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Acta Pharmaceutica Sinica B ; (6): 1071-1092, 2023.
Article in English | WPRIM | ID: wpr-971758


Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

Medical Journal of Chinese People's Liberation Army ; (12): 851-856, 2020.
Article in Chinese | WPRIM | ID: wpr-849661


Objective To evaluate the clinical effects of multi-detector computed tomography (MDCT) multi-postprocessing techniques in the evaluation of small bowel obstruction (SBO). Methods Clinical and MDCT imaging data of 90 patients with SBO were collected. Three radiologists respectively applied two protocols (protocol 1 consisted of conventional axial and coronal reformations and protocol 2 involved integration of multiple post-processing techniques) to image post-processing and interpretation of patients' MDCT volume data, and completed condition evaluation reports. Two protocols were compared regarding relevant diagnostic self-confidence, clinical satisfaction, clinical treatment decisions, and radiological adverse events. Results In the same protocol, the diagnostic self-confidence showed no significant difference between three radiologists for any evaluation parameter (P>0.05), but the diagnostic self-confidence of three radiologists was significantly higher in the protocol 2 than in the protocol 1 (P<0.01). The clinical satisfaction was also significantly higher in the protocol 2 than in the protocol 1 for all the individual and compositive illness assessment reports (P<0.01). After protocol 2 was applied clinically, it changed the previous treatment decisions based on protocol 1 in 11 patients (12.22%). About radiological adverse events, regardless of minor, major, or the sum of them, protocol 1 was significantly higher than protocol 2 (P<0.05). Conclusion Integration of multi-postprocessing techniques can improve diagnostic self-confidence and clinical satisfaction of MDCT for assessing SBO and effectively reduce radiological adverse events.

Journal of Central South University(Medical Sciences) ; (12): 317-325, 2015.
Article in Chinese | WPRIM | ID: wpr-815184


OBJECTIVE@#To assess the effect of premolar extractions on third molar angulation changes in orthodontic patients.@*METHODS@#The Cochrane library, PubMed, Embase, China Science and Technology Periodical Database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM) and Wanfang database were searched from January 1, 1990 to May 20, 2014 to identify all the studies about third molar angulation changes in orthodontic patients with or without premolars extraction, which was assigned as a extraction group and a control group. Th e extraction group was further divided into a fi rst premolar extraction subgroup and a second premolar extraction subgroup. Literature filtering, data extraction and methodological quality evaluation were finished independently by two researchers. After cross checking, the disagreements were solved by discussion. Meta-analysis was carried out by RevMan 5.3.3 software.@*RESULTS@#Ten studies involving 712 patients were included. Meta-analysis revealed that: compared with the control group, the changes of third molar angulation in maxillary and mandible in the extraction group were statistically significantly different (all P0.05).@*CONCLUSION@#The orthodontic treatment involving first or second premolar extractions can improve the maxillary third molar angulation, and the second premolar extraction is the best option.

Humans , Asian People , Bicuspid , China , Mandible , Maxilla , Molar, Third , Tooth Extraction