OBJECTIVE To determine the functional role of hydrogen sulfide(H_2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca^(2+)/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ) us...OBJECTIVE To determine the functional role of hydrogen sulfide(H_2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca^(2+)/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ) using wild type and CSE knockout mouse models.METHODS Continuous subcutaneous injection isoprenaline(7.5 mg·kg^(-1) per day),once a day for 4 weeks to induce heart failure in male C57BL/6(6-8 weeks old) mice and CSE-/-mice.150 μmol·L^(-1) H_2O_2 was used to induce oxidative stress in H9c2 cells.Echocardiograph was used to detect cardiac parameters.H&E stain and Masson stain was to observation histopathological changes.Western blot was used to detect protein expression and activity.The si RNA was used to silence protein expression.HPLC was used to detect H_2S level.Biotin assay was used to detect the level of S-sulfhydration protein.RESULTS Treatment with S-propyl-L-cysteine(SPRC) or sodium hydrosulfide(Na HS),modulators of blood H_2S levels,attenuated the development of heart failure in animals,reduced lipid peroxidation,and preserved mitochondrial function.The inhibition Ca MKⅡ phosphorylation by SPRC and Na HS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds.Interestingly,Ca MKⅡ activity was found to be elevated in CSE-/-mice as compared to wild type animals and the phosphorylation status of Ca MK Ⅱ appeared to relate to the severity of heart failure.Importantly,in wild type mice SPRC was found to promote S-sulfhydration of Ca MKⅡ leading to reduced activity of this protein however,in CSE-/-mice S-sulfhydration was abolished following SPRC treatment.CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of Ca MKⅡ is presented.SPRC mediated S-sulfhydration of Ca MKⅡ was found to inhibit Ca MKⅡ activity and to preserve cardiovascular homeostasis.展开更多
Objective:To explore the effect of adjuvant tiotropium bromide therapy on the oxygenation function and inflammatory response in patients with COPD and type Ⅱ respiratory failure. Methods:a total of 58 patients with C...Objective:To explore the effect of adjuvant tiotropium bromide therapy on the oxygenation function and inflammatory response in patients with COPD and type Ⅱ respiratory failure. Methods:a total of 58 patients with COPD and type II respiratory failure treated in our hospital between August 2012 and January 2016 were collected and divided into observation group (n=29) and control group (n=29) according to the single blind randomized control method. Control group of patients received clinical routine treatment, and observation group of patients received adjuvant tiotropium bromide treatment on the basis of routine treatment. Before treatment and 30d after treatment, spirometer was used to determine pulmonary ventilation function;blood gas analyzer was used to test oxygenation function indexes;enzyme-linked immunosorbent assay (ELISA) was used to detect serum inflammatory factor levels.Results: Before treatment, differences in pulmonary ventilation function, oxygenation function and serum inflammatory factor levels were not statistically significant between two groups of patients. 30 d after treatment, FEV1, FEF75%, PEF, PaO2/FiO2, DO2 and O2ER levels of observation group were significantly higher than those of control group while VO2 level was significantly lower than that of control group;serum IL-1β, IL-18, IL-27 and CRP levels were significantly lower than those of control group.Conclusion:Adjuvant tiotropium bromide treatment can optimize the pulmonary ventilation and oxygenation function and reduce systemic inflammatory response in patients with COPD and type II respiratory failure.展开更多
AIM:To investigate the change in intestinal dendritic cell(DC)number in fulminant hepatic failure(FHF).METHODS:An animal model of FHF was created.Intestinal CD11b/c was detected by immunohistochemistry and Western blo...AIM:To investigate the change in intestinal dendritic cell(DC)number in fulminant hepatic failure(FHF).METHODS:An animal model of FHF was created.Intestinal CD11b/c was detected by immunohistochemistry and Western blot.Quantitative real-time polymerase chain reaction(PCR)was used to detect intestinal integrin-αm RNA expression.Intestinal CD83,CD86,CD74,CD3 and AKT were detected by immunohistochemistry,Western blot and PCR.Phosphorylated-AKT(p-AKT)was detected by immunohistochemistry and Western blot.RESULTS:In the FHF group[D-galactosamine(D-Galn)+lipopolysaccharide(LPS)group],the mice began to die after 6 h;conversely,in the D-Galn and LPS groups,the activity of mice was poor,but there were no deaths.Immunohistochemistry results showed that in FHF,the expression of CD11b/c(7988400±385941vs 1102400±132273,P<0.05),CD83(13875000±467493 vs 9257600±400364,P<0.05),CD86(7988400±385941 vs 1102400±13227,P<0.05)and CD74(11056000±431427 vs 4633400±267903,P<0.05)was significantly increased compared with the normal saline(NS)group.Compared with the NS group,the protein expression of CD11b/c(5.4817±0.77 vs 1.4073±0.37,P<0.05)and CD86(4.2673±0.69 vs 1.1379±0.42,P<0.05)was significantly increased.Itg-α(1.1224±0.3 vs 0.4907±0.19,P<0.05),CD83(3.6986±0.40 vs 1.0762±0.22,P<0.05)and CD86(1.5801±0.32 vs 0.8846±0.10,P<0.05)m RNA expression was increased significantly in the FHF group.At the protein level,expression of CD74in the FHF group(2.3513±0.52)was significantly increased compared with the NS group(1.1298±0.33),whereas in the LPS group(2.3891±0.47),the level of CD74 was the highest(P<0.05).At the gene level,the relative expression of CD74 m RNA in the FHF group(1.5383±0.26)was also significantly increased in comparison to the NS group(0.7648±0.22;P<0.05).CD3 expression was the highest in the FHF group(P<0.05).In the FHF,LPS and D-Galn groups,the expression of AKT at the protein and m RNA levels was elevated compared with the NS group,but there wasno statistical significance(P>0.05).The p-AKT protein expression in the FHF(1.54±0.06),LPS(1.56±0.05)and D-Galn(1.29±0.03)groups was higher than that in the NS group(1.07±0.03)(P<0.05).CONCLUSION:In FHF,a large number of DCs mature,express CD86,and activate MHC classⅡmolecular pathways to induce a T cell response,and the AKT pathway is activated.展开更多
BACKGROUND The lymphocyte-to-white blood cell ratio(LWR)is a blood marker of the systemic inflammatory response.The prognostic value of LWR in patients with hepatitis B virus-associated acute-on-chronic liver failure(...BACKGROUND The lymphocyte-to-white blood cell ratio(LWR)is a blood marker of the systemic inflammatory response.The prognostic value of LWR in patients with hepatitis B virus-associated acute-on-chronic liver failure(HBV-ACLF)remains unclear.AIM To explore whether LWR could stratify the risk of poor outcomes in HBV-ACLF patients.METHODS This study was conducted by recruiting 330 patients with HBV-ACLF at the Department of Gastroenterology in a large tertiary hospital.Patients were divided into survivor and non-survivor groups according to their 28-d prognosis.The independent risk factors for 28-d mortality were calculated by univariate and multivariate Cox regression analyses.Patients were divided into low-and high-LWR groups according to the cutoff values.Kaplan-Meier analysis was performed according to the level of LWR.RESULTS During the 28-d follow-up time,135 patients died,and the mortality rate was 40.90%.The LWR level in non-surviving patients was significantly decreased compared to that in surviving patients.A lower LWR level was an independent risk factor for poor 28-d outcomes(hazard ratio=0.052,95%confidence interval:0.005-0.535).The LWR level was significantly negatively correlated with the Child-Turcotte-Pugh,model for end-stage liver disease,and Chinese Group on the Study of Severe Hepatitis B-ACLF II scores.In addition,the 28-d mortality was higher for patients with LWR<0.11 than for those with LWR≥0.11.CONCLUSION LWR may serve as a simple and useful tool for stratifying the risk of poor 28-d outcomes in HBVACLF patients.展开更多
OBJECTIVE: To explore the effects of Tanshinone combined with western medicine on clinical symptoms and cardiac function in patients with acute heart failure. METHODS: The medical records of 96 patients with acute hea...OBJECTIVE: To explore the effects of Tanshinone combined with western medicine on clinical symptoms and cardiac function in patients with acute heart failure. METHODS: The medical records of 96 patients with acute heart failure were randomly divided into 2 groups(48 cases in observation group and 48 cases in control group). The control group was treated with conventional western medicine, and the observation group was treated with Tanshinone IIA sulfonic acid natrium on the basis of western medicine. The traditional Chinese medicine(TCM) syndromes scores before and after treatment(after 28 d of treatment), clinical efficacy, and cardiac echocardiographic indexes and serum biochemical indicators before and after treatment were observed in the 2 groups. RESULTS: After treatment, the scores of TCM syndromes in the 2 groups were significantly decreased(P < 0.05), and the change in observation group was significantly greater than that in control group(P < 0.05). The total clinical effective rate in observation group was significantly higher than that in control group(91.67% vs 75.00%)(P < 0.05). After treatment, the echocardiographic indexes of left ventricular end-diastolic diameter(LVEDD) and left ventricular end-systolic diameter(LVESD) values were significantly reduced in the 2 groups while the left ventricular ejection fraction(LVEF) and stroke volume(SV) value were significantly increased, and the changes in observation group were significantly larger than those in control group(P < 0.05). After treatment, the levels of serum nuclear factor-kappaB(NF-KB), interleukin-1β(IL-1β) and N-terminal pro-brain natriuretic peptide(NT-proBNP) were significantly decreased in the 2 groups(P < 0.05), while the 6-keto-prostaglandin F1α(6-ketoPGF1α) level was significantly increased. And the changes in observation group were significantly greater than those in control group(P < 0.05). CONCLUSION: Tanshinone combined with western medicine can significantly improve the clinical symptoms of patients with acute heart failure, improve cardiac function, reduce the myocardial damage degree, and effectively reduce the risk of short-term recurrence and death, and it has exact clinical efficacy.展开更多
文摘OBJECTIVE To determine the functional role of hydrogen sulfide(H_2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca^(2+)/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ) using wild type and CSE knockout mouse models.METHODS Continuous subcutaneous injection isoprenaline(7.5 mg·kg^(-1) per day),once a day for 4 weeks to induce heart failure in male C57BL/6(6-8 weeks old) mice and CSE-/-mice.150 μmol·L^(-1) H_2O_2 was used to induce oxidative stress in H9c2 cells.Echocardiograph was used to detect cardiac parameters.H&E stain and Masson stain was to observation histopathological changes.Western blot was used to detect protein expression and activity.The si RNA was used to silence protein expression.HPLC was used to detect H_2S level.Biotin assay was used to detect the level of S-sulfhydration protein.RESULTS Treatment with S-propyl-L-cysteine(SPRC) or sodium hydrosulfide(Na HS),modulators of blood H_2S levels,attenuated the development of heart failure in animals,reduced lipid peroxidation,and preserved mitochondrial function.The inhibition Ca MKⅡ phosphorylation by SPRC and Na HS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds.Interestingly,Ca MKⅡ activity was found to be elevated in CSE-/-mice as compared to wild type animals and the phosphorylation status of Ca MK Ⅱ appeared to relate to the severity of heart failure.Importantly,in wild type mice SPRC was found to promote S-sulfhydration of Ca MKⅡ leading to reduced activity of this protein however,in CSE-/-mice S-sulfhydration was abolished following SPRC treatment.CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of Ca MKⅡ is presented.SPRC mediated S-sulfhydration of Ca MKⅡ was found to inhibit Ca MKⅡ activity and to preserve cardiovascular homeostasis.
文摘Objective:To explore the effect of adjuvant tiotropium bromide therapy on the oxygenation function and inflammatory response in patients with COPD and type Ⅱ respiratory failure. Methods:a total of 58 patients with COPD and type II respiratory failure treated in our hospital between August 2012 and January 2016 were collected and divided into observation group (n=29) and control group (n=29) according to the single blind randomized control method. Control group of patients received clinical routine treatment, and observation group of patients received adjuvant tiotropium bromide treatment on the basis of routine treatment. Before treatment and 30d after treatment, spirometer was used to determine pulmonary ventilation function;blood gas analyzer was used to test oxygenation function indexes;enzyme-linked immunosorbent assay (ELISA) was used to detect serum inflammatory factor levels.Results: Before treatment, differences in pulmonary ventilation function, oxygenation function and serum inflammatory factor levels were not statistically significant between two groups of patients. 30 d after treatment, FEV1, FEF75%, PEF, PaO2/FiO2, DO2 and O2ER levels of observation group were significantly higher than those of control group while VO2 level was significantly lower than that of control group;serum IL-1β, IL-18, IL-27 and CRP levels were significantly lower than those of control group.Conclusion:Adjuvant tiotropium bromide treatment can optimize the pulmonary ventilation and oxygenation function and reduce systemic inflammatory response in patients with COPD and type II respiratory failure.
基金Supported by National Natural Science Foundation of China,No.30871158 and No.81170604Outstanding Scientific Fund of Shengjing Hospital
文摘AIM:To investigate the change in intestinal dendritic cell(DC)number in fulminant hepatic failure(FHF).METHODS:An animal model of FHF was created.Intestinal CD11b/c was detected by immunohistochemistry and Western blot.Quantitative real-time polymerase chain reaction(PCR)was used to detect intestinal integrin-αm RNA expression.Intestinal CD83,CD86,CD74,CD3 and AKT were detected by immunohistochemistry,Western blot and PCR.Phosphorylated-AKT(p-AKT)was detected by immunohistochemistry and Western blot.RESULTS:In the FHF group[D-galactosamine(D-Galn)+lipopolysaccharide(LPS)group],the mice began to die after 6 h;conversely,in the D-Galn and LPS groups,the activity of mice was poor,but there were no deaths.Immunohistochemistry results showed that in FHF,the expression of CD11b/c(7988400±385941vs 1102400±132273,P<0.05),CD83(13875000±467493 vs 9257600±400364,P<0.05),CD86(7988400±385941 vs 1102400±13227,P<0.05)and CD74(11056000±431427 vs 4633400±267903,P<0.05)was significantly increased compared with the normal saline(NS)group.Compared with the NS group,the protein expression of CD11b/c(5.4817±0.77 vs 1.4073±0.37,P<0.05)and CD86(4.2673±0.69 vs 1.1379±0.42,P<0.05)was significantly increased.Itg-α(1.1224±0.3 vs 0.4907±0.19,P<0.05),CD83(3.6986±0.40 vs 1.0762±0.22,P<0.05)and CD86(1.5801±0.32 vs 0.8846±0.10,P<0.05)m RNA expression was increased significantly in the FHF group.At the protein level,expression of CD74in the FHF group(2.3513±0.52)was significantly increased compared with the NS group(1.1298±0.33),whereas in the LPS group(2.3891±0.47),the level of CD74 was the highest(P<0.05).At the gene level,the relative expression of CD74 m RNA in the FHF group(1.5383±0.26)was also significantly increased in comparison to the NS group(0.7648±0.22;P<0.05).CD3 expression was the highest in the FHF group(P<0.05).In the FHF,LPS and D-Galn groups,the expression of AKT at the protein and m RNA levels was elevated compared with the NS group,but there wasno statistical significance(P>0.05).The p-AKT protein expression in the FHF(1.54±0.06),LPS(1.56±0.05)and D-Galn(1.29±0.03)groups was higher than that in the NS group(1.07±0.03)(P<0.05).CONCLUSION:In FHF,a large number of DCs mature,express CD86,and activate MHC classⅡmolecular pathways to induce a T cell response,and the AKT pathway is activated.
基金Supported by the National Natural Science Foundation of China,No.81960120 and 81660110the Postgraduate Innovation Special Foundation of Jiangxi Province,No.YC2022-B052“Gan-Po Talent 555”Project of Jiangxi Province,No.GCZ(2012)-1.
文摘BACKGROUND The lymphocyte-to-white blood cell ratio(LWR)is a blood marker of the systemic inflammatory response.The prognostic value of LWR in patients with hepatitis B virus-associated acute-on-chronic liver failure(HBV-ACLF)remains unclear.AIM To explore whether LWR could stratify the risk of poor outcomes in HBV-ACLF patients.METHODS This study was conducted by recruiting 330 patients with HBV-ACLF at the Department of Gastroenterology in a large tertiary hospital.Patients were divided into survivor and non-survivor groups according to their 28-d prognosis.The independent risk factors for 28-d mortality were calculated by univariate and multivariate Cox regression analyses.Patients were divided into low-and high-LWR groups according to the cutoff values.Kaplan-Meier analysis was performed according to the level of LWR.RESULTS During the 28-d follow-up time,135 patients died,and the mortality rate was 40.90%.The LWR level in non-surviving patients was significantly decreased compared to that in surviving patients.A lower LWR level was an independent risk factor for poor 28-d outcomes(hazard ratio=0.052,95%confidence interval:0.005-0.535).The LWR level was significantly negatively correlated with the Child-Turcotte-Pugh,model for end-stage liver disease,and Chinese Group on the Study of Severe Hepatitis B-ACLF II scores.In addition,the 28-d mortality was higher for patients with LWR<0.11 than for those with LWR≥0.11.CONCLUSION LWR may serve as a simple and useful tool for stratifying the risk of poor 28-d outcomes in HBVACLF patients.
文摘OBJECTIVE: To explore the effects of Tanshinone combined with western medicine on clinical symptoms and cardiac function in patients with acute heart failure. METHODS: The medical records of 96 patients with acute heart failure were randomly divided into 2 groups(48 cases in observation group and 48 cases in control group). The control group was treated with conventional western medicine, and the observation group was treated with Tanshinone IIA sulfonic acid natrium on the basis of western medicine. The traditional Chinese medicine(TCM) syndromes scores before and after treatment(after 28 d of treatment), clinical efficacy, and cardiac echocardiographic indexes and serum biochemical indicators before and after treatment were observed in the 2 groups. RESULTS: After treatment, the scores of TCM syndromes in the 2 groups were significantly decreased(P < 0.05), and the change in observation group was significantly greater than that in control group(P < 0.05). The total clinical effective rate in observation group was significantly higher than that in control group(91.67% vs 75.00%)(P < 0.05). After treatment, the echocardiographic indexes of left ventricular end-diastolic diameter(LVEDD) and left ventricular end-systolic diameter(LVESD) values were significantly reduced in the 2 groups while the left ventricular ejection fraction(LVEF) and stroke volume(SV) value were significantly increased, and the changes in observation group were significantly larger than those in control group(P < 0.05). After treatment, the levels of serum nuclear factor-kappaB(NF-KB), interleukin-1β(IL-1β) and N-terminal pro-brain natriuretic peptide(NT-proBNP) were significantly decreased in the 2 groups(P < 0.05), while the 6-keto-prostaglandin F1α(6-ketoPGF1α) level was significantly increased. And the changes in observation group were significantly greater than those in control group(P < 0.05). CONCLUSION: Tanshinone combined with western medicine can significantly improve the clinical symptoms of patients with acute heart failure, improve cardiac function, reduce the myocardial damage degree, and effectively reduce the risk of short-term recurrence and death, and it has exact clinical efficacy.
