This study is to evaluate the HAART pharmacodynamics with dolutegravir as the "anchor" in vitro. A nucleoside reverse transcriptase inhibitors (NRTIs) resistant recombinant virus model (VSVG/HIV-1(RT-D67N,K70R,T215F)) and an integrase inhibitors (INIs) resistant recombinant virus model (VSVG/HIV-1(IN-G140S,QI48H)) were constructed and established. The anti-viral pharmacodynamics was evaluated with drug combinations including two NRTIs along with one INI or one NNRTI. The results showed that the combination with an INI gave a stronger synergism on wild type HIV-1 replication comparing to that with an NNRTI. Comparing the two INIs as the "anchor" for HAART, DTG exhibited an equivalent CI to that of RAL on wild type HIV-1 replication; but a greater synergy than RAL on INI-resistant HIV-1 replication. Besides of the pharmacodynamics results of DTG-based drug combination, the results may contribute to clinical antiviral therapy.
Antiretroviral Therapy, Highly Active ; Cells, Cultured ; Drug Resistance, Viral ; HIV Integrase Inhibitors ; pharmacology ; HIV-1 ; drug effects ; physiology ; Heterocyclic Compounds, 3-Ring ; pharmacology ; Humans ; Virus Replication ; drug effects

Objective To compare the effect of inhaled corticosteroids and montelukast in children with asthma .Methods Data were obtained from Pubmed ,Embase and Central databases ,CNKI and VIP .Only randomized controlled trials (RCT ) that evalua-ting inhaled corticosteroids and montelukast for children were included .The Cochrane collaboration risk bias tools was used to eval-uated the quality of literature .Results The patients with inhaled corticosteroids had a better effect in FEV 1% and PEF than pa-tients with montelukast ,the incidences of adverse drug reactions had no statistically significant difference .The patients with inhaled corticosteroids combined with montelukast had a better effect in FEV 1% or PEF than patients with inhaled corticosteroids only . Conclusion The effect of inhaled corticosteroids is better than montelukast ,the effect of inhaled corticosteroids combined with montelukast is better than inhaled corticosteroids only ,and has drug safety .

The incidence of severe acute pancreatitis in children is lower.But it has abrupt onset and atypical symptoms.The fatality rate is relatively high.This paper will review the progress on the diagnosis and treatment of severe acute pancreatitis.

Adult ; Blood Cell Count ; Control Groups ; Female ; Humans ; Male ; Physicians ; Radiography, Interventional

Objective To investigate the effect of fluoride on expression of Runx2 mRNA and protein in bone tissue of rats. Methods Fourteen SD rats were randomly divided into two groups: control group(tap water with fluoride ＜ 0.06 mg/L), and fluorosis group(fluoride 50 mg/L in water). After 4 moths, expressions of both mRNA and protein of Runx2 in rat bone tissue were determined by RT-PCR and Western blotting. Results The results showed that the expression of Runx2 mRNA and protein in fluoride-treated bone tissue were 2.287 ± 0.261 and 0.929 ± 0.229, respectively, both of which were significantly higher than those of control group(0.995 ± 0.123,0.317 ± 0.068, t = 11.85,6.78, P ＜ 0.05). Conclusions Fluoride can increase the expression of Runx2 mRNA and protein in bone tissue of rats, and Runx2 may be involved in the pathogenesis of bone injury caused by fluoride.

Objective To investigate the value of the combined detection of serum human epididymal secretory protein 4(HE4) and carbohydrate antigen 125(CA125) in diagnosing ovarian and uterine tumor .Methods Serum levels of HE4 and CA125 were detected in 112 cases of ovarian cancer ,92 cases of uterine cancer ,145 cases of ovarian benign diseases ,138 cases of uterine adeno-myoma and 56 cases of healthy controls by ELISA and electrochemiluminescence(ECL) immunoassay respectively .Results Serum levels of HE4 and CA125 were (246 .80 ± 52 .81)pmol/L and (439 .20 ± 305 .80)U/L in the ovarian malignant tumor group , (196 .50 ± 38 .15)pmol/L and (463 .80 ± 127 .60) U/mL in the uterine malignant tumor group and (19 .76 ± 16 .45)pmol/L and (15 .67 ± 11 .19)U/mL in the control group ,the differences had statistical significance (P<0 .05) .Serum levels of HE4 and CA125 before operation and in postoperative 2 weeks in the ovarian cancer group and the uterine cancer group had statistical difference (P<0 .05) .Conclusion The combination detection of serum HE4 and CA125 can improve the accuracy and sensitivity in the diag-nosis of pelvic tumors .

Objective To establish a non-traumatic mouse model of acid aspiration-induced lung injury which al-lows longitudinal studies.Method C57BL/6 mice were anesthetized and orotracheally intubated with a 20 gauge angio-catheter guided by optical fiber.The mice were subsequently placed in the right lateral decubitus position and external com-pression to the left lung was manually applied.A polyethylene catheter was advanced into the right lung and used to instill either hydrochloric acid (2.5μL/g, 0.1 mol/L, pH 1.5) or saline as control.Then the mice were recovered with supple-mental oxygen for 4 hours.The pulmonary physiological function and survival of mice within 2 weeks after surgery were as-sessed.Results Methylene blue instillation showed that the staining fluid went into the right lung of the non-traumatically intubated mice.The survival rate of the mice with non-traumatic instillation was 80%, statistically significantly higher than those with tracheostomy instillation.Histological examination and lung function ( wet/dry ratio, elastance and arterial oxy-gen saturation) assay demonstrated that acid instillation caused a profound pathological changes and functional impairment of the lung.Besides, acid aspiration into the mouse lung caused a significant increase in neutrophil infiltration in mouse pulmonary alveoli and high concentrations of inflammatory factors (TNF-α, IL-6, CXCL1 and CXCL2) in the bronchoalve-olar lavage fluid.Conclusions We successfully established a mouse model of acid aspiration-induced lung injury, which may serve as a reliable model for longitudinally studying pulmonary immune-inflammatory mechanism in humans.

Objective To observe the changes of pulmonary oxidative stress after cigarette smoking exposure,its re-lationship with inflammatory cytokines,and the effects of smoking cessation. Methods Fifty male BALB / c mice were randomly divided into the smoke exposure group,smoke cessation group,and the controls. Mice in smoke cessation group were exposed to cigarette smoking for 16 weeks. On 4,8,and 12 week after smoking cessation mice were executed and the bronchoalveolar lavage fluid(BALF)and lung tissue were collected. The morphologi-cal alternations of lung tissue were observed. Mean length of interval and mean alveolar number were measured. Total cell numbers in BALF were counted. Superoxide dismutase(SOD)activity was measured with hydroxylamine method,malondialdehyde(MDA)level was measured with TBA method. The levels of pulmonary interleukin-8 (IL-8)and tumor necrosis factor-α(TNF-α)in BALF and lung tissue homogenate were measured with ELISA. Re-sults Compared with the mice in the controls,emphysematous changes were remarkable in the lung of cigarette ex-posed mice,the total cell numbers in BALF were increased significantly(P < 0. 05)and reduced gradually after smoking cessation(P < 0. 05). SOD and MDA levels increased remarkably in the cigarette exposure group(P <0. 05),and declined gradually after smoking cessation. The levels of IL-8 and TNF-α in BALF and lung tissue ho-mogenate in the smoke exposure group increased significantly( P < 0. 05),and lowered time-dependently after smoking cessation,but not reached to normal level even 12 weeks after smoking cessation. SOD and MDA levels were positively correlated with the cytokine changes. Conclusion Abnormal oxidative stress in the airways caused by cigarette smoking exposure was merely partially reversed after smoking cessation. And the inflammation remains persistent concomitantly.

Objective To investigate the expression of apoptosis regulating protein Bcl-2 and Bax,and the spontaneous apoptotic index(AI) in malignant mesothelioma,and their relationship to the survival time of patients.Methods Hematoxylin-eosin and immunohistochemical stainings were used for the sections of paraffin embedded tissues of 79 specimens of malignant mesothelioma.The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) was used to identify the apoptotic tumor cells.Results The age of the patients with malignant mesothelioma ranged from 11 to 79 years.The peak incidence of malignant mesothelioma was at the age of 40-50 years.The ratio of male to female was 1.47∶1.The survival time of the 79 cases was between 5 and 160 months,and the medial survival time was 23 months.According to histological pictures,these tumors were diagnosed as epithelioid type(51 cases),mixed type(8 cases) and sarcomatous type(20 cases).The tumor spontaneous apoptotic index(AI) was 0.14%-6.9%.The survival time of the patients with higher AI was significantly shorter than those with lower AI(P

Objective To report immune-reconstruction in two patients with acute radiation sickness due to 60Co radiation accident after stem cell transplantation.Methods Patient “A” and “B” were diagnosed as intestinal form of acute radiation sickness(ARS)and extremely severe degree bone marrow form of ARS,respectively.Peripheral blood stem cell transplantation was successfully performed in these two patients.During their whole disease course,absolute lymphcyte count,neutrophil leukocyte count,T-lymphocyte subsets,natural killer(NK),and immunoglobulin were sequentially determined.Results Immunoglobulin was decreased after irradiation without any recovery tendency after the transplantation.After irradiation,absolute lymphcyte count decreased rapidly,but recovered partially after the transplantation(maintained at 0.5?109/L).Neutrophilic leukocyte count rose rapidly to normal after the transplantation.NK was lowered obviously after irradiation,and it rapidly recovered to normal level after the transplantation,and maintained at a level higher than normal.After irradiation,the proportion of CD4/CD8 showed a transient rise,followed by an abrupt lowering.After the transplantation,it showed a tendency of elevation,but it did not recover to normal.Conclusions The tendency of lowering of immunoglobulin,lymphocyte count,NK cell count,and CD4/CD8 ratio indicate that there is a rapid deterioration of both cellular and humoral immunity after irradiation.Following the homogeneic peripheral blood transplantation,neutrophil count and NK cell count showed a rapid recovery,lymphocyte count and CD4/CD8 ratio also showed a tendency of slow elevation,but there is no sign of recovery of immunoglobulin.The results indicate that there is a faster recovery of cellular immunity.