Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver condition globally, lacks adequate and effective therapeutic remedies in clinical practice. Recent studies have increasingly highlighted the close connection between the ubiquitin-proteasome system (UPS) and the progression of MASLD. This relationship is crucial for understanding the disease's underlying mechanism. As a sophisticated process, the UPS govern protein stability and function, maintaining protein homeostasis, thus influencing a multitude of elements and biological events of eukaryotic cells. It comprises four enzyme families, namely, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), ubiquitin-protein ligases (E3), and deubiquitinating enzymes (DUBs). This review aims to delve into the array of pathways and therapeutic targets implicated in the ubiquitination within the pathogenesis of MASLD. Therefore, this review unveils the role of ubiquitination in MASLD while spotlighting potential therapeutic targets within the context of this disease.

Objective:To observe the pathological changes of myocardial tissue under differentdegrees of coronary atherosclerotic le-sions,to measure the expression levels of proteins associated with the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway in coronary arteries,and to investigate the role of cGAS-STING in the development and progression of coronary heart disease.Methods:Eligible cases of coronary heart disease and control cases were selected and divided into control group with normal coronary arteries and grade Ⅰ,Ⅱ,Ⅲ,and Ⅳ coronary artery stenosis groups.HE staining was used to observe and evaluate the pathological conditions of coronary arteries,Western blotting was used to measure the expression levels of downstream pro-teins of the cGAS-STING pathway in coronary tissue,and ELISA was used to measure the levels of inflammatory factors in coronary tis-sue.A correlation analysis was performed to investigate the correlation of the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors with the development and progression of coronary heart disease.Results:Mi-croscopic examination showed that compared with the control group,the other four groups had varying degrees of pathological changes such as vascular wall thickening and luminal stenosis,with a gradual increase in the degree of stenosis from grade Ⅰ to grade Ⅳ coronary lesions.Compared with the control group,the grade Ⅰ,Ⅱ,Ⅲ,and Ⅳ coronary artery stenosis groups had significant increases in the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors in coronary tis-sue,with a trend of increase from grade Ⅰ to grade Ⅳ coronary le-sions.The expression levels of downstream proteins of the cGAS-STING signaling pathway in coronary tissue were positively correlated with the development and progression of coronary heart disease(cGAS:r=0.927,P<0.001;p-Sting:r=0.889,P<0.001;p-TBK1:r=0.910,P<0.001;p-IRF3:r=0.936,P<0.001;IFN-1:r=0.936,P<0.001;TNF-α:r=0.945,P<0.001;IL-1β:r=0.962,P<0.001;IL-6:r=0.933,P<0.001).Conclusion:There are significant differences in the expression levels of downstream proteins of the cGAS-STING signaling pathway and related inflammatory factors,and this signaling pathway may be a potential target for the treatment of coronary heart disease.

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribo-somopathy genes have also been found to be intimately associated with cancer development.The cor-relation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

Objective The objective of this study was to analyze the incidence and mortality of female breast cancer in canc-er registration areas of Gansu province in 2019 and the change trend of female breast cancer incidence and mortality from 2010 to 2019,so as to provide data support for the prevention and treatment of breast cancer.Methods The incidence and mortality data of breast cancer and related demographic data in all cancer registration areas in Gansu province from 2010 to 2019 were collected.The incidence,mortality,age-standardized incidence by Chinese standard population(ASIRC),age-standardized mortality by Chinese standard population(ASMRC),age-standardized incidence by World standard population(ASIRW)and age-standardized mortality by World standard population(ASMRW),cumulative incidence and other key indicators of female breast cancer in each cancer registra-tion area were calculated according to urban and rural distribution and age groups.Joinpoint linear regression was used to analyze the annual change trend of incidence and mortality of female breast cancer in cancer registration areas in Gansu province from 2010 to 2019.Results In 2019,the number of new cases from female breast cancer in the cancer registration areas of Gansu province was 1,502 cases,accounting for 13.14%of all new malignant tumors in women.The incidence was 33.00/100,000,ASIRC and ASIRW were 23.83/100,000 and 23.81/100,000,respectively,and a cumulative rate of 0-74 years old was 2.34%.The incidence of breast cancer in urban and rural areas was 22.25/100,000 and 26.59/100,000,respectively.In 2019,the number of female breast cancer deaths in the cancer registration areas of Gansu province was 254,accounting for 5.61%of all female malignant tumor deaths.The crude mortality was 5.58/100,000,ASMRC and ASMRW were 3.70/100,000 and 3.90/100,000,respectively.The cumulative rate of 0-74 years old was 0.39%.The ASMRC of breast cancer in urban and rural areas was 3.63/100,000 and 3.79/100,000,respec-tively.The annual change trend in the ASIRC of female breast cancer in the province from 2010 to 2019 was not statistically significant(APC=-0.35%,P=0.81),while ASMRC decreased by an average of 9.85%per year(APC=-9.85%,P=0.03).Conclusion Breast cancer is a high incidence malignant tumor that threatens the physical and mental health of female residents in Gansu province,and it is a kind of cancer that women focus on.We should actively screen the risk group of women.

OBJECTIVES: To investigate the effects and mechanisms of deubiquitinating enzyme Josephin domain containing 2 (JOSD2) on susceptibility of non-small cell lung carcinoma (NSCLC) cells to anti-cancer drugs. METHODS: The transcriptome expression and clinical data of NSCLC were downloaded from the Gene Expression Omnibus. Principal component analysis and limma analysis were used to investigate the deubiquitinating enzymes up-regulated in NSCLC tissues. Kaplan-Meier analysis was used to investigate the relationship between the expression of deubiquitinating enzymes and overall survival of NSCLC patients. Gene ontology enrichment and gene set enrichment analysis (GSEA) were used to analyze the activation of signaling pathways in NSCLC patients with high expression of JOSD2. Gene set variation analysis and Pearson correlation were used to investigate the correlation between JOSD2 expression levels and DNA damage response (DDR) pathway. Western blotting was performed to examine the expression levels of JOSD2 and proteins associated with the DDR pathway. Immunofluorescence was used to detect the localization of JOSD2. Sulforhodamine B staining was used to examine the sensitivity of JOSD2-knock-down NSCLC cells to DNA damaging drugs. RESULTS: Compared with adjacent tissues, the expression level of JOSD2 was significantly up-regulated in NSCLC tissues (P<0.05), and was significantly correlated with the prognosis in NSCLC patients (P<0.05). Compared with the tissues with low expression of JOSD2, the DDR-related pathways were significantly upregulated in NSCLC tissues with high expression of JOSD2 (all P<0.05). In addition, the expression of JOSD2 was positively correlated with the activation of DDR-related pathways (all P<0.01). Compared with the control group, overexpression of JOSD2 significantly promoted the DDR in NSCLC cells. In addition, DNA damaging agents significantly increase the nuclear localization of JOSD2, whereas depletion of JOSD2 significantly enhanced the sensitivity of NSCLC cells to DNA damaging agents (all P<0.05). CONCLUSIONS Deubiquitinating enzyme JOSD2 may regulate the malignant progression of NSCLC by promoting DNA damage repair pathway, and depletion of JOSD2 significantly enhances the sensitivity of NSCLC cells to DNA damaging agents.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Antineoplastic Agents/pharmacology* ; Lung Neoplasms/genetics* ; DNA Damage ; DNA ; Deubiquitinating Enzymes/genetics*

Objective:To explore the effects of serum triglyceride (STAG) level within 48 hours after hospitalization on the complications of acute pancreatitis (AP).Methods:From January 2012 to June 2016, 1 006 hospitalized patients diagnosed with AP at the Third People′s Hospital of Chengdu were collected. According to the STAG level within 48 hours after hospitalization, AP patients were divided into normal to mild hypertriglyceridemia (HTG) group(STAG <2.3 mmol/L, 877 cases), moderate HTG group(STAG: 2.3 to <8.5 mmol/L, 82 cases) and severe HTG group (≥8.5 mmol/L, 47 cases). The general clinical data and the incidence of local complications of AP including acute necrotizing pancreatitis, pancreatic necrosis, acute peripancreatic fluid collection (APFC) and acute necrotic collection (ANC) and AP-associated gastrointestinal abnormal changes were compared in the three groups. The severity of the complications of AP was scored by modified-magnetic resonance severity index (M-MRSI). Wilcoxon rank sum test and chi-square test were used for statistical analysis, and multivariate logistic regression analysis was used to analyze the correlation between STAG level and persistent organ failure (POF).Results:Compared with that of the normal to mild HTG group and moderate HTG group, the age of the patients of the severe HTG group was the youngest (52 years old, 19 to 82 years old and 47 years old, 21 to 62 years old vs. 35 years old, 18 to 43 years old), the proportion of male was the highest (46.3%, 406/877 and 64.6%, 53/82 vs. 85.1%, 40/47), and the differences were statistically significant( Z=3.943, 2.841, χ2=26.912, 6.224, all P<0.017). The proportion of body mass index (BMI)≥30 kg/m 2 in severe HTG group was higher than that in normal to mild HTG group (38.3%, 18/47 vs. 20.2%, 177/877), and the difference was statistically significant ( χ2=8.792, P=0.003). The proportions of patients with history of diabetes and severe alcohol intake of moderate HTG group and severe HTG group were all higher than those of normal to mild HTG group (31.7%, 26/82 and 29.8%, 14/47 vs. 15.4%, 135/877; 37.8%, 31/82 and 46.8%, 22/47 vs. 9.6%, 84/877), and the differences were statistically significant ( χ2=14.286, 6.833, 56.613 and 60.844, all P<0.017). Compared with those of the normal to mild HTG group and moderate HTG group, the incidences of pancreatic necrosis, APFC, and the M-MRSI score of the severe HTG group were all the highest (8.2%, 72/877 and 15.9%, 13/82 vs. 38.3%, 18/47; 17.8%, 156/877 and 36.6%, 30/82 vs. 59.6%, 28/47; 2, 0 to 10 and 3, 0 to 10 vs. 5, 0 to 10), and the differences were statistically significant( χ2=45.936, 8.244, 48.842 and 6.381, Z=2.711 and 3.049, all P<0.017). The incidence rates of acute necrotizing pancreatitis and ANC of moderate HTG group and severe HTG group were all higher than those of normal to mild HTG group(28.0%, 23/82 and 48.9%, 23/47 vs. 13.3%, 117/877; 26.8%, 22/82 and 42.6%, 20/47 vs. 13.3%, 117/877), and the differences were statistically significant ( χ2=13.011, 43.965, 11.008 and 30.144, all P<0.017). The incidence rate of POF of severe HTG group was higher than those of normal to mild HTG group and moderate HTG group (46.8%, 22/47 vs.14.8%, 130/877 and 24.4%, 20/82), and the differences were statistically significant ( χ2=33.205 and 6.838, both P<0.017). The results of multivariate logistic regression analysis showed that age ≥ 60 years old (odds ratio ( OR)=1.84, 95% confidence interval ( CI) 1.26 to 3.03), BMI≥30 kg/m 2 ( OR=2.41, 95% CI 1.61 to 3.77), alcohol intake ( OR=3.81, 95% CI 2.09 to 5.47), moderate HTG( OR=1.89, 95% CI 1.78 to 5.23) and severe HTG ( OR=3.65, 95% CI 1.98 to 6.49) were independent risk factors of POF(all P<0.05). Conclusion:The STAG level is related to the complications of AP, and moderate HTG and severe HTG(STAG ≥2.3 mmol/L) are independently associated with the risk of POF.

Objective:To explore the application effect of health education based on knowledge, attitude and practice model in improving readiness for hospital discharge and quality of discharge guidance for patients undergoing intracranial aneurysm surgery.Methods:Using the convenient sampling method, a total of 152 patients who underwent craniotomy and intravascular interventional embolization in Neurosurgery Department of the First Affiliated Hospital of Xinjiang Medical University from July 2019 to May 2020 were selected. According to the random number table method, they were divided into in the control group and the experimental group, with 76 cases in each group. The experimental group was given health education based on knowledge, attitude and practice model at basis of routine discharge guidance health education, while the control group was given routine discharge guidance health education. The scores of readiness for hospital discharge and quality of discharge guidance of the two groups were compared.Results:The total score of readiness for hospital discharge in experimental group was (90.80±7.63) , which was higher than that in control group (55.34±9.80) . The total score of quality of discharge guidance of the experimental group was (159.11±10.79) , which was higher than (80.45±12.65) of the control group, and the differences were statistically significant ( t= -24.893, -41.230; P<0.01) . Conclusions:The implementation of health education based on knowledge, attitude and practice model can effectively improve readiness for hospital discharge and quality of discharge guidance for patients undergoing intracranial aneurysm surgery.

Objective To explore the effect of clinical practice on clinical practice ability in master of nursing specialist and evaluation measures of the clinical practice ability.Methods A total of 17 masters of nursing specialist engaged in clinical practice were selected in the First Affiliated Hospital of Xinjiang Medical University from March 2014 to February 2016.They were cultivated with two-level management methods of instruction between tutors and clinical teachers along with following up the requirements of “Nursing Postgraduates Clinical Practice Handbook”.The clinical practice ability evaluation form of master of nursing specialist was used to evaluate the clinical practice ability of 17 postgraduates from 4 aspects including graduate teachers,clinical teachers,classmates,self evaluation from 360°feedback.Results After clinical practice, the score of 4 aspects and the total score of clinical practice ability were higher than those before clinical practice with significant differences (P <0.05 ).However,the results of 360°feedback showed that there were no statistically significant differences in the score of theoretical level,professional ethics,ability to research and the total score among different evaluation subjects (P >0.05 ).Besides,the results revealed that there were statistically significant differences in the evaluation of practice ability of nursing and teaching management ability (P <0.05).In addition,the score of practice ability of nursing care and management capacity of teaching evaluated by classmates were higher than those evaluated by other subjects (P <0.05).Conclusions Scientific clinical practice teaching mode of master of nursing specialist can effectively improve clinical practice ability of postgraduates.Besides,the 360°feedback can be seen as an effective tool to objectively and fairly evaluate clinical practice ability of high-quality and utility-type nursing talents.