HUVECs affect HuT-78 cell apoptosis and cytokine production via the HIF-1α-PD-L1/PD-1 pathway under hypoxia.

We investigated whether human umbilical vein endothelial cells (HUVECs) under hypoxic conditions can suppress the production of cytokines in Hut-78 cells via the HIF-1α/PD-L1/PD-1 pathway, and the intervention effect of Nivolumab. HUVECs and HuT-78 cells were monocultured or cocultured in a tri-gas incubator with or without Nivolumab pretreatment. Real-time PCR, western blotting, and protein chips were used. Transcriptional regulation of PD-L1 and PD-1 by HIF-1α was analyzed by ChIP-qPCR and luciferase reporter gene assays. Apoptosis was assessed by flow cytometry. In HuT-78 cells, hypoxic monoculture significantly increased the expression of HIF-1α, PD-1, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-α, and Bax, decreased the expression of Bcl-2, and resulted in increased apoptosis. In comparison to hypoxic monoculture, hypoxic coculture significantly reduced the expression of IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, and IFN-α, as well as Bcl-2, in HuT-78 cells. Meanwhile, Bax expression was significantly increased with elevated apoptosis in HuT-78 cells. However, pretreatment with Nivolumab significantly antagonized the reduction in cytokines and the elevation in apoptosis in HuT-78 cells. Chip-qPCR and luciferase reporter gene assays demonstrated that hypoxia significantly increased the binding of HIF-1α to the upstream regulatory regions of PD-1 at -63 and -66 bp and PD-L1 at -571 bp, promoting their transcription. Therefore, HUVECs under hypoxia can reduce cytokine production and inhibit their own apoptosis in co-culture with HuT-78 cells via the HIF-1α/PD-L1/PD-1 pathway. These findings provide new clues for exploring the combined use of immune checkpoint inhibitors and anti-angiogenic drugs in clinical settings.

Efficacy and safety of short-term intensive statin therapy in patients with acute coronary syndrome / 中华全科医师杂志

Objective To evaluate the clinical efficacy and safety of short-term intensive statin therapy in patients with acute coronary syndrome ( ACS) .Methods A total of 218 ACS patients admitted in Hangzhou First People′s Hospital from March 2013 to July 2013 were enrolled into this study .The patients were randomly assigned to receive atorvastatin 80 mg/d during hospitalization , and 40 mg/night after discharge for one month ( intensive group , n=107 );or receive atorvastin 20 mg during hospitalization and 20 mg/night after discharge for one month ( control group, n =111 ).The biochemical indexes were measured on the admission and after one-month treatment.Results After one-month treatment, the total cholesterol, triglycerides and LDL cholesterol of intensive group were significantly lower , and the high density lipoprotein cholesterol was higher than baseline values ( 0.75 ±0.14 ) mmol/L vs.( 1.52 ±0.88 ) mmol/L, P<0.05;(2.21 ±0.78)mmol/L vs.(4.55 ±1.12)mmol/L, P<0.05;(1.76 ±0.31)mmol/L vs.(2.23 ±0.77) mmol/L, P<0.05; (1.15 ±0.34) vs.(1.52 ±0.41) mmol/L, P<0.05.The liver enzymes creatine kinase in intensive group was not significantly changed , but the creatinine levels decreased (82.53 ±23.85)μmol/L vs.(57.81 ±15.27) μmol/L, P<0.05, and the blood homocysteine and ultra-sensitivity C-reactive protein levels also decreased compared with the baseline ( 10.52 ±4.66 ) mmol/L vs.(30.70 ±18.82 ) mmol/L, P <0.05;( 8.06 ±2.68 ) mg/L vs.( 19.75 ±11.91 ) mg/L, P <0.05. Conclusions Short-term intensive statin therapy can effectively reduce blood lipid , cholesterol and homocysteine levels and raise HDL cholesterol levels; also with its anti-inflammatory and renal protective effect the therapy can provide more clinical benefit for patients with ACS .

Diagnostic value of cardiopulmonary exercise test for coronary heart disease / 中华全科医师杂志

Cardiopulmonary exercise test and electrocardiogram exercise test were performed in 68 patients with suspected coronary artery disease,the diagnostic value of two tests was compared with coronary angiography results as the gold standard.The results show that the sensitivity,specificity,positive predictive value and negative predictive value of electrocardiogram exercise test for coronary heart disease were 51.28％,68.97％,68.97％ and 51.28％ respectively; those for ratio of O2 pulse peak in cardiopulmonary exercise test were 51.28％,75.86％,74.07％ and 53.66％ respectively.It suggests that the results of cardiopulmonary exercise test may have the same value as electrocardiogram exercise test in diagnosis of coronary artery disease.