Objective To investigate the effects of active vitamin D (VD) on the expression of triggering receptor expressed on myeloid cells-1 (TREM-1) in renal tissue of diabetic nephropathies (DN) rats and to explore the impact of TREM-1 on adhesion and migration capacity of macrophage.Methods DN rat models were established by streptozotocin.Rats were randomly distributed into four groups:control (NC) group,VD group,DN group and DN+VD group (DN rats with 0.1 μg · kg-1 · d-1 calcitriol by garages).Rats were sacrificed respectively at 8 weeks and 12 weeks after treatment.Pathological changes in kidney tissue were detected and the expressions of CD68 and TREM-1 were acquired by immunohistochemistry stain and Western blotting.In vitro,RAW264.7 cells were divided into NC group,VD group,high glucose (HG) group and HG+VD group.In HG+VD group rats were treated by high glucose with 10-8 mol/L 1,25(OH)2D3.TREM-1 expression was measured by immunohistochemistry stain and Western blotting,and the ability of macrophage in migration and adhesion was evaluated by Transwell migration assay and adhesion assay.TREM-1 siRNA was transferred to silence TREM-1 expression,while plasmid of TREM-1 was transferred for high expression.Their ability of adhesion and migration in macrophage and the effect of 1,25(OH)2D3 were examined.Results (1) Compared with the NC group,the expressions of CD68 and TREM-1 were increased in DN group (P ＜ 0.05),whereas markedly decreased in DN+VD group (P ＜ 0.05).(2) The number of adhesion and migration cells,and the expression of TREM-1 protein in macrophage were obviously increased in HG group as compared with those in NC group (all P ＜ 0.05);whereas above changes were markedly decreased in HG+VD group than those in HG group (P ＜ 0.05).(3) The number of adhesion and migrated macrophage was reduced after TREM-1 siRNA intervention (all P ＜ 0.05).VD could significantly decrease the effect of high glucose on adhesion and migrated macrophages after TREM-1 siRNA (all P ＜ 0.05).(4) Adhesion and migration of macrophage were increased via TREM-1 overexpression (all P ＜ 0.05),but the effects of VD on high glucose-induced adhesion and migration of macrophage were disappeared.Conclusions VD can suppress the adhesion and migration of macrophage via reducing the expression of TREM-1,and inhibit infiltration of macrophage in renal tissue of DN rats.

Objective To investigate the effect of macrophages on podocytes apoptosis in diabetic nephropathy. Methods Differentiated mouse macrophages (RAW264.7) were exposed to normal glucose, high glucose, then the conditioned media (CM) was collected and considered as NC-CM or HG-CM, respectively. Western blotting and immunofluorescent staining were used to detect the specific markers for M1 macrophages (iNOS) and M2 macrophages (MR). ELISA was used to detect the concentration of TNF-α in the CM. Then normal PRMI 1640 media (control), NC-CM or HG-CM was added to podocytes. In some experiments, ROS inhibitors (Tempo), p38 MAPK inhibitor (SB203580), anti-TNF-α neutralizing antibody, and IgG1 isotype control were respectively added to cells with HG-CM. Besides, recombinant mouse TNF-α alone was applied to incubate podocytes. Podocytes apoptosis was accessed by Annexin V-FITC/PI and Hoechst33342 staining. DCFH-DA staining was used to analyse ROS level. Western blotting was used to detect cleaved casepase-3, p38MAPK, and p-p38MAPK protein. Results Macrophages were activated when exposed to high glucose, displaying pro-inflammatory M1 polarization with higher iNOS and lower MR expression. HG-CM but not NC-CM trigged podocytes apoptosis, up-regulated ROS, cleaved casepase-3 and p-p38MAPK. However, the podocytes apoptosis trigged by HG-CM was abolished by either a ROS inhibitor (Tempo) or a p38 MAPK inhibitor (SB203580). Additionally, TNF-α was increased in the HG-CM. TNF-α protein in macrophage was aslo increased when exposed to high glucose. Anti-TNF-α neutralizing antibody blunted the apoptotic response, excess ROS generation and p-p38 MPAK expression in podocytes induced by HG-CM. Moreover, addition of recombinant TNF-α similarly led to podocytes apoptosis, increased ROS and p38 MPAK expression. Conclusion M1 macrophages activated by high glucose released TNF-α to promote podocytes apoptosis via ROS-p38 MAPK pathway.

Objective To introduce the development strategy of“Internet Plus”AIDS prevention services and its implementation results from 2010 to 2015 in Guangzhou, China. Methods A gay men's health column was created for an active website aimed at men who have sex with men (MSM), in collaboration with local community organizations and the Guangzhou CDC. We designed intervention tools (including scenario-based applications and HIV risk self-assessment systems) and an online HIV testing service platform, integrated with applied psychology and behavioral theory as well as the“Internet Plus”concept, to intervene in HIV infection risk factors among MSM. Data of clients who accessed the“Internet Plus”AIDS services from 2010 to 2015 were used to evaluate service operation. Six-year consecutive surveys, conducted between April and July of each service year, were collected using a national AIDS sentinel surveillance questionnaire. For each year of surveillance, information on HIV prevalence, HIV interventions received during the past year, unprotected anal intercourse in the past 6 months, and HIV testing in the past year were compared using the chi-squared (χ2) test, to roughly reflect the effect of“Internet Plus”AIDS prevention services. Results As of 31 December 2015, a total of 34 395 MSM had received“Internet Plus”services and HIV testing. The number of MSM tested increased from 2 338 in 2010 to 8 054 in 2015. From 2010 to 2015, newly identified HIV cases in each year were 59, 166, 312, 283, 291, and 270, which accounted for 25.0%, 32.8%, 38.8%, 35.1%, 30.5%, and 23.2% of MSM HIV cases of Guangzhou, respectively. Sentinel surveillance data showed that during the study period, 3 047 MSM were investigated, with 405, 400, 401, 633, 608, and 600 each year, respectively. The proportion of participants who had received any HIV intervention during the past year was 74.3% (301), 70.8% (283), 83.3% (334), 85.0%(538), 69.1%(420), and 83.8%(503) each year, respectively (trend χ2=6.53, P=0.011). HIV testing done during the past year accounted for 44.0%(178), 44.3%(177), 49.4%(198), 53.4%(338), 56.1%(341), and 60.2%(361) each year, respectively (trendχ2=40.83, P<0.001). Unprotected anal intercourse in the past 6 months accounted for 59.3% (240), 62.0% (248), 56.6% (227), 57.0% (361), 48.4% (294), and 43.7%(262) each year, respectively (trend χ2=42.21, P<0.001). Conclusion The“Internet Plus”AIDS prevention services in this study represent a manner to enhance traditional HIV prevention strategies. We found these services to be effective in implementation of the national AIDS control and prevention strategy, especially for the expansion of intervention, testing, and case identification among high-risk populations.

Objective To introduce the development strategy of“Internet Plus”AIDS prevention services and its implementation results from 2010 to 2015 in Guangzhou, China. Methods A gay men's health column was created for an active website aimed at men who have sex with men (MSM), in collaboration with local community organizations and the Guangzhou CDC. We designed intervention tools (including scenario-based applications and HIV risk self-assessment systems) and an online HIV testing service platform, integrated with applied psychology and behavioral theory as well as the“Internet Plus”concept, to intervene in HIV infection risk factors among MSM. Data of clients who accessed the“Internet Plus”AIDS services from 2010 to 2015 were used to evaluate service operation. Six-year consecutive surveys, conducted between April and July of each service year, were collected using a national AIDS sentinel surveillance questionnaire. For each year of surveillance, information on HIV prevalence, HIV interventions received during the past year, unprotected anal intercourse in the past 6 months, and HIV testing in the past year were compared using the chi-squared (χ2) test, to roughly reflect the effect of“Internet Plus”AIDS prevention services. Results As of 31 December 2015, a total of 34 395 MSM had received“Internet Plus”services and HIV testing. The number of MSM tested increased from 2 338 in 2010 to 8 054 in 2015. From 2010 to 2015, newly identified HIV cases in each year were 59, 166, 312, 283, 291, and 270, which accounted for 25.0%, 32.8%, 38.8%, 35.1%, 30.5%, and 23.2% of MSM HIV cases of Guangzhou, respectively. Sentinel surveillance data showed that during the study period, 3 047 MSM were investigated, with 405, 400, 401, 633, 608, and 600 each year, respectively. The proportion of participants who had received any HIV intervention during the past year was 74.3% (301), 70.8% (283), 83.3% (334), 85.0%(538), 69.1%(420), and 83.8%(503) each year, respectively (trend χ2=6.53, P=0.011). HIV testing done during the past year accounted for 44.0%(178), 44.3%(177), 49.4%(198), 53.4%(338), 56.1%(341), and 60.2%(361) each year, respectively (trendχ2=40.83, P<0.001). Unprotected anal intercourse in the past 6 months accounted for 59.3% (240), 62.0% (248), 56.6% (227), 57.0% (361), 48.4% (294), and 43.7%(262) each year, respectively (trend χ2=42.21, P<0.001). Conclusion The“Internet Plus”AIDS prevention services in this study represent a manner to enhance traditional HIV prevention strategies. We found these services to be effective in implementation of the national AIDS control and prevention strategy, especially for the expansion of intervention, testing, and case identification among high-risk populations.

Objective: To understand the characteristics and dynamics of individuals with HIV-1 subtype infection among injected drug users (HIV infection IDU) in Guangzhou between 2008 and 2015. Methods: HIV-1 RNAs were extracted from serum samples of the individuals that were newly diagnosed with HIV-1 infection among IDUs living in Guangzhou, between 2008 and 2015. The Pol gene segments of HIV-1 genome from these RNA samples were amplified by nested reverse transcription polymerase chain reaction (Nested-PCR) and sequenced. Subsequently, phylogenetic tree was reconstructed using both pol sequences of samples and references before the subtype of HIV-1 was determined. Distributions of HIV-1 subtypes detected in IDUs with different demographic characteristics in different years were compared. Results: A total of 437 pol gene segments were successfully obtained from 517 serum samples of HIV infection IDUs. The average age of 437 HIV infected IDUs was 37.37 years with standard deviation as 8.17 years. 51.5% (225/437) of the HIV infected IDU that registered residence were not in Guangdong. The Guangxi Registered residents were accounted for 54.2% (122/225). Proportion of subtype CRF07_BC (46.5%) appeared the highest, followed by CRF01_AE (24.3%), CRF08_BC (23.3%) and other subtypes (5.9%). The annual proportions of subtype CRF07_BC (trend χ²=19.703, P=0.006) and CRF08_BC (trend χ²=25.718, P=0.001) were significantly different. The proportion of subtype CRF07_BC decreased from 56.9% to 34.2% (trend χ²=15.139, P=0.000), while the proportion of CRF08_BC increased from 11.8% to 37.0% (trend χ²=22.577, P=0.000). The proportion of CRF08_BC was significantly higher in the HIV infected IDUs with Guangxi residence (Monte Carlo simulation of exact probability P=0.000, 99%CI: 0.000-0.000). Conclusions CRF07_BC, CRF01_ AE and CRF08_BC were the predominant HIV-1 subtypes while multiple subtypes were co-circulated among the HIV infected IDUs in Guangzhou, between 2008 and 2015. Behavioral intervention set for HIV infected IDUs with Guangxi residence should be strengthened in Guangzhou.

Objective: This article was to evaluate the applicability and feasibility of "Lingnanzhun" -an "Internet Plus-based HIV Self-testing Tool" targeting MSM in Guangzhou. Hopefully, the results could be used to improve the existing HIV testing services and to support the implementation and scale-up of HIV self-testing programs. Methods: Data were collected from a survey on HIV testing preferences among the Internet-using MSM in April to June, 2015. Univariate and multivariate logistic regression analysis were applied to identify factors associated with the use of HIV self-testing service provided by Lingnanzhun. Information related to the users of Lingnanzhun during September 2014 and December 2018 was also collected. Results: 769 MSM were recruited as participants. Of them, age distribution was 16-77(28.6±6.8) years old, 88.3%(679/769) were unmarried, 42.2%(325/769) were registered residents of Guangzhou, 82.1%(631/769) had university or college education. Among them, 195 (25.4%) used the HIV self- testing program of Lingnanzhun while 574 (74.6%) using the clinic service. Compared with the clinic service users, the Lingnanzhun users showed the following characteristics: longer experience in the MSM community ≥10 years (32.8% vs. 20.9%, 64/195 vs. 120/574); having male casual sexual partners ≥2 (42.1% vs. 29.6%, 82/195 vs. 170/574); having group sex (6.2% vs. 2.6%, 12/195 vs. 15/574) and having commercial sex with men (13.8% vs. 3.0%, 27/195 vs. 17/574). Data from the Lingnanzhun users showed that a total of 3 000 users had practised 5 038 times of self HIV-testings. 11.4% (343/3 000) of the Lingnanzhun users had never been tested. Conclusions It was applicable and feasible to provide Internet-based HIV self-testing service to MSM as a significant complement to the traditional facility-based HIV testing services. It was also useful in accessing those who were having higher risk or had never received HIV testing so as to increase the testing uptake and the frequency.

Objective: To analyze the characteristics of levels related to the risk through self-evaluation system, among MSM users in Guangzhou, between 2015 and 2017. Methods: Between 2015 and 2017, data was collected from the users of a self-evaluation system network related to HIV infection, based on the previous 'HIV health risk appraisal model’. Information on risk factors was collected to calculate the scores and levels of risks and to estimate the incidence of HIV. Taking the reference of R value on risks as (R=0.9-1.1) in general population. The ones with very low risk, with low risk, moderate risk, high risk and very high risk were set as R≤0.5, 0.5<R≤0.9, 0.9<R≤1.1, 1.1< R≤2.0 and R>2.0, respectively. The scores of modifiable risk factors were compared with different subgroups of MSM. Results: A total of 4 601 MSM were involved in this study, with the following features presented as: aged 16-64 (28.38±7.11) years, proportions of residence from Guangzhou, Guangdong province or other provinces as 38.6%(1 776/4 601)、35.4%(1 629/4 601) and 26.0%(1 197/4 601), 59.6%(2 742/4 601) received bachelor or above degrees. 81.3%(3 741/4 601) of them claimed as having homosexual orientation. R values of risk level on very low risk, low risk level, moderate risk, high risk and very high risk appeared as 12.9%(594/4 601), 50.9%(2 342/4 601), 17.0%(783/4 601), 14.8%(682/4 601) and 4.3%(200/4 601), respectively. Scores of modifiable risk factors decreased year by year (P<0.05), among MSM in this study. In either of the groups that experiencing insertive or receptive sex, the ones with heterosexual orientation presented the highest scores of modifiable risk factors (P<0.05). Conclusions The risk levels on HIV infections called for special attention among the users of the self-evaluation network system. Among the MSM that carrying either insertive or receptive sex role, the ones with heterosexual orientation had the highest risk levels and scores of modifiable risk factors in Guangzhou. Further study should be explored to better understand the causes of related risks.

Objective: To analyze the characteristics of the "Interner Plus-based AIDS Comprehensive Prevention Service System" among MSM who frequently using the Internet in Guangzhou. Methods: An online survey was conducted among MSM who were recruited through gay-website portals between August and September, 2018 in Guangzhou, to collect information regarding the use of and attitudes on the "Interner Plus-based AIDS Comprehensive Prevention Service System" . Logistic regression was used to explore the association between the use of Internet intervention tools and related behavioral characteristics. Information on the awareness of AIDS, HIV testing, and condomless anal sex behavior were compared between the core or non-core services users. Results: A total of 777 Internet-based MSM were recruited as participants including 638 men (82.1%) as core service users. MSM were satisfied in using the the "Interner Plus-based AIDS Comprehensive Prevention Service System" while more than 80.0% of the users felt that the tools were helpful in: increasing the HIV awareness, promoting test uptake, and reducing those related risk behavior. Comparing with those who did not use the tools, the users showed higher rates in practising condomless anal intercourse (1.50-1.86 times), commercial sex with men (11.60-21.21 times), and unprotected vaginal intercourse (13.62-20.67 times), in the last 6 months. Proportions of core service users appeared as: [96.6% vs. 74.8%, aOR (95%CI): 8.80 (4.85-15.97)] on HIV testing, [56.4% vs. 22.3%, aOR (95%CI): 4.54 (2.94-7.02)] on regular HIV testing and [86.2% vs. 80.6%, aOR (95%CI): 1.75 (1.06-2.89)] on awareness of HIV knowledge respectively, which were all significantly higher than the non-core service users. Conclusions The frequent Internet using MSM in Guangzhou claimed to have had high acceptance and satisfaction on the local Internet HIV intervention service tools. The "Internet Plus-based AIDS Comprehensive Prevention Service System" had effectively reached the high-risk subgroups of MSM, increasing the awareness on related risk and promoting testing on HIV.