The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Objective:To explore the mediating effect of psychological resilience between perceived stress and job burnout among standardized gastroenterology nursing training students.Methods:A total of 156 nursing trainees who received standardized training in the Department of Gastroenterology at Shaanxi Provincial People's Hospital between December 2022 and July 2024 were selected by the convenience sampling method. Data were collected using a general information questionnaire, the Connor-Davidson Resilience Scale, the Chinese Perceived Stress Scale, and the Maslach Burnout Inventory-General Survey. A Pearson correlation analysis was used to examine the relationship among perceived stress, psychological resilience, and job burnout in standardized gastroenterology nursing training students. AMOS 24.0 statistical software was used to construct a structural equation model to analyze the mediating effect of psychological resilience between perceived stress and job burnout in standardized gastroenterology nursing training students. The bias-corrected bootstrap method was applied to test the mediating effect of psychological resilience.Results:The averaged total scores of 156 standardized gastroenterology nursing training students were (29.89±0.30) for perceived pressure, (62.45±2.44) for psychological resilience, and (57.85±3.44) for job burnout. Of the trainees, 88 (56.41%) exhibited job burnout, including 39 (25.00%) with mild burnout, 41 (26.28%) with moderate burnout, and 8 (5.13%) with severe burnout. The Pearson correlation analysis showed that perceived stress was positively correlated with job burnout ( r=0.543, P<0.05) and negatively correlated with psychological resilience ( r=-0.443, P<0.05), and psychological resilience was negatively correlated with job burnout ( r=-0.478, P<0.05). The results of bias-corrected bootstrap test showed that psychological resilience had a partial mediating effect between perceived stress and job burnout among standardized gastroenterology nursing training students ( P<0.05), accounting for 32.63% of the total effect. Conclusions:Moderate job burnout was observed in standardized gastroenterology nursing training students. Job burnout was closely related to perceived stress and psychological resilience. Psychological resilience partly mediated the relationship between perceived stress and job burnout. Therefore, clinical managers may alleviate the perceived psychological pressure and subsequently reduce the occurrence of job burnout among standardized nursing training students by increasing psychological resilience.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

ObjectiveTo analyze the expression level of triggering receptor expressed on myeloid cells-1 （TREM-1） in serum and ascites of patients with cirrhotic ascites， and to investigate its correlation with clinical features and inflammatory markers and its role in the diagnosis of infection and prognostic evaluation. MethodsA total of 110 patients with cirrhotic ascites who were hospitalized in The Fifth Hospital of Shijiazhuang from January 2019 to December 2020 were enrolled， and according to the presence or absence of intra-abdominal infection， they were divided into infection group with 72 patients and non-infection group with 38 patients. The patients with infection were further divided into improvement group with 38 patients and non-improvement group with 34 patients. Clinical data and laboratory markers were collected from all patients. Serum and ascites samples were collected， and ELISA was used to measure the level of TREM-1. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between indicators. A multivariate Logistic regression analysis was used to identify the influencing factors for the prognosis of patients with cirrhotic ascites and infection. The receiver operating characteristic （ROC） curve was used to evaluate the diagnostic and prognostic efficacy of each indicator， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsThe level of TREM-1 in ascites was significantly positively correlated with that in serum （r=0.50， P<0.001）. Compared with the improvement group， the non-improvement group had a significantly higher level of TREM-1 in ascites （Z=-2.391， P=0.017） and serum （Z=-2.544， P=0.011）， and compared with the non-infection group， the infection group had a significantly higher level of TREM-1 in ascites （Z=-3.420， P<0.001）， while there was no significant difference in the level of TREM-1 in serum between the two groups （P>0.05）. The level of TREM-1 in serum and ascites were significantly positively correlated with C-reactive protein （CRP）， procalcitonin （PCT）， white blood cell count， and neutrophil-lymphocyte ratio （r=0.288， 0.344， 0.530， 0.510， 0.534， 0.454， 0.330， and 0.404， all P<0.05）. The ROC curve analysis showed that when PCT， CRP， and serum or ascitic TREM-1 were used in combination for the diagnosis of cirrhotic ascites with infection， the AUCs were 0.715 and 0.740， respectively. The multivariate Logistic regression analysis showed that CRP （odds ratio ［OR］=1.019， 95% confidence interval ［CI］： 1.001‍ ‍—‍ ‍1.038， P=0.043） and serum TREM-1 （OR=1.002， 95%CI： 1.000‍ ‍—‍ ‍1.003， P=0.016） were independent risk factors for the prognosis of patients with cirrhotic ascites and infection， and the combination of these two indicators had an AUC of 0.728 in predicting poor prognosis. ConclusionThe level of TREM-1 is closely associated with the severity of infection and prognosis in patients with cirrhotic ascites， and combined measurement of TREM-1 and CRP/PCT can improve the diagnostic accuracy of infection and provide support for prognostic evaluation.

Objective:To analyze the hepatitis C virus（HCV）infection status and genotype of patients with digestive system tumors in Shanxi Cancer Hospital from 2020 to 2024 and provide a basis for formulating and adjusting prevention and control strategies，optimizing diagnosis and treatment plans.Methods:Selecting Shanxi Cancer Hospital as the research site，a continuous sampling method was used from January 2020 to December 2024 to investigate the population of patients with digestive system tumors who met the inclusion criteria during the survey period. Blood samples were collected and HCV antibodies were detected by enzyme-linked immunosorbent assay（ELISA）. HCV RNA was detected by reverse transcription nested polymerase chain reaction（RT-PCR），and genotyping was performed. The positive rate of HCV antibodies and the characteristics of HCV RNA genotypes were analyzed.Results:A total of 2 068 outpatients of Shanxi Cancer Hospital were investigated from 2020 to 2024. The total number of HCV antibody positive cases was 59，with an HCV antibody positive rate of 2.85%；Among the 59 HCV antibody positive patients，38 were HCV-RNA positive，accounting for 64.41% of HCV antibody positive patients；the basic information of HCV infected patients showed that the proportion of males was higher than females，and the age group with the highest proportion was 40 to 59 years old，followed by those aged 60 and above，and the proportion of patients in rural areas was higher than that in urban areas，and the HCV infection rate of liver cancer patients was the highest，followed by gastric cancer and colorectal cancer；the overall HCV antibody positivity rate showed a downward trend from 2020 to 2024（ χ2=4.718， P<0.05）. Among the 59 HCV antibody positive patients，38 were HCV RNA positive，accounting for 64.41% of the HCV antibody positive patients. Among the 38 HCV RNA positive patients，24 were genotype 1b（63.16%），5 were genotype 2a（13.16%），2 were genotype 3a（5.26%），4 were genotype 3b（10.53%），and 3 were genotype 6a（7.89%）. Genotypes 4，5，and mixed genotypes were not found. The distribution of genotypes 1b，2a，3a，3b，and 6a among patients of different genders showed statistically significant differences（ χ2=14.710， P<0.05）. The distribution of genotypes 1b，2a，3a，3b，and 6a among patients of different age groups also showed statistically significant differences（ χ2=15.179， P<0.05）. The distribution of genotypes 1b，2a，3a，3b，and 6a among patients from different residential areas also showed statistically significant differences（ χ2=10.126， P<0.05）. The average HCV RNA quantification of genotype 1b patients was（8.91±0.83）IU/ml，that of genotype 2a patients was（4.23±0.65）IU/ml，and that of patients with other genotypes was（5.06±0.98）IU/ml. The HCV RNA quantification of genotype 1b patients was significantly higher than that of genotype 2a patients（ t=11.813， P<0.001）. There were no statistically significant differences in HCV RNA quantification among genotype 1b，2a，and other genotypes（ F=0.815， P=0.665）. Conclusion:From 2020 to 2024，the HCV antibody positivity rate among patients with digestive system tumors at Shanxi Cancer Hospital was relatively high. Male，middle-aged and elderly，and rural populations were high-risk factors for HCV infection，and the HCV-RNA genotype was mainly genotype 1b，with differences in genotype distribution among different genders，ages，and residential areas.