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.

Female ; Humans ; Infant, Newborn ; Maple Syrup Urine Disease ; diagnosis ; therapy

Objective We sought to establish the standard operation procedures in department of cardiology.Methods According to the method of constructing standard operation procedures,the standard operation procedures for the department of cardiology was constructed through induction and consulting literature materials.Results 16 standard operation procedures for the department of cardiology were developed,including 8 SOP of common diseases to rescue,2 SOP of common operation in perioperative period,4 SOP for common instruments,2 SOP for common drugs usage.Conclusions Construction of standard operation procedures in department of cardiology can provide the basis for clinical nursing work,it can also supply methodological reference to build the standard operation procedures in other departments.

Objective Blood pressure variability (BPV) is an independent risk factor for the death of patients with maintenance hemodialysis (MHD).There is no study on the influencing factors of BPV at home in HD patients in China.The article aimed to investigate MHD patients'BPV at home and related influencing factors in order to provide theoretical basis for reducing home BPV (HBPV) clinically. Methods We chose 103 patients who were treated with MHD in the Renal Medicine Room of Nephrology Department in three upper first -class hospitals including Jiangsu Provincial People 's Hospital, the First Affiliated Hospital of Suzhou University and the Affiliated Hospi -tal of Jiangsu University from March 2017 to October 2017.We col-lected their 7 days'blood pressure monitoring at home and blood pressure before dialysis, average value and standard deviation in sys -tolic blood pressure monitoring at home, and took the coefficient of variation of systolic blood pressure as the expression of HBPV .The patients were divided into high BPV group (BPV≥5.8％) and low BPV group (BPV<5.8％) according to the average BPV.At the same time, we recorded indexes such as sex , age, dialysis age, primary disease, BMI, inter-dialytic weight gain (IDWG), left ven-tricular mass index(LVMI) and analyzed relative influencing factors by multiple linear regression . Results The age, IDWG and LV-MI were positive independent influencing factors of HBPV (R 2 =0.467,F=10.945,P<0.001).According to standardized regression co-efficient, the contribution of each variable to HBPV was as follows : PIBWG >Age>LVMI. Conclusion In clinical nursing, we should actively control the IDWG of patients , encourage patients to monitor their blood pressure at home , and increase their awareness of the importance of home BPV.Meanwhile, HBPV is an important index for predicting left ventricular hypertrophy and can be used as an objective tool to improve patients 'self-management ability.

OBJECTIVETo explore the protection of high intensity microwave radiation on hypothalamo-pituitary-adrenal axis (HPAA) activity and hippocampal CA1 structure in rats and the protectiveeffect of Qindan Granule (QG) on radiation injured rats.

METHODSTotally 48 Wistar rats were randomlydivided into 8 groups, i.e., the normal control group, post-radiation day 1, 7, and 10 groups, 7 and 10days prevention groups, day 7 and 10 treatment groups, 6 in each group. Rats in prevention groups wererespectively administered with QG liquid (1 mL/100 g, 4. 75 g crude drugs) for 7 days and 10 days bygastrogavage and then microwave radiation. Then preventive effect for radiation injury was statisticallycalculated with the normal control group and the post-radiation day 1 group. Rats in treatment groupswere firstly irradiated, and then administered with QG liquid (1 mL/100 g, 4.75 g crude drugs). Finally preventive effect for radiation injury was statistically calculated with the normal control group, post-radiation day 7 and 10 groups. Contents of corticotrophin releasing hormone (CRH), beta endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and heat shock protein 70 (HSP70) were detected. Morphological changes and structure of hippocampal CA1 region were observed under light microscope.

RESULTSCompared with the normal control group, contents of CRH and beta-EP significantly decreased in each radiation group. Serum contents of ACTH and beta-EP significantly increased in post-radiation day 1 and 7 groups (P < 0.05). Compared with radiation groups, beta-EP content in serum and pituitary significantly increased, and serum ACTH content significantly decreased in prevention groups (P < 0.05). Pituitary contents of CRH and beta-EP significantly increased in prevention groups. Serum contents of ACTH, beta-EP, and HSP70 were significantly lower in day 7 treatment group than post-radiation day 7 group (P < 0.05). Morphological results showed that pyramidal neurons in the hippocampal CA1 region arranged in disorder, with swollen cells, shrunken and condensed nucleus, dark dyeing cytoplasm, unclear structure. Vessels in partial regions were dilated with static blood; tissues were swollen and sparse. In prevention and treatment groups pathological damage of hippocampal CA1 region was obviously attenuated; neurons were arranged more regularly; swollen, pycnotic, or deleted neuron number were decreased; vascular dilatation and congestion was lessened.

CONCLUSIONQG could affect HPAA function and activity of high intensity microwave radiated rats, showing certain preventive and therapeutic effects of microwave radiated rats by adjusting synthesis and release of partial bioactive peptides and hormones in HPAA, improving pathological injury in hippocampal CA1 region.

Adrenocorticotropic Hormone ; blood ; Animals ; CA1 Region, Hippocampal ; drug effects ; pathology ; radiation effects ; Corticotropin-Releasing Hormone ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; HSP70 Heat-Shock Proteins ; blood ; Hypothalamo-Hypophyseal System ; drug effects ; radiation effects ; Microwaves ; adverse effects ; Pituitary-Adrenal System ; drug effects ; radiation effects ; Random Allocation ; Rats ; Rats, Wistar ; beta-Endorphin ; blood ; metabolism

OBJECTIVETo investigate clinical feasibility and technical features of immediate loading with linear occlusion on 2-implant-supported overdenture and to evaluate short-term effect of the treatment

METHODSSix edentulous patients with severe residual ridge resorption were enrolled. Two interforaminal implants were inserted for each patient and then immediate impressions were taken. Implant-supported bar-retained overdentures were restored for the patients within 24 hours. Clinical and radiographic examinations were conducted post-operative 1 week and 1, 3, 6, and 12 months. Thereafter at every 6 months the stability of implants, tissue situations around implants, radiographs and satisfaction level of patients were examined for each patient.

RESULTSSix cases and 12 implants were followed from 9 to 30 months. No implant was loosened or dropped. Sulculus bleeding index was 0-1 and probing depth of sulcus was less than 2 mm. The gingival tissues around the implants were healthy. Radiographic examination showed that bone resorption was less than 1 mm in the first year. The alveolar bone around the implants hasn't show obvious resorption stable height. Patients were satisfied with the implants.

CONCLUSIONSThe results of this study indicate that immediate loading using linear occlusion on implant-supported bar-retained overdenture is predictable in some cases and can achieve satisfaction in the short-term service. Further study is needed to assess the long-term results.

Aged ; Dental Implantation, Endosseous ; Dental Implants ; Dental Prosthesis, Implant-Supported ; Denture Retention ; Denture, Complete, Immediate ; Denture, Overlay ; Female ; Follow-Up Studies ; Humans ; Jaw, Edentulous ; surgery ; Male ; Mandible ; surgery ; Middle Aged

Axons ; chemistry ; Myelin Sheath ; chemistry ; Staining and Labeling ; methods

OBJECTIVETo investigate whether single nucleotide polymorphism (SNP) in DNA repair gene XPD751 is associated with sensitivity and time to progression (TTP) for platinum-containing combination chemotherapy in advanced colorectal carcinoma.

METHODSA total of 98 patients pathologically diagnosed as advanced colorectal cancer were treated with FOLFOX chemotherapy. TheDNA of peripheral blood-leukocytes was obtained before treatment, and XPD genetype was detected by PCR-RFLP analysis.

RESULTSThe frequency of XPD751 Lys/lys was 76 cases (77.6%), lys/Gln 17 cases (17.4%), and Gln/Gln genetype 5 cases (5.1%). The effective rate of FOLFOX chemotherapy among patients with XPD751 Lys/lys was 50.0%, lys/Gln 29.4%, and Gln/Gln genetypes 20.0%. The difference between Lys/lys and lys/Gln was statistically significant, χ(2) = 4.04, P < 0.05. The results indicated that the failure of chemotherapy in patients with Lys/Lys genetype was 3.8-fold to those with Lys/Gln, by adjusting of gender, age, and tumor metastasis (OR = 3.800). The MTTP of the 98 patients was 10.1 months. The MTTP was 11.3 months for patients with Lys/Lys genotypes of XPD751 gene and 2.9 months for patients with Lys/Gln and Gln/Gln genotypes of XPD751 gene, the difference between Lys/Lys and at least one Gln was significant (P < 0.05).

CONCLUSIONSSingle nucleotide polymorphism of XPD751 correlates with the clinical response to FOLFOX chemotherapy. XPD751 genetic polymorphisms may be associated with TTP of advanced colorectal carcinoma patients treated with oxaliplatin as the first line chemotherapy. XPD751 genotype detected by the PCR-RFLP method may be a predictor of prognosis for FOLFOX chemotherapy.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; genetics ; pathology ; DNA Repair ; Disease Progression ; Female ; Fluorouracil ; therapeutic use ; Follow-Up Studies ; Genotype ; Humans ; Leucovorin ; therapeutic use ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; therapeutic use ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Proportional Hazards Models ; Xeroderma Pigmentosum Group D Protein ; genetics

BACKGROUNDFamilial hypercholesterolemia (FH) is an autosomal disorder associated with elevated plasma low density lipoprotein (LDL) levels leading to premature coronary heart disease (CHD). As a result of long-term hyperlipemia, FH patients will present endarterium thickening and artherosclerosis. In the present study we scanned the related gene of a clinically diagnosed autosomal genetic hypercholesterolemia family for the possible mutations and established eukaryotic expression vector of mutation of proprotein convertase subtilisin/kexin type 9 (PCSK9) gene with gene recombination technique to investigate the contributions of the variation on low density lipoprotein receptor (LDL-R) metabolism and function alternation.

METHODSMutation detection was conducted for LDL-R, apolipoprotein B(100) (apoB(100)) and PCSK9 gene with nucleotide sequencing in a Chinese FH family. The full-length cDNA of wild type PCSK9 gene (WT-PCSK9) was obtained from Bel-7402. Site mutagenesis was used to establish the recombinant eukaryotic expression vector carrying pathogenic type of PCSK9 gene and the inserted fragment was sequenced. With the blank vector as control, liposome transfection method was used to transfect the Bel-7402 cells with recombinant plasmid. The expression of LDL-R mRNA was examined by RT-PCR. PCSK9 and the expression of LDL-R protein were determined by Western blotting.

RESULTSThe G-->T mutation at the 918 nucleotide of PCSK9 gene resulted in the substitution of the arginine by a serine at the codon 306 of exon 6. After sequencing, it was confirmed that the inserted fragment of established expression vector had correct size and sequence and the mutant was highly expressed in Bel-7402 cells. There was no significant variation in the levels of LDL-R mRNA. LDL-R mature protein was decreased by 57% after the cells were transfected by WT-PCSK9 plasmid. Mature LDL-R was significantly decreased by 12% after the cells were transfected by R306S mutant as evidenced by gray scale scanning, suggesting that the new mutant R306S can significantly decrease the expression of mature LDL-R protein.

CONCLUSIONSA novel missense mutation of PCSK9 gene, R306S, was found and the eukaryotic expression vectors of mutant and wild-type of PCSK9 gene were established. There was no significant variation in the levels of LDL-R mRNA. The R306S mutation could significantly lead to the decrease of LDL-R mature protein expression, which might be the pathogenic gene of the FH family.

Adolescent ; Adult ; Female ; Humans ; Hyperlipoproteinemia Type II ; genetics ; Lipids ; blood ; Male ; Mutation ; Pedigree ; Proprotein Convertase 9 ; Proprotein Convertases ; Serine Endopeptidases ; genetics

Objective To explore the Electrocardiography (ECG) changes of residents in Keshan disease area and the status of growth and decline of Keshan disease in Shaanxi Province. Methods Using stratified randomized sampling method,2 mild,2 moderate and 2 serious disease counties were selected respectively in 2005 and 2006. A total of 6 counties were sampled,2 villages,one with severe disease and one with mild,were selected from each sampled county. A total of 12 villages were selected. The clinical examination and ECG were conducted in 3-year old children of agricultural population of the selected villages. Results ECG of 5692 cases were performed in the selected 12 village in the 6 counties,in which 4917 cases showed normal electrocardiogram,up to 86.38% (4917/5692). Two hundred and fifty-two cases showed roughly normal electrocardiograms,up to 4.43%(252/5692). Five hundred and twenty-three cases had abnormal electrocardiogram,accounting for 9.19% (523/5692). Among them,the abnormal electrocardiogram rates in mild,moderate and serious disease areas were 7.07% (144/2036), 11.41%(167/1646) and 10.54%(212/2010),respectively. Atrioventricular block was the major abnormal electrocardiogram change,followed by arrhythmia,ST-T changes,and low voltage. One hundred and thirty-nine cases were confirmed as latent and chronic Keshan diseases. One hundred and thirty-one cases were latent Keshan, and detection rate was 2.30%(131/5692). Eight cases were chronic Keshan,and the detective rate was 0.14% (8/5692). Complete right bundle branch block [37.06% (63/170) ],ST-T changes [22.35% (38/170) ],multiple premature ventricular beats [12.94% (22/170)] were the major abnormal electrocardiogram change of Keshan patients. Conclusions Atrioventricular block and arrhythmia are the major abnormal electrocardiogram changes. Keshan disease incidences are controlled under a stable condition.