0787) for the control group. The total cost of the exposed group (2869.50 CNY) was higher than the control group (2186.04 CNY). The ICER of daily methadone dosage (41.15), VAS (17.86), and PSQI (313.51) were shown to be economically efficient. While ICUR (310,663.64 CNY/QYLY) was higher than the cost suggested by WHO. Conclusion: Acupuncture as an adjuvant therapy for MMT patients realizes its cost-effectiveness by reducing the dosage of methadone, improving drug cravings, and alleviating insomnia. It helps to improve quality of life, but since its cost exceeds what society is willing to pay, further study is needed.

Effect of acupuncture for methadone maintenance treatment patients: study protocol of a randomized clinical trial.

BACKGROUND: Opioid dependence is an increasing public health problem all over the world. Patients with opioid dependence have to receive methadone maintenance therapy (MMT) as replacement therapy for years or even for their entire life. Acupuncture as a kind of therapy has been used to treat substance dependence for many years. Jin's three-needle acupuncture (JTN), a type of acupuncture technique, has been applied to treat various diseases for several decades. However, JTN as an acupuncture technique has not been used to treat patients receiving MMT. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of acupuncture as adjunctive therapy for patients receiving MMT. METHODS/DESIGN: This study is a parallel-arm, randomized controlled trial that aims to evaluate the efficacy and safety of acupuncture as adjunctive therapy for patients receiving MMT. A total of 140 eligible participants who range in age from 18 to 60 years and fulfil the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V), for opiate dependence will be enrolled into this study. All eligible participants will be randomly assigned to the acupuncture group or routine group in a 1:1 allocation ratio. Participants who are enrolled in the acupuncture group will receive MMT and JTN treatment for 30 min per session. Meanwhile, those who are assigned to the routine arm will receive MMT only. All 18 sessions of JTN treatment will be delivered over 6 weeks (3 per week) and followed by a 4-week follow-up period. The primary outcome measure will be the visual analogue scale (VAS) for drug craving and the daily consumption of methadone (DCOM). Secondary outcome measures will include the urine test for opioid use, the 36-item Short Form Survey (SF-36), the Beck Anxiety Inventory (BAI), the Beck Depression Inventory II (BDI-II) and Pittsburgh sleep quality index (PSQI). VAS, DCOM, BAI, BDI-II and the urine test for opioid use will be evaluated at baseline, the second week, the fourth week, the sixth week and the tenth week. SF-36 and PSQI will be assessed at baseline, the fourth week, the sixth week and the tenth week. DISCUSSION: The results of this trial will provide evidence on the efficacy and safety of acupuncture as adjunctive therapy for patients receiving MMT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900026357 . Registered on 2 October 2019.

Neurotropin® alleviates hippocampal neuron damage through a HIF-1α/MAPK pathway.

AIMS: The main purpose was to verify the potent capacity of Neurotropin® against neuronal damage in hippocampus and to explore its underlying mechanisms. METHODS: HT22 cells were treated with 40 µmol/L Aß25-35 in the presence of various concentrations of Neurotropin® or in its absence. The cell viability was assessed with a CCK-8 assay, and flow cytometry was used to measure cell apoptosis, intracellular ROS levels, and mitochondrial membrane potential. Aß plaques were examined by Bielschowsky silver staining, and the activities of antioxidants were detected in hippocampus of APP/PS1 mice after Neurotropin® treatment. The expression of proteins, including HIF-1α, Bcl-2, Bax, and MAPKs signaling molecules was evaluated by Western blot. RESULTS: Neurotropin® significantly reversed the cell injury induced by Aß25-35 through increasing cell viability and mitochondrial membrane potential, decreasing intracellular ROS and cell apoptosis of HT22 cells (P<.05). Furthermore, Neurotropin® markedly reduced the formation of Aß plaques and upregulated the activities of antioxidants (P<.05). Additionally, the protein expression of HIF-1α, p-ERK1/2, p-JNK, and p-P38 was significantly inhibited in hippocampus of APP/PS1 mice. CONCLUSIONS: Neurotropin® exhibited a potent neuroprotective effect on inhibiting Aß-induced oxidative damage and alleviating Aß deposition in hippocampus via modulation of HIF-1α/MAPK signaling pathway.

Late-onset radiation-induced optic neuropathy after radiotherapy for nasopharyngeal carcinoma.

Radiation-induced optic neuropathy (RION) is a rare but devastating late complication of radiotherapy, usually manifesting months to years after cancer treatment of the head and neck, resulting in rapidly progressive blindness in one or both eyes. The incidence of radiation-induced complications following radiotherapy, especially RION, is correlated with survival time of patients. Nasopharyngeal carcinoma (NPC), the most common type of cancer in southern China, has been primarily treated with radiotherapy, with associated neural injuries. To our knowledge, there are few reports of RION among patients with NPC who have undergone radiotherapy. To study this further, we reviewed nine patients with NPC and RION after radiotherapy and examined the clinical manifestations of RION, characteristics of the ophthalmologic examination, MRI results and the treatments used. Of the nine patients with RION, the most frequent clinical presentation was a decline of vision with visual field defects in one or both eyes. Ophthalmologic examinations showed flame hemorrhages in the retina, optic nerve atrophy and cotton wool spots. T1-weighted enhanced MRI showed enhancement of the optic nerve and optic chiasm in six patients. Treatment with corticosteroids, anticoagulation and hyperbaric oxygen (HBO) treatment did not reduce visual loss or blindness in patients.

Ginkgo biloba extract EGb761 protects against aging-associated mitochondrial dysfunction in platelets and hippocampi of SAMP8 mice.

Standardized Ginkgo biloba extract, EGb761, has been shown to possess polyvalent properties, such as anti-oxidation, anti-apoptosis and anti-inflammation. Recently, it has also been proposed to have direct protective effects on mitochondria. The effects of EGb761 make it a potential anti-aging drug. Despite that, the 'anti-aging' effect of EGb761, particularly its effect on the central nervous system, is still inconclusive. Using two age groups (3-week-old and 40-week-old) of SAMP8 mice (a senescence-accelerated strain of mice), the effects of EGb761 on mitochondrial function in platelets and hippocampi were investigated in this study. It was found that mitochondrial functions, evaluated as cytochrome c oxidase (COX) activity, mitochondrial ATP (adenosine-5'-triphosphate) content and mitochondrial glutathione (GSH) content, decreased with age. EGb761 protected against mitochondrial dysfunction in platelets of young and old mice, suggesting a peripheral effect of this herb in the prevention and treatment of age-associated degeneration. In contrast, in hippocampi, protective effects of EGb761 were observed only in the old mice, probably due to an age-associated increase in the permeability of the blood brain barrier (BBB). Therefore, while EGb761 has a potential anti-aging effect, its central effect can be affected by in vivo factors such as the BBB permeability. A better understanding of the in vivo pharmacological actions of EGb761 may contribute to a better understanding of the effectiveness and complexity of this drug.