1.The role of phosphatidylinositide 3-kinase gamma (P13Kγ) in mediating acinar cell necrosis in rat models with acute pancreatitis
Wenzhuo JIA ; Jianhua SUN ; Junmin WEI
Chinese Journal of Hepatobiliary Surgery 2012;18(6):462-465
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.
2.Influence of PI3K gamma on pancreatic acinar cells autophagy in experimental acute pancreatitis in mice
Wenzhuo JIA ; Jianhua SUN ; Junmin WEI
Chinese Journal of Pancreatology 2011;11(6):417-419
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.
3.Epigenetic modification and hepatocellular carcinoma
Qikai SUN ; Wei WANG ; Weidong JIA
Chinese Journal of Digestive Surgery 2013;12(9):717-720
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.
4.Risk factors of acute respiratory dysfunction after a type aortic dissection surgery
Wei SHANG ; Nan LIU ; Xiaolei YAN ; Lizhong SUN ; Shijie JIA
Chinese Journal of Thoracic and Cardiovascular Surgery 2011;27(6):349-352
Objective Acute respiratory dysfunction (ARD) can occur after aortic surgery with the use of cardiopulmonary bypass and deep hypothermic circulation arrest, but relatively little is known about acute respiratory dysfunction in the patients with type A aortic dissection. This study aims to analyze the independent risk factors of acute respiratory dysfunction after A type aortic dissection surgery and to assess possible prevention and treatment option in the future. Methods Clinical data of the 252 patients including 193 male patients and 59 female patients who underwent type A aortic dissection surgery from February 2009 to October 2010 were collected. The mean age was 47 years. Postoperative acute respiratory dysfunction was defined as oxygenation impairment (PaO2/FiO2 < 150) that occurred within 72 h of surgery except pleural effusion, cardiogenic pulmonary edema, pneumonia, pulmonary embolism and haemato-/ pneumothorax. There were 187 acute A type aortic dissection patients and 65 chronic type A aortic dissection patients. Clinical characteristics including age, gender, weight, height, history of hypertension, history of smoking, preoperative complications such as preoperative shock and acute renal failure, pericardial effusion, previous cardiac surgery, time from event to surgery, malperfusion syndrome, cardiopulmonary time, cross-clamp time,deep hypothermia circulation arrest time, surgical procedure, duration of intensive care unit stay and postoperative complications including tracheotomy, dialysis dependent renal failure and hospital mortality were gathered. Arterial blood analysis, chest X ray, ventilator parameters, number of blood transfusion and flood balance were assayed after operation. All the factors were evaluated by means of univariate and multivariate logistic regression analysis to identify relative risk factors of ARD. Results Acute respiratory dysfunction occurred in 32 (12.7% ) patients. The in-hospital mortality was significant difference between acute respiratory dysfunction group and non- acute respiratory dysfunction group (P < 0.05). The value of BMI, incidence of acute aortic dissection, preoperative SBP level, cardio-pulmonary bypass time, aortic clamp time and total arch replacement in acute respiratory dysfunction group were significantly higher than the values in non- acute respiratory dysfunction group. Multivariate Logistic regression analysis showed blood transfusion more than 10 units and cardio-pulmonary bypass time more than 160 minutes were independent risk factors of early stage acute respiratory dysfunction after type A aortic dissection surgery.Conclusion Acute respiratory dysfunction after type A aortic dissection was a severe early stage postoperative complication and was associated with in-hospital mortality. The patients in acute aortic dissection were prone to have acute respiratory dysfunction. The independent risk factors of acute respiratory dysfunction included blood transfusion more than 10 units and cardio-pulmonary bypass time more than 160 minutes.
5.Paroxysmal diagonistic ideomotor apraxia in ischemic infarction of the corpus callosum
Tingting WANG ; Zhirong JIA ; Wei SUN ; Tao PAN
Chinese Journal of Neurology 2011;44(7):479-481
Objectives To report the clinical features and treatment in a case with paroxysmal diagonistic ideomotor apraxia after ischemic infarction of the corpus callosum.Methods The neuropsychological tests,brain MRI,the TCD and carotid duplex sonography were carried out in the patient who is right handed and had had presentation of paroxysmal diagonistic ideomotor apraxia for ten days.Results Neuropsychological tests confirmed the diagnosis of paroxysmal diagonistic apraxia in this patient.MRI showed ischemic infarction in the right corpus callosum.The symptomsin the patient were improved after the treatment with aspirin for three months.Conclusion The infarction of corpus callosum may induce paroxysmal diagonistic apraxia.
6.The analysis of the nutritional status among children with autism
Wei XIA ; Jia WANG ; Caihong SUN ; Limin WANG ; Lijie WU
Chinese Journal of Disease Control & Prevention 2009;0(01):-
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.
7.Drug resistance mediated by outer membrane porin F (OmpF) and its regulatory gene of micF in Shigella strains
Haojie ZHANG ; Yang SUN ; Fengyun LIU ; Yuchi JIA ; Wei QI
Chinese Journal of Microbiology and Immunology 2016;36(9):686-691
Objective To investigate the mechanism of drug resistance mediated by micF gene and outer membrane porin F ( OmpF) in Shigella strains. Methods Shigella strains were isolated from stool samples of patients who presented to the Second Hospital of Tianjin Medical University with acute diar-rhea in 2015. Antibiotic susceptibility test was performed to screen out the multidrug-resistant and non-multi-drug-resistant strains. The ompF gene was amplified by PCR. The micF and ompF genes at transcriptional levels in the two groups of strains were detected by quantitative real-time RT-PCR. Intracellular concentra-tions of ciprofloxacin in the two groups of Shigella strains were measured by automatic microplate reader. Re-sults According to the result of antibiotic susceptibility test, 13 strains that were resistant to 3 or more than 3 antibiotics were classified into the multidrug-resistant group, while the other 8 strains that were sensitive to all antibiotics used in this study or only resistant to 1 or 2 antibiotic were classified into the non-multidrug-re-sistant group. All of the 21 Shigella strains carried the ompF gene. Compared with the non-multidrug-resist-ant strains, the multidrug-resistant strains showed higher expression of micF gene, but lower expression of ompF gene. The differences in micF and ompF genes between the two groups were statistically significant. The result of correlation analysis suggested that there was a negative correlation between micF and ompF genes (r=-0. 244). The intracellular concentrations of ciprofloxacin in multidrug-resistant strains were low-er than those in the non-multidrug-resistant strains (P<0. 001). Conclusion The decreased expression of OmpF was one of the possible mechanisms of multidrug-resistance in Shigella strains. The micF gene was negatively related to the expression of OmpF. Moreover, the decreased intracellular concentrations of cipro-floxacin in multidrug-resistant strains might be related to the decreased expression of OmpF.
8.Protective effects of curcumin or dexamethasone on ischemia-reperfusion injury of rat lung grafts
Jia-Yuan SUN ; Wei-Gang GUO ; Yong BEN ;
Chinese Journal of Organ Transplantation 2005;0(07):-
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
9.Hydrogen-rich saline can inhibit apoptosis of spinal cord motor neurons in rabbits with spinal cord ischemia-reperfusion injury
Yanqing SUN ; Xiongsheng CHEN ; Dong CAO ; Wei ZHU ; Lianshun JIA
Chinese Journal of Tissue Engineering Research 2014;(18):2861-2866
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.