Bone marrow-derived mesenchymal stem cells ameliorate severe acute pancreatitis-induced lung injury in rats via suppression of ferroptosis / 中国临床药理学与治疗学

AIM: To evaluate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on ferroptosis in lung injury caused by severe acute pancreatitis (SAP). METHODS: BMSCs were obtained from male SD rats (3 weeks of age). 30 male SD rats (6 weeks of age) were randomly divided into 5 groups: Sham group, SAP group, SAP+PBS group, SAP+BMSCs group, and SAP+BMSCs+ML385 group, with 6 rats in each group. SAP model induced by sodium taurocholate (NaT) was established. Rats in the SAP+MSCs+ML385 group were intraperitoneally injected with ML385 (5 mg/kg) 2h before SAP induction. For PBS control and BMSCs treatment groups, PBS and BMSCs were respectively injected into rats via the tail vein 6 h after creation of the SAP model. All rats were sacrificed 3 days after SAP induction, and pancreas and lung tissue and serum samples were collected. Pancreatic and pulmonary injury was assessed using H&E staining. Serum levels of amylase and lipase and inflammatory factors, as well as tissue levels of iron, malondialdehyde (MDA), glutathione (GSH) were evaluated. The expressions of ferroptosis-associated proteins, including iron responsive element binding protein 2 (IREB2), ferritin heavy chain 1 (FTH1), acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11), as well as the expressions of PI3K/AKT/Nrf2 pathway-related proteins were assessed. RESULTS: The serum levels of amylase, lipase and proinflammatory factors, as well as pathological scores were significantly increased after SAP induction (P<0.05). Changes above were effectively alleviated by BMSCs (P<0.05). Compared with SAP group, the iron and MDA contents were decreased, the GSH activity was increased, the expression of IREB2 and ACSL4 were downregulated and the expression of FTH1, GPX4 and SLC7A11 were upregulated in SAP+BMSCs group (P<0.05). Injection of ML385 partially offset the anti-lipid peroxidation effect of BMSCs (P<0.05). In addition, BMSCs upregulated the total protein levels of PI3K and p-AKT, and the nuclear protein level of Nrf2 in lung tissue (P<0.05). CONCLUSION: BMSCs can effectively reduce systemic inflammatory response and local tissue injury in SAP; BMSCs can inhibit iron deposition and lipid peroxidation in SAP-induced lung injury, and the anti-lipid peroxidation effect may be achieved via activating the PI3K/AKT/Nrf2 signaling pathway.

The suppression of IL-24 on pancreatic cancer mediated by tumor-targeting oncolytic adenovirus in immune-competent mice / 中华肝胆外科杂志

Objective To investigate whether IL-24 can inhibit the growth of pancreatic cancer in immune-competent mice,which could be mediated by tumor-targeting oncolytic adenovirus (ZD55-IL-24).Methods Crystal violet staining assay was used to evaluate the anti-proliferative influence of ZD55-IL-24 on Panc02.The tumor growth curve,the tumor formation curve,TUNEL assay,cytotoxic T lymphocyte (CTL) killing assay and serum cytokines detection were used to assess anti-tumor efficacy of ZD55-IL-24 for pancreatic cancer in immune-competent mice.Results ZD55-IL-24 significantly inhibited the growth of pancreatic cancer cells in vitro.Lower tumor formation and slower tumor growth were identified in ZD55-IL-24 group,compared with ZD55-EGFP group or PBS group.ZD55-IL-24 induced pancreatic cancer cells'apoptosis,and mediated anti-cancer immunity by increasing killing responses of CTL to cancer cells and up-regulating serum γ-IFN and IL-6 levels.Conclusion ZD55-IL-24 can induce anti-tumor immunity and suppress pancreatic cancer growth in immune-competent mice.

Expression and clinical significance of heat shock transcription factor 1 protein in human hepatocellular carcinoma tissues / 中华消化外科杂志

ObjectiveTo investigate the expression and clinical significance of heat shock transcription factor 1 (HSF1) protein in human hepatocellular carcinoma (HCC) tissues,and deduce the probable molecular mechanism of HSF1 in the development and advancement of HCC.MethodsSixty-seven samples of HCC tissue and 21 samples of normal liver tissue were obtained from March 2006 to March 2007 at the Xijing Hospital.The expressions of HSF1 protein and heat shock protein 70 (HSP70) were detected by using immunohistochemistry.The probable molecular mechanism of HSF1 in the development and advancement of HCC was deduced according to the relationship between the expressions of HSF1 protein and HSP70.Positive rates of HSF1 protein in different tissues and the relationship between HSF1 protein expression in the HCC tissues and clinical pathological factors were analyzed by the chi-square test and by calculating Fisher exact probability,respectively.The correlation between the expressions of HSF1 protein and HSP70 in the HCC tissue was analyzed by the Spearman correlation coefficient.The survival curve was drawn by the Kaplan-Meier method,and the survival rate was analyzed by the Log-rank test.ResultsThe positive rates of HSF1 protein expression was 69％ (46/67) in the HCC tissue,which was significantly higher than 29％ (6/21) in the normal liver tissue ( x2 =10.628,P ＜ 0.05 ),The positive rates of HSP70 expression in the HCC tissue was 57％ (38/67),which was significantly higher than 24％ (5/21) in the normal liver tissue ( x2 =6.929,P ＜ 0.05 ).The expression of HSF1 protein in the HCC tissue was positively correlated with that of HSP70 (r=0.319,P ＜0.05).The high expression of HSF1 protein was correlated with the integrity of capsule of HCC,tumor differentiation and TNM stage (x2 =5.935,9.762,5.159,11.267,P＜0.05 ),while the high expression of HSF1 protein was not correlated with the gender,age,levels of hepatitis B surface antigen and alpha fetoprotein,and portal vein tumor thrombus ( x2 =0.822,0.172,2.059,P ＞0.05 ).The survival time was (21.4 ± 1.9 )months for patients with positive HSF1 protein expression and (29.8 ± 2.7 ) months for patients with negative HSF1 protein expression.There was a significant difference in the survival time between patients with positive and negative HSF1 protein expression ( x2 =4.276,P ＜ 0.05 ).Conclusions HSF1 is correlated with the development,advancement,invasion,metastasis and malignant prognosis of HCC.HSF1 takes effects by regulating the expression of HSP70,and it has a good perspective of clinical application for the diagnosis and treatment of HCC.

The effect of HIFU ablation combined with UCA on normal tissue around VX2 liver tumor in rabbits / 中华普通外科杂志

Objective To explore the optimized range of normal tissue ablation around the tumor by HIFU in combination with UCA for VX2 liver tumors in rabbits. Methods In this study,51 rabbit models with implanted fiver VX2 tumors were randomly divided into 3 groups:ablating the tumor only(group A)、ablating the tumor and 2 mm eircumferential normal tissue(group B)、and 4 mm normal tissue around the tumor(group C).After HIFU+UCA treatment,the pathology of the targeting tissues,the level of serum ALT,the metastases in the liver、lungs and abdominal cavity,and the survival time were compared with each other. Results After treatment coagulative necrosis was observed in all the target tissues.Serum ALT level between each two groups were statistically different on d3 and d5(F=12.933、18.37,P＜0.01、＜0.01),and the level of ALT in group C was the hightest.The ALT level in group A was significantly higher than group B or group C on the 14th day(F=17.2,P＜0.01).Metastases in group A was significantly higher than group B or group C,and there were no statistically different between group B and C (P=0.353、0.332、0.380).The survival time both in group B and group C were significantly longer than group A(48±13.6,51±12.1 vs 29±5.4),and there were no statistically difference between group B and C(P＞0.05). Conclusions Tumor eradication can be significantly promoted when 2mm normal liver tissue around the tumor is ablated by HIFU+UCA.

RhoA gene expression and clinicopathology parameters in HCC patients / 中华普通外科杂志

Objective To investigate the expression of RhoA gene in human hepatocellular carcinoma (HCC) and to discuss its significance during hepatocellular carcinogenesis. Methods Intratumor RhoA expression level was determined and compared with that in adjacent nontumorous hepatic tissues using quantitative real time reverse transcription polymerase chain reaction and Western blot in 64 HCC patients. Results The mRNA levels of RhoA were significantly higher in tumor tissues than that in the unaffected portions (t =3.445 ,P =0.0006). The expression of RhoA mRNA in the primary lesion was higher in patients with venous invasion (t = 2.667, P = 0.009), microscopic satellite lesions (t=2.172,P =0.038), and advanced pTNM stage (stage Ⅱ/Ⅳ; t=2.551,P=0.013) than in those without. There was a significant difference between high RhoA protein levels in the tumor tissues and noncancerous liver tissues in HCC patients (t = 3.532, P = 0.0002), and there was a significant association between high tumor RhoA protein levels and the presence of venous invasion (t = 2.087, P = 0.042), microscopic satellite lesions (t = 2.254, P = 0.031), and advanced pTNM stage (t = 2.812, P = 0.007). Conclusions There is a significant correlation between RhoA expression, tumor stage, and intrahepatic metastasis. The expression of RhoA could be used as a good tumor marker for invasive and advanced carcinoma as well as a prognosis predictor.

Morphological diversification in heterotopic auxiliary liver transplantation in rats / 医学研究生学报

Objective:In order to study the morphological diversification in heterotopic liver auxiliary transplantation(HLAT). Methods:HLAT model in rats was established, the status of rats survival and graft function was evaluated postoperatively by rheometer, SPECT electrical microscope etc. Results:Rat HLAT model was feasible, the operative success rate was 93.3%, one week postoperative survival rate was 80%,the survival time without complications was more than 3 months. The function of the native liver was not affected, as the time goes by, the graft become atrophic after 45 days postoperatively. Conclusion:In HLAT model, the function of the native liver was not affected, 45-days-after the transplantation, the graft become atrophic.

Transdifferentiating of adult human pancreatic stem cells into islet cells / 中华外科杂志

<p><b>OBJECTIVE</b>To understand and improve the transdifferentiation of pancreatic stem cells into islet cells through isolation, cultivation and transdifferentiation of adult human pancreatic duct cells.</p><p><b>METHODS</b>A portion of adult human pancreas was digested with collagenase, followed by incontinuous density gradient to separate islets from the acinar and ductal tissue. Duct epithelial cells were cultivated in CMRL1066 and then in serum-free DMEM/F12 medium with the addition of growth factors for 27 days. Samples were taken at different time points for light and electron microscopic examination and for immunocytochemical study with antibodies against transdifferentiation gene PDX-1 and protein CK-19. Amylase and insulin contents in the medium were assayed.</p><p><b>RESULTS</b>A large number of duct epithelial cells were harvested after the isolation of islets. Some duct epithelial cells were PDX-1 and CK-19 positive at day one and duct epithelial cells proliferated and expanded rapidly and then transdifferentiated into stem cells and finally 3D islets. 760 islets were harvested from each gram of pancreatic tissue on day 27.</p><p><b>CONCLUSIONS</b>Adult pancreatic duct cells are potential stem cells and could be transdifferentiated into islet cells in vitro under appropriate conditions.</p>

Value of MELD score system for the prediction of operative mortality in patients undergoing liver transplantation / 中国普通外科杂志

Objective This study was to evaluate the usefulness of the model of end-stage liver disease (MELD) score in comparison with the Child-Pugh classification to predict postoperative mortality and short-term survival in liver transplant patients. MethodsMELD score and Child-Pugh score were computed for each patient according to the original formula on admission day. Kaplan-Meier survival curves were made using the cut-off points calculated by Youden index. ResultsSix out of 40 patients died within three months, MELD scores and Child-Pugh scores for non-survivors (32.2?8.0, 12.3?2.0) were higher than those for survivors (13.4?6, 9.12?2.31) significantly (P

Studies on hepatic carcinoma cell invasion in vitro through Rho/Rho kinase pathway / 中国普通外科杂志

Objective To investigate the role of Rho/Rho kinase -associated cell migration of hepatic carcinoma cell line and inhibition of tumor cell invasion by Rho kinase inhibitor Y-27632. Methods Western blot was used to estimate the expression of Rho protein in the cells. After treatment of SMMC7721 cell with Y-27632, cell biological behaviors such as colony-forming efficiency, adhesiveness, cell motility, in vitro invasiveness, metastatic potential were observed. Results The ability of Y-27632 treated SMMC7721 cells to invade the reconstituted basement membrane decreased significantly ( P

ACCIDENTAL INJURY OF EXTRAHEPATIC BILE DUCTS DURING CHO-LECYSTECTOMY / 解放军医学杂志

From 1978 to 1985, 14 patients with accidental injury of extrahepatic bile ducts at cholecystecto-my were reported. The incidence was 0.12%. The injury caused suffering, severe after effects for the patients.In the analysis of the causes, half of the cases occurred due to over-confidence and negligence of operating surgeons. Other causes were as unsatisfactory anesthesia, improper operative incision, blind clamping for control of hemorrhage in the area of the bile ducts, difficult dissection of the Calot's triangle because of anatomical anomaly, fibrosis, inflammation or adhesion. The methods of the prevention were discussed.According to various types of injury, different therapy should be taken. Early intervention, Roux-Y jejunal reconstruction, judicious use of Y tube and prolonged dilatation of hilar strictures will improve the outlook. No mortality and malfunction occurred.