11ß­hydroxysteroid dehydrogenase­1 is associated with the activation of hepatic stellate cells in the development of hepatic fibrosis.

Hepatic fibrosis (HF) is a common complication of numerous chronic liver diseases, but predominantly results from persistent liver inflammation or injury. If left untreated, HF can progress and develop into liver cirrhosis and even hepatocellular carcinoma. However, the underlying molecular mechanisms of HF remain unknown. The present study aimed to investigate the role of 11ß­hydroxysteroid dehydrogenase­1 (11ß­HSD1) during the development of hepatic fibrosis. An experimental rat model of liver fibrosis was induced using porcine serum. 11ß­HSD1 gene expression levels and enzyme activity during hepatic fibrogenesis were assessed. 11ß­HSD1 gene knockdown using small interfering RNA and overexpression were performed in LX2­human hepatic stellate cells (HSCs). HSCs were stimulated with transforming growth factor­ß1 (TGF­ß1). Cell cycle distribution, proliferation, collagen secretion and 11ß­HSD1 gene activity in HSCs were compared before and after stimulation. As hepatic fibrosis progressed, 11ß­HSD1 gene expression and activity increased, indicating a positive correlation with typical markers of liver fibrosis. 11ß­HSD1 inhibition markedly reduced the degree of fibrosis. The cell proliferation was increased, the number of cells in the G0/G1 phase decreased and the number of cells in the S and G2/M phases increased in the pSuper transfected group compared with the N group. In addition, the overexpression of 11ß­HSD1 enhanced the TGF­ß1­induced activation of LX2­HSCs and enzyme activity of connective tissue growth factor. 11ß­HSD1 knockdown suppressed cell proliferation by blocking the G0/G1 phase of the cell cycle, which was associated with HSC stimulation and inhibition of 11ß­HSD1 enzyme activity. In conclusion, increased 11ß­HSD1 expression in the liver may be partially responsible for hepatic fibrogenesis, which is potentially associated with HSC activation and proliferation.

Salmonella-Mediated Cancer Therapy: An Innovative Therapeutic Strategy.

Bacterial-mediated cancer therapy (BMCT) has become a hot topic in the area of antitumor treatment. Salmonella has been recommended to specifically colonize and proliferate inside tumors and even inhibit tumor growth. Salmonella typhimurium (S. typhimurium) is one of the most promising mediators, which can be easily manipulated. S. typhimurium has been engineered and designed as cancer-targeting therapeutics, and can be improved by combining with other therapeutic methods, e.g. chemotherapy and radiotherapy, which regulate the tumor microenvironment synergistically. In view of all these strengths, the engineered attenuated strains have significant advantages for tumor diagnosis and treatment. This treatment has also been approved by the FDA for clinical trial. In this review, we summarized the recent progress and research in the field of Salmonella -mediated cancer therapy.

Increased serum malondialdehyde levels are associated with grey matter volume loss in patients with non-alcoholic cirrhosis.

BACKGROUND: Grey matter volume (GMV) loss has been observed in patients with non-alcoholic cirrhosis, but the underlying mechanisms are unknown. Oxidative stress (OS) is a recognized feature and systemic phenomenon of cirrhosis. However, little is known about whether OS is associated with GMV loss in cirrhosis. This study aimed to assess the relationship between oxidative damage and GMV loss in patients with non-alcoholic cirrhosis. METHODS: Thirty-four patients with non-alcoholic cirrhosis and 27 age- and sex-matched healthy controls were enrolled in this prospective study. All subjects underwent brain magnetic resonance imaging (MRI), and voxel-based morphometry (VBM) was performed to assess normalized global GMV. As an OS marker, serum malondialdehyde (MDA) levels were determined in all subjects. In the patient group, a correlation analysis was used to investigate the relationship between serum MDA levels and normalized global GMV. RESULTS: Compared with healthy controls, cirrhotic patients displayed a significant decrease in normalized global GMV and a significant increase in serum MDA levels. In the patient group, serum MDA levels were negatively correlated with normalized global GMV adjusted for age, sex and Child-Pugh class. CONCLUSIONS: Increased serum MDA levels were associated with GMV loss in patients with non-alcoholic cirrhosis, suggesting that oxidative damage may be involved in GMV loss observed in cirrhotic patients.

Intravoxel incoherent motion derived liver perfusion/diffusion readouts can be reliable biomarker for the detection of viral hepatitis B induced liver fibrosis.

BACKGROUND: Recent two studies reported that intravoxel incoherent motion (IVIM) analysis can separate healthy livers and viral hepatitis B (VHB) induced liver fibrosis. However, in these two studies the starting b value for bi-exponential decay analysis was b =10 and 15 s/mm2 respectively. The current study has two primary aims. The first is to further confirm the diagnostic value of IVIM in detecting liver fibrosis. The second is to test whether by sampling very low b value densely, then b =0 s/mm2 image could be included to improve IVIM's diagnostic performance. METHODS: This was a prospective study with data acquired at the Third Xiangya Hospital of Central South University, Changsha, China. Healthy volunteers and patients suspected of VHB induced liver fibrosis with liver biopsy performed, as well as hepatocellular carcinoma patients scheduled for surgery, were recruited. All the hepatocellular carcinoma patients had liver fibrosis. After exclusions based on pre-defined criteria for image data quality, for IVIM analysis this study included 20 healthy volunteers; 4 chronic VHB patients with biopsy showing no liver fibrosis; 11 stage-1 liver fibrosis patients, 10 stage-2 liver fibrosis patients, 2 stage-3 liver fibrosis patients, and 5 stage-4 liver fibrosis patients. In the liver fibrosis patients, 1, 19, and 8 cases had inflammation grade-0, grade-1, and grade-2 respectively. The reference IVIM bi-exponential decay curve fitting analysis was segmented fitting performed with b =2 s/mm2 image as the starting point and a threshold-b of 60 s/mm2. This reference fitting method was compared with threshold-b of 40 s/mm2, full fitting, fitting starting from b =0, 5, and 10 s/mm2 respectively. The potential correlation between IVIM readouts and liver function was assessed for the liver fibrosis patients. RESULTS: Based on the smaller coefficient of variation (CoV) for the volunteer group and the smaller patient/volunteer ratios [= (mean measurement for patient groups)/(mean measurement for healthy volunteers)], the comparison of fitting methods favored the reference approach starting from b =2 s/mm2 with a threshold-b of 60 s/mm2. The IVIM measures of four patients without liver fibrosis resembled those of healthy subjects. PF offered the best diagnostic value for separating healthy livers and fibrotic livers, and a threshold of PF =0.1406 separated all fibrotic livers and healthy livers with an exception of one hepatocellular carcinoma patient (fibrosis grade-2/inflammation grade-2). The correlation between fibrosis grading and inflammation grading was weakly positive; while compared with fibrotic livers with inflammation grade-1, fibrotic livers with inflammation grade-2 showed a trend of higher Dfast. A weak correlation is shown with lower PF and lower Dfast associated with lower total protein, lower albumin; higher alanine transaminase, higher aspartate transaminase; higher total bilirubin, and higher direct bilirubin. CONCLUSIONS: Segmented-fitting with threshold-b =60 s/mm2 and starting from non-zero very low b value outperforms other methods. IVIM has high sensitivity in detecting liver fibrosis, and PF and Dfast have potential correlation with serum liver function biomarkers. IVIM measures and liver fibrosis grading are not in a linear relationship.

Hippocampal volume reduction in elderly patients at risk for postoperative cognitive dysfunction.

PURPOSE: Postoperative cognitive dysfunction (POCD) is a formidable public health issue, which would not only affect the quality of life among elderly patients but also lead to pulmonary infection and increased mortality. While, there is a lack of an effective indicator in predicting POCD. As one pivotal part of the limbic system in brain, hippocampus is associated with cognitive function. Hippocampal atrophy could indicate the degree of changes in cognitive function. METHODS: Forty-one ASA II or III patients (23 male, 18 female) aged ≥65 years undergoing open gastrointestinal tract surgery were enrolled in this study. MRI was performed to measure the volume of hippocampal formation before surgery and the results were standardized according to individual intracranial volume. All patients underwent a battery of neuropsychological tests including sensitive tests on the Wechsler adult memory scale and Wechsler adult intelligence scale, trail making test and the grooved pegboard test. We used the Z score to identify POCD as recommended by ISPOCD. All patients were then divided into POCD group and non-POCD group according to the results of the neuropsychological tests. The results of the tests were correlated with the volume of hippocampal formation measured by MRI. The value of MRI measurement of hippocampal volume in predicting POCD was analyzed. Multivariate linear correlation analyses of compositive Z score using potential contributing factors such as age, duration of anesthesia, education and hippocampal volume was carried out. RESULTS: Thirty-six patients completed the whole battery of neuropsychological tests after surgery. Thirteen of the 36 patients were found to have POCD (36 %) on the postoperative 4th day. The hippocampal volume was significantly smaller in POCD group (4.75 ± 0.23) than in non-POCD group (5.06 ± 0.31). Hippocampal volume had great influence on Z score, and had negative correlation with Z score. CONCLUSION: The MRI measurement of hippocampal volume is suggested to be valuable as a predictor of POCD in the elderly.

Magnetic fluid hyperthermia induced by radiofrequency capacitive field for the treatment of transplanted subcutaneous tumors in rats.

Magnetic fluid hyperthermia (MFH) induced by a magnetic field has become a new heating technology for the treatment of malignant tumors due to its ability to heat the tumor tissue precisely and properly, and due to its significant therapeutic effects. In this study, MFH induced by radiofrequency capacitive field (RCF) for the treatment of transplanted subcutaneous tumors in rats, was investigated. A total of 50 rats bearing subcutaneous tumors were randomly divided into five groups, including i) a pseudo-treatment (PT) control group, ii) magnetic fluid (MF) group, iii) pure hyperthermia (PH) group, iv) magnetic fluid hyperthermia 1 (MFH1) group, and v) magnetic fluid hyperthermia 2 (MFH2) group. Tumors were irradiated for 30 min in the MFH1 group 24 h following injection of MF. Tumors were irradiated for 30 min in the MFH2 group 24 h following injection of MF, and irradiation was repeated for 30 min 72 h following injection of MF. Tumor volumes, tumor volume inhibition ratios and survival times in the rat model were examined. Temperatures of tumor cores and rims both rapidly reached the desired temperature (∼50°C) for tumor treatment within 5 to 10 min in the MFH1 and MFH2 groups, and we maintained this temperature level by manually adjusting the output power (70-130 W). Tumor volumes of the MFH1 and MFH2 groups were reduced compared to those of the PT, MF and PH groups. The inhibitory effect on tumor growth in the MFH2 group (91.57%) was higher compared to that in the MFH1 group (85.21%) and the other groups. The survival time of the MFH2 group (51.62±2.28 days) and MFH1 group (43.10±1.57 days) was increased compared to that of the PH, MF and PT groups. The results obtained show that MFH induced by RCF may serve as a potential and promising method for the treatment of tumors.

[Correlation of multi-slice CT findings to clinical staging and prognosis of mesenteric blood vessel infarction].

OBJECTIVE: To explore the correlation of multi-slice CT findings to the clinical staging and prognosis of intestinal obstruction due to mesenteric blood vessel infarction. METHODS: Fifty-four patients with intestinal obstruction resulting from infarction of the mesenteric vein or artery underwent multi-slice CT scanning, and the CT findings were analyzed for their relation with the intestinal ischemia and prognosis. RESULTS: Sixteen patients were confirmed to have mesenteric arterial thrombosis (29%) and 40 had mesenteric venous thromboses (71%) by multi-slice CT scanning. The total mortality rate was 29%, of which mesenteric artery infarction took up 87% and mesenteric vein infarction 5%. The prognosis of the patients was closely related to the cause of the bowel infarction. Such CT findings as increased intensity of the intestinal canal and decreased enhancement and thickening of the bowel wall indicated favorable prognosis, whereas the signs of paper-thin wall sign, fecal sign, pneumatosis of the bowel wall, mesenteric veno gas and pneumoperitoneum all suggested poor prognosis. CONCLUSION: Multi-slice CT scanning can identify mesenteric blood vessel infarction resulting in intestinal obstruction, and the CT signs can offer objective and valuable information for clinical staging and prognostic evaluation.

[Potential risk of porcine endogenous retrovirus cross-species transmission in neonatal pig islets under xenotransplanted condition].

OBJECTIVE: To evaluate the potential risk of porcine endogenous retrovirus (PERV) cross-species transmission xenotransplanted with microencapsulated neonatal pig islets (NPIs). METHODS: Ten dogs were randomly divided into an experiment group and a control group. The experiment group was transplanted with microencapsulated NPIs, and the control group was transplanted with non-microencapsulated NPIs. Glucose tolerance test (GTT) was performed to evaluate the function of microencapsulated NPIs after the transplantation; immunity histochemistry was used to detect the microencapsulated NPIs in the liver of dogs which had been transplanted after 28 days; PCR and RT-PCR were performed to detect PERV and pig mitochondrial (mt) DNA in the blood samples obtained from recipients at various time points after the transplantation. RESULTS: The level of serum special porcine C peptide increased significantly after the injection of glucose for 15 approximately 30 min in dogs which were transplanted with the micro-encapsulated NPIs over 2 weeks, while special porcine C peptide could not be detected in the control group. Immunity histochemistry showed that a few microencapsulated NPIs were still alive in the liver of the dog, and the liver was not damaged. PCR and RT-PCR showed that pig mt DNA and PERV could not be detected in the experiment group 1 approximately 28 days after the transplantation, while very weak expression of that in the control could be detected in the first 4 days and disappeared 10 days after the transplantation. CONCLUSION: Microencapsulated NPIs can survive and have biological function in dogs. There is no evidence of PERV replication, suggesting that the xenotransplantation with microencapsulated NPIs can prevent PERV effectively, and may have great value.