Objectives To explore the expression, biological function, and mechanism of MKI67 in pancreatic cancer and its clinical significance. Methods The expression level, diagnosis, and prognostic value of MKI67 in pancreatic cancer were analyzed using public databases. We also investigated the association between the MKI67 with immune cell infiltration and immune checkpoint molecules. We analyzed the functional pathway enrichment to uncover the possible molecular mechanisms. qRT-PCR and Western blot assay were used to verify the expression of MKI67 mRNA and protein. Immunohistochemistry staining was used to detect the expression of MKI67 in tissue protein. Results The high expression of MKI67 was significantly associated with high histological grades and poor outcomes in pancreatic cancer. High MKI67 expression was correlated with poor prognosis of pancreatic cancer patients (P=0.009). MKI67 was an independent risk factor for the patient outcome (95%CI: 1.084-1.743, P<0.05). The MKI67 expression was positively correlated with the helper T cell 2 levels but negatively correlated with plasmacytoid DC, NK cells, mast cells, the T follicular helper, immune DC, and CD8 T cells. Conclusion MKI67 may serve as a biomarker for the diagnosis and prognosis of pancreatic cancer and the mechanism might be associated with immune escape or immunosuppression.

Objective:To investigate the impacts and mechanisms of the GCH1-S81A mutants of the rate-limiting enzyme GTP cyclohydrolase 1 (GCH1) at key phosphorylation sites on the radiosensitivity of esophageal cancers during the de novo synthesis of tetrahydrobiopterin (BH4). Methods:The KYSE-150 cell lines of esophageal squamous cell carcinoma with stable GCH1 overexpression at different phosphorylation levels were constructed in this study. Based on GCH1′s phosphorylation levels and radiation doses, the experimental groups were divided into the blank control group, the empty virus group, the empty virus + irradiation group, the wild-type GCH1 group, the GCH1 phosphorylation group, the GCH1 dephosphorylation group, the GCH1 dephosphorylation + irradiation group, the validation group, and the validation + irradiation group. The Western blot and the CCK-8 assay were employed to detect the infection efficiency and the survival rates of tumor cells in various groups, respectively. The flow cytometry was applied to detect the changes in the apoptosis rate, reactive oxygen species (ROS) level, and lipid peroxide level of tumor cells in various groups. The colony formation assay was used to detect the changes in the radiosensitivity of tumor cells. Besides, the Western blot was performed to detect the changes in the expression of ferroptosis-related proteins.Results:The GCH1 dephosphorylation group showed a significantly decreased expression level of phosphorylated GCH1-S81 protein in the cells at 48 h after infection ( t=9.35, 16.57, P<0.05). Compared to the empty virus + irradiation group, the GCH1 dephosphorylation + irradiation group exhibited a significantly decreased cell survival rate 24 h after 10 Gy X-ray irradiation ( t=26.97, P<0.05). The ROS levels in KYSE-150 cells at 8 h after 10 Gy X-ray irradiation, and the apoptosis rates and lipid peroxide levels at 48 h after irradiation, all showed a significant increase ( t=17.89-131.1, P<0.05), which was further aggravated following the addition of GCH1-S81A mutants ( t=157.06-97.81, P<0.05). This phenomenon could be inhibited by complementing wild-type GCH1 ( t=66.38-23.08, P<0.05). Compared to the empty virus + irradiation group, the GCH1 dephosphorylation + irradiation group manifested decreased colony formation capacity under various X-ray doses (2, 4, 6 and 8 Gy, t=7.31-8.16, P<0.05). The GCH1-S81A mutation reduced the expression level of the ferroptosis-related protein GPX4 ( t=4.55, P<0.05), which was further decreased after 10 Gy X-ray irradiation ( t=12.98, P<0.05). Conclusions:The GCH1-S81A dephosphorylated mutants can inhibit the growth of esophageal carcinoma cells KYSE-150 and enhance their radiosensitivity, which may hold promise as a novel approach to improve the efficacy of radiotherapy for esophageal cancers.

Objective:To investigatethe relationship between right ventricular blood flow components and right ventricular function in patients with pulmonary hypertension (PH) by 4D-FLOW cardiovascular MR (4D-FLOW CMR).Methods:Thirty patients with PH were prospectively enrolled in this study. All patients underwent right heart catheterization to measure hemodynamics and CMR to measure right ventricular blood flow and right ventricular function within 1 week. The long-axis 4-chamber and contiguous short axis cineslices were acquired with balanced steady-state free precession sequence to calculate RV functional metrics including right ventricular end diastolic volume, end systolic volume, ejection fraction, stroke output and other functional parameters. Ventricular flow was acquired in sagittal direction, using a 3D retrospectively ECG-triggered, navigator-gated prototype sequence to analyze.RV function and flow parameters were correlated with Spearman correlation analysis.Results:Right ventricular percent of direction flow(RVPDF),percent of delayed eject flow (RVPDEF),percent of retained flow (RVPRI) and percent of residual volume(RVPRV) of PH patients measured with 4D-FLOW were 16.4%±9.2%, 16.1%±5.6%, 16.8%±6.1%, and 50.5%±12.3%, respectively. RVPDF negatively correlated with RVPRVo ( r=-0.703, P<0.001) while RVPDEF positively correlated with RVPRI( r=0.955, P<0.001). RVPDF was positively correlated with right ventricular stroke volume index (RVSVI)( r=0.38, P=0.041) and right ventricular eject fraction(RVEF)( r=0.69, P<0.001), and negatively correlated with right ventricular end systolic volume index(RVESVI)( r=-0.65, P<0.001) and right ventricular mass index(RVMI)( r=-0.45, P=0.004). RVPRVo was negatively correlated with RVEF( r=-0.58, P=0.007). The sum of RVPDF and RVPDEF (RVPDF+RVPDEF) was 35.2%±11.4%. RVEF correlated with RVPDF+RVPDEF ( r=0.825, P<0.001) and comparable to RVPDF+RVPDEF ( t=1.427, P=0.164). RVPDF was negatively correlated with pulmonary vascular resistance (PVR) ( r=-0.52, P=0.007) while RVPRVo was positively correlated with PVR ( r=0.54, P=0.004). Conclusions:4D-FLOW CMR can be used to measure right ventricular ejection fraction in PH patients without respiratory control. In PH patients, the right ventricular direct blood flow was significantly decreased, while the residual blood flow was significantly increased. The right ventricular direct blood flow and residual blood flow were related to the right ventricular function and pulmonary vascular resistance, which were important parameters to evaluate the right ventricular function and afterload in PH.

The avian influenza A (H7N9) virus is a zoonotic virus that is closely associated with live poultry markets. It has caused infections in humans in China since 2013. Five waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017. H7N9 with low-pathogenicity dominated in the first four waves, whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave, causing wide concern. Specialists and officials from China and other countries responded quickly, controlled the epidemic well thus far, and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness efforts. Here, we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the disease. It was summarized and discussed from the perspectives of molecular epidemiology, clinical features, virulence and pathogenesis, receptor binding, T-cell responses, monoclonal antibody development, vaccine development, and disease burden. These data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses, such as SARS-CoV-2.
Animals ; COVID-19 ; China/epidemiology* ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza in Birds/epidemiology* ; Influenza, Human/prevention & control* ; Poultry ; SARS-CoV-2

OBJECTIVE: To explore the effect of heparanase (HPSE) on apoptosis of microvascular endothelial cells (MVECs) and trans-endothelial migration of hepatocellular carcinoma (HCC) cells. METHODS: A HCC cell line with high HPSE expression was selected by real-time quantitative PCR (qRT-PCR) and Western blotting and transefected with a lentiviral vector containing an interfering RNA sequence of HPSE. Transwell migration assay was performed to detect the trans-endothelial migration (TEM) rate of the transfected HCC cells across human umbilical vein endothelial cells (HUVECs). In a Transwell indirect co-culture system, the effect of HPSE silencing in the HCC cells was determined on apoptosis of HUVECs . A nude mouse model of HCC was used to verify the effect of HPSE on apoptosis of MVECs and liver metastasis of the tumor. RESULTS: HCCLM3 cell line highly expressing HPSE was selected for the experiment. Transfection of the HCC cells with the lentiviral vector for HPSE interference the HCC cells resulted in significantly lowered TEM rate as compared with the cells transfected with the control vector ( < 0.01). In the indirect co-culture system, the survival rate of HUVECs co-cultured with HCCLM3 cells with HPSE interference was significantly higher and their apoptotic index was significantly lower than those in the control group ( < 0.05). Ultrastructural observation showed no obvious apoptosis of HUVECs co-cultured with HCCLM3 cells with HPSE interference but revealed obvious apoptotic changes in the control group. In the animal experiment, the tumor formation rate in the liver was 100% (6/6) in the control group, significantly higher than that in RNAi group (33.3%, 2/6) ( < 0.05). Under optical microscope, necrosis and apoptosis of the MVECs was detected in the liver of the control mice, while the endothelial cells remained almost intact in RNAi group. CONCLUSIONS HPSE promotes the metastasis of HCC cells by inducing apoptosis of MVECs.
Animals ; Apoptosis ; Carcinoma, Hepatocellular ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Endothelial Cells ; Gene Expression Regulation, Neoplastic ; Glucuronidase ; Humans ; Liver Neoplasms ; Mice

Objective To explore the application of 64 slice low dose spiral CT in pediatric paranasal sinus examination.Methods Sixty children with paranasal sinuses were randomly divided into three groups(control group,low dose 1 group,low dose 2 group),and were given conventional dose scanning(100 KV in tube voltage,100 mA in tube current),low dose scanning(100 KV in tube voltage,45 mA in tube current),and low dose scanning (100KV in tube voltage,25 mA in tube current).The single scan weighted CT dose index (CTDIw) of each patient was recorded and compared;and the quality of the scanned images of each group was evaluated by two chief physicians by blind method.Results Compared with conventional dose group,low dose 1,2 groups had significantly lower CTDIw,and the dose decreased for 59.23％ and 72.42％ respectively.The image quality of the low-dose 1 group did not change significantly,and all the images could meet the requirements of clinical diagnosis;but the image quality of the low-dose 2 group decreased significantly,and the images of 3 patients could not meet the requirements of clinical diagnosis.Conclusion Appropriate reduction of scanning parameters for paranasal sinuses children can not only obtain good quality images,but also effectively reduce the radiation dose of patients.

Objective To explore the application of 64 slice low dose spiral CT in pediatric paranasal sinus examination.Methods Sixty children with paranasal sinuses were randomly divided into three groups(control group,low dose 1 group,low dose 2 group),and were given conventional dose scanning(100 KV in tube voltage,100 mA in tube current),low dose scanning(100 KV in tube voltage,45 mA in tube current),and low dose scanning (100KV in tube voltage,25 mA in tube current).The single scan weighted CT dose index (CTDIw) of each patient was recorded and compared;and the quality of the scanned images of each group was evaluated by two chief physicians by blind method.Results Compared with conventional dose group,low dose 1,2 groups had significantly lower CTDIw,and the dose decreased for 59.23％ and 72.42％ respectively.The image quality of the low-dose 1 group did not change significantly,and all the images could meet the requirements of clinical diagnosis;but the image quality of the low-dose 2 group decreased significantly,and the images of 3 patients could not meet the requirements of clinical diagnosis.Conclusion Appropriate reduction of scanning parameters for paranasal sinuses children can not only obtain good quality images,but also effectively reduce the radiation dose of patients.

Objective To examine characteristics of patients with blood urea nitrogen (BUN) levels higher and lower than the normal limit.Methods During January 2012 to January 2015,116 patients with upper gastrointestinal diseases were selected to study,according to the patient's blood urea nitrogen level,all the patients were divided into high BUN group and low BUN group,and there were 76 patients in the high BUN group,and 40 patients in low BUN group,compared the biochemical indices,gastrointestinal bleeding forrest grading and disease severity of the two groups,and univariate logistic regression analysis.Results The serum white blood cell count,blood urea nitrogen,creatinine and glycated hemoglobin levels in patients of high BUN group [(9 593±5 012)× 102/μl,368.1±162.3 mg/L,11.2±3.7 mg/L and 6.38±1.08％] were significantly higher than that of low BUN patients [(6 804 ± 2 087) × 102/μl,121.0 ± 39.3 mg/L,8.1 ± 3.2 mg/L and 5.51 ± 0.42 ％] (t =3.645～12.659,all P＜0.05),and the hemoglobin levels (87.3±35.1 g/L) of the patients in high BUN group was significantly lower than that of the low BUN patients (108.0 ± 31.2 g/L) (t=3.252,P=0.032).Logistic regression analysis showed the presence of hemoglobin and glycosylated hemoglobin levelst of wo groups of patients was significantly different (P＜0.05),and showed that showed the highest correlation with BUN.Gastrointestinal bleeding forrest hierarchical data of the two groups of patients showed no significant difference (P＞0.05).The proportion of patients with gastric ulcers of high BUN patients was significantly higher than that of the low BUN patients (x2 =39.655,P=0.000).Conclusion Patients with high expression of serum urea nitrogen had more severe upper gastrointestinal bleeding,and it is worthy of attention in the process of clinical diagnostic.

Objective To investigate the changes of left ventricular structure and function in patients with liver cirrhosis and their correlation with the model for end-stage liver disease (MELD) score. Methods A total of 89 cirrhotic patients admitted between June, 2012 and June, 2014 and 30 healthy control subjects were enrolled in the study. According to MELD score, the cirrhotic patients were divided into 3 groups with MELD scores≤9, between 10 and 19, and≥20. The parameters of the left ventricle in resting state were measured using Doppler echocardiography, including left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left atrial diameter (LAD), ejection fraction (LVEF), cardiac output (CO), mitral flow velocity, and E wave deceleration time (DT), and evaluated their relationship with MELD score. Results Compared with the control subjects, the cirrhotic patients showed significantly increased LVESD, LVEDD, IVST, LAD, CO and DT but reduced VE/VA ratio (P<0.05 or 0.01). The values of LVESD, LVEDD, IVST, LAD and DT increased gradually with MELD scores (P<0.05 or 0.01). VE/VA ratio was higher in patients with MELD score of 10-19 than in those with MELD score≤9, and decreased significantly in those with MELD score≥20. Of the cirrhotic patients, 55%were found to have left atrial enlargement and 44%had a VE/VA ratio≤1;left atrial enlargement and a VE/VA ratio below 1 were more common in patients with a MELD score≥20 than in those with lower MELD scores. The LAD, LVEDD and DT were positively correlated with MELD scores (r=0.208, 0.319 and 0.197, respectively;P<0.05 or 0.01). Conclusion The patients with liver cirrhosis can have cardiac function deficiency manifested mainly by left ventricular diastolic dysfunction in positive correlation with the severity of liver disease.

Objective To investigate the changes of left ventricular structure and function in patients with liver cirrhosis and their correlation with the model for end-stage liver disease (MELD) score. Methods A total of 89 cirrhotic patients admitted between June, 2012 and June, 2014 and 30 healthy control subjects were enrolled in the study. According to MELD score, the cirrhotic patients were divided into 3 groups with MELD scores≤9, between 10 and 19, and≥20. The parameters of the left ventricle in resting state were measured using Doppler echocardiography, including left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left atrial diameter (LAD), ejection fraction (LVEF), cardiac output (CO), mitral flow velocity, and E wave deceleration time (DT), and evaluated their relationship with MELD score. Results Compared with the control subjects, the cirrhotic patients showed significantly increased LVESD, LVEDD, IVST, LAD, CO and DT but reduced VE/VA ratio (P<0.05 or 0.01). The values of LVESD, LVEDD, IVST, LAD and DT increased gradually with MELD scores (P<0.05 or 0.01). VE/VA ratio was higher in patients with MELD score of 10-19 than in those with MELD score≤9, and decreased significantly in those with MELD score≥20. Of the cirrhotic patients, 55%were found to have left atrial enlargement and 44%had a VE/VA ratio≤1;left atrial enlargement and a VE/VA ratio below 1 were more common in patients with a MELD score≥20 than in those with lower MELD scores. The LAD, LVEDD and DT were positively correlated with MELD scores (r=0.208, 0.319 and 0.197, respectively;P<0.05 or 0.01). Conclusion The patients with liver cirrhosis can have cardiac function deficiency manifested mainly by left ventricular diastolic dysfunction in positive correlation with the severity of liver disease.