Transcatheter arterial chemoembolization (TACE) has already been a mature and an effective treatment for advanced hepatocellular carcinoma (HCC).Clinically,it is very important to quickly and accurately evaluate the postoperative curative effect with minimally invasive technique so as to determine the next treatment options.At present,postoperative conventional CT and MRI are the main means to assess the curative effect of TACE,but it is a pity that after the treatment the functional changes of the tumor occur earlier than the morphological changes.In recent years,functional MRI techniques,such as diffusionweighted imaging (DWI),multi-b value DWI,dynamic contrast-enhanced (DCE) imaging,etc.have been more and more used for quantitative evaluation of the diffusion of water molecules and the blood microcirculation perfusion within the tumor tissue,and some progresses have been achieved in the evaluation of curative efficacy for tumor.This paper aims to make a comprehensive review about the research progress of the above mentioned functional imaging methods as well as their current application status in evaluation of the curative effect of TACE.

[ ABSTRACT] AIM:To explore the regulatory effect of intermedin ( IMD) on pulmonary collagen synthesis and ac-cumulation in rats with pulmonary hypertension induced by high pulmonary blood flow.METHODS: Healthy male SD rats (n=20) were randomly divided into control group (n=7), shunt group (n=7) and shunt with IMD group (n=6).The shunting of abdominal aorta and inferior vena cava was produced in rats of shunt group and shunt with IMD group.After 8 weeks, IMD was administered into the rats of shunt with IMD group subcutaneously by mini-osmotic pump for 2 weeks.Mean pulmonary artery pressure (mPAP), relative medial thickness (RMT) of pulmonary arteries, contents of hydroxyproline, collagen type I and III, bone morphogenetic protein-2 (BMP-2), and the mRNA expression of procollagen I and III in lung tissues were measured and compared.RESULTS:Compared with control group, mPAP and RMT of medium and small pul-monary arteries in the rats of shunt group were significantly increased.Meanwhile, the lung hydroxyproline, collagens I and III and BMP-2 contents, and the mRNA expression of lung procollagen I and III were all significantly increased compared with control group.However, IMD significantly decreased mPAP, alleviated the changes of pulmonary vascular micro-struc-ture, decreased the collagen accumulation and pulmonary tissue homogenate BMP-2 contents, and inhibited the mRNA ex-pression of procollagen I and III in the lung tissue of shunting rats.CONCLUSION:IMD plays a protective role in the de-velopment of pulmonary hypertension and pulmonary vascular structural remodeling induced by high blood flow by inhibiting pulmonary collagen synthesis and accumulation, possibly in association with the BMP-2 pathway.

The method for preparation of models of myocardial ischemia in rats have been well described in the literature, are of practical value and have been chosen by many researchers for pharmacological studies of drugs for human diseases.However, there is still lack in some details of their operability and practicability.We re-selected the coronary artery ligation site, simplified the procedures and improved the experimental method for preparation of the models, and made satisfactory result.In this paper we will review the selection of method for preparing myocardial ischemia model in rats, describe some details of the surgical operation, explored the influencing factors and so on, and provide a reference for selecting most appropriate animal model in research.

Objective:To investigate the value of radiomics based on unenhanced CT texture analysis in predicting the WHO/International Society of Urological Pathology (ISUP) grading of clear cell renal cell carcinoma (ccRCC).Methods:Postoperative pathology-confirmed ccRCC subjects ( n=90) who received CT scanning and had a definite pathological grading in Cancer Hospital of the University of Chinese Academy of Sciences were collected retrospectively from December 2016 to May 2019. The cases were randomly divided into training group ( n=63) and test group ( n=27) as a ratio of 7∶3. All cases were classified into low grade (grades Ⅰ and Ⅱ, n=57) and high grade (grades Ⅲ and Ⅳ, n=37) according to the new pathological grading (WHO/ISUP grading, version 2016) of renal carcinoma. 3D-ROI segmentation was performed on unenhanced CT images and 93 texture features were extracted. The least absolute shrinkage and selection operator (LASSO) regression was used to reduct dimension of texture parameters and then the radiomics score (Rad-score) was established. The logistic regression was used to develop the prediction model with the pathological grading as the gold standard. The ROC curve and calibration curve were used to evaluate the predictive performance of the model, and the area under the curve (AUC), accuracy, sensitivity and specificity were calculated. The Hosmer-Lemeshow test was used to evaluate calibration degree of the model. Results:The 10 non-zero coefficient texture features were screened out through dimension reduction steps. The Rad-score was formed according to the linear combination of these ten features and corresponding coefficients, and then the prediction model was developed. The AUC of the model in training group was 0.933 (95%CI 0.862-1.000), the sensitivity was 92.3%, the specificity was 89.2%, and the model accuracy was 90.5%. The calibration curve showed the good calibration ( P=0.257). The AUC value in test group was 0.875 (95%CI 0.734-1.000), the sensitivity, specificity and accuracy were 72.7%, 87.5% and 81.5%. The calibration curve showed the good calibration ( P=0.125). Conclusion:The radiomics prediction model based on unenhanced CT texture analysis have application potential for the evaluation of WHO/ISUP grading of ccRCC.

AIM: To explore the regulatory effect of adrenomedullin (ADM) on pulmonary oxidative stress in the rats with pulmonary hypertension induced by high blood flow.METHODS: Healthy male SD rats (n=22) were randomly divided into control group, shunt group and shunt with ADM group.Abdominal aorta and inferior vena cava shunting was produced in the rats in shunt group and shunt with ADM group.After 8 weeks, ADM (1.5 μg·kg-1·h-1) was administered into the rats in shunt with ADM group subcutaneously by mini-osmotic pump for 2 weeks.Mean pulmonary artery pressure (mPAP) was evaluated by a right cardiac catheterization procedure.The ratio of right ventricular mass to left ventricular plus interventricular septal mass [RV/(LV+SP)] and relative medial thickness (RMT) in pulmonary muscularized arteries were calculated.The content of malonaldehyde (MDA), total antioxidative capacity (T-AOC), and activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissues were detected by colorimetry.The expression of NADPH oxidase 4 (NOX4) in the lung tissue was analyzed by Western blot.RESULTS: Compared with control group, the mPAP, RV/(LV+SP) and RMT in pulmonary muscularized arteries in shunt group were all significantly increased.The content of MDA and the expression of NOX4 in the lung tissues were significantly increased.The T-AOC, and activity of SOD and GSH-Px in the lung tissues were significantly decreased.However, mPAP, RV/(LV+SP) and RMT in pulmonary muscularized arteries in shunt with ADM group were significantly decreased as compared with shunt group.Meanwhile, ADM decreased the content of MDA and the expression of NOX4 in the lung tissues, but increased the T-AOC, and activity of SOD and GSH-Px in the lung tissue of shunt rats.CONCLUSION: ADM inhibits oxidative stress response in the development of pulmonary hypertension and pulmonary vascular structural remodeling induced by high pulmonary blood flow in the rats by down-regulating the NOX4 expression and strengthening the anti-oxidation response.

Objective: To investigate the status of immunization of National Immunization Program (NIP) and its adverse reaction rate in children with tuberous sclerosis. Method: Questionnaire survey was adopted to identify the vaccination coverage and its adverse events; 72 cases of children with tuberous sclerosis and 78 normal controls (healthy children completing age-appropriate NIP) admitted to Chinese People′s Liberation Army General Hospital from December 2014 to November 2015 were involved into this study. Result: The age-appropriate NIP coverage rate of tuberous sclerosis was 36%(26/72). The coverage rate of bacillus calmette-guerin (BCG), hepatitis B vaccine 1^st to 3^rd doses (HepB1-3), oral poliovaccine 1^st dose (OPV1), diphtheria, pertussis and tetanus 1^st dose (DPT1), DPT1-3, meningococcal polysaccharide vaccine group A (MPVA), measles amd rubella vaccine/measles vaccine 1^st dose (MRV/MCV1), and Japanese encephalitis vaccine 1^st dose (JEV1) were 100%(72 cases), 75%(51 cases), 97%(66 cases), 91%(62 cases), 82%(56 cases), 66%(45 cases), 69%(42 cases), and 61%(37 cases) respectively. The reasons why the children did not complete the vaccination plan were that parents were concerned about vaccination-induced seizures or seizures had not been controlled. Among 72 children with TSC, the rate of adverse events or suspected adverse events after vaccination was 17% (12 cases), which was higher than the normal control children (2 cases, 3%) (χ²=8.799, P<0.05). The main adverse events were seizure events, which accounted for 92%(11 cases). Conclusion The age-appropriate NIP coverage rate among children with tuberous sclerosis is low. The high incidence of adverse events may be associated with a fact that there are some nervous system abnormalities in cases with tuberous sclerosis. TSC children vaccination is relatively safe, with no serious adverse events.

Objective To explore the value of CT radiomics model in predicting three-year survival time in patients with primary hepatocellular carcinoma (HCC). Methods Eighty one patients pathologically or clinically confirmed HCC and B stageof Barcelona clinical liver cancer before transcatheter arterial chemoembolization (TACE) in Zhejiang Cancer Hospitalwere retrospectively enrolled from January 2010 to June 2014.A primary cohort consisted of 64 patients and an independent validation cohort consisted of 17 patients. The patients were divided into survival group of 39 cases and death groupof 42 cases duringthree-year follow-up. All the patients underwentnon-enhanced and contrast-enhanced CTimages scan before TACE. Three hundered and seventy six quantization radiomics features were extracted from the arterial phase and portal phase CTimages of target lesion. LASSO regression model was used for data dimension reduction. Logistic regression was used to develop the prediction model. The predictive ability of the model was validated using the area under the curve (AUC) of receiver operating characteristic(ROC) analysis. Results The radiomics features selected from the arterial and portal phase were 8 and 5, respectively. The arterial prediction model showed AUC=0.833, sensitivity=83.9％(26/31), specificity=81.8％(27/33), accuracy=82.8％(53/64)in primary datasetand AUC=0.861, sensitivity=75.0％(6/8), specificity=100.0％(9/9), accuracy=88.2％(15/17)in independent validation dataset.The portal prediction model showed AUC=0.858, sensitivity=83.3％(25/30), specificity=85.3％(29/34), accuracy=84.4％(54/64)in primary dataset and AUC=0.750, sensitivity=75.0％(6/8), specificity=100.0％(9/9), accuracy=88.2(15/17)in independent validation dataset. Conclusion This study shows CT radiomics model can be conveniently used to facilitate the preoperative individualized prediction of three-year survival time in patients with HCC.

Objective To discuss the application of routine CT three-phase perfusion parameter,that is arterial enhancement fraction (AEF) value,in evaluating the curative effect of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Methods The clinical data of a total of 30 patients with pathologically proved HCC were enrolled in this study.Routine CT three-phase perfusion scan was performed 1-3 days before as well as 30-40 days after TACE in all patients.AEF value was calculated by using CT Kinetics software (GE Healthcare).The formula for calculating AEF value was as follows:AEF value=(arterial phase CT value-plain scan CT value)÷(portal phase CT value-plain scan CT value).The results were statistically analyzed.Results Effective treatment group had 17 patients,and ineffective treatment group had 13 patients.The postoperative AEF values in the effective treatment group and the ineffective treatment group were (0.351±0.090) and (0.438±0.050) respectively,the difference between the two groups was statistically significant (P＜0.05).Taking postoperative AEF value of 0.392 as the critical value to predict the postoperative effect of TACE,the sensitivity and specificity were 86.7％ and 73.2％ respectively,and the area under the curve was 0.876 (P＜0.001).Conclusion The routine CT three-phase perfusion parameter (AEF) can quantitatively reflect the hemodynamic changes of HCC after TACE,which is helpful for making early evaluation of TACE effect,meanwhile,no additional radiation dose will be added.

OBJECTIVE: To analyze the clinical manifestation and genetic basis for four children with delayed onset Ornithine transcarbamylase deficiency (OTCD). METHODS: Clinical data of four children with OTCD admitted to the Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2020 to April 2021 were reviewed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Bioinformatic analysis and Sanger sequencing verification were carried out to verify the candidate variants. Impact of the candidate variants on the protein structure was also predicted. RESULTS: The clinical manifestations of the four children included vomiting, convulsion and disturbance of consciousness. WES revealed that the child 1 was heterozygous for a c.421C>T (p.R141X) variant in exon 5, children 2 and 3 were hemizygous for a c.119G>A (p.R40H) variant in exon 2, and child 4 was hemizygous for a c.607T>A (p.S203T) variant in exon 5 of the OTC gene. Among these, the c.607T>A variant was unreported previously and predicted to be pathogenic (PM1+PM2_Supporting+PP3+PP4). Bioinformatic analysis has predicted that the variant may result in breakage of hydrogen bonds and alter the protein structure and function. Sanger sequencing confirmed that the variants in children 2 to 4 have derived from their mothers. CONCLUSION The pathogenic variants of the OTC gene probably underlay the delayed OTCD in 4 children. The discovery of the c.607T>A variant has enriched the mutational spectrum of the OTC gene.
Child ; Humans ; Ornithine Carbamoyltransferase Deficiency Disease/genetics* ; Exons ; Seizures ; Computational Biology ; Heterozygote

OBJECTIVE： To observe the effects of Zhuangtongyin （ZTY） water extract on blood vessels diastolic and systolic function and cardiac function in rats with coronary heart disease （CHD） and its potential mechanism. METHODS： SD rats were randomly divided into control group， sham operation group， model group， positive group （Compound danshen dripping pills， 0.08 g/kg） and ZTY water extract low-dose， medium-dose and high-dose groups （6.8， 13.6， 27.2 g/kg， by weight of water extract）， with 10 rats in each group. Except for control group （no operation） and sham operation group （only open chest without ligation）， CHD model were set up in other groups by ligating the left ventricle cyclotron endings. One week after modeling， control group， sham operation group and model group were given constant volume of water intragastrically， and administration groups were given relevant medicine intragastrically； once a day， for consecutive 4 weeks. Two hours after last administration， cardiac function indexes （LVEDV， LVESV， SV， LVEF） of rats were detected in each group. The levels of inflammatory factors （CRP， IL-1β， IFN-γ and ET-1） in myocardial tissue were determined by ELISA. Histomorphological characteristics of myocardial tissue were determined by HE staining. RESULTS： The structure of myocardial fibers in control group and sham operation group was clear and orderly； there was no statistical significance in difference of each index between 2 groups （P＞0.05）. Compared with control group， myocardial fibers were disorderly arranged in model group， and the phenomena of rupture， dissolution and necrosis were observed， accompanied by infiltration of inflammatory cells. The levels of LVEDV and LVESV as well as the levels of CRP， IL-1β， ET-1 and IFN-γ were increased significantly， while the levels of SV and LVEF were decreased significantly （P＜0.05 or P＜0.01）. Compared with model group， above symptoms of rats in each administration group were improved to different extents； the levels of LVEDV and LVESV as well as the levels of CRP， IL-1β， ET-1 and IFN-γ in positive group， the levels of LVEDV in ZTY water extract medium-dose and high-dose groups， the levels of LVESV and CRP， IL-1β， ET-1， IFN-γ in ZTY water extract groups were decreased significantly. The levels of SV and LVEF in positive group， the levels of SV in ZTY water extract groups as well as the levels of LVEF in ZTY water extract medium-dose and high-dose groups were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： ZTY water extract could reduce the level of ET-1 and improve blood vessels diastolic and systolic function in CHD model rats， then restore blood supply of myocardial tissue and strengthen cardiac function， by acting on inflammation cycle.