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It has been generally believed that cancer-associated fibroblasts (CAFs) have the ability to increase the process of tumor angiogenesis. However, the potential mechanisms by which cancer-derived exosomes in lung cancer (LC) remains to be investigated. LC-derived exosomes were administrated to NIH/3T3 cells. A variety of experiments were conducted to investigate the proangiogenic factors of CAFs, including Western blot, RT-PCR, colony formation assay, tube formation assay, Matrigel plug assay et al. In addition, the impact of JAK2/STAT3 signaling pathway were also explored. The role of hsa-miR-210 was identified with microarray profiling and validated in vitro and in vivo assays. The target of miR-210 was screened by RNA pull down, RNA-sequencing and then verified. It was shown that LC-derived exosomes could induce cell reprogramming, thus promoting the fibroblasts transferring into CAFs. In addition, the exosomes with overexpressed miR-210 could increase the level of angiogenesis and vice versa, which suggested the miR-210 secreted by the LC-derived exosomes may initiate the CAF proangiogenic switch. According to our analysis, the miR-210 had the ability of elevating the expression of some proangiogenic factors such as MMP9, FGF2 and vascular endothelial growth factor (VEGF) a (VEGFa) by activating the JAK2/STAT3 signaling pathway, ten-eleven translocation 2 (TET2) was identified as the target of miR-210 in CAFs which has been involved in proangiogenic switch. miR-210 was overexpressed in serum exosomes of untreated non-small cell LC (NSCLC) patients. We concluded that the promotion effect of exosomal miR-210 on proangiogenic switch of CAFs may be explained by the modulation of JAK2/STAT3 signaling pathway and TET2 in recipient fibroblasts.

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BackgroundSex plays an important role in the clinical expression and prognosis of various cardiovascular diseases. This study was designed to observe the effects of sex on hypertrophic cardiomyopathy (HCM).Methods and ResultsA total of 621 unrelated patients with HCM without heart failure (460 males) were enrolled from 1999 to 2011. Compared to male patients, at baseline female patients were older at diagnosis (49.6±17.2 years vs. 46.7±14.4 years, P = 0.033), and had greater frequency of left ventricular outflow tract obstruction (72/161, 44.7% vs. 149/460, 32.4%, P = 0.005). During the average four year follow-up period (range 2–7 years), survival analysis showed that the incidences of mortality from all causes, cardiovascular death and progression to chronic heart failure were greater in women than in men (P = 0.031, 0.040 and 0.012, respectively). After adjustment for multiple factors that may confound survival and cardiac function, female sex remained an independent risk factor for all-cause mortality, cardiovascular death, and chronic heart failure [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.21–3.95, P = 0.010; HR 2.19, 95% CI 1.17–4.09, P = 0.014; HR 1.73, 95% CI 1.12–2.69, P = 0.014, respectively] in HCM patients. Subgroup analysis revealed that female sex as a risk factor was identified only in patients younger than 50 years old (P = 0.011, 0.011 and 0.009, respectively), but not for those 50 years or older.ConclusionOur results suggest that female sex is associated with worse survival and heart failure in HCM patients. Further studies are required to determine whether female hormones modify the clinical expression and prognosis of HCM.

Objectives: The clinical outcomes of hypertrophic cardiomyopathy (HCM) are largely unpredictable. This study aimed to investigate the relationship between atrial fibrillation (AF) and its prognostic implications in Chinese patients with HCM. Methods: From 1999 to 2011, 654 unrelated HCM patients were consecutively recruited at Fuwai Hospital. Medical history, including electrocardiographic and echocardiographic data, was analyzed. Results: AF was documented in 158 patients (24%). During follow-up of 4.2 ± 2.8 years, Kaplan-Meier analysis revealed that the presence of AF was associated with an increased risk for all-cause death (p = 0.001), cardiovascular death (p < 0.001), severe heart failure (p < 0.001) and ischemic stroke (p < 0.001). Multivariate analysis identified AF as an independent predictor of stroke-related death (HR 6.71, 95% CI 1.23-38.58, p = 0.03), advanced heart failure (HR 1.83, 95% CI 1.04-3.22, p = 0.04) and ischemic stroke (HR 9.98, 95% CI 4.06-24.53, p < 0.001). Furthermore, enlarged left atrial diameter was positively related to all-cause death (HR 1.09, 95% CI 1.05-1.13, p < 0.001), cardiovascular death (HR 1.08, 95% CI 1.04-1.20, p < 0.001) and development of advanced heart failure (HR 1.05, 95% CI 1.01-1.10, p = 0.01). Conclusions: AF predicts poor outcomes for patients with HCM. Left atrial dilation is also related to an adverse prognosis and provides additional prognostic information.

Rationale: The relationship between treatment-related impairment of pulmonary function in adult survivors of childhood cancer and subsequent physical function has not been studied. Objectives:In this prospective evaluation of 606 adult survivors of childhood cancer, we sought to determine the risk factors for, as well as the functional impact of, clinically ascertained pulmonary function impairment.Methods: We measured FEV 1 , FVC, total lung capacity (TLC), and single-breath diffusing capacity of the lung for carbon monoxide corrected for hemoglobin (DL COcorr ), expressing the results as percent predicted and lower limit of normal (LLN) values, and we also assessed functional exercise capacity (6-minute-walk distance). Lung radiation exposure was expressed as the estimated percentage of lung tissue that received at least 10 Gy (V10). Associations of clinical and treatment factors with pulmonary function measures were assessed using log-binomial regression to calculate relative risks and 95% confidence intervals. Measurements and Main Results:The participants' median age at evaluation was 34.2 years, and the median elapsed time from diagnosis was 21.9 years. Among the sample population, 50.7% had an FEV 1 percent predicted less than 80%, 47.2% had an FVC percent predicted less than 80%, 31.2% had a TLC percent predicted less than 75%, and 44.6% had DL COcorr percent predicted less than 75%. Also, 49.0% had FEV 1 less than the LLN on the basis of the Global Lung Function Initiative (GLI) criteria, and 45.4% had FVC less than LLN. Obstructive lung defects (FEV 1 /FVC, ,0.7) were found in 0.8%, but none had obstructive lung defects on the basis of the GLI criterion of FEV 1 /FVC less than the LLN. Restrictive lung defects (TLC, ,75%) were found in 31.2% of participants. V10 and elapsed time since diagnosis were associated with abnormal FEV 1 and FVC based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 criteria, and with abnormal FEV 1 using the GLI criterion. Age at diagnosis was an additional risk factor for abnormal FVC based on the GLI criteria. Age at diagnosis and V10 were associated with abnormal TLC. Increased body mass index, V10, and elapsed time since diagnosis were risk factors for abnormal DL COcorr . Abnormal pulmonary function tests were associated with decreased 6-minute walk distance.Conclusions: Impaired pulmonary function in adult survivors of childhood cancer is associated with decreased physical function. These patients may benefit from interventions designed to preserve and/or improve pulmonary function.

BackgroundElevated high‐sensitivity C‐reactive protein (hsCRP) has been associated with increased risks of adverse outcomes of various cardiovascular diseases. The relationship between hsCRP and the prognosis of hypertrophic cardiomyopathy remains to be evaluated.Methods and ResultsThe study used an observational cohort methodology. A total of 490 patients were enrolled in the Fuwai Hospital from 2001 to 2011 and were followed for 3.7±2.0 years. According to the risk category of hsCRP, subjects in the high hsCRP group (>3.0 mg/L) had a higher risk of developing adverse events than the low hsCRP group (<1.0 mg/L): cardiovascular death (adjusted hazard ratios[HR] 5.41, 95% CI 1.96–14.93, P=0.001), all‐cause mortality (adjusted HR 4.78, 95% CI 1.99–11.47, P<0.001), sudden cardiac death (adjusted HR 11.29, 95% CI 1.38–92.20, P=0.024), and heart failure–related death (adjusted HR 4.38, 95% CI 1.15–16.60, P=0.030). Similarly, the continuous variable of hsCRP was also an independent predictor for adverse outcomes: cardiovascular death (adjusted HR 1.15, 95% CI 1.06–1.25, P=0.001), all‐cause mortality (adjusted HR 1.17, 95% CI 1.09–1.26, P<0.001), sudden cardiac death (adjusted HR 1.20, 95% CI 1.06–1.36, P=0.003), and heart failure–related death (adjusted HR 1.15, 95% CI 1.02–1.30, P=0.020).ConclusionsOur results indicate that elevated plasma hsCRP is associated with increased risk for adverse outcomes in patients with hypertrophic cardiomyopathy.