Frontiers of Medicine最新文献

With the successive release of the CONSORT extensions for acupuncture, moxibustion, cupping, and Tuina/massage, this review aims to assess the reporting characteristics and quality of randomized controlled trials (RCTs) based on these specific guidelines. A comprehensive review was conducted by searching multiple databases, including Embase, Ovid MEDLINE(R), All EBM Reviews, AMED, CNKI, VIP Chinese Medical Journal Database, and Wanfang Data, for publications from January 1 to December 31, 2022. Two reviewers independently evaluated the eligibility of the records, extracted predetermined information, and assessed the reporting based on the STRICTA, STRICTOM, STRICTOC, and STRICTOTM checklists. Among the included 387 studies (acupuncture, 213; Tuina/massage, 85; moxibustion, 73; cupping, 16), the overall reporting compliance averaged 56.0%, with acupuncture leading at 62.6%, followed by cupping (60.2%), moxibustion (53.1%), and Tuina/massage (47.9%). About half of the evaluated items showed poor reporting (compliance rate < 65%). Notably, international journals demonstrated significantly higher reporting quality than Chinese journals (P < 0.05). Although acupuncture trials had relatively higher compliance rates, deficiencies persist in reporting non-pharmacological therapies of Chinese medicine, particularly in areas like treatment environment details and provider background information.

Although many susceptibility loci for IgA nephropathy (IgAN) have been identified, they only account for 11.0% of the overall IgAN variance. We performed a large genome-wide meta-analysis of IgAN in Han Chinese with 3616 cases and 10 417 controls to identify additional genetic loci of IgAN. Considering that inflammatory bowel disease (IBD) and asthma might share an etiology of dysregulated mucosal immunity with IgAN, we performed cross-trait integrative analysis by leveraging functional annotations of relevant cell type and the pleiotropic information from IBD and asthma. Among 8 669 456 imputed variants, we identified a novel locus at 4p14 containing the long noncoding RNA LOC101060498. Cell type enrichment analysis based on annotations suggested that PMA-I-stimulated CD4⁺CD25^-IL17⁺ Th17 cell was the most relevant cell type for IgAN, which highlights the essential role of Th17 pathway in the pathogenesis of IgAN. Furthermore, we identified six more novel loci associated with IgAN, which included three loci showing pleiotropic effects with IBD or asthma (2q35/PNKD, 6q25.2/SCAF8, and 22q11.21/UBE2L3) and three loci specific to IgAN (14q32.32/TRAF3, 16q22.2/TXNL4B, and 21q21.3/LINC00113) in the pleiotropic analysis. Our findings support the involvement of mucosal immunity, especially T cell immune response and IL-17 signal pathway, in the development of IgAN and shed light on further investigation of IgAN.

Identifying biomarkers for predicting radiotherapy efficacy is crucial for optimizing personalized treatments. We previously reported that rs1553867776 in the miR-4274 seed region can predict survival in patients with rectal cancer receiving postoperative chemoradiation therapy. Hence, to investigate the molecular mechanism of the genetic variation and its impact on the radiosensitivity of colorectal cancer (CRC), in this study, bioinformatics analysis is combined with functional experiments to confirm peroxisomal biogenesis factor 5 (PEX5) as a direct target of miR-4274. The miR-4274 rs1553867776 variant influences the binding of miR-4274 and PEX5 mRNA, which subsequently regulates PEX5 protein expression. The interaction between PEX5 and Ku70 was verified by co-immunoprecipitation and immunofluorescence. A xenograft tumor model was established to validate the effects of miR-4274 and PEX5 on CRC progression and radiosensitivity in vivo. The overexpression of PEX5 enhances radiosensitivity by preventing Ku70 from entering the nucleus and reducing the repair of ionizing radiation (IR)-induced DNA damage by the Ku70/Ku80 complex in the nucleus. In addition, the enhanced expression of PEX5 is associated with increased IR-induced ferroptosis. Thus, targeting this mechanism might effectively increase the radiosensitivity of CRC. These findings offer novel insights into the mechanism of cancer radioresistance and have important implications for clinical radiotherapy.

Cancer is a major public health problem and represents substantial disparities worldwide. This study reported estimates for 36 cancers across 185 countries by incidence, mortality, 5-year prevalence, mortality-to-prevalence ratio (MPR), and mortality-to-incidence ratio (MIR) to examine its association with human development index (HDI) and gross national income (GNI). Data were collected from the GLOBOCAN 2020. MPR and MIR were calculated by sex, age group, country, and cancer type and then summarized into totals. Segi's population and global cancer spectrum were used to calculate age- and type-standardized ratios. Correlation analyses were conducted to assess associations. Results showed that breast cancer was the most diagnosed cancer globally. Low- and middle-income countries had high MPR and MIR. Cancers of esophagus, pancreas, and liver had the highest ratios. Males and the older population had the highest ratios. HDI and GNI were positively correlated with incidence and mortality but negatively correlated with MPR/MIR. Substantial disparities in cancer burden were observed among 36 cancer types across 185 countries. Socioeconomic development may contribute to narrowing these disparities, and tailored strategies are crucial for regional- and country-specific cancer control.

To investigate the epidemiological characteristics of anemia of varying severity among women of reproductive age, we conducted a nationwide, cross-sectional study between January 1, 2019 and December 31, 2019, including 4 184 547 nonpregnant women aged 18-49 years from all 31 provinces in the mainland of China. Anemia was defined as having hemoglobin concentration < 120.0 g/L and categorized as mild, moderate, and severe. Multivariate logistic models with cluster effect were used to explore the association of anemia and metabolic risk factors. The standardized prevalence of anemia and moderate and worse anemia among women of reproductive age in China was 15.8% (95% CI 15.1%-16.6%) and 6.6% (6.3%-7.0%), respectively. The prevalence of anemia and the proportion of moderate and worse anemia significantly increased with age. We also observed great geographic variations in the prevalence of anemia, with a high likelihood in south, central, and northwest China. Moderate and/or severe anemia was positively associated with overweight and obesity, diabetes, and impaired kidney function. In conclusion, anemia remains a significant challenge for women of reproductive age in China. Geographic variations and metabolic risk factors should be considered in the comprehensive and targeting strategy for anemia reduction.

SETD2 is the only enzyme responsible for transcription-coupled histone H3 lysine 36 trimethylation (H3K36me3). Mutations in SETD2 cause human diseases including cancer and developmental defects. In mice, Setd2 is essential for embryonic vascular remodeling. Given that many epigenetic modifiers have recently been found to possess noncatalytic functions, it is unknown whether the major function(s) of Setd2 is dependent on its catalytic activity or not. Here, we established a site-specific knockin mouse model harboring a cancer patient-derived catalytically dead Setd2 (Setd2-CD). We found that the essentiality of Setd2 in mouse development is dependent on its methyltransferase activity, as the Setd2^CD/CD and Setd2^-/- mice showed similar embryonic lethal phenotypes and largely comparable gene expression patterns. However, compared with Setd2^-/-, the Setd2^CD/CD mice showed less severe defects in allantois development, and single-cell RNA-seq analysis revealed differentially regulated allantois-specific 5' Hoxa cluster genes in these two models. Collectively, this study clarifies the importance of Setd2 catalytic activity in mouse development and provides a new model for comparative study of previously unrecognized Setd2 functions.

Cancer is a heterogeneous and multifaceted disease with a significant global footprint. Despite substantial technological advancements for battling cancer, early diagnosis and selection of effective treatment remains a challenge. With the convenience of large-scale datasets including multiple levels of data, new bioinformatic tools are needed to transform this wealth of information into clinically useful decision-support tools. In this field, artificial intelligence (AI) technologies with their highly diverse applications are rapidly gaining ground. Machine learning methods, such as Bayesian networks, support vector machines, decision trees, random forests, gradient boosting, and K-nearest neighbors, including neural network models like deep learning, have proven valuable in predictive, prognostic, and diagnostic studies. Researchers have recently employed large language models to tackle new dimensions of problems. However, leveraging the opportunity to utilize AI in clinical settings will require surpassing significant obstacles-a major issue is the lack of use of the available reporting guidelines obstructing the reproducibility of published studies. In this review, we discuss the applications of AI methods and explore their benefits and limitations. We summarize the available guidelines for AI in healthcare and highlight the potential role and impact of AI models on future directions in cancer research.

Human cells contain two types of adenosine deaminases (ADA) each with unique properties: ADA1, which is present in all cells where it modulates intracellular functions and extracellular signaling, and ADA2, which is secreted by immune cells. The exact intracellular functions of ADA2 remain undetermined and less defined than those of ADA1. ADA2 has distinct characteristics, such as low adenosine affinity, heparin-binding ability, and putative lysosomal entry. Here, we confirm that ADA2 is a lysosomal protein that binds toll-like receptor 9 (TLR9) agonists, specifically CpG oligodeoxynucleotides (CpG ODNs). We show that interferon-alpha (IFN-α) is secreted in response to TLR9 activation by CpG ODNs and natural DNA and markedly increases when ADA2 expression is downregulated in plasmacytoid dendritic cells (pDCs). Additionally, the pretreatment of pDCs with RNA further stimulates IFN-α secretion by pDCs after activation with CpG ODNs. Our findings indicate that ADA2 regulates TLR9 responses to DNA in activated pDCs. In conclusion, decreasing ADA2 expression or blocking it with specific oligonucleotides can enhance IFN-α secretion from pDCs, improving immune responses against intracellular infections and cancer.