医学最新文献

Women's reproductive life encompasses dynamic phases, including menarche, menstrual cycles, pregnancy, lactation, and menopause, as well as transitional periods of variable duration. These stages drive physiological changes that influence both physical and mental well-being and may modulate susceptibility to autoimmunity. The interplay between autoimmunity and reproductive milestones is bidirectional: reproductive stages can affect disease onset and progression, while autoimmune disorders influence fertility, pregnancy outcomes, and the timing of menopause. Persistent challenges in detecting autoimmune diseases, particularly within rheumatology and gastroenterology, underscore the need for targeted screening, multidisciplinary collaboration, and patient-centered strategies. Fertility preservation, preconception counseling, and individualized pregnancy management are essential to safeguard reproductive rights and optimize maternal and neonatal outcomes. Post-reproductive life, especially the menopause transition, represents a vulnerable period in which immune, hormonal, and metabolic changes converge. This manuscript highlights the importance of a comprehensive, lifespan-oriented approach to reproductive well-being in women with autoimmune diseases, integrating preventive, diagnostic, and therapeutic strategies across all stages of reproduction.

Hashimoto thyroiditis (HT) is closely associated with the development of papillary thyroid carcinoma (PTC); however, the tumor immune microenvironment and the molecular mechanisms underlying the 'inflammation-to-cancer' transition in HT-PTC coexistence remain poorly understood. In this study, we integrated single-cell RNA sequencing (scRNA-seq) data from HT-associated and PTC tissues, annotating 11 distinct cell subtypes, including endothelial cells, red blood cells, fibroblasts, follicular epithelial cells (FECs), macrophages, monocytes, T cells, NK cells, B cells, plasma cells, and mast cells. Malignant epithelial cells were identified through copy number variation (CNV) analysis, followed by differential gene expression screening and functional enrichment analysis. Cell-cell communication analysis was employed to delineate intercellular interactions, and key findings were validated using a lipopolysaccharide (LPS)-stimulated Transwell co-culture model incorporating TPC-1 cells, Nthy-ori 3-1 cells, and mast cells. We found that IL1B was significantly upregulated in malignant FECs, and differentially expressed genes were enriched in immune-related processes including antigen presentation and lymphocyte activation. Notably, IL1B^- FECs specifically communicated with mast cells via the FN1/CD44 signaling axis. In vitro experiments further confirmed that, under inflammatory conditions, mast cells secreted IL-8, which activated the PI3K/AKT pathway and promoted malignant phenotypes. Collectively, these findings suggest that IL1B⁻ FECs recruit mast cells through the FN1/CD44 axis, and mast cell-derived IL-8 subsequently activates the PI3K/AKT pathway to drive the transformation from HT to PTC, providing novel mechanistic insights into the "inflammation-to-cancer" transition.

Timely breast cancer care remains challenging in South Africa, where both health-system and patient-level barriers contribute to delayed diagnosis and treatment. This study explored healthcare providers' experiences and perspectives on breast cancer care at Chris Hani Baragwanath Academic Hospital in Soweto and its two referring secondary hospitals in Johannesburg. Using a cross-sectional qualitative design informed by phenomenology, we conducted in-depth interviews with 30 providers involved in breast cancer care. Thematic analysis identified intersecting structural and individual barriers, together with provider-led strategies to improve care delivery. System-level constraints included high patient volumes, staff shortages, limited diagnostic capacity, referral delays, inconsistent treatment supplies, and the absence of radiation oncology services at CHBAH, necessitating referral to an affiliated hospital 25 km away. Providers also described patient-related contributors to delay, including fear, denial, symptom misinterpretation, socioeconomic hardship, and limited self-efficacy, often exacerbated by poor communication. Suggested priorities included community and primary care education, provider training, high-risk screening in primary care, and expanded diagnostic and treatment infrastructure, particularly radiation oncology services at CHBAH. Furthermore, providers described pragmatic mitigation strategies, including expedited diagnostic workup, multidisciplinary coordination, electronic records, NGO-supported patient navigation, and temporary disability grants to offset transport costs. In conclusion, these findings provide a foundation for a coordinated response to strengthen oncology care in resource-constrained settings.

Objective: This review comprehensively explores the potential relationship between the microbiota and adenomyosis, aiming to identify specific microbial biomarkers, elucidate the molecular mechanisms underlying the involvement of the microbiota in the disease, and provide insights into more precise and personalized therapeutic strategies for patients with adenomyosis.

Methods: This article adopts the narrative review method to comprehensively analyze the literature on the relationship between the microbiota and adenomyosis. A comprehensive literature search was conducted in PubMed, Embase and Web of Science databases. A total of 8 articles were included, among which one was an animal experiment. This review focuses on analyzing the differences in the composition of the microbiota between patients with adenomyosis and healthy control groups, as well as the potential molecular mechanisms by which the microbiota participates in the development of adenomyosis.

Results: Studies have demonstrated that the composition of the microbiota in women with adenomyosis differs significantly from that in healthy controls.The potential mechanisms by which microbiota may be involved in adenomyosis are closely associated with immune-inflammatory responses and estrogen regulation, which further affect the progression of adenomyosis.

Conclusions: Microbiota may play an important role in the pathogenesis of adenomyosis. Elucidating the specific microbial biomarkers and the underlying molecular mechanisms of microbiota in adenomyosis is crucial for developing novel, precise, and personalized therapeutic strategies, which may provide new options for the treatment of adenomyosis.

Maternal and perinatal death surveillance and response (MPDSR) aims to prevent maternal and perinatal deaths by analysing clinical and social data after the death and using these insights to generate knowledge in the form of recommendations. This requires collaboration between health professionals and community members to co-produce knowledge to prevent future deaths. Our study asked: how do interactions between community members and health workers shape knowledge co-production in MPDSR processes? And what are the implications for policy and practice? This qualitative study used interviews, focus groups, and observations of MPDSR sessions in two Kenyan counties. MPDSR aims to prevent deaths by learning from past experiences, yet we found that the policies and tools used in MPDSR may prevent learning. Health workers questioned community members' competence as knowers and undervalued community knowledge. Community members worried that MPDSR sessions were intended to expose 'bad' deaths. These dynamics created contested spaces where different ways of knowing competed for legitimacy. Our findings show MPDSR processes must examine how and why certain forms of knowledge are deemed to be credible and others are excluded. Without recognising diverse perspectives, MPDSR risks producing fragmented understanding, limiting its potential as a participatory and transformative tool for preventing deaths.

Aging impairs vaccine responses. Dai et al. reported that defective cDC2 migration in immunized old mice, diminishing humoral and cellular immunity. Oral yeast-derived nanoparticles restore DC migration and vaccine efficacy. These findings establish impaired DC migration as a key mechanism of age-related immune decline, introducing a noninvasive strategy to correct immunosenescence.

Introduction: Little is known about the associations between reallocating time from one movement behaviour to another within 24 h with the risk of chronic obstructive pulmonary disease (COPD), particularly in the context of genetics.

Methods: This study included 87 656 participants from the UK Biobank with valid wrist-worn accelerometer data and without prevalent COPD for the primary analysis. The isotemporal substitution model was used to evaluate the potential impact on COPD incidence of replacing one behaviour with an equivalent duration of another.

Results: Our study showed that replacing 1 h/day of sleep, sedentary behaviours (SB), or light-intensity physical activity (LIPA) with an equal amount of time spent in moderate-to-vigorous physical activity (MVPA) was associated with 40%, 43%, and 39% lower risk of incident COPD, respectively. Stratified by genetic risk, within each subgroup, the inverse relationship between replacing sleep, SB, and LIPA with MVPA and COPD remained significant. In the joint association analysis of genetic susceptibility and MVPA duration with COPD, participants with intermediate and low genetic predisposition plus low MVPA duration were significantly associated with a 1.72- (95% CI: 1.32-2.24) and 1.39- (95% CI: 1.04-1.87) fold higher risk of incident COPD, respectively, compared to those with a high genetic predisposition and high MVPA duration.

Conclusion: Irrespective of genetic susceptibility, substituting MVPA for other movement behaviours was associated with a lower risk of incident COPD. More MVPA involvement seemed to be able to mitigate the genetic risk of COPD.

Objective: Preeclampsia is a serious pregnancy complication associated with substantial maternal and infant morbidity worldwide. The adverse outcomes related to preeclampsia increase healthcare costs, highlighting the importance of quantifying its economic burden to inform healthcare policy and resource allocation. This systematic review aimed to synthesize evidence on the economic burden of preeclampsia and identify key cost drivers.

Methods: MEDLINE, PubMed, Web of Science, and the Cochrane Library were searched for English-language studies published between 2014 and 2024. Studies reporting healthcare resource utilization or costs associated with preeclampsia were included. The review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42025650091).

Results: Of 3,107 records identified, 12 studies were included; most were conducted in high-income countries. All cost estimates were converted to 2024 US dollars for comparability. Direct medical costs ranged from US$109.84 to US$87,339.71, with a mean cost of US$33,585.48 per patient. National healthcare system costs were estimated at €6.5-€9.1 million in Ireland and US$2.18 billion in the United States.

Conclusion: Preterm birth was identified as a major driver of economic burden, with earlier gestational age significantly increasing maternal and infant costs. Indirect costs and regional disparities remain underexplored, highlighting important gaps for future research.

Background: The combination of doravirine and islatravir (DOR/ISL) is a novel two-drug regimen for HIV-1. Early development faced challenges due to dose-dependent immunological signals. We aimed to synthesize the evidence on the efficacy and safety of DOR/ISL across all treatment-experience categories, specifically evaluating the impact of islatravir dosage (0.25 mg vs 0.75 mg) on clinical and immunological outcomes.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following PRISMA guidelines. We searched PubMed, Embase, Cochrane Library, and Google Scholar from inception through April 2026. Primary outcomes were virological suppression (<50 copies/mL) and mean change in CD4+ T-cell count at week 48. Data were pooled using random-effects models. Islatravir dose was evaluated as a pre-specified moderator. Quality was assessed using Cochrane RoB 2.0 and certainty of evidence was graded using the GRADE approach.

Results: Seven RCTs (n = 3,600 participants) were included. At Week 48, DOR/ISL showed non-inferior suppression rates (RR 1.01 [95% CI 0.99-1.02]; p = 0.516; moderate-certainty evidence) and a statistically significant reduction in virological failure risk (RR 0.55 [0.33-0.92]; p = 0.022) compared to active control. Overall CD4+ gain was lower with DOR/ISL (MD -34.55 cells/μL; low-certainty evidence); however, a profound moderator effect of dose was observed (p < 0.0001). The 0.75 mg dose was associated with significant CD4+ and lymphocyte declines, whereas the approved 0.25 mg dose was immunologically neutral. DOR/ISL was weight-neutral compared to bictegravir/emtricitabine/tenofovir alafenamide (MD -0.25 kg [-0.66 to 0.16]; low-certainty evidence).

Conclusion: DOR/ISL 100/0.25 mg once daily achieved virological suppression comparable to standard-of-care ART regimens and was associated with lower rates of virological failure compared with active comparators. The immunological safety concerns observed in early trials were successfully resolved by dose optimization. These findings support the use of DOR/ISL (IDVYNSO) as a potential treatment option for both treatment-naïve and virologically suppressed adults while emphasizing long-term safety surveillance.

Although Southern Afrikan governments implement child protection programs, children and youth who work and/or live on the streets remain a persistent challenge. Guided by Ubuntu and Adaptive Calibration frameworks, this cross-sectional survey examined socioecological factors at individual, family and street levels to inform child protection interventions that is linked to the UN sustainable development goal 1 (SDG). Bivariate analyses of 217 purposively sampled street-connected participants aged 6 to 21 in urban Namibia showed that early adolescence (mean age 13.5) remains a high-risk period for transitioning to street life. Multivariable logistic regression showed that higher odds of homelessness were associated with out-of-school, living with siblings or extended family before street involvement, leaving home due to neglect; sexual, physical, or psychological abuse; or parental alcohol abuse, earning less than N$100 and utilising shelter services. These associations reflect participants adaptive calibration of psychosocial stressors and economic realities of the urban landscape but, is in tension with the Ubuntu principle of belonging and interdependence. Findings suggest that family poverty is a key driver to enter the street economy while maltreatment and school dropout sever ties to the home, highlighting the need for longitudinal studies, strategies to prevent street-involvement and ultimately achieve SDG-1.