[Predictive value of plasma TMAO combined with NT-proBNP on the prognosis and length of hospitalization of patients with ischemic heart failure].

Objective: To explore the value of the assessment of plasma trimethylamine N-oxide (TMAO) combined with N-terminal pro-B-type natriuretic peptide (NT-proBNP) on predicting the all-cause mortality, length of hospitalization, and hospital cost in ischemic heart failure (IHF) patients. Methods: This prospective cohort study included 189 patients (157 males, mean age (64.0±10.5) years) with a left ventricular ejection fraction<45% caused by coronary artery disease, who hospitalized in our department from March 2016 to December 2020. Baseline data, including demographics, comorbid conditions and laboratory examination, were analyzed. The cumulative rate of all-cause mortality was evaluated using the Kaplan-Meier method and compared between the groups according to the log-rank test. Relative risks were reported as hazard ratios (HR) and 95% confidence interval (95%CI) calculated using the Cox proportional-hazards analysis, with stepwise adjustment for covariables. Spearman correlation analysis was then performed to determine the relationship between TMAO combined with NT-proBNP and length of hospitalization and hospital cost. Results: There were 50 patients in the low TMAO+low NT-proBNP group, 89 patients in high TMAO or high NT-proBNP group, 50 patients in high TMAO+high NT-proBNP group. The mean follow-up period was 3.0 years. Death occurred in 70 patients (37.0%), 27 patients (54.0%) in high TMAO+high NT-proBNP group, 29 patients (32.6%) in high TMAO or high NT-proBNP group and 14 patients (28.0%) in low TMAO+low NT-proBNP group. TMAO, in combination with NT-proBNP, improved all-cause mortality prediction in IHF patients when stratified as none, one or both biomarker(s) elevation, with the highest risk of all-cause mortality in high TMAO+high NT-proBNP group (HR=3.62, 95%CI 1.89-6.96, P<0.001). ROC curve analysis further confirmed that TMAO combined with NT-proBNP strengthened the prediction performance on the risk of all-cause death (AUC=0.727(95%CI 0.640-0.813), sensitivity 55.0%, characteristic 83.1%). Spearman correlation analysis showed that IHF patients with high TMAO and high NT-proBNP were positively associated with longer duration of hospitalization (r=0.191,P=0.009), but not associated with higher hospital cost (r=0.030, P=0.686). Conclusions: TMAO combined with NT-proBNP are valuable prediction tool on risk stratification of patients with IHF, and those with two biomarkers elevation face the highest risk of mortality during follow-up period, and are associated with the longer hospital stay.

[Clinical characteristics and outcome comparison between atrial fibrillation patients underwent catheter ablation under general aesthesia or local anesthesia and sedation].

Objective: To compare the outcome of radiofrequency catheter ablation under local anesthesia/sedation (S) or general anesthesia(GA) in atrial fibrillation patients. Methods: Data of 498 patients with atrial fibrillation undergoing radiofrequency catheter ablation in our departmentfrom January 2014 to December 2015 were retrospectively analyzed. Two hundred and twenty patients assigned to the GA group, the other 278 patients to the S group. Patients were followed clinically every 3 months within one year after procedure. Immediate electrocardiogram was performed in patients with palpitation or choking sensation in chest. The end point of the study was recurrence of any atrial tachyarrhythmia lasting >30 seconds in device interrogation, 24-hour Holter monitoring or 12-lead electrocardiogram after a single procedure. After the ablation procedure, a blanking period of 3 months was allowed according to the guidelines. Procedure time, radiofrequency time, fluoroscopy time, the detection of paroxysmal supraventricular tachycardia, the success rate and the complications were compared between the two groups. Results: There was no difference in the baseline characteristics between the two groups, such as age, gender, BMI, complications, LVEF, LAD (all P>0.05). The duration of procedure ((117.8±51.7)minutes vs.(115.4±36.9)minutes, P=0.79), duration of fluoroscopy((12.5±11.2)minutes vs. (10.4±10.2)minutes, P=0.35), duration of radiofrequency((40.1±12.9)minutes vs. (48.6±44.3)minutes, P=0.48) were similar between the two groups (P>0.05). Compared with S group, discovery of the frequency of atrioventricular node reentrant tachycardia (AVNRT) was significantly lower in GA group (0 vs. 3.6%(10/278), P<0.01), but the difference disappeared with repeat electrophysiological examination when patients become conscious from GA(3.2%(7/220) vs. 3.6%(10/278), P=0.311). The difference of atrioventricular reentrant tachycardia (AVRT) was similar between the two groups(0.9%(2/220) vs. 0.7%(2/278), P=0.841). Compared with S group, reflection of vagus nerve was less in GA group (1.4%(3/220) vs. 8.6%(24/278), P=0.026). After following up of (356±92) days, freedom from atrial fibrillation/atrial flutter/atrial tachyarrhythmia was similar between the two groups(77.9%(162/208) vs. 79.9%(215/269), P=0.818). Conclusion: General anesthesia is a promising method to atrial fibrillation ablation, in view of stable patient status and safety for the procedure. There is no difference in complications, recurrence of arrhythmia between the two groups, but detection rate of AVNRT is lower in GA group.

Dust mite allergen, glutathione S-transferase, induces T cell immunoglobulin mucin domain-4 in dendritic cells to facilitate initiation of airway allergy.

BACKGROUND: Allergens from dust mites play a critical role in the pathogenesis of airway allergy. The mechanism by which dust mite allergens induce allergic diseases is not fully understood yet. OBJECTIVE: This study tests a hypothesis that the eighth subtypes of Dermatophagoides farina allergen (Derf8) play an important role in the induction of airway allergy. METHODS: The protein of Derf8 was synthesized via molecular cloning approach. Dendritic cells (DC) were stimulated with Derf8 in the culture, and then, the expression of T cell immunoglobulin mucin domain 4 (TIM4) in dendritic cells (DC) was analysed. The role of Derf8 in the induction of airway allergy was evaluated with a mouse model. RESULTS: Exposure to Derf8 markedly induced the TIM4 expression in DCs by modulating the chromatin at the TIM4 promoter locus. Derf8 played a critical role in the expansion of the T helper 2 response in the mouse airway via inducing DCs to produce TIM4. Administration with Derf8-depleted dust mite extracts (DME) inhibited the allergic inflammation and induced regulatory T cells in mice with airway allergy. CONCLUSION: Derf8 plays an important role in the initiation of dust mite allergy. Vaccination with Derf8-deficient DME is more efficient to inhibit the dust mite allergic inflammation than using wild DME.

The absence of Brm exacerbates photocarcinogenesis.

Brm is an ATPase subunit of the SWI/SNF chromatin-remodelling complex. Previously, we identified a novel hotspot mutation in Brm in human skin cancer, which is caused by exposure to ultraviolet radiation (UVR). As SWI/SNF is involved in DNA repair, we investigated whether Brm-/- mice had enhanced photocarcinogenesis. P53+/- and Brm-/-p53+/- mice were also examined as the p53 tumor suppressor gene is mutated early during human skin carcinogenesis. Mice were exposed to a low-dose irradiation protocol that caused few skin tumors in wild-type mice. Brm-/- mice with both p53 alleles intact had an increased incidence of skin and ocular tumors compared to Brm+/+p53+/+ controls. Brm loss in p53+/- mice did not further enhance skin or ocular cancer incidence beyond the increased photocarcinogenesis in p53+/- mice. However, the skin tumors that arose early in Brm-/- p53+/- mice had a higher growth rate. Brm-/- did not prevent UVR-induced apoptotic sunburn cell formation, which is a protective response. Unexpectedly, Brm-/- inhibited UVR-induced immunosuppression, which would be predicted to reduce rather than enhance photocarcinogenesis. In conclusion, the absence of Brm increased skin and ocular photocarcinogenesis. Even when one allele of p53 is lost, Brm has additional tumor suppressing capability.

Directional differentiation of chicken spermatogonial stem cells in vitro.

BACKGROUND: Mammalian spermatogonial stem cells (SSC) are able to differentiate into different cell types in vitro, which are valuable sources for regenerative medicine and gene transfer studies. We investigated the differentiation potential of chicken SSC into osteoblasts, neuron-like cells and adipocytes in vitro. METHODS: Chicken SSC from the testes of 18- and 20-day-old chicken embryos were cultured in different induction media for three passages in vitro. For differentiation into osteoblasts, SSC were cultured in Dulbecco's modified Eagle medium (DMEM) supplemented with 1 x 10(-4) micromol/mL desamethasone, 10 micromol/mL (beta-sodium glycerophosphate and 0.05 mg/mL vitamin C, and examined by microscopy after Von Kossa's, cytochemical and immunohistochemical staining. For differentiation into neuron-like cells, SSC were cultured in DMEM supplemented with 1 x 10(-3) micromol/mL retinoic acid (RA), 5.0 micromol/mL 3-isobutyl-1-methylxanthine (IBMX) and examined by microscopy after toluidine blue or immunohistochemical staining. For differentiation into adipocytes, SSC were cultured in DMEM supplemented with 1 x 10(-3) micromol/mL dexamethasone, 0.01 mg/mL insulin, 0.5 micromol/mL IBMX and examined by microscopy after Oil red O staining and reverse transcriptase-polymerase chain reaction (RT-PCR) for gene expression of peroxisome proliferation activation receptor-gamma (PPAR-gamma). RESULTS: After 15 and 21 days of culture in the induction medium for osteoblast differentiation, 75% and 80% chicken SSC differentiated into osteoblasts, as confirmed by Von Kossa's, calcium-cobalt and collagen I antibody staining. After 3 and 7 days of culture in the induction medium for neuron-like cell differentiation, 78% and 85% SSC became neuron-like cells, as confirmed by staining with toluidine blue and the monoclonal antibody against neuron-specific enolase, nestin and glial fibrillary acidic protein. After 7 days of culture in the induction for adipocyte differentiation, 85% SSC differentiated into adipocytes, as confirmed by Oil red O staining and RT-PCT for PPAR-gamma gene expression. DISCUSSION: Our results show that chicken SSC can differentiate into osteoblasts, neuron-like cells and adipocytes under similar conditions as for directional differentiation of mammalian SSC in vitro. The findings show the feasibility of using SSC-derived cells for developmental biology and gene transfer studies in chickens.

Combination pharmacological cardioversion of permanent atrial fibrillation in post-prosthetic mitral valve replacement outpatients: a novel approach for the treatment of atrial fibrillation.

This study explored the efficacy and safety of combination pharmacological cardioversion of permanent atrial fibrillation in outpatients following prosthetic mitral valve replacement. The study group comprised 99 outpatients who were randomly divided into two groups. In group 1 (n = 50), only ventricular heart rate was controlled. In group 2 (n = 49), combination pharmacological cardioversion therapy with low-dose oral amiodarone (2 mg/kg), captopril (0.25 mg/kg) and simvastatin (0.3 mg/kg) was administered daily. During 12 months of serial pharmacological treatment, the cardioversion rate was 6% for group 1 and 39% for group 2; the likelihood of cardioversion differed significantly between the two groups. In group 2, one patient developed severe pruritus that necessitated withdrawal from the study and six patients ceased captopril treatment after contracting a persistent cough. In summary, combination pharmacological cardioversion was found to be effective and safe in outpatients who had undergone prosthetic mitral valve replacement.