Objective To explore the efficacy and safety of a raltegravir (RAL)-containing regimen among patients on methadone maintenance therapy.Methods From January 2010 to November 2010, 30 virus (HIV) treatment naive patients who were on methadone maintenance therapy were enrolled from a HIV clinic in Kunming, Yunnan Province and a HIV clinic in Hengyang, Hunan Province.All patients were given RAL, tenofovir (TDF) and lamivudine (3TC) as highly active antiretroviral therapy (HARRT).Patients were followed up for 48 weeks to evaluate the adjustment of methadone dose, opiate withdrawal reaction, antiretroviral efficacy and safety.Results From January 2010 to November 2010, 30 HIV patients were enrolled from the two appointed HIV clinics.The mean age was 39±6 years, with 73.3% male patients and 97% Han population.Before the treatment, their mean CD4+T lymphocyte counts was 210 /μL.Ninety percent of patients were co-infected with hepatitis C.Twenty-nine patients who completed study follow-up were included in final analysis.Five (17.8%) patients reported opiate withdrawal symptoms and increased methadone dose 4 weeks after HARRT.At 24 weeks and 48 weeks of HARRT, the average increase of CD4+T lymphocyte counts were (136±71) /μL and (185±88)/μL, respectively.Among patients who provided valid HIV-1 RNA testing results, 82.6% (19/23) and 95.8% (23/24) of patients had undetectable viral load at week 24 and week 48.Six grade 1-2 adverse events were reported in 4 patients.Conclusions In this pilot study, the new regimen containing RAL, TDF and 3TC appears to be an ideal option for patients on methadone maintenance therapy, because of its limited impact on methadone dose and good efficacy and safety profile.

Objective To understand the changes of cardiac systolic and diastolic function in human immunodeficiency virus (HIV)-infected patients without evidence of cardiac disease in China.Methods Forty-two HIV-infected patients who were followed up in the Department of Infectious Diseases at Peking Union Medical College Hospital without cardiac involvement were recruited.All the HIV-infected patients had received highly active antiroviral therapy (HAART) for more than 12 months with viral suppression.And 30 age and sex matched healthy subjects without cardiac disease manifestations were enrolled as controls.Every group members underwent transthoracic echocardiography evaluation.The indexes of cardiac systolic and diastolic function between HIV-infected patients and healthy controls were compared.Results Diastolic abnormality occurred in 20 cases in HIV-infected group and 6 cases in control group, with statistically significant difference (χ2=5.79, P=0.007).The E wave deceleration time (EDT) in HIV-infected patients were significantly decreased than healthy controls ([161.87±21.64] ms vs.[190.34±37.22], t=-3.20, P=0.002).There were no significant differences of E/A ratio ([1.16±0.35] vs.[1.19±0.26]), E/Ea ratio ([5.43±1.99] vs.[5.78±0.91]), isovolumic relaxation time (IVRT), ([93.18±20.34] ms vs.[93.57±18.55]ms), Ea ([10.18±2.80] cm/s vs.[11.45±2.75] cm/s) between HIV-infected patients and controls (t=1.13,1.53,0.67 and 0.29, respectively, all P>0.05).Among cardiac systolic function markers, left ventricular ejection fractions in HIV-infected patients and control group were (66.7±6.4)% and (68.7±4.2)%, respectively.And left ventricular shortening rates were (37.08±4.79)% and (38.17±3.96)%, respectively.Both showed no significant difference between the two groups (t=-1.51 and-1.00, respectively, both P>0.05).Conclusions Compared with control group, subclinical cardiac diastolic dysfunction is more frequently observed in HIV-infected patients.However, there are no significant differences of cardiac systolic function markers between HIV-infected patients and controls.

Objective To evaluate the predictive value of serum presepsin (sCD14-ST) for septic myocardial depression (SMD) in patients with severe sepsis or septic shock.Methods This was a prospective cohort study.A total of 84 patients with severe sepsis or septic shock were monitored by pulse indicator continuous cardiac output (PiCCO) system and divided into myocardial depression group (cardiac function index [CFI]<4.1 L/min, n=37) and non-myocardial depression group (CFI≥4.1 L/min, n=47) according to cardiac function index (CFI).Left ventricular ejection fraction (LVEF) was measured by doppler echocardiography at admission.The patients were divided into survival group (n=40) and non-survival group (n=44) based on 28-day mortality.Serum sCD14-ST,B-type natriuretic peptide(BNP), tumor necrosis factor-α(TNF-α), cardiac troponin Ⅰ (cTnⅠ) levels and hemodynamic parameters were observed dynamically at day 1,3,5 after admission.Quantitative data with normal distribution were analyzed using t-test and abnormal distribution data were analyzed using Mann-Whitney U test.Categorical data were analyzed using χ2 test.Results The serum levels of cardiac index (CI), global ejection fraction (GEF) and left ventricular contractility index (dPmax) in myocardial depression group were all significantly lower than those in non-depression group at day 1 after admission (all P<0.01).The serum levels of sCD14-ST, TNF-α and BNP in myocardial depression group were all significantly higher than those in non-depression group (all P<0.01).Serum sCD14-ST levels in 84 septic patients were positively correlated with both BNP and TNF-α (r=0.204, P<0.05 and r=0.516, P<0.01, respectively).The area under the receiver operating characteristics curve (AUC) of sCD14-ST was 0.782 for myocardial depression in patients with sepsis, with a sensitivity of 89.2% and a specificity of 78.0% at the cut-off point of 988 mg/mL.The predictive value of sCD14-ST was inferior to BNP and TNF-α (both P<0.05).The combination of sCD14-ST, TNF-α and BNP could provide better prediction value in septic myocardial depression.Logistic regression analysis showed that serum sCD14-ST was not the in dependent predictor for septic myocardial depression (P>0.05).There were 24 cases died in myocardial depression group.The mortality of myocardial depression group was significantly higher than that of non-depression group (64.9% vs 42.6%, χ2=4.132, P =0.042).The serum levels of sCD14-ST at day 1 and day 3 in myocardial depression group were significantly higher than those in non-myocardial depression group (both P<0.01).sCD14-ST levels in both groups showed downtrend.The serum level of sCD14-ST in non-survival group was significantly higher than that in survival group (P<0.01).Conclusions Myocardial depression is common in patients with severe sepsis and septic shock.High serum level of sCD14-ST is correlated with myocardial depression to some extent, but not an independent predictor.The combination of sCD4-ST, BNP and TNF-α can improve the predictive value for myocardial depression.

Objective To explore the role of basic leucine zipper ATF-like transcription factor (BATF) in active tuberculosis, and to provide clues for diagnosis and therapy of tuberculosis.Methods Sixteen patients with active tuberculosis (ATB), ten cases of latent tuberculosis infection (LTBI) and fourteen healthy controls (HC) were included in this study.Flow cytometry was applied to detect the expressions of BATF and programmed death-1 (PD-1) in T lymphocytes, and the changes of BATF by blockade of PD-1/PD-L pathway using specific blocking antibody antiPD-1, antiPD-L1 and antiPD-L2.The expressions of BATF were compared using Mann-Whitney U test.And the relation of BATF and PD-1 was analyzed using Pearson correlation analysis.Results The CD4+ T lymphocytes expressing BATF accounted for 5.16% (2.96%,8.71%) of CD4+ T lymphocytes in ATB group, which was higher than 1.05% (0.40%,1.27%) in LTBI group and 0.71%(0.43%,1.21%) in HC group, and the difference were statistically significant (U value were 6.5 and 9.0, respectively, both P<0.01).The CD8+ T lymphocytes expressing BATF accounted for 4.10% (2.27%,8.17%) of CD8+ T lymphocytes in ATB group, which was higher than 0.55% (0.34%,1.18%) in LTBI group and 0.84% (0.41%,1.29%) in HC group, and the difference were statistically significant (U value were 5.0 and 8.0, respectively, both P<0.01).Furthermore, the percentage of BATF+ PD-1+ CD4+ T lymphocytes in the peripheral blood of ATB was significantly higher than those in the peripheral blood of LTBI and HC, the difference were statistically significant (Uvalue were 16.0 and 14.5, respectively, both P<0.01), and the percentage of BATF+ PD-1+ CD8+ T lymphocytes in the peripheral blood of ATB was significantly higher than those in the peripheral blood of LTBI and HC, the difference were statistically significant (Uvalue were 10.0 and 16.5, respectively, both P<0.01).In addition, there was a positive correlation between the percentage of BATF+ T cells and PD-1+ T cells, both in CD4+ T cells (r=0.676,P=0.016) and CD8+ T cells (r=0.610,P=0.035).The expressions of BATF both in CD4+ T cells and CD8+ T cells were decreased followed by blockade of PD-1/PD-L pathway (P<0.05).Conclusions BATF may be involved in the regulation of immune pathogenesis of tuberculosis.In order to provide a theory for anti-tuberculosis immunotherapy fargeting BATF, further research need to be proceeded.

Objective To explore the efficacy and protective mechanism of calpain, a calcium activated neutral proteinase as a vaccine candidate molecule. Methods Anti calpain sera were prepared by immunized BALB/c mice with recombinant calpain. Anti calpain sera, schistosomula of Schistosoma japonicum , and mouse eosinophils were incubated at 37 ?C , 5% CO 2 for 48 hours, and the adherence of eosinophils to schistosomula and its schistosomulacidal efficacy were observed. Results Mice immunized with recombinant calpain produced a high level IgG antibodies specific to the antigen immunized. Immunoblotting analysis showed murine anti recombinant calpain sera bound specifically to recombinant calpain. Ninety six percent of schistosomula were surrounded by cells when incubated with mouse eosinophils, and a significant number of dead schistosomula was observed at 48 hours when incubated with mouse serum and eosinophils as compared with control serum and eosinophils ( P

Objective To study the dynamic changes of soluble interleukin 2 recepter (sIL 2R) level and lymphocyte subsets over clinical course, the relationship between them and biochemical parameters of renal function, and to explore the role of the disturbance of celluar immune function in the pathogenesis of hemorrhagic fever with renal syndrome (HFRS). Methods The level of sIL 2R in sera was detected by double antibody sandwich ELISA method. The percentages of lymphocyte subsets were measured by flow cytometry. Results The level of sIL 2R in patients with HFRS increased significantly in febrile phase, reached its peak in hypotensive and oliguric phase and then decreased gradually in diuretic phase but still higher than that of normal in convalescent phase with values being (463.06?157.02) pmol/ml, (636.85?270.36) pmol/ml, (287.75?118.74) pmol/ml and (191.75?55.60) pmol/ml in different stages, respectively ( P 0.05). The percentage of CD3 +,CD4 + cells decreased significantly while the percentage of CD3 +, CD8 + cells increased significantly, which resulted in the decrease or reverse of CD4 +/CD8 + ratio in febrile phase. These changes were most obvious in hypotensive and oliguric phase, returned gradually in diuretic phase, but still abnormal in convalescent phase ( P

Objective To monitor the distribution and resistance of enteric pathogenic bacteria in Beijing area to offer the data for guiding epidemiologic study and clinical treatment. Methods Enteric pathogenic bacteria were cultured and identified to spicies, group, and serotype with the biochemical and serologic test. Then, the susceptibility of bacterium to antimicrobial agents were tested. Results Enteric pathogenic bacteria infection occurred with male, children, and youth being prominant. It peaked in June and July. Shigellae spp and Vibrio spp were the main pathogenic bacteria of intestinal tract. There presented difference among the sensitive rates of differential spicies, or groups to antimicrobial agents. Conclusions There are many spicies of enteric pathogenic bacteria causing infective diarrhea in Beijing area. Their distributions are different in sex, age and season. The is resistance rate are different needing surveillance.

Objective To study the Genotype of local clinical isolates of Enterobacteriaceae producing extended spectrum ? lactamases. Methods K B test, conjugative transfer test, plasmid profile analysis, PCR, PCR RFLP, and DNA sequencing were used to detect the phenotype and genotype of 33 isolates of Enterobacteriaceae producing ESBLs. Results Eighty five percent of 33 isolates was resistant to cefotaxime which was obviously higher than that to ceftazidime. blaCTX M ESBLs was detected in 28 isolates by PCR, blaTEM DNA in 24 isolates, and blaSHV DNA in 9 isolates. Mutation of E104K was only identified in one TEM ? lactamase produced by EC98A7 by PCR RFLP. No substitution of G238S occurred in 9 SHV ? lactamases. DNA sequencing and DNA alignment showed the blaCTX M DNA fragments from 4 clinical isolates of EC98A7,EB56,CFR78 and, KP9941 belonged to CTX M type 1, with highest identity to blaCTX M 3 or blaCTX M 12 respectively. Conclusions CTX M ESBLs is carried in 85% isolates of Enterobacteriaceae producing ESBLs in this city. Most of the isolates carry 2 or more ? lactamases. E. coli EC98A7 produces two ESBLs, a TEM ESBL and a CTX M ESBL.

Objective To study the HBsAg specific CTL activities activated by dendritic cells derived from human monocytes on the HepG2/S target cells, and further to probe into the anti HBV effect of HBsAg DC (dendritic cell) vaccine. Methods DCs are proliferated from human peripheral blood monocytes by adding GM CSF and IL 4 and then HBsAg specific CTL are activated by DCs pulsed by HBsAg; The target cell line (HepG2/S) expressing HBsAg was set up by transfecting recombinated plasmid with HBV/S gene (PLXSN/S) into HepG2/S cell line; HBsAg specific CTL and HepG2/S target cells were cocultured in 96 well flat bottomed microtiter plates for 48 hours at 37 ?C in 5% CO 2, and then HBsAg specific CTL activities activated by DCs pulsed by HBsAg were detected by counting the number of killed target cells. Results HBsAg specific CTL activated by dendritic cells derived from human monocytes could produce strong killing effect on the target cells HepG2/S cells. It's specific CTL activities were 3.8%, 69.5% and 85.1% in different concentration (0 ?g/L,50 ?g/L and 100 ?g/L) respectively. While, it had no killing effect on the HepG2 cells, so the HBsAg specific killing effect was specific. Conclusions The result shows that HBsAg specific CTL activated by dendritic cells derived from human monocytes has strong killing effect on the HBV.

Objective To establish practical cell model of HCV infection, and investigate the susceptibility of a human liver cell line HepG2 to hepatitis C virus in vitro. Methods A human liver cell line HepG2 was incubated with serum from a chronic hepatitis C patient for 6～8 hours. Both the plus and minus strands of HCV RNA in infected cells or supernatant were examined by reverse transcription polymerase chain reaction (RT PCR). The HCV NS 3,NS 5 antigens in infected cells were respectively detected with the monoclonal antibodies to antigens of their own by immunohistochemical assay. The minus strand of HCV RNA in infected cells were localized by in situ hybridization. Results The intracellular plus or minus stands of HCV RNA were first detected on day 3 post incubation and then could be intermittently detected until day 35 post incubation in cells or supernatant. The positive signals of NS 3,NS 5 antigens could be expressed within cytoplasm of infected cells. The minus strand of HCV RNA was located within cytoplasm by in situ hybridization. Conclustions These results show that a human liver cell line HepG2 is not only susceptible to HCV but also able to support its long time replication in vitro.