Objective:To analyze the epidemic characteristics and trends of newly reported HIV-infected people among Chinese and Burmese in Dehong Dai and Jingpo Autonomous Prefecture (Dehong Prefecture) of Yunnan Province, China, from 2000 to 2023, and provide evidence for formμlating AIDS prevention and control measures for the Burmese living in Dehong.Methods:The data were obtained from the Chinese Disease Control and Prevention Information System. The distribution of HIV-infected people with different population characteristics was analyzed, and the Joinpoint regression model was used to analyze the temporal trend of crude detection rate in different genders, ethnicities, and ages.Results:From 2000 to 2023, 24 989 newly HIV infections were reported in Dehong Prefecture, of which 14 594 (58.4%) were Chinese and 10 395 (41.6%) were Burmese. Compared with Chinese, Burmese women (32.9%, 3 416/10 395), those aged 20-29 (40.9%, 4 248/10 395), and Jingpo people (26.7%, 2 773/10 395) accounted for a higher proportion. The new diagnosis rate of Chinese nationals increased from 1.0/10 000 in 2000 to 15.4/10 000 in 2004, and then showed a downward trend, falling to 1.2/10 000 in 2023. Among them, compared with other age groups, Dai and other ethnic groups and women, the new diagnosis rate among 20-49 age group, Jingpo and men were relatively higher, at 1.7/10 000, 2.3/10 000 and 1.3/10 000 respectively. Regarding the method of detection, the Chinese HIV-infected people were mainly detected by key population testing (35.7%), while the Burmese HIV-infected people by key population testing (28.9%) and physical examination for entry-exit personnel (25.3%). The transmission routes of both nationalities were mainly heterosexual transmission, but compared with Chinese HIV-infected persons, the proportion of Burmese infected persons through non-marital non-commercial transmission was relatively higher (66.4% vs. 60.6%). The proportion of Chinese nationals with a first CD4 +T lymphocyte (CD4) counts of <200 cells/μl (28.9%) was higher than that of Burmese nationals (19.8%). Conclusions:The rising trend of HIV infection among Chinese and Burmese people in Dehong Prefecture from 2000 to 2023 slowed down. The new diagnosis rate was higher in the 20-49 age group, Jingpo and men. Compared with Burmese HIV-infected people, the proportion of Chinese HIV-infected people with first CD4 counts <200 cells/μl was relatively higher. Comprehensive interventions should be further carried out for Myanmar nationals, and efforts should be made to expand testing for Chinese nationals.

Introduction::The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.Methods::We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.Results::At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Conclusion::Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Objective: To understand the cognition and medication use of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in China and its associated factors. Method: From August 25 to September 5, 2021, 2 447 MSM were recruited in 24 cities to complete the online questionnaire through a male social interaction platform, Blued 7.5 software. The survey contents included demographic information of the respondents, PrEP awareness and usage, and risk behaviors. Descriptive analysis and multi-level logistic regression were performed for data analysis. SPSS 24.0 and SAS 9.4 software were used for statistical analysis. Results: Among the 2 447 respondents of MSM, 1 712 (69.96%) had heard of PrEP, 437 (17.86%) ever used PrEP, 274 (11.20%) were on PrEP, and 163 (6.66%) had discontinued PrEP; among the 437 cases (whoever used PrEP), more than 61.88% (388/627) adopted emtricitabine/tenofovir disoproxil fumarate regimen, and most of them adopted on-demand regimen. The average PrEP dosage reported in the past year is 1.12 tabletsper person per week. PrEP purchase was primarily via an online channel, and the most concerned factor was the PrEP effectiveness on HIV prevention. The most common reasons for discontinuing PrEP, reported by 163 cases, were the lack of HIV risk perception, the use of a condom to prevent HIV, and the economic burden of PrEP use. The logistic regression analysis showed that PrEP use among MSM in 24 cities was statistically associated with age, monthly income, ever having unprotected anal sex in the past year, used sexual drugs and sexually transmitted disease (STD) diagnosis in the past year. Compared with MSM aged 18-24, the proportion of MSM was relatively lower among those aged 25-44, who discontinued the PrEP (aOR=0.54,95%CI:0.34-0.87) or never used PrEP (aOR=0.62,95%CI:0.44-0.87). The proportion of unprotected anal sex among MSM currently on PrEP use was higher than those who have stopped PrEP and never used PrEP (all P<0.05). Those MSM group, with monthly income higher than 5 000 Yuan, used sexual drugs and STD diagnosis in the past year were more likely to have a higher rate for PrEP usage (all P<0.05). Conclusions: Currently, pre-exposure prophylaxis in the MSM group is primarily obtained via the online channel and adopted in an on-demand mode. Although the PrEP users have reached a certain proportion, it is still necessary to strengthen health education on the PrEP effects and side effects of MSM and to improve the awareness and use rate, especially for young MSM group, which can be combined with the advantages of the internet targeting its needs and use barriers.
Humans ; Male ; Homosexuality, Male ; Pre-Exposure Prophylaxis ; Cities ; Sexual and Gender Minorities ; Sexual Behavior ; China ; HIV Infections/prevention & control*

Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [¹⁸F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/μmol). We confirmed that [¹⁸F]FBTA has a strong STING binding affinity (K_d = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [¹⁸F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG).

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia.However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/ S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

Objective: To analyze the work indicators of China Comprehensive AIDS Response Program (China CARES) and provide reference for future work of the program. Methods: The scores of each indicator were calculated, and different scores among different types of program areas were compared. The M(Q₁,Q₃) was used to describe the score of each indicator. The entropy weight method was used to calculate the composite score of each indicator and the composite score was translated into a 100-point system and compared among indicators. Results: In terms of the first-level indicators, organizational leadership and management (96.0 points), publicity and education (94.0 points), and innovative strategies and measures (98.0 points) got relatively high scores; while comprehensive social governance of AIDS prevention (72.0 points) was with the lowest score. The scores of publicity and education and comprehensive intervention in county-level program areas were significantly lower than those in urban areas. For secondary indicators, the indicator with relatively lower scores included "condom use among female sex workers last time" (70.0 points)", "at least one local key population has an increase in the number of people receiving HIV testing compared with the previous year" (70.0 points)", "colleges and occupational schools set up AIDS-related self-service facilities" (65.0 points), "HIV testing among the arrested people suspected of prostitution, adultery, drug users and traffickers" (55.0 points) and "condom use among men who have sex with men during last episode" (50.0 points). The "indicator 3 comprehensive intervention" contributed most to the evaluation, while "indicator 7 innovation strategies and measures" played a minor role in the evaluation results. Conclusions: The overall situation of AIDS Response Program in 2020 was good, but the progress in different word areas was not yet balanced. The two areas of comprehensive intervention and comprehensive social governance of AIDS prevention should be strengthened. It is also suggested that relevant indicators be adjusted appropriately to improve evaluation indicators system and comprehensively promote the program.
Acquired Immunodeficiency Syndrome/prevention & control* ; China/epidemiology* ; Female ; HIV Infections/epidemiology* ; Homosexuality, Male ; Humans ; Male ; Program Evaluation ; Sex Workers ; Sexual and Gender Minorities

Objective: To understand the prevalence of HIV, hepatitis C virus (HCV) and syphilis and related factors among cross-border couples in Mangshi county, Dehong autonomous prefecture, Yunnan province. Methods: From May, 2017 to April, 2019, 2 500 couples with 5 000 cross-border marriages were selected by using cluster sampling method. The demographic characteristics, AIDS-related health services, HIV, HCV, syphilis infection and other information were collected through questionnaires and laboratory tests. The influencing factors of HIV, HCV and syphilis infection were analyzed by multivariate logistic regression model. Results: A total of 2 500 couples with cross-border marriage were investigated, among which 2 438 (97.5%) couples were Chinese men with Myanmar women. The average age of 5 000 participants was (34.16±9.00) years. Most of them were minority groups (59.9%), farmers (98.5%), education years ≤6 years (81.4%), marriage years>3 years (80.0%), and from mountainous areas (61.7%). The HIV prevalence of Chinese and Myanmar populations was 1.7% (43/2 500) and 2.0% (49/2 500), respectively. The HCV infection rates were 2.0% (49/2 500) and 1.3% (32/2 500), respectively and the infection rates of syphilis were 0.4% (10/2 500) and 0.2% (4/2 500), respectively. There were no statistically significant differences in the prevalence of three diseases among Chinese and Myanmar populations (P>0.05). The multivariate analysis showed that compared with those aged ≤ 30 years, having lower AIDS awareness, never receiving HIV testing, without HCV and syphilis infection, HIV prevalence was higher among those aged>30 years (OR=3.21, 95%CI: 1.80-5.73), having higher AIDS awareness (OR=17.41, 95%CI: 4.27-70.91), receiving HIV testing (OR=4.93, 95%CI: 2.72-8.92), with HCV infection (OR=5.64, 95%CI: 2.72-11.70) and syphilis infection (OR=8.37, 95%CI: 1.63-43.08). Compared with those aged ≤ 30 years, having marriage years ≤ 3 years, and with HIV negatives, HCV infection rate was higher among those age>30 years (OR=3.02, 95%CI: 1.69-5.38), having marriage years>3 years (OR=2.24, 95%CI: 1.34-3.74), and with HIV positives (OR=6.69, 95%CI: 3.29-13.59). Compared with those having HIV negatives, the syphilis infection rate was relatively higher among participants with HIV positives (OR=9.07, 95%CI: 2.00-41.10). Conclusion: The prevalence of HIV, HCV, and syphilis among cross-border couples in Mangshi county, Dehong autonomous prefecture of Yunnan province is relatively high. Age, AIDS awareness, HIV testing history, and the length of marriage are associated with the HIV, HCV, and syphilis infection.
Acquired Immunodeficiency Syndrome ; China/epidemiology* ; Female ; HIV Infections/epidemiology* ; Hepacivirus ; Hepatitis C/epidemiology* ; Humans ; Male ; Prevalence ; Risk Factors ; Syphilis/epidemiology*

Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by ¹H NMR, ¹³C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC₅₀ = 0.26 μmol·L^-1) was 6.7 times than the lead compound A (IC₅₀ = 1.73 μmol·L^-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.

Aim To study the effect of different hepa- ry.Methods First, heparin derivatives with different rin sulfation patterns on bleomycin induced lung inju- sulfation patterns,6-desulfated heparin (6-DeH) and N-acetvlated heparin ( N-AcH ) , were synthesized.Secondly, the effect of these compounds on BLM-in¬duced bronchial epithelial cell ( BEARS-2B) injury was evaluated via lactate dehydrogenase activity, MTT experiment, Annexin V/ PI staining and Hoechst 33258 staining.Then , immunofluorescence staining and West¬ern blotting were used to investigate the shedding of Svndecan-1 and the activation of c-Met by 6-DeH/Akt j j signaling pathway.Finally, a BLM-induced lung injury mouse model was used to further verify the protective effect of 6-DeH by HE staining, Svndecan-1 immunos- taining,bodv weight change,and survival rate.Results In the BLM-induced BEARS-2B injury model, 6- DeH was selected as the best candidate, which exerted their effect by competitively binding to BLM, thereby reducing the damage of heparan sulfate barrier (Svnde- can-1 ) on cell surface, and improving cell survival by activating the downstream c-Met/Akt pathway.In the BLM-induced lung injury mouse model, it was further confirmed that 6-DeH reduced the shedding of Svnde- can-1 in the early stage, and delayed the lung injury and fibrosis process.Conclusions 6-DeH protects the bronchial epithelial cells against BLM-induced lung in¬jur)' through inhibiting the shedding of Svndecan-1 and activating the c-Met/Akt signaling pathway.

Objective:To summarize the clinical manifestations, epidemiological features and progress of diagnosis and treatment of gout in the spinal canal.Methods:A 59-year-old male patient was admitted to the hospital due to back pain, weakness in both lower limbs, hypoaesthesia and feeling of walking and stepping on cotton for more than one month. The preoperative imaging examination showed there were space-occupying lesions in the spinal canal at the T 8, 9 level with severe canal stenosis. The patient underwent posterior T 8, 9 laminectomy decompression, debridement and T 7-T 10 pedicle screw internal fixation under general anesthesia. The thoracic spinal gout was diagnosed by postoperative pathology. Further, the following keywords, "gout", "gout of spinal canal", "gout of spine" and "intraspinal gout", were used to search in the Chinese and English databases. A total of 62 patients with intraspinal gout were retrieved. The age, gender, involved disease, history of gout or hyperuricemia, laboratory indicators and imaging data of 63 patients were collected. Results:A total of 63 patients with intraspinal gout were retrieved. The gender of one patient was unknown. The remaining patients included 54 males (87.1%, 54/62) and 8 females (12.9%, 8/62) with the ratio of male to female 6.75∶1. The average age was 52(35, 67) years (range 20-82 years) and the peak onset period was 60-79 years. Fifty-six cases (88.9%, 56/63) of all patients suffered the disease from one single site of the spine, including 26 cases in the lumbar-sacral (46.4%), 22 cases (39.3%) in the thoracic spine and 8 cases (14.3%) in the cervical spine. However, only 7 patients had the disease at more than two sites at the same time accounting for 11.1% of all patients (7/63). Fifty-three patients (91.4%, 53/58) had a history of hyperuricemia with an average duration of 8.6 years (range 3 months to 28 years). The clinical symptoms of intraspinal gout were not specific. There were 70.5% (43/61) patients had local pain and up to 98.4% (60/61) patients had varying degrees of neurological dysfunction. X-ray examinations often showed no positive results due to technical limitations. Among 41 patients with CT imaging data, 31 cases showed mid-to-high density elliptical or irregular calcifications in the spinal canal and the remaining 10 patients showed medium-low density soft tissue masses. There were 96.2% (51/53) of patients with intraspinal gout showed medium or low signal on T1WI MRI examination but without high signal or low signal on T2WI (40 cases of high signal, 13 cases of high signal or mixed signal). All 63 patients were finally diagnosed by pathological examination and 5 of them with histological features. The main pathological features included foreign body granuloma, red-stained crystal-like deposits in the cytoplasm of foreign body giant cells, birefringent spindle or needle-like crystals under polarized light microscope.Conclusion:Gout in the spinal canal is a rare condition. Dual-energy CT has high sensitivity and specificity in identifying gout and it can provide a more accurate method in diagnosis of spinal gout. However, the final diagnosis depends on postoperative pathology. If case of spinal instability or neurological dysfunction, surgery had to be performed. Hyperuricemia should be treated in order to reduce the risk of acute attacks.