Recombinant Slit2 attenuates tracheal fibroblast activation in benign central airway obstruction by inhibiting the TGF-ß1/Smad3 signaling pathway.

Airway fibrosis is among the pathological manifestations of benign central airway obstruction noted in the absence of effective treatments and requires new drug targets to be developed. Slit guidance ligand 2-roundabout guidance receptor 1 (Slit2-Robo1) is involved in fibrosis and organ development. However, its significance in airway fibrosis has not yet been reported. The study explored how the recombinant protein Slit2 functions in transforming growth factor-ß1 (TGF-ß1)-mediated airway fibrosis in vivo and in vitro. In this study, Slit2 expression initially increased in the tracheal granulation tissues of patients with tracheobronchial stenosis but decreased in the fibrotic tissue. In primary rat tracheal fibroblasts (RTFs), recombinant Slit2 inhibited the expression of extracellular matrices such as Timp1, α-SMA, and COL1A2, whereas recombinant TGF-ß1 promoted the expression of Robo1, α-SMA, and COL1A2. Slit2 and TGF-ß1 played a mutual inhibitory role in RTFs. Slit2 supplementation and Robo1 downregulation inhibited excessive extracellular matrix (ECM) deposition induced by TGF-ß1 in RTFs via the TGF-ß1/Smad3 pathway. Ultimately, exogenous Slit2 and Robo1 knockdown-mediated attenuation of airway fibrosis were validated in a trauma-induced rat airway obstruction model. These findings demonstrate that recombinant Slit2 alleviated pathologic tracheobronchial healing by attenuating excessive ECM deposition. Slit2-Robo1 is an attractive target for further exploring the mechanisms and treatment of benign central airway obstruction.

Combination therapy with long-acting bronchodilators and the risk of major adverse cardiovascular events in patients with COPD: a systematic review and meta-analysis.

INTRODUCTION: Accumulated high-quality data from randomised controlled trials (RCTs) indicate that long-acting muscarinic antagonist (LAMA)/long-acting ß2 agonist (LABA) combination therapy significantly improves clinical symptoms and health status in patients with chronic obstructive pulmonary disease (COPD) and reduces exacerbation risk. However, there is a growing concern that LAMA/LABA therapy may increase the risk of cardiovascular disease in patients with COPD. The aim of this paper is to determine whether the use of LAMA/LABA combination therapy modifies the risk of cardiovascular disease in patients with COPD. METHODS: Two reviewers independently searched Embase, PubMed and Cochrane Library to identify relevant RCTs of LAMA/LABA or LABA/LAMA/inhaled corticosteroids (ICS) for the management of patients with COPD that reported on cardiovascular end-points. The primary outcome was major adverse cardiovascular events (MACE), which was a composite of cardiovascular death, myocardial infarction or stroke. RESULTS: A total of 51 RCTs enrolling 91 021 subjects were analysed. Both dual LAMA/LABA (1.6% versus 1.3%; relative risk 1.42, 95% CI 1.11-1.81) and triple therapy (1.6% versus 1.4%; relative risk 1.29, 95% CI 1.03-1.61) significantly increased the risk of MACE compared with ICS/LABA. The excess risk was most evident in RCTs in which the average underlying baseline risk for MACE was >1% per year. Compared with LAMA only, LABA only or placebo, dual LAMA/LABA therapy did not significantly increase the risk of MACE, though these comparisons may have lacked sufficient statistical power. CONCLUSION: Compared with ICS/LABA, dual LAMA/LABA or triple therapy increases cardiovascular risk in patients with COPD. This should be considered in the context of the incremental benefits of these therapies for symptoms and exacerbation rates in patients with COPD, especially in those with a MACE risk of >1% per year.

GDF15 alleviates the progression of benign tracheobronchial stenosis by inhibiting epithelial-mesenchymal transition and inactivating fibroblasts.

Benign tracheobronchial stenosis (BTS) is a fatal and incurable disease. Epithelial repair and matrix reconstruction play an important role in the wound repair process. If the interstitial context is not restored and stabilized in time, it can lead to pathological fibrosis. Here we attempted to identify cytokines that are involved in promoting wound repair. Growth differentiation factor 15 (GDF15) is a cytokine secreted by tracheal epithelial cells, which is indispensable for the growth of epithelial cells and inhibits the overgrowth of fibroblasts. GDF15 can counteract transforming growth factor-ß (TGFß1) stimulation of epithelial-mesenchymal transition (EMT) in tracheal epithelial cells and inhibit fibroblast activation via the TGFß1-SMAD2/3 pathway. In a rat model of tracheal stenosis, GDF15 supplementation alleviated the degree of tracheal stenosis. These results suggest that GDF15 prevents fibroblast hyperactivation and promotes epithelial repair in injured trachea. GDF15 may be a potential therapy to improve benign tracheobronchial stenosis.

Evaluation of Transbronchial Lung Cryobiopsy Freezing Time, Biopsy Size, Histological Quality, and Incidence of Complication: A Prospective Clinical Trial.

BACKGROUND: Transbronchial cryobiopsy (TBCB), a novel way of obtaining a specimen of lung tissue using a flexible cryoprobe, can obtain large lung biopsies without crush artifacts. The freezing time of TBCB was empirically selected from 3 to 7 s in the previous studies. However, no consensus has yet been reached regarding the optimal freezing time used in TBCB. OBJECTIVES: The primary endpoint was biopsy size in different freezing times. The secondary endpoints included sample histological quality, diagnostic confidence, and complications in different freezing times. METHODS: Patients who were suspected of DPLD requiring histopathological examination for further evaluation were enrolled in this study. Distinct biopsies were obtained by using different freezing times increased from 3 to 6 s sequentially. Samples were reviewed by 2 external expert pathologists. RESULTS: A total of 33 patients were enrolled, and 143 transbronchial cryobiopsies were taken in this trial. An average of 4.33 samples were taken from each patient. The mean biopsy size of different freezing times from 3 to 6 s was 9.10 ± 4.37, 13.23 ± 5.83, 16.26 ± 5.67, and 18.83 ± 7.50 mm2, respectively. A strong correlation between freezing time and biopsy size was observed (r = 0.99, p < 0.01). Statistically significant difference of biopsy size was detected in the freezing time of 3 s versus 4 s (p < 0.01) and 4 s versus 5 s (p = 0.02), but not in the freezing time of 5 s versus 6 s (p = 0.10). Overall bleeding in different freezing times from 3 to 6 s was 53.33%, 67.50%, 89.47%, and 77.14%, respectively. A significantly higher overall bleeding was observed when the freezing time exceeded 4 s (RR = 1.67, p < 0.01). Pneumothorax occurred in 4 cases (12.12%). One lethal case (3.03%) was noted 25 days after TBCB. Lung parenchyma was preserved well in all cryobiopsy samples. Thirty-one (93.94%) patients' histopathological findings were identified as sufficient to establish a CRP diagnosis. There was no statistical difference in diagnostic confidence between different freezing times. CONCLUSION: A longer freezing time was associated with a larger size of the biopsy sample but a higher risk of bleeding. The optimal transbronchial cryobiopsy freezing time is 3-4 s, which is easily achievable and provides an adequate biopsy size whilst creating a safety threshold from complications.

Effect of rebiopsy methods and clinical features on T790M mutation after first-line EGFR-TKI treatment failure.

Aim: This study investigated the association between clinical data and T790M mutation in rebiopsy after EGFR tyrosine kinase inhibitors (EGFR-TKIs) failure, and explored the prognosis of T790M-positive patients. Methods: Patients with non-small-cell lung cancer undergoing rebiopsy after first-generation TKI failure were reviewed. Results & conclusion: Patients with brain metastases, negative TP53, initial 19del and longer initial PFS had higher positive rate of T790M. The median progression-free survival (PFS) of T790M-positive patients with cytology and tissue rebiopsy were longer than patients with liquid rebiopsy. The median PFS of T790M-positive patients rebiopsied by ordinary bronchoscope and endobronchial ultrasound-guided transbronchial lung biopsy with a guided sheath (EBUS-GS-TBLB) were longer than that of the patients rebiopsied by EBUS transbronchial needle aspiration (TBNA).

Lay abstract A specific genetic mutation, T790M, is the main cause of drug resistance in patients with lung cancer receiving a type of drug called EGFR tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib. We explored the factors that influence the prognosis of T790M-positive patients and how this mutation causes resistance. We found a number of biomarkers that are linked to higher expression of T790M, including brain metastases and longer initial treatment period of EGFR-TKI. The median length of time before tumors started progressing in T790M-positive patients who underwent cytology and tissue rebiopsy was longer than patients who received a blood biopsy. The length of time before progression in patients undergoing different rebiopsy methods (such as ordinary bronchoscope and endobronchial ultrasound bronchoscope) was different.

Left Main Bronchus Stenosis Lesion, Neutrophil Count, and Platelet Count Are Predictors of Post-Tuberculosis Bronchomalacia.

BACKGROUND Post-tuberculosis bronchomalacia (PTBM) is one of the main conditions occurring in patients after tracheobronchial tuberculosis (TBTB), and is also associated with the recurrence of symptoms. The present study aimed to investigate the predictors of PTBM in patients who had been undergoing appropriate TB treatment. MATERIAL AND METHODS Clinical data of 104 patients with symptomatic airway stenosis after TBTB between January 01, 2019 and June 31, 2020 were recorded and analyzed. The association between baseline clinical characteristics, laboratory results, and PTBM was calculated with logistical regression. The time from onset of bronchoscopic intervention was examined by Kaplan-Meier estimates; differences between the 2 groups were tested by the log-rank test. RESULTS Fifty-seven patients (54.81%) had PTBM. In the multivariate logistical analysis, the left main bronchus stenosis lesion (odds ratio [OR]=3.763), neutrophil (NEUT) count (OR=1.527), and platelet (PLT) (OR=1.010) count were predictors of PTBM. During follow-up, patients with BM had a significantly longer duration from onset of bronchoscopic intervention than patients without BM (hazard ratio=2.412, P<0.0001). Further, all patients needing long-term bronchoscopic intervention therapy were subsequently identified as having PTBM. Additionally, blood PLT counts were significantly decreased to normal levels in the non-BM group (P<0.05), but not in the BM group (P>0.05). CONCLUSIONS PTBM is most likely to occur in the left main bronchus. The inflammatory and immune responses associated with NEUT and PLT may represent therapeutic targets of PTBM. Our study is the first to report that decreased blood PLT count has the potential to monitor the treatment response.

A Large Central Bronchopleural Fistula Closed by Bronchoscopic Administration of Recombinant Bovine Basic Fibroblast Growth Factor: A Case Report.

A large central bronchopleural fistula (BPF) surrounded by mediastinal tissue was successfully closed by local administration of recombinant bovine basic fibroblast growth factor (rbFGF) using the bronchoscope. No complications were observed during and after this bronchoscopic treatment. This is the first report of the bronchoscopic treatment of a large central BPF by the local spray of rbFGF. The bronchoscopic treatment with rbFGF is a potentially cost-effective method for central BPF surrounded by mediastinal tissue.

Use of high-flow nasal cannula and noninvasive ventilation in patients with COVID-19: A multicenter observational study.

BACKGROUND: The use of high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) in patients with COVID-19 is debated. METHODS: This study was performed in four hospitals of China from January to March 2020. We retrospectively enrolled 23 and 13 COVID-19 patients who used HFNC and NIV as first-line therapy, respectively. RESULTS: Among the 23 patients who used HFNC as first-line therapy, 10 experienced HFNC failure and used NIV as rescue therapy. Among the 13 patients who used NIV as first-line therapy, one (8%) used HFNC as rescue therapy due to NIV intolerance. The duration of HFNC + NIV (median 7.1, IQR: 3.5-12.2 vs. 7.3, IQR: 5.3-10.0 days), intubation rate (17% vs. 15%) and mortality (4% vs. 8%) did not differ between patients who used HFNC and NIV as first-line therapy. In total cohorts, 6 (17%) patients received intubation. Time from initiation of HFNC or NIV to intubation was 8.4 days (IQR: 4.4-18.5). And the time from initiation of HFNC or NIV to termination in patients without intubation was 7.1 days (IQR: 3.9-10.3). Among all the patients, C-reactive protein was independently associated with intubation (OR = 1.04, 95% CI: 1.01-1.07). In addition, no medical staff got nosocomial infection who participated in HFNC and NIV management. CONCLUSIONS: In critically ill patients with COVID-19 who used HFNC and NIV as first-line therapy, the duration of HFNC + NIV, intubation rate and mortality did not differ between two groups. And no medical staff got nosocomial infection during this study.

Endobronchial closure of the bronchopleural fistula with the ventricular septal defect occluder: a case series.

OBJECTIVES: The ventricular septal defect (VSD) occluder has been reported to be a novel method for the closure of bronchopleural fistula (BPF). Our study was to confirm the use of VSD occluder in treating BPF after pneumonectomy or lobectomy. METHODS: We performed a single-center, retrospective study of 10 consecutive patients (8 men and 2 women aged 29-70 years) with postoperative BPF receiving the VSD occluder treatment. We used the HeartR™ Membranous VSD occluder (Lifetech Scientific Co., Shenzhen, China) for the closure of BPF through flexible bronchoscopy under general anesthesia. Demographic characteristics, BPF characteristics, and clinical outcomes were collected from patients' files using the standardized data abstraction forms. RESULTS: The underlying diseases were lung cancer in 6 patients, pulmonary tuberculosis in 3, and bronchiectasis in 1. Right-sided BPFs occurred in 6 patients, and left-sided BPFs occurred in 4. Five patients were underweight with a body mass index < 18.5 kg/m2. The VSD was placed in all 10 patients with a 100% technical success rate and a 70% complete closure rate during follow-up with no complications, on a median follow-up period of 115 days (range 46-975 days). In 1 patient, the VSD occluder was reinstalled with complete closure; in 1 and 2 patients with underweight and chronic empyema, the VSD occluders partially and completely failed with good physical tolerance, respectively. CONCLUSIONS: Our study demonstrated the bronchoscopic closure of BPF after lung resection using the VSD occluder is an off-label but safe and effective method. We prefer to stabilize the BPF by eradicating the underlying diseases and providing nutritional support to those receiving VSD occluder closure treatment.

Diagnostic value of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions.

OBJECTIVE: To evaluate the applied value of rapid on-site evaluation during endobronchial ultrasound (EBUS) with a guide sheath for peripheral pulmonary lesions (PPLs). METHODS: Consecutive patients who underwent EBUS with a guide sheath for PPLs at our hospital from December 2015 to June 2017 in this retrospective study. The samples obtained from each operation were made rapid on-site evaluation at the same time. The results of rapid on-site evaluation were compared with the pathological diagnosis. RESULTS: A total of 127 PPLs in 124 patients were included in the study. 70 lesions were malignancy in the final pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of rapid on-site evaluation for malignancy during EBUS with a guide sheath for PPLs was 88.6%, 98.2%, 98.4%, 87.5% and 92.9%, respectively. CONCLUSIONS: Rapid on-site evaluation during EBUS with a guide sheath has a high diagnostic value for malignant PPLs.

Primary Tracheal Mucosa-Associated Lymphoid Tissue Lymphoma Treated with a Water-Jet Hybrid Knife: A Case Report.

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the trachea is very rare and is easily misdiagnosed as a bronchogenic carcinoma or benign tracheal tumor. Here, we report a clinical case where a new clinical approach involving a water-jet hybrid knife was employed in the diagnosis and treatment of primary tracheal MALT lymphoma.

Clinical Outcomes of Myocardial Bridging versus No Myocardial Bridging in Patients with Apical Hypertrophic Cardiomyopathy.

OBJECTIVE: To determine the prevalence and clinical effects of myocardial bridging (MB) in patients with apical hypertrophic cardiomyopathy (AHCM). METHODS: Angiograms from 212 AHCM patients were reviewed to identify MB. The patients were classified into 2 groups: AHCM with and AHCM without MB. We reviewed patient records on cardiovascular (CV) risk factors, symptoms, CV events, and CV mortality. RESULTS: In all, 60 patients with MB and 100 without MB were included. Rates of angina (61.7 vs. 40%; p = 0.008), mimicking non-ST-segment elevation myocardial infarction (15 vs. 3%, p = 0.013), and Canadian Cardiovascular Society class III/IV angina (18.3 vs. 4%; p = 0.003) were higher in patients with MB than in those without. Mean follow-up periods (65.5 ± 50.5 vs. 64.4 ± 43.6 months, p = 0.378) and CV mortality (3.3 vs. 1%; p = 0.652) were similar in the 2 groups. Kaplan-Meier estimates demonstrated that CV event-free survival rates were lower in patients with MB than in those without (71.7 vs. 88%; p = 0.022). MB, late gadolinium enhancement, and female sex were independent risk factors for CV events in a multivariate Cox regression analysis adjusted for other risk factors. CONCLUSION: More serious symptoms and a higher risk of CV events were observed in AHCM patients with MB than in those without MB. CV mortality was similar in these 2 groups.

Comparison of Long-Term Outcome between Apical and Asymmetric Septal Hypertrophic Cardiomyopathy.

OBJECTIVES: As reported, diagnostic age, gender and presence of outflow tract obstruction have an impact on prognosis in patients with hypertrophic cardiomyopathy. The aim of this study was to compare the long-term outcome between apical hypertrophic cardiomyopathy (ApHCM) and asymmetric septal hypertrophic cardiomyopathy (ASHCM) after the exclusion of these factors. METHODS: A total of 540 patients (270 with ApHCM and 270 with ASHCM) identified in a consecutive single-center cohort were retrospectively studied. The two groups were matched by diagnostic age, gender and the presence of outflow tract obstruction. Clinical characteristics and long-term outcomes were compared. RESULTS: The mean follow-up duration in ASHCM and ApHCM were 6.6 ± 5.5 and 7.6 ± 4.1 years, respectively. During follow-up, 16 patients experienced cardiovascular death in the ASHCM group, while 2 patients experienced cardiovascular death in the ApHCM group (6.3 vs. 0.7%, p < 0.01). Cardiovascular morbidity in the ASHCM and ApHCM groups were 39.9 and 18.5% (p < 0.01). In the multivariate Cox regression analysis late gadolinium enhancement (LGE; HR 4.81, 95% CI 1.28-78.0, p = 0.03) and unexplained syncope (HR 9.68, 95% CI 1.9-17.2, p < 0.01) were independent predictors for cardiovascular mortality. Unexplained syncope was independently associated with a higher risk for sudden cardiac death (HR 4.3, 95% CI 1.2-15.3, p = 0.02). CONCLUSIONS: After eliminating the interference of diagnostic age, gender and outflow tract obstruction, ASHCM represented a worse prognosis with a higher incidence of cardiovascular mortality and morbidity than ApHCM. LGE was a strong predictor for cardiovascular death.

Effectiveness of Alcohol Septal Ablation Versus Transaortic Extended Myectomy in Hypertrophic Cardiomyopathy with Midventricular Obstruction.

OBJECTIVES: Investigate the effectiveness of alcohol septal ablation (ASA) and transaortic extended myectomy (TEM) in hypertrophic cardiomyopathy (HCM) with midventricular obstruction (MVO). BACKGROUND: MVO is less common than subaortic obstruction. Data on the effectiveness of ASA and TEM in MVO are lacking. METHODS: The clinical profiles of 22 patients undergoing ASA and 37 patients undergoing TEM were compared. No patient had apical aneurysm, abnormal chordae, mitral valve replacement or repair. RESULTS: Baseline midventricular pressure gradient and symptoms were comparable between the ASA and TEM groups. During follow-up, both groups demonstrated substantial reduction in pressure gradient (the ASA group: 79.7 ± 21.2 mm Hg to 43.7 ± 28.9 mm Hg, P < 0.001; the TEM group: 69.0 ± 23.9 mm Hg to 15.0 ± 16.9 mm Hg, P < 0.001). The reduction in pressure gradient was greater (78.9 ± 18.6% vs. 46.4 ± 33.4%, P < 0.001) and the residual pressure gradient was lower after TEM versus ASA (P < 0.001). Patients with New York Heart Association class III/IV dyspnea decreased from 59.1 to 18.2% (P = 0.022) in the ASA group and from 56.8 to 5.6% (P < 0.001) in the TEM group. Patients with Canadian Cardiovascular Society class III/IV angina decreased from 40.9 to 9.1% (P = 0.016) in the ASA group and from 32.4 to 0% (P < 0.001) in the TEM group. CONCLUSIONS: While ASA and TEM both improve gradients and symptoms, TEM may provide a more reliable reduction in gradients compared to ASA.

The Prevalence and Long-Term Outcomes of Extreme Right versus Extreme Left Ventricular Hypertrophic Cardiomyopathy.

OBJECTIVES: Extreme left ventricular hypertrophy (LVH) is a known risk factor for sudden cardiac death in hypertrophic cardiomyopathy (HCM). Extreme right ventricular hypertrophy (RVH) is rare, and whether it is linked to a poor outcome is unknown. This study was designed to investigate differences between HCM patients with extreme RVH and those with extreme LVH. METHODS: Among 2,413 HCM patients, 31 with extreme RVH (maximum right ventricular wall thickness ≥ 10 mm) and 194 with extreme LVH (maximum left ventricular wall thickness ≥ 30 mm) were investigated. The main clinical features and natural history were compared between the 2 groups. RESULTS: The prevalence of extreme RVH and extreme LVH was 1.3 and 8.0%, respectively. Patients with extreme RVH tended to be younger and female (p < 0.01). Cardiovascular-related mortality and morbidity within 10 years were significantly greater in the extreme RVH group (p < 0.05). Multivariate analysis demonstrated 3 independent predictors for cardiovascular mortality - extreme RVH, left ventricular end-diastolic dimension ≥ 50 mm, and age ≤ 18 years at baseline - and 2 for morbidity - extreme RVH and presyncope. CONCLUSIONS: Compared with extreme LVH, extreme RVH was quite uncommon in HCM and had a worse prognosis. A right ventricle examination should be performed in routine HCM evaluation.

Incidence of ischemic stroke and systemic embolism in patients with hypertrophic cardiomyopathy, nonvalvular atrial fibrillation, CHA2DS2-VASc score of ≤1 and without anticoagulant therapy.

Data on the risk of ischemic stroke and systemic embolism (iSSE) events in patients with nonvalvular atrial fibrillation (NVAF), a CHA2DS2-VASc score of ≤1, hypertrophic cardiomyopathy (HCM), and without anticoagulant therapy are still lacking. The aim of this study was to investigate the incidence of iSSE events in these patients. We consecutively screened medical records of patients with HCM and NVAF referred to Fuwai Hospital between January 1994 and March 2014. The primary end point was iSSE events, defined as a composite of ischemic stroke and systemic embolism. Follow-up was carried out to ascertain end point status. Medical records of 522 patients with NVAF and HCM were screened. A total of 108 patients (20.7 %) with a CHA2DS2-VASc score of ≤1 and without anticoagulant therapy were enrolled and constituted our study population. After a median follow-up of 2.4 years (range 0.6-14.1 years; 376.2 patient-years), ischemic stroke occurred in 2 patients, resulting in death of 1 patient in the first year and paralysis of the other patient in the fourth year. No other iSSE events occurred. The incidence of iSSE was 0.9 % [95 % confidence interval (CI) 0.0-5.0 %] in the first year, and 0.5 % per 100 patient-years (95 % CI 0.1-1.9 %). The risk of iSSE events seems low in patients with NVAF, a CHA2DS2-VASc score of ≤1, HCM, and without anticoagulant therapy. Multicenter studies with sizeable study populations are needed to validate the risk of iSSE events in these patients.

The association of HDL-apoCIII with coronary heart disease and the effect of statin treatment on it.

BACKGROUND: Apolipoprotein CIII (apoCIII) is considered to impair the anti-atherogenic effect of high density lipoprotein (HDL) in coronary heart disease (CHD) patients, and apoCIII content in HDL (HDL-apoCIII) predicts CHD more accurately. However, the relationship between HDL-apoCIII and CHD, and the effect of statin treatment on HDL-apoCIII are still unclear. The aims of the study are to establish the association of HDL-apoCIII with CHD, and investigate the effect of statin treatment on HDL-apoCIII in CHD patients. METHODS: We conducted a hospital-based observational study. Totally 80 non-CHD patients and 120 CHD patients without statin treatment were previously enrolled in this study. All the CHD patients received statin treatment, and 63 of them were followed after 3 months of regular statin treatment. HDL sample of each patient was isolated by density gradient ultracentrifugation from fasting venous plasma, and HDL-apoCIII of each patient was measured by ELISA method. RESULTS: HDL-apoCIII was significantly higher in CHD patients than non-CHD patients (p < 0.05), and it was still an independent predictor of CHD after adjusting for other factors. Total plasma apoCIII, especially HDL-apoCIII was significantly elevated after statin treatment in CHD patients, whereas total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and apolipoprotein B (apoB) were decreased significantly (p < 0.05). Compared with CHD patients without diabetes mellitus (DM), the effect of statin treatment on apoCIII markers was minor in CHD patients with DM. And HDL-apoCIII correlated with plasma TG significantly in non-CHD and CHD patients (p < 0.05), but the correlation in CHD patients did not exist after statin treatment (p > 0.05). CONCLUSIONS: HDL-apoCIII has a significant and positive association with CHD. Although conventional atherogenic lipid markers have a significantly decrease in CHD patients after statin treatment, HDL-apoCIII has a further elevation at the same time.

[Clinical features and long-term outcome comparison of patients with midventricular obstructive hypertrophic cardiomyopathy and apical hypertrophic cardiomyopathy].

OBJECTIVE: To compare the clinical features and long-term outcome of patients with midventricular obstructive hypertrophic cardiomyopathy (MVOHCM) and patients with apical hypertrophic cardiomyopathy (AHCM) in China. METHODS: This retrospective study analyzed clinical data of 66 patients with MVOHCM and 263 patients with AHCM from a consecutive single-center cohort consisting of 2 413 patients with HCM. The clinical features, cardiovascular mortality and morbidity were compared between the two groups. RESULTS: Compared with the AHCM, patients in the MVOHCM group was younger and more likely to be symptomatic over a mean follow-up of 7 years. The proportion of MVOHCM and AHCM were 2.7% (66/2 413) and 10.9% (263/2 413) (P < 0.001), respectively, in this cohort. Cardiovascular mortality of the two groups were 13.6% (9/66) and 0.8% (2/263) (P < 0.001), and cardiovascular morbidity of the two groups were 53.0% (35/66) and 14.4% (38/263) (P < 0.001). CONCLUSION: MVOHCM is rarer, but the clinical manifestations and long-term outcomes are worse compared with AHCM in this patient cohort.

Nebulized PPARγ agonists: a novel approach to augment neonatal lung maturation and injury repair in rats.

BACKGROUND: By stimulating lipofibroblast maturation, parenterally administered peroxisome proliferator-activated receptor γ (PPARγ) agonists promote lung homeostasis and injury repair in the neonatal lung. In this study, we determined whether PPARγ agonists could be delivered effectively via nebulization to neonates, and whether this approach would also protect against hyperoxia-induced lung injury. METHODS: One-day old Sprague-Dawley rat pups were administered PPARγ agonists rosiglitazone (RGZ, 3 mg/kg), pioglitazone (PGZ, 3 mg/kg), or the diluent, via nebulization every 24 h; animals were exposed to 21% or 95% O2 for up to 72 h. Twenty-four and 72 h following initial nebulization, the pups were sacrificed for lung tissue and blood collection to determine markers of lung maturation, injury repair, and RGZ and PGZ plasma levels. RESULTS: Nebulized RGZ and PGZ enhanced lung maturation in both males and females, as evidenced by the increased expression of markers of alveolar epithelial and mesenchymal maturation. This approach also protected against hyperoxia-induced lung injury, since hyperoxia-induced changes in bronchoalveolar lavage cell and protein contents and lung injury markers were all blocked by nebulized PGZ. CONCLUSION: Nebulized PPARγ agonist administration promotes lung maturation and prevents neonatal hyperoxia-induced lung injury in both males and females.

The efficacy and safety of ivabradine hydrochloride versus atenolol in Chinese patients with chronic stable angina pectoris.

PURPOSE: The aim of this study was to assess the efficacy and safety of ivabradine (Iva) noninferiority to atenolol (Aten) in Chinese patients with chronic stable angina pectoris. METHODS: In this double-blind, double-dummy trial, patients with symptomatic angina pectoris and positive exercise tolerance test were randomized into the Iva [5 or 7.5 mg bis in die (BID)] or Aten group (12.5 or 25 mg BID) according to computer-generated random numbers for 12 weeks. RESULTS: One hundred and sixty-eight patients were randomized to the Iva group and 166 to the Aten group. In a full analysis set, increases in the total exercise duration (TED) were 54.3 ± 120.1 seconds with Iva 5 mg and 58.8 ± 114.7 seconds with Aten 12.5 mg at the fourth week, and at the 12th week, TED improved by 84.1 ± 130.5 seconds with Iva and 77.8 ± 126.6 seconds with Aten (95%CI: -21.4-34.1 seconds, p = 0.0011 for noninferiority). The analysis of per protocol set yielded similar results (95%CI: -31.4-33.0 seconds, p = 0.0131 for noninferiority). Heart rate was reduced in both groups at rest and during peak exercise. There were small, nonsignificant differences in the number of adverse events between the two groups (66 in Iva and 73 in Aten, p > 0.05). Nine patients (5.42%) were reported to develop phosphenes/luminous phenomena and blurred vision in the Iva group (p = 0.0035). CONCLUSIONS: Iva is effective in reducing heart rates and improving exercise capacity and noninferior to Aten in Chinese patients with chronic stable angina pectoris. Iva is well tolerated and safe.