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The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.
ABSTRACT
Objective@#To investigate the perception about illness and identify its influencing factors among patients with non-alcoholic fatty liver disease ( NAFLD ) , so as to provide insights into the management of NAFLD patients. @*Methods@#NAFLD patients admitted to Hangzhou First People's Hospital Affiliated to Medical School of Zhejiang University from January to June, 2020, were selected as the study subjects, and subjects' demographic features were collected using questionnaires, including gender, age and education level. The perception about illness, coping models and social support were assessed using the Brief Illness Perception Questionnaire (BIPQ), Medical Coping Modes Questionnaire ( MCMQ ) and Social Support Rating Scale ( SSRS ), respectively, and factors affecting the perception about illness were identified using multivariable linear regression analysis among NAFLD patients.@*Results@#The 286 respondents included 151 males ( 52.80% ) and 135 females ( 47.20% ), and had a mean age of ( 55.27±10.39 ) years. The mean illness perception score was 38.55±9.21 among the respondents. The mean SSRS score was 42.90±8.64. The mean coping mode scores of confronce, avoidance and resignation were 23.51±4.30, 17.49±2.82, and 7.12±2.05, respectively. Multivariable linear regression analysis identified education level ( high school, β'=-0.216; diploma and above, β'=-0.355 ), household monthly income per capita ( β'=-0.372 ), regular exercise ( β'=-0.310 ), coping modes ( confronce, β'=-0.326; avoidance, β'=-0.191 ) and social support level ( β'=-0.259 ) as factors affecting the perception about illness among NAFLD patients.@*Conclusion@#Negative perceptions about illness are found among NAFLD patients, and household income, education level, regular exercise and coping modes are factors affecting the illness perception among NAFLD patients.
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Objective:To investigate the value of high-frequency ultrasound and shear wave elastography in preoperative evaluation of basal cell carcinoma (BCC) .Methods:A total of 95 patients with histopathologically confirmed cutaneous BCC were enrolled from Department of Dermatology, Hospital of Traditional Chinese Medicine of Zhongshan from January 2017 to December 2020, all of whom had underwent preoperative conventional ultrasonography and shear wave elastography. Conventional ultrasonography parametres including the maximum diameter, maximum infiltration depth, maximum blood flow velocity and resistance index were recorded, so were shear wave elastography parametres including the average Young′s modulus (Eave) , Young′s modulus standard deviation (Esd) and average Young′s modulus ratio (Eratio) . All the patients were divided into high- and low-risk BCC groups according to pathologic subtypes. Paired t-test was used to compare conventional ultrasonography and shear wave elastography findings between the 2 groups. Results:There were 15 cases in the high-risk BCC group and 80 cases in the low-risk BCC group. Compared with the low-risk BCC group, the high-risk BCC group showed significantly increased maximum depth of tumor infiltration (8.5 ± 4.6 mm vs. 4.5 ± 1.6 mm, t = 6.150, P < 0.001) , Eave (32.7 ± 11.2 kPa vs. 20.6 ± 5.1 kPa, t = 4.065, P = 0.001) and Esd (7.0 ± 4.1 kPa vs. 4.2 ± 2.1 kPa, t = 2.632, P = 0.018) , while there were no significant differences in the other measurement data between the two groups (all P > 0.05) . The areas under the receiver operating characteristic curves of the maximum infiltration depth, Eave and Esd for the diagnosis of high-risk BCC were 0.775, 0.909 and 0.822 respectively, and Eave showed the best diagnostic performance. Using 25.7 kPa as the cut-off value, the sensitivity and specificity of Eave were 86.7% and 85.0% for the diagnosis of high-risk BCC, respectively. Conclusion:High-frequency ultrasound and shear wave elastography can facilitate differential diagnosis between high- and low-risk BCC.
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Objective:To study the effect of overdose fluoride on Smad3 expression during development course of Wistar rat's incisor,and then to explore pathogenesis of dental fluorosis.Methods:20 Wistar rats(10 male rats and 10 female rats)were randomly divided into two groups.Experiment group was feed with water contained 0.1 g/L fluorin and normal group with distilled water was served as control.After 8 weeks all rats were sacrificed.Immunohistochemistry was used to observe the effect of overdose fluorin on Smad3 expression in rat's ameloblast and odontoblast.Results:The immunohistochemistry results demonstrated that in experiment group,Smad3 expression in rat's ameloblast and odontoblast was lower than those in control group,and statistic analysis showed there were significant differences between the two groups(P