Objective To investigate the influence of low-dose,long-term arsenite exposure on keratinocyte (HaCat) cell apoptosis and the expression of Bcl-2 and Bax proteins.Methods HaCat cells were exposed to different concentrations of NaAsO2[0(control group),0.05,0.10 μmol/L] for 15 weeks.A total of 10 000 cells in each group were measured to detect the level of apoptosis by flow cytometry.The protein expressions of Bcl-2 and Bax were determined by Western blotting method.Results The cell apoptosis rate was significantly different between groups (F =17.19,P ＜ 0.05).Compared with that of the control [(1.42 ± 0.13)％],the apoptosis rates of the 0.05 and 0.10 μmol/L groups [(1.23 ± 0.08)％ and (1.04 ± 0.06)％] decreased significantly (all P ＜ 0.05); the 0.10 μmol/L group was significantly lower than that of the 0.05 μmol/L group(P ＜ 0.05).The protein expressions of Bcl-2 and Bax were significantly different between groups (F=107.38,346.45,all P＜ 0.05).The protein expression of Bcl-2 of the 0.05 and 0.10 μmol/L groups were (143.89 ± 7.74)％ and (199.96 ± 12.18)％,respectively,which were significantly higher than that of the control group[(100.00 ± 1.45)％,all P ＜ 0.05] ; the 0.10 μmol/L group was significantly higher than that of the 0.05 μmol/L group (P ＜ 0.05).The protein expression of Bax of the 0.05 and 0.10 μmol/L groups were (70.78 ± 1.53)％ and (54.80 ± 1.34)％,respectively,which were markedly lower than that of the control group[(100.00 ± 3.09)％,all P ＜ 0.05]; the 0.10 μmoL/L group was significantly lower than that of the 0.05 μmol/L group(P ＜ 0.05).Conclusion Decreased level of apoptosis induced by low level and long-term arsenic exposure may be associated with increased expression of Bcl-2 protein and decreased expression of Bax protein.

Objective To perform the bibliometric research on the literatures of the endoscopic retrograde cholangio pancreatog-raphy(ERCP) in the last ten years to provide reference for accurately grasping the international research situation and selecting the cutting-edge technological topics .Methods The literatures of ERCP in the database Web of Science from 2001 to 2011 were collect-ed .The CiteSpace software was adopted to analyze the distribution characteristics ,key point literature ,hotspots fields and research frontier of articles of ERCP .Results 2 921 citations of the research articles were retrieved .The analysis showed that America was strongest in the ERCP research field ;10 key point articles were detected .The high frequency keywords were complications ,manage-ment ,sphincterotomy ,etc .,the concentricity ranged 0 .06-0 .24 .The high frequency burst words were gold standard ,procedure-re-lated-complications ,biliary-stents ,but the concentricity was 0 .Conclusion The research hotspots of ERCP field are the occurrence rate of ERCP postoperative complications ,diagnosis and treatment ,but no obvious research cutting-edge is formed .

Objective To evaluate surgical therapies in patients with popliteal aneurysms (PA).Method The clinical data of 25 PA patients admitted from January 1988 to January 2012 were retrospectively analyzed.There were 21 men and 4 women,the mean age was (56 ± 16)years.There were 27 PA in these 25 patients,with bilateral PA in 2 cases.The main symptoms were pulsatile mass in the popliteal fossa,limb pain,acute or chronic distal limb ischemia and limb edema.Result In this series 23out of 25 PA cases recieved operations,17 of them were treated with aneurysmectomy and saphenous vein interposition or bypass grafting,4 of them were treated with aneurysmectomy and prosthetic grafts interposition,1 was treated with aneurism ligation and 1 underwent end-to-end anastomosis after aneurysm resection.There was no perioperative mortality.One patient recieved amputation for distal anastomotic thrombosis and severe limb ischemia.The mean follow-up time is (6.5 ± 0.5) years.After 4 years,a right subclavian artery aneurysm was found in a bilateral PA case and treated surgically.Conclusions Early elective surgical treatment is recommended for patients with PA because PA may go rupture or induce dital limb ischemia and these patients may have good outcome after surgical treatment.Long-term follow-up is warranted to detect the new aneurysm formation.

ObjectiveTo learn the rpoB mutation difference in rifampicin/rifabutin cross-resistant (RIF/Rfb-R)clinical isolates and in rifampicin-resistant/rifabutin-susceptible (RIF-R/Rbo-S)clinical isolates of Mycobacterium tuberculosis.Methods To sequence the full-length genome of rpoB gene,and analyze the rpoB full-length gene mutation differences in 278 RIF/Rfb-R clinical isolates,40 RIF-R/Rfb-S clinical isolates,30 rifampicin-susceptible/rifabutin-susceptible (RIF-S/Rfb-S) and in 1 reference strain ofH37Rv.ResultsNo mutations of rpoB full-length gene were found in H37Rv reference strain and RIF-S/Rfb-S clinical isolates.In RIF/Rfb-R clinical isolates,531 (70.5％ ) and 526 (20.9％ ) were the most frequent mutation codons.223 (80.2％ ) isolates possesed single mutations as S531L,S531W,H526D,H526Y,H526R,Q513K,Q513P,Q510H,V176F,P287R,Y395C and H404Y.55 (19.8％) isolates had multiple mutations,and among these the S531L,H526 R,H526Y,H526D,D516G and Q513K were the main substitutions which were in combination with other points.In RIF-R/Rfb-S clinical isolates,516 (65.0％),526 ( 17.5％ ) and 533 ( 10.0％ ) were the most frequent mutation codons.21 (52.5％ ) isolates possesed single mutations as L533P,H526L,H526S,S522L,D516V,D516Y and D516F.19 (47.5％)isolates had multiple mutations and among these the D516V and L533P were the main substitutions which were in combination with other points.CondusionsIn our study,100％ rifamycin-resistant clinical isolates of Mycobacterium tuberculosis had rpoB mutations,but the mutations in RIF/Rfb-R clinical isolates were sharply different from RIF-R/Rfb-S clinical isolates in mutation positions or amino acids substitutions of single mutations strains,mutation positions or combination types and the most frequently mutation codons or amino acids substitutions of multiple mutations strains.Thus,DNA sequencing is instructive and meaningful to choose rifampicin or rifabutin for tuberculosis treatment.

Objective To investigate the expression and significance of caveolin-1 in breast carcinoma.Methods Using immunohistochemical method the protein expression of caveolin-1 were analyzed in 105 cases of breast carcinoma and 50 cases of non-cancerous breast tissues.The relationship between caveolin-1 expression and CK5/6,EGFR,and E-cadherin expression was investigated.Clinical data of 105 cases of breast carcinoma were retrospectively analyzed.Results Among 105 cases of breast carcinoma,there were 20 cases of basal-like subtype,22 cases of luminal subtype A,23 cases of luminal subtype B,23 cases of HER2 over-expressing subtype,17 cases of normal breast-like subtype.Positive rate of caveolin-1 was significantly lower in breast carcinoma than in non-cancerous breast tissues (24.8％ vs.88.0％,P ＜ 0.05).Positive rate of caveolin-1 (75.0％) was higher in breast carcinoma than in luminal subtype A ( 4.8％ ),luminal subtype B ( 17.4％ ),HER2 over-expressing subtype ( 17.4％ ) or normal breast-like subtype( 11.8％ ),all P ＜0.05.Caveolin-1 expression was associated with expression of CK5/6 and EGFR(P ＜0.01 ).In univariate analysis,positive caveolin-1 was associated with higher lymph node metastasis rate (18/26,69.2％ )than negative (37/79,46.8％ ),P =0.047,and shorter 5-year-disease-free survival (38.46％ vs.74.68％,P =0.0004 ),but in multivariate analysis caveolin-1 was not an independent predictor of 5-year- disease-free survival (P ＞ 0.05).Conclusions Caveolin-1 can be seen as a screening mark of basal-like breast carcinoma,it may promote the invasiveness of breast cancer cells,but it is not an independent prognostic predictor of breast cancer patients.

Adenine ; analogs & derivatives ; Fanconi Syndrome ; Humans ; Organophosphonates

Objective To observe the protective effects of soluble Nogo-66 receptor (NgR1 )antagonist (sNgR1-Fc) on cortical axons after cortical infarction in rats,and to study the phenomenon and molecular mechanism of its protective effects on and regeneration of axons.Methods The cortical infarction was induced by photochemistry,termed photothrombotic cortical injury (PCI).Fifteen Sprague Dawley rats were randomly divided into three groups:Sham-operated group,PBS (phosphate buffered solution) group,and s-NgR1-Fc group.In PBS group,PBS was injected into the lateral ventricle of rats; and in sNgR1-Fc group,sNgR1-Fc was injected instead of PBS. The ipsilateral cortex with lesion was harvested for histomorphometry and transmission electron microscope observation 7 days after PCI. Proteins including GTP-RhoA,p-JNK,p-c-JUN and p-ATF-2 were detected by Western blot,as well as Total-J and Total-RhoA.Results The cortical infarction in rats was successfully induced by photochemistry.Compared with sham-operated group,the pathological changes in PBS groups were more serious,including extensive edema or disappearance of axoplasm of fiber without medulla sheath involved and extensive thickening or layer derangement in axoplasm of fiber with medulla sheath involved.These changes were improved significantly after sNgR1-Fc treatment.The levels of GTP-RhoA,p-JNK1,p-JNK2,p-c-JUN and p-ATF-2 in the PBS group were significantly higher than those in the sham-operation group ( P ＜ 0.05 ),whereas the levels of Total-RhoA,Total-JNKl and Total-JNK2 were not different significantly between these two groups (P ＞0.05 ).The sNgR1-Fc treatment up-regulated the levels of these proteins ( P ＜ 0.05 ).Conclusions There is pathological change in axon induced by cerebral hypoxia-ischemia for a long period after cortical infarction.The mechanisms may be associated with RhoA/ROCK/JNK/c-Jun signal way,which is activated by ischemia injury and related to the inhibition of regeneration in axon.Our study shows that NgR1-Fc may inhibit this pathway significantly,and then promote the regeneration of axon partially.

Objective To analyze the clinical features and gene mutation in mthylmalonic acidemia (MMA) accompanied by homocysteinemia (cblC), and review the relevant literatures. Methods The clinical features of 3 cases of MMA diagnosed by gene detection were retrospectively analyzed, and meanwhile the pertinent literatures of pathogenesis of MMA, especially combined with late-onset cblC and its gene detection, were reviewed. Results Patient 1 (26 days old) suffered from intermittent convulsions for 3 days, with isosuccinic acid 175.8 μmol/L, C3/C2 rate 1.363, homocysteine >?65 μmol/L and abnormal EEG. MMACHC gene detection found an exon deficiency (delEXON1), which has not been reported. Patient 2 ( 12 year old) was hospitalized for limb shaking, hyperspasmia and vomiting. His isosuccinic acid level was 334.3 μmol/L, C3/?C2 rate was 0.37, homocysteine >?65 μmol/L, and had abnormal EEG. MMACHC gene detection found the mutations of c.482G?>?A and c.609G?>?A. Patient 3 was hospitalized for intermittent convulsions for 20 days, whose isosuccinic acid, C3/?C2 rate, and homocysteine were increased. MMACHC gene detection found the mutations of c.394C?>?T and c.540del8 and c.540del8 had not been reported. Review of literatures discovered that MMA was combined with epileptic seizure in some patents, which further validate that the mutation in MMACHC gene c.482G?>?A may be related to the late-onset of cblC. Conclusions Gene detection contributes to the diagnosis of MMA; the mutation of MMACHC gene c.482G>A may be related to the late-onset of cblC; delEXON1 and c.540del8 are new mutations which have not been reported.

Objective To study the effect of neuronal Nogo-66 receptor (NgR1) antagonist,soluble Nogo-66 receptor (sNgR1-Fc),on promoting the endogenous neural precursor cells (NPCs) differentiating into neurons in order to clarify the mechanism.Methods The cortical infarction was induced by photochemistry,named photothrombotic cortical injury (PCI).Twelve Sprague Dawley rats were randomly divided (random number) into three groups:Sham-operated group,PBS group,and sNgR1-Fc group.PBS (PBS group) or sNgR1-Fc (sNgR1-Fc group) was injected into the lateral ventricle of brain with a minipump.BrdU (Bromodeoxyuridine) was injected into the peritoneal cavity 4-6 days after PCI.The subdentate gyrus zone (SGZ) of brain from sacrificed rat was harvested for Immunohistochemistry to observe the ratio of NeuN +/BrdU + cells 35 days after PCI.Proteins including Nestin、Notch1 and Mash1 were detected by Western Blot.Results The cortical infarction in rat was successfully induced by photochemistry.Thirty-five days after PCI,the BrdU + cells number and theratio of NeuN +/BrdU + in the SGZ of the ipsilateral cerebrum hemisphere with PCI were significantly higher in sNgR1-Fc group than those in PBS group (P ＜ 0.05).The levels of Notch1,Mash1 and Neuro D in the sNgR1-Fc group were significantly higher than those in the PBS group (P ＜ 0.05),which were significantly higher than those in the Sham-operated group.Conclusions sNgR1-Fc could promote the endogenous NPCs differentiating into neurons in a cortical infarction model.The mechanisms may be attributed to the Notch/bHLH (proneural basic helix-loop-helix genes) signaling way.

Objective To explore the feasibility of mechanical chest compression to establish a rat model of car?diopulmonary resuscitation ( CPR) . Methods 4?month old healthy male Sprague Dawley rats were randomly divided into control group ( n=6 ) and model group ( n=10 ) . After induction of anaesthesia with 10% chloraldurate ( 3 ml/kg, i. p. ) , tracheal intubation and left femoral artery cannulation were performed. Under electrocardiographic and artery blood pressure monitoring, tracheal obstruction ( TO) was performed to rats in model group. At 2 min after the cardiac arrest ( CA) occurred, CPRs were administered to the rats using a self?made animal chest compressor, which provided chest?com?pression at a rate of 200 bpm. Results Shortly after TO, rats in the model group had respiratory arrest, cyanosis and ar?rhythmia. Electrocardiography indicated that CA occurred within 4-5 min, with a decreased artery systolic blood pressure ( <40 mmHg) and a zero pulse pressure. Return of spontaneous circulation ( ROSC) after the CPR was successfully a?chieved in 8 rats (80%), with a transient reperfusion arrhythmia. Finally, 60% of the rats (n=6) recovered to con?sciousness and survived for 24 hrs. The serum biochemical analysis indicated that there were electrolyte disturbances, aci?dosis, impaired renal functions and increased myocardial enzyme spectrum. Pathological examination revealed cardiac rhab? domyolysis, no?reflow phenomenon in renal glomeruli, decrease of neurons and pulmonary congestion in the model group rats. Conclusions Mechanical chest compression can provide minimal cardiac output for the requirement of CPR incardiac arrestin rats. It is feasible to establish rat CPR model with the mechanical chest compression.