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Comorbidities will inevitably lead to an increase in the number of medications used and adverse drug reaction events in elderly patients.Therefore, it is urgent to implement precision medicine in the elderly population.pharmacogenomic testing can increase the opportunity of individualized drug selection for elderly patients, reduce the risk of adverse drug reactions, reduce the cost-effectiveness ratio of medication, improve elderly patients' medication compliance, and thus reduce their readmission rate.Therefore, it is necessary to promote pharmacogenetic testing for elderly patients with comorbidities and polypharmacy, so as to provide measures for the implementation of personalized medicine in the elderly.
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BackgroundDysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients.MethodsA total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics.ResultsCompared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer.ConclusionDiabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.
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OBJECTIVE：To prov ide reference for mobilizing the work enthusiasm of clinical pharmacists ，and further promoting the strategic objectives of performance appraisal in three-level public hospitals （“National examination ”for short ）. METHODS：A department performance appraisal team was established ，and a key performance indicator system consisting of 4 first-level indicators and 9 second-level indicators was constructed by using literature retrieval and expert consultation. The performance distribution method of double assessment of performance score and performance score was established ，and a performance publicity and feedback performance mechanism was formed. Relevant data were collected to compare the core work indicators of clinical pharmacists ，use intensity of antibiotics ，compliance rate of essential drugs in our hospital from Apr. to Dec. 2019（before implementation ）and Apr. to Dec. 2020（after implementation ）. RESULTS ：After the implementation of performance appraisal scheme ，the total number of medication recommendations of clinical pharmacists increased from 1 192 to 5 226，with an increase of 338.42％；the number of medication suggestions received increased from 846 to 4 855，with an increase of 473.88％； and the rate of drug suggestions received increased from 70.97％ to 92.90％；the number of pharmaceutical consultation increased from 195 to 1 284，with an increase of 558.46％；the number of drug counseling increased from 1 203 to 2 719，increasing by 126.02％. Form Apr. to Dec. 2020，the number of patient safety medication evaluation forms reached 660. The antibiotics use density（AUD）in clinical departments of 13 clinical pharmacists were decreased to different extent after the implementation of performance appraisal scheme ，the decine rate was 92.31％（12/13），and the compliance rate was 69.23％（9/13）；utilization rate of essential medicine among outpatients of 11 clinical pharmacists ’clinical departments had achieved positive growth ，and those among inpatients of 2 clinical pharmacists ’clinical departments had achieved positive growth. CONCLUSIONS ：The performance appraisal system of clinical pharm acists formulated by our hospital links the “National examination ”index with the performance ， appraisal of clinical pharmacists ，which can provide ideas for No.2018sxzx57，No.2020jyxm2328，No.2020jyxm2307） the performance appraisal of three-level public hospitals and help to promote the high-quality and sustainable development of hospital pharmaceutical care.
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OBJECTIVES@#To study the role of adrenomedullin (ADM) in hyperoxia-induced lung injury by examining the effect of ADM on the expression of calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein 2 (RAMP2), extracellular signal-regulated kinase (ERK), and protein kinase B (PKB) in human pulmonary microvascular endothelial cells (HPMECs) under different experimental conditions.@*METHODS@#HPMECs were randomly divided into an air group and a hyperoxia group (@*RESULTS@#Compared with the air group, the hyperoxia group had significant increases in the mRNA and protein expression levels of ADM, CRLR, RAMP2, ERK1/2, and PKB (@*CONCLUSIONS@#ERK1/2 and PKB may be the downstream targets of the ADM signaling pathway. ADM mediates the ERK/PKB signaling pathway by regulating CRLR/RAMP2 and participates in the protection of hyperoxia-induced lung injury.
Subject(s)
Humans , Adrenomedullin/genetics , Endothelial Cells , Hyperoxia/complications , Lung Injury , Receptor Activity-Modifying ProteinsABSTRACT
BackgroundDysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients.MethodsA total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics.ResultsCompared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer.ConclusionDiabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.
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Objective: The objective was to evaluate the feasibility and safety of computed tomography (CT)-guided percutaneous irreversible electroporation (IRE) in porcine kidneys. Materials and Methods: Under CT guidance, two monopole probes were used to precisely puncture through the renal parenchyma into the renal hilum in nine anesthetized adult Bama miniature pigs. After which, IRE ablation was performed. Biochemical and pathological examinations were carried out 2 h, 2, 7, and 14 days after the procedure. Results: All procedures were performed successfully without any serious complications such as bleeding, infection, or death. All pigs survived until the end of the study. Pathological examinations showed that cells in the ablation area were dead within 2 days after the procedure, whereas the vascular endothelium showed only slight damage. After 2 days, endothelialization ensued and regrowth of smooth muscle cells was observed after 14 days. Hemogram tests indicated a transient increase but gradually returned to baseline levels 14 days after the procedure. Conclusion: IRE was essentially safe, however further studies on tumor ablation using several different animal models are needed
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Background@#Dysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients. @*Methods@#A total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics. @*Results@#Compared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower.Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP.The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer. @*Conclusion@#Diabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.
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Objective To analyze the effects of bone morphogenetic protein 7 (BMP 7) on insulin signaling pathway in mice and its involved molecular mechanisms. Methods To increase BMP7 expression in liver, adenovirus bearing BMP7 was injected into mice via tail vein. The impact of BMP7 overexpression on glucose metabolism was assayed by glucose tolerance test and insulin tolerance test. The levels of proteins involved in insulin signaling pathway and c-Jun N-terminal kinase ( JNK) signaling pathway were analyzed by Western blot. Results The blood glucose level was increased by BMP7 overexpression (P>0. 05), while the glucose tolerance and insulin tolerance were decreased by BMP7. The p-Akt and p-GSK3βin liver and epididymal white adipose tissue (WAT) were reduced in the BMP7-overexpressed mice (P>0. 01), indicating insulin signal transduction was inhibited. In gastrocnemius muscle, the insulin signal transduction was not altered by BMP7. Mechanistically, the JNK pathway was activated by BMP7 in liver and epididymal WAT (P>0. 01), while the JNK pathway in skeletal muscle was not changed. Conclusions In mice, BMP7 elevated blood sugar and decreased glucose and insulin tolerance. BMP7 inhibited the insulin signaling pathway in liver and WAT. These inhibitory effects on insulin signaling pathway was likely to be achieved by an activating JNK signaling pathway.
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AIM To establish an LC-MS/MS method for the simultaneous content determination of paeoniflorin,albiflorin,neochlorogenic acid,chlororogenic acid,catechin,epicatechin,ethyl gallate,danshensu,ferulic acid,caffeic acid,gallic acid,protocatechuic acid,protocatechualdehyde and rosmarinic acid in Yangxue Qingnao Granules (Angelicae sinensis Radix,Chuanxiong Rhizoma,Paeoniae Radix Alba,etc.).METHODS The analysis of methanol extract of this drug was performed on a 20 ℃ thermostatic Waters Symmetry Shield RP C18 column (3.9 mm × 150 mm,5 μm),with the mobile phase comprising of acetonitrile-water (containing 0.1％ formic acid) flowing at 0.4 mL/min in a gradient elution manner.RESULTS Fourteen constituents showed good linear relationships within their own ranges,whose average recoveries were 85.5％-107.0％ with the RSDs of 2.0％-5.0％.CONCLUSION This simple,sensitive,accurate and reproducible method can be used for the quality control of Yangxue Qingnao Granules.
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Objectives To explore the correlation between the heteroplasmy level of mt5178C＞A mutation in ND2 gene of mitochondria DNA and essential hypertension(EH)in middle-aged and elderly adults.Methods EH patients and normotensive controls were recruited consecutively from 2014-2015 from general population.Demographics,clinical characteristics and blood leukocytes were collected.The mt5178C＞A mutation heteroplasmy level was quantified by the rapid and sensitive realtime polymerase chain reaction(PCR) method for each participant.Results A total of 108 EH patients and 109 controls were recruited.The mt5178C＞A mutation heteroplasmy level was(42 ± 11％)in EH patients and (54± 13)％ in control subjects,with statistically significant difference between the two groups(P＜0.01).Using a two-step cluster analysis,the mt5178C＞A heteroplasmy level exceeding 44％ was associated with a decreased risk of EH(OR=0.18,95％,CI:0.10-0.31,P＜0.01).Correlation analysis showed mt5178C＞ A heteroplasmy level was significantly negatively correlated with both systolic blood pressure (r =-0.38,P＜ 0.001) and diastolic blood pressure (r =-0.49,P＜ 0.01)in 109 controls.Logistic regression analysis demonstrated that in single-factor analysis,mt5178C ＞ A heteroplasmy level (OR =0.82,95 ％ CI:0.77 0.87,P ＜ 0.01) was protective factor for EH,however,BMI(OR=1.30,95％CI:1.12-1.45,P＜0.01),total cholesterol(OR=2.13,95％CI:1.39-3.28,P=0.00),triglyceride(OR=7.62,95％CI:3.45-16.84,P＜0.01)and blood urea nitrogen(OR =1.35,95 ％ CI,P =0.03) were risk factors for EH.And a multiple logistic regression analysis showed that mt5178C＞ A heteroplasmy level (OR =0.83,95 ％ CI:0.78-0.89,P＜ 0.01) was independent protective factor for E H,however,only total cholesterol (OR =2.17,95 ％ CI:1.58-2.98,P =0.02) and low density lipoprotein cholesterol (OR =0.06,95％ CI:0.01-0.83,P =0.04) were independent risk factors for EH,and the P at critical 0.05 value.Conclusions Mitochondrial ND2 gene 5178C＞ A mutation heteroplasmy level exerts protective role against EH in middle-aged and elderly adults in Chinese population.
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Objective:To study the effect of quality control circle(QCC)on the reasonable ratio of clinical prescriptions. Methods:The dispensed prescriptions in orthopedic emergency department were reviewed in our hospital,and the reasons of unreasonable prescriptions were analyzed. According to the QCC technique,the activities were implemented,the standardized work process was made out and the results were studied. Results:After the six-month QCC activities,the unreasonable ratio of emergency orthopedics prescriptions was reduced from 70% to 21% ,and the target yield rate was 140% and the improvement rate was 70% . Conclusion:The QCC has obvious effect on the improvement of reasonable ratio of emergency orthopedics prescriptions.
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<p><b>OBJECTIVE</b>To investigate the effect of liraglutide, an analogue of glucagon-like peptide-1, on the proliferation and migration of cardiac microvascular endothelial cells (CMECs) and explore the mechanism.</p><p><b>METHODS</b>In vitro cultured CMECs of SD rats were purified by differential adhesion method and identified immunocytochemically using CD31 antibody and factor VIII. MTT assay was performed to assess the proliferation of the first-generation cells exposed to different concentrations (0-1000 nm/L) of liraglutide. Western blotting was used to detect the activation of PI3K/Akt and MAPK/ERK signaling pathways. BrdU fluorescent labeling and scratch assay were performed to observe the proliferation and migration of CMECs following liraglutide treatment, and PI3K/Akt and MAPK/ERK pathway inhibitors LY294002 and PD98059, respectively, were used to further confirm the role of these signaling pathways in regulating the proliferation and migration of CMECs.</p><p><b>RESULTS</b>Immunocytochemical staining demonstrated a proportion of double positive cells exceeding 95%. The cells exhibited a logarithmic growth 48 h after plating. Liraglutide exposure concentration-dependently promoted the proliferation of CMECs with the optimal concentration of 100 nmol/L (P<0.05). Liraglutide exposure of the cells for 24 h significantly increased the levels of intracellular phosphorylated Akt and ERK (P<0.05), but pretreatment of the cells with Akt and ERK signaling pathway inhibitors 1 h before liraglutide obviously reversed such effect (P<0.05). BrdU and scratch assay showed that 100 nmol/L liraglutide significantly promoted the proliferation and migration of CMECs (P<0.05), but such effects were obviously suppressed by Akt and ERK inhibitors (P<0.05).</p><p><b>CONCLUSION</b>Liraglutide promotes the proliferation and migration of CMECs in vitro via PI3K/Akt and MAPK/ERK signaling pathways.</p>
Subject(s)
Animals , Rats , Cell Movement , Cell Proliferation , Cells, Cultured , Chromones , Endothelial Cells , Cell Biology , Flavonoids , Glucagon-Like Peptide 1 , Pharmacology , Liraglutide , MAP Kinase Signaling System , Morpholines , Myocardium , Cell Biology , Phosphatidylinositol 3-Kinases , Metabolism , Phosphorylation , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To study the relationship between mitochondrial DNA (mtDNA) mutations and hypertension.</p><p><b>METHODS</b>Clinical data of two pedigrees with maternally transmitted hypertension was collected. Whole mtDNA sequence was analyzed.</p><p><b>RESULTS</b>The family members on the maternal side presented with various levels of hypertension, with the onset age ranging from 44 to 55 years old. Analysis of the mtDNA sequence of the two families members showed all patients have carried a matrilineal 4329C> G mutation of the tRNA(Ile) and tRNA(Gln) genes. The same mutation was not found in 366 healthy controls. The 4329C site of mtDNA is highly conserved across species, and has been associated with the fidelity of amino acid accept arm of the tRNAs, as well as functionality and stability in the formation of tRNAs.</p><p><b>CONCLUSION</b>The 4329C> G point mutation in tRNA(Ile) and tRNA(Gln) probably has contributed to the pathogenesis of hypertension, possibly in association with other modifying factors.</p>
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Adult , Female , Humans , Male , Middle Aged , Base Sequence , DNA Mutational Analysis , DNA, Mitochondrial , Chemistry , Genetics , Family Health , Genetic Predisposition to Disease , Genetics , Hypertension , Genetics , Molecular Sequence Data , Pedigree , Point Mutation , RNA, Transfer, Gln , Genetics , RNA, Transfer, Ile , Genetics , Sequence Homology, Amino AcidABSTRACT
The study aimed to investigate the age-related changes and drug reactions of transient outward potassium current (Ito) of ventricular myocytes. Twenty-eight Sprague Dawley rats were divided into young (3-5 months), adult (13-15 months) and aged (22-24 months) groups, and Ito currents of isolated myocytes from each group were recorded respectively by patch-clamp. The perfusion of 2.0 mmol/L 4-AP or 1.0 μmol/L isoproterenol was added respectively in each group, and the changes of Ito were observed. In comparison with young and adult groups, Ito densities of ventricular myocytes in aged group was significantly increased, the curve of steady-state activation of Ito shifted to the left, the close-state inactivation rate significantly decreased, and recovery rate from the steady-state inactivation became quicker. However, no significant changes could be detected for the Ito steady-state inactivation of ventricular myocytes in aged group. The similar responsiveness to 4-AP was observed in all three groups, but the responsiveness to isoproterenol was weaker in the aged group (55.9%) than in the other two groups (127.5% and 125.8%). In conclusion, the results show that Ito of rat ventricular myocyte of aging heart has increased current density and decreased response to isoproterenol.
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Animals , Rats , 4-Aminopyridine , Pharmacology , Aging , Cells, Cultured , Heart Ventricles , Cell Biology , Isoproterenol , Pharmacology , Myocytes, Cardiac , Physiology , Potassium Channels , Physiology , Rats, Sprague-DawleyABSTRACT
<p><b>BACKGROUND</b>Patients with the genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A are expected to require the lowest dose of warfarin, and to have a greatly increased risk of bleeding. The experience for the dosing of warfarin in such extremely rare cases has been seldom reported.</p><p><b>METHODS</b>Demographic and clinical data from two cases with stable low dose of warfarin in China were studied by resequencing the corresponding gene segments in their whole blood DNA. The potential clinical value of the pharmacogenetic algorithm for them was evaluated by calculating the stable dose of warfarin in pharmacogenetic algorithm developed by International Warfarin Pharmacogenetics Consortium.</p><p><b>RESULTS</b>Both cases (68-year-old female and 50-year-old male) were diagnosed as chronic nonvalvular atrial fibrillation needing warfarin treatment, with target international normalized ratio (INR) 2 to 3. Case 1 had stable warfarin dose of 0.625 mg/d and case 2 1.25 mg/d. They needed more than 1 month to stabilize their anticoagulation. Exceeding INR values were recorded for them when the dose of warfarin was no more than 2 mg/d. Hemorrhagic complication appeared in case 1 when the dose was titrated from 2.5 to 1.25 mg/d. No concomitant medicine to increase or decrease the INR value was recorded for them. Genotyping CYP2C9 and VKORC1 showed both patients were the carriers of the homozygous alleles -CYP2C9*3/*3 and VKORC1-1639 A/A. Their stable doses of warfarin calculated by the pharmacogenetic dose algorithm (0.672 mg/d for case 1 and 1.16 mg/d for case 2) were comparable with their actual stable therapeutic doses.</p><p><b>CONCLUSIONS</b>Two Chinese with the rare genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A were found to require the extremely low dose of warfarin. The pharmacogenetic algorithm incorporating the variances of VKORC1 and CYP2C9 genotypes, as well as the non-genetic factors could predict their stable dose of warfarin with high accuracy.</p>
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Aged , Female , Humans , Male , Middle Aged , Anticoagulants , Aryl Hydrocarbon Hydroxylases , Genetics , Cytochrome P-450 CYP2C9 , Genotype , Hemorrhage , Mixed Function Oxygenases , Genetics , Pharmacogenetics , Vitamin K Epoxide Reductases , WarfarinABSTRACT
@# ObjectiveTo explore the effect of the individualized intervention for the anxiety-depression after cardiovascular diseases. Methods80 inpatients with cardiovascular diseases were surveyed with Hospital Anxiety and Depressions Scale (HAD). The patients with anxiety-depression received individualized psychological intervention. Results14 of them suffered anxiety-depression. 13 cases recovered after the intervention. ConclusionThe individualized psychological intervention can improve anxiety-depression in the inpatients with cardiovascular diseases.
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<p><b>OBJECTIVE</b>To construct the plasmid pSG5/TRIF and investigate its expression in Huh7 cells.</p><p><b>METHODS</b>The plasmid pCX4pur/Myc-TRIF was digested with Not I and the digestion product was blunted followed by further digestion with EcoR I to obtain the insert Myc-TRIF. pSG5 was digested sequentially with Sma I and EcoR I. All the digested products were analyzed with agarose gel electrophoresis. The products with the expected size were extracted and ligated, and the positive clones were screened by ampicillin and amplified. The recombinant pSG5/TRIF was extracted, purified, and identified by restriction endonuclease BamH I and agarose gel electrophoresis. The recombinant plasmids were transfected into Huh7 cells with FuGene 6 reagents and into Huh7 cells previously infected with recombinant vaccinia virus (rVV) via Lipofectin. Immunofluorescence and Western blotting were performed to detect the expression of the recombinant plasmids, and the transfection efficiency with different transfection reagents was compared.</p><p><b>RESULTS</b>BamH I digestion resulted in a fragment with the expected size. Immunofluorescence staining showed successful expression of Myc-TRIF protein in Huh7 cells, and the transfection efficiency was enhanced in Huh7 cells previously infected with rVV. SDS-PAGE analysis showed that the relative molecular mass of the expressed product by pSG5/Myc-TRIF was about 100 ku, and prior infection of the cells with rVV obviously increased transfection efficiency, as was consistent with the results of immunofluorescence.</p><p><b>CONCLUSION</b>pSG5/Myc-TRIF is successfully constructed and expressed in Huh7 cells. The expression efficiency can be increased by prior infection of the cells with rVV.</p>
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Humans , Adaptor Proteins, Vesicular Transport , Genetics , Cell Line, Tumor , Gene Expression , Genetic Vectors , Hepacivirus , Genetics , Plasmids , Recombinant Fusion Proteins , Genetics , TransfectionABSTRACT
Objective To observe the surface structures of cardiovascular endothelial cells in situ with atomic force microscope (AFM). Methods Fresh aorta and aortic valve were dissected from 10 healthy male New Zealand white rabbits. Before fixed in 1% formaldehyde, the fresh tissues were washed in the buffer phosphate solution. Under general microscope, the fixed aorta or valve was spread on the double side stick tape which had already been stuck on the glass slide. The intima of aorta or the aorta side of valve was towards upside. Then the specimen was dried under 37 degrees centigrade in an attemperator and was washed with pure water. After dried again, the specimen was loaded on the platform ofNanoScope llla AFM and was scanned in tapping mode with the scanning speed of 0.5 HZ. Results The surface structures of endothelial cell on the fixed and dried tissue could be obsserved clearly in situ with AFM. Aortic endothclial cells were large, branched and arranged sparsely and parallel to the direction of blood flow, whereas endothelial cells on aorta valve surface were small, less branched and arranged intensively and vertical to the direction of blood flow. When the scanning range was dwindled, granular ultra-structures could be observed on the surface of endothelial cells, and, as the scanning range was dwindled further, fissure and convolution could be seen on the surface of granules from aortic endothelial cells. Centre cavity and surrounding swelling volcano-like structure could be seen on the surface of granules from endothelial cells of aortic valve. Conclusions It's feasible to observe the surface ultra-structures of cardiovascular endothelial cells in situ with AFM and morphological information provided by A FM might be of clinical value in future histopathological diagnosis.
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Protein S deficiency is an autosomal dominant disorder that results from mutations in the protein S gene (PROS1). Inherited deficiency of protein S constitutes a risk factor for venous thromboembolism. Protein S functions as a nonenzymatic cofactor for activated protein C in the proteolytic degradation of coagulation factors V a and Villa. The frequency of protein S deficiency seems to differ between populations. More than 200 rare mutations in PROS1 have been identified in patients with protein S deficiency. Among the prevalent mutations within PROS1, the S460P substitution (known as Heerlen polymorphism) detected in Caucasians and the K196E substitution (known as protein S Tokushima) found in Japanese have been intensively studied for their structures and potential functions in the disorder of protein S deficiency. Until now, causative mutations in PROS1 have been found in only approximately 50% of cases with protein S deficiency. Co-segregation analysis of microsatellite haplotypes with protein S deficiency in families with protein S deficiency suggests that the causative defects in the PROS1 mutation-negative patients are located in or close to the PROS 1 gene. Large PROS 1 gene deletions have been identified in 3 out of 9 PROS 1 mutation-negative Swedish VTE families with protein S deficiency and 1 out of 6 PROS1 mutation-negative Japanese patients with protein S deficiency. Intensive sequencing of the entire PROS 1 gene, including introns, may be needed to identify the cryptic mutations in those patients, and these efforts might uncover the pathogenesis of protein S deficiency.
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Objective To study the characteristics and influencing factors on hearing impairment among elderly population in the community of Taiyuan city. Methods 384 ageing people above 60 years old were selected from Chaoyang and Guandi community in Taiyuan city by multi-stage sampling. Data on influencing factors of hearing impairment were collected by questionnaire. 5 ml fasting blood samples were drawn to detect the level of glucose, triglyceride and cholesterin in the blood samples. All the objects were tested with binaural hearing. The level of binaural hearing threshold at 0.5 kHz, 1 kHz, 2 kHz, 3 kHz, 4 kHz, 8 kHz were measured by GVSLN-TC-GK2000 hearing-assistant evaluative apparatus. The level of 3 kHz, 4 kHz, average hearing threshold from ear with better audition was chosen as dependent variable. Socio-demographic data, environmental factors and biochemical indicator were chosen as independent variables, t test, ANOVA and accumulative logistic regression were performed to analyze the influencing factors on hearing impairment by software SPSS 13.0. Results The prevalence of hearing impairment among elderly population was 90.9%. The hearing disorder was 78.6% with 1.3% of them using hearing-assistant apparatus. Results from single factor analysis showed that the average levels of 3 kHz, 4 kHz, 8 kHz hearing thresholds were significantly different among elderly with different age, sex, education background and the levels of glucose and cholesterin (P<0.01). Results of accumulative logistics regression showed that except glucosein which was the only one included in regression model of lower median frequency group, all the others were included in regression model of frequency group. Being male, older age and with higher level of glucose and cholesterin in blood were risk factors causing hearing impairment. Higher education level seemed to be a preventive factor. Conclusion Hearing impairment appeared in higher prevalence among the elderly population, suggesting that proper measures should be taken. It is beneficial for abating hearing impairment to decrease the level of glucose and cholesterin in blood.