Objective To identify mutations site and clinical characteristics of a familial hypercholesterolemia(FH) proband diagnosed clinically through DNA sequencing and family analysis in the proband and his family members of 3 generations.Methods Blood samples and clinical data of the kindred of total 29 from 3 generations members were collected.Proband had a physical examination electrocar-diogrom and vascular ultrasound.The proband and his family members took routine clinical exams,and genomic DNA was isolated.The promoter region and the 18 exons of low density liporotein receptor(LDLR) gene were screened by Touch down polymerase chain reaction -single strand conformation polymorphism(PCR-SSCP) and DNA sequencing.The result of sequencing were matched gene sequence published in the BLAST database.Results 1.Increased intima-media thickness and plaque were detected in the common carotid artery,right subclavian artery of the proband.Aortic valve regurgitation was found by echocardiography.2.No mutation R3500Q of ApoB100 was observed.3.Two heterozygous mutations in exon 10 and 13 of LDLR gene (W462X and A606T) were identified.The proband and 5 members of paternal relatives showed W462X heterozygosis mutation in exon 10 of LDLR gene which introduced the change from tryptophone to a new stop codon.The proband's mother and grandmother harboured A606T heterozygous mutation in exon 13 of LDLR gene due to a single base pair substitution of G for A in the codon for residue 1 879.Conclusions Disease causing mutations of proband are W462X and A606T compound heterozygosis mutation in exon 10 and 13 of LDLR gene inherited from mother and father.Proband shows homozyous phenotype though the genotype analysis indicates heterozygous mutations.

Ataxia Telangiectasia Mutated Proteins ; Breast ; metabolism ; pathology ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; metabolism ; pathology ; Cell Cycle Proteins ; metabolism ; Checkpoint Kinase 2 ; DNA-Binding Proteins ; metabolism ; Female ; Humans ; Lymphatic Metastasis ; Neoplasm Grading ; Protein-Serine-Threonine Kinases ; metabolism ; Tumor Burden ; Tumor Suppressor Protein p53 ; metabolism ; Tumor Suppressor Proteins ; metabolism

Objective:To evaluate the feasibility of delineating subvolume target in radiotherapy for brain tumors using Gd-based contrast clearance difference.Methods:Twenty-six patients with malignant brain tumors were scanned with MRI. The first and second acquisitions of standard T 2-weighted images (T 2WI) and T 1-weighted images (T 1WI) were performed at 5 min and 60 min after injection of contrast agent. Delayed contrast extravasation (DCEM) MRI computed by Brainlab comprised regions of contrast agent clearance representing active tumors and regions of contrast accumulation representing non-tumor tissues. Based on T 2WI images, 14 patients with liquefaction necrosis were divided into group A, and 12 patients without liquefaction necrosis into group B, respectively. Then, gross target volume (GTV) was delineated on T 1WI images. Based on the GTV, active tumor (GTV tumor) and non-tumor regions (GTV non-tumor) were delineated on T 1WI-DCEM fusion images, while liquefaction necrosis (GTV liquefaction) and non-liquefaction (GTV non-liquefaction) were delineated on T 1-T 2WI fusion images. Finally, the differences between different subvolumes were compared by paired t-test. Results:In group A, the GTV non-liquefaction and GTV liquefaction were (13.65±18.15) cm 3 and (6.30±7.57) cm 3. The GTV tumor was (10.40±13.52) cm 3 and the GTV non-tumor was (9.55±14.57) cm 3. The GTV non-liquefaction was significantly increased by 16.3% on average compared with the GTV tumor ( P<0.05). The GTV non-tumor was significantly increased by 16.3% on average compared with the GTV liquefaction ( P<0.05). In group B, The GTV non-tumor was significantly reduced by 68.8% on average compared with the GTV tumor ( P<0.05). Conclusions:Compared with T 2WI, DCEM has advantages in identifying the liquefaction area and can clearly differentiate the subvolume of active tumors from non-liquefaction necrosis. DCEM provides evidence for guiding the delineation of subvolume in primary and metastatic brain tumors.

Objective: To explore the structural domains of the CENP-E protein that interact with Mps1 protein.Methods: Two recombinant vectors named pEGFP-CENPE2(containing 674-1085 amino acids of CENP-E protein) and pEGFP-CENPE 3(containing 1200~2134 amino acids of CENP-E protein) were transfected into human embryo kidney 293(HEK293) cells respectively.The respective energy transfer efficiency(Ef) between either EGFP-CENPE2 and Mps1,or EGFP-CENPE3 and Mps1 were detected by FRET through selective photobleaching of the acceptors.Results: Both recombinant proteins expressed in HEK293 cells transfected by the recombinant plasmids were found to co-localize with the Mps1 protein as confirmed by confocal microscopy.The Ef between EGFP-CENPE3 and Mps1 protein was [(12.63?0.48)%,n=30] and that between EGFP-CENPE3 and Mps1 protein was [(3.17?0.21)%,n=30] as revealed by the results from FRET,the result of FRET was confirmed by co-Immunoprecipitate(CO-IP) method.When compared with that between the control and Mps1,the Ef between EGFP-CENPE3 and Mps1 was significantly higher(p

A series of tacrine-methoxybenzene hybrids (5a-5i) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs). All the compounds had better ChEs inhibitory activities than tacrine with IC50 values at the nanomolar range. Compound 5h exhibited the strongest inhibition on acetylcholinesterase (AChE) with an IC50 value of 6.74 nmol x L(-1) and compound 5f showed the most potent inhibition on butyrylcholinesterase with IC50 value of 3.83 nmol x L(-1). Kinetic and molecular modeling studies showed that these hybrids targeted both the catalytic active site and the peripheral anionic site of AChE.
Acetylcholinesterase ; metabolism ; Anisoles ; chemical synthesis ; chemistry ; pharmacology ; Binding Sites ; Butyrylcholinesterase ; metabolism ; Catalytic Domain ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Inhibitory Concentration 50 ; Tacrine ; chemical synthesis ; chemistry ; pharmacology

BACKGROUNDTo evaluate the safety of intracytoplasmic sperm injection (ICSI) with epididymal or testicular sperm, this study compared children born after ICSI treatment with epididymal or testicular sperm with children conceived after ICSI with ejaculated sperm.

METHODSThis retrospective study included 317 children born after ICSI with percutaneous epididymal sperm aspiration (PESA), 103 children born after ICSI with testicular sperm aspiration (TESA), and a control group of 1008 children born after ICSI with ejaculated sperm. All of the patients received their assisted reproductive treatment in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2004 to December 2011. Data, such as the rate of stillbirths, perinatal mortality, gestational age, birth weight, and the rate of congenital malformations of the three groups, were compared.

RESULTSPESA and TESA children were not different from ICSI children in the rate of stillbirths, perinatal mortality, infant mortality rate, gestational age, the rate of prematurity, and the rate of malformations (P > 0.05). A slight increase in birth defects was reported in the TESA group compared with those in the control group, but there was no significant difference between the groups (P > 0.05).

CONCLUSIONICSI with epididymal or testicular sperm does not lead to more stillbirths or congenital malformations compared with ICSI using ejaculated sperm.

Adult ; Congenital Abnormalities ; epidemiology ; Epididymis ; Female ; Fetal Death ; epidemiology ; Follow-Up Studies ; Humans ; Infant, Newborn ; Male ; Pregnancy ; Retrospective Studies ; Sperm Injections, Intracytoplasmic

Objective To investigate the effect of high power microwave(HPM) irradiation on neuropeptide Y (NPY) and neural nitric oxide synthase (nNOS) expression in the cerebral cortex and hippoeampus of Wistar rats. Methods A total of 110 Wistar rats were used for this study.Three groups of 30 Wistar rats were exposed to HPM irradiation at intensities of 3,10,30 and 100 mW/cm~2,respectively.Twenty rats served as controls and were ex- posed to sham HPM irradiation.At 6 h,and at 1,3,7,14 and 28 d after irradiation,five rats from each group were sacrificed,and their cerebral cortices and hippocampi were harvested.HE staining was used to highlight any change in the structure of the cerebral cortex or hippocampus.Immunohistochemistry techniques and image analysis were used to study the changes in NPY and nNOS expression.Results 10 to 100 mW/cm~2 HPM irradiation caused pyc- nosis and deep staining of some neurons in the cerebral cortex and hippocampus.The increase in nNOS expression and decrease in NPY expression observed were significant at 3 days after irradiation.Conclusion HPM irradiation can induce injury in neurons of the cerebral cortex and hippoeampus,and abnormal NPY and nNOS expression.

OBJECTIVETo analyze the genetic polymorphism, distribution of haplotypes, common and well-documented (CWD) and rare alleles of high-resolution HLA-A, B and DRB1 alleles by analysis from hematopoietic stem cell (HSC) donors in Jiangsu Han Chinese.

METHODSPCR-sequence-based typing and PCR-sequence specific oligonucleotide probes methods were applied for HLA-A, B and DRB1 high-resolution genotyping of 3238 unrelated healthy donors of hematopoietic stem cells in Jiangsu branch of Chinese National Marrow Donor Program registry.

RESULTS46 alleles of HLA-A,85 HLA-B and 51 HLA-DRB1 locus were found. The frequencies of the most common alleles were A * 11:01 (16.52%), B * 13:02 (11.60%) and DRB1 *07:01 (15.78%). That of the most common haplotype was A * 30: 01-B * 13: 02-DRB1 * 07: 01 (8.87%). 40 alleles of HLA-A,77 alleles of HLA-B, and 47 HLA-DRB1 alleles of HLA-DRB1 were CWD, which account for 99. 8% of total number of samples, and a few rare alleles not reported in Chinese population were found.

CONCLUSIONThe results of high-resolution, CWD and rare alleles showed the characteristics of HLA distribution in Jiangsu Han population, which may be useful for finding HLA matched unrelated donors, as well as for HLA correlation with population genetics and disease association studies.

Alleles ; Asian Continental Ancestry Group ; genetics ; Genotype ; HLA-A Antigens ; genetics ; HLA-B Antigens ; genetics ; HLA-DRB1 Chains ; genetics ; Haplotypes ; Hematopoietic Stem Cells ; Humans ; Tissue Donors

OBJECTIVE: To investigate the frequency of transfusion transmitted virus (TTV) infection in healthy blood donors in Hangzhou area and the mutation of TTV genomic fragment. METHODS DNA in serum samples of 203 healthy donors was extracted by phenol-chloroform method to detect TTV by semi-nested polymerase chain reaction and nucleotide sequences of partial amplification products were determined after T-A cloning. RESULTS TTV infection rate in 203 cases of blood donors in Hangzhou area was 15.3%. The homology of the amplified products of partial TTV positive samples compared with thereported nucleotide and putative amino acid sequences of TTV TA278 were 63.51% approximate, equals 67.12% and 59.46% approximate, equals 66.22% respectively. CONCLUSIONS TTV infection rate in the blood donors in Hangzhou is relatively high. The TTV infecting blood donors in the area may be a kind of novel genotype.

BACKGROUNDDifferential diagnosis of isolated calf muscle vein thrombosis (ICMVT) and gastrocnemius hematoma is essential for early identification of deep vein thrombosis (DVT). This study aimed to investigate the diagnostic value of high-frequency color Doppler ultrasound for differential diagnosis of ICMVT and gastrocnemius hematoma.

METHODSA retrospective case series of 35 ICMVT (M:F, 21:14; mean age (64.5 ± 10.6) years) and 23 gastrocnemius hematoma (M:F, 16:7; mean age (75.4 ± 11.8) years) patients with bilateral/unilateral lower limb pain was conducted between January 2006 and September 2012. Characteristics and the morphology of high-frequency color Doppler ultrasonography of the lower limb deep vein, great saphenous vein, calf muscles, skin, and soft tissue were examined.

RESULTSICMVT hypoechoic signals were characterized by long, tube-like masses on longitudinal sections and oval masses on transverse sections, with apparent muscle thrombosis boundaries, distal and proximal venous connections, and, often, lower limb DVT. Gastrocnemius hematoma hypoechoic signals were characterized by large volumes, enhanced posterior hematoma echo, hyperechoic muscle boundaries, no hematoma blood flow, and no DVT, and clear differences in trauma/exercise- and oral anticoagulant-induced hematomas were readily apparent. According to the measurement, the ratio of long diameter/transverse diameter (D/T) in ICMVT patients was about less than 2.0, whereas in gastrocnemius hematoma patients the ratio was more than 2.0. Early stage isoechoic and hypoechoic signals were detected with gradually increasing ovular anechoic areas. Partial muscle fibers in the hematoma due to muscle fractures were apparent.

CONCLUSIONHigh-frequency color Doppler ultrasound was found to be a sensitive and reliable method for differential diagnosis of ICMVT and gastrocnemius hematoma due to trauma and exercise or prolonged oral anticoagulant use.

Aged ; Diagnosis, Differential ; Female ; Humans ; Leg ; diagnostic imaging ; Male ; Middle Aged ; Muscle, Skeletal ; diagnostic imaging ; Retrospective Studies ; Ultrasonography ; Venous Thrombosis ; diagnostic imaging