HIV/STD prevalence and test uptake among african in Guangzhou, China: an analysis of data from hospital-based surveillance.

Human immunodeficiency virus (HIV) and sexually transmitted diseases (STDs) cause substantial morbidity and mortality both in African and China. However, there is limited data available on the prevalence of HIV/STDs and the uptake of testing experience ever during in China among African migrants. A venue-based survey was conducted at a tertiary hospital in Guangzhou to investigate the prevalence of HIV/STDs through laboratory testing and identify the associated factors. A total of 200 eligible participants completed the survey and bring into the analysis from April to October 2019, and the temporary visitors were excluded. The prevalence rates of HIV, syphilis, NG, CT, and HBsAg among the participants were 1.0%, 2.5%, 1.0%, 1.5%, and 5.5%, respectively. The overall reported rate of HIV/STD testing was 37.0%, with rates of 23.0% for HIV, 16.5% for syphilis, 12.5% for NG, 6.5% for genital herpes, 5.0% for condyloma acuminata, and 2.5% for CT. HIV/STD testing was associated with living environment in Guangzhou, having medical insurance in China, and utilizing health services in China in the past year. HIV/STDs are prevalent among Africans in Guangzhou, and the epidemic is likely to spread due to a significant proportion of unprotected sexual behaviors and low rates of HIV/STD testing. Urgent interventions, including targeted health education, promotion of health service utilization, and active surveillance of HIV/STDs, are needed to reduce the risk of HIV/STD transmission.

Ras inhibitor farnesylthiosalicylic acid conjugated with IR783 dye exhibits improved tumor-targeting and altered anti-breast cancer mechanisms in mice.

Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of the conjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2-10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes it possible to return FTS back to the clinic with a better efficacy.

Gonorrhoea treatment guideline compliance and influence factors in Guangdong province, China: a cross-sectional survey.

BACKGROUND: The indiscriminate use of antibiotics has accelerated antimicrobial resistance (AMR) in Neisseria gonorrhoeae (NG), emphasising the need to follow treatment guidelines. This study aimed to assess the rate of adherence to standard treatment among patients with gonorrhoea and identify influencing factors. METHODS: A survey was conducted in Guangdong province, China, involving uncomplicated gonorrhoea cases registered in the Chinese Information System for Disease Control and Prevention. Data on demographic characteristics and medical information were collected to determine the standard treatment rate, defined as the proportion of patients receiving treatment according to national guidelines (ie, a single dose of ceftriaxone 250 mg, spectinomycin 2 g, cefotaxime 1 g or other third-generation cephalosporins). Medication choices were documented. χ² tests and multilevel logistic regression were used to analyse factors associated with standard treatment. RESULTS: The survey included 2424 patients with gonorrhoea from 59 hospitals. The standard treatment rate was 30.7% (743/2424), with 36.2% for females and 29.6% for males. Common reasons for substandard treatment included the use of non-guideline medications (42.3%, 710/1681) and incorrect dosing (36.2%, 605/1681). Factors associated with the standard treatment rate included gender, address, educational level, department, physicians' training, number of diagnosed gonorrhoea cases and hospital level. CONCLUSION: The standard treatment rate for gonorrhoea in Guangdong province, China, is below expectations. Comprehensive measures, such as establishing a goal-directed monitoring system and implementing promotional activities, are needed to improve adherence to treatment guidelines.

Screening of differentially methylated genes in skeletal fluorosis of rats with different types and involvement of aberrant methylation of Cthrc1.

Fluoride is a widespread pollutant in the environment. There is a high risk of developing skeletal fluorosis from excessive fluoride exposure. Skeletal fluorosis has different phenotypes (including osteosclerotic, osteoporotic and osteomalacic) under the same fluoride exposure and depends on dietary nutrition. However, the existing mechanistic hypothesis of skeletal fluorosis cannot well explain the condition's different pathological manifestations and their logical relation with nutritional factors. Recent studies have shown that DNA methylation is involved in the occurrence and development of skeletal fluorosis. DNA methylation is dynamic throughout life and may be affected by nutrition and environmental factors. We speculated that fluoride exposure leads to the abnormal methylation of genes related to bone homeostasis under different nutritional statuses, resulting in different skeletal fluorosis phenotypes. The mRNA-Seq and target bisulfite sequencing (TBS) result showed differentially methylated genes in rats with different skeletal fluorosis types. The role of the differentially methylated gene Cthrc1 in the formation of different skeletal fluorosis types was explored in vivo and in vitro. Under normal nutritional conditions, fluoride exposure led to hypomethylation and high expression of Cthrc1 in osteoblasts through TET2 demethylase, which promoted osteoblast differentiation by activating Wnt3a/ß-catenin signalling pathway, and participated in the occurrence of osteosclerotic skeletal fluorosis. Meanwhile, the high CTHRC1 protein expression also inhibited osteoclast differentiation. Under poor dietary conditions, fluoride exposure led to hypermethylation and low expression of Cthrc1 in osteoblasts through DNMT1 methyltransferase, and increased the RANKL/OPG ratio, which promoted the osteoclast differentiation and participated in the occurrence of osteoporotic/osteomalacic skeletal fluorosis. Our study expands the understanding of the role of DNA methylation in regulating the formation of different skeletal fluorosis types and provides insights into new prevention and treatment strategies for patients with skeletal fluorosis.

Design, synthesis and immunological evaluation of monophosphoryl lipid A derivatives as adjuvants for a RBD-hFc based SARS-CoV-2 vaccine.

Toll-like receptor 4 (TLR4) is a reliable target for the development of vaccine adjuvants. To identify novel TLR4 ligands with improved immunological properties for use as adjuvants for a RBD-hFc based SARS-CoV-2 vaccine, herein, natural E. coli monophosphoryl lipid A (MPLA) and nine of its derivatives were designed and synthesized. Immunological evaluation showed that compounds 1, 3, 5 and 7 exhibited comparative or better adjuvant activity than clinically used Al adjuvants, and are expected to be a promising platform for the development of new adjuvants used for a RBD-hFc based SARS-CoV-2 vaccine. Preliminary structure-activity relationship analysis of the MPLA derivatives showed that the replacement of the functional groups at the C-1, C-4' or C-6' position of E. coli MPLA has an effect on its biological activity. In addition, we found that the combination of MPLA and Al was feasible for immunotherapy and could further enhance immune responses, providing a new direction toward the immunological enhancement of RBD-hFc based SARS-CoV-2 vaccines.

Oral delivery of the intracellular domain of the insulinoma-associated protein 2 (IA-2ic) by bacterium-like particles (BLPs) prevents type 1 diabetes mellitus in NOD mice.

Antigen-specific immune tolerance, which possesses great potential in preventing or curing type 1 diabetes mellitus (T1DM), can be induced by oral vaccination with T1DM-related autoantigens. However, direct administration of autoantigens via oral route exhibits a low tolerance-inducing effect as a result of the digestion of protein antigens in the gastrointestinal tract (GIT) and therefore, a large dosage of autoantigens may be needed. In this study, bacterium-like particles (BLPs) made from food-grade lactic acid bacteria were used to deliver the intracellular domain of the insulinoma-associated protein 2 (IA-2ic). For this purpose, BLPs-IA-2ic vaccine in which IA-2ic bound to the surface of BLPs was constructed. BLPs enhanced the stability of the delivered IA-2ic based on the stability analysis in vitro. Oral administration of BLPs-IA-2ic significantly reduced T1DM incidence in NOD mice. The mice fed BLPs-IA-2ic exhibited a significant reduction in insulitis and preserved the ability to secrete insulin. Immunologic analysis showed that oral vaccination with BLPs-IA-2ic induced antigen-specific T cell tolerance. The results revealed that the successful induction of immune tolerance was dependent on the immune deviation (in favor of T helper 2 responses) and CD4+CD25+FoxP3+ regulatory T cells. Hence, oral vaccination with BLPs-IA-2ic shows potential for application in preventing T1DM.

The Relationship Between Negative Life Events and Nonsuicidal Self-Injury Among Chinese Adolescents: A Moderated-Mediation Model.

Objective: This study aimed to investigate whether anxiety mediates the relationship between negative life events and nonsuicidal self-injury (NSSI) in adolescents and whether this mediating role is moderated through social support. Methods: The model consisted of an anonymous questionnaire survey of 506 Chinese adolescents (253 boys and 253 girls, mean age 15.11 years (SD = 1.83, range 11-18 years)). Self-designed questionnaires were used to collect demographic data. The frequency of NSSI, state anxiety, and social support degree of adolescents was assessed by the Adolescent Life Events Scale, the Chinese version of the Beck Anxiety Inventory, and the social support scale, respectively. Results: Negative life events were significantly and positively correlated with anxiety and the frequency of NSSI, and anxiety was significantly and positively correlated with the frequency of NSSI. The positive association between negative life events and the frequency of NSSI among adolescents was mediated by anxiety after controlling for demographic variables. Furthermore, this mediated relationship was moderated by social support. Conclusion: Anxiety was a potential mechanism linking negative life events to NSSI in adolescents and low social support important risk factor for amplifying this indirect effect. Our findings provide an empirical basis for reducing NSSI in adolescents.