Objective To evaluate the application of pooling HIV nucleic acid amplification testing (NAAT) among men who had sex with men (MSM) population, and to investigate suitable HIV screening strategy and the feasibility of calculation of HIV incidence using pooling NAAT among MSM population in China.Methods Four thousand eight hundred and fifty-six samples were collected from MSM population from April 2008 to September 2009 among with 4 156 were in Heilongjiang province and 700 were in Beijing in China. After standard testing with an HIV ELISA and WB confirmation testing, HIV antibody-negative samples were pooled and screened for HIV using NAAT.A three-stage pooling strategy was adopted.The HIV positive rate estimated by the four HIV screening strategies was calculated.In addition, 4 156 HIV positive specimens from Heilongjiang province were screened with the BED capture enzyme immunoassay (BED-CEIA).The HIV-1 incidences were estimated by BED-CEIA assay and pooling NAAT individually.ResultsOne hundred and forty-three of 4 856 subjects were HIV infected.130 were 3rd and 4th generation ELISA positive; 13 were antibody-negative but acutely HIV infected.According to the evaluation of four HIV screening strategies, routine HIV screening test together with pooling NAAT was more effective than other strategies for screening out window period generation ELISA+WB+pooling NAAT' were 2.68%(95% confidence interval CI=2.22%-3.14%), 2.82%(95%CI=2.35%-3.29%), 2.94%(95%CI=2.46%-3.42%) and 2.94%(95%CI=2.46%-3.42%), respectively.The differences were not significant (χ2=0.854 3, P=0.836 4).Of the 88 HIV positive samples from Heilongjiang province, 44 participants were tested as recent HIV infections by BED-CEIA assay. The estimated HIV-1 incidence was 2.36% (95%CI=1.63%-3.08%) and 2.92% (95%CI=1.01%-4.83%) based on BED-CEIA assay and pooling NAAT,respectively.Conclusions Pooling NAAT is a effective screening test in HIV negative population to detect window period infection among MSM population in China.

Objective To investigate the molecular mechanism of solanine-induced apoptosis of prostate cancer cells Du145 and LNCaP.Methods The effects of solanine on the viability of Du145 and LNCaP cells were evaluated by MTT assay.The generation of intracellular reactive oxygen species (ROS) and solanine-induced apoptosis were measured by flow cytometry.The protein levels of p38 and p-p38 expressions were examined by Western blot.Results Solanine significantly inhibited the viability of Du145 and LNCaP cells in a dose-dependent manner (P＜0.01).The inhibition of solanine on cell viability was suppressed by the ROS scavenger NAC.ROS generation,apoptosis and phosphorylation of p38 were induced by treatment with solanine at 40 μmol/L for 24 h.The expression of p38 and solanine-induced apoptosis were suppressed by NAC and SB203580.Conclusion Solanine induces the apoptosis of human prostate cancer cell via the RO.S-p38 signaling pathway.

Abstract: Objective　To explore the spatial epidemiological characteristics of severe cases hand, foot and mouth disease (HFMD) in Guangxi, China, from 2014 to 2018, and to provide a basis for identifying the high-risk regions as well as the prevention and control of severe cases of HFMD in Guangxi. Methods　Spatial-temporal scanning analysis, global and local spatial autocorrelation analysis were used to analyze the spatial clustering of HFMD. The trend surface analysis was used to evaluate the spatial distribution trend of HFMD. Results　From 2014 to 2018, the incidence and severe case fatality rates of HFMD were 3.89/100 000 and 4.23%, respectively. Monte Carlo scanning analysis showed that the first cluster region was Cenxi City, the second cluster was mainly concentrated in northwest of Guangxi, and the aggregation time was mainly concentrated in April to May and August to October. The global spatial autocorrelation analysis showed that the severe HFMD was significant clustering distribution, and the Moran's I coefficients of the sever cases, severe morbidity and severe case fatality rate were 0.088, 0.118, 0.197, respectively (P<0.05). Local spatial autocorrelation analysis showed that hotspots of severe HFMD cases were concentrated in the southern Guangxi, mainly in Lingshan County. Anselin local Moran's I clustering and outlier analysis indicated that 5 high-high (H-H) clustering regions for fatality were Lingshan, Pubei, Zhongshan, Zhaoping and Pinggui County. There were 6 high-high (H-H) clustering regions for severe incidence rate, namely Lingshan, Qinnan, Lingyun, Youjiang, Bama Yao Autonomous and Pinggui County, and 1 high-low (H-L) clustering region, Cenxi County. The trend surface analysis showed that the overall number of severe cases of death decreased from east or west to the middle, and increased from north to middle, and then decreased to south. Conclusions　Severe HFMD cases in Guangxi have obvious spatial-temporal clustering, and the hop spots are mainly concentrated in southern Guangxi. The prevention and control of HFMD in areas with high incidence of severe cases should be strengthened to reduce the burden of HFMD cases.

OBJECTIVETo compare the results of detecting HIV-1 load by using NucliSens HIV-1 QT and Amplicor HIV-1 monitor 1.5 assays.

METHODSEighty-two clinical samples were collected and HIV viral load was determined with the above-mentioned two methods.

RESULTSThe number of samples in which values obtained by NucliSens HIV-1 QT and Amplicor HIV-1 monitor 1.5 differed by <0.5 log10 RNA copies/ml and in which the viral load was undetectable accounted for 88.9 percent of the measures. The correlation coefficient between the two methods was 0.956 in 56 samples of Deltalog10 VL<0.5.

CONCLUSIONThe results of HIV-1 viral load determination with the two methods are highly comparable.

HIV Infections ; virology ; HIV-1 ; genetics ; isolation & purification ; Humans ; Nucleic Acid Amplification Techniques ; instrumentation ; methods ; RNA, Viral ; genetics ; Viral Load

During the routine impurity profile of lisinopril bulk drug by HPLC (high-performance liquid chromatography), a potential impurity was detected. Using multidimensional NMR (nuclear magnetic resonance) technique, the trace-level impurity was unambiguously identified to be 2-(-2-oxo-azocan-3-ylamino)-4-phenyl-butyric acid after isolation from lisinopril bulk drug by semi-preparative HPLC. Formation of the impurity was also discussed. To our knowledge, this is a novel impurity and not reported elsewhere.
Butyrates ; analysis ; isolation & purification ; Drug Contamination ; Lisinopril ; analysis ; Magnetic Resonance Spectroscopy ; Models, Molecular

Objective: To evaluate the association between atmospheric inhalable particulate matter (PM₁₀) concentration and cardiovascular diseases burden in Tianjin. Methods: The data on daily mean concentrations of main pollutants (PM₁₀, nitrogen dioxide(NO₂) and sulfur dioxide(SO₂)), meteorological factors (temperature and relative humidity) and population death monitoring data in Tianjin, from January 1, 2001 to December 31, 2010, were collected and analyzed in this study. The death counts and years of life lost were simultaneously used as the indicators of disease burden. The generalized additive model was used to assess the associations between PM₁₀ and daily death counts and years of life lost due to cardiovascular system diseases in Tianjin by adjusting the confounding factors such as long-term trend, seasons, meteorological factors and other factors related to the long-term variability. Results: The daily average concentration of PM₁₀ was 117.6 μg/m³ in Tianjin during 2001 to 2011. The daily average number of deaths of cardiovascular system diseases, cerebrovascular diseases and ischemic heart diseases in Tianjin were 38.4, 14.8 and 17.2 people respectively, and the daily average years of life lost were 776.8, 306.5 and 326.1 person years respectively. The effects of PM₁₀ on the daily death counts of the three diseases categories were statistically significant (all P<0.01) in Tianjin and the maximum effect occurs at the moment when PM₁0 was at moving average concentration of today and lagged 1-day (Lag01). The effects of decreasing order were ischemic heart diseases, cardiovascular system diseases and cerebrovascular diseases, excess risks were 0.53% (95% CI 0.35%-0.71%), 0.40% (95%CI 0.28%-0.53%) and 0.38% (95%CI 0.19%-0.56%). The effects of atmospheric PM₁₀ on the years of life lost of the three diseases were also statistically significant on the different lag days (all P<0.01) in Tianjin and the maximum effect of PM₁₀ appeared in Lag01. The effects from the largest to the lowest were 2.86 (95%CI 1.79-3.93) person years for cardiovascular system diseases, 1.59 (95%CI 0.95-2.23) person years for ischemic heart diseases and 1.07 (95%CI 0.43-1.71) person years for cerebrovascular diseases, respectively. In multi-pollutant models, after controlling SO₂, the effect of PM₁₀ on the daily life loss of above 3 kinds of diseases was higher than that of single pollutant model. In contrast, after controlling SO₂ or SO₂ with NO₂, the effect was lower. After controlling NO₂, the effect of PM₁₀ on the daily life loss of cerebrovascular disease was no longer statistically significant (P>0.05). Conclusions Exposure to atmospheric PM₁₀ can significantly increase the cardiovascular diseases burden in Tianjin, especially for ischemic heart diseases. These results suggested that particular attention should be paid to reduce the exposure to atmospheric inhalable particulate matter for patients with ischemic heart diseases.

To investigate the molecular mechanisms of all-trans retinoic acid (ATRA)-induced rig-g gene expression and to better understand the signal transduction of ATRA during acute promyelocytic leukemia (APL) cell differentiation, the luciferase reporter assay, co-immunoprecipitation and chromatin immunoprecipitation were used to clarify the basic transcriptional factors, which directly initiated the expression of rig-g gene. The results showed that the expression of STAT2, IRF-9 and IRF-1 could be upregulated by ATRA with different kinetics in NB4 cells. IRF-9 was able to interact with STAT2 to form a complex, which could bind the rig-g gene promoter and trigger the rig-g expression. IRF-1 alone could also activate the reporter gene containing rig-g gene promoter, but C/EBPalpha could strongly inhibit this transcription activity of IRF-1. It is concluded that during ATRA-induced APL cell differentiation, IRF-1 is first upregulated by ATRA, and then IRF-1 increases the protein levels of IRF-9 and STAT2 with the downregulation of C/EBPalpha. The complex of IRF-9 and STAT2 is the primary transcriptional factor for rig-g gene induction. This study will be helpful for better understanding the signal transduction networks of ATRA during the course of APL cell differentiation.
CCAAT-Enhancer-Binding Protein-alpha ; metabolism ; Gene Expression Regulation, Leukemic ; drug effects ; Genes, Regulator ; drug effects ; Humans ; Interferon Regulatory Factor-1 ; metabolism ; Interferon-Stimulated Gene Factor 3, gamma Subunit ; metabolism ; Intracellular Signaling Peptides and Proteins ; genetics ; Leukemia, Promyelocytic, Acute ; genetics ; STAT2 Transcription Factor ; metabolism ; Signal Transduction ; Tretinoin ; pharmacology ; Tumor Cells, Cultured

OBJECTIVETo study the regulatory role of interferon-stimulated response elements (ISREs) located on the retinoic acid-induced gene G (RIG-G) promoter in RIG-G expression.

METHODSBy using point mutation technique, the authors constructed the wide type and site mutant reporter gene plasmids according to the ISRE sequence on RIG-G promoter, and detected the functional activities by luciferase reporter assay.

RESULTSMutation in ISRE II alone had no obvious effect on the expression of the reporter gene, whereas mutation in ISRE I dramatically inhibited the transactivity of RIG-G promoter. Mutation in both ISRE I and ISRE II resulted in complete loss of its response to the transcription factors for the reporter gene.

CONCLUSIONBoth ISRE I and ISRE II on the RIG-G promoter are the binding sites for the complex of transcription factors. They are required for RIG-G expression, and ISRE I has a preferential role over ISRE II.

Cell Line, Tumor ; Humans ; Interferon Regulatory Factor-1 ; genetics ; metabolism ; Interferons ; genetics ; metabolism ; Intracellular Signaling Peptides and Proteins ; genetics ; Mutation ; Promoter Regions, Genetic ; genetics ; Response Elements ; genetics ; STAT2 Transcription Factor ; genetics ; metabolism

OBJECTIVETo study the impact of an agonist anti-CD(40) monoclonal antibody 5C11 on the induction and biological characteristics of leukemic dendritic cells.

METHODSCombinations of 5C11 and different cytokines were used to induce differentiation of leukemic blasts into dendritic cells. Morphology was observed by light microscopy. Surface antigens of the induced cells were analyzed by fluorescence-activated cell sorting (FACS), the yields of dendritic cell by cell counting, the levels of IL-6 and IL-12 by ELISA, T cell proliferating activity by allo-mixed lymphocyte reaction (MLR) in vitro. Allogeneic T cells were stimulated with leukemic dendritic cells and T-cell cytotoxicity was measured by MTT assay.

RESULTSWhen cultured with combinations of 5C11 and different cytokines, the leukemic cells isolated from the patients could differentiate into dendritic cells. The morphology showed typical features of dendritic cells, which expressed high levels of CD(40), CD(80) and CD(86). In comparison with the original leukemia cells, the leukemic dendritic cells secreted less IL-6 but more IL-12 (P < 0.05). The leukemic dendritic cells were potent to stimulate the proliferation of allogeneic T cells, and the latter was able to lyse the original leukemia cells.

CONCLUSIONLeukemic blasts could be induced to differentiate into functional dendritic cells. It may be of great value in the adoptive immunologic therapy of leukemia.

Antibodies, Monoclonal ; immunology ; CD40 Antigens ; physiology ; Cell Differentiation ; Dendritic Cells ; immunology ; Humans ; Immunophenotyping ; Immunotherapy ; Interleukin-12 ; biosynthesis ; Interleukin-6 ; biosynthesis ; Leukemia ; immunology ; pathology ; therapy

OBJECTIVETo retrospectively evaluate the effects of Gamma knife in the treatment of cerebral hemangioblastomas.

METHODSFrom 1993 to 1996, seventeen patients with 29 hemangioblastomas were treated with Gamma knife. The patients mean age was 35 years (range: 16 - 61 years). The mean tumor diameter was 16 mm (range: 6 - 55 mm). Thirteen patients had recurrent or residual hemangioblastomas. Four with primary hemangioblastomas were diagnosed using CT, MRI and DSA. The maximum dose to the tumors was 21.0 - 50.0 Gy, with mean dose of 33.7 Gy. The radiation dose to the periphery of tumors was 12.0 - 24.0 Gy, with mean dose of 17.6 Gy.

RESULTSAll the patients had been followed up for 18 to 62 months, with mean 46 months. Five patients experienced clinical improvement and reduction in tumor volume, and 5 remained stable and tumor unchanged in volume during the follow-up period. Three patients died of tumor progression, surgery and cancer after treatment 18, 22, 25 months respectively. Four patients underwent surgery respectively at 3, 4, 29 and 48 months after gamma knife operation. The local control rate of the tumors at 1 year was 92%, 2 years 88%, 3 years 80% and 4 years 75%. Pathological findings in these patients showed varying degrees of small vessel thickening and occlusion together with degeneration, necrosis in the center of tumor and loss of tumor cells at periphery.

CONCLUSIONSGamma knife is not adequately reliable for the control of hemangioblastoma cysts, it is an effective treatment of small or medium-size solid tumors, but long-term follow-up is needed. The recommended dose is 16 to 20 Gy.

Adolescent ; Adult ; Brain Neoplasms ; surgery ; Female ; Follow-Up Studies ; Hemangioblastoma ; surgery ; Humans ; Male ; Middle Aged ; Radiosurgery ; adverse effects ; methods ; Treatment Outcome ; Young Adult