Background and purpose:The ovarian mucinous tumor is one of the major subtypes of the ovari-an epithelial cancer. Ubiquitination is one of the main post-translational modifications, which has proven to be involved in tumorigenicity. Deubiquitinase is the protein enzyme that could reverse the process of ubiquitination to affect the initiation and progression of malignancies. This study aimed to analyze the expression and clinical application of deubiquitinase OTUB1 (OTU deubiquitinase, ubiquitin aldehyde binding 1) in ovarian primary mucinous tumors. Methods:This study collected 90 cases of ovarian primary mucinous tumors during 2010-2015 in Obstetrics and Gynecology Hospital of Fudan University, and then collected the clinicopathological information and performed the immunochemistry.Results:Fourteen out of 90 cases were ovarian primary mucinous cystadenoma, 17 were borderline mucinous tumor (intestinal type and intraepithelial carcinoma), and 59 were ovarian primary mucinous carcinoma. The expression rate and intensity of OTUB1 were much higher in malignant cases than those in benign ones (P<0.05). The expression rate and intensity of OTUB1 were much higher in cases with mucinous intraepithelial carcinoma than those in cases with intestinal type borderline mucinous tumor (P<0.05). The expression rate and intensity of OTUB1 increased with the advance of FIGO staging (P<0.05). The expression rate and intensity of OTUB1 were much higher in cases with involved fallopian tubes than those in cases without involved fallopian tubes (P<0.05). The expression rate and intensity of OTUB1were much higher in cases with involved uterus and omentum than those in cases with-out involvement (P<0.05). The expression rate and intensity of OTUB1were much higher in cases with lymph node metastasis than those in cases without involvement (P<0.05).Conclusion:There is significant difference in OTUB1 expression between ovarian primary mucinous carcinoma and benign mucinous cystadenoma. It is highly correlated to FIGO staging and invasion and metastasis of tumor. OTUB1 could be used in differential diagnosis and in monitoring the tumor initiation and progression in ovarian mucinous carcinoma.

Objective To assess the cardiovascular structure and function in children with confirmed primary hypertension,and to explore the impact of hypertension and related risk factors on cardiovascular structure and function of children.Methods Parameters related to cardiac structure,vascular structure and function were measured in 213 hypertensive children,who were confirmed upon repeated measurements on separate occasions.A total of 197 healthy children were recruited as controls.Results 1) In hypertensive children,left ventricular end-diastolic diameter (LVEDd),left ventricular end-systolic diameter (LVESd),left ventricular mass (LVM),left ventricular mass index (LVMI),left ventricular posterior wall thickness (LVPT) and interventricular septal thickness (IVST) were all significantly higher than their counterparts (P＜0.05).No statistical differences were found in carotid intima-media thickness (cIMT),relative wall thickness (RWT) and brachial ankle pulse wave velocity (ba-PWV).2) Compared with controls,LVEDd,LVESd,LVM,LVMI were all significantly higher in hypertensive children (P＜0.05),regardless of age group or weight-status.No statistical differences were found in ccIMT and RWT,while ba-PWV was statistically higher in controls among children aged 6-12 years.3) Data from multiple linear regression analysis noticed that LVMI was associated with age,sex,BMI and hypertension while RWT was associated with age and BMI.Conclusion In children with primary hypertension,changes of vascular structure and function were not shown but left ventricular remodeling and early changes of function had been developed in children under 12 years old.

Objective To discuss the values of three screening methods for the detection of early breast cancer,and to analyze the features of the screening cancer.Methods The first screening of breast cancer were performed in 5307 women who aged from 20 to 76 years with median age of 49 years.The three screening methods included physical examination with ultrasound and mammography,physical examination with mammography and mammography only.The rate of recall,biopsy,cancer detection of three methods were analyzed and the mammographic findings were reviewed Chi-square test or Fisher's exact test were used for the statistics.Results The recall rates were 4.90% (49/1001),6.90%(166/2407)and 4.48% (85/1899) in three methods respectively,the biopsy rates were 1.60% (16/1001),1.04% (25/2407) and 0.63%(12/1899),the cancer detection rates were 0.50% (5/1001),0.17% (4/2407) and 0 (0/1899).There were statistical differences among the three groups (X2=12.99,6.264,8.764,P < 0.05).Physical examination with ultrasound and mammnography had the highest cancer detection rate,ten breast cancers were detected and 8 were early stage breast cancer.Of seven cancers detected by mammography,only two were found by ultrasound.A cluster of calcifications were found in 2 cases,linear calcifications in 2 cases.One case presented as a asymmetric density,one as a asymmetric density with calcifications,one as multiple nodules with a duster of calcifications.Two breast cancers presented as asymmetric density were missed on mammography and diagnosed correctly after retrospective review.Conclusion Physical examination with ultrasound and mammography is the best method for breast cancer screening.The breast cancer can be detected by mammography earlier than other methods.

Objective:To investigate the role and regulatory mechanism of triggering receptor expressed on myeloid cell 2 (TREM2) in mice lung ischemia/reperfusion injury (LIRI).Methods:Thirty-six healthy male C57BL/6 mice were divided into six groups according to the random number method ( n = 6): normal control group, and LIRI 2, 6, 12, 24, 48 hours group. Mice LIRI models were established by clamping the left hilum. The wet/dry weight ratio (W/D) of left lung tissue was measured. Lung injury was observed and evaluated by hematoxylin-eosin (HE) staining and electron microscopy. The levels of interleukins (IL-1β, IL-18) in lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of TREM2 and caspase-1 were determined by polymerase chain reaction (PCR). The protein expressions of TREM2, caspase-1, Gasdermin-D (GSDMD) were determined by Western blotting. Results:At 2 hours after LIRI, lung injury began to appear, the lung ultrastructure changed, and the lung injury score increased; at 6 hours, the degree of lung injury was the most serious; after 12 hours, the lung injury gradually reduced and the lung injury score gradually decreased. Compared with the normal control group, lung W/D ratio and lung injury score of LIRI 2, 6, 12, 24, 48 hours groups were significantly higher, the differences were statistically significant (lung W/D ratio: 7.06±0.52, 8.34±0.17, 6.42±0.35, 5.34±0.25, 5.59±0.45 vs. 4.69±0.23; lung injury score: 5.50±0.54, 9.75±0.89, 5.88±0.84, 3.63±0.74, 4.13±0.64 vs. 1.13±0.35, all P < 0.05). Compared with the normal control group, the levels of IL-1β and IL-18 in lung tissue were significantly increased at 2 hours after LIRI, reached a peak at 6 hours [IL-1β (ng/L): 502.76±12.25 vs. 56.50±8.07, IL-18 (ng/L): 414.02±10.75 vs. 81.63±5.29, both P < 0.05], then decreased gradually, and were still significantly higher than the normal control group at 48 hours. The PCR and Western blotting showed that the expression of TREM2 was significantly lower than that in the normal control group at 2 hours after LIRI, and reached a valley at 6 hours [TREM2 mRNA (2 -ΔΔCt): 0.47±0.05 vs. 1.02±0.05, TREM2/GAPDH: 0.23±0.13 vs. 0.48±0.17, both P < 0.05], then gradually increased, and reached the peak at 24 hours [TREM2 mRNA (2 -ΔΔCt): 3.98±0.15 vs. 1.02±0.05, TREM2/GAPDH: 0.71±0.17 vs. 0.48±0.17, both P < 0.05]. The trend of expression of caspase-1 and GSDMD were opposite to that of TREM2, which increased at first and then decreased, and reached a peak at 6 hours after reperfusion [caspase-1 mRNA (2 -ΔΔCt): 2.20±0.13 vs. 1.01±0.02, caspase-1/GAPDH: 0.64±0.02 vs. 0.20±0.06, GSDMD/GAPDH: 1.23±0.01 vs. 0.87±0.02, all P < 0.05]. Conclusions:TREM2 might be involved in LIRI in mice. The mechanism may be related to the effect of TREM2 on caspase-1-mediated pyroptosis.

ObjectiveTo investigate the features of liver injury in patients with coronavirus disease 2019 (COVID-19), and to provide a reference for clinical diagnosis and treatment. MethodsMedical records were collected from 201 patients with COVID-19 who were admitted to Xiangyang Central Hospital from January 19 to March 5, 2020, and these patients were divided into non-critical (mild/common type) group with 173 patients and critical (severe/critical type) group with 28 patients. The data on alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), and albumin (Alb) were collected. The t-test was used for comparison of normally distributed continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and the Wilcoxon rank-sum test was used for comparison of ranked data between groups. ResultsAmong the 201 patients, 37 (18.4%) had liver injury, with 19 in the critical group and 18 in the non-critical group, and there was a significant difference in the incidence rate of liver injury between the two groups (67.9% vs 10.4%, χ2=52.963, P＜0.05). There were significant differences between the 19 patients with liver injury in the critical group and the 18 patients with liver injury in the non-critical group in the duration of abnormal ALT and/or AST (on admission and during hospitalization) (χ2=11.906, P＜0.05) and the increase in ALT and/or AST (Z=-2.869, P＜0.05), and most patients had mild or moderate liver injury. Among the 201 patients, only one patient had elevated bilirubin (TBil ＜2 × upper limit of normal, mainly indirect bilirubin) and had non-critical liver injury. The critical group had a significantly lower level of Alb than the non-critical group (t=-8.002, P＜0.05). Among the 201 patients, 75 had a reduction in Alb, among whom 50 (50/201, 24.9%) had a reduction on admission and 25 (25/201, 12.4%) had a reduction during hospitalization, and there were significant differences in Alb (t=-4.967, P＜0.05) and hypoalbuminemia (χ2=26.645, P＜0.05) between the two periods of time. ConclusionLiver injury is relatively common in patients with COVID-19, mainly mild or moderate liver injury. There is a low incidence rate of abnormal bilirubin and a high incidence rate of the reduction in Alb. There are significant differences in the incidence rate and severity of liver injury between the crucial and non-critical patients. Alb level can be used as one of the indicators to evaluate and predict the severity of COVID-19 patients.

Objective:To investigate the role of vitamin D analogue paricalcitol in activating vitamin D receptor/glutathione peroxidase 4 (VDR/GPX4) pathway in ventilator-induced lung injury (VILI).Methods:Twenty-four male C57BL/6J mice were randomly divided into control group, high tidal volume (HVT) induced VILI model group (HVT group), paricalcitol control group (P group), and paricalcitol pretreatment group (P+HVT group), with 6 mice in each group. The mice were endotracheal intubated and ventilated at 40 mL/kg tidal volume to prepare VILI model, while those in the control group were intubated without ventilation. The mice in the P+HVT group were intraperitoneally injected with paricalcitol 0.2 μg/kg once a day 1 week before modeling, while those in the P group were intraperitoneally injected paricalcitol 0.2 μg/kg once a day for 1 week before the experiment. After ventilation for 4 hours, the mice were sacrificed for lung tissue collection. Lung injury was evaluated by wet/dry (W/D) ratio, hematoxylin-eosin (HE) staining and Masson staining. The expressions of VDR and GPX4 were determined by Western blotting and immunohistochemistry. Malondialdehyde (MDA) and glutathione (GSH) contents were determined by micro method.Results:After HVT for 4 hours, compared with the control group, lung injury score and W/D ratio were significantly higher (lung injury score: 0.430±0.035 vs. 0.097±0.025, lung W/D ratio: 4.860±0.337 vs. 3.653±0.332, both P < 0.05), collagen fiber deposition was significantly increased, the content of MDA in lung tissue was significantly increased (nmol/g: 212.420±8.757 vs. 97.073±5.308, P < 0.05), GSH content and the protein expressions and immunoreactive score (IRS) of VDR and GPX4 were significantly decreased [GSH (μg/g): 44.229±1.690 vs. 70.840±0.781; VDR protein (VDR/GAPDH): 0.518±0.029 vs. 0.762±0.081, GPX4 protein (GPX4/GAPDH): 0.452±0.032 vs. 0.649±0.034; IRS score: VDR was 4.168±0.408 vs. 10.167±0.408, GPX4 was 4.333±1.033 vs. 10.333±0.516; all P < 0.05], which meant that the mice in HVT group showed obvious lung injury. After VDR was activated by paricalcitol, compared with the HVT group, lung injury score and W/D ratio were significantly decreased (lung injury score: 0.220±0.036 vs. 0.430±0.035, lung W/D ratio: 4.015±0.074 vs. 4.860±0.337, both P < 0.05), collagen fiber deposition was reduced, MDA content in lung tissue was decreased (nmol/g: 123.840±8.082 vs. 212.420±8.757, P < 0.05), GSH content and the protein expressions and IRS score of VDR and GPX4 were significantly up-regulated [GSH (μg/g): 63.094±0.992 vs. 44.229±1.690; VDR protein (VDR/GAPDH): 0.713±0.056 vs. 0.518±0.029, GPX4 protein (GPX4/GAPDH): 0.605±0.008 vs. 0.452±0.032; IRS score: VDR was 9.000±0.632 vs. 4.168±0.408, GPX4 was 8.833±0.408 vs. 4.333±1.033; all P < 0.05], which meant that lung injury in P+HVT group was significantly improved. Conclusion:Vitamin D analogue paricalcitol ameliorates pulmonary oxidation-reduction imbalance by activating the VDR/GPX4 pathway, thereby alleviating VILI.