Genome-Wide Analysis of the Membrane Attack Complex and Perforin Genes and Their Expression Pattern under Stress in the Solanaceae.

The Membrane Attack Complex and Perforin (MACPF) proteins play a crucial role in plant development and adaptation to environmental stresses. Heretofore, few MACPF genes have been functionally identified, leaving gaps in our understanding of MACPF genes in other plants, particularly in the Solanaceae family, which includes economically and culturally significant species, such as tomato, potato, and pepper. In this study, we have identified 26 MACPF genes in three Solanaceae species and in the water lily, which serves as the base group for angiosperms. Phylogenetic analysis indicates that angiosperm MACPF genes could be categorized into three distinct groups, with another moss and spikemoss lineage-specific group, which is further supported by the examination of gene structures and domain or motif organizations. Through inter-genome collinearity analysis, it is determined that there are 12 orthologous SolMACPF gene pairs. The expansion of SolMACPF genes is primarily attributed to dispersed duplications, with purifying selection identified as the principal driving force in their evolutionary process, as indicated by the ω values. Furthermore, the analysis of expression patterns revealed that Solanaceae genes are preferentially expressed in reproductive tissues and regulated by various environmental stimuli, particularly induced by submergence. Taken together, these findings offer valuable insights into and a fresh perspective on the evolution and function of SolMACPF genes, thereby establishing a foundation for further investigations into their phenotypic and functional characteristics.

A Study of Familial Amyloid Polyneuropathy Induced by the TTR Val30Leu Mutation in China.

INTRODUCTION: Familial amyloid polyneuropathy is currently prevalent worldwide as the transthyretin (TTR) Val30Met mutation, and there are other types of mutations. The purpose of this study was to understand the clinical manifestations, electrophysiological characteristics, and outcomes of hormone-related therapy in patients with the TTR Val30Leu mutation in China. METHODS: Clinical data were collected from 9 members of a family with the TTR Val30Leu mutation in China, and blood samples of 7 members of the family were sequenced. The electrophysiological examinations of 4 of them were collected and analysed. RESULTS: A total of 7 people had the TTR gene c.148G>T missense mutation and the TTR protein Val30Leu mutation in this family, and the positive members all had similar symptoms, such as limb paraesthesia and gastrointestinal symptoms. In addition, electrophysiological examination showed abnormal nerve conduction velocity in all 4 patients. CONCLUSIONS: The clinical manifestations of this mutation involve mainly limb sensory or motor disorders or gastrointestinal symptoms or both, and the electrophysiological examination shows neurogenic damage.

The association between ECG criteria and Echo criteria for left ventricular hypertrophy in a general Chinese population.

BACKGROUND: Several ECG criteria have been widely used for diagnosis of left ventricular hypertrophy (LVH) in clinical practice. However, their performance in a general Chinese population is limited. METHODS AND RESULTS: A multi-stage, stratified cluster sampling across China was performed and 7415 representative Chinese adults aged 18-85 years were analyzed. ECG was collected by using GE MAC 5500 machine. The association between five ECG-LVH criteria (i.e., Peguero-Lo Presti, Cornell, Cornell product, Sokolow-Lyon and Sokolow-Lyon product) and echocardiographic LVH (Echo-LVH) was assessed by Pearson's correlation, diagnostic statistics like predictive values, and receiver operating characteristics (ROC) curve. We found that the prevalence of the Echo-LVH was 11% while ECG-LVH ranged from 3% to 27%. All ECG-LVH criteria had high negative predictive value (NPV) (89%) and specificity (73-96%) but low positive predictive value (PPV) (12-24%) and sensitivity (4-29%). The newly Peguero-Lo Presti criteria had higher sensitivity (29%) but lower specificity (73%) and accuracy (68%) compared with other criteria. Cornell product had the best diagnostic performance (AUC: 0.59), as well as the highest specificity (96%) and accuracy (86%) but lowest sensitivity (4%). Among single-lead components of ECG criteria, RaVL voltage and QRS duration performed relatively better than others. Hypertensive and older individuals had higher sensitivity but lower specificity and accuracy than their counterparts. CONCLUSION: ECG-LVH criteria had high NPV to detect Echo-LVH. Though with higher sensitivity, Peguero-Lo Presti criteria did not have better diagnostic performance to detect Echo-LVH. RaVL and QRS duration had stronger association with Echo-LVH among all single-lead components.

Transfemoral extraction of pacemaker and implantable cardioverter defibrillator leads using Needle's Eye Snare: a single-center experience of more than 900 leads.

The femoral approach with the Needle's Eye Snare (NES) is often used for bailout after failure of the superior approach for transvenous lead extraction (TLE). The safety and efficacy of the NES as a first-line tool for TLE remain unclear. The medical records of patients who underwent TLE via the femoral approach utilizing the NES from May 2014 to June 2019 in Peking University People's Hospital were retrospectively reviewed. Nine hundred and eighty-five leads were extracted in 492 patients (369 men; mean age 72.8 ± 29.0 years). The median (range) number of leads extracted per patient was 2 (1-6). The mean indwelling time of all extracted leads was 112.6 ± 52.0 months. The complete procedure success rate, clinical success rate, and failure rate were 94.1% (463/492), 97.8% (481/492), and 1.1% (11/492), respectively. Major complications including death occurred in nine patients (1.9%), of whom eight developed cardiac tamponade. Among these eight patients, emergency pericardiocentesis followed by rescue surgical repair if necessary was successful in 6 (75.0%) and failed in 2 (25.0%). No significant differences were found in the clinical success rate or major complications rate between patients with pacemakers and implantable cardioverter defibrillators, or between patients with infected and uninfected leads. A femoral approach with the NES is safe and effective for TLE of both pacing and defibrillator leads and could be considered a first-line approach. Cardiac tamponade was the most frequent cardiovascular complication. A strategy of emergency pericardiocentesis followed by a rescue surgical approach seems to be reasonable technique to treat a cardiac tamponade.

Effects of a high-fat diet on intracellular calcium (Ca2+) handling and cardiac remodeling in Wistar rats without hyperlipidemia.

A high-fat diet is often associated with cardiovascular diseases. Research has suggested that consumption of a high-fat diet for 10 weeks is associated with cardiac dysfunction, including arrhythmias, through alterations in cardiac remodeling and myocardial intracellular calcium (Ca2+) handling. In this study, rats were randomly divided into two groups: the standard diet (N = 5) and high-fat diet (N = 5) groups. To evaluate the effects of a high-fat diet on cardiac remodeling, we investigated the myocardium obtained from male Wistar rats fed a high-fat diet or standard diet for ten weeks via scanning electron microscopy, polarization microscopy, and RT-PCR. We found that compared with the standard diet cohort, the high-fat diet cohort exhibited increased levels of SERCA2a and SERCA2b mRNA and a decreased level of PLB mRNA (P < .05). These findings showed that a high-fat diet may lead to cardiac upregulation of Ca2+ transport-related genes in the sarcoplasmic reticulum. Additionally, we observed endocardial injury accompanied by focal dense layered collagen, increased spacing between endocardial cells that was often filled with collagen debris, and increased amounts of collagen fibers among enlarged cardiomyocytes in the high-fat diet cohort. The abnormal intracellular calcium (Ca2+) handling and cardiac remodeling may be contributing factors in arrhythmias and sudden cardiac death in high-fat diet-fed rats.

Remodeling of myocardial energy and metabolic homeostasis in a sheep model of persistent atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common progressive cardiac arrhythmia and is often associated with rapid contraction in both atria and ventricles. The role of atrial energy and metabolic homeostasis in AF progression is under-investigated. OBJECTIVES: To determine the remodeling of energy metabolism during persistent AF and the effect of eplerenone (EPL), an aldosterone inhibitor, on metabolic homeostasis. METHODS: A nonsustained atrial pacing sheep model was developed to simulate the progression of AF from paroxysmal to persistent. Metabolomic and proteomic analyses at termination of the experiment were used to analyze atrial tissues obtained from sheep in sham, sugar pill (SP) and EPL-treated groups. RESULTS: Proteomic analysis indicated that compared to the sham group, in SP group, fatty acid (FA) synthesis, FA oxidation, tricarboxylic acid (TCA) cycle processes and amino acids (AAs) transport and metabolism were reduced, while glycolytic processes were increased. In metabolomic analysis, the levels of intermediate metabolites of the glycolytic pathways, including 2-phosphoglyceric acid (2 PG), 1,3-bisphosphoglyceric acid (1,3 PG), and pyruvate, HBP (uridine diphosphate-N-acetylglucosamine, UDP-GlcNAc), TCA (citrate) and AAs were greater while the levels of the majority of lipid classes, including phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylglycerol (PG), glycerophosphoglycerophosphates (PGP), glycerophosphoinositols (PI) and glycerophosphoserines (PS), were decreased in the atria of SP group than in those of sham group. EPL-pretreatment decreased the expression of glut4 and increased the content of acylcarnitines and lipids, such as lyso phospholipids, phospholipids and neutral lipids. CONCLUSION: In the metabolic remodeling during AF, glucose and lipid metabolism were up- and down-regulated, respectively, to sustain TCA cycle anaplerosis. EPL partialy reversed the metabolic shifting.

XRCC2 mutation causes meiotic arrest, azoospermia and infertility.

BACKGROUND: Meiotic homologous recombination (HR) plays an essential role in gametogenesis. In most eukaryotes, meiotic HR is mediated by two recombinase systems: ubiquitous RAD51 and meiosis-specific DMC1. In the RAD51-mediated HR system, RAD51 and five RAD51 paralogues are essential for normal RAD51 function, but the role of RAD51 in human meiosis is unclear. The knockout of Rad51 or any Rad51 paralogue in mice exhibits embryonic lethality. We investigated a family with meiotic arrest, azoospermia and infertility but without other abnormalities. METHODS: Homozygosity mapping and whole-exome sequencing were performed in a consanguineous family. An animal model carrying a related mutation was created by using a CRISPR/Cas9 system. RESULTS: We identified a 1 bp homozygous substitution (c.41T>C/p.Leu14Pro) on a RAD51 paralogue, namely, XRCC2, in the consanguineous family. We did not detect any XRCC2 recessive mutation in a cohort of 127 males with non-obstructive-azoospermia. Knockin mice with Xrcc2-c.T41C/p.Leu14Pro mutation were generated successfully by the CRISPR/Cas9 method. The homozygotes survived and exhibited meiotic arrest, azoospermia, premature ovarian failure and infertility. CONCLUSION: A XRCC2 recessive mutation causing meiotic arrest and infertility in humans was duplicated with knockin mice. Our results revealed a new Mendelian hereditary entity and provided an experimental model of RAD51-HR gene defect in mammalian meiosis.

[Value of ventricular tachycardia score in diagnosing pre-excited tachycardia].

OBJECTIVE: To investigate the value of ventricular tachycardia (VT) score in diagnosing pre-excited tachycardia.
 Methods: Twelve-lead electrocardiograph results were obtained from 30 patients at pre-excited tachycardia attacking stage who were diagnosed by electrophysiology. We scored pre-excitation tachycardia based on the VT score. To analyze the electrocardiogram of pre-excited tachycardia using 7 diagnostic indicators of the VT score and calculate the specificity of 7 diagnostic indicators and right superior axis (-90º to ±180º), the differences were compared among VT score of 2 points and brugada, Wellens, and Vereckei algorithms in diagnosing pre-excited tachycardia. According to the specificity of Vereckei, Wellens, and Brugada algorithms, and VT scores from low to high, their prediction value and differences were analyzed.
 Results: Single indicator such as atrioventricular (AV) dissociation or right superior axis (-90º to ±180º) showed the highest specificity (100%) for identifying pre-excited tachycardia. No patient with VT score was ≥3 points, and the specificity was 100%. The specificity of VT score of 2 point was higher than that of Brugada, Wellens, or Vereckei algorithms in the diagnosing pre-excited tachycardia (76.7% vs 50.0%, 23.3% or 20.0%, P<0.05). The specificity of Vereckei, Wellens, and Brugada algorithms and VT score were gradually increased after each of stepwise individually eliminated VT (20.0%, 40.0%, 66.7%, 83.3%, P<0.05). However, there was no significant difference in the specificity in the remaining false positive cases between the 4 methods and VT score.
 Conclusion: VT score ≥3 points can identify pre-excited tachycardia and VT with 100% specificity. VT score of 2 points cannot completely distinguish pre-excited tachycardia from VT, but specificity of VT score with 2 points is obviously higher than that of Brugada, Wellens, and Vereckei algorithms.

Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer: A real-world retrospective study in Chinese patients.

OBJECTIVE: To assess the long-term effectiveness and safety of trastuzumab in adjuvant therapy for Chinese patients with early-stage human epidermal growth factor 2 (HER2)-positive breast cancer in a real-world setting. METHODS: This retrospective observational study analyzed the medical records of HER2-positive breast cancer patients between 2000 and 2012 at the Chinese Academy of Medical Sciences. Patients who received adjuvant chemotherapy alone or adjuvant chemotherapy followed by/combined with trastuzumab were included. The Kaplan-Meier method was used to estimate disease-free survival (DFS) and overall survival (OS). Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated using the Cox regression model. RESULTS: Of the 1,348 patients analyzed, 909 received chemotherapy alone and 439 received chemotherapy plus trastuzumab. The 3-year, 5-year and 10-year DFS rates were 83.70%, 76.38% and 68.94%, respectively, in the chemotherapy-alone cohort, and 90.21%, 86.19% and 83.45% in the chemotherapy plus trastuzumab cohort. The 3-year, 5-year and 10-year OS rates were 96.10%, 91.40% and 81.88% in the chemotherapy-alone cohort, and 98.17%, 94.91% and 90.01% in the chemotherapy plus trastuzumab cohort. The chemotherapy plus trastuzumab group had a significantly lower risk of disease recurrence and death than the chemotherapy-alone group (DFS: HR=0.50, 95% CI, 0.37-0.68; P<0.001; OS: HR=0.53, 95% CI, 0.34-0.81; P=0.004) after adjusting for covariates. In the 439 patients treated with trastuzumab, multivariate analysis suggested that lymph node positivity, higher T stages, and hormone receptor-negative status were significantly associated with higher risks of disease recurrence, and lymph node positivity and hormone receptor-negative status were significantly associated with higher risks of death. Grade 3/4 adverse events (incidence ≥1%) were more common in patients receiving trastuzumab (54.44%vs. 15.73%). CONCLUSIONS: Early-stage HER2-positive breast cancer patients treated with trastuzumab plus adjuvant chemotherapy have a significant survival benefit compared with chemotherapy-alone in real-world settings. Lymph node positivity, hormone receptor-negative status, and higher T stages may be associated with higher risks of recurrence, and effective therapy for patients with these factors is required.

Video-Assisted Thoracoscopic Left Cardiac Sympathetic Denervation in Chinese Patients with Long QT Syndrome.

Long QT syndrome is a rare but potentially lethal cardiac channelopathy. The primary aim of the study was to investigate the long-term effects of video-assisted thoracoscopic (VATS) left cardiac sympathetic denervation (LCSD) in Chinese patients with long QT syndrome.VATS-LCSD was performed in eight Chinese patients with LQTS. Twelve-lead ECGs and 24-hour Holter monitoring ECGs were recorded before and after surgery. The medical charts were reviewed to obtain patient data, and the patients who had been lost to follow-up were contacted through telephone.The average QTc was shortened from 534 ± 52.7 to 503 ± 43.7 ms (P = 0.030) 24 hours post-surgery and down to 486 ± 34.8 ms (P = 0.021) 1 week post-surgery, with the heart rate unchanged. The average QT dispersion was reduced from 67 ± 17.5 to 21 ± 3.9 ms (P < 0.001) 24 hours post-surgery and remained shortened 1 week later (30 ± 8.1 ms, P < 0.001). Moreover, the 24-hour ECG showed that the QTc was shortened from 552 ± 95.9 to 497 ± 19.7 ms at the minimum heart rate (P = 0.008), and was decreased from 594 ± 144 to 495 ± 74.1 ms at the maximum heart rate (P= 0.04), while the minimum and maximum heart rates were comparable before and after surgery. No death was observed during the follow-up period and the clinical symptoms improved in all patients. The annual event rate decreased from 4 ± 3.50 to 0.63 ± 1.37 events/year (P = 0.034) after surgery.These findings indicate that LCSD shortens the QTc, with the heart rate remaining unchanged. QTd might be a useful parameter for evaluating the efficacy of VATS-LCSD. LCSD could improve patients' life quality by reducing cardiac events.

Trisomy 3 mosaicism in a 5-year-old boy with multiple anomalies: A very rare case.

Trisomy 3 mosaicism in live birth is exceedingly rare. In this study, we report a 5-year-old boy with trisomy 3 mosaicism who exhibits skeletal anomalies, atypical form of ectodermal dysplasias, refractory diarrhea, and normal intelligence. Fluorescence in situ hybridization and microsatellite marker analyses confirmed the existence of trisomy 3 mosaicism and suggested that the parental origin of the additional chromosome 3 in the trisomic cells was maternal. This report further delineated the trisomy 3 mosaicism in live births. The authors propose that both common phenotypes and phenotypic diversity exist on cases with trisomy 3 mosaicism. © 2016 Wiley Periodicals, Inc.

Interstitial deletion 5q14.3q21.3 associated with lethal epilepsy.

The 5q14.3 deletion syndrome is a heterogeneous disorder with remarkable phenotypic diversity ranging from severe to mild manifestation. In this paper, we report on a patient with 5q14.3 q21.3 deletion who exhibited the severe phenotype and died at 5.5 months. This patient can be classified as having sudden unexplained death in epilepsy (SUDEP) [Tomson et al., 2008]. The deleted region (21.02 Mb, Chr.5: 88, 047, 621-109,072,596 × 1 dn), which included MEF2C and EFNA5, was a 16.5 Mb sequence that overlapped with previously reported deletions in a patient with the mild phenotype. This study further demonstrated the complexity of clinical cytogenetic correlation of the 5q14.3 deletion.

First report of CTNS mutations in a Chinese family with infantile cystinosis.

Infantile cystinosis (IC) is a rare autosomal recessive disorder characterized by a defect in the lysosomal-membrane transport protein, cystinosin. It serves as a prototype for lysosomal transport disorders. To date, several CTNS mutations have been identified as the cause of the prototypic disease across different ethnic populations worldwide. However, in Asia, the CTNS mutation is very rarely reported. For the Chinese population, no literature on CTNS mutation screening for IC is available to date. In this paper, by using the whole exome sequencing and Sanger sequencing, we identified two novel CTNS splicing deletions in a Chinese IC family, one at the donor site of exon 6 of CTNS (IVS6+1, del G) and the other at the acceptor site of exon 8 (IVS8-1, del GT). These data give information for the genetic counseling of the IC that occurred in Chinese population.

Prevalence of venous occlusion in patients referred for lead extraction: implications for tool selection.

AIMS: Data concerning the incidence of venous obstruction in patients referred for lead extraction is limited. Thus, we aimed to assess the incidence of venous obstruction in patients referred for lead extraction and the implications for tool selection. METHODS AND RESULTS: Contrast venography of the access vein was obtained in 202 patients (147 men; mean age, 62.4 ± 14.5 years) scheduled for lead extraction. The indication for lead extraction included infection (n = 145, 72%) and other causes (n = 57, 28%). Two patients with device infection had superior vena caval occlusion. Access vein occlusion occurred in 6 (11%) patients without infection vs. 46 (32%) patients with infection [P = 0.002; odds ratio (OR) 3.94; 95% confidence interval (CI) 1.58-9.87]. No significant differences between occluded and non-occluded patients were seen for age, sex, device type, number of leads, time from implant of the initial lead, or anticoagulation therapy (all P>0.05). Procedural duration and fluoroscopy exposure time were significantly lower in the open group than in the occluded group (P < 0.05). Patients with venous occlusion required more advanced tools for lead extraction, such as dilator sheaths, evolution sheaths, and needle's eye snares (P = 0.019). CONCLUSION: Both systemic and local infections are associated with increased risk of access vein occlusion. We found no support for the hypothesis that venous occlusion increases with the number of leads present. Lead extraction was more difficult in patients with venous occlusion, requiring advanced tools and more time.

Reuse of infected cardiac rhythm management devices in the same patients: a single-center experience.

BACKGROUND: In developing countries, patients with a cardiac rhythm management device (CRMD) that has become infected cannot always afford a new device, and reuse of the infected CRMD may be appropriate. To evaluate the safety of this practice, a cohort of consecutive patients with reused pacemakers was compared with a control group. METHODS: A single-center cohort of consecutive patients treated from 2007 to 2012 was analyzed in a two-way noninferiority study. Patients who had infected CRMDs removed at the Cardiovascular Center of The Peking University People's Hospital were enrolled, including those who had the same CRMD reimplanted and those who had a new CRMD implanted. RESULTS: This study included 212 patients, of who 99 (study group) had the same CRMD reimplanted, and 113 (control group) had a new CRMD implanted. During a mean follow-up period of 3.52 years (interquartile range: 2.1-4.7 years), 10 patients reached the primary end point of the study (infection, unexpected battery depletion, or device malfunction), including five (5%) in the study group and five (4.3%) in the control group. Recurrent infection occurred in three patients in the study group and two patients in the control group (3.0% vs 1.7%, relative risk: 1.29, 95% confidence interval: 0.62-2.29, P = 0.561). There were no cases of unexpected battery depletion in either group. CONCLUSIONS: Reuse of infected CRMDs in the same patients is noninferior to the implantation of new devices. In developing countries without full medical coverage, careful reuse of infected CRMDs can be considered.

[Efficacy and safety of trastuzumab plus different chemotherapy regimens in treatment of the patients with HER-2-positive advanced breast cancer].

OBJECTIVE: To evaluate the efficacy and safety of trastuzumab plus different chemotherapy regimens in treatment of patients with HER-2-positive advanced breast cancer. METHODS: 132 patients with advanced HER-2-positive breast cancer were treated with trastuzumab plus different regimens. The clinical characteristics, efficacy and toxicity of the 132 patients were retrospectively analyzed. RESULTS: Five patients had complete response (CR), 61 patients had partial response (PR), 39 patients had stable disease (SD), and 27 patients had progressive disease (PD). The objective response rate was 50.0% and the disease control rate was 79.5%. The median progression-free survival was 9.3 months. The median overall survival time was 46.2 months. The 1-, 2-, 5- year survival rates were 98.3%, 81.9% and 40.2%, respectively. Trastuzumab combined with chemotherapy is superior to trastuzumab monotherapy (51.2% vs. 33.3%). The number of metastatic sites, efficacy, different previous treatment lines were independent prognostic factors of PFS (P = 0.002, P < 0.0001 and P < 0.0001, respectively). Visceral metastases, pathological grade, and PFS were independent prognostic factors of OS (P = 0.041, P = 0.001, P = 0.025, P < 0.001, P < 0.0001 and P < 0.0001, respectively). Regarding the toxicities, one case discontinued treatment due to the decrease of left ventricular ejection fraction to 47%, two cases had heartbeat tachycardia, 6 cases had palpitation, 17 cases had a fever during first input trastuzumab. No other serious cardiac toxicity was observed. The most common toxicities were chemotherapy-related hematological and non-hematological toxicities. CONCLUSIONS: Trastuzumab combined with chemotherapy is superior to trastuzumab monotherapy. Patients may get benefits for early use of trastuzumab. Trastuzumab plus chemotherapy is effective and well tolerated in patients with advanced HER-2 positive breast cancer. No heart failure occurred in this series of patients, and cardiac safety seems better than that in Caucasians because of younger age at the onset in Chinese advanced breast cancer patients.

[The efficacy of permanent epicardial pacing in the treatment of pacing-dependent patients with cardiac device related endocarditis].

OBJECTIVE: Permanent epicardial pacemaker is seldom used clinically and it is even less likely to be used for the treatment of seriously ill pacing-dependent patients with cardiac electronic device related endocarditis. METHOD: We retrospectively analyzed the feasibility and efficacy of permanent epicardial pacing for the treatment of 3 pacing-dependent patients with cardiac electronic device related endocarditis, who were treated by removal of all pacemaker devices and reimplantation of permanent epicardial pacing system combined with antibiotics. The reason of using epicardial pacing system was as follows: uncontrolled sepsis (case 1); big vegetation on the electrode of pacemaker and tricuspid valve but not a candidate for open heart surgery because of high operative risk (case 2); occlusion of superior vena cava (case 3). RESULTS: All 3 patients were cured with the treatment of extraction of infected pacing system, re-implanted permanent epicardial pacing system and antibiotics. The permanent epicardial pacemaker worked well during the 2-12 months follow-up period and there was no recurrence of infection. CONCLUSIONS: Permanent epicardial pacing is useful and efficient in treatment of seriously ill and high risk pacing-dependent patients with cardiac device related endocarditis.

Mosaic variegated aneuploidy syndrome with tetraploid, and predisposition to male infertility triggered by mutant CEP192.

In this study, we report on mosaic variegated aneuploidy (MVA) syndrome with tetraploidy and predisposition to infertility in a family. Sequencing analysis identified that the CEP192 biallelic variants (c.1912C>T, p.His638Tyr and c.5750A>G, p.Asn1917Ser) segregated with microcephaly, short stature, limb-extremity dysplasia, and reduced testicular size, while CEP192 monoallelic variants segregated with infertility and/or reduced testicular size in the family. In 1,264 unrelated patients, variant screening for CEP192 identified a same variant (c.5750A>G, p.Asn1917Ser) and other variants significantly associated with infertility. Two lines of Cep192 mice model that are equivalent to human variants were generated. Embryos with Cep192 biallelic variants arrested at E7 because of cell apoptosis mediated by MVA/tetraploidy cell acumination. Mice with heterozygous variants replicated the predisposition to male infertility. Mouse primary embryonic fibroblasts with Cep192 biallelic variants cultured in vitro showed abnormal morphology, mitotic arresting, and disruption of spindle formation. In patient epithelial cells with biallelic variants cultured in vitro, the number of cells arrested during the prophase increased because of the failure of spindle formation. Accordingly, we present mutant CEP192, which is a link for the MVA syndrome with tetraploidy and the predisposition to male infertility.

True complete left bundle branch block morphology strongly predicts good response to cardiac resynchronization therapy.

AIMS: To determine whether patients with congestive heart failure and true left bundle branch block (LBBB) morphology have better response to cardiac resynchronization therapy (CRT) than do patients without true LBBB. METHODS AND RESULTS: We defined true LBBB as conventional LBBB plus QRS duration ≥ 130 ms and mid-QRS notching/slurring in at least two of the leads I, aVL, V1, V2, V5, or V6. We prospectively enrolled 58 patients with heart failure and allocated them to three groups: true LBBB (t-LBBB, n = 22); non-true LBBB (nt-LBBB, LBBB with no notch or notches in fewer than two of the leads, n = 17); and non-specific intraventricular conduction delay (IVCD, n = 19). At 6 month follow-up, mean absolute increases in left ventricular ejection fraction were 16.0% ± 11.6% in t-LBBB, 8.1% ± 11.2% in nt-LBBB (P = 0.02), and 3.3% ± 7.8% in IVCD (P < 0.001, t-LBBB vs. IVCD) and changes in mean New York Heart Association class were -1.2 ± 0.6 in t-LBBB, -0.8 ± 0.6 in nt-LBBB (P = 0.071), and -0.5 ± 0.6 in IVCD (P = 0.01, t-LBBB vs. IVCD). All patients with t-LBBB were responders, some were super-responders. Multivariate analysis showed that t-LBBB (odds ratio, OR, 11.680; 95% confidence interval, CI, 1.966-69.390; P = 0.007) and left ventricular end-diastolic dimension (OR, 0.891; 95% CI, 0.797-0.996; P = 0.043) are independent predictors of super-response to CRT. CONCLUSION: In patients with conventional wider LBBB morphology, the presence of mid-QRS notching or slurring is a strong predictor of better response to CRT.

Re-evaluation of transvenous lead extraction with modified standard technique: a prospective study in 229 patients.

As new-type powered sheaths are expensive and unavailable, the standard lead extraction techniques remain the mainstay in clinical applications in many countries. The purpose of this study was to re-evaluate the clinical application of the standard lead extraction techniques and equipment, and make some procedural modifications and innovations. In our center, between January 2006 and May 2012, 229 patients (median, 66 years) who underwent lead extraction due to infection and lead malfunction were registered and followed up prospectively with respect to clinical features, reasons for lead extraction, technical characteristics, and clinical prognosis. A total of 440 leads had to be extracted transvenously by using special tools from 229 patients (male, 72.1%). Vegetations ≥1 cm were detected in six patients. Locking Stylets were applied for 398 (90.5%) leads. Telescoping dilator polypropylene sheaths and counter traction technique were used for 202 (45.9%) leads due to lead adhesion, and the mean implant duration of the 202 leads was longer than the other 238 leads (48.9±22.6 vs. 26.6±17.8 months; P <0.01). In addition, modified isolation and snare techniques were used for 56 leads (12.7%). Minor and major procedure-related complications occurred in three (1.3%) and four (1.7%) cases respectively, including one death (0.4%). Severe lead residue occurred in one case. Complete procedural success rate was 96.1% (423/440), and clinical success rate was 98.9% (435/440). The median follow-up period was 18 (1-76) months. No infection- and procedure-related death occurred in our series. Our data demonstrated that high clinical success rate of transvenous lead extraction can be guaranteed by making full use of the standard lead extraction techniques and equipment with individualized modifications.