Objective To investigate the expression of DNA damage and repair gene Apurinic/apyrimidinic endonuclease (APE1) protein in nasal NK/T cell lymphoma, and elucidate its clinical implication. Methods Expression of APE1 proteins was detected immunohistochemically in 10 normal lymph nodes and human nasal NK/T cells from lymphoma of 64 patients and their integral optical density was determined by means of image analytic system. The proliferation index and apoptosis index were determined by means of immunohistochemical staining and terminal dUTP nickend labeling (TUNEL) technique. Results 1. Nuclear, nucleus/cytoplasmic and cytoplasmic types of APE1 positive staining could be noted in nasal NK/T cell lymphoma. Expression of APE1 gene in nucleus was significantly strengthened compared to that in nucleus/cytoplasm and cytoplasm. In relapse or refractory group, no relapse or refractory group, and normal control group, the positive degree of cytoplasmic staining diminished significantly in the above order (P

Objective To investigate the role of APE1 in the carcinogenesis and progression of colorectal carcinoma (CRC). Methods Expression of APE1 was determined with SP immunohistochemical technique in 40 specimens of normal colorectal mucosa, 60 specimens of colorectal mucosa adjacent to CRC, 72 specimens of colorectal adenoma, and 125 specimens of colorectal carcinoma. Results In normal colorectal mucosa, APE1 was detected in nuclei of epithelial cells. Shift of APE1 from nucleus to cytoplasm was observed in 6 of 60 (10%) specimens of mucosa adjacent to cancer. Such shift was observed in 92 of 125 (73.6%) CRC tissues and 60 of 72 (83.3%) colorectal adenoma, the incidence of both of them was significantly higher than that observed in normal colorectal mucosa and colorectal mucosa adjacent to CRC (P

Objective To evaluate the effect of dexmedetomidine on brain injury in the patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).Methods Eighty patients of both sexes, aged 18-64 yr, with body surface area of 1.6-2.0 m2, with left ventricular ejection fraction＞30％, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ (New York Heart Association Ⅱ or Ⅲ), scheduled for elective cardiac surgery with CPB, were equally and randomly divided into control group (group C) and dexmedetomidine group (group D) using a random number table.Before induction of anesthesia, dexmedetomidine was given as a bolus of 1 μg/kg over 10 min followed by an infusion of 0.5 μg · kg-1 · h-1 throughout the surgery in group D, and the equal volume of normal saline was given in group C.After induction and before skin incision (T0) , at 30 min after beginning of CBP (T1) , at 30 min after the end of CBP (T2) , at the end of surgery (T3) , and at 24 and 72 h after surgery (T4.5) , blood samples from jugular bulb were drawn for determination of serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-10, S-100β protein and neuron-specific enolase (NSE).Results Compared with group C, the serum concentrations of TNF-α and S100β at T1-3 and IL-6 and NSE at T1.4 were significantly decreased, and the serum concentrations of IL-10 at T1-4 were increased in group D (P＜0.05).Conclusion Dexmedetomidine given as a bolus of 1 μg/kg over 10 min followed by an infusion of 0.5 μg · kg-1 · h-1 throughout the surgery can reduce the brain injury in the patients undergoing cardiac surgery with CPB, and the mechanism is related to inhibited inflammatory responses.

Objective To investigate the effects of autologous blood withdrawal-reinfusion on the perioperative coagulation function in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB ) . Methods Eighty-four ASA physical status Ⅱ-Ⅳ patients ,without impairment of coagulation function ,scheduled for cardiac surgery with CPB ,were equally and randomly divided into 2 groups using a random number table :autologous blood withdrawal-reinfusion group (group ABWR , n= 44 ) and control group (group C , n= 40 ) . Decreased coagulation function was diagnosed based on the following two criteria :laboratory standard of decreased coagulation function and clinical signs .After anesthesia and before the beginning of operation (T1 ) ,at 5 min after heparin was reversed with protamine (T2 ) ,at the end of operation (T3 ) and at 24 h after the end of operation (T4 ) ,venous blood samples were obtained to measure the blood routine and parameters of coagulation function . Blood routine included the red blood cell (RBC ) , hemoglobin (Hb ) , hematocrit (Hct ) , platelet count , and plasma fibrinogen concentration (Fib) .The parameters of coagulation function included thrombelastography (TEG) variables and prothrombin time (PT ) ,activated partial thromboplastin time (APTT ) ,international normalized ratio (INR ) , and activated clotting time (ACT ) . The volume of intraoperative blood loss , amount of mediastinal drainage at 6 and 24 h after operation , consumption of tranexamic acid and heparin during operation , and consumption of fibrinogen after operation ,and requirement for transfusion of allogeneic RBCs ,fresh frozen plasma (FFP) and platelet during operation and within 24 h after operation were recorded .The development of decreased coagulation function during operation and within 24 h after operation .Results Compared with group C , perioperative consumption of allogeneic RBCs were decreased ,reaction time (R) measured by celite-activated TEG was increased at T3 (P<0.05) ,and no significant change was found in the blood routine index ,incidence of decreased coagulation function ,volume of intraoperative blood loss ,amount of mediastinal drainage ,consumption of tranexamic acid and heparin , and postoperative consumption of fibrinogen in group ABWR ( P> 0.05 ) . Conclusion Autologous blood withdrawal-reinfusion provides similar effects on coagulation function with allogeneic blood transfusion ,and does not increase the development of decreased coagulation function in patients undergoing cardiac surgery with CPB .

Objective To investigate the effect of APE1 on differentiation of peripheral blood mononuclear cells into osteoclast-like cells(OCL) which induced by macrophage colony stimulating factor (RANKL) and macrophage colony stimulating factor (M-CSF) .Methods Human peripheral blood mononuclear cells (PBMCs) were collected by density gradient separation ;Constructed APE1 siRNA expression vector Ad5v-APE1 siRNA was used to transfect PBMCs .Tartrate-resistant acid phosphatase (TRAP) method was conducted to identify the cells ,the expression level of APE1 was detected by Western blot ,the mRNA expression levels of Cathepsin K(CK) and V-ATPase were detected by RT-PCR .Results PBMCs transfected with APE1 siRNA had significantly lower protein expression of APE1 than untransfected cells (P< 0 .05) ;PBMCs could differentiate into OCL under the stimulation of RANKL and M-CSF ,the mRNA expression levels of CK and V-ATPase increased ;After APE1 siRNA treatment ,the number of OCL was reduced and the levels of CK and V-ATPase mRNA decreased .Conclusion PBMCs can differentiate into a large number of OCL induced by RANKL and M-CSF ,APE1 siRNA significantly inhibited differentiation of PBMCs into osteoclast-like cells , APE1 may be involved in the regulation of osteoclast-like differentiation process .

Objective To evaluate the effect of dexmedetomidine (DEX) on inflammatory responses in patients performed cardiac surgery with cardiopulmonary bypass (CPB) at perioperative period,and explore the influencing factors of postoperative cognitive dysfunction (POCD) in these patients.Methods Eighty patients scheduled for cardiac surgery with CPB at hospital from July 2013 to June 2014 were randomized into control group and DEX group (n=40).Before induction of anesthesia,DEX was administered to the patients from DEX group with a loading dose of 1 μg/kg followed by maintenance dose of 0.5 μg/ (kg·h),while the same dose of normal saline was administered to patients from control group.Before incision (T0),30 min after beginning of CBP (T1),30 min after end of CBP (T2),end of surgery (T3),24 h after end of surgery (T4) and 72 h after end of surgery (T5),venous blood samples from jugular bulb catheters were drawn,and serum concentrations of tumor necrosis factor α (TNF-αt),interleukin (IL)-6 and IL-10 were determined.One d before operation,3nd,7th,90th and 180th day after operation,the cognitive functions of patients were tested with mini-mental state examination (MMSE),digit span subtest (DSpan),digit symbol subtest (DSy) and trail making test (TMT).The DSpan contained digit span forward subtest (DSpan-F) and digit span reverse subtest (DSpan-R).Results The serum concentrations of TNF-α,IL-6 and IL-10 in two groups at T1,T2 and T3 were significantly higher than those at T0 (P＜0.05);the serum concentrations of TNF-α and IL-6 in DEX group were significantly lower than those in control group (P＜0.05),while that of IL-10 in DEX group was significantly higher than that in control group (P＜0.05).In the control group,all results excepted for TMT on the 3nd d after operation,MMSE and DSpan-R results on the 7th d after operation,and DSpan-R results on the 90th d after operation were significantly lower than those results one d before operation (P＜0.05);in the DEX group,MMSE and DSpan-R results on the 3nd d after operation were significantly lower than those results one d before operation (P＜0.05);MMSE and DSpan-R results on the 3nd and 7th d after operation,and DSpan-R results on the 90th d after operation in the DEX group were significantly higher than those in the control group (P＜0.05);TMT on the 3nd after operation in the DEX group was significantly lower than that in the control group (P＜0.05).The incidence rate of POCD in the DEX group on the 3nd and 7th d after operation (23.5％ and 14.7％) was significantly lower than that in the control group (46.9％ and 37.5％,P＜0.05).Conclusion DEX with a loading dose of 1 iμg/kg followed by maintenance dose of 0.5 μg/ (kg· h) can reduce the early incidence of POCD in cardiac surgery with cardiopulmonary bypass,but can not reduce the late incidence.

OBJECTIVETo synthesize novel aryl-substituent benzyl acid compounds targeting HIV gp41 and characterize their anti-HIV activities.

METHODSTwelve analogues of aryl-substituent benzyl acid were designed and synthesized by Suzuki- Miyaura cross-coupling and Knoevenagel condensation reactions using halo-benzyl acid or 3-carboxybenzeneboronic acid as the raw material. The inhibitory activities of these compounds on gp41 six-helix bundle formation were tested by ELISA, and their anti-HIV activities were determined using a luciferase assay.

RESULTSThe structures of the compounds were characterized by nuclear magnetic resonance and mass spectrography. Among the 12 compounds, 5 (7b, 7c, 7d, 7e, and 7g) could inhibit the gp41 six-helix bundle formation, and 7d showed the most potent effect, and could also inhibit the replication of HIV-1 SF33 strain with an IC(50) of 20 µmol/L.

CONCLUSIONThe synthesized aryl-substituent benzyl acid compound 7d could inhibit HIV replication by blocking the gp41 six-helix bundle formation.

Anti-HIV Agents ; chemical synthesis ; pharmacology ; Benzoates ; chemical synthesis ; pharmacology ; Drug Design ; HIV-1 ; drug effects ; Hydrocarbons, Aromatic ; chemical synthesis ; pharmacology ; Virus Replication ; drug effects

Objective we assessed our institutional outcomes of hybrid treatment for aortic arch disease with supra-aortic debranching and endovascular stent graft repair.Methods From March 2016 to November 2016,6 patients underwent Hybrid total aortic arch repair:1 had aortic arch pseudoaneurysm;1 had type Ⅲ aortic dissection;4 had aortic arch aneurysm because of hypotension,of whom 1 with aneurysm prerupture and 1 with Aortic intramural hematoma.Supra-aortic vessels were involved and high-risk for traditional operations in all patients.Bifurcated artificial vessels were used,main vessel was end-to-side anastomosed with ascending aorta.Branching vessel were end-to-end anastomosed with right innominate artery and left subclavian artery,end-to-side anastomosed with left common carotid artery.Then,stent graft was implanted into ascending aorta and aortic arch.All patients were followed postoperatively,with regularly contrast computed tomography angiogram (CTA) and echocardiography(discharge,three months,six months,and yearly).Results Hybrid procedure with supra-aortic debranching and endovascular stent graft repair were completed in all patients,technical success rate was 100％.There were no perioperative obvious morbidity and mortality,follow-up period were 2-9 months.1 patients had stroke during follow-up period,condition improved after treatment.Supra-aortic vessels were patency and there were no endoleak in all patients.There were no recurrent aortic disease during follow-up period.Conclusion Hybrid aortic arch replacement can be performed with good postoperative and early results in high-risk patients for traditional open repair.

Objective To investigate the effects of risk factors on non thyroidal Illness syndrome (NTIS) in elderly inpatients.Methods A total of 819 elderly inpatients who met inclusion criteria were consecutively recruited in thiscross-sectional study.Physicalmeasurements and mini nutritional assessment using the mini nutritional assessment-short form (MNA-SF) score were conducted.A serum levels of thyroid stimulating hormone (TSH),free triiodothyronine (FT3),free thyroxine (FT4),brain natriuretic peptide (BNP) and C-reactive protein (CRP) were examined.Data were analyzed with multivariatelogistic regression.Results The significant differences were found between NTIS group (n=145) versus control group (n=674)inage (78.5±8.1) years vs.(75.1±8.6) years(t=5.422,P＜0.01),in body mass index (23.0 ±3.8) kg/m2 vs.(24.1±3.6) kg/m2,in MNA-SF score 11.2±2.3 vs.12.3± 1.8(t=-3.315,6.754,P＜0.01),in level of serum albumin (36.0±4.5) g/L vs.(38.4±3.6) g/L (t=-6.977,P＜0.01),in triglyceride level (1.3± 0.9) mmol/L vs.(1.5±1.0) mmol/L(t=-3.039,P＜0.01),inCRP (Z=-8.857,P＜0.01)),and in BNP (t=6.331,P＜0.01).Logistic regression analysis revealed that age＞ =80 years (OR=2.433,95％CI:1.357 4.361),malnutrition (OR=1.946,95％CI:1.261-3.001),renal insufficiency (eG FR＜60 ml/min,OR =2.131,95％ CI:1.367-3.322),and high level of CRP (10 mg/L and 50 mg/L:OR=3.446,95％CI:2.117-5.611;over 50 mg/L:OR =10.029,95％CI:4.693-21.432,all P＜0.01)) were risk factors for NTIS.Conclusions Non-thyroidal illness syndrome in elderly inpatients is correlated with advanced age,renal insufficiency,malnutrition and stress,which are the independent risk factors.

OBJECTIVETo identify potential mutation of ectodysplasin A (EDA) gene in a Chinese family affected with X-linked hypohidrotic ectodermal dysplasia.

METHODSBlood samples were collected from the affected male proband, his family members and 103 unrelated individuals. Following extraction of genomic DNA, coding sequence of the EDA gene was amplified with PCR, and DNA sequencing was performed to detect potential mutation.

RESULTSA novel missense mutation, c.822G>T (p.W274C), was identified in exon 7 of the EDA gene in the proband, whilst his mother was found to be a heterozygous carrier. The same mutation was also found in 5 other family members including one affected male and four females, but was absent in unaffected males and 103 unrelated individuals.

CONCLUSIONA c.822G>T mutation in exon 7 of the EDA gene probably underlies the disease in this Chinese family.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Ectodermal Dysplasia 1, Anhidrotic ; diagnosis ; genetics ; Ectodysplasins ; genetics ; Exons ; Female ; Humans ; Male ; Mutation ; Pedigree ; Phenotype ; Young Adult