Safety and efficacy of 650 nm invasive laser acupuncture on non-specific chronic low back pain: A protocol for a multicenter randomized placebo-controlled trial.

Background: We aim to obtain clinical trial data regarding the safety, efficacy, and usefulness of invasive laser acupuncture (ILA) for non-specific chronic low back pain (NSCLBP) through a randomized placebo-controlled trial. Methods: Our clinical trial will be an assessor- and patient-blinded, prospective, parallel-arm, multi-center, randomized placebo-controlled clinical trial. One hundred and six participants with NSCLBP will be allocated evenly to the 650 ILA or control group. All participants will receive education on exercise and self-management. The 650 ILA group will undergo 650 nm ILA for 10 min, and the control group will undergo sham ILA for 10 min per visit, twice a week for 4 weeks, at bilateral GB30, BL23, BL24, and BL25. The primary outcome will be the proportion of responders (≥30% reduction in pain visual analogue scale [VAS] without increased use of painkillers) at 3 days after the intervention ends. The secondary outcomes will include changes in the scores of the VAS, European Quality of Life Five Dimension Five Level scale, and Korean version of the Oswestry Disability Index at 3 days after the intervention ends and 8 weeks after the intervention ends. Discussions: The results of our study will provide clinical evidence concerning the safety and efficacy of 650 nm ILA for the management of NSCLBP. Clinical trial registration: https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&focus=reset_12&search_page=M&pageSize=10&page=undefined&seq=21591&status=5&seq_group=21591, identifier KCT0007167.

Cognitive improvement effects of Tian Wang Bu Xin Dan (Cheonwangbosimdan) in patients with mild cognitive impairment: protocol for a randomized placebo-controlled pilot clinical trial.

BACKGROUND: It is important to develop effective treatments to prevent the progress of mild cognitive impairment to Alzheimer's disease. Cheonwangbosimdan has been widely prescribed for palpitation, anxiety, insomnia, and memory decline. We aimed to obtain clinical trial data concerning the safety and efficacy of Cheonwangbosimdan for mild cognitive impairment. METHODS: This clinical trial would be a single-center, double-blinded, parallel-arm, prospective, randomized controlled trial. Forty-eight participants with mild cognitive impairment would be randomly allocated evenly to the placebo or Cheonwangbosimdan groups. Participants will be educated on self-management and exercise at baseline and will receive the trial medication (Cheonwangbosimdan group, Cheonwangbosimdan; placebo group, placebo) once daily for 24 weeks. Primary outcome would include the changes in the Montreal Cognitive Assessment scale scores at the end of the intervention. Secondary outcomes would include the changes in the Montreal Cognitive Assessment scale scores at 12 weeks following the first intervention and changes in the scores of the Alzheimer's Disease Assessment Scale-cognitive subscale-3, the European Quality of Life Five Dimension Five Level scale, Korean Instrumental Activities of Daily Living, Korean Activities of Daily Living, and Geriatric Depression Scale at 12 and 24 weeks following the first intervention. DISCUSSION: The results of our trial would provide clinical trial data concerning the usefulness, safety, and efficacy of Cheonwangbosimdan in the management of mild cognitive impairment. TRIAL REGISTRATION: Clinical Research Information Service (Date: November 26, 2021; Registration No. KCT0006787; https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&search_page=M&pageSize=10&page=undefined&seq=20869&status=5&seq_group=20869).

Pharmacokinetic improvement provided by microneedle patch in delivering bee venom, a case study in combating scopolamine-induced neurodegeneration in mouse model.

Much research has shown Bee venom to be an effective neuroprotective agent. However, the usual transdermal injection of bee venom poses many pharmacokinetic disadvantages. Here, we compared the administration of bee venom via subcutaneous injection (SC) and via Microneedle patch (MN). Both administrated routes produce significant recovery effects, however: the MN significantly prolongs the bio-significant-and-yet-lower concentration of bee venom in mice bodies. In contrast, SC could produce only a short period of much higher bee venom levels in the blood and brain. We also see that due to the concentration-response-curve of bee venom (represented by melittin): mice bodies do not require much higher bee venom concentration (seen in the SC group) to produce a much more significant neuroprotective effect (than seen in those treated with the MN method). Therefore, a MN could maintain bee venom levels in mice bodies at lower-yet-more-efficient concentrations. This is important, as bee venom can cause more adverse effects and pain sensations, at higher concentrations. For the first time, we confirmed that the pharmacokinetic advantages of MN delivered bee venom also guarantee a holistic neuroprotection effect (which was shown by SC delivered bee venom in previous research). This was proven via the results of the water maze experiments for long-term learning memory assessment and protein analysis of key neuronal regulatory proteins: BDNF, p-CREB, iNOS, and mArhR 1. In conclusion, for situations where we ought to administrate drugs at a more downward amount, such as bee venom, MN can keep the therapeutic concentrations at a lower, yet interestingly, more-efficient level.

Adverse Events Associated with the Clinical Use of Bee Venom: A Review.

Bee venom is used to treat various diseases but can cause a tickling sensation and anaphylaxis during clinical treatment. Adverse events (AEs) associated with bee venom may vary depending on the dosage, method, route of administration, and the country, region, and user. We summarized the AEs of bee venom used in various ways, such as by the injection of extracts, venom immunotherapy (VIT), live bee stings, or external preparations. We conducted a search in eight databases up to 28 February 2022. It took one month to set the topic and about 2 weeks to set the search terms and the search formula. We conducted a search in advance on 21 February to see if there were omissions in the search terms and whether the search formula was correct. There were no restrictions on the language or bee venom method used and diseases treated. However, natural stings that were not used for treatment were excluded. A total of 105 studies were selected, of which 67, 26, 8, and 4 were on the injection of extracts, VIT, live bee stings, and external preparation, respectively. Sixty-three studies accurately described AEs, while 42 did not report AEs. Thirty-five randomized controlled trials (RCTs) were evaluated for the risk of bias, and most of the studies had low significance. A large-scale clinical RCT that evaluates results based on objective criteria is needed. Strict criteria are needed for the reporting of AEs associated with bee venom.

Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aß1-42.

Honeybee venom has recently been considered an anti-neurodegenerative agent, primarily due to its anti-inflammatory effects. The natural accumulation of amyloid-beta (Aß) in the brain is reported to be the natural cause of aging neural ability downfall, and oxidative stress is the main route by which Aß ignites its neural toxicity. Anti-neural oxidative stress is considered an effective approach for neurodegenerative therapy. To date, it is unclear how bee venom ameliorates neuronal cells in oxidative stress induced by Aß. Here, we evaluated the neuroprotective effect of bee venom on Aß-induced neural oxidative stress in both HT22 cells and an animal model. Our results indicate that bee venom protected HT22 cells against apoptosis induced by Aß1-42. This protective effect was explained by the increased nuclear translocation of nuclear factor erythroid 2-like 2 (Nrf2), consequently upregulating the production of heme oxygenase-1 (HO-1), a critical cellular instinct antioxidant enzyme that neutralizes excessive oxidative stress. Furthermore, bee venom treatment activated the tropomyosin-related kinase receptor B (TrkB)/cAMP response element-binding (CREB)/brain-derived neurotrophic factor (BDNF), which is closely related to the promotion of cellular antioxidant defense and neuronal functions. A mouse model with cognitive deficits induced by Aß1-42 intracerebroventricular (ICV) injections was also used. Bee venom enhanced animal cognitive ability and enhanced neural cell genesis in the hippocampal dentate gyrus region in a dose-dependent manner. Further analysis of animal brain tissue and serum confirmed that bee venom reduced oxidative stress, cholinergic system activity, and intercellular neurotrophic factor regulation, which were all adversely affected by Aß1-42. Our study demonstrates that bee venom exerts antioxidant and neuroprotective actions against neural oxidative stress caused by Aß1-42, thereby promoting its use as a therapeutic agent for neurodegenerative disorders.

[Factors effecting health promoting behaviors in middle-aged women].

PURPOSE: This study was to evaluate the casual relationship between the factors in the Pender's model and to explain health promoting behaviors among middle-aged women in order to facilitate nursing interventions for this population group. METHOD: 116 women between 40-60 years old living in Incheon were asked to complete a questionnaire about their health. The data was collected between March and November, 2003. The data was analyzed by descriptive statistics and the correctional analysis SPSSWIN 11.5 program. The LISREL 8.12 program was used to find the best fit model which explained a causal relationship of the variables. RESULTS: The climacteric symptoms of middle-aged women negatively correlated with health promoting behaviors. However, marital satisfaction positively correlated with health promoting behaviors. CONCLUSION: Marital satisfaction and climacteric symptoms had an effect on health promoting behaviors. Therefore, based on this study, we plan to develop a health education program to decrease climacteric symptoms and to promote marital satisfaction for health promotion.