IntroductionAlzheimer’s disease (AD) is the most common form of dementia worldwide. The biological mechanisms underlying the pathogenesis of AD aren’t completely clear. Studies have shown that the gut microbiota could be associated with AD pathogenesis; however, the pathways involved still need to be investigated.AimsTo explore the possible pathways of the involvement of gut microbiota in AD pathogenesis through metabolites and to identify new AD biomarkers.MethodsSeven-month-old APP/PS1 mice were used as AD models. The Morris water maze test was used to examine learning and memory ability. 16S rRNA gene sequencing and widely targeted metabolomics were used to identify the gut microbiota composition and fecal metabolic profile, respectively, followed by a combined analysis of microbiomics and metabolomics.ResultsImpaired learning abilities were observed in APP/PS1 mice. Statistically significant changes in the gut microbiota were detected, including a reduction in β-diversity, a higher ratio of Firmicutes/Bacteroidota, and multiple differential bacteria. Statistically significant changes in fecal metabolism were also detected, with 40 differential fecal metabolites and perturbations in the pyrimidine metabolism. Approximately 40% of the differential fecal metabolites were markedly associated with the gut microbiota, and the top two bacteria associated with the most differential metabolites were Bacillus firmus and Rikenella. Deoxycytidine, which causes changes in the pyrimidine metabolic pathway, was significantly correlated with Clostridium sp. Culture-27.ConclusionsGut microbiota may be involved in the pathological processes associated with cognitive impairment in AD by dysregulating pyrimidine metabolism. B. firmus, Rikenella, Clostridium sp. Culture-27, and deoxyuridine may be important biological markers for AD. Our findings provide new insights into the host-microbe crosstalk in AD pathology and contribute to the discovery of diagnostic markers and therapeutic targets for AD.
ObjectiveConstraint-induced movement therapy (CIMT) is a common treatment for upper extremity motor dysfunction after a stroke. However, whether it can effectively improve lower extremity motor function in stroke patients remains controversial. This systematic review comprehensively studies the current evidence and evaluates the effectiveness of CIMT in the treatment of post-stroke lower extremity motor dysfunction.MethodsWe comprehensively searched randomized controlled trials related to this study in eight electronic databases (PubMed, Embase, The Cochrane Library, Web of Science, CBM, CNKI, WAN FANG, and VIP). We evaluated CIMT effectiveness against post-stroke lower extremity motor dysfunction based on the mean difference and corresponding 95% confidence interval (95% CI). We assessed methodological quality based on the Cochrane Bias Risk Assessment Tool. After extracting the general information, mean, and standard deviation of the included studies, we conducted a meta-analysis using RevMan 5.3 and Stata 16.0. The primary indicator was the Fugl-Meyer Assessment scale on lower limbs (FMA-L). The secondary indicators were the Berg balance scale (BBS), 10-meter walk test (10MWT), gait speed (GS), 6-min walk test (6MWT), functional ambulation category scale (FAC), timed up and go test (TUGT), Brunnstrom stage of lower limb function, weight-bearing, modified Barthel index (MBI), functional independence measure (FIM), stroke-specific quality of life questionnaire (SSQOL), World Health Organization quality of life assessment (WHOQOL), and National Institute of Health stroke scale (NIHSS).ResultsWe initially identified 343 relevant studies. Among them, 34 (totaling 2,008 patients) met the inclusion criteria. We found that patients treated with CIMT had significantly better primary indicator (FMA-L) scores than those not treated with CIMT. The mean differences were 3.46 (95% CI 2.74–4.17, P < 0.01, I2 = 40%) between CIMT-treated and conventional physiotherapy-treated patients, 3.83 (95% CI 2.89–4.77, P < 0.01, I2 = 54%) between patients treated with CIMT plus conventional physiotherapy and patients treated only with conventional physiotherapy, and 3.50 (95% CI 1.08–5.92, P < 0.01) between patients treated with CIMT plus western medicine therapy and those treated only with western medicine therapy. The secondary indicators followed the same trend. The subgroup analysis showed that lower extremity CIMT with device seemed to yield a higher mean difference in FMA-L scores than lower extremity CIMT without device (4.52, 95% CI = 3.65–5.38, P < 0.01 and 3.37, 95% CI = 2.95–3.79, P < 0.01, respectively).ConclusionCIMT effectively improves lower extremity motor dysfunction in post-stroke patients; however, the eligible studies were highly heterogeneous.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=277466.
Background The circadian locomotor output cycles kaput (CLOCK) gene and the alcohol dehydrogenase 4 (ADH4) gene are promising candidates for susceptibility to cluster headaches (CH). Associations of the three single nucleotide polymorphisms (SNPs)—CLOCK SNP rs1801260 and ADH4 SNPs rs1800759, and rs1126671—with CH were studied previously, but the results were inconsistent. Methods Associations between the three SNPs (rs1801260, rs1126671, and rs1800759) and CH risk were separately assessed by pooled odds ratios (ORs) along with 95% confidence intervals (95% CIs) based on five different genetic models. Methodological quality was assessed using the Newcastle–Ottawa Quality Assessment Scale (NOS). All statistical analyses were carried out with RevMan 5.3 software. Results Eight studies involving 1437 CH patients and 2541 healthy controls were selected for quantitative synthesis, from five studies on CLOCK rs1801260, five on ADH4 rs1800759, and three on ADH4 rs1126671. Our pooled data did not support associations between the three SNPs (rs1801260 in the CLOCK gene, rs1800759 and rs1126671 in the ADH4 gene) and susceptibility to CH (rs1801260: OR 1.10, 95% CI: 0.95–1.28; p = 0.19; rs1800759: OR 1.06, 95% CI: 0.93–1.22; p = 0.37; and rs1126671: OR 1.09, 95% CI: 0.92–1.28; p = 0.32). Conclusion We found no significant associations between the three SNPs (rs1801260 in the CLOCK gene and rs1800759 and rs1126671 in the ADH4 gene) and the susceptibility to CH across both Caucasian and Asian ethnicities in our meta‐analysis.
Background: Obesity is a widespread chronic metabolic disease that significantly impairs quality of life. Studies have demonstrated the efficacy of both acupuncture and acupoint catgut embedding (ACE) in the management of obesity. However, the superiority of acupuncture combined with ACE over acupuncture alone remains a subject of controversy. This study aims to elucidate this controversy and provide robust clinical evidence. Methods: A comprehensive search of relevant literature from the initiation to July 2022 was carried out in 8 databases (PubMed, EMBASE, Cochrane database, Web of Science, CBM Database, CNKI, Wan-fang Database, and VIP Database). We included randomized controlled trials (RCTs) that investigated the treatment of simple obesity using acupuncture paired with ACE, with acupuncture alone as the control group. The pooled outcomes included body mass index (BMI), body weight (BW), %BF, waist circumference (WC), hip circumferences (HC), waist-to-hip ratio (WHR), therapeutic effective rate (TER), and adverse events. Two independent reviewers performed screening (using EndNote X9) and quality assessment (using the Cochrane Risk of Bias tool) for the included studies. with the software RevMan 5.3 was used to perform pooling of effect sizes. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: A total of 20 trials involving 15 datasets (1616 participants) were included. The findings demonstrated significant improvements in outcome measures when acupuncture was combined with ACE, compared with acupuncture alone (BMI: MD = −1.49 kg/m2, 95% confidence interval [CI] = −1.93 to −1.04, P < .01; BW: MD = −2.38, 95% CI = −3.86 to −0.89, P < .01; %BF: MD = −2.19, 95% CI = −3.23 to −1.15, P < .01; WC: MD = −2.01, 95% CI = −3.66 to −0.35, P < .05; HC: MD = −0.83, 95% CI = −1.64 to −0.02, P < .05; WHR: MD = −0.02, 95% CI = −0.03 to −0.01, P < .01; TER: OR = 2.68, 95% CI = 1.93–3.74, P < .01). Adverse effects were reported in 4 studies. Conclusion subsections: The results of this meta-analysis indicate that acupuncture combined with ACE is superior to acupuncture alone in the treatment of obesity, which is supported by the subgroup analysis. The assessment of efficacy may have been influenced by variations in study quality, potentially amplifying the observed effects. RCTs with larger sample sizes and improved methodological quality are needed to enhance the validity of the findings.
Background Randomised controlled trials (RCTs) evaluating Problematic internet use (PIU) have reported many different outcomes, which are themselves often defined and measured in distinct ways. Numerous clinical trials have been conducted on the efficacy and safety of different interventions in the treatment of PIU, resulting in many different outcome measures and different ways of measuring them. In order to facilitate the future research of PIU, it is necessary to produce the core Outcome Set (COS), which can help to translate the results into high-quality evidence. Methods and analysis: This mixed-method project has a three-phase tool: Phase 1, a scoping review of the literature to identify outcomes that have been reported in clinical trials and systematic reviews of interventions for PIU. Phase 2, a systematic review of PIU literature was conducted to identify potential outcome indicators. Phase 3, final outcome indicators were determined through Modified Delphi Method, Consensus Meetings, Stakeholder Perspectives and Stakeholder Consultations. Conclusions We will develop a COS that should be reported in future clinical trials of PIU. Trial registration: Core Outcome Measures in Effectiveness Trials (COMET) Initiative database registration: www.comet-initiative.org/Studies/Details/2109. Registered in August 2022.
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