Chinese Medical Journal最新文献

Abstract: The gut-brain axis is a complex, bidirectional network of communication systems that integrates neural, endocrine, and immune pathways, as well as metabolic processes, to regulate homeostasis and maintain physiological and cognitive equilibrium. Central to this axis is the gut microbiota, which exerts a profound influence on brain function through microbial metabolites, including short-chain fatty acids, tryptophan metabolites, and bile acids. Disruption of this microbial balance, known as dysbiosis, has been implicated in the onset and progression of major neuropsychiatric and neurodegenerative disorders, including depression, Alzheimer's disease, and Parkinson's disease. This review critically examines the mechanistic underpinnings of the gut-brain axis, emphasizing metabolic, immunological, and neuroendocrine signaling as key mediators. Furthermore, it explores how dietary components, particularly fiber, polyphenols, and fermented foods, modulate gut microbial composition and function to influence brain health. Emerging therapeutic strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, are discussed, along with the potential of personalized targeted intervention. By integrating current findings, this review underscores the gut-brain axis as a dynamic interface that not only influences neurological and psychiatric outcomes but also represents a promising target for therapeutic intervention.

Abstract: Pancreatic ductal adenocarcinoma (PDAC), the deadliest epithelial malignancy, is increasingly prevalent and contributes significantly to cancer-related mortality. Research over the past decade has demonstrated that microbiota may play a pivotal role in both PDAC oncogenesis and its resistance to chemotherapy. Emerging preclinical and clinical data highlight the impact of microbiota on therapeutic outcomes in PDAC patients. This review systematically explores the role and underlying mechanisms of microbiota in PDAC, with a particular focus on their clinical implications and translational potential in disease progression and therapeutic responses. Finally, this review addresses the potential of microbiome-based therapies to enhance the efficacy of PDAC treatments.

Background: Intron retention (IR) is an important biological process associated with disease development. However, the role of IR in the progression of tuberculosis (TB) remains unexplored. Therefore, this study aimed to characterize the dynamic IR landscape during TB progression and elucidate the role of DNASE1L2-IR in this process.

Methods: We conducted a comprehensive high-throughput sequencing analysis using 1729 samples from 19 public datasets and identified candidate IR events associated with TB progression. We then validated these candidate IR events in three macrophage infection models by quantitative polymerase chain reaction and revealed the underlying molecular mechanisms by investigating the subcellular localization and functional roles of their associated isoforms.

Results: In an analysis of 1729 clinical specimens, we found genome-wide intron-splicing reprogramming in host cells during TB progression. Notably, deoxyribonuclease 1 like 2 (DNASE1L2, a gene encoding deoxyribonuclease)-IR exhibited striking differences among healthy controls, individuals with latent TB infection, and individuals with active TB (Padj <0.05), particularly between progressors and nonprogressors (Padj <0.0001). Similar differences were observed in Mycobacterium tuberculosis (M. tuberculosis) infection models in vitro; as the stimulation increased in concentration or duration, IR initially increased but subsequently decreased. DNASE1L2-IR generated two transcript isoforms: a long isoform (DNASE1L2-L) and a short isoform (DNASE1L2-S). Upon stimulation, DNASE1L2-L appeared in the cytoplasm, whereas DNASE1L2-S remained membrane-anchored. Deoxyribonuclease activity assays revealed that compared with DNASE1L2-S, DNASE1L2-L exhibited significantly greater enzymatic activity against plasmid and M. tuberculosis DNA substrates and more effectively suppressed the release of interleukin-1beta and tumor necrosis factor alpha, indicating isoform-specific functional divergence in inflammatory regulation.

Conclusion: These findings identify DNASE1L2-IR splicing dynamics as a novel biomarker for monitoring TB progression and reveal a host-defense mechanism in which DNASE1L2-IR regulates M. tuberculosis DNA degradation to modulate TB progression.

Background: Metabolic-associated steatotic liver disease (MASLD) is a heterogeneous condition with highly variable outcomes. We aimed to distinguish the subtypes of MASLD that were associated with varying risks of hepatic and extrahepatic outcomes.

Methods: An innovative multi-task deep least absolute shrinkage and selection operator (LASSO) algorithm was developed for feature selection in the discovery cohort (n = 1111, 87.6% [973/1111] of biopsy-proved MASLD), followed by clustering analysis in MASLD. Validation was performed in 6172 individuals who undertook health check-ups (MASLD: 43.9% [2710/6172], mean follow-up 27.6 months) and 7406 participants from the Third National Health and Nutrition Examination Survey (NHANES III) (MASLD: 37.3%, mean follow-up 280.2 months).

Results: Four clusters with distinct risks of hepatic and extrahepatic outcomes were identified in the discovery cohort: Cluster 1 characterized by subcutaneous adiposity, modest metabolic disorders, but lower risk of cardiovascular disease (CVD); Cluster 2 characterized by significant hyperlipidemia, substantial liver damage, and increased hepatic fibrosis risk; Cluster 3 characterized by low muscle mass, remarkable chronic systemic inflammation, and a higher risk of cardiovascular-kidney complications; and Cluster 4 characterized by severe insulin resistance, visceral adiposity, poor glucose and lipid control, and severe liver damage, conferring a high risk of cardiovascular-liver-kidney complications. Additionally, Cluster 4 exhibited the highest frequencies of PNPLA3 risk alleles. The prognostic relevance was further confirmed in external validation cohorts. Specifically, Clusters 3 and 4 had increased risks of all-cause and CVD-related mortality.

Conclusions: We developed a novel algorithm that identified four MASLD clusters, each characterized by distinct clinical features and varying risks of hepatic and extrahepatic outcomes. This classification facilitates the precise integration of MASLD risk stratification and management within the cardiovascular-liver-kidney-metabolic framework.

Abstract: Circulating cell-free DNA (cfDNA) has firmly established itself as a cornerstone of liquid biopsy, advancing the noninvasive diagnosis and monitoring of pulmonary diseases. Its molecular characteristics, particularly methylation profiles, fragmentation patterns, and mutations, now enable a range of clinical applications-from early detection of lung cancer to rapid pathogen identification and severity assessment in pneumonia, and to precise risk stratification in chronic conditions such as chronic obstructive pulmonary disease and asthma. Beyond diagnostic applications, dynamic changes in cfDNA levels and profiles provide critical insights into disease monitoring across a spectrum of pulmonary disorders. While challenges in detection sensitivity, analytical standardization, and clinical validation remain, the ongoing integration of multi-omics data and artificial intelligence is refining the predictive power of cfDNA-based models. Future developments are expected to consolidate the role of cfDNA analysis as an indispensable tool in precision pulmonology, ultimately transforming diagnostic pathways and enabling more personalized, proactive management of respiratory health.

Abstract: Pediatric health is the foundation for people's lifelong health. The co-evolution of host genetics and the gut microbiome fosters a symbiotic relationship that is important for pediatric growth and the pathogenesis of various diseases. However, a comprehensive overview of the human genetic-gut microbiome axis in pediatric diseases remains unavailable. This review summarizes the human genetic variants that are associated with pediatric diseases, affecting the nervous, respiratory, and immune systems, as well as those linked to preterm birth (PTB), as identified by genome-wide association studies (GWAS). As the gut microbiome plays a crucial role in pediatric health, we have systematically discussed microbial biomarkers associated with the onset and progression of pediatric diseases, with an emphasis on their clinical impact across four key axes: the gut-brain, gut-lung, gut-skin, and gut-immune axes. The GWAS on the gut microbiome revealed numerous genetic variants that intricately regulate its composition. These variants predispose individuals to gut microbiome dysbiosis, potentially initiating or exacerbating pediatric disease manifestations, as discussed below. Moreover, the underrepresentation of populations from low- and middle-income countries in existing microbiome-related data, coupled with technical challenges, limits our understanding of the association between microbiome and health. Finally, we emphasize the promising potential of elucidating and modulating host gene-gut microbiome interactions to offer novel insights for advancing precision pediatric medicine and developing innovative therapeutic strategies.

Background: The "Healthy China 2030" initiative, which aims to achieve a 30% reduction in premature mortality by 2030, recognizes leukemia as the primary cause of cancer-related deaths. Given the limited previous research, providing comprehensive national and subnational estimates and temporal trends of the premature leukemia mortality burden from 2005 to 2020 is crucial.

Methods: Using data from various sources acquired through the national surveillance mortality system, estimates were derived and compared across 31 provincial-level administrative regions in the Chinese mainland, revealing the magnitude of mortality rates and years of life lost (YLL) due to leukemia in the Chinese population between 2005 and 2020.

Results: In 2020, the estimated number of leukemia-related deaths decreased from 61.93 thousand in 2005 to 54.86 thousand, accompanied by a decline in age-standardized mortality rate (ASMR) from 4.97 per 100,000 population in 2005 to 3.49 per 100,000 population. The burden of premature mortality caused by leukemia exhibited a significant reduction, as indicated by a nationwide decline of -39.37% (from 239.46 to 145.18 per 100,000 population) in the age-standardized YLL rate. Despite a notable decrease (-11.41%) in leukemia mortality, China has the highest burden of leukemia-related deaths due to its large population, primarily driven by population aging (12.76%), which has contributed to an upsurge in leukemia fatalities, followed by population growth (7.67%). Leukemia mortality exhibited distinct variations among different provinces and demonstrated a positive correlation with economic activity, particularly in coastal provinces characterized by higher levels of economic development. Xizang is currently the only province experiencing a significant increase in mortality rate, necessitating urgent government support.

Conclusions: Significant disparities in premature mortality attributed to leukemia were observed across diverse regions of China, underscoring the need for targeted interventions aimed at promoting a health-protective lifestyles and expanding timely access to basic medical insurance for diagnosis and cost-effective therapy, particularly among high-risk populations and regions with limited healthcare resources.