Macrophage-specific FGFR1 deletion alleviates high-fat-diet-induced liver inflammation by inhibiting the MAPKs/TNF pathways.

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease that is substantially associated with obesity-induced chronic inflammation. Macrophage activation and macrophage-medicated inflammation play crucial roles in the development and progression of NAFLD. Furthermore, fibroblast growth factor receptor 1 (FGFR1) has been shown to be essentially involved in macrophage activation. This study investigated the role of FGFR1 in the NAFLD pathogenesis and indicated that a high-fat diet (HFD) increased p-FGFR1 levels in the mouse liver, which is associated with increased macrophage infiltration. In addition, macrophage-specific FGFR1 knockout or administration of FGFR1 inhibitor markedly protected the liver from HFD-induced lipid accumulation, fibrosis, and inflammatory responses. The mechanistic study showed that macrophage-specific FGFR1 knockout alleviated HFD-induced liver inflammation by suppressing the activation of MAPKs and TNF signaling pathways and reduced fat deposition in hepatocytes, thereby inhibiting the activation of hepatic stellate cells. In conclusion, the results of this research revealed that FGFR1 could protect the liver of HFD-fed mice by inhibiting MAPKs/TNF-mediated inflammatory responses in macrophages. Therefore, FGFR1 can be employed as a target to prevent the development and progression of NAFLD.

Long duration of atrial high-rate episode is more favorable in predicting ischemic stroke than high CHA2 DS2 -VASc score.

OBJECTIVE: This study aimed to explore the roles of duration and burden of atrial high-rate episode (AHRE) on ischemic stroke in patients with pacemaker implantation. METHODS: Patients with pacemaker implantation for bradycardia from 2013 to 2017 were consecutively enrolled. Data such as gender, age, combined diseases, type of AF, left atrial size, left ventricular size, left ventricular ejection fraction, CHA2 DS2 -VASc score, and anticoagulants were collected. The burden and duration of AHRE based on different interval partition were also recorded in detail to evaluate the impacts on ischemic stroke. Cox regression analysis with time-dependent covariates was conducted. RESULTS: A total of 220 patients with AHRE were enrolled. The average follow-up time was 48.42 ± 17.20 months. Univariate regression analysis showed that diabetes (p = .024), high CHA2 DS2 -VASc score (≥ 2) (p = .021), long mean AHRE burden (p = .011), long maximal AHRE burden (p = .015), long AHRE duration lasting≥48 h (p = .001) or 24 h (p = .001) or 12 h (p = .005) were prone to ischemic stroke. Further multivariate regression analysis showed that long duration of AHRE (≥48 h) (HR 10.77; 95% CI 3.22-55.12; p = .030) were significantly correlated with stroke in patients with paroxysmal AF. There was no significant correlation between the type of AF and stroke (p = .927). CONCLUSION: The longer duration of AHRE (≥48 h) was more favorable in predicting ischemic stroke than high CHA2 DS2 -VASc score (≥2).

Predictors of pacing-induced cardiomyopathy detection and outcomes demonstration after conduction system pacing upgrade on patients with long-term persistent atrial fibrillation.

OBJECTIVE: To identify the predictors of pacing-induced cardiomyopathy (PICM) and illustrate the safety and feasibility of conduction system pacing (CSP) upgrade on patients with long-term persistent atrial fibrillation (AF). METHODS: All patients with long-term persistent AF and normal left ventricular ejection fraction (LVEF) ≥50% were consecutively enrolled from January 2008 to December 2017, and all the patients with atrioventricular block (AVB) and high right ventricular pacing (RVP) percentage of at least 40%. The predictors of PICM were identified, and patients with PICM were followed up for at least 1 year regardless of CSP upgrade. Cardiac performances and lead outcomes were investigated in all patients before and after CSP upgrade. RESULTS: The present study included 139 patients, out of which 37 (26.62%) developed PICM, resulting in a significant decrease in the left ventricular ejection fraction (LVEF) from 56.11 ± 2.56% to 38.10 ± 5.81% (p< .01). The median duration for the development of PICM was 5.43 years. Lower LVEF (≤52.50%), longer paced QRS duration (≥175 ms), and higher RVP percentage (≥96.80%) were identified as independent predictors of PICM. Furthermore, the morbidity of PICM progressively increased with an increased number of predictors. The paced QRS duration (183.90 ± 22.34 ms vs. 136.57 ± 20.71 ms, p < .01), LVEF (39.35 ± 2.71% vs. 47.50 ± 7.43%, p < .01), and left ventricular end-diastolic diameter (LVEDD) (55.53 ± 5.67 mm vs. 53.20 ± 5.78 mm, p = .03) improved significantly on patients accepting CSP upgrade. CSP responses and complete reverse remodeling (LVEF ≥50% and LVEDD < 50 mm) were detected in 80.95% (17/21) and 42.9% (9/21) of patients. The pacing threshold (1.52 ± 0.78 V/0.4 ms vs. 1.27 ± 0.59 V/0.4 ms, p = .16) was stable after follow-up. CONCLUSION: PICM is very common in patients with long-term persistent AF, and CSP upgrade was favorable for better cardiac performance in this patient population.

Conduction system pacing improves the outcomes on patients with high percentage of ventricular pacing and heart failure with mildly reduced ejection fraction.

Aims: This study aimed to investigate the efficacy and safety of CSP in patients with a high percentage of ventricular pacing and heart failure with HFmrEF. Methods: Patients who underwent CSP for HFmrEF and ventricular pacing >40% were consecutively enrolled from January 2018 to May 2021. All participants were followed up at least 12 months. Clinical data including cardiac performance and lead outcomes were compared before and after the procedure. Left ventricular ejection fraction (LVEF) was measured using the biplane Simpson's method. HFmrEF was defined as heart failure with the LVEF ranging from 41%-49%. Results: CSP was successfully performed in 64 cases (96.97%), which included 16 cases of left bundle branch pacing (LBBP) and 48 cases of His bundle pacing (HBP). After a mean of 23.12 ± 8.17 months follow-up, NYHA classification (P < 0.001), LVEF (42.45 ± 1.84% vs. 49.97 ± 3.57%, P < 0.001) and left ventricular end diastolic diameter (LVEDD) (55.59 ± 6.17 mm vs. 51.66 ± 3.48 mm, P < 0.001) improved significantly. During follow-up, more than half (39/64,60.9%) of patients returned to normal LVEF and LVEDD with complete reverse remodeling. The pacing threshold in LBBP was lower (0.90 ± 0.27 V@0.4 ms vs. 1.61 ± 0.71 V@0.4 ms, P < 0.001) than that in HBP. No perforation, electrode dislodging, thrombosis or infection was observed during follow-up. Conclusions: CSP could improve the clinical outcomes in patients with HFmrEF and a high percentage of ventricular pacing. LBBP might be a better choice because of its feasibility and safety, especially in patients with infranodal atrioventricular block.

Short QRS Duration After His-Purkinje Conduction System Pacing Predicts Left Ventricular Complete Reverse Remodeling in Patients With True Left Bundle Branch Block and Heart Failure.

Objective: This study aimed to explore the outcomes of His-Purkinje conduction system pacing (HPCSP) and to screen the predictors of left ventricular (LV) complete reverse remodeling in patients with true left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF). Methods: Patients who underwent HPCSP for true LBBB and HFrEF from April 2018 to August 2020 were consecutively enrolled. All participants were followed up for at least 1 year. Thrombosis, infection, lead dislodgement, perforation, and other complications were observed after HPCSP. Clinical data, including echocardiographic parameters, electrocardiogram measurements, and cardiac function, were assessed before and after the procedure. Results: A total of 46 patients were enrolled. HPCSP was successfully deployed in 42 cases (91.30%), which included 37 cases with His bundle pacing (HBP) and 5 cases with left bundle branch pacing (LBBP). The QRS duration decreased significantly (169.88 ± 19.17 ms vs. 113.67 ± 20.68 ms, P < 0.001). Left ventricular end-systolic volume (LVESV) (167.67 ± 73.20 ml vs. 85.97 ± 62.24 ml, P < 0.001), left ventricular end-diastolic diameter (LVEDD) (63.57 ± 8.19 mm vs. 55.46 ± 9.63 mm, P = 0.003) and left ventricular ejection fraction (LVEF) (26.52 ± 5.60% vs. 41.86 ± 11.56%, P < 0.001) improved dramatically. Complete reverse remodeling of the LV with normalized LVEF and LVEDD was found in nearly half of the patients (45.24%). A short QRS duration after HPCSP was a strong predictor of normalized LVEF and LVEDD (P < 0.001). The thresholds increased markedly in two patients approximately 6 months after HBP. No patients died during the total follow-up period of 20.07 ± 6.45 months. Conclusion: Complete reverse remodeling of the LV could be found in nearly half of the patients with HFrEF and true LBBB after HPCSP, and the short QRS duration after HPCSP was a strong predictor.

Comparative analysis of C-type lectin domain proteins in the ghost moth, Thitarodes xiaojinensis (Lepidoptera: Hepialidae).

Insects have a large family of C-type lectins involved in cell adhesion, pathogen recognition and activation of immune responses. In this study, 32 transcripts encoding C-type lectin domain proteins (CTLDPs) were identified from the Thitarodes xiaojinensis transcriptome. According to their domain structures, six CTLDPs with one carbohydrate-recognition domain (CRD) were classified into the CTL-S subfamily. The other 23 CTLDPs with two CRDs were grouped into the immulectin (IML) subfamily. The remaining three with extra regulatory domains were sorted into the CTL-X subfamily. Phylogenetic analysis showed that CTL-S and CTL-X members from different insects could form orthologous groups. In contrast, no T. xiaojinensis IML orthologues were found in other insects. Remarkable lineage-specific expansion in this subfamily was observed reflecting that these CTLDPs, as important receptors, have evolved diversified members in response to a variety of microbes. Prediction of binding ligands revealed that T. xiaojinensis, a cold-adapted species, conserved the ability of CRDs to combine with Ca2+ to keep its receptors from freezing. Comparative analysis of induction of CTLDP genes after different immune challenges indicated that IMLs might play critical roles in immune defenses. This study examined T. xiaojinensis CTLDPs and provides a basis for further studies of their characteristics.

Living near a Major Road in Beijing: Association with Lower Lung Function, Airway Acidification, and Chronic Cough.

BACKGROUND: The effects of near-road pollution on lung function in China have not been well studied. We aimed to investigate the effects of long-term exposure to traffic-related air pollution on lung function, airway inflammation, and respiratory symptoms. METHODS: We enrolled 1003 residents aged 57.96 ± 8.99 years living in the Shichahai Community in Beijing. Distances between home addresses and the nearest major roads were measured to calculate home-road distance. We used the distance categories 1, 2, and 3, representing <100 m, 100-200 m, and >200 m, respectively, as the dose indicator for traffic-related air pollution exposure. Lung function, exhaled breath condensate (EBC) pH, and interleukin 6 levels were measured. As a follow-up, 398 participants had a second lung function assessment about 3 years later, and lung function decline was also examined as an outcome. We used regression analysis to assess the impacts of home-road distance on lung function and respiratory symptoms. As the EBC biomarker data were not normally distributed, we performed correlation analysis between home-road distance categories and EBC biomarkers. RESULTS: Participants living a shorter distance from major roads had lower percentage of predicted value of forced expiratory volume in 1 s (FEV1% -1.54, 95% confidence interval [CI]: -0.20 to -2.89). The odds ratio for chronic cough was 2.54 (95% CI: 1.57-4.10) for category 1 and 1.97 (95% CI: 1.16-3.37) for category 2, compared with category 3. EBC pH was positively correlated with road distance (rank correlation coefficient of Spearman [rs] = 0.176, P < 0.001). CONCLUSIONS: Long-term exposure to traffic-related air pollution in people who live near major roads in Beijing is associated with lower lung function, airway acidification, and a higher prevalence of chronic cough. EBC pH is a potential useful biomarker for evaluating air pollution exposure.

Effect of Inhaled Budesonide on Interleukin-4 and Interleukin-6 in Exhaled Breath Condensate of Asthmatic Patients.

BACKGROUND: Studies of interleukin (IL)-4 and IL-6 in the exhaled breath condensate (EBC) of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid (ICS) treatment on IL-4 and IL-6 in the EBC of asthmatic patients. METHODS: In a prospective, open-label study, budesonide 200 µg twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma (mean age 42.7 years) for 12 weeks. Changes in asthma scores, lung function parameters (forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEF50], forced expiratory flow at 75% of forced vital capacity, maximum mid-expiratory flow rate) and the concentrations of IL-4 and IL-6 in EBC were measured. RESULTS: Both asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 ± 0.56 pmol/L before treatment to 1.60 ± 0.36 pmol/L after 8 weeks of treatment (P < 0.05) and 1.54 ± 0.81 pmol/L after 12 weeks of treatment (P < 0.01). However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEV1, PEF and FEF50 values (correlation coefficients -0.468, -0.478, and -0.426, respectively). CONCLUSIONS: The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics.

[The relationship between chronic obstructive pulmonary disease and Chlamydiae pneumoniae infection].

OBJECTIVE: To determine the possible association between Chlamydiae pneumoniae (Cpn) infection and chronic obstructive pulmonary disease (COPD). METHODS: This work comprised of two studies. The first was an animal study which involved 40 male Wistar rats. The animals were divided into 4 groups, 10 rats in each group. They were treated with cigarette smoking alone (group A), cigarette smoking and Cpn inoculation (group B), and Cpn inoculation alone (group C), respectively, with a group D as the control. After 6 weeks, Cpn DNA in the lung tissue was detected by PCR, and pulmonary function of the animals was measured. Lung pathological characteristics were scored. In the second study we used PCR to detect Cpn DNA in lung tissues from patients with COPD and control group, meanwhile Cpn IgG and IgA antibodies were also measured. RESULTS: The animal model of COPD was successfully replicated in most rats of group A (88.9%) and all of group B (100%). Group A was greater than group B in changes of pulmonary function, and higher in pulmonary pathological scores, predominantly in inflammatory cell infiltration and proliferation of small airway smooth muscle. There were no statistical differences between group C and group D in changes of pulmonary function. Pulmonary pathological scores were higher in group C than in group D, with statistical value, also predominantly in inflammatory cell infiltration and proliferation of small airway smooth muscle. The positive incidence of Cpn PCR were 88.9% and 80.0% in group A and C respectively. The positive rate of IgG and IgA were 82.4% and 58.8%, respectively. All pulmonary biopsy specimens of COPD and control group were negative. CONCLUSIONS: There were no direct relationship between COPD with Cpn infection. Infection with Cpn cannot induce COPD simply. But it can exacerbated the air obstruction of COPD on the bases of pulmonary impairment by cigarette smoking.