OBJECTIVE:To compare in vivo and in vitro permeation behaviors of the ethosome gels of testosterone,testoster-one propionate and testosterone undecanoate. METHODS:The ethosome gels of testosterone,testosterone propionate and testoster-one undecanoate were prepared. With cumulative permeating amount and permeation rate as the indexes,Franz diffusion cell and HPLC were employed to compare in vitro permeation behaviors of 3 kinds of ethosome gels in mouse skin. With testosterone patch as the positive control drug, electrochemistry method was adopted to detect the concentration of testosterone in plasma 0,3,6, 9,12,24,36 and 48 h after applying such 3 kinds of ethosome gels on the back of rats,and then pharmacokinetic parameters were calculated with DAS 2.0 software. RESULTS:24 h cumulative permeating amounts of the ethosome gels of testosterone,tes-tosterone propionate and testosterone undecanoate were(234.31±13.8),(175.63±41.1)and(72.60±15.3)μg/cm2,and the per-meation rates were(10.25±1.9),(7.64±1.4)and(2.96±0.8)μg/(cm2·h),respectively. The pharmacokinetic parameters of the above-mentioned three kinds of ethosome gels and the positive control drug were respectively as follows as cmax of(20.19±2.57), (17.50±2.91),(0.23±0.04),(14.97±2.12)ng/ml,t1/2Ka of(2.80±0.45),(3.36±0.59),(4.02±0.62),(4.20±0.71)h,AUC0-48 h of(13.85±1.96),(13.93±2.13),(0.35±0.07),(11.76±2.31)ng·h/ml. CONCLUSIONS:in vivo and in vitro permeation behav-iors of the ethosome gels of testosterone and testosterone propionate are fairly good.

To study the immunopathological characteristics and differential diagnosis of hepatic angiomyolipoma(AML).Methods:Thirty-six surgically resected hepatic AML were investigated clinicopathologically and immunohistochemically with 10 antibodies.Results:Hepatic AML occurred in 21 females and 15 males,with the mean age of 41.6 years(26-60 years old).The patients with AML often had no special symptoms even had large space-occupying lesions in the liver.The diameter of AML was 2.5 cm to 14 cm(mean 6.8 cm).Histologically,AML was composed of varying heterogeneous mixture of 3 tissue components:blood vessels,smooth muscle and adipose cells.Extramedullary hemopoiesis sometimes existed.According to tissue components,AML was subcategorized into mixed type(19.4%,n=7),lipomatous type(11.1%,n=4),myomatous type(66.7%,n=24),and angiomatous type(2.8%,n=1).The epithelioid smooth muscle cells were sensitive to HMB-45(100%),SMA(100%),and CD117(66.7%) staining.Conclusion:Hepatic AML often contains smooth muscle elements,which have varied morphological features and should be carefully differentiated from hepatocellular carcinoma,mesenchymal hamartoma，and tumors with rich fat or blood vessels.Immunohistochemical staining with HMB-45 and SMA are the best available markers for the diagnosis of hepatic AML.

Objective: To explore the effects of cardiac resynchronization therapy (CRT) in patients with dispersion of re-polarization and ventricular arrhythmia.
Methods: A total of 86 consecutive patents with CRT implantation were enrolled. According to weather absolute value of LVEF increased≥10% from baseline at 6 months after CRT implantation, the patients were divided into 2 groups: Response group and Non-response group,n=43 in each group. Dispersion of re-polarization indexes as QRS duration, QTc interval, TpTe interval and the events of ventricular arrhythmia were compared between 2 groups at different time points after CRT.
Results:①In Response group, compared with pre-operation, QRS duration and TpTe interval were shorter at 1 year and within 24h after CRT implantation, allP<0.05, while the above indexes were similar in Non-response group, allP>0.05.②During 1 year after CRT implantation, the incidences of PVCs and PVC runs in Response group were much less than those in Non-response group, for lgPVCs: (1.78 ± 0.77) vs (2.73 ± 0.61), for lgPVC runs: (0.64 ± 0.48) vs (1.98 ± 0.72),P<0.05.③Multi liner regression analysis demonstrated that TpTe interval within 24h after CRT implantation was an independent predictor for both lgPVCs: (B=0.143, OR=1.154,P=0.001) and lgPVC runs: (B=0.122, OR=1.047,P=0.001).
Conclusion: CRT ventricular reverse remodeling may reduce dispersion of re-polarization and the risk of ventricular arrhythmia, therefore improve the prognosis in relevant patients; TpTe interval within 24h after CRT had the predictive value for ventricular arrhythmia.

To analyze the predictors and prognosis for super-response to cardiac resynchronization therapy (CRT) in patients with different etiology. Methods: A total of 181 patients received CRT in our hospital from 2012-01 to 2016-01 were enrolled. The patients were divided into 3 groups: Non-response group, n=63, Response group, n=62 and Super-response group, n=56. The patients were followed-up at 6 months after CRT. Results: There were 30.9% (56/181) patients having super-response. Compared with the other 2 groups, Super-response group had more patients with NYHA II-III and less NYHA IV, the patients were with the smaller LAD, LVESD, LVEDD andless patients had CRT-D implantation. The baseline cardiac function was obviously improved at 6 months after CRT in all 3 groups. The basic LVEDD, LVESD, CRT-D implantation, non-ischemic cardiomyopathy (NICM) and NYHA IV were the independent predictors for super-response occurrence. In addition, compared with ischemic cardiomyopathy (ICM), NICM patients had the higher ratio for super-response occurrence (37.6% vs 7.5%), P<0.001. Survival analysis indicated that NICM patients had the lower risk of all cause mortality (HR=0.31, 95% CI 0.14-0.80), cardiac death (HR=0.27, 95% CI 0.09-0.48) and combined endpoints (HR=0.36, 95% CI 0.27-0.78). Conclusion: At baseline condition, the patients with less degree of left ventricular reconstruction, CRT-D implantation, NICM and NYHA IV had more chance to suffer from super-response after CRT. NICM patients had the better response and prognosis to CRT.

In this study, the rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry (RRLC-QTOF/MS) was used to profile the metabolites of urine samples from chronic heart failure (CHF) patients and healthy controls to find the differential metabolites which could provide the scientific evidence to explain the pathogenesis of the disease and supply a better therapy plan.Urine samples from 15 CHF patients (age (62.27±3.14) years) and 15 healthy controls (age (65.41±4.63) years) were analyzed by RRLC-QTOF/MS.After processing the data, the multivariate statistical analysis (principal component analysis, PCA) was performed to find the potential biomarkers.Result showed that urine samples of CHF patients were successfully distinguished from those of healthy controls.Two significantly differentially expressed metabolites, uridine and alanyltryptophan, were found and identified as potential biomarkers.The result showed that the LC-MS based metabolomics approach had good performance to identify potential biomarkers, and the disorder of uracil metabolism and Tryptophan metabolism may play an important role in the mechanism of CHF.

Animals ; DNA, Complementary ; genetics ; Genome, Viral ; Humans ; Influenza Vaccines ; genetics ; immunology ; Orthomyxoviridae ; genetics ; immunology ; RNA, Viral ; genetics

Objective: To analyze the clinical features and outcomes of cardiac resynchronization therapy (CRT) in patients with dilated-phase hypertrophic cardiomyopathy (DHCM). Methods: A total of 16 DHCM patients received CRT in our hospital from 2007-03 to 2016-01 were retrospectively studied to analyze their clinical features and outcomes. Results: There were 12 male and 4 female patients at the mean age of (53.3±13.5) years. Pre-operative QRS duration of ECG was (158.7±32.2) ms, left ventricular ejection fraction (LVEF) was (33.6±6.3) %, the patient with NYHA class I, II, III and IV were 1, 5, 8 and 2 respectively. 13 patients received new CRT device, 3 received upgraded device and 8 (50%) combining atrial fibrillation (AF). The patients were followed-up for (2.56±2.13) years, 5 of them died including 3 of heart failure, 1 of sudden death and 1 of stroke. At 6 months follow-up time, 7 patients had the response to CRT which was defined by the improvement of NYHA class≥1 and the absolute elevation of LVEF≥5%; NYHA class improved from (2.69±0.79) to (2.38±0.89), P=0.02; LVEF increased from (33.6±6.3) % to (40.03±9.83) %, P=0.01. Conclusion: DHCM patients with CRT indication had the higher incidence to suffer from AF, those were more in patients with traditional pacemaker or ICD upgrading. DHCM patients with CRT had the poor general prognosis, while there was still certain proportion of patients had the response to CRT.

This study was purposed to investigate the efficacy of different whole flow lysis reagents for lysis of red blood cells in flow cytometric analysis. The expression of immunocytes was detected by flow cytometry after lysis of red blood cells using commercial reagents (Optilyse C, FACS Lysing Solution) and self-made red blood cell lysis reagents (RBC Lysis Buffer), the detection results were analyzed comparatively. The results showed that there was no significant difference in the percentage of CD3e(+), CD3e(+)CD4(+), CD3e(+)CD8a(+), CD3e(-)CD19(+), CD3e(-)NK1.1(+) and Gr-1(+) cells between 3 different lysis reagent groups. However OptiLyse C solution was suitable to Gr-1(+) cell detection, but did not suit to Foxp3(+) Treg detection. The self-made RBC Lysis Buffer and FACS Lysing Solution were suited to Foxp3(+) Treg detection. It is concluded that the use of self-made RBC Lysis Buffer for flow cytometry can get the lysis efficiency of commercially available lysis solutions when samples are prepared in accordance with standardized procedure. The self-made RBC Lysis Buffer not only can satisfy experimental requirements, but also can reduce the experimental costs.
Animals ; Erythrocyte Count ; Erythrocytes ; immunology ; metabolism ; Flow Cytometry ; instrumentation ; methods ; Immune System ; immunology ; Indicators and Reagents ; analysis ; Mice ; Mice, Inbred C57BL

Aging ; physiology ; Animals ; Female ; Male ; Mitochondria, Heart ; enzymology ; Mitochondrial Membrane Transport Proteins ; physiology ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Ventricular Function, Left ; physiology

BACKGROUNDNifekalant may prevent atrial fibrillation (AF) and possibly be useful in treatment of atrial tachyarrhythmia in patients with severe heart failure. This study investigated the electophysiologic effect of nifekalant on the acute atrial remodeling in rapid atrial pacing (RAP) model of canine.

METHODSTwelve mongrel dogs subjected to rapid stimulation (400 beats/min) at left atrial appendage (LAA) for 24 hours, were randomized into the control group (rapid pacing only, n = 6) and the nifekalant group (intravenous nifekalant therapy immediately after RAP, n = 6). Atrial electrophysiological parameters were measured in right atrium, coronary sinus, LAA, posterior wall of left atrium (PWLA) and left superior pulmonary vein (LSPV), before and after the RAP.

RESULTSIn the control group, the effective refractory periods (ERP) were shortened greatly at all sites, paced dogs had substantially shorter ERPs in the high right atrium, LAA, and LSPV, but fewer changes in the PWLA, the coefficient variation of ERP (COV ERP) was increased significantly. After rapid atrial stimulation, the inducibility of AF increased significantly [induction number: pre-RAP vs post-RAP, 1.00 +/- 0.89 vs 8.17 +/- 2.79, P < 0.01; duration of AF: pre-RAP vs post-RAP, (450.34 +/- 362.59) ms vs (9975.77 +/- 4376.99) ms, P < 0.01]. In the nifekalant group, although the ERPs were prolonged at all sites compared with those in pre-RAP state, only the value at LSPV differed significantly from that in pre-RAP state [pre-RAP vs post-RAP, (102.50 +/- 5.24) ms vs (132.51 +/- 5.20) ms, P < 0.01]; the COV ERP did not change statistically in this group. The inducibility of AF slightly increased but insignificantly after pacing [induction number: pre-RAP vs post-RAP, 0.83 +/- 0.75 vs 1.67 +/- 0.82, P = 0.19; duration of AF: pre-RAP vs post-RAP, (378.67 +/- 317.88) ms vs (1124.08 +/- 1109.77) ms, P = 0.06]. Conduction time values did not alter significantly in either of the two groups after RAP.

CONCLUSIONSIn canine RAP model, nifekalant inhibited ERP shortening and ERP heterogeneity increasing, decreased AF induction. Nifekalant can reverse acute electrical remodeling effect in this model.

Animals ; Anti-Arrhythmia Agents ; pharmacology ; Cardiac Pacing, Artificial ; Dogs ; Female ; Male ; Pyrimidinones ; pharmacology ; Refractory Period, Electrophysiological ; drug effects