Objective To explore the effects of maternal cypermethrin exposure during lactation on testicle development and steroidogenesis of weaning offspring, and to provide a theoretical basis for the toxicity study of cypermethrin on reproduction.Methods Twenty-one healthy pregnant mice(clean animal) were randomly divided into three groups.Maternal mice were orally administered with different doses of cypermethrin [0,6.25 and 25 mg(/kg?d),10 ml/kg] dissolved in corn oil daily from postnatal day 1(PND1) to PND21.Fifteen male pups were randomly selected from each group and sacrificed at PND21 after exposure.The testicle organ coefficients were calculated.Serum testosterone(T) and estrogen(E2),testicle T were measured by radioimmunoassay(RIA).Histopathological changes in the testicle tissues were observed by HE stain.Testicle cells apoptosis was detected by TdT-mediated dUTP nick end labeling(TUNEL).Results A significant decrease was observed in body weight and the testicle organ coefficients in cypermethrin-treated group was in a dose-dependent manner(P0.05).Histological examination showed that maternal cypermethrin exposure markedly decreased the number and layers of spermatogenic cells,increased the inside diameter(ID) of seminiferous tubules,and disturbed the array of spermatogenic cells in testicle sections of pups at PND21.No significant effect on apoptosis of testicle cells was seen.Conclusion Maternal cypermethrin exposure during lactation may damage testicles and steroidogenesis of weaning offspring.

ObjectiveTo analyze the long term efficacy and prognosis of ursodeoxycholic acid (UDCA) combined immunosuppressive therapy in primary biliary cirrhosis-autoimmune hepatitis overlap syndrome (PBC-AIH). Methods A total of 44 PBC-AIH cases were selected from 387 autoimmune liver diseases cases in The General Hospital of Tianjin Medical University from January 2001 to January 2011,and the medical data,treatments and efficacies were retrospective analyzed.ResultsThe serum levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),γ glutamyl transpeptidase (GGT) and total bilirubin (TBil) increased in different degrees in 44 PBC-AIH patients.Globulin or immunoglobulin G(IgG) increased in 84.09％(37/44) patients,immunoglobulin M(IgM) increased in 38.63％ (17/44) patients.The positive rate of antinuclear anti-body (ANA), anti-mitochondrial antibody (AMA)and anti-smooth muscle antibodies (SMA) was 97.73％,90.91％ and 11.36％,respectively. Pathological features were interface hepatitis and different degrees of intrahepatic bile ducl injuries. After UDCA combined immunosuppressant treatment,the remission rate was 61.36 ％ (27/44),the incomplete response rate was 29.55％ (13/44) and the treatment failure rate was 9.09％ (4/44).Six cases with remission withdrawal medicine,and the recurrence rate was 5/6.By the end of follow-up,the levels of ALT,AST,ALP,GGT and TBil significantly decreased in PBC-AIH patients compared with those before treatment.ALP,GGT,ALT and AST levels significantly decreased in the first 6 months while ALP and GGT showed slight upward trend at the end of follow up. The disease progression rate was 25.33％ in PBC-AIH patients (13/44) during the follow-up,and the 10 year survival rate was 93.33％ (28/30).ConclusionUDCA combined immunosuppressive therapy in PBC AIH treatment can significantly improve patients' blood biochemical indexes,delay disease progression,improve survival rate,and the remission rate is also high.However the recurrence rate is high after withdrawal of medicine.

Objective To evaluate the value of technetium-99m methoxy isobutyl isonitrile (99Tcm-MIBI)tomography and integrated CT in preoperative localization diagnosis of secondary hyperparathyroidism (SHPT).Methods 28 patients with SHPT were selected.15 minutes and 90 minutes (delayed images)after intravenous administration of 99Tcm-MIBI 370 MBq,static anterior planar images of the neck and chest were obtained.99Tcm-MIBI tomography and integrated CT scan were acquired after the delayed imaging.The imaging findings were compared to the pathological results.Results The detection rate of SHPT lesions by 99Tcm-MIBI dua-phase imaging and 99Tcm-MIBI tomography and registration with integrated CT scan was 53.3％ and 70.7％ respectively.The difference had statistical significance(X2 =5.903,P＜0.05).The fusion imaging with integrated CT can provide detailed anatomy data and more information for surgical doctors.Conclusion 99Tcm-MIBI tomography and registration with integrated CT scan can improve the detection rate of SHPT compared with 99Tcm-MIBI dua-phase imaging,provide more detailed anatomy data,and has high clinical value in preoperative localization and diagnosis of SHPT.

Objective To explore the risk factors of stroke- associated pneumonia (SAP) in stroke patients. Methods A retrospective study was designed to analyze the clinical data of 159 patients with stroke. They were divided into SAP group (n=35) and non-SAP group (n=124). Their age, gender, hypertension, diabetes mellitus, gastric mucosal protective agents, dysphagia after stroke (DAS), stroke history, type of stroke, hypoproteinemia, disturbance of consciousness, nasal feeding and smoking were analyzed with univariate analysis and multivariate Logistic regression analysis. Results 22% of the 159 patients suffered from SAP. Univariate analysis showed, there was statistical difference in age (P<0.01), gastric mucosal protective agents (P<0.01), DAS (P<0.01), hypoalbuminemia (P<0.05), disturbance of consciousness (P<0.05), nasal feeding (P<0.001) and smoking (P<0.01) between two groups. Binary Logistic regression for the multivariate analysis indicated that age≥70 years old, DAS, nasal feeding and smoking were the risk factors related with SAP. After adjusting for all other variables, the odds of SAP were 5.119 times higher for patients requiring nasal feeding than those without nasal feeding. Conclusion There is a high morbidity for SAP, which is attributed to multiple factors. Age≥70, DAS, nasal feeding and smoking may be the most important risk factors related with SAP.

The challenge of the emergence of drug-resistant influenza strains, which is caused by wide spread utilization of direct-acting antivirals (DAAs), accelerates the research and exploration towards host targeted agents. In contrast to DAAs targeting viral replication components, host targeted agents, which regulate host factors and pathways linked to viral replication, can interfere the replication of influenza. Additionally, the innate immune system is activated by influenza during the early stage of infection, so manipulating the innate immune response may prevent the viral infection. However, the excessive inflammatory response induced at the late phase of influenza infection would lead to severe tissue injures. Thus, it is very important to explore drugs with anti-inflammatory actions to suppress these immune imbalances and tissue injures. Here we overview the current progresses about host targets related to anti-influenza drugs.
Anti-Inflammatory Agents ; pharmacology ; Antiviral Agents ; pharmacology ; Humans ; Immunity, Innate ; Influenza, Human ; drug therapy ; Virus Replication

Objective To investigate the influencing factors of successfully switching to sequential ventilation in patients with prolonged weaning due to acute respiratory failure (ARF) after thoracolaparotomy based on the initial rapid shallow breathing index (RSBI) at 60 min after spontaneous breathing trial (SBT), namely, the f/VT optimal value range of 80-120 times/ (min · L), thus providing the basis for determining the ideal timing of weaning in clinical practice.Methods A prospective observational study of sequential ventilation [RSBI during the initial SBT (60 min), 80-120 breaths/ (min · L)] was carried out in 42 patients on mechanical ventilation (≥ 48 h) due to post-thoracolaparotomy ARF in the ICUs.According to the duration of the mechanical ventilation, the patients were divided into 2 groups : successfully prolonged weaning group (≥ 7 days, n =24) and refractory weaning group (＜ 7 days, n =18).The patients with cardiac failure, aged less 18 or over 80, with hepatic dysfunction, or those needing gastrointestinal decompression after esophageal surgery or upper abdomen surgery were excluded.The demographics, APACHE Ⅱ scores and duration of mechanical ventilation of both groups were recorded, and the respiratory work and oxygen metabolism variables before the switch to sequential ventilation (within 24 hours after admission to ICU) and at the time of switching (24 hours in the ICU after admission) were recorded, respectively: clinical puhnonary infection score (CPIS), assessment of cough severity, pH, PaO2, PaCO2 and PaO2/FiO2;hemodynamic and microcirculation-related variables: HR, MAP, fluid balance, BNP and Lac;endocrine and metabolism variables : Hb, ALB and random serum cortisol (COR).The clinical features and the changes of the above-mentioned variables before and at the time of switching were compared between both groups.The independent sample t test was used for the single factor comparison and Mann-Whitney U test was applied to the non-normal distributions.The Fisher exact probability test was used for the single factor comparison of ranked data such as categorical variables.Results There were no significant differences in age, gender and severity of disease between two groups (P ＞ 0.05);the successfully prolonged weaning group had longer duration of invasive mechanical ventilation and ICU stay compared with the refractory weaning group (P ＜ 0.05).There were significant differences in cough severity, PaCO2, pH, HR and fluid balance between two groups before switching (P ＜ 0.05).Compared with those before switching, in the refractory weaning group there were marked decrease in Lac (P ＜ 0.05), obvious increase in cough severity, pH, Hb and ALB (P ＜ 0.05), but there was no significant difference in COR (P ＞ 0.05);while in the successfully delayed weaning group, there were significant decrease in CPIS, PaCO2, HR, MAP, BNP, fluid balance and Lac (P ＜ 0.05), and cough severity, pH, ALB and COR showed an upward trend (P ＜ 0.05).Conclusions The key of successful sequential ventilation is within the values of RSBI ranging from 80 to 120 times/ (min · L) during the initial SBT (60 min) selected as the switching point in patients with prolonged weaning after thoracolaparotomy.The major influencing factors for determining the ideal timing of switching include the matching status between respiratory endurance and respiratory work, the balance between myocardial strength and both cardiac preload and afterload, the severe disease associated with adrenal insufficiency, and malnutrition.

Objective To study the apoptosis-inducing effects and mechanisms of influenza virus A H_ 3 N_ 2 on a self-established endometrial adenocarcinoma cell line JEC. Methods JEC cells were infected with different concentrations of H_3N_2, the apoptosis were detected using the HE staining, DNA agarose gel electrophoresis and flow cytometry. The expressions of Fas, FasL and TGF-? were examined by immunocytochemical staining. Results After infection, the JEC cells showed the morphological apoptosis; DNA agarose electrophoresis demonstrated a ladder-like pattern of DNA fragments; FITC/PI stained FCM showed the apoptotic rate of JEC had been decreased along with the prolonging of infected time and elevated with the increase of the virus concentrations. Immunocytochemical staining showed that enhanced expression of Fas, attenuated expression of TGF-?, and no expression of FasL after H_3N_2 infection. Conclusion Influenza virus A H_3N_2 can induce JEC cells to apoptosis in time- and concentration- dependent manners, which may be related with the expressions of Fas and TGF-?.

Background Choroidal neovascularization (CNV) is one of the causes of blindness in multiple eye diseases.Researches showed that complement system participates in the pathogenesis of CNV.Objective This study was to construct the recombinant of complement factor B-small interference RNA (CFB-siRNA) expression vector and to observe its inhibitory effect on human umbilical vein endothelial cells (ECV-304).Methods CFB gene primers were designed based on human CFB gene,and an expression vector of CFB-siRNA was constructed by inserting CFB-siRNA into pRNAT-U6.1/Neo plasmid.Recombinant plasmids were confirmed by the digestion analysis of restriction endonuclease,and all inserted sequences were verified by DNA sequencing.The recombinant pRNAT-U6.1/CFB-siRNA plasmid and the blank plasmid were transfected into ECV-304 cells in the CFB-siRNA group and blank plasmid group by electroblot,respectively,and non-transfected cells served as the normal control group.The cells were observed under the fluorescence microscope 48 hours after transfection,and the transfective efficiency was calculated.The relative expression of CFB mRNA in the cells of different groups was detected by semi-quantitative reverse transcription PCR (RT-PCR).MTT was employed to calculated the growth inhibitory rates of the cells 24,48 and 72 hours after transfection.The percentages of the cells in different cell cycles were detected by flow cytometry.Results The sequence of the target vector was identical to the designed sequence.The green fluorescence protein (GFP) was seen in both the CFB-siRNA group and the blank plasmid group.The relative expression levels of CFB mRNA were 0.07 ±0.04,0.14 ±0.02 and 0.14 ±0.03 in the CFB-siRNA group,the blank plasmid group and the normal control group,respectively,a significant difference was obtained among the three groups (F=233.05,P =0.00);the expression level of CFB mRNA in the CFB-siRNA group was significantly declined in comparison with the blank plasmid group and the normal control group (both at P＜0.05).The growth inhibitory rates of the cells were (23.45 ±0.01) ％,(33.48 ±0.02) ％ and (45.49±0.01) ％ at 24,48 and 72 hours after transfection,respectively,a significant difference was obtained among the three groups (Fgroup =212.99,P =0.00);the growth inhibitory rates in CFB-siRNA group were significantly higher than that in the blank plasmid group and normal control group (all at P＜ 0.05).The percentages of G1 phase cells were (44.4 ±0.5) ％,(25.8 ±0.4) ％ and (27.9 ± 0.6) ％ in the CFB-siRNA group,the blank plasmid group and the normal control group respectively,a significant difference was obtained among the three groups (F=58.98,P=0.00).The percentages of G1 phase and G2 phase cells in the CFB-siRNA group were significantly higher than those in the blank plasmid group and the normal control group (all at P＜0.05).Conclusions Recombinant pRNAT-U6.1/CFB siRNA inhibits the proliferation of ECV-304 cells effectively by arresting the cells in G1 intermediate phase of the growth cycle.

Objective To explore the feasibility of 7.0T MR scanner in mouse aorta atherosclerosis models.Visualising the TN-C in atherosclerotic plaque by immunohistochemistry and its correlation with CD68 to provide experimental basis for the feasibility of TN-C in targeted MRI.Methods ApoE-/- mice and wild type C57 mice were fed on high fat diet to establish aorta atherosclerosis model (n=10),the aorta were observed by MRI after 14 weeks.The aorta specimens were taken to stain with HE to observe the pathological changes.The plaque was stained with oil red O,anti-TNC and TN-C antibody respectively to observe the fat,CD68 and TN-C in plaque.Results 7.0 MRI showed the aortic wall of the experimental group was thicker,high signal on T1 WI and PDWI,and low signal on T2 WI after 14 weeks.The histopathlogic examination showed the intima was obviously thicker,and the lumen was ir-regulary narrow.Both of CD68 and TN-C were highly expressed in plaque,and the distribution of TN-C correlated with CD68.In the control group,no case showed hyper-signal in the vessel wall of aorta or narrow lumen by MRI,and the histopathlogy showed no for-mation of atherosclerotic plaque in the aorta.Conclusion Aorta atherosclerotic plaque can be established through high fat diet on ApoE-/- mouse,and 7.0 MR can successfully detect it.TN-C is high expressed in AS plaque and the expression is correlated with CD68,which may suggest that they may collaborate in the development of AS.Detecting TN-C could be useful for the further study of atherosclerotic plaque.

Objective To investigate clinical characteristics of tuberous sclerosis(TSC)without nervous system abnormalities in infants. Methods Clinical manifestations of 12 infants with TSC were analyzed. Reflectance confocal microscopy (RCM)was performed in 5 of the 12 infants. Two patients underwent histopathological examination and electron microscopic examination. Results The age at first clinic visit for TSC ranged from 2 to 18 months (median, 8.6 months)among these patients. Before occurrence of nervous symptom, TSC mainly manifested as hypomelanotic macules, nodules in the subependymal layer or walls of lateral ventricles of the brain, cardiac rhabdomyoma and multiple renal cysts. RCM revealed intact dermal papillary rings with low reflectivity and obscure boundaries in 5 infants. Histopathological examination showed a local decrease in melanocytes and pigment granules in basal cells. Electron microscopic examination showed a normal number of melanin granules in the cytoplasm of melanocytes in the basal layer. Conclusions Before appearance of nervous system abnormalities, TSC mainly manifests as hypomelanotic macules in infants, and is easily confused with vitiligo in clinic. RCM examination may serve as a useful method to distinguish infant TSC from hypopigmented diseases.