Chronic myelogenous leukemia (CML) has a high proportion in hematologic malignancy.Past decade,the appearance and development of tyrosine kinase inhibitors (TKIs) is the milestone of the treatment of CML.TKIs have antitumor effect with inhibition of the phosphorylation of kinases and the downstream signal transduction.In recent years,many large medical institutions at home and abroad worked on clinical experiment researches to investigate the mechanism of TKIs and how to choose TKIs in CML patients.This work is of great significance to the clinic.

Objective To investigate the effect of astilbin on expression of CTLA-4 in activated T cells of mouse heart transplantation model with acute rejection.Methods Cardiomyocytes of BALB/ c mouse and spleen cells of C57BL/6 mouse were separated.The cardiomyocytes(2?10~5/ml)as irri- tation cells and spleen cells(1?10~6/ml)as responsers were mixed and cultured.The model of mouse heart transplantation with acute rejection in vitro was established.Three groups were set up:control group,Astilbin(15/?g/ml) group,Astilbin+anti-CTLA-4 mAb 9H10 (30?g/ml)group.Apoptosis of T cells was observed by TUNEL.The expression of CTLA-4 in activated T cells was detected by RT-PCR and Western blot.Results Apoptosis indexes of activated T cells in Astilbin group were sig- nificantly higher than those in the control group(73.4%?12.5% vs 35.1%?9.2%,P＜0.01). The expression of CTLA-4 in Astilbin group was significantly higher than control group(P＜0.01), but there was no apparently difference between control group and Astilbin+CTLA-4 mAb group(P＞0.05).Conclusion Astilbin induces apoptosis of activated T cells in heart transplantation,which may be partially related to its enhanced expression of CTLA-4.

Background Vancomycin has been increasingly recommended for the management of endophthalmitis,but few research report has been published about the pharmacokinetics of intravitreal vancomycin up to now.It is necessary to have an exact method to measure the concentration of vancomyein in animal eyes after intravitreal injection.Objective This study was to observe and compare the phamacokinetical process of vancomycin in serum,vitreous and aqueous humor between normal and infected rabbit eyes.Methods Seventy-two healthy adult rabbits were randomly divided into normal group and infected group and 36 rabbits for each.The animal models of endophthalmitis were established by intravitreal inoculation of 2000 CFU/ml staphylococcus aureus in the right eyes of rabbits in the infected group.Once endophthalmitis developed,0.1 ml vancomycin ( 10 g/L) solution was injected into the vitreous of every rabbit.The peripheral blood,vitreous and aqueous humor samples were respectively collected in 4 rabbits for each group at 0.5,2,4,6,12,24,48,72 and 84 hours after injection for detection of vancomycin concentration by high performance liquid chromatography(HPLC-UV).3p97 software was used to create fit parameters of pharmacokinetics.This experiment followed the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission (Version 1988).Results The accuracy of HPLC fitted the detecting request of biological specimen.The concentration-time data of vancomycin in normal rabbit aqueous humor and vitreous was subject to two-compartment model.The pharmacokinetic parameters were separately as following:Cmax was 50.16 mg/L and 751.42 mg/L,t1/2was 51.04 hours and 53.21 hours.The concentration-time data of vancomycin in infected rabbit aqueous humor and vitreous was subject to one-compartment model.The pharmacokinetic parameters were separately as following:Cmaxwas 24.94 mg/L and 687.66 mg/L,t1/2was 11.42 hours and 12.91 hours.The concentration of vancomycin in serum was much lower and almost undectable.The concentration of vancomycin in vitreous was gradually reduced as the prolong of time after injection in both normal group and infected group,but a obvious decline after increased level was scen in aqueous humor.Compared with normal group,the concentrations of vancomycin in both vitreous and aqueous humor were reduced at various time points(P＜0.05,P＜0.01 ).Conclusions HPLC is simple,highly sensitive and specific for the pharmacokinetic analysis of vancomycon.These results indicate that pharmacokinetic parameters of vancomycin alter in pathological condition,which is helpful for us to establish the better treatment guidelines for endophthalmitis.

Adult ; Carcinoma, Papillary ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Thyroid Gland ; pathology ; surgery ; Thyroid Neoplasms ; pathology ; surgery ; Thyroidectomy ; methods ; Video-Assisted Surgery ; methods ; Young Adult

OBJECTIVETo evaluate the histopathological characteristics and clinical implication of sarcolemma tissue in prepubertal concealed penis.

METHODSAfter measurement of the penile length, 10 prepubertal children with congenital concealed penis underwent modified Devine's operation (treatment group), and another 10 normal prepubertal children received circumcision (control group). The anatomic features of the penile sarcolemma tissue was observed intraoperatively, and its fibrosis was evaluated by Masson trichrome staining.

RESULTSThe penile length of the treatment group was significantly shorter than that of the control group preoperatively ([1.49 +/- 0.17 ] cm vs [4.26 +/- 0.23 ] cm, P < 0.01). The degree of penile concealment was correlated with the distal point of the attachment of its sarcolemma fibrous tissue: the closer the distal attachment point was to the coronary ditch, the more serious was penile concealment. The proportion of the area of collagen fibers in the penile sarcolemma tissue was significantly higher in the treatment group than in the control ([65.6 +/- 6.9]% vs [37.1 +/- 4.7]%, P < 0.01).

CONCLUSIONSarcolemma fibrosis was obvious in congenital concealed penis, and the key to its management is drastic removal of all the fibrous sarcolemma tissue.

Child ; Circumcision, Male ; Fibrosis ; Humans ; Male ; Penis ; abnormalities ; pathology ; surgery ; Phimosis ; pathology ; surgery ; Sarcolemma ; pathology

Objective To explore the effects and the molecular mechanism of synergistic hepatocarcinogenesis of HBV and AFB1 in the development of HCC by studying the difference in protein expression profiles in hepatocellular carcinoma exposed to hepatitis B virus and Aflatoxin B1.Method 32 HCC specimens were labeled under four categories based on their biomarkers of HBV and AFB1 exposure:group A:HBV(+)/AFB1 (+),10 cases,group B:HBV(+)/AFB1 (-),10 cases,group C:HBV(-)/AFB1(+),6 cases,groupD:HBV(-)/AFB1(-),6 cases.Normal hepatic tissues from 10 cases of hepatic hemangioma,liver resection and liver transplant donor were chosen as the normal control group.Isobaric Tagging Reagent Quantitative (iTRAQ) Proteomics together with 2DLC MS/MS were applied to analyze the differentially expressed proteins among the 4 groups.Result (1) A total of 117 unique differentially expressed proteins including 53 up-regulated proteins and 64 down-regulated proteins were identified in the four groups.The number of unique differentially expressed proteins,including up-regulated and down-regulated proteins,in group A,group B,group C and group D were 106,97,104 and 74 respectively.(2) Among the 117 differentially expressed proteins,9 proteins were heat shock proteins or chaperones,and they were up regulated in group A,B and C.Besides,15 proteins were detoxification and drug metabolism pathway related proteins,12 of them were down-regulated in group A,and more than half of them were also down-regulated in group B and C.(3) The Reverse Transcriptase PCR result showed the mean expression level of AKR1B10 mRNA in group A was significantly higher than group B,C and D (all P＜0.05,respectively).Group C also showed significantly a higher expression level of AKR1B10 mRNA than group D (P＜0.05).The Western-blot results showed the mean expression level of AKR1B10 protein in group A was significantly higher than group B and D (all P＜0.05,respectively).Conclusions The up-regulated expression of heat shock protein and the down-regulated expression of most protein enzymes related to detoxification and drug metabolism were the common molecular biological events of HCC associated with exposure to HBV and AFB1.This suggested the synergistic hepatocarcinogenesis effects of HBV and AFB1 may be related to dysregulation of protein enzymes related to detoxification and drug metabolism.The overexpression of AKR1B10 may be involved in the AFB1-related hepatocarcinogenesis process.

Xiatianwu tablet is based on the theory of traditional Chinese medicine (TCM), combined with modern TCM pharmacology and selected 33 famous traditional Chinese crude drugs to compose. Its recipe helps cure rheumatism, relax tendons, promote blood circulation to relieve pain, et al. Although Xiatianwu tablets are widely applied to clinical remedy such as rheumatic arthritis, lumbar disc hernia, osteoarthritis and so on, there is no report about its application in fracture. This article is to observe the efficacy of compound Xiatianwu tablets in elderly patients with osteoporotic distal radius fractures and its impact on the wrist function and complications. 180 elderly patients with osteoporotic distal radius fractures, from January 2011 to June 2014, were divided into observation group and control group by the method of random number table, each group had 90 cases. The control group were gave Caltrate D after manipulative reduction and plaster immobilization, observation group were treated with compound Xiatianwu tablets in the basis of the control group. Efficacy, wrist function and complication rates were observed in two groups after treatment. The excellent and good rate was 95.56% in observation group better than 77.78% in control group, the difference was statistically significant (χ2 = 4.712, P < 0.05). The complication rate in observation group was significantly lower compared with the control group (P < 0.05). This study shows that compound Xiatianwu tablets can improve the efficacy in elderly patients with osteoporotic distal radius fractures, reduce the incidence of complications and relieve the pain of patients which plays a significant role in improving the quality of life.
Aged ; Aged, 80 and over ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Fractures, Bone ; drug therapy ; Humans ; Male ; Middle Aged ; Osteoarthritis ; drug therapy ; Radius Fractures ; drug therapy ; Tablets ; administration & dosage ; Treatment Outcome

AIM:To detect the activation of macrophage autophagy caused by lipopolysaccharide ( LPS) and the possible related signaling pathways .METHODS:The macrophage cell line RAW264.7 cultured in vitro was divided into 5 groups according to the culture environment , including normal culture group , starvation-activated sautophagy group , LPS group, LPS+PI3K inhibitor (hVps34) group and LPS+mTOR inhibitor (rapamycin) group.Fluorescent expression vector pcDNA3.1-GFP-LC3 constructed in previous work was transfected into the macrophages .The fluorescence microscopy was used to detect the formation of autophagosome .The mRNA expression of autophagy-associated genes Atg5, Atg7, LC3-II and Bnip3 in the macrophages was detected by qRT-PCR.The protein levels of LC3-II, p-Akt and p-mTOR were deter-mined by Western blotting , so as to evaluate the molecular pathways of autophagy in LPS-activated macrophages .RE-SULTS:The macrophages stably expressing GFP-LC3 were successfully established , which were used to observe the auto-phagy under fluorescence microscope .Compared with normal culture group , the autophagy in starvation group , LPS +hVps34 group and LPS+rapamycin group was significantly increased .The mRNA expression levels of Atg5, LC3-II and Bnip3 were significantly increased in starvation group , LPS+hVps34 group and LPS +rapamycin group , while in LPS group, those decreased slightly .The protein level of p-Akt in starvation group , LPS group and LPS+rapamycin group was significantly increased , while p-mTOR in starvation group , LPS+hVps34 group and LPS+rapamycin group significantly declined .LC3-II expression level in starvation group , LPS+hVps34 group and LPS+rapamycin group was higher than that in control group and LPS group .CONCLUSION: LPS regulates macrophage autophagy , and its possible pathway is the PI3K/Akt/mTOR pathway, but there are some other effective regulatory pathways .

OBJECTIVETo investigate the electrophysiological effect of Xin' an granule (XAG) on ventricular muscle cell in ischemic rabbits.

METHODSA total of 48 rabbits were divided into the normal group and the ischemic group, and then subdivided into three groups, the control group, the high and low-dose XAG groups, 8 in each group. Rabbits in the low-dose XAG group and the high-dose XAG group were gastrogavaged XAG at the daily dose of 0. 85 g/kg and 3.40 g/kg, while the others in the control group were given the equal dosage of normal saline. All the rabbits were treated three times per day for successive 10 days. The rabbit model of ischemia was established by intravenous injected with 2. 5 U/kg posterior pituitary injection. Five minutes later, the monophasic action potential (MAP) and electrocardiogram (ECG) of each rabbit in the different groups were recorded and compared.

RESULTS(1) To normal rabbits, XAG could significantly shorten the action 50% and 90% potential duration (APD)50 and APD90 of ventricular muscle cell (P < 0.05 ), and high-dose of XAG could significantly increased the Vmax of MAP(P <0. 05). (2) While to ischemic rabbits, XAG could significantly prolong APD50 and APD90, and significantly increased the action potential amplitude (APA) and Vmax of MAP (P < 0. 05).

CONCLUSION(1) XAG can significantly shorten APD50 and APD90 of ventricular muscle cell, and high-dose XAG significantly increase the Vmax of MAP of normal rabbits. (2) XAG can delay and alleviate the manifestation characteristics of action potential of ventricular muscle cell during ischemia.

Action Potentials ; drug effects ; Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Electrocardiography ; Heart Ventricles ; cytology ; drug effects ; Medicine, Chinese Traditional ; Myocardial Ischemia ; physiopathology ; Myocytes, Cardiac ; drug effects ; physiology ; Rabbits

OBJECTIVETo explore the effect of plasma cross-linked D-dimer (XDP) and neuron-specific enolase (NSE) on the infarct volume and neurological function deficit in patients with cerebral infarction (CI).

METHODSPlasma XDP and NSE levels were measured in 66 CI patients on the different days after onset and also in 46 normal individuals, and the changes in XDP and NSE levels were analyzed in the CI patients with different infarct volume and neurological function deficit scores.

RESULTSWithin 48 h following CI onset, plasma XDP and NSE levels increased significantly (P<0.01) and reached the highest levels on day 5 (P<0.001), recovering the normal level till day 18. Plasma XDP and NSE levels were significantly higher in patients with moderate to large infarct volume and in those with moderate to severe neurological deficits than in those with small infarct volume and mild neurological deficits (P<0.001).

CONCLUSIONIncrement of XDP and NSE levels is an important pathological process in CI in close relation to the infarct volume and neurological deficits. XDP and NSE may serve as reliable indices for early diagnosis and evaluation of CI.

Aged ; Biomarkers ; Cerebral Infarction ; blood ; pathology ; Cross-Linking Reagents ; chemistry ; Female ; Fibrin Fibrinogen Degradation Products ; chemistry ; metabolism ; Humans ; Male ; Middle Aged ; Phosphopyruvate Hydratase ; blood