Effects of clinical P-glycoprotein inhibitors on oral bioavailability and brain penetration of gefitinib / 中国药科大学学报

@#To investigate the effects of clinical P-glycoprotein inhibitors on oral bioavailability and brain penetration of gefitinib, 16 inhibitors and gefitinib were co-administered orally to ICR mice. The suspension of gefitinib and CMC-Na were co-administered to the control group. The suspension of gefitinib and clinical P-glycoprotein inhibitors were co-administered to the control group. Blood samples and brain homogenate samples were extracted by protein precipitation with acetonitrile and determinated by LC-MS/MS. It was found that ritonavir can significantly increase the oral bioavailability of gefitinib, and the area under the plasma concentration-time curves(AUC)of gefitinib was increased by 2 times; while brain exposure was increased, there was no increment in brain penetration. Some other drugs can also increase the plasma AUC of gefitinib, but can not enhance the brain penetration; After we corrected brain concentration with fraction of unbound drug in brain, it was found that the brain concentration of gefitinib in both control group and ritonavir group did not achieve the in vitro IC50 of inhibiting non-small cell lung cancer(NSCLC)cell growth. Our results suggest that clinical doses of the 16 clinical P-glycoprotein inhibitors can not specifically increase brain tissue exposure, more specific and safer P-gp inhibitors are required. After we corrected brain concentrations with fraction of unbound drug in brain, our preclinical studies found that insufficient brain exposure may be one of the reasons for the unsatisfactory efficacy of gefitinib in the treatment of brain metastases.

Cardioversion efficacy of nifekalan in patients with sustained atrial fibrillation after radiofrequency ablation / 中华心血管病杂志

Objective@#To evaluate the efficacy and safety of nifekalan (NIF) on cardioversion in atrial fibrillation (AF) patients post radiofrequency ablation, and investigate the relevant factors related to the cardioversion efficacy of NIF.@*Methods@#We screened patients with sustained AF rhythm after radiofrequency ablation between November 2016 and July 2018. Participants were treated with intravenous NIF 0.4 mg/kg within 5-10 minutes after ablation. We observed the adverse reaction, and monitored the rhythm, heart rate, QT interval and QTc interval before the medication and at 5, 10, 20, 120 min after the medication. According to the drug outcome of NIF, patients were divided into conversion group and non-conversion group, related factors affecting conversion efficacy were evaluated using logistic regression analysis.@*Results@#(1)A total of 116 patients were enrolled in the study (63 males and 53 females, mean age was (64±18) years). Among them, 72 patients were converted to sinus rhythm, and the overall successful rate was 62.1%. There were 84 patients with persistent AF, of which 50 cases (59.2%) were restored to sinus rhythm. There were 32 patients with paroxysmal AF, 22 cases (68.8%) of them were restored to sinus rhythm. The conversion time was 1.5 to 12 (6.8±3.4)min. (2) In 116 patients, the QT interval and QTc interval were significantly longer after medication than before the drug administration (P<0.01), and peaked at about 10th min, and restored to the level before drug administration at about 120th min. (3) There were 8 cases of bradycardia (6.9%), 3 cases of frequent and short ventricular tachycardia (2.6%). (4) The duration of atrial fibrillation was shorter and left atrial diameter was smaller in the cardioversion group than in the non-cardioversion group (both P<0.05). There were no significant differences in gender, disease history, atrial fibrillation type and structural heart disease between the two groups (P>0.05). (5) Multifactorial logistic regression analysis showed that the duration of atrial fibrillation (OR=0.980, 95%CI 0.966-0.994, P=0.004) and the left atrial diameter (OR=0.888, 95%CI 0.814-0.967, P=0.007) were the factors that influence the cardioversion efficacy of NIF on atrial fibrillation post ablation.@*Conclusions@#The total effective rate of NIF was 62.1% in patients witrh sustained AF post radiofrequency ablation, was 68.8% in patients with paroxysmal AF. Besides, NIF has the advantage of short conversion time and few adverse reactions. Left atrium diameter and AF duration were relevant factors that influence the efficacy of NIF of cardioversion in patients with sustained AF after radiofrequency ablation.

Homocysteine induces calcium overload in neonatal rat atrial cells through activation of sodium current and CaMKⅡδ / 中华心血管病杂志

Objective@#To investigate the effect and related mechanism of homocysteine (Hcy) on calcium overload in neonatal rat atrial cells (NRICs).@*Methods@#NRICs were assigned to 9 groups after culture for 3 days: (1) control group; (2) Hcy group (0, 50, 100, 200, 500 μmol/L for 48 hours); (3) antioxidant group (NAC, 10 μmol/L for 24 hours); (4) Hcy+NAC group (500 μmol/L Hcy for 48 hours, then treated with 10 μmol/L NAC for 24 hours); (5) calcium/calmodulin dependent protein kinase Ⅱδ (CaMKⅡδ) inhibitor group (KN-93, 3 μmol/L KN-93 for 5 hours); (6) specific sodium current inhibitor group (ELE, 1 μmol/L ELE for 5 hours); (7) Hcy+KN-93 group (500 μmol/L Hcy for 48 hours, then treated with 3 μmol/L KN-93 for 5 hours); (8) Hcy+ELE group (500 μmol/L Hcy for 48 hours, then treated with 1 μmol/L ELE for 5 hours; (9) Hcy+KN-93+ELE group (500 μmol/L Hcy for 48 hours, then treated with 3 μmol/L KN-93 and 1 μmol/L ELE for 5 hours). Moreover, NRICs were also treated with CaMKⅡδ-siRNA lentivirus, and Nav1.5-siRNA lentivirus, negative lentivirus carrier containing green fluorescent protein (GFP) for 24 hours. The MOI values of the three groups were 10. Infection efficiency of lentivirus was determined by observing the percentage of GFP fluorescence under inverted fluorescence microscope after transfection for 24 hours, and cultured regularly with simultaneous Puro screening, then cells were grouped as Hcy+CaMKⅡδ-siRNA group, Hcy+Nav1.5-siRNA group and Hcy+negative group. The concentration of Ca2+ in NRICs ([Ca2+]i) of various groups was detected through Fluo-4/AM fluorescence probe, then 2', 7'- two chlorofluorescein diacetate (DCFH-DA) was used as a probe to detect reactive oxygen species (ROS) in NRICs by flow cytometry. The malondialdehyde (MDA) was detected by the activity of superoxide dismutase (SOD) and xanthine oxidase was detected by thiobarbituric acid colorimetry. The protein and mRNA expression level of CaMKⅡδ and Nav1.5 in NRICs were detected by Western blot and quantitative real-time PCR.@*Results@#(1) ROS, MDA and SOD were similar between NAC group and control group, ROS and MDA were significantly increased, while SOD was significantly reduced in Hcy group in a concentration-dependent manner. (2) [Ca2+]i: The level of [Ca2+]i was (155.57+7.25), (187.43+13.07), (248.98+27.22) and (307.36+15.09) nmol/L in 50, 100, 200 and 500 μmol/L Hcy groups, which was significantly higher than that in the control group ((123.18+7.24) nmol/L, P<0.01). In addition, the level of [Ca2+]i in Hcy+NAC group ((222.87+23.71)nmol/L) was significantly lower than that in Hcy 500 μmol/L group ((305.15+39.45) nmol/L, P<0.05), while [Ca2+]i level was similar between NAC group and the control group. (3) The protein expression of CaMKⅡδ and Nav1.5 was significantly upregulated in Hcy groups than in the control group. The protein expression level of CaMKⅡδ-Thr287 was significantly lower in NAC group than in Hcy 500 μmol/L group (P<0.01), however, there was no significant difference on the protein expression levels of CaMKⅡδ-Thr287 and Nav1.5 between NAC group and control group (all P>0.05). (4) The protein expression levels of CaMKⅡδ-Thr287 and the concentration of [Ca2+]i were significantly lower in Hcy+KN-93 group and Hcy+KN-93+ELE group than in Hcy 500 μmol/L group (P<0.05). [Ca2+]i concentration was significantly lower in Hcy+KN-93 group, Hcy+ELE group and KN-93+ELE+Hcy group than in Hcy 500 μmol/L group (P<0.05). (5) The mRNA and protein expression levels of CaMKⅡδ and Nav1.5 in each group infected with lentivirus: the GFP expression was ideal post lentivirus transfection for 24 hours (up to 90%), which was significantly lower in the CaMKⅡδ-siRNA group and Nav1.5-siRNA group than in the negative infection group (all P<0.05), which was similar between negative infection group and control group (P>0.05). Moreover, the mRNA and protein expression levels of CaMKⅡδ and CaMKⅡδ-Thr287 was significantly lower in Hcy+Nav1.5-siRNA group than in Hcy+negative infection group (P<0.05). The protein and mRNA levels of Nav1.5 were similar between Hcy+CaMKⅡδ-siRNA group and Hcy+negative infection group (P>0.05).@*Conclusions@#Hcy can induce calcium overload in NRICs by increasing oxidative stress, upregulating the sodium channel protein, and activating the late sodium current and phosphorylating CaMKⅡδ.

Prevalence and influential factors of stroke in Jiangxi Province in 2014 / 中华预防医学杂志

Objective@#To discuss the prevalence and influential factors of stroke among population in Jiangxi Province.@*Methods@#Four cities in urban areas and four counties in rural areas were selected firstly, in which two districts or townships were selected; and then three communities or villages were chosen from each district and township, respectively, using the simple random sampling (SRS) method. Finally 15 269 subjects aging 15 years old or above, living in Jiangxi Province ≥6 months were randomly selected to participate in this survey from November 2013 to August 2014. Information of population characteristics, life behavior way, individual disease history were collected through questionnaire survey, and height, weight, waist circumference, blood pressure, body fat rate, visceral fat index and so on were measured by instruments. Risk factors of stroke prevalence were analyzed by the unconditioned logistic regression analysis.@*Results@#A total of 15 269 participants (6 267 males) from 15 364 eligible participants were included in the statistical analysis. Out of which, 7 793 participants came from urban areas, and their average age was (53.04±17.91) years old. In this study, 226 stroke patients (117 males) were found among15 269 participants, including 122 urban participants and 104 rural participants, whose average age was (67.76±9.74) years old. The prevalence of stroke was 1 480.12/100 000 in 2014, which was separately 1 866.92/100 000 and 1 210.84/100 000 among males and females. The prevalence of people aging (45-49) years old was 413.79/100 000 (6/1 450) , while which among people aging 75 years old and above was 3 311.62/100 000 (61/1 842) . The prevalence of stroke among residents in Jiangxi presented an uprising tendency with age increasing (linear-by-linear association χ2=62.23, P<0.01). The research showed that when other influencing factors including gender, BMI, waist circumference, pulse-pressure difference, VAI, and sleeping time in non-working days were controlled, hypertensive patients had a higher risk of stroke than people without hypertension (OR=6.88, 95%CI: 4.90-9.67), drinkers had a higher risk of stroke than non-drinkers (OR=1.56, 95%CI: 1.17-2.08), compared with people <65 years old, people aged 65-74 years old and ≥75 years old had a higher risk of stroke, the value of OR (95%CI) were 1.88 (1.36-2.59) and 1.97 (1.39-2.80), respectively, compared with people with normal body fat percentage, people whose body fat percentage on high side and people who with high body fat percentage had a higher risk of stroke, the value of OR (95%CI) were 1.71 (1.18-2.48) and 1.74 (1.18-2.56), respectively, people with sleep time >8 h had a higher risk of stroke than those with sleep time of 6-8 h.@*Conclusion@#There was a high stroke prevalence among residents in Jiangxi province. Hypertension, drinking, age, BFP and sleep duration were associated with stroke prevalence. Corresponding measures for high-risk population and risk factors should be strengthened to prevent and control the stroke.

Correlation Study of Monocyte to HDL-C Ratio and Post-operative Slow flow or No reflow in Acute Myocardial Infarction Patients After Percutaneous Coronary Intervention / 中国循环杂志

Objective: To explore the correlation of monocyte to HDL-C ratio (MHR) and post-operative slow lfow or no relfow in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). Methods: A total of 216 STEMI patients treated in our hospital from 2014-10 to 2016-05 were enrolled. The patients were divided into 2 groups: Slow lfow or no relfow group, the patients with TIMI grade≤2,n=43 and Normal lfow group, n=173. Receiver operating characteristic (ROC) curve was performed to assess the best cut-off value for MHR predicting slow lfow or no relfow with its sensitivity and speciifcity; Logistic regression analysis was conducted to studied weather MHR could be used as an independent risk factor for coronary slow lfow or no relfow in STEMI patients after PCI. Results: Compared with Normal lfow group, Slow lfow or no relfow group had the higher MHR (18.6±9.8) vs (10.9±5.5), P<0.001. Univariate Regression analysis indicated that MHR was a risk factor of slow lfow or no relfow occurrence (OR=2.22, 95% CI 1.58-3.28); multivariate regression analysis presented that MHR was an independent risk factor of slow lfow or no relfow occurrence (OR=1.55, 95% CI 1.01-2.38). ROC curve showed that the best cut-off value for MHR predicting slow lfow or no relfow occurrence was 13.37 with the sensitivity and speciifcity at 67.4% and 70.5% respectively, the area under curve (AUC) was 0.734, 95% CI 0.646-0.822. Conclusion: MHR was an independent risk factor for slow lfow or no relfow occurrence in STEMI patients after PCI.

Test of Sepsis 3.0 for diagnosis and prognosis of the septic patients in the intensive care unit / 中国中西医结合急救杂志

Objective To investigate the estimated values of sequential organ failure assessment (SOFA) and quick SOFA (qSOFA) for diagnosis and prognosis in patients with sepsis according to the new diagnostic criteria in Sepsis 3.0.Methods A retrospective study was conducted.All the clinical data were collected from patients with definite diagnosis of infection and they were admitted into the Intensive Care Unit (ICU) of Beijing Traditional Chinese Medicine Hospital Affiliated to Capital Medical University from July 2014 to June 2016.The patients' gender,age,infectious location,respiratory rate (RR),oxygenation index (PaO2/FiO2),Glasgow coma scale (GCS),total bilirubin (TBil),platelet count (PLT),serum creatinine (SCr),serum lactate level,etc.general data on admission were collected to carry out SOFA and qSOFA scorings.And then the septic patients in accord with the diagnostic criteria of Sepsis 3.0 were screened out.According to outcome after admission,the septic patients were divided into survival group and death group,and the differences in diagnosis and in estimation value of prognosis between SOFA scoring and qSOFA scoring were assessed as SOFA group and qSOFA group.Results From 545 septic patients enrolled,189 septic patients consistent with the diagnostic criteria of Sepsis 3.0 were selected.In SOFA scoring group,the morbidity of septic patients was 34.68％,while in qSOFA scoring group,it was 15.96％,the difference between the two groups being statistically significant (P ＜0.01).The mortality was significantly lower in SOFA scoring group than that in qSOFA scoring group [28.04％ (53/189)vs.42.53％ (38/87),P ＜ 0.05].The mortality of qSOFA scoring group was about 1.52 times that of SOFA scoring group.On the aspect of scoring,in patients with SOFA scoring the score of death group was significantly higher than that in survival group (8.74 ± 0.417 vs.7.10 ± 0.235,P ＜ 0.01);in the patients with qSOFA scoring,the score in death group compared with that in survival group showed uo statistical significant difference (2.32 ± 0.48 vs.2.16 ± 0.37,P ＞ 0.05).On the aspect of laboratory indexes,the levels of GCS score in death group was significantly lower than that in the survival group (8.15 ± 0.67 vs.12.48 ± 0.36),blood lactate level in death group was significantly higher than that in the survival group (mmol/L:8.55 ± 4.66 vs.2.31 ± 0.16,P ＜ 0.01);the PaO2/FiO2,TBil,PLT and SCr showed no significant differences between the two groups (all P ＞ 0.05).Conclusions The new diagnostic criteria (Sepsis 3.0) can be used for diagnosis of sepsis in ICU.Compared with qSOFA scoring,the SOFA scoring is more suitable to be used for diagnosis and predicting prognosis of septic patients in ICU;SOFA scoring,GCS scoring and serum lactate level can be applied to estimate outcome of septic patients.

Effect and mechanism of Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia through connexin43 (cx43)

OBJECTIVE@#To explore the effect and mechanism of angiotensin II receptor blockers - Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia.@*METHODS@#Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan + ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43 (Cx43) mRNA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group (SO), myocardial infarction group (MI), Irbesartan group and MI + Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorphology of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mRNA and protein level.@*RESULTS@#The intervention of Irbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia (P < 0.05), but in the presence of Irbesartan, the expression of Cx43 was increased compared with the ischemia group (P < 0.01). The results of WB assay showed the similar trend of change at mRNA level. There was the significant difference in the score of ventricular arrhythmia between MI group and SO group (P < 0.01). The incidence of ventricular tachycardia or ventricular fibrillation was significantly increased compared with the one in SO group (P < 0.05). There was the significant difference in the overall score between MI + Irbesartan group and MI group (P < 0.05). The expression of Cx43 in the cardiac muscular tissue in MI group was significantly decreased (P < 0.01 vs SO group). But the expression of Cx43 was increased after the treatment with Irbesartan.@*CONCLUSIONS@#Irbesartan can inhibit the injury of H9c2 cardiomyocytes and the decreased expression of Cx43 that are induced by the ischemic myocardial infarction. Irbesartan can also improve the reconstruction of Cx43 in rats with ischemic myocardium to inhibit the myocardial infarction-induced arrhythmias.

Effect and mechanism of Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia through connexin43 (cx43)

Objective To explore the effect and mechanism of angiotensin II receptor blockers – Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. Methods Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan + ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43 (Cx43) mRNA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group (SO), myocardial infarction group (MI), Irbesartan group and MI + Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorphology of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mRNA and protein level. Results The intervention of Irbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia (P < 0.05), but in the presence of Irbesartan, the expression of Cx43 was increased compared with the ischemia group (P < 0.01). The results of WB assay showed the similar trend of change at mRNA level. There was the significant difference in the score of ventricular arrhythmia between MI group and SO group (P < 0.01). The incidence of ventricular tachycardia or ventricular fibrillation was significantly increased compared with the one in SO group (P < 0.05). There was the significant difference in the overall score between MI + Irbesartan group and MI group (P < 0.05). The expression of Cx43 in the cardiac muscular tissue in MI group was significantly decreased (P < 0.01 vs SO group). But the expression of Cx43 was increased after the treatment with Irbesartan. Conclusions Irbesartan can inhibit the injury of H9c2 cardiomyocytes and the decreased expression of Cx43 that are induced by the ischemic myocardial infarction. Irbesartan can also improve the reconstruction of Cx43 in rats with ischemic myocardium to inhibit the myocardial infarction-induced arrhythmias.

Effect of livin-modified BM-MSCs transplantation on cardiac function fol-lowing acute myocardial infarction in a rat model / 中国病理生理杂志

[ ABSTRACT] AIM:To study the effect of livin gene-modified bone marrow mesenchymal stem cells ( BM-MSCs) transplantation on the cardiac function following acute myocardial infarction in a rat model and the expression of livin , caspase-3, caspase-7 and caspase-9 in the livin gene-modified BM-MSCs.METHODS: The MSCs were obtained by the whole bone marrow culture method , and the apoptosis of the MSCs after infection with adenovirus vector carrying enhanced green fluorescent protein ( EGFP) gene and livin recombinant vector ( rAd-livin) were detected by flow cytometry .The ex-pression of livin, caspase-3, caspase-7 and caspase-9 was detected by Western blot .After permanent left anterior descend-ing artery occlusion , the rats were randomized to receive intramyocardial injection of DMEM without cells ( vehicle group ) , or containing MSCs ( MSCs group ) , MSCs ( EGFP ) ( rAd-control/MSCs group ) or MSCs ( livin ) ( rAd-livin/MSCs group).Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum in-creased rate of left ventricular pressure ( -dp/dtmax ) and the maximum decline rate of left ventricular pressure ( +dp/dtmax ) were recorded for evaluating the cardiac functions .RESULTS: The apoptosis of rAd-livin/MSCs was significantly decreased as compared with MSCs and rAd-control/MSCs (P<0.05).Meanwhile, the expression of caspase-3, caspase-7 and caspase-9 was significantly downregulated as compared with the other 2 groups ( P<0.05 ) .The cardiac function in rAd-livin/MSCs group was significantly improved as compared with DMEM group , and those in the other 2 groups got the similar results, but the function in rAd-livin/MSCs group was better improved .Meanwhile, the number of surviving cells in rAd-livin/MSCs group was significantly improved as compared with the other 2 groups .CONCLUSION:The apoptosis of MSCs is decreased after rAd-livin transfection, and the expression of caspase-3, caspase-7 and caspase-9 is also significant-ly downregulated while the expression of livin is significantly upregulated .Transplantation of livin-modified BM-MSCs by lentiviral vector results in better prognosis for treating myocardial infarction by enhancing cell survival .

Epidemiological investigation on the atypical pathogen infection of children in Maoming district / 国际检验医学杂志

Objective To investigate the infectious rates of 9 common pathogens and epidemiology in children with acute respira‐tory tract infections(ARI) in Maoming district .Methods The serum were collected from 6 241 children with acute respiratory in‐fection .IgM of 9 common pathogen including Mycoplasma pneumoniae (MP) ,Legionella pneumophila (LP) ,Coxiella burnetii (C .burnetii) ,Chlamydophila pneumoniae(CP) ,adenovirus(ADV) ,respiratory syncytial virus(RSV) ,type A and type B influenza virus(INFA and INFB) ,and parainfluenza virus(PIVS) ,were detected using immunofluorescence assay .Results Among 6 241 ca‐ses ,1 320 showed atypical pathogens infection ,and infection rate was 21% .The positive rate of MP was 15 .12% ,the highest infec‐tious pathogen;followed by the positive rate of INFB ,LP ,ADV and PIVS were 3 .03% ,1 .92% ,0 .54% and 0 .22% respectively . The pathogens with the lowest positive rate were RSV ,COX ,INFA and CP ,their infectious rates were 0 .14% ,0 .11% ,0 .048%and 0 .016% respectively .Conclusion The infection rate of atypical pathogen among children is high in this area ,which should be taken seriously .MP is the most common pathogen in children with ARI in Maoming district .The pathogen positive rate has rela‐tionship with season .

Expression of CXC chemokine receptor 7 in atherosclerotic ApoE-defi-cient mice and therapeutic impact by atorvastatin / 中国病理生理杂志

AIM:To evaluate the expression level of CXC chemokine receptor 7 (CXCR7) in atherosclerotic apolipoprotein E-deficient ( ApoE-/-) mice induced by high-fat diet ( HFD) and the effects of atorvastatin on it .METH-ODS:ApoE-/-male mice (8-week-old) were used and were randomly divided into 3 groups following 1-week normal ro-dent diet:normal diet control (NDC) group , HFD group and HFD+statins (HFD+Sat) group.HE staining and oil red O staining were used to observe the atherosclerotic lesion burdens in the aortas .The expression of CXCR7 on the aortas was detected by Western blot and immunohistochemistry .The expression of Akt and endothelial nitric oxide synthase ( eNOS) in the aorta was determined by Western blot .RESULTS: Few lesions were found in the aortas in NDC group .Apparent atherosclerotic plaque burdens were seen in HFD group and HFD +Sat group, while the atherosclerotic plaque burdens in HFD+Sat group were notably reduced compared with HFD group .The protein levels of CXCR7, eNOS and Akt in aorta in HFD group and HFD+Sat group were significantly decreased compared with NDC group , while those in HFD+Sat group were increased compared with HFD group .The protein level of p-eNOS in the aorta and the concentration of NO in the plas-ma in HFD group were decreased compared with NDC group and HFD +Sat group.CONCLUSION: In ApoE-/-mice, HFD increases the lipid level and promotes the development of atherosclerosis by downregulating the expression of CXCR 7, Akt and eNOS.Atorvastatin reverses the above effect of hypercholesterolemia on the expression of CXCR 7, Akt and eNOS, thus playing the role in treating atherosclerosis .

The role of meridian touching on neonatal hyperbilirubinemia / 中国实用护理杂志

Objective To investigate the meridian touching on neonatal hyperbilirubinemia effect of adjuvant therapy.Methods 120 cases of neonatal hyperbilirubinemia were randomly divided into the observation group and the control group,60 cases in the control group were treated with modified simple touch of domestic law,on the basis of modified simple touch,the observation group increased meridian touching,2 times per day,once every 15 min.The nursing effect was compared between two groups.Results The observation group was significantly better than the control group in items such as daily intake of milk,sleep time,meconium drained time,jaundice.Conclusions On the basis of modified simple touch of domestic law,the addition of meridian touching can effectively reduce neonatal hyperbilirubinemia serum bilirubin levels,prevent high bilirubin encephalopathy,and promote the growth and development of newborns.

Aortic expression of HSP22, TNF-αand eNOS in rats with hyperlipi-demia and effects of atorvastatin / 中国病理生理杂志

AIM:To establish a rat hyperlipidemia model for studying the aortic expression of heat shock protein 22 (HSP22), tumor necrosis factor alpha (TNF-α) and endothelial nitric oxide synthase (eNOS) and the effect of atorvasta-tin intervention.METHODS:Hyperlipidemia model was established in SD rats.Afterwards, the rats were divided into nor-mal control group, high fat group and high fat+atorvastatin intervention group.The expression of HSP22 and TNF-αin the rat aortas was detected by immunohistochemical assay and the expression of eNOS was assessed by Western blotting.RE-SULTS:No detectable expression of HSP22 and TNF-αin the normal control group was observed.However, the expression of HSP22 and TNF-αwas positive in the high fat group and the atorvastatin intervention group.The mean densities of HSP22 and TNF-αpositive particles were significant lower in the atorvastatin intervention group as compared with high fat group ( both P<0.05) .The expression of eNOS protein in the high fat group and atorvastatin intervention group was significantly lower than that in normal control group (P<0.01).However, no marked difference of eNOS protein expression between high fat group and atorvastatins intervention group was observed.CONCLUSION:The expression of HSP22 and TNF-αin the rat aortas is increased in the hyperlipidemia rat model.This effect can be restored by atorvastatin treatment.The expression of eNOS in the rat aortas is decreased in the hyperlipidemia rat model, but this tendency could not be attenuated by atorvastatin.

The clinical application of symmetrical occluder in treating intercristal ventricular septal defect / 介入放射学杂志

Objective To investigate the interventional treatment strategy for occluding the intercristal ventricular septal defect (VSD) in order to improve the surgical safety and success rate. Methods During the period from January 2012 to December 2013, a total of 31 patients with intercristal VSD were admitted to authors’ hospital to receive interventional catheter occlusion therapy. Preoperative color Doppler ultrasound echocardiography showed that on the short axis view of the aorta the VSD interrupted port was situated at 12:00 - 1:00 o’clock region. Left ventricular and above aortic valve angiography indicated that the VSD location, shape and size, the split vent size on the left ventricle side and its distance from the aortic valve could be correctly measured when the VSD shunt was visualized , which were very helpful in guiding the operator to select the suitable occluder as well as to adjust the release pattern of the occluder. Postoperative imaging findings of the left ventricular and above aortic valve angiography were compared with the preoperative ones. Results Successful occlusion of VSD was obtained in 22 patients , in 13 among them the left ventricular angiography showed that the direction of blood flow beam at the defect hole was from the left ventricle to the right ventricle in an obliquely upward direction. The basal width of the defect on the left ventricle side was (5.12 ± 1.38) mm, and(6 - 10) mm occluder was employed. In the remaining 9 patients the left ventricular angiography showed that the direction of blood flow beam at the defect hole was from the left ventricle to the right ventricle in a direction almost parallel to the aortic valve , and the basal width of the defect on the left ventricle side was (7.18 ± 1.26) mm, and (9 - 12) mm zero-bias occluder was adopted. Interventional occlusion of VSD was unsuccessful in 9 cases as the intercristal hole was rather larger, and two of them had coexisting aortic sinus aneurysm complicated by mid-to-severe degree aortic valve regurgitation. Conclusion Based on the precise analysis of angiographic images by experienced radiologists optimal treatment scheme can be worked out. If conditions permit, symmetrical occluder should be employed so far as possible in order to reduce the degree of operation difficulty and improve the surgical safety and the success rate as well.

Method and significance of ultrasonographic assessment of the uterine weight before pelvic floor reconstruction / 中华妇产科杂志

Objective To investigate the accuracy of ultrasonographic assessment of the total uterine weight and the feasibility of using this method in the pelvic floor reconstruction.Methods Firstly,81 cases with hysterectomy due to benign uterine diseases or uterine prolapse were studied.The preoperative dimensions and gravities of corpus uteri and cervix were calculated by formulas,and were then compared with the postoperative measurements.Subsequently,46 cases with pelvic floor reconstruction and preserved the uterus were subjected to retrospectively analysis of uterine measurement parameters.Results There were no statistically differences between the preoperative and postoperative diameters of corpus uteri and cervix (P ＞ 0.05),and no statistically differences between the weight of corpus uteri and cervix estimated by the formulas [(87±55),(32±6) g] and the true weight [(88±57),(33±6) g; P＞0.05].In 46 cases that underwent the pelvic floor reconstruction by transvaginal mesh repair and preserved the uterus,42 cases were successful treated and the average weight of total uterus was (49 ± 13) g (95％CI:39.90-49.88 g) ; the 4 relapsed cases were treated with hysterectomy and the weight of total uterus were 85.24,82.69,92.67 and 120.06 g which were consistent with the weights estimated by the formulas (87.36,82.00,90.88,123.12 g ; all P ＞ 0.05).Conclusions The uterine weight might be a significant factor for uterus preservation in pelvic floor reconstruction,while ultrasonographic assessment can accurately estimate the uterine weight preoperatively.All these raised the feasibility of assessing uterine weight preoperatively in pelvic floor reconstruction.

Effect of trimetazidine and atorvastatin on coronary no or slow flow phenomenon after emergency percutaneous coronary intervention / 中国综合临床

Objective To investigate the therapeutic effect of trimetazidine(TMZ) and atorvastatin on coronary no-flow/slow-flow phenomenon (CNFP/CSFP) emergency pereutaneous coronary intervention (PCI)Methods Thirty-two patients with acute myocardial infarction were selected as our subjects,who hospitalized from April 2007 to May 2012 after PCI with CNFP/CSFP.Patients were administrated with the TMZ (60 mg/d)and atorvastatin (20 mg/d) for 6 months besides the routine therapy.The changes of the clinical symptoms including ECG exercise test,coronary flow of coronary angiography(CAG) were recorded and the level of serum high sensitivity C-reactive protein (hs-CRP),matrix metalloproteinase-9 (MMP-9),tumor necrosis factor-α (TNF-α) and interleukin-6(IL-6) were measured before and after the treatment.Results (1)The symptoms of the patients were improved remarkably;the effective rate was 87.5％ (28/32).The improving rate of ECG was 90.6％.The CTFC of patients after treatment was (20.17 ± 4.36),significantly lower than that of before treatment (35.34 ± 7.43,t =2.409,P ＜ 0.05).(2) The levels of hs-CRP,MMP-9,TNF-a and IL-6 at after treatment were (3.34 ±0.47) mg/L,(173.09 ±42.19) μg/L,(8.47 ±2.09) μg/L,(89.37 ± 18.72) ng/L,lower than that of before treatment ((12.34 ± 2.43) mg/L,(972.68 ± 131.91) μg/L,(23.54 ± 7.48) μg/L,(154.39 ± 42.07) ng/L),and difference were significant (t =2.537,2.789,2.691,2.430,P ＜ 0.01 or P ＜0.05).Conclusion The therapy approach of TMZ and atorvastatin plus routine treatment of nitrate and aspirin showed a better therapeutic effect on CNFP/CSFP.The causes of CNFP/CSFP may relate to inflammation.

Correlation of invasive central arterial pressure with peripheral arterial pressure and coronary sclerosis / 中华老年医学杂志

Objective To study the consistency among non-invasive and invasive brachial artery pressure,radial artery pressure and invasive central arterial pressure,and to explore the correlation between the severe degree of coronary artery disease and invasive central aortic pressure.Methods A total of 331 patients who underwent coronary angiography in our hospital were selected.The invasive central aortic pressure,invasive and non-invasive brachial arterial pressure,radial artery pressure in all patients were measured.The severe degrees of atherosclerosis were recorded.The differences among invasive brachial arterial pressure and invasive radial artery pressure,non-invasive brachial artery pressure and non-radial artery pressure and invasive central aortic pressure were compared.Results The systolic pressure values measured in invasive and non-invasive brachial artery and radial artery were higher than that measured by central aortic pressure,while the diastolic pressure values measured in the four peripheral artery were lower than that measured in central aorta.The pressure values measured by non-invasive brachial artery pressure were more close to that measured by invasive central aortic pressure (P＞0.05).The systolic pressure was increased and the diastolic pressure was reduced in central aortic pressure with the coronary vessel lession numbers increased.The values of systolic pressure in patients with single-vessel,double-vessel and triple-vessel lesions were (118.2± 19.5) mm Hg,(124.9 ± 19.7) mm Hg and (137.7 ± 20.6) mm Hg,respectively and the values of diastolic pressure were (86.8±8.4) mm Hg,(85.3± 10.3) mm Hg and (83.1± 9.4) mm Hg,respectively.There were significant differences in systolic and diastolic pressure values among patients with single-vessel lesions,double vessel lesions and triple-vessel lesions(F=3.93,4.31,both P＜ 0.05).Conclusions The blood pressure values measured by noninvasive brachial artery pressure are more close to that measured by invasive central aortic pressure.There is a significant correlation between the severe degree of coronary heart disease and invasive central aortic pressure.Non invasive brachial artery pressure can be used in the early detection of cardiovascular dysfunction.

Species analysis of fungi isolated in a laboratory from patients with mycoses during 1960-2006 / 中华皮肤科杂志

Objective To analyze fungal isolates from patients with superficial fungal infections during 1960-2006.Methods Fungal strains isolated from patients with superficial (mucocutaneous and cutaneous)fungal infections and identified in the Medical Mycology Clinical Laboratory,Department of Dermatology and Venereology,Union Hospital,from 1960 to 2006 (data from September 1991 to July 1992 were unavailable),were subjected to a classification and statistical analysis.Clinical samples for mycological examination were taken from outpatients or inpatients of different departments in hospitals of Hubei province and surrounding areas.Morphological,physiological and biochemical methods were applied for species identification.Results A total of 11 989 Candida strains were isolated,which belonged to 23 species and 16 genera.They fell into 3 groups,i.e.,dermatophytes,Candida and yeasts (including Malassezia),and non-dermatophyte moulds.Since 287 strains of moulds were suspected to be contaminating fungi,11 702 residual isolates were analyzed.Of the analyzed isolates,Candida species (5642/11 702,48.2％ )and dermatophytes (5279/11 702,45.1％ )predominated,followed by yeasts (449/11 702,3.8％) and Malassezia species (332/11 702,2.8％).The most frequently isolated species was Trichophyton rubrum (3865/11 702,33.0％),Candida albicans (3110/11 702,26.6％ ) and non-albicans Candida species (2532/11 702,21.6％ ).Dermatophyte strains were mostly isolated from lesions of smooth skin with an exception of palmoplantar and interdigit regions (1787/5279,37.7％).The most common dermatophyte species was Trichophyton rubrum,followed by Trichophyton violanceum.Candida was mainly isolated from mucous membrane lesions (4099/5642,72.7％),with Candida albicans being the predominant species.Conclusions Candida species and dermatophytes predominate in patients with superficial fungal infections during 1960-2006,with Trichophyton rubrum being the most common species.

Effects of echinomycin on endothelin-2 expression and ovulation in immature rats primed with gonadotropins

Echinomycin is a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity, which plays a crucial role in ovarian ovulation in mammalians. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1alpha-mediated endothelin (ET)-2 expressions contributed to ovarian ovulation in response to human chorionic gonadotropin (hCG) during gonadotropin-induced superuvulation. By real-time RT-PCR analysis, ET-2 mRNA level was found to significantly decrease in the ovaries after echinomycin treatment, while HIF-1alpha mRNA and protein expression was not obviously changed. Further analysis also showed that these changes of ET-2 mRNA were consistent with HIF-1 activity in the ovaires, which is similar with HIF-1alpha and ET-2 expression in the granulosa cells with gonadotropin and echinomycin treatments. The results of HIF-1alpha and ET-2 expression in the granulosa cells transfected with cis-element oligodeoxynucleotide (dsODN) under gonadotropin treatment further indicated HIF-1alpha directly mediated the transcriptional activation of ET-2 during gonadotropin-induced superuvulation. Taken together, these results demonstrated that HIF-1alpha-mediated ET-2 transcriptional activation is one of the important mechanisms regulating gonadotropin-induced mammalian ovulatory precess in vivo.

Effects of xeroderma pigmentosum B gene on proliferation and apoptosis of vascular smooth muscle cells induced by interleukin-6 / 中华老年医学杂志

Objective To investigate effects of xeroderma pigmentosum B(XPB) gene on IL-6 induced proliferation and apoptosis in human vascular smooth muscle cells (VSMC).Methods Recombinant plasmid pcDNA3.1-XPB and vacant vector plasmid pcDNA3.1 were transfected stably into VSMC by liposome,and these cells were incubated with IL-6 at a 100 U/ml for 48 hours.The experiments were divided into six groups:blank control group; pcDNA3.1 group; pcDNA3.1-XPB group;IL-6 group; IL-6 + pcDNA3.1 group; IL-6 + pcDNA3.1-XPB group.The expression levels of XPB,Bcl-2,Bax and wild type p53 (wt-p53) were detected through reverse transcription polymerase chain reaction (RT-PCR) and Western blotting.The cell survival,cell cycle and apoptosis were examined with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry,respectively.Results The transfection of pcDNA3.1-XPB increased the expression of XPB,Bax and wt-p53 (P＜0.05 or P＜0.01),decreased the expression of Bcl-2 (P＜0.05 or P＜0.01),and reduced the IL-6 induced effects on decreasing the expression of Bax and wt-p53 and increasing the expression of Bcl-2(P＜0.05 or P＜0.01).The over expression of XPB inhibited the cell growth(q=2.95,P＜ 0.05),and reduced the positive effects of IL-6 on VSMC growth ( 102.6 +6.2) ％ vs.(124.5 + 7.9) ％,q=3.49,P＜0.05.The over expression of XPB increased the apoptosis rate of VSMC(P＜0.01 ) and the cell amounts of G0/G1 phase (q=2.99,P＜ 0.05),decreased the cell amounts of S phase(q=3.05,P＜0.05),and reduced the IL-6 induced effects on decreasing the apoptosis rate of VSMC(5.9±2.1)％ vs.(0.3±0.1)％,q=7.53,P＜0.01; the cell amounts of G0/G1 phase(70.9±6.7) ％ vs.(54.8±2.9) ％,q=6.91,P＜0.01 ;and on increasing the cell amounts of Sphase(20.2+3.6)％ vs.(36.4+7.2)％,q=8.54,P＜0.01.Conclusions XPB gene could inhibit VSMC proliferation,promote VSMC apoptosis,and reduce the effects that IL-6 promotes VSMC proliferation and inhibits VSMC apoptosis.Therefore,XPB gene is likely to be potential molecular target for treatment of atherosclerosis.