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Nian-Fang Lu,1 Hong-Xia Niu,2 An-Qi Liu,1 Ya-Lei Chen,1 Hu-Nan Liu,1 Pei-Hong Zhao,1 Jun Shao,3 Xiu-Ming Xi4 1Department of Critical Care Medicine, Capital Medical University Electric Teaching Hospital/Beijing Electric Power Hospital, Beijing, People’s Republic of China; 2Department of Emergency, Capital Medical University Electric Teaching Hospital/Beijing Electric Power Hospital, Beijing, People’s Republic of China; 3Department of Critical Care Medicine, Subei People’s Hospital of Jiangsu Province, Yangzhou, People’s Republic of China; 4Department of Critical Care Medicine, Capital Medical University Fuxing Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xiu-Ming Xi, Department of Critical Care Medicine, Capital Medical University Fuxing Hospital, No. 20 Fuxingmenwai Street, Xicheng District, Beijing, 100038, People’s Republic of China, Tel +86 13801244610, Email xixuimingxxm@126.com Jun Shao, Department of Critical Care Medicine, Subei People’s Hospital of Jiangsu Province, No. 98 Nantong West Road, Guangling District, Jiangsu, Yangzhou, People’s Republic of China, Tel +86 18051061365, Email shaojunsj_08@126.comObjective: To explore the prognostic outcomes associated with different types of septic cardiomyopathy and analyze the factors that exert an influence on these outcomes.Methods: The data collected within 24 hours of ICU admission included cardiac troponin I (cTnI), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP); SOFA (sequential organ failure assessment) scores, and the proportion of vasopressor use. Based on echocardiographic outcomes, septic cardiomyopathy was categorized into left ventricular (LV) systolic dysfunction, LV diastolic dysfunction, and right ventricular (RV) systolic dysfunction. Differences between the mortality and survival groups, as well as between each cardiomyopathy subgroup and the non-cardiomyopathy group were compared, to explore the influencing factors of cardiomyopathy.Results: A cohort of 184 patients were included in this study, with LV diastolic dysfunction having the highest incidence rate (43.5%). The mortality group had significantly higher SOFA scores, vasopressor use, and cTnI levels compared to the survival group; the survival group had better LV diastolic function than the mortality group (p < 0.05 for all). In contrast to the non-cardiomyopathy group, each subgroup within the cardiomyopathy category exhibited elevated levels of cTnI. The subgroup with left ventricular diastolic dysfunction demonstrated a higher prevalence of advanced age, hypertension, diabetes mellitus, coronary artery disease, and an increased mortality rate; the RV systolic dysfunction subgroup had higher SOFA scores and NT-proBNP levels, and a higher mortality rate (P < 0.05 for all); the LV systolic dysfunction subgroup had a similar mortality rate (P > 0.05).Conclusion: Patients with advanced age, hypertension, diabetes mellitus, or coronary artery disease are more prone to develop LV diastolic dysfunction type of cardiomyopathy; cardiomyopathy subgroups had higher levels of cTnI. The RV systolic dysfunction cardiomyopathy subgroup had higher SOFA scores and NT-proBNP levels. The occurrence of RV systolic dysfunction in patients with sepsis significantly increased the mortality rate.Keywords: cardiac function, echocardiography, influencing factors, prognosis, sepsis, septic cardiomyopathy

Nian-Fang Lu,1 Jun Shao,2 Hong-Xia Niu,3 Wen-Yong Han,4 Ya-Lei Chen,1 An-Qi Liu,1 Hu-Nan Liu,1 Xiu-Ming Xi5 1Department of Critical Care Medicine, Capital Medical University Electric Teaching Hospital/Beijing Electric Power Hospital, Beijing, 100073, People’s Republic of China; 2Department of Critical Care Medicine, Subei People’s Hospital of Jiangsu Province, Yangzhou, Jiangsu, 225001, People’s Republic of China; 3Department of Emergency, Capital medical university electric teaching hospital/Beijing Electric Power Hospital, Beijing, 100073, People’s Republic of China; 4Department of Anesthesiology, Capital Medical University Electric Teaching Hospital/Beijing Electric Power Hospital, Beijing, 100073, People’s Republic of China; 5Department of Critical Care Medicine, Capital Medical University Fuxing Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xiu-Ming Xi, Department of Critical Care Medicine, Capital Medical University Fuxing Hospital, A 20, Fuxingmenwai Street, Xicheng District, Beijing, People’s Republic of China, Tel +86 010 13801244610, Email xixuimingxxm@126.comObjective: To analyze the epidemiological data of patients with septic cardiomyopathy and investigate the relationship between ultrasonic parameters and prognosis of patients with sepsis.Methods: In this study, we enrolled patients with sepsis who were treated at the Department of Critical Care Medicine in the Beijing Electric Power Hospital (No.1 Taipingqiao Xili, Fengtai District, Beijing) from January 2020 to June 2022. All patients received standardized treatment. Their general medical status and 28-day prognosis were recorded. Transthoracic echocardiography was performed within 24 hours after admission. We compared the ultrasound indexes between the mortality group and the survival group at the end of 28 days. We included parameters with significant difference in the logistic regression model to identify the independent risk factors for prognosis and evaluated their predictive value using receiver operating characteristic (ROC) curve.Results: We included 100 patients with sepsis in this study; the mortality rate was 33% and the prevalence rate of septic cardiomyopathy was 49%. The peak e’ velocity and right ventricular systolic tricuspid annulus velocity (RV-Sm) of the survival group were significantly higher than those of the mortality group (P < 0.05). Results of logistic regression analysis showed that the peak e’ velocity and RV-Sm were independent risk factors for prognosis. The area under curve of the peak e’ velocity and the RV-Sm was 0.657 and 0.668, respectively (P < 0.05).Conclusion: The prevalence rate of septic cardiomyopathy in septic patients is high. In this study, we found that the peak e’ velocity and right ventricular systolic tricuspid annulus velocity were important predictors of short-term prognosis.Keywords: peak e’ velocity by tissue Doppler imaging, prognosis, right ventricular systolic tricuspid annulus velocity, septic cardiomyopathy

Objective: To investigate the advantages of adjustable angle needle path template compared with CT-guided 125 I seeds free-hand implantation in the treatment of non-small cell lung carcinoma. Methods: This randomized controlled trial involved the retrospective analysis of the clinical data of 45 patients with non-small cell lung carcinoma who underwent 125 I seeds implantation at the Shandong Cancer Hospital, Shaanxi Provincial Tumor Hospital and The Third Affiliated Hospital of Shandong First Medical University from May 2018 to January 2023. Patients were divided into the template ( n =21) and free-hand ( n =24) groups, according to the modality used. The template group comprised 16 males and 5 females, aged (66±12) years, while the free-hand group comprised 16 males and 8 females, aged (62±8) years. The dose distribution, implant quality, intraoperative computed tomography (CT) scan times, and 125 I seed reseeding numbers after implantation were compared between the two groups to evaluate the potential advantages of adjustable angle needle path template-assisted implantation over free-hand 125 I implantation. Results: Statistical comparison revealed no significant differences in age ( t =1.16, P =0.253), tumor volume [(71±26) vs. (71±22) cm 3 , t =0.21, P =0.837), or any other baseline characteristics between the template and free-hand groups. Overall, 45 patients successfully completed the operation. In the template group, the mean values of the D90 (dose that was delivered to 90% of the target volume), V100 (the target volume receiving 100% of the prescription dose), coverage index (CI), relative dose homogeneity index (HI), and external volume index (EI) pre-and post-implantation were (131.0±2.1) vs. (131.1±5.5) Gy, 90.0%±0.4% vs. 91.0%±2.8%, 0.83±0.07 vs. 0.82±0.05, 41%±11% vs. 37%± 13%, and 4.3%(2.9%, 14.0%) vs.8.8%(5.2%,14.6%), respectively. None of these parameters showed any significant difference (all P >0.05). In the free-hand group, the mean value of D90 pre- and post-implantation was (131.4±2.9) vs.(128.6±8.6) Gy, showing no significant difference ( P >0.05), the mean values of V100, CI, HI, and EI pre-and post-implantation were 90.0%±0.5% vs. 89.0%± 3.0%, 0.84±0.04 vs. 0.71±0.09, 41%±9% vs. 34%±10%, and 7.7% (4.9%,11.0%) vs.24.2% (14.3%, 35.3%), respectively, showing significant differences (all P <0.05). The number of reseeding seeds in the template group was lower than that in the free-hand group [2.0 (0,2.5) vs. 4.0 (2.0, 7.0), Z =-3.36, P =0.001], showing a statistically significant difference. Further, the number of CT scans in the template group was significantly less than that in the free-hand group (3.9±0.5 vs. 4.6±1.2, t =-2.54, P =0.016). The incidences of adverse reactions were 23.8% (5/21) and 33.3% (8/24) ( χ 2 =12.86, P =0.002) in the template and free-hand groups, respectively, indicating a significant difference. Conclusion: Compared with free-hand implantation, use of the adjustable angle needle path template technique can shorten the operation time, reduce the number of scans, reduce the incidence of complications, and improve treatment efficacy to a certain extent.

Objectives: Synchronous adenomas of the major and minor duodenal papilla are seldom reported. The aim of this study was to describe the characteristics of synchronous major and minor papilla adenomas and to evaluate the safety and efficacy of endoscopic papillectomy (EP) for the management of the disease., Methods: Consecutive patients who underwent endoscopy for synchronous major and minor papilla adenomas from January 1, 2013 to August 31, 2023 were analyzed retrospectively. Patients' characteristics, clinical manifestations, laboratory, imaging and endoscopic findings were collected., Results: The nine patients with synchronous major and minor papilla adenomas had an average age of 50.78 ± 10.70 years. The diameter of major and minor papilla adenomas was 12.11 ± 3.41 mm and 6.11 ± 1.05 mm, respectively. Most major papilla adenomas had R0 horizontal margins (n = 8), while R0 vertical margins were achieved in all patients. While minor papilla adenomas were resected with both R0 horizontal and vertical margins in all patients. Post-EP bleeding was observed in one patient, which was classified as mild. Post-EP hyperamylasemia and pancreatitis was observed in two and four patients, respectively; the latter consisted of three with mild pancreatitis and one with severe pancreatitis. No perforation was observed. The mean follow-up duration was 9.22 ± 5.99 months. Histologically confirmed recurrence at the resection site was detected in one patient at 3 months after the procedure., Conclusions: Synchronous major and minor papilla adenomas may not be as rare as previously speculated. EP may be an effective and safe alternative modality for their management., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Introduction: The long-term efficacy of high-power (50 W) ablation guided by lesion size index (LSI-guided HP) for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) remains undetermined. Our study sought to assess the clinical efficacy of LSI-guided HP ablation for PVI in patients with AF and explore the potential predictors associated with clinical outcomes., Methods: We consecutively included 186 patients with AF who underwent LSI-guided HP (50 W) ablation at Fuwai Hospital from June 2019 to October 2021. The target LSI values of 4.5-5.5 and 4.0-4.5 at the anterior and posterior walls, respectively, were used in our study. The baseline clinical characteristics, procedural and ablation data, and clinical outcomes were evaluated. The independent potential predictors associated with AF recurrence were further evaluated., Results: The incidence rate of first-pass PVI was 83.9% (156/186). A total of 11 883 lesions were analyzed, and compared with posterior walls of pulmonary veins, anterior walls had significantly lower mean contact force (8.2 ± 3.0 vs. 8.3 ± 2.3 g, p = .015), longer mean radiofrequency duration (16.9 ± 7.2 vs. 12.9 ± 4.5 s, p < .001) and higher mean LSI (4.8 ± 0.2 vs. 4.4 ± 0.2, p < .001). The overall incidence of periprocedural complications was 3.7%, and steam pops without pericardial effusion occurred in three patients (1.6%). During a mean follow-up of 24.0 ± 8.4 months, the overall AF recurrence-free survival was 87.1% after a single procedure. Patients with paroxysmal AF had a higher incidence of freedom from AF recurrence than those with persistent AF (91.2% vs. 80.8%, log-rank p = .034). Higher LSI (HR 0.50, p < .001) and paroxysmal AF (HR 0.39, p = .029) were significantly associated with decreased AF recurrence. By receiver operating characteristic analysis, the LSI of 4.7 and 4.3 for the anterior and posterior walls of the PVs had the highest predictive value for AF recurrence, respectively., Conclusion: LSI-guided HP (50 W) ablation for PVI was an efficient and safe strategy and led to favorable single-procedure 2-year AF recurrence-free survival in patients with AF. Higher LSI and paroxysmal AF were independent predictors of decreased 2-year AF recurrence. The LSI of 4.7 for the anterior wall and 4.3 for the posterior wall of the PVs were the best cutoff values for predicting AF recurrence after LSI-guided HP ablation., (© 2023 Wiley Periodicals LLC.)

Objectives: This study concerns a new technique that aims to achieve precise interstitial brachytherapy of pelvic recurrent tumors under transvaginal ultrasound (US) guidance, enhance the conformity index of the brachytherapy (BT), and improve the curative effect of radiotherapy for gynecological oncology patients with pelvic relapse., Methods: A real-time transvaginal US-guided interstitial implant device was developed to assist in implant BT. Prior to implant brachytherapy, the size and location of the tumor in the pelvis and the interrelationship with adjacent organs were first assessed with intracavitary ultrasound. The transvaginal US-guided interstitial implant device was then placed on the endoluminal ultrasound probe, the probe was oriented intravaginally to determine a safe needle path, the implant needle was placed into the needle passage of the device, and the implant needle was inserted into the tumor tissue in the direction guided by the ultrasound puncture guide line. After the implant needle was placed in place, the cover of the transvaginal US-guided interstitial implant device was opened perpendicular to the ultrasound probe, and the needle was separated from the ultrasound probe smoothly, and then the cover was re-covered for subsequent implantation., Results: In this study, 56 patients who underwent real-time transvaginal ultrasound-guided implantation for gynecologic oncology were enrolled, and insertion of 736 implant needles was completed. Among them, 13 patients had recurrent pelvic tumors after cervical cancer surgery and 6 patients had recurrent pelvic tumors after endometrial cancer surgery. Thirty-two patients who underwent radical radiation therapy for cervical cancer did not have adequate regression of parametrial invaded tissue after completion of standard EBRT treatment; and 5 patients had recurrent tumors in the radiation field after previous standard course of pelvic radiotherapy. The accuracy of the implant therapy was improved. The radiotherapy dose for recurrent pelvic masses was successfully increased, and the cumulative dose of external irradiation combined with BT was augmented to 80-100 Gy. The use of a new device for transvaginal implant for recurrent masses located in the lateral wall of the pelvic cavity was successful., Conclusion: This intravascular US-guided interstitial implant device can realize interstitial implant with the shortest path under transvaginal US guidance. With convenient operation, high precision, and good security, the device not only improves the accuracy of implant therapy, but it also reduces the risks of anesthesia and organ injury, so it is suitable for widespread promotion and use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yan, Yang, Chen, Wang, Niu, Niu and Liu.)

Background: Although both high-power (HP) ablation and lesion size index (LSI) are novel approaches to make effective lesions during pulmonary vein isolation (PVI) for atrial fibrillation (AF), the optimal LSI in HP ablation for PVI is still unclear. Our study sought to explore the association between LSI and acute conduction gap formation and investigate the optimal LSI in HP ablation for PVI., Methods: A total of 105 consecutive patients with AF who underwent HP ablation guided by LSI (LSI-guided HP) for PVI in our institute between June 2019 and July 2020 were retrospectively enrolled. Each ipsilateral PV circle was subdivided into four segments, and ablation power was set to 50 W with target LSI values at 5.0 and 4.0 for anterior and posterior walls, respectively. We compared the LSI values with and without acute conduction gaps after the initial first-pass PVI., Results: PVI was achieved in all patients, and the incidence of first-pass PVI was 78.1% (82/105). A total of 6,842 lesion sites were analyzed, and the acute conduction gaps were observed in 23 patients (21.9%) with 45 (0.7%) lesion points. The gap formation was significantly associated with lower LSI (3.9 ± 0.4 vs. 4.6 ± 0.4, p < 0.001), lower force-time integral (82.6 ± 24.6 vs. 120.9 ± 40.4 gs, p < 0.001), lower mean contact force (5.7 ± 2.4 vs. 8.5 ± 2.8 g, p < 0.001), shorter ablation duration (10.5 ± 3.6 vs. 15.4 ± 6.4 s, p < 0.001), lower mean temperature (34.4 ± 1.4 vs. 35.6 ± 2.6°C, p < 0.001), and longer interlesion distance (4.4 ± 0.3 vs. 4.3 ± 0.4 mm, p = 0.031). As per the receiver operating characteristic analysis, the LSI had the highest predictive value for gap formation in all PVs segments, with a cutoff of 4.35 for effective ablation (sensitivity 80.0%; specificity 75.4%, areas under the curve: 0.87). The LSI of 4.55 and 3.95 had the highest predictive value for gap formation for the anterior and posterior segments of PVs, respectively., Conclusion: Using LSI-guided HP ablation for PVI, more than 4.35 of LSI for all PVs segments showed the best predictive value to avoid gap formation for achieving effective first-pass PVI. The LSI of 4.55 for the anterior wall and 3.95 for the posterior wall were the best cutoff values for predicting gap formation, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cai, Wang, Niu, Chu, Hua, Zhang and Yao.)

Background: The prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) is well-established. However, whether it could facilitate the risk stratification of HF patients with implantable cardioverter-defibrillator (ICD) is still unclear., Objective: To determine the associations between baseline NT-proBNP and outcomes of all-cause mortality and first appropriate shock due to sustained ventricular tachycardia/ventricular fibrillation (VT/VF) in ICD recipients., Methods and Results: N-terminal pro-B-type natriuretic peptide was measured before ICD implant in 500 patients (mean age 60.2 ± 12.0 years; 415 (83.0%) men; 231 (46.2%) Non-ischemic dilated cardiomyopathy (DCM); 136 (27.2%) primary prevention). The median NT-proBNP was 854.3 pg/ml (interquartile range [IQR]: 402.0 to 1,817.8 pg/ml). We categorized NT-proBNP levels into quartiles and used a restricted cubic spline to evaluate its nonlinear association with outcomes. The incidence rates of mortality and first appropriate shock were 5.6 and 9.1%, respectively. After adjusting for confounding factors, multivariable Cox regression showed a rise in NT-proBNP was associated with an increased risk of all-cause mortality. Compared with the lowest quartile, the hazard ratios (HRs) with 95% CI across increasing quartiles were 1.77 (0.71, 4.43), 3.98 (1.71, 9.25), and 5.90 (2.43, 14.30) for NT-proBNP ( p for trend < 0.001). A restricted cubic spline demonstrated a similar pattern with an inflection point found at 3,231.4 pg/ml, beyond which the increase in NT-proBNP was not associated with increased mortality ( p for nonlinearity < 0.001). Fine-Gray regression was used to evaluate the association between NT-proBNP and first appropriate shock accounting for the competing risk of death. In the unadjusted, partial, and fully adjusted analysis, however, no significant association could be found regardless of NT-proBNP as a categorical variable or log-transformed continuous variable (all p > 0.05). No nonlinearity was found, either ( p = 0.666). Interactions between NT-proBNP and predefined factors were not found (all p > 0.1)., Conclusion: In HF patients with ICD, the rise in NT-proBNP is independently associated with increased mortality until it reaches the inflection point. However, its association with the first appropriate shock was not found. Patients with higher NT-proBNP levels might derive less benefit from ICD implant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Deng, Cheng, Hua, Cai, Zhang, Niu, Chen, Gu, Cai, Liu, Huang and Zhang.)

Introduction: Left bundle branch pacing (LBBP) is a rapidly growing conduction system pacing technique. However, little is known regarding the electrophysiological characteristics of different types of LBBP. We aimed to evaluate the electrophysiological characteristics and anatomic lead location with pacing different branches of the left bundle branch. Methods: Consecutive bradycardia patients with successful LBBP were enrolled and classified into groups according to the paced electrocardiogram and the lead location. Electrocardiogram, pacing properties, vectorcardiogram, and lead tip location were analyzed. Results: Ninety-one patients were enrolled, including 48 with the left bundle trunk pacing (LBTP) and 43 with the left bundle fascicular pacing (LBFP). The paced QRS duration in the LBTP group was significantly shorter than that in the LBFP group (108.1 ± 9.9 vs. 112.9 ± 11.2 ms, p = 0.03), with a more rightward QRS transition zone ( p = 0.01). The paced QRS area in the LBTP group was similar to that during intrinsic rhythm (35.1 ± 15.8 vs. 34.7 ± 16.6 μVs, p = 0.98), whereas in the LBFP group, the paced QRS area was significantly larger compared to intrinsic rhythm (43.4 ± 15.8 vs. 35.7 ± 18.0 μVs, p = 0.01). The lead tip site for LBTP was located in a small fan-shaped area with the tricuspid valve annulus summit as the origin, whereas fascicular pacing sites were more likely in a larger and more distal area. Conclusions: Pacing the proximal left bundle main trunk produced better electrical synchrony compared with pacing the distal left bundle fascicles. A visualization technique can facilitate achieving LBTP., Competing Interests: XZ is an employee of Medtronic. MGo receives consulting fees from Medtronic and Boston Scientific. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Gu, Niu, Chen, Cai, Zhao, Cai, Zhou, Gold, Zhang and Hua.)

Purpose: We aimed to evaluate the electrical characteristics and pacing parameters at different locations of His-Purkinje system pacing., Methods: Patients who successfully underwent His-Purkinje system pacing with bradycardia indications from April 2018 to August 2019 were retrospectively analyzed according to the lead location confirmed by visualization of the tricuspid value annulus, postoperative echocardiography, and pacing electrocardiogram. The electrical characteristics and pacing parameters were compared among these patients., Results: A total of 135 patients were retrospectively analyzed. Among them, 30 patients received atrial side HBP (aHBP group), 52 received ventricular side HBP (vHBP group), and 53 received left bundle branch pacing (LBBP group). The proportion of non-selective pacing was significantly lower in aHBP group (30.0%) than in vHBP (75.0%) and LBBP group (90.6%). LBBP had significantly shorter procedural and fluoroscopic duration than aHBP and vHBP. The capture threshold was significantly higher (1.07 ± 0.26 V/1.0 ms vs. 0.89 ± 0.22 V/1.0 ms vs. 0.77 ± 0.18 V/0.4 ms, P < 0.01, respectively), and the R-wave amplitude was significantly lower (3.71 ± 1.72 mV vs. 5.81 ± 2.37 mV vs. 10.27 ± 4.71 mV, P < 0.05 respectively) in aHBP group than those in the other two groups at implantation and during 3-month follow-up. No significant differences were observed in complications among groups during 3-month follow-up., Conclusion: VHBP and LBBP had better pacing performances than aHBP and might be more ideal pacing methods for bradycardia patients., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: For patients who develop atrioventricular block (AVB) following transcatheter aortic valve replacement (TAVR), right ventricular pacing (RVP) may be associated with adverse outcomes. We assessed the feasibility of conduction system pacing (CSP) in patients who developed AVB following TAVR and compared the procedural and clinical outcomes with RVP. Methods: Consecutive patients who developed AVB following TAVR were prospectively enrolled, and were implanted with RVP or CSP. Procedural and clinical outcomes were compared among different pacing modalities. Results: A total of 60 patients were enrolled, including 10 who were implanted with His bundle pacing (HBP), 20 with left bundle branch pacing (LBBP), and 30 with RVP. The HBP group had significantly lower implant success rate, higher capture threshold, and lower R-wave amplitude than the LBBP and RVP groups ( p < 0.01, respectively). The RVP group had a significantly longer paced QRS duration (153.5 ± 6.8 ms, p < 0.01) than the other two groups (HBP: 121.8 ± 8.6 ms; LBBP: 120.2 ± 10.6 ms). During a mean follow-up of 15.0 ± 9.1 months, the LBBP group had significantly higher left ventricular ejection fraction (LVEF) (54.9 ± 6.7% vs. 48.9 ± 9.1%, p < 0.05) and shorter left ventricular end-diastolic diameter (LVEDD) (49.7 ± 5.6 mm vs. 55.0 ± 7.7 mm, p < 0.05) than the RVP group. While the HBP group showed trends of higher LVEF ( p = 0.016) and shorter LVEDD ( p = 0.017) than the RVP group. Four patients in the RVP group died-three deaths were due to progressive heart failure and one was due to non-cardiac reasons. One death in the LBBP group was due to the non-cardiac reasons. Conclusions: CSP achieved shorter paced QRS duration and better cardiac structure and function in post-TAVR patients than RVP. LBBP had a higher implant success rate and better pacing parameters than HBP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Niu, Liu, Gu, Chen, Cai, Cai, Zhang and Hua.)

Introduction: His bundle pacing (HBP) is the most widely used physiological pacing modality, but difficulties in locating the His bundle lead to high fluoroscopic exposure. An electroanatomical mapping (EAM) system can be an efficient tool to achieve HBP implantation with near-zero fluoroscopic visualization. Methods: In the study, 20 patients who had indications for pacemaker implantation were prospectively enrolled and underwent HBP implantation either with the conventional fluoroscopy approach (the standard group) or guided by a novel KODEX-EPD mapping system (the EAM-guided group). The success rate, procedural details, pacing parameters, and procedure-related complications were compared between the two groups. Results: In the study, 20 consecutive patients were randomized with 10 patients in each group. HBP was successfully achieved in nine patients in the standard group and nine patients in the EAM-guided group. The procedural time was similar between the EAM-guided group vs. the standard group (85.40 ± 22.34 vs. 86.50 ± 15.05 min, p = 0.90). In comparison with the standard group, the EAM-guided group had a significant shorter total fluoroscopic time (FT) (1.45 ± 0.58 vs. 12.36 ± 5.46 min, p < 0.01) and His lead fluoroscopic time (HL-FT) (0.84 ± 0.56 vs. 9.27 ± 5.44 min, p < 0.01), while lower total fluoroscopic dose (3.13 ± 1.24 vs. 25.38 ± 11.15 mGy, p < 0.01) and His lead fluoroscopic dose (1.85 ± 1.17 vs. 19.06 ± 11.03 mGy, p < 0.01). No significant differences were observed in paced QRS duration and pacing parameters between the two groups. During a 3-month follow-up, one patient had a capture threshold increased >1 V/1.0 ms in the standard group, while no other complications were recorded in either group. Conclusion: The KODEX-EPD system could facilitate HBP implantation with significantly reduced FT and dose without compromising the procedural time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hua, Liu, Gu, Niu, Chen, Tang and Zhang.)

Background: Left bundle branch pacing (LBBP) is a novel conduction system pacing modality, but pacing lead deployment remains challenging., Objectives: This study aimed to evaluate the feasibility of visualization-enhanced lead deployment for LBBP implantation and to assess LBBP characteristics on the basis of lead tip location., Methods: Successful LBBP with a well-defined lead tip location by visualization of the tricuspid value annulus in 20 patients was retrospectively analyzed to develop an image-guided technique to identify the LBBP target site. This technique was then prospectively tested in 60 patients who were randomized into 2 groups, one using the standard approach (the standard group) and the other using the image-guided technique (the visualization group). The procedural details, electrophysiological characteristics, and short-term follow-up were compared between groups., Results: LBBP was successfully achieved in 28 patients in the standard group and in 29 in the visualization group. The procedural and fluoroscopic durations in the visualization group (66.76 ± 14.62 and 7.83 ± 2.05 minutes) were significantly shorter than those in the standard group (85.46 ± 20.19 and 11.11 ± 3.51 minutes) (P < .01). The number of lead deployment attempts in the visualization group was lower than that in the standard group (2.03 ± 1.18 vs 2.96 ± 1.17; P < .01), and the proportion of left bundle branch potential recorded was higher (79.3% vs 46.4%; P = .01)., Conclusion: Using a visualization technique, the procedural and fluoroscopic durations for LBBP implantation were significantly shortened with fewer lead repositioning attempts., (Copyright © 2021 Heart Rhythm Society. All rights reserved.)

Background: A low appropriate therapy rate indicates that a minority of patients will benefit from their implantable cardioverter defibrillator (ICD). Quantitative measurements from 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) may predict ventricular arrhythmia (VA) occurrence after ICD placement., Methods: We performed a prospective observational study and recruited patients who required ICD placement. Pre-procedure image scans were performed. Patients were followed up for VA occurrence. Associations between image results and VA were analyzed., Results: In 51 patients (33 males, 53.9 ± 17.2 years) analyzed, 17 (33.3%) developed VA. Compared with patients without VA, patients with VA had significantly larger values in scar area (17.7 ± 12.4% vs. 7.0 ± 7.9%), phase standard deviation (51.4° ± 14.0° vs. 34.0° ± 15.0°), bandwidth (172.9° ± 39.8° vs. 128.7° ± 49.9°), sum thickening score (STS, 29.5 ± 11.1 vs. 17.8 ± 13.2), and sum motion score (42.9 ± 11.5 vs. 33.0 ± 19.0). Cox regression analysis and receiver operating characteristic curve analysis showed that scar size, dyssynchrony, and STS were associated with VA occurrence (HR, 4.956, 95% CI 1.70-14.46)., Conclusion: Larger left ventricular scar burden, increased dyssynchrony, and higher STS quantified by 18 F-FDG PET may indicate a higher VA incidence after ICD placement.

Objectives: It is important to identify super-responders who can derive most benefits from cardiac resynchronization therapy (CRT). We aimed to establish a scoring model that can be used for predicting super-response to CRT., Methods: We retrospectively reviewed 387 CRT patients. Multivariate logistic regression analysis was performed to identify predictors for super-response (defined as an absolute increase in left ventricular ejection fraction of ≥15% at 6-month follow-up) and to create a score model. Multivariate Cox proportional-hazard regression analysis was conducted to assess associations with the long-term endpoint (defined as cardiac death/heart transplant, heart failure (HF) hospitalization, or all-cause death) across the score categories at follow-up., Results: Among 387 patients, 109 (28.2%) met super-response. In multivariable analysis, 5 independent predictors (QQ-LAE) were identified: prior no fragmented QRS (odds ratio (OR) = 3.10 (1.39, 6.94)), QRS duration ≥170 ms (OR = 2.37 (1.35, 4.12)), left bundle branch block (OR = 2.57 (1.04, 6.37)), left atrial diameter <45 mm (OR = 3.27 (1.81, 5.89)), and left ventricular end-diastolic dimension <75 mm (OR = 4.11 (1.99, 8.48)). One point was attributed to each predictor, and three score categories were identified. The proportion of super-response after 6-month CRT implantation in patients with scores 0-3, 4, and 5 was 14.6%, 40.3%, and 64.1%, respectively ( P < 0.001). Patients with score 5 had an 88% reduction in the risk of cardiac death/heart transplant ( P =0.042), a 71% reduction in the risk of HF hospitalization ( P =0.048), and an 89% reduction in the risk of all-cause mortality ( P =0.028) compared to patients with scores 0-3., Conclusions: The QQ-LAE score can be used for prediction of super-response to CRT and selection of most suitable patients in clinical practices., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Xi Liu et al.)

Background: The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and induces the trimethylation of histone H3 lysine 27 (H3K27me3) in the promoter of many key genes; EZH2 acts as a transcriptional repressor and is an epigenetic regulator for several cancers. However, the role of EZH2 in nonneoplastic diseases, such as kidney diseases, is unknown and has been investigated., Materials and Method: NRK-52E cells were treated with DZNep, a potent inhibitor of EZH2, with different concentrations and for different times to evaluate the apoptosis level of NRK-52E cells by Western blot and Flow cytometry analysis. The binding of EZH2 to the Deptor promoter was determined by ChIP assay., Results: The inhibition of EZH2 with 3-deazaneplanocin A (DZNep), a specific inhibitor of EZH2, led to the apoptosis of NRK-52E cells and the inhibition of mTORC1 and mTORC2 activity. A ChIP assay demonstrated that EZH2 bound the promoter region of Deptor, an endogenous inhibitor of mTORC1 and mTORC2, and regulated the transcription of Deptor by modulating H3K27me3 in its promoter region. Further experiments were performed to examine the effects of EZH2 inhibition on cisplatin-induced injured cells. Cisplatin induced the activation of mTORC1 and mTORC2 and apoptosis in NRK-52E cells, and DZNep inhibited mTORC1 and mTORC2 activity and aggravated cell apoptosis., Conclusions: These data suggested that EZH2 inhibition increased the transcription of Deptor by modifying H3K27me3 in its promoter region, subsequently inhibited mTORC1 and mTORC2 activities, downregulated the expression of apoptosis suppressor genes, and finally led to apoptosis in renal tubular cells. The inhibition of EZH2 aggravated the cisplatin-induced injury in renal tubular cells by inactivating the mTOR complexes. The present study provides new insight into renal protection and suggests that EZH2 might be a target., Competing Interests: Competing interestsWe declare that we do not have any commercial or associative interest that represents a competing interest in connection with the work submitted., (© The Author(s) 2020.)

Purpose: To evaluate the clinical and echocardiographic effects of prolonged cessation and resumption of left ventricular pacing among patients with chronic cardiac resynchronization therapy (CRT)., Methods: This was a retrospective analysis of patients with long-term CRT who had loss of left ventricular pacing because of battery depletion. Clinical assessment and echocardiographic data were analyzed with comparisons between implant, chronic CRT, loss of CRT, and after resumption of CRT., Results: There were 7 CRT responders who underwent 8 successful pulse generator replacements due to loss of CRT 6.3 ± 2.3 months after reaching elective replacement interval. With initial CRT implantation, QRS duration decreased from 171 ± 25 to 145 ± 28 ms (P < 0.001) and left ventricular ejection fraction increased from 27.6 ± 8.1 to 53.9 ± 9.6% (P < 0.001). At pulse generator replacement, worsening heart failure was present 6 of 7 patients with significant deterioration of left ventricular function and the left ventricular ejection fraction decreased to 43.4 ± 8.4%(P = 0.001). After resumption of CRT, clinical status and cardiac function recovered with left ventricular ejection fraction increasing to 53.7 ± 8.7% (P = 0.001)., Conclusions: Prolonged loss of CRT is associated with significant deterioration of left ventricular function and functional status that is fully reversible with resumption of left ventricular pacing.

The transfer of genetic material from the mitochondria and plastid to the nucleus gives rise to nuclear integrants of mitochondrial DNA (NUMTs) and nuclear integrants of plastid DNA (NUPTs). This frequently occurring DNA transfer is ongoing and has important evolutionary implications. In this review, based on previous studies and the analysis of NUMT/NUPT insertions of more than 200 sequenced plant genomes, we analyzed and summarized the general features of NUMTs/NUPTs and highlighted the genetic consequence of organellar DNA insertions. The statistics of organellar DNA integrants among various plant genomes revealed that organellar DNA-derived sequence content is positively correlated with the nuclear genome size. After integration, the nuclear organellar DNA could undergo different fates, including elimination, mutation, rearrangement, fragmentation, and proliferation. The integrated organellar DNAs play important roles in increasing genetic diversity, promoting gene and genome evolution, and are involved in sex chromosome evolution in dioecious plants. The integrating mechanisms, involving non-homologous end joining at double-strand breaks were also discussed.

Background: Tpeak-Tend interval (TpTe), a measurement of transmural dispersion of repolarization (TDR), has been shown to predict ventricular tachyarrhythmia in cardiac resynchronization therapy with defibrillator (CRT-D) patients. However, the ability of TpTe to predict ventricular tachyarrhythmia and mortality for heart failure patients with a cardioverter-defibrillator (ICD) is not clear. The purpose of this study was to assess the predictive ability of TpTe in heart failure patients with ICD., Methods and Results: We enrolled 318 heart failure patients treated after ICD. Patients were divided into 3 groups according to their post-implantation TpTe values and were evaluated every 6 months. The primary endpoint was appropriate ICD therapy. The secondary endpoint was all-cause mortality. During long-term follow-up, the TpTe > 110 ms group (n = 111) experienced more VT/VF episodes (45%) and all-cause mortality (25.2%) than the TpTe 90-110 ms group (n = 109) (26.4%, 14.5%) and TpTe < 90 ms group (n = 98) (11.3%, 11.3%) (overall P < .05, respectively). In Cox regression, longer post-implantation TpTe was associated with an increased number of VT/VF episodes [HR: 1.017; 95% CI: 1.008-1.026; P < .001], all-cause mortality [HR: 1.015; 95% CI: 1.004-1.027; P = .010] and the combined endpoint [HR: 1.018; 95%CI: 1.010-1.026; P < .001]., Conclusions: Post-implantation TpTe was an independent predictor of both ventricular arrhythmias and all-cause mortality in heart failure patients with an implanted ICD.

Limb-girdle myasthenia with tubular aggregates, a subtype of congenital myasthenic syndrome, is an extremely rare autosomal recessive genetic disease characterized by prominent limb-girdle weakness and good response to acetylcholinesterase inhibitor therapy. Herein, we reported two novel mutations of GFPT1 gene in a Chinese pedigree. Two siblings presented with fatigue, weakness of limb-girdle and decrement of the muscle action potential with repetitive nerve stimulation. Thus, myasthenia gravis was initially suspected, but anti-AChR antibodies were negative. Two novel missense mutations (p.Lys154Asn and p.Asn363Ser) in GFPT1 were identified through genetic testing conducted on 167 well-established genes associated with muscular diseases by targeted high throughput sequencing. Both mutations have not been recorded in the dsSNP database, Exome Aggregation Consortium database and 1000 Genomes Project database. The mutation sites were co-segregated with the phenotype and conserved between the different species. The mutations were not found in the 200 unrelated normal controls. Muscle biopsies revealed tubular aggregates, in accordance with previous reports with GFPT1 mutations. Subsequently, dramatic improvement in strength occurred following anti-cholinesterase therapy. Our study will be helpful for the diagnosis and treatment for Limb-girdle myasthenia with tubular aggregates., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cardiac resynchronization therapy (CRT) is a highly effective treatment in patients with a class I recommendation. However, a small proportion of the strictly selected patients still fail to respond. This study was designed to identify predictors of non-response in patients with class I indications for CRT and determine the non-response probability of the patients., Methods: A total of 296 consecutive patients with a class I recommendation received CRT from January 2009 to January 2017 were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify predictors for non-response (defined as cardiac death, heart transplantation, or HF hospitalization during 1-year follow-up)., Results: Among 296 patients, 30 (10.1%) met non-response. Multivariate analysis demonstrated that non-response to CRT was associated with a fragmented QRS (odd ratio (OR) = 2.86, 95% CI: 1.14-7.12; P = 0.025) and left ventricular end-diastolic dimension (LVEDD) ≥ 77 mm (OR = 3.02, 95% CI: 1.17-7.82; P = 0.022). Patients with both of the predictors had a non-response probability of 46.2% (95% CI: 19.1%-73.3%)., Conclusion: In patients with left bundle branch block and wider QRS duration, the proportion of non-response to CRT is not low in real world. The presence of the dilated LVEDD or fragmented QRS is a strong predictor of non-response to CRT. The probability of non-response in the patients with the two predictors was 46.2%.

Background: Whether cardiac resynchronization therapy super-responders (CRT-SRs) still have indications for neuro-hormonal antagonists or not remains uninvestigated., Methods: We reviewed clinical data from 376 patients who underwent CRT implantation in Fuwai Hospital from 2009 to 2015 and followed up to 2017. CRT-SRs were defined by an improvement of the New York Heart Association functional class and left ventricular ejection fraction to ≥ 50% in absolute values at 6-month follow-up. All CRT-SRs were assigned into two groups on the basis of whether persistently receiving neuro-hormonal antagonists (NHA) (defined as angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and β-blockers) after 6-month follow-up and then we compared long-term outcome., Results: A total of 60 patients met criteria for super-response. One of thirteen (7.7%) CRT-SRs without NHA had all-cause death, which also occurred in 2 of 47 (4.3%) in CRT-SRs with NHA ( P = 0.526). However, 3 of 13 (23.1%) CRT-SRs without NHA had heart failure (HF) hospitalization, 1 of 47 (2.1%) CRT-SRs with NHA had this endpoint ( P = 0.040). Besides, subgroup analysis indicated that, for ischemic etiology group, CRT-SRs receiving NHA had considerably lower incidence of HF hospitalization than those without NHA (0 vs. 75%, P = 0.014), which was not observed in non-ischemic etiology group (2.6% vs. 0, P = 1.000) during long-term follow-up., Conclusions: Our study found that for ischemic etiology, compared with CRT-SRs with NHA, CRT-SRs without NHA were associated with a higher risk of HF hospitalization. However, for non-ischemic etiology, we found that CRT-SRs with NHA or without NHA at follow-up were associated with similar outcomes, which needed further investigation by prospective trials.

The aim of this paper was to investigate the inhibitory effect of extract of Coptidis Rhizoma(ECR) on invasion of Candida albicans hyphae in vitro.XTT reduction method was used to evaluate the metabolic activity of C.albicans.The colony edge growth of C.albicans was observed by solid medium.The growth of C.albicans hyphae was determined on semi-solid medium.The morphology and viability changes of C.albicans hyphae were assessed by scanning electron microscope and fluorescence microscope.qRT-PCR method was used to detect the ALS3 and SSA1 expression of C.albicans invasin genes.The results showed that the metabolic viability by XTT method detected that the activity of C.albicans was gradually decreased under the intervention of 64,128 and 256 mg·L-1 of ECR respectively.128,256 mg·L-1 of ECR significantly inhibited colony folds and wrinkles on solid medium and the hyphal invasion in semi-solid medium.Scanning electron microscopy and fluorescence microscopy showed that 128,256 mg·L-1 of ECR could inhibit the formation of C.albicans hyphae.qRT-PCR results showed that the expression of invasin gene ALS3 and SSA1 was down-regulated,and especially 256 mg·L-1 of ECR could down-regulate the two genes expression by 4.8,1.68 times respectively.This study showed that ECR can affect the invasiveness of C.albicans by inhibiting the growth of hyphae and the expression of invasin.

A major feature of the injury sustained by the kidney during obstructive nephropathy is a profound induction of apoptosis in the tubular epithelium. In this study, we explored the central roles of mitochondria and the mechanism of the protective effect of the mitochondrial targeted peptides in tubular cell apoptosis and interstitial fibrosis during obstructive nephropathy. Unilateral ureter obstruction (UUO) was performed on rats, and the animals were randomly assigned to intravenous treatment with normal saline, rat serum albumin (RSA), or HOCl-rat serum albumin (HOCl-RSA) in the presence or absence of SS-31. A sham-operation control group was set up by left ureteral dissociation but not ligation. Compared with the control group, UUO animals displayed fibrotic abnormalities, accompanied by increased expression of collagen-I, fibronectin, α-SMA protein and mRNA in the renal interstitium. They also displayed oxidative stress, as evidenced by increased levels of HOCl-alb, TBARS, and mitochondrial reactive oxygen species (ROS) and a decrease in MnSOD activity in the renal homogenate. Damage to mitochondrial structure and functions was observed, as evidenced by a decrease in the mitochondrial membrane potential (MMP), ATP production, mtDNA copy number alterations and release of cytochrome C (cyto C) from the mitochondria to the cytoplasm. These changes were accompanied by activation of caspase-3, caspase-7, caspase-9, and PARP-1 and increased apoptotic cells in the proximal tubules. HOCl-RSA challenge further exacerbated the above biological effects in UUO animals, but these effects were prevented by administration of SS-31. These data suggested that accumulation of HOCl-alb may promote tubular cell apoptosis and interstitial fibrosis, probably related to mitochondrial oxidative stress and damage, and that SS-31 might contribute to apoptotic pathway suppression via scavenging of ROS in the mitochondria.

Inhibition of ionotropic glutamate receptors (iGluRs) is a potential target of therapy for ischemic stroke. Perampanel is a potent noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) antagonist with good oral bioavailability and favorable pharmacokinetic properties. Here, we investigated the potential protective effects of perampanel against focal cerebral ischemia in a middle cerebral artery occlusion (MCAO) model in rats. Oral administration with perampanel significantly reduced MCAO-induced brain edema, brain infarct volume, and neuronal apoptosis. These protective effects were associated with improved functional outcomes, as measured by foot-fault test, adhesive removal test, and modified neurological severity score (mNSS) test. Importantly, perampanel was effective even when the administration was delayed to 1 h after reperfusion. The results of enzyme-linked immunosorbent assay (ELISA) showed that perampanel significantly decreased the expression of pro-inflammatory cytokines IL-1β and TNF-α, whereas it increased the levels of anti-inflammatory cytokines IL-10 and TGF-β1 after MCAO. In addition, perampanel treatment markedly decreased the expression of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS), and also inhibited nitric oxide (NO) generation in MCAO-injured rats at 24 and 72 h after reperfusion. In conclusion, this study demonstrated that the orally active AMPAR antagonist perampanel protects against experimental ischemic stroke via regulating inflammatory cytokines and NOS pathways.

Background: Super-responders (SRs) are defined as patients who show crucial cardiac function improvement after cardiac resynchronization therapy (CRT). The purpose of this study is to identify and validate predictors of SRs after CRT., Methods: This study enrolled 201 patients who underwent CRT during the period from 2010 to 2014. Clinical and echocardiographic evaluations were conducted before CRT and 6 months after. Patients with a decrease in New York Heart Association (NYHA) functional class ≥ 1, a decrease in left ventricular end-systolic volume (LVESV) ≥ 15%, and a final left ventricular ejection fraction (LVEF) ≥ 45% were classified as SRs., Results: 29% of the 201 patients who underwent CRT were identified as SRs. At baseline, SRs had significantly smaller left atrial diameter (LAD), LVESV, left ventricular end-diastolic volume (LVEDV) and higher LVEF than the non-super-responders (non-SRs). The percentage of patients using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) was higher in SRs than non-SRs. Most SRs had Biventricular (BiV) pacing percentage greater than 98% six months after CRT. In the multivariate logistic regression analysis, the independent predictors of SRs were lower LVEDV [odd ratios (OR): 0.93; confidence intervals (CI): 0.90-0.97], use of ACEI/ARB (OR: 0.33; CI: 0.13-0.82) and BiV pacing percentage greater than 98% (OR: 0.29; CI: 0.16-0.87)., Conclusion: Patients with a better compliance of ACEI/ARB and a less ectatic ventricular geometry before CRT tends to have a greater probability of becoming SRs. Higher percentage of BiV pacing is essential for becoming SRs.

Background: This study aimed to investigate whether repetitive optimizing left ventricular pacing configurations (LVPCs) with quadripolar leads (QUAD) can improve response to cardiac resynchronization therapy (CRT)., Methods: Fifty-two eligible patients were enrolled and 1:1 randomized to either the quadripolar LV leads (QUAD) group or the conventional bipolar leads (CONV) group. In the QUAD group, optimization of LVPC was performed for all patients before discharge and for nonresponders at 3 months follow-up. Clinical evaluations and transthoracic echocardiograms were performed before, 3, and 6 months after CRT implantation., Results: At 3 months follow-up, 16 of 25 (64%) patients in the CONV group (1 patient was lost to follow-up) and 18 of 26 (69%) patients in the QUAD group were classified as responders. After optimizing the LVPCs in 3-month nonresponders in the QUAD group, 21 of 26 (80.8%) patients in the QUAD group were classified as responders at 6 months as compared with 17 of 25 (68%) patients in the CONV group. Left ventricular end-systolic volume (LVESV) reduction, left ventricular ejection fraction (LVEF) increase, and New York Heart Association (NYHA) functional class reduction at 6 months were significantly greater in the QUAD group than in the CONV group (LVESV: -26.9 ± 13.8 vs -17.2 ± 13.3%; P = .013; LVEF: +12.7 ± 8.0 vs +7.8 ± 6.3 percentage points; P = .017; NYHA: -1.27 ± 0.67 vs -0.72 ± 0.54 functional classes; P = .002)., Conclusions: Compared with conventional bipolar leads, CRT using quadripolar leads with repetitive optimized LVPCs resulted in an additional increase in LVEF and reduction in LVESV and NYHA functional class at 6-month follow-up.

Background: The 9-hole peg test (9-HPT) and 10-meter walk test (10-MWT) are commonly used to test finger motor function and walking ability. The aim of this present study was to investigate the efficacy of these tests for evaluating functional loss in Chinese Charcot-Marie-Tooth (CMT) disease., Methods: Thirty-four Chinese CMT patients (CMT group) from August 2015 to December 2016 were evaluated with 9-HPT, 10-MWT, CMT disease examination score, overall neuropathy limitation scale (ONLS), functional disability score, and Berg Balance Scale (BBS). Thirty-five age- and gender-matched healthy controls (control group) were also included in the study. Student's nonpaired or paired t-test were performed to compare data between two independent or related groups, respectively. The Pearson test was used to examine the correlations between recorded parameters., Results: The mean 9-HPT completion time in the dominant hand of CMT patients was significantly slower than that in the healthy controls (29.60 ± 11.89 s vs. 19.58 ± 3.45 s; t = -4.728, P < 0.001). Women with CMT completed the 9-HPT significantly faster than men with CMT (dominant hand: 24.74 ± 7.93 s vs. 33.01 ± 13.14 s, t = 2.097, P = 0.044). The gait speed of the average self-selected velocity and the average fast-velocity assessed using 10-MWT for CMT patients were significantly slower than those in the control group (1.03 ± 0.18 m/s vs. 1.44 ± 0.17 m/s, t = 9.333, P < 0.001; 1.31 ± 0.30 m/s vs. 1.91 ± 0.25 m/s, t = 8.853, P < 0.001, respectively). There was no difference in gait speed between men and women. Both 9-HPT and 10-MWT were significantly correlated with the ONLS, functional disability score, and BBS (P < 0.05 for all)., Conclusion: The 9-HPT and 10-MWT might be useful for functional assessment in Chinese patients with CMT.

Oxidative stress aggravates renal fibrosis, a pathway involved in almost all forms of chronic kidney disease (CKD). However, the underlying mechanism involved in the pathogenesis of renal oxidative stress has not been completely elucidated. In this study, we explored the role and mechanism of hypochlorite-modified albumin (HOCl-alb) in mediating oxidative stress and fibrotic response in a remnant-kidney rat model. Five-sixths nephrectomy (5/6 NX) was performed on the rats and then the animals were randomly assigned to intravenous treatment with either vehicle alone, or HOCl-rat serum albumin (RSA) in the presence or absence of SS-31 (administered intraperitoneally). A sham-operation control group was set up concurrently. Compared with the control group, 5/6 NX animals displayed marked mitochondrial (mt) dysfunction, as evidenced by decrease of mitochondrial membrane potential (MMP), ATP production, mtDNA copy number alterations and manganese superoxide dismutase (MnSOD) activity, release of cytochrome C (Cyto C) from mitochondria to the cytoplasm, and increase of mitochondrial reactive oxygen species in renal tissues. They also displayed increased levels of HOCl-alb in both plasma and renal tissues. These changes were accompanied by accumulation of extracellular matrix, worsened proteinuria, deteriorated renal function, and a marked increase of macrophage infiltration along with up-regulation of monocyte chemoattractant protein (MCP)-1 and transforming growth factor (TGF)-β1 expression. HOCl-alb challenge further exacerbated the above biological effects in 5/6 NX animals, but these adverse effects were prevented by administration of SS-31, a mitochondrial targeted antioxidant peptide. These data suggest that accumulation of HOCl-alb may promote renal inflammation and fibrosis, probably related to mitochondrial oxidative stress and dysfunction and that the mitochondrial targeted peptide SS-31 might be a novel therapy for renal fibrosis and chronic renal failure (CRF)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Backgrounds: Clinical trials have demonstrated that cardiac resynchronization therapy (CRT) is effective in patients with "non-ischemic cardiomyopathy". However, patients with dilated-phase hypertrophic cardiomyopathy (DHCM) have been generally excluded from such trials. We aimed to compare the clinical outcome of CRT in patients with DHCM, idiopathic dilated cardiomyopathy (IDCM), or ischemic cardiomyopathy (ICM)., Methods: A total of 312 consecutive patients (DHCM: n = 16; IDCM: n = 231; ICM: n = 65) undergoing CRT in Fuwai hospital were studied respectively. Response to CRT was defined as reduction in left ventricular end-systolic volume (LVESV) ≥ 15% at 6-month follow-up., Results: Compared with DHCM, IDCM was associated with a lower total mortality (HR: 0.35, 95% CI: 0.13-0.90), cardiac mortality (HR: 0.29; 95% CI: 0.11-0.77), and total mortality or heart failure (HF) hospitalizations (HR: 0.34, 95% CI: 0.17-0.69), independent of known confounders. Compared with DHCM, the total mortality, cardiac mortality and total mortality or HF hospitalizations favored ICM but were not statistically significant (HR: 0.59, 95% CI: 0.22-1.61; HR: 0.59, 95% CI: 0.21-1.63; HR: 0.54, 95% CI: 0.26-1.15; respectively). Response rate to CRT was lower in the DHCM group than the other two groups although the differences didn't reach statistical significance., Conclusions: Compared with IDCM, DHCM was associated with a worse outcome after CRT. The clinical outcome of DHCM patients receiving CRT was similar to or even worse than that of ICM patients. These indicate that DHCM behaves very differently after CRT.

Aim: Membranous nephropathy and minimal change disease (MCD) have been involved in mercury-induced nephrotic syndrome. IgA nephropathy is not known to be a common pathological type. In the present article, we report a case of IgA nephropathy with MCD following exposure to mercury-containing skin lightening cream., Material and Methods: The patient was a 39-year-old woman who presented with nephrotic syndrome. She had a 6-month history of using as many as 8 kinds of skin-lightening creams, and urinary mercury excretion was high. Renal biopsy revealed IgA nephropathy with MCD. The use of cosmetics was stopped and chelation therapy was given. After 4 courses (1 month) of chelation therapy, there was a complete remission of proteinuria and hematuria, and urine tests remained normal during the 5-year follow-up period., Results and Conclusions: The unique clinical and pathological features of IgA nephropathy with MCD had raised the controversial question of whether MCD and IgA deposition are separate entities or a common pathophysiology. Repeated renal biopsy and similar cases were helpful and should be carried out as far as possible.
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BACKGROUND Whether quadripolar leads can provide sufficient viable left ventricular pacing sites (LVPSs) for device optimization and multipoint pacing remains unclear. This study aimed to evaluate the acute and 3-month availability of viable LVPSs provided by a quadripolar LV pacing lead. MATERIAL AND METHODS A single-center cohort study evaluated consecutive patients who underwent a CRT implant with the QuartetTM LV lead under local guidelines. The availability of viable LVPSs was assessed at the pre-discharge and 3-month follow-up visit. Bipolar lead configurations, which served as the control group, were modeled by eliminating the 2 proximal electrodes on the Quartet™ LV lead. RESULTS A total of 24 patients were enrolled and finished 3-month follow-up. The mean follow-up period was 93±3 days. At pre-discharge, the Quartet™ LV lead provided more viable LVPSs compared with the bipolar equivalents (median 3 [IQR 2-4] vs. median 2 [IQR 1-2], P<0.001). The percentage of patients with at least 1, 2, 3, and 4 viable LVPSs were 100% (24/24), 91.7% (22/24), 58.3% (14/24), and 33.3% (8/24) for Quartet™ leads and 91.7% (22/24), 70.8% (17/24), 0% (0/24), and 0% (0/24) for bipolar lead configurations, respectively. The median and IQR values of viable LVPSs provided by the Quartet™ LV lead remained the same (3 [IQR 2-4]) between pre-discharge and 3-month follow-up (P=0.45). CONCLUSIONS Compared with the bipolar equivalent, QuartetTM LV lead provides more viable LVPSs and opportunities for CRT optimization and multipoint LV pacing. The number of LVPSs provided by Quartet™ leads remained unchanged between pre-discharge and 3-month follow-up.

Objective: Whether statins can slow down the progression of chronic kidney disease (CKD) remains controversial. We performed a meta-analysis to evaluate the effects of statin therapy on disease progression in adult patients with CKD who did not require dialysis therapy., Methods: We searched the electronic databases for relevant randomized controlled trials (RCTs) published by February 2015. Random-effects meta-analysis of RCTs was used to pool the renal outcomes of the patients., Results: Twenty-eight studies (30 RCTs) involving a total of 45 688 participants were included in the analysis. Compared with the control groups, statins produced no effects in preventing end-stage renal disease (ESRD) [relative risks (RR) 0.98, 95% confidence intervals (CI): 0.91-1.05] and in reducing the risk of doubling of the serum creatinine level (RR 1.43, 95% CI: 0.26-7.79). Statin therapy was associated with a lowered risk of estimated glomerular filtration rate (eGFR) reduction by 25% or more (RR 0.91, 95% CI: 0.83-0.99) and delayed the reduction of eGFR [standardized mean differences (SMD) 0.04, 95% CI: 0.02-0.07]. In subgroup analyses, the benefit of statins on changes in eGFR was statistically significant in patients with moderate CKD (SMD 0.09, 95% CI 0.04-0.13). Among different statins, atorvastatin was associated with a beneficial effect on kidney function (SMD 0.10, 95% CI 0.03-0.17). Patients who received high-intensity statin therapy showed significant changes in eGFR (SMD 0.12, 95% CI: 0.02-0.21)., Conclusion: Statin therapies may not prevent ESRD or doubling of serum creatinine level, but can improve GFR or delay the reduction of GFR in CKD patients. The therapeutic effects are associated with the patients' baseline eGFR levels, statin types and therapy intensity.

Hypochlorite-modified albumin (HOCl-alb) has been linked to endothelial dysfunction, which plays an important role in the development of hypertension, diabetes, and chronic kidney disease. However, whether HOCl-alb induces endothelial dysfunction via vascular inflammation and whether a signaling pathway is involved are unknown and have not been investigated. HOCl-alb was found to upregulate ICAM-1 expression in human umbilical vein endothelial cells (HUVECs) in a time- and dose-dependent manner. HOCl-alb time-dependently phosphorylated ERK1/2 and p38(MAPK). HOCl-alb also activated NF-κB. ICAM-1 expression was dose-dependently inhibited by U0126 (a specific inhibitor of MEK1/2, a signal upstream from ERK1/2), SB203580 (a specific inhibitor of p38(MAPK)), and SN50 (a specific inhibitor of NF-κB). U0126 and SB203580 both counteracted the activation of NF-κB, whereas the phosphorylation of ERK1/2 and p38(MAPK) was not blocked by SN50. ERK1/2 phosphorylation was blocked by U0126 but not by SB203580, and p38(MAPK) activity was reduced by SB203580 but not by U0126. Apocynin, a specific NADPH oxidase (NOX) inhibitor, inhibited ICAM-1 expression and the activity of ERK1/2, p38(MAPK), and NF-κB. These results indicate that HOCl-alb-induced ICAM-1 expression is caused by the activation of a redox-sensitive intracellular signal cascade involving ERK1/2 and p38(MAPK), culminating in the activation of NF-κB and involving NOXs among the upstream signals.

The receptor activator of NF-κB ligand (RANKL) and its receptor RANK are overexpressed in focal segmental glomerular sclerosis (FSGS), IgA nephropathy (IgAN), and membranous nephropathy (MN). However, the expression and the potential roles of RANKL and RANK in diabetic nephropathy (DN) remain unclear. Irbesartan (Irb) has beneficial effects against diabetes-induced renal damage, but its mechanisms are poorly understood. Our present study investigated the effects of Irb in DN and whether the renal protective effects of Irb are mediated by RANKL/RANK and the downstream NF-κB pathway in db/db mice. Our results showed that db/db mice revealed severe metabolic abnormalities, renal dysfunction, podocyte injury, and increased MCP-1; these symptoms were reversed by Irb. At the molecular level, RANKL and RANK were overexpressed in the kidneys of db/db mice and Irb downregulated RANKL and RANK and inhibited the downstream NF-κB pathway. Our study suggests that Irb can ameliorate DN by suppressing the RANKL-RANK-NF-κB pathway.

The time-averaged serum potassium was more comprehensive to reflect the all-time changes of serum potassium levels during peritoneal dialysis (PD). However, the association of fluctuation of time-averaged serum potassium level with long-time survival of PD patients remains unknown. In this retrospective study, we included 357 incident PD patients in 2 centers from January 1, 2007 to October 31, 2012 with follow-up through October 31, 2014. Our data demonstrated that it was the lower time-averaged serum potassium level rather than baseline of serum potassium level that was associated with high risk of death. Patients with higher standard deviation (SD) had significantly poorer all-cause (p = 0.016) and cardiovascular mortality (p = 0.041). Among the patients with time-averaged serum potassium levels below 4.0 mEq/L, a lower mean value was more important than its SD to predict death risk. In contrast, the patients with time-averaged serum potassium levels above 4.0 mEq/L, those with serum potassium SD < 0.54 mEq/L, exhibited a higher 3-year and 5-year survival rate for both all-cause and cardiovascular mortality compared to the control groups. Our data clearly suggested both time-averaged serum potassium and its fluctuation contributed disproportionately to the high death risk in PD patients.

Objective: To investigate feasibility and safety of stent implantation technique through percutaneous endoscopic gastrostomy (PEG)-like pathway for treatment of malignant gastroduodenal obstructions., Methods: Twelve patients with malignant gastroduodenal obstructions accepted PEG-like operations. A stent implantation pathway was established in abdominal wall under endoscopic guide. A guide wire and a stent release device were introduced through this pathway followed by an intestinal stent implantation. After operation, efficacy and safety of this technique were assessed by collecting data such as operation time, complications, postoperative medication, and hospitalization time during postoperative 2-12 months of follow-up., Results: Twelve patients were successfully treated with stent implantation technique through PEG-like pathway for the first time. The average operation time was 31 minutes. No severe complications occurred during treatment. On the fourth days after operation, patents were give liquid diet and treatment of rehydration, acid suppression, hemostasis and anti-inflammation. The average hospitalization time was 5 days. The follow-up time was 2-12 months. Twelve (100%) patients achieved complete remissions. The stent related complications and obstruction did not appear within 2 months after operations. The quality of life improved significantly., Conclusion: The stent implantation technique through PEG-like pathway for treatment of malignant gastroduodenal obstruction is a feasible, effective, and safe choice.

We used a combined approach of whole-exome sequencing and candidate mutation validation to identify the disease-causing gene in a hereditary spastic paraplegia (HSP) patient with lower motor neuron involvement, mild cerebellar signs and dysgenesis of the corpus callosum. HSP is a clinically and genetically heterogeneous neurodegenerative disorder characterized by degeneration of the corticospinal tract motor neurons and resulting in progressive lower limb spasticity, often with a complicated phenotype. We identified novel compound heterozygous mutations in the SPG11 gene in this patient as follows: a mutation in exon 32, c.6194C > G transition (p.S2056X) and a novel c.5121+1C > T splicing mutation. Our finding suggests that these novel compound heterozygous mutations in SPG11 are associated with HSP and lower motor neuron involvement, mild cerebellar signs and dysgenesis of the corpus callosum. This study also demonstrates that exome sequencing is an efficient and rapid diagnostic tool for identifying the causes of some complex and genetically heterogeneous neurodegenerative diseases., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This study investigated the biochemical composition of ovarian fluid and its effect on the fertilization capacity of turbot Scophthalmus maximus during the spawning season. The fertilization rate and pH of ovarian fluid varied throughout the spawning season, with the highest values recorded at the mid-season. Positive correlations were found between the fertilization rate and the ovarian fluid pH. The composition of major inorganic ions (Na(+) , K(+) , Ca(2+) and Cl(-) ) showed no significant changes during the spawning season. Alkaline phosphatase (AKP) activity was significantly higher during mid-season than other seasons. The lowest levels of protein, acid phosphatase (ACP) and aspartate aminotransferase (AAT) were in the ovarian fluid released at the mid-season. Moreover, significant relationships were observed between the fertilization rate and the levels of protein, ACP, AKP and AAT. These observations suggest that the biochemical profile of ovarian fluid affects the insemination microenvironment as well as the fertilization capacity of S. maximus eggs. Determination of such profiles may prove to be a useful strategy to improve S. maximus breeding techniques., (© 2015 The Fisheries Society of the British Isles.)

Background: We designed a novel, spherical magnetic compression colorectal anastomosis device and established a swine model to assess the feasibility and safety, as well as advantages, of the device., Methods and Materials: Fifteen animals were divided into five groups (sacrificed on Days 3, 5 7, 9, and 14) with 3 in each group. In each group, a magnetic compression device was used in 2 animals (experimental animals), and a stapled device was used in 1 animal (control animal). Feeding status, bowel movements, the discharge time of the magnetic anastomosis device, burst pressure, and magnetic field strength were recorded. Gross anatomical and histological examinations were performed., Results: The average device discharge time was 7.5 days. The burst pressure increased over time for both the experimental and control animals. Both the gross anatomical and histological examinations suggested that the inflammatory reaction was milder. Healing occurred more quickly, and the incidence of complications was lower for the experimental animals than for the control animals., Conclusions: The potential benefits of the spherical magnetic compression colorectal anastomosis device, relative to the stapled device, were in terms of effectiveness and complication incidence, which encourages us to further study its application in gastrointestinal anastomosis.

Background: Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA worldwide, and runs a slowly progressive and unremitting disease course. There is currently no curable treatment available. Growing evidence has suggested that nerve growth factor (NGF) may have therapeutic effects in neurodegenerative diseases, and possibly also in SCA3. The objective of this study was to test the efficacy of NGF in SCA3 patients., Methods: We performed an open-label prospective study in genetically confirmed adult (>18 years old) SCA3 patients. NGF was administered by intramuscular injection (18 μg once daily) for 28 days consecutively. All the patients were evaluated at baseline and 2 and 4 weeks after treatment using the Chinese version of the scale for assessment and rating of ataxia (SARA)., Results: Twenty-one SCA3 patients (10 men and 11 women, mean age 39.14 ± 7.81 years, mean disease duration 4.14 ± 1.90 years, mean CAG repeats number 77.57 ± 2.27) were enrolled. After 28 days of NGF treatment, the mean total SARA score decreased significantly from a baseline of 8.48 ± 2.40 to 6.30 ± 1.87 (P < 0.001). Subsections SARA scores also showed significant improvements in stance (P = 0.003), speech (P = 0.023), finger chase (P = 0.015), fast alternating hand movements (P = 0.009), and heel-shin slide (P = 0.001)., Conclusions: Our preliminary data suggest that NGF may be effective in treating patients with SCA3.

Inflammation is a relevant factor in the pathogenesis of diabetes nephropathy (DN). Sesquiterpene lactones (SLs), originally isolated from Tanacetum parthenium, have been reported to exhibit anti-inflammatory effects but few studies have examined their effects on DN. To determine whether advanced oxidation protein products (AOPPs) can induce the expression of chemokine monocyte chemoattractant protein- (MCP-) 1 in cultured mouse podocytes and to explore the mechanisms of the potential renoprotection of SLs, we treated podocytes with AOPPs and SLs (parthenolide and its derivatives micheliolide, compound 1, and compound 2). MCP-1 mRNA and protein expression were tested using quantitative real-time PCR and ELISA, respectively, and the protein levels of IKKβ, phospho-IKKβ, IκBα, NF-κB p65, phospho-NF-κB p65, and tubulin were analyzed by Western blotting. AOPPs activated the expression of MCP-1 mRNA and protein in a dose- and time-dependent manner, activated IKKβ and NF-κB p65, and promoted IκBα degradation. The IKK/NF-κB inhibitor parthenolide decreased AOPP-induced MCP-1 expression. Pretreatment with SLs inhibited MCP-1 mRNA and protein expression and suppressed IKKβ and NF-κB p65 phosphorylation and IκBα degradation. Taken together, these findings provide a novel explanation for the anti-inflammatory effects of SLs that will ultimately benefit DN and potentially other inflammatory and immune renal diseases.

Objectives: This study sought to determine whether a 50%-reduced radiation dose protocol using iterative reconstruction (IR) preserves image quality and diagnostic accuracy at coronary computed tomography angiography (CTA) as compared with a routine dose protocol using traditional filtered back projection (FBP)., Background: IR techniques show promise to decrease radiation requirements at coronary CTA. No study has performed a direct head-to-head, intraindividual comparison of IR algorithms with FBP vis-à-vis diagnostic accuracy and radiation dose at coronary CTA., Methods: Sixty consecutive subjects (45 men, 53.3 ± 9.4 years of age) prospectively underwent coronary catheter angiography (CCA) and 2 coronary CTA scans. One coronary CTA acquisition used routine radiation dose settings and was reconstructed with FBP. For another scan, the tube current-time product was reduced by 50%, and data were reconstructed with IR. Studies were blindly and randomly interpreted. Image quality, radiation dose, and diagnostic accuracy were compared using CCA as the reference standard., Results: Sensitivity and specificity for diagnosing ≥50% coronary artery stenosis on a per-segment level were 88.5% and 92.1% with FBP and 84.2% and 93.4% with IR, respectively. On a per-patient level, sensitivity and specificity were 100% and 93.1% with FBP and 96.8% and 89.7% with IR, respectively (all p > 0.05). With FBP versus IR, the area under the receiver-operating characteristic curve was 0.903 (95% confidence interval [CI]: 0.881 to 0.922) and 0.888 (95% CI: 0.864 to 0.909) on a per-segment level, and 0.966 (95% CI: 0.883 to 0.996) and 0.932 (95% CI: 0.836 to 0.981) on a per-patient level, respectively (p = 0.290 and 0.330). Compared with FBP, the iterative series showed no significant (p > 0.05) differences in image quality analyses. Median dose-length product was 52% lower for the IR protocol compared with the FBP protocol (109.00 [interquartile range: 82.00 to 172.50] mGy·cm vs. 52.00 [interquartile range: 39.00 to 84.00] mGy·cm, p < 0.001)., Conclusions: Compared with a routine radiation dose FBP protocol, 50% reduced dose acquisition using IR preserves image quality and diagnostic accuracy at coronary CTA., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the diagnostic accuracy of sub-milliSievert (mSv) coronary CT angiography (cCTA) using prospectively ECG-triggered high-pitch spiral CT acquisition combined with iterative image reconstruction., Methods: Forty consecutive patients (52.9 ± 8.7 years; 30 men) underwent dual-source cCTA using prospectively ECG-triggered high-pitch spiral acquisition. The tube current-time product was set to 50 % of standard-of-care CT examinations. Images were reconstructed with sinogram-affirmed iterative reconstruction. Image quality was scored and diagnostic performance for detection of ≥50 % stenosis was determined with catheter coronary angiography (CCA) as the reference standard., Results: CT was successfully performed in all 40 patients. Of the 601 assessable coronary segments, 543 (90.3 %) had diagnostic image quality. Per-patient sensitivity for detection of ≥50 % stenosis was 95.7 % [95 % confidence interval (CI), 76.0-99.8 %] and specificity was 94.1 % (95 % CI, 69.2-99.7 %). Per-vessel sensitivity was 89.5 % (95 % CI, 77.8-95.6 %) with 93.2 % specificity (95 % CI, 86.0-97.0 %). The area under the receiver-operating characteristic curve on per-patient and per-vessel levels was 0.949 and 0.913. Mean effective dose was 0.58 ± 0.17 mSv. Mean size-specific dose estimate was 3.14 ± 1.15 mGy., Conclusions: High-pitch prospectively ECG-triggered cCTA combined with iterative image reconstruction provides high diagnostic accuracy with a radiation dose below 1 mSv for detection of coronary artery stenosis., Key Points: • Cardiac CT with sub-milliSievert radiation dose is feasible in many patients • High-pitch spiral CT acquisition with iterative reconstruction detects coronary stenosis accurately. • Iterative reconstruction increases who can benefit from low-radiation cardiac CT.