Association of lipid accumulation product with all-cause and cardiovascular disease mortality: Result from NHANES database.

BACKGROUND AND AIM: At present, there are few studies on the relationship between lipid accumulation product (LAP) and mortality. This study aims to explore the relationship between adult LAP and all-cause and cardiovascular disease (CVD) mortality. METHODS AND RESULTS: The study people from the National Health and Nutrition Examination Survey (NHANES). Results of the mortality study were based on death data up to December 31, 2019. Cox proportional risk model was used to estimate the risk ratio (HR) and 95 % CI of all-cause and CVD mortality. A total of 50162 people were included in the study (the weighted average age and male proportion were 48.14 years and 48.64 % respectively). During the follow-up of 203460871 person-years, 6850 deaths were recorded, including 1757 CVD deaths. After multivariable adjustment, the increase of LAP was significantly correlated with all-cause and CVD mortality. Compared with the participants of Quartile 1 of LAP, the multivariable adjusted HRs and 95 % CI of the participants of Quartile 4 of LAP were 1.54 (1.32, 1.80) all-cause mortality (P for trend<0.001), and 1.55 (1.16, 2.09) CVD mortality (P for trend = 0.04). For every increase of natural log-transformed LAP, the all-cause mortality increased by 22 %, and the CVD mortality increased by 14 % (both P < 0.05). CONCLUSIONS: Our cohort study based on NHANES showed that higher LAP was significantly associated with higher all-cause and CVD mortality. Maintaining a low LAP status may reduce the risk of death.

The RING-domain E3 ubiquitin ligase RNF146 promotes cardiac hypertrophy by suppressing the LKB1/AMPK signaling pathway.

The RING-domain E3 ubiquitin ligase RNF146 is an enzyme that plays an important role in ubiquitin-proteasomal protein degradation and participates in various pathophysiological processes. However, its role in cardiac hypertrophy is unclear. In the present work, thoracic transverse aortic constriction (TAC) was performed in transgenic mice with RNF146 knockout mice (KO) and wild-type mice, and neonatal rat cardiomyocytes (NRCMs) were subjected to angiotensin II (Ang II) stimulation to induce cardiac hypertrophy in vitro and in vivo. RNF146 expression was significantly increased in hypertrophied murine hearts and Ang II-stimulated NRCMs. RNF146-KO mice and knockdown of RNF146 NRCMs attenuated TAC- or Ang II-stimulated cardiac hypertrophy. Conversely, enforced expression of RNF146 aggravated these changes. Mechanistically, we found that RNF146 KO or knockdown increased the activation of the AMP-activated protein kinase (AMPK) pathway. Furthermore, we found that RNF146 KO or knockdown decreased ubiquitination of Liver kinase B1 (LKB1), which promoted the activation of the AMPK pathway in a dependent manner. In conclusion, RNF146 targets LKB1 protein for ubiquitin-proteasome degradation in cardiomyocytes and subsequently promotes cardiac hypertrophy by suppressing the activation of the AMPK signaling pathway.

Efficacy and Safety of Gabapentin vs. Carbamazepine in the Treatment of Trigeminal Neuralgia: A Meta-Analysis.

To evaluate the safety and efficacy of gabapentin in comparison with carbamazepine in the treatment of trigeminal neuralgia, a meta-analysis of randomized controlled trials was performed. Two reviewers independently selected studies, assessed study quality, and extracted data. Sixteen randomized controlled trials that included 1,331 patients were assessed. The meta-analysis showed that the total effective rate of gabapentin therapy group was similar with carbamazepine therapy group (OR = 1.600, 95% CI 1.185, 2.161, P = 0.002). While the effective rate of gabapentin therapy for 4 weeks was higher than that of carbamazepine therapy (OR = 1.495, 95% CI 1.061, 2.107, P = 0.022, heterogeneity: x2 = 7.12, P = 0.625, I2 = 0.0%), the life satisfaction improvement is also better in the gabapentin therapy group after a 4-week treatment (SMD = 0.966, 95% CI 0.583, 1.348, P < 0.001). Furthermore, our meta-analysis suggested that the adverse reaction rate of gabapentin therapy group was significantly lower than that of carbamazepine therapy group (OR = 0.312, 95% CI 0.240, 0.407, P < 0.001). In conclusion, present trials comparing gabapentin with carbamazepine are all poor in terms of methodological quality. Based on the available evidence, it is not possible to draw conclusions regarding the efficacy and side effects of gabapentin being superior to carbamazepine.

Risk of Stroke in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

OBJECTIVE: Observational studies, to date, have provided inconsistent findings on whether inflammatory bowel disease (IBD) is associated with an increased risk of stroke. We therefore performed a meta-analysis to evaluate the association of IBD and its specific subtypes with risk of stroke. DESIGN: We searched electronic databases for studies through May 13, 2015 assessing risk of stroke in patients with IBD. Cohort and case-control studies that reported incident cases of stroke in patients with IBD and a non-IBD control population were eligible. We calculated pooled hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 8 articles (126,493 IBD patients and 4748 cases of stroke) were included in this meta-analysis. The presence of IBD revealed a trend toward a modest increase in the risk of stroke incidence (HR = 1.29; 95% CI, 1.16-1.43). After subgroup analysis, Crohn's disease showed an increased risk of stroke incidence (7 studies: HR = 1.32; 95% CI, 1.13-1.56), and a significant association was also identified in ulcerative colitis (6 studies: HR = 1.18; 95% CI, 1.06-1.31). In addition, this risk is higher in women (6 studies: HR = 1.49; 95% CI, 1.24-1.79) than in men (HR = 1.22; 95% CI, 1.12-1.32). In the overall analysis we found considerable heterogeneity. CONCLUSION: Our results show a positive association between IBD and the risk of stroke.

Causal relationship between sleep disorders and the risk of Alzheimer's disease: A Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Epidemiological studies have shown that sleep disorders are risk factors for Alzheimer's disease (AD), but the causal relationship between sleep disorders and AD risk is unknown. We aim to assess the potential genetic causal association between sleep characteristics and AD, which may contribute to early identification and prediction of risk factors for AD. METHODS: Seven sleep-related traits and the outcome phenotype AD were selected from published genome-wide association studies (GWASs). These sleep-related characteristics and instrumental variables (IVs) for AD were extracted. Two-sample and multivariate Mendelian randomization (MR) analyses were performed to assess the causal relationships between sleep characteristics and AD. The inverse variance weighted (IVW), weighted median (WME), weighted mode (WM), MR-Egger regression (MR-Egger) and simple mode (SM) models were used to evaluate causality. The existence of pleiotropy was detected and corrected by MR-Egger regression, MR pleiotropy residuals and outliers. RESULTS: A two-sample MR study revealed a positive causal association between sleep duration and the onset of AD (OR = 1.002, 95 % CI: 1.000-1.004), and the risk of AD increased with increasing sleep duration. The MR-Egger regression method and MR-PRESSO were used to identify and correct pleiotropy, indicating that there was no horizontal pleiotropy. Heterogeneity was evaluated by Cochran's Q, which indicated no heterogeneity. In a multivariate MR study with seven sleep characteristics corrected for each other, we found that sleep duration remained causally associated with AD (OR = 1.004, 95 % CI: 1.000-1.007). Moreover, we found that after mutual correction, daytime napping had a causal relationship with the onset of AD, and daytime napping may reduce the risk of AD (OR = 0.995, 95 % CI: 0.991-1.000). CONCLUSION: This study is helpful for the early identification and prediction of risk factors for AD, long sleep durations are a risk factor for AD, and daytime napping can reduce the risk of AD.

Analysis of sleep for the American population: Result from NHANES database.

OBJECTIVES: To assess the contemporary prevalence and decade-long trends of sleep duration, sleep disorders and trouble sleeping among adults in the United States, as well as their risk factors, from 2005 to 2018. MATERIALS AND METHODS: We used National Health and Nutrition Examination Survey data to calculate the sleep duration and weighted prevalence of sleep disorders and trouble sleeping in adults aged 20 years or older. Sleep duration, sleep disorders and trouble sleeping were assessed by questionnaire. RESULTS: A total of 27,399 people were included in the survey on sleep duration, with a weighted percentage of normal sleep (7-8 h/night) of 56.33 % (95 % CI, 53.06-59.60 %) and a weighted percentage of short sleep (5-6 h/night) of 31.73 %. In stratified descriptions, participants aged 40-49 years were more likely to sleep less than five hours, while women aged 80 years and older were more likely to sleep longer and blacks were more likely to sleep shorter. A total of 27,406 participants were included in the survey for sleep disorders. The weighted proportion of the population with sleep disorders was 8.44 % (95 % CI, 7.79-9.8 %). Independent risk factors for sleep disorders were being 40-69 years old, being white, having a high education level, smoking, having hypertension, diabetes, heart disease, and BMI ≥ 25. From 2005 to 2014, the prevalence of sleep disorders increased year by year, from 7.44 % in 2005-2006 to 10.40 % in 2013-2014 (P for Trend<0.001). A total of 38,165 participants were included in the survey on trouble sleeping. The weighted proportion of the population with troubled sleeping was 27.30 % (25.70-28.90 %). Independent risk factors for troubled sleeping were being 30-79 years old, being white, having a high education level, smoking, drinking, having hypertension, diabetes, heart disease and BMI ≥ 25. From 2005 to 2018, the prevalence of trouble sleeping increased annually, from 24.44 % in 2005-2006 to 30.58 % in 2017-2018 (P for trend<0.001). CONCLUSION: Adults in the United States are likely to have abnormal sleep durations, and the prevalence of sleep disorders and troubled sleeping is on the rise.

Targeting STAT6 to mitigate sepsis-induced muscle atrophy and weakness: Modulation of mitochondrial dysfunction, ferroptosis, and CHI3L1-Mediated satellite cell loss.

Sepsis-induced muscle weakness is a debilitating consequence of prolonged critical illness, often associated with a poor prognosis. While recent research has shown that STAT6 functions as an inhibitor of myogenesis, its role in sepsis-induced muscle weakness remains unclear. In this study, we hypothesized that inhibiting STAT6 could attenuate sepsis-induced muscle atrophy and weakness, and we explored the underlying mechanisms. Leveraging a microarray dataset from sepsis patients, we identified significant enrichment of genes related to muscle function, ferroptosis, and the p53 signalling pathway in muscle tissue from sepsis patients. Using a murine sepsis model induced by cecum ligation and puncture (CLP), we explore the multifaceted role of STAT6 inhibition. Our findings demonstrate that STAT6 inhibition effectively attenuates muscle atrophy, enhances grip strength, preserves mitochondrial integrity, and modulates ferroptosis in septic mice. Additionally, we identify elevated levels of CHI3L1 in septic muscle tissue, which are significantly reduced by STAT6 inhibition. In-depth analysis of primary muscle satellite cells reveals that CHI3L1 overexpression is associated with increased expression of key regulators of satellite cell myogenicity, while negatively impacting cell viability. Silencing CHI3L1 expression mitigates satellite cell injury and loss, highlighting its pivotal role in sepsis-induced muscle damage. In summary, this study unveils the potential of STAT6 as a therapeutic target for mitigating sepsis-induced muscle atrophy and weakness. Our findings underscore the regulation of mitochondrial dysfunction, ferroptosis, and CHI3L1-mediated satellite cell damage by STAT6, offering promising avenues for therapeutic intervention in the management of sepsis-induced muscle weakness.

Case report: COVID-19-associated refractory thrombotic thrombocytopenic purpura complicated with Guillain-Barré syndrome.

Thrombotic thrombocytopenic purpura (TTP), a rare and lethal thrombotic microangiopathy, is an autoimmune disease that can be triggered by viral infections such as COVID-19. This condition is characterized by hemolytic microangiopathy, thrombocytopenia, and neurologic alterations, possibly accompanied by fever and renal damage. Moreover, more than 220 patients with Guillain-Barré syndrome (GBS) have been reported in association with the COVID-19 infection. In this report, we present a case of a patient who developed refractory TTP complicated by GBS following a SARS-CoV-2 infection. We aimed to highlight the importance of accurately diagnosing neurological complications associated with a COVID-19 infection and to demonstrate our strategies for treating a patient with COVID-19 infection-related refractory TTP complicated by GBS.

Early Versus Late Tracheostomy in Stroke Patients: A Retrospective Analysis.

Objective: The timing of tracheostomy (TR) in severe stroke patients receiving mechanical ventilation has not been determined. In this study, we compared some prognostic indicators of early tracheostomy (ET) and late tracheostomy (LT). A meta-analysis was performed to obtain a higher level of evidence of the timing of TR in patients with severe stroke receiving mechanical ventilation. Methods: The study was a retrospective single-center study. We divided the severe stroke patients who received TR from June 2020 to June 2022 into the ET group and LT group. The demographic characteristics, clinical characteristics and prognostic indices were compared. For this meta-analysis, we systematically searched PubMed and other databases. The compared prognostic indicators included mechanical ventilation time, ICU length of stay (LOS), total LOS, ventilator-related pneumonia (VAP) incidence, and mortality. Results: A total of 61 patients were included in our study, including 32 patients in the ET group and 29 patients in the LT group. Univariate and multivariate analyses showed that the NIHSS score in the ET group was higher than that in the LT group (P < 0.05). In terms of outcome indicators, compared with the LT group, the median mechanical ventilation time in the ET group was shortened by 5.5 days (P = 0.034). The ICU LOS and total LOS in the ET group were significantly lower than those in the LT group (median 14.5 days vs 22 days, P = 0.004; 21 days vs 27 days, P = 0.019). The meta-analysis showed that ET could significantly shorten the ICU LOS (MD -3.89 [95% CI: -6.86, -0.92]) and the total LOS (MD -7.70 [95% CI: -8.57, -6.83]) and significantly reduce the occurrence of VAP (OR 0.75 [95% CI: 0.64, 0.87]). Conclusion: The results of our retrospective study and meta-analysis support that ET can shorten the ICU LOS and total LOS and reduce the occurrence of VAP. Therefore, it has a positive effect on the prognosis of patients with severe stroke who need mechanical ventilation support.

New physics searches at the BESIII experiment.

The standard model (SM) of particle physics, comprised of the unified electroweak and quantum chromodynamic theories, accurately explains almost all experimental results related to the micro-world, and has made a number of predictions for previously unseen particles, most notably the Higgs scalar boson, that were subsequently discovered. As a result, the SM is currently universally accepted as the theory of the fundamental particles and their interactions. However, in spite of its numerous successes, the SM has a number of apparent shortcomings, including: many free parameters that must be supplied by experimental measurements; no mechanism to produce the dominance of matter over antimatter in the universe; and no explanations for gravity, the dark matter in the universe, neutrino masses, the number of particle generations, etc. Because of these shortcomings, there is considerable incentive to search for evidence for new, non-SM physics phenomena that might provide important clues about what a new, beyond the SM theory (BSM) might look like. Although the center-of-mass energies that BESIII can access are far below the energy frontier, searches for new, BSM physics are an important component of its research program. This report reviews some of the highlights from BESIII's searches for signs of new, BSM physics by: measuring rates for processes that the SM predicts to be forbidden or very rare; searching for non-SM particles such as dark photons; performing precision tests of SM predictions; and looking for violations of the discrete symmetries C and CP in processes for which the SM expectations are immeasurably small.

Blood Pressure and the Risk of Alzheimer's Disease: Is There a Link?

Alzheimer disease is one of the most common neurodegenerative disorder, and the incidence is increasing. Many epidemiologic studies have considered the association between blood pressure and Alzheimer disease, yet the relationship is still controversial. The objective of this study was to validate whether or not blood pressure is indeed associated with AD. We compared different prospective studies and ultimately found that it is also a controversial issue. Large prospective double-blinded and placebo-controlled studies conducted with the use of standardized outcome measures in different levels are necessary to assess the association of blood pressure and Alzheimer disease.