Sean Xiao Leng

UNSTRUCTURED Vaccine uptake among older adults remains below policy targets even in high-income health systems. Digital interventions, such as text reminders, patient-portal nudges, electronic letters, mobile applications, conversational chatbots, and social-media campaigns have been increasingly employed to close the behavioral and delivery gaps related to vaccination coverage. While each of these measures showed situational effects in randomized trials, population-scale evaluations have largely produced null findings when these tools are deployed to populations whose dominant barrier is mistrust, hesitancy, or service inaccessibility. Here, we propose Digital Vaccine Prescription (DVP) as a testable, hypothesis-generating framework that adds value to the empirically established existing reminder/recall systems, immunization information systems, and digital outreach tools. The framework links six components - eligibility identification, trusted recommendation, tailored communication, actionable access, reminder/recall, and verification - into a recurrent immunization pathway supported by four implementation pillars: data infrastructure, clinical workflow, equity safeguards, and governance. For older adults, the framework's most distinctive commitment is that digital identification is paired with human-supported follow-up. This is because older adults represent an at-risk population with challenges in terms of trust, multimorbidity, sensory impairment, and caregiver dependence that cannot be addressed by digital deployment alone. A research agenda is also proposed to test whether DVP as a coherent intervention improves vaccination coverage more than its individual components.

Background: Stroke rehabilitation can generate substantial inpatient expenditure, yet evidence on how payment modality is associated with cumulative expenditure and expenditure composition remains limited. We examined these associations among rehabilitation patients in five Chinese hospitals and assessed whether they varied by hospital tier and disease chronicity. Methods: This retrospective observational study included 8,041 eligible admissions from January 2018 to December 2025, aggregated to 4,945 unique patients by identification number. Expenditures and length of stay were summed across included admissions for each patient. Total gross inpatient expenditure was divided into rehabilitative therapy, hospital bed, nursing care, medications, laboratory/examination, and other recorded services. Patient characteristics included sex, age, insurance, disease chronicity, hospitalization count, cumulative length of stay, and Charlson Comorbidity Index (CCI). Generalized linear models with a gamma distribution and log link and robust standard errors estimated adjusted associations; payment-by-tier and payment-by-chronicity interactions were examined. Results: Mean cumulative hospitalization expenditure was US$11,317 (SD US$15,231; median US$6,313, IQR US$2,677–13,925). Rehabilitative therapy represented 31.2% of expenditure, medications 24.4%, other recorded services 19.0%, hospital bed 12.1%, laboratory/examination 7.6%, and nursing care 5.7%. Compared with fee-for-service, DRG/DIP payment was associated with significantly lower total expenditure ( β = −0.077, p = 0.010) and per-diem payment with a larger negative association ( β = −0.418, p < 0.001). The per-diem association was more negative in tertiary than in secondary hospitals (interaction β = −0.161, p = 0.017) and among patients with longer disease chronicity (3–6 months: β = −0.203, p = 0.004; >6 months: β = −0.351, p < 0.001). Conclusion: DRG/DIP and per-diem payment were associated with lower cumulative hospitalization expenditure than fee-for-service after adjustment for measured patient and hospital characteristics. Because payment assignment was non-random and key clinical severity measures were unavailable, these findings should be interpreted as associations rather than causal effects.

Bacterial heteroresistance, characterized by the presence of antibiotic-resistant subpopulations within phenotypically susceptible bacterial colonies, poses significant challenges to clinical antimicrobial susceptibility testing and treatment outcomes. While heteroresistance has been increasingly recognized across diverse bacterial species, the underlying mechanisms in Pseudomonas aeruginosa remain incompletely understood, particularly regarding carbapenem and monobactam resistance. In this study, we employed a multi-omics approach that integrates phenotypic screening, whole-genome sequencing, core genome multilocus sequence typing, and quantitative transcriptomic analysis to systematically investigate the phenotypic characteristics and mechanistic basis of heteroresistance in 38 non-duplicative clinical Pseudomonas aeruginosa samples. The findings reveal a high prevalence of heteroresistance among clinical isolates, and it is difficult to detect using currently commonly used automated detection methods, such as the VITEK 2 system. The comparative genomic analysis demonstrated that resistant and non-resistant subpopulations exhibit identical resistance gene repertoires, with no detectable genetic mutations, gene amplification, or plasmid acquisition. Instead, we identify differential expression of key resistance genes ( mexA , ampC, and oprD ) as the primary driver of heteroresistance, with the two-component system ParS/ParR negatively correlating with oprD expression ( r = −0.797, P < 0.05). Furthermore, phenotypic validation using efflux pump and AmpC inhibitors substantiated the functional contribution of these mechanisms. Our findings indicate that Pseudomonas aeruginosa utilizes dynamic transcriptional regulation rather than genetic alteration to evade antibiotic pressure, representing a distinct evolutionary strategy for survival under antimicrobial stress. IMPORTANCE: The clinical implications of our findings are profound. The stable inheritance of HR phenotypes implies that resistant subpopulations can persist as cryptic reservoirs within susceptible populations, evading routine antimicrobial susceptibility testing and potentially leading to relapse or treatment failure. Moreover, the fact that HR is driven by transcriptional rather than genetic mechanisms means that standard molecular diagnostics targeting resistance genes would fail to identify these strains. This highlights the urgent need for diagnostic approaches that capture functional resistance phenotypes or transcriptional signatures.

Invasive meningococcal disease (IMD) in older adults frequently presents with atypical clinical manifestations, including bacteremic pneumonia, often without classical meningeal signs or sepsis, which presents clinicians with diagnostic challenges, and may delay treatment, which contributes to the high mortality observed in older adults. Within the broader resurgence of IMD observed since relaxation of quarantine measures introduced to mitigate the impact of the COVID-19 pandemic, there has been a notable increase in reporting of such atypical cases. The aim of this review is to summarize epidemiological, diagnostic, and treatment aspects of non-meningeal forms of IMD in older patients, with a focus on meningococcal pneumonia. By convention, laboratory confirmation requires N. meningitidis detection by culture, polymerase chain reaction (PCR), or antigen detection. In most cases, presentation of meningococcal pneumonia is similar to that of other forms of community-acquired pneumonia, and cerebrospinal fluid sampling may be non-informative. This places a premium on early blood culture for N. meningitidis, allied with testing of respiratory samples (e.g., broncho-alveolar washes). Many cases are linked to isolates of serogroups Y and W. When confirmed, treatment with third-generation cephalosporins is generally preferred. Chemoprophylaxis and vaccination of close contacts is essential for controlling onward meningococcal disease transmission and prevention of further cases.

Background: Influenza presents significant risks to older adults; however, vaccination coverage in China remains low despite robust recommendations. Factors such as vaccine hesitancy, physician recommendations, health status, and socioeconomic conditions influence vaccination rates. This study uses large-scale influenza vaccination data from urban older adults in six cities and applies structural equation modeling to investigate the determinants of both influenza vaccination uptake and future intention. Methods: A cross-sectional survey was conducted from December 2024 to January 2025 across six major Chinese cities, involving 13,363 community-dwelling adults aged ≥60 years. Vaccine hesitancy was measured using the validated 5C scale. Structural equation modeling with weighted least squares mean and variance adjusted estimation was employed to assess direct and indirect effects of physician recommendation, socioeconomic status, medical status, and subjective health on influenza vaccination uptake. Results: The vaccination uptake rate is 34.05%, while the intention rate is 32.20%. Vaccine hesitancy is the strongest negative predictor of vaccination (β = −0.488, p < 0.001). Physician recommendation has the largest total effect (β = 0.351), with 45.60% of this effect mediated through reduced vaccine hesitancy. Medical status is directly associated with lower uptake; it consistently promoted intention. Higher socioeconomic status also positively affected vaccination (total effect = 0.167), partly via lower hesitancy. Conclusions: Vaccine hesitancy serves as a pivotal mediator in influenza vaccination uptake and intention among Chinese older adults. Strengthening physician recommendations and addressing socioeconomic disparities are key strategies to reduce hesitancy and improve coverage.

Despite its rapid economic rise over the past four decades, China now grapples with the challenge of accommodating and supporting its expanding aging population. In 2020, 18% of its population were over age 60, and 2.5% were over age 80, projected to rise to 39% and 10%, respectively, by 2050. This demographic shift places China at the forefront of diverse individual, familial and societal challenges. Here, we review these challenges in the context of emerging breakthroughs in basic and translational research, shifts in healthcare paradigms, evolving socioeconomic and political dynamics, and policy innovations. We synthesize China’s current policies toward promoting healthy longevity in the general population, focusing on social health insurance, long-term care insurance, community and home-based care and palliative care, as well as gerontological research, public health prevention, nutritional and medical interventions, while identifying strengths and gaps. Finally, we propose suggestions to promote a more inclusive, resilient and happier aging society within China’s distinctive sociopolitical and cultural context.

Sex differences in the humoral immune responses to the seasonal quadrivalent influenza vaccine (QIV) in young adults (YA; 18-49yo) or high dose QIV in old adults (OA; 75+yo) were analyzed to evaluate how age-related changes in steroids impact sex differences in B cell responses. Prior to vaccination, CD19+ B cells from OAs, regardless of sex, showed greater enrichment of hallmark pathways associated with inflammatory responses than YAs. Among YAs, females had greater H3N2, but not H1N1, neutralizing antibody titers and greater proportions of hemagglutinin (HA)+CD19+ B cells and HA+ memory B cells than males through 28 days post-vaccination (DPV), which was not observed among OAs. CD19+ B cells from YA females had greater transcriptional activity at 7 DPV than YA males, with upregulation of estrogen-responsive genes and NF-κB-mediated inflammatory pathways in B cell subsets. HA stimulation and treatment of antibody secreting cells (ASCs) from YAs and OAs with estradiol increased the number and size of HA+IgG+ ASCs from YA females and to a lesser extent OA females, but not males, which was inhibited by estrogen receptor antagonism. Machine learning algorithms illustrated that baseline (0 DPV) steroids, including 17-hydroxyprogesterone, estrogens, and testosterone, as well as HA+CD19+ B cells and HA+ ASCs were major predictors of subsequent seroconversion at 28 DPV, particularly in YA. This study provides mechanistic insights into steroid mediation of greater influenza vaccine-induced immunity among reproductive-aged females as compared with age-matched males and explains how sex differences in vaccine-induced immunity are reduced with old age. One Sentence Summary Estrogenic activity in B cells causes greater influenza vaccine-induced immunity in young adult females than age-matched males, with these sex differences being mitigated in old adults.

As age increases, the immune function of elderly individuals gradually decreases, increasing their susceptibility to infectious diseases. Therefore, further research on common viral infections in the elderly population, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses, is crucial for scientific progress. This review delves into the genetic structure, infection mechanisms, and impact of coinfections with these two viruses and provides a detailed analysis of the reasons for the increased susceptibility of elderly individuals to dual viral infections. We evaluated the clinical manifestations in elderly individuals following coinfections, including complications in the respiratory, gastrointestinal, nervous, and cardiovascular systems. Ultimately, we have summarized the current strategies for the prevention, diagnosis, and treatment of SARS-CoV-2 and influenza coinfections in older adults. Through these studies, we aim to reduce the risk of dual infections in elderly individuals and provide a scientific basis for the prevention, diagnosis, and treatment of age-related viral diseases, thereby improving their health status.

Late-onset rheumatoid arthritis (LORA) refers to rheumatoid arthritis (RA) with initial symptoms and signs appearing after the age of 60 or 65. A higher frequency of HLA-DRB1*01:01, *04:03, and *14:02 alleles and a lower frequency of HLA-DRB1*04 are observed in patients with LORA compared to young-onset RA (YORA). Due to immunosenescence, the immune response in LORA differs from that in YORA. Specifically, in LORA, there is an increase in M1 macrophages and CD56^dim NK cells, whereas the numbers of M2 macrophages, Mer proto-oncogene tyrosine kinase, and CD56^bright NK cells are reduced. Elevated levels of age-related B cells in older individuals may contribute to more swollen and tender joints, as well as higher disease severity scores in LORA than in YORA. Additionally, impaired DNA repair mechanisms, an increased ratio of CD4⁺/CD8⁺ T cells, and elevated CD28^- T cells may contribute to a higher risk of both articular and extra-articular complications in LORA. Conventional disease-modifying antirheumatic drugs (DMARDs) used in LORA are similar to those used in YORA. Methotrexate is often the first choice for LORA; however, the dosage should be adjusted according to renal function. Biologic DMARDs is used less frequently in LORA than in YORA, as patients with LORA may be at a higher risk for serious infections. Furthermore, patients with LORA are at an increased risk of cardiovascular disease, fragility fractures, and malignancy compared to those with YORA; they also exhibit a higher prevalence of geriatric syndrome features. Furthermore, the use of antirheumatoid drugs can influence geriatric syndromes.