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Metastatic pancreatic ductal adenocarcinoma (mPDAC) is one of the most aggressive malignancies with a very poor prognosis. Currently, there is no standardized therapeutic approach for third-line systemic treatment. The aim of this retrospective/prospective study was to evaluate survival outcomes in patients treated in the third-line setting and to analyze the impact of nutritional and inflammatory biomarkers on overall survival (OS) and progression-free survival (PFS). The analysis retrospectively and prospectively included 95 patients with mPDAC treated with third-line systemic therapy. Data were collected from the Slovak Pancreas Registry. Data were collected from 13 hospitals. Baseline chemotherapy regimens, ECOG, nutritional, and inflammatory parameters were recorded and used to calculate prognostic scores (PNI, CRP, NLR, SII, SIRI, GPS). Their association with OS and PFS was analyzed using the log-rank test and Kaplan-Meier survival analysis. The most frequently used regimen was FOLFOX/CAPOX (56 patients), followed by nanoliposomal irinotecan (nal-IRI, 24 patients) and capecitabine (11 patients). The median OS was 5.55 months and the median PFS was 3.29 months. A PNI > 40.5 was significantly associated with longer OS (6.34 vs. 3.32 months, p=0.001) and PFS (3.71 vs. 2.76 months, p=0.009). Lower GPS scores were significantly associated with improved OS (p=0.006) and PFS (p=0.027). Other inflammatory markers (NLR, SIRI, SII, CRP) did not show a statistically significant impact on OS or PFS. Third-line systemic therapy may offer clinical benefit in selected mPDAC patients, particularly in those with favorable nutritional-inflammatory profiles. The Prognostic Nutritional Index (PNI) and Glasgow Prognostic Score (GPS) appear to be potentially useful tools for identifying candidates suitable for further systemic treatment. However, further prospective studies are needed to confirm these findings.

The global tuberculosis (TB) epidemic imposes a substantial burden. As a high-burden country, China faces a significant gap from the World Health Organization (WHO)'s 2025-2030TB prevention and control targets. This study analyzed the temporal trends of TB epidemiology in mainland China to provide an evidence base for the early achievement of TB control goals. We integrated TB surveillance data (2004-2024) from the National Health Commission of the People's Republic of China and population data from the National Bureau of Statistics. Joinpoint regression was used to identify trend changes, with the average annual percent change (AAPC) quantifying trend magnitudes. Interrupted time series model was applied to assess intervention effects, and seasonal autoregressive integrated moving average models were employed to predict future incidence and mortality trends. A total of 19.4854 million cumulative TB cases and 508,000 cumulative deaths were reported during 2004-2024. The incidence rate decreased from 74.644 to 49.888 per 100,000 population (AAPC = -2.83%, P < 0.001), showing a "winter peak and summer trough" pattern-with a 32.7% higher incidence in winter than in summer. The mortality rate first decreased and then increased: it declined immediately after the full coverage of Directly Observed Treatment, Short-course in 2010 but rose to 0.283 per 100,000 population after 2021. Projections indicate that the achievement rate of the WHO incidence target will be only 43.24% by 2025 (target: 31.708 per 100,000 population) and 39.48% by 2030 (target: 12.683 per 100,000 population). The mortality rate is projected to reach 0.333 per 100,000 population by 2030, compared with the target of 0.013 per 100,000 population. Despite notable achievements in TB control in China, significant gaps remain from the WHO's targets. It is imperative to strengthen precision stratification-based prevention and control, establish a TB diagnosis and treatment guarantee mechanism, and implement remote supervision relying on informatization.

Infectious diseases remain a leading cause of morbidity and mortality in resource-limited settings, exacerbated by inadequate health literacy, poor adherence to preventive measures, and constrained healthcare infrastructure. This paper proposes the Community-Level Infectious Disease Education and Adherence Model (CIDEAM), an integrated, culturally sensitive framework designed to enhance disease prevention, treatment adherence, and health outcomes in underserved populations. The model emphasizes participatory education strategies, community health worker engagement, and context-appropriate communication channels to bridge knowledge gaps and foster behavioral change. Drawing from evidence-based interventions and socio-behavioral theories, CIDEAM incorporates peer-led workshops, visual and audio educational tools in local languages, and interactive community dialogues to improve understanding of disease transmission, symptoms, treatment protocols, and prevention methods. It also integrates adherence monitoring mechanisms such as mobile health (mHealth) reminders, household follow-up visits, and social support groups to reinforce compliance with medical regimens, particularly for chronic and high-burden infections like tuberculosis, HIV/AIDS, and malaria. The model accounts for socio-economic determinants of health by incorporating strategies to address stigma, misinformation, and barriers to accessing healthcare services, thereby promoting trust and collaboration between communities and healthcare providers. Implementation in resource-limited contexts is supported by capacity-building initiatives for community health workers, partnerships with local leaders, and the leveraging of low-cost digital technologies. Pilot studies suggest that CIDEAM can significantly improve treatment adherence rates, reduce infection incidence, and strengthen community resilience against outbreaks. The model’s adaptability ensures relevance across diverse cultural and epidemiological contexts, making it a scalable and sustainable solution for global health initiatives targeting infectious disease control in marginalized populations. By integrating education, adherence support, and socio-cultural considerations, CIDEAM offers a pathway to reducing infectious disease burdens while empowering communities to take ownership of their health outcomes. Keywords: Community Health Education, Infectious Disease Prevention, Treatment Adherence, Resource-Limited Settings, Health Literacy, Mhealth, Community Engagement, Behavioral Change, Disease Control, Global Health.

Abstract Objective : High heterogeneity and poor therapeutic response are major challenges in hepatocellular carcinoma (HCC). This study aimed to identify core hepatocyte subsets and key genes driving HCC progression via a multi-omics approach to inform precise diagnosis and treatment. Methods : We analyzed public data from GEO (GSE282701), TCGA-LIHC, and IEU-Open-GWAS (bbj-a-158). scRNA-seq, scPagwas, BayesPrism, and WGCNA were used to identify core HCC cell subsets and genes. SF3B4 expression was validated by Western blot and RT-qPCR in HCC tissues and cell lines. Functional impacts on proliferation and migration were assessed using colony formation, Transwell, and wound healing assays in HepG2 and Huh7 cells. Results : Integrated scRNA-seq and scPagwas analysis identified PKHD1⁺ hepatocytes as a core HCC subset, showing significantly higher trait relevance scores versus other subtypes and a positive correlation with HCC (P &lt; 0.05). BayesPrirm quantification in the TCGA-LIHC cohort confirmed that high abundance of PKHD1⁺ hepatocytes correlated with poor prognosis (P &lt; 0.05), immune microenvironment remodeling (increased CAFs and MDSCs), and distinct somatic mutation profiles (elevated CTNNB1 and reduced TP53 mutation rates). SF3B4 was identified as the key gene associated with this subset via WGCNA and differential expression analysis. SF3B4 was upregulated in HCC tissues and cells, and its knockdown suppressed proliferation and migration in HepG2 and Huh7 cells. Conclusion : The PKHD1⁺ hepatocyte subset and SF3B4 represent key regulators of HCC malignancy, offering novel potential targets for prognostic assessment and targeted therapy.

Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are common etiologic agents of reproductive tract infections (RTIs) with high global prevalence and the potential to cause adverse genital outcomes. This study assessed the positivity rates and co-infection patterns of UU, CT, NG, and HSV among women in Xihu District, Hangzhou, Zhejiang Province, China. We analyzed 5,577 female genital tract specimens collected from January 2018 to December 2024 at Tongde Hospital of Zhejiang Province. Pathogen DNA was detected using real-time PCR. UU susceptibility testing was performed with the Mycoplasma Identification and Susceptibility Test Kit. Among 5,577 specimens, positivity rates were 49.11% for UU, 7.48% for CT, 1.88% for NG, and 10.52% for HSV. A total of 118 mixed infections involving two or more pathogens were identified; the most frequent combination was UU + CT, accounting for 73.73% of mixed infections. UU was the most common organism in co-infections, present in more than 96% of mixed-infection cases. Significant associations were observed between UU and CT (p < 0.001) and between UU and NG (p < 0.05). The overall pathogen positivity rate increased over the seven-year period (p < 0.01). Younger women (≤ 19 years) had the highest positivity for UU, CT, NG, and HSV-1, whereas older women (> 60 years) had the highest HSV-2 positivity. More than 95% of UU isolates were susceptible to doxycycline, minocycline, and josamycin. This study characterizes the epidemiology of UU, CT, NG, and HSV in real-world obstetrics and gynecology outpatient settings in Xihu District, Hangzhou. Given the elevated positivity among younger women, targeted health education and management strategies are warranted.