This article mainly introduces the new development of signal processing techniques used in analyzing electrophysiological signals of atrial fibrillation. Discussions and suggestions are given differently in the view of start, methods and values of clinical applications. The introduction is hoped to give some guidance to the domestic research in the correspondent fields.

BACKGROUND: It has been demonstrated that the C-106T polymorphism at promotor region of aldose reductase gene and GLU298ASP (894G→T) polymorphism at exon 7 of endothelial nitric oxide synthase (eNOS) gene are associated with diabetic nephropathy, it should be further studied wnether the risk for diabetic nephropathy will increase when the above polymorphic sites coexist.OBJECTIVE: To investigate the association between the coexistence of the polymorphisms of both the C-106T at promotor region of aldose reductase gene and GLU298ASP (894G→T) at axon 7 of eNOS gene in chromosome 7q35 region and the genesis of diabetic nephropathy in northern Chinese Hah people.DESIGN: A case-controlled, comparative observation.SETTING: Department of Endocrinology, the Affiliated Hospital of Medical College, Qingdao University.PARTTCIPANTS; Totally 139 inpatients with type 2 diabetes mellitus were selected from the Department of Endocrinology, the Affiliated Hospital of Medical College, Qingdao University from November 2002 to April 2005,including 54 males and 85 females, (64±8) years of age. Inclusive criteria: Accorded with the standards of diabetic diagnosis and classification by WHO in 1999. According to the 24-hour urinary albumin excretion rate (UAER), they were divided into diabetic nephropathy group (n =61) and non-diabetic nephropathy group (n =78). Meanwhile, 63 healthy controls were selected as the control group, including 24 males and 39 females, 50-78 years of age. All the enrolled subjects were Han people. Informed contents were obtained from all the subjects.METHODS: The genotypes and alleles of polymorphisms of GLU298ASP(894G→T) at exon 7 of eNOS gene and C-106T at promotor region of aldose reductase gene were detected by polymerase chain reaction restriction-fragment length polymorphism technique (PCR-RFLP), DNA sequencing technique and agarose gel electrophoresis separation technique.Then the frequency of genotypes and alleles were compared.MAIN OUTCOME MEASURES: ① Polymorphisms of eNOS gene and aldose reductase gene; ② Results of the multivariant stepwise regression analysis of risk factors for diabetic nephropathy; ③ Polymorphisms of aldose reductase C-106T and eNOS 894G→T and the relative risk of diabetic nephropathy.RESULTS: All the 139 patients with type 2 diabetes mellitus and 63 healthy adults were involved in the analysis of results. ① The frequencies of the T allele and TG genotype at exon 7 894G→T polymorphic site of eNOS gene in the diabetic nephropathy group were significantly higher than those in the non-diabetic nephropathy group and control group (χ2=8.261, 19.629, P ＜ 0.05). ② The frequencies of the T allele and CT genotype at promotor region of aldose reductase gene in the diabetic nephropathy group were significantly higher than those in the non-diabetic nephropathy group and control group (χ2=6.343, 8.940, P ＜ 0.05, 0.01). ③ After associated analysis on the above gene polymorphisms, it was found that the frequency of TG/CT genotype in the diabetic nephropathy group were significantly higher than that in the non-diabetic nephropathy group and control group (χ2=6.972, P ＜ 0.01); whereas the frequency of GG/CC genotype was significantly lower than that in the non-diabetic nephropathy group and control group (χ2=13.304, P ＜ 0.05). ④Glycosylated hemoglobin (GHbA1c), systolic blood pressure, total cholesterol, polymorphisms of 894G→T at exon 7 of eNOS gene and C-106T at promotor region of aldose reductase gene were all the independent risk factors for diabetic nephropathy (Wald =5.627, 4.92, P ＜ 0.05). ⑤ GG/GC genotype might be the protective genotype for diabetic nephropathy (OR=0.25, P ＜ 0.01); The risk for diabetic nephropathy in the carrier of GG/CT or TG/CC genotype increased by 2.3 times and risk for diabetic nephropathy in the carrier of TG/CT genotype increased by 4.8 times.CONCLUSION: The coexistence of polymorphisms of 894G→T at exon 7 of eNOS gene and C-106T at promotor region of aldose reductase gene can increase the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. And the TG/CT haplotype formed by the coexistence of polymorphism of these two genes is probably the predisposing genotype for diabetic nephropathy.

Objective To explore the regularity of hematopoietic materials during the clonal evolution of aplastic anemia(AA), paroxysmal nocturnal hemoglobinuria (PNH) , myelodysplastic syndrome (MDS) and acute leukemia(AL). Methods Patients diagnosed as AA, PNH, MDS and AL were recruited as cases and health volunteers were recruited as controls. Serum folic acid, vitamin B12 and ferritin levels were measured by radioimmunoassay and competitive enzyme immunoassay,before and after-treatment. Results Before treatment,the level of serum folic acid in PNH group were significantly lower than that in the control group(P<0. 05). Vitamin B12 and ferritin levels of MDS patients were higher than the control group (P < 0. 05); Serum Folic acid level in AL patients was significantly lower than the control group (P < 0. 05). In contrast, vitamin B12 and ferritin levels were higher than the control group(P <0. 05). Compared to pre-treatments AA patients, vitamin B12 and ferritin levels of MDS patients were significantly higher(P <0. 01) ;Serum folic acid level in AL patients was significantly lower(P < 0.05). However,vitamin B12 and ferritin levels were higher. Compared to pre-treatments MDS patients, serum folic acid level in AL patients was significantly lower(P < 0. 05) , whereas vitamin B12 and ferritin levels were higher(P < 0. 05). The comparison of hematopoietic materials between pre-and post-treatments among the groups showed that there was no significant difference for AA patients between pre- and post-treatments in the levels of serum folic acid and vitamin Bl2 (P > 0. 05), whereas ferritin was significantly higher after treatment caused by transfusion in AA patients(P<0. 05) ;ln PNH patients,serum folic acid was significantly higher after treatment(P<0. 05) ,and there was no significant difference in the levels of vitamin B12 and ferritin between pre-and post-treatments (P >0. 05). In MDS patients, there was no significant difference in the level of ferum folic acid between pre-and post-treatments (P > 0. 05) , whereas vitamin B12 and ferritin levels were significantly lower after treatment (P < 0. 05); In AL patients,serum folic acid was significantly higher after treatment(P <0. 05) .whereas the levels of vitamin B12 and ferritin were significantly lower after treatment (P <0. 05). Conclusions There are significant difference in serum folic acid,vitamin B12 and ferritin among the patitents of AA,PNH,MDS and AL and would be helpful in discovering the interrelationship among the four diseases pertinent to the clonal evolution,prognosis,treatment and prognosis.

AIM: To prepare a soluble hemangiopoietin(HAPO) protein and to construct pET22b(+) expression vector, to obtain pure recombinant HAPO protein and to measure its bioactivity. METHODS: HAPO cDNA was amplified using RT-PCR method from a commercial human fetal liver cDNA library. The resulting product was cloned into pET22b(+) vector and transformed into E.coli BL21(DE3). The recombinant protein was isolated and purified by Ni~(2+)-NTA chelating resin and the chromatographies of SP Sepharose FF. The adhesion of human umbilical vein endothelial cells (HUVEC) were measured by adhesion assay. RESULTS: HAPO gene with a reading frame of 897 bp was successfully cloned from human fetal liver cDNA library, the expressed pET22b(+)-HAPO fused protein existed in a soluble form, with the yield above 10% total bacterial protein and its purity achieved above 80%. The activity assay showed that the treatment of HAPO enhanced total adherence of HUVEC in a concentration-dependent manner. CONCLUSION: HAPO protein can be expressed in a soluble form. HAPO may facilitate the homing of hematopoietic stem/progenitor cells in vitro.

Objective To investigate the association between SLCO1B1/ApoE gene polymorphisms and lipid-lowering efficacy and safety of rosuvastatin.Methods DNA samples were extracted from blood using nano paramagnetic particle method.The SLCO1B1 521T＞C and ApoE gene polymorphisms were screened by PCR-pyrophosphate sequencing method.Totally 152 patients received rosuvastatin orally at a dose of 10 mg/d.The lipidlowering efficacy was evaluated through detecting serum low-density lipoprotein cholesterol (LDL-C) level before and 8 weeks after the treatment.The incidence of myopathic adverse effect was assessed by follow-up of the occurrence of myalgia.Results The gene distribution of SLCO1B1 521T＞C was 73.7％,23.7％ and 2.6％ respectively for TT,TC and CC in 152 patients,and the distribution of ApoE gene was 65.8％,13.2％ and 21.0％ respectively for ε3/ε3,ε3/ε2 and ε4/ε3.The genotype ε4/ε4,ε2/ε2 and ε4/ε2 were not detected.After orally receiving rosuvastatin 10 mg daily for 8 weeks,the decreased LDL-C levels showed significant differences (P＜0.05) among ApoE genotype ε3/ε2,ε3/ε3 and ε4/ε3 groups,and the frequencies of myalgia showed significant differences in the three genotype groups of SLCO1B1 521T＞C (P＜0.05).Conclusion The gene polymorphism of SLCO1B1/ApoE was correlated with efficacy and safety of rosuvastatin.The combined detection of SLCO1B1/ApoE genes can be utilized to predict efficacy and risk,and then realize individualized medication.

Objective To observe the ameloblast morphology and ultrastructure changes of dental fluorosis in rats.Methods Forty SD rats were divided into experimental group and control group (20 rats in each group) by body weight using random number table method.Rats in experimental group were given drinking water with 50 mg/L fluoride to establish dental fluorosis model,and rats in control group were given drinking water without fluoride.All rats were killed at the 56th day,then ameloblast morphology and ultrastructure were observed by means of HE staining and transmission electron microscopy (TEM) at secretory,transition,maturation and post-maturation stages.Results Rats in experimental group showed typical symptoms of dental fluorosis,and lower incisors presented brown and white stripes on enamel surface,chalk color patches and other typical dental fluorosis changes,rats in control group no abnormality.HE staining results showed that differences were not observed between the two groups at the secretory and transformation stages,and few distortions and interstitial space widened were found in the experimental group at maturation and post-maturation stages.TEM displayed ultrastructure changes of ameloblasts,and no differences were observed between the two groups at secretory and transformation stages.Apoptosis was observed in some ameloblasts at the maturation stage in the experimental group,such as rough endoplasmic reticulum expansion,swelling,some ribosome particles exfoliating from endoplasmic reticulum,mitochondrial swelling and disappearance of crista,some nuclear membrane broken down,chromatin condensation and karyolysis.At post-maturation stage,intercellular space of the experimental group was wider than that of the control group.Conclusions Morphological and ultrastructure damage of ameloblasts may have occurred at the maturation stage in the process of dental fluorosis.Ameloblasts may be more sensitive to fluoride in dental enamel formation at maturation stage.

ObjectiveTo observe the effect of indomethacin on the migration of breast cancer cell line MCF-7 in vitro and investigate the mechanism involved.MethodsThe migration of MCF-7 cell line stimulated with or without indomethacin were tested using transwell plates consisting upper and lower chambers separated by Millipore polycarbonate membrance filters with 8 μm pore sizes; the levels of chemokine receptor 4(CXCR4),cyclooxygenase(COX-2),epidermal growth factor receptor(EGFR) and vascular endothelial growth factor(VEGF)expression in MCF-7 cell line were detected by flow cytometry,Real-time PCR and ELISA,respectively.Results Indomethacin decreased the migration ability of MCF-7 cell line significandy.CXCR4 membrane expression was significantly reduced in a time-dose dependent manner,and CXCR4,COX-2 and EGFR mRNA levels were significantly downregulated after indomethacin stimulation.However,exposure to indometahcin had no major effect on VEGF production of cells.ConclusionThe downregulation of CXCR4,COX-2 and EGFR expression might be the primary mechanism involved in the inhibitory effect of indomethacin on the migration of MCF-7 cell line.

BACKGROUND: Recent studies have found that hyperuricemia and gout are closely correlated with the occurrence and development of diabetes, coronary heart disease, hypertension and cerebrovascular diseases. It is of significance to investigate their prevalence so as to find way of early interventions.OBJECTIVE: To determine the prevalence and risk factors of gout and hyperuricemia among residents above 20 years old in Shandong coastal area.DESIGN: A randomized, stratified cluster sampling survey.SETTING: Department of Endocrinology, Affiliated Hospital of Qingdao University Medical College.PARTICIPANTS: A random, stratified cluster sampling was conducted in Shandong coastal area including Qingdao,Yantai, Weihai, Rizhao and Dongying. Residents lived in these areas for 5 years or more, aged between 20 to 80 years, were selected, and they were surveyed by family as a unit.METHODS: A randomized, stratified cluster sampling survey was conducted. The prevalence of gout and hyperuricemia were investigated among about 5 000 residents in Qingdao, Yantai, Weihai, Rizhao and Dongying. The serum uric acid, lipids, glucose and creatinine were detected with Sysmex chemix-180 total automatic biochemical analyzer. Those with uric acid higher than reference level were reexamined by collecting fasting blood sample on the third day. The comparison between rates was taken with the Chi-square test, means between two groups with the t test, means between multiple groups with analysis of variance, correlation between dependent and independent variables with logistic regression analysis.MATN OUTCOME MEASURES: Prevalance of hyperuricemia; Level of serum uric acid; Prevalence of gout in patients with hyperuricemia; Influencing factor of hyperuricemia.RESULTS: This investigation planned to include 5 500 subjects while in fact 5 003 subjects were investigated and the response rate was 91%, in which males were 2 395 (47.87%) and females were 2 608 (52.13%). ① The prevalence of hyperuricemia was 13.19% with standardized rate of 13.27% according to the Shandong population in 2000; The pevalence was higher in males than in females (18.32%, 8.56%, x2=108.52, P＜ 0.01). The risk in males was 2.5 times higher than that in females (OR =2.5). The prevalence of gout was 1.14% with standardized rate of 1.10%; and the prevalence in males was higher than that in females (1.94%, 0.42%, x2=30.38, P ＜ 0.01). The risk in males was 5.3 times higher than that in females (OR =5.3). ②The average value of serum uric acid in normal males was higher than in normal females [(343.40±84.54), (258.90±70.90) μmol/L, t =48.03, P ＜ 0.01]. It was obviously higher in male patients with hyperuricemia than in female ones [(469.43±48.08), (399.73±104.91) μmol/L, t =11.70, P ＜ 0.01]. It was higher in male patients with gout than in female ones [(502.44±106.76), (403.48±52.72) μmol/L, t =2.07, P ＜ 0.05]. ③The prevalence of gout in patients with hyperuricemia was 8.34%. ④ The prevalence of hyperuricemia and gout were climbing up with age after 40 years old in females and those elder than 70 years old were of high risk; while in males,the prevalence of hyperuricemia and gout increased with age before 60 years old and those aged 50-59 years were of high risk, yet after 60 years, it climbed up with age again. Nevertheless, the mean ages of hyperuricemia and gout in females were older than male. The average episode ages of hyperuricemia and gout in females were later than in males respectively by 7.5 and 8.5 years. ⑤ Non-conditional Logistic regression analysis showed that drinking frequency,drinking quantity, the quantity and frequency of seashell intake, BUN, Cr, TG, TC, BMI and WHR were the independent risk factors of male patients with hyperuricemia [OR =1.016-30.217, 95%C/ (1.010-1.023)-(9.955-214.869)]; while HDL-C and heavy physical labour were the protective factors (OR =0.492, 95%C/ 0.339-0.713; OR =0.755, 95% CI 0.575-0.991).As for females, age, hypertension, the quantity of seashell food intake, BUN, Cr, TG, WHR and light physical labour were the independent risk factors of hyperuricemia [OR =1.022-27.34, 95%CI (1.006-1.040)-(9.955-214.869)]. Similarly, HDL-C was a protective factor (OR =0.428, 95%CI0.223-0.820).CONCLUSION: ① The prevalence of hyperuricemia and gout are different between genders: ② The risk factors of hyperuricemia and gout among residents in Shandong coastal area include the high intake of marine products such as seashell foods, less physical activity, abdominal obesity and kidney insufficiency, as well as the existence of metabolic syndrome. Drinking is also involved in the increased prevalence in males, and age in females. ③ Higher risk for hyperuricemia and gout are noticed in all age groups in males, whereas in females after 50 years old.

AIM: To investigate the expression of transcription factor GATA-3 gene in the bone marrow stromal cells (BMSCs) from patients with aplastic anemia (AA) and normal controls. METHODS: The expression of GATA-3 gene was analyzed by using RT-PCR-ELISA in BMSCs from 34 normal cases and 9 cases with AA. The standardized semi-quantitative expression level of GATA-3 gene in BMSCs from patients with AA was compared with normal controls. RESULTS: The expression of GATA-3 gene was detected in BMSCs from both normal controls and the cases with AA. The expression level of GATA-3 gene in BMSCs from AA was significant higher than that from the normal controls (P

AIM: To investigate the expression of SCL (stem cell leukemia) gene in bone marrow stromal cells (BMSCs) and bone marrow hematopoietic cells from patients with aplastic anemia (AA) and normal individuals. METHODS: Bone marrow stromal cells from AA (9 cases) and normal individuals (33 cases) were amplified by long-term in vitro culture. The adherent and nonadherent cells were collected respectively. RT-PCR-ELISA assay was then performed to detect the expression of SCL gene and the housekeeping gene ?_2 microglobulin (?_2M). The expression ratio of SCL gene were analyzed and its expression level was normalized by ?_2M gene acting as an internal calibration for the purpose of semi-quantitative analysis. RESULTS: The expression ratio of SCL gene was lower in BMSCs from AA (22.2%) than that in normal controls (69.7%, P