Research progress of non-coding RNA in doxorubicin-induced cardiotoxicity / 中国医师杂志

Doxorubicin is an effective anthracycline chemotherapeutic drug, which is widely used in single or combined chemotherapy for various malignant tumors. However, the cardiotoxicity caused by doxorubicin has limited its clinical application. Despite a large amount of research investment, no suitable target has been found to reduce cardiotoxicity caused by doxorubicin while guaranteeing the effect of chemotherapy. Recent studies have found that non-coding RNA is related to doxorubicin-induced cardiomyopathy. Further explaining the relationship between the two may provide new strategies for the diagnosis, prevention and treatment of doxorubicin-induced cardiotoxicity.

Impact of Herpud1 in the homocysteine-induced phenotypic switching of vascular smooth muscle cells / 中华心血管病杂志

Objective@#To investigate the impact of homocysteine inducible endoplasmic reticulum(ER) protein with ubiquitin like domain 1 protein (Herpud1) in the homocysteine (Hcy) -induced phenotypic switching of vascular smooth muscle cells (VSMCs).@*Methods@#VSMCs were derived from thoracic aortic artery of male Sprague Dawley rats and cultured VSMCs (4-7 passage) were treated with various concentrations of Hcy (0, 100, 500 and 1 000 μmol/L) and applied to immunofluorescence to observe the morphological changes of VSMCs via SM-actin staining. Western blot was used to detect the expression of VSMCs phenotypic markers, including Osteopontin, Calponin and smooth muscle myosin heavy chain (SM-MHC) and the expression of endoplasmic reticulum stress (ERS) related proteins, including C/EBP-homologous protein (CHOP), inositol-requiring kinase 1 (IRE-1) and glucose regulating protein 78 (GRP78) in the absence and presence of non-selective inhibitor of ERS, 4-phenylbutyric acid (4-PBA, 2 mg/ml). The Herpud1 mRNA and protein levels were determined in Hcy-stimulated VSMCs treated with 4-PBA or transfected with specific siRNA targeting Herpud1.@*Results@#Compared with the control group, SM-actin staining results showed that the shape of VSMCs treated with different concentrations of Hcy for 24 hours changed from long fusiform into round form, arrangement of myofilament became irregular and the most significant alteration was found in the 500 μmol/L Hcy group. After intervention of 24 hours, various concentration of Hcy increased protein expression of Osteopontin, and reduced Calponin and SM-MHC protein expressions in VSMCs (all P<0.05). In addition, the results showed that Hcy increased the expression of CHOP, IRE-1 and GRP78 in a dose-dependent manner, which could be reversed by 4-PBA treatment (all P<0.05). However, 4-PBA inhibited Hcy induced upregulation of Osteopontin and downregulation of Calponin and SM-MHC, suggesting that ERS was involved in Hcy-induced phenotypic switching of VSMCs. Herpud1 protein was mostly expressed in the cytoplasm and was also expressed in the nucli, both in the control, Hcy and Hcy+4-PBA groups. Moreover, Hcy increased mRNA and protein levels of Herpud1 (P<0.05), whereas treatment with 4-PBA could significantly reduce Hcy-induced upregulation of Herpud1 (P<0.05). Furthermore, knockdown of Herpud1 abrogated the effects of Hcy on VSMCs phenotype markers.@*Conclusion@#Herpud1 plays an important role in Hcy-induced phenotypic switching of VSMCs.

Research progress on the protective effects of polyphenols against doxorubicin-induced cardiotoxicity / 中国医师杂志

Doxorubicin is a major culprit in chemotherapy-induced cardiotoxicity,which is the chief limiting factor in delivering optimal chemotherapy to cancer patients.Although extensive efforts have been devoted,no chemical synthesized drugs or natural compounds are available to prevent the harmful action of doxorubicin without reducing its anti-cancer efficacy.Accumulative experimental evidence has shown that polyphenols can prevent doxorubicin-induced cardiotoxicity largely due to their anti-cancer and cardio protective properties.We elaborated on the potential mechanisms associated with doxorubicin-induced cardiotoxicity and reviewed published literatures about the protective effects of polyphenols on doxorubicin-induced cardiotoxicity to provide novel strategies for the study of cardioprotective drugs.

Practice of Improving Doctor-patient Friendly Level in Shaoxing City People's Hospital / 中国医院管理

Through taking patient as the center,doctor-patient friendliness concept is actively learned from,the information service,the full range of volunteer service,humanized hospice,fine process of transformation,standardized window service,electronic medical ethics appraisal,persistent humanistic management,three-dimensional health promotion and other eight core work,patient satisfaction is improved,and harmony between doctors and patients is promoted.

From traditional Chinese medicine syndrome differentiationpoint of view to discuss blood glucose control strategy in patients with different etiological factors and treated by mechanical ventilation / 中国中西医结合急救杂志

Objective From the perspective of traditional Chinese medicine (TCM) syndrome differentiation to investigate the blood glucose control strategies of patients with different etiological factors and treated by mechanical ventilation.Methods One hundred and twenty-six mechanical ventilation patients admitted to the Department of Intensive Care Unit (ICU) of Hangzhou Third People's Hospital from February 2016 to February 2017 were enrolled, they were divided into a heart failure group (64 cases) and a pneumonia group (62 cases) according to the cause of disease. Altogether 4 cases due to death, giving up the treatment or being transferred to other hospital were excluded in each group, thus, 60 cases in heart failure group and 58 cases in pneumonia group were finally enrolled. Both groups received at least 4 days of formal blood glucose monitoring and control program. The differences in TCM syndromes, the number of patients necessary to use insulin to control the blood glucose, the daily use of insulin dosage, the incidence of hypoglycemia and prognosis of patients were compared between the two groups.Results According to TCM syndrome differentiation, deficiency was the primary syndrome in the heart failure group, while in the pneumonia group, excess was the primary syndrome, the proportion of deficiency syndrome in heart failure group was significantly higher than that in the pneumonia group [63.33% (38/60) vs. 31.03% (18/58),P < 0.05]. Within 4 days, the incidence of hyperglycemia [50.0% (29/58) vs. 13.3% (8/60)], daily insulin dose (U/d: 85.35±6.35 vs. 20.13±8.20) in pneumonia group were higher than those in the heart failure group (bothP < 0.05). The incidence of hypoglycemia in heart failure group was higher than that in pneumonia group [16.67% (10/60) vs. 3.45% (2/58),P < 0.01].Conclusions It is necessary to use different blood glucose control strategies in patients with heart failure and pneumonia to undergo mechanical ventilation, and the TCM syndrome differentiation can provide theoretical references.

Effects of Chinese yellow wine on homocysteine-induced dysfunction in rat endothelial progenitor cells / 中国病理生理杂志

AIM:To investigate whether Chinese yellow wine has influences on homocysteine ( Hcy )-induced dysfunction in rat endothelial progenitor cells (EPCs).METHODS:Rat bone marrow was extracted to harvest mononucle-ar cells ( MNCs) by density gradient centrifugation .The MNCs were plated on fibronectin-coated culture dishes , and were induced into EPCs by EGM-2 complete medium supplemented with cell growth factor .The adherent cells were collected 7 d later for all studies .EPCs were characterized as adherent cells double positive for DiI-ac-LDL uptaking and lectin binding by direct fluorescent staining under a laser scanning confocal microscope .The viability, migration, apoptosis and in vitro vasculogenic activity of the EPCs were determined by MTT assay , Transwell chamber assay , apoptosis kit and in vitro vas-culogenesis kit, respectively.RESULTS:Compared with control group, the viability, migration and in vitro vasculogenic capacity of the EPCs in Hcy group were significantly decreased (P<0.01).Compared with Hcy group, yellow wine group and red wine group both significantly improved the viability , migration and in vitro vasculogenic capacity of Hcy-induced EPCs (P<0.01).Compared with control group, yellow wine group and red wine group both significantly improved the a-bove-mentioned functions of EPCs (P<0.05).However, no significant difference of apoptosis in all groups was observed . CONCLUSION:Hcy may result in dysfuction of EPCs .Treatment with yellow wine improves Hcy-induced EPC functions .

Rosuvastatin inhibits homocysteine-induced smooth muscle cell phenotype transformation and its signal pathway / 西安交通大学学报(医学版)

ABSTRACT:Objective To verify whether rosuvastatin can inhibit homocysteine (Hcy)‐induced rat aortic vascular smooth muscle cell (VSMC ) phenotype transformation and its potential mechanism .Methods The primary culture and identification of rat VSMCs were conducted , using VSMCs in passage4‐7 for the following experiments .The VSMCs were divided into 4 groups:control group ,Hcy (100μmol/L) group ,Hcy+ rosuvastatin group ,and Hcy+ rapamycin group .MTT was used to investigate the proliferation of VSMCs .Transwell chambers and wound healing were employed to test the migration ability of VSMCs . ICC was used to detect the VSMCs'morphology .Western blotting was used to investigate the expressions of SM‐actin ,SM‐MHC ,calponin ,OPN ,and p‐P70S6K1 in VSMCs of each group .Results Compared with those in control group , the proliferation and migration ability of VSMCs were significantly increased in Hcy modulation group (P< 0 .01) .The expressions of SM‐MCH and calponin increased but those of OPN and p‐P70S6K1 decreased in Hcy group compared with control group (P<0 .01) .The expression of SM‐actin did not significantly differ between the groups .Compared with those in Hcy modulation group , the proliferation and migration ability of VSMCs were significantly decreased in rosuvastatin and rapamycin groups ( P<0 .01) .The expressions of SM‐MCH and calponin increased while OPN and p‐P70S6K1 expressions decreased in rosuvastatin and rapamycin groups compared with Hcy group ( P< 0 .01 ) . Conclusion Hcy can induce the dedifferentiation of VSMCs ,and rosuvastatin can inhibit this effect of Hcy .Its potential mechanism may be realized via the mTOR/P70S6K1 signal pathway .

The imapct of anti-anxiety therapy on vascular endothelium function and platelet activation in patients with acute coronary syndrome / 中华急诊医学杂志

Objective To investigate the effects of anxiety and anti - anxiety therapy on vascular endothelium function and platelet activation in patients with acute coronary syndrome (ACS).Methods One hundred and thirty -nine ACS patients were enrolled in this prospective and controlled clinical study from January 2009 through December 2010.Patients with severe heart failure,liver and renal dysfunction,infection,allergy to benzodiazepines and taking antipsychotic drugs in recent 2 weeks as well as patients unable to complete the questionnaire were excluded.All these patients were divided into the anxiety group ( n =68 ) and the non - anxiety group ( n =71 ) according to Hamilton Anxiety Scale (HAMA).The plasma levels of NO,ET,CD62p,CD63 and flow- mediated diastolic functions (FMD) of humeral arteries were measured.The patients in anxiety group were randomly assigned to group A ( n =34 ) and group B ( n =34).Lorazepam in a dose of 0.5 mg twice a day and Vitamin B6 in dose of 10 mg twice a day as placebo were prescribed for patients of Group A and B respectively.After 2 weeks,all above variables of group A and group B were measured once again as well as the score of Hamilton Anxiety Scale.The chi - square test was used for constituent ratios,while t - test was applied to analysis of differences in above variables between two groups.Results The plasma level of NO and FMD of humeral artery in the anxiety group were significantly lower than those in the non -anxiety group (t =2.090 and 2.558,P =0.038 and 0.012,respectively),and the plasma levels of ET,CD62p and CD63 in the anxiety group were significantly higher than those in the non - anxiety group ( t =2.082,2.042 and 2.145,P =0.039,0.043 and 0.034,respectively).There were no statistical differences in all above variables as well as HAMA score between group A and group B before anti - anxiety treatment.Two weeks after treatment,the level of NO and FMD of humeral artery in group A were significantly higher than those in group B ( t =2.821 and 2.246,P =0,006 and 0.028,respectively) and the levels of ET,CD62p,CD63 and HAMA score in group A were significantly lower than those in group B ( t =2.107,3.242,2.079 and 7.779,P =0.039,0.002,0.041 and ＜0.01,respectively).Conclusions Anxiety mood markedly aggravates the disorder of vascular endothelial function and platelet activation,and both of them can be improved by anti - anxiety therapy.Consequently,the intervention in anxiety mood may improve the outcomes of ACS patients.

Effects of rosuvastatin on matrix metalloproteinase 2 expression and cell migration of rat vascular smooth muscle cells / 中华老年医学杂志

Objective To observe the effects of rosuvastatin on the homocysteine (Hcy)-induced expression of matrix metalloproteinase 2 (MMP 2) and cell migration in rat vascular smooth muscle cells (VSMCs), and to explore the possible mechanism of Hcy-induced atherosclerosis and the role of statins in reversing atherosclerosis. Methods In one cell culture plate, the cultured rat VSMCs were incubated with different concentrations of Hcy (0, 50, 100, 500, 1000 μmol/L and 5000 μmol/L) in vitro for 24 h, 48 h and 72 h. And in another cell culture plate, the different concentrations of rosuvastatin (10-9, 10-8, 10-7, 10-6, 10-5 mol/L and 0 mol/L) were added to the cultured rat VSMCs (while the concentration of Hcy was 1000 μmol/L). The MMP 2 expression and enzyme activity were determined by gelatin zymography and Western blotting. The effects of Hcy and rosuvastatin on cell migration and invasiveness of VSMCs were observed. Results Hcy (50-5000 μmol/L) increased the protein expression, and Hcy (50-1000 μmol/L) increased enzyme activity of MMP 2 significantly. But Hcy (5000 μmol/L) inhibited activity of MMP 2 (F=9.31, 6.44 and 5.97, all P＜0.05). Rosuvastatin (10-9-10-5 mol/L) inhibited Hcy-induced expression and enzyme activity increasing of MMP 2. The counts of cell migration of VSMCs were 18.32±2.17, 32.68±4.34, 44.75±4.08, 61.39±5.21, 79.74±5.54 and 90.78±5.83, while the concentration of Hcy was 0, 50, 100, 500, 1000 μmol/L and 5000 μmol/L respectively (F=5.31, P＜0.05). The counts of cell migration of VSMCs were 79.74±5.54, 62.53±6.41, 48.37±5.66, 31.41±4.79, 19.27±3.62 and 11.17±2.33, while the concentration of rosuvastatin was 10-9, 10-8, 10-7, 10-6 and 10-5 mol/L respectively (F=4.99, P＜0.05). Rosuvastatin could decrease the stimulation of Hcy-induced migration of VSMCs. Conclusions Hcy can influence the MMP 2 protein expression/activity in VSMCs, and rosuvastatin can inhibit augmentation of Hcy-induced MMP 2 expression/activity and migration of VSMCs. It may be one of the multiple-effects of rosuvastatin reducing atherosclerosis.

Yellow wine and red wine inhibit matrix metalloproteinase-2 and improve pathological changes of atherosclerosis in LDL receptor knockout mice / 中国病理生理杂志

AIM: To study the possibility that yellow wine improves the pathological changes of atherosclerosis in vivo. METHODS: Six weeks old LDL receptor knockout mice (n=48) on a high-fat and L-methionine diet developed plasma hyperhomocysteinemia and atherosclerosis. The animals were randomly divided into yellow wine group, red wine group, ethanol group and control group (n=12 in each group) and were sacrificed after 14 weeks. The levels of plasma lipids and homocysteine in serum were examined. The morphological changes of aorta artery and the atherosclerosis of aorta sinus were observed under microscope. The expression and activation of matrix metalloproteinase-2 (MMP-2) were determined by the method of immunohistochemistry. RESULTS: No significant difference of plasma total cholesterol, triglyceride or high density lipoprotein cholesterol among groups was observed. Plasma homocysteine was significantly decreased in yellow wine group as compared to other three groups (P<0.01). Compared to ethanol and control groups, use of yellow wine and red wine significantly reduced the atherosclerosis lesion area (P<0.01). However, no significant discrepancy between the yellow wine group and red wine group was found. Compared to control group, the expression of MMP-2 in yellow wine group, red wine group and ethanol group decreased by 26.3%, 27.6% (P<0.01) and 5.7% (P>0.05), respectively. The activity of MMP-2 in yellow wine group, red wine group and ethanol group decreased by 31.7%, 32.5% (P<0.01) and 6.7% (P>0.05), respectively. CONCLUSION: Yellow wine and red wine inhibit the expression of MMP-2 and improve the pathologic changes of atherosclerosis, indicating that they have benefic effects on cardiovascular system.