Effect of different non-pharmacologic placebo treatments on migraine prevention: a network meta-analysis of randomized controlled trials.

BACKGROUND: Placebo control plays an important role in evaluating the effectiveness of interventions. Specifying differential effects of various placebo controls on migraine prevention would be essential in the explanation of preventive treatment for migraine and the indirect comparison between different prophylactic therapeutics. OBJECTIVES: To access the impact of different non-pharmacologic placebo types on different outcomes in migraine patients. METHODS: We searched PubMed, Cochrane Controlled Register of Trials, Embase, and Web of Science databases from the date of creation to June 19, 2023. Randomized controlled trials of migraine that included sham intervention of acupuncture or cognitive behavioural therapy (CBT) or non-invasive Vagus Nerve Stimulation (nVNS) or repetitive Transcranial Magnetic Stimulation (rTMS) or transcranial Direct Current Stimulation (tDCS) were conducted. The primary outcome was the migraine days, and the secondary outcomes were the number of migraine attacks, headache days, headache frequency, and responder's rate. Placebo effects were assessed using five individual placebos for network meta-analysis, using mean differences to measure the relative effect of pair-wise comparisons between interventions. RESULT: A total of 50 trials with 4880 subjects were included. Twenty-seven trials were evaluated for low risk of bias. The results of indirect comparisons show that sham rTMS and sham tDCS had optimal and similar effects in reducing migraine days; sham acupuncture has the greatest effect on reducing the number of migraine attacks and relieving headache frequency; sham rTMS had a highly significant advantage in reducing headache days compared with the other placebo controls. CONCLUSION: Based on the network meta-analysis results, we found that sham acupuncture had the greatest effect on migraine prophylaxis. The strong placebo effect of sham acupuncture should be considered when assessing the therapeutic effect.

Risk factors of systemic lupus erythematosus: an overview of systematic reviews and Mendelian randomization studies.

BACKGROUND: The etiology of systemic lupus erythematosus is complex and incurable. A large number of systematic reviews have studied the risk factors of it. Mendelian randomization is an analytical method that uses genetic data as tool variables to evaluate the causal relationship between exposure and outcome. OBJECTIVE: To review the systematic reviews and Mendelian randomization studies that focused on the risk factors of systemic lupus erythematosus and shed light on the development of treatments for its prevention and intervention. METHODS: From inception to January 2022, we systematically searched MEDLINE (via PubMed) and Embase for related systematic reviews and Mendelian randomization studies. Extract relevant main data for studies that meet inclusion criteria. The quality of systematic reviews was assessed by using Assessment of Multiple Systematic Reviews 2 (AMSTAR-2). Finally, the risk factors are scored comprehensively according to the results' quantity, quality, and consistency. RESULTS: Our study involved 64 systematic reviews and 12 Mendelian randomization studies. The results of systematic reviews showed that diseases (endometriosis, atopic dermatitis, allergic rhinitis), lifestyle (smoking, drinking, vaccination), and gene polymorphism influenced the incidence of systemic lupus erythematosus. The results of Mendelian randomization studies identified the role of disease (periodontitis, celiac disease), trace elements (selenium, iron), cytokines (growth differentiation factor 15), and gut microbiome in the pathogenesis of systemic lupus erythematosus. CONCLUSION: We should pay attention to preventing and treating systemic lupus erythematosus in patients with endometriosis, celiac disease, and periodontitis. Take appropriate dietary supplements to increase serum iron and selenium levels to reduce the risk of systemic lupus erythematosus. There should be no excessive intervention in lifestyles such as smoking and drinking.

Probiotics for the management of irritable bowel syndrome: a systematic review and three-level meta-analysis.

OBJECTIVE: Previous systematic reviews demonstrated a potentially beneficial effect of probiotics on irritable bowel syndrome (IBS). However, these studies are either affected by the inclusion of insufficient trials or by the problem of dependent data across multiple outcomes, and an overall effect size has not been provided. We aimed to determine the effect of probiotics on IBS through a three-level meta-analysis and clarify potential effect moderators. METHODS: We searched MEDLINE, Embase, and Web of Science, screening for randomized controlled trials (RCTs) that examine the effect of probiotics on IBS. The primary outcome was the improvement in the severity of global IBS symptoms at the end of treatment. The secondary outcomes were the improvement in abdominal pain and the quality of life. The effect sizes of the probiotics were measured by using the standardized mean difference (SMD) and pooled by a three-level meta-analysis model. RESULTS: We included 72 RCTs in the analysis. The meta-analysis showed significantly better overall effect of probiotics than placebo on the global IBS symptoms (SMD -0.55, 95% CI -0.76 to -0.34, P <0.001), abdominal pain (SMD -0.89, 95% CI -1.29 to -0.5, P <0.001) and quality of life (SMD 0.99, 95% CI 0.45 to 1.54, P <0.001), respectively. Moderator analysis found that a treatment duration shorter than 4 weeks was associated with a larger effect size in all the outcomes, and Bacillus probiotics had better improvement on the abdominal pain. CONCLUSIONS: Probiotics had a short-term effect and a medium effect size on the global IBS symptoms. Treatment duration and types of probiotics affected the effect size of probiotics, and shorter durations and Bacillus probiotics were associated with better treatment effects. REGISTRATION: Open Science Framework.

Efficacy of acupuncture for tension-type headache prophylaxis: systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Acupuncture has been shown to reduce tension-type headache (TTH) frequency in previous studies. Nevertheless, repeated significance testing might inflate type I error. We aimed to verify the effectiveness and safety of acupuncture in reducing TTH frequency by meta-analysis and trial sequential analysis (TSA). METHODS: Ovid Medline, Embase, and Cochrane Library were searched until September 29, 2022. Randomized controlled trials comparing acupuncture with sham acupuncture, no acupuncture, or other active therapies in adults with TTH were included. The primary outcome was TTH frequency. The secondary outcomes were responder rate and adverse event. RESULTS: Fourteen studies involving 2795 participants were included. Acupuncture had more reduction than sham acupuncture in TTH frequency, both after treatment (standardized mean difference [SMD] - 0.80, 95% CI - 1.36 to - 0.24, P = 0.005) and at the follow-up period (SMD - 1.33, 95% CI - 2.18 to - 0.49, P = 0.002), while TSA showed the included sample size did not exceed required information size (RIS). Acupuncture was superior over no acupuncture after treatment (SMD - 0.52, 95% CI - 0.63 to - 0.41, P < 0.001), and cumulative sample size reached RIS. In terms of responder rate, acupuncture had a higher responder rate compared with sham acupuncture both after treatment (relative ratio [RR] 1.28, 95% CI 1.12 to 1.46, P = 0.0003) and the follow-up period (RR 1.37, 95% CI 1.19 to 1.58, P < 0.0001), but the sample size is inadequate. CONCLUSION: Acupuncture is an efficacious and safe treatment for TTH prevention, but this conclusion might be limited by the generally very low to low quality evidence. TSA suggested that high-quality trials are needed to verify the efficacy and safety of acupuncture compared to sham acupuncture.

Matching adjusted indirect comparison of acupuncture versus fremanezumab in the preventive treatment of episodic migraine.

OBJECTIVE: Acupuncture and fremanezumab are second-line treatments for migraine prophylaxis. We aimed to compare acupuncture with fremanezumab in the preventive treatment of episodic migraine by using a matching-adjusted indirect comparison analysis (MAIC). METHODS: We acquired participant-level data from an acupuncture trial recruiting 302 participants and summary-level data from a fremanezumab trial recruiting 875 participants (290 participants received monthly fremanezumab [MF] and 291 received single-dose fremanezumab [SF]). The primary outcome was the mean reduction in monthly headache days. The secondary outcomes were the mean reduction in monthly moderate-to-severe headache days, days with acute medication, and the adverse events rate. RESULTS: Before matching, the acupuncture arm had significantly lower BMI, fewer headache days with at least moderate severity, and fewer days with acute medication. After matching, the baseline variables were comparable between groups. The three arms had no difference in the change of monthly migraine days (MF vs. acupuncture: mean difference 0.3, 95%CI -0.5 to 1.1, p-value = 0.473; SF vs. acupuncture: mean difference 0.5, 95%CI -0.3 to 1.3, p-value = 0.214). The results were similar in the analyses of secondary outcomes sensitivity analyses. Thirty-six (25%) participants in the acupuncture arm reported adverse events, versus 192(66%) participants in the MF arm and 193 (66%) in the SF arm. CONCLUSION: The preventive treatment effect of acupuncture is equivalent to fremanezumab, and it presented with a lower adverse event rate, which indicates that acupuncture can be an alternative to fremanezumab.

Risk factors of systemic lupus erythematosus: an overview of systematic reviews and Mendelian randomization studies

Abstract Background The etiology of systemic lupus erythematosus is complex and incurable. A large number of systematic reviews have studied the risk factors of it. Mendelian randomization is an analytical method that uses genetic data as tool variables to evaluate the causal relationship between exposure and outcome. Objective To review the systematic reviews and Mendelian randomization studies that focused on the risk factors of systemic lupus erythematosus and shed light on the development of treatments for its prevention and intervention. Methods From inception to January 2022, we systematically searched MEDLINE (via PubMed) and Embase for related systematic reviews and Mendelian randomization studies. Extract relevant main data for studies that meet inclusion criteria. The quality of systematic reviews was assessed by using Assessment of Multiple Systematic Reviews 2 (AMSTAR-2). Finally, the risk factors are scored comprehensively according to the results' quantity, quality, and consistency. Results Our study involved 64 systematic reviews and 12 Mendelian randomization studies. The results of systematic reviews showed that diseases (endometriosis, atopic dermatitis, allergic rhinitis), lifestyle (smoking, drinking, vaccination), and gene polymorphism influenced the incidence of systemic lupus erythematosus. The results of Mendelian randomization studies identified the role of disease (periodontitis, celiac disease), trace elements (selenium, iron), cytokines (growth differentiation factor 15), and gut microbiome in the pathogenesis of systemic lupus erythematosus. Conclusion We should pay attention to preventing and treating systemic lupus erythematosus in patients with endometriosis, celiac disease, and periodontitis. Take appropriate dietary supplements to increase serum iron and selenium levels to reduce the risk of systemic lupus erythematosus. There should be no excessive intervention in lifestyles such as smoking and drinking.

Genetically proxied inhibition of tumor necrosis factor and the risk of colorectal cancer: A drug-target mendelian randomization study.

Background: Previous studies suggested that anti-TNF drugs might be repurposed as a preventive treatment for colorectal cancer. We aimed to examine whether genetically proxied inhibition of tumor necrosis factor receptor 1 (TNFR1) reduces the absolute risk of colorectal cancer through mendelian randomization (MR) analysis. Methods: We obtained 28 single nucleotide polymorphisms (SNPs) that were located within a ±15 kilobase window of the TNFRSF1A-the gene that encodes the TNFR1 protein, and we used genetic data from three GWAS studies of circulating levels of TNFR1, C-reactive protein (CRP), and white blood counts (WBC) to screen SNPs that proxied the inhibition of TNFR1. Positive control analyses were then performed by using another three GWAS data from the ulcerative colitis cohort (n = 45,975), Crohn's disease cohort (n = 40,266), and multiple sclerosis cohort (n = 115,803) to confirm the effect of the included SNPs. A two-sample mendelian randomization analysis was performed to examine the association between TNFR1 inhibition and the absolute risk reduction (ARR) of colorectal cancer. Results: We finally included seven SNPs to proxy the anti-TNF effect, and these SNPs caused lower levels of TNFR1, CRP, and white blood counts. In positive control analyses, the included SNPs caused lower odds ratio of ulcerative colitis and Crohn's disease but a higher odds ratio of multiple sclerosis, consistent with drug mechanistic actions and previous trial evidence. By using the inverse-variance weighted analyses to combine the effects of the seven SNPs, we found that the anti-TNF effect was associated with a 0.988 (95%CI 0.985-0.991) mg/L decrease in CRP levels and a reduction in the risk of colorectal cancer (absolute risk reduction -2.1%, 95%CI -3.8% to -0.4%, p = 0.01). Conclusion: Our study confirmed that anti-TNF drugs were associated with a risk reduction in colorectal cancer. Physicians could consider using anti-TNF drugs for the prevention of colorectal cancer, especially in patients with high risks of developing cancer.

Highly Site Selective Formal [5+2] and [4+2] Annulations of Isoxazoles with Heterosubstituted Alkynes by Platinum Catalysis: Rapid Access to Functionalized 1,3-Oxazepines and 2,5-Dihydropyridines.

Platinum-catalyzed formal [5+2] and [4+2] annulations of isoxazoles with heterosubstituted alkynes enabled the atom-economical synthesis of valuable 1,3-oxazepines and 2,5-dihydropyridines, respectively. Importantly, this Pt catalysis not only led to unique reactivity dramatically divergent from that observed under Au catalysis, but also proceeded via unprecedented α-imino platinum carbene intermediates.

Atom-Economic Synthesis of Fully Substituted 2-Aminopyrroles via Gold-Catalyzed Formal [3+2] Cycloaddition between Ynamides and Isoxazoles.

A concise and flexible synthesis of fully substituted 2-aminopyrroles via gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles has been developed. Under mild reaction conditions, various 2-aminopyrrole derivatives were obtained in good to excellent yields, thus providing an efficient and atom-economic way for the construction of fully substituted 2-aminopyrroles.

Flexible and practical synthesis of 3-oxyindoles through gold-catalyzed intermolecular oxidation of o-ethynylanilines.

A novel gold-catalyzed intermolecular oxidation of o-ethynylanilines has been developed. A range of functionalized 3-oxyindoles are readily accessed by utilizing this strategy. Importantly, this gold-catalyzed oxidative process outcompetes the typical indole formation.

[Optimization for supercritical CO2 extraction with response surface methodology and component analysis of Sapindus mukorossi oil].

OBJECTIVE: To study the extraction conditions of Sapindus mukorossi oil by Supercritical CO2 Extraction and identify its components. METHODS: Optimized SFE-CO2 Extraction by response surface methodology and used GC-MS to analysie Sapindus mukorossi oil compounds. RESULTS: Established the model of an equation for the extraction rate of Sapindus mukorossi oil by Supercritical CO2 Extraction, and the optimal parameters for the Supercritical CO2 Extraction determined by the equation were: the extraction pressure was 30 MPa, temperature was 40 degrees C; The separation I pressure was 14 MPa, temperature was 45 degrees C; The separation II pressure was 6 MPa, temperature was 40 degrees C; The extraction time was 60 min and the extraction rate of Sapindus mukorossi oil of 17.58%. 22 main compounds of Sapindus mukorossi oil extracted by supercritical CO2 were identified by GC-MS, unsaturated fatty acids were 86.59%. CONCLUSION: This process is reliable, safe and with simple operation, and can be used for the extraction of Sapindus mukorossi oil.

[Research of the essential oil of Plumeria rubra var. actifolia from Laos by supercritical carbon dioxide extraction].

The orthogonal test and the supercritical carbon dioxide fluid extraction were used for optimizing the extraction of the essential oil from Plumeria rubra var. actifolia for the first time. Compared with the steam distillation, the optimal operation parameter of extraction was as follows: extraction pressure 25 MPa, extraction temperature 45 degrees C; separator I pressure 12 MPa, separator I temperature 55 degrees C; separator II pressure 6 MPa, separator II temperature 30 degrees C. Under this condition the yield of the essential oil was 5.8927%. The components were separated and identified by GC-MS. 53 components of Plumeria rubra var. actifolia measured by SFE method were identified and determined by normalization method. The main components were 1, 6, 10-dodecatrien-3-ol, 3, 7, 11-trimethyl, benzoic acid, 2-hydroxy-, phenylmethyl ester, 1, 2-benzenedicarboxylic acid, bis(2-methylpropyl) ester,etc.. 1, 2-Benzenedicarboxylic acid, bis (2-methylpropyl) este. took up 66.11% of the total amount, and there was much difference of the results from SD method.