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Objective: To study the effects of combination of angiopoietin-1 (ANG-1) and vascular endothelial growth factor₁₆₅ (VEGF₁₆₅) gene transfer mediated by recombinant adeno-associated viral vector on the neovascularization in chronic ischemic porcine myocardium., Methods: An ameroid constrictor was implanted around the left circumflex coronary artery (LCX) via endoscopy. Six weeks later, coronary angiography revealed that the myocardial ischemia was established by gradual occlusion of the left circumflex coronary artery (LCX). Sixteen swine with the total occlusion or partial stenosis (> 85 %) of the LCX were divided into 4 groups (4 in each group): group I, group II and group IV (control) received direct myocardium injection of rAAV₂ VEGF₁₆₅, rAAV₂ ANG-1 or PBS alone, respectively; group III received rAAV₂ VEGF₁₆₅ and rAAV₂ ANG-1. Selective coronary angiography and ultrasonography were performed perioperatively to evaluate the cardiac function and the formation of collateral circulation. The expression of VEGF₁₆₅ and ANG-1 proteins were assessed using ELISA or Western blot. The degree of angiogenesis was assessed by use of immunohistochemical analysis., Result: Angiography showed that the occlusion of all LCX was completed or exceeded 95% 6 weeks after ameroid constrictor implantation, indicating the successful establishment of animal model. The expression levels of VEGF₁₆₅ in group I and III and ANG-1 in groups II and III began to increase at d7 after transfection and reached the peak at d14; then decreased gradually to the normal level after 3 months. The expression levels of VEGF₁₆₅ in group II and group IV or that of ANG-1 protein in group I and group IV had no markedly changes at different time after transfection. There were significant increase in capillary density and arteriole density and more side branch vessels formed in group III compared with other groups. Echocardiographic measurements showed that the left ventricular systolic function of animals in groups I, II and III increased significantly after gene transfection, especially in group III; but there was no changes in group IV., Conclusion: Myocardial perfusion and the left ventricular systolic function are improved after rAAV₂ VEGF₁₆₅ or rAAV₂ ANG-1 transfection, which is associated with the angiogenesis in porcine model of chronic myocardial ischemia.

Objective: To evaluate the feasibility and safety of retroperitoneal laparoscopic adrenalectomy for larger adrenal tumor., Methods: A retrospective cohort study of patients who underwent retroperitoneal laparoscopic adrenalectomy in a single unit from July 2004 to December 2008 was undertaken, in which 53 cases were divided into 2 groups according to size as estimated by group A [n=13; age: 45+/-18 years; size: (7.6+/-1.2) cm, maximum diameter of tumor larger than 6 cm] and group B [n=40; age: (49+/-12) years; size: (4.0+/-0.9) cm, between 3 and 6 cm]., Results: All procedures were performed successfully. In comparison between the 2 groups ,the mean operative time [(127+/-77) min vs (107+/-47) min, P<0.05] and estimated blood loss [(167+/- 223) mL vs (65+/-60) mL,P<0.01] had significant difference. The intraoperative complications and blood transfusion rate in group A were higher than those of group B (23% vs 12.5% and 15% vs 2.5%),no difference was noted in their hospital stay after operation [(7.1+/-1.1) d vs (5.5+/-0.7) d, P>0.05]. Group A was followed up for 25+/-14 months,during which time no local recurrence was noted in 8 cases, 3 cases were missed ,and 2 cases were alive with hydronephrosis. Group B was followed up for 29+/-14 months, during which time 30 cases were free, 9 cases were lost, and 1 case was found with real disfunction. The pathology of most tumors in group A included medullary lipoma(30.8%), pheochromocytoma(23%) and ganglioneuroma(23%), the others included adenoma(32.5%), pheochromocytoma(25%) and ganglioneuroma(17.5%) in group B., Conclusion: Retroperitoneal laparoscopic adrenalectomy has best value in patients with larger adrenal tumor and it is a minimally invasive and safe procedure for skillful surgeons in the treatment of tumor size larger than 6 cm.

Objective: To analyze the incidence and cause of complications during and after interventional therapy for congenital heart disease (CHD)., Methods: From April 1986 to April 2009, 388 out of 6029 patients with CHD developed complications during and post interventional therapy, another 5 patients died post procedure, clinical data from these 393 patients were retrospectively analyzed. The patients with severe functional insufficiency requiring intervention or surgery during and after interventional therapy were classified as severe complications., Results: The overall complication rate was 6.44% [7.69% post atrial septal defect occlusion, 4.20% post patent ductus arteriosus (PDA) occlusion, 1.31% post percutaneous balloon pulmonary valvuloplasty, 14.94% post ventricular septal defect occlusion, 3.13% post percutaneous closure of aortopulmonary collaterals, 30.95% post catheter embolotherapy of pulmonary arteriovenous malformations, 12.50% post transcatheter closure of coronary artery fistulae, 20.00% post transcatheter closure of ruptured sinus of Valsava aneurysm, 66.67% post percutaneous balloon aortic valvuloplasty]. The severe complication rate was 0.65%(39/6029). The procedure-related mortality rate was 0.08% (5/6029), 0.26% (2/761) post percutaneous balloon pulmonary valvuloplasty, 0.05% (1/2070) post PDA occlusion, 9.10% (1/11) post balloon atrial septostomy, 33.33% (1/3) post percutaneous balloon aortic valvuloplasty. Emergency Cardiovascular surgery rate was 0.22% (13/6029). Selective surgery was required in 0.13% (8/6029) of patients post procedure. Two patients (0.03%) received permanent pacemaker implantation., Conclusions: The severe complications and mortality rate of interventional therapy for CHD are relative low. Post procedure follow-up is needed fro monitoring possible procedure-related complications.

Objective: To explore the influences of intervention on the abilities of detecting pulmonary tuberculosis cases in general hospitals., Methods: We selected 6 general hospitals at 3 different levels (A, B, and C). The intervened group included hospitals A1, B1, and C1, and the non-intervened group included hospitals A2, B2, and C2. The results after intervention were compared., Results: The report rate of pulmonary tuberculosis, sputum positive rate of reported cases, and sputum check rate of reported cases were significantly higher in hospital A1 than grouping hospital A2 (P = 0.000, P = 0.045, and P = 0.017, respectively). The report rate and sputum examination rate of reported cases were significantly higher in hospital B1 than grouping hospital B2 (P = 0.000, P = 0.024, respectively). The report rate and sputum examination rate of reported cases were significantly lower in hospital C1 than grouping hospital C2 (P = 0.000, P = 0.001, respectively). In hospital A1, the report rate, sputum positive rate of reported cases, and sputum check rate of reported cases were not significantly different before and after intervention (P = 0.182, P = 0.116, and P = 0.583, respectively). In hospital B1, the report rate were significantly different before and after intervention (P = 0.004), while the sputum positive rate of reported cases and sputum check rate of reported cases were not significantly different (P = 0.909, P = 0.052, respectively). In hospital C1, the report rate was significantly higher after intervention (P = 0.025). In hospital C2, the sputum check rate significantly increased (P = 0.000)., Conclusions: Intervention influences the hospitals abilities to detect pulmonary tuberculosis cases. However, more optimized and long-term intervention mechanism should be established to increase case detection rate of pulmonary tuberculosis.

Objective: To construct recombinant adeno-associated virus (rAAV) vector containing angiopoietin-1 (ANG-1) gene and to express the ANG-1 in targeting cells., Methods: ANG-1 cDNA was obtained from human spleen by RT-PCR and was inserted into AAV vectors to form rAAV ANG-1, the virus stocks in high titer were harvested. The rAAVANG-1 and rAAV GFP were transferred into pig mesenchymal stem cells and the expression of ANG-1 was detected by Western blot., Results: The cloned ANG-1 cDNA was 1515bp in length which was in accordance with that reported previously. Titration of rAAVANG-1 stock was 9 X 10(11)v.g/ml. The expression of ANG-1 gene was detected in transfected cells. Forty-eight hours after rAAV GFP was transfected into mesenchymal stem cells, 55% cells expressed GFP., Conclusion: The constructed rAAV ANG-1 vector has successfully transfered and expressed in pig mesenchymal stem cells.

In this paper, the toxicity of Vitex negundo seed dichloromethane extract, imidacloprid, and omethoate to Aphis citricola, Aphis gossypii, and Myzus persicae was determined by impregnation method, and the co-toxicity of the seed extract and imidacloprid to A. gossypii as well as the repellent effect of the extract and test insecticides to M. persicae were tested by topical application of capillary tube and by selection in culture dish, respectively. The results showed that the LC50 of V. negundo seed dichloromethane extract to A. citricola, A. gossypii, and M. persicae was 334.59, 362.79, and 2685.8 mg x L(-1), respectively, indicating that V. negundo seed dichloromethane extract was highly toxic to A. citricola and A. gossypii. The co-toxicity coefficient of the seed extract and imidacloprid was 177.45 when the mixture was in 1000:1, showing an obvious synergism. The repellent effect of V. negundo seed dichloromethane extract and imidacloprid to M. persicae was 55.75% and 39.44%, and 69.89% and 65.43% after treated for 24 and 48 hours, respectively, while that of thiamethoxam and acetamiprid to M. persicae was 16.52%-33.68% after treated for 24 and 48 hours.

In this paper, the chemical constituents, pharmacological activities and clinical applications of Capparis spinosa had been reviewed. The constituents of C. spinosa include the saccharides and glycosides, flavonoids, alkaloids, terpenoids and volatile oils, fatty acids and steroides and so on. C. spinosa had many extensive pharmacological effects such as anti-inflammatory, odynolysis, antifungus, hepatoprotective effect, hypoglycemic activity, antioxidation, anti-hyperlipemia, anticoagulated blood, smooth muscle stimulation, anti-stress reaction, improve memory. It was used to treat arthrolithiasis, rheumarthritis and dermatosis in clinic in domestic, and it would have a broad application prospects.

Objective: To study the developmental toxicity of Caowu and its mechanism on rat embryos., Methods: Whole embryo culture was applied to test the effects of Caowu on rat embryos during the critical period of organogenesis. All embryos isolated on gestational day 9.5 were exposed to different concentrations of Caowu. The growth and differentiation of the embryos at the end of the 48 h culture period were observed., Results: The embryonic growth and development were adversely affected by Caowu at the concentration of 2.5 mg/mL, which were represented as reduced yolk sac diameters, decreased number of somites, and lower morphological scores. With the increase of the concentrations of Caowu, more severe teratogenic effects appeared, including cardiac defect (undivided cardiac tube and inflated pericardial cavity), irregular somites, and brain malformation such as narrow brain vesicles., Conclusion: Caowu has direct embryotoxic effects on rats during the organogenesis period. We suggest that pregnant women in the first trimester use Caowu with cautions before a conclusion has been made.

Objective: To study the effects and its possible mechanisms of total alkaloids (TA) from rhizoma Coptis chinensis on H. pylori LPS induced gastric lesion in rats., Method: H. pylori lipopolysaccharide was applied to rat intragastrically for 4 days to induce a pattern of mucosal responses resembling that of acute gastritis. After treatment with 50, 100, 200 mg x kg(-1) TA, we identified the changes on gastric histopathology, the effects on the activities of cNOS and NOS-2, the contents of TNF-alpha and the gastric mucus epithelial cell apoptosis., Result: H. pylori LPS could significantly induce the epithelial cell apoptosis of gastric mucus, increase the expression of NOS-2 and decline the expression of cNOS, and enhance the content of TNF-alpha in serum. Treatment with 50, 100, 200 mg x kg(-1) TA led to reduction in the extent of mucosal inflammatory changes elicited by H. pylori LPS and decrease in epithelial cell apoptosis. Furthermore, this effect of TA was associated with decrease in content of TNF-alpha in serum, decline in NOS-2, and increase in cNOS., Conclusion: The findings suggest that TA is a potent protective agent against H. pylori LPS induced gastric mucosal inflammation. The concerned mechanisms may be related to its inhibition on epithelial cell apoptosis, and the suppression of the inflammatory responses by upregulating cNOS and interfering with the events propagated by NOS-2, and reducing the content of TNF-alpha.

Objective: To investigate the differentiation status of autologous bone marrow mononuclear cells (BM-MNC) and peripheral endothelial progenitor cells (EPC) transplanted into myocardial ischemia reperfusion injury region in swine., Methods: BM-MNC marked with PKH26 (n = 9), EPC marked with CM-DiI (n = 7), phosphate buffer saline (control, n = 7) were transplanted into myocardial ischemia reperfusion injury region of swine by intracoronary artery injection. Specimens were harvested 4 weeks after injection for histological analysis (HE, immunochemical stain for vWF, alpha-sarcomeric-actin and fibronectin antibody). Cell differentiation was observed under transmission electronmicroscope., Results: The number of small blood vessels was similar between BM-MNC group and EPC group (13.39 +/- 6.96/HP vs.12.39 +/- 4.72/HP, P < 0.05), but was significantly higher than that of control group (P < 0.05). Responsive intensity of immunochemical stain for fibronectin antibody was significantly lower in BM-MNC and EPC groups than that in control group. Responsive intensity of immunochemical stain for alpha-sarcomeric-actin antibody was similar among the three groups. Cluster cells were observed in one swine from BM-MNC group which might relate to the proliferation of stem cells in situ. Immature endothelial cells and myocytes were also detected by transmission electronmicroscope in BM-MNC and EPC group., Conclusion: BM-MNC and EPC transplanted into myocardial ischemia reperfusion injury region in swine stimulated the formation of blood vessels and inhibited fibrogenesis.

Objective: To explore the change of brain cognition function in severe head injury and the correlation between P300 in event-related potential (ERP) and intelligence quotient (IQ)., Methods: Auditory P300 was measured and intelligence quotient was tested by Wechsler Adult Intelligence Scale Revised in China (WAIS-RC) in 40 severe head injury patients. Auditory P300 was measured in 40 normal healthy people as control group., Results: The latencies of P300 in severe head injury patients group were longer than in control group. There was a significant difference between the two groups (P< 0.01). There were significant negative correlations between P300 latency and VIQ and FIQ respectively (r=-0.335,-0.344, P<0.05)., Conclusion: ERP might be taken as an objective index for measuring the change of the brain cognition function in patients with severe head injury.

Objective: To evaluate the diagnostic value of magnetic resonance imaging (MRI) for arrhythmogenic right ventricular cardiomyopathy (ARVC)., Methods: MRI was performed in 27 (male 21, mean age: 37.4 y, ranging from 15 - 67 y) clinically diagnosed ARVC patients according to the 1994 ARVC diagnosis criteria of WHO from Oct. 2004 to Jun. 2006. Heart chamber size, fat infiltration, local or global ventricular function, myocardium perfusion of contrast first pass and late enhancement were examined., Results: Fat infiltration was found in 24 (88.89%), trabecular disarray in 17 (62.96%), significant dilated right ventricle outlet (RVOT) in 18 (66.67%), dilated RV apex in 14 (51.85%), dilated RV free wall and posterior wall in 18 (66.67%) and right atrium enlargement in 11 (40.74%) patients. Local RV dysfunction was found in 18.52% (5/27), global RV dysfunction in 70.37% (19/27) of patients with mean RV ejection fraction (EF) of 35%. Left ventricle was affected in 40.74% (11/27) of patients. Perfusion defects were found in only 10.52% (2/19) of patients. Positive late enhancement of myocardium were found in 36.84% (7/19) of patients and affecting mainly the wall of RVOT and the free wall associated with lateral wall enhancement of LV. Five patients received heart transplantation and histology on transplanted hearts confirmed the MRI findings., Conclusion: "One-stop-shop" MRI scanning can be used for the diagnosis of ARVC. While for some ARVC cases with dominant abnormality in LV, it is difficult for MRI to differentiate ARVC from dilated cardiomyopathy or coronary heart disease. We found fibrosis of lateral wall of LV can be a characteristic sign of ARVC.

Objective: The aim of this study was to investigate the feasibility and accuracy of delayed enhancement magnetic resonance imaging (DE-MRI) for the assessment of myocardial viability in patients with myocardial infarction in comparison with (99)Tc(m)-sestamibi (MIBI) single photon emission computed tomography (SPECT) and (18)F-fluorodeoxyglucose (FDG) SPECT. Scar was defined as regionally increased MRI signal intensity 15 minutes after injection of 0.2 mmol/kg gadolinium-diethylenetriamine pentaacetic acid or reduced perfusion and glucose metabolism defined by SPECT., Methods: A total of 34 patients with myocardial infarction (29 males, 58.0 +/- 9.8 years) were imaged with MRI and SPECT., Results: A total of 578 segments were analyzed. DE-MRI and SPECT identified 431 and 336 viable segments respectively and SPECT also identified 30 ischemic segments. Necrotic segments identified by DE-MRI and SPECT were 147 and 212 respectively. Sensitivity and specificity of DE-MRI in identifying segments with matched flow/metabolism defects (scar tissues) was 61.3% and 95.4%, respectively. Quantitatively assessed relative MRI infarct area correlated well with SPECT infarct size. The value of Kappa was 0.51., Conclusion: DE-MRI provides a good tool for differentiating viable myocardium from scar tissues and the detection accuracy is comparable between DE-MRI and SPECT.

Objective: To observe the clinical and magnetic resonance imaging (MRI) characterizations in patients with isolated left ventricular noncompaction (LVNC)., Methods: All patients were examined by MRI. The LV was divided into 9 segments for localizing non compacted segments. A new value, C/VS, was introduced to assess the degree of non compacted segments., Results: A total of 31 patients was diagnosed as LVNC (23 males; 39.9 +/- 15.7 years). Palpitations presented in 74% of patients, abnormal EKG found in 93.5% of patients, 33.3% segments were affected and most commonly in the mid-ventricular and apical segments, 84% of patients had > or = 2 affected segments. Right ventricle was affected in 2 patients. Left ventricular thrombi were detected in 3 patients. LVEF was 37.2% +/- 16.5% (14% - 70%), N/C was 3.6 +/- 1.4 (2.2 - 9.2) and C/VS was 0.43 +/- 0.11 (0.27 - 0.69)., Conclusions: Cardiac MRI allows accurate LVNC assessment.

Event-related potentials (ERPs) develop promptly as one kind of special evoked potentials. And it is one of the most effective methods to investigate human's cognition function in these years. P300 is the component of ERPs which is widely and maturately researched and has intimate relation with attention, memory and other high psychological activity. The evaluation of recognition change after brain injury is the focus of the research. With the development of relatively research, it is deemed that this technique has wide application perspective in many aspects such as forensic clinical medicine and forensic psychiatry.

Objective: To understand the immune level of the purified protein derivative (PPD) and the present conditions of the tuberculosis among the collegians., Methods: Standardized tuberculin testing with PPD 5 IU, social-demographic and epidemiological feature of tuberculosis were conducted in 105,239 freshmen from 33 universities in Beijing., Results: The scar rates of freshmen were 72.21%. The rates coming from cities were higher than those from countries. The scar rates were near equal for freshmen in different ages. However the rates were different evidently with the region where the students come from. The scar rates of freshmen from cities were 75.84%. The scar rates of the freshmen from countries were 62.78%. Tuberculosis infection rate of the freshmen was 51.99% and the strong positive rate was 14.63%. Tuberculosis positive rate of city students was obviously higher than that of rural ones. Tuberculosis positive rate of city students was 55.17% and the strong positive rate was 15.37%. Tuberculosis positive rate of rural students was 44.69% and the strong positive rate was 12.70%. There appeared great difference between them. Moreover, Tuberculosis infection rate was varied with age and region. The tuberculosis positive rate of students from north-east areas was the highest (72.10%, 7,746/10,744), and those come from the middle-north areas were the lowest (41.50%, 6,560/15,808). The tuberculosis positive rate (62.49%, 47,489/75,992) of the freshmen with the scar was higher than that of those without the scar (24.72%, 7,230/29,247). The tuberculosis positive rate of the freshmen having a touch with the tuberculosis cases (60.75%) was higher than those having not (51.96%)., Conclusion: As students in universities are susceptible population of tuberculosis, it should be emphasized to find out tuberculosis in university and to treat them early for the purpose of preventing the episode and explosion of the disease.

Cardiac hypertrophy is a major cause of morbidity and mortality worldwide. Recent in vitro and in vivo studies have suggested that reactive oxygen species (ROS) may play an important role in cardiac hypertrophy. It was therefore thought to be of particular value to examine the effects of antioxidants on cardiac hypertrophy. Epigallocatechin-3-gallate (EGCG) is a major bioactive polyphenol present in green tea and a potent antioxidant. The current study was designed to test the hypothesis that EGCG inhibits cardiac hypertrophy in vitro and in vivo. In this study, we investigated the effects of EGCG on angiotensin II- (Ang II) and pressure-overload-induced cardiac hypertrophy. Our results showed that EGCG attenuated Ang II- and pressure-overload-mediated cardiac hypertrophy. Both reactive oxygen species generation and NADPH oxidase expressions induced by Ang II and pressure overload were suppressed by EGCG. The increased hypertension by pressure overload was almost completely blocked after EGCG treatment. Further studies showed that EGCG inhibited Ang II-induced NF-kappaB and AP-1 activation. Inhibition of the activity of NF-kappaB was through blocking ROS-dependent p38 and JNK signaling pathways, whereas inhibition of AP-1 activation was via blocking EGFR transactivation and its downstream events ERKs/PI3K/Akt/mTOR/p70(S6K). The combination of these actions resulted in repressing the reactivation of ANP and BNP, and ultimately preventing the progress of cardiac hypertrophy. These findings indicated that EGCG prevents the development of cardiac hypertrophy through ROS-dependent and -independent mechanisms involving inhibition of different intracellular signaling transductional pathways.

Aim: To investigate the changes of lymphocyte subpopulations, especially CD4(+)CD25(+) T regulatory cells in Smad3(-/-) mice., Methods: Hematological changes and changes of lymphocyte subpopulations were detected in Smad3(-/-) mice using cell counter and flow cytometry, respectively, and compared to their littermate controls., Results: The numbers of neutrophils and lymphocytes in peripheral blood were significantly increased in Smad3(-/-) mice compared to littermate controls. CD19(+) expressing cells in blood and spleen, and CD8(+) T cells in thymus were all markedly decreased in Smad3(-/-) mice. More important, Smad3(-/-) mice had an increased population of CD4(+)CD25(+) T cells in peripheral lymphoid tissues, including thymus, spleen, and lymph nodes., Conclusion: These observations suggest that the changes of lymphocyte subpopulations might play a role in susceptibility to inflammation of Smad3(-/-) mice.

Aim: To evaluate the relaxant effect of verapamil on human corpus cavernosum in vitro and to assess the drug's potential as a treatment for erectile dysfunction (ED)., Methods: Preparations of the human corpus cavernosum were obtained from recently deceased young men who had had normal erectile function. The isometric tension and detailed curves were recorded when contractions induced by 10 micromol/L phenylephrine were reduced by different doses of verapamil or the vehicle control (sterile water). The tension of human corpus cavernosum preparations are described as a percentage of their top tension before adding verapamil or the vehicle. ANOVA and least significant difference tests were used for statistical analysis., Results: Doses of 1 micromol/L, 10 micromol/L and 100 micromol/L verapamil resulted in relaxation of (35.28+/-7.96)%, (55.91+/-6.41)%, (85.68+/-4.16)% after 30 min, respectively. The vehicle control at the same time point produced relaxation of (-0.06+/-10.57)% (P<0.05)., Conclusion: Verapamil is significantly effective in relaxing normal human corpus cavernous smooth muscle induced by phenylephrine in vitro and the relaxant effect depends on the concentration of verapamil.

Multi-slice spiral CT has been an outstanding progress in developmental history of CT technology. The technical indexes of all three respects, ie scanning range time and spatial resolution are all marked improved. And several robust post-processing techniques have been imported into CT data post-scanning reconstruction, which help massive volume data being sufficiently and optimally interpreted. Therefore, newer advances have been achieved both in clinical applications and diagnostic efficacy.

Bcl-xL belongs to a family of proteins which inhibit apoptosis in a number of stimuli including ionizing radiation. To better understand the effects and mechanisms of Bcl-xL on the apoptosis of lymphocytes and provide experimental basis to treat immune injury induced by radiation, we used normal human lymphoblastoid AHH-1 cells that were engineered to overexpress Bcl-xL proteins. Our results showed that overexpressed Bcl-xL reduced time-dependent increase of apoptosis induced by ionizing radiation. Reactive oxygen species (ROS) generation and Bax protein expression in the transfected AHH1-Bcl-xL cells were also lower compared to parental AHH-1 cells. Unexpectedly, the fluorescence intensity of Rhodomine 123 (Rh 123) for measuring mitochondrial membrane potential (MMP) did not change at all detected time points. These results possess a vital significance for insights into a new strategy for gene therapy of radiation-induced immune injury.

Objective: To evaluate the safety of recombinant human interferon alpha-2b for nasal spray for the prevention of SARS and other upper respiratory viral infections., Methods: Field epidemiologic evaluation was conducted, the design was randomized and had a synchronously parallel control group. In the study, the drugs were given for five days and all subjects were followed up for ten days., Results: During the period of using interferon, body temperature of the experimental group was normal compared to the control group. Experimental group had more influenza-like symptoms than the control group (P < 0.05), such as headache (4.83%-7.09%), dizziness (7.17%-11.63%), lassitude (8.55%-15.06%), muscular soreness (4.43%-7.09%), pharynx dryness (12.10%-17.85%), angina (6.25%-8.72%), abdominal pain (2.30%-5.50%) and diarrhea (2.45%-5.66%). Most of side effects reached their peak with in the first 3 days. Except for pharynx dryness, the incidences of all other side effects declined after completion of the use of the trial drug, and incidences of some symptoms in experimental group were lower than those of the control group. There were no significant differences in the symptoms of cough and expectoration between the experimental group and the control group. The incidence of exanthem in the control group was significantly higher than that in the experimental group. The side effect of bloody nasal mucus was not observed in experimental group, which had been reported by other authors in several volunteer studies., Conclusion: Using recombinant human interferon alpha-2b for nasal spray could lead to some influenza-like symptoms, however, all those symptoms were mild , reversible, and relieved after completion of the use of the trial drug. No serious side effects were found during the period of following up. The authors conclude that the drug is safe.

Aim: To investigate the biological impacts of "hot-spot" mutations on genotype B and C HBV X proteins (HBx)., Methods: Five types of "hot-spot" mutations of genotype B or C HBV X genes, which sequentially lead to the amino acid substitutions of HBx as I127T, F132Y, K130M+V131I, I127T+K130M+V131I, or K130M+V131I+F132Y, respectively, were generated by means of site-directed mutagenesis. To evaluate the anti-proliferative effects, HBx or related mutants' expression vectors were transfected separately to the Chang cells by lipofectamine, and the cells were cultured in hygromycin selective medium for 14 d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa dyes and scored (increase of the colonies indicated the reduction of the anti-proliferation activity, and vice versa). Different types of HBx expression vectors were co-transfected separately with the reporter plasmid pCMVbeta to Chang cells, which were lysed 48 h post-transfection and the intra-cellular beta-galactosidase activities were monitored (increase of the beta-galactosidase activities indicated the reduction of the transactivation activity, and vice versa). All data obtained were calculated by paired-samples t-test., Results: As compared to standard genotype B HBx, mutants of I127T and I127T+K130M+V131I showed higher transactivation and anti-proliferative activities, while the mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As compared to standard genotype C HBx, I127T mutant showed higher transactivation activity, while the other four types of mutants showed no differences. With regard to anti-proliferative activity, compared to standard genotype C HBx, F132Y and K130M+ V131I mutants showed lower activities, and K130M+V131I +F132Y mutant, on the other hand, showed higher activity, while the mutants of I127T and I127T+K130M+V131I showed no differences., Conclusion: "Hot-spot" mutations affect the anti-proliferation and transactivation activities of genotype B and/or C HBx, and the biological impacts of most "hot-spot" mutations on HBx are genotype B and C differentiated.

Apoptosis or programmed cell death is an active form of cell death which is essential for tissue homeostasis. Many proteins are involved in the molecular signal transduction of apoptosis. The caspase enzymes, a family of specific cysteine proteases, play a central role in cell death machinery. In this review, we mainly discuss the current understanding of several pathways to activate caspases and some key proteins related to these pathways.

Cardiac hypertrophy is a major cause of morbidity and mortality worldwide. The hypertrophic process is mediated, in part, by oxidative stress-mediated signaling pathways. We hypothesized that isorhapontigenin (ISO), a new resveratrol analog, inhibits cardiac hypertrophy by blocking oxidative stress and oxidative stress-mediated signaling pathways. We treated cardiomyocytes with angiotensin II (Ang II) with or without ISO and found that ISO inhibited Ang II-induced cardiac hypertrophy. These effects were associated with a decrease in the levels of reactive oxygen species and H2O2 and the content of intracellular malonaldehyde and an increase in the activities of superoxide dismutase and glutathione peroxidase. Ang II induced the phosphorylation of PKC, Erk1/2, JNK, and p38 in cardiomyocytes and such phosphorylation was inhibited by ISO. ISO also blocked the PKC-dependent PI3K-Akt-GSK3beta/p70S6K pathway. These effects lead to direct or indirect inhibition of NF-kappaB and AP-1 activation. Our results revealed that pretreatment with ISO significantly inhibited Ang II-mediated NF-kappaB through affecting the degradation and phosphorylation of IkappaBalpha and the activity of IKKbeta and AP-1 activation by influencing the expression of c-Fos and c-Jun proteins. In addition, we also established the molecular link between activation of PKC and MAPKs and activation of NF-kappaB and AP-1 in cardiomyocytes. We also found that ISO treatment significantly attenuated heart weight/body weight ratio by approximately 25%, decreased posterior wall thickness and left ventricle diastolic and systolic diameters, and increased 10% fractional shortening in an aortic-banded rat model. Furthermore, treatment with ISO significantly decreased cardiac myocyte size and systolic blood pressure. These findings suggest that ISO prevents the development of cardiac hypertrophy through an antioxidant mechanism involving inhibition of different intracellular signaling transduction pathways.

Aim: Despite the presence of lymphocyte infiltration, human hepatocellular carcinoma (HCC) is typically a rapidly progressive disease. The mechanism of regulation of lymphocyte migration is poorly understood. In this study, we investigated various factors regulating T cell migration in HCC patients. We examined serum CXC chemokine levels in HCC patients and demonstrated the production of CXC chemokines by HCC cell lines. We determined the effect of both HCC patient serum and tumor cell conditioned supernatant upon lymphocyte expression of chemokine receptor CXCR3 as well as lymphocyte migration. Lastly, we examined the chemotactic responses of lymphocytes derived from HCC patients., Methods: The serum chemokines IP-10 (CXCL10) and Mig (CXCL9) levels were measured by cytometric bead array (CBA) and the tumor tissue IP-10 concentration was measured by ELISA. The surface expression of CXCR3 on lymphocytes was determined by flow cytometry. The migratory function of lymphocytes to the corresponding chemokines was assessed using an in vitro chemotactic assay. Phosphorylation of extracellular signal-regulated kinase (ERK) was determined by Western blot analysis., Results: Increased levels of IP-10 and Mig were detected in HCC patient serum and culture supernatants of HCC cell lines. The IP-10 concentration in the tumor was significantly higher than that in the non-involved adjacent liver tissues. HCC cell lines secreted functional chemokines that induced a CXCR3-specific chemotactic response of lymphocytes. Furthermore, tumor-cell-derived chemokines induced initial rapid phosphorylation of lymphocyte ERK followed by later inhibition of ERK phosphorylation. The culture of normal lymphocytes with HCC cell line supernatants or medium containing serum from HCC patients resulted in a significant reduction in the proportion of lymphocytes exhibiting surface expression of CXCR3. The reduction in T cell expression of CXCR3 resulted in reduced migration toward the ligand IP-10, and both CD4+ and CD8+ T cells from HCC patients exhibited diminished chemotactic responses to IP-10 in vitro compared to T cells from healthy control subjects., Conclusion: This study demonstrates functional desensitization of the chemokine receptor CXCR3 in lymphocytes from HCC patients by CXCR3 ligands secreted by tumor cells. This may cause lymphocyte dysfunction and subsequently impaired immune defense against the tumor.

The antibacterial pharmacodynamics against E. coli of Chinese medicine (CM) Rhizoma coptidis (Coptis Root) and its formula Sanhuang, and the control antibiotics enoxacin, were analyzed by a concentration-killing curve (CKC) approach, and the novel parameters BC50 and r for antibacterial potency were proposed. Using the agar plate method, about 400 cells of E. coli were evenly inoculated into LB agar plates containing a series of different concentrations of CM or antibiotic, and after a 24 hour incubation at 37 degrees C, all the viable colonies were enumerated. This resulted in a sigmoid concentration-killing curve , in which No, that could be closely fitted (R2 > 0.9) with the function: N = 1 + e(r(x-BC50))/N0 in which N0, BC50 and r represent meaningfully inoculums size, median bactericidal concentration, and bactericidal intensity, respectively. N modeled the survival of colony-forming units on each plate (CFU/plate) in a concentration series x of the drug. The CKC was symmetrical about its single inflexion (BC50, N0/2). Therefore theoretically, 2BC50 can replace MBC (minimum bactericidal concentration). BC1 = BC50 + r/ln(N0-1), the drug concentration at r which only one colony survived, was the least critical value of MBC in CKC. The parameters 2BC50 and BC1 agreed more closely with the definition of MBC, and were little affected by either the biochemical basis of the antibacterial or the inoculum's size (200-400 CFU/plate), and were determined by a multi-point curve. As a result, these were more accurate, reproducible and practical as metrics than was the endpoint of MBC. The two-dimensional CKC, involving BC50 and r, captures the intrinsic dynamics of the antibacterial effect of CM/strain versus concentration, and it is consistent with the Logistic equation of the bacterial growth curve in the format. This verified approach has considerable value as a tool for the accurate and proper administration of CM. The CKC of CM, different from that of antibiotics, is likely to be the resultant force of each ingredient in certain CM, which provides a clue to solve the problem of antibiotic resistance.

Acetone extracts of engine exhaust particulate matter (PM) and of vapor-phase semi-volatile organic compounds (SVOCs) collected from a set of 1998-2000 model year normal emitter diesel engine automobile or light trucks and from a set of 1982-1996 normal emitter gasoline engine automobiles or light trucks operated on the California Unified Driving Cycle at 22 [degree]C were assayed for in vitro genotoxic activities. Gasoline and diesel PM were comparably positive mutagens for Salmonella typhimurium strains YG1024 and YG1029 on a mass of PM extract basis with diesel higher on a mileage basis; gasoline SVOC was more active than diesel on an extracted-mass basis, with diesel SVOC more active on a mileage basis. For chromosomal damage indicated by micronucleus induction in Chinese hamster lung fibroblasts (V79 cells), diesel PM expressed about one-tenth that of gasoline PM on a mass of extract basis, but was comparably active on a mileage basis; diesel SVOC was inactive. For DNA damage in V79 cells indicated by the single cell gel electrophoresis (SCGE) assay, gasoline PM was positive while diesel PM was active at the higher doses; gasoline SVOC was active with toxicity preventing measurement at high doses, while diesel SVOC was inactive at all but the highest dose.

Objective: To detect adverse effects on the pregnant/lactating dams and on the development of the offspring following exposure to sibutramine hydrochloride of the dams from the closure of the hard palate through weaning., Methods: Studies on the effects of this new drug on pre- and postnatal development, including maternal function of mice were conducted. The pregnant mice were randomly divided into four groups. The dose levels were 32 mg/(kg.d) (1/5 LD50), 2.83 mg/(kg.d), 0.25 mg/(kg.d) for three groups respectively, and the fourth group was for negative control. Females were administered sibutramine hydrochloride in drink water from the closure of the hard palate (pregnant 15 d) to the end of lactation. Adverse effects on pregnant mice, pre- and postnatal deaths of offspring, altered growth and development, functional deficits in offspring were assessed. Terminal examinations included: necropsy (macroscopic examination) of all adults, abnormalities, live offspring at birth, body weight at birth, pre- and postweaning survival and growth/body weight, maturation, physical development, sensory functions and reflexes and behavior., Results: The increase of death (above 10%) of pregnant and lactating mice was observed in the group of 32 mg/(kg.d). No other adverse effects on the maternal animals and offspring were observed., Conclusion: The data of these studies on mice showed no evidence for the reproductive toxicity to pregnant mice and the developmental toxicity to offspring induced by sibutramine hydrochloride.

Objective: To investigate the estrogenic activity of para-nonylphenol in immature SD rats and explore the mechanism and sensitive indicators of its action in uterotrophic assay., Methods: The vehicle control (peanut oil), positive control(estradiol benzoate, E2B, 0.4 mg/kg) and p-NP(60 mg/kg, 90 mg/kg and 120 mg/kg) were given orally (by gavage) q.d. on the 21st, 22nd, 23rd postnatal days. Then the rats were sacrificed 24 hours after the last administration. By using ABC immunohistochemistry, the progesterone receptor (PR), estrogen receptor (ER), and proliferating cell nuclear antigen (PCNA) of the rat uterine were analysed., Results: Uterine weight, uterine/body weight significantly increased in E2B 0.4 mg/kg, p-NP 90 mg/kg and 120 mg/kg groups as compared with those of vehicle control group (P < 0.01), and a dose-response relationship was observed. The expressions of PR, ER and PCNA in the nuclei of stromal and myometrial cells of uterus were detected in all the p-NP groups, and a dose-effect relationship was noted., Conclusion: Expressions of PR, ER and PCNA as indicators tested by immunohistochemical technique are more sensitive than uterine weight in uterotrophic assay. Hyperplasia of stromal and myometrial cells of uterus is the reason why the uterine weight of the rat increased.