Objective:To evaluate the efficacy and safety of conventional diuretic therapy versus Tolvaptan in elderly chronic heart failure patients combined with mild to moderate renal insufficiency with hyponatremia, in order to provide clinical evidence for the treatment of heart failure in the elderly.Methods:This was a randomized control trial.A total of 88 elderly chronic heart failure patients combined with mild to moderate renal insufficiency with hyponatremia were randomly divided into the control group(n=46)and the experimental group(n=42). Once enrolled both groups stopped taking oral loop diuretics.In addition to routine treatment, the control group was treated with furosemide 40 mg once a day, while the experimental group was treated with Tolvaptan 15 mg once a day.The rate of effectiveness in relieving heart failure, the diuretic effects and improvement in heart and kidney function were monitored, and changes in serum potassium and sodium levels and the incidences of thirst and other adverse events were compared between the two groups.Results:The effectiveness rate on heart failure was higher in the experimental group than in the control group(85.7% or 36/42 vs.65.2% or 30/46, χ2=17.855, P<0.001). After treatment, greater changes in average 24-hour urine volume from baseline(787.4±219.6 ml vs.388.6±179.6 ml, t=322.588, P<0.001), more weight loss(-2.4±2.1 kg vs.-1.7±1.6 kg, t=6.942, P=0.009), smaller changes in N-terminal pro-B-type natriuretic peptide(NT-proBNP)from baseline(-897.6±432.1 ng/L vs.-578.4±476.9 ng/L, t=539.400, P<0.001), greater changes in left ventricular ejection fraction(LVEF)from baseline(6.5±5.6 % vs.1.5±5.7 %, t=3.966, P=0.048), smaller changes in serum creatinine from baseline(-8.6±12.4 μmol/L vs.9.6±11.3 μmol/L, t=87.161, P<0.001), and greater changes in estimated glomerular filtration rate(eGFR)from baseline(1.4±1.8 ml·min -1·1.73m -2vs.-4.1±5.6 ml·min -1·1.73m -2, t=63.856, P<0.001)and in serum sodium from baseline(6.2±2.1 mmol/L vs.1.4±1.9 mmol/L, t=234.065, P<0.001)were observed in the experimental group than in the control group.There was no significant difference in the incidences of thirst, dry mouth and other adverse events between the two groups(16.7% or 7/42 vs.10.9% or 5/46, χ2=0.626, P=0.429). Conclusions:Tolvaptan can effectively improve the clinical symptoms and cardiac function and correct hyponatremia in elderly chronic heart failure patients combined with mild to moderate renal insufficiency, with a good safety profile.

Objective To evaluate the effect of curcumin on the proliferation of and apoptosis in HaCaT cells induced by tumor necrosis factor α (TNF-α).Methods HaCaT cells were cultured with the presence of different concentrations (0,1,5,10,25,50,100 ng/ml) of recombinant TNF-α,curcumin of 20 μmol/L,or the combination of recombinant TNF-α (25 ng/ml) and curcumin (20 μmol/L),for 24 hours followed by the determination of cell proliferation with methyl thiazolyl tetrazolium (MTT) assay.Western blot was conducted to measure the protein expression of proliferating cell nuclear antigen (PCNA) and Notch-1 in HaCaT cells treated with recombinant TNF-α (25 ng/ml) and curcumin (20 μ mol/L) alone or in combination for 24 hours.Flow cytometry using annexin-V/propidium iodine (PI) was performed to assess the early apoptosis in HaCaT cells incubated with recombinant TNF-α of 25 ng/ml and curcumin of 20 μmol/L alone or in combination for 12 hours.Statistical analysis was carried out with one-way analysis of variance.Results Recombinant TNF-α promoted the proliferation of HaCaT cells in a dose-dependent manner,with the maximum proliferation activity observed in HaCaT cells treated with TNF-α of 25 ng/ml,while curcumin of 20 μmol/L effectively inhibited the proliferation of HaCaT cells induced by TNF-α of 25 ng/ml (P ＜ 0.01).TNF-α of 25 ng/ml had no obvious effect on cell apoptosis,while curcumin of 20 μ mol/L markedly induced the apoptosis in HaCaT cells,and there was a synergy between TNF-α of 25 ng/ml and curcumin of 20 μmol/L in the induction of apoptosis in HaCaT cells,with the apoptosis rate being 2.3％,3.4％,11.6％ and 16.8％ respectively in untreated cells,cells treated with TNF-α,curcumin,and the combination of TNF-α and curcumin,respectively.Conclusions Curcumin could enhance the inductive effect of TNF-α on the apoptosis in,but suppress the promotive effect of TNF-α on the proliferation of,HaCaT cells.

Objective To estimate the effect of glycyrrhetinic acid on epidermal growth factor (EGF)-induced proliferation of HaCaT cells,and to investigate its possible mechanism.Methods Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the proliferation of HaCaT cells treated with different concentrations of EGF (0,1,5,10,25,50,100 μg/L) and glycyrrhetinic acid (0,0.1,1.0,10,25,50,100μmol/L) alone,or the combination of 25 μg/L EGF with 25 μ mol/L glycyrrhetinic acid or 10 μ mol/L U0126 (an inhibitor of MEK1/2).Western blot was carried out to measure the protein expression of proliferating cell nuclear antigen (PCNA),Notch-1,ERK 1/2 and phosphorylated ERK 1/2 in HaCaT cells treated with 25 μg/L EGF,10 μmol/L U0126,25μmol/L glycyrrhetinic acid alone or in combination.Data were statistically analyzed by using t test,analysis of variance and correlation analysis with SPSS 17.0 software.Results EGF of 0-100 μg/L promoted the proliferation of HaCaT cells in a dose-dependent manner (r =0.798,P ＜ 0.05),and there was a linear correlation between the effect and concentration within the concentration range 0-50 μg/L (r =0.859,P ＜ 0.05).However,glycyrrhetinic acid of 10-100 μmol/L inhibited the proliferation of HaCaT cells in a dose-dependent manner (r =-0.945,P ＜0.01),and 10 μmol/L glycyrrhetinic acid could suppress the EGF (25 μg/L)-induced proliferation and phosphorylation of ERK1/2 in HaCaT cells.Also,both 25 μmol/L glycyrrhetinic acid and 10 μmol/L U0126 could attenuate the increase in PCNA and Notch-1 expression in HaCaT cells induced by 25 μg/L EGF.Conclusion Glycyrrhetinic acid can inhibit the EGF-induced proliferation of HaCaT cells,likely by suppressing the activation of ERK1/2 signaling pathway.

ObjectiveTo estimate the clinical efficacy and immunomodulatory effect of polysaccharidenucleic acid fraction of bacillus calmette guerin(BCG-PSN) combined with a traditional Chinese medicine in patients with vitiligo.MethodsThis study recruited 99 patients with vitiligo aged from 13 to 65(35,6 ± 5.8) years.The patients were classified into 3 groups to be treated with BCG-PSN and a traditional Chinese medicine (Baidianfeng granules) alone or in combination.BCG-PSN was intramuscularly injected at a dose of 2 ml every other day and baidianfeng granules were given orally thrice a day,for 3 months.Peripheral blood samples were obtained from the patients at the baseline and after the end of treatment and from 30 healthy controls.Flow cytometry and enzyme linked immunosorbent assay(ELISA) were performed to detect T cell subsets and expression level of Fas and Fas ligand(FasL),respectively.Data were analyzed by t test and chi-square test.Results The response rate was significantly higher in patients treated with BCG-PSN combined with Baidianfeng granules than in those with BCG-PSN alone(82.86％ vs.40.63％,P ＜ 0.01 ).Before the treatment,patients showed a lower percentage of CD3+ cells,CD3+CD4+ cells and CD3+CD8+ cells in peripheral blood(all P ＜0.01 ),weaker expression of Fas (P ＜ 0.01 ),but a higher CD4/CD8 ratio (P ＜ 0.01 ) compared with the controls.The treatment with BCG-PSN and Baidianfeng granules alone or in combinatiou all induced an increase in the percentage of CD3+ cells,CD3+CD4+ cells and CD3+CD8+ cells in peripheral blood(P ＜ 0.05) and in the expression of Fas(P ＜ 0.01),but a decrease in CD4/CD8 ratio(P ＜ 0.05).ConclusionsBCG-PSN may induce the normal apoptosis in lymphocytes via reversing the abnormality in the expression of Fas/FasL by peripheral blood lymphocytes,and the effect of BCG-PSN may be enhanced by a traditional Chinese medicine,Baidianfeng granules.

Objective:To evaluate the therapeutic effects of Tolvaptan on refractory heart failure in patients aged 75 years and older.Methods:This was a randomized controlled trial.A total of 68 patients with refractory heart failure aged 75 years and older were divided into the control group(n=38)and the experimental group(n=30)by randomly generated numbers.Patients in the control group were given levosimendan and recombinant human brain natriuretic peptide intravenously plus routine treatments such as diuresis and electrolyte correction.In the experimental group, 30 patients were given a single dose of 15 mg Tolvaptan per day in addition to what was received by the control group.The effects on heart failure were compared between the two groups 1 week after treatment.Changes in rehospitalization rate, emergency intervention frequency and mortality rate were recorded after a 3-month follow-up.Results:Clinical symptoms of heart failure were alleviated in both the experimental and control groups after treatment.Improvements in 24-h urine volume, body weight and 6-minute walking distance were more significant in the experimental group than in the control group after treatment[(1 470.5±200.6)ml vs.(972.5±201.7)ml, (-6.4±2.1)kg vs.(-2.8±1.9)kg, (189.3±13.7)m vs.(151.3±12.5)m, P<0.05]. Changes in serum sodium levels and improvement of LVEF were greater and reduction of N-terminal B-type brain natriuretic peptide(NT-proBNP)levels was more significant in the experimental group than in the control group after treatment[(5.2±2.1)μmol/L vs.(-1.1±2.4)μmol/L, (10.1±4.1)% vs.(7.0±4.0)%, (-6 670±1 815.7)ng/L vs.(-5 025.3±1 876.7)ng/L, P<0.05]. There was no significant difference in the incidence of adverse reactions between the two groups( P>0.05). The experimental group had shorter hospital stays, while the rehospitalization rate, emergency intervention times and mortality had no significant difference between the two groups during the follow-up period( P>0.05). Conclusions:Addition of Tolvaptan to treatment can increase urine volume, improve cardiac function, correct hyponatremia and shorten the length of hospitalization in refractory heart failure patients aged 75 years and older with good safety and has no significant impact on renal function.

Objective:To investigate the influence of frailty on post-treatment outcomes in elderly heart failure patients with reduced ejection fraction treated with Sacubitril/Valsartan.Methods:The 231 heart failure patients aged 60 years or over with reduced ejection fraction were enrolled from October 2017 to October 2018 in Department of Geriatric Medicine, Henan Provincial People's Hospital.Patients were divided into the frailty group(n=116)and the control group(n=115). Frailty diagnosis was made by five indexes suggested by LP Fried.Both groups were treated with sacubitril/valsartan(49/51 mg)for 1 year.The left ventricular ejection(LVEF), estimated glomerular filtration rate(eGFR), N-terminal pro B-type natriuretic peptide(NT-proBNP)and other clinical and laboratory indexes were detected before and after treatment and compared between the frailty group and the control group.Results:16 subjects in the frailty group and 11 subjects in the control group dropped out of the study.The frailty group versus the control group showed a higher mortality rate of cardiovascular causes(13.0% or 13/100 vs.6.7% or 7/104, χ2=6.437, P=0.027), a higher first re-hospitalization rate(18.0% or 18/100 vs.11.5% or 12/104, χ2=4.458, P=0.043)and a higher all-cause mortality(16.0% or 16/100 vs.8.6% or 9/104, χ2=3.875, P=0.039). In the frailty group, levels of serum NT-proBNP and creatinine were higher and eGFR was lower after treatment than before treatment[(2 253±144) ng/L vs.(2 094±136) ng/L, (137±24) μmol/L vs.(125±23) μmol/L, (49.2±5.9) ml·min -1·1.73 m -2vs.(56.7±6.3) ml·min -1·1.73 m -2, t=3.674, 2.893 and 2.068, P=0.017, 0.026 and 0.029]. In the control group, serum NT-proBNP levels were lower after treatment than before treatment[(1 828±123) ng/L vs.(1 945±128) ng/L, t=1.896, P=0.043], while serum creatinine levels[(120±22) μmol/L vs.(117±19) μmol/L, t=2.099, P=0.650]and eGFR[(59.8±6.5) ml·min -1·1.73 m -2vs.(61.6±6.8) ml·min -1·1.73 m -2, t=2.444, P=0.173]had no significant difference between post-treatment and pre-treatment. Conclusions:Frailty has adverse affects on the mortality, re-hospitalization rate and renal function in elderly heart failure patients with reduced ejection fraction treated with Sacubitril/Valsartan.

Objective: To investigate the impact of comprehensive geriatric assessment(CGA)on treatment outcomes of chronic heart failure(CHF)complicated with emotional disorders in the elderly. Methods: A total of 216 CHF patients with emotional disorders at Henan Provincial People’s Hospital were recruited from September 2017 to March 2019 and were randomly divided into a CGA group and a control group with 108 cases in each group.The control group was given standard drug treatment and psychological counseling, whereas individualized treatment was given to participants in the CGA group in compliance with CGA guidelines.The clinical effects after intervention for 8 weeks in the two groups were examined, using measures such as Hamilton Depression Rating Scale for Depression(HAMD)-24, Hamilton Anxiety Scale(HAMA)-14, amino-terminal pro-brain natriuretic peptide(NT-proBNP), the 6 minute walk test(6MWT)and left ventricular ejection fraction(LVEF). The changes of cognitive status, nutritional status, fall risk and other indicators in patients were comprehensively assessed and statistically analyzed. Results: Compared with pre-treatment data, 8 weeks of treatment for both the control group and the CGA group resulted in decreased HAMD-24 scores(Control group: 31.78±9.08, 23.69±10.16; CGA group: 32.09±8.98, 15.35±7.91; P<0.05), HAMA-14 scores(Control group: 22.38±7.09, 15.28±6.54; CGA group: 21.99±8.12, 10.48±6.82; P<0.05)and NT-proBNP levels[Control group: (4672±392)ng/L, (3279±282)ng/L; CGA group: (4861±378)ng/L, (2387±215)ng/L; P<0.05], and increased LVEF(%)[Control group(34.5±6.2)%, (39.8±7.5)%; CGA group(35.1±3.9)%, (42.5±6.1)%; P<0.05]and 6MWT scores[Control group(298±79±7.5)m, (358±102)m; CGA group(305±98)m, (402±178)m; P<0.05], with more marked changes in all the measures in the CGA group than in the control group(P<0.05). Conclusions The early application of CGA can improve the condition and prognosis in elderly heart failure patients complicated with emotional disorders.

Objective:To investigate the relationship between serum albumin(SA)levels and left atrial thrombosis(LAT)in elderly patients with nonvalvular atrial fibrillation(NVAF), and to evaluate the clinical value of SA in predicting LAT in elderly NVAF patients.Methods:Clinical data of 180 elderly patients with NVAF undergone transesophageal echocardiography(TEE)in our hospital were retrospectively analyzed.According to whether there was thrombosis in the left atrium, patients were divided into the thrombus group(n=42)and the non-thrombus group(n=138). Logistic regression was used to analyze factors related to left atrial appendage thrombosis in NVAF patients.The receiver operating characteristic(ROC)curve was used to evaluate the value of serum albumin levels in predicting LAT formation in elderly NVAF patients.Results:The duration of AF was longer in the thrombus group than in the non-thrombus group(all P<0.05). C-reactive protein(CRP)levels and platelet(PLT)counts were higher, and SA levels and the international normalization ratio(INR)were lower in the thrombus group than in the non-thrombus group(all P<0.05). The left atrial diameter(LAD)was larger in the thrombus group than in the non-thrombus group( P<0.05). Multiple Logistic regression analysis showed that the duration of AF and CRP levels were independent risk factors for LAT( P<0.05), and SA levels and INR were independent protective factors for LAT( P<0.05). ROC curve results showed that the area under the curve(AUC)of SA in predicting LAT was 0.778(95% CI: 0.711-0.837, P<0.001). Conclusions:Low serum albumin levels are closely related to LAT in NVAF patients and can be regarded as a predictor of LAT.Serum albumin levels should be monitored in clinical practice to reduce the incidence of stroke events in patients with AF.