Objective To observe effect of lidocaine pretreatment to malondialdehyde(MDA) and endothelin(ET) of patient ac-cepeted brain tumor removing and discuss the optimized pretreatment time .Methods 60 brain tumor patients in the hospital from March 2009 to September 2011 .according to the different pretreatment time ,the patients were randomly divided into five groups :group A(preoperative 48 h) ,group B(preoperative 24 h) ,group C(preoperative 12 h) ,group D(0 h or anesthesia induced) ,group E (control group) and group F(blank control group) ,10 cases in each group .Group A ,B ,C ,D with 1% lidocaine 1 .5 mg/kg intrave-nous pretreatment on schedule ,then induced conventional anesthesia ;group E were supplemented with 1% lidocaine 2 .5 mg · kg -1 · h-1 intravenous injection after anesthesia induction ;group F was performed routine program without lidocaine .The spontaneous breathing time ,awake time and tracheal extubation time was recorded ,while NIHSS score for evaluation of neural function defect was applied ,and peripheral serum level of MDA and ET was detected by colorimetric technique and radio-immunity .Results In group C ,the spontaneous breathing time ,awake time and tracheal extubation time were shorter than other groups ,but the difference had no statistically significant(P>0 .05) .There was no significant difference among each group in the aspect of NIHSS score 1 day before surgery(P>0 .05) ,after 14 days of operation ,NIHSS of group C was statistically lower than that of group E and group F (P<0 .05) .Before anesthesia induction ,there was no significant difference among groups (P> 0 .05) .MDA and ET content in group C was significantly lower than those in other groups after surgery (P<0 .05) .Conclusion Lidocaine given 12 h before cere-bral ischemia has varying degree protection against cerebral ischemia-reperfusion injury .The protection has relation with the de-crease of MDA and ET content .

Objective To explore the effects and possible mechanism of calcium-sensing receptor(CaSR) in rat myocardial H9c2 cells hypertrophy model using angiotensin Ⅱ (Ang Ⅱ).Methods Cardiac hypertrophy model was established by treating cultured H9c2 cells with Ang Ⅱ in vitro.Hypertrophic H9c2 cells were treated with gadolinium chloride (GdCl3,a specific agonist of CaSR) and/or with Calhex231 (a specific inhibitor of CaSR) and 3-methyladenine (3-MA,a specific inhibitor of autophagy) to divided into 5 groups (six in each group):control,Ang Ⅱ,GdCl3 + Ang lⅡ,GdCl3 + Calhex231 + Ang Ⅱ,GdCl3 + 3-MA + Ang Ⅱ groups.To evaluate the status of H9c2 cells hypertrophy,protein content was determined through a coomassie brilliant blue protein kit and the expression of Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) and the phosphorylation form (pCaMK Ⅱ/CaMK Ⅱ) was analyzed by Western blotting.The protein expression of CaSR,autophagy maker [Beclin-1,micmtubule-associated protein 1 light chain 3(LC3)Ⅱ/LC3 Ⅰ,P62] and Ca2+/calmodulin-dependent-protein kinase-kinase-β (CaMKKβ)-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway was analyzed by Western blotting.Results ①GdCl3 further increased H9c2 cells protein content [control group:(2.52 ± 0.84) g/L,Ang Ⅱ group:(8.72 ± 3.60) g/L GdCl3 + Ang Ⅱ group:(14.17 ± 4.49) g/L,all P ＜ 0.05] and the expression of CaSR (control group:0.22 ± 0.04,Ang Ⅱ group:0.43 ± 0.02,GdCl3 + Ang Ⅱ group:0.63 ± 0.08,all P ＜ 0.05) and pCaMK Ⅱ/CaMKⅡ (control group:0.25 ± 0.05,AngⅡ group:0.51 ± 0.03,GdCl3 + AngⅡ group:0.77 ± 0.06,all P＜ 0.05) induced by Ang Ⅱ.Calhex231 suppressed the increasing of hypertrophy indicators induced by GdCl3 [GdCl3 + Calhex231 + AngⅡ group,CaSR:0.41 ± 0.16,protein content:(9.92 ± 2.54) g/L,pCaMK Ⅱ/CaMKⅡ:0.58 ± 0.08,all P ＜ 0.05].②GdCl3 promoted the effect of Ang Ⅱ in regulation of autophagy such as Beclin-1 protein increased (control group:0.31 ± 0.06,AngⅡ group:0.55 ± 0.09,GdCl3 + AngⅡ group:0.74 ± 0.08,all P ＜ 0.05),LC3 Ⅱ/LC3 Ⅰ increased (control group:0.28 ± 0.06,Ang Ⅱ group:0.56 ± 0.10,GdCl3 + Ang Ⅱ group:1.00 ± 0.15,all P ＜ 0.05) and P62 protein decreased (control group:0.54 ± 0.03,AngⅡ group:0.34 ± 0.02,GdCl3 + AngⅡ group:0.15 ± 0.03,all P ＜ 0.05).Moreover,Calhex231 suppressed autophagy induced by GdCl3 (GdCl3 + Calhex231 + Ang Ⅱ group,Beclin-1:0.53 ± 0.14,LC3 Ⅱ/LC3 Ⅰ:0.57 ± 0.12,P62:0.28 ± 0.05,all P ＜ 0.05).③GdCl3 increased pCaMKKβ/CaMKKβ (control group:0.43 ± 0.09,AngⅡ group:0.76 ± 0.12,GdCl3 + AngⅡ group:1.19 ± 0.21,all P ＜ 0.05),pAMPK/AMPK (control group:0.38 ± 0.11,AngⅡ group:0.68 ± 0.08,GdCl3 + AngⅡ group:1.18 ± 0.08,all P ＜ 0.05) and decreased pmTOR/mTOR (control group:0.90 ± 0.10,Ang Ⅱ group:0.54 ± 0.04,GdCl3 + AngⅡ group:0.29 ± 0.09,all P ＜ 0.05).Furthermore,Calhex231 blocked the effect of GdCl3 on the above-mentioned proteins changes (GdCl3 + Calhex231 + Ang Ⅱ group,pCaMKKβ/CaMKKβ:0.75 ± 0.06,pAMPK/AMPK:0.57 ± 0.05,pmTOR/mTOR:0.51 ± 0.08,all P ＜ 0.05).Conclusion Inhibiting calcium-sensing receptor expression has reversed H9c2 cell hypertrophy induced by Ang Ⅱ,which may be related to suppressing autophagy and suppressing CaMKKβ-AMPK-mTOR pathway.

Accidents ; statistics & numerical data ; Causality ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Risk Factors ; Rural Population ; Wounds and Injuries ; epidemiology

Female ; Humans ; Neoplasms ; physiopathology ; Thoracic Neoplasms ; pathology ; physiopathology ; Thoracic Wall ; pathology ; Young Adult

AIM:To explore the expression level of tristetraprolin(TTP)in rats after subarachnoid hemor-rhage(SAH)as well as the potential role of TTP in the early brain injury(EBI)after SAH in rats.METHODS:In the first experiment setting,total 56 adult male SD rats were randomly divided into sham group and SAH group.The SAH mod-el was performed by endovascular perforation.The brain tissues were taken out after SAH at 5 different time points(0,12, 24,48,72 h and 1 week).The expression of TTP in the brain tissues was detected by Western blot.In the second experi-ment,a total of 60 SD rats were divided into 4 groups: sham group, SAH group, SAH +vector group and SAH +TPP group.Neurological score,brain water content and blood-brain barrier were evaluated at 48 h after SAH.TUNEL staining was performed to detect cell apoptosis in the rat brain tissue.ELISA method was used for quantitative detection of interleu-kin-6(IL-6)and tumor necrosis factor-α(TNF-α).The protein levels of TTP,Bax,Bcl-2 and cleaved caspase-3 in the rat brain tissue were detected by Western blot.RESULTS:The protein expression of TTP in the brain was downregulated markedly from 12 h after SAH,reached the lowest level at 48 h,and then had an upward trend.After modeling for 48 h, Garcia neurological score was significantly reduced,and brain water content and Evans blue(EB)content of the brain tis-sue of the rats in SAH group were significantly higher than those in sham group(P<0.05).SAH induced significant in-creases in IL-6 and TNF-αlevels in the brain tissue(P<0.05).The number of TUNEL-stained cells was increased in the subcortical brain region after SAH compared with sham group.In addition,a lower level of Bcl-2 and higher levels of Bax and cleaved caspase-3 in the rat brains were observed at 48 h after SAH.However,the neurological deficit score was signif-icantly increased,and the brain water content and EB content in the rat brains were significantly reduced in SAH +TTP group in comparison with SAH +vector group(P<0.05).Over-expression of TTP dramatically suppressed the levels of IL-6 and TNF-αin the rat brains,and reduced the number of TUNEL positive cells.Furthermore,upregulation of TTP signifi-cantly decreased the levels of cleaved caspase-3 and Bax, and evidently enhanced the expression of Bcl-2(P<0.01). CONCLUSION:The expression of TTP is significantly decreased in early period after SAH, and enhancing the level of TTP effectively inhibits EBI following SAH in rats.

OBJECTIVEIn order to explore the risk factors of the papillary thyroid carcinoma(PTC), a hospital-based matched case-control study was carried out in Shanghai.

METHODSMatched by gender, age (+/- 3 years old) and native place,205 pairs of cases and controls were recruited and studied. Database was established with Epi Info 6.0 software. Univariate and multivariate conditional logistic regression analysis were carried out with SPSS 11.5 software.

RESULTSData from multivariate conditional logistic regression analysis showed that often drinking tea and having better economic living standard 20 years ago were protective factors of PTC, with ORs of 0.456 and 0.221 respectively. Personal history of CT examination, familial history of cancer and the mother's age was older than 22 years when the research subject was delivered, were risk factors of PTC, with ORs of 12.935, 7.027 and 3.729 respectively. Results data from multivariate analysis on female subjects showed that the history of CT examination, mother's age was older than 22 (when the subject was delivered) and the history of gynecological disease were the risk factors of PTC,with ORs of 107.453,29.246 and 59.521 respectively. Taking bean products frequently and having higher standard of living 20 years ago were the protective factors of PTC,with ORs of 0.025 and 0. 144 respectively.

CONCLUSIONHistory of CT examination, familial history of cancer and the mother's age(older than 22 when the subject was delivered) were the risk factors of PTC. Frequent tea drinking habit and having higher standard of living 20 years ago were the protective factors of PTC. History of CT examination,mother's age (older than 22 when the subject was delivered) and the history of gynecological disease appeared the risk factors of PTC for women. Habit on frequent bean products taking and had higher standard of living 20 years ago were the protective factors of PTC to women.

Carcinoma, Papillary ; epidemiology ; Case-Control Studies ; China ; epidemiology ; Diet ; Female ; Humans ; Male ; Risk Factors ; Social Class ; Thyroid Neoplasms ; epidemiology

OBJECTIVETo study the association of polymorphisms in the X-ray repair cross-complementing gene 1 (XRCC1) and papillary thyroid carcinoma (PTC).

METHODSA hospital based, matched case-control study was carried out. The polymorphisms in XRCC1 for 105 pairs of cases with PTC and controls were identified by PCR-RFLP.

RESULTSThe frequencies of Arg/Arg, Arg/Trp and Trp/Trp genotypes at XRCC1 Arg194Trp site were 47.6%, 49.5% and 2.9% among cases compared to 45.7%, 48.6% and 5.7% among controls. There was no statistically significant difference between the two groups (chi(2) = 1.07, P = 0.59). The frequencies of Arg/Arg, Arg/Gln and Gln/Gln genotypes at XRCC1 Arg399Gln site were 46.7%, 41.9% and 11.4% among cases, while 54.2%, 42.9% and 2.9% among controls respectively. There was statistically significant difference between the two groups (chi(2) = 6.40, P = 0.04). Individuals with Gln/Gln genotype had a 3.65-fold increased risk of developing PTC compared to Arg/Arg genotype (OR = 4.65, 95% CI: 1.24 - 17.45). The multivariate conditional logistic regression analysis showed that the XRCC1 Arg399Gln polymorphism, negative life events and X-irradiation history were associated with PTC, with odds ratios of 2.71 (95% CI: 1.22 - 6.05), 5.34 (95% CI: 1.40 - 20.38) and 0.38 (95% CI: 0.12 - 0.72) respectively. However, XRCC1 Arg194Trp polymorphism, drinking tea, fruit and economic levels did not show statistically significant associations with PTC.

CONCLUSIONThe Gln/Gln genotype at XRCC1 Arg399Gln site and negative life events significantly increased while X-irradiation history decreased the risk of developing PTC.

Adult ; Carcinoma, Papillary ; etiology ; genetics ; Case-Control Studies ; DNA Repair ; genetics ; DNA, Neoplasm ; genetics ; DNA-Binding Proteins ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Thyroid Neoplasms ; etiology ; genetics ; X-ray Repair Cross Complementing Protein 1

Many antineoplastic agents can cause myelosuppression and thrombocytopenia. Thrombopoietin (TPO) is believed to be the major cytokine affecting the proliferation and maturation of megakaryocytes and increasing circulating platelet levels. We have designed and synthesized a TPO mimetic peptide, it can increase circulating platelet levels in vivo. For increasing half-life and forming dimer, the peptide was expressed as chimeric proteins with human IgG1 Fc fragments. The cDNA of TPO mimetic peptide was synthesized chemically and linked respectively to 5' terminus of human IgG1 Fc cDNA fragments in various length (Fc1: Fc 5' 648 bp; Fc2: Fc 5' 270 bp; Fc3: Fc 5' 267 bp; Fc4: Fc 5' 90 bp), and cloned into expression plasmid pET28a (+) for constructing four recombinant plasmids. By transforming the four recombinant plasmids into E. coli. BL21 (DE3) respectively, we got 3 kinds of engineered E. coli which express TPO + Fc chimeric proteins(28 kD TPO + Fc1, 12 kD TPO + Fc2 and 12 kD TPO + Fc3) at high level respectively, the expressed proteins were purified with DEAE-Sepharose FF and S-Sepharose FF column. The bioactivities of the expressed chimeric proteins(TPO + Fc1, TPO + Fc2 and TPO + Fc3), TPO mimetic peptide, and PEG4000 coupled TPO mimetic peptide were evaluated with Ba/F3-mp1 in vitro and with carboplatin-induced thrombocytopenia mice in vivo, the expressed chimeric proteins have higher activity than TPO mimetic peptide both in vitro and in vivo, the EC50 on Ba/F3-mp1 cells were 13, 10, 10, 50, and 25 nmol/L respectively, all of them can increase circulating platelet counts. Their imol/Lunogenicity were valuated in mice, none of them can elicit mice to produce antibodies to TPO mimetic peptide, meanwhile three TPO + Fc chimeric proteins can elicit mice to produce antibodies to human IgG1 Fc. These studies have laid basis for production of TPO mimetic peptide by genetic engineering.
Animals ; Base Sequence ; Blood Platelets ; drug effects ; Cell Division ; drug effects ; Female ; Humans ; Immunoglobulin Fc Fragments ; genetics ; immunology ; pharmacology ; Immunoglobulin G ; genetics ; Male ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Oligopeptides ; chemical synthesis ; genetics ; pharmacology ; Recombinant Fusion Proteins ; genetics ; immunology ; pharmacology ; Thrombocytopenia ; blood ; immunology ; Thrombopoietin ; genetics ; immunology ; pharmacology

OBJECTIVETo observe the effect of Chinese herbal compound on variance of neurotransmitters in rat telencephalon and to further discuss the mechanism underlying Chinese herbal compound in improving exercise capacity and promoting recovery from exercise-induced fatigue.

METHODS64 rats (8 week old) were randomly divided into medicine group (MG) and control group (CG). Chinese herbal compound was administered to rats of MG for 8 weeks. 8 weeks later, every group was divided into 4 subgroups and all were killed at different time point separately, and then neurotransmitter in rat brain was tested.

RESULTSThe exhaustion time of MG was significantly longer than that in CG (P < 0.01). In rest conditions, glutamic acid (GLU) of MG was significantly higher than that in CG (P < 0.01), while, there were no significant differences between MG and CG in other indexes. After fixed quantitative load exercise, the content of 5-hydroxytryptamineZZ(5-HT), 5-hydroindole acetic (5-HIAA), gamma-aminobutyric acid (GABA), Dopamine (DA) and 5-HT/5-HIAA were significantly lower than those in CG, while, GLU, GLU/GABA and DA/5-HT were significantly higher than those in CG. Compared with CG, exhaustion significantly (P < 0.05) decreased 5-HT, GABA and 5-HT/5-HIAA, and significantly (P<0.05) increased GLU, DA/5-HT and GLU/GABA level in MG. 12 h after exhaustion, in contrast to CG, level of 5-HT and 5-HT/5-HIAA in MG were significantly (P < 0.01) lower while GLU, DA, GABA and DA/5-HT were significantly (P < 0.01) higher.

CONCLUSIONDuring exhaustion exercise, Chinese herbal compound demonstrated strong inhibiting effect on synthesis of 5-HT, 5-HIAA, DA, GABA and promoting effect on GLU synthesis, this had been confirmed by the combined effect, including increase of excitatory transmitter and excitability of central nervous system and the prolongation of exhaustion time and promoting recovery from fatigue.

Amino Acids ; metabolism ; Animals ; Biogenic Monoamines ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Fatigue ; metabolism ; physiopathology ; Hydroxyindoleacetic Acid ; metabolism ; Male ; Neurons ; metabolism ; Physical Conditioning, Animal ; physiology ; Physical Exertion ; physiology ; Rats ; Rats, Wistar ; Serotonin ; metabolism ; Telencephalon ; drug effects ; metabolism

BACKGROUND: The perioperative hemorrhage of knee surgeries is a difficulty in clinic, and the efficacy of tranexamic acid to reduce postoperative bleeding has attracted more attention, but choosing which administrations remains controversial. OBJECTIVE: To investigate the efficacy of tranexamic acid by intravenous injection or articular injection for reducing the perioperative hemorrhage of total knee arthroplasty. METHODS: Sixty patients undergoing unilateral total knee replacement were enrolled, and were then randomized into three groups (n=20 per group): no tranexamic acid administration (group A); intravenous dropping of 15 mg/kg tranexamic acid before tourniquet application plus 10 mg/kg tranexamic acid at 3 hours postoperatively (group B); articular injection of 50 mL saline diluted with 1 g tranexamic acid through a drainage tube (group C). Two-hour closure of drainage tube was performed in all patients. The postoperative dominant and hidden blood loss, blood transfusion rate, pulmonary embolism as well as lower extremity deep venous thrombosis were recorded. RESULTS AND CONCLUSION: (1) The dominant and hidden blood loss in the groups B and C were significantly less than those in the group A (P < 0.05); the dominant blood loss showed no significant difference between groups B and C (P > 0.05); the group B exhibited a significantly less hidden blood loss compared with group C (P < 0.05). (2) The blood transfusion rate in the groups B and C was significantly lower than that in the group A (P < 0.05). (3) No pulmonary embolism or lower extremity deep venous embolism occurred during 3-month follow-up. (4) That is to say, tranexamic acid can obviously reduce perioperative blood loss and blood transfusion rate without pulmonary embolism or lower extremity deep venous thrombosis, and intravenous administration exerts better clinical effectiveness.