Effects of optimized left atrioventricular conduction time on hemodynamics and prognosis in patients with third degree atrioventricular block implanted with dual chamber pacemakers

Objective: To investigate the effect of optimized left atrioventricular conduction time (Lavi) on hemodynamics and prognosis of patients with third degree atrioventricular block implanted with dual chamber pacemakers. Methods 120 patients with third degree atrioventricular block implanted with dual chamber pacemaker were randomly divided into Lavi optimized group and non optimized group. Oesophageal electrocardiography was performed 3 months after pacemaker implantation (observation base point). The atrial conduction time (IACT) and interventricular conduction time (ivct) of the two groups were measured and the Lavi under the default atrioventricular delay (AVD) state of the pacemaker was calculated. The optimization group then adjusted the AVD of the pacemaker under the guidance of echocardiography to obtain the optimal Lavi under the best mechanical synchronization state of the left atrioventricular. All patients were examined by echocardiography at 6, 12 and 18 months after operation. ECG conduction parameters, related clinical manifestations and prognostic indicators were observed, and the relationship between optimal Lavi and heart rate was analyzed. Results a. In the optimization group, the average optimal Lavi was (130.8 ± 11.9) ms, which was longer than the default Lavi value (120.7 ± 18.7ms) (p<0.05). B. In the optimization group, the optimal Lavi was negatively correlated with heart rate (r=-0.955, p<0.05), heart rate <70 beats / min, and the optimal Lavi was 140ms; the heart rate was 70~80 beats / min, and the optimal Lavi was 130ms; heart rate >80 beats / min, and the optimal Lavi is 120ms. C. Optimization of Lavi could immediately improve e-peak deceleration time (EDT) and isovolumic relaxation time (IVRT) in the optimization group (p<0.05). D. The left ventricular ejection fraction (LVEF), EDT and IVRT of the optimized group were better than those of the non optimized group at 6 months after operation (p<0.05), and the left atrial volume index and e/e ‘(the ratio of early diastolic flow velocity of mitral orifice to early diastolic movement velocity of mitral annulus) were better than those of the non optimized group at 12 months after operation (p<0.05). E. LVEF and EDT in the non optimized group decreased gradually during the follow-up period of 18 months (P <0.05); ivrt and left atrial volume index increased gradually during the whole follow-up period (P <0.05). E/e ‘in the optimization group increased gradually during the follow-up period (p<0.05), while EDT decreased gradually during the follow-up period (p<0.05). F. The cumulative incidence of new paroxysmal atrial fibrillation in the optimization group was significantly lower than that in the non optimization group (8.3%vs23.3%, p<0.05). Conclusion optimization of Lavi can improve hemodynamics and reduce the incidence of atrial fibrillation in patients with third degree atrioventricular block implanted with dual chamber pacemakers

From Blood to the Brain: Can Systemically Transplanted Mesenchymal Stem Cells Cross the Blood-Brain Barrier?

Systemically infused mesenchymal stem cells (MSCs) are emerging therapeutics for treating stroke, acute injuries, and inflammatory diseases of the central nervous system (CNS), as well as brain tumors due to their regenerative capacity and ability to secrete trophic, immune modulatory, or other engineered therapeutic factors. It is hypothesized that transplanted MSCs home to and engraft at ischemic and injured sites in the brain in order to exert their therapeutic effects. However, whether MSCs possess the ability to migrate across the blood-brain barrier (BBB) that separates the blood from the brain remains unresolved. This review analyzes recent advances in this area in an attempt to elucidate whether systemically infused MSCs are able to actively transmigrate across the CNS endothelium, particularly under conditions of injury or stroke. Understanding the fate of transplanted MSCs and their CNS trafficking mechanisms will facilitate the development of more effective stem-cell-based therapeutics and drug delivery systems to treat neurological diseases and brain tumors

Discovery and identification of potential biomarkers of papillary thyroid carcinoma

<p>Abstract</p> <p>Background</p> <p>Thyroid carcinoma is the most common endocrine malignancy and a common cancer among the malignancies of head and neck. Noninvasive and convenient biomarkers for diagnosis of papillary thyroid carcinoma (PTC) as early as possible remain an urgent need. The aim of this study was to discover and identify potential protein biomarkers for PTC specifically.</p> <p>Methods</p> <p>Two hundred and twenty four (224) serum samples with 108 PTC and 116 controls were randomly divided into a training set and a blind testing set. Serum proteomic profiles were analyzed using SELDI-TOF-MS. Candidate biomarkers were purified by HPLC, identified by LC-MS/MS and validated using ProteinChip immunoassays.</p> <p>Results</p> <p>A total of 3 peaks (<it>m/z </it>with 9190, 6631 and 8697 Da) were screened out by support vector machine (SVM) to construct the classification model with high discriminatory power in the training set. The sensitivity and specificity of the model were 95.15% and 93.97% respectively in the blind testing set. The candidate biomarker with <it>m/z </it>of 9190 Da was found to be up-regulated in PTC patients, and was identified as haptoglobin alpha-1 chain. Another two candidate biomarkers (6631, 8697 Da) were found down-regulated in PTC and identified as apolipoprotein C-I and apolipoprotein C-III, respectively. In addition, the level of haptoglobin alpha-1 chain (9190 Da) progressively increased with the clinical stage I, II, III and IV, and the expression of apolipoprotein C-I and apolipoprotein C-III (6631, 8697 Da) gradually decreased in higher stages.</p> <p>Conclusion</p> <p>We have identified a set of biomarkers that could discriminate PTC from non-cancer controls. An efficient strategy, including SELDI-TOF-MS analysis, HPLC purification, MALDI-TOF-MS trace and LC-MS/MS identification, has been proved successful.</p

4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells

The estrogenic chemical 4-nonylphenol (NP) is known to impair testicular devolopment and spermatogenesis in rodents. The objective of this study was to explore the effects of NP on autophagy induction and AMPK-mTOR signaling pathway in Sertoli cells (SCs), which are the “nursemaid cells” for meiosis of spermatocytes. In this study we exposed 7-week-old male rats to NP by intra-peritoneal injection at 0, 20, 50 or 100 mg/kg body weight/2 days for 20 consecutive days. Our results showed that exposure to NP dose-dependently induces the formation of autophagosomes in SCs, increases the expression of Beclin-1, the conversion of LC3-I to LC3-II and the mRNA expression of Atg3, Atg5, Atg7 and Atg12 in testis, and these effects are concomitant with the activation of AMPK, and the suppression of TSC2-mTOR-p70S6K/4EBP1 signaling cascade in testis. Furthermore, 10 µM Compound C or AMPKα1 siRNA pre-treatment effectively attenuated autophagy and reversed AMPK-mTOR-p70S6K/4EBP1 signaling in NP-treated SCs. Co-treatment with 1 mM AICAR remarkably strengthened NP-induced autophagy and mTOR inhibition in SCs. Together, these data suggest that NP stimulates Sertoli cell autophagy and inhibits mTOR-p70S6K/4EBP1 activity through AMPK activation, which is the potential mechanism responsible for the regulation of testis function and differentiation following NP exposure

Combination of Decitabine and a Modified Regimen of Cisplatin, Cytarabine and Dexamethasone: A Potential Salvage Regimen for Relapsed or Refractory Diffuse Large B-Cell Lymphoma After Second-Line Treatment Failure

ObjectiveThe prognosis for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R-DLBCL) after second-line treatment failure is extremely poor. This study prospectively observed the efficacy and safety of decitabine with a modified cisplatin, cytarabine, and dexamethasone (DHAP) regimen in R/R-DLBCL patients who failed second-line treatment.MethodsTwenty-one R/R-DLBCL patients were enrolled and treated with decitabine and a modified DHAP regimen. The primary endpoints were overall response rate (ORR) and safety. The secondary endpoints were progression-free survival (PFS) and overall survival (OS).ResultsORR reached 50% (complete response rate, 35%), five patients (25%) had stable disease (SD) with disease control rate (DCR) of 75%. Subgroup analysis revealed patients over fifty years old had a higher complete response rate compared to younger patients (P = 0.005), and relapsed patients had a better complete response rate than refractory patients (P = 0.031). Median PFS was 7 months (95% confidence interval, 5.1-8.9 months). Median OS was not achieved. One-year OS was 59.0% (95% CI, 35.5%-82.5%), and two-year OS was 51.6% (95% confidence interval, 26.9%-76.3%). The main adverse events (AEs) were grade 3/4 hematologic toxicities such as neutropenia (90%), anemia (50%), and thrombocytopenia (70%). Other main non-hematologic AEs were grade 1/2 nausea/vomiting (40%) and infection (50%). No renal toxicity or treatment-related death occurred.ConclusionDecitabine with a modified DHAP regimen can improve the treatment response and prognosis of R/R-DLBCL patients with good tolerance to AEs, suggesting this regimen has potential as a possible new treatment option for R/R-DLBCL patients after second-line treatment failure.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03579082

Complexity-Entropy Causality Plane Based on Return Intervals: A Useful Approach to Quantify the Aeroengine Gas Path Parameters

The complexity-entropy causality plane, as a powerful tool for discriminating Gaussian from non-Gaussian process, has been recently introduced to describe the complexity among time series. We propose to use this method to distinguish the stage of climb-cruise-decline of aeroengine. Our empirical results demonstrate that this statistical physics approach is useful. Further, the return intervals based complexity-entropy causality plane is introduced to describe the complexity of aeroengine fuel flow time series. The results can infer that the cruise process has lowest complexity and the decline process has highest complexity

Collaborative Optimization Method for Multi-Train Energy-Saving Control with Urban Rail Transit Based on DRLDA Algorithm

With the traffic congestion problem deteriorating, people increasingly choose urban rail transit (URT) to travel. Although URT alleviates traffic congestion, the long-term operation of a large number of trains leads to huge energy consumption. In order to adapt the major social development concept of “Low carbon”, a multi-train energy-saving control collaborative optimization method is proposed in this paper. First, the composition of single train operating conditions is determined by the conversion of operating conditions between stations and the force changes under the premise of ensuring safe and on-time train operation. A single-train energy consumption calculation combinatorial optimization model with the dual control objectives of reducing passengers’ average waiting time as well as train traction energy consumption is established. The energy saving control strategy of a single train is investigated by ARMA-Radial Basis Function Neural Network (ARMA-RBFNN) and Genetic Algorithm (GA). Next, the queuing theory is introduced to analyze the variation in passenger waiting time for multiple trains at different arrival intervals. A Deep Reinforcement Learning (DRL) algorithm is designed to obtain the correlation among passenger waiting time, arrival interval and train stopping time. The optimization objective is to minimize the multi-train traction energy consumption and the average passenger waiting time while considering conditions such as train operating safety interval, speed limit, multiple operating state and single train energy-saving models, etc. Then, a multi-train cooperative energy-saving control model is proposed based on the Dragonfly Algorithm (DA). Finally, a case study of Beijing Metro Line 4 is conducted to illustrate the effectiveness of the proposed method. The results demonstrate that the total traction energy consumption and passenger waiting time are reduced by 3.1% and 5 s, respectively, compared with the method of independently optimizing the single-train control strategy. The findings can aid in the development of energy-saving strategies and also provide a basis for energy-saving operation control of multiple trains

Experimental Study of Spray Characteristics of Kerosene-Ethanol Blends from a Pressure-Swirl Nozzle

Partial replacement of kerosene by ethanol in a gas turbine is regarded as a good way to improve the spray quality and reduce the fossil energy consumption. The present work is aimed at studying the spray characteristics of kerosene-ethanol blends discharging from a pressure-swirl nozzle. The spray cone angle, discharge coefficient, breakup length, and velocity distribution are obtained by particle image velocimetry, while droplet size is acquired by particle/droplet imaging analysis. Kerosene, E10 (10% ethanol, 90% kerosene), E20 (20% ethanol, 80% kerosene), and E30 (30% ethanol, 70% kerosene) have been considered under the injection pressure of 0.1–1 MPa. The results show that as injection pressure is increased, the discharge coefficient and breakup length decrease, while the spray cone angle, drop size, and spray velocity increase. Meanwhile, the drop size decreases and the spray velocity increases with ethanol concentration when the injection pressure is lower than 0.8 MPa. However, the spray characteristics are not affected obviously by the ethanol concentration when the injection pressure exceeds 0.8 MPa. A relation to breakup length for kerosene-ethanol blends is obtained. The findings demonstrate that the adding of ethanol into kerosene can promote atomization performance

Exploring proximal mechanisms behind intergenerational association between maternal childhood abuse and Chinese preschool children's executive function

Background: Maternal personal history of childhood abuse has been found to predict child social -emotional problems; however, little is known about the intergenerational associations between maternal childhood abuse and child cognitive outcomes.Objective: This study aims at examining the intergenerational associations of maternal childhood emotional abuse and physical abuse with child executive functions among Chinese families with preschoolers, and exploring how these associations are mediated by maternal perspective-taking skills and mother-child conflict.Methods: Participants were 309 preschoolers (152 boys) aged 2-6 years and their mothers. Mothers reported on their childhood abuse histories, perspective taking, and mother-child conflict at baseline (T1). Five months later (T2), child executive functions including working memory, inhibitory control, and cognitive flexibility were assessed using five computerized tasks. Results: After controlling for child gender and age, associations with child executive functions were found for maternal childhood emotional abuse, but not physical abuse. Specifically, severer childhood emotional abuse directly predicted lower levels of child cognitive flexibility. Furthermore, chained mediation paths were found from maternal childhood emotional abuse to lower levels of child working memory and inhibitory control through worse maternal perspective taking skills and then more mother-child conflicts.Conclusions: Our findings provide evidence for less optimal executive functions among pre-schoolers with emotionally abused mothers. Developing strategies to resolve the long-lasting impacts of maternal childhood emotional abuse may be important for reducing the risks of being unable to fully achieve the cognitive potentials of the next generation