Objective To investigate the relationship between V-raf murine sarcoma viral oncogene homolog B1 (BRAF)v600E mutation and radioactive iodine (RAI) uptake in distant metastases from papillary thyroid cancer(PTC).Methods From January 2011 to December 2012,40 PTC patients (21 males,19 females,average age 39.8 years) with distant metastases were recruited and divided into mutation group and wild group according to the BRAFv600E mutation in primary lesions.The clinical,pathological and serological differences were compared between the two groups.The relationship between BRAFv600E mutation and RAI uptake capability in distant metastases from PTC,as well as its relationship with Tg change after 131I treatment were investigated.Statistical analysis was performed with two-sample t test,x2 test or Fisher exact test.Results The BRAFv600E mutation rate was 30.0％ (12/40) in patients with metastases from PTC.There was no significant difference in clinical,pathological and serological features between mutation group (n =12) and wild group (n=28; t:from-0.533 to 1.728,x2:from-1.951 to 1.088,all P＞0.05).Twelve PTC patients had no RAI uptake in the distant metastases,of which 10 belonged to mutation group (83.3％,10/12) and 2 belonged to wild group (7.1％,2/28; x2=19.734,P＜0.05).BRAFv600E mutation group was more likely to have no RAI uptake in the distant metastases.Tg change after 131I treatment in 30 patients were analyzed.In the wild group,Tg level decreased in 66.7％ (14/21) patients,stabilized in 19.0％ (4/21)and increased in 14.3％ (3/21)patients.While there was no decrease of Tg in the mutation group (0/9).Two patients had increased Tg level and 7 patients (with no RAI uptake) kept stable in mutation group.Conclusions Due to poor RAI uptake capability in PTC patients with BRAFv600E mutation,both primary and metastatic sites may have poor response to 131I treatment.Molecular detection of BRAFv600E mutation might be helpful for choosing PTC with distant metastases and predicting the effect of 131 I treatment.

BACKGROUND:Valgus-varus constrained polyethylene insert is selected in strict accordance with the principle of“to obtain reliable stability using minimum restriction”. The stability of the prosthesis is elevated, but the restriction is not increased.
OBJECTIVE:To retrospectively analyze the application experience of constrained polyethylene insert in valgus and varus instability of primary total knee arthroplasty for older patients and to summarize the indications and clinical effects of this kind of implements.
METHODS:From March 2010 to March 2012, a total of 70 patients combined valgus and varus malfomation who accepted primary total knee arthroplasty were enrol ed in this study, including 56 varus patients (averagely 15°-30°) and 14 valgus patients (averagely 10°-20°). Constrained polyethylene insert was performed in 23 patients (25 knees) who stil had remaining unilateral valgus or varus<6 mm (18 patients were varus instability and 7 patients were valgus instability) when finished operation of standard osteotomy and soft tissue balancing. The bone cement knee prostheses in 23 cases were purchased from Smith&Nephew. The stem implant was not used in al cases. Cement or autografts were used in 11 valgus knees to fil the bone defects.
RESULTS AND CONCLUSION:Patients were fol owed up for 2 years on average (18-42 mouths). The knee pain symptoms of al cases disappeared. The joint stability was obviously improved. The lower limb power lines were correct. The Knee Society Score scores were improved from an average of 39.4 points preoperation to an average of 88.5 points postoperation. Al cases did not need the protection of knee braces. The maximum degree of flexion was 110°(96°-130°). The satisfaction degree of 36-Item Short Form Health Survey was 98%. No dislocation or infection happened. Results indicated that constrained polyethylene insert could be applied in the cases of less than 6 mm valgus and varus instability when finished operation of standard osteotomy and soft tissue balancing in total knee arthroplasty for older patients. This kind of implements can preserve bone mass, simplify operational process and have good clinical outcome in a short period.

Objective To investigate the change of serum Tg levels of DTC patients with positive stimulated Tg (Tg ≥ 10.00 μg/L),negative 131I-diagnostic whole body scan(Dx-WBS) and no distant metastasis 6 months after initial 131I therapy.Methods Fifty-six DTC patients (20 males,36 females,average age 43.11 (21-70) y) with intermediate or low risk of recurrence according to American Thyroid Association (ATA) guideline were enrolled into the retrospective study.All patients were grouped according to stimulated Tg level after initial 131I therapy:group with positive Tg (Tg+ group,n =19) and group with negative Tg (Tgˉ group,n=37).Changes of suppressed Tg at 1 year and 2.5 years (Tg1ysup and Tg2.5ysup) after initial therapy were compared between the two groups.Serum TSH level,TgAb level,neck ultrasound and chest CT results were also evaluated.The two-sample t test and x2 test were used for statistical analysis with SPSS 17.0.Results Stimulated Tg and Tglysup levels in Tg+ group were remarkably higher than those in Tgˉ group:(24.27±4.10) μg/L vs (2.73±3.01) μg/L,t=7.191,P＜0.05(6 months after initial 131I therapy) ; (2.21±0.55) vs (0.48±0.10) μg/L,t=3.102,P＜0.05(1 year after initial 131I therapy),respectively.In Tg+ group,suppressed Tg level decreased with time in 68.4％ (13/19) of patients,of whom the Tg2.5ysup level was much lower than Tglysup level ((0.53±0.15) μg/L vs (1.38±0.50) μg/L).Tg2.5sup level in Tg+ group became comparable to that in Tgˉ group ((1.44±0.52) μg/L vs (0.38±0.07) μg/L; t =2.001,P＞0.05).In each group,one case of recurrence with suppressed Tg of 1.4 μg/L and 0.1 μg/L respectively,was observed using neck ultrasound after 2 years of follow-up.Conclusions Serum Tg levels decreased with time for Tg+/131I-Dx-WBS-DTC patients with intermediate or low risk of recurrence.It might not be necessary to follow up these patients with Tg and 131 I-DxWBS after 6 months of initial 131I therapy.

OBJECTIVEto investigate the changes of γ-aminobutyric acid (GABA) and glutamate (Glu) in the cerebral cortex following acute bromoxynil intoxication in mice and the protective effect of sodium dimercaptopropane sulfonate (Na-DMPS).

METHODS30 ICR mice were randomly divided into blank control group (10), exposure group (10) and Na-DMPS protection group (10). The levels of GABA and Glu in the cerebral cortex were measured by RP-HPLC. The glutamine (Gln) level and the glutamine synthetase (GS), glutamate decarboxylation enzyme (GAD), γ-aminobutyric acid transaminase (GABA-T) activity in the cerebral cortex were determined by UV colorimetric.

RESULTScompared with the control group [GABA: (3.41 ± 0.12) micromol/g, Glu (14.00 ± 0.16) micromol/g, Gln (1.25 ± 0.19) micromol/g, GAD (13.50 ± 0.25) micromol × g(-1) × h(-1), GABA-T (25.51 ± 0.21) micromol × g(-1) × h(-1), GS(142.19 ± 1.31) U/mg pro], the level of GABA [(3.14 ± 0.14) micromol/g] was decreased (P < 0.05), whereas the level of Glu [(17.54 ± 0.40) micromol/g] and Gln [(3.35 ± 0.27) micromol/g] were increased (P < 0.05), the activity of GAD [(11.93 ± 0.15 micromol × g(-1) × h(-1)], GABA-T [(24.15 ± 0.22) micromol × g(-1) × h(-1)], GS [(140.75 ± 1.01) U/mg pro] was decreased (P < 0.05) in acute intoxication group; Compared with the acute intoxication group, the level of GABA [(3.52 ± 0.30) micromol/g] was increased (P < 0.05), whereas the level of Glu [(14.20 ± 0.32) micromol/g] and Gln [(1.32 ± 0.17) micromol/g] were decreased (P < 0.05), the activity of GAD [(13.01 ± 0.45 micromol × g(-1) × h(-1)], GABA-T [(25.19 ± 0.26) micromol × g(-1) × h(-1), GS [(142.35 ± 1.20) U/mg pro] was increased (P < 0.05); In contrast, the levels of GABA, Glu, Gln and the activity of GAD, GABA-T, and GS in Na-DMPS protection group were not significantly different in comparison with control group (P > 0.05).

CONCLUSIONthe central toxic effects of mice with acute bromoxynil intoxication may be related to the changes of GABA and Glu content in the cerebral cortex;Na-DMPS can protect mice from bromoxynil-induced central toxic effects and GABA and Glu abnormal change in the cerebral cortex.

Animals ; Cerebral Cortex ; drug effects ; metabolism ; Female ; Glutamic Acid ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Nitriles ; poisoning ; Toxicity Tests, Acute ; Unithiol ; pharmacology ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo analyze alterations in the gene expression profiles of Velcade-treated K562 cells using bioinformatics methods.

METHODSThe total RNAs of Velcade-treated and control K562 cells were amplified and labeled with fluorescent dyes. The labeled RNAs were hybridized to Agilent Human 1A Microarray, and the raw expression data were processed with Agilent Feature Extraction Software. GeneSifter and GATHER were used for data analysis of the differentially expressed genes to perform gene ontology classification, KEGG pathway analysis, functional protein association network construction and literature mining.

RESULTSTotally 228 differentially expressed genes were identified in the Velcade-treated K562 cells. including 84 up-regulated and 144 down-regulated genes. Chymase 1 gene had the greatest down-regulation by 10.80 folds (log ratio), and interferon alpha-21 gene was also down-regulated by 2.31 folds. Gene ontology classification suggested enhanced aging and leukocyte activity. KEGG pathway analysis showed significant impact of Velcade on JAK-STAT signaling pathway, cytotoxicity mediated by natural killer cells, and antigen processing and presentation pathways. Protein-protein interaction analysis revealed that ubiquitin-dependent protein catabolism, antigen presentation and immune response, as well as JAK-STAT signaling pathway were the major elements of the protein network. Literature mining showed that the differentially expressed genes were strongly associated with terms such as leukemia, apoptosis, cell cycle, proteasome, inhibitor, aging and IkappaB, etc.

CONCLUSIONSVelcade may inhibit the cell survival pathways such as NF-kappaB and JAK-STAT signaling pathways to enhance the cytotoxicity and inducing tumor cell apoptosis. Velcade might also be involved in antigen processing and presentation, immune response and inflammation. Chymase 1 gene is probably the key target of Velcade.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Chymases ; genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; K562 Cells ; Oligonucleotide Array Sequence Analysis ; methods ; Pyrazines ; pharmacology

AIMTo study the preparation conditions and its oral pharmacokinetic characteristics of cyclosporine A (CyA) pH sensitive nanoparticles.

METHODSThe CyA pH sensitive nanoparticles were prepared by the quasi-emulsion solvent diffusion technique (QESD). Male Sprague-Dawley (SD) rats weighing (250 +/- 20) g were selected and randomly divided into five groups. The bioavailability of CyA from nanoparticles and Neoral microemulsion were assessed at a dose of 15 mg x kg(-1) by gavage. The concentration of CyA in whole blood samples was detected by HPLC to evaluate the relative bioavailability of CyA pH sensitive nanoparticles.

RESULTSThe blood concentration profiles of CyA pH sensitive nanoparticles in rats fitted to two compartment models using 3P87 pharmacokinetic calculation program. Compared with the Neoral microemulsion, the relative bioavailability of CyA was 94.8%, 115.2%, 113.6% and 132.5% for CyA-E100, CyA-L100, CyA-L100-55 and CyA-S100 nanoparticles respectively.

CONCLUSIONCyA-S100 nanoparticles was shown to significantly improve the oral bioavailability of CyA compared with Neoral microemulsion (P < 0.05). While there were no significant differences between Neoral microemulsion and other CyA pH sensitive nanoparticles. With these results, the potential of pH-sensitive nanoparticles for the oral delivery of CyA was confirmed. Furthermore, this formulation approach can be used to improve the oral bioavailability of other poorly soluble and poorly absorbable drugs.

Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; Hydrogen-Ion Concentration ; Male ; Nanostructures ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective To investigate the relation between 25-hydroxyvitamin D3[25(OH)D3] and coronary artery disease. Methods Three hundred and ten patients with selective coronary angiogram (CAG) were enrolled in this study and they were divided into two groups: non-coronary artery stenosis group with 76 patients and coronary artery stenosis group with 234 patients. The degree of coronary artery stenosis was evaluated by the international general Gensini integration system. The levels of fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C) were detected by automatic biochemistry analyzer. The level of 25(OH)D3 was detected by tandem mass spectrometry. The relationship of Gensini integration scores and risk factors were analyzed. Logistic regression analysis was used in multicity factors analysis. Results The levels of age, Gensini integration scores, 25(OH)D3, FPG and LDL-C in non-coronary artery stenosis group and coronary artery stenosis group had significant differences (P<0.05). The number of coronary stenosis and Gensini integration scores in 25(OH) D3 deficiency group were significantly higher than those in non-25 (OH)D3 deficiency group (P<0.01). Logistic regression analysis showed that age, FPG and 25(OH)D3 levels were risk factors for coronary artery stenosis (P<0.01 or<0.05), and the level of 25(OH)D3 had negative correlation with coronary artery stenosis (B =- 0.100), and it was a protection factor (OR =0.904, 95%CI:0.911-0.983, P=0.000). Conclusions 25(OH)D3 deficiency is one of the risk factor of coronary artery disease.

Objective To compare the different effects of 1% diatrizoate meglumine,2.5% mannitol and water as oral contrasts in PET/CT scan in gastrointestinal tract delineation and 18F-fluorodeoxyglucose (FDG) uptake. Methods Sixty-one patients referred for PET/CT scan without gastrointestinal diseases were divided into three groups randomly ( random number method). One liter of 1% diatrizoate meglumine,2.5% mannitol,or water was orally taken by groups 1 (25 cases),2 (20 cases) and 3 ( 16 cases),respectively before scan. The scan was performed with GE Discovery LS PET/CT scanner in two-dimensional (2D) mode 50 min after 18F-FDG (5.55 MBq/kg) injection. Patients with abdominal lesions were excluded from this study. The degree of gastrointestinal filling and 18F-FDG uptake was evaluated by 3 nuclear medicine physicians using visual analysis according to a 4-grade classification method:none,mild,moderate,and high. Statistically analysis was performed by Kruskal-Wallis,Mann-Whitney and paired t tests.Results Both the differences of serum glucose and insulin levels were not significant before and after contrast taken in group 2. Group 2 had better gastrointestinal filling than that of group 1 and also better than group 3 except in rectum. The stomach,jejunum,ascending,and transverse colon were better filled in group 1 than in group 3. The degree of 18F-FDG uptake of group 3 was significantly higher than that of group 2 in stomach,jejunum and ileum (z= -3. 192,-3.290,-3.290,all P＜0.05),and was also significantly higher than that of group 1 (z = - 3. 603,P ＜ 0.05) in jejunum. The degree of 18 F-FDG uptake of group 3 was significantly lower than that of group 1 in ascending colon (z = - 2. 706,P ＜ 0. 05 ) and was significantly lower than that of group 1 and 2 in transverse and descending colon (z= - 3. 503,- 2.403,- 4.225,-4. 027,all P ＜0.05),and was also significantly lower than that of group 2 in rectum (z = -4. 128,P ＜0. 01 ). The maximum CT values in stomach,jejunum,ileum and ascending colon in group 1 were ( 132 ±23),(191 ±31),(313 ±47) and (374±53) HU,respectively,whose difference was significant (t = -7.088--1.781,all P ＜0. 01 ). Conclusion Oral iso-osmotic mannitol intake has better gastrointestinal filling and less physiological 18F-FDG uptake compared to diatrizoate meglumine and water.

To explore influence of platelet donation on donor's megakaryocytopoiesis, platelet counts and plasma concentrations of thrombopoietin (TPO), interleukin-3 (IL-3), IL-6 and nitric oxide (NO) were determined in 42 frequent platelet donors (undergoing plateletpheresis more than once a month for 24 months and their mean platelet yield of collection was 2.5 x 10(11)), in 62 limited platelet donors (undergoing plateletpheresis less than once a month for 24 months) after a donation-free period of > 5 weeks and in 40 whole blood donors who never undergoing plateletpheresis after a donation-free period of > 6 months. The results showed that the TPO levels was significantly lower in frequent platelet donors than in limited platelet donors (P < 0.01) and whole blood donors (P < 0.01). There were no significant differences between three groups in platelet counts, IL-3, IL-6 and NO. These findings suggest that the number of megakarocytes significantly increased in frequent platelet donors.
Adult ; Blood Donors ; Humans ; Interleukin-3 ; blood ; Interleukin-6 ; blood ; Megakaryocytes ; cytology ; Platelet Count ; Plateletpheresis ; adverse effects ; Thrombopoiesis ; Thrombopoietin ; blood

Objective:To explore the category,prevalence and related factors of comorbidities associated with Tourette syndrome.Methods:125 patients with TS according to CCMD-3(Chinese Classification of Mental Disorders,3rd edition)were assessed with a self-designed family circumstance questionnaire,YGTSS,CBCL,Leyton obsessive-compulsive scale,and Conner's Child Behavior Checklist.Results:Of 125 TS patients,the comorbidities included attention deficit and hyperactivity disorder(ADHD,41.6%),obsessive-compulsive disorder(OCD,25.6%), anxiety disorders(8.0%),depressive disorders(4.8%),conduct disorders(8.0%),self-injurious behavior(3.2%),and sleep disorder(2.4%).Conclusion:There are many kinds of comorbid disorders at high prevalence in TS patients. These comorbidities adversely influence the therapy and prognosis of TS and are taken as the possible reasons for social function deficit.