Chinese Medical Journal最新文献

Abstract: Recent studies have revealed aberrant expression patterns of the autophagy-associated transmembrane protein etoposide-induced 2.4 (EI24) in diverse cancer types, prompting investigations into its potential as a biomarker for cancer. These findings underscore the multifaceted roles of EI24 in regulating critical processes such as tumor metastasis, proliferation, angiogenesis, drug resistance, tumor microenvironment, and autophagy, both indirectly and directly. Such insights also provide a foundation for further elucidating the underlying mechanisms of EI24's involvement in tumorigenesis, thereby facilitating the development of novel therapeutic approaches. In this review, we present the latest advancements in EI24 research within the realm of tumor biology. We delve into the intricate molecular mechanisms governing EI24's functions across various tumor types and its diagnostic and prognostic significance. In addition, we analyze emerging therapeutic strategies targeting EI24 in tumors, offering insights into its potential as a future therapeutic target. A comprehensive understanding of EI24's role in tumor biology is crucial for devising innovative therapeutic approaches tailored to the diverse complexities of various cancer types. By integrating mechanistic insight with translational potential, EI24 represents a key node linking biological understanding to next-generation diagnostic and therapeutic innovations.

Background: The CUG-binding protein Elav-like family member 2 ( CELF2 ) gene has been linked to the pathogenesis of epilepsy, but its precise role remains unclear. This study aimed to investigate the pathogenic mechanisms of CELF2  mutation in epilepsy, utilizing zebrafish models to explore its molecular pathways and biological impact.

Methods: Whole-exome sequencing was performed to identify CELF2  mutations associated with epilepsy. CELF2 zebrafish model was generated using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-related protein 9 technology and morpholinos, followed by behavioral and electroencephalographic analyses to confirm epileptic phenotypes. Proteomic and metabolomic analyses were conducted to examine the impact of CELF2  deficiency on metabolic pathways, and single-cell sequencing was used to assess alterations in neuronal cell populations.

Results: An infant with infantile epileptic spasms syndrome associated with a CELF2 (p.Pro520Arg) gene mutation was reported. We established zebrafish models with celf2  gene knockout and knockdown and found that zebrafish with celf2  mutations exhibited epilepsy-like behaviors, which could be rescued by injection of CELF2 wild-type mRNA. Significant changes were observed in crucial marker genes associated with the nervous system in the celf2+/-  group, including FOS , BDNF , NPAS4 , GABRA1 , GABRG2 , and PYYA . Disruptions in lipid metabolism, heat shock protein 90 beta1 (Hsp90b1), were identified in proteomic and metabolomic analyses. Single-cell sequencing showed changes in nucleosome localization, nucleosome DNA binding, arginine and proline metabolic pathways, gonadotropin-releasing hormone signaling pathway, and nucleotide-binding oligomerization domain receptor signaling pathway.

Conclusions: Our study has revealed a promising association between defects in the CELF2  gene and epilepsy using a zebrafish model, suggesting that CLEF2 is a causative gene in epilepsy. These findings not only indicate the potential impact on the biological process influenced by the CELF2  gene defect but also offer hopeful insights into the pathogenesis of epilepsy and potential therapeutic targets.

Background: Breast cancer is the most common malignancy among women, posing major health, social, and economic challenges worldwide. This study analyzed global breast cancer incidence and mortality in 2022 using Global Cancer Observatory (GLOBOCAN) 2022 data and projected the disease burden to 2050.

Methods: Breast cancer incidence and mortality were categorized by region and age. Correlations between age-standardized rates (ASRs) and the Human Development Index (HDI) were assessed using Spearman's rank correlation coefficient (ρ). Future burden estimates for 2050 were projected based on current trends.

Results: In 2022, approximately 2.30 million new breast cancer cases and 666,103 deaths were reported globally. Age-specific patterns of breast cancer incidence and mortality differed across development HDI levels with incidence peaking at ages 45-69 years and mortality at ages 50-≥85 years across HDI levels. The proportion of cases and deaths among women aged ≥50 years relative to those aged ≤49 years increased with HDI, ranging from 79% vs . 21% for incidence and 90% vs . 10% for deaths in very high HDI countries to 51% vs . 49% and 59% vs . 41% in low HDI countries. HDI showed strong positive correlations with age-standardized incidence rates (ρ = 0.773), period incidence rates (ρ = 0.958), and period mortality rates (ρ = 0.907), and a negative correlation with mortality-to-incidence ratios (ρ = -0.817). Projections indicate that by 2050, breast cancer cases may rise to 3.55 million and deaths to 1.14 million if current patterns continue.

Conclusions: Breast cancer remains a major global health concern. Strengthening prevention, early detection, and therapeutic strategies is essential to reduce incidence, improve survival, and alleviate its global burden.

Background: Liver cancer continues to pose a global health challenge. In 2020, China accounted for nearly half of new liver cancer cases worldwide, with a low 5-year survival. This study aims to evaluate the evolving landscape of the liver cancer burden in China.

Methods: Data on prevalence, incidence, death, and disability-adjusted life year (DALY) attributed to liver cancer and its six etiologies in China between 1990 and 2021 were extracted from the Global Burden of Disease Study 2021. Temporal trends in liver cancer burden were determined by percent changes and average annual percent change (AAPC). Decomposition analysis was conducted to understand the contributions of population aging, population growth, and epidemiological change to the observed trends.

Results: In 2021, there were 265,539 prevalence cases of liver cancer in China accounting for 35.9% of the global total (739,300 prevalence cases). From 1990 to 2021, the prevalence cases, incidence cases, deaths, and DALYs attributed to liver cancer in China increased by 99.99%, 103.91%, 81.24%, and 48.41%, respectively, primarily driven by population aging, then population growth. Males experienced higher burden and percentage changes in prevalence, incidence, and DALYs than females. Meanwhile, decreasing trends were observed in overall age-standardized incidence, death, and DALY rates (AAPC: -0.32%, -0.79%, and -1.03%) and generally across sex groups and the six etiologies. Notably, there were increasing trends in age-standardized incidence rate of liver cancer due to alcohol use (AAPC: 0.36%) and metabolic dysfunction-associated steatotic liver disease (MASLD) (AAPC: 0.44%). In 2021, hepatitis B, hepatitis C, and alcohol use were the main causes of liver cancer burden in China. There were age differences in the burden of liver cancer. The overall 5-year relative survival rate was 12.27% in 2021.

Conclusions: Liver cancer cases increased dramatically over the past 30 years, primarily driven by population aging and growth, posing challenges to the control of liver cancer. Targeted interventions by sex, etiology, and age are needed to address the burden effectively.

Abstract: Liver disease is one of leading causes of death worldwide. However, current liver models have limited research progress. Therefore, models that accurately reflect the physiological functions of the human liver are urgently needed in both clinical and laboratory research. Over the past decade, liver organoids have emerged as valuable research tools offering significant breakthroughs and demonstrating great promise as advanced liver models. Liver organoids derived from pluripotent stem cells (PSCs), including embryonic and induced pluripotent stem cells, have shown significant potential for modeling liver diseases and drug responses. These miniature three-dimensional (3D) structures replicate the complexity of the liver and offer a platform for studying liver development and disease progression. The ability to create personalized organoids from patient-derived cells paves the way for precision medicine and drug screening. Owing to the pluripotency of PSCs, PSC-derived liver organoids (PSC-LOs) closely mimic the true structure of the liver and offer a wide range of applications. With advances in research, bioengineered liver organoids have the potential to revolutionize regenerative medicine, disease modeling, and the understanding of liver pathophysiology. This review provides an overview of liver organoid development and discusses their applications in liver regeneration, disease modeling, drug screening, toxicity assessment, organ transplantation, and regenerative medicine. Finally, we discuss the limitations and future development directions of PSC-LOs.