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OBJECTIVE@#To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills (STDP) on heart failure (HF).@*METHODS@#Isoproterenol (ISO)-induced HF rat model and angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast (CFs) model were used in the present study. HF rats were treated with and without STDP (3 g/kg). RNA-seq was performed to identify differentially expressed genes (DEGs). Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson's stainings were taken to assess cardiac fibrosis. The levels of collagen I (Col I) and collagen III (Col III) were detected by immunohistochemical staining. CCK8 kit and transwell assay were implemented to test the CFs' proliferative and migratory activity, respectively. The protein expressions of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9, Col I, and Col III were detected by Western blotting.@*RESULTS@#The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways, such as the extracellular matrix (ECM)-receptor interaction, cell cycle, and B cell receptor interaction. Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function, inhibiting myocardial fibrosis, and reversing increases in Col I and Col III expression levels in the hearts of HF rats. Moreover, STDP (6, 9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang II in vitro (P<0.05). The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP, also the synthesis of MMP-2 and MMP-9, as well as ECM components Col I, Col III, and α-SMA were decreased in Ang II-induced neonatal rats' CFs.@*CONCLUSIONS@#STDP had anti-fibrotic effects in HF, which might be caused by the modulation of ECM-receptor interaction pathways. Through the management of cardiac fibrosis, STDP may be a compelling candidate for improving prognosis of HF.
Subject(s)
Rats , Animals , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , RNA-Seq , Transcriptome/genetics , Heart Failure/drug therapy , Collagen , Collagen Type I/metabolism , Fibrosis , Myocardium/pathologyABSTRACT
【Objective】 To evaluate the associations of total fat and fatty acid consumption with the risk of hypertension among rural residents in Hanzhong, Shaanxi Province. 【Methods】 A cross-sectional survey on dietary status with a semi-quantitative food frequency questionnaire was conducted among rural residents aged between 18 and 80 years old in Hanzhong of Shaanxi. Multivariate log-binomial regression models and restricted cubic spline were used to explore the associations of dietary total fat, saturated fatty acid, polyunsaturated fatty acid and monounsaturated fatty acids with hypertension and as well as association between dose and response. 【Results】 A total of 2241 individuals were included, with 774 males and 1467 females. Monounsaturated fatty acid accounted for 51.9% of total dietary fat intake, while the other two fatty acids for 48.1%. The intake of dietary fat and any fatty acid in men was significantly in men higher than in women (P<0.001). Results of multivariable log-binomial regression indicated that after adjustment of energy, socio-demographic and lifestyles, the risk of hypertension reduced significantly in Q4 group, compared with that in Q1 (PR: 0.71, 95% CI: 0.54-0.92; P-trend: 0.022) in females. A nonlinear dose-response relationship between monounsaturated fatty acids and hypertension was detected by restricted cubic spline in women (Pnon-linear<0.01). No association was observed of total fat, saturated fatty acid and polyunsaturated fatty acid with hypertension regardless of the gender. 【Conclusion】 In women, increased consumption of monounsaturated fats might play a positive role in reducing the risk of hypertension. Further research is warranted to verify the rationality of causal inference and break-point.
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Objective To investigate the current status of hand hygiene(HH) among health care workers(HCWs) in clinical laboratories in medical institutions in Xi'an City.Methods HH status of HCWs in clinical laboratories in medical institutions in Xi'an was performed random on-the-spot sampling and monitoring.Results A total of 240 HH specimens of HCWs in clinical laboratories in 80 medical institutions in Xi'an City were collected, 127 detected results were qualified, the total qualified rate was 52.92%.The qualified rates of medical institutions were as follows: municipal hospitals 62.67%,workers' hospitals 55.95%,private hospitals 40.74%;comprehensive medical institutions 67.68%,specialized medical institutions 42.55%;tertiary medical institutions 79.63%(n=43),secondary and below medical institutions 45.16%(n=84),there were significant differences in HH qualified rate among HCWs in different types of medical institutions(all P<0.01).Of different HH detection items, detection rates of Escherichia coli and Staphylococcus aureus were 0.83% and 8.33% respectively.There were significant differences in HH compliance rates among HCWs of all age groups(χ2=9.103,P<0.05), HCWs aged≥50 years had the highest qualified rate of HH(71.43%), followed by those aged<30 years (67.82%),HCWs in 40~ year age group had the lowest HH qualified rate (39.66%).Conclusion The qualified rate of HH of HCWs in clinical laboratory of medical institutions in Xi'an City is low, it is necessary to enhance the procaution awareness of HCWs in clinical laboratories, strengthen quality control of HH, strictly implement standard hand-washing procedures to reduce occurrence of HAI.
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Objective To understand the current situation of pressure steam sterilization in medical institutions in Xi'an city,and provide reference for the monitoring and quality control of pressure steam sterilization.Methods Central sterile supply departments(CSSDs) in medical institutions in Xi'an in 2012-2014 were investigated.Physical,chemical,and biological monitoring methods were used to evaluate the pressure steam sterilizers.Results A total of 135 medical institutions in Xi' an were monitored,including 40 tertiary medical institutions and 95 secondary and below medical institutions.A total of 540 specimens were collected,454 were qualified,overall qualified rate was 84.07 ％.Qualified rate of monitoring result of pressure steam sterilization of tertiary medical institutions was higher than secondary and below medical institutions(93.13 ％ vs 80.26 ％,x2 =13.91,P＜0.01).Qualified rates of chemical PCD and biological test pack of tertiary as well as secondary and below medical institutions were 100％ and ＞90％ respectively.The qualified rate of recoded temperature in secondary and below medical institutions was 88.42 ％,but actually measured temperature was 38.95 ％,which was significantly lower than 72.50 ％ of tertiary medical institutions(x2 =12.68,P＜0.01).The rates of the measured temperature＞ 134℃ of pressure steam sterilizer in each year were all low,but measured temperature＜132℃ was about 50.00 ％,difference between actually measured temperature and recorded temperature was-4℃-1 ℃,difference between-2.5 ℃-0.5℃ accounted for 80.00％,the main unqualified temperature was 130℃-131 ℃,accounting for 82.61 ％.Conclusion Efficacy of pressure steam sterilization is different in different levels of medical institutions in Xi'an,physical monitoring measures are not standardized,the supervision of physical parameters in key sectors should be strengthened to ensure the sterilization quality of medical institutions and reduce the occurrence of iatrogenic infection.
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Objective To understand environmental quality status of clean operating rooms in municipal hospitals of Xi’an,and provide reference for ensuring the clean quality of operating rooms.Methods On-site specimen collec-tion and detection were conducted to detect and analyze the cleanlinss of air in clean operating rooms in 15 hospital of Xi’an.Results A total of 51 operating rooms were monitored,secondary and tertiary hospitals had 24 and 27 operating rooms respectively;26 were grade-I and 25 were grade-Ⅲ operating rooms.The qualified rates of dust particle≥0.5μm/particle size in grade-I and grade-Ⅲ clean operating rooms were 76.92% and 80.00% respective-ly,≥5μm/ particle size were 73.08% and 88.00% respectively.The qualified rates of dust particle counts in grade-I and grade-Ⅲ clean operating rooms were 61 .54% and 80.00% respectively,difference was not significant(χ2=2.092,P >0.05 ).The qualified rate of dust particle counts in clean operating rooms in tertiary hospitals was significantly higher than secondary hospitals(85.19% vs 58.33%,χ2 =4.600,P 0.05),in surrounding zone were 95.83% and 92.59% respectively (both P >0.05).Conclusion Dust particle and airborne microbes in some clean operating rooms in municipal hospitals of Xi’an are beyond the standard,supervi-sion and management should be strengthened.
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Cell-penetrating peptides (CPPs) have been widely used to enhance the membrane translocation of various carriers for many years, but the non-specificity of CPPs seriously limits their utility in vivo. In this study, cholesterol-anchored, reduction-sensitive PEG (first synthesized by our laboratory) was applied to develop a co-modified liposome with improved tumor targeting. Following optimization of the formulation, the in vitro and in vivo properties of the co-modified liposome were evaluated. The co-modified liposome had a much lower cellular uptake and tumor spheroid uptake, but a much higher tumor accumulation compared to CPP-modified liposome, indicating the non-specific penetration of CPPs could be attenuated by the outer PEG coating. With the addition of exogenous reducing agent, both the in vitro and in vivo cellular uptake was markedly increased, demonstrating that the reduction-sensitive PEG coating achieved a controllable detachment from the surface of liposomes and did not affect the penetrating abilities of CPPs. The present results demonstrate that the combination of cholestervsitive PEG and CPPs is an ideal alternative for the application of CPP-modified carriers in vivo.
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The preparation method, serum stability, efficiency of cellular uptake and apoptosis induction of the cell penetrating peptide TAT and cleavable PEG co-modified liposomes loaded with paclitaxel (C-TAT-Lipo) were investigated. The best preparation procedure was performed by orthogonal test based on single factor screening method. First, the paclitaxel (PTX)-loaded liposomes were prepared by filming-rehydration method, evaluated with entrapment efficiency and polydispersity index. The morphology of C-TAT-Lipo was characterized by transmission electron microscopy. Turbidity variations were monitored in the presence of fetal bovine serum (FBS) to evaluate the serum stability of the liposomes developed here. Next, the efficiency of cellular uptake of different Rho-PE-labeled liposomes on B16F1 cells in vitro was evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry. The quantitative analysis of apoptosis induced by different PTX-loaded liposomes was performed by Annexin V-FITC/PI double staining. The optimal formulation was as follows: Chol : lipid: 1 : 8 (molar ratio); drug : lipid: 1 : 40 (mass ratio); lipid concentration: 3 mmol x L(-1); temperature of hydration: 25 degrees C. The mean size and polydispersity index of C-TAT-Lipo were about (97.97 +/- 3.68) nm and 0.196 +/- 0.037, the zeta potential was (-0.89 +/- 0.45) mV, the entrapment efficiency of paclitaxel was (90.16 +/- 1.53)%. The particle sizes did not exhibit significant variations in 50% FBS over 24 h at 37 degrees C. The efficiency of cellular uptake of the C-TAT-Lipo increased 1.40 fold following the cleavage of PEG. Apoptosis analysis showed 59.3% increase of the apoptosis and necrosis profile of C-TAT-Lipo after the detachment of PEG shells, which was markedly higher than that of N-TAT-LP with or without glutathione and SL, respectively. The results indicate that the C-TAT-Lipo is successfully prepared by filming-rehydration method and shows significant antitumor activities.
Subject(s)
Animals , Mice , Annexin A5 , Apoptosis , Cell Line, Tumor , Cell-Penetrating Peptides , Pharmacology , Fluorescein-5-isothiocyanate , Liposomes , Chemistry , Melanoma, Experimental , Microscopy, Confocal , Paclitaxel , Pharmacology , Particle Size , Polyethylene Glycols , ChemistryABSTRACT
The preparation method, serum stability, efficiency of cellular uptake and apoptosis induction of the cell penetrating peptide TAT and cleavable PEG co-modified liposomes loaded with paclitaxel (C-TAT-Lipo) were investigated. The best preparation procedure was performed by orthogonal test based on single factor screening method. First, the paclitaxel (PTX)-loaded liposomes were prepared by filming-rehydration method, evaluated with entrapment efficiency and polydispersity index. The morphology of C-TAT-Lipo was characterized by transmission electron microscopy. Turbidity variations were monitored in the presence of fetal bovine serum (FBS) to evaluate the serum stability of the liposomes developed here. Next, the efficiency of cellular uptake of different Rho-PE-labeled liposomes on B16F1 cells in vitro was evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry. The quantitative analysis of apoptosis induced by different PTX-loaded liposomes was performed by Annexin V-FITC/PI double staining. The optimal formulation was as follows: Chol : lipid: 1 : 8 (molar ratio); drug : lipid: 1 : 40 (mass ratio); lipid concentration: 3 mmol x L(-1); temperature of hydration: 25 degrees C. The mean size and polydispersity index of C-TAT-Lipo were about (97.97 +/- 3.68) nm and 0.196 +/- 0.037, the zeta potential was (-0.89 +/- 0.45) mV, the entrapment efficiency of paclitaxel was (90.16 +/- 1.53)%. The particle sizes did not exhibit significant variations in 50% FBS over 24 h at 37 degrees C. The efficiency of cellular uptake of the C-TAT-Lipo increased 1.40 fold following the cleavage of PEG. Apoptosis analysis showed 59.3% increase of the apoptosis and necrosis profile of C-TAT-Lipo after the detachment of PEG shells, which was markedly higher than that of N-TAT-LP with or without glutathione and SL, respectively. The results indicate that the C-TAT-Lipo is successfully prepared by filming-rehydration method and shows significant antitumor activities.
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Objective To investigate the clinical value of Color Doppler Ultrasound in diagnosis of lymph node diseases. Methods We observed the ultrasound features of the 93 cases of swelled lymph nodes with Color Doppler ultrasound. The ultrasound features included pseudokidney sign, assessment on blood flow distribution, the Doppler resistive Index (RI), maximal flow rate (Vmax),the longitudinal axis compared to the diameter of a node (L/D ratio) . Results Out of 93 cases of clinically confirmed swelled lymph nodes,the concordance rate of Color Doppler Ultrasound was 86%and 88%in diagnosis of malignant lymph node disease and benign lymph node disease, respectively. 4 cases of lymph tuberculosis were misdiagnosed as lymphoma due to the similar ultrasound characteristics found in malignant lymph group,the rate of misdiagnosis was 8%. In the cases of proliferative lymph node diseases with Pseudokidney sign, 93% of the blood flow distribution was classified as grade 0-I. 90% of lymphadenitis were found with Pseudokidney sign,and 95%of those cases with blood flow distribution was classified as grade II-III. Malignant lymph diseases had no Pseudokidney sign, and 86%of blood flow distribution grade was as III. There was statistically significant difference in the L/D ratio and RI between benign lymph group and malignant lymph group (P<0.01) . There was statistically significant difference in Vmax between lymphoproliferative group and other groups (P<0.01) . Conclusions Pathological characteristics on different lymph node disease determin the ultrasound characteristics. Combined clinical data based on Pseudokidney sign, Blood Flow Distribution, RI value,Vmax value and L/D ratio can enhance the accuracy of various lymph node disease diagnosis.
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<p><b>OBJECTIVE</b>To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.</p><p><b>METHODS</b>Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.</p><p><b>RESULTS</b>After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7 +/- 12.1 mmHg vs. 2.8 +/- 5.2 mmHg, P < 0.01; 12.2% +/- 12.0% vs. 2.5% +/- 4.4%, P < 0.001, respectively). There was a similar trend for diastolic blood pressure (8.4 +/- 6.4 mmHg vs. 3.7 +/- 6.4 mmHg, P = 0.052; 13.2% +/- 10.6% vs. 6.8% +/- 10.1%, P = 0.053, respectively).</p><p><b>CONCLUSIONS</b>Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.</p>
Subject(s)
Adolescent , Female , Humans , Male , Aging , Physiology , Blood Pressure , Blood Volume , Furosemide , Pharmacology , Infusions, Intravenous , Sodium Chloride , Pharmacology , SystoleABSTRACT
AIM: To observe the effect of hypoxia on cardiaomyocytes apoptosis and the role of ALDH2 in the process. METHODS: Cultured cardiomyocytes of neonatal rats were used. Hypoxia was imposed to the cardiomyocytes with or without daidzin pretreatment. ALDH2 activity was measured by the method of acetaldehyde metabolism. Apoptosis was measured by Hoechest 33324 staining, fluorescence activated cell sorting (FACS) and the DeadEnd~ TM fluorometric TUNEL system. RESULTS: ALHD2 enzyme activity in myocytes was inhibited by daidzin (24 h, 60 ?mol/L) without induction of apoptosis. When exposed to hypoxia, however, the apoptisis was significantly increased in the cells pretreated with daidzin compared to those without the pretreatment. CONCLUSION: The reduction of ALDH2 activity might increase the susceptivity of myocytes to apoptosis following hypoxia, suggesting a protective role of ALDH2 in hypoxia-induced myocardial injury.