1.Deubiquitinase OTUD6A alleviates acetaminophen-induced liver injury by targeting EZH2 to reduce cell death in hepatocytes.
Yanni ZHAO ; Tianyang JIN ; Tingxin XU ; Yi FANG ; Qingsong ZHENG ; Wu LUO ; Weiwei ZHU ; Yue CHEN ; Jiong WANG ; Yi CHEN ; Wei ZUO ; Lijiang HUANG ; Guang LIANG ; Yi WANG
Acta Pharmaceutica Sinica B 2025;15(9):4772-4788
Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.
2.Prevalence, associated factors and patterns of multimorbidity of non-communicable diseases among adults in Shaanxi Province
Heng LIU ; Jiao MA ; Hao HUANG ; Qian ZHANG ; Yaqiong WANG ; Wanrong LUO ; Binghua CHEN ; Binguo YAN ; Ziyi YANG ; Hangzhao FAN ; Tianyang ZHAI ; Tianhui TANG ; Leilei PEI ; Fangyao CHEN ; Baibing MI ; Tianyou MA ; Shaonong DANG ; Hong YAN ; Yaling ZHAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(3):473-480
【Objective】 To estimate the prevalence, associated factors and patterns of multimorbidity of non-communicable diseases among adults in Shaanxi Province so as to provide evidence for the prevention and control of non-communicable diseases. 【Methods】 We used the data of adults aged 18 years and older collected in the baseline survey of Shaanxi Project in the Regional Ethnic Cohort Study in Northwest China. Multinomial logistic regression was used to explore the associated factors for multimorbidity. Exploratory factor analysis was used to extract patterns of multimorbidity. 【Results】 The prevalence of multimorbidity was 10.7% among the 44 442 participants. Age increase, being males, urban residence, and being overweight or obesity were positively associated with multimorbidity. Compared with women, men had a higher risk of multimorbidity. The OR and 95% CI was 1.25 (1.12-1.39). The risk of multimorbidity increased with age among adults. Compared with participants aged 18.0-34.9 years, the ORs and 95% CIs of those aged 35.0-44.9, 45.0-54.9, 55.0-64.9, and ≥65.0 years were 4.73 (3.47-6.46), 15.61 (11.60-21.00), 41.39 (30.76-55.70) and 90.04 (66.58-121.77), respectively. The primary multimorbidity patterns among adults in Shaanxi were cardiovascular-metabolic multimorbidity (5.4%), viscero-articular multimorbidity (1.0%), and respiratory multimorbidity (0.3%). 【Conclusion】 More than one in ten adults in Shaanxi Province had multimorbidity, and the predominant pattern of multimorbidity was cardiovascular-metabolic multimorbidity. The prevention and control of non-communicable diseases should be reinforced in middle-aged and older people, males, people living in the urban, and overweight or obese people. More attention should be paid to the prevention and control of cardiovascular-metabolic diseases.
3.Association between dietary quality and bone mass among middle-aged and elderly people in Gansu Province
Wanrong LUO ; Yi ZHAO ; Jiao MA ; Qian ZHANG ; Tianhui TANG ; Hao HUANG ; Heng LIU ; Binghua CHEN ; Hangzhao FAN ; Tianyang ZHAI ; Yaqiong WANG ; Binguo YAN ; Leilei PEI ; Fangyao CHEN ; Wanli XUE ; Shaonong DANG ; Xinhua WANG ; Hong YAN ; Yaling ZHAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(3):481-488
【Objective】 To evaluate the dietary quality with the dietary balance index (DBI_16) and the association between dietary quality and bone mass among middle-aged and elderly people in Gansu Province so as to provide evidence for improving dietary quality and bone health status of Gansu population. 【Methods】 Based on the information of the type and quantity of food intake and the bone mass of middle-aged and elderly people aged 35 years and above collected by the Gansu Project in the Regional Ethnic Cohort Study in Northwest China, DBI_16 was used to evaluate the intake level of cereals, vegetables, fruits, milk, beans, fish and shrimp, eggs and other foods, and the degree of inadequate, excessive and unbalanced dietary intake of the participants. Multiple linear regression was used to evaluate the associations of three component indexes of DBI_16, high bound score (DBI_HBS), low bound score (DBI_LBS), diet quality distance (DBI_DQD), and seven single indexes of DBI_16 with bone mass. 【Results】 Analyses of the dietary and bone mass data of 11,840 participants showed that 44.8% of participants consumed excessive amounts of cereals compared to the dietary recommendation. 96.3%, 90.6%, 90.1%, 71.9%, 95.1% and 60.3% of participants’ intake of vegetables, fruits, milk, soybeans, fish and shrimp, and eggs, respectively, were inadequate. 47.7% participants consumed less than 10 types of food. 2.3% participants’ DBI_LBS levels were appropriate. 54.7% participants’ DBI_HBS levels were appropriate. Only 1.2% participants’ DBI_DQD reached a balanced level. The bone mass level in the study population was (2.5±0.6) kg [(2.8±0.5) kg for men and (2.3±0.5) kg for women]. After adjusting for sociodemographic characteristics, lifestyle, total dietary energy intake and body mass index, DBI_LBS and DBI_DQD were negatively associated with bone mass [β and 95% CI was -0.002 01 (-0.003 62--0.000 40) and -0.001 76 (-0.003 09--0.000 43), respectively]. 【Conclusion】 Dietary intake imbalance is common among middle-aged and elderly people in Gansu Province, and the more severe the dietary intake imbalance, the lower the bone mass level.
4.Advances of CLDN18.2 protein in the therapy of malignant tumors
Liang'e XU ; Tianyang HE ; Li ZHANG ; Yidan LU ; Cong LUO
Chinese Journal of Clinical Oncology 2019;46(6):311-315
With the development of molecular biology research, targeted therapy has become the fourth effective method for the treatment of malignant tumors after surgery, radiotherapy, and chemotherapy. Unlike the traditional chemotherapeutic drugs, molecular targeted drugs possess the advantages of high specificity, definite curative effects, and less adverse effects. CLDN18.2 protein is a transmembrane protein that is highly selective and stably overexpressed during the development of various malignant tumors, especially gastrointestinal tumors, and metastases. A specific antibody against this protein, claudiximab (zolbetuximab/IMAB362), has achieved great success in recent clinical trials. Thus, CLDN18.2 protein is expected to be a safe and effective molecular target for targeted therapy in some malignancies.
5.Value of contrast-enhanced computed tomography and magnetic resonance imaging in diagnosis of residual or recurrent lesion after transcatheter arterial chemoembolization in hepatocellular carcinoma: A Meta-analysis
Dong LI ; Tianyang LUO ; Yawei RAN
Journal of Clinical Hepatology 2019;35(10):2214-2219
ObjectiveTo systematically evaluate the value of contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CEMRI) in the diagnosis of residual or recurrent lesion after transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). MethodsPubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang Data were searched for studies on CECT and/or CEMRI in the diagnosis of residual or recurrent lesion after TACE published up to April 2019. After two reviewers independently performed literature screening, data extraction, and assessment of the risk of bias using the QUADAS-2 tool, Stata 12.0 and RevMan 5.3 were used to analyze pooled sensitivity, specificity, and area under the receiver operator characteristic curve (AUC). ResultsA total of 13 studies on CECT and 13 studies on CEMRI in the diagnosis of residual or recurrent HCC lesion after TACE were included, with 934 lesions from 748 patients and 847 lesions from 557 patients, respectively. High heterogeneity was observed in the 13 studies on CECT in the diagnosis of residual or recurrent HCC lesion after TACE (P=0.001, Q=12.56, I2=84.08%), while no significant heterogeneity was observed in the 13 studies on CEMRI (P=0.473, Q=0.11, I2=0). In the diagnosis of residual or recurrent HCC lesion after TACE, CECT had a sensitivity of 72% (95% confidence interval [CI]: 66%-78%), a specificity of 99% (95% CI: 93%-100%), and an AUC of 0.87 (95% CI: 0.83-0.89), and CEMRI had a sensitivity of 88% (95% CI: 82%-93%), a specificity of 96% (95% CI: 91%-98%), and an AUC of 0.98 (95% CI: 0.96-0.99). CECT had a significantly lower sensitivity than CEMRI in the diagnosis of residual or recurrent HCC lesion after TACE (Z=2.12, P=0.03). ConclusionIn comparison with CECT, CEMRI has an extremely higher diagnostic efficiency in the diagnosis of residual or recurrent HCC lesion after TACE and is thus an effective method for diagnosis.

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