Pioglitazone Alleviates ß1-Adrenergic Receptor Antibody-Induced Atrial Fibrillation Susceptivity via Mitigation of PPAR-γ-Mediated Metabolic Inflexibility.

BACKGROUND: Beta-1-adrenergic receptor antibodies (ß1-AAbs) function as arrhythmogenic molecules in autoimmune-related atrial fibrillation (AF). This study examined the potential impact of pioglitazone, an agonist for peroxisome proliferator-activated receptor-γ (PPAR-γ), on atrial remodeling induced by ß1-AAbs. METHODS: An in vivo study was performed to confirm the protective effects of pioglitazone on ß1- AAbs-induced atrial remodeling. GW9662, a PPAR-γ antagonist, was employed to identify the potential therapeutic target of pioglitazone. The rats were administered subcutaneous injections of the second extracellular loop peptide for 8 weeks to establish active immunization models. Pioglitazone was then administered orally for 2 weeks. Epicardial electrophysiologic studies, multielectrode array measurements, and echocardiography were conducted to examine atrial remodeling. Glucose metabolism products and key metabolic molecules were measured to evaluate the atrial substrate metabolism. Mitochondrial morphologies and function indices were tested to depict the underlying links between atrial metabolism and mitochondrial homeostasis under the pioglitazone treatment. RESULTS: Pioglitazone significantly reversed ß1-AAbs-induced AF susceptibility, ameliorated atrial structural remodeling, decreased the global insulin resistance reflected in the plasma glucose and insulin levels, and increased the protein expressions of glycolipid uptake and transportation (GLUT1, CD36, and CPT1a). These trends were counterbalanced by the GW9662 intervention. Mechanistically, pioglitazone mitigated the atrial mitochondrial network damage and partly renovated the mitochondrial biogenesis, even the mitochondrial dynamics, which were reversed by inhibiting the PPAR-γ target. CONCLUSION: Pioglitazone effectively reduced the AF vulnerability and recovered the atrial myocardial metabolism and mitochondrial damage. The potential anti-remodeling effect of pioglitazone on the atrium was associated with the moderately increased expression of key membrane proteins related to glucose transporter and fatty acid uptake, which may promote the increased myocardial preference for utilization of FA as the key cardiac oxidative fuel and ameliorate the atrial metabolic inflexibility.

Safety and efficacy of cardioneuroablation for vagal bradycardia in a single arm prospective study.

Cardioneuroablation (CNA) is currently considered as a promising treatment option for patients with symptomatic bradycardia caused by vagotonia. This study aims to further investigate its safety and efficacy in patients suffering from vagal bradycardia. A total of 60 patients with vagal bradycardia who underwent CNA in the First Affiliated Hospital of Xinjiang Medical University from November 2019 to June 2022. Preoperative atropine tests revealed abnormal vagal tone elevation in all patients. First, the electroanatomic structures of the left atrium was mapped out by using the Carto 3 system, according to the protocol of purely anatomy-guided and local fractionated intracardiac electrogram-guided CNA methods. The upper limit of ablation power of superior left ganglion (SLGP) and right anterior ganglion (RAGP) was not more than 45W with an ablation index of 450.Postoperative transesophageal cardiac electrophysiological examination was performed 1 to 3 months after surgery. The atropine test was conducted when appropriate. Twelve-lead electrocardiogram, Holter electrocardiogram, and skin sympathetic nerve activity were reviewed at 1, 3, 6 and 12 months after operation. Adverse events such as pacemaker implantation and other complications were also recorded to analyze the safety and efficacy of CNA in the treatment of vagus bradycardia. Sixty patients were enrolled in the study (38 males, mean age 36.67 ± 9.44, ranging from 18 to 50 years old). None of the patients had a vascular injury, thromboembolism, pericardial effusion, or other surgical complications. The mean heart rate, minimum heart rate, low frequency, low/high frequency, acceleration capacity of rate, and skin sympathetic nerve activity increased significantly after CNA. Conversely, SDNN, PNN50, rMSSD, high frequency, and deceleration capacity of rate values decreased after CNA (all P < 0.05). At 3 months after ablation, the average heart rate, maximum heart rate, and acceleration capacity of heart rate remained higher than those before ablation, and the deceleration capacity of heart rate remained lower than those before ablation and the above results continued to follow up for 12 months after ablation (all P < 0.05). There was no significant difference in other indicators compared with those before ablation (all P > 0.05). The remaining 81.67% (49/60) of the patients had good clinical results, with no episodes of arrhythmia during follow-up. CNA may be a safe and effective treatment for vagal-induced bradycardia, subject to confirmation by larger multicenter trials.

Geographical traceability of soybean: An electronic nose coupled with an effective deep learning method.

The quality of soybeans is correlated with their geographical origin. It is a common phenomenon to replace low-quality soybeans from substandard origins with superior ones. This paper proposes the adaptive convolutional kernel channel attention network (AKCA-Net) combined with an electronic nose (e-nose) to achieve soybean quality traceability. First, the e-nose system is used to collect soybean gas information from different origins. Second, depending on the characteristics of the gas information, we propose the adaptive convolutional kernel channel attention (AKCA) module, which focuses on key gas channel features adaptively. Finally, the AKCA-Net is proposed, which is capable of modeling deep gas channel interdependency efficiently, realizing high-precision recognition of soybean quality. In comparative experiments with other attention mechanisms, AKCA-Net demonstrated superior performance, achieving an accuracy of 98.21%, precision of 98.57%, and recall of 98.60%. In conclusion, the combination of the AKCA-Net and e-nose provides an effective strategy for soybean quality traceability.

Platelet-to-Lymphocyte Ratio Improves the Predictive Ability of the Risk Score for Atrial Fibrillation Recurrence After Radiofrequency Ablation.

Purpose: To investigate the effect and comprehensive predictive value of the platelet-to-lymphocyte ratio (PLR) for long-term recurrence in patients with atrial fibrillation (AF) post ablation. Patients and Methods: We retrospectively analysed 638 consecutive AF patients who underwent ablation, including 302 (47.3%) with paroxysmal AF and 336 (52.7%) with nonparoxysmal AF. Patients were grouped into the recurrence and nonrecurrence groups. Results: After a mean follow-up of 15.1±9.3 months, 175 patients (27.4%) with AF had long-term recurrence, including 114 patients (33.9%) with nonparoxysmal AF and 61 patients (20.2%) with paroxysmal AF. In the entire cohort and in patients with nonparoxysmal AF, but not in those with paroxysmal AF, the PLR was significantly higher in the recurrence group than in the nonrecurrence group (P<0.05). After adjusting for the APPLE score, the PLR as a continuous variable independently predicted AF recurrence (hazard ratio [HR], 1.003; 95% confidence interval [CI], 1.001-1.005; P<0.01). The addition of the PLR to the APPLE score improved its predictive ability for recurrence (the C-statistic value increased from 0.645 to 0.675, P=0.02; the net reclassification improvement was 0.221, 95% CI 0.049-0.394, P=0.01; and the integrated discrimination improvement was 0.029, 95% CI 0.013-0.045, P<0.01). For nonparoxysmal AF, the PLR was stratified into tertiles, the PLR independently increased the nonparoxysmal AF recurrence risk after adjusting for multiple confounding factors (HR, 1.393; 95% CI, 1.102-1.762; P<0.01), and the addition of the PLR to the left atrial diameter improved its predictive ability for arrhythmia recurrence (the C-statistic value increased from 0.601 to 0.667, P<0.01). Conclusion: The PLR is an independent predictive factor of long-term AF recurrence post ablation after adjusting for the APPLE score and can improve the predictive ability and clinical usefulness of the APPLE score. However, the PLR is an effective predictor of recurrence in patients with nonparoxysmal AF rather than in paroxysmal AF.

Including hemoglobin levels and female sex provide the additional predictive value of the APPLE score for atrial fibrillation recurrence post-catheter ablation.

OBJECTIVE: We probed whether the addition of hemoglobin (HGB) or the female sex (SEX) as variables would provide additional prognostic value to the APPLE score. METHODS: An optimized APPLE score was used to evaluate the AF recurrence risk in the consecutive populations with AF post-catheter ablation including the development (n = 562) and validation (n = 239) cohorts. RESULTS: In the populations of AF recurrence, most patients were female sex (103/164, 62.8%), and had the lower HGB levels. After adjusting for the APPLE score, HGB level (Odds Ratio [OR], 0.828; 95% Confidence Interval [CI], 0.749-0.915; P < 0.001) and female sex (OR, 1.596; 95% CI, 1.140-2.235; P = 0.006) independently predicted AF recurrence. Adjusting the APPLE score by HGB variable improved its predictive ability for AF recurrence (C-statistic value from 0.675 to 0.711, P = 0.010), which also increased the C-indexes in the external validation (from 0.653 to 0.725, p = 0.023). The female sex variable also enhanced the C-statistic value of the APPLE score for AF recurrence at both development and external validation (C-indices from 0.675 to 0.691, P = 0.004; C-indices from 0.653 to 0.704, p = 0.037, respectively). Decision curve analysis showed that the HGB plus APPLE score was better than the SEX plus APPLE score in predicting AF recurrence in two following AF populations. CONCLUSION: The inclusion of HGB level and female sex variables improved the predictability and clinical usefulness of adjusted APPLE score. Adjustment of the APPLE score by HGB levels may provide better predictive value than inclusion of the female sex variable.

Post-TAVR patients with atrial fibrillation: are NOACs better than VKAs?-A meta-analysis.

Objective: This study aimed to compare the efficacy of novel oral anticoagulants (NOACs) with traditional anticoagulants vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) post transcatheter aortic valve replacement (TAVR). Methods: Studies comparing the usage of NOACs and VKAs in AF patients with oral anticoagulant indication post-TAVR were retrieved from PubMed, EMBASE, Medline, and Cochrane databases from their building-up to Jan. 2023. The literature was screened in line of inclusion and exclusion criteria. Risk ratio (RR) or odds ratio (OR),95% confidence interval (CI) and number needed to treat (NNT) were calculated for four main indexes that composite endpoints composed mainly of any clinically relevant risk events, stroke, major bleeding, and all-cause mortality. Subsequently, a meta-analysis was performed using the RevMan5.3 and Stata 16.0 software. Results: In the aggregate of thirteen studies, contained 30388 post-TAVR patients with AF, were included in this meta-analysis. Our results indicated that there was no significant difference in stroke between the NOACs group and the VKAs group, and the NOACs group had a numerically but non-significantly higher number of composite endpoint events compared with the other group. Nevertheless, the incidence of major bleeding [11.29% vs. 13.89%, RR 0.82, 95%CI (0.77,0.88), P < 0.00001, I² = 69%, NNT = 38] and all-cause mortality [14.18% vs. 17.61%, RR 0.83, 95%CI (0.79,0.88), p < 0.00001, I² = 82%, NNT = 29] were significantly lower in the NOACs group than another group. Conclusion: Taken together, our data indicated that the usage of NOACs reduced the incidence of major bleeding and all-cause mortality compared to VKAs in post-TAVR patients with AF.

Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics. / ç©¿å¿ƒèŽ²å† é ¯é€šè¿‡ç¼“è§£æ°§åŒ–åº”æ¿€å’Œä¿ƒè¿›çº¿ç²’ä½“èƒ½é‡åˆæˆå¯¹å¿ƒæˆ¿é¢¤åŠ¨å‘æŒ¥é¢„é˜²ä½œç”¨.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.

Establishment of Risk Model and Analysis of Immunoinfiltration Based on Mitophagy-Related Associated Genes in Atrial Fibrillation.

Objective: Atrial fibrillation (AF) is a common tachyarrhythmia whose pathogenesis remains elusive. In the present study, we aimed to investigate the pathological mechanism of mitophagy and immunoinfiltration in AF. Methods: First, we identified differentially expressed mitophagy-related genes (DEMRGs) based on the GSE79768 and GSE115574 datasets, subjecting them to functional enrichment analysis. STRING, TRRUST, miRNet, miRwalk, and Cytoscape were used to explore the potential regulatory roles of downstream signaling pathways. Subsequently, the random forest method was used to construct the AF risk model, and the DEMRGs most correlated with AF risk were determined by combining the Gini index. ssGSEA algorithm, NMF algorithm, and unsupervised clustering were used to subdivide AF molecular types. We then studied the characteristics of mitophagy- and immune infiltration-related genes in AF. Ultimately, we detected the expression of key genes in canine atrial tissues and HL-1 cells by immunofluorescence and Western blot. Results: Mitophagy and immune infiltration were significantly enriched and activated in AF samples. Thirty-seven DEMRGs were screened, of which MAPK1, VDAC1, MAPK14, and MTERF3 were most associated with AF risk. The risk model based on these could identify patients at a high risk of AF. The infiltration of immunocells such as mast cells and neutrophils was significantly different among AF types. Finally, expression verification indicated that the expression trend of four key genes in canine atrial muscle tissue and HL-1 cells was consistent. Conclusion: We found that mitophagy may participate in AF progression through immune activation. In addition, the AF risk prediction model composed of VDAC1, MAPK1, MAPK14, and MTERF3 has a good AF prediction performance, which provides new ideas for the study of AF pathogenesis and potential therapeutic targets.

Long non-coding RNA DANCR alleviates acute myocardial infarction damage via regulating microRNA-509-5p/KLF transcription factor 13 pathway.

Acute myocardial infarction (AMI) is the most important cause of death among cardiovascular diseases. Long noncoding RNAs (lncRNAs) have been widely implicated in the regulation of AMI progression. Discrimination antagonizing nonprotein coding RNA (DANCR) alleviated hypoxia-caused cardiomyocyte damages, and the underlying mechanisms remain unclear. Here, we investigated the function and mechanism of DANCR in hypoxia-induced cardiomyocytes and AMI model by enzyme-linked immunosorbent assay, reactive oxygen species and adenosine triphosphate measurement, and mitochondrial activity determination. Additionally, luciferase reporter assay, immunoblotting, and qRT-PCR were performed to validate the interactions between DANCR/miR-509-5p and miR-509-5p/Kruppel-like factor 13 (KLF13). The role of DANCR was also verified in AMI model by overexpression. Our results showed that DANCR expression was significantly downregulated in hypoxia-induced cardiomyocytes or AMI model. Overexpression of DANCR significantly alleviated mitochondrial damages, reduced inflammation, and improved cardiac function in the AMI model. Furthermore, we demonstrated that miR-509-5p/KLF13 axis mediated the protective effect of DANCR. The current study highlighted the critical role of DANCR in alleviating AMI progression through targeting the miR-509-5p/KLF13 signaling axis, suggesting that DANCR may serve as a potential diagnostic marker or therapeutic target for AMI.

Weight-adjusted waist index is not superior to conventional anthropometric indices for predicting type 2 diabetes: a secondary analysis of a retrospective cohort study.

BACKGROUND: Weight-adjusted waist index (WWI) is a new anthropometric indicator to assess adiposity. Current knowledge regarding its association with type 2 diabetes mellitus (T2DM) is limited. This present study aims to evaluate the association of WWI with the risk of T2DM in the Japanese population, and to compare its predictive ability with body mass index (BMI) and waist circumference (WC). METHODS: This was a secondary analysis of a retrospective cohort study involving 15,464 participants. Participants were divided into quartiles based on baseline WWI levels. Cox regression model, Kaplan-Meier curve, and smooth curve fitting were used to explore the relationship between WWI and T2DM. The discriminative ability of obesity indices in predicting T2DM was compared by the receiver operating characteristic (ROC) curve. RESULTS: After a mean follow-up of 6.05 years, 373 participants were diagnosed with T2DM. In fully adjusted models, the risk of incident T2DM was 1.96 times higher for each 1-unit increment in WWI levels (95% CI: 1.61-2.39, P < 0.001). Smooth curve fitting analysis showed a linear positive association between baseline WWI and new-onset T2DM. Subgroup analysis showed consistent results which subjects in the 4th WWI quartile had the highest risk of developing T2DM in different age, gender, and BMI groups. WWI did not exhibit better predictive ability compared with BMI and WC in the results of ROC curve. CONCLUSION: WWI, a new metabolic index, can be used to predict new-onset T2DM in the Japanese population. However, its predictive capability was not superior to conventional anthropometric indices.

Renal denervation alleviates chronic obstructive sleep apnea-induced atrial fibrillation via inhibition of atrial fibrosis and sympathetic hyperactivity.

OBJECTIVE: Previous studies have reported that renal denervation (RDN) prevents the occurrence of atrial fibrillation (AF) related to obstructive sleep apnea (OSA). However, the effect of RDN on chronic OSA (COSA)-induced AF is still unclear. METHODS: Healthy beagle dogs were randomized into the OSA group (sham RDN + OSA), OSA-RDN group (RDN + OSA), and CON group (sham RDN + sham OSA). The COSA model was built via repeated apnea and ventilation rounds for 4 h each day lasting 12 weeks, and RDN was employed after 8 weeks of modeling. All dogs were implanted Reveal LINQ™ to detect spontaneous AF and AF burden. Circulating levels of norepinephrine, angiotensin II, and interleukin-6 were determined at baseline and end of the study. In addition, measurements of the left stellate ganglion, AF inducibility, and effective refractory period were conducted. The bilateral renal artery and cortex, left stellate ganglion, and left atrial tissues were collected for molecular analysis. RESULTS: Of 18 beagles, 6 were randomized to each of the groups described above. RDN remarkably attenuated ERP prolongation and AF episodes and duration. RDN markedly suppressed the LSG hyperactivity and atrial sympathetic innervation, decreased the serum concentrations of Ang II and IL-6, further inhibited fibroblast-to-myofibroblast transformation via the TGF-ß1/Smad2/3/α-SMA pathway, and reduced the expression of MMP-9, thus decreasing OSA-induced AF. CONCLUSIONS: RDN may reduce AF by inhibiting sympathetic hyperactivity and AF in a COSA model.

Increased ß1-adrenergic receptor antibody confers a vulnerable substrate for atrial fibrillation via mediating Ca2+ mishandling and atrial fibrosis in active immunization rabbit models.

BACKGROUND: Autoimmune disorder is the emerging mechanism of atrial fibrillation (AF). The ß1-adrenergic receptor antibody (ß1-AAb) is associated with AF progress. Our study aims to investigate whether ß1-AAbs involves in atrial vulnerable substrate by mediating Ca2+ mishandling and atrial fibrosis in autoimmune associated AF. METHODS: Active immunization models were established via subcutaneous injection of the second extracellular loop (ECL2) peptide for ß1 adrenergic receptor (ß1AR). Invasive electrophysiologic study and ex vivo optical mapping were used to evaluate the changed electrophysiology parameters and calcium handling properties. Phospho-proteomics combined with molecular biology assay were performed to identify the potential mechanisms of remodeled atrial substrate elicited by ß1-AAbs. Exogenous ß1-AAbs were used to induce the cellular phenotypes of HL-1 cells and atrial fibroblasts to AF propensity. RESULTS: ß1-AAbs aggravated the atrial electrical instability and atrial fibrosis. Bisoprolol alleviated the alterations of action potential duration (APD), Ca2+ transient duration (CaD), and conduction heterogeneity challenged by ß1-AAbs. ß1-AAbs prolonged calcium transient refractoriness and promoted arrhythmogenic atrial alternans and spatially discordant alternans, which were partly counteracted through blocking ß1AR. Its underlying mechanisms are related to ß1AR-drived CaMKII/RyR2 activation of atrial cardiomyocytes and the myofibroblasts phenotype formation of fibroblasts. CONCLUSION: Suppressing ß1-AAbs effectively protects the atrial vulnerable substrate by ameliorating intracellular Ca2+ mishandling and atrial fibrosis, preventing the process of the autoimmune associated AF.

Acute and long-term outcomes of pulmonary vein isolation and left atrial substrate modification for non-paroxysmal atrial fibrillation: a non-randomized trial.

Background: The long-term success rate of nonparoxysmal atrial fibrillation (AF) treated with pulmonary vein isolation (PVI) alone is not ideal. This may indicate atrial fibrosis as a major cause of recurrence. Therefore, the aim of this study is to investigate the efficacy of left atrial substrate modification (LASM) by targeting low-voltage area. Methods: A total of 157 consecutive patients with drug-refractory nonparoxysmal AF who underwent radiofrequency ablation during hospitalization in the Third People's Hospital of Chengdu from April 2017 to August 2021 were prospectively included. Stepwise ablation was performed in two different orders: LASM first (n=53) and PVI first (n=104) group. All patients underwent ablation during AF, and the procedural endpoint was AF termination during ablation. In the LASM first group, LASM was performed first and if AF was terminated, PVI was not performed. Similarly, in the PVI first groups, LASM was performed if AF was not terminated. The primary outcome were AF termination and freedom from AF. The secondary outcome was adverse events. Cox regression analysis was used to define predictors of AF termination, and Kaplan-Meier analysis was used to assess differences between groups in AF freedom. Results: The baseline characteristics of the two groups were similar. At a median follow-up of 16 months, the 112 patients (39 in LASM first group and 73 in PVI first group) with AF termination had a higher success rate than the 45 patients who had no AF termination (78.6% vs. 57.8%; P<0.01). The AF termination rate (24/53, 45.3% vs. 12/104, 11.5%; P<0.01) and AF freedom (20/24, 83.3% vs. 7/12, 58.3%; P=0.13) by LASM alone was higher than PVI alone. There were 3 cases of heart failure and 1 case of stroke (4/53) in the LASM first group, and 1 case of pericardial tamponade, 5 cases of heart failure and 1 case of stroke (7/104) in the LASM first group (7.5% vs. 6.7%; P>0.05). Conclusions: LASM provides higher immediate success and a slightly better long-term success rate compared to PVI. Patients who terminated AF were more likely to have AF freedom than those who did not. AF termination during procedure may improve symptoms and reduce hospitalization.

Evaluation of pelvic floor muscle function (PFMF) in cervical cancer patients with Querleu-Morrow type C hysterectomy: a multicenter study.

INTRODUCTION: To evaluate the pelvic floor muscle function (PFMF) of cervical cancer patients after type QM-C hysterectomy and to explore the relationship between decreased PFMF and related factors. METHODS: This was a multi-centered retrospective cohort study. 181 cervical cancer patients who underwent type QM-C hysterectomy were enrolled from 9 tertiary hospitals. Strength of PFMF were measured using neuromuscular apparatus (Phenix U8, French). Risk factors contributing to decreased PFMF were analyzed by univariate and multivariate ordinal polytomous logistic regression. RESULTS: Totally 181 patients were investigated in this study. 0-3 level of type I muscle fibre strength (MFSI) was 52.6% (95/181), 0-3 level of type IIA muscle fibre strength (MFSIIA) was 50% (91/181). Subjective stress urinary incontinence was 46% (84/181), urinary retention was 27.3% (50/181), dyschezia was 41.5% (75/181), fecal incontinence was 9% (18/181). ① MFSI: Multivariate ordinal polytomous logistic regression shows that the follow-up time (p < 0.05), chemotherapy and radiotherapy (p = 0.038) are independent risk factors of MFSI's reduction after type QM-C hysterectomy. ② MFSIIA: multivariate ordinal polytomous logistic regression shows that the follow-up time (p < 0.05) are independent risk factors of MFSIIA's reduction after type QM-C hysterectomy. The pelvic floor muscle strength (PFMS) increased after 9 months than in 9 months after operation, which showed that the PFMS could be recovered after operation. CONCLUSIONS: We advocate for more attention and emphasis on the PFMF of Chinese female patients with cervical cancer postoperation. PEKING UNIVERSITY PEOPLE'S HOSPITAL: PFMF after QM-C hysterectomy has not been analyzed by current study. The contribution is that patients with radical hysterectomy should do pelvic floor rehabilitation exercises in 3 months after operation. Clinical Trails NCT number of this study is 02492542.

Cholinergic Elicitation Prevents Ventricular Remodeling via Alleviations of Myocardial Mitochondrial Injury Linked to Inflammation in Ischemia-Induced Chronic Heart Failure Rats.

BACKGROUND: Cholinergic anti-inflammatory pathway (CAP) is implicated in cardioprotection in chronic heart failure (CHF) by downregulating inflammation response. Mitochondrial injuries play an important role in ventricular remodeling of the CHF process. Herein, we aim to investigate whether CAP elicitation prevents ventricular remodeling in CHF by protecting myocardial mitochondrial injuries and its underlying mechanisms. METHODS AND RESULTS: CHF models were established by ligation of anterior descending artery for 5 weeks. Postoperative survival rats were assigned into 5 groups: the sham group (sham, n = 10), CHF group (CHF, n = 11), Vag group (CHF+vagotomy, n = 10), PNU group (CHF+PNU-282987 for 4 weeks, n = 11), and Vag+PNU group (CHF+vagotomy+PNU-282987 for 4 weeks, n = 10). The antiventricular remodeling effect of cholinergic elicitation was evaluated in vivo, and H9C2 cells were selected for the TNF-α gradient stimulation experiment in vitro. In vivo, CAP agitated by PNU-282987 alleviated the left ventricular dysfunction and inhibited the energy metabolism remodeling. Further, cholinergic elicitation increased myocardium ATP levels and reduced systemic inflammation. CAP induction alleviates macrophage infiltration and cardiac fibrosis, of which the effect is counteracted by vagotomy. Myocardial mitochondrial injuries were ameliorated by CAP activation, including the reserved ultrastructural integrity, declining ROS overload, reduced myocardial apoptosis, and enhanced mitochondrial fusion. In vitro, TNF-α intervention significantly exacerbated the mitochondrial damage in H9C2 cells. CONCLUSION: CAP elicitation effectively improves ischemic ventricular remodeling by suppressing systemic and cardiac inflammatory response, attenuating cardiac fibrosis and potentially alleviating the mitochondrial dysfunction linked to hyperinflammation reaction.

Insomnia Promotes Hepatic Steatosis in Rats Possibly by Mediating Sympathetic Overactivation.

Background: Insomnia is a widespread problem that can lead to the occurrence of other diseases and correlates closely with sympathetic nerve hyperactivation. Obesity-induced hepatic steatosis is mediated by sympathetic overactivation. However, it remains unclear whether insomnia may cause hepatic steatosis. The goal of this study was to preliminarily investigate whether insomnia caused hepatic steatosis in rats via sympathetic hyperactivation. Methods: A total of 32 Sprague-Dawley male rats were divided randomly into four groups: model, sympathetic denervation (Sd), estazolam, and control (eight rats/group). Model group received sustained sleep deprivation using the modified multiple platform method. In the Sd group, rats underwent sleep deprivation after receiving Sd by 6-hydroxydopamine (6-OHDA). Estazolam group: the rats concurrently received sleep deprivation and treatment with estazolam. The other eight rats housed in cages and kept in a comfortable environment were used as control. Blood samples were obtained for analysis of plasma lipids and hepatic function. Sympathetic hyperactivation-related indexes and hepatic steatosis in liver tissues were tested. Results: Liver enzymes, plasma lipid levels, and hepatic steatosis were elevated in insomnia rats, and sympathetic hyperactivation was found. Insomnia-induced hepatic steatosis was effectively lowered with pharmacological ablation of the hepatic sympathetic nerves. Furthermore, the treatment of insomnia with estazolam inhibited sympathetic activation and reduced hepatic steatosis. Conclusion: Sustained sleep deprivation-induced insomnia promotes hepatic steatosis in rats possibly by mediating sympathetic overactivation.

Association Between Chinese Visceral Adiposity Index and Incident Type 2 Diabetes Mellitus in Japanese Adults.

BACKGROUND: Obesity is a well-known risk factor for type 2 diabetes mellitus (T2DM). Studies have shown that the Chinese visceral adiposity index (CVAI), a novel visceral adiposity indicator, is positive associated with the risk of T2DM in the Chinese population. This study aimed to investigate the correlation between CVAI and incident T2DM in a Japanese population. METHODS: We performed a secondary analysis of open-access data from a retrospective cohort study. This study included 15,464 participants who received regular medical examinations at Murakami Memorial Hospital. All participants underwent a questionnaire survey, physical examination, and blood biochemical testing at baseline. The main outcome was new-onset T2DM during follow-up. Cox regression analysis and Kaplan-Meier analysis were used to analyze the risk of CVAI on T2DM, and we conducted smooth curve fitting. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of CVAI, body mass index (BMI), and waist circumference (WC) for incident T2DM. RESULTS: During a median follow-up time of 5.39 years, 373 new-onset T2DM events were observed. Kaplan-Meier curves showed that the incidence of T2DM increased as the CVAI increased (log-rank χ 2 = 187.1076 and 129.6067 in males and females, respectively, both P <0.001). After adjustment for covariates, per 1 increase of CVAI was associated with a 1.0133-fold and 1.0246-fold higher risk of incident T2DM in males and females, respectively (both P <0.001). Those individuals in the top CVAI quartile group had the highest risk of new-onset T2DM (HR = 3.1568 and 5.8415 in males and females, respectively, both P <0.05). A nonlinear relationship was identified by the smooth fitting curve between CVAI and T2DM events in both genders. ROC analysis indicated that CVAI had better predictive power than BMI and WC in both genders. CONCLUSION: Our results demonstrate that CVAI was significantly associated with an increased risk of new-onset T2DM in Japanese adults.

A Review of Biomarkers for Ischemic Stroke Evaluation in Patients With Non-valvular Atrial Fibrillation.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide and results in a significantly increased ischemic stroke (IS) risk. IS risk stratification tools are widely being applied to guide anticoagulation treatment decisions and duration in patients with non-valvular AF (NVAF). The CHA2DS2-VASc score is largely validated and currently recommended by renowned guidelines. However, this score is heavily dependent on age, sex, and comorbidities, and exhibits only moderate predictive power. Finding effective and validated clinical biomarkers to assist in personalized IS risk evaluation has become one of the promising directions in the prevention and treatment of NVAF. A number of studies in recent years have explored differentially expressed biomarkers in NVAF patients with and without IS, and the potential role of various biomarkers for prediction or early diagnosis of IS in patients with NVAF. In this review, we describe the clinical application and utility of AF characteristics, cardiac imaging and electrocardiogram markers, arterial stiffness and atherosclerosis-related markers, circulating biomarkers, and novel genetic markers in IS diagnosis and management of patients with NVAF. We conclude that at present, there is no consensus understanding of a desirable biomarker for IS risk stratification in NVAF, and enrolling these biomarkers into extant models also remains challenging. Further prospective cohorts and trials are needed to integrate various clinical risk factors and biomarkers to optimize IS prediction in patients with NVAF. However, we believe that the growing insight into molecular mechanisms and in-depth understanding of existing and emerging biomarkers may further improve the IS risk identification and guide anticoagulation therapy in patients with NVAF.