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

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 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 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.

A novel method based on the separation and enrichment effect of magnetic beads and the fully complementary hybridization of two DNA strands was developed for highly sensitive detection of bacterial DNA using a surface-enhanced Raman spectroscopy (SERS) with 5,5’-dithio-bis(2-nitrobenzoic acid) (DTNB)-modified gold nanoparticles as reporter probes. Capture probe was immobilized onto the surface of streptavidin-enwrapped magnetic beads ( SA-MB ) through high affinity between biotin and avidin, by which the target bacterial DNA sequences that connected with the reported probe decorated AuNPs with DTNB and SH-DNA ( AuNPs@DTNB@DNA) were captured and loaded onto the magnetic beads by the hybridization reaction with the capture probe. Compared with previous methods, this design shortened the distance between particles by the ways that the magnetic beads tempted to nanoparticles aggregation, and produced the plasma resonance coupling effect, which increased the SERS signal significantly. The results showed that, under the optimized conditions and in the concentration range from 5 pmol/L to 5 nmol/L, the method performed a good linear relationship between Raman intensity and DNA concentration. The limit of detection ( LOD) of bacterial DNA was estimated to be 5 pmol/L. The method is simple and low cost, and can be used in the sensitive and selective detection of bacterial DNA.

Aim To determine the effects of Qiliqian-gxin injected into lateral ventricle on Cardiac function, angiotensin Ⅱ( Ang Ⅱ) , angiotensin converting en-zyme(ACE), angiotensin type 1 receptor(AT1R) and the sympathetic nervous system in the hypothalamic pa-raventricular nucleus of rats with chronic heart failure. Methods Rat model of heart failure was prepared by acute myocardial infarction that was induced by ligation of the left anterior descending coronary artery. Four weeks after heart failure, Qiliqiangxin and Losartan were continuously administered via a syringe pump in-jector connected to lateral ventricle. After four weeks, echocardiogram was used to evaluate the cardiac func-tion and HE was used to observe myocardial tissue morphology, and enzyme linked immunosorbent assay was used to measure plasma norepinephrine( NE) , ser-um NT-proBNP and Ang Ⅱ in the paraventricular nu-cleus. The expression of ACE and AT1 R at mRNA and protein levels in the paraventricular nucleus was deter-mined by Real-time PCR and Western blot, and the RSNA was measured by PowerLab in anesthetized rats. Results Compared with the sham control, the cardiac function was significantly lower while the AngII, ACE, AT1 R expression in the paraventricular nucleus and RSNA were significantly increased in rats with heart failure. Compared with heart failure control, Qiliqian-gxin and Losartan decreased the RSNA and the AngII, ACE, AT1 R expression in the paraventricular nucleus. Conclusion Giving traditional Chinese medicine to the lateral ventricles can decrease the activation of the RAS system, reduce the renal sympathetic nerve activi-ty and improve cardiac function.