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.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

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.

Objective The "heuristic" teaching rounds were applied to cardiovascular diseases and we observed the application effect . Methods From January to March 2017, 56 resident physicians at internal medicine base in the First Affiliated Hospital of Xinjiang Medical University were randomly divided into the experimental group and the control group, with 28 people of each group. The experimental group mainly adopted heuristic teaching rounds, and the control group adopted conventional teaching rounds. Interview method was used to interview the instructors , resident physicians , doctors and nurses in preparation for teaching rounds, the implementation process, the expected goals and effects. 56 resident physicians evaluated the preparation, guidance process, guidance methods and outcomes of ward rounds. SPSS 19.0 was used for statistical analysis, and rank sum test was used for evaluation results. Results As to the familiarity of the instructor on the condition (82.15％vs. 30.86％), guiding the training of humanistic care (92.86％ vs. 39.29％), physical examination (96.43％ vs. 28.57％), analysis of auxiliary examination (85.71％vs. 35.71％), writing medical records (85.72％ vs. 14.29％), summarizing the characteristics of cases (78.57％vs. 35.71％), diagnosis and differential diagnosis (85.71％vs. 21.43％), treatment plan making (85.71％vs. 25.00％), question formulation (89.29％vs. 30.72％), explanation of difficult problems and new progress ( 78 . 57％ vs . 17 . 86％) , content summary ( 92 . 85％ vs . 28 . 58％) the experimental group was significantly higher than the control group. In the experimental group, the teaching rounds of communication (96.43％vs. 46.43％), history acquisition techniques (85.72％vs. 21.43％), examination techniques (92.86％vs. 28.57％), clinical thinking (92.86％ vs. 28.57％), learning interests (96.43％ vs. 25.00％) and efficiency (85.71％ vs. 14.28％), the understanding and memory of knowledge (85.72％ vs. 28.57％), the problem solving ability (89.29％ vs. 21.43％), improvement of team collaboration (67.86％ vs. 28.57％) were significantly higher than those in the control group (P<0.05). Conclusion The "heuristic" teaching rounds attached great importance to preparation before and after class, focusing on resident physicians' active participation and teamwork, integrating humanistic care and communication skills, giving full play to the resident physicians motivation so as to ensure their efficient learning.

Objective: To investigate whether diffusion tensor imaging (DTI) and motor evoked potentials (MEP) can be used as biomarkers to assess the degree of motor dysfunction of stroke survivors. Methods: Sixty partially-paralyzed stroke survivors were given Fugl-Meyer assessments (FMAs) and MEP tests and assessed using DTI seeking any correlations among the results. The receiver operating characteristics curves (ROCs) were prepared to determine the tests′ efficacy in assessing severe motor dysfunction. Results: ① Asymmetry in the fractional anisotropy (aFA) of the peduncles cerebra as measured by DTI was negatively correlated with the FMA scores of the upper and lower limbs on the affected side. The aFA values of the posterior limb of the internal capsule (PLIC) were negatively correlated with the FMA scores of the affected upper limb, but not with the FMA scores of the affected lower limbs. The abnormalities in central motor conduction time and motor threshold, which are MEP parameters, were negatively correlated with the FMA scores of the affected limbs. ② The ROCs showed that the aFA value of the PLIC was the best indicator for assessing severe upper limb motor dysfunction, with a cut-off value of 0.167 giving the best discrimination. MEP waveform loss could also be used. It has high sensitivity but low specificity. ③ A combination of DTI and MEP can improve specificity in assessing severe motor dysfunction in the upper limbs. Conclusion DTI and MEP can both be used to evaluate motor dysfunction in stroke survivors. They have high clinical value for assessing severe motor dysfunction of the upper limbs.