Qingyuan People's Hospital

Screening recommendations for early onset prostate cancer (EOPC) vary significantly across countries and regions, with differences in the recommended starting age and screening frequency. Given these variations, a comprehensive global analysis of EOPC epidemiology and disease burden is essential to inform evidence-based, region-specific screening and intervention strategies.

Using data from the Global Burden of Diseases Study (1990-2021), we analyzed EOPC incidence, mortality, and disability-adjusted life-years (DALYs) across 204 countries, stratified by Sociodemographic Index (SDI) levels. Age-standardized rates and trends were assessed through estimated annual percentage change values. Risk factors, including smoking, milk intake, and calcium intake, were evaluated. Frontier analysis identified regions needing urgent intervention, while Bayesian age-period-cohort modeling projected EOPC trends through 2040.

In 2021, there were 58,694 new EOPC cases and 7927 related deaths globally. The highest burden was observed in high-SDI regions. Incidence, mortality, and DALYs increased across most SDI regions, except for a decline in mortality in high-SDI areas. Age-specific analysis showed rising EOPC burden across all age groups from 1990 to 2021, with the sharpest increases in the 45-49 and 50-54 years age groups. Risk factor analysis attributed 1% of DALYs to smoking, while low milk and calcium intake were protective (-10.2 and -2.8%, respectively). Projections indicate a continued rise in global EOPC burden through 2040.

This study provides critical insights into the global burden of EOPC, emphasizing the need for region-specific screening and prevention strategies to mitigate its impact.

Neisseria gonorrhoeae (NG), a bacterium characterised by multidrug resistance, is traditionally treated with ceftriaxone, either as a monotherapy or in conjunction with azithromycin. However, the emergence of strains resistant to these antibiotics presents a considerable challenge to current therapeutic approaches, which necessitates the exploration of alternative treatment strategies.

Agar dilution and broth microdilution to determine the minimum inhibitory concentrations (MICs) of antibiotics and 7,8-dihydroxyflavone. The development of 7,8-dihydroxyflavone drug resistance was detected under the treatment of sublethal concentration for 30 passages. Genotypic analysis was conducted to examine penA, 23S rRNA alleles and multilocus sequence typing.

55 clinical NG isolates emphasised the high-level rates of the current antimicrobial resistance, with a notable prevalence of the penA-60.001 FC428 clone and high-level azithromycin-resistant clones characterised by the 23S rRNA-1 (A2059G) and 23S rRNA-2 (C2611T) alleles. Among the strains that are representative of clinical circulation, 7,8-dihydroxyflavone demonstrated inhibitory activity, with MIC50 and MIC90 values of 10 mg/L and 20 mg/L, respectively, which are unlikely to induce drug resistance in NG.

7,8-dihydroxyflavone may represent a promising antimicrobial agent in the context of escalating antibiotic resistance.

Degradable polyester microspheres are commonly utilized in bone tissue engineering due to their excellent biocompatibility and controlled drug-release profiles. While poly(lactic-co-glycolic acid) (PLGA) microspheres offer rapid degradation but lack sufficient mechanical strength for prolonged implantation, polycaprolactone (PCL) microspheres, with their slower degradation rate and hydrophobic nature, are less suitable for short-term drug-release applications. In this study, PLGA-based degradable polyester microspheres were modified by introducing mesoporous calcium silicate (MCS) with a high specific surface area of 623.59 m²/g and a pore volume of 1.81 cm³/g and PCL and loaded with bone morphogenetic protein-2 (BMP-2). The self-catalytic hydrolysis of composite microspheres (BMGACL) enables sustained and controlled BMP-2 release over 98 days, supporting the entire bone regeneration process. Additionally, mesoporous calcium silicate enhances the microspheres' mechanical properties, providing effective structural support for bone defects. Compared to other groups, BMGACL microspheres significantly promoted the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). Notably, the BMP-2 released by composite microspheres can regulate macrophage polarization to M2 phenotype through multiple signaling pathways including cGMP-PKG and TGF-β. In an immune microenvironment enriched with M2-associated macrophages, this process induces BMSCs to express osteogenic genes. Simultaneously, it enhances the deposition of bone formation markers such as alkaline phosphatase (AP) and calcium nodules, with levels reaching 3.7 times and 20.5 times higher than those in the control group, respectively. In summary, this study proposes an efficient biodegradable polyester drug-loaded microsphere system that holds promise for advancing clinical translation of bone defect repair materials.