医学最新文献

Objectives: Despite increasing emphasis on clinical research ethics and quality assurance, Good Clinical Practice (GCP) training remains inadequately incorporated into postgraduate medical education. This qualitative study investigates postgraduate medical students' experiences with GCP education, exploring their learning outcomes, professional identity development, and suggestions for curriculum enhancement.

Methods: This qualitative study recruited twelve first-year postgraduate students participating in a newly established GCP elective course at a Chinese medical university. Semi-structured interviews were performed and analysed using Systematic Text Condensation. The data were interpretation employed a competency-based medical education (CBME) framework, specifically examining the aspects of role formation and contextual learning aspects.

Results: Five interrelated themes emerged from the analysis: (1) prior exposure to and foundational understanding of clinical trials; (2) motivations for enrolling in the GCP course enrolment, encompassing knowledge acquisition, practical application, and career planning; (3) evolving awareness of ethical, legal, and professional responsibilities through GCP training; (4) holistic professional development through GCP education; and (5) student recommendations for improving the practical relevance and key interested parties engagement in GCP courses. Participants universally acknowledged the value of GCP education for their future roles as clinician-investigators. However, fragmented prior knowledge and limited early exposure hindered their initial engagement. The course stimulated profound reflection on ethical responsibility and professional identity formation. Students consistently advocated for more competency-based, practice-oriented learning opportunities to better align theoretical knowledge with the practical demands of clinical research.

Conclusion: This study underscores the pressing need to integrate GCP education within structured, competency-based medical curriculum. By aligning course design with learners' emerging professional needs and addressing current implementation limitations, GCP training can more effectively support the development of ethically responsible physician-investigators.

Autoimmune gastritis (AIG) is an autoimmune disease characterized primarily by the destruction of gastric parietal cell structure and atrophy of the gastric fundic and body mucosa. The global prevalence of AIG is approximately 3.85%. Its main complications include pernicious anemia, gastric neuroendocrine tumors, and gastric cancer, which pose significant health risks. Currently, targeted treatment options for AIG are lacking worldwide. Animal models of AIG are crucial for investigating its pathogenesis and for developing drug therapies. However, reproducible methods for establishing AIG animal models remain scarce. This article provides a systematic review of internationally employed methods for modeling AIG in animals. These methods are categorized and discussed based on the modeling approaches and mechanisms, including neonatal thymectomy, genetically modified animals such as TxA23 and Ctox mice, inducer-based methods such as H⁺/K⁺-ATPase immunization, viral infection, and combined modeling strategies. In addition, the types of modeling agents and the time required for model establishment are also examined. This review highlights existing challenges, such as the lack of uniform modeling standards and evaluation criteria, and aims to provide a foundation for further exploration of AIG.

The current clinical classification of coronavirus disease 2019 (COVID-19) does not adequately capture the biological heterogeneity observed among patients. To address this gap, the present study aimed to identify distinct subtypes of severe COVID-19 through unsupervised clustering analysis. We analyzed nine publicly available RNA sequencing datasets of peripheral blood samples from the GEO database. After identifying differentially expressed genes (DEGs), we applied a consensus clustering algorithm to classify the samples into distinct subtypes. To further characterize these subtypes, we performed gene set enrichment analysis and assessed immune cell infiltration to understand their underlying biological mechanisms. Based on the 139 upregulated DEGs of severe COVID-19 infection, patients were divided into subtype A, subtype B, and subtype C, each with different molecular and cellular characteristics. Subtype A was characterized by activated neutrophils that undergo degranulation and respond to bacteria or fungi. Subtype B showed significant activation in canonical pathways associated with interferon-alpha/beta signaling. Subtype C was characterized by immune cell activation associated with pathways of mitotic and cell cycle. These results facilitate the development of a precise classification framework, which informs the design of molecular diagnosis and provides actionable guidelines for stratified therapy in severe COVID-19 infection in the future.

Background: CD276/B7-H3 is an immune checkpoint molecule often overexpressed in cancers, representing a potential therapeutic target. The underlying mechanisms for CD276 upregulation remain unclear. This study investigates how glutamine metabolism affects CD276 protein stability and esophageal squamous cell carcinoma (ESCC) progression.

Methods: CD276 and SLC1A5 expression were analyzed in 90 ESCC clinical tissues and TCGA/GEO datasets. CCK-8, colony formation, wound healing and transwell assays were performed in KYSE150 and KYSE450 cells. Autophagy was quantified by immunofluorescence and western blot. Mitochondrial reactive oxygen species (ROS) levels measured by flow cytometry. Rescue experiments used N-acetylcysteine (NAC) and chloroquine (CQ). Finally, antitumor effects of SLC1A5 inhibitor V9302 in the presence or absence of CD276 were evaluated in NOD/SCID mice (n = 5 per group) bearing KYSE150 xenografts.

Results: CD276 and SLC1A5 upregulated in ESCC tissues (P < 0.05). CD276 overexpression enhanced ESCC cell proliferation and migration by 42.3% and 58.7%, respectively (P < 0.01). CQ but not MG-132 increased CD276 expression in ESCC cells. SLC1A5 stabilized CD276 protein without altering CD276 mRNA levels, by suppressing ROS-dependent autophagic degradation. NAC reversed ROS-induced CD276 degradation, while CQ abrogated CD276 downregulation upon glutamine metabolism inhibition. Inhibiting glutamine metabolism could reverse ESCC cell proliferation induced by CD276 overexpression. Moreover, combination of V9302 and CD276 knockout significantly reduced KYSE150 cell-derived xenograft tumor volume by 65.2% (95% CI 58.3-72.1%, P < 0.001) in NOD/SCID mice, without affecting mouse body weight (P > 0.05).

Conclusion: SLC1A5 enhances CD276 stability by suppressing ROS-autophagy signaling, promoting ESCC progression. Targeting glutamine metabolism to enhance CD276 degradation might be a novel therapeutic strategy for ESCC.

Hypercholesterolemia is a major risk factor for atherosclerotic cardiovascular disease; however, current therapeutic options such as statins are limited by issues including hepatotoxicity and patient intolerance. Probiotics and their metabolites show promise in modulating cholesterol metabolism through the gut‒liver axis, yet the specific commensal bacteria and molecular mechanisms underlying these effects remain poorly understood. In this study, we isolated and characterized EPS-D1, a novel exopolysaccharide (15.003 kDa) derived from Lactiplantibacillus plantarum H6, which is composed primarily of mannose (46.10%) and glucose (33.98%) and features a highly branched structure (branching degree of 29.5%). The administration of EPS-D1 significantly reduced the serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) by 40.31%, 37.55%, and 43.15%, respectively, in high-cholesterol diet (HCD) mice. Additionally, it improved hepatic steatosis and reduced markers of liver injury. Through 16S rRNA sequencing and fecal microbiota transplantation (FMT), we identified Muribaculum as the key commensal bacterium enriched by EPS-D1. Direct administration of Muribaculum (Muribaculum intestinale) replicated the cholesterol-lowering effects, decreasing ileal and fecal cholesterol levels by 74.79% and 53.16%, respectively. Mechanistically, both EPS-D1 and M. intestinale activated the enterohepatic FXR‒FGF15 axis, which resulted in the upregulation of hepatic cholesterol 7α-hydroxylase (CYP7A1) expression and the downregulation of ileal ASBT and NPC1L1, thereby promoting bile acid synthesis and inhibiting cholesterol absorption. Furthermore, M. intestinale increased intestinal short-chain fatty acids (SCFAs), particularly acetic acid and caproic acid, by 37.88% while also modulating the composition of the bile acid pool. These findings establish M. intestinale as a precise microbial target for cholesterol management and demonstrate that EPS-D1 from L. plantarum H6 enhances cholesterol metabolism through microbiota-mediated activation of the enterohepatic FXR‒FGF15 axis, providing a novel therapeutic strategy for managing hypercholesterolemia.

Oral insulin delivery represents a transformative approach to diabetes management, offering improved patient compliance and physiological insulin delivery patterns compared to subcutaneous injection. However, multiple gastrointestinal barriers, including enzymatic degradation, mucus entrapment, epithelial impermeability, and first-pass metabolism, have limited oral bioavailability to below 1% for unmodified insulin. This review comprehensively examines contemporary strategies to overcome these barriers. We analyze structural modifications of insulin, including PEGylation, lipidation, cyclization, and glycoengineering, which enhance stability while maintaining biological activity. The analysis extends to sophisticated formulation technologies incorporating nanocarriers (polymer-based, lipid-based, inorganic nanocarriers, and metal organic frameworks), biomimetic systems, and stimuli-responsive mechanisms for protection and delivery. A central focus is on absorption-enhancing strategies, which range from chemical permeation enhancers to precise biological mechanisms like receptor-mediated transcytosis and other active transport pathways. Emerging tools such as microbiome-based carriers and smart devices are also discussed. Despite significant progress in preclinical models, challenges remain in manufacturing scalability, inter-patient variability, long-term safety, and regulatory approval. Future directions emphasize hybrid delivery systems, digital health integration, and personalized formulations. Realizing clinically viable oral insulin requires continued multidisciplinary collaboration addressing biological, technological, and translational barriers to transform diabetes care.

Purpose: Undocumented Afghan women migrants in Pakistan face profound barriers to reproductive healthcare. This study examines the informal reproductive healthcare strategies of undocumented Afghan women migrants living in Peshawar, focusing on the invisible safety nets they construct in response to legal and institutional exclusion.

Method: The study employed a qualitative research method by conducting narrative in-depth interviews, focus group discussions with undocumented Afghan women migrants, and five key informant interviews. The study conducted a narrative-informed thematic analysis grounded in concepts of social networks, everyday bordering, and reproductive justice.

Results: The study findings revealed that public facilities are widely perceived as sites of document checking, humiliation, and potential exposure to immigration authorities, leading women to anticipate exclusion and pre-emptively turn away from formal care. In this context, traditional birth attendants, small private clinics, pharmacies, and home-based remedies form a plural, informal care landscape, accessed and evaluated through dense kinship and neighborhood networks. Community-based practices, rotating loans, information sharing, accompaniment, and emotional support, operate as invisible safety nets that partially compensate for state neglect..

Conclusion: The study calls for decoupling reproductive care from immigration control while engaging pragmatically with existing informal providers and community networks to promote reproductive justice and well-being.

Research performance in the Middle East and North Africa (MENA) is often assessed using national aggregates that mask substantial institutional variation. Evidence on how output, quality, and excellence relate to economic resources and institutional capacity across the region remains limited. Data from the SCImago Research Centers Rankings were used to analyze 321 non-university, non-health research centers across 22 MENA countries. Indicators included research output, Quality, Excellence, collaboration, innovation, and Institutional Citation Impact per researcher (ICI/T). Analyses were conducted at both country and institutional levels using descriptive statistics, correlation analysis, and clustering. The analysis reveals extreme heterogeneity within and across countries. National income is strongly associated with research Excellence but shows a much weaker relationship with baseline Quality. ICI/T is strongly associated with Excellence and displays reduced variance at higher values, indicating increasing stability of elite performance. Clustering identifies multiple tiers of research systems that cut across income categories. A small group of countries exhibits disproportionately high Excellence relative to weak institutional impact, consistent with structural decoupling. International collaboration supports Quality but does not predict Excellence, while regional and industry collaboration remain limited. Economic resources accelerate elite research performance but do not guarantee high baseline quality. Long-term research performance in the MENA region depends primarily on institutional alignment, governance, and sustained capacity building rather than output expansion alone.

Mycobacterial lung diseases, including tuberculosis (TB) and nontuberculous mycobacterial pulmonary disease (NTM-PD), are increasingly recognized as disorders influenced not only by host immunity but also by microbiota. Emerging evidence identifies the gut-lung axis (GLA) as a key bidirectional communication network linking intestinal and pulmonary homeostasis. Mycobacterial infection itself induces airway and gut dysbiosis through immune and metabolic disturbances, which is further exacerbated by prolonged antibiotic therapy. Dysbiosis within either site reciprocally affects the other via GLA, leading to reduced microbial diversity, impaired epithelial integrity, and systemic inflammation. These alterations disrupt metabolite-mediated immunoregulation and attenuate IL-22-driven epithelial defense, thereby weakening bacterial clearance and promoting chronic inflammation. Distinct microbial features, such as the depletion of beneficial SCFA-producing taxa and enrichment of pro-inflammatory anaerobes, are observed in both TB and NTM-PD. Moreover, therapy-induced microbiome remodeling influences treatment response and disease relapse. Restoring microbial balance through probiotics, prebiotics, postbiotics, dietary modulation, or fecal microbiota transplantation offers a promising adjunctive strategy. This review integrates current evidence linking microbiome dysbiosis to mycobacterial pathogenesis and highlights microbiome-targeted interventions as an emerging therapeutic frontier in pulmonary mycobacterial diseases.