[Estimating HIV incidence among female sex workers and injection drug users in Dehong Prefecture, 2009-2017].

Objective: To obtain HIV incidence among injection drug users (IDU) and female sex workers (FSW) in Dehong Prefecture, Yunnan Province during 2009-2017. Methods: We recruited drug users and female sex workers from all sentinel surveillance sites across Dehong Prefecture during 2009-2017. A total of 10 480 IDU and 18 126 FSW in Dehong Prefecture were recruited by fingerprint technique. Data about drug uses, commercial sexual behavior, sociodemographic characteristics was collected by structured questionnaire. HIV-positive patients who were long-term infected or with CD4(+) T cell count was ≤200 were not included for further HIV incidence testing. Also, those who self-identified as on antiretroviral treatment (ART) or AIDS cases were also excluded. A total of 841 and 157 plasma specimens from IDU and FSW that met the inclusion criterion were finally included, respectively. Limiting antigen avidity enzyme immunoassay(LAg-Avidity EIA) were performed to calculate the HIV incidence among these two sub-populations. Results: A total of 3 444 IDU were HIV-positive, among which 884 (25.7%) were Burmese with age of (30.4±7.7), and 2 560 were Chinese with age of (36.6±7.3). Among 228 HIV-positive FSW, 109 (47.8%) were Burmese with age of (27.1±6.3), 119 (52.5%) were Chinese with age of (29.9±11.1). For IDU, the estimated HIV incidence among Burmese in 2009-2010, 2011-2012, 2013-2014, 2015-2017 was 4.20% (95%CI: -0.55%-8.95%), 7.75% (95%CI: 2.95%-12.55%), 11.79% (95%CI: 5.38%-18.20%), 10.30% (95%CI: 5.67%-14.94%), respectively, while Chinese were 3.11% (95%CI: 1.59%-4.64%), 0.03% (95%CI: -0.03%-0.08%), 1.55% (95%CI: 0.54%-2.57%), 0.58% (95%CI: -0.06%-1.04%), respectively. In 2009-2011, 2012-2014, 2015-2017, estimated HIV incidence among Burmese FSW was 0.22% (95%CI: -0.21%-0.64%), 1.24%(95%CI: 0.15%-2.32%), 0.55%(95%CI: 0.01%-1.08%). Whereas, estimated HIV incidence among Chinese FSW was 0.62% (95%CI: 0.25%-0.98%), 0.11% (95%CI: -0.04%-0.26%), 0.22% (95%CI: 0-0.44%). Conclusion: HIV incidences among Chinese IDU and FSW are on the downward trend, while Burmese IDU and FSW seem to be gaining momentum.

[Hesperetin inhibits PM(2.5)-induced apoptosis in H9c2 cells by attenuating oxidative stress and mitochondrial damage].

Objective: To investigate the effects of hesperetin on fine particulate matter (PM(2.5)) induced apoptosis in H9c2 cells and related mechanisms. Methods: H9c2 cells were divided into 4 groups: control group (cells were cultured without intervention), PM(2.5) group (cells were treated with 800 µg/ml PM(2.5)), hesperetin group (H group, cells were treated by 40 µmol/L hesperetin for 1 h at 37 ℃), and hesperetin+PM(2.5) group (H+PM(2.5) group, cells were pretreated with hesperetin before PM(2.5) treatment). Cells were cultured for corresponding interval. Apoptotic cells were detected by Annexin Ⅴ-FITC/PI apoptosis detection kit and Hoechst staining. The intracellular reactive oxygen species (ROS) levels were measured by DCFH-DA Fluorescence Probe and mitochondrial membrane potential (MMP) was detected with JC-1 staining, respectively in these groups. Apoptotic related protein and phosphorylated MAPK expression levels were determined by Western blot. Results: (1) Flow cytometry results showed that the apoptosis rate of PM(2.5) group ((48.94±3.20)%) was significantly higher than that of control group ((8.13±1.40)%, P<0.01), which was significantly reduced in H+PM(2.5) group ((34.80±2.21)%) (P=0.003 2 vs. PM(2.5) group, P<0.01 vs. control group). The number of Hoechst 33258 positive apoptotic cells was distinctly less in H+PM(2.5) group than in PM(2.5) group. (2) The ROS levels was significantly higher in PM(2.5) group ((49.69±5.05)%) than in control group (10.57±1.33)%, P<0.01), which was significantly reduced in H+PM(2.5) group ((35.08±3.90)%) (P=0.000 2 vs. PM(2.5) group, P<0.01 vs. control group). (3) Green fluorescence indicating the JC-1 monomer form, which represented MMP loss of H9c2 cells, was significantly higher in PM(2.5) group ((20.28±4.69)%) than in control group ((10.50±2.72)%, P<0.01), which was significantly decreased in H+PM(2.5) group ((13.41±2.89)%) (P<0.01 vs. PM(2.5) group, P=0.029 4 vs. control group). (4) The expression levels of Bcl-2 protein of H9c2 cells was lower in PM(2.5) group ((76.94±4.52)%) than in control group (100%, P=0.000 9), which was significantly upregulated in H+PM(2.5) group ((92.95±6.82)%) (P=0.027 5 vs. PM(2.5) group, P=0.15 vs. control group). The expression levels of cleaved caspase-3 protein of H9c2 cells was significantly higher in PM(2).5 group ((243.98±17.94)%) than in control group (100%, P=0.000 2), which was significantly downregulated in H+PM(2.5) group ((200.45±4.31)%) (P=0.015 vs. PM(2.5) group, P<0.01 vs. control group). (5) The expression levels of phosphorylated p38 MAPK protein of H9c2 cells was higher in PM(2.5) group ((118.90±4.78)%) than in control group(100%, P=0.002 7), which could be significantly downregulated in H+PM(2.5) group ((103.30±1.27)%) (P=0.01 vs. PM(2.5) group, P=0.05 vs. control group). The expression levels of phosphorylated ERK protein of H9c2 cells was higher in PM(2.5) group ((163.50±4.98)%) than in control group (100%, P<0.01), which was significantly downregulated in H+PM(2.5) group ((139.10±2.72)%) (P=0.001 6 vs. PM(2.5) group, P<0.01 vs. control group). Conclusions: Hesperetin protects H9c2 cells from PM(2.5) stimulation through reducing oxidative stress and protecting mitochondrial function, regulating the expression of apoptotic associated proteins as well as MAPK signal pathway, thus inhibiting H9c2 cells apoptosis.

[Neurocognitive impairment and characteristics of neurocognitive performance among people with HIV on antiretroviral treatment].

Objective: Using two measuring tools to examine the prevalence and correlates of neurocognitive impairment (NCI) as well as characteristics of neurocognitive performance among people with HIV (PWH) on antiretroviral treatment (ART). Methods: A total of 2 250 treated PWH from the Comparative HIV and Aging Research in Taizhou (CHART) were recruited in Taizhou, Zhejiang province. The Chinese version of the Mini-mental State Examination (MMSE) and the International HIV Dementia Scale (IHDS) were used to evaluate their neurocognitive performance. Cluster analysis was conducted on the seven cognitive domains in the scale. Results: Among 2 250 treated PWH, 48.0% (1 080/2 250) were aged 45 to 89, 79.2% (1 782/2 250) were male, and 37.8% (852/2 250) had primary school education or below. The prevalence of neurocognitive impairment judged by MMSE and IHDS among HIV-infected people was 14.3% (321/2 250) and 31.8% (716/2 250), respectively. Aged 60 to 89 (aOR=2.63, 95%CI:1.52-4.56), depressive symptoms (aOR=5.58, 95%CI:4.20-7.40) and treatment with EFV (aOR=2.86, 95%CI:1.89-4.34) were main risk factors of NCI diagnosed by MMSE. Male (aOR=0.71, 95%CI:0.51-1.00), overweight (aOR=0.63, 95%CI:0.44-0.89), and high education level (aOR=0.11, 95%CI:0.05-0.25) were protective factors of NCI diagnosed by MMSE. Aged 60 to 89 (aOR=3.10, 95%CI:2.09-4.59), depressive symptoms (aOR=1.78, 95%CI:1.44-2.20) and treatment with EFV (aOR=1.79, 95%CI:1.41-2.29) were risk factors of NCI diagnosed by IHDS. Male (aOR=0.75, 95%CI:0.58-0.97), underweight (aOR=0.67, 95%CI:0.47-0.96), baseline CD4+ T lymphocyte (CD4) counts ≥350 cells/µl (aOR=0.69, 95%CI:0.53-0.91) and high education level (aOR=0.23, 95%CI:0.14-0.39) were protective factors of NCI diagnosed by IHDS. The neurocognitive performance of HIV-infected people can be divided into four main types. Among four types, age, gender, education level, alcohol drinking, depressive symptoms, waist-to-hip ratio, hypertension, diabetes, baseline CD4 counts and treatment with EFV were different statistically (all P<0.05). Conclusions: There are four main types of neurocognitive performance in treated PWH. The prevalence of NCI is high among this population, underscoring the need for tailored prevention and intervention.

Metabolic effects of thiopurine derivatives against human CCRF-CEM leukaemia cells.

UNLABELLED: BACKGROUND and aims. To compare the metabolic effects induced by the anticancer drugs, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG) and 6-methylmercaptopurine riboside (MMPR), which may inhibit the de novo biosynthesis of purine nucleotides or be mis-incorporated into DNA or RNA. METHODS: Leukaemia cells were grown in culture, exposed to a thiopurine and cell extracts were analyzed for NTPs, dNTPs, drug metabolites and P-Rib-PP. RESULTS: In leukaemia cells, 6-MP was converted to MPR-MP, thio-XMP, thio-GMP, thio-GDP and thio-GTP. Metabolites of 6-TG included thio-XMP, thio-GMP, thio-GDP and thio-GTP, while MMPR-MP was the only major metabolite of MMPR, MMPR (25 microM, 4 h) induced a 16-fold increase in P-Rib-PP and 6-MP (25 microM, 4 h) induced a delayed 5.2-fold increase. MPR-MP, thio-GMP and MMPR-MP are inhibitors of amido phosphoribosyltransferase from leukaemia cells with Ki values of 114 +/- 7.10 microM, 6.20 +/- 2.10 microM and 3.09 +/- 0.30 microM, respectively. CONCLUSION: The nucleoside-5'-monophosphate derivatives of the 3 thiopurines inhibit amido phosphoribosyltransferase in growing leukaemia cells but there is also an initial inhibition of the further conversion of IMP in the pathway. In growing cells, MMPR acts solely as an inhibitor of de novo purine biosynthesis while 6-TG and to a lesser extent, 6-MP, are converted to significant concentrations of di- and tri-phosphate derivatives which may have other mechanisms of cytotoxicity.

Rapid blood separation is superior to fluoride for preventing in vitro reductions in measured blood glucose concentration.

AIMS: To determine whether tubes containing sodium fluoride negatively bias blood glucose concentration by directly comparing glucose concentrations in paired blood samples collected in tubes containing lithium heparin (Li-Heparin) and tubes containing sodium fluoride/potassium oxalate (NaF-KOx). METHODS: Paired blood samples from a group of patients (n = 1040) were collected in tubes containing Li-Heparin and tubes containing NaF-KOx at the same time. All Li-Heparin samples were centrifuged soon after collection and were kept cool in transport along with NaF-KOx samples, which were centrifuged at the receiving location after an average transport time of 4 h, but immediately before analysis. Glucose concentrations in the paired samples were determined simultaneously by an automated oxidase method. RESULTS: The mean glucose concentrations for NaF-KOx samples and Li-Heparin samples were 5.7 mmol/l and 6.1 mmol/l, respectively, with a mean difference of 0.39 mmol/l. CONCLUSION: Rapid separation of heparinised blood is superior to fluoride alone for abrogating glycolytic effects on blood glucose measurements in the clinical laboratory.

Development of an enzyme-linked immunosorbent assay with monoclonal antibody for quantification of homovanillic acid [corrected] in human urine samples.

A monoclonal antibody to homovanillic acid (HVA) was prepared by synthesis of a HVA-protein conjugate (HVA-ovalbumin) as an immunogen, immunization of mice, and the subsequent hybridization technique. Monoclonal antibodies were screened on the basis of sensitivity, specificity, and accuracy. An indirect ELISA was developed for quantification of HVA in human urine. The assay was characterized and shown to have high specificity, with cross-reactivities to vanillylmandelic acid and normetanephrine at 0.18% and <0.1%, respectively. The assay coefficients of variation were <10% within the working range of 0.5-40 mg/L. Initial results from testing urine samples of patients with neuroblastoma and other diseases were validated by HPLC, suggesting that this ELISA method is a reliable and convenient system for quantification of HVA in urine and can be used in the mass screening of neuroblastoma in infants.