Effect of propofol pretreatment on dephosphorylation of Drp1 Ser637 during kidney injury induced by hepatic ischemia-reperfusion in mice / 中华麻醉学杂志

Objective To evaluate the effect of propofol pretreatment on dephosphorylation of phospho-dynamin-related protein 1 (p-Drp1) Ser637 during kidney injury induced by hepatic ischemia-reperfusion (I/R) in mice.Methods Thirty healthy SPF male C57 mice,weighing 20-25 g,were divided into 3 groups (n=10 each) using a random number table method:sham operation group (group S),hepatic I/R group (group HI/R) and propofol pretreatment group (group P).Hepatic I/R was produced by occluding the blood supply to the left lateral and median lobes of liver for 60 min followed by reperfusion in anesthetized mice.In group P,1％ propofol 30 mg/kg was intraperitoneally injected at 30 min before operation,while the equal volume of normal saline was given instead in S and HI/R groups.Blood samples were collected from the left ventricle at 6 h of reperfusion for determination of the concentrations of serum blood urea nitrogen (BUN) and creatinine (Cr).Renal tissues were obtained for determination of cell apoptosis (by TUNEL) and expression of Drp1,p-Drp1 Ser637,cytochrome c (Cyt c) and cleaved caspase-3 (by Western blot) and for examination of the ultrastructure of mitochondria (by transmission electron microscopy).Apoptosis index was calculated.Results Compared with group S,the serum BUN and Cr concentrations and apoptosis index were significantly increased,the expression of p-Drp1 Ser637 was down-regulated,and the expression of Cyt c and cleaved caspase-3 was up-regulated (P＜0.05),and microscopic examination showed that mitochondria was swollen with vacuolization and mitochondrial cristae was irregularly distributed or disrupted and shortened in HI/R and P groups.Compared with group HI/R,serum BUN and Cr concentrations and apoptosis index were significantly decreased,the expression of p-Drp1 Ser637 was up-regulated,the expression of Cyt c and cleaved caspase-3 was down-regulated (P＜0.05),and the ultrastructure of mitochondria was markedly improved in group P.There was no significant difference in the expression of Drp1 in renal issues between the three groups (P＞0.05).Conclusion The mechanism by which propofol pretreatment mitigates hepatic I/R-induced kidney injury is related to inhibiting dephosphorylation of Drpl Ser637 in mice.

Hypothermia mechanical perfusion alleviates microcirculation injury in isolated pig small intestine / 中华器官移植杂志

Objective To study the effect of hypothermia mechanical perfusion (HMP) preservation on microcirculation injury of isolated pig small intestine.Methods Ten healthy Bama miniature pigs were selected.The experimental animals were randomly divided into two groups.In HMP group (n =5),the intestine of 200 cm in length and corresponding blood vessels were cut and then connected to HMP storage device at 4 ℃ for 6 h.In UW group (n =5),the intestine of 200 cm in length and corresponding blood vessels were cut and then preserve in 4 ℃ UW solution for 6 h.Situ small intestine transplantation was performing when preservation finished.The serum NO and ET-1,the dry-wet ratios of intestine tissue,blood flow velocity of intestinal microcirculation and pathological changes of tissues were detected before and after preservation.Results There was no significant difference in serum ET-1 and NO between HMP group and UW group (P＞0.05) before laparotomy.The levels of serum ET-1 increased and serum NO decreased after 30 min of blood flow opening in the transplanted intestine in both groups,more significantly in UW group.There was no significant difference in dry-wet ratio of small intestine before transplantation between the two groups (P＞ 0.05).When the blood flow was opened for 30 min,the dry wet ratio of small intestine in UW group was significantly lower than that in HMP group.There was no significant difference in blood flow velocity of intestinal microcirculation between the two groups before transplantation (P＞0.05),and the blood flow velocity of the two groups decreased significantly after 30 min of blood flow opening,more significant in UW group (P＜0.05).When the blood flow was opened for 30 min,there was mild edema of the lamina propria in the small intestinal tissue of the HMP group,scattered infiltration of the lymphocytes,no exuviation on the surface of the villi and no capillary congestion;In the small intestinal tissue of the UW group,there were edema and congestion of the intrinsic membrane,infiltration of the lymphocytes,the partial exuviation of the villi epithelial cells,focal erosion of the office,and capillary congestion.Conclusion Compared with cold preservation of UW solution,preservation of pig small intestine by HMP can reduce microvascular damage and alleviate the edema and injury caused by ischemia and hypoxia.

Effect of dexmedetomidine on Src-mediated NR2A tyrosine phosphorylation in hippocampal neurons subjected to hypoxia-reoxygenation in mice / 中华麻醉学杂志

Objective To evaluate the effect of dexmedetomidine on Src-mediated NR2A tyrosine phosphorylation in hippocampal neurons subjected to hypoxia-reoxygenation (H/R) in mice.Methods C57 mice at 18 days of gestation were sacrificed by pulling neck,fetal mice were obtained by caesarean section,and hippocampal neurons were isolated.Neurons were cultured in culture medium for 7 days and then divided into 3 groups (n =30 each) using a random number table method:control group (group C),H/R group and dexmedetomidine group (D group).Hippocampal neurons were exposed to 95％ N2-5％ CO2 in an incubator at 37 ℃ for 4 h followed by reoxygenation with 95％ O2-5％ CO2 for 24 h to establish the model of H/R.Dexmedetomidine was given at a final concentration of 1 μ mol/L,and neurons were incubated for 4 h before establishing the model.The viability of hippocampal neurons was measured by MTT assay,TUNEL staining was used to observe apoptosis in hippocampal neurons,and the expression of c-Src,phosphorylated Src Y416 (p-Src Y416),NR2A,phosphorylated NR2A Y1325 (p-NR2A Y1325) and cleaved caspase-3.was determined by Western blot.Apoptosis index was calculated.Results Compared with group C,the viability of hippocampal neurons was significantly decreased,apoptosis index was increased,and the expression of p-Src Y416,p-NR2A Y1325 and cleaved caspase-3 was up-regulated in group H/R (P＜0.05).Compared with group H/R,the viability of hippocampal neurons was significantly increased,apoptosis index was decreased,and the expression of p-Src Y416,p-NR2A Y1325 and cleaved caspase-3 was down-regulated in group D (P＜0.05).There was no significant difference in the expression of c-Src and NR2A among three groups (P＞0.05).Conclusion Dexmedetomidine can inhibit apoptosis in hippocampal neurons subjected to H/R,and the mechanism may be associated with decreasing Src-mediated NR2A tyrosine phosphorylation in mice.

The application value of DCE-MRI in the preoperative TN staging of rectal cancer / 实用放射学杂志

Objective To study the application of dynamic contrast-enhanced MRI (DCE-MRI)in preoperative TN staging of rectal cancer. Methods Seventy-two patients with rectal cancer confirmed by surgery and pathology underwent preoperative conventional MRI and DCE-MRI.The consistencies between conventional MRI and pathology,conventional MRI combined with DCE-MRI and pathology in diagnosing the TN staging were analyzed retrospectively.The quantitative parameters of DCE-MRI including Ktrans,Veand Kepwere measured to analyze the correlation with T staging and lymph nodes metastasis.Results The accuracy of conventional MRI and conventional MRI combined with DCE-MRI in diagnosing the T staging were 72.2% and 84.7%,respectively,in diagnosing the N staging were 65.3% and 77.8%, respectively.The DCE-MRI quantitative parameters (Ktransvalue,Vevalue and Kepvalue)were positively related to the T staging and lymph nodes metastasis(P<0.05).Conclusion DCE-MRI can improve the accuracy of the preoperative TN staging of rectal cancer. DCE-MRI quantitative parameters of Ktrans,Ve,Kepvalues can help to determine T staging and lymph node properties of rectal cancer.

Research progress of matrix metalloproteinase-9 in kidney disease / 中国医师杂志

Kidney plays an important role in maintaining the homeostasis as an important excretory and endocrine organ.The occurrence and development of kidney disease is closely associated with glomerular filtration barrier dysfunction and renal interstitial remodeling.Matrix metalloproteinase-9 (MMP-9),a major enzyme in the extracellular matrix (ECM),plays an important role in the process of kidney disease by regulating the ECM components and its interaction with cytokines.The paper reviews the pathophysiology of MMP-9 in glomerular filtration barrier dysfunction and renal fibrosis to provide a theoretical basis for clinical treatment of kidney disease.

Efficacy of PCIA with oxycodone mixed with dexmedetomidine for analgesia after combined pancreas-kidney transplantation / 中华麻醉学杂志

Objective To evaluate the efficacy of patient-controlled intravenous anesthesia (PCIA) with oxycodone mixed with dexmedetomidine for analgesia after combined pancreas-kidney transplantation.Methods Forty American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients,aged 18-64 yr,weighing 40-100 kg,scheduled for elective combined allogeneic pancreas-kidney transplantation,were randomly divided into 2 groups (n =20 each):sufentanil group (group S) and oxycodone combined with dexmedetomidine group (group OD).PCIA was performed at the end of surgery.PCIA solution contained sufentanil 2.0 μg/kg and tropisetron 5 mg in 100 ml of normal saline in group S,and oxycodone 0.6 mg/kg,dexmedetomidine 0.48 μg/kg and tropisetron 5 mg in 100 ml of normal saline in group OD.The PCIA pump was set up with a 0.5 ml bolus dose,a 15 min lockout interval and background infusion at a rate of 2 ml/h.Ramsay sedation score and visual analog scale score were recorded at 4,12,24 and 48 h after surgery.The development and degree of agitation were recorded within 48 h after surgery.The development of adverse reactions such as nausea and vomiting,pruritus and respiratory depression was recorded.Venous blood samples were collected at 12 and 24 h after surgery for determination of serum blood urea nitrogen,creatinine and cystatin C concentrations,and the urine volume was calculated.Results Compared with group S,visual analog scale score was significantly decreased,Ramsay sedation score was increased,the rate of satisfactory sedation was increased,the incidence of agitation,nausea and vomiting was decreased,the serum blood urea nitrogen,creatinine and cystatin C concentrations were decreased,and the urine volume was increased at each time point after surgery (P＜0.05),and no significant change was found in the degree of agitation or incidence of pruritus in group OD (P＞0.05).Conclusion PCIA with oxycodone mixed with dexmedetomidine provides reliable efficacy and higher safety when used for analgesia after combined pancreas-kidney transplantation and is helpful in promoting recovery of the function of the transplanted kidney.

Clinical value of early enteral nutrition combined with parenteral nutrition in postoperative nutritional support for patients with obstructive jaundice / 中国综合临床

Objective To investigate the effect of early early enteral nutrition combined with parenteral nutrition support on postoperative gastrointestinal function,nutritional status and liver function of patients with obstructive jaundice.Methods Sixty-two patients with obstructive jaundice of hepatobiliary who were treated in the General Surgery Department of the Affiliated Hospital of North China University of Science and Technology from July 2013 to July 2014 were randomly divided into the control group and the observation group,31 cases in each group.The control group were treated with simple parenteral nutrition,and were injected by central venous catheter at the first day after operation,with the injection tiem of 12-15 h and continuous infusion of 7 d or more.The observation group were received enteral nutrition combined with parenteral nutrition,parenteral nutrition was given first,and the preparation method of the nutrient solution was identical with that of the control group;and then slowly dropped 250 ml physiological saline into the jejunum nutrition tube at the second day,dropped into the enteral nutrition liquid at the third day with the initial dose of 300 to 500 ml per day,slowly dropped in the speed of 20-30 ml/h.Results The first exhaust time,first defecation time and hospitalization time in the observation group were (41.37±6.85) h,(46.85±7.13) h and (12.79±3.76) d,significantly shorter than those in the control group ((57.21 ± 9.23) h,(61.43 ± 10.62) h and (16.94 ± 4.33) d;t =7.67,6.35,4.03;P＜O.05),daily hospitalization expenses was (1637.65± 138.24)yuan,significantly less than that in the control group((2121.42±112.38)yuan;t=15.12;P＜0.05).The serum albumin berofe and after the operation in the control group and observation group were (28.73±3.24) g/L and (29.21±3.31) g/L,(36.85±4.05) g/L and (47.21±4.13) g/L,respectively.The serum pre albumin berofe and after the operation in the control group and observation group were (162.81±31.27) g/L and (163.14±30.56) g/L,(248.95±58.62) g/L and(324.24±61.34) g/L,respectively.There was no difference before operation between the two groups (P＞0.05),while the serum protein levels were significantly increased in observation group than the control group (P＜0.01).There were no difference in ALT,total bilirubin and direct bilirubin levels between the two groups before operation (P ＞ 0.05),after treatment,the levels of ALT,total bilirubin and direct bilirubin in the observation group were significantly higher than those in the control group(P＜0.01).The patients in the two groups recovered well,and no serious adverse reactions occurred.Conclusion Early enteral and parenteral nutrition support in patients with obstructive jaundice has better effect and safety in the clinical treatment.

Role of TNF-αin promoting migration and invasion of colon cancer cells / 天津医药

Objective To explore the effect of TNF-αon expression of TROP-2 and to explore the role of TROP-2 in the metastasis and invasion of colon cancer HCT-116 cells. Methods HCT-116 cells were cultured and treated with 0, 10, 20, 30, 50, 100 and 200μg/L TNF-α. Cell viability was assessed by MTT. The expression of TROP-2 was determined by western blot. The effects of 20μg/L TNF-αon cell migration and invasion were investigated by wound healing assay and Transwell method. Small interfering RNA (siRNA) was used to knock down endogenous TROP-2 expression. The transcrip?tion and translation levels of TROP-2 were detected by qPCR and Western blot respectively. The migratory and invasive ca?pability of HCT-116 cells transfected with TROP-2 siRNA were checked by wound healing assay and Transwell method re?spectively. Results There is no significant change of cell viability between HCT-116 cells treated with 0,10, 20, 30 and 50μg/L TNF-α, but cell viability of HCT-116 decreased significantly with treatment of 100μg/L and 200μg/L TNF-α. Low concentration of TNF-α(≤50μg/L) led to increase of TROP-2 protein expression that peaks when 20μg/L TNF-αwas add?ed. High concentration of TNF-α(100, 200μg/L) result in decrease of TROP-2 protein. TROP-2 siRNA significantly down-regulated the expression of TROP-2 at both mRNA and protein levels in colon cancer HCT-116 cells. Compared with con?trol group, silencing TROP-2 by TROP-2 siRNA inhibited the migratory and invasive capability of HCT-116 cells. Wound healing rate and the number of transwell cell both decreased in siRNA group compared with those of control group ( P <0.05). Conclusion The mechanism that low concentration of TNF-α promoted HCT-116 cells migration and invasion might be through up-regulating the expression of TROP-2.

Study of the prevention of carboplation-induced reproduction damage by gonadotropin-releasing hormone agonist / 中国综合临床

Objective To study the effect of gonadotropin releasing hormone agonist(GnRHa)against car-boplation-induced gonadotoxicity in rats. Methods Forty Wistar rats were divided into four groups which received carboplation, GnRHa + carboplation, GnRHa and normal saline respectively(n=10 for each group). Blood samples were collected from the abdominal aorta and the levels of blood follicle stimulation hormone (FSH) and estradiol (E<2>) were determined. Both ovaries and uterus of each rat were removed to measure the amount and the maturity of follicles. Body mass and morphological and pathological features of the rats were also observed. Results Compared with that in control group, the body mass of ovary and uterus decreased (P<0.05), and a significant reduction was observed in the number of ovarian follicles at each grade (P<0.05). The levels of E2 significantly lowered (P<0.05) and the level of FSH markedly ascended in group carboplation. Compared with that in group carboplation, the amount of primitive follicles significantly increased in group GnRHa + carboplation (P<0.05), and carboplation showed markedly protective effect on the ovarian and uterine morphological construction of rats. Conclusion Gn-Rha, appliying to preventing the rat reproduction damage in advance, has the certain protective function.

Synthesis and identification of antigenic conjugates of podophyllotoxin / 药学学报

Aim To synthesize and identify artificial antigen of podophyllotoxin for the production of podophyllotoxin polyclonal antibody. Methods The hapten was synthesized by two different chemical approaches and characterized by TLC, IR, NMR, and MS. Mixed anhydride reaction (MAR) and active ester method (AEM) were used to couple the podophyllotoxin to carrier proteins (BSA and OVA). Characterization of artificial antigens was done by using spectroscopy and electrophoresis. The anti-podophyllotoxin polyclonal antibodies were obtained through immunizing rabbits. Results The results from IR, NMR and MS showed that 4-O-succinoyl podophyllotoxin (hapten) was successfully synthesized. The coupling molar ratios of the hapten and carrier proteins were 88.6 for Hapten-BSA1, 40.3 for Hapten-BSA2, 17.8 for Hapten-OVA1, and 54.2 for Hapten-OVA2. Hapten conjugates coupled with BSA yielded two sets of the specific and affinitive polyclonal antibodies. One set of antibodies showed an IC50 value of 2.21 μg·mL -1 with a detection limit of 0.12 μg·mL -1. Conclusion Antigenic conjugates were artificially synthesized, and based on these artificial antigens, polyclonal antibodies against podophyllotoxin were raised from rabbits immunized with two different immunogens and characterized with an indirect ELISA format.