Objective:To investigate whether chlorogenic acid can inhibit the proliferation, migration, invasion and promote apoptosis of lung cancer A549 cells by causing mitochondrial dysfunction through PI3K-Akt pathway.Methods:A549 cells were treated with chlorogenic acid at concentrations of 0, 25, 50, 100, 150, and 200 μg/ml for 48 h. CCK-8 assay was used to detect the cell proliferation rate and calculate the half maximal inhibitory concentration (IC 50). A549 cells were divided into three groups: control group, chlorogenic acid group (IC 50) and chlorogenic acid + 740-YP group (IC 50 chlorogenic acid +50 μg/ml 740YP). After 48 h of intervention, the cell migration distance was detected by cell scratch assay. Cell invasion assay was used to detect cell invasion ability. Cell cycle, apoptosis and mitochondrial membrane potential were detected by flow cytometry. The content of malondialdehyde (MDA) in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the protein expression of p-PI3K, p-Akt and Caspase3. Results:The IC 50 of chlorogenic acid to A549 cells was 57.45 μg/ml. The results of cell scratch assay showed that the 48 h migration distances of the control group, chlorogenic acid group and chlorogenic acid + 740YP group were (424.80±14.43), (289.67±18.93) and (402.22±17.99) μm, respectively. The results of cell invasion assay showed that the numbers of invasive cells after 48 h were 96.00±6.24, 35.33±7.64 and 83.00±2.00, and the results of flow cytometry showed that the 48 h apoptosis rates were (6.15±0.17) %, (54.63±0.72) % and (17.27±0.39) %, respectively, among the three groups with statistically significant differences ( F=105.98, P<0.001; F=90.62, P<0.001; F=8 321.99, P<0.001). Compared with the control group, the cell migration distances and invasive numbers of chlorogenic acid group and chlorogenic acid + 740YP group were decreased (all P<0.05), while the apoptosis rates were significantly increased (both P<0.001). Compared with chlorogenic acid group, the cell migration distance of chlorogenic acid + 740YP group increased ( P<0.001), the number of cell invasion increased ( P<0.001), and the apoptosis rate decreased ( P<0.001). The results of flow cytometry showed that the proportions of cells in G 0/G 1 phase in the control group, chlorogenic acid group and chlorogenic acid + 740YP group were (65.75±0.58) %, (55.84±0.78) % and (55.24±1.37) %, respectively. The proportions of G 2/M phase were (11.21±1.03) %, (20.23±0.62) % and (9.96±0.33) %, and the proportions of S phase were (23.04±0.49) %, (23.92±1.36) % and (34.80±1.15) %, respectively, with statistically significant differences ( F=111.02, P<0.001; F=181.26, P<0.001; F=113.05, P<0.001). Compared with the control group, the proportions of G 0/G 1 phase cells in chlorogenic acid group and chlorogenic acid + 740YP group decreased (both P<0.001), and the proportion of G 2/M phase in chlorogenic acid group increased ( P<0.001), and the proportion of S phase cells in chlorogenic acid + 740YP group increased ( P<0.001). Compared with chlorogenic acid group, the proportion of G 2/M phase cells decreased and the proportion of S phase cells increased in chlorogenic acid + 740YP group (both P<0.001). The results of mitochondrial membrane potential detection showed that the JC-1 fluorescence intensity of mitochondria in the control group, chlorogenic acid group and chlorogenic acid + 740YP group were 39.51±1.32, 10.05±0.19 and 21.85±1.45, respectively, with a statistically significant difference ( F=508.82, P<0.001). Compared with the control group, the fluorescence intensity of chlorogenic acid group and chlorogenic acid + 740YP group decreased (both P<0.001). Compared with chlorogenic acid group, the fluorescence intensity of chlorogenic acid + 740YP group increased ( P<0.001). ELISA results showed that the MDA contents of the control group, chlorogenic acid group and chlorogenic acid + 740YP group were (0.47±0.01), (0.61±0.01) and (0.56±0.01) nmol/ml, respectively, with a statistically significant difference ( F=162.30, P<0.001). Compared with the control group, MDA contents in chlorogenic acid group and chlorogenic acid + 740YP group increased (both P<0.001). Compared with chlorogenic acid group, MDA content in chlorogenic acid + 740YP group decreased ( P=0.001). Western blotting results showed that the relative protein expression levels of p-PI3K in the control group, chlorogenic acid group and chlorogenic acid + 740YP group were 1.01±0.33, 0.28±0.14 and 0.34±0.20, respectively. The relative protein expression levels of p-Akt were 1.00±0.16, 0.43±0.05 and 0.95±0.14, and the relative protein expression levels of Caspase3 were 1.00±0.04, 1.41±0.05 and 0.70±0.13, respectively, and there were statistically significant differences ( F=8.48, P=0.018; F=19.11, P=0.002; F=57.50, P<0.001). Compared with the control group, the expressions of p-PI3K and p-Akt protein in chlorogenic acid group decreased, and the expression of Caspase3 protein increased (all P<0.05). The expressions of p-PI3K and Caspase3 protein in chlorogenic acid + 740YP group decreased (both P<0.05). Compared with chlorogenic acid group, the expression of p-Akt protein in chlorogenic acid + 740YP group increased, and the expression of Caspase3 protein decreased (both P<0.05) . Conclusion:Chlorogenic acid may inhibit the PI3K-Akt pathway by reducing the phosphorylation of PI3K and Akt proteins, resulting in the damage of mitochondrial function and the accumulation of MDA, which eventually leads to the damage of lung cancer A549 cells function and the reduction of cells activity, and then promotes cells apoptosis.

OBJECTIVE: To establish a method for detecting the contents of 12 toxic elements such as beryllium,vanadium and thallium in human whole blood,urine and hair by inductively coupled plasma-mass spectrometry( ICP-MS).METHODS: Whole blood( 0.25 mL) and urine( 10.00 mL) were diluted 20 times into suspension by 0.1% TritonX-100 + 0.5% nitric acid,and analyzed by ICP-MS.The hair( 0.20 g) was mixed with nitric acid and digested by microwave,then made up to 10.00 mL with purified water.The analysis was performed by ICP-MS.RESULTS: The linear correlation coefficients of all the 12 elements,such as beryllium,vanadium,chromium,manganese,cobalt,nickel,arsenic,cadmium,tin,antimony,tellurium and lead were≥0.999 5.The detection limit for whole blood and urine was 0.097-1.995 μg/L,and the detection limit for hair was 0.001-0.012 μg/g.The recovery rates for whole blood,urine and hair were 92.3%-105.0%,93.7%-115.5% and 92.5%-111.0%,respectively.The within-run relative standard deviation( RSD) were 0.7%-5.8%,0.8%-4.6% and 2.2%-8.4%,respectively; the between-run RSD were 1.6%-7.1%,3.5%-7.5% and 2.8%-8.8%,respectively.CONCLUSION: This method has good accuracy,high sensitivity and good precision,which is suitable for rapid screening for various elements in human biological samples.

Objective: To assess the relationship between serum albumin level and clinical outcome in heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). Methods: In this retrospective cohort study, 357 consecutive chronic heart failure patients receiving CRT between January 2010 and December 2015 were enrolled and divided into two groups based on pre-CRT serum albumin (albumin≥40 g/L, n=244; albumin<40 g/L, n=113). Clinical outcomes were defined as all-cause mortality (including heart transplantation) and rehospitalization due to worsening HF.Baseline characteristics were compared and all-cause mortality (including heart transplantation) and rehospitalization due to worsening heart failure (HF) were analyzed using Kaplan-Meier curves.Prognostic value of albumin level was evaluated in Cox proportional-hazards regression models. Results: Over a median follow-up time of 21 months, 45 patients (12.6%) died, 4 patients (1.1%) underwent heart transplantation and 100 patients (28.0%) were rehospitalized due to worsening HF. HF patients with pre-CRT albumin<40 g/L were related with worse NYHA function class, lower HDL-C level and ACEI/ARB use compared to HF patients with pre-CRT albumin≥40 g/L. Kaplan-Meier analyses evidenced lower survival rate in HF patients (log-rank test: P=0.000 4, χ²=12.60) and higher rehospitalization rate due to worsening HF (log-rank test: P=0.009, χ²=6.82) in HF patients with pre-CRT albumin<40 g/L.Multivariate Cox analyses indicated that serum pre-CRT albumin <40 g/L was an independent risk factor for all-cause mortality (HR=2.019, 95%CI 1.125-3.622, P=0.018) and HF rehospitalization (HR=1.517, 95%CI 1.014-2.270, P=0.043). Conclusion Pre-CRT serum albumin level is associated with the severity of heart failure in CRT recipients.Patients with lower pre-CRT albumin level face increased risk of all-cause mortality and HF rehospitalization in chronic heart failure patients receiving cardiac resynchronization.

Objective: To create and validate a scoring system for predicting clinical prognosis in patients with cardiac resynchronization therapy (CRT). Methods: A cohort of 367 consecutive patients received CRT in our hospital from 2010-01 to 2015-12 were enrolled. The endpoint follow-up events were all-cause death including heart transplantation and heart failure re-admission. The patients were randomly categorized into 2 groups: Modeling group, to develop HEAL scoring system,n=300 and Veriifcation group, to validate HEAL model,n=67. HEAL system was established by Cox proportional hazards regression model, discrimination between HEAL and EARRN scoring systems was evaluated by AUC of ROC, HEAL calibration was assessed by Hosmer-Lemeshow test and clinical endpoint evaluation by 2 scoring systems were compared by Kaplan-Meier method. Results: Modeling group analysis indicated that hs-CRP (HR=1.137, 95% CI 1.072-1.205,P<0.001), big endothelin-1 (HR=1.934, 95% CI 1.066-3.507,P=0.03), left atrial diameter (HR=1.045, 95% CI 1.007-1.084,P=0.02) and NYHA IV (HR=2.583, 95% CI 1.331-5.013,P=0.005) were the independent risk factors of adverse prognosis in CRT patients. Based on β partial regression coefifcient, HEAL scoring system was established to classify the patient's risk levels: low risk<4, moderate risk 4-10 and high risk>10. AUC for risk classification in Modeling group and Verification group were 0.719(95% CI 0.629-0.809) and 0.708 (95% CI 0.539-0.878), HEAL can well distinguish clinical prognosis in patients at different risk levels (log-rank test showed in Modeling groupP<0.001 and in Veriifcation groupP=0.002); Hosmer-Lemeshow test presented good calibration,P=0.952. All 367 patients were respectively evaluated by HEAL and EARRN scoring systems, HEAL had the better discrimination than EARRN as AUC 0.763 (95% CI 0.692-0.833) vs AUC 0.602 (95% CI 0.517-0.687). Conclusion: HEAL scoring system can effectively predict adverse prognosis in CRT patients, it had the better discrimination than EARRN system and was valuable to distinguish high risk patients in clinical practice.

BACKGROUNDRenal insufficiency (RI) is significantly associated with clinical prognosis in patients with heart failure (HF), but direct evidences on the relation between renal function and clinical outcome in patients receiving cardiac resynchronization therapy (CRT) are limited. The aim of the current study was to systematically evaluate the association of baseline and 6-month renal function with cardiac reverse remodeling and long-term outcome after CRT.

METHODSWe retrospectively evaluated 190 consecutive patients who underwent CRT at Fuwai Hospital from January 2008 to April 2013. Renal function tests, echocardiographic measurement, and clinical parameters at baseline and after 6 months of CRT were performed. Primary endpoint events included all-cause mortality, cardiac transplantation, and unplanned hospitalizations for HF.

RESULTSAt baseline, compared with normal renal function or mild RI (estimated glomerular filtration rate (eGFR) ≥60 ml×min(-1)×1.73 m(-2)), moderate-to-severe RI (eGFR <60 ml×min(-1)×1.73 m(-2)) exerted a negative influence on cardiac reverse remodeling parameters. At 6-month follow-up, 114 (60.0%) patients were classified as responders and showed significant renal function improvement, whereas renal function deteriorated in non-responders and subsequently 41 (25.6%) patients developed worsening renal function (WRF). During the mean follow-up of (24.3±17.1) months, both patients with baseline eGFR <60 ml×min(-1)×1.73 m(-2) and those with WRF experienced worse event-free survival (P < 0.01, respectively).

CONCLUSIONSThis analysis identified that baseline eGFR as well as WRF after CRT were found to be independent determinants of the combined endpoints of all-cause mortality and HF-related hospitalizations in CRT recipients.

Aged ; Cardiac Resynchronization Therapy ; adverse effects ; Disease-Free Survival ; Female ; Heart Failure ; etiology ; physiopathology ; Humans ; Kidney ; physiopathology ; Kidney Function Tests ; Male ; Middle Aged ; Receptor, Epidermal Growth Factor ; Retrospective Studies

Background The data on the prognostic values of high sensitivity C-reactive protein (hsCRP) levels in patients with advanced symp-tomatic heart failure (HF) receiving cardiac resynchronization therapy (CRT) are scarce. The aim of present study was to investigate the association of serum hsCRP levels with left ventricle reverse remodeling after six months of CRT as well as long-term outcome. Methods A total of 232 CRT patients were included. The assessment of hsCRP values, clinical status and echocardiographic data were performed at baseline and after six months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for HF. Results During the mean follow-up periods of 31.3 ± 31.5 months, elevated hsCRP (>3 mg/L) prior to CRT was associated with a significant 2.39-fold increase (P=0.006) in the risk of death or HF hospitalizations. At 6-month follow-up, patients who responded to CRT showed significant reductions or maintained low in hsCRP levels (–0.5 ± 4.1 mg/L reduction) compared with non-responders (1.7 ± 6.1 mg/L increase, P=0.018). Com-pared with patients in whom 6-month hsCRP levels were reduced or remained low, patients in whom 6-month hsCRP levels were increased or maintained high experienced a significantly higher risk of subsequent death or HF hospitalizations (Log-rank P<0.001). The echocardio-graphic improvement was also better among patients in whom 6-month hsCRP levels were reduced or remained low compared to those in whom 6-month hsCRP levels were raised or maintained high. Conclusions Our findings demonstrated that measurement of baseline and follow-up hsCRP levels may be useful as prognostic markers for timely potential risk stratification and subsequent appropriate treatment strategies in patients with advanced HF undergoing CRT.

Background Renal insufficiency (RI) is significantly associated with clinical prognosis in patients with heart failure (HF),but direct evidences on the relation between renal function and clinical outcome in patients receiving cardiac resynchronization therapy (CRT) are limited.The aim of the current study was to systematically evaluate the association of baseline and 6-month renal function with cardiac reverse remodeling and long-term outcome after CRT.Methods We retrospectively evaluated 190 consecutive patients who underwent CRT at Fuwai Hospital from January 2008 to April 2013.Renal function tests,echocardiographic measurement,and clinical parameters at baseline and after 6 months of CRT were performed.Primary endpoint events included all-cause mortality,cardiac transplantation,and unplanned hospitalizations for HF.Results At baseline,compared with normal renal function or mild RI (estimated glomerular filtration rate (eGFR) ＞-60 ml·min-1·1.73 m-2),moderate-to-severe RI (eGFR ＜60 ml·min-1·1.73 m-2) exerted a negative influence on cardiac reverse remodeling parameters.At 6-month follow-up,114 (60.0％) patients were classified as responders and showed significant renal function improvement,whereas renal function deteriorated in non-responders and subsequently 41 (25.6％) patients developed worsening renal function (WRF).During the mean follow-up of (24.3±17.1) months,both patients with baseline eGFR ＜60 ml.min-1·1.73 m-2 and those with WRF experienced worse event-free survival (P ＜0.01,respectively).Conclusions:This analysis identified that baseline eGFR as well as WRF after CRT were found to be independent determinants of the combined endpoints of all-cause mortality and HF-related hospitalizations in CRT recipients.

Background Intrathoracic impedance monitoring has emerged as a promising new technique for the detection of impending heart failure (HF). Although false positive episodes have been reported in case reports and clinical trials, the efficacy and false positive rate in real-world practice remain unclear. Objective The aim of this study is to investigate the utility and reliability of the OptiVol alert feature in clinical practice. Methods We continuously recruited patients who underwent implantable cardioverter-defibrillator (ICD) or cardiac re-synchronization therapy with defibrillator (CRT-D) implantation with feature of intrathoracic impedance monitoring system in our center from Sep. 2010 to Oct. 2012. Regular in-office follow-up were required of all patients and the following information was collected at each visit: medical history, device interrogation, N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement and an echocardiogram. Worsening HF was defined as hospitalization or the presentation of signs or symptoms of HF. Results Forty three patients (male:76.7%, mean age:57 ± 15 years, left ventricular ejection fraction (LVEF):33%± 14%) were included in this observational study. Fifty four alert events and 14 adjudicated worsening HF were detected within 288 ±163 days follow-up. Eleven (20.4%) alert episodes were associated with acute cardiac decompensation in 9 patients with a positive predictive value of 78.6%. Forty three audible alerts showed no connection to worsening HF. The unexplained alerts rate was 79.6%and 1.27 per person-year. Thirty seven alarm alerts were detected in patients with EF<45%, among which 9 accompanied with HF, 17 alerts detected in patients with LVEF≥45%and 2 associated with HF. There was no sig-nificant difference between the two groups (9/37 vs. 2/17;P=0.47). Conclusions Patients with normal or nearly normal left ventricular systolic function also exhibited considerable alert events. The OptiVol fluid index predicted worsening cardiac events with a high unex-plained detection rate, and any alert must therefore be analyzed with great caution. Efforts to improve the specificity of this monitoring sys-tem represent a significant aspect of future studies.

OBJECTIVE To investigate the bacterial contamination of office telephones and computers in an infectious disease hospital to provide evidence for their disinfection.METHODS A total of 206 bacterial samples were collected from 73 telephones and 30 computers in offices in our hospital to determine the bacterial contamination of these office tools.RESULTS The contamination rate was 100% and sanitary qualification rate 32.5%.The highest bacterial colony count was 46 CFU/cm2 and the lowest one 2 CFU/cm2,The sanitary qulification rate of the telephones and computers in clean region was only 30.95%.CONCLUSIONS There was severe bacterial contamination in office telephones and computers,which should be paid close attention to.

OBJECTIVE To discuss management in the prevention and treatment of infectious diseases and influenza A(H1N1) the according to law.METHODS The requirements of prevention and treatment for infectious diseases and influenza A(H1N1),were set out according to "Communicable Disease Prevention Act" and other relevant laws and regulations.RESULTS The prevention and control strategies and measures of influenza A(H1N1) still existed some problems.CONCLUSIONS The key doing a good job of prevention and control for infectious diseases and influenza A(H1N1) is according to the law scientificly and orderly.