Exploration for the Priority of HIV Intervention: Modelling Health Impact and Cost-Effectiveness - Six Cities, Eastern China, 2019-2028.

Introduction: In order to enhance the effectiveness of resource allocation, regions must tailor their responses to their specific epidemiological and economic situations. Methods: Utilizing Spectrum software, we projected the cost-effectiveness of 10 chosen HIV interventions in six cities in eastern China from 2019 to 2028. We assessed three scenarios - Base, Achievable, and Idealized - for each city. The analysis included the projected number of HIV infections and deaths averted, as well as the incremental cost-effectiveness ratios for each intervention in the six cities. Results: In Shijiazhuang, Wuxi, Yantai, and Zhenjiang, cities with initially low antiretroviral therapy (ART) coverage, ART showed significant effectiveness, especially for males. Conversely, in Foshan and Ningbo, where ART coverage was notably high, oral pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM) proved effective in the Idealized scenario. MSM outreach, ART for males, and ART for females demonstrated cost-effectiveness across all six cities in both Achievable and Idealized scenarios at the predefined thresholds for each city. Discussion: Maintaining an appropriate coverage rate for outreach to MSM can lead to cost-effectiveness. In cities with low ART coverage, scaling up ART remains a crucial intervention. In regions with high ART coverage, consideration may be given to the utilization of oral PrEP for MSM individuals, requiring budget allocation.

Suppression of lysosome metabolism-meditated GARP/TGF-ß1 complexes specifically depletes regulatory T cells to inhibit breast cancer metastasis.

Regulatory T cells (Tregs) prevent autoimmunity and contribute to cancer progression. They exert contact-dependent inhibition of immune cells through the production of active transforming growth factor-ß1 (TGF-ß1). However, the absence of a specific surface marker makes inhibiting the production of active TGF-ß1 to specifically deplete human Tregs but not other cell types a challenge. TGF-ß1 in an inactive form binds to Tregs membrane protein Glycoprotein A Repetitions Predominant (GARP) and then activates it via an unknown mechanism. Here, we demonstrated that tumour necrosis factor receptor-associated factor 3 interacting protein 3 (TRAF3IP3) in the Treg lysosome is involved in this activation mechanism. Using a novel naphthalenelactam-platinum-based anticancer drug (NPt), we developed a new synergistic effect by suppressing ATP-binding cassette subfamily B member 9 (ABCB9) and TRAF3IP3-mediated divergent lysosomal metabolic programs in tumors and human Tregs to block the production of active GARP/TGF-ß1 for remodeling the tumor microenvironment. Mechanistically, NPt is stored in Treg lysosome to inhibit TRAF3IP3-meditated GARP/TGF-ß1 complex activation to specifically deplete Tregs. In addition, by promoting the expression of ABCB9 in lysosome membrane, NPt inhibits SARA/p-SMAD2/3 through CHRD-induced TGF-ß1 signaling pathway. In addition to expose a previously undefined divergent lysosomal metabolic program-meditated GARP/TGF-ß1 complex blockade by exploring the inherent metabolic plasticity, NPt may serve as a therapeutic tool to boost unrecognized Treg-based immune responses to infection or cancer via a mechanism distinct from traditional platinum drugs and currently available immune-modulatory antibodies.

Anti-prostate cancer mechanism of black ginseng during the "nine steaming and nine sun-drying" process based on HPLC analysis combined with vector space network pharmacology.

HPLC analysis determined six small-molecule organic acids, maltol, 5-hydroxymethylfurfural (5-HMF), 17 ginsenosides, four oligosaccharides, and 20 amino acids in black ginseng samples with different processing times. Based on the content determination results, the differential ingredients in the processing of black ginseng were screened by multivariate statistical analysis. Network pharmacological methods obtained the core targets and pathways of the above ingredients against prostate cancer. Finally, the entropy weight method was used to assign values to the above ingredients, targets, and pathways, and the vector space network pharmacology method was established to study the anti-prostate cancer mechanism of black ginseng in the process of "nine steaming and nine sun-drying". Based on principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), fructose, glucose, dencichin, glutamate, ginsenoside 20 (S)-Rg3, 20 (R)-Rg3, 20 (S)-Rh2, Rg1, Re, and Rc were the main differential ingredients in various steaming and sun-drying cycle periods of black ginseng. The results of vector space network pharmacology showed that the main reason for the change in the anti-prostate cancer pathway of black ginseng with the number of steaming and sun-drying was the different regulatory ability of black ginseng on the PI3K-Akt signaling pathway and chemical carcinogenesis-receptor activation pathway. It gave researchers a fresh perspective for exploring the anti-prostate cancer active components of black ginseng and the change in the mechanism of the effect of traditional Chinese medicine in processing.

Effects of personality traits on bus drivers' prosocial and aggressive behaviours: The moderated mediating role of risk perception and gender.

PURPOSE: The present study aimed to examine the effects of personality traits on bus drivers' self-reported prosocial and aggressive driving behaviours as well as the mediating role of risk perception and the moderating role of gender in this relationship. METHODS: Three hundred and ten bus drivers who were 24-57 years old agreed to participate in this study. The measures utilized included personality scales, a risk perception scale and a prosocial and aggressive driving behaviour scale. RESULTS: A moderated mediation model was established. The effects of normlessness/anger on prosocial driving behaviour are mediated by risk perception. Risk perception has a stronger promoting effect on the prosocial driving behaviour of male drivers (b = 0.358, p < 0.01) than it does on that of female drivers (b = 0.072, p > 0.05). The effects of normlessness/anger on the aggressive driving behaviour of both male and female drivers are also mediated by risk perception. Moreover, gender plays a moderating role in the influences of personality and risk perception on aggressive driving behaviour. Drivers with higher risk perception and less anger exhibit less aggressive driving behaviour, and this effect is clearer among male drivers than it is among female drivers. CONCLUSION: The present study revealed the relationship between personality traits and the prosocial and aggressive driving behaviours of bus drivers through a moderated mediation model. These findings highlight the importance of taking risk perception and gender into consideration when examining the effects of personality on bus drivers' driving behaviours.

Estimating Costs of the HIV Comprehensive Intervention Using the Spectrum Model - China, 2015-2019.

Introduction: In order to facilitate human immunodeficiency virus (HIV) treatment and prevention, the resource needs for HIV national strategic planning in developing regions were estimated based on Spectrum, the universal HIV cost-effectiveness analysis software. Methods: Based on the theoretical framework of Spectrum, the study developed a cost measurement tool for HIV, and calculated the cost of HIV prevention and control in 6 sampled cities in China during 2015-2019 using the Spectrum model. Results: From 2015 to 2019, the average annual costs for HIV prevention and control for Shijiazhuang, Yantai, Ningbo, Zhenjiang, Foshan, and Wuxi cities were 46.78, 47.55, 137.49, 24.73, 74.37, and 58.30 million Chinese yuan (CNY), respectively. The per capita costs were 4.37, 6.73, 17.33, 7.77, 17.56, and 8.91 CNY, respectively. In terms of the cost structure, the ratio of preventive intervention funds to therapeutic intervention funds (antiviral treatment) varied in sampled cities. Discussion: Developing comprehensive and systematic HIV fund calculation methods can provide a research basis for rational resource allocation in the field of HIV.

Stated preferences for family doctor contract services: a survey of the rural elderly in Anhui Province, China.

OBJECTIVE: A number of factors contribute to the utilisation of family doctor contract services (FDCS) in China. This study aims to measure the preferences of the elderly for the FDCS and identify the key factors (and their relative importance) that may guide policymakers in more accurately providing the FDCS. PARTICIPANTS AND METHODS: A discrete choice experiment was performed to elicit the preferences for FDCS among the rural elderly in China. Attributes and levels were established based on qualitative methods. Four attributes were included: service type, service package, physician's reputation and annual contract costs. A D-efficient design was used to create a set of profiles that represented FDCS. The survey was conducted face to face using a sample of participants aged 60 and above in rural areas of Anhui Province. The data were analysed using a latent class logit (LCL) model. RESULTS: A total of 545 valid questionnaires were included in the analysis. The average age of the participants was 69.44 (SD 5.80). Two latent classes were identified with the LCL model. All four attributes proved statistically significant at the level of both the population mean and the two classes. The rural elderly showed a preference for FDCS with a relatively good reputation, lower annual contract costs, the basic service with the add-on of chronic disease service and home visit. Age, gender, education, self-reported health status and the number of chronic diseases were found to be associated with latent class membership. CONCLUSION: In this study, the physician's reputation had the largest impact on the rural elderly's choice of FDCS. Policy recommendations included the need to strengthen family doctor team training, devote greater attention to improving the family doctor's medical skills and service approaches, and increased FDCS efficiency for the care of the rural elderly.

Scoparone protects neuronal cells from oxygen glucose deprivation/reoxygenation injury.

Ischemic stroke is one of the leading causes of death and disability in the world. The cerebral ischemia/reperfusion (I/R) injury is considered as the major molecular mechanism in the pathogenesis of ischemic stroke. Scoparone, a major constituent of Artemisia capillaries, has been found to exhibit protective effects against I/R-induced myocardial injury. However, the role of scoparone in cerebral I/R injury has not been elucidated. In the current study, the hippocampal neurons were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate I/R injury in vitro. The results showed that scoparone improved OGD/R-induced inhibitory effect on cell viability of hippocampal neurons. Scoparone displayed anti-oxidative activity as proved by the decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in OGD/R-induced hippocampal neurons. In addition, cell apoptosis was markedly decreased after scoparone treatment in OGD/R-induced hippocampal neurons. The expression of bax was significantly decreased, while bcl-2 expression was increased in the scoparone pretreated hippocampal neurons. Furthermore, the expressions of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were obviously induced by scoparone. Knockdown of Nrf2 by siRNA transfection dramatically attenuated the protective effects of scoparone on OGD/R-induced hippocampal neurons. Collectively, scoparone protected hippocampal neurons from OGD/R-induced injury via activating Nrf2/HO-1 signaling pathway, suggesting that scoparone might be a potential agent for the ischemic stroke therapy.

Tangeretin protects human brain microvascular endothelial cells against oxygen-glucose deprivation-induced injury.

Tangeretin, a citrus flavonoid extracted from the peel of citrus fruits, was reported to possess antiasthmatic, antioxidant, anti-inflammatory, and neuroprotective properties. However, the effect of tangeretin on human brain microvascular endothelial cells (HBMECs) has not been examined. This study was designed to investigate the protective effects of tangeretin on oxygen-glucose deprivation (OGD)-induced injury of HBMECs, and explore the underlying mechanisms. Our results showed that tangeretin improved HBMECs viability in response to OGD. In addition, tangeretin was able to increase the activity of superoxide dismutase and decrease the levels of reactive oxygen species and malondialdehyde (MDA), as well as ameliorate cell apoptosis in OGD-stimulated HBMECs. Mechanistic studies showed that tangeretin prevented the activation of JNK signaling pathway in OGD-stimulated HBMECs. Taken together, our current study demonstrated that tangeretin could ameliorate OGD-induced HBMECs injury through the JNK signaling pathway. Thus, tangeretin might be used as a therapeutic strategy for ischemia-reperfusion brain injury and related diseases.

Telmisartan regulates the development of cerebral ischemia by alleviating endoplasmic reticulum stress.

Recent studies have shown that telmisartan (TMS) is effective for the protection against ischemia/brain damage in rat models. However, the specific underlying mechanism is poorly understood. In line with previous results, our data showed that TMS improves CBF and physiological variables, including pH, pCO2, pO2. Through CD31 immunofluorescence staining, reduction of blood vessel density was found in MCAO group, but TMS treatment could enhance the cerebral vascular density in the ischemic area. Meanwhile, TMS treatment could enhance the number of BrdU/lectin double-positive cells. Furthermore, the reduction of nestin-positive cells was identified in the brain of MCAO rats, while the number of nestin-positive cells was significantly increased after TMS administration. Furthermore, the expression of ERS-related proteins, including GRP78, CHOP/GADD153, Caspase12 was increased after MCAO, but was decreased after administration of TMS, thereby enhancing angiogenesis and neuron regeneration.

Gender disparities in the association between socio-demographics and non-communicable disease risk factors among adults with disabilities in Shanghai, China.

BACKGROUND: Non-communicable disease (NCD) risk factors can co-exist with disability and cause a greater burden on the health status of adults with disabilities. A lack of egalitarian social policies in China may result in gender disparities in the NCD risk factors of adults with disabilities. However, little is known about the gender disparities in the association between socio-demographics and NCD risk factors among adults with disabilities in China; consequently, we examined this association among adults with disabilities in Shanghai, China. METHODS: We used the health examination data of 44,896 adults with disabilities in Shanghai in 2014. Descriptive analyses and logistic regression models were conducted to estimate gender disparities in the association between socio-demographics, disability characteristics, and four selected NCD risk factors among adults with disabilities-including high blood pressure, high blood glucose, high blood lipids, and being overweight. We estimated marginal effects (MEs) on NCD risk factors between gender and other confounders. RESULTS: Women with disabilities were about 11.6 percentage points more likely to suffer from high blood lipids and less likely to develop the other three risk factors than men were. The association of age group, residence permit, education level, marital status, and disability type with health outcomes varied by gender among adults with disabilities. The difference in age effects between men and women was more pronounced in older age groups. Urban residence was associated with less risk of high blood pressure risk among women (ΔME =  - 0.035, p < 0.01), but no significant difference in other NCD risk factors. Education remained a major protective factor against high blood pressure, high blood glucose and being overweight among women with disabilities (MEs < 0, p < 0.05); however, this did not hold for men. The difference in marriage effects between men and women was observed in high blood lipids (ΔME =  - 0.048 for the married group and -0.054 for the divorced or widowed group) and overweight individuals (ΔME =  - 0.091 for the married group and -0.114 for the divorced or widowed group). Women with intellectual disabilities or mental disabilities reported worse health conditions than men did. DISCUSSION: Preventive strategies and interventions on NCD risk factors for adults with disabilities should take into account gender disparities in these socio-demographic effects. Rural women or poorly educated women with disabilities can be a vulnerable population that requires more health education and promotion strategies. Health education for caregivers of women with intellectual or mental disabilities may also play a vital role in preventing their NCD risk factors.

The complete mitochondrial genome of the Parastromateus niger (Perciformes, Carangidae).

In this study, we have sequenced the complete mitochondrial genome of the Parastromateus niger. The mitochondrial genome is 16,561 bp long and contains 13 protein-coding genes, two rRNA genes, 22 tRNA genes and a control region. The gene order and composition of Parastromateus niger mitochondrial genome is similar to that of most other vertebrates. The nucleotide compositions of the light strand are 28.23% of A, 29.51% of C, 26.01% of T and 16.16% of G. With the exception of five tRNA genes, all other mitochondrial genes are encoded on the heavy strand.