Although the etiology of primary biliary cirrhosis (PBC) remains enigmatic, there are several pieces of data supporting the thesis that a strong genetic predisposition and environmental factors interact to produce a selective loss of tolerance. The striking female predominance of PBC has suggested that this sex predisposition may be secondary to epigenetic alterations on the X chromosome. In the present study, we rigorously defined the X chromosome methylation profile of CD4, CD8, and CD14 cells from 30 PBC patients and 30 controls. Genomic DNA from sorted CD4, CD8, and CD14 subpopulations was isolated, sonicated, and immunoprecipitated for analysis of methylation. All products were hybridized to a custom-tiled four-plex array containing 27,728 CpG islands annotated by UCSC and 22,532 well-characterized RefSeq promoter regions. Furthermore, bisulfite sequencing was then used for validation on a subsequent group of independent samples from PBC patients and controls. Thence, expression levels of selected X-linked genes were evaluated by quantitative real-time PCR with cDNA samples from all subjects. We report herein that a total of 20, 15, and 19 distinct gene promoters reflected a significant difference in DNA methylation in CD4+ T, CD8+ T, and CD14+ cells in patients with PBC. Interestingly, there was hypermethylation of FUNDC2 in CD8+ T cells and a striking demethylation of CXCR3 in CD4+ T cells, which inversely correlated with CXCR3 expression levels in CD4+ T cells from early-stage PBC patients. Our data provides a set of genes with epigenetic alteration likely to be indicators of autoimmunity and emphasizes the role of CXCR3 in the natural history of PBC.

Background: In this study, we applied the small private online course (SPOC) and team-based learning (TBL) blended teaching model to dermatology and venereology to ensure a higher quality learning experience for clinical medical students.Methods: A total of 52 fifth-grade clinical undergraduates from Xiangya School of Medicine of Central South University were randomly divided into an experimental (n= 26) and a control group (n= 26). In March 2018, we used the SPOC and TBL blended teaching model in the experimental group and explored the effects of innovative teaching in the dermatology and venereology course, compared with the control group receiving the conventional teaching method. We analyzed the two groups’ theoretical assessment scores and questionnaire results to evaluate the efficiency of the new pedagogy.Results: Students in the experimental group had a better understanding than the control group of the dermatology and venereology content and higher scores on the case analysis questions in the final theoretical examination. The results revealed that the majority of the experimental group students agreed that the novel teaching model blended with SPOC&TBL helped them significantly stimulate motivation and develop their ability in self-directed learning, independent thinking, literature retrieval, presentation board, teamwork, communication, and systematic clinical thinking. The teaching satisfaction survey of the two groups showed that the students’ satisfaction in the experimental group was significantly higher than in the control group (p< 0.05).Conclusions: The SPOC&TBL teaching model is better than the traditional one in enriching students’ professional knowledge and cultivating their comprehensive ability. It can effectively promote educational quality, improve students’ learning effects, and enhance their satisfaction. This method has broad application prospects.

Circadian rhythm, an inherent 24-hour periodic rhythm in organisms, is regulated by circadian clock genes. As a key component of the transcription-translation feedback loop, the core circadian gene period ( PER) 1 , not only maintains circadian rhythm homeostasis but also plays a significant role in the pathophysiological processes of various human diseases. This review summarizes the biological characteristics and regulatory mechanisms of PER1 , as well as its roles and molecular mechanisms in cardiovascular diseases, nervous system diseases, metabolic disorders, immune-related diseases, and tumors. In cardiovascular diseases, PER1 helps regulate blood pressure, renal function, and vascular inflammation. In the nervous system, it influences ischemic brain injury, sleep homeostasis, and neurodegenerative diseases. In metabolic disorders, PER1 modulates endocrine function, glucose-lipid metabolism, and energy balance. In immune-related diseases, it regulates immune cell functions and inflammatory signaling. In tumors, PER 1 has tumor-suppressive effects, with low expression correlating to poor prognosis. This review highlights the critical role of PER1 as a core circadian gene in maintaining physiological homeostasis and regulating disease progression, providing a comprehensive perspective for understanding its complex functions in physiological and pathological processes, offering new insights for developing precision therapies targeting PER1 and its associated signaling pathways.