ObjectiveTo investigate the effect of human umbilical cord mesenchymal stem cells （hUCMSCs） in the treatment of mice with liver fibrosis and its mechanism. MethodsA total of 18 specific pathogen-free C57BL/6 mice， aged 6 weeks， were selected and divided into control group （n=6）， carbon tetrachloride （CCl₄） model group （CCl₄ group， n=6）， and hUCMSCs treatment group （MSC group， n=6） using a random number table. The mice in the CCl₄ group and the MSC group were given intraperitoneal injection of CCl₄ solution to establish a mouse model of liver fibrosis， while those in the control group were injected with the same dose of corn oil， and the mice in the MSC group were injected with hUCMSCs via the caudal vein during the injection of CCl₄. At the end of week 8， mouse serum was collected， and the mice were sacrificed to collect and fix the liver. Enzyme-linked immunosorbent assay was used to measure the levels of inflammatory factors； an automatic biochemical detector was used to measure liver function parameters； HE staining， Masson staining， Sirius Red staining， and α-SMA immunofluorescence assay were used to evaluate liver fibrosis. Hepatic stellate cells （HSCs） stimulated by TGF-β were co-cultured with hUCMSCs in the medium with or without chitinase-3 like-protein-1 （CHI3L1）， and Western blot was used to measure the expression levels of proteins. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsMasson staining and Sirius Red staining showed that the CCl₄ group had a significantly higher degree of fibrosis than the control group （both P<0.05）， and the MSC group had significant alleviation of fibrosis compared with the CCl₄ group （both P<0.05）. Compared with the control group， the CCl₄ group had significant increases in the levels of interleukin-1β， interleukin-6 （IL-6）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， and alkaline phosphatase （ALP） （all P<0.05）， and compared with the CCl₄ group， the MSC group had significant reductions in the levels of IL-6， AST， ALT， and ALP （all P<0.05）. The CCl₄ group had significantly higher expression levels of CHI3L1 and α-SMA than the control group and the MSC group （all P<0.05）. The cell culture experiment showed that the MSC+HSC group had a significantly higher expression level of Bax than the HSC group and the MSC+CHI3L1 group （both P<0.05）， suggesting that CHI3L1 reversed the pro-apoptotic effect of MSC on activated HSCs. ConclusionThis study shows that hUCMSCs can improve liver fibrosis in mice， possibly by inhibiting CHI3L1 to promote the apoptosis of HSCs.

Background and Purpose:The early prediction of local tumor progression-free survival(LTPFS)after radiofrequency ablation(RFA)for colorectal cancer(CRC)lung metastases has significant clinical importance.The application of radiomics in the prediction of tumor prognosis has been explored.This study aimed to construct a radiomics-based nomogram for predicting LTPFS after RFA in CRC patients with lung metastases.Methods:This study retrospectively analyzed 172 CRC patients with 401 lung metastases admitted to Department of Interventional Radiology,Fudan University Shanghai Cancer Center from August 2016 to January 2019.This study was reviewed by the medical ethics committee of Fudan University Shanghai Cancer Center(ethics number:2402291-24).After augmentation of pre-ablation and immediate post-ablation computed tomography(CT)images,the target metastases and ablation regions were segmented manually to extract the radiomic features.Maximum relevance and minimum redundancy algorithm(MRMRA)and least absolute shrinkage and selection operator(LASSO)regression models were applied for feature selection.The clinical model,the radiomics model,and the fusion model were constructed based on the selected radiomic features and clinical variables screened by the multivariate analysis.The Harrell concordance index(C-index)and area under receiver operating characteristic(ROC)curves(AUC)were calculated to evaluate the prediction performance.Finally,the corresponding nomogram of the best model was drawn.Results:Among all the lung metastases,102(25.4%)had final recurrence,and 299(74.6%)had complete response(CR).The median follow-up time was 21 months(95%CI:19.466-22.534),and the LTPFS rates at 1,2,and 3 years after RFA were 76.5%(95%CI:72.0-80.4),72.1%(95%CI:66.6-76.9)and 69.9%(95%CI:64.0-75.1).In both the training and test dataset,the fusion model based on the final 12 radiomic features through the LASSO regression and 4 clinical variables screened by multivariate analysis achieved the highest AUC values for LTPFS,with C-index values of 0.890(95%CI:0.854-0.927)and 0.843(95%CI:0.768-0.916),respectively.Conclusion:The fusion model based on radiomic features and clinical variables is feasible for predicting LTPFS after RFA of CRC patients with lung metastases,whose performance is superior to the single radiomic and clinical model.At the same time,the nomogram of the fusion model can intuitively predict the prognosis of CRC patients with lung metastases after RFA,thus assisting clinicians in developing individualized follow-up review plans for patients and adjusting treatment strategies flexibly.

Background::Hypertension and non-alcoholic fatty liver disease (NAFLD) share several pathophysiologic risk factors, and the exact relationship between the two remains unclear. Our study aims to provide evidence concerning the relationship between hypertension and NAFLD by analyzing data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 and Mendelian randomization (MR) analyses.Methods::Weighted multivariable-adjusted logistic regression was applied to assess the relationship between hypertension and NAFLD risk by using data from the NHANES 2017-2018. Subsequently, a two-sample MR study was performed using the genome-wide association study (GWAS) summary statistics to identify the causal association between hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and NAFLD. The primary inverse variance weighted (IVW) and other supplementary MR approaches were conducted to verify the causal association between hypertension and NAFLD. Sensitivity analyses were adopted to confirm the robustness of the results.Results::A total of 3144 participants were enrolled for our observational study in NHANES. Weighted multivariable-adjusted logistic regression analysis suggested that hypertension was positively related to NAFLD risk (odds ratio [OR] = 1.677; 95% confidence interval [CI], 1.159-2.423). SBP ≥130 mmHg and DBP ≥80 mmHg were also significantly positively correlated with NAFLD. Moreover, hypertension was independently connected with liver steatosis ( β = 7.836 [95% CI, 2.334-13.338]). The results of MR analysis also supported a causal association between hypertension (OR = 7.203 [95% CI, 2.297-22.587]) and NAFLD. Similar results were observed for the causal exploration between SBP (OR = 1.024 [95% CI, 1.003-1.046]), DBP (OR = 1.047 [95% CI, 1.005-1.090]), and NAFLD. The sensitive analysis further confirmed the robustness and reliability of these findings (all P >0.05). Conclusion::Hypertension was associated with an increased risk of NAFLD.

Delirium is a common and serious multifactorial syndrome in elderly inpatients and may have serious consequences for patients, their families and society.This review summarizes the epidemiology, risk factors, pathogenesis, evaluation criteria, prevention and treatment of delirium in elderly inpatients.

Objective To observe the differential expression of high mobility group box - 1 protein (HMGB1) in renal tissues of heat stroke mice models, and to explore its role in the pathogenesis of heat stroke associated acute kidney injury(HS-associated AKI). Methods According to random number table, 20 healthy male C57BL/6J mice were randomly divided into 2 groups, including normal control (n=10) and heat stroke group (n=10). The mice in heat stroke group were given with a 2-hour-exposure in biological simulation chamber (temperature 41℃, humidity 70％). Heat stroke was defined as anal temperature lasting more than 40 degrees Celsius. A 18F - deoxyglucose nuclide labeled vivo imaging was conducted with micro - positron emission tomography(PET)/computer tomography (CT). Serum creatinine was examined with blood example. In order to evaluate the pathological changes, HE stain was conducted with kidney tissue, and mitochondrial morphological changes in kidney tissue were observed by transmission electron microscopy. The expressions of HMGB1 and apoptosis inducing factor mitochondria associated 2 (Aifm2) were examined by immunohistochemical method, and the levels of HMGB1 and RAGE were examined by Western blotting. The cell apoptosis of renal tissue was detected by terminal deoxynucleotidyl transferase -mediated dUTP - biotin nick end labeling assay (TUNEL). The metabolomics of kidney tissue in mice were detected by liquid chromatography - mass spectrometry (LC - MS), and the pathway enrichment analysis was carried out by KEEG database. Results (1) The body temperature of the mice in heat shock group was significantly higher than that in normal control group 45 min after model establishment (P＜0.05). The level of serum creatinine in heat shock group was significantly higher than that in normal control group (P＜0.05), and the levels of 18F - deoxyglucose increased in skeletal muscle and visceral tissue of the mice in heat - shock group. (2) HE staining showed hemorrhage in collecting duct and tubular endothelial cell swelling, and mitochondrial swelling and deformation were observed by transmission electron microscopy in kidney tissue of the heat shock group. (3) Immunohistochemical method showed that the levels of Aifm2 and HMGB1 in heat shock group were higher (P＜0.05). (4) Western blotting showed that the levels of HMGB1 and RAGE in heat shock group were higher than those in normal control group (P＜0.05). (5) TUNEL showed that the number of cells with positive stain in kidney tissue of the heat shock group was higher than that in normal control group (P＜0.05). (6) Between normal control group and heat shock group, 136 differential metabolites were detected in kidney tissues. After analysis by KEGG database, pathway abnormalities such as unsaturated fatty acid metabolism disorder may be associated with HS - associated AKI, and many differential metabolites such as adrenic acid may be important regulatory points in the pathogenesis. Conclusion Acute kidney injury is a common complication of heat shock. It may be related to the dysfunction of renal mitochondria and activation of apoptotic pathway caused by systemic hypercatabolism, which may be related to the disorder of unsaturated fatty acid metabolism and activation of HMGB1. Some differential metabolites may be of high value in HS- associated AKI studies.

OBJECTIVE: To observe the hepatic injury induced by combined exposure to diethylhexyl phthalate( DEHP) and bisphenol A( BPA) in rats and explore the mechanism of oxidative stress. METHODS: Thirty-two specific pathogen free healthy male SD rats were randomly divided into control group,DEHP(750 mg/kg body weight) group,BPA(100 mg/kg body weight) group and combined exposure group,with 8 rats in each group. The rats were gavaged once per day,7 days per week,for 6 weeks. The changes of liver organ coefficient and histopathology were observed. The activities of superoxide dismutase( SOD), glutathione peroxidase( GSH-Px) and the levels of hydrogen peroxide( H2 O2),malondialdehyde( MDA) were detected by spectrophotometry. The relative mRNA expression of antioxidant gene nuclear factor erythroid-2 related factor 2( Nrf2),heme oxygenase-1( HO-1),glutamate cysteine ligase catalytic subunit( Gclc),thioredoxin reductase( Txnrd),superoxide dismutase 3( Sod3) and glutathione peroxidase 1( Gpx1) in liver tissue were examined by real-time fluorescent quantitative polymerase chain reaction. RESULTS: The body weight of DEHP exposure group was lower than that of control group from the beginning of the 2 nd week( P < 0. 05),and the body weight of combined exposure group was lower than control group from the beginning of the 3 rd week( P < 0. 05). The liver mass and organ coefficients in DEHP group and combined exposure group were significantly higher than that of control group( P <0. 05). The results of pathology examination showed that there was necrosis of liver cells in DEHP group,vacuolar degeneration in cytoplasm of BPA group,and severe inflammatory cell infiltration in combined exposure group. The activity of SOD and GSH-Px of each exposure group was reduced( P < 0. 05),the H2 O2 level of each exposure group was increased(P < 0. 05),meanwhile the MDA level in the liver tissue of the BPA group and the combined exposure group increased compared with the control group( P < 0. 05). The relative mRNA expression of Nrf2,HO-1 and Gpx1 in each exposure group were decreased( P < 0. 05),the relative mRNA expression of Gclc,Txnrd and Sod3 in DEHP group and mixed exposure group were decreased compared with the control group( P < 0. 05). The relative mRNA expression of Nrf2,HO-1,Gclc,Txnrd and Sod3 in combined exposure group were decreased compared with the BPA group( P < 0. 05).CONCLUSION: Under the conditions of this study,DEHP and BPA alone or in combination could cause hepatic injury. The combined effect was greater than single effect. The effect of DEHP was greater than that of BPA. The liver injury induced by DEHP and BPA was related to Nrf2 signaling pathway.

Objective Both QBC Star and Sysmex XP-100 hematology analyzers are convenient to carry,which can be used nor-mally under the condition of the field(emergency).This study would compare their test results and operating performance,so to provide guidance for rational use of the instruments.Methods 100 fresh blood samples of 100 health soldiers anti-coagulated by EDTA-K2 were detected by QBC Star and Sysmex XP-100 haematology analyzers respectively,the results of two analyzers were comparatively analyzed and their test time and operating convenience were analyzed.Results There was no significant difference in the results of hemoglobin concentration (HGB),hematocrit (HCT)tested by the two methods (P >0.05).There were significant difference of the mean corpuscular hemoglobin concentration (MCHC),the sum of lymphocyte percent and middle type cells (LYM%+MID%),neutrophil percentage(NEUT%),white blood cell count(WBC),platelet count(PLT)tested by the two meth-ods(P <0.05).The values of MCHC and LYM%+MID% tested by the QBC Star were significantly lower than that detected by Sysmex XP-100(P <0.05),while the rest indicators tested by the former were higher than that of the latter.It took about 5 minutes to complete a blood sample analysis with QBC Star,while about 1 min was needed for Sysmex XP-100.Conclusion The test results of QBC Star and Sysmex XP-100 hematology analyzers couldn′t exchanged except for that of HCT and HGB.Under the condition of field(emergency),QBC Star hematology analyzer is suitable for individual medical examination,and Sysmex XP-100 hematology an-alyzer can be used for the batch medical examination.

Objective To summarize the clinical experience of immunosuppressive therapy for recipients suffering from psoriasis after liver transplantation. Methods Five patients diagnosed with cirrhosis or hepatocellular carcinoma (HCC)complicated with psoriasis after liver transplantation were recruited in this clinical trial. All participants were positive for serum biomarkers of hepatitis B virus (HBV). Induction therapy was adopted before surgery. Immunosuppressive regime of tacrolimus (FK506),mycophenolate mofetil (MMF)and adrenal cortical hormone (hormone) was implemented early after surgery. The hormone use was terminated within 1 week. Three cases of cirrhosis complicated with HCC due to chronic HBV infection were gradually switched to sirolimus substitution treatment within 1 month after liver transplantation. Two patients with cirrhosis were administered with FK506 with or without MMF following liver transplantation. All patients received anti-HBV therapy. Baseline data,changes in psoriasis area and severity index (PASI)score and adjustment of postoperative immunosuppressive agents were analyzed. Results Five patients undergoing transplantation were followed up until the submission date with a mean duration of (8. 3 ±1 . 5 )years and survived. Compared with preoperative values,PASI score was significantly reduced at postoperative 6 months (P<0. 05 ). Two patients with cirrhosis had recurrent psoriasis at 2 years after liver transplantation. PASI score was significantly increased and steadily declined after sirolimus substitution therapy. These patients remained physically stable and did not progress at postoperative 3 years. Three patients suffering from cirrhosis complicated with HCC presented with no recurrence of psoriasis postoperatively. Conclusions Sirolimus-based immunosuppressive therapy can effectively control the progression of psoriasis in liver transplantation recipients. Anti-HBV treatment should be simultaneously implemented for HBV positive patients.

Background and purpose:Early evaluating the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) in patients with hepatic cancer is still a diffcult clinical problem. The purpose of this study was to evaluate the ability of the apparent diffusion coeffcient (ADC) to help predict early disease progression after TACE.Methods:Institutional review board approval was obtained, and all patients signed informed consent. Magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) (b=50, 500, 1 000 mm2/s) were performed before and 1 month after initiating TACE for 23 patients with hepatic cancer (14 were male, 9 were female; mean age: 53.3 years;range: 21-85 years). Contrast-enhanced MRI was performed 3 months after initiating TACE. Patients were classiifed as either progressing or non-progressing according to RECIST 1.1. The preoperative ADC values of tumor and the ADC values of tumor 1 month after TACE were analyzed by pairedt-test in both progressing and non-progressing group. Unpairedt-test was used to compare ADC parameters between progressing and non-progressing group. In all the 23 hepatic cancer patients, receiver operating characteristic (ROC) curve analysis was performed to determine a threshold ADC ratio (ADC%) to differentiate progressing from non-progressing patients.Results:Thirteen progressing and 9 non-progressing patients were evaluated. Increase in ADCs of tumor was observed in non-progressing patients at 1 month after TACE compared with preoperative ADCs. There was a signiifcant difference between the 2 groups (P=0.01). In progressing group, preoperative ADCs of tumor were similar to those at 1 month after TACE (P=0.221). There was no significant difference in preoperative ADCs of tumor and ADC% between the progressing and non-progressing groups. In patients with hepatic cancer, 1 month ADC ratio in non-progressing patients were signiifcantly higher than those of progressing patients (P=0.029). Using ROC to evaluate the ability of ADC% could predict early disease pro-gression after TACE. Using -6.455% as the threshold, the area under the ROC curve was 0.867 (95%CI: 0.643-1.000). The sensitivity was 100%, and the speciifcity was 66.7%.Conclusion:One month after TACE, the increases in ADCs of tumor were observed only in the non-progressing group; and the ADC ratio seems to be a promising tool for helping predict the early disease progression after TACE in patients with hepatic cancer.

10.3969/j.issn.1007-3969.2013.05.005