Identifying major drivers of incident HIV infection using recent infection testing algorithms (RITAs) to precisely inform targeted prevention.

BACKGROUND: Recent infection testing algorithms (RITAs) incorporating clinical information with the HIV recency assay have been proven to accurately classify recent infection. However, little evidence exists on whether RITAs would help in precisely identifying major drivers of the ongoing HIV epidemic. METHODS: HIV recency test results and clinical information were collected from 1152 newly diagnosed HIV cases between 2015 and 2017 in Dehong prefecture of Yunnan province, and the efficacy of four different RITAs in identifying risk factors for new HIV infection was compared. RESULTS: RITA 1 uses the recency test only. RITA 2 and RITA 3 combine the recency test with CD4+ T cell count and viral load (VL), respectively. RITA 4 combines both CD4+ T cell count and VL. All RITAs identified the MSM group and young people between 15 and 24 years as risk factors for incident HIV infection. RITA 3 and RITA 4 further identified the Dai ethnic minority as a risk factor, which had not been identified before when only the HIV recency test was used. CONCLUSIONS: By comparing different RITAs, we determined that greater accuracy in classifying recent HIV infection could help elucidate major drivers impacting the ongoing epidemic and thus inform targeted interventions.

Circulating lncRNA ITSN1-2 is upregulated, and its high expression correlates with increased disease severity, elevated inflammation, and poor survival in sepsis patients.

BACKGROUND: This study aimed to assess the correlation of long noncoding (lnc) RNA intersectin (ITSN) 1-2 expression with disease risk, severity, inflammation, and survival in sepsis patients. METHODS: Three hundred and nine intensive care unit (ICU)-treated sepsis patients and 300 healthy controls were consecutively recruited in this study. Blood samples were collected from all sepsis patients within 24 hours after admitted to ICU and from healthy controls at the time of health screening, and the expression of lncRNA ITSN1-2 in plasma was detected by quantitative polymerase chain reaction. Disease severity was assessed by physicians using acute physiology and chronic health evaluation (APACHE) II score on day 1 after ICU admission. Additionally, the plasma inflammatory cytokines (including tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), IL-6, IL-8, IL-10, and IL-17) were measured by enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: lncRNA ITSN1-2 was highly expressed in sepsis patients compared to healthy controls and could differentiate sepsis patients from healthy controls with area under the curve (AUC) 0.777 (95% CI: 0.740-0.813). lncRNA ITSN1-2 expression was positively correlated with APACHE II score, C-reactive protein (CRP), TNF-α, IL-6, and IL-8 levels, but negatively correlated with IL-10 level. In addition, lncRNA ITSN1-2 was highly expressed in non-survivors compared to survivors and could distinguish survivors from non-survivors in sepsis patients with AUC 0.654 (95% CI: 0.581-0.726). CONCLUSION: Circulating lncRNA ITSN1-2 is upregulated, and its high expression associates with increased disease severity and inflammation as well as poor prognosis in sepsis patients.

[Incidence and risk factors of HIV infection among sero-negative spouses of people living with HIV/AIDS in Dehong prefecture, Yunnan province].

OBJECTIVE: To study the incidence rate and risk factors of HIV infection among sero-negative spouses of people living with HIV/AIDS (HIV/AIDS) in Dehong prefecture, Yunnan province. METHODS: A prospective cohort study was conducted from February 2009 to December 2014 in Dehong prefecture, Yunnan province. Questionnaire survey and HIV related tests were carried out once a year. RESULTS: By the end of December 2014, 2 091 sero-negative spouses had been recruited, of whom 1 692 were followed-up for at least one time. RESULTS showed that 34 new HIV infections were identified within 5 494.52 person years of follow-up, for an overall incidence of 0.62 per 100 person years. HIV incidence rates appeared as 0.79 per 100 person years, 0.62 per 100 person years, 0.47 per 100 person years in 2009-2010, 2011-2012, 2013-2014, respectively. Data from the Cox proportional hazard regression model indicated that risk factors of HIV infection among sero-negative spouses of HIV/AIDS were: non-consistent condom use (HR=4.64, 95%CI: 1.89-11.40,P= 0.001), HIV/AIDS delayed antiviral retrovirus therapy (ART) for more than one year (HR=3.70, 95% CI: 1.44-9.49,P=0.007) after the HIV negative spouses were initially recruited, HIV/AIDS did not receive any ART (HR=3.62, 95% CI: 1.14-11.51,P=0.029). CONCLUSIONS: The incidence of HIV infection among sero-negative spouses in Dehong prefecture was relatively low. Publicity on consistent condom use program should be emphasized among sero-negative spouses of HIV/AIDS, together with the timely provision of ART to those HIV/AIDS.

[Analysis of follow-up and administration of HIV-infected Burmese in Dehong prefecture of Yunnan province].

OBJECTIVE: To compare follow-up and administration of HIV-infected local Chinese and Burmese in Dehong prefecture of Yunnan province, for scientific development of prevention and control measures. METHODS: 14 270 HIV-infected local Chinese and 5 436 HIV-infected Burmese reported from 1989 to December 31, 2013 in Dehong prefecture were recruited as the subjects of study, comparing the differences of follow-up and management, CD4⁺ T lymphocyte count tests and antiretroviral therapy (ART) between the two groups. RESULTS: The proportion of HIV-infected Burmese identified in Dehong prefecture was 27.6% (5 436/19 706) during 1989-2013. The number had been growing rapidly from 17.1% in 1989-2003, 12.4% in 2004 and 14.7% in 2005 to over 51.4% in 2012, hitting 59.4% in 2013 (trends χ² = 1 732.84, P < 0.000 1). The proportion of HIV-infected Burmese among case reports of various characteristics kept rising over the years. By the end of 2013, 8 095 HIV-infected local Dehong residents and 5 326 HIV-infected Burmese were still alive. 95.8% of them were under follow-up, 88.5% having CD4⁺ T lymphocyte count tests, and 78.3% under ART. Among the HIV-infected B urmese, only 19.2% of them were under follow-up, 13.0% having CD4⁺ T lymphocyte count tests, and 6.1% under ART, significantly lower than the local Dehong residents (P < 0.000 1). CONCLUSION: The proportion of follow-up and administration, CD4⁺ T lymphocyte count tests, and ART of HIV-infected Burmese was low in Dehong prefecture, Yunnan province, which called for more effective follow-up and administration measures.

CYP2J2 and EETs protect against lung ischemia/reperfusion injury via anti-inflammatory effects in vivo and in vitro.

BACKGROUND: Injurious inflammatory response is critical to the development of lung ischemia/reperfusion injury (LIRI). The cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), which exert an anti-inflammatory effect on the cardiovascular system. We therefore cytochrome hypothesized that CYP2J2 overexpression and pretreatment with exogenous EETs may have the potential to reduce LIRI. METHODS: A rat model was used to mimic the condition of LIRI by clamping the left pulmonary hilum for 60 minutes, followed by reperfusion for 2 hours. Moreover, we developed a cell model using human pulmonary artery endothelial cells by anoxia for 8 hours, followed by reoxygenation for 16 hours to determine the anti-inflammatory effect and mechanism of CYP2J2 overexpression and exogenous 11,12-EET. RESULTS: Lung ischemia/reperfusion increased lung wet/dry and lung weight/body weight ratios, protein concentration in bronchoalveolar lavage fluid and concentrations of pro-inflammatory, including mediators in serum IL-1ß, IL-8, TNF-α, sP- and sE-selectin, and decreased concentration of anti-inflammatory mediator IL-10. Ischemia/reperfusion also leaded to pulmonary edema and inflammation under light microscopy. Furthermore, activation of NF-κB p65 and degradation of IκBα were remarkably increased in ischemia/reperfusion lung tissues. While CYP2J2 overexpression significantly inhibited the above effects (p<0.05). In vitro data further confirmed the anti-inflammatory effect of CYP2J2 overexpression and 11,12-EET, an effect that may probably be mediated by PPARγ activation. CONCLUSION: CYP2J2 overexpression and administration of exogenous EETs can protect against LIRI via anti-inflammatory effects. This can be a novel potential strategy for prevention and treatment of LIRI.

CYP2J2 and EETs Protect against Oxidative Stress and Apoptosis in Vivo and in Vitro Following Lung Ischemia/Reperfusion.

BACKGROUND: Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acids to epoxyeicosatrienoic acids (EETs). EETs exert various biological effects, including anti-inflammatory, anti-apoptotic, pro-proliferation, pro-angiogenesis, anti-oxidation, and anti-fibrosis effects. However, little is known about the role of CYP2J2 and EETs in lung ischemia/reperfusion injury. In this study, we examined the effects of exogenous EETs or CYP2J2 overexpression on lung ischemia/reperfusion injury in vivo and in vitro. METHODS AND RESULTS: CYP2J2 gene was stably transfected into rat lungs via pcDNA3.1-CYP2J2 plasmid delivery, resulting in increased EETs levels in the serum and lung. A rat model of lung ischemia/reperfusion injury was developed by clamping the left lung hilum for 1 hour, followed by reperfusion for 2 hours. We found that CYP2J2 overexpression markedly decreased the levels of oxidative stress and cell apoptosis in lung tissues induced by ischemia/reperfusion. Moreover, we observed that exogenous EETs, or CYP2J2 overexpression, enhanced cell viability, decreased intracellular reactive oxygen species (ROS) generation, inhibited mitochondrial dysfunction, and attenuated several apoptotic signaling events in a human pulmonary artery endothelial cells (HPAECs)-based anoxia/reoxygenation model. These apoptotic events included activation of NADPH oxidase, collapse of mitochondrial transmembrane potential, and activation of pro-apoptotic proteins and caspase-3. These effects were mediated, at least partially, by the PI3K/Akt signaling pathway. CONCLUSION: These results reveal that CYP2J2 overexpression and exogenous EETs can protect against oxidative stress and apoptosis following lung ischemia/reperfusion in vivo and in vitro, suggesting that increasing the level of EETs may be a novel promising strategy to prevent and treat lung ischemia/reperfusion injury.

The COX-2 rs20417 polymorphism and risk of coronary artery disease: evidence from 17,621 subjects.

BACKGROUND: The Cyclooxygenase-2 (COX-2) rs20417 polymorphism has been implicated in coronary artery disease (CAD) risk, but individually published studies have shown inconsistent results. The aim of this study was to clarify the effects of COX-2 rs20417 polymorphism on CAD risk. METHODS: A systematic literature search up to October 27, 2013 was carried out in PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases, and the references of retrieved articles were screened. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were analysed for co-dominant model (CC vs. GG), additive model (C vs. G), dominant model (CC+GC vs. GG), and recessive model (CC vs. GG+GC) to assess the association using fixed- or random-effect model. RESULTS: We identified nine articles (10 case-control studies) that included 3,439 cases and 14,182 controls for the present meta-analysis. Significant association between COX-2 rs20417 polymorphism and risk of CAD was observed in co-dominant model (OR=0.64, 95% CI=0.43-0.95, p=0.026) and recessive model (OR=0.77, 95% CI=0.61-0.97, p=0.025). Moreover, in the subgroup analysis stratified by ethnicity, significant associations were observed in Asians (OR=0.28, 95% CI=0.13-0.61, p=0.001 for CC vs. GC+GG; OR=0.24, 95% CI=0.11-0.51, p<0.001 for CC vs. GG) but not in Caucasians. CONCLUSIONS: These results suggest that COX-2 rs20417 polymorphism may contribute to CAD development, especially in Asians.

[Study on the mortality and risk factors among HIV-infected individuals during 1989 - 2011 in Dehong prefecture, Yunnan province].

OBJECTIVE: To examine the mortality and risk factors among HIV-infected patients during 1989 - 2011 in Dehong prefecture, Yunnan province. METHODS: All HIV-infected patients reported during 1989 - 2011 in Dehong prefecture who held local residency were included in the study. Mortality rates and cumulative survival rates were calculated. Multiple regression analysis under Cox proportional hazard model was conducted to examine the risk factors for deaths. RESULTS: A total of 13 006 HIV-infected patients were included in this study including 73.2% males, 79.1% peasants and 48.7% married at the time of reporting. 64.5% of the patients were ethnic minorities, and 68.7% were illiterate or having received only primary school education. All the patients were followed-up for a total of 55 962.30 person-years with 4648 patients died, with overall mortality rate as 8.31/100 person-years. The mortality rate had been increasing from 1990 to 2004 but decreasing since 2005. The average survival time since the identification of HIV infection was 9.48 years overall, and was 16.65 years for those having received antiretroviral treatment (ART) and 7.67 years for those without ART. Data from multiple regression analysis indicated that ART and socio-demographic characteristics such as age, gender, ethnicity, occupation, marital status, education background etc. were significantly associated with death among HIV-infected patients. CONCLUSION: The comprehensive AIDS campaigns including ART had significantly reduced the deaths among HIV-infected patients in Dehong prefecture. More efforts on the scaling up program of ART as well as the enhanced management and follow-up program tailored for HIV-infected patients with different socio-demographic characteristics were needed to further reduce the deaths in the area.

[Adherence and related determinants on methadone maintenance treatment among heroin addicts in Dehong prefecture, Yunnan province].

OBJECTIVE: To determine the adherence to and its determinants of methadone maintenance treatment (MMT) among heroin addicts in Dehong prefecture in Yunnan province from 2005 to 2009. METHODS: A dynamic cohort analysis was conducted with the time of treatment initiation as the time of cohort entry, to calculate the proportion of adhering to the treatment at different time points after initiation of the treatment, and to study the determinants of adherence. RESULTS: A total of 3758 had been treated. Among them, 95.8% were males, 75.8% aged between 20 - 39 years, 90.4% were peasants or unemployed, 57.0% were ethnic minorities, 35.0% were single and 55.5% were married with spouses, 43.9% were illiterate or educated at most primary school. The age of first using drugs averaged at 23.93 years. About 96.3% of the study subjects had used heroin and 21.7% were HIV-infected. The minimum time under MMT was less than 1 month and the maximum 61 months. The median methadone dose at first delivery was 25 ml, with the minimum 1 ml and the maximum 330 ml. By the end of the study or observation period, a total of 1798 patients had withdrawn from treatment and 1960 were still under treatment. The proportions of adherence to or still being under the treatment after 1, 3, 6, 9, 12, 24, 36, 48 and 60 months treatment were 0.919, 0.847, 0.756, 0.690, 0.637, 0.519, 0.417, 0.360 and 0.321, respectively. Multiple regression analysis using Cox proportional hazard model indicated that withdraw from the methadone maintenance treatment was significantly associated with location of the treatment clinics, year of treatment initiation, marital status, HIV infection status, methadone dose of first delivery and the result of last urine test for heroin use. CONCLUSION: MMT attendants in Dehong prefecture had a relatively high withdraw rate and low adherence rate. More efforts are needed to provide tailored counseling and education to MMT attendants, to provide family and community support, appropriate methadone dose at first delivery, and to better coordinate with local police department.

[Studies on the determinants and changes related to the natural CD4(+) T cell counts among antiretroviral treatment-naive HIV/AIDS patients in Dehong prefecture, Yunnan province].

OBJECTIVE: To explore the determinants and changes of CD4(+) T cell counts among antiretroviral treatment-naive HIV/AIDS patients in Dehong prefecture, Yunnan province. METHODS: A retrospective cohort analysis was conducted on HIV-infected local residents, being reported during 1989 through May 2010, in Dehong prefecture. The patients had received at least two CD4(+) T cell counting tests before receiving the antiretroviral treatment (ART). Difference between the first and the last CD4(+) T cell counts was calculated and described. Logistic regression analysis was conducted to examine the determinants of significant depletion of CD4(+) T cell counts among them. RESULTS: A total of 4487 HIV/AIDS patients were included in the study. The change of CD4(+) T cell counts between the first and the last CD4(+) T cell count tests had a median of -2.0 cells/µl in month (IQR: -8.2 - 3.6) and was significantly associated with socio-demographic characteristics, HIV transmission mode, the first or baseline CD4(+) T cell counts and the time interval between the first and the last CD4(+) T cell counting tests etc. About 60.0% (2693/4487) of the HIV/AIDS patients had deletions of CD4(+) T cell counts, and 31.2% (1400/4487) had significant (≥ 30%) deletions of CD4(+) T cell counts. Results from the multiple logistic regression analysis indicated that age, ethnicity, marital status, HIV transmission mode, the first CD4(+) T cell counts and the interval between the first and the last CD4(+) T cell counting tests were significantly associated with the significant depletion of CD4(+) T cell counts. CONCLUSION: The changing rate of CD4(+) T cell count among ART-naive local HIV-infected patients in Dehong prefecture, Yunnan province was relatively slow. However, substantial proportion of them showed significant decreases of CD4(+) T cell counts, which was determined by many factors. More efforts were needed to systematically and consistently follow-up those HIV-infected patients and measure their CD4(+) T cell counts in China, in order to instantaneously monitor the disease progression, and the initiation of ART, if necessary.

[Causes of death among HIV-infected patients in Dehong prefecture, Yunnan province: 1989-2010].

OBJECTIVES: To analyze the fatality and causes of death related to comprehensive prevention and care programs among HIV-infected patients in Dehong prefecture of Yunnan province, from 1989 to 2010. METHODS: Data on HIV/AIDS death cases in Dehong prefecture were extracted from the "Chinese National Comprehensive HIV/AIDS Prevention and Care Information System" and were analyzed. RESULTS: From 1989 to the end of 2010, a total of 13 493 HIV/AIDS cases registered as local residents or currently living in Dehong, had been reported. Among them, 8569 were reported as HIV cases with 2036 deaths and the other 4924 were reported as AIDS cases with 2251 deaths. A few of the cases had survived for 15 - 20 years. By the end of 2010, the number of deaths was higher than the number of survivors among HIV/AIDS cases reported before 2004, whereas the number of survivors was higher than the number of deaths among HIV/AIDS cases reported in 2004 and there after. During the twenty years' period, the proportion of reported HIV/AIDS cases died in the same year showed a secular trend of being low-highest-low, rising up to > 10.0% in 2001, peaking at 18.9% in 2003 and then continuously going down to 5.8% in 2010. The proportion of HIV/AIDS cases who survived at the beginning but died later in the year was going down since 2007. The proportion of HIV/AIDS deaths died directly from AIDS was increasing whereas the proportion of HIV/AIDS deaths dying directly from overuse of drugs was decreasing in the recent years. Among HIV/AIDS deaths, the proportion of ever received CD4(+) T-cell testing and the proportion of ever having received antiretroviral treatment were also increasing in the past years, reaching to 89.9% and 25.5% in 2010, respectively. CONCLUSION: The case fatality of HIV/AIDS was decreasing in the past years in Dehong prefecture. More efforts were needed to scale up the CD4(+) T-cell count testing and antiretroviral treatment in order to further reduce both morbidity and mortality among HIV/AIDS patients in Dehong prefecture. It is critical to improve surveillance program on HIV/AIDS deaths in the rural areas.