The role of lifestyle in the association between long-term ambient air pollution exposure and cardiovascular disease: a national cohort study in China.

BACKGROUND: Cardiovascular disease (CVD) caused by air pollution poses a considerable burden on public health. We aim to examine whether lifestyle factors mediate the associations of air pollutant exposure with the risk of CVD and the extent of the interaction between lifestyles and air pollutant exposure regarding CVD outcomes. METHODS: We included 7000 participants in 2011-2012 and followed up until 2018. The lifestyle evaluation consists of six factors as proxies, including blood pressure, blood glucose, blood lipids, body mass index, tobacco exposure, and physical activity, and the participants were categorized into three lifestyle groups according to the number of ideal factors (unfavorable, 0-1; intermediate, 2-4; and favorable, 5-6). Satellite-based spatiotemporal models were used to estimate exposure to ambient air pollutants (including particles with diameters ≤ 1.0 µm [PM1], ≤ 2.5 µm [PM2.5], ≤ 10 µm [PM10], nitrogen dioxide [NO2], and ozone [O3]). Cox regression models were used to examine the associations between air pollutant exposure, lifestyles and the risk of CVD. The mediation and modification effects of lifestyle categories on the association between air pollutant exposure and CVD were analyzed. RESULTS: After adjusting for covariates, per 10 µg/m3 increase in exposure to PM1 (HR: 1.09, 95% CI: 1.05-1.14), PM2.5 (HR: 1.04, 95% CI: 1.00-1.08), PM10 (HR: 1.05, 95% CI: 1.03-1.08), and NO2 (HR: 1.11, 95% CI: 1.05-1.18) was associated with an increased risk of CVD. Adherence to a healthy lifestyle was associated with a reduced risk of CVD compared to an unfavorable lifestyle (HR: 0.65, 95% CI: 0.56-0.76 for intermediate lifestyle and HR: 0.41, 95% CI: 0.32-0.53 for favorable lifestyle). Lifestyle played a significant partial mediating role in the contribution of air pollutant exposure to CVD, with the mediation proportion ranging from 7.4% for PM10 to 14.3% for PM2.5. Compared to an unfavorable lifestyle, the relative excess risk due to interaction for a healthier lifestyle to reduce the effect on CVD risk was - 0.98 (- 1.52 to - 0.44) for PM1, - 0.60 (- 1.05 to - 0.14) for PM2.5, - 1.84 (- 2.59 to - 1.09) for PM10, - 1.44 (- 2.10 to - 0.79) for NO2, and - 0.60 (- 1.08, - 0.12) for O3. CONCLUSIONS: Lifestyle partially mediated the association of air pollution with CVD, and adherence to a healthy lifestyle could protect middle-aged and elderly people from the adverse effects of air pollution regarding CVD.

Design of a single-center, phase II trial to explore the efficacy and safety of 'R-ISV-RO' treatment in advanced tumors.

Background: The authors' preclinical study has confirmed that RO adjuvant (composed of TLR 7 agonists [imiquimod/R837] and OX40 agonists) injected into local lesions induces the regression of both primary tumor and distant metastasis. The authors propose to realize local control and exert abscopal effect through an 'R-ISV-RO' in situ strategy plus anti-PD-1 monoclonal antibody in advanced tumors. Methods: This study is a single-center, exploratory, phase II trial to evaluate the efficacy and safety of R-ISV-RO plus anti-PD-1 monoclonal antibody in advanced tumors. 30 patients with one or more measurable extracerebral lesions that are accessible for radiation or injection will be enrolled. The primary endpoint is the objective response rate of target lesions. Discussion/Conclusion: The efficacy and safety of the novel strategy will be further validated through this clinical trial.Clinical trial registration: ChiCTR2100053870 (www.chictr.org.cn/).

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An investigator-initiated clinical study in patients with refractory or recurrent solid tumors: 'R-ISV-FOLactis' trial.

Aim: In situ vaccination, a kind of therapeutic cancer vaccine, can be realized by radiotherapy and intratumoral immune injection. This study combines intratumoral injection, radiotherapy and PD-1 blockade for synergistic antitumor effect. Materials & methods: Patients with advanced solid tumors who are unresponsive or intolerant to standard treatment will be treated with hypofractionated radiotherapy, intratumoral injection of FOLactis, PD-1 blockade. The primary end point is to observe the efficacy and safety, with the secondary end point to evaluate abscopal effects and the correlation between the immunological rationale and efficacy. Discussion: The combined regimen will be utilized to trigger antitumor immunity and is expected to be feasible and effective and provide a novel option for the comprehensive treatment of cancer.Clinical Trial Registration: ChiCTR2200060660 (ChiCTR.gov.cn).

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The association between serum uric acid / serum creatinine ratio and in-hospital outcomes in elderly patients with acute myocardial infarction.

BACKGROUND: The role of Serum uric acid (SUA) in acute myocardial infarction (AMI) was controversial, which might be influenced by the renal clearance function of the patients. The present study aimed to explore the association between serum uric acid to serum creatinine ratio (SUA/Scr), reflecting a net production of SUA, and the in-hospital outcomes of elderly patients with AMI. METHODS: In this retrospective study, a total of 330 elderly AMI patients (≥ 75 years) were enrolled. Data of SUA and Scr on admission were collected to calculate SUA/Scr ratio. Logistic regression analysis and receiver-operating curves were performed to assess the association between SUA/Scr ratio and in-hospital major adverse cardiovascular events (MACEs) and all-cause death. RESULTS: Among the 330 patients, 68 patients had MACEs and 44 patients died. Patients with MACEs or died had lower SUA/Scr values compared with those without MACEs or survival (P < 0.05). Univariate logistic analysis showed that a lower value of SUA/Scr (< 3.45) was significantly associated with in-hospital MACEs (odd ratios (OR): 2.359, 95% confidential interval (CI): 1.369-4.065, P = 0.002) and death (OR: 2.424, 95% CI: 1.275-4.608, P = 0.007). After correcting for confounding factors, a lower SUA/Scr value was still independently associated with in-hospital MACEs (OR: 2.144, 95% CI: 1.169-3.934, P = 0.014) and death (OR: 2.125, 95% CI: 1.050-4.302, P = 0.036). Subgroup analysis showed that the association between a lower SUA/Scr ratio and increased risk of in-hospital outcomes could observed only in males (OR: 2.511, 95%CI: 1.211-5.207, P = 0.013 for MACEs; OR: 2.730, 95% CI: 1.146-6.502, P = 0.023 for death). CONCLUSIONS: A lower SUA/Scr ratio was associated with an increased risk of in-hospital adverse events in elderly patients with AMI, especially in males, which maybe a marker of poor outcomes for elderly AMI patients.

Remnant cholesterol, preinflammatory state and chronic kidney disease: association and mediation analyses.

Blood lipid management is a key approach in the prevention of chronic kidney disease (CKD). Remnant cholesterol (RC) plays an important role in the development of multiple diseases via chronic inflammation. The aim of our study was to determine the relationship between RC and CKD and explore the role of inflammation in this relationship. The 7696 subjects from the Chinese Health and Nutrition Survey were divided into four subgroups according to the quartile of RC. The estimated glomerular filtration rate was calculated using the CKD Epidemiology Collaboration equation. Fasting RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Logistic regression analysis was employed to evaluate the relationships between RC and CKD. Mediation analysis was undertaken to identify potential mediators of high-sensitivity C-reactive protein (hs-CRP) and white blood cells (WBCs). Of all participants, the mean age was 51 years, and the male accounted for 47.8%. The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of remnant cholesterol were 1.40 (1.10-1.78, p for trend = 0.006) for CKD. RC and preinflammatory markers have combined effect on CKD. The preinflammatory state, presented by increased hs-CRP or WBCs, partially mediated the association between RC and CKD with proportion of 10.14% (p = 0.002) and 11.65% (p = 0.012), respectively. In conclusion, this study suggested a positive relationship between RC and CKD, which was partially mediated by preinflammatory state. These findings highlight the importance of RC and inflammation in renal dysfunction.IMPACT STATEMENTWhat is already known on this subject?: Dyslipidemia plays an important role in the development of chronic kidney disease (CKD). Remnant cholesterol (RC), as a triglyceride-rich particle, can contribute to target organ damage, primarily through inflammatory pathways. However, the relationship between RC and CKD in the community-dwelling population, particularly the role of inflammation, is not yet fully understood.What do the results of this study add?: This study shows that RC was significantly associated with CKD. RC and preinflammatory status exhibit a combined effect on CKD. Preinflammatory state, presented by increased high-sensitivity C-reactive protein or white blood cells, partially mediated the association between RC and CKD.What are the implications of these findings for clinical practice and/or further research?: The study provides us with a better understanding of the role of RC and inflammation in kidney dysfunction and raises the awareness of RC in the management of CKD.

Prognostic implications of machine learning-derived echocardiographic phenotypes in community hypertensive patients.

BACKGROUND: Echocardiogram is commonly used to evaluate cardiac remodeling in hypertension (HTN). However, study on echocardiographic phenotypes and their prognostic implications in HTN is limited. OBJECTIVE: We aimed to evaluate the prognostic implications echocardiographic phenotypes in community hypertensive patients. METHOD: A total of 1881 community hypertensive patients without overt cardiovascular disease and severe renal disease (mean age 62.8 years, women 57.9%) were included. Using Two-Step cluster analysis with four conventional echocardiographic variables, two clusters with distinct echocardiographic phenotypes were identified. RESULT: The Cluster 1 (namely "mild-remodeling" HTN; n = 1492) had low prevalence of enlarged left atrium (LA; 0.9%) and left ventricular hypertrophy (LVH; 16.2%) and better LV diastolic function. They were younger and more likely to be men and had lower comorbid burden. The Cluster 2 (namely "severe-remodeling" HTN; n = 389) had higher prevalence of enlarged LA (26.0%) and LVH (83.0%) and worse LV diastolic function. They were older and more likely to be women and had higher comorbid burden. After a median follow-up of 4.2 years, compared to the Cluster 1, the Cluster 2 had higher incidence of cardiovascular (4.1% vs 1.7%; P = .006) and all-cause (9.8% vs 4.8%; P < .001) death, with adjusted hazard ratio of 2.80 (95% CI 1.39-5.62; P = .004) and 2.04 (95% CI 1.32-3.14; P < .001) respectively. CONCLUSION: These findings indicate that the conventional echocardiographic variables-based algorithm could help identify asymptomatic community hypertensive patients at risk for cardiovascular and all-cause death. Further studies are needed to develop and validate phenotype-specific prevention and intervention strategies in HTN.

The role of remnant cholesterol beyond low-density lipoprotein cholesterol in diabetes mellitus.

BACKGROUND: Previous research has linked elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) with diabetes mellitus (DM). The present study aims to estimate the RC-related DM risk beyond LDL-C, and to investigate the extent to which the association of RC and DM is mediated via insulin resistance and inflammation. METHODS: We enrolled 7308 individuals without previous history of DM into the present study from the China Health and Nutrition Survey. Fasting RC was calculated as total cholesterol minus LDL-C and high-density lipoprotein cholesterol. Subjects were divided into four groups according to their LDL-C (100 mg/dL) and RC (24 mg/dL) levels to evaluate the role of LDL-C vs. RC on DM. A logistic regression analysis was then employed to evaluate the relationships between the discordant/concordant LDL-C and RC and DM. A mediation analysis was undertaken to identify potential mediators. RESULTS: Of all the participants, a total of 625 (8.55%) patients were newly diagnosed with DM. Compared to the high LDL-C/low RC group, the low LDL-C/high RC group was more common in DM patients. After a multivariate adjustment, elevated LDL-C and RC were associated with DM. Moreover, the low LDL-C/high RC group and the high LDL-C/low RC group manifested a 4.04-fold (95% CI 2.93-5.56) and 1.61-fold (95% CI 1.21-2.15) higher risk of DM, relative to those with low LDL-C/low RC. The subgroup analysis indicated that low LDL-C/high RC was more likely to be related to DM in females. Similar results were also shown when the sensitivity analyses were performed with different clinical cut-points of LDL-C. Insulin resistance and inflammation partially mediated the association between RC and DM. CONCLUSIONS: Our findings provided evidence for RC beyond the LDL-C associations with DM that may be mediated via insulin resistance and the pro-inflammatory state. In addition, women are more susceptible to RC exposure-related DM.

Elevated uric acid is related to the no-/slow-reflow phenomenon in STEMI undergoing primary PCI.

BACKGROUND: No-/slow-reflow phenomenon (NRP) is a severe complication in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). This study aimed to explore the relationship between elevated serum uric acid (SUA) and NRP in patients with STEMI undergoing pPCI, focusing on inflammation and angiographic findings. METHODS: A total of 610 patients who received pPCI for STEMI were retrospectively enrolled. Patients were divided into a hyperuricaemia group and a non-hyperuricaemia group according to SUA levels. Clinical information and angiographic indicators were compared between the two groups. Thrombolysis in myocardial infarction (TIMI) flow and TIMI myocardial perfusion grade (TMPG) <3 after stent implantation were defined as TIMI-NRP and TMPG-NRP, respectively. A logistic model was used to analyse the relationship between hyperuricaemia and NRP. RESULTS: The hyperuricaemia group had a higher incidence of TIMI-NRP (24.9% vs 14.0%, p < .001) and TMPG-NRP (33.0% vs 24.9%, p = .03), higher levels of C-reactive protein (7.2 vs 4.1 mg/L, p < .001) and worse left ventricular ejection fraction (51.5% vs 54.0%, p = .002) than the non-hyperuricaemia group. As for angiographic findings, there was no significant difference between the two groups in terms of lesion characteristics measured by quantitative coronary angiography. After multivariable adjustment, elevated SUA was significantly associated with TIMI-NRP (odds ratio: 1.94, 95% confidence interval: 1.24-3.01, p = .003). Subgroup analysis showed that the effect of hyperuricaemia in TIMI-NRP was more pronounced in patients with delayed perfusion as well as in patients with diabetes mellitus. CONCLUSIONS: Elevated SUA is associated with severe inflammation and has higher incidence of TIMI-NRP in patients with STEMI undergoing pPCI, especially in those with delayed perfusion or diabetes mellitus.

Air quality improvement and cognitive function benefit: Insight from clean air action in China.

INTRODUCTION: Epidemiological evidence suggests associations between long-term exposure to air pollution and accelerated cognitive decline. China implemented a strict clean air action plan in 2013; however, it is unclear whether the improvement of air quality has alleviated cognitive impairment in the population. METHODS: From the China Health and Retirement Longitudinal Study, 8536 Chinese adults were enrolled in 2011 and followed up in 2015. Satellite-based spatiotemporal models were used to estimate exposure to air pollutants (including particles with diameters ≤1.0 µm [PM1], ≤2.5 µm [PM2.5], ≤10 µm [PM10], nitrogen dioxide [NO2], and ozone [O3]). Cognitive function was evaluated using a structured questionnaire in three dimensions: episodic memory, orientation and attention, and visuoconstruction. The associations between changes in the levels of air pollutants and cognitive function were elucidated by a logistic model. The Bayesian Kernel Machine Regression (BKMR) model was applied to evaluate the cumulative effect of air pollutants. RESULTS: The mean (standard deviation) age of all participants was 58.6 (8.7) years. The odds ratio (95% confidence interval) between the highest and the lowest quartile of PM1 exposure reduction for cognitive impairment was 0.46 (0.41, 0.53) after adjusting for confounders. Similar protective effects of cognitive function were observed with the decrease in the level of PM2.5 (0.34 [0.30, 0.39]), PM10 (0.54 [0.48, 0.62]), and NO2 (0.59 [0.51, 0.67]), while the reduction in O3 appeared to be less related to changes in cognitive function (OR: 0.97 [0.85, 1.10]). The protective association of PM1 reduction was stronger in males than in females. Decreased in PM2.5 dominate the cognitive function benefit relative to PM1, PM10, NO2. CONCLUSIONS: The implementation of the clean air action plan led to a significant reduction in PM1, PM2.5, PM10, and NO2, which could slow the decline of cognitive function, while a reduction in O3 may not.

Elevated serum uric acid was associated with pre-inflammatory state and impacted the role of HDL-C on carotid atherosclerosis.

BACKGROUND AND AIMS: Uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) are positively and negatively associated with atherosclerosis, respectively. UA and HDL-C are involved in the balance of proinflammatory and anti-inflammatory processes in atherosclerosis. However, it is still unclear whether UA affects the effect of HDL-C on atherosclerosis. METHODS AND RESULTS: In this retrospective study, we enrolled 1437 patients with multiple risk factors for atherosclerosis. Patients were categorized into two groups according to their baseline UA level. Multivariate logistic regression analysis and restricted cubic spline curves were used to assess the relationship between HDL-C and carotid atherosclerosis (abnormal carotid intima-media thickness [cIMT] and carotid artery plaque) at different UA levels. Compared to patients with normouricemia, patients with hyperuricemia were older and had a more extensive history of disease and unhealthy behavior. In the normouricemia group, multivariate-adjusted odds ratios (95% CIs) for HDL-C were 0.55 (0.33-0.92) for abnormal mean cIMT, 0.59 (0.35-1.00) for abnormal maximum cIMT, and 0.53 (0.29-0.94) for the occurrence of carotid artery plaque, while the correlation between each of these three indicators with HDL-C were not significant in those with hyperuricemia. Spline regression models yielded similar results. The effect of UA on the association between HDL-C and carotid atherosclerosis remained in the subset of patients with optimal low-density lipoprotein cholesterol. CONCLUSION: Elevated UA marks a pre-inflammatory state and impacts the role of HDL-C on carotid atherosclerosis.

Association between sociodemographic status and cardiovascular risk factors burden in community populations: implication for reducing cardiovascular disease burden.

BACKGROUND: We aimed to evaluate the burden of cardiovascular (CV) risk factors in the community populations of Guangdong Province and its association with sociodemographic status (SDS). METHOD: The data were from the community populations of Guangdong Province who have participated in the China PEACE Million Persons Project between 2016 and 2020 (n = 102,358, women 60.5% and mean age 54.3 years). The prevalence of CV risk factors (smoking, drinking, overweight/obesity, hypertension, dyslipidemia and diabetes mellitus) and its association with SDS (age, sex and socioeconomic status [SES]) was evaluated cross-sectionally. RESULTS: The prevalence of overweight/obesity was 48.9%, hypertension 39.9%, dyslipidemia 18.6%, smoking 17.2%, diabetes mellitus 16.1% and drinking 5.3%. Even in young adults (aged 35-44), nearly 60% had at least 1 CV risk factor. Overweight/obesity often coexisted with other risk factors, including smoking, hypertension, dyslipidemia and diabetes mellitus. The proportion of people with no risk factor decreased with increasing age. Women were more likely than men to have no CV risk factor (29.4% vs. 12.7%). People with ≥ high school degree were more likely than those with < high school to have no risk factor (28.5% vs. 20.4%), and farmers were less likely than non-farmers to have no risk factor (20.8% vs. 23.1%). CONCLUSION: The burden of CV risk factors is high and varied by SDS in the community populations of Guangdong Province. Cost-effective and targeted interventions are needed to reduce the burden of CV risk factors at the population level.

Comparison of Prognostic Value Among 4 Risk Scores in Patients with Acute Coronary Syndrome: Findings from the Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) Project.

BACKGROUND Accurate risk assessment and prospective stratification are of great importance for treatment of acute coronary syndrome (ACS). However, the optimal risk evaluation systems for predicting different type of ACS adverse events in Chinese population have not been established. MATERIAL AND METHODS Our data were derived from the Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) Project, a multicenter registry program. We incorporated data on 44 750 patients in the study. We compared the performance of the following 4 different risk score systems with regard to prediction of in-hospital adverse events: the Global Registry for Acute Coronary Events (GRACE) risk score system; the age, creatinine and ejection fraction (ACEF) risk score system, and its modified version (AGEF), and the Canada Acute Coronary Syndrome (C-ACS) risk assessment system. RESULTS Admission AGEF risk score was a better prognosis index of potential for in-hospital mortality for patients with ST segment elevation myocardial infarction (STEMI) than GRACE risk score (AUC: 0.845 vs 0.819, P=0.012), ACEF (AUC: 0.845 vs 0.827, P=0.014), C-ACS (AUC: 0.845 vs 0.767, P<0.001). In patients with non-ST segment-elevation acute coronary syndrome (NSTE-ACS), there was no statistically significant difference between the GRACE risk scale and AGEF (AUC: 0.853 vs 0.832, P=0.140) for in-hospital death. CONCLUSIONS AGEF risk score showed a non-inferior utility compared with the other 3 scoring systems in estimating in-hospital mortality in ACS patients.

Correlation of left ventricular longitudinal strain and E/e' ratio in primary hypertension patients.

Objectives: The aim of this study is to explore and compare the relationships of both global longitudinal strain (GLS) and strain (SR) with E/e' ratio in a population of asymptomatic patients with systemic hypertension.Methods: Retrospectively included 210 cases of essential hypertension patients. Dynamic images were analyzed for left ventricular myocardial systolic global longitudinal strain (GLS), left ventricular longitudinal peak systolic strain rate (SRs), early diastolic peak strain rate (SRe), late diastolic peak strain rate (SRa). According to the 2012 baseline E/e' ratio, the population was divided into three groups, group A (E/e'<8), group B (8 ≤ E/e'≤14), and group C (E/e'>14).Results: Systolic function parameters left ventricular ejection fraction (LVEF) remained at normal rage and no different, but patients with elevated E/e' ratio had significantly lower GLS, lower early diastolic strain rate(SRe), lower ratio of early diastolic strain rate to late diastolic strain rate (SRe/a) and higher E/SRe. Positive relationships were observed between GLS, E/SRe and E/e' ratio, inverse relationships were observed between SRe, SRe/a and E/e' ratio. E/SRe >0.73 had a sensitivity of 87.7% and a specificity of 38.2% for predicting an elevated E/e' ratio (E/e'>14). In multivariable analysis, IVS-e' <7 cm/s showed almost 2.5-fold increased risk for decreased GLS (OR 2.48[95% CI 1.36-4.53]; p = 003).Conclusions: Our current study demonstrated that hypertensive patients with preserved LVEF and elevated E/e' ratio have systolic and diastolic abnormalities in longitudinal directions as detected by speckle imaging. E/SRe correlates well with E/e' and predicted elevated left ventricular filling pressure.

Free thoracodorsal artery polyfoliate perforator flaps for repairing multiple soft tissue defects in the hand.

BACKGROUND: Hand injury is commonly associated with multiple soft tissue defects. Polyfoliate flaps grafting is the optimal approach for multiple wounds.The feasibility of clinical using of free thoracodorsal artery polyfoliate perforator flaps for repairing multiple soft tissue defects in the hand needs to be confirmed in clinical practice. METHODS: Fifteen patients with hand soft tissue defects that were repaired using free thoracodorsal artery polyfoliate perforator flaps from January 2015 to February 2018 was retrospectively analysed. The survival rate, the operative time, the appearance and sensory recovery of the flaps, and hand function were evaluated. RESULTS: The flaps of all 15 patients survived. Vascular crisis occurred in one patient, and the flap was saved after exploratory operation. The 15 patients were followed up for 12-26 months. Sensation in the flaps was partially recovered in all 15 patients. The wound in the donor area was closed directly with sutures. Mean score of scars at the donor site were assessed using the modified Vancouver scar scale (VSS) was 2.7. A puffed appearance in the recipient area was noted in four patients. To obtain a more satisfactory appearance, revision of the flap was performed once in these four patients. The Total Active Movement (TAM) evaluation system was used to assess the results, which were considered excellent in seven patients, good in six patients, fair in two patients, and poor in none of the patients. Ten of the 15 patients returned to their primary jobs. CONCLUSION: Free thoracodorsal artery polyfoliate perforator flaps are appropriate for repairing multiple soft tissue defects in the hand, offer a satisfactory appearance, require a short operative time, and have little impact on the function and aesthetics of the donor site.

Lnc-Ang362 is a pro-fibrotic long non-coding RNA promoting cardiac fibrosis after myocardial infarction by suppressing Smad7.

BACKGROUND: Cardiac fibrosis following myocardial infarction (MI) leads to cardiac remodeling and dysfunction. Dysregulation of Smad7 which negatively regulates the profibrotic transforming growth factor-ß1 (TGF-ß1)/Smad signaling promotes cardiac fibrosis. However, the molecular mechanisms underlying TGF-ß1/Smad7 dysregulation remain elusive. Long non-coding RNAs (lncRNAs) are recently emerging as important regulators of cardiac diseases. Here, we report lnc-Ang362 is a novel lncRNA mediating MI-induced fibrosis through TGF-ß1/Smad7 signaling pathway. METHODS AND RESULTS: The MI model was established by artificial coronary artery occlusion in rats. Microarray analysis identified 215 lncRNAs (fold change > 2.0, P < 0.05) differentially expressed between MI hearts and the sham group 4 weeks after MI. Lnc-Ang362 had the highest fold upregulation and the change was validated by reverse transcription polymerase chain reaction. Also, MI caused a marked increase in TGF-ß1 and collagen I/III expression, but significantly downregulated Smad7 expression. Adult rat cardiac fibroblasts (RCFs) treated with TGF-ß1 showed increased lnc-Ang362 expression and decreased Smad7 expression. Moreover, overexpression and knockdown of lnc-Ang362 by small interfering RNAs reduced and increased Smad7 expression, respectively. Importantly, this result was negatively correlated with the expression of collagen I/III in RCFs. Furthermore, the luciferase reporter assays confirmed that Smad7 was a validated lnc-Ang362 target. Further silencing Smad7 attenuated the effects of lnc-Ang362 knockdown on decreasing collagen I/III expression in RCFs. CONCLUSIONS: These results suggested lnc-Ang362 promoted cardiac fibrosis after MI via directly suppressing Smad7, which may decrease the inhibitory feedback regulation of TGF-ß1/Smad signaling pathway. Thus, lnc-Ang362 may be a novel profibrotic lncRNA in the regulation of cardiac fibrosis post MI.

Myricitrin regulates proliferation, apoptosis and inflammation of chondrocytes treated with IL-1ß.

Osteoarthritis (OA) is a clinical disease which seriously affects the quality of life of sufferers. Although the pathogenesis of OA has not been fully unraveled, it is may be due to increased levels of pro-inflammatory cytokines, activation of inflammation-related signaling pathways, and degradation of extracellular matrix. Osteoarthritis is characterized by chronic joint pain, swelling, stiffness, limited movement or joint deformity, all of which seriously affect the quality of life and health of the affected individuals. Myroside (Myr) is a polyphenolic hydroxyflavone glycoside extracted from the fruits, bark and leaves of myroside and other natural plants. It has many pharmacological properties, especially anti-inflammatory effects. In the present study, primary chondrocytes of IL-1ß rats were used to simulate pathological environment of chondrocytes in OA, and to explore the effect of Myr on chondrocytes. It was found that Myr improved the viability and proliferation of chondrocytes, and also inhibited apoptosis in these cells. Moreover, Myr reduced the expressions of inflammatory factors, and inhibited inflammatory reactions in chondrocytes. These findings provide good experimental basis for the clinical application of Myr in the prevention and treatment of progressive degeneration of cartilage in OA.

Upregulation of miR-361-3p suppresses serotonin-induced proliferation in human pulmonary artery smooth muscle cells by targeting SERT.

BACKGROUND: Abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is a key mechanism in pulmonary arterial hypertension (PAH). Serotonin (5-hydroxytryptamine, 5-HT) can induce abnormal proliferation of PASMCs. The role of miR-361-3p in serotonin-induced abnormal PASMCs proliferation remains unclear. METHODS: The miR-361-3p level was analyzed in plasma from PAH patients and normal controls and in human PASMCs (hPASMCs) using RT-PCR. The hPASMCs were transfected with an miR-361-3p mimic and then treated with serotonin. Untransfected hPASMCs were used as the control. Cell proliferation was evaluated using an MTS assay and 5-ethynyl-2'-deoxyuridine (EdU) staining. The cell cycle stages were evaluated using flow cytometry. The association between miR-361-3p and serotonin transporter (SERT) was determined using a luciferase reporter assay and anti-AGO2 RNA immunoprecipitation assay. The protein expression was evaluated via western blotting. RESULTS: The miR-361-3p level was lower in plasma from PAH patients than in plasma from the any of the normal control subjects. The mean pulmonary arterial pressure, pulmonary vascular resistance and pulmonary vascular resistance index were higher in PAH patients whose miR-361-3p level was lower than the median value for patients than in those whose miR-361-3p level was higher than the median. Serotonin treatment reduced miR-361-3p expression in the hPASMCs. MiR-361-3p overexpression suppressed cell proliferation, promoted apoptosis, induced G1 arrest, and decreased the phosphorylation level of ERK1/2 in serotonin-treated hPASMCs. SERT was identified as an miR-361-3p target. Its overexpression alleviated the effect of miR-361-3p overexpression on serotonin-induced hPASMC proliferation and upregulation of phosphorylated ERK1/2. CONCLUSIONS: The miR-361-3p level is lower in the plasma of PAH patients. Upregulation of miR-361-3p suppresses serotonin-induced proliferation of hPASMCs by targeting SERT. Our results suggest that miR-361-3p is a potential therapeutic target in PAH.

Lipoprotein (a) as a residual risk factor for atherosclerotic renal artery stenosis in hypertensive patients: a hospital-based cross-sectional study.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-c) has been proven to be a risk factor for atherosclerotic cardiovascular disease (CVD), while lipoprotein (a) (Lp(a)) is a residual risk factor for CVD, even though LDL-c is well controlled by statin use. Importantly, the role of Lp(a) in atherosclerotic renal artery stenosis (ARAS) is still unknown. METHODS: For this hospital-based cross-sectional study, patients who simultaneously underwent coronary and renal angiography were examined. ARAS was defined as a 50% reduction in the cross-sectional (two-dimensional plane) area of the renal artery. Data were collected and compared between ARAS and non-ARAS groups, including clinical history and metabolite profiles. Univariate analysis, three tertile LDL-c-based stratified analysis, and multivariate-adjusted logistic analysis were conducted, revealing a correlation between Lp(a) and ARAS. RESULTS: A total of 170 hypertensive patients were included in this study, 85 with ARAS and 85 with non-RAS. Baseline information indicated comparability between the two groups. In the univariate and multivariate analysis, common risk factors for atherosclerosis were not significantly different. Stratified analysis of LDL-c revealed a significant increase in the incidence of ARAS in patients who had high Lp(a) concentrations at low LDL-c levels (odds ratio (OR): 4.77, 95% confidence interval (CI): 1.04-21.79, P = 0.044). Further logistic analysis with adjusted covariates also confirmed the result, indicating that high Lp(a) levels were independently associated with ARAS (adjusted OR (aOR): 6.14, 95%CI: 1.03-36.47, P = 0.046). This relationship increased with increasing Lp(a) concentration based on a curve fitting graph. These results were not present in the low and intermediate LDL-c-level groups. CONCLUSION: In hypertensive patients who present low LDL-c, high Lp(a) was significantly associated with atherosclerotic renal artery stenosis and thus is a residual risk factor.

Association of mean arterial pressure with all-cause and cardiovascular mortality in young adults.

BACKGROUND: Mean arterial pressure (MAP) is a predictor of all-cause and cardiovascular disease (CVD) mortality in middle-aged population and elderly, but less evidence has been shown in young adults. OBJECTIVES: We examined the associations of MAP with all-cause and CVD mortality in young adults aged between 18 and 40 years. METHODS: Data were from the National Health and Nutrition Examination Survey (1999-2006) and participants were followed up to 31 December 2015. MAP was categorised by quartiles. Multivariable Cox proportional hazards models and Kaplan-Meier survival curves were performed to estimate the association between MAP, all-cause and CVD mortality. RESULTS: There were a total of 8356 (4598 women (55.03%)) participants with the mean age of 26.63±7.01 years, of which 265 (3.17%) and 10 (0.12%) cases of all-cause and cardiovascular mortality occurred during a median follow-up duration of 152.96±30.45 months, respectively. There was no significant difference in the survival rate by MAP quartiles (p=0.058). When MAP was treated as a continuous variable, the multivariable adjusted HRs for all-cause and CVD mortality were 1.00 (95% CI 0.96 to 1.04; p=0.910) and 0.94 (95% CI 0.77 to 1.14; p=0.529), respectively. When using the lowest quartile (Q1) as referent, the adjusted HRs for all-cause mortality from Q2 to Q4 were 1.16 (95% CI 0.56 to 2.42), 1.06 (95% CI 0.48 to 2.32) and 0.91 (95% CI 0.37 to 2.24; p for tend was 0.749) after adjusting for potential confounders. CONCLUSION: There was no significant association of MAP with all-cause and CVD mortality in young adults with a relatively short follow-up time.

Left atrial volume index is superior to left atrial diameter index in relation to coronary heart disease in hypertension patients with preserved left ventricular ejection fraction.

Objective: Research hypothesis is that left atrial (LA) volume index is superior to LA diameter index for coronary heart disease and LA volume index is important to refine risk stratification.Methods: We retrospectively enrolled 222 asymptomatic non-ischemic patients with hypertension who had stored digital images in 2012. Patients were followed up for coronary heart disease over a median of 3.2 years. The Area under receiver operating characteristic curve for LA parameters with coronary heart disease was evaluated. Cox regression was used to assess the association between left atrial parameters and coronary heart disease.Results: The mean age of patients was 62 years, 45% were men, and mean left atrial diameter, mean left atrial volume, mean LA diameter index, mean LA volume index was 32 mm, 43 ml, 21 mm/m2, 27 ml/m2, respectively. After 3.2 years follow up, 10 patients experienced coronary heart disease. Compared with patients without coronary heart disease, LA diameter index and LA volume index increased in coronary heart disease group (P < 0.05). Multivariate cox regression analysis showed, adjusted for age, sex, smoking, cholesterol, fasting plasma glucose, diabetes, systolic blood pressure, left ventricular mass index, and E/e' ratio, a unit rise in LA volume index was associated with a 15% increase in the risk of coronary heart disease. (HR:1.155; 95% CI 1.002-1.332). Compared with LA diameter index, the area under receiver operating characteristic curve values for predicting coronary heart disease were higher for LA volume index (0.797).Conclusions: Our study showed that LA volume index was superior to LA diameter index. LA volume index had independent prognostic implications in terms of coronary heart disease prediction in hypertension patients with preserved left ventricular ejection fraction.