Risk Factors for Left Ventricular Thrombus Formation in Patients with Dilated Cardiomyopathy.

BACKGROUND: Left ventricular thrombus (LVT) is a common complication of dilated cardiomyopathy (DCM), causing morbidity and mortality. METHODS: This study retrospectively analyzed patients with DCM from January 2002 to August 2020 in Beijing Anzhen Hospital. Clinical characteristics were compared between the LVT group and the age and sex 1:4 matched with the LVT absent group. The receiver operator characteristic (ROC) curve was plotted to evaluate the diagnostic value of D-dimer predicting LVT occurrence in DCM. RESULTS: A total of 3,134 patients were screened, and LVT was detected in 72 (2.3%) patients on echocardiography. The patients with LVT had higher D-dimer, fibrinogen, and lower systolic blood pressure than those without LVT. The ejection fraction (EF) was lower and left ventricular end-systolic diameter was larger in the LVT group. Severe mitral regurgitation (MR) was more common in the LVT absent groups. The prevalence of atrial fibrillation was lower in the LVT group. The ROC curve analysis yielded an optimal cut-off value of 444 ng/mL DDU (D-dimer units) for D-dimer to predict the presence of LVT. Multivariable binary logistic regression analysis revealed that EF (OR = 0.90, 95% CI = 0.86-0.95), severe MR (OR = 0.19, 95% CI = 0.08-0.48), and D-dimer level (OR = 15.4, 95% CI = 7.58-31.4) were independently associated with LVT formation. CONCLUSION: This study suggested that elevated D-dimer levels (>444 ng/mL DDU) and reduced EF were independently associated with increased risk of LVT formation. Severe MR could decrease the incidence of LVT.

What is optimal timing of warming for transferring vitrified cleavage stage of day 3 slow-growing embryos? A cohort retrospective study.

PURPOSE: To evaluate optimal warming time, the early warming or the routine warming time, for transferring vitrified-warmed and cultured overnight cleavage stage of the slow-growing embryos on day 3 in frozen embryo transfer (FET) cycle. METHODS: This was a retrospective cohort study from January 2017 to July 2018. A total of 705 FET patients aged < 40 years were included and 1486 embryos were formed, of which 1366 embryos were eventually transferred. RESULTS: For slow-growing embryos, the clinical pregnancy rate of early warming group [152/468 (32.5%)] was significantly higher than that of routine warming group (55/235 (23.4%)) [OR 1.39 (CI 1.06-1.81), p = 0.01], while there was no statistically significant difference in pregnancy loss in early warming group [39/170 (22.9%)] versus in routine warming group [16/62 (25.8%)] [OR 0.89 (CI 0.53-1.47), p = 0.65]. CONCLUSION: For slow-growing embryos, higher pregnancy outcomes were shown in early warming strategy as compared to the routine warming, which suggested that the improvement of endometrium-embryo synchronism may correct the time difference brought by the slow-growing embryos.

Laser-assisted hatching zona thinning does not improve the pregnancy outcomes of poor-quality blastocysts in frozen-thawed embryo transfer cycle: a retrospective cohort study.

It had been suggested, after facilitating the hatching process, improved pregnancy outcomes could be attained in embryos with thick and hard zona. This study aimed to determine the effect of zona thinning on pregnancy outcomes in poor-quality frozen-thawed blastocysts. This retrospective study included 230 women (≤ 40 years) who underwent frozen embryo transfer of poor-quality blastocysts (scored < 3BB). In total, 105 patients were in the assisted hatching group in which the zona was thinned by laser before transfer and 125 patients were in the control group in which the blastocysts were non-manipulated. Patients' demographics, cycle characteristics, and pregnancy outcomes were compared between the assisted hatching group and the control group. Further, regression analysis was applied to test the correlation between assisted hatching and live birth. All parameters in the patients' demographic characteristics and the cycle's characteristics were not significantly different between two groups. As for pregnancy outcomes, the second trimester pregnancy loss was significantly higher in the assisted hatching group (P = 0.035). Other pregnancy outcomes, including implantation rate, clinical pregnancy rate, biochemical miscarriage rate, the first trimester pregnancy loss, ongoing pregnancy rate, and live birth rate were comparable between two groups. The logistic regression analysis demonstrated no association between live birth and assisted hatching (univariate, OR = 0.787, P > 0.05; multivariate, OR = 0.652, P > 0.05), and the area under the receiver operating characteristic curve of the regression model was almost 0.7. It suggested that zona thinning may not be supposed to perform on poor-quality, frozen-thawed blastocysts. The indications of assisted hatching were still needed to further investigate.

New-Onset Atrial Fibrillation and Adverse In-Hospital Outcome in Patients with Acute Pulmonary Embolism.

Atrial fibrillation (AF) can be secondary to acute pulmonary embolism (PE). This study aimed to investigate the prognostic impact of new-onset AF on patients with acute PE. In this study, 4,288 consecutive patients who were diagnosed with acute PE were retrospectively screened. In total, 77 patients with acute PE and new-onset AF were analyzed. Another 154 acute PE patients without AF were selected as the age- and sex-matched control group. Adverse in-hospital outcome comprised one of the following conditions: all-cause death, endotracheal intubation, cardiopulmonary resuscitation, and intravenous catecholamine therapy. The patients with new-onset AF had higher prevalence of congestive heart failure, higher simplified PE severity index (sPESI), higher creatinine, and larger left atrium diameter. The incidences of adverse in-hospital outcomes were 10.4 and 2.6% in patients with new-onset AF and no AF, respectively (p = 0.02). Patients with sPESI ≥ 1 had higher incidence of adverse in-hospital outcomes than those with sPESI = 0 (9.4 vs. 0.9%, p < 0.01). The area under the receiver operating characteristic curve of sPESI and sPESI + AF (adding 1 point for new-onset AF) scores in assessing the adverse in-hospital outcome were 0.80 (95% confidence interval [CI]: 0.68-0.93) and 0.84 (95% CI: 0.72-0.96), respectively. In multivariable analysis, sPESI ≥ 1 (odds ratio, 8.88; 95% CI: 1.10-72.07; p = 0.04) was an independent predictor of adverse in-hospital outcome. However, new-onset AF was not an independent predictor. In the population studied, sPESI is an independent predictor of adverse in-hospital outcomes, whereas new-onset AF following acute PE is not, but it may add predictive value to sPESI.

Left-sided accessory pathways successfully ablated from the aortomitral continuity region: distinctive atrial activation patterns and anatomic concerns.

AIMS: Accessory pathways (APs) successfully ablated at the aortomitral continuity (AMC) were sporadically reported but relevant data are very limited. We aimed to describe the electrophysiological characteristics of AMC-AP and the related anatomy. METHODS AND RESULTS: This study involved eight (male/female = 3/5, mean age 42.6 ± 10.5 years) patients with left-sided AP successfully ablated in the AMC region. The retrograde atrial activation sequence was analysed and compared via recordings at the His-bundle (HB), coronary sinus (CS), and roving catheter during tachycardia, and the peak of QRS from the same cardiac circle used as time reference. Of the eight patients, two received prior ablations. During tachycardia, the activation time at the proximal CS (CSp), lateral CS (CSl), and HB region averaged 120 ± 26 ms, 124 ± 29 ms, and 117 ± 21 ms following the reference, respectively (P = 0.86). The latest atrial activation was recorded in the posterior CS which averaged 135 ± 25 ms following the reference. Placing the ablation catheter to AMC via retrograde approach was attempted in all cases but stable positioning achieved in none. Via transseptal approach, the ablation catheter could be easily placed at the AMC and recorded the earliest retrograde atrial activations with 60 ± 27 ms earlier than the relatively 'earliest' CS/HB recordings, and ablation at this site successfully eliminated AP conduction. No patients had recovered AP conduction after at least 12-month follow-up. CONCLUSION: AMC-AP is featured by recording comparable retrograde atrial activation times at CSp, CSl, and HB with the latest recordings at the posterior CS. Stable placement and successful ablation in the AMC via retrograde aortic approach was difficult but can be achieved via transseptal approach.

Long-term outcome of catheter ablation for atrial fibrillation in patients with apical hypertrophic cardiomyopathy.

INTRODUCTION: To assess the long-term outcome of catheter ablation in patients with hypertrophic cardiomyopathy (HCM), especially in patients with apical HCM (ApHCM). METHODS AND RESULTS: From 9,249 AF ablation cases, 97 patients (28 with ApHCM and 69 with non-ApHCM) were enrolled. Another 97 patients matched by age, AF type, AF duration, and left atrial diameter were selected as the control group. After a mean follow-up of (44.3 ± 29.6) months, success rate after a single procedure was 42.9% in the ApHCM patients (P  =  0.725), 36.2% in the non-ApHCM patients (P  =  0.136) versus 50.5% in the control group. After multiple procedures, success rate both in the ApHCM group (50%, P  =  0.047) and in the non-ApHCM group (50.4%, P  =  0.017) were lower than in the controls (68.0%). More patients in the ApHCM and in the non-ApHCM group suffered very late recurrence beyond 1 year after the index procedure. Left atrial diameter (hazard ratio [HR] 1.04, 95% confidential interval [CI] 1.01-1.08, P  =  0.018) and AF duration (HR 1.01, 95% CI 1.00-1.01, P  =  0.005) were independent predictors of recurrence after the index ablation. There was no difference in thromboembolic events between the HCM group and the control group (8.2% vs. 3.1%, P  =  0.082). CONCLUSIONS: Patients with ApHCM or non-ApHCM had similar success rate of AF ablation after single procedure and lower success rate after multiple procedure compared with the control group.

Transseptal puncture and catheter ablation of atrial fibrillation in patients with atrial septal occluder: initial experience of a single centre.

Aims: Catheter ablation is underutilized in atrial septal defect (ASD) patients who have undergone implantation of an atrial septal occluder (ASO). This study evaluates the feasibility and safety of catheter ablation of atrial fibrillation (AF) in this subset of patients. Methods and results: Sixteen patients (age 56 ± 12 years, 10 men) with drug-refractory AF (10 paroxysmal and 6 persistent) and previously implanted ASO were enrolled. Balloon dilatation of the closure device was performed if the native septum passage could not be achieved. For paroxysmal AF, the ablation strategy was circumferential pulmonary vein isolation (CPVI), and for persistent AF, additional linear ablation was performed. Transseptal access was achieved through the native septum in 11 patients (Group A) and through the ASO using balloon dilatation in 5 patients (Group B). Circumferential pulmonary vein isolation was achieved in all 16 patients, and linear block was achieved in all persistent patients except for 1 patient who did not achieve mitral isthmus block. The transseptal, total fluoroscopy, and procedural durations were 5 ± 3 vs. 38 ± 8 min, 31 ± 11 vs. 54 ± 15 min, and 165 ± 35 vs. 224 ± 36 min, respectively, in Group A vs. Group B, respectively (all P < 0.05). No shunt at atrial level was detected by transthoracic echocardiography at 3-month follow-up. During a follow-up of 16 ± 6 months, sinus rhythm was maintained in 12 of 16 patients. No severe complications were observed. Conclusion: In ASD patients with ASO, catheter ablation of AF is feasible, safe, and effective. The balloon dilatation technique can facilitate transseptal access through the ASO.

Combined Influence of Insulin Resistance and Inflammatory Biomarkers on Type 2 Diabetes: A Population-based Prospective Cohort Study of Inner Mongolians in China.

This prospective study was designed to examine the combined influence of insulin resistance (IR) and inflammatory biomarker levels on type 2 diabetes mellitus (T2DM) among 1,903 Inner Mongolians. During follow-up, 205 (10.77%) participants developed T2DM, and the incidence of T2DM was higher among subjects with IR, elevated C-reactive protein (CRP), elevated sICAM-1, elevated sE-selectin, or the coexistences of IR with elevated CRP, elevated sICAM-1, elevated sE-selectin, and elevated angiotensin II (all P < 0.05) compared with patients without IR or any elevated biomarkers. In multivariate analysis, the odd ratios [OR, (95% confidence intervals)] for these conditions were 1.944 (1.405-2.691), 2.003 (1.449-2.767), 1.706 (1.232-2.362), 1.560 (1.123-2.165), 2.708 (1.809-4.054), 1.885 (1.155-3.078), 2.101 (1.340-3.295), and 2.260 (1.426-3.582), respectively. Our findings demonstrated that IR and elevated inflammatory biomarkers were associated with T2DM, and that the coexistence of IR and elevated inflammatory biomarkers increased the risk of T2DM.

[The Mechanism of Combination using mTORC1/2 Inhibitor and Imatinib to Suppress Cell Proliferation of Ph +ALL Cell Line].

OBJECTIVES: To investigate the anti-leukemia effect and mechanism of mTORC1/2 inhibitor PP242 combined with imatinib (IM) on the proliferation of Ph+ acute lymphoblastic leukemia (ALL) cell line SUP-B15. METHODS: SUP-B15 cell line was treated with PP242, imatinib (IM), or PP242 plus IM for 72 h, IC50 values (the concentration of drug required to kill 50% of the cells) and the combination index (CI ) of synergistic cytotoxicity was determined using MTT methods. The expressions of PI3K/Akt/mTOR and apoptosis associated proteins were examined by Western blot test. RESULTS: The IC50 value of IM alone was (1.50±0.09) µmol/L, however, the IC50 values were (0.81±0.030) µmol/L, (0.36±0.140) µmol/L and (0.02±0.002) µmol/L combined with 20 nmol/L, 30 nmol/L and 50 nmol/L of PP242, and the CI values were 0.764, 0.545 and 0.507, indicating two drugs had highly synergistic effect on anti-proliferation in the SUP-B15 cell line. The expressions of p-Akt, p-4EBP1, p-elF4E, p-cAbl, p-mTOR and p-P70 were down-regulated significantly in a dose-dependent and time-dependent manner after PP242 treatment#.Compared with PP242 or IM alone, the down-regulation of PI3K/Akt/mTOR signaling pathway and the up-regulation of the apoptosis associated proteins (bax and cleaved caspase-3) were more significant in the combination of two drugs. CONCLUSION: The combination of IM and PP242 could increase the inhibition of PI3K/Akt/mTOR signaling pathway and apoptosis mediated by bax and caspase-3 in SUP-B15 cell line.

Current Status and Time Trends of Oral Anticoagulation Use Among Chinese Patients With Nonvalvular Atrial Fibrillation: The Chinese Atrial Fibrillation Registry Study.

BACKGROUND AND PURPOSE: Reported rates of oral anticoagulation (OAC) use have been low among Chinese patients with atrial fibrillation (AF). With improved awareness, changing guidelines, this situation may be changing over time. We aimed to explore the current status and time trends of OAC use in Beijing. METHODS: We used the data set from the Chinese Atrial Fibrillation Registry (CAFR), a prospective, multicenter, hospital-based registry study involving 20 tertiary and 12 nontertiary hospitals in Beijing. A total of 11 496 patients with AF were enrolled from 2011 to 2014. RESULTS: Seven thousand nine hundred seventy-seven eligible patients were included in this ancillary study. The proportions of OAC use were 36.5% (2268/6210), 28.5% (333/1168), and 21.4% (128/599) for patients with CHA2DS2-VASc scores ≥2, 1, and 0, respectively. Persistent AF, history of stroke/transient ischemic attack/peripheral embolism, diabetes mellitus, higher body mass index, and tertiary hospital management were factors positively associated with OAC use, whereas older age, previous bleeding, hypercholesterolemia, and established coronary artery disease were factors negatively associated with OAC use. Among patients with CHADS2 scores ≥2 and CHA2DS2-VASc scores ≥2, the proportion of OAC use increased from 31.3% to 64.5% and 30.2% to 57.7%, respectively, from 2011 to 2014. Variation in OAC use was substantial among different hospitals. CONCLUSIONS: An improvement of OAC use among Chinese patients with AF in Beijing is observed in recent years although only 36.5% of patients with CHA2DS2-VASc score ≥2 received OAC. However, variations between different hospitals were large, suggesting that better education and awareness are needed to improve efforts for stroke prevention among AF patients. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729.

Alcohol Drinking, Dyslipidemia, and Diabetes: A Population-based Prospective Cohort Study among Inner Mongolians in China.

OBJECTIVE: No previous studies have evaluated the association between dyslipidemia, alcohol drinking, and diabetes in an Inner Mongolian population. We aimed to evaluate the co-effects of drinking and dyslipidemia on diabetes incidence in this population. METHODS: The present study was based on 1880 participants from a population-based prospective cohort study among Inner Mongolians living in China. Participants were classified into four subgroups according to their drinking status and dyslipidemia. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to evaluate the association between alcohol drinking, dyslipidemia, and diabetes. RESULTS: During the follow-up period, 203 participants were found to have developed diabetes. The multivariable-adjusted odds ratios (95% confidence interval) for the incidence of non-dyslipidemia/drinkers, dyslipidemia/non-drinkers, and dyslipidemia/drinkers in diabetic patients were 1.40 (0.82-2.37), 1.73 (1.17-2.55), and 2.31 (1.38-3.87), respectively, when compared with non-dyslipidemia/non-drinkers. The area under the ROC curve for a model containing dyslipidemia and drinking status along with conventional factors (AUC=0.746) was significantly (P=0.003) larger than the one containing only conventional factors (AUC=0.711). CONCLUSION: The present study showed that dyslipidemia was an independent risk factor for diabetes, and that drinkers with dyslipidemia had the highest risk of diabetes in the Mongolian population. These findings suggest that dyslipidemia and drinking status may be valuable in predicting diabetes incidence.

QTc Interval Prolongation Predicts Arrhythmia Recurrence After Catheter Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: In hypertrophic cardiomyopathy (HCM) patients complicated with atrial fibrillation (AF), catheter ablation has been recommended as a treatment option. Meanwhile, prolongation of QTc interval has been linked to an increased AF incidence in the general population and to poor outcomes in HCM patients. However, whether QTc prolongation predicts arrhythmia recurrence after AF ablation in the HCM population remains unknown. METHODS AND RESULTS: Thirty-nine HCM patients undergoing primary AF ablation were enrolled. The ablation strategy included bilateral pulmonary vein isolation (PVI) for paroxysmal AF (n=27) and PVI plus left atrial roof, mitral isthmus and tricuspid isthmus linear ablations for persistent AF (n=12). Pre-procedural QTc was corrected by using the Bazett's formula. At a 14.8-month follow up, 23 patients experienced atrial tachyarrhythmia recurrence. Recurrent patients had longer QTc than non-recurrent patients (461.0±28.8 ms vs. 434.3±18.2 ms, P=0.002). QTc and left atrial diameter (LAD) were independent predictors of recurrence. The cut-off value of QTc 448 ms predicted arrhythmia recurrence with a sensitivity of 73.9% and a specificity of 81.2%. A combination of LAD and QTc (global chi-squared=13.209) was better than LAD alone (global chi-squared=6.888) or QTc alone (global chi-squared=8.977) in predicting arrhythmia recurrence after AF ablation in HCM patients. CONCLUSIONS: QTc prolongation is an independent predictor of arrhythmia recurrence in HCM patients undergoing AF ablation, and might be useful for identifying those patients likely to have a better outcome following the procedure.

Transcription factor SCL/TAL1 mediates the phosphorylation of MEK/ERK pathway in umbilical cord blood CD34⁺ stem cells during hematopoietic differentiation.

Transcription factor stem cell leukemia (SCL), also known as the T-cell acute lymphocytic leukemia 1 (TAL1), plays a key role in the regulation of hematopoiesis, but the molecular mechanisms are not well understood. The aim of the present study is to elucidate the effects of the epidermal growth factor receptor (EGFR) signal pathways underlying the biologic activity of SCL/TAL1 on normal hematopoietic development. Lentiviral vectors with up or down-regulation of SCL/TAL1 were transfected into umbilical cord blood CD34 stem cells. EGFR signaling pathways (including MEK/ERK and Akt/mTOR) and surface hematopoietic markers were analyzed in the process of hematopoietic differentiation. The data revealed that up or down-regulation of SCL/TAL1 gene was accompanied positively by the expressions of p-MEK and p-ERK1/2 protein, but the changes of Akt/mTOR were unobvious. MEK/ERK inhibitor U0126 and SCL/TAL1 down-regulation showed similar inhibitory effects on erythroid, myeloid, and megakaryoid differentiation. However, Akt/mTOR pathway altered insignificantly. MEK/ERK inhibitor U0126 could not affect the expression of SCL/TAL1 mRNA or protein. Taken together, these findings fully illustrated that SCL/TAL1 is located in the up-stream of MEK/ERK pathway and partially regulates hematopoiesis by modulating the phosphorylation level of the key proteins in MEK/ERK pathway.

Predictors of recurrence after a repeat ablation procedure for paroxysmal atrial fibrillation: role of left atrial enlargement.

AIMS: This study sought to explore the predictors of recurrence in patients with paroxysmal atrial fibrillation (AF) undergoing repeat catheter ablation, especially the impact of left atrial (LA) remodelling after the original procedure on the outcome of repeat procedure. METHODS AND RESULTS: Ninety-five patients undergoing repeat ablation were enrolled in this study. Repeat procedure endpoints were pulmonary vein isolation, linear block when linear ablation is performed, and non-inducibility of atrial tachyarrhythmia by burst pacing. Patients with LA enlargement between the pre-original procedure and pre-repeat procedure were categorized as Group 1 (35 patients), while individuals with no change or decrease of LA diameter were categorized as Group 2 (60 patients). The mean duration from the original procedure to the repeat procedure was 12 months (1-40 months). After 29.6 ± 20.5 (3-73) months follow-up from the repeat procedure, 33 patients experienced recurrence (34.7%). The recurrence rate was significantly higher in Group 1 than in Group 2 (51.4 VS. 25.0%, P = 0.017). In univariate analysis, LA remodelling was the only predictor of recurrence. In multivariate analysis, after adjustment for age and LA diameter, Group 1 had a greater risk of recurrence after the repeat procedure (hazard ratio = 2.22, 95% confidence interval: 1.02-4.81, P = 0.043). CONCLUSIONS: Left atrial enlargement after undergoing the original catheter ablation of paroxysmal AF was an independent risk factor of recurrence after repeat ablation.

Effects of atrioventricular conduction delay on the outcome of cardiac resynchronization therapy.

BACKGROUND AND PURPOSE: First-degree atrioventricular (AV) block in relation to the outcome of cardiac resynchronization therapy (CRT) has not been well examined. METHODS: Patients who received a CRT defibrillator or pacemaker between January 2002 and September 2010 at Mayo Clinic were classified into 2 groups: normal PR interval and prolonged PR interval. Standard sensed (100 milliseconds) and paced (130 milliseconds) AV delay was programmed after CRT. Clinical presentations and echocardiography were assessed before CRT and at a median of 6 months after CRT. RESULTS: The normal PR interval group (n=199) had greater improvements in heart failure functional class (mean [SD], 0.7 [0.8] vs 0.5 [0.9]; P=.03) and left ventricular ejection fraction (9.4% [12.4%] vs 5.9% [9.5%]; P=.007) than the prolonged PR group (n=204). CONCLUSION: Compared with prolonged PR interval, the presence of normal PR interval was associated with a greater improvement in heart failure.

Fabrication of multifunctional ethyl cellulose/gelatin-based composite nanofilm for the pork preservation and freshness monitoring.

In this study, an active and intelligent nanofilm for monitoring and maintaining the freshness of pork was developed using ethyl cellulose/gelatin matrix through electrospinning, with the addition of natural purple sweet potato anthocyanin. The nanofilm exhibited discernible color variations in response to pH changes, and it demonstrated a higher sensitivity towards volatile ammonia compared with casting film. Notably, the experimental findings regarding the wettability and pH response performance indicated that the water contact angle between 70° and 85° was more favorable for the smart response of pH sensitivity. Furthermore, the film exhibited desirable antioxidant activities, water vapor barrier properties and also good antimicrobial activities with the incorporation of ε-polylysine, suggesting the potential as a food packaging film. Furthermore, the application preservation outcomes revealed that the pork packed with the nanofilm can prolong shelf life to 6 days, more importantly, a distinct color change aligned closely with the points indicating the deterioration of the pork was observed, changing from light pink (indicating freshness) to light brown (indicating secondary freshness) and then to brownish green (indicating spoilage). Hence, the application of this multifunctional film in intelligent packaging holds great potential for both real-time indication and efficient preservation of the freshness of animal-derived food items.

Mechanic study based on untargeted metabolomics of Pi-pa-run-fei-tang on pepper combined with ammonia induced chronic cough model mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Pi-pa-run-fei-tang (PPRFT), a traditional Chinese medicine formula with long-standing history, demonstrated beneficial effect on chronic cough. However, the mechanism underlying efficacy unclear. In current research, we explored the impact and molecular mechanism of chronic cough mouse stimulating with capsaicin combined with ammonia. AIM OF THE STUDY: To investigate the metabolic modulating effects, and potential mechanisms underlying the therapeutic effect of PPRFT in chronic cough. MATERIALS AND METHODS: Chronic cough mouse models were created by stimulating mice by capsaicin combined with ammonia. Number of coughs and cough latency within 2 min were recorded. With lung tissue and serum samples collected for histopathology, metabolomics, RT-qPCR, immunohistochemistry, and WB analysis. Lymphocytes were isolated and flow cytometric assays were conducted to evaluate the differentiation between Th17 and Treg cell among CD4+ cells. RESULTS: Results indicated that PPRFT obviously reduced the number of coughs, prolonged cough latency, reduced inflammatory cell infiltration and lung tissues damage, and decreased the serum level of IL-6, IL-1ß, TNF-α, and IL-17 while increasing IL-10 levels. Notably, PPRFT suppressed Th17 cell divergence and promoted Treg cell divergence. Furthermore, serum metabolomic assays showed that 46 metabolites differed significantly between group, with 35 pathways involved. Moreover, mRNA levels of IL-6, NF-κB, IL-17, RORγT, JAK2, STAT3, PI3K and AKT in lung tissues remarkably reduced and mRNA levels of IL-10 and FOXP3 were elevated after PPRFT pretreatment. Additionally, PPRFT treatments decreased the protein levels of IL-6, NF-κB, IL-17, RORγT, p-JAK2, p-STAT3, p-PI3K, and p-AKT and increased the protein levels of IL-10 and FOXP3, but no significantly effects to the levels on JAK2, STAT3, PI3K, and AKT in the lungs. CONCLUSION: Conclusively, our result suggested the effect with PPRFT on chronic cough may be mediated through IL-6/JAK2/STAT3 and PI3K/AKT/NF-κB pathway, which regulate the differentiation between Th17 and Treg cell. This beneficial effect of PPRFT in capsaicin and ammonia-stimulated chronic cough mice indicates its potential application in treating chronic cough.

Measles Virus-Based Vaccine Expressing Membrane-Anchored Spike of SARS-CoV-2 Inducing Efficacious Systemic and Mucosal Humoral Immunity in Hamsters.

As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2).

Outcomes of cardiac resynchronization therapy in the elderly.

BACKGROUND: Octogenarians (>80 years) have been underrepresented in clinical trials of cardiac resynchronization therapy (CRT). OBJECTIVE: To determine the benefit of CRT with or without a defibrillator in older elderly patients. METHODS: We retrospectively studied consecutive patients who received CRT at our institution from 2002 through 2008. New York Heart Association (NYHA) class and echocardiographic parameters were assessed before and after CRT. Thirty-day complications after device implant were collected. Survival data were obtained from the national death and location database. Data were compared between those 80 years and younger and those older than 80 years. RESULTS: Of 728 patients identified, 90 (12.4%) were older than 80 years. After CRT, older and younger patients had similar improvements in NHYA class (P = 0.41), ejection fraction (P = 0.48), and mitral valve regurgitation (MR) severity (P = 0.42). In the older patients, defibrillator implantation was associated with comparable improvement in NYHA class, ejection fraction, and MR grade severity (P > 0.05), as in those without a defibrillator. Overall survival was worse in octogenarians than in the younger patients by Kaplan-Meier estimates (P = 0.001). Multivariate analysis showed similar survival between the younger and older subjects (hazard ratio, 1.23; 95% confidence interval, 0.83-1.84; P = 0.31). The observed complication rate in all study subjects was 12.2%, with no difference between the two age groups. CONCLUSION: Octogenarian patients who received CRT with or without a defibrillator for advanced heart failure had similar clinical benefits as younger patients. CRT should not be withheld from octogenarians meeting current selection guidelines.

Encapsulation of quercetin into zein-ethyl cellulose coaxial nanofibers: Preparation, characterization and its anticancer activity.

In order to efficiently improve the colon-targeted delivery of quercetin, the hydrophobic core-shell nanofibers were fabricated to encapsulate quercetin using ethyl cellulose as the shell and zein as the core by coaxial electrospinning. The encapsulation efficiency of coaxial nanofibers reached >97 %. FTIR and XRD results revealed the interactions between quercetin and wall materials and quercetin was encapsulated in an amorphous state. The thermal stability and surface hydrophobicity of coaxial nanofibers were improved compared to the uniaxial zein fibers. After in vitro gastrointestinal digestion, the quercetin release from core-shell nanofibers was <12.38 %, while the corresponding value for zein fibers was 36.24 %. DPPH and FRAP assays showed that there was no significant difference in the antioxidant activity of quercetin before and after encapsulation. Furthermore, the encapsulated quercetin exhibited similar anti-proliferative activity against HCT-116 cells compared to the free form. The results suggest these coaxial nanofibers have potential applications in functional foods.