Objective:To understand the incidence of diabetes and influencing factors, the trend of FPG change and risk for mortality in HIV-infected individuals after antiretroviral therapy (ART) in Dehong Dai and Jingpo Autonomous Prefecture (Dehong).Methods:The HIV/AIDS treatment database was collected from China Information System for Disease Control and Prevention. This retrospective cohort study was conducted in HIV-infected individuals with access to ART in Dehong during 2004-2020.The Cox proportional hazard regression model was used to analyze the incidence density of diabetes, the influencing factors and risk for mortality in HIV-infected individuals with access to ART, mixed linear effects model was used to analyze the trend of FPG change and predict FPG in those with different glucose metabolic status at baseline survey. Statistical analysis was performed using software SAS 9.4.Results:A total of 8 763 HIV-infected individuals were included, in whom 8 432 (96.2%) had no diabetes, 331 had diabetes. The incidence density of diabetes was 2.31/1 000 person years. Multivariate Cox proportional hazard regression analysis revealed that 30- 59 years old, BMI ≥24.0 kg/m 2, Efavirenz (EFV) based initial treatment regimen and impaired fasting glucose (IFG) at baseline survey were significantly and positively associated with incidence of diabetes. Mixed effect model revealed that FPG was positively correlated with the duration of ART, age and baseline FPG. Suffering from diabetes was a risk factor for mortality in HIV-infected individuals both at baseline survey and during follow-up. Conclusions:The risk for diabetes increased in HIV-infected individuals who were 30-59 years old, baseline BMI ≥24.0 kg/m 2, received EFV based initial treatment, and IFG in HIV-infected individuals after antiretroviral therapy in Dehong, 2004-2020. It is important to pay close attention to their blood glucose, and patients with high blood glucose should receive treatment as early as possible.

Objective:To investigate the incidence of anemia and risk factors in HIV/AIDS patients with access to antiretroviral therapy (ART) during 2004-2018 in Dehong Jingpo and Dai Autonomous Prefecture (Dehong).Methods:A retrospective cohort study was conducted in HIV/AIDS patients receiving ART in Dehong during 2004-2018 based on the data extracted from the National HIV/AIDS antiretroviral therapy database. Cox proportional risk model was used to analyze the factors associated with the incidences of anemia and moderate or severe anemia in the HIV/AIDS patients. And the piecewise linear mixed-effects model was used to depict the trajectory of hemoglobin changes over time after initiating ART according to baseline level.Results:A total of 8 044 HIV/AIDS patients were included, in whom 6 337 (78.8%) were without anemia at baseline survey and had a median follow up time of 4.43 ( P 25, P 75: 1.50, 6.71) years. The median follow up time for 1 291 new anemia cases and 293 new moderate or severe anemia cases was 0.16 ( P 25, P 75: 0.07, 1.99) years and 0.48 ( P 25, P 75:0.09, 2.97) years, respectively. The incidence rate of anemia and moderate or severe anemia was 4.40 per 100 person-years and 0.41 per 100 person-years respectively. In multivariable Cox regression analysis, older age, being female, being in Dai and Jingpo ethnic group, baseline BMI <18.5 kg/m 2, baseline CD4 +T lymphocyte cell counts (CD4) <200 cells/μl, and zidovudine (AZT) -based initial treatment regimen were factors significantly and positively associated with incidence of anemia after treatment. Factors as being female, being in Dai ethnic group, baseline BMI <18.5 kg/m 2, mild baseline anemia, and AZT-based initial treatment regimen were significantly and positively associated with incidence of moderate or severe anemia after treatment. Conclusion:The risk for anemia was higher in HIV/AIDS patients with specific characteristics, such as age ≥60 years , being female, being in Dai and Jingpo ethnic groups, lower BMI, CD4 <200 cells/μl, and treatment of AZT, after initiation of ART in Dehong during 2004-2018. Additional efforts are needed to strengthen the screening, prevention and treatment of anemia in this population.

Objective: To study the prevalence and correlates of diabetes among HIV/AIDS who were on antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefectures (Dehong), Yunnan province. Methods: The database of HIV/AIDS receiving ART in Dehong was downloaded by using the basic information system of AIDS prevention and control in China. In this cross-sectional study, HIV/AIDS patients who were currently on ART and aged 18 years or above, were consecutively recruited, between July 2017 and June 2018, in Dehong. All the subjects underwent hemoglobin A1c (HbA1c) testing. Patient with diabetes was defined as meeting any of these indicators (HbA1c ≥6.5%, baseline FPG ≥7.0 mmol/L, FPG ≥7.0 mmol/L in the most recent visit). Both univariate and multivariate logistic regression analysis were carried on to evaluate the correlates of diabetes among the HIV/AIDS patients. Results: In total of 4 376 HIV/AIDS patients were included for analysis, with the average age as (43.7±10.1) years, proportion of males as 53.8% (2 356/4 376) and the HCV positive rate as 24.1% (1 055/4 376). The mean years was (8.9±3.8) years after the HIV diagnosis was made, and the mean duration on treatment was (6.8±2.9) years. The prevalence of diabetes was 11.4% (500/4 376). Through multivariate logistic regression analysis, data showed that the risk factors of diabetes of HIV/AIDS on ART were: aged 40 years or above, being male, HCV positive, baseline body mass index ≥24.0 kg/m², elevated TG ≥1.70 mmol/L in the most recent visit and baseline antiretroviral regimens under Efavirenz (EFV). Conclusions Prevalence rate of diabetes appeared higher in HIV/AIDS patients who were on ART in Dehong. Prevention and control measures should be targeted on HIV/AIDS patients who were with risk factors of diabetes as being elderly, male, HCV positive, overweight and higher TG. Further esearch is needed to evaluate the association between the use of EFV and diabetes.

OBJECTIVETo examine the proportion and reasons of drop-out from antiretroviral therapy (ART) among 8 367 adult HIV-infected individuals in Dehong prefecture, Yunnan province.

METHODSAll adult HIV-infected patients receiving ART before September 30 of 2014 were examined for the situation of drop-out from ART.

RESULTSThe proportion of drop-out from ART among adult HIV-infected patients in Dehong prefecture was 14.4% (1 202/8 367). Results from the univariate logistic regression analyses indicated that drop-out from ART was significantly correlated with factors as: living area, gender, age, marital status, HIV transmission route, baseline CD4⁺ T cell counts and initial treatment regimen of the patients. After adjusted for potential confounding variables by multiple logistic regression model, drop-out from ART was significantly correlated with residential area, marital status, HIV transmission route, baseline CD4⁺ T cell count and initial treatment regimen of the patients. HIV-infected patients who were living in Mangshi city, Lianghe county or Yingjiang County, being married or living with partner, HIV infection through sexual contact, with baseline CD4⁺ T cell counts ≤ 200 cells/mm³, and ART included in the initial treatment regimen etc., were less likely to drop out from ART. The proportion of drop out from ART was significantly decreasing along with the increasing time of ART. Data from specific investigation revealed that among the 1 202 patients who dropped out from ART, 704 (58.6%) were lost to follow-up, 303 (25.2%) did not adhere to treatment, 74 (6.2%) moved out the region, 64 (5.3%) were Burmese that had returned to Burma, 29 (2.4%) stopped the treatment according to doctors' advice, 18 (1.5%) were incarcerated and 10 (0.8%) were under other reasons. Reasons for the drop-out varied, according to the situation of patients.

CONCLUSIONThe proportion of drop-out from ART varied significantly according to the characteristics of HIV-infected patients in Dehong prefecture that underscoring the needs for tailored responses to reduce drop-out of ART. Focus should be targeted on reducing the loss to follow-up and improving the treatment adherence.

Objective To examine the proportion and reasons of drop-out from antiretroviral therapy(ART)among 8 367 adult HIV-infected individuals in Dehong prefecture,Yunnan province. Methods All adult HIV-infected patients receiving ART before September 30 of 2014 were examined for the situation of drop-out from ART. Results The proportion of drop-out from ART among adult HIV-infected patients in Dehong prefecture was 14.4%(1 202/8 367). Results from the univariate logistic regression analyses indicated that drop-out from ART was significantly correlated with factors as:living area,gender,age,marital status,HIV transmission route,baseline CD4+T cell counts and initial treatment regimen of the patients. After adjusted for potential confounding variables by multiple logistic regression model,drop-out from ART was significantly correlated with residential area,marital status,HIV transmission route,baseline CD4+T cell count and initial treatment regimen of the patients. HIV-infected patients who were living in Mangshi city,Lianghe county or Yingjiang county,being married or living with partner,HIV infection through sexual contact,with baseline CD4+T cell counts≤200 cells/mm3,and ART included in the initial treatment regimen etc.,were less likely to drop out from ART. The proportion of drop out from ART was significantly decreasing along with the increasing time of ART. Data from specific investigation revealed that among the 1 202 patients who dropped out from ART,704(58.6%)were lost to follow-up,303(25.2%) did not adhere to treatment,74(6.2%)moved out the region,64(5.3%)were Burmese that had returned to Burma,29 (2.4%) stopped the treatment according to doctors’advice,18(1.5%)were incarcerated and 10 (0.8%) were under other reasons. Reasons for the drop-out varied,according to the situation of patients. Conclusion The proportion of drop-out from ART varied significantly according to the characteristics of HIV-infected patients in Dehong prefecture that underscoring the needs for tailored responses to reduce drop-out of ART. Focus should be targeted on reducing the loss to follow-up and improving the treatment adherence.

Objective To examine the proportion and reasons of drop-out from antiretroviral therapy(ART)among 8 367 adult HIV-infected individuals in Dehong prefecture,Yunnan province. Methods All adult HIV-infected patients receiving ART before September 30 of 2014 were examined for the situation of drop-out from ART. Results The proportion of drop-out from ART among adult HIV-infected patients in Dehong prefecture was 14.4%(1 202/8 367). Results from the univariate logistic regression analyses indicated that drop-out from ART was significantly correlated with factors as:living area,gender,age,marital status,HIV transmission route,baseline CD4+T cell counts and initial treatment regimen of the patients. After adjusted for potential confounding variables by multiple logistic regression model,drop-out from ART was significantly correlated with residential area,marital status,HIV transmission route,baseline CD4+T cell count and initial treatment regimen of the patients. HIV-infected patients who were living in Mangshi city,Lianghe county or Yingjiang county,being married or living with partner,HIV infection through sexual contact,with baseline CD4+T cell counts≤200 cells/mm3,and ART included in the initial treatment regimen etc.,were less likely to drop out from ART. The proportion of drop out from ART was significantly decreasing along with the increasing time of ART. Data from specific investigation revealed that among the 1 202 patients who dropped out from ART,704(58.6%)were lost to follow-up,303(25.2%) did not adhere to treatment,74(6.2%)moved out the region,64(5.3%)were Burmese that had returned to Burma,29 (2.4%) stopped the treatment according to doctors’advice,18(1.5%)were incarcerated and 10 (0.8%) were under other reasons. Reasons for the drop-out varied,according to the situation of patients. Conclusion The proportion of drop-out from ART varied significantly according to the characteristics of HIV-infected patients in Dehong prefecture that underscoring the needs for tailored responses to reduce drop-out of ART. Focus should be targeted on reducing the loss to follow-up and improving the treatment adherence.

Objective To knock out the Abcb1 gene of rat,and establish the Abcb1 humanized rat model based on the Abcb1 knock out rat.Methods The animal model was established using BAC and CRISPR/Cas9 technology,and was analyzed by PCR, RT-PCR and real-time PCR.Results Establishing a rat model expressing human Abcb1 stably by transfer the 153 kb BAC containing human Abcb1 promoter and cDNA into rat genome, and establishing the Abcb1 knock out rat at the same time.Establishing the Abcb1 humanized model by crossing these two strains together.The expression pattern of Abcb1 in Abcb1 humanized rat is different from the wild type rat.The Abcb1 humanized model express not only the human Abcb1 gene but also has similar expression pattern as human.Conclusions The Abcb1 knock out rat and the Abcb1 humanized rat were successfully established, and this model is close to human concerning about the drug metabolism related to Abcb1.

Objective To study the relationship of insulin receptor substrate-1 (Irs1) and metabolic disease, we generated Irs1 gene knockout rat by CRISPR/Cas9 system.Methods Two sgRNA targeting sites were designed for Irs1 targeting.The Cas9 and sgRNAs were transcribed by T7 RNA polymerase in vitro.Cas9 mRNA and sgRNA mixtures were pooled and microinjected into one-cell fertilized eggs of SD rats to generate rats with targeted mutation .Results Five rats with the mutations were detected with the efficiency of 83%.Conclusion The Irs1 gene knockout rats generated in this study can be transmitted by germline .

Objective To establish the sperm specific Sleeping Beauty ( SB ) transposase-expression transgenic mouse for the study of the genetic modification mediated by transposon system in mouse .Methods Prm1 promoter was cloned from mouse genomic DNA to drive the expression of SB transposase .The transgenic mice were generated by microinjection .The gene type of transgenic line was identified by PCR .The expressing level in testis was determined by western blot and immunohistochemistry (IHC) staining.Results Five lines of transposase transgenic mice were obtained by microinjection and three can be germline .One mouse line with higher expression level of transposase in the testis was obtained.Conclusion One transgenic mouse model with Sleeping Beauty transposase - expression was successfully established .This model will greatly contribute to the research of genetic modification mediated by transposon in mouse.

Objective To study the effects of NRG2 on cardiac structure and function , we established the cardiac-specific human NRG2 transgenic mice and investigate the effect of NRG2 on cardiac structure and function under pressure overload situation .Methods The transgenic vector was constructed by insertion of the human NRG2 gene under the α-MHC promoter.The transgenic mice were generated by microinjection and were all maintained on a C57BL/6J genetic background .The genotype of transgenic mice was identified by PCR and the expression level of target gene was determined by western blot .Transverse aortic constriction ( TAC) was applied to prepare the pressure overload induced cardiomyopathy mice model .The cardiac structure and function of the transgenic mice were compared and analysized by echocardiographic and pathological observation .Results Transgenic mice with high level of NRG2 in heart tissues were established.The left ventricular wall thickness (LVPWD) was increased, and to 15.6% at 3 months old compared with that of the non transgenic ( NTG) mice.The hypertrophy of left ventricular wall caused by pressure overload was removed due to the expression of NRG2 .Meanwhile, cardiac disarray and fibrosis were increased obviously compared with that of the NTG mice.Conclusion The transgenic expression of NRG2 in heart tissues could shorten the pathological process of hypertrophy, but accelerated the process of heart failure (HF).