The noncanonical inflammasome-induced pyroptosis and septic shock.

Sepsis remains one of the most common and lethal conditions globally. Currently, no proposed target specific to sepsis improves survival in clinical trials. Thus, an in-depth understanding of the pathogenesis of sepsis is needed to propel the discovery of effective treatment. Recently attention to sepsis has intensified because of a growing recognition of a non-canonical inflammasome-triggered lytic mode of cell death termed pyroptosis upon sensing cytosolic lipopolysaccharide (LPS). Although the consequences of activation of the canonical and non-canonical inflammasome are similar, the non-canonical inflammasome formation requires caspase-4/5/11, which enzymatically cleave the pore-forming protein gasdermin D (GSDMD) and thereby cause pyroptosis. The non-canonical inflammasome assembly triggers such inflammatory cell death by itself; or leverages a secondary activation of the canonical NLRP3 inflammasome pathway. Excessive cell death induced by oligomerization of GSDMD and NINJ1 leads to cytokine release and massive tissue damage, facilitating devastating consequences and death. This review summarized the updated mechanisms that initiate and regulate non-canonical inflammasome activation and pyroptosis and highlighted various endogenous or synthetic molecules as potential therapeutic targets for treating sepsis.

Emerging Roles and Therapeutic Applications of Arachidonic Acid Pathways in Cardiometabolic Diseases.

Cardiometabolic disease has become a major health burden worldwide, with sharply increasing prevalence but highly limited therapeutic interventions. Emerging evidence has revealed that arachidonic acid derivatives and pathway factors link metabolic disorders to cardiovascular risks and intimately participate in the progression and severity of cardiometabolic diseases. In this review, we systemically summarized and updated the biological functions of arachidonic acid pathways in cardiometabolic diseases, mainly focusing on heart failure, hypertension, atherosclerosis, nonalcoholic fatty liver disease, obesity, and diabetes. We further discussed the cellular and molecular mechanisms of arachidonic acid pathway-mediated regulation of cardiometabolic diseases and highlighted the emerging clinical advances to improve these pathological conditions by targeting arachidonic acid metabolites and pathway factors.

LncRNA DANA1 promotes drought tolerance and histone deacetylation of drought responsive genes in Arabidopsis.

Although many long noncoding RNAs have been discovered in plants, little is known about their biological function and mode of action. Here we show that the drought-induced long intergenic noncoding RNA DANA1 interacts with the L1p/L10e family member protein DANA1-INTERACTING PROTEIN 1 (DIP1) in the cell nucleus of Arabidopsis, and both DANA1 and DIP1 promote plant drought resistance. DANA1 and DIP1 increase histone deacetylase HDA9 binding to the CYP707A1 and CYP707A2 loci. DIP1 further interacts with PWWP3, a member of the PEAT complex that associates with HDA9 and has histone deacetylase activity. Mutation of DANA1 enhances CYP707A1 and CYP707A2 acetylation and expression resulting in impaired drought tolerance, in agreement with dip1 and pwwp3 mutant phenotypes. Our results demonstrate that DANA1 is a positive regulator of drought response and that DANA1 works jointly with the novel chromatin-related factor DIP1 on epigenetic reprogramming of the plant transcriptome during the response to drought.

NAFLD: An Emerging Causal Factor for Cardiovascular Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide that poses a significant threat to human health. Cardiovascular disease (CVD) is the leading cause of mortality in NAFLD patients. NAFLD and CVD share risk factors such as obesity, insulin resistance, and type 2 diabetes. However, whether NAFLD is a causal risk factor for CVD remains a matter of debate. This review summarizes the evidence from prospective clinical and Mendelian randomization studies that underscore the potential causal relationship between NAFLD and CVD. The mechanisms of NAFLD contributing to the development of CVD and the necessity of addressing CVD risk while managing NAFLD in clinical practice are also discussed.

Cardiovascular health and cancer mortality: evidence from US NHANES and UK Biobank cohort studies.

BACKGROUND: The American Heart Association recently introduced a novel cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the relationship between LE8 and cancer mortality risk remains uncertain. METHODS: We investigated 17,076 participants from US National Health and Nutrition Examination Survey (US NHANES) and 272,727 participants from UK Biobank, all free of cancer at baseline. The CVH score, based on LE8 metrics, incorporates four health behaviors (diet, physical activity, smoking, and sleep) and four health factors (body mass index, lipid, blood glucose, and blood pressure). Self-reported questionnaires assessed health behaviors. Primary outcomes were mortality rates for total cancer and its subtypes. The association between CVH score (continuous and categorical variable) and outcomes was examined using Cox model with adjustments. Cancer subtypes-related polygenic risk score (PRS) was constructed to evaluate its interactions with CVH on cancer death risk. RESULTS: Over 141,526 person-years in US NHANES, 424 cancer-related deaths occurred, and in UK Biobank, 8,872 cancer deaths were documented during 3,690,893 person-years. High CVH was associated with reduced overall cancer mortality compared to low CVH (HR 0.58, 95% CI 0.37-0.91 in US NHANES; 0.51, 0.46-0.57 in UK Biobank). Each one-standard deviation increase in CVH score was linked to a 19% decrease in cancer mortality (HR: 0.81; 95% CI: 0.73-0.91) in US NHANES and a 19% decrease (HR: 0.81; 95% CI: 0.79-0.83) in UK Biobank. Adhering to ideal CVH was linearly associated with decreased risks of death from lung, bladder, liver, kidney, esophageal, breast, colorectal, pancreatic, and gastric cancers in UK Biobank. Furthermore, integrating genetic data revealed individuals with low PRS and high CVH exhibited the lowest mortality from eight cancers (HRs ranged from 0.36 to 0.57) compared to those with high PRS and low CVH. No significant modification of the association between CVH and mortality risk for eight cancers by genetic predisposition was observed. Subgroup analyses showed a more pronounced protective association for overall cancer mortality among younger participants and those with lower socio-economic status. CONCLUSIONS: Maintaining optimal CVH is associated with a substantial reduction in the risk of overall cancer mortality. Adherence to ideal CVH correlates linearly with decreased mortality risk across multiple cancer subtypes. Individuals with both ideal CVH and high genetic predisposition demonstrated significant health benefits. These findings support adopting ideal CVH as an intervention strategy to mitigate cancer mortality risk and promote healthy aging.

Artificial sweeteners and risk of incident cardiovascular disease and mortality: evidence from UK Biobank.

BACKGROUND: Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM). METHODS: This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed. RESULTS: In our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI < 30 kg/m2) also tended to be at greater risk of incident CVD from artificial sweetener, although the obesity interaction is not significant. Meanwhile, the CVD risk associated with artificial sweeteners is independent of genetic susceptibility, and no significant interaction exists between genetic susceptibility and artificial sweeteners in terms of either additive or multiplicative effects. Furthermore, our study revealed that the relationship between artificial sweetener intake and overall CVD is significantly mediated, in large part, by prior T2DM (proportion of indirect effect: 70.0%). In specific CVD subtypes (CAD, PAD, and HF), the proportion of indirect effects ranges from 68.2 to 79.9%. CONCLUSIONS: Our findings suggest significant or marginally significant associations between artificial sweeteners and CVD and its subtypes (CAD, PAD, and HF). The associations are independent of genetic predisposition and are mediated primarily by T2DM. Therefore, the large-scale application of artificial sweeteners should be prudent, and the responses of individuals with different characteristics to artificial sweeteners should be better characterized to guide consumers' artificial sweeteners consumption behavior.

Hypertensive Heart Disease: Mechanisms, Diagnosis and Treatment.

Hypertensive heart disease (HHD) presents a substantial global health burden, spanning a spectrum from subtle cardiac functional alterations to overt heart failure. In this comprehensive review, we delved into the intricate pathophysiological mechanisms governing the onset and progression of HHD. We emphasized the significant role of neurohormonal activation, inflammation, and metabolic remodeling in HHD pathogenesis, offering insights into promising therapeutic avenues. Additionally, this review provided an overview of contemporary imaging diagnostic tools for precise HHD severity assessment. We discussed in detail the current potential treatments for HHD, including pharmacologic, lifestyle, and intervention devices. This review aimed to underscore the global importance of HHD and foster a deeper understanding of its pathophysiology, ultimately contributing to improved public health outcomes.

The E3 Ligase TRIM16 Is a Key Suppressor of Pathological Cardiac Hypertrophy.

BACKGROUND: Pathological cardiac hypertrophy is one of the leading causes of heart failure with highly complicated pathogeneses. The E3 ligase TRIM16 (tripartite motif-containing protein 16) has been recognized as a pivotal regulator to control cell survival, immune response, and oxidativestress. However, the role of Trim16 in cardiac hypertrophy is unknown. METHODS: We generated cardiac-specific knockout mice and adeno-associated virus serotype 9-Trim16 mice to evaluate the function of Trim16 in pathological myocardial hypertrophy. The direct effect of TRIM16 on cardiomyocyte enlargement was examined using an adenovirus system. Furthermore, we combined RNA-sequencing and interactome analysis that was followed by multiple molecular biological methodologies to identify the direct target and corresponding molecular events contributing to TRIM16 function. RESULTS: We found an intimate correlation of Trim16 expression with hypertrophy-related heart failure in both human and mouse. Our functional investigations and unbiased transcriptomic analyses clearly demonstrated that Trim16 deficiency markedly exacerbated cardiomyocyte enlargement in vitro and in transverse aortic constriction-induced cardiac hypertrophy mouse model, whereas Trim16 overexpression attenuated cardiac hypertrophy and remodeling. Mechanistically, Prdx1 (peroxiredoxin 1) is an essential target of Trim16 in cardiac hypertrophy. We found that Trim16 interacts with Prdx1 and inhibits its phosphorylation, leading to a robust enhancement of its downstream Nrf2 (nuclear factor-erythroid 2-related factor 2) pathway to block cardiac hypertrophy. Trim16-blocked Prdx1 phosphorylation was largely dependent on a direct interaction between Trim16 and Src and the resultant Src ubiquitinational degradation. Notably, Prdx1 knockdown largely abolished the anti-hypertrophic effects of Trim16 overexpression. CONCLUSIONS: Our findings provide the first evidence supporting Trim16 as a novel suppressor of pathological cardiac hypertrophy and indicate that targeting the Trim16-Prdx1 axis represents a promising therapeutic strategy for hypertrophy-related heart failure.

Meta-Analysis of Single-Cell RNA-Seq Data Reveals the Mechanism of Formation and Heterogeneity of Tertiary Lymphoid Organ in Vascular Disease.

BACKGROUND: Tertiary lymphoid organs (TLOs) are ectopic lymphoid organs developed in nonlymphoid tissues with chronic inflammation, but little is known about their existence in different types of vascular diseases and the mechanism that mediated their development. METHODS: To take advantage of single-cell RNA sequencing techniques, we integrated 28 single-cell RNA sequencing data sets containing 5 vascular disease models (atherosclerosis, abdominal aortic aneurysm, intimal hyperplasia, isograft, and allograft) to explore TLOs existence and environment supporting its growth systematically. We also searched Medline, Embase, PubMed, and Web of Science from inception to January 2022 for published histological images of vascular remodeling for histological evidence to support TLO genesis. RESULTS: Accumulation and infiltration of innate and adaptive immune cells have been observed in various remodeling vessels. Interestingly, the proportion of such immune cells incrementally increases from atherosclerosis to intimal hyperplasia, abdominal aortic aneurysm, isograft, and allograft. Importantly, we uncovered that TLO structure cells, such as follicular helper T cells and germinal center B cells, present in all remodeled vessels. Among myeloid cells and lymphocytes, inflammatory macrophages, and T helper 17 cells are the major lymphoid tissue inducer cells which were found to be positively associated with the numbers of TLO structural cells in remodeled vessels. Vascular stromal cells also actively participate in vascular TLO genesis by communicating with myeloid cells and lymphocytes via CCLs (C-C motif chemokine ligands), CXCL (C-X-C motif ligand), lymphotoxin, BMP (bone morphogenetic protein) chemotactic, FGF-2 (fibroblast growth factor-2), and IGF (insulin growth factor) proliferation mechanisms, particularly for lymphoid tissue inducer cell aggregation. Additionally, the interaction between stromal cells and immune cells modulates extracellular matrix remodeling. Among TLO structure cells, follicular helper T, and germinal center B cells have strong interactions via TCR (T-cell receptor), CD40 (cluster of differentiation 40), and CXCL signaling, to promote the development and maturation of the germinal center in TLO. Consistently, by reviewing the histological images from the literature, TLO genesis was found in those vascular remodeling models. CONCLUSIONS: Our analysis showed the existence of TLOs across 5 models of vascular diseases. The mechanisms that support TLOs formation in different models are heterogeneous. This study could be a valuable resource for understanding and discovering new therapeutic targets for various forms of vascular disease.

Exosomal transfer of miR-195-5p restrains lung adenocarcinoma progression.

Exosome is an important way for tumor cells to communicate with other cells and plays an important role in tumor progression. Previous studies revealed that miR-195-5p acts as a tumor suppressor in lung cancer. However, the role and molecular mechanism of exosomal transferred miR-195-5p in lung adenocarcinoma (LAC) remains unknown. Here, we found that miR-195-5p expression in circulating exosomes of LAC patients was lower than that of healthy controls. Meanwhile, the expression of exosomal miR-195-5p from normal bronchial epithelial cell line BEAS-2B cells was significantly higher than that of lung cancer cell lines. The exosome labeling assay confirmed that BEAS-2B cells-derived exosomes could be captured by lung cancer cells. Furthermore, exosomal miR-195-5p derived from BEAS-2B cells remarkably inhibited the proliferation, migration, invasion of lung cancer cells, and tumor growth in vivo. In addition, exosomal miR-195-5p from BEAS-2B cells also suppressed the tube-forming ability of vascular endothelial cells. Moreover, we verified that miR-195-5p decreased apelin (APLN) expression to inactivate the Wnt signaling pathway, thereby inhibiting tumor invasiveness and angiogenesis. In conclusion, our research shows that exosomal miR-195-5p from normal bronchial epithelial cells hinders the progression of LAC, suggesting that regulation of exosomal miR-195-5p provides a novel strategy for LAC treatment.

The connection between the antibiotic resistome and nitrogen-cycling microorganisms in paddy soil is enhanced by application of chemical and plant-derived organic fertilizers.

Antibiotic resistant genes (ARGs) present significant risks to environments and public health. In particular, there is increasing awareness of the role of soil nitrogen in ARG dissemination. Here, we investigated the connections between antibiotic resistome and nitrogen-cycling microbes in paddy soil by performing five-year field experiments with the treatments of no nitrogen fertilization (CK), reduced chemical nitrogen fertilization (LN), conventional chemical nitrogen fertilization (CN) and plant-derived organic nitrogen fertilization (ON). Compared with CK treatment, CN and ON treatments significantly increased soil NH4+ and TN concentrations by 25.4%-56.5% and 10.4%-20.1%, respectively. Redundancy analysis revealed significantly positive correlation of NH4+ with most ARGs, including tetA, macB and barA. Correspondingly, CN and ON treatments enhanced ARG abundances by 21.9%-23.2%. Moreover, CN and ON treatments promoted nitrate/nitrite-reducing bacteria and linked the corresponding N-cycling functional genes (narG, narH, nirK and nrfA) with most ARGs. Metagenomic binning was performed and identified Gemmatimonadaceae, Caulobacteraceae, Ilumatobacteraceae and Anaerolineaceae as hosts for both ARGs and nitrate/nitrite reduction genes that were enriched by CN and ON treatments. Soil resistome risk score analysis indicated that, although there was increased relation of ARG to nitrogen-cycling microorganisms with nitrogen fertilizer application, the environmental risk of ARGs was not increased due to the lower distribution of ARGs in pathogens. This study contributed to a deeper understanding of the role of soil nitrogen in shaping ARG profiles and controlling soil resistome risk.

The use of peripheral nerve block decrease incidence of postoperative cognitive dysfunction following orthopedic surgery: A systematic review and meta-analysis.

BACKGROUND: Postoperative neurocognitive disorders (PNDs) frequently occur following orthopedic surgery and are closely associated with adverse prognosis. PNDs are an emerging concept that includes both postoperative cognitive dysfunction (POCD) and postoperative delirium (POD). The prevention of combined use of peripheral nerve block (PNB) and general anesthesia (GA) on POCD and/or POD incidence following orthopedic surgery remains unknown. We aimed to investigate the effect of this combined anesthesia method on POCD/POD incidence after orthopedic surgery, compared with GA. METHODS: The databases of PubMed, Web of Science, Embase via Ovid, and the Cochrane Central Register of Controlled Trials were searched for all available randomized controlled trials (RCTs). The incidence of POD/POCD was the primary outcome. Continuous and dichotomous outcomes are represented as standardized mean differences [SMD, 95% confidence interval (CI)] and risk ratios [RR, 95%CI], respectively. RESULTS: Meta-analysis of twelve RCTs with a total of 1488 patients revealed that compared with GA, PNB plus GA decreased the incidence of POCD (RR: 0.58, 95%CI: 0.35 to 0.95, P = 0.03, I2 = 0%), while the incidence of POD had no significant difference (RR: 0.87, 95%CI: 0.54 to 1.40, P = 0.57, I2 = 67%). Compared with GA alone, a significant decrease of intraoperative and postoperative opioid consumption (SMD: -1.54, 95%CI: -2.26 to -0.82, P < 0.0001, I2 = 89%; SMD: -7.00, 95%CI: -9.89 to -4.11, P < 0.00001, I2 = 99%) and postoperative nausea and vomiting incidence (RR: 0.16, 95%CI: 0.06 to 0.44, P = 0.0004, I2 = 0%) was found with PNB plus GA. CONCLUSIONS: The combined use of PNB and GA decreases the incidence of POCD but not POD following orthopedic surgery. TRIAL REGISTRATION: The protocol of this study was registered with PROSPERO (Registration Number: CRD42022366454).

Epilepsy and long-term risk of arrhythmias.

BACKGROUND AND AIMS: Previous evidence has mainly supported transient changes in cardiac function during interictal or peri-ictal phases in people with epilepsy, but the long-term risk of cardiac arrhythmias is poorly described. This study aimed to assess the long-term association of epilepsy with cardiac arrhythmias, considering the potential role of genetic predisposition and antiseizure medications (ASMs) in any associations observed. METHODS: This population-based study evaluated UK Biobank data for individuals recruited between 2006 and 2010. Cox proportional hazards models and competing risk models were used to examine the association of epilepsy history with the long-term incidence risk of cardiac arrhythmias and arrhythmias subtypes. Polygenic risk scores (PRS) were calculated to investigate the effect of genetic susceptibility. The role of ASMs was also evaluated by integrating observational and drug target Mendelian randomization (MR) evidence. RESULTS: The study included 329 432 individuals, including 2699 people with epilepsy. Compared with those without epilepsy, people with epilepsy experienced an increased risk of all cardiac arrhythmias [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.21-1.53], atrial fibrillation (HR 1.26, 95% CI 1.08-1.46), and other cardiac arrhythmias (HR 1.56, 95% CI 1.34-1.81). The associations were not modified by genetic predisposition as indicated by PRS. Competing and sensitivity analyses corroborated these results. Individuals with epilepsy using ASMs, especially carbamazepine and valproic acid, were at a higher risk for cardiac arrhythmias. This observation was further supported by drug target MR results (PSMR < .05 and PHEIDI > .05). CONCLUSION: This study revealed the higher risk of cardiac arrhythmias persists long term in people with epilepsy, especially among those using carbamazepine and valproic acid. These findings highlight the need for regular heart rhythm monitoring and management in people with epilepsy in order to reduce the risk of further cardiovascular complications.

Ill-fitting prosthesis is associated with an increased risk of elevated blood pressures.

OBJECTIVE: Previous studies focused on the benefits of adequate prosthodontic treatment, while few studies have investigated the prosthodontic-related risks to health. As a modifiable oral health indicator, the association of ill-fitting prosthesis (IFP) with hypertension has not been fully explored. METHODS: This cross-sectional study involved 158,659 adults in Beijing (2009-2017) receiving intra-oral examinations and blood pressure measurements. Logistic regression models were applied to assess the association of IFP with the prevalence of hypertension, systolic blood pressure (SBP) ≧ 140 mmHg and diastolic blood pressure (DBP) ≧ 90 mmHg, as well as subgroup analyses by different fixed IFP subgroups (according to involved teeth number) and removable IFP subgroup. We further investigated effect modifications among stratified populations. RESULTS: 158,659 individuals were included for analysis, 346 (26.86%) in IFP group and 27,380 (17.40%) in non-IFP group (p < 0.001) were hypertensive. After adjustment of sex, age, obesity, dyslipidaemia, diabetes, hsCRP, family history of CVD, self-reported smoking, self-reported drinking and WC, ORs of hypertension, SBP ≧ 140 mmHg and DBP ≧ 90 mmHg were 1.330 (95% CI: 1.162-1.522), 1.277 (95% CI: 1.098-1.486) and 1.376 (95% CI: 1.186-1.596), respectively (p < 0.05). Furthermore, after full adjustment, the number of involved teeth showed a significant incremental trend with hypertension risk in the population with and without IFP (p for trend <0.001). The IFP-blood pressure associations were more pronounced in females, 18-60 years, non-obese and diabetic participants. CONCLUSION: As a modifiable oral indicator, IFP was significantly associated with a higher risk of hypertension.

Clinical efficacy of cyclosporin and natamycin for fungal keratitis.

Objectives: To investigate the clinical efficacy of cyclosporin (CYSP) and natamycin (NAT) as a combination therapy in patients with fungal keratitis. Methods: This is a retrospective study. A total of 64 patients (64 eyes) with fungal keratitis treated by Baoding No.1 Central Hospital between December 2018 and May 2022 according to their treatment methods were divided into a monotherapy (MT) group receiving NAT eye drops solely and a combination therapy (CT) group given CYSP eye drops in addition to the exact treatment provided for the MT group. The clinical responses, visual acuity changes, severity of eye symptoms, and adverse reactions were compared between the two groups. Results: At two and four weeks post-treatment, the CT group had an overall response rate (ORR) significantly higher than that of the MT group (P< 0.05, respectively); both groups showed improved visual acuity and eye symptoms compared with the pre-treatment condition, and these improvements were more pronounced in the CT group (P < 0.05, respectively). Compared with the MT group, the CT group experienced a significantly shorter duration of eye symptoms (P < 0.05). The adverse reaction rate(ARR) was 9.38% in the CT group and 6.25% in the MT group, and the difference was not significant (P > 0.05). Conclusion: Using CYSP and NAT as a combination therapy for fungal keratitis can substantially heighten the therapeutic effects, promote visual acuity recovery, and induce rapid remission of eye symptoms without increasing the risk of adverse reactions.

The Transition of Cardiovascular Disease Risks from NAFLD to MAFLD.

The increased burden of nonalcoholic fatty liver disease (NAFLD) parallels the increased incidence of overweight and metabolic syndrome worldwide. Because of the close relationship between metabolic disorders and fatty liver disease, a new term, metabolic-related fatty liver disease (MAFLD), was proposed by a group of experts to more precisely describe fatty liver disease resulting from metabolic disorders. According to the definitions, MAFLD and NAFLD populations have considerable discrepancies, but overlap does exist. This new definition has a nonnegligible impact on clinical practices, including diagnoses, interventions, and the risk of comorbidities. Emerging evidence has suggested that patients with MAFLD have more metabolic comorbidities and an increased risk of all-cause mortality, particularly cardiovascular mortality than patients with NAFLD. In this review, we systemically summarized and compared the risk and underlying mechanisms of cardiovascular disease (CVD) in patients with NAFLD or MAFLD.

Nonalcoholic Fatty Liver Disease: An Emerging Driver of Cardiac Arrhythmia.

Cardiac arrhythmias and the resulting sudden cardiac death are significant cardiovascular complications that continue to impose a heavy burden on patients and society. An emerging body of evidence indicates that nonalcoholic fatty liver disease (NAFLD) is closely associated with the risk of cardiac arrhythmias, independent of other conventional cardiometabolic comorbidities. Although most studies focus on the relationship between NAFLD and atrial fibrillation, associations with ventricular arrhythmias and cardiac conduction defects have also been reported. Mechanistic investigations suggest that a number of NAFLD-related pathophysiological alterations may potentially elicit structural, electrical, and autonomic remodeling in the heart, contributing to arrhythmogenic substrates in the heart. NAFLD is now the most common liver and metabolic disease in the world. However, the upsurge in the prevalence of NAFLD as an emerging risk factor for cardiac arrhythmias has received little attention. In this review, we summarize the clinical evidence and putative pathophysiological mechanisms for the emerging roles of NAFLD in cardiac arrhythmias, with the purpose of highlighting the notion that NAFLD may serve as an independent risk factor and a potential driving force in the development and progression of cardiac arrhythmias.

The Expression of HPV E6/E7 mRNA In Situ Hybridization in HPV Typing-negative Cervical Cancer.

High-risk human papillomavirus (HPV) persistent infection is the major tumorigenesis factor for cervical cancer (CC). However, the incidence of HPV-negative CC is 5% to 30% with different HPV detection methods. High-risk HPV E6/E7 mRNA in situ hybridization (RISH) can detect HPV-driven tumors. Our study aimed to explore whether HPV typing-negative CC was caused by HPV infection. The tissues of CC patients with HPV typing results, collected from cervical biopsies, conization, or hysterectomies, were submitted to RISH using RNAscope chromogenicin. Immunohistochemistry was performed to evaluate the expression of p16INK4a and Ki-67. A total of 308 women with HPV typing results were enrolled, and 30 (9.74%) cases of HPV typing were negative. In HPV typing-negative CCs, 28/30 (93.3%) were positive for RISH, which contained 22/22 (100%) squamous cell carcinomas and 6/8 (75%) adenocarcinomas. RISH was positive in 278/278 (100%) HPV typing-positive CCs, which included 232/232 (100%) squamous cell carcinomas and 46/46 (100%) adenocarcinomas. Positive RISH in HPV typing-negative CC was significantly lower than in the HPV typing-positive group ( P =0.002, 95% confidence interval: 0.848-1.027). However, this significant difference only existed in adenocarcinoma. No significant differences were seen in the expression of p16INK4a and Ki-67 (all P >0.05). HPV typing may cause misdiagnosis in 9.74% of CC patients, and HPV E6/E7 mRNA can detect HPV in CC with HPV typing-negative patients. This approach could provide a novel option to accurately detect high-risk HPVs in cervical tumors and help to eliminate the percentage of misdiagnosed HPV-related cases.

Path analysis of social engagement, loneliness and cognitive function among Chinese older adults.

This study established a research model to fully understand the relationship of social engagement, loneliness and cognitive function among Chinese older adults. In the latest wave (2018) of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a total of 12,852 participants aged 65 years and older were included in the study. Path analysis was performed to examine our hypotheses. The social engagement had a positive relationship with normal cognitive function while loneliness had a negative one, and the standardized regression weights were 0.618 (p < 0.01) and -0.046 (p < 0.01), respectively. Watching TV or listening to the radio had the greatest association with cognitive function, followed by housework, outdoor activities, reading newspapers or books, playing cards or mahjong, and raising domestic animals or pets. Loneliness played a mediating role between social engagement and cognitive function. Social engagement could be considered as one of the interventions to improve older adults' health.

Association between dietary antioxidant capacity and atherosclerotic carotid stenosis in patients with ischemic stroke.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the relationship between dietary total antioxidant capacity (DTAC) and atherosclerotic carotid stenosis in patients with ischemic stroke. METHODS: Patients with acute ischemic stroke were consecutively enrolled. Daily food consumption was estimated by a semi-quantitative food frequency questionnaire (FFQ). DTAC was calculated based on classified food intake. Antioxidant potential value was measured by ferric-reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) methods. Evaluation of carotid artery stenosis was based on computed tomography angiography (CTA). Logistic regression was used to assess the relationship between DTAC and degree of carotid stenosis. RESULTS: Of the 608 enrolled, 232 patients (38.2%) had moderate or severe carotid stenosis. After adjusting for major confounding factors, FRAP (OR =0.640; 95% CI: 0.410-0.998; P =0.049) and ORAC (OR =0.625; 95% CI: 0.400-0.976; P =0.039) were associated with lower degree of carotid artery stenosis (third vs first tertile). Spearman analysis indicated that FRAP (r =-0.121, P =0.003) and ORAC (r =-0.147, P <0.001) were correlated with degree of carotid stenosis. CONCLUSIONS: DTAC may influence the initiation and development of atherosclerosis, and, therefore, the risk of ischemic stroke.