Precision Clinical Medicine最新文献

More than 500 million Chinese adults suffered from overweight or obesity in 2023. The pandemic of obesity consumes healthcare and economic resources by imposing enormous burden from its complications such as cardiovascular, kidney and metabolic diseases. In response, China launched a series of important policy changes including "Weight Management Year", facilitating the engagement of public health, clinical practitioners, industry and stakeholders in different fields. The shift triggered rapid evolution of technologies in obesity care including both treatment and prevention, which added great opportunities for all stakeholders. Nevertheless, challenges exist, including misdiagnosis of obesity secondary to other diseases, population disparity, indirect evidence supported by trials conducted in other ethnic groups, health inequalities and the collaboration across stakeholders with diverse backgrounds. Traditional Chinese diets such as Jiangnan Diet and activities such as Tai Chi represent tradition-based lifestyle interventions that provide Chinese people with cultural benefits. The evolution of technologies, especially digital healthcare and novel medications, will play critical roles in future obesity care in China. Policy makers and clinical and public health practitioners must make every effort to address the urgent crisis posed by obesity pandemic in China.

RNA modifications encompass a series of dynamic chemical changes and editing events on RNA molecules, playing a pivotal role in essential physiological processes such as embryonic development, immune response, and the maintenance of cell homeostasis. By influencing RNA stability, splicing, translation, and intermolecular interactions, RNA modifications serve as crucial mechanisms regulating gene expression at the post-transcriptional level. Dysregulation of the modification machineries or aberrant modification patterns is closely associated with the onset and progression of various diseases, including tumors, metabolic disorders, cardiovascular diseases, and neurological and immune conditions, making them potential biomarkers for disease diagnosis, prognosis, and treatment. In this review, we summarize the molecular mechanisms of major RNA modifications, emphasize their functions in health and disease, and discuss their diagnostic and therapeutic value in pathological contexts.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Early diagnosis and effective treatment are crucial for improving the prognosis of children with HB. In recent years, microRNAs (miRNAs), an important class of noncoding RNA molecules, have been increasingly recognized for their key regulatory roles in the occurrence, development, and treatment of HB. This review systematically reviews the expression characteristics, molecular mechanisms, and potential application value of miRNAs in the diagnosis and treatment of HB. Research indicates that the interaction network between miRNAs and long noncoding RNAs and circular RNAs has a significant effect on the development of HBs. miRNAs regulate signaling pathways, such as the Wnt/β-catenin, mitogen-activated protein kinase, phosphatidylinositol 3-kinase/protein kinase B, and Janus kinase 2/signal transducer and activator of transcription 3 pathways, and also play critical roles in the biological behavior of HBs. Furthermore, the progress of preclinical research on miRNAs as biomarkers and therapeutic targets provides new ideas and directions for precision medicine in HB. Finally, this article looks forward to the future development directions of miRNAs in precision medicine for HBs, emphasizing their important potential in improving diagnostic accuracy and treatment efficacy.

Background: Shenzhuo Formula (SZF), a modified Didang Tang, is used for diabetic kidney disease (DKD), though high-quality evidence is limited.

Methods: In a randomized, double-blind, double-dummy, active-controlled, multicenter trial, irbesartan (IRB) was the control. A Bayesian model assessed efficacy. Mechanistic studies included Olink inflammation proteomics, single-cell RNA sequencing (scRNA-seq) of KK-Ay mouse kidneys, and in vivo experiments.

Results: A total of 120 DKD patients with macroalbuminuria were randomized (SZF n = 57, IRB n = 63). At 24 weeks, 24 h urinary total protein change was -0.03 (-0.24 to 0.18) g/24 h in the SZF group and 0.08 (-0.30 to 0.14) g/24 h in the IRB group (P = 0.61). Estimated glomerular filtration rate improved with SZF by 5.91 (1.80 to 10.01) mL/min/1.73m² but declined with IRB by -1.67 (-5.18 to 1.84) mL/min/1.73m² (P < 0.01). Serum creatinine decreased with SZF by -5.15 (-9.73 to -0.56) μmol/L but increased with IRB by 3.39 (-0.84 to 7.61) μmol/L (P < 0.01). Traditional Chinese medicine syndrome response was higher with SZF (89.47% vs. 63.49%, P < 0.01). Safety and metabolic parameters were comparable. Bayesian analysis favored SZF for renal benefit. Mechanistically, SZF downregulated CX3CL1 in endothelial cells and MCP-1 in mesangial and tubular cells, suggesting anti-inflammatory effects restoring endothelial function and attenuating fibrosis.

Conclusions: SZF matched IRB in proteinuria reduction but was superior in preserving renal function and improving traditional Chinese medicine symptoms in DKD, with good safety. Benefits may involve suppression of CX3CL1/MCP-1-mediated inflammation.

Cancer is becoming one of the leading causes of death among patients with diabetes. Hyperglycemia and obesity, two key characteristics of type 2 diabetes, modify the risks of cancer in patients with type 2 diabetes. However, recent studies suggested that glycemic control and weight loss mediated by anti-diabetic medications might not be sufficient to lower the risks of cancer in patients with type 2 diabetes. Thus, there is a need to explore the association between anti-diabetic medications and cancer beyond glycemic and body weight control. This review has summarized the preclinical and clinical evidence between various anti-diabetic drugs and cancer. More importantly, this review focused on the underlying links between anti-diabetic medications and cancer beyond glycemic and body weight control, including modified cell proliferation, altered levels of some hormones, inflammation and oxidative stimuli, autophagy and apoptosis, intestinal flora shift, and angiogenesis and epithelial-mesenchymal transition. This review may provide insights for future clinical and mechanistic studies to further elucidate the association between anti-diabetic medications and cancer.

Background: Relapsed soft tissue sarcomas (STS) have poor prognosis and limited treatment options. However, the molecular mechanism underlying recurrence and the prognostic predictor for STS are unclear.

Methods: We enrolled 35 extremity and trunk STS patients. Tumor specimens of 20 relapsed and 15 primary STS underwent sequencing to detect DNA mutation, RNA expression, and DNA methylation. Moreover, 206 STS cases from The Cancer Genome Atlas (TCGA) were utilized to construct the relapse-associated risk score model (RRSM), validated using three Gene Expression Omnibus datasets. Key model genes, COL6A3, FZD7, ITPKA, and PRKAG1, were validated in formalin-fixed paraffin-embedded tissue sections from primary and relapsed STS patients, confirming their potential involvement in STS recurrence.

Results: The primary STS exhibited an immune-enriched tumor microenvironment, whereas the tumor microenvironment of relapsed STS had features that promote tumor recurrence or metastasis. The RRSM could predict relapse-free survival in TCGA STS and performed well in the validation cohort. Multivariate analysis revealed that RRSM was an independent prognostic factor. Moreover, the nomogram developed had excellent predictive ability.

Conclusions: This study revealed different multi-omic profiles between relapsed and primary STS. RRSM is a potential prognostic predictor for STS and lays a foundation for early intervention of high-risk STS patients. The expression of genes FZD7, ITPKA, and PRKAG1 may guide STS treatment decisions.