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Background: Pulmonary embolism (PE) is a life-threatening thromboembolic disease for which there is limited evidence for effective prevention and treatment. Our goal was to determine whether genetically predicted circulating blood cell traits could influence the incidence of PE. Methods: Using single variable Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) analyses, we identified genetic associations between circulating blood cell counts and lymphocyte subsets and PE. GWAS blood cell characterization summary statistics were compiled from the Blood Cell Consortium. The lymphocyte subpopulation counts were extracted from summary GWAS statistics for samples from 3757 individuals that had been analyzed by flow cytometry. GWAS data related to PE were obtained from the FinnGen study. Results: According to the SVMR and reverse MR, increased levels of circulating white blood cells (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.81-0.95, p = 0.0079), lymphocytes (OR: 0.90, 95% CI: 0.84-0.97, p = 0.0115), and neutrophils (OR: 0.88, 95% CI: 0.81–0.96, p = 0.0108) were causally associated with PE susceptibility. MVMR analysis revealed that lower circulating lymphocyte counts (OR: 0.84, 95% CI: 0.75-0.94, p = 0.0139) were an independent predictor of PE. According to further MR results, this association may be primarily related to HLA-DR+ natural killer (NK) cells. Conclusions: Among European populations, there is a causal association between genetically predicted low circulating lymphocyte counts, particularly low HLA-DR+ NK cells, and an increased risk of PE. This finding supports observational studies that link peripheral blood cells to PE and provides recommendations for predicting and preventing this condition. [ABSTRACT FROM AUTHOR]

Simple Summary: SMARCA4-mutated tumors are associated with poor prognosis. However, it is not clear if male and female patients have the same or different prognosis and if additional common mutations within the tumor play a role in prognosis. We have found that male patients had substantially worse prognosis than female patients whose tumor carried a SMARCA4 mutation. In addition, different co-existing mutations including the mutation of TP53, KRAS, CDKN2A, STK11, and Keap1 were associated with differential prognosis. Our study provides helpful insight for prognostic stratification in clinical practice and for understanding the pathogenic mechanism of this unique subtype of malignancy. Background: Whether sex and co-mutations impact prognosis of patients with SMARCA4-mutated (mutSMARCA4) malignancies is not clear. Methods: This cohort included patients from Northern California Kaiser Permanente with next-generation sequencing (NGS) performed from August 2020 to October 2022. We used Cox regression modeling to examine the association between sex and overall survival (OS), adjusting for demographics, performance status, Charlson comorbidity index, receipt of treatment, tumor mutation burden (TMB), and TP53, KRAS, CDKN2A, STK11, and Keap1 co-mutations. Results: Out of 9221 cases with NGS performed, 125 cases (1.4%) had a mutSMARCA4. The most common malignancies with a mutSMARCA4 were non-small cell lung cancer (NSCLC, 35.2%), esophageal and stomach adenocarcinoma (12.8%), and cancer of unknown primary (11.2%). The most common co-mutations were p53 (mutp53, 59.2%), KRAS (mutKRAS, 28.8%), CDKN2A (mutCDKN2A, 31.2%), STK11 (mutSTK11, 12.8%), and Keap1 (mutKeap1, 8.8%) mutations. Male patients had substantially worse OS than female patients both among the entire mutSMARCA4 cohort (HR = 1.71, [95% CI 0.92–3.18]) with a median OS of 3.0 versus 43.3 months (p < 0.001), and among the NSCLC subgroup (HR = 14.2, [95% CI 2.76–73.4]) with a median OS of 2.75 months versus un-estimable (p = 0.02). Among all patients with mutSMARCA4, mutp53 versus wtp53 (HR = 2.12, [95% CI 1.04–4.29]) and mutSTK11 versus wtSTK11 (HR = 2.59, [95% CI 0.87–7.73]) were associated with worse OS. Among the NSCLC subgroup, mutp53 versus wtp53 (HR = 0.35, [0.06–1.97]) and mutKRAS versus wtKRAS (HR = 0.04, [0.003-.45]) were associated with better OS, while mutCDKN2A versus wtCDKN2A (HR = 5.04, [1.12–22.32]), mutSTK11 versus wtSTK11 (HR = 13.10, [95% CI 1.16–148.26]), and mutKeap1 versus wtKeap1 (HR = 5.06, [95% CI 0.89–26.61}) were associated with worse OS. Conclusion: In our cohort of patients with mutSMARCA4, males had substantially worse prognosis than females, while mutTP53, mutKRAS, mutCDKN2A, mutSTK11 and mutKeap1were differentially associated with prognosis among all patients and among the NSCLC subgroup. Our results, if confirmed, could suggest potentially unidentified mechanisms that underly this sex and co-mutation-dependent prognostic disparity among patients whose tumor bears a mutSMARCA4. [ABSTRACT FROM AUTHOR]

Background: Debates exist in the repeat ablation strategy for patients with recurrence presenting as persistent atrial fibrillation (AF) after initial persistent AF ablation. Objective: To compare the outcome between the "2C3L" and "extensive ablation" approach in patients undergoing repeat procedures for recurrent persistent AF. Methods: Propensity‐score matching was performed in 196 patients with AF recurrence undergoing repeat ablation, and 79 patients treated with "2C3L" strategy were matched to 79 patients treated with "extensive ablation" strategy. The "2C3L" approach included pulmonary vein isolation, mitral isthmus, left atrial roof, and cavotricuspid isthmus ablation, while the "extensive ablation" strategy included extensive ablation of a variety of other targets aiming to terminate the AF. The primary outcome was freedom from any atrial tachyarrhythmia after 24‐h ambulatory monitoring follow‐up for 12 months. Results: No statistically significant difference was found between the primary outcome between the "2C3L" and the "extensive ablation" group [70.9% vs. 69.6%, p =.862; 95% confidence interval (CI) ‐12.8 to 15.3], although the "extensive ablation" group had a significantly high proportion of AF termination (19.0% for "2C3L" vs. 41.8% for "extensive ablation" group, p =.002; 95% CI 8.5–35.9). And AF termination was not related to the primary outcome in multifactorial regression. At 40 ± 22 months after the repeat procedure, the primary outcome was also comparable (57.0 % for "2C3L" vs. 48.1% for "extensive ablation" group, p =.265; 95% CI ‐6.6 to 23.7). Conclusion: The outcome between the "2C3L" and "extensive ablation" approaches was comparable in patients undergoing repeat procedures for recurrent persistent AF. [ABSTRACT FROM AUTHOR]

This research aims to explore the influence of transient pressure fluctuation inside high-speed trains passing throught tunnels on the fetal growth of Sprague – Dawley (SD) rats. A pressure variation simulation system was designed and exposure experiments were performed on SD rats. Forty-eight SD rats are divided into two control groups and two experimental groups, and are then exposed to transient pressure alternation (−1200 Pa ~1200 Pa) from gestation day 0 to gestation day 5 (GD 0–5). Fetal growth and development indicators on GD12 and GD18 between experimental and control groups were compared. Statistical results showed that, compared to the control group, the key indicators in the experimental group, including placental weight, placental diameter, fetal weight, and crown-to-rump length have decreased by 4.77%, 3.38%, 6.20%, and 3.75% respectively on GD18. The findings imply that the pressure fluctuation environment of high-speed trains has potential effects on the fetal growth of SD rats. [ABSTRACT FROM AUTHOR]

Background: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long‐term outcomes of patients with AF and LBBB after catheter ablation. Methods: Forty‐two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non‐LBBB group. Late recurrence and a composite endpoint of stroke, all‐cause mortality, and cardiovascular hospitalization were compared between the two groups. Results: Late recurrence rate was significantly higher in the LBBB group than that in the non‐LBBB group (54.8% vs. 31.5%, p =.034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09–4.40, p =.031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64–9.64, p =.002). Conclusions: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether circular RNA hsa_circ_0002874 could serve as a novel biomarker for the diagnosis of gastric cancer (GC). The expression level of hsa_circ_0002874 mean (interquartile range [IQR]) in the plasma of patients with GC, patients with benign gastric lesions, and healthy individuals was 3.482 (IQR, 1.524–9.048), 1.261 (IQR, 0.817–2.000), and 1.00 (IQR, 0.726–1.382), respectively, whereas there was no significant difference between the latter 2 groups. The plasma expression level of hsa_circ_0002874 was significantly correlated with tumor stage (U  = 234.0; P < .001) and lymph node metastasis (U  = 240.0; P < .001). The receiver operating characteristic (ROC) curve showed that the sensitivity of the combined determination of hsa_circ_0002874 and the serum markers CEA and CA19-9 was 95.8% in patients with GC compared with that of the healthy group and 93.0% compared with that of patients with benign gastric tumor lesions. The specificity of hsa_circ_0002874 in differentiating GC from benign lesions was 98.3%. The results showed that plasma hsa_circ_0002874 may prove to be a useful biomarker for auxiliary diagnosis, the grading of malignant neoplasms, and the prognostic prediction of GC. [ABSTRACT FROM AUTHOR]

Background: Atrial esophageal fistula (AEF) is a lethal complication that can occur post atrial fibrillation (AF) ablation. Esophageal injury (EI) is likely to be the initial lesion leading to AEF. Endoscopic examination is the gold standard for a diagnosis of EI but extensive endoscopic screening is invasive and costly. This study was conducted to determine whether fecal calprotectin (Fcal), a marker of inflammation throughout the intestinal tract, may be associated with the existence of esophageal injury. Methods: This diagnostic study was conducted in a cohort of 166 patients with symptomatic AF undergoing radiofrequency catheter ablation from May 2020 to June 2021. Fcal tests were performed 1–7 days after ablation. All patients underwent endoscopic ultrasonography 1 or 2 days after ablation. Results: The levels of Fcal were significantly different between the EI and non‐EI groups (404.9 µg/g (IQR 129.6–723.6) vs. 40.4 µg/g (IQR 15.0–246.2), p <.001). Analysis of ROC curves revealed that a Fcal level of 125 µg/g might be the optimal cut‐off value for a diagnosis of EI, giving a 78.8% sensitivity and a 65.4% specificity. The negative predictive value of Fcal was 100% for ulcerated EI. Conclusions: The level of Fcal is associated with EI post AF catheter ablation. 125 µg/g might be the optimal cut‐off value for a diagnosis of EI. Negative Fcal could predict the absence of ulcerated EI, which could be considered a precursor to AEF. [ABSTRACT FROM AUTHOR]

Background: Due to the anatomically adjacent relationship between the left atrium (LA) and esophagus, energy delivery on the posterior wall of LA is limited. The aim of this study was to evaluate the feasibility of a novel esophageal retractor (SAFER) with an inflatable C‐curve balloon during atrial fibrillation (AF) ablation. Method: Nine patients underwent AF ablation assisted with the SAFER. After inflation, the esophagus was deviated laterally away from the intended ablation site of the posterior wall under local anesthesia. The extent of mechanical esophageal deviation (MED) was evaluated under fluoroscopy, defined as the shortest distance from the trailing esophageal edge to the closest point of the ablation line. Gastroscopy was performed before and after ablation. The target ablation index used in all LA sites including the posterior wall was 400–450 after effective MED. All adverse events during the periprocedural period were recorded. Results: The mean deviation distance achieved 16.2 ± 9.6 mm away from the closest ablation point of the pulmonary vein lesion set. With respect to the individual left and right pulmonary vein lesion sets, the deviation distance was 19.7 ± 11.5 and 12.7 ± 6.8 mm, respectively. The extent of deviation was 0 to 5 mm, 5.1 to 10 mm, or >10 mm in 0(0%), 7(38.9%), and 11(61.1%), respectively. Procedural success was achieved in all patients without acute reconnection. There was only one esophageal complication which manifested as esophageal erosion and this patient experienced throat pain possibly related to the SAFER retractor with no clinical sequelae. Conclusion: Esophageal deviation with the novel eccentric balloon is a novel feasible choice during AF ablation, enabling adequate energy delivery to the posterior wall of LA. Additional prospective randomized controlled studies are required for further validation. [ABSTRACT FROM AUTHOR]

Background and objective: Atrioesophageal fistula (AEF) is a rare but devastating complication with high mortality post atrial fibrillation (AF) ablation. The purpose of current study was to determine the epidemiology, clinical features, pathogenesis, and management of AEF after AF ablation. Methods and results: Patients with diagnosed AEF were included and retrospectively analyzed according to the registry of 11 centers in China from January 2010 to December 2019. A total of 16 AEF cases were identified from 44 794 patients who received a left atrial ablation procedure (0.035% per procedure). The interval from procedure to clinical onset of AEF averaged 18.3 days (3‐39 days). The fever ranked the most common symptom, occurred in 14 of the 16 cases, followed by neurological deficits (n = 11), chest pain (n = 5), and hematemesis (n = 4). Patients undergoing surgical repair had a better prognosis compared to those receiving nonsurgical management ([4 of 8] 50.0% vs [8 of 8] 100%, P <.05) with an overall mortality rate of 75.0%. Conclusion: AEF is highly characterized by varied manifestations. Early diagnosis and urgent surgical repair are vital to those patients and associated with improved survival rates. [ABSTRACT FROM AUTHOR]

Background: Data on management of maternal arrhythmia among Chinese were limited. Radiofrequency catheter ablation (RFCA) proved to be a reliable treatment choice for sustained tachyarrhythmia but it has rarely been performed during pregnancy due to radiation exposure. Objective: To investigate the incidence of idiopathic sustained maternal arrhythmia and the feasibility of RFCA in the pregnant patients without fluoroscopy. Methods: From January of 2015 to December of 2018, the medical records on pregnancy‐related admissions in Beijing Anzhen Hospital (Beijing, China) were retrospectively analyzed. Patients who had sustained tachyarrhythmia episodes without structural heart disease were identified. Catheter ablation was performed in those with drug resistant and severely frequent tachyarrhythmia under the guidance of electroanatomical mapping system and intracardiac echocardiography catheter (ICE), if appropriate. Results: During the study period, 12 584 consecutive pregnant women were admitted for pregnancy‐related reasons, 156 (1.2%) of them were identified as sustained maternal tachyarrhythmia. Twenty‐eight patients (age 21‐37 years) received catheter ablation because the arrhythmias were drug resistant and severely frequent. The RFCA was successfully performed in all patients with zero fluoroscopy after 72.4 ± 24.7 min. Transseptal puncture was performed in 11 patients under the guidance of ICE. In a median of 37 (interquartile range [IQR]: 34‐39) weeks' pregnancy, 28 healthy fetuses were delivered. No cardiac‐related adverse event occurred during delivery. During later follow‐up, all patients were free of arrhythmia, and all the infants were well developed. Conclusion: Sustained maternal tachyarrhythmia is not uncommon in the clinical practice. To those with drug resistant and severely frequent arrhythmia, RFCA with zero fluoroscopy could be safely performed with acceptable efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma (GBM) is the most lethal adult primary brain tumor, and has no cure. This study investigated the membrane protein sortilin as a prognosis biomarker for glioblastoma (GBM). We found that sortilin is overexpressed in GBM tumors and can be detected in the blood of GBM patients. In addition, in cell cultures, targeting sortilin resulted in the inhibition of GBM cell invasion. These data highlight the value of sortilin as a potential clinical biomarker and therapeutic target for GBM and warrant further translational investigation. Glioblastoma (GBM) is a devastating brain cancer with no effective treatment, and there is an urgent need for developing innovative biomarkers as well as therapeutic targets for better management of the disease. The membrane protein sortilin has recently been shown to participate in tumor cell invasiveness in several cancers, but its involvement and clinical relevance in GBM is unclear. In the present study, we explored the expression of sortilin and its potential as a clinical biomarker and therapeutic target for GBM. Sortilin expression was investigated by immunohistochemistry and digital quantification in a series of 71 clinical cases of invasive GBM vs. 20 non-invasive gliomas. Sortilin was overexpressed in GBM and, importantly, higher expression levels were associated with worse patient survival, pointing to sortilin tissue expression as a potential prognostic biomarker for GBM. Sortilin was also detectable in the plasma of GBM patients by enzyme-linked immunosorbent assay (ELISA), but no differences were observed between sortilin levels in the blood of GBM vs. glioma patients. In vitro, sortilin was detected in 11 brain-cancer-patient-derived cell lines at the anticipated molecular weight of 100 kDa. Interestingly, targeting sortilin with the orally bioavailable small molecule inhibitor AF38469 resulted in decreased GBM invasiveness, but cancer cell proliferation was not affected, showing that sortilin is targetable in GBM. Together, these data suggest the clinical relevance for sortilin in GBM and support further investigation of GBM as a clinical biomarker and therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Perimitral atrial tachycardia (PMAT) is the most frequent type of iatrogenic atrial tachycardia (AT) after atrial fibrillation (AF) ablation. Vein of Marshall ethanol infusion (EIVOM) is a promising technique in mitral isthmus (MI) ablation. Methods: A total of 165 patients with PMAT were divided into three groups according to ablation strategies, including RF only group (n = 89), RF‐EIVOM group (initial RF ablation with adjunctive EIVOM, n = 28), and EIVOM‐RF group (first‐step EIVOM with touch‐up RF ablation, n = 48). Acute and follow‐up procedure outcomes were evaluated. Results: PMAT terminated in 89.9%, 89.3%, and 93.7% of patients in RF only, RF‐EIVOM and EIVOM‐RF groups, respectively (p =.715), with complete MI block achieved in 80.9%, 89.3%, and 95.8% of patients (EIVOM‐RF vs. RF only, p =.012). First‐step utilization of EIVOM was associated with a significant shortening of RF ablation time at MI (EIVOM‐RF 2.1 ± 1.3 min, RF only 7.9 ± 5.9 min, RF‐EIVOM 6.8 ± 5.8 min; p <.001) and a decrease in the proportion of patients need ablation within coronary sinus (CS, EIVOM‐RF 14.6%, RF only 61.8%, RF‐EIVOM 64.3%; p <.001). After a mean follow‐up of 12.1 ± 6.2 months, AF/AT recurred in 39 (43.8%), 6 (21.4%), and 12 (25.0%) patients in RF only, RF‐EIVOM, and EIVOM‐RF group (RF‐EIVOM vs. RF only, p =.026; EIVOM‐RF vs. RF only, p =.022). Conclusions: EIVOM was associated with an enhanced acute MI block rate as well as reduced AF/AT recurrence. First‐step utilization of EIVOM promises to significantly simplify the RF ablation process. PMAT is the most common type of iatrogenic AT after AF ablation procedures. EIVOM contributed to a higher acute MI block rate and lower arrhythmia recurrence risk during follow‐up. First‐step utilization of EIVOM significantly reduced the need for radiofrequency ablation at MI and inside CS with the advantage of creating a homogenous, transmural lesion and eliminating epicardial connections. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) and stable coronary artery disease (SCAD) frequently coexist. This study aimed to assess the long‐term outcome of catheter ablation in patients with paroxysmal AF and SCAD. Methods: In total, 12,104 patients with paroxysmal AF underwent catheter ablation in the Chinese Atrial Fibrillation Registry between 2011 and 2019 were screened. A total of 441 patients with SCAD were matched with patients without SCAD in a 1:4 ratio. The primary endpoint was AF recurrence after single ablation. The composite secondary endpoints were thromboembolism, coronary events, major bleeding, all‐cause death. Results: Over a mean follow‐up of 46.0 ± 18.9 months, the recurrence rate in patients with SCAD was significantly higher after a single ablation (49.0% vs. 41.9%, p =.03). The very late recurrence rate of AF in the SCAD group was also significantly higher than that in the control group (38.9% vs. 31.2%;p =.04). In multivariate analysis, adjusted with the female, smoking, duration of AF, previous thromboembolism, COPD, and statins, SCAD was independently associated with AF recurrence (adjusted HR, 1.19 [1.02–1.40], p =.03). The composite secondary endpoints were significantly higher in the SCAD group (12.70% vs. 8.54%, p =.02), mainly due to thromboembolism events (8.16% vs. 4.41%, p <.01). Conclusions: SCAD significantly increased the risk of recurrence after catheter ablation of paroxysmal AF. The incidence of thromboembolic events after catheter ablation of paroxysmal AF in the patients with SCAD was significantly higher than that in those without SCAD. [ABSTRACT FROM AUTHOR]

The outbreak of the COVID-19 pandemic has caused negative impacts on people's lifestyles, as well as considerable indirect social impacts, which has even overshadowed the direct impact of virus infection itself. This study is aimed at examining the changes in physical health-related indexes of Chinese college students before and after the COVID-19 lockdown. The data of this study are from the National Physical Health Testing Program, covering 43 college students (male: 22) from a class of a Chinese university. Paired t -tests were performed on the physical health test data separately collected in November 2019 before the COVID-19 pandemic and October 2020 after the COVID-19 lockdown was lifted. As shown by the test results, compared to the prelockdown data, college students had an increased body mass index (BMI) (0.43 (SD 0.94) P = 0.004), decreased vital capacity (VC) (-128.98 (SD 310.13) ml P = 0.009), and lowered performance in the 800/1000 m endurance (-6.21 (SD 8.81) points P < 0.001) and standing long jump tests (-2.44 (SD 7.37) points P = 0.036) after the lockdown, and the differences in these regards all were significant. In addition, for the students in the overweight/obese group, their pre- and postlockdown physical fitness test results were found to have no statistically significant difference (P > 0.05), but the students in the control group showed a significantly increased BMI, as well as significantly decreased vital capacity and performance in the 800/1000 m endurance and standing long jump tests (P < 0.05). The findings of this study are expected to help government departments and policymakers better understand the impacts of school closures and online learning on the physical health of adolescents, while providing a basis for the formulation of measures that are aimed at reversing adolescents' physical health decline. [ABSTRACT FROM AUTHOR]

Endometriosis (EMs) is characterized by inflammatory lesions, dysmenorrhea, infertility, and chronic pelvic pain. Single-target medications often fail to provide systemic therapeutic results owing to the complex mechanism underlying endometriosis. Although traditional Chinese medicines—such as Juan-Tong-Yin (JTY)—have shown promising results, their mechanisms of action remain largely unknown. To elucidate the therapeutic mechanism of JTY in EMs, focusing on endoplasmic reticulum (ER) stress-induced autophagy. The major components of JTY were detected using high-performance liquid chromatography–mass spectrometry (HPLC–MS). The potential mechanism of JTY in EMs treatment was predicted using network pharmacological analysis. Finally, the pathogenesis of EMs was validated in a clinical case-control study and the molecular mechanism of JTY was validated in vitro using endometrial stromal cells (ESCs). In total, 241 compounds were analyzed and identified from JTY using UPLC–MS. Network pharmacology revealed 288 targets between the JTY components and EMs. Results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses indicated that regulating autophagy, migration, apoptosis, and inflammation were the key mechanisms of JTY in treating EMs. Meanwhile, we found that protein kinase R-like endoplasmic reticulum kinase (PERK), Beclin-1, and microtubule-associated protein light chain 3 B (LC3B) expressions were lower in endometria of patients with EMs than in those with normal eutopic endometria (p < 0.05). Additionally, during in vitro experiments, treatment with 20% JTY-containing serum significantly suppressed ESC proliferation, achieving optimal effects after 48 h. Electron microscopy revealed significantly increased autophagy flux in the JTY group compared with the control group. Moreover, JTY treatment significantly reduced the migratory and invasive abilities of ESCs and upregulated protein expression of PERK, eukaryotic initiation factor 2α (eIF2α)/phospho-eukaryotic initiation factor 2α (p-eIF2α), activating Transcription Factor-4 (ATF4), Beclin-1, and LC3BII/I, while subsequently downregulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin 18 (IL-18) expression. However, administration of GSK2656157—a highly selective PERK inhibitor—reversed these changes. JTY ameliorates EMs by activating PERK associated with unfolded protein reaction, enhancing cell ER stress and autophagy, improving the inflammatory microenvironment, and decreasing the migration and invasion of ESCs. [Display omitted] • We examined the therapeutic mechanism of Juan-Tong-Yin in endometriosis. • Juan-Tong-Yin suppressed endometrial cell proliferation. • Juan-Tong-Yin increased autophagy in endometrial stromal cells. • Juan-Tong-Yin ameliorates endometriosis by activating the unfolded protein reaction triggered endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

Objective: To investigate theoptimal idarucizumab (dabigatran antagonist) usage strategy for patients with acute pericardial tamponade receiving uninterrupted dabigatran during catheter ablation for atrial fibrillation (AF). Methods: Ten patients presenting acute pericardial tamponade while receiving uninterrupted dabigatran during catheter ablation for AF in Beijing Anzhen Hospital from January 2019 to July 2020 were enrolled and retrospectively analyzed. A "wait and see" strategy of idarucizumab was carried out for all patients; in brief, idarucizumab was applied following pericardiocentesis, comprehensive evaluation of bleeding and hemostasis. Results: There were five males, five paroxysmal AF, and the average age of the patients was 64.0 ± 9.8 years. Among the 10 patients, four were treated with dabigatran 110 mg, six were treated with dabigatran 150 mg, and one was simultaneously given clopidogrel. The average time from pericardial tamponade to the last dose of dabigatran was 8.2 ± 3.4 h. All patients underwent pericardiocentesis successfully, and the average drainage volume was 322.5 ml (220.0 ± 935.0 ml). For reversal anticoagulation, six patients received protamine, and five patients received idarucizumab. Of the five patients who were treated with idarucizumab, four presented exact hemostasis, except for one patient who underwent continuous drainage and finally received surgery repair. The average time to restart anticoagulation was 1.1 ± 0.3 days after the procedure, and no rebleeding, embolism or deaths were observed. Conclusion: The "wait and see" strategy of idarucizumab for acute pericardial tamponade during the perioperative period of catheter ablation for AF may be safe and feasible. [ABSTRACT FROM AUTHOR]

Controversy persists regarding the treatment of immunoglobulin A nephropathy (IgAN), thereby highlighting the demand for safer more effective therapeutic drugs. Although supplementary treatment using Yi-Shen-Hua-Shi (YSHS) granules has distinct advantages with respect to improving renal function in IgAN, a lack of clarity regarding the underlying mechanisms limits their clinical application. In this study, we aimed to elucidate the therapeutic mechanisms underlying the efficacy of YSHS granules in the treatment of IgAN. A rat model of IgAN was established based on lipopolysaccharide, carbon tetrachloride, and bovine serum albumin induction. In order to evaluate the effects of YSHS granules, we performed a range of techniques, including immunofluorescence assays, hematoxylin and eosin staining, and flow cytometry, to assess inflammation, immunity, and other relevant factors. Direct data-independent acquisition–mass spectrometry (DIA-MS) analysis and parallel reaction monitoring (PRM) were used for functional characterization and quantitative validation of differentially expressed proteins (DEPs), and Western blot analysis is used to identify downstream proteins associated with DEPs. Compared with the model group, the levels of proteinuria, urine red blood cells, serum creatinine, blood urea nitrogen, low-density lipoprotein-cholesterol, triglycerides, and pathological kidney damage were reduced in the YSHS group. A high dose of YSHS granules was found to raise the levels of CD8 T cells and reduce the CD4/CD8 ratio in the peripheral serum. To examine the mechanisms underlying the therapeutic effects YSHS granules, we performed direct DIA-MS analysis to identify proteins that were differentially expressed among the model, YSHS, and control groups. A total of 29 proteins were identified as being commonly expressed in all three groups. Further KEGG and protein–protein interaction (PPI) network analysis revealed that YSHS granules can contribute to the regulation of N -glycosylation-associated proteins, such as ALG3 and STT3A, in rats with IgAN. Detected changes in the expression of ALG3 and STT3A were consistent with the PRM results. We also established that the administration of YSHS granules can contribute to regulation of the ALG3-associated PPAR-γ/NF-κB signaling pathway. Our findings in this study provide evidence to indicate the efficacy of YSHS granules in the treatment of IgAN, the putative underlying mechanisms of which involve the modulation of N-glycosylation, mediated via the PPAR-γ/NF-κB pathway. A detailed flow chart of the study design. The effects of YSHS granules on immune disorders, inflammatory injury, and metabolic disorders in IgAN rats were assessed using a rat model in which IgAN was induced by lipopolysaccharide (LPS), carbon tetrachloride (CCl4), and bovine serum albumin (BSA). To investigate the mechanisms underlying the therapeutic effects of YSHS granules, we performed direct data-independent acquisition mass spectrometry (DIA-MS) analysis. Further Kyoto Encyclopedia of Genes and Genomes and protein–protein interaction network analysis indicated that YSHS granules regulate N-glycosylation-associated proteins, including ALG3 and STT3A, in rats with IgAN. On the basis of Western blot analysis, we demonstrated that YSHS granules regulate the ALG3-associated PPAR-γ/NF-κB signaling pathway. [Display omitted] • YSHS granule improves IgAN renal function but mechanism unknown. • Proteomic data reveals 29 targets and N-glycosylation in YSHS against IgAN. • ALG3, a key protein，regulates immune and inflammation related proteins. • YSHS granule regulates ALG3/PPAR-γ/NF-κB in the treatment of IgAN. [ABSTRACT FROM AUTHOR]

Introduction: Catheter ablation for atrial fibrillation (AF‐CA) in patients with situs inversus dextrocardia (SID) can be challenging because of the contrary anatomy and associated anomalies. Cases and literature regarding AF‐CA in SID are rare and provide little information. Our study aims to present an improved procedure, ablation strategies, and evaluate the safety and outcomes of AF‐CA in patients with AF and SID. Methods: A total of 10 patients with AF‐SID (mean age, 60.4 ± 15.7 years; six paroxysmal AF, four persistent atrial fibrillation [PeAF]) were enrolled. For the improved procedure, images obtained by preacquired computed tomography and three‐dimensional electroanatomical mapping, integrating intracardiac echocardiography, and x‐ray imaging data are necessary to optimize the transseptal puncture and ablation procedure. Results: All patients successfully underwent 13 AF‐CA procedures without complications, including three patients received repeat procedures. However, two PeAF patients presented sick sinus syndrome (SSS) after the AF‐CA procedure, and one underwent permanent pacemaker implantation therapy during hospitalization. During the follow‐up period (6‐72 months), the outcomes were not favorable: three patients (30%) maintained sinus rhythm (SR) after the initial procedure; after repeated procedures, the overall SR rate was 40% (four patients). Conclusion: With the improved strategy, AF‐CA can be safely and effectively performed with low radiation exposure in patients with SID. However, the long‐term outcomes were not favorable, even when managed at a tertiary center by a team of specialists. Moreover, patients with PeAF might also have masked SSS, which should be carefully considered. [ABSTRACT FROM AUTHOR]

Introduction: The best management strategy for patients with atrial fibrillation (AF) with heart failure (HF) and preserved left ventricular ejection fraction (LVEF) is unknown. Methods and Results: This cohort study was conducted in Olmsted County, Minnesota, with resources of the Rochester Epidemiology Project. Patients with incident AF occurring between 2000 and 2014 with a prior or concurrent HF were included. Patients with LVEF ≥ 50% were designated as HF and preserved ejection fraction (HFpEF) and those with LVEF < 50% were designated as HF and reduced ejection fraction (HFrEF). Rhythm control in the first year after AF diagnosis was defined as prescriptions for an antiarrhythmic drug, catheter ablation, or maze procedure. The primary endpoint was all‐cause mortality. The secondary endpoints were cardiovascular death, cardiovascular hospitalization, and stroke or transient ischemic attack. Of 859 patients (age, 77.2 ± 12.1 years; 49.2%, female), 447 had HFpEF‐AF, and 412 had HFrEF‐AF. There was no difference in all‐cause mortality (10‐year mortality, 83% vs 79%; p =.54) or secondary endpoints between the HFpEF‐AF and HFrEF‐AF, respectively. Compared with the rate control strategy, rhythm control in HFpEF‐AF patients (n = 40, 15.9%) offered no survival benefits (adjusted HR, 0.70; 95% CI, 0.42–1.16; p =.16), whereas rhythm control in HFrEF‐AF patients (n = 52, 22.5%) decrease cardiovascular mortality (HR, 0.38; 95% CI, 0.17–0.86; p =.02). Conclusions: Patients with HFpEF‐AF and HFrEF‐AF had similar poor prognoses. Rhythm control strategy was seldom adopted in community care in patients with HF and AF. A rhythm control strategy may provide survival benefit for patients with HFrEF‐AF and the benefit of rhythm control in patients with HFpEF‐AF warrants further study. [ABSTRACT FROM AUTHOR]

Objective: To investigate the feasibility and safety of wire‐guided pericardial access without contrast. Methods: From January 2014 to February 2019, patients who received epicardial mapping and ablation of ventricular tachycardia in the Beijing Anzhen Hospital were entered into the current study. They were divided into contrast‐guided access group or wire‐guided access group according to the pericardial puncture technique used. The baseline variables, procedure parameters, complications were collected and compared. Results: During the study period, a consecutive of 73 patients received epicardial access. The initial 32 patients received contrast‐guided puncture with success achieved in 30 patients, the remaining 41 patients underwent wire‐guided puncture with success achieved in 40 patients (30/32 and 40/41, P =.581). Fluoroscopy time (4.45 ± 0.52 and 4.38 ± 0.46 minutes, P =.891) and access time (5.14 ± 0.58 and 5.34 ± 0.50 minutes, P =.657) were comparable between the two groups. Inadvertent right ventricular puncture occurred more commonly in the contrast‐guided group (5/32 and 1/41, P =.038). Though more pericardial effusions (2/32 and 1/41, P =.575), tamponade (2/32 and 1/41, P =.575), and surgical repair (1/32 and 0/41, P =.432) occurred in the contrast‐guided group, they reached no statistical difference. Conclusion: Wire‐guided pericardial puncture exhibits better safety and similar success rates to contrast‐guided technique with a trend towards less complications. [ABSTRACT FROM AUTHOR]

Background Atrial tachycardia (AT) from the right superior pulmonary vein (RSPV) may mimic right atrial (RA)-AT due to its proximity to the superior vena cava (SVC) and the preferential connections between the left atrium and right atrium. Objective RA electroanatomical mapping was performed and analyzed during RSPV-AT to differentiate it from RA-AT. Methods Electroanatomical mapping of the RA was performed in 16 consecutive patients with RSPV-AT and eight consecutive patients with SVC-AT served as control group. Results RA mapping revealed single breakthrough in six patients and double breakthroughs in 10 patients in the RSPV-AT group. The initial 10-ms atrial depolarization area averaged 4.3 ± 1.5 cm2. None of the SVC-ATs exhibited double breakthrough sites with an initial 10-ms atrial depolarization area of 2.0 ± 0.6 cm2 (P = 0.001). A cutoff value of activation area of initial 10 ms > 3.15 cm2 was able to predict RSPV-AT with a sensitivity of 87.5% and a specificity of 100%. Preceding far-field RSPV potentials could be documented in the RA in six patients during RSPV-AT. Conclusions During RSPV-AT, diffused initial depolarization and one or two separated breakthrough sites consistent with the preferential connections as revealed by RA mapping could help rule out RA-AT and avoid unnecessary ablation at the RA. [ABSTRACT FROM AUTHOR]