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.

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 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.

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.

Objective To determinate the risk factors of gout in patients with hyperuricemia.Methods Patients detected with hyperuricemia both in epidemiological survey of Shandong coastal areas in 2004 and in health examination of our hospital were followed up for three years to observe the incidence of gout, relationship of diet and gout, and changes of biochemical indicators.Results During 3 years, 102 patients (19%) out of 536 patients with hyperuricemia developed gout. Age(OR=1.046, P＜0.05), serum uric acid(OR=1.021, P＜0.05), fasting plasma glucose(OR=1.021, P＜0.05), triglyceride(OR=1.008, P＜0.05), tony crab intake ( OR=5.992, P＜0.05),and beer intake(OR=1.012, P＜0.05) were the risk factors of gout attack in patients with hyperuricemia.Conclusions Excess intake of tony crab and beer resulting in fluctuation of serum uric acid is the main risk factor of gout in patients with hyperuricemia. Correcting metabolic disorder of glucose and lipid, reducing the intake of high-purine food, and controlling the level of serum uric acid are the measures to reduce gout attack.

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.

Objective To investigate and evaluate the correlation between brain natriuretic peptide (BNP) and gestational hypertension and preeclampsia of hypertensive disorder complicating pregnancy (HDCP).Methods Fifty cases with HDCP and 46 cases with mild and 83 cases with sever stage preeclampsia were selected as our subjects.And 33 cases with regular pregnancy and 31 with irregular pregnancy were served as control group.Plasma brain natriuretic peptide,urinary protein quantity(UBQ),24-hour urinary protein assay (UPA) were measured.The correlations of brain natriuretic peptide and UBQ,UPA,systolic pressure (SP),diastolic pressure (DP) were analyzed.Results The levels of brain natriuretic peptide in the group with gestational hypertension and mild,severe preeclampsia groups were (48.54± 18.27),(79.46± 32.18) and (292.24±213.08) ng/L,higher than that in normal pregnancy and non pregnant group ((27.84± 14.58) and (20.63± 8.28) n/L;F =49.583,P＜0.05).While no significant difference exists between normal pregnancy group and non pregnant group.Grouped on the median values (199) of brain natriuretic peptide of the severe preeclampsia group,the levels of 24-hour UPA,systolic pressure and diastolic pressure were (5.46±2.68) g,(174.55± 13.58) mmHg,(113.74±9.91) mmHg in patients with brain natriuretic peptide ≥ 199 ng/L(n=42),significant higher than those in patients with brain natriuretic peptide ＜ 199 ng/L(n =41;(4.34± 1.95)g,(165.31±11.12) mmHg,(106.05±8.02) mmHg;t=2.603,3.396,2.308;P=＞0.010,0.001,0.024).The levels of 24-hour UPA,systolic pressure and diastolic pressure of patients with brain natriuretic peptide ≥ 86ng/L(n=20) in mild preeclampsia were (1.68±0.27) g,(163.69±8.29) mmHg,(105.45±6.71) mmHg,significant higher than those in patients with brain natriuretic peptide ＜ 86 ng/L (n =26;(1.16 ± 0.31) g,(152.90±7.32) mmHg,(99.19 ± 5.25) mmHg;t =3.180,2.508,2.32;P =0.010,0.016,0.025).Brain natriuretic peptide was closely correlated with UPA,systolic pressure and diastolic pressure in hypertensive disorder complicating pregnancy (HDCP) (r =0.29,0.30;P ＜ 0.01).Brain natriuretic peptide was closely correlated with UPA systolic pressure and diastolic pressure in mild preeclampsia (r =0.39,0.37,0.40;P ＜0.01).And correlation efficacy of brain natriuretic peptide with UPA,systolic pressure and diastolic pressure were 0.44,0.42 and 0.53 (P＜0.01).Conclusion The level of brain natriuretic peptide is closely associated with the severity of gestational hypertension and preeclampsia of hypertensive disorder complicating pregnancy.Correlation of brain natriuretic peptide to the severity of gestational hypertension and preeclampsia is independent of urinary protein and hypertension.Brain natriuretic peptide is an important indicator for the severity of gestational hypertension and preeclampsia of hypertensive disorder complicating pregnancy.

OBJECTIVE: To investigate the occurring mechanism and clinical characteristics of severe acute pancreatitis (SAP) associated with hypoalbuminemia in early stage and its influence on prognosis of SAP and the preventive and therapeutic management of this disease. METHODS: One hundred and thirty-eight cases diagnosed as SAP complicated by hypoalbuminemia in early stage were accepted in our hospital from August 1, 2003 to December 31, 2004, and they were divided into 2 groups according to the level of plasma albumin: mild hypoalbuminemia (30 to 35 g/L) group and severe hypoalbuminemia (<30 g/L) group. The complications in the early stage, related parameters, and the incidence rate of infection and mortality in the later stage were evaluated respectively. RESULTS: The incidence rates of renal dysfunction, shock, cardiovascular failure and gastrointestinal hemorrhage, the score of acute physiology and chronic health evaluation II (APACHE II ) and the frequencies of pulse and breath in the severe hypoalbuminemia group were all higher than those in the mild hypoalbuminemia group (P<0.05 or P<0.01). The differences of incidence rate of hepatic failure and the scores of Ranson and Balthazar CT between these two groups had no statistical significance (P>0.05). The incidence rate of infection and the mortality in the severe hypoalbuminemia group were higher than those in the mild hypoalbuminemia group (P<0.01) in the later stage of SAP. CONCLUSION: Hypoalbuminemia in the early stage can accelerate the deterioration in pathophysiology of SAP. The lower level of the plasma albumin is in the early stage, the more complications and the higher incidence rate of infection and mortality will be in the later stage. To relieve the extent of systemic inflammatory response syndrome (SIRS) and abundant supplement of albumin, amino acid and lipid in time may be crucial to prevent the occurrence and deterioration of hypoalbuminemia.