ABSTRACT
Excessive N-acetyl-p-benzoquinone imine(NAPQI)formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen(APAP)overdose caused acute liver failure(ALF).S-glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity.Glutaredoxin-1(Glrx1),a glutathione-specific thioltransferase,is a primary enzyme to catalyze deglutathionylation.The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP.The Glrx1 knockout mice(Glrx1-/-)and liver-specific overexpression of Glrx1(AAV8-Glrx1)mice were produced and underwent APAP-induced ALF.Pirfenidone(PFD),a potential inducer of Glrx1,was administrated preceding APAP to assess its protective effects.Our results revealed that the hepatic total protein S-glutathionylation(PSSG)increased and the Glrx1 level reduced in mice after APAP toxicity.Glrx1-/- mice were more sensitive to APAP overdose,with higher oxidative stress and more toxic metabolites of APAP.This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the S-glutathionylation of cytochrome p450 3a 11(Cyp3a11),which likely increased the activity of Cyp3a11.Conversely,AAV8-Glrx1 mice were defended against liver damage caused by APAP overdose by inhibiting the S-glutathionylation and activity of Cyp3a11,which reduced the toxic metabolites of APAP and oxidative stress.PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress.We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose.Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.
ABSTRACT
Objective To investigate the characteristics of the early gastroesophageal junction(GEJ)can-cer under the white-light endoscopy.Method We analyzed 70 cases of pathology-proven early GEJ cancer retrospec-tively. We investigated the predilection sites of different Siewert types,the lesion features under the white-light endoscopy,and the associations among the Siewert types,Barrett esophagus and the intestinal metaplasia. Results Siewert Ⅱ was the most of the early GEJ cancer(64%). Barrett esophagus was the most of SiewertⅠ(85%).No statistical significances of the intestinal metaplasia were found among different Siewert types.SiewertⅠlesion was located on the right front wall the most.Of Siewert Ⅱlesion was located on the back wall the most.The main endoscopic type was Type 0~Ⅱ.The most of the early GEJ cancer under the white-light endoscopy has clear demarcation(89%)and irregular surface appearance(81%),and the main color of mucosa lesion was red(76%). Conclusion The early GEJ cancer under the white-light endoscopy shows the subtle characteristic changes.Under-standing and paying attention to the above characteristics will help to improve the diagnosis of the early GEJ cancer.
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Objective To investigate the levels of IL-6 in serum and gastric mucosa of servicemen before and after mili-tary maneuver and their significance .Methods The level of serum IL-6 in 60 servicemen was studied by enzyme-linked immunosorbent assay .The expression of IL-6 in gastric mucosa from the 60 servicemen was detected by immunochemical staining.Results The level of IL-6 in serum of servicemen after military maneuver was significantly higher than that before military maneuver (P<0.01).IL-6 was found to be expressed in the cytoplasm of epithelioglandular cells and also in the cytoplasm of mesenchymal cells .The expression of IL-6 in gastirc mucosa was significantly stronger after military maneuver than before military maneuver (P<0.01).Conclusion IL-6 might be involved in the development of pathological changes in gastric mucosa caused by military stress in troops .Examination of the level of IL-6 in the early stage of military stress might help assess the chance of gastric mucosa lesion and its severity .
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Objective To discuss application value of intestinal electromyography in patients with hepatic cirrhosis and to observe intestinal myoeletric activity.Methods There were 65 cases of hepatic cirrhosis in expermental group and 30 cases in control group. All the cases were recorded body surface intestinal electromyography using gastrointestinal myoelectric analyzer(WCDF-4B, Hefei , P.R.China). The parameters included average peak range-Ap, main frequency-Fp, average over zero frequency-Fz and special wave form were surveyed.Results Sharp higher Fz abnormal rate and emergence rate of special wave form in hepatic cirrhosis group were higher than in control group,P0 05.Conclusions In hepatic cirrhosis group,Fz was much higher than that in control group. And the intestinal myoelectric activity increased in the patients with hepatic cirrhosis,which represented by appearance of characteristic wave form that was frequent micromigration wave as well as load wave. Those changes accounted for heighten and irregularity of excitability intestinal myoelectric activity. Moreover, it will increase for the incidence of abnormality of intestinal myoelectric activity along with damage degree of hepatic function. Intestinal electromyography is a reliable method to judge intestinal myoelectric activity, the method has characteristics of harmless,free pain, convenient, safty and steady.
ABSTRACT
Purpose:To study the mutual relationships between apoptosis,cell proliferation correlative gene PCNA and tumor suppressor gene P27 Kip1 as well as to investigate if they have something to do with the occurrence,development,and prognosis in esophagus squamous cell carcinoma.Methods:47 cases of primary esophagus squamous cell carcinoma were put into investigative group whose tumor samples from operation resection were studied. 20 cases with normal esophagus cell mucous membrane tissue were put into the control group. Expression level of PCNA,P27 Kip1 was detected by immunohistochemistry method (S-ABC) in both groups. Apoptotic index was detected by TdT mediated deoxyuridylic acid(dUMP)nicking end labeling (TUNEL method) in both groups.Results:①In the group of 47 cases of esophagus squamous cell carcinoma,there were 17 cases of positive expression in P27 Kip1 ,and the positive rate was 36.17% , average proliferation index(PI) was 45.86?19.11%,average apoptotic index is 1.05%?0.59%,ratio of PI/AI is 57.37? 45.17 ,all of which were statistically significant for difference between normal tissue and carcinoma in esophagus squamous cell (P