Marein Alleviates High Glucose-Induced Human Retinal Microvascular Endothelial Cell Injury by Up-Regulating SNHG7 Expression.

BACKGROUND: Marein has been shown to possess therapeutic effects against diabetic retinopathy, but whether it can protect against high glucose (HG)-induced human retinal microvascular endothelial cell (HRMEC) injury remains unclear. Our study aimed to explore the effect of marein on HG-induced HRMEC injury and the mechanism underlying this purported therapeutic effect. METHODS: HRMEC was divided into normal glucose group, high glucose (HG) group, HG+marein low, medium and high (L, M, H) concentrations group, HG+pcDNA group, HG+pcDNA-small nucleolar RNA host gene 7 (SNHG7) group, HG+marein+si-negative control (NC) group, and HG+marein+si-SNHG7 group. Flow cytometry and Western blotting were performed to determine apoptosis rate and apoptosis-related protein levels. Superoxide dismutase (SOD) activity, lactate dehydrogenase (LDH) level and malondialdehyde (MDA) content were detected to assess cellular oxidative stress. SNHG7 expression was examined using real-time quantitative PCR. RESULTS: After treatment with low, medium and high concentrations of marein, apoptosis rate, Bax level, LDH level and MDA content were decreased, while B-cell lymphoma-2 (Bcl-2) level, SOD activity, and SNHG7 expression were promoted in HG-induced HRMEC injury in a concentration-dependent manner (p < 0.05). After overexpression of SNHG7, apoptosis rate, Bax level, LDH level and MDA content were decreased, while Bcl-2 level and SOD activity were enhanced in HG-induced HRMEC injury (p < 0.05). In contrast, SNHG7 knockdown reversed the effect of marein on HG-induced HRMEC injury. CONCLUSIONS: Marein could alleviate HG-induced HRMEC injury by up-regulating SNHG7 expression.

Valsartan Regulates PI3K/AKT Pathways through lncRNA GASL1 to Improve Isoproterenol-Induced Heart Failure.

OBJECTIVE: This study is aimed at determining the expression and function of the GASL1 and PI3K/AKT pathways in isoproterenol- (ISO-) induced heart failure (HF). To determine the moderating effect of valsartan (VAL) on the progression of ISO-induced HF and to elucidate the related mechanism. MATERIALS AND METHODS: First, in in vivo experiment, we examined the effect of VAL on cardiac function in rats with ISO-induced HF. Similarly, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the effect of VAL on ISO-treated rat primary cardiomyocytes. Then, si-GASL1-transfected primary cardiomyocytes were constructed and Ad-si-GASL1 was injected through rat tail vein to achieve the effect of lowering GASL1 expression, so as to investigate the role of GASL1 in VAL's treatment of ISO-induced HF. RESULTS: In ISO-induced HF rat models, the GASL1 decreased while PI3K and p-AKT expressions were abnormally elevated and cardiac function deteriorated, and VAL was able to reverse these changes. In primary cardiomyocytes, ISO induces apoptosis of cardiomyocytes, and expression of GASL1 decreased while PI3K and p-AKT were abnormally elevated, which can be reversed by VAL. The transfection of primary cardiomyocytes with si-GASL1 confirmed that GASL1 affected the expression of PI3K, p-AKT, and the apoptosis of primary cardiomyocytes. Rat myocardium injected with Ad-si-GASL1 was found to aggravate the cardiac function improved by VAL. CONCLUSIONS: This study was the first to confirm that VAL improves ISO-induced HF by regulating the PI3K/AKT pathway through GASL1. And this study demonstrated a significant correlation between HF, VAL, GASL1, and the PI3K/AKT pathway.

[Primary clinical investigation of cardiopulmonary exercise gas exchange in pulmonary hypertension patients with and without right-to-left shunt].

Objective: The aim of this study is to determine the changes of gas exchange parameters during ramp incremental cardiopulmonary exercise test (CPET) in patients with pulmonary hypertension (PH) could identify the right to left shunt (R-L Shunt). Methods: We did a retrospective analysis of exercise gas exchange parameters for 73 PH patients and 14 normal subjects as control, in Fuwai Hospital from October 2016 to August 2017, who did CPET with signature on content form. The gas exchange data of CPET were double-blindly independently interpreted by four export-doctors. According to the reading results of CPET, the PH patients were divided into four groups: ① R-L shunt positive group, ② R-L shunt suspicious group, ③R-L shunt negative group, ④late open R-L Shunt positive group. Results: Minute ventilation (VE), ventilatory equivalents for carbon dioxide and oxygen (VE/VCO2, VE/VO2), end-tidal partial pressure of oxygen (PETO2)in R-L shunt positive group were significantly increased ((7.36 ± 2.72) L/min, (1.84± 3.59), (5.02 ±4.34), (3.75±2.64) mmHg) at the beginning of exercise, and were also significantly higher than the control ((4.26 ± 2.59) L/min, (2.22± 2.08), (1.46 ±4.68), (3.96 ± 2.82) mmHg); Partial pressure of carbon dioxide in end expiratory gas (PETCO2) was decreased (-1.63 ±1.66) mmHg, and was significantly lower than control (2.22 ± 2.08) mmHg (P<0.01). Respiratory quotient (RER), carbon dioxide, VE/VCO2, VE/VO2, PETO2 in late open R-L Shunt positive group were suddenly increased ((0.40 ± 0.08), (11.07 ± 5.60),(30.55 ±7.89), (13.72 ±2.21) mmHg) at the end of exercise near the peak, significantly higher than control too ((0.38± 0.12), (5.67± 4.60), (4.54 ± 3.83), (5.51± 4.24) mmHg); PETCO2 was suddenly decreased at the end of the exercise compared to the resting stage (-6.82 ± 1.96) mmHg, and was significantly different from the control (5.67 ±4.60) mmHg. Carbon dioxide ventilatory efficiency, oxygen uptake ventilatory efficiency relative to the peak power (-8.38 ±3.24, -13.14 ± 6.47) at the recovery stage in late open R-L shunt positive group are significantly lower than control (6.22 ±2.87, 16.56± 4.20) (P<0.01). Conclusion: Cardiopulmonary function and ventilation efficiency of patients withpulmonary hypertension are significantly decreased; pulmonary hypertension and right to left shunt in patients not only resting ventilation efficiency is limited more serious; The characteristics of R-L shunt are the sudden increase of PETO2, VE/ VCO2, VE, RER and sudden decrease of PETCO2 and VO2/ VE at the beginning of exercise, and commonly companied with decreased SpO2. For the delay open R-L shunt, these changes occurred near the peak exercise rather than the beginning, and these characteristic changes quickly reversed after stopping exercise.

[Clinical study on the characteristics of exercise pathophysiological in patients with severe heart failure].

Objective: The cardiopulmonary function of patients with chronic heart failure (CHF) was severely limited, but the holistic integrative exercise pathophysiology is still unclear. Methods: After signed the consent form, Eighty three patients with severe CHF from October 2016 to October 2017 in Fuwai Hospital were performed Ramp incremental loading program CardioPulmonary Exercise Testing (CPET), and 12 normal subjects served as control. CPET were performed according to standard of Harbor-UCLA MC and the circulatory, respiratory and metabolic parameters during CPET were measured and analyzed. Results: Peak oxygen uptake (Peak VO2) in CHF (14.33±2.69) ml/(min·kg), (44.25±14.74)%pred was significantly lower than control ((29.42±5.46) ml/(min·kg), (83.88±6.28)%pred). Other core parameters of CPET such as anaerobic threshold (AT), peak oxygen pulse, oxygen uptake efficiency platform (OUEP), the lowest of carbon dioxide output ventilation ratio (Lowest VE/VCO2), and carbon dioxide output ventilation slope (VE/VCO2 Slope) in CHF were significantly different with the control group(P<0.01). The core parameters of lung function, such as forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, and carbon monoxide diffusion (DLCO) were significantly decreased (P<0.01). Systolic blood pressure during all stages of CPET in CHF was significantly lower than control group (P<0.05); Heart rate at AT, peak and recovery stages were significantly lower than control (P<0.01). Minute ventilation, tidal volume and respiratory frequency at rest, warm-up were significantly higher than control (P<0.05). Tidal volume at recovery was significantly higher than control (P<0.05). VO2 at AT, peak and recovery stages in CHF were significantly higher than control (P<0.01). Oxygen pulse at AT and peak were significantly higher than control (P<0.01). Pulse oxygen saturation during all stages of CPET in CHF were significantly lower than control (P<0.01). Conclusion: The decreased holistic functional capacity of cardiogenic CHF dominantly due to circulatory limitation, and secondly due to respiratory and metabolic limitation.

[The preliminary report of investigation: Using mask for cardiopulmonary exercise testing in Chinese children may result misinterpretation and misdiagnosis].

Objective: Observe the increased anatomical dead space of the mask, summarize the law of exercise induced oscillatory breathing (EIOB) in the results of CPET's new 9 figure, and analyze its incidence and age groups that are prone to oscillatory breathing. Methods: After signed the informed consent form by guardian, 501 children from pre-school to middle-school, aged 3~14 year, performed Harbor-UCLA standard protocol CPET with strict quality control in the CPET laboratory of Liaocheng Children's Hospital since 2014. CPET data was interpreted second by second from the breath by breath collection, averaged by 10s and then display by 9 plots. We analyzed the trends, pattern, incidence and age difference for EIOB and gas leakage. Results: The incidence of EIOB was the highest in the 3 to 6-year-old group, which was 42%. The 7 to 10-year-old group was 29.4% and the 11- to 14-year-old group was 29.9%. The three groups were tested by chi-square (x2=7.512), and the difference was statistically significant (P<0.05). 14 out of 508 children had air leakage during CPET, the incidence rate was 2.7%. Conclusion: The phenomenon of oscillatory breathing (OB) in children may be caused by the increased anatomical dead space of the mask, and it is not caused by disease. To improve the quality of CPET and to reduce clinical misdiagnosis, it is recommended to use a mouthpiece to decrease the dead space rather than the musk.