Beyond traditional therapies: a network meta-analysis on the treatment efficacy for chronic phantom limb pain.

BACKGROUND: Phantom limb pain (PLP) frequently affects individuals with limb amputations. When PLP evolves into its chronic phase, known as chronic PLP, traditional therapies often fall short in providing sufficient relief. The optimal intervention for chronic PLP remains unclear. OBJECTIVE: The objectives of this network meta-analysis (NMA) were to examine the efficacy of different treatments on pain intensity for patients with chronic PLP. EVIDENCE REVIEW: We searched Medline, EMBASE, Cochrane CENTRAL, Scopus, and CINAHL EBSCO, focusing on randomized controlled trials (RCTs) that evaluated interventions such as neuromodulation, neural block, pharmacological methods, and alternative treatments. An NMA was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was pain score improvement, and the secondary outcomes were adverse events. FINDINGS: The NMA, incorporating 12 RCTs, indicated that neuromodulation, specifically repetitive transcranial magnetic stimulation, provided the most substantial pain improvement when compared with placebo/sham groups (mean difference=-2.9 points, 95% CI=-4.62 to -1.18; quality of evidence (QoE): moderate). Pharmacological intervention using morphine was associated with a significant increase in adverse event rate (OR=6.04, 95% CI=2.26 to 16.12; QoE: low). CONCLUSIONS: The NMA suggests that neuromodulation using repetitive transcranial magnetic stimulation may be associated with significantly larger pain improvement for chronic PLP. However, the paucity of studies, varying patient characteristics across each trial, and absence of long-term results underscore the necessity for more comprehensive, large-scale RCTs. PROSPERO REGISTRATION NUMBER: CRD42023455949.

Metabolic profiles of Fufang Xiling Jiedu capsule in rats by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.

Fufang Xiling Jiedu capsule (FXJC), a traditional Chinese medicine that evolved from "Yinqiao Powder", is widely used for the treatment of cold and influenza. However, due to a lack of in vivo metabolism research, the chemical components responsible for the therapeutic effects still remain unclear. Hence, this study aimed to describe the metabolic profiles of the FXJC in rat plasma, urine, and feces. A combined data mining strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was employed and 201 xenobiotics, including 117 prototype components and 84 metabolites were detected. Phenolic acids, flavonoids, triterpenes, and lignans were prominent ingredients absorbed in vivo, and the major metabolic pathways of the detected metabolites were glucuronidation, sulfation, methylation, and oxidation. This is the first systematic study on the metabolism of the FXJC in vivo, providing valuable information for future studies on the efficacy, toxicity, and mechanism of the FXJC.

High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis.

Migraine is a highly prevalent neurologic disorder with prevalence rates ranging from 9% to 18% worldwide. Current pharmacologic prophylactic strategies for migraine have limited efficacy and acceptability, with relatively low response rates of 40% to 50% and limited safety profiles. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are considered promising therapeutic agents for migraine prophylaxis. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various dosages of EPA/DHA and other current Food and Drug Administration-approved or guideline-recommended prophylactic pharmacologic interventions for migraine. Randomized controlled trials (RCTs) were eligible for inclusion if they enrolled participants with a diagnosis of either episodic or chronic migraine. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed were 1) changes in migraine frequency and 2) acceptability (i.e., dropout for any reason). Secondary outcomes included response rates, changes in migraine severity, changes in the frequency of using rescue medications, and frequency of any adverse events. Forty RCTs were included (N = 6616; mean age = 35.0 y; 78.9% women). Our analysis showed that supplementation with high dosage EPA/DHA yields the highest decrease in migraine frequency [standardized mean difference (SMD): -1.36; 95% confidence interval (CI): -2.32, -0.39 compared with placebo] and the largest decrease in migraine severity (SMD: -2.23; 95% CI: -3.17, -1.30 compared with placebo) in all studied interventions. Furthermore, supplementation with high dosage EPA/DHA showed the most favorable acceptability rates (odds ratio: 1.00; 95% CI: 0.06, 17.41 compared with placebo) of all examined prophylactic treatments. This study provides compelling evidence that high dosage EPA/DHA supplementation can be considered a first-choice treatment of migraine prophylaxis because this treatment displayed the highest efficacy and highest acceptability of all studied treatments. This study was registered in PROSPERO as CRD42022319577.

Primary antibiotic resistance of Helicobacter pylori in the Asia-Pacific region between 1990 and 2022: an updated systematic review and meta-analysis.

BACKGROUND: We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic resistance continues to rise is unknown. Therefore, we aimed to assess the latest prevalence of H pylori antibiotic resistance in this region. METHODS: We did an updated systematic review and meta-analysis of observational studies and randomised controlled trials published in PubMed, Embase, and Cochrane Library between Jan 1, 1990, and July 12, 2023. Studies investigating primary H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline in individuals naive to eradication therapy in the Asia-Pacific region (as defined by the UN geoscheme) were eligible for inclusion. There were no language restrictions. Studies that focused on specific subpopulations (eg, children) were excluded. Using a standardised extraction form, two authors independently reviewed and extracted summary data from all eligible articles. The updated prevalence of antibiotic resistance was generated by meta-analysis under a random-effects model and subgroup analyses were done by countries and periods of study. Between-study variability was assessed by use of I2. The study is registered in PROSPERO, CRD42022339956. FINDINGS: A total of 351 studies, including 175 new studies and 176 studies from our previous analysis, were included in this meta-analysis. The overall prevalence of primary antibiotic resistance of H pylori between 1990 and 2022 was 22% (95% CI 20-23; I2=96%) for clarithromycin, 52% (49-55; I2=99%) for metronidazole, 26% (24-29; I2=96%) for levofloxacin, 4% (3-5; I2=95%) for tetracycline, and 4% (3-5; I2=95%) for amoxicillin. Prevalence varied considerably between countries and across study periods. From 1990 to 2022, the prevalence of primary resistance increased for clarithromycin, metronidazole, and levofloxacin but remained stable for amoxicillin and tetracycline. The latest primary resistance prevalences were 30% (95% CI 28-33; I2=93%) for clarithromycin, 61% (55-66; I2=99%) for metronidazole, 35% (31-39; I2=95%) for levofloxacin, 4% (2-6; I2=96%) for tetracycline, and 6% (4-8; I2=96%) for amoxicillin in the Asia-Pacific region. INTERPRETATION: Treatment guidelines should be adapted in response to the rising primary resistance of key antibiotics for H pylori eradication. A global policy to control and monitor the antibiotic resistance of H pylori is urgently needed. FUNDING: Ministry of Health and Welfare of Taiwan, National Science and Technology Council of Taiwan, and National Taiwan University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Association between potential supplement-drug interactions and liver diseases in patients with cancer: A large prospective cohort study.

BACKGROUND & AIMS: The concurrent use of herbal and dietary supplements and conventional drugs can lead to interactions in patients with cancer, of which hepatotoxicity is one of the most concerning sequelae. This study examined the potential supplement-drug interactions involving the hepatic system, and their associations with documented liver diseases, among patients with cancer in a large population-based cohort in the UK Biobank. METHODS: Participants diagnosed with cancer and had completed supplement-use assessment after diagnosis were included. Potentially interacting supplement-drug combinations that involved CYP enzymes or increased the risk of hepatotoxicity were identified from four tertiary databases. Liver diseases were identified using ICD-codes K70-77. Log-binomial regression was used to investigate the associations between potentially-interacting supplement-drug combinations and liver diseases documented (1) at any time, and (2) confined to only after the time of supplement-use assessment, adjusting for age, sex and pre-existing comorbidities. RESULTS: This analysis included 30,239 participants (mean age = 60.0 years; 61.9% female). Over half (n = 17,698, 58.5%) reported the use of supplements after cancer diagnoses. Among supplements users, 36.9% (n = 6537/17,698) were on supplement-drug combinations with interacting potential involving the hepatic system. Patients taking supplements and drugs who had hepatic comorbidities were more likely to take potentially interacting pairs (adjusted risk ratio = 1.14, 95% CI = 1.06-1.23, p < 0.001). However, no significant association was observed between the use of these combinations and subsequent liver diseases (all p > 0.05). CONCLUSION: Approximately one-third of the participants who had cancer and were supplement users had a risk of potential supplement-drug interactions that contribute to adverse liver effect. Healthcare professionals should communicate with patients with cancer, especially those with pre-existing liver diseases, about supplement use and proactively assess the clinical significance of potential interactions.

Effects of oral nutritional supplements on the nutritional status and inflammatory markers in patients on maintenance dialysis: a systematic review and meta-analysis of randomized clinical trials.

Background and aims: Patients on hemodialysis (HD) or peritoneal dialysis (PD) often have insufficient energy and protein intake, resulting in poor nutritional status and adverse outcomes. Oral nutritional supplements (ONSs) are the most commonly used to increase such patients' energy and protein intakes. Methods: In this systematic review and meta-analysis, we analyzed studies on nutritional status, inflammatory markers, and electrolyte levels in patients on dialysis receiving ONSs. We searched four electronic databases from inception until 31 December 2022, for randomized controlled trials comparing ONS treatment versus placebo or routine care. Results: 22 studies with 1185 patients on dialysis were included in our meta-analysis. Compared with the control group, the ONS group exhibited significantly increased serum albumin levels [1.26 g/l (95%CI, 0.50-2.02, P < 0.0001; I2 = 80.4%)], body mass indexes (BMIs) [0.30 kg/m2 (95%CI, 0.09-0.52, P = 0.005; I2 = 41.4%)], and handgrip strength (HGS) [0.96 kg (95%CI, 0.07-1.84, P = 0.034; I2 = 41.4%)] from baseline to the end of intervention. No significant differences were observed between the groups in lean body mass, phase angle, C-reactive protein, and serum phosphorus and potassium levels. In terms of improving albumin, the subgroup analyses show that ONS use seems to be more inclined to three variations: HD patients, short-term use, and non-intradialytic supplementation. Conclusion: In conclusion, ONS use can improve the nutritional status of patients on dialysis in terms of their serum albumin, BMI, and HGS without significant effects on serum phosphorus, potassium, and C-reactive protein levels. However, it remains uncertain whether these results translate to improvement in clinically relevant outcomes. Large-scale high-quality studies are still required in this population.

Effects of Vitamin D Supplementation on Cognitive Outcomes: A Systematic Review and Meta-Analysis.

Clinical studies examining the effects of vitamin D on cognition have reported inconsistent results. To date, no comprehensive study has examined this effect on the basis of sample characteristics or intervention model-related factors. This systematic review and meta-analysis of randomized controlled trials investigated the effects of vitamin D supplementation on global cognitive function and specific cognitive domains. This review was preregistered in the PROSPERO database (CRD42021249908) and comprised 24 trials enrolling 7557 participants (mean age: 65.21 years; 78.54% women). The meta-analysis revealed that vitamin D significantly influenced global cognition (Hedges' g = 0.128, p = .008) but not specific cognitive domains. A subgroup analysis indicated that the effect size of vitamin D was stronger for vulnerable populations (Hedges' g = 0.414) and those with baseline vitamin D deficiency (Hedges' g = 0.480). On the basis of subgroup analyses in studies without biological flaws (Hedges' g = 0.549), we suggest that an intervention model should correct baseline vitamin D deficiency. Our results indicate that vitamin D supplementation has a small but significant positive effect on cognition in adults.

Omega-3 polyunsaturated fatty acids in sarcopenia management: A network meta-analysis of randomized controlled trials.

Sarcopenia frequently occurs with aging and leads to major adverse impacts on activities of daily living and quality of life in elderly individuals. Omega-3 polyunsaturated fatty acid (omega-3 PUFAs) supplements are considered promising therapeutic agents for sarcopenia management; however, the evidence remains inconsistent. We reviewed randomized controlled trials (RCTs) about omega-3 PUFA supplementation in patients with sarcopenia or in those at high risk for sarcopenia. Network meta-analysis (NMA) procedures were conducted using a frequentist model. The primary outcomes were (1) upper-extremity muscle strength and (2) lower-extremity physical function. The NMA of 16 RCTs showed that the high-dose (more than 2.5 g/day omega-3 PUFAs) group yielded the greatest improvement in both upper-extremity muscle strength and lower-extremity physical function [compared to placebo/standard care groups, standardized mean difference (SMD)= 1.68, 95% confidence interval (95%CI)= 0.03-3.33, and SMD= 0.73, 95%CI= 0.16-1.30, respectively], and the effects were reaffirmed in subgroup analyses of placebo-controlled RCTs or those excluding concurrent resistance training programs. None of the investigated omega-3 PUFAs supplementation was associated with significantly increased skeletal muscle mass, fat mass, or overall body weight. Our findings provide a basis for future large-scale RCTs to investigate the dose effects and clinical application of omega-3 PUFA supplementation in sarcopenia management. TRIAL REGISTRATION: The current study was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (TSGHIRB No. B-109-29) and registered in PROSPERO (CRD42022347161).

Comparisons Between Endoscopic Band Ligation, Radiofrequency Ablation and Endoscopic Thermal Therapy for Gastric Antral Vascular Ectasia: A Meta-Analysis.

BACKGROUND: Endoscopic band ligation (EBL) and radiofrequency ablation (RFA) have emerged as alternative therapies of gastric antral vascular ectasia (GAVE) in addition to endoscopic thermal therapy (ETT), but the optimum choice remains inconclusive. AIM: We conducted a meta-analysis in order to compare these three treatments for GAVE. METHODS: We searched the electronic databases of PubMed, Embase and Cochrane Central Register of Controlled Trials without any language restrictions and also performed a manual literature search of bibliographies located in both retrieved articles and published reviews for eligible publications prior to December 8, 2021. We included comparative trials which had evaluated the efficacy and safety of interventions in adults (aged ≥ 18 years) diagnosed with symptomatic GAVE and was confirmed according to clinical backgrounds and upper gastrointestinal endoscopy. We included reports that compared three interventions, ETT, EBL, and RFA. The study was comprised of adults diagnosed with GAVE and focused on overall mortality, bleeding cessation, endoscopic improvement, complications, hospitalization, hemoglobin improvement, number of sessions and transfusion requirements. RESULTS: Twelve studies were performed involving a total of 571 participants for analysis. When compared with ETT, EBL achieved better bleeding cessation (OR 4.48, 95% CI 1.36-14.77, p = 0.01), higher hemoglobin improvement (MD 0.57, 95% CI 0.31-0.83, p < 0.01) and lower number of sessions (MD - 1.44, 95% CI - 2.54 to - 0.34, p = 0.01). Additionally, EBL was superior to ETT in endoscopic improvement (OR 6.00, 95% CI 2.26-15.97, p < 0.01), hospitalization (MD - 1.32, 95% CI - 1.91 to - 0.74, p < 0.01) and transfusion requirement (MD - 2.66, 95% CI - 4.67 to - 0.65, p = 0.01) with statistical significance, with the exception of mortality (OR 0.58, 95% CI 0.19-1.77, p = 0.34) and complication rate (OR 5.33, 95% CI 0.58-48.84, p = 0.14). CONCLUSION: For GAVE, we suggest that EBL be initially recommended, and APC and RFA be used as alternative treatment choices based upon a very low quality of evidence.

Efficacy and acceptability of anti-inflammatory eicosapentaenoic acid for cognitive function in Alzheimer's dementia: A network meta-analysis of randomized, placebo-controlled trials with omega-3 fatty acids and FDA-approved pharmacotherapy.

Alzheimer's dementia (AD) is a major contributor to global disability, and effective therapies to modify disease progression are currently lacking. The neuro-inflammatory theory is a potential etiology underlying this neurodegenerative disease. Previous randomized, controlled trials (RCTs) have provided inconclusive results regarding efficacy of omega-3 polyunsaturated fatty acids (PUFAs) regimens, which might provide anti-inflammatory benefits in the management of AD, in improving cognitive function among participants with AD. The objective of this frequentist-model based network meta-analysis (NMA) was to evaluate the potential advantages of omega-3 PUFAs and currently FDA-approved medications for AD on overall cognitive function in AD individuals. The primary outcomes were: (1) changes in cognitive function, and (2) acceptability, which refers to all-cause discontinuation. Additionally, secondary outcomes included quality of life, behavioral disturbances and safety/tolerability, which was assessed through the frequency of any reported adverse event. This NMA included 52 RCTs (6 with omega-3 PUFAs and 46 with FDA-approved medications) involving 21,111 participants. The results showed that long-term high-dose (1500-2000 mg/day) of eicosapentaenoic acid (EPA)-dominant omega-3 PUFAs augmented with anti-oxidants had the highest potential for cognitive improvement among all investigated treatments [standardized mean difference = 3.00, 95% confidence intervals (95 %CIs) = 1.84-4.16]. Compared to placebo, omega-3 PUFAs had similar acceptability [odds ratio (OR) = 0.46, 95 %CIs = 0.04 to 5.87] and safety profiles (OR = 1.24, 95 %CIs = 0.66 to 2.33)o. These findings support the potential neurotherapeutic effects of high dosage EPA-dominant omega-3 PUFAs for the amelioration of cognitive decline in patients with AD. Future large-scale, long-term RCTs should focus on different dosages of EPA-dominant omega-3 PUFAs regimens on improving cognitive dysfunction in patients with AD at different levels of inflammatory status and psychopathology.

Black cohosh extracts in women with menopausal symptoms: an updated pairwise meta-analysis.

OBJECTIVE: Menopausal symptoms are common in midlife women and have broad impacts on their daily functioning and quality of life. Black cohosh extracts have been widely used to relieve menopausal symptoms. However, the comparative benefits of different combined black cohosh regimens remain inconclusive. The aim of the current updated meta-analysis is to address the comparative efficacies of different black cohosh regimens in improving menopausal symptoms. METHODS: Random-effect model pairwise meta-analysis of randomized controlled trials was conducted to investigate the treatment effect on menopausal symptoms by the black cohosh extract both alone or combined with other related active ingredients. The outcomes studied were changes in menopausal symptoms after treatment with black cohosh extracts in menopausal women. RESULTS: Twenty-two articles including information on 2,310 menopausal women were included in the analyses. Black cohosh extracts were associated with significant improvements in overall menopausal symptoms (Hedges' g = 0.575, 95% CI = 0.283 to 0.867, P < 0.001), as well as in hot flashes (Hedges' g = 0.315, 95% CIs = 0.107 to 0.524, P = 0.003), and somatic symptoms (Hedges' g = 0.418, 95% CI = 0.165 to 0.670, P = 0.001), compared with placebo. However, black cohosh did not significantly improve anxiety (Hedges' g = 0.194, 95% CI = -0.296 to 0.684, P = 0.438) or depressive symptoms (Hedges' g = 0.406, 95% CI = -0.121 to 0.932, P = 0.131). The dropout rate for black cohosh products was similar to that for placebo (odds ratio = 0.911, 95% CI = 0.660 to 1.256, P = 0.568). CONCLUSIONS: This study provides updated evidence regarding the potentially beneficial effects of black cohosh extracts for relieving menopausal symptoms in menopausal women.

[Network Meta-analysis of single Hirudo prescriptions in treatment of ischemic cerebrovascular disease].

This study intended to evaluate the efficacy and safety of single Hirudo prescriptions in the treatment of ischemic cerebrovascular disease(ICVD) by frequency network Meta-analysis and traditional Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library databases were searched to collect the randomized controlled trial(RCT) of single Hirudo prescriptions for ICVD from the inception of the databases to May 2022. The quality of the included literature was evaluated by Cochrane risk of bias tool. Finally, 54 RCTs and 3 single Hirudo prescriptions were included. Statistical analysis was conducted by RevMan 5.3 and Stata SE 15. Network Meta-analysis showed that in terms of the clinical effective rate, the surface under the cumulative ranking curve(SUCRA) of intervention measures was as follows: Huoxue Tongmai Capsules+conventional treatment>Maixuekang Capsules+conventional treatment>Naoxuekang Capsules+conventional treatment>conventional treatment. Traditional Meta-analysis revealed that in terms of the safety of ICVD treatment, Maixuekang Capsules+conventional treatment had higher safety than conventional treatment alone. According to the network Meta-analysis and traditional Meta-analysis, it was found that conventional treatment combined with single Hirudo prescriptions improved the clinical efficacy of ICVD patients, and compared with that of conventional treatment alone, the incidence of adverse reactions of combined treatment was low and the safety was high. However, the methodological quality of the articles included in this study was generally low and there were large differences in the number of articles on the three combined medication. Therefore, the conclusion of this study needed to be confirmed by subsequent RCT.

The Effectiveness of Whole-Body Vibration and Heat Therapy on the Muscle Strength, Flexibility, and Balance Abilities of Elderly Groups.

Whole-body vibration (WBV) is a novel exercise training measure that promotes the muscle strength, flexibility, and balance abilities of elderly groups. The feasibility and applicability of 20-30 min (lowering a heat pack at 73 °C by wrapping it in multiple layers of towels to 40-43 °C before it touched the skin) thermotherapy are increasingly being demonstrated by applications and clinical trials. Studies show that it increases the flexibility of macules and ligament. However, no studies have examined the interactions between the pre-exercise and post-exercise application of heat therapy (duration a training course). Therefore, this study investigates the effects of WBV and heat therapy on the muscle strength, flexibility, and balance abilities of elderly groups. Eighty middle-age and elderly participants with no regular exercise habits were enrolled in this study. They were randomly assigned to a WBV group, a WBV plus heat therapy group, a heat therapy alone group, and a control group. The WBV groups underwent 5-min, fixed-amplitude (4 mm), thrice-weekly WBV training sessions for 3 consecutive months on a WBV training machine. Participants' balance was measured using the limits of stability (LOS) test on a balance system. The pretest and posttest knee extensor and flexor strength were tested using an isokinetic lower extremity dynamometer. Pretest and posttest flexibility changes were measured using the sit-and-reach test. Significantly larger pretest and posttest differences in flexibility and muscle strength were observed in the WBV and WBV plus heat therapy groups. The addition of heat therapy to WBV resulted in the largest flexibility improvements.

Correlation between Mild Cognitive Impairment and Sarcopenia: The Prospective Role of Lipids and Basal Metabolic Rate in the Link.

There is evidence of correlation between mild cognitive impairment (MCI) and sarcopenia (SA). However, the influencing factors and the mechanism, such as age-related lipid redistribution, remain unknown. This study aimed to clarify the role of dietary fats and erythrocyte lipids profile combined with basal metabolic rate (BMR) in the link between MCI and SA. A total of 1050 participants aged 65 to 85 were divided into control, MCI, SA and MCI and SA groups. Bioelectrical impedance analysis was used to evaluate appendicular lean mass and BMR. Cognition and dietary nutrition were detected by neuropsychological tests and food frequency questionnaires. UHPLC-QExactive-MS/MS and UHPLC-Qtrap-MS/MS were used to conduct the lipidomics analysis. Lower dietary intake of different phospholipids, unsaturated fatty acids and kinds of choline were significantly associated with MCI and SA. Least absolute shrinkage and selection operator, multivariate logistic regression, receiver operating characteristic curve and validation tests provided evidence that specific phospholipids, unsaturated fatty acids and BMR might be the critical factors in the processing of MCI and SA, as well as in their link. The lipidomic analysis observed a clear discrimination of the lipid profiles in the individuals who are in MCI, SA, or MCI and SA, compared with the control. Lower expressions in certain phospholipid species, such as sphingomyelin and phosphatidylethanolamines, decreased phosphatidylcholine with more unsaturated double bonds, lower level of lipids with C20:5 and C20:4, higher level of lipids with C18:2 and lipids with a remodeled length of acyl chain, might be closely related to the link between MCI and SA. Inadequate dietary intake and lower concentrations of the erythrocyte lipid profile of phospholipids and unsaturated fatty acids with a lower level of BMR might be the key points that lead to progress in MCI and SA, as well as in their link. They could be used as the prospective biomarkers for the higher risk of cognitive decline and/or SA in elderly population.

Comparative efficacy of omega-3 polyunsaturated fatty acids on major cardiovascular events: A network meta-analysis of randomized controlled trials.

The role of omega-3 polyunsaturated fatty acids (PUFAs) in primary and secondary prevention on major cardiovascular events (MCE) is inconclusive due to the potential heterogeneity in study designs of formulas, dosages, and ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from the findings of previous randomized controlled trials (RCTs). Here we conducted a comprehensive narrative review of pre-clinical studies and updated a network meta-analysis (NMA) to determine the comparative efficacy against MCE with different EPA/DHA dosages and formulas. We found that pure EPA was ranked the best option in the secondary prevention (hazard ratio: 0.72, 95% confidence interval: 0.65 to 0.81) from the NMA of 39 RCTs with 88,359 participants. There was no evidence of omega-3 PUFAs' efficacy in primary prevention. The mechanisms of omega-3 PUFAs' cardiovascular protection might link to the effects of anti-inflammation and stabilization of endothelial function from PUFA's derivatives including eicosanoids and the special pre-resolving mediators (SPMs).

The Effects of Patchouli Alcohol on Diarrhea-Predominant Irritable Bowel Syndrome are Correlated with Phenotypic Plasticity in Myenteric Neurons and the Targeted Regulation of Myosin Va.

Patchouli alcohol (PA) has been widely used for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in traditional Chinese medicine, and the related mechanism remains to be fully understood. Our previous study has indicated that PA significantly reduced visceral sensitivity and defecation area in IBS-D rats. In this study, we prepared an IBS-D rat model and observed the dynamic intestinal motility and colonic longitudinal muscle and myenteric plexus (LMMP) neurons, as well as their subtypes at D14, D21, and D28. After PA administration, we observed the effects on the changes in intestinal motility, colonic LMMP neurons, and LMMP Myosin Va in IBS-D rats and their co-localization with inhibitory neurotransmitter-related proteins. The results indicated that PA treatment could alleviate IBS-D symptoms, regulate the abnormal expression of LMMP neurons, increase Myosin Va expression, up-regulate co-localization levels of Myosin Va with neuronal nitric oxide synthase (nNOS), and promote co-localization levels of Myosin Va with vasoactive intestinal polypeptide (VIP). In conclusion, this study demonstrated the neuropathic alterations in the colon of chronic restraint stress-induced IBS-D rat model. PA reversed the neuropathological alteration by affecting the transport process of nNOS and VIP vesicles via Myosin Va and the function of LMMP inhibitory neurons, and these effects were related to the mechanism of enteric nervous system (ENS) remodeling.

Comparative efficacy of exercise regimens on sleep quality in older adults: A systematic review and network meta-analysis.

The efficacies of various exercise modalities in improving older adults' sleep quality remain unclear. Therefore, in this study, network meta-analysis was performed by comparing the efficacies of various exercise regimens in improving sleep quality in this age group. Six electronic databases were searched for relevant studies between the date of database creation and August 13, 2021. Only randomized controlled trials reporting the effects of exercise on sleep quality in this population were included. Random-effects network meta-analysis based on a frequentist framework was conducted. In total, 35 trials involving 3519 older adults were included. Cognitive behavioral therapy for insomnia, muscle endurance training combined with walking, Tai chi, Baduanjin, resistance training combined with walking, and resistance training significantly improved sleep quality to a greater degree than did usual care (P < 0.05). Muscle endurance training combined with walking led to significantly higher sleep quality than did regimens involving sleep hygiene, Pilates, only walking, health education, resistance training, Taichi, resistance training combined with walking, or yoga. Muscle endurance training combined with walking was identified as the optimal exercise program (88.9%) for enhancing sleep quality in older adults. The results of this study support the claim that exercise can improve sleep quality in this population. PROSPERO registration number: CRD42020178209.

Serum lipopolysaccharide-binding protein levels and cardiovascular events in hemodialysis patients: A prospective cohort study.

INTRODUCTION: Patients with end-stage kidney disease (ESKD) exhibit an elevated cardiovascular risk. Chronic inflammation is one of the main mechanisms of cardiovascular disease (CVD). Lipopolysaccharide has been proposed as a link between systemic inflammation and CVD. Herein, we evaluated whether lipopolysaccharide-binding protein (LBP), a surrogate marker of lipopolysaccharide and consequent inflammation, is associated with cardiovascular events in ESKD. METHODS: We performed a prospective cohort study of maintenance haemodialysis patients. Baseline serum LBP levels were categorized into tertiles and also modelled continuously for analyses. Cox regression methods were used to evaluate the association of serum LBP levels with cardiovascular events. RESULTS: A total of 360 haemodialysis patients were included in this analysis. During a median follow-up of 3.1 years, 90 (25.0%) patients had cardiovascular events. Patients in the upper tertile of serum LBP levels had a significantly greater risk of cardiovascular events [hazard ratio (HR) 4.87; 95% confidence intervals (CI), 2.12-11.15] than those in the lower tertile, independent of age, sex, hypertension, diabetes, CVD, dialysis vintage, body mass index, non-high-density lipoprotein cholesterol, albumin, phosphorus, high-sensitivity C-reactive protein, and interleukin-6. The association was consistent regardless of whether competing risk of death was accounted for (subdistribution HR 4.87; 95% CI, 1.96-12.11 for upper versus lower tertiles) or serum LBP was analysed as a continuous variable (HR 1.30; 95% CI, 1.02-1.66 per 1 SD increment). CONCLUSIONS: Serum LBP levels were independently associated with cardiovascular events in heomodialysis patients. LBP might serve as a novel biomarker for CVD in ESKD.

Benefits of Curcumin in the Vasculature: A Therapeutic Candidate for Vascular Remodeling in Arterial Hypertension and Pulmonary Arterial Hypertension?

Growing evidence suggests that hypertension is one of the leading causes of cardiovascular morbidity and mortality since uncontrolled high blood pressure increases the risk of myocardial infarction, aortic dissection, hemorrhagic stroke, and chronic kidney disease. Impaired vascular homeostasis plays a critical role in the development of hypertension-induced vascular remodeling. Abnormal behaviors of vascular cells are not only a pathological hallmark of hypertensive vascular remodeling, but also an important pathological basis for maintaining reduced vascular compliance in hypertension. Targeting vascular remodeling represents a novel therapeutic approach in hypertension and its cardiovascular complications. Phytochemicals are emerging as candidates with therapeutic effects on numerous pathologies, including hypertension. An increasing number of studies have found that curcumin, a polyphenolic compound derived from dietary spice turmeric, holds a broad spectrum of pharmacological actions, such as antiplatelet, anticancer, anti-inflammatory, antioxidant, and antiangiogenic effects. Curcumin has been shown to prevent or treat vascular remodeling in hypertensive rodents by modulating various signaling pathways. In the present review, we attempt to focus on the current findings and molecular mechanisms of curcumin in the treatment of hypertensive vascular remodeling. In particular, adverse and inconsistent effects of curcumin, as well as some favorable pharmacokinetics or pharmacodynamics profiles in arterial hypertension will be discussed. Moreover, the recent progress in the preparation of nano-curcumins and their therapeutic potential in hypertension will be briefly recapped. The future research directions and challenges of curcumin in hypertension-related vascular remodeling are also proposed. It is foreseeable that curcumin is likely to be a therapeutic agent for hypertension and vascular remodeling going forwards.

The Dose and Duration-dependent Association between Melatonin Treatment and Overall Cognition in Alzheimer's Dementia: A Network Meta- Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: While Alzheimer's dementia (AD) has a prevalence as high as 3-32% and is associated with cognitive dysfunction and the risk of institutionalization, no efficacious and acceptable treatments can modify the course of cognitive decline in AD. Potential benefits of exogenous melatonin for cognition have been divergent across trials. OBJECTIVE: The current network meta-analysis (NMA) was conducted under the frequentist model to evaluate the potential beneficial effects of exogenous melatonin supplementation on overall cognitive function in participants with AD in comparison to other FDA-approved medications (donepezil, galantamine, rivastigmine, memantine, and Namzaric). METHODS: The primary outcome was the changes in the cognitive function [measured by mini-mental state examination (MMSE)] after treatment in patients with Alzheimer's dementia. The secondary outcomes were changes in the quality of life, behavioral disturbance, and acceptability (i.e., drop-out due to any reason and rate of any adverse event reported). RESULTS: The current NMA of 50 randomized placebo-controlled trials (RCTs) revealed the medium-term lowdose melatonin to be associated with the highest post-treatment MMSE (mean difference = 1.48 in MMSE score, 95% confidence intervals [95% CIs] = 0.51 to 2.46) and quality of life (standardized mean difference = -0.64, 95% CIs = -1.13 to -0.15) among all of the investigated medications in the participants with AD. Finally, all of the investigated exogenous melatonin supplements were associated with similar acceptability as was the placebo. CONCLUSION: The current NMA provides evidence for the potential benefits of exogenous melatonin supplementation, especially medium-term low-dose melatonin, in participants with AD.