Objective To explore whether Yes-associated protein(YAP)affects occurrence and progression of liver fibrosis by regulating epithelial-mesenchymal transition(EMT).Methods In a 8-week-old C57BL/6 mouse model of CCl4-induced liver fibrosis,the effect of verteporfin(a YAP inhibitor)intervention was assessed with HE staining and by detecting liver biochemistry and expressions of YAP and EMT-related genes using immunohistochemistry and Western blotting.Transcriptome and proteomic sequencing and informatics analysis were used to investigate the main downstream pathways of YAP in liver fibrosis.Serum levels of YAP,N-cadherin,vimentin and Twist were examined in 60 healthy individuals,60 patients with chronic hepatitis B(CHB),and 60 patients with HBV-related liver cirrhosis.In another 24 C57BL/6 mice,the effects of Twist inhibitor alone or in combination with harmine(a YAP activator)on CCl4-induced liver fibrosis were evaluated by histopathological examination and Western blotting.Results The mouse models of liver fibrosis showed obvious structural damages of the liver lobes with formation of pseudolobules,and verteporfin treatment significantly improved these pathologies and lowered plasma ALT and AST levels of the mice.Transcriptome and proteomic sequencing and informatics analysis suggested that N-cadherin and Twist were differentially expressed in liver fibrosis in close correlation with YAP.Inhibition of YAP obviously downregulated hepatic N-cadherin and Twist protein expressions in the mice with liver fibrosis.In patients with CHB and liver cirrhosis,serum levels of YAP elevated obviously with the severity of liver fibrosis and were significantly correlated with N-cadherin,vimentin and Twist levels.In mice with liver fibrosis,inhibiting Twist effectively improved liver inflammation and fibrosis,while the combined treatment with YAP activator worsened hepatic collagen fiber deposition and increased hepatic YAP and α-SMA expressions.Conclusion EMT is an important pathogenic mechanism of liver fibrosis,and inhibiting YAP can alleviate liver fibrosis by reducing EMT.

Objective:To analyze the clinical application value of serum heme oxygenase (HO)-1expression level in non-alcoholic fatty liver disease (NAFLD) and, based on that, establish a diagnostic model combined with glucose regulatory protein 78 (GRP78) so as to clarify its diagnostic effectiveness and application value.Methods:A total of 210 NAFLD patients diagnosed by abdominal B-ultrasound and liver elastography were included, and at the same time, 170 healthy controls were enrolled. The general clinical data, peripheral blood cell counts, and biochemical indicators of the research subjects were collected. The expression levels of HO-1 and GRP78 were detected using an enzyme-linked immunosorbent assay. Multivariate analysis was used to screen independent risk factors for NAFLD. Visual output was performed through nomogram diagrams, and the diagnostic model was constructed. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the diagnostic effectiveness of NAFLD. Measurement data were analyzed using a t-test or Mann-Whitney U rank sum test to detect data differences between groups. Enumeration data were analyzed using the Fisher's exact probability test or the Pearson χ2 test. Results:Compared with the healthy control group, the white blood cell count, aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyl transferase (GTT), fasting blood glucose (Glu), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), serum HO-1, and GRP78 levels were significantly increased in the NAFLD group patients ( P ?

Objective To explore whether Yes-associated protein(YAP)affects occurrence and progression of liver fibrosis by regulating epithelial-mesenchymal transition(EMT).Methods In a 8-week-old C57BL/6 mouse model of CCl4-induced liver fibrosis,the effect of verteporfin(a YAP inhibitor)intervention was assessed with HE staining and by detecting liver biochemistry and expressions of YAP and EMT-related genes using immunohistochemistry and Western blotting.Transcriptome and proteomic sequencing and informatics analysis were used to investigate the main downstream pathways of YAP in liver fibrosis.Serum levels of YAP,N-cadherin,vimentin and Twist were examined in 60 healthy individuals,60 patients with chronic hepatitis B(CHB),and 60 patients with HBV-related liver cirrhosis.In another 24 C57BL/6 mice,the effects of Twist inhibitor alone or in combination with harmine(a YAP activator)on CCl4-induced liver fibrosis were evaluated by histopathological examination and Western blotting.Results The mouse models of liver fibrosis showed obvious structural damages of the liver lobes with formation of pseudolobules,and verteporfin treatment significantly improved these pathologies and lowered plasma ALT and AST levels of the mice.Transcriptome and proteomic sequencing and informatics analysis suggested that N-cadherin and Twist were differentially expressed in liver fibrosis in close correlation with YAP.Inhibition of YAP obviously downregulated hepatic N-cadherin and Twist protein expressions in the mice with liver fibrosis.In patients with CHB and liver cirrhosis,serum levels of YAP elevated obviously with the severity of liver fibrosis and were significantly correlated with N-cadherin,vimentin and Twist levels.In mice with liver fibrosis,inhibiting Twist effectively improved liver inflammation and fibrosis,while the combined treatment with YAP activator worsened hepatic collagen fiber deposition and increased hepatic YAP and α-SMA expressions.Conclusion EMT is an important pathogenic mechanism of liver fibrosis,and inhibiting YAP can alleviate liver fibrosis by reducing EMT.

Objective To investigate the effects of YAP on the occurrence and progression of acute liver failure by regulating the ferroptosis pathway and its underlying mechanism. Methods A total of 20 8-week-old C57BL/6 mice were randomly divided into four groups: a control group, an acute liver failure model group, a YAP agonist XMU-MP-1 treatment group and a YAP inhibitor verteporfin treatment group, five mice for each group. HE staining was used to observe the pathological changes of hepatic inflammation and necrosis. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected by liver biochemistry. Iron (Fe), malondialdehyde (MDA), glutathione (GSH) determination kits were used to measure their levels in liver tissues of each group. The changes of hepatocyte mitochondrial in each group were observed by electron microscopy. Real time PCR and Western blot analysis were used to detect the mRNA and protein expressions of YAP, glutathione peroxidase 4 (GPX4) and 5-lipoxygenase (5-LOX). Results Compared with the control group, mice in the acute liver failure model group and the YAP inhibitor verteporfin treatment group showed severe liver tissue congestion with inflammatory cell infiltration and structural damage to hepatic lobules. Liver injury was alleviated in the XMU-MP-1 treatment group. With the occurrence of liver failure, plasma ALT and AST levels significantly increased, and liver function was improved in XMU-MP-1 treatment group. Electron microscopy showed that mitochondria in hepatocytes of mice with liver failure became smaller and bilayer membrane density increased, while mitochondria changes in the XMU-MP-1 group were alleviated. In addition, the acute liver failure model group showed an increase in Fe and MDA contents, decreased protein expressions of GPX4, and enhanced expression of 5-LOX, suggesting that ferroptosis was involved in acute liver failure in C57BL/6 mice. Ferroptosis was inhibited by activation of YAP. Conclusion Activation of YAP may ameliorate liver injury by inhibiting ferroptosis.
Animals ; Mice ; Ferroptosis ; Glutathione ; Liver Failure ; Liver Failure, Acute/drug therapy* ; Mice, Inbred C57BL ; Verteporfin ; YAP-Signaling Proteins/metabolism*

Based on the development requirements of the Clinical Skills Teaching Center of modern hospitals and the needs of clinical practice teaching, the innovative human resource management model is applied to the management of the clinical skills teaching team of Bengbu Medical College, thereby promoting the fine teaching of the business in the new era.The construction of an excellent teaching team has achieved obvious initial results.This research analyzes specific management measures in combination with the actual situation, and aims to provide a reference for improving the quality of clinical skills teaching teams in Bengbu Medical College, and even promoting the reform and management of clinical skills teaching teams in the country.

OBJECTIVE: To observe the clinical effect of plasma exchange and tocilizumab in treatment of patients with severe coronavirus disease 2019 (COVID-19). METHODS: Six patients with severe COVID-19 admitted in First Affiliated Hospital of Bengbu Medical College from January 25 to February 25, 2020. Three patients were treated with plasma exchange and three patients were treated with tocilizumab. The effect on excessive inflammatory reaction of plasma exchange and tocilizumab was observed. RESULTS: The C-reactive protein (CRP) and IL-6 levels were significantly decreased and the lymphocyte and prothrombin time were improved in 3 patients after treatment with plasma exchange; while inflammation level was not significantly decreased, and lymphocyte and prothrombin time did not improve in 3 patients treated with tocilizumab. CONCLUSIONS For severe COVID-19 patients with strong inflammatory reaction, plasma exchange may be preferred.
Antibodies, Monoclonal, Humanized ; administration & dosage ; Betacoronavirus ; isolation & purification ; Coronavirus Infections ; blood ; immunology ; therapy ; Cytokine Release Syndrome ; therapy ; Humans ; Pandemics ; Plasma Exchange ; standards ; Pneumonia, Viral ; blood ; immunology ; therapy ; Prothrombin Time ; Treatment Outcome

Objective To discuss the application value of DWI and ADC on predicting therapeutic effect of radiotherapy treatment in NPC. Methods Twenty four local recurrent cases and 38 non-recurrent cases after radiotherapy treatment in NPC were reviewed. MRI and DWI-MRI were performed at pre-radiotherapy and 3, 6, 12 months after treatment, the ADC values of the lesions were analyzed by SPSS 18.0 statistical software. ROC curves based on the ADC values were measured in 3, 6, 12 months after treatment plotted to analyze the threshold ADC value for confirming recurrence. Results The recurrent group and newly diagnosed group showed significantly high signal on DWI, while the non-recurrent group acquired low or mixed signal. The ADC values of the primary tumor in the recurrent group and the non-recurrent group were (0.709 ± 0.078) × 10-3 and (0.693 ± 0.089) × 10-3mm2/s, respectively, t=-0.717,P>0.05, respectively.The ADC values of the primary and recurrent tumor in the recurrent group were (0.730± 0.068) × 10-3mm2/s and (0.709 ± 0.078) × 10-3mm2/s, t=-1.000,P>0.05 , respectively.There were statistical differences between the recurrent group and the non-recurrent group for ADC in 3, 6, 12 months after treatment:(1.128 ± 0.179) × 10-3 and (1.358 ± 0.145) × 10-3mm2/s, t=5.567,P<0.01;(1.164 ± 0.174) and (1.450 ± 0.102) × 10-3mm2/s, t=7.310,P<0.01;(1.107 ± 0.180) × 10-3 and (1.584 ± 0.125) × 10-3mm2/s, t=11.189,P<0.01;respectively. Take 1.29 × 10-3 mm2/s,1.32 × 10-3mm2/s,1.37 × 10-3mm2/s respectively in 3, 6, 12months after treatment as the diagnostic threshold to predict tumor recurrence. The sensitive , specificity, and accuracy were (83.3%, 73.7%, 77.4%), (83.3%, 89.5%, 87.1%), (100.0%, 94.7%, 96.3%).Conclusions Both DWI and ADC value are important for diagnosing and predicting recurrent NPC after radiotherapy treatment, DWI and ADC can be used to regular follow-up after radiotherapy, to further improve the rate of early diagnosis of recurrent NPC.

Objective To summarize the CT and MRI features of radiation-induced sarcoma (RIS) after radiotherapy in patients with nasopharyngeal carcinoma (NPC).Methods From January 1997 to October 2012,a total of 73 NPC patients with RIS after radiotherapy were confirmed by pathology.The clinical data and imaging findings (CT and MRI findings) were retrospectively reviewed.Of the 73 patients,43 underwent CT examination,24 underwent MRI,and the remaining 6 underwent both CT and MRI scans.Results Fibrosarcoma [45.3％ (33/73)] was the most frequently histologic type,followed by osteosarcoma[31.5％ (23/73)] and malignant fibrous histiocytoma [9.6％ (7/73)].The top three common sites were maxillary sinus [26.7％ (20/73)],followed by the neck soft tissue [17.8％ (13/73)] and mandible[13.7％ (10/73)].The main characteristics of the RIS on CT and MRI were soft tissue masses[78.1％ (57/73)] with an irregular shape and ill-defined margin,or rounded masses with welldefined margin [21.9％ (16/73)].CT of 49 patients showed masses with isodensity or mixed density on precontrast CT.MRI of 30 patients showed lesions with isointensity signal on T1WI and intermediate signal intensity on T2WI.On post-contrast images,65.8％ (48/73) tumors showed markedly homogeneous or inhomogeneous enhancement,23.2％ (17/73) lesions showed moderate enhancement,and 11.0％ (8/73) masses showed mild enhancement.Among the 23 patients with radiation-induced osteosarcomas,78.3％ (18/23) presented tumor bone formation.Conclusions RIS has a characteristic imaging features.Clinical history,tumor sites and serial imaging follow-up are necessary for early detection of RIS in patients with NPC.

Objective To evaluate the signal changes of the skull base after salvage surgury via endoscopic transnasal approach for local recurrent nasopharyngeal carcinoma.Methods Twenty patients with nasopharyngeal carcinoma after radiation failure underwent nasophargeryngectomy via an endoscopic transnasal approach were selected from April 2006 to December 2011,including 16 males and 4 females with 31 to 67 years old.Each patient had previously received irradiation and experienced recurrence after 8 to 83 months of completed irradiation.All patients underwent MRI no more than 2 weeks before the salvage surgery and were subjected to repeat MRI scans 2 weeks,3 months,6 months later and semi-annually thereafter,with the follow-up time of 6 to 45 months(median 18 months).A two-sided Chi-square test was used to compare the signal changes and the tendency of changes on all presurgical and postsurgical MR images.Results The MRI signal changes were detected at 92 sites of skull-base between 2 weeks and 3 months after the surgery,which was hypointense on T1 WI with moderate to marked contrast enhancement.In the follow-up period,the signal abnormalities at 36 sites of skull base had resolved or restored to the normal,and 34 sites remained stable,while in 22 sites,the MR signal changes became more obvious.The skull base bones adjacent to the region of the resection were more likely to show signal changes than nonadjacent areas (72 vs.20,x2 =33.128,P ＜0.01).The signal changes were more common on the ipsilateral skull base to the recurrent tumor in contrast to the contralateral skull base (68 vs 24,x2 =21.182,P ＜ 0.01).Conclusions The skull base signal changes after salvage surgury via endoscopic transnasal approach for local recurrent nasopharyngeal carcinoma,and it occurs in specific location.Most of sites tend to resolve or be stable at the follow up.

Objective To characterize the features of Nasopharyngeal non-Hodgkin's lymphoma (NHL) on MR imaging and find the main points to differentiate it from the other nasopharyngeal tumors.Methods The MR images of 41 patients with pathologically and immunohistochemically proven nasopharyngeal NHLs were reviewed retrospectively. Images were assessed by the size, invasive extent,signal intensity of primary nasopharyngeal tumor, and the distribution of cervical lymphadenopethy. The difference of regional tissues invasion and cervical lymphadenopathy distribution between the patients with B-cell NHLs and the patients with T-cell or NK/T-cell NHLs were analyzed by Pearson's Chi-Square test or Fisher's exact test Results Of the 41 patients, 26 patients had mature B-cell lymphoma, two patients with mature T-cell Iymphoma, and thirteen patients showed Nature killer/T-cell lymphoma in nasopharynx. MRI revealed that NHLs of nasopharynx can be showed as thickening of nasopharyngeal mucosa and (or) lumps in nasopharynx, which were slightly hyper-intensity on T2-weighted images, and intermediate signal intensity (similar to muscle) on T1 -weighted images, with mild or moderated enhancement following contrast medium administration. Twenty four cases had symmetrical disease of all walls of nasopharynx, and 17 cases had unsymmetrical tumor. Of all cases, 5 cases had superficial ulcerations, 9 cases had exceed nasoharynx invasion spreads superficially along the mucosa, 23 cases had invasion of lingual and (or) palatine tonsils,20 cases showed invasion of parapharygeal muscles, 12 cases suffered from skull base bone infiltration,25 cases had retropaharyngeal lymphadenopathy, and 27 cases had cervical lymhadenopathy. Patient with nasopharyngeal Nature killer/T-cell lymphoma had a higher incidence of exceed nasopharynx invasion,parapharyngeal structures invasion, and superficial ulcerations (the cases were 8, 11, 4 in patient with T-cell or N K/T-cell lymphoma, and 4, 10, 1 in patients with B-cell lymphoma, respectively). Patients with nasopharyngeal B-cell lymphoma had a higher incidence of inasion of lingual and (or) palatine tonsils.Conclusions Nasopharyngeal NHL is a homogeneous tumor that tends to diffusely involve all walls of the nasopharynx and spread in an exophytic fashion to fill the airway, rather than infiltrating into the deep tissues. Different pathological types of nasopharyngeal NHLs have some different appearance on MRI between each other. A large tumor in nasopharynx that fills the nasopharynx cavity, with no or minimal invasion into deep structures, but with invasion extend down into the lingual and(or)palatine tonsils, may suggest the diagnosis of nasopharyneal NHL.