Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV / 中华心血管病杂志

Objective: To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease （CVD). Methods: A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU, n=16) and general group (n=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection. Results: Compared with the general group, the lymphocyte count (0.74 (0.34, 0.94)×109/L vs. 0.99 (0.71, 1.29)×109/L, P=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L, P<0.001) and PCT (0.20 (0.15,0.48) μg/L vs. 0.11 (0.06,0.20) μg/L, P<0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m2 vs. 22.0 (20.0, 24.0) kg/m2，P=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI> 25.0 kg/m2, which was significantly higher than that of survivors (18.95% (18/95), P<0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444), P<0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L, P<0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors （all P>0.05). Conclusion: COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.

Changes of blood lipids in colorectal cancer patients with coronary heart disease and value of lipid-lowering therapy with statins / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes of blood lipid in patients with colorectal cancer complicated by coronary heart disease (CHD) and the effect of lipid-lowering therapy with statins in these patients.</p><p><b>METHODS</b>In 32 pathologically confirmed colorectal cancer patients with CHD, the concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and lipoprotein (a) (Lp(a)) were detected at the baseline, before and after the operation, and at 6 months of postoperative atorvastatin treatment. Thirty patients with TC over 5.70 mmol/L and established coronary artery disease served as the control group.</p><p><b>RESULTS</b>TC, TG and LDL-C in the 30 control patients were significantly decreased after 6 months of 20 mg atorvastatin treatment, and even further decreased till 12 months (P<0.01), but no significant changes occurred in HDL-C and Lp(a). The baseline level of TC, TG, LDL-C and HDL-C were significantly decreased (P<0.01), while Lp(a) increased (P<0.05) in the 32 cancer patients with CHD. Continuing atorvastatin treatment further decreased TC, TG and LDL-C (P<0.05) and increased HDL-C (P<0.05) without affecting Lp(a). The cancer patients had significantly lower TC and LDL-C levels than the control group (P<0.05), but had significantly increased Lp(a) (P<0.05). Six months of atorvastatin treatment further decreased LDL-C and HDL-C in the cancer patients (P<0.05), while TC and Lp(a) had no significant changes.</p><p><b>CONCLUSIONS</b>Increased Lp(a) in colorectal cancer patients can be associated with its anti-tumor effect. Alterations in the blood lipid profile raises a new issue concerning the safety of lipid-lowering therapy in colorectal cancer patients complicated by CHD.</p>

High extracellular potassium ion concentration attenuates the blockade action of ketanserin on Kv1.3 channels expressed in xenopus oocytes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Ketanserin (KT), a selective serotonin (5-HT) 2-receptor antagonist, reduces peripheral blood pressure by blocking the activation of peripheral 5-HT receptors. In this study electrophysiological method was used to investigate the effect of KT and potassium ion on Kv1.3 potassium channels and explore the role of blocker KT in the alteration of channel kinetics contributing to the potassium ion imbalances.</p><p><b>METHODS</b>Kv1.3 channels were expressed in xenopus oocytes, and currents were measured using the two-microelectrode voltage-clamp technique.</p><p><b>RESULTS</b>KCl made a left shift of activation and an inactivation curve of Kv1.3 current and accelerated the activation and inactivation time constant. High extracellular [K(+)] attenuated the blockade effect of KT on Kv1.3 channels. In the presence of KT and KCl the activation and inactivation time constants were not influenced significantly no matter what was administered first. KT did not significantly inhibit Kv1.3 current induced by tetraethylammonium (TEA).</p><p><b>CONCLUSIONS</b>KT is a weak blocker of Kv1.3 channels at different concentrations of extracellular potassium and binds to the intracellular side of the channel pore. The inhibitor KT of ion channels is not fully effective in clinical use because of high [K(+)](o) and other electrolyte disorders.</p>

Effect of human bone marrow mesenchymal stem cells on allogeneic regulatory T cells and its possible mechanism / 中国实验血液学杂志

The study was purposed to investigate the immune regulatory effects of human bone marrow mesenchymal stem cells (hMSCs) on Foxp3 expressing CD4(+)CD25(+) regulatory T cells and to explore the mechanism of immune modulation by hMSCs. Human MSCs were isolated and expanded from bone marrow cells, and identified with cell morphology, and the phenotypes were assessed by immunohistochemistry. Human peripheral blood mononuclear cells (hPBMNCs) were prepared by centrifugation on a Ficoll Hypaque density gradient. The hMSCs (1 x 10(3), 1 x 10(4), 1 x 10(5)) were added into wells containing hPBMNCs (1 x 10(6)) from an unrelated donor in the presence of rhIL-2. After 5 days of co-culture, the percentage of CD4(+)CD25(+) T cells was detected by flow cytometry. T cell proliferation was assessed by [(3)H] thymidine incorporation using a liquid scintillation counter. The expression of Foxp3 in CD4(+)CD25(+) T cells was detected by reverse transcription polymerase chain reaction (RT-PCR). Cytokines (TGF-beta, IL-12, IFN-gamma, IL-10) concertrations of cultured supernatants were measured with ELISA. The results indicated that in all the experiments, the presence of hMSCs with hPBMNCs resulted in a statistically significant decrease in T cell proliferation, in dose-dependent manner. The increase of percentage of CD4(+)CD25(+) T cells in the peripheral CD4(+) T cell was observed after coculturing lymphocytes with hMSCs (p < 0.01). The expression of Foxp3-mRNA (Foxp3/beta-actin) in hMSCs groups was significantly higher than that in the control and was negatively associated with the value of CPM representing T proliferation. The levels of TGF-beta and IL-10 were higher in hMSCs groups than that in the control, and the levels of TGF-beta and IL-10 correlated positively with Foxp3-mRNA expression and the percentage of CD4(+)CD25(+) T cells. However, the secretion of IL-12 and IFN-gamma was significantly attenuated by hMSCs coculture, and there was no correlation with Foxp3-mRNA expression and the percentage of CD4(+)CD25(+) T cells. It is concluded that the Foxp3 expressing regulatory T cells may play an important role in the immune regulatory by hMSCs. Its mechanism is related to that the hMSCs-mediated TGF-beta and IL-10 convert CD4(+)CD25(-) T cells into CD4(+)CD25(+) T regulatory T cells, which specifically inhibits the proliferation of T cells.

Time course of G-CSF, estrogen and various doses of atorvastatin on endothelial progenitor cells mobilization / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the time course of granulocyte-colony-stimulating-factor (G-CSF), estrogen and various doses of atorvastatin on endothelial progenitor cells (EPCs) mobilization.</p><p><b>METHOD</b>A total of 48 male New Zealand White rabbits were treated with placebo, estrogen (0.25 mg.k(-1).d(-1)), Atorvastatin (2.5, 5, or 10 mg) and G-CSF (50 microg/rabbit/d), respectively. Peripheral EPCs number was surveyed weekly for 4 weeks by FACS analysis (double-positive for PE-CD34/FITC-CD133) and under fluorescent microscope (double-positive for FITC-UEA-1/Dil-acLDL). Serum nitric oxide (NO) and lipids were also measured at the third week.</p><p><b>RESULTS</b>Peripheral EPCs was significantly increased in G-CSF treated animals and remained constant for 4 weeks compared to placebo treated animals. Atorvastatin increased peripheral EPCs dose-dependently from 2.5 to 5 mg and peaked at the third week while peripheral EPCs number was not affected by 10 mg.k(-1).d(-1) atorvastatin during the first 3 weeks and was significantly higher only in the fourth week compared to placebo group. Estrogen also significantly increased peripheral EPCs at the third and fourth week compared to placebo group. At the third week, serum NO was similar in G-CSF group, significantly higher in atorvastatin 5 mg.k(-1).d(-1) and estrogen groups while significantly lower in atorvastatin 10 mg.k(-1).d(-1) group compared to placebo group. Serum lipids were similar among various groups.</p><p><b>CONCLUSION</b>Atorvastatin, estrogen and G-CSF could mobilize EPCs. The mobilization efficacy is as follows: G-CSF > atorvastatin 5 mg.k(-1).d(-1) > estrogen > atorvastatin 2.5 mg.k(-1).d(-1) > atorvastatin 10 mg.k(-1).d(-1). NO might partly contribute to the mobilizing effect of estrogen and atorvastatin.</p>

Effects of Ginkgo leaf extract on function of dendritic cells and Th1/Th2 cytokines in patients with unstable angina pectoris / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Ginkgo leaf extract (GLE) on function of dendritic cells (DC) and Th1/Th2 cytokines in patients with unstable angina pectoris (UAP).</p><p><b>METHODS</b>Fifty-four patients with UAP were equally assigned into two groups, the treated group and the control group, both treated with conventional Western medicine, but with GLE given additionally to the treated group. Blood of all patients was taken before and 4 weeks after treatment to prepare the peripheral mononuclear cells, then which were incubated in the completed medium containing granulocyte-macrophage colony stimulatory factor (GM-CSF) and interleukin-4 (IL-4) to induce mature DC. The expression of co-stimulating factor CD86 (B7-2) on the surface of DC was detected by flow cytometry, and the stimulating capacity of DC was determined by mixed lymphocyte reaction (MLR). The blood levels of cytokines, interferon-gamma (IFN-gamma), and IL-4, were analyzed by ELISA, and blood C-reactive protein (CRP) level by turbidimetry. Moreover, the direct effect of Ginkgolide B on CD86 expression on DC were also tested in vitro.</p><p><b>RESULTS</b>After treatment, CD86 expression on DC, the stimulating capacity of DC as well as levels of IFN-gamma and CRP were lowered in both groups (P < 0.05 or P < 0.01), but the changes were much more significant in the treated group than those in the control group. Ginkgolide B showed a direct inhibitory effect on the CD86 expression on DC.</p><p><b>CONCLUSION</b>The inhibition of GLE on DC and thereby the suppression on inflammatory reaction may be one of the mechanisms of GLE in treating patients with UAP.</p>

Mechanism of the angiogenic effect of bone marrow stromal cells implantation on acute myocardial infarction / 中国应用生理学杂志

<p><b>AIM</b>To study the mechanism of the therapeutic angiogenesis effect of bone marrow stromal cells (BMSCs) implantation on rat acute myocardial infarction models.</p><p><b>METHODS</b>The rat acute myocardial infarction models were made by coronary artery ligation and divided into 2 groups at random. In the experiment group, twice passaged BMSCs were labeled with BrdU and then implanted into the infarction region of the recipients in 4 weeks. The control group was the model rats received only DMEM injection. In control group, the hearts were harvested on the day 3, 7, 14, 28, 42 and 56. The infarction regions were examined to identify the angiogenesis and the expression of the VEGF and bFGF. In experiment group, the hearts were examined on the day 42 and 56 after AMI (the day 14 and 28 after cells implantation).</p><p><b>RESULTS</b>Viable cells labeled with BrdU could be identified in host hearts. Histologic examination found most donor cells within the infarction region expressed fibroblastic and endothelial phenotype. The transplantation regions had a greater capillary density than the control regions did (14 +/- 4.7/HPF vs 6 +/- 2.4/HPF, P < 0.05). In the control group, the expression of VEGF and bFGF within the infarction regions peaked on day 7, and then decreased over time. In the experiment groups, the expression of bFGF and VEGF on the day 42 and 56 had a higher level than the control group did.</p><p><b>CONCLUSION</b>The expression of VEGF and bFGF is significantly increased after cells therapy during the late phase of AMI. It indicates that BMSCs implantation promoted the angiogenesis is mediated by its differentiation into endothelium and the increased release of VEGF and bFGF.</p>