Clinical comparison of one recovered case and one fatal case of human infection with H7N9 avian influenza in Shanghai Public Health Clinical Center in China

H7N9 avian influenza is the latest subtype of influenza virus to emerge in the world. By April 17, 2013 in Shanghai, a total of 31 confirmed cases were reported, and 11 of these patients died. The epidemiological characteristics and the clinical progress of this new human flu infection are still not clear. Thirteen confirmed patients have now been treated in Shanghai Public Health Clinical Center. Among the first batch of patients, hospitalised at the beginning of April 2013, two who were admitted with the same estimated date of onset of disease had very different outcomes. After active treatment at the Centre, one recovered by April 18, 2013, but one patient entered critical condition and died on April 11, 2013. The clinical and laboratory characteristics in hospital are here analysed and compared to learn more about H7N9 avian influenza. Confirmation that the observed differences are valuable for prognosis and treatment decisions for H7N9 patients awaits authentication by analysis of more patients.

A 72-week on-treatment efficacy of de novo combination of tenofovir plus lamivudine based highly active antiretroviral therapy for HBV-HIV co-infected patients / 中华临床感染病杂志

Objective To evaluate the efficacy and safety of de novo combination of tenofovir (TDF) plus lamivudine (LAM) based highly active antiretroviral therapy (HAART) for HBV-HIV coinfected patients.Methods Sixty patients with HBV-HIV co-infections admitted to Wuxi Fifth People's Hospital and Shanghai Public Health Clinical Center during January 2009 and December 2012 were enrolled.The patients were randomly divided into TDF + LAM based HAART group (TDF + LAM group,n =30) and LAM based HAART group (LAM group,n =30).All patients were treated for 72 weeks.SPSS 17.0 was used to compare the ALT normalization rate,HBV DNA negative conversion rate,serological response,HIV RNA negative conversion rate and CD4 + lymphocyte counts elevation rate between two groups at 24-,24-,48-and 72-week.Drug resistance and adverse reaction were observed.Results ALT normalization rates in TDF + LAM group at 24-,48-and 72-week were 83.3％,90.0％ and 93.3％,respectively,which were higher than those in LAM group (x2 =5.079,4.812 and 5.455,P ＜0.05).After 48 weeks of treatment,there were 28 patients (93.3％) in TDF + LAM group with the elevation of CD4 + lymphocyte counts ≥ 150 cells/μL,the rate was higher than that in LAM group (21/30,70.0％) (x2 =5.455,P ＜ 0.05).HBV DNA negative conversion rates in TDF + LAM group at 12-,24-,48-and 72-week were 60.0％,90.0％,93.3％ and 96.7％,respectively,which were higher than those in LAM group (x2 =4.800,5.963,5.455 and 9.017,P ＜0.05).No drug resistance and severe adverse reaction was observed in TDF + LAM group.Conclusion TDF + LAM based HAART is better in HBV viral suppression and liver function normalization,and has lower HBV resistance and higher CD4 + T lymphoeyte counts elevation rate than LAM based HAART for HBV-HIV co-infected patients.

Characteristics of opportunistic infection in hospitalized acquired immunodeficiency syndrome patients / 中华传染病杂志

Objective To investigate the characteristics of opportunistic infections in acquired immunodeficiency syndrome (AIDS) patients.Methods A comprehensive retrospective chart review study was conducted of 603 AIDS patients with different opportunistic infections in a special hospital authorized for AIDS patients.Results In all 603 patients,327 cases (54.2％) were infected with Pneumocystisjiroveci,251 cases (41.6％) were infected with fungus and 210 cases (34.8％) were infected with mycobacterium.Totally 367 cases (60.9％) had only one pathogen and 236 cases (39.1％) were co-infected with more than one pathogen.A total of 390 cases (64.7％) had a single site of infection with the respiratory tract being most frequently involved (271 cases,69.5％),and 213 cases (35.3％) had more than one infected site.The most common coinfected sites were oropharynx and respiratory tract (111 cases,52.1％).Conclusions AIDS patients are usually coinfected with multiple pathogenic organisms and multi-systems involved.Most of the opportunistic infections can be cured by timely diagnosis and effective treatment to prolong life and improve the quality of life of AIDS patients.

Overexpression of sigma-1 receptor inhibits ADAM10 and ADAM17 mediated shedding in vitro

The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain. Recent studies linked it to many diseases, such as drug addition, Alzheimer's disease, stroke, depression, and even cancer. Sigma-1 receptor is enriched in lipid rafts, which are membrane microdomains essential in signaling processes. One of those signaling processes is ADAM17- and ADAM10-dependent ectodomain shedding. By using an alkaline phosphatase tagged substrate reporter system, we have shown that ADAM10-dependent BTC shedding was very sensitive to both membrane lipid component change and sigma-1 receptor agonist DHEAS treatment while ADAM17-dependent HB-EGF shedding was not; and overexpression of sigma-1 receptor diminished ADAM17- and ADAM10-dependent shedding. Our results indicate that sigma-1 receptor plays an important role in modifying the function of transmembrane proteases.

Markers of endothelial injury and plasma adipocytokine in antiretroviral-naive HIV patients / 中华内科杂志

Objectives To investigate the markers of endothelial injury, adipocytokine and thrombotic activity and explore whether there are cardiovascular disease risk factors in antiretroviral-naive HIV patients. Methods Clinical data and venous blood samples were collected from 43 anti-retroviral naive HIV-infected patients during February -October 2009 in our center, and compared with 17 healthy subjects.Plasma leptin, adiponectin, soluble intercellular adhesion molecule-1 ( sICAM-1 ), D-dimer were measured by ELISA. Four markers and cholesterol, triglyceride, fasting plasma glucose were compared between the two groups. The CD4+ T cells and percentages of CD38, HLA-DR on CD8+ T were determined by flow cytometry and plasma HIV copies were detected with bDNA analyzer among HIV-infected participants.Spearman correlations between the significant markers and CD4+ T cells, CD8+ CD38+/CD8+, CD8+ HLA-DR +/CD8+, HIV viral load were examined among HIV-infected participants. Analyses were conducted by using Stata version 7. Results Thirty-eight of the 43 patients were sexually infected by HIV and the median absolute CD4+ T cell count was ( 133 ± 82 ) cells/μl, HIV RNA was (4. 42 ± 0. 66 ) lg copies/ml. HIV-infected patients, compared with healthy subjects, had lower leptin [11.41 (7.91,14. 53 )μg/L vs 55.31( 16. 49,229.65 ) μg/L, P= 0. 0005], adiponectin [1.79 ( 1.40,4. 00 ) mg/L vs 3.36 ( 2. 92,4. 18 ) mg/L,P =0. 003] and higher sICAM-1 [1.71 (1.11,2.40) mg/L vs 0. 69 ( 0. 57, 0. 80 ) mg/L, P = 0. 0000].No significant differences exist in cholesterol, triglyceride, fasting plasma glucose. For HIV-infected participants, sICAM-1 tended to correlate with CD8+ CD38+/CD8+ and HIV viral load ( r= 0.3378, P= 0.0267;r = 0.3904,P = 0.0096). Conclusion Patients with untreated HIV infection have lower leptin, adiponectin and higher sICAM-1 levels and the relationship of these markers to HIV-mediated atherosclerotic risk requires further study.

Long-term and stable expression of transgene mediated by piggyBac transposon in gynecological malignant tumor cells / 中华妇产科杂志

Objective To investigate the expression of exogenous gene transferred by piggyBac (PB) transposon in various gynecological malignant cell lines and reveal its potential application of gene therapy in gynecological cancer.Methods Amplified herpes simplex virus thymidine kinase (HSV-tk) gene coding region by PCR and integrated it into PB expression vector, PB[Act-RFP]DS, for reconstructing PB[Act-RFP, HSV-tk]DS (pPB/TK).By using different transfection reagents: FuGENE HD, jetPEI, lipofectamine 2000, pPB/TK together with helper plasmid Act-PBase were cotransfected into four mostly common gynecological malignant tumor cell lines HeLa, JEG-3, SKOV3 and HEC-1B.The mRFP1 report gene expressions was observed and detected by fluorescence microscope and flow cytometry to analyze transfection efficiency.The expressions of HSV-tk and mRFP1 gene were detected by reverse transcription PCR (RT-PCR).The cytotoxic effect of various concentration of pro-drug ganciclovir (GCV) for transfected cells was detected by methyl thiazole tetrazolium assay.The transfected cells were positive sorted by flow cytometry and limiting diluted to obtain the stable transfected cell line.The insertion sites of foreign gene tranferred by PB transposon in genome were analyzed by inverse PCR.Results (1) Double digests analysis and sequences test demonstrated that pPB/TK vector was reconstructed successfully.(2) Using three different transfective reagents, PB trausposon transferred HSV-tk gene and mRFP1 gene into HeLa, HEC-1 B, SKOV3 and JEG-3 cell efficiently, and the transfection efficiency of pPB/TK for the same cell was different by using different transfective reagents; in Hela cell, the transfection efficiency of FuGENE HD [(78.7 ± 9.2) %]was higher than that of lipofectamine 2000 [(54.1 ± 11.4) %]and jetPEI [(46.5 ± 7.4) %, all P < 0.05] ; using the same transfective reagent, the transfection efficiency of pPB/TK was also different on various cell lines, using FuGENE HD, the transfeetion efficiency of pPB/TK on HeLa, JEG-3 and SKOV3 cell was (78.7 ± 9.2) %, (74.4 ± 8.9) % and (83.2 ± 9.7) % respectively, which all were higher than that on HEC-1B [(39.5 ± 8.7) %, P < 0.05] .(3) RT-PCR showed that there were the mRNA expression of HSV-tk and mRFP1 in all cell lines.(4) 50% inhibitory concentration of GCV for transfected cells, HeLa, JEG-3, SKOV3 and HEC-1B, was 1.29, 3.35, 0.09 and 13.28 μg/ml respectively.Inhibitory effect of GCV (10 μg/ml) on SKOV3 transfected with pPB/TK was (86 ± 9) %, which was superior to that transfected with pORF-HSVtk alone [(52 ± 12)%, P < 0.05] .(5) The insertion sites of PB transposon in the target cells genome were located at TTAA sites, mRFP1 expression still could be detected in three months after transfected.Conclusions PB transposon could transfer exogenous gene into various gynecological malignant cells, which could integrated into genome and obtain a long-term and stable expression.It is expected that PB transposon may supply a more efficient and safer transgene technology platform for gene therapy in gynecological cancer.

Concentrations of amphotericin B in body fluid from patients with AIDS-associated cryptococcal meningitis / 中华临床感染病杂志

Objective To determine the concentrations of amphotericin B in serum and cerebrospinal fluid from patients with AIDS-associated cryptococcal meningitis.Methods Ten patients with AIDS-associated cryptococcal meningitis were enrolled in the study.Blood samples were collected before drug administrated at the 7th.14th and 21 th day after maintenance dose achieved.Cerebrospinal fluid samples were collected from lumbar puncture or taken before intrathecal drug administration at least one week after maintenance dose achieved.The concentrations of amphoteriein B in blood and cerebrospinal fluid samples were determined using RP-HPLC.Results When maintenance doses varied from 25 to 40 mg/d,the blood steady-state trough concentration range of amphotericin B was 1.34-2.27 ms/L,and that of cerebrospinal fluid was 44.0-9 1.7μg/L.Conclusions The concentrations of amphotericin B in the cerebrospinal fluid would be lower than the desired concentration if amphotericin B administrated only through intravenous or integrated with irregular intrathecal administration.It suggests that higher dosage of intravenous injection and regular intrathecal administration should be applied to achieve the desired concentration.

First-line highly active antiretroviral therapy regimen:safety and tolerance / 中华临床感染病杂志

Objective To evaluate the safety and tolerance of the first-line hiighly active antiretroviral therapy(HAART)regimen in Chinese HIV/AIDS patients.Methods The clinical data and laboratory results were retrospectively reviewed in 95 HIV/AIDS outpatients receiving first-line HAART regimen of zidovudine,lamivudine and efavirenz(or nevirapine)in Public Heahh Clinical Center Affiliated to Fudan University during January 2005 and August 2008.Mixed effects model and X2 test or Fisher test were used to analyze panel data and ratio data respectively.Results Totally 81%(77/95)patients had adverse events in the course of treatment,11.6%(11/95)developed grade 3 or higher adverse effects.Hematological adverse events and hepatotoxity were the most common in term of laboratory events with the total incidence of 46.3%(44/95)and 27.4%(26/95)respectively;8.4%(8/95)and 6.3%(6/95)were grade 3 or higher.In clinical events,30.5%(29/95),37.8%(36/95)and 27.4%(26/95)patients had dermatological,gastrointestinal and neurological adverse events respectively,however,only 1.1%(1/95)experienced grade 3 or higher dermatological adverse events.Conclusion The first line HAART regimen is safe and well tolerated in Chinese HIV/AIDS patients.

The causes of death for 89 HIV/AIDS patients / 中华临床感染病杂志

Objective To analyze the causes of death for 89 HIV/AIDS patients,and the association of CD4+ T lymphocyte counts with the mortality.Methods Data were collected from 89 deceasedpatients who were admitted to Shanghai Public Health Clinical Center from Jan 1996 to Sep 2007,and wereretrospectively analyzed with t-test.Results Heterosexual,blood transfusion and blood products were themajor transmission routs for 89 deceased HIV/AIDS patients.The primary causes of death varied with different levels of CD4+ T lymphocyte counts.With higher CD4+T lymphocyte counts,patients were more likelyto die from non-AIDS-related opportunistic infections such as upper digestive tract hemorrhage.Serious pulmonary infection induced by various etiologies was the primary cause of death.Co-infections of multiple etiologics were often seen in these death cases.Conclusion Opportunistic infection is the primary cause of death for HIV/AIDS patients.Appropriate therapies should be based on CD4+ T lymphocyte counts and patients' specific conditions to reduce the mortality.

A cross-sectional survey of occult hepatitis B virus infection in HIV-infected patients / 中华内科杂志

Objectives Occult HBV infection is defined by positive HBV DNA in individuals with undetectable levels of HBsAg.The objective of this study was to assess the prevalence of occult HBV infection in HIV-infected patients.Methods Serum samples were obtained from 105 HBs Ag-negative HIV patients who were hospitalized and were not giyen anti-virus treatment at Shanghai Public Health Clinical Center.Microparticle enzyme immunoassay(MEIA)was used to detect HBV serologic markers(HBsAg,anti-HBs,HBeAg,anti-Hbe and anti-HBc).EUSA was used to detect HCV antibody.CD4+ T cell count was examined with flow cytometry.Nested PCR was used to amplify surface protein region of HBV.Results 32(30.5%)patients(27 men,5 women)were HBV DNA positive in the 105 HBsAg-negative HIV-infected patients(92 men and 13 women).22 patients(including 5 patients with HBV DNA+)were in 16-30 years group,44 patients(including 15 patients with HBV DNA+)were in 31-49 years group and 39 patients(including 12 patients with HBV DNA+)were in 50-75 years group.5 patients were negative for all HBV serologic markers and 27 patients detected with at least one of anti-HBc.anti.Hbe or anti-HBs.14 patients (29.8%)with HBV DNA+in 47 HIV-infected patients were coinfected with HCV,18 patients(31.0%)were HBV DNA+in 58 HIV-monoinfected patients.The median absolute CD4+T eell count was 145.1cells/μ1(4-623 cells/μ1),26 patients(34.7%)were HBV DNA+in 75 AIDS patients with CD4+T cell＜200 cells/μ1 and 6 patients(20.0%)HBV DNA+in 30 HIV-infected patients with CD4+ T cell＞200cells/μ1.No statistical significant association could be established between the above factors.Conclusions It is found tIlatoccult HBV did occur in HIV-infected patients.No statistical significant association could be established between occult HBV infection and gender,age,HBV serologic markers,coinfected HCV and CD4+T cell count.

Value of urinary nucleosides determination for the diagnosis of colorectal carcinoma / 中国普通外科杂志

Objective To evaluate urinary nucleosides determination for the diagnosis of colorectal carcinoma. Methods The concentrations of 14 different urinary nucleosides from 42 colorectal carcinoma patients, 10 patients with villous adenoma and 62 normal adults were determined by high-performance liquid chromatography (HPLC); Principal component analysis was applied to classify colorectal cancer patients and normal adults. Results The levels of Pseu、 C、 m1A、 mU、 m22G、 I、 m1G、 ac4C、 m6A in colorectal carcinoma group were (42.67?21.89)、(0.44?0.51)、(2.72?0.83)、(0.13?0.08)、(1.79?0.55)、(0.50?0.36)、(1.44?0.52)、(0.82?0.30)、(0.07?0.08)nmol/(?mol creatinine) respectively, which were much higher than those in normal adults (P