AIM To study the effects of polydatin on free radical induced rat cortex mitochondria injury. METHODS Fe 2++VitC system was used to produce ?OH. The mitochondria was isolated. Mitochondria membrane fluidity, swelling and contents of phospholipid were determined to measure the function of mitochondria membrane. The activities of ATPase and Cytochrome C oxidase were determined to measure the ability of mitochondria energy metabolism. The activity of superoxide dismutase (SOD) and content of malondial dehyde (MDA) were determined to measure the ability of anti oxygenation. RESULTS ?OH resulted in severe neuronal mitochondria injuries and the injuries and the injuries was alleviated by Polydatin (content of 100,200,400 mg?L -1). The swelling of mitochondria was ameliorated, the decomposability of mitochondrion membrane phospholipid was decreased, the membrane fluidity of mitochondria was increased. Polydatin also significantly inhibited the decrease in SOD, Cytochrome C oxidase and ATPase activity and the increase in MDA levels caused by free radical. CONCLUSION Polydatin has a protective action against the rat neuronal mitochondria injuries induced by oxygen free radical. The mechanisms may be derived from scavenging free radicals, reducing lipid peroxides, and improving the energy metabolism.

Liver transplantation is an effective method for the treatment of hepatocellular carcinoma (HCC). In order to reduce the high recurrence rate of tumor after liver transplantation for HCC, some scholars put forward the famous Milan criteria. Since the Milan criteria are too strict, some HCC patients with relatively “good biological behavior” and large lesions or multiple nodules are excluded from the waiting list for liver transplantation, and thus a large number of “expanded versions of the Milan criteria” appeared around the world. As for the histopathology of HCC, microvascular invasion (MVI) and poorly differentiated tumor tissue are significantly associated with the high recurrence rate after liver transplantation for HCC. This article reviews and summarizes the articles on the application of 18F-FDG PET/CT in liver transplantation for HCC in China and foreign countries and points out that the uptake of 18F-FDG in HCC lesions reflects the difference in the biological behavior (i.e., invasion) of tumor tissue. The intense uptake of 18F-FDG is positively correlated with MVI and poor differentiation of HCC. In addition, 18F-FDG can detect extrahepatic metastatic lesions sensitively and accurately. Preoperative 18F-FDG PET/CT findings have a high value in predicting the prognosis of liver transplantation for HCC, and it is a trend to incorporate such findings into the criteria for liver transplantation in HCC. It is also expected to unify the various expanded versions of the Milan criteria. The new criteria for liver transplantation may be defined as follows: the Milan criteria should be followed in general; as for the patients who do not meet the Milan criteria, liver transplantation can be performed for those who have lesions with negative 18F-FDG PET/CT results, without the involvement of major blood vessels or extrahepatic metastasis.

Objective To generate mice with whole-body overexpression of human METRNL gene.Methods Based on Cre-loxP system,Dppa3-Cre mice were mated with Rosa26-LSL-METRNL knock-in mice(R26-LSL-METRNL+/-)to generate R26-L-METRNL+/-mice.The genotypes of the offsprings were identified,and tissues of the blood,heart,liver,spleen,lung,kidney,brain,white adipose and muscle were collected.The expression of human METRNL gene in mice was investigated by quantitative real-time PCR,western blot and enzyme linked immunosorbent assay.Results Compared with wild type control mice,human METRNL in R26-L-METRNL+/-mice significantly expressed at both mRNA and protein levels in tissues,with abundant METRNL protein in blood.Conclusion The mouse model overexpressing human METRNL gene(R26-L-METRNL+/-mouse)was successfully constructed.

Objective:To compare the efficacy between chemotherapy with granulocyte colony-stimulating factor (G-CSF) and chemo-therapy with G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF) for the mobilization of peripheral blood hemato-poietic stem cells and hematological recovery post-transplantation in patients with malignant lymphoma. Methods:Autologous pe-ripheral blood hematopoietic stem cell mobilization data of 61 malignant lymphoma patients who were treated with chemotherapy plus G-CSF or chemotherapy plus G-CSF and GM-CSF from May 2008 to October 2016 were included in this study. The mobilization effi-cacy and hematopoietic recovery were analyzed. Results:During mobilization, White blood cells (WBC) of all patients decreased to 1.0×109/L and platelets (PLT) dropped to 40×109/L. The successful mobilization rates of CD34+cell are 52.5%in chemotherapy plus G-CSF group and 90.5%in chemotherapy plus G-CSF+GM-CSF group (P=0.003). All patients successfully underwent hematopoietic recon-struction without transplantation-related mortality. Conclusion: Although chemotherapy with G-CSF+GM-CSF can significantly in-crease the effect of autologous peripheral blood hematopoietic stem cell mobilization, the reconstruction of hematopoietic function after transplantation and side reaction between the two groups are the same. Thus, chemotherapy with G-CSF+GM-CSF is not superior to chemotherapy with G-CSF in mobilizing autologous peripheral blood hematopoietic stem cells.

Objective Nicotinamide phosphoribosyltransferase (Nampt) is a new therapeutic target for ischemic stroke. The aim of this study was to investigate protective effect of liver-derived Nampt on ischemic stroke. Methods Liver-specific Nampt knockout mice were generated using the Cre/loxP system. Nampt^loxP/loxP mice were crossed with liver-specific Cre recombinase expression mice (Alb-Cre), and the progeny genotypes were identified by polymerase chain reaction. Body weight of knockout mice and control mice were measured. Nampt in liver and brain was determined by Western blot assay. Middle cerebral artery occlusion (MCAO), a classical ischemic stroke model, was generated in liver-specific Nampt knockout mice and control mice by electrocoagulation. After 24 h of modeling, neurological deficit scores of each group were evaluated and TTC staining was performed to determine the cerebral infarction volume. The level of plasma Nampt in each group was determined by ELISA. Results Liver-specific Nampt knockout mice with the genotype of Nampt^loxP/loxPAlb-Cre were successfully constructed. The hepatic Nampt expression in knockout mice was significantly decreased by 74.2% compared to control mice, while there was no significant difference in the expression of brain Nampt protein between the knockout group and the control group. Specific knockout of liver Nampt gene expression had no effect on the body weight of mice. Under normal physiological conditions, there was no significant difference in plasma Nampt levels between liver-specific Nampt knockout mice and control mice of the same gender. 24 h after MCAO modeling, there were no significant differences in neurological deficit scores, cerebral infarct volume and plasma Nampt concentration between liver-specific Nampt knockout group and control group. Conclusion Liver-specific Nampt knockout mice are successfully constructed. Liver-derived Nampt has no significant protective effects on ischemic stroke.

Objective The three-dimensional finite element model of the normal ankle joint was established to simulate the changes of stress and displacement under stress from different directions and of different magnitudes so as to provide a theoretical basis for the biomechanical mechanism of the ankle joint injury.Methods Spiral CT scan was performed on the left ankle of a 30 year old healthy male volunteer to obtain the original CT image data.The three-dimensional digital model of ankle joint generated by Mimics and Geomagic softwares was imported into the software Ansys.The three-dimensional finite element model of ankle joint with complete anatomical structure was obtained after the main steps of meshing,central node,element linking and module loading using finite element method.Stress from different directions and of different magnitudes were loaded unto the model.The stress changes were measured by foot stress distribution measurement system.The stress changes,displacement change distribution,the stress peak value of heel are,metatarsal stress,and plantar contact stress area as well as the maximum,minimum,and contact are of the tibial articular surface contact stress were compared between the finite element model and the volunteer himself to verify the consistency.Results For the finite element model of normal ankle joint,the plantar peak stress was [(0.33 ± 0.10) MPa],the metatarsal stress was [(0.13 ± 0.21)MPa],the foot contact stress area was [(78.60 ±0.32)mm2],the tibial articular surface maximum contact stress was [(2.72 ± 0.10) MPa],the minimum contact stress was [(1.35 ±0.12)MPa],and the contact stress area was [(79.1 ± 0.14)mm2].For the volunteer,double foot plantar peak stress was [(0.35 ± 0.12)MPa],the metatarsal stress [(0.13 ±0.16)MPa],the foot contact stress area was [(77.3 ± 0.42)mm2],the tibial articular surface maximum contact stress was [(2.79 ± 0.23) MPa],the minimum contact stress was [(1.37 ± 0.20) MPa],and the contact stress area was [(79.10 ±0.14)mm2] (P ＜0.05).Therefore,the three finite element model of ankle joint was basically consistent with the real human ankle joint because of the similiar distribution,trend,and values.Conclusion The three-dimensional finite element model of normal ankle joint can objectively reflect the anatomical structure and biomechanical characteristics of the joint,which is of great value to understand the changes of the internal mechanics and ankle joint injury.

Intracerebral hemorrhage (ICH) refers to bleeding within the brain parenchyma due to the rupture of blood vessels ,and is a highly lethal stroke subtype ,accounting for nearly 10%-15% of all strokes .The morbidity and mortality of ICH are very high and its pathophysiological mechanisms are currently not fully understood .Therefore ,based on current clini-cal evidence-based medicine ,there is no definite and effective medical treatment that can improve the prognosis and survival of patients available yet .As an important tool for basic research ,the development and application of the ICH animal model pro-moted the understanding of the pathophysiological mechanisms and molecular mechanisms leading to brain injury by ICH .Re-cently ,the ICH animal model studies contributed to a number of proposed potential therapeutic strategies ,such as the inhibi-tion of thrombin and the reduction of pro-inflammatory pathways .In addition ,recent research of stem cells suggested that cell transplantation therapy for the treatment of ICH may also have good prospects .In this review ,we discuss the development and application of animal models for studies on ICH and the advances regarding the potential therapeutic strategies for ICH .

Objective To construct and explore the in vivo and in vitro D-galactose induced cognitive impairment models and evaluate the application value of the combined models in the study of cognitive impairments.Methods The cognitive impairment mice model induced by D-gal was prepared by continuous intraperitoneal injection of D-gal saline solution for 8weeks, followed by detection of learning and memory functions with Morris water maze.The related molecular markers in the brain tissue were assayed to evaluate the effect and application value.D-gal cell model was prepared by adding D-gal in different concentrations into the cell cultural medium of neurons harvested from the hippocampus of young mice.The effect and application value were evaluated by detecting the molecular markers related to the level of cell injury.Results The Morris water maze on the D-gal model showed that the learning and memory functions of mice in the model group were significantly lower than those in the control group.Meanwhile, the levels of apoptosis and oxidative stress in the model group were significantly higher than those in the control group.In the hippocampal neuron model of D-gal, the neurons showed a dose-dependent morphologic and functional change with the increase of D-gal dose and the levels of apoptosis and oxidative stress were significantly higher than those in the negative control.Conclusion D-galactose can be successfully used to induce cognitive impairment models both in vivo and in vitro through the decrease of the learning and memory functions of mice and induction of apoptosis and oxidative stress in neurons.Combined application of the two models of D-gal can be one of effective and promising tools for the study of cognitive impairment and pharmacodynamic evaluation.

Background and objective The combination therapy of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has attracted the attention of more and more investigators. The aim of this meta-analysis is to evaluate the clinical effcacy and safety of intercalated combination of chemotherapy and EGFR- TKIs versus chemotherapy alone in the ifrst-line therapy of advanced non-small cell lung cancer (NSCLC).Methods We retrieved the Co-chrane Library, PubMed, EMBASE, CBM, CNKI and Wanfang databases for randomized controlled trials which involved the intercalated combination of chemotherapy and EGFR-TKIs, and chemotherapy alone in the first-line treatment of advanced NSCLC. hTe progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events were analyzed. hTe quality evaluation and cross-checked data were independently performed by two in-vestigators according to the Cochrane Systematic Reviews Handbook. hTe Stata 12.0 sotfware was used to conduct themeta-analysis.Results This study included 933 NSCLC patients from 6 RCTs. Themeta-analysis demonstrated that the intercalated combination of chemotherapy and EGFR-TKIs signiifcantly prolonged the PFS (HR=0.72, 95% CI: 0.53-0.98,P=0.037) of advanced NSCLC patients compared with mono-chemotherapy. However, there was no statistical difference in OS (HR=0.85, 95%CI: 0.72-1.01,P=0.060), ORR (OR=1.59, 95%CI: 0.86-2.95,P=0.142) and DCR (OR=1.09, 95% CI: 0.95-1.25,P=0.226) between the two groups. Further, the subgroup analysis showed that the intercalated combination markedly improved the PFS in female, adenocarcinoma, never smoking,EGFR mutant patients. In the aspect of safety, the main side effects of the interca-lated combination therapy were rash (OR=7.81, 95%CI: 3.74-16.34,P<0.001) and diarrhea (OR=2.73, 95% CI: 1.92-3.89, P<0.001).Conclusion hTe intercalated combination of chemotherapy and EGFR-TKIs signiifcantly prolonged the PFS in the first-line therapy of advanced NSCLC patients compared with mono-chemotherapy, and the main adverse events were toler-able rash and diarrhea. Together, the intercalated combination shows promising results, and more large-scale and high-quality RCTs are still needed.