Objective： To discover HER2/neu tyrosine kinase inhibitor through computer-aided drug design approach. Methods： The three-dimensional(3D) structure of HER2/neu and EGFR tyrosine kinase domain was modeled using MODERLAR software. To search database and pick up candidate compounds based 3D structure of HER2/neu tyrosine kinase domain. Inhibition of HER2/neu tyrosine kinase phosphorylation by the compounds was detected using Western blot analysis. Inhibition of cell proliferation was determined by MTT assay. Results： The amino acid identity and similarity between HER2/neu and EGFR kinase domain, insulin receptor kinase domain, FGFR1 kinase domain, Src kinase domain were compared. The identity was 35％ -41％ and the similarity was 52％ -55％ . The 3D structure of HER2/neu and EGFR was obtained by MODERLAR software. Through searching, screening and optimization, the authors found that ST2325 had significantly inhibitory effect on HER2/neu tyrosine kinase phosphorylation with IC50 of 6.6 μ mol/L. The inhibition of HER2/neu phosphorylation was selective and reversible. ST2325 inhibited cell proliferation of HER2/neu-overexpressing MDA-MB-453m1 preferentially compared with EGFR-overexpressing MDA- MB-468, The IC50 values were 29.05 and 60.4 μ mol/L. Conclusion： ST2325 which was discovered through structure-based approach had notable inhibitory effect on HER2/neu tyrosine kinase.

OBJECTIVETo analyze the mechanics of distalizating lower cuspid with the light-segmented archwire.

METHODSAn experiment, which imitated the loading of distalizating lower cuspid with the light-segmented archwire, was performed on the three-dimensional finite element method model of lower cuspid. The patterns of stress distribution of the root were analyzed.

RESULTSUnder the loading of the light-segmented archwire, the lower cuspid root presented an even pressing force distribution on the distal and lingual side and an even stretching force distribution on the mesial and buccal side.

CONCLUSIONSThe light-segmented archwire would lead to bodily movement of the cuspid.

Cuspid ; physiopathology ; Dental Stress Analysis ; Finite Element Analysis ; Humans ; Orthodontic Wires ; Tooth Movement Techniques ; methods

OBJECTIVEThe aim of this study is to investigate the changes of hard tissue profile in anterior-posterior and vertical direction in bimaxillary protrusion patients after orthodontic treatment.

METHODSA total of 24 bimaxillary protrusion patients (male 8, female 16), aged from 11.2 to 29.0 (average 16.9 years old), were selected to be treated with standard edgewise technique consisted of 4 first premolars extraction. Cephalometrics were taken before and after treatment. The changes of hard tissue profile were studied using the computer-aid X-ray cephalometric analysis.

RESULTS1. The length of the maxillary and the mandible increased significantly, but the anterior-posterior relationship of the maxillary and the mandible did not change significantly. 2. The anterior and posterior facial height increased significantly, but the ratio of anterior and posterior facial height and the angle of MP-FH which reflected the inclination of the mandible plane did not change significantly. 3. The height of the upper and lower first molar increased significantly along with the increase of the anterior and posterior facial height. 4. The height of the upper incisors increased significantly, but the height of the lower incisors decreased significantly.

CONCLUSIONThe anchorage in anterior-posterior and vertical direction were controlled preferably, the patients did not manifest disadvantageous vertical growth trend.

Adolescent ; Adult ; Cephalometry ; Child ; Facial Bones ; pathology ; Female ; Humans ; Male ; Orthodontic Wires ; Orthodontics, Corrective ; Prognathism ; therapy ; Skull ; pathology

OBJECTIVETo compare the application of HE and enzyme histochemical staining in assessing the viability of hepatocellular carcinoma (HCC) cells coagulated by microwave ablation at different temperatures.

METHODSTwo groups of mice (n=6) with transplanted homogenic HCC were treated by microwave ablation at 60 degrees C and 50 degrees C for 3 min, respectively. Before and after microwave ablation, paraffin sections and frozen sections of the tumors were prepared for routine HE staining and enzyme histochemical staining with nicotinamide adenine dinucleotide diaphorase (NADH-diaphorase), respectively, and observed under microscope.

RESULTSShortly after microwave ablation, the morphology and arrangements of the nucleus of the ablated tumor cells in the two groups showed no obvious alteration in HE stained sections, but in sections with enzyme histochemical staining, the activity of NADH-diaphorase in ablated tumor tissue at 60 degrees C disappeared, suggesting the death of HCC cells; sporadic activity of the enzyme was detected in the coagulated tumor at 50 degrees C, indicating tumor cells surviving the ablation. The ablation effect was markedly different between the two groups (P<0.01).

CONCLUSIONHE staining is not suitable for evaluation of HCC destruction immediately after microwave ablation, and detection of NADH-diaphorase activity with the enzyme histochemical method better suits this purpose.

Animals ; Catheter Ablation ; methods ; Dihydrolipoamide Dehydrogenase ; metabolism ; Female ; Histocytochemistry ; methods ; Liver Neoplasms ; enzymology ; pathology ; therapy ; Liver Neoplasms, Experimental ; enzymology ; pathology ; therapy ; Mice ; Mice, Inbred C57BL ; Microwaves ; therapeutic use ; Temperature

OBJECTIVETo explore the mutations of 15 short tandem repeat (STR) loci in PlowerPlex16 System which are world-widely used in parentage testing.

METHODSMutations of 15 STR loci in PlowerPlex16 System were investigated in 1921 parentage testing cases from Chinese population.

RESULTSIn 1921 parentage cases, seventy cases (3.644%) were found to have mutations. Among these were one case with double mutations (D21S11 and PentaD) and another case with two different mutations (D7S820 and D16S539) in two children. The total number of mutated STR loci observed was 72 over 3764 meiosis with a mutation rate of 0.128% +/- 0.1104% x 10(-3). The highest mutation rate was 0.292% at vWA and D21S11. No mutation was observed at TH01 or at TPOX. The mutated alleles coming from father were five times more than those from mother. The majority (98.611%) of mutated alleles were the results of one-step mutation. The ratio of one-step gain versus loss was 1.826:1. There was only one multiple-step mutation with a double-repeat gain observed at PentaD locus. In the PlowerPlex16 System, nine loci, namely D8S1179, Penta D, D13S317, D16S539, D7S820, D5S818, D3S1358, TH01 and TPOX, have lower mutation rates and are more suitable for parentage testing.

CONCLUSIONMutation of STR is relatively common and often makes parentage testing more complicated. Selecting stable STR locus with low mutation rate is more important in parentage testing.

Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Genetics, Population ; Humans ; Microsatellite Repeats ; genetics ; Mutation ; Polymerase Chain Reaction

BACKGROUNDNeovascular glaucoma (NVG) is a refractory disease which is difficult to manage. This study aimed at evaluating the efficacy and safety of adjunctive intravitreal bevacizumab (IVB) injection in conjunction with Ahmed glaucoma valve implantation (AGVI) in the management of NVG.

METHODSThis was a retrospective study of patients with NVG in whom AGVI was performed between October 2008 and May 2012. The sample was divided into two groups according to the pretreatment: with adjunctive IVB injection (the IVB group, n = 25 eyes) and without adjunctive IVB injection (the control group, n = 28 eyes). The surgical success rate, number of antiglaucoma medications used, best-corrected visual acuity (BCVA), postoperative complications, regression, and recurrence of iris neovascularization (NVI) were analyzed between the groups.

RESULTSThe surgical outcomes of the two groups were compared. The complete success rates in the IVB and control groups were 84.0% and 64.3% at 12 months and 80.0% and 53.6% at 18 months, respectively. There was a significant difference between the two groups (P = 0.041). Mean postoperative intraocular pressures, mean number of postoperative antiglaucoma medications, and BCVA were not significant between the two groups. The NVI in 22 (88.0%) eyes had completely regressed within 2 - 8 days after IVB. However, NVI recurred in 10 eyes (40.0%) 2 - 9 months later after IVB. The IVB group had only 1 case (4.0%) of hyphema out of 25 eyes, while there were 8 (28.6%) cases of hyphema out of 28 eyes in the control group (P = 0.026).

CONCLUSIONSThis study showed that preoperative IVB injection reduced NVI remarkably, decreased hyphema, and led to higher surgical success rates. Pre-operative IVB injection may be an effective adjunct to AGVI in the management of NVG.

Adult ; Aged ; Angiogenesis Inhibitors ; administration & dosage ; Antibodies, Monoclonal, Humanized ; administration & dosage ; Bevacizumab ; Female ; Glaucoma Drainage Implants ; adverse effects ; Glaucoma, Neovascular ; therapy ; Humans ; Intraocular Pressure ; Intravitreal Injections ; Male ; Middle Aged ; Prosthesis Implantation ; methods ; Retrospective Studies ; Visual Acuity

OBJECTIVE: To explore the distribution and genetic pattern of heteroplasmy of mtDNA control region among Chinese Han population. METHODS: The human mtDNA control region was amplified into 6 amplicons overlapped partially each other. Then these amplicons were analyzed by DHPLC which we developed to detect low heteroplasmic signals. RESULTS: There were 51 heteroplasmic cases (34%) found from different tissues of 150 unrelated individuals of the Chinese Han population. mtDNA heteroplasmy shows non-uniform distribution in various tissues. The highest occurrence of heteroplasmy was in brain tissues (50/150) and myocardium (48/150), the lowest was in bone tissues (22/150). 36 sites of heteroplasmy were identified in our samples. Three sites of mtDNA heteroplasmy rarely co-existed in one individual. No sex differences were detected in the frequency of mtDNA heteroplasmy. No change in the mtDNA heteroplasmy profile was detected of blood samples from the same individuals within 2 years. Individuals older than 41 years showed a heteroplasmy frequency significantly higher than their younger counterparts. Members from the same maternal pedigree in a family can share the same sites of mtDNA heteroplasmy but may have different heteroplasmy contents at those sites. CONCLUSION DHPLC is a highly sensitive technique in detecting heteroplasmy. mtDNA heteroplasmy widely exists in the Chinese Han population. The results shown here could potentially have a guidable value in forensic individual identification and parentage testing.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian People/genetics* ; Base Sequence ; Blood Stains ; Child ; China/ethnology* ; Chromatography, High Pressure Liquid/methods* ; DNA Mutational Analysis/methods* ; DNA, Mitochondrial/genetics* ; Genetic Heterogeneity ; Hair/chemistry* ; Humans ; Middle Aged ; Mutation ; Polymorphism, Genetic/genetics* ; Young Adult

OBJECTIVE: To investigate the changes of collagen fibers and the expression of osteopontin in the left ventricle in cases of hypertrophic cardiomyopathy (HCM), along with the significance of their potential forensic application. METHODS: Fifteen cases of HCM, 15 cases of coronary heart disease with cardiac hypertrophy and 20 cases of traffic accidents were selected as HCM group, coronary heart disease group and control group, respectively. Collagen volume fraction and osteopontin expression were observed and compared by HE staining, Masson trichrome staining and immunohistochemistry methods. Imaging and statistical methods were used for quantitative analysis. RESULTS: Collagen volume fraction in left ventricle of HCM and coronary heart disease were significantly higher than that in the control group (P < 0.05), which was not significantly different between the HCM group and the coronary heart disease group. The integral light density value of osteopontin in left ventricular cardiomyocytes of the HCM group and the coronary heart disease group were significantly higher than that of the control group (P< 0.05), and the value of the HCM group was also significantly higher than that of coronary heart disease group (P < 0.05). CONCLUSION The increased contents of collagen fibers and the overexpression of osteopontin may play an important role in myocardial fibrosis, and they can be used as markers in aid of diagnosing sudden death due to HCM.
Cardiomyopathy, Hypertrophic/physiopathology* ; Case-Control Studies ; Collagen/metabolism* ; Coronary Disease/physiopathology* ; Death, Sudden, Cardiac/etiology* ; Female ; Fibrosis ; Forensic Pathology ; Heart Ventricles/pathology* ; Humans ; Immunohistochemistry ; Male ; Myocardium/pathology* ; Osteopontin/metabolism* ; Staining and Labeling

OBJECTIVE: To observe the expression and distribution of vascular cell adhesion molecule-1 (VCAM-1) and caspase-3 in myocardium of persons who died from viral myocarditis and to explore its pathogenesis and death mechanism. METHODS: Twenty cases died from viral myocarditis were selected as the experimental group. Ten cases died from traumatic shock and massive hemorrhage shock after traffic accidents were selected as the control group. The sections of myocardium were stained by immunohistochemistry for VCAM-1 and caspase-3, and observed under microscope. The positive expressions of VCAM-1 and caspase-3 of the two groups were compared with each other by image analysis and statistical analysis. RESULTS: (1) The vascular endothelial cells expressed VCAM-1 with dark-brown colors in the experimental group, and weak expression was observed in the control group. The average optical density in the experimental group was higher than that in the control group (P < 0.05). (2) The caspase-3 positive cells were mostly inflammatory cells around the myocardial vessels with brown-red granules in the experimental group. The positive cell number in the experimental group was higher than that in the control group (P < 0.05). CONCLUSION VCAM-1 may play an important role in the inflammatory cells exudation caused by viral myocarditis, and may provide the reference for diagnosis of viral myocarditis in forensic pathology. However, the myocardial apoptosis mediated by caspase-3 doesn't affect the lethal mechanism in the late stage of viral myocarditis.
Adolescent ; Adult ; Caspase 3/metabolism* ; Child ; Death, Sudden, Cardiac/etiology* ; Female ; Forensic Pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Myocarditis/virology* ; Myocardium/pathology* ; Myocytes, Cardiac/pathology* ; Shock, Traumatic/pathology* ; Vascular Cell Adhesion Molecule-1/metabolism* ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of postoperative adjuvant chemotherapy with imatinib in gastrointestinal stromal tumor(GIST) patients who had high risk of recurrence.

METHODSA prospective, open-label, multi-center trial conducted in sixteen teaching hospitals in China was carried out. The criteria of the enrolled patients included age more than 18 years old, CD117 positive GIST, tumor size more than 5 cm, pathological mitosis counts more than 5/50 HPF, and treatment beginning within 4 weeks after complete resection and with imatinib (400 mg, once a day) for at least 12 months. The 1, 3 year recurrence rates, disease free survival, overall survival rate and quality of life were evaluated.

RESULTSFrom Aug. 16th 2004 to Sep. 13th 2005, there were totally 74 patients screened and 57 patients (34 men, 23 women) enrolled in the imatinib treatment group. The primary tumors were located in the stomach in 50.9%, the small intestine in 38.6% and the colorectum in 10.5% of the cases. All the patients received radical resection. Until the cut-off date of interim analysis, there was no evidence of tumor relapse or metastasis in all patients and no death was reported either. Among the 57 enrolled patients with intention to treat(ITT), twelve patients finished the protocol (per protocol, PP). The disease free survival was (268.3 +/-120.2) d in ITT analysis, and (396.7+/-38.2) d in the PP analysis. The incidence of adverse effect was 44.4% . The score in quality of life showed no statistically significant difference between the baseline visit and the follow-up visits.

CONCLUSIONImatinib is a promising postoperative adjuvant chemotherapy in GISTs patients with high risk of recurrence, and the adverse effects are receivable.

Adult ; Aged ; Aged, 80 and over ; Benzamides ; Chemotherapy, Adjuvant ; Female ; Gastrointestinal Stromal Tumors ; drug therapy ; Humans ; Imatinib Mesylate ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Piperazines ; therapeutic use ; Postoperative Period ; Prospective Studies ; Pyrimidines ; therapeutic use ; Young Adult