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 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.

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

This study was aimed to investigate the distribution of tumor necrosis factor-alpha (TNF-alpha)-308 gene polymorphism and its correlation with asthma in TCM syndromes between Han and Uyghur People in Xin-jiang. The polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method was applied in the detection of TNF-alpha-308 gene polymorphism among 160 bronchial asthma cases and 40 healthy con-trols. Traditional Chinese medicine (TCM) syndrome differentiation standard on bronchial asthma was applied in the syndrome differentiation of 160 bronchial asthma cases. And gene distributions of TCM syndrome differentia-tion were compared. The results showed that there was no significant difference between the genotypes (wild-type and mutant) and allele distribution between the asthma group and the normal control group, the Uyghur asthma group and Uyghur normal control group, the Han asthma group and Han normal control group, Uyghur normal control group and Han normal control group (P > 0.05). There was no significant difference on the TNF-alpha-308 genotype distribution among different TCM syndromes. There was no significant difference on TCM syndrome distribution between Han asthma patients and Uyghur asthma patients. It was concluded that bronchial asthma in Xinjiang may be nothing to do with ethnic group, TNF-alpha-308 gene polymorphism. And the bronchial asthma syndrome differentiation type may be nothing to do with the TNF-alpha-308 genotype distribution.

Objective To observe the clinical findings about the endothelial cell injury related to the genesis of inflammatory cytokines and coagulation.Methods A total of 70 critically ill patients with SIRS (systemic inflammatory response syndrome) admitted to intensive care unit (ICU) between September 2009 and February 2010 were enrolled for a prospective and control study.According to diagnostic criteria of Sepsis/SIRS,the patients were divided into two groups:sepsis group (n =38) and SIRS group (n =32),and another 20 healthy volunteers served as control group.Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure,diabetes and its complications.The demographics of patients including age,sex,body mass index (BMI),smoking and alcohol addict were comparable among the different groups.The 6 ml peripheral blood samples were collected within 24 h after admission to ICU for enzyme-linked immunosorbent assay (ELISA) to detect the plasma levels of s-CD62P,TNF-α,and hsCRP.And variables of coagulation function such as platelet (PLT),prothrombin time (PT),activated partial thromboplastin time (APTT),D-dimer and antithrombin-Ⅲ (AT-Ⅲ) were analyzed during 24 h after admission to ICU.Meanwhile sequential organ failure assessment (SOFA) score of critically ill patients was evaluated.Data were expressed in mean ± standard deviation and were statistically analyzed by using SPSS 17.0 statistical software.The differences in plasma levels of s-CD62P of patients in each group were analyzed by ANOVA and Kruskal Wallis test.The relationship between s-CD62P and inflammatory cytokines as well as with coagulation were determined by Pearson correlation analysis.Changes were considered as statistically significant if P value was less than 0.05.Results ① Compared with control group and SIRS group,the levels of s-CD62P,TNF-α and high sensitive C-reactive protein (hs-CRP) were significantly higher in sepsis group (P ＜ 0.05).② The plasma levels of D-dimer,PT,APTT in sepsis group and SIRS group were significantly higher than those in control group,while the platelet count (PLT) and the activity of AT-Ⅲ were obviously lower (P ＜ 0.05).③ In sepsis group,the plasma levels of hs-CRP and TNF-α positively correlated with PT,APTT,D-dimer,and negatively correlated with AT-Ⅲ,PLT (P ＜ 0.05).④ Plasma levels of s-CD62P were significantly correlated with plasma levels of TNF-α,hs-CRP,D-dimer,PT,APTT,whereas correlated negatively well with PLT,AT-Ⅲ (P ＜ 0.05).Conclusions The plasma s-CD62P concentration is elevated as a early biomarker in patients with sepsis,and it acted as one of pathogenic factors responsible for endothelial cell damage.Coagulation and mediators of inflammation promotes each other,aggravating the severity of the sepsis.The plasma s-CD62P may be the important factor associated with initiation of coagulation development and inflammatory reaction.

Objective To investigate the effects of GR82334 caudal veins injection(iv)or intrathecal injection(ith)on the increase of dopamine (DA)content in rats anterior cingulate gyrus(ACG)induced by heavy current stimulation of saphenous nerve(SN). Methods Totally 42 male Wi-star rats were randomly divided into six groups,including control group,sham stimulation group,SN stimulation group,GR82334(ith)group,NS (ith)group,GR82334(iv)group,and NS(iv)group. At the end of the study,rats of different groups were sacrificed,then the right side ACG were collected and weighted. ACG samples were then homogenized with 0.1 mol/L perchloric acid solution. After spinning at 10 000 r/min(4℃)for 20 min,20μL of the supernatant were harvest from each sample. High performance liquid chromatography electrochemical detection was used to mea-sure DA content. Results Heavy current stimulation of SN caused obvious increase of the DA content in ACG. GR82334(iv or ith)antagonized the significant increase of DA content in ACG induced by the stimulating SN. However,GR82334(ith)did not completely antagonized the increase of DA content in ACG induced by electric stimulating SN. Conclusion The results indicated that there is connection between SN and the dopami-nergic nervous system in ACG,and SN afferent nociceptive signals can activate ACG dopaminergic neurons to release DA. Peripheral and central NK-1 receptors are involved in the process of significant increase of DA content in ACG induced by SN afferent signals. However,there are other central paths of SN information input to ACG to induce obvious increases of DA content,in which other neurotransmitters and receptors may be involved.

Objectives To determine the prevalence of Staphylococcus aureus (S. Aureus) colonization and S. aureus-derived exotoxins in lesions of childhood atopic dermatitis (AD) and evaluate the role of S.aureus-derived exotoxins in the pathogenesis of childhood AD. Methods Specimens were taken from the skin lesions of 148 patients, non-lesional skin of 30 patients, and the skin of 250 controls for bacterial cultures. S. aureus-derived exotoxins were detected by reverse passive latex agglutination. Total IgE levels were determined with immunoradiometric assay. Results The prevalence of S. aureus colonization was significantly increased in both the lesional and non-lesional skin of patients with AD in comparison with the controls (P 0.05). However, patients with increased total IgE levels showed significantly high SCORAD indices (P

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.