ObjectiveTo investigate the influence of phosphoinositide 3-Kinase-C2-gamma (PI3Kγ)on pancreas acinar cells autophagy in experimental acute pancreatitis in mice and explore its significance.MethodsEighteen C57BL/6 wild type (WT) and eighteen PI3Kγ knockout (KO) mice were randomly divided into control group (n =6) and acute panereatitis (AP) group (n =12),respectively.AP models were induced by intraperitoneal injection of 50 μg cerulein/kg body weight,once the other hour for seven times.The mice were sacrificed 7 hours after model induction.The pathological changes of the pancreas were observed through microscope,LC3 dots were determined by immunofluorescence,the trypsin activity was measured by fluorescence spectrophotometer,and the expression of autophagy related protein beclin1,p62 and LC3- Ⅱ were measured by Western blot.ResultsThe autophagy vacuoles counts in pancreatic tissue of WT mice and KO mice were (5.14 ±0.85),(2.25 ±0.54)/HPF,the LC3 immunofluorescence dots counts were (78.6 ±9.38),( 26.4 ± 4.21 )/HPF,the trypsin activities were ( 0.827 ± 0.126 ),( 0.358 ± 0.098 ) pmol/mg protein,the difference between the two groups was statistically significant ( P ＜ 0.05 ).The p62 protein expression was greatly decreased in WT mice compared with their KO counterpart (0.11 vs 0.92,P ＜ 0.05 ),while the expressions of LC3 Ⅱ,beclin1 were greatly increased in WT mice compared with their KO counterpart ( 1.82 vs 0.93,1.43 vs 1.05,P ＜ 0.05 ).Conclusions PI 3 Kγmay up- regulate autophagy of pancreatic acinar cells during acute pancreatitis in mice,then promote trypsinogen activation and necrosis of acinar cells.

Objective To study the role and mechanism of phosphatidylinositide 3-kinase gamma (P13Kγ) in mediating acinar cell necrosis in rat models with acute pancreatitis.Methods Twelve male C57BL/6 wild-type and twelve male P13Ky knockout mice were randomly divided into saline group and pancreatitis group.The pancreatitis group received an intraperitoneal injection of cerulean (50 μg/kg) to induce acute panreatitis.Pathologic changes in the two groups were observed by measuring the trypsin,cathepsin B,and cathepsin L activity.The protein expressions of cathepsin B and cathepsin L were detected by the Western blot assay.Results Compared with the wild-type mice,the P13Kγγknockout mice had fewer acinar cell necrosis [(2.25± 0.54)/HP vs (5.14±0.85)/HP] and vacuoles [(1.24±0.21)/HP vs (2.36± 0.34)/HP]according to histology.The cathepsin B activity [(1232± 21)pmolAMC/min/mg vs (1891 ±35)pmolAMC/min/mg] and trypsin activity [(0.358± 0.098)pmol/mg vs (0.827± 0.126)pmol/mg] were significantly decreased in the pancreatitis group (P＜0.05) compared to the saline group.However,the cathepsin L activity [ (415 ±11 ) pmolAMC/ min/mg vs (346 ± 6)pmolAMC/min/mg] was significantly higher in P13Kγγ knockout mice than in wild-type mice(P＜0.01).Conclusions P13Kγmay promote cell necrosis in acute pancreatitis by possibly changing the balance between eathepsin B and cathepsin L levels to promote the activation of trypsinogen.

Epigenetics refers to steady phenotypic changes in gene expression without modifications in the genetic nucleotide sequence.Disorder of epigenetic mechanisms plays an important role in the occurrence and development of human malignant tumors including hepatocellular carcinoma.A large number of gene targets and pathways related to epigenetics were discovered.For instance,DNA methylation,histone modification and RNA regulator gene silencing were associated with the development of hepatocellular carcinoma.Exploring the abnormal epigenetics is of great significance for prevention and treatment of hepatocellular carcinoma.

Objective To explore whether combined olmesartan angiotensin Ⅱ receptor type 1 blocker(ARB) and angiotensin-converting enzyme inhibitor(ACEI) temocapril have synergistic effect on reversal of left ventricular hypertrophy (LVH) in stroke-prone spontaneously hypertensive rats (SHRsp). Methods Fourty-four SHRsps and 11 Wistar-Kyoto rats(WKY) were divided randomly into 5 groups:WKY-control group, SHRsp-control group, SHRsp-olmesartan 10 mg/(kg?d)group, SHRsp-temocapril 10 mg/(kg?d)group, and SHRsp-Olmesartan 3 mg/(kg?d)+temocapril 3 mg/(kg?d) group for 6 weeks. Hearts weight were measured and histologically studied. The mRNA expression of angiotensin Ⅱ receptor type 1(AT1R) and integrin ?1 in myocardium was detected by RT-PCR. Results Olmesartan, temocapril and the their combination significantly reduced systolic blood pressure in a similar magnitude. Combination therapy was shown not greater effect in reversal of LVH than by olmesartan alone, although the effect by both of them was greater than temocapril monotherapy. The mRNA levels of AT1R and integrin ?1 in SHRsp were significantly decreased by treatment with olmesartan, temocapril, or combination therapy. Olmesartan and combination therapy result in greater decreases in expression of AT1R and integrin ?1 mRNA in myocardium than that by temocapril. Conclusion Compared with olmesartan alone, the combination of ARS and ACEI didn't show synergistic effect on reversal of left ventricular hypertrophy as were down-regulation of AT1R and suppression of integrin ?1 mRNA in myocardium.

Objective To investigate the intakes of dietary nutrients and the growth and development status among children with autism,to propose scientific basis for developing further interventions.Methods Dietary intakes of nutrients were obtained with the method of 24-hour dietary review for 3 days.Meanwhile,the height and weight were detected among the subjects;Z-score was also adopted to evaluate nutritional status.Results 1.About 31.5% of the 111 cases with autism were overweight or obesity and 8.1% of the children were acute or chronic malnutrition.2.The intakes of 11 nutrients were insufficient,especially VA,VC,VB6,folate,calcium and zinc,had a serious shortage that less than 60% of the recommended intakes.3.The crowd was widespread lack of nutrients,39.6% of the cases with nutritional deficiency in varying degrees,the incidences of calcium and zinc deficiency were reach up to 88%.Conclusions The nutritional deficiency and overnutrition were simultaneous among the children with autism,their dietary nutritional supplement were generally inadequate.More sufficient measures and rational diet are necessary to improve the nutritional status for the autistic children.

Background Tumstatin is the most active endogenous angiogenesis inhibitor,which has a marked inhibitory effect on pathological neovascularization,and Tum5 is an angiogenesis inhibitors fragment of fulllength tumstatin.Objective This study was to investigate the effects of adenovirus-mediated overexpression of recombinant Tum5 gene on the proliferation,migration and tube formation of human umbilical vein endothelial cells (HUVECs) in physiological status.Methods The empty adenoviral vector expressing green fluorescent protein (rAd-GFP) and the viral vector expressing recombinant Tum5 gene were constructed.The HUVECs cultured in RPMI1640 medium were divided into normal control group,empty vector group (rAd-GFP group) and Tum5 gene infection group (rAd-GFP-Tum5 group).The rAd-GFP and rAd-GFP-Tum5 adenoviral particles at the density of 1 × 1010/ml were added into the medium to infect the cells for 48 hours.The proliferation of the cells was assayed at 24,48 and 72 hours by cell counting kit-8 (CCK-8) to evaluate the proliferative rate;the migration number of the cells was detected at 48 hours after infection by Transwell chamber;the tube formation number of the cells were detected by Matrigel method.The concentration of vascular endothelial growth factor (VEGF) in cell supernatants was assayed by ELISA at 24,48,and 72 hours following adenoviral infection.Results The cultured cells showed green fluorescence in the rAd-GFP group and rAd-GFP-Tum5 group under the inverted fluorescence microscope,and the infection efficiency of rAd-GFP and rAd-GFP-Tum5 was 55.13％ and 50.31％,respectively.No significant difference was found in cell proliferative rate among normal control group,rAd-GFP group and rAd-GFP-Tum5 group both at 24 and 48 hours after infection (both at P＞0.05),and the cell proliferative rate was significantly lower in the rAd-GFP-Tum5 group than that in the normal control group and rAd-GFP group at 72 hours after infection (both at P＜0.01).The migration number of the cells at 48 hours after infection was 2 260.25-±930.44,2 370.00±441.06 and 723.75± 363.80 in the normal control group,rAd-GFP group and rAd-GFP-Tum5 group,showing a significant difference among the groups (F =8.524,P =0.008),and the migrated cells were evidently decreased in the rAd-GFP-Tum5 group compared with the rAd-GFP group and the normal control group (both at P＜ 0.01).The tube number at 48 hours after infection was 95.67±5.86,88.00±4.58 and 20.67±3.51 in the normal control group,rAd-GFP group and rAdGFP-Tum5 group,showing a significant difference among the groups (F=226.498,P＜0.01),and the tube number in the rAd-GFP-Tum5 group was significantly reduced in comparison with the normal control group and rAd-GFP group (both at P＜ 0.01).The considerably differences in VEGF concentration in the cell supernatants were found in different groups and various time points (Fgroup =73.260,P＜0.01;Ftime =73.477,P＜0.01),and VEGF concentration in the cell supernatants was significantly decreased in the rAd-GFP-Tum5 group compared with the rAd-GFP group at both 48 hours and 72 hours (both at P＜0.01).Conclusions The overexpression of the recombinant Tum5 can inhibit the proliferation,migration and tube formation of the HUVECs in physiological status,which may be associated with Tum-5-mediated down-regulation of VEGF protein in the cell supernatant.

Abstract: Occupational epidemiology aims to explore the effect of occupational hazards on the health of workers and understand ， their mechanisms. It plays an important role in occupational health and occupational medicine.Currently occupational ， ， exposures in the workplace are complex and diverse and multiple factors affect workers´ health at the same time. Therefore it is important to elucidate the pathogenesis of occupational disease caused by occupational hazards and implement early - - intervention. System epidemiology collects data on multi level exposure and multi omics information to conduct network analysis - on the relationship amongrisk factors. and to study the mechanisms of exposures and health outcomes based on multi level data. ， ， ， ， Using the study design of system epidemiology occupational environmental lifestyle and social factors are combined as a ， system to evaluate the health of workers which can better evaluate the adverse health effects caused by occupational hazards. - ， ， The studies base on multi omics design will explore the pathogenesis of occupational diseases at the molecular cellular and tissue levels to evaluate the impact of occupational hazards on workers´ health and to explore interventions from multiple - perspectives to reduce the occurrence of occupational or work related diseases.

Objective To investigate the curative effects of curcumin(CUR)or dexamethasone (DXM)on ischemia-reperfusion injury(IRI)of rat lung grafts.Methods Male SD rats were randomly divided 4 groups:CUR group(CUR was administered intraperitoneally to both donors and recipients at 3 h prior to operation);DXM group(DXM was administered intraperitoneally at 30 min prior to operation);vehicle group(Animals were injected with the DMSO to both donors and recipients at 3 h prior to operation);sham group(Time-matched control animals underwent the same surgery,except that no graft was implanted).Six animals were sacrificed at different reperfusion periods of 2 h and 24 h,respectively.Oxygenation indexes(PO_2/FiO_2),lung injury scores,wet/dry ratio(W/D)and myeloperoxidase(MPO)activity in the transplanted lung were measured.Malondialdehyde(MDA), total anti-oxidative capacity(TAOC),tumor necrosis factor(TNF)-?and interleukin(IL)-6 in the transplanted lung and serum were determined.Results The levels of LPV PO_2/FiO_2 were significant- ly higher in the CUR and DXM groups than in the vehicle groups both 2 and 24 h after reperfusion,re- spectively(P

BACKGROUND:Spinal cord ischemia-reperfusion injury is a serious secondary injury of the spinal cord. Multifactor could contribute to the mechanism of this injury, and many therapeutic measures emerge, but the therapeutic effect is not ideal.
OBJECTIVE:To investigate the protective effects and mechanism of hydrogen-rich saline on spinal cord ischemia-reperfusion injury in rabbits.
METHODS:ZIVIN method was adopted to prepare the model of spinal cord ischemia-reperfusion injury. The rabbit models were randomly divided into model group, sham operation group, and hydrogen-rich saline group.
RESULTS AND CONCLUSION:Improved Tarlov scores for the evaluation of motor function were significantly increased in hydrogen-rich saline group compared with the model group at 6, 12, 24, 72 hours after reperfusion (P<0.01). The contents of malondialdehyde were significantly lower (P<0.05), while catalase activity was significantly higher (P<0.05) in hydrogen-rich saline group than that in model group at 72 hours after reperfusion. Hematoxylin-eosin staining revealed that, spinal cord anterior-horn motor neurons maintained intact structure in sham operation group;more necrotic spinal cord anterior-horn motor neurons were found in model group, and granular-vacuolar degeneration occurred in the endochylema. In hydrogen-rich saline group, the structure of spinal cord anterior-horn motor neurons was basical y intact, only a smal amount of spinal cord anterior-horn motor neurons appeared vacuolar degeneration. TUNEL staining showed no apoptotic spinal cord anterior-horn motor neurons in sham operation group. Many inflammatory cel s and apoptotic neurons were found in model group. There were few inflammatory cel s and apoptotic neurons in hydrogen-rich saline group. Hydrogen-rich saline can prevent the apoptosis of spinal cord anterior-horn motor neurons in rabbits with spinal cord ischemia-reperfusion injury, and the underlying mechanism is associated with antioxidative effect.