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OBJECTIVE@#To investigate the effect of emodin on high glucose (HG)-induced podocyte apoptosis and whether the potential anti-apoptotic mechanism of emodin is related to induction of adenosine-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)-mediated autophagy in podocytes (MPC5 cells) in vitro.@*METHODS@#MPC5 cells were treated with different concentrations of HG (2.5, 5, 10, 20, 40, 80 and 160 mmol/L), emodin (2, 4, 8 µ mol/L), or HG (40 mmol/L) and emodin (4 µ mol/L) with or without rapamycin (Rap, 100 nmol/L) and compound C (10 µ mol/L). The viability and apoptosis of MPC5 cells were detected using cell counting kit-8 (CCK-8) assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy marker light chain 3 (LC3) I/II, and AMPK/mTOR signaling pathway-related proteins were determined by Western blot. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy.@*RESULTS@#HG at 20, 40, 80 and 160 mmol/L dose-dependently induced cell apoptosis in MPC5 cells, whereas emodin (4 µ mol/L) significantly ameliorated HG-induced cell apoptosis and caspase-3 cleavage (P<0.01). Emodin (4 µ mol/L) significantly increased LC3-II protein expression levels and induced RFP-LC3-containing punctate structures in MPC5 cells (P<0.01). Furthermore, the protective effects of emodin were mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 µ mol/L) reversed emodin-induced autophagy activation.@*CONCLUSION@#Emodin ameliorated HG-induced apoptosis of MPC5 cells in vitro that involved induction of autophagy through the AMPK/mTOR signaling pathway, which might provide a potential therapeutic option for diabetic nephropathy.
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Emodina/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Podócitos , Caspase 3/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais , Apoptose , Sirolimo/farmacologia , Glucose/metabolismo , AutofagiaRESUMO
Hypertrophic cardiomyopathy(HCM)is one of the leading causes of sudden cardiac death(SCD)in children and young adults. The incidence of HCM in adults is 1/500,which is mainly coding sarcomere-associated protein gene mutations. The most common are MYH7 and MYBPC3. The incidence of HCM in children is unclear,and the etiology is more complicated. The clinical manifestations are highly heterogeneous. There are many kinds of non-sarcomere mutations,including metabolic storage diseases,RASopathies,neurodegenerative diseases and mitochondrial diseases. Up to now,more than 40 genes are associated with pediatric HCM. Multiple modes of inheritance account for HCM,among which autosomal dominant inheritance is the most common mode. Others include autosomal recessive,X-linked,and mitochondrial inheritance.
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Guanxinshutong capsule (GXSTC) is an effective and safe traditional Chinese medicine used in the treatment of cardiovascular diseases (CVDs) for many years. However, the targets of this herbal formula and the underlying molecular mechanisms of action involved in the treatment of CVDs are still unclear. In the present study, we used a systems pharmacology approach to identify the active ingredients of GXSTC and their corresponding targets in the calcium signaling pathway with respect to the treatment of CVDs. This method integrated chromatographic techniques, prediction of absorption, distribution, metabolism, and excretion, analysis using Kyoto Encyclopedia of Genes and Genomes, network construction, and pharmacological experiments. 12 active compounds and 33 targets were found to have a role in the treatment of CVDs, and four main active ingredients, including protocatechuic acid, cryptotanshinone, eugenol, and borneol were selected to verify the effect of (GXSTC) on calcium signaling system in cardiomyocyte injury induced by hypoxia and reoxygenation. The results from the present study revealed the active components and targets of GXSTC in the treatment of CVDs, providing a new perspective to enhance the understanding of the role of the calcium signaling pathway in the therapeutic effect of GXSTC.
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Animais , Ratos , Animais Recém-Nascidos , Canfanos , Química , Cardiotônicos , Química , Farmacologia , Células Cultivadas , Medicamentos de Ervas Chinesas , Química , Farmacologia , Eugenol , Química , Expressão Gênica , Hidroxibenzoatos , Química , Espectrometria de Massas , Modelos Biológicos , Miócitos Cardíacos , Óxido Nítrico Sintase Tipo III , Genética , Fenantrenos , Química , Ratos Sprague-Dawley , Receptor PAR-1 , Genética , Biologia de SistemasRESUMO
Guanxinshutong capsule (GXSTC) is an effective and safe traditional Chinese medicine used in the treatment of cardiovascular diseases (CVDs) for many years. However, the targets of this herbal formula and the underlying molecular mechanisms of action involved in the treatment of CVDs are still unclear. In the present study, we used a systems pharmacology approach to identify the active ingredients of GXSTC and their corresponding targets in the calcium signaling pathway with respect to the treatment of CVDs. This method integrated chromatographic techniques, prediction of absorption, distribution, metabolism, and excretion, analysis using Kyoto Encyclopedia of Genes and Genomes, network construction, and pharmacological experiments. 12 active compounds and 33 targets were found to have a role in the treatment of CVDs, and four main active ingredients, including protocatechuic acid, cryptotanshinone, eugenol, and borneol were selected to verify the effect of (GXSTC) on calcium signaling system in cardiomyocyte injury induced by hypoxia and reoxygenation. The results from the present study revealed the active components and targets of GXSTC in the treatment of CVDs, providing a new perspective to enhance the understanding of the role of the calcium signaling pathway in the therapeutic effect of GXSTC.
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Animais , Ratos , Animais Recém-Nascidos , Canfanos , Química , Cardiotônicos , Química , Farmacologia , Células Cultivadas , Medicamentos de Ervas Chinesas , Química , Farmacologia , Eugenol , Química , Expressão Gênica , Hidroxibenzoatos , Química , Espectrometria de Massas , Modelos Biológicos , Miócitos Cardíacos , Óxido Nítrico Sintase Tipo III , Genética , Fenantrenos , Química , Ratos Sprague-Dawley , Receptor PAR-1 , Genética , Biologia de SistemasRESUMO
Background Although Leber hereditary optic neuropathy (LHON) and optic neuritis have different causes and managements,their clinical manifestations are difficult to be distinguished.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR) is a high flux,simple,rapid and specific detecting technology,so establishing a specific diagnosis method of LHON with RTFQ-PCR has a practical significance.Objective Purpose of the present study was to establish a real-time Taqman probe for mitochondrial DNA (mtDNA)11778G>A mutation in LHON patients.Methods Primers and Taqman probe for mtDNA 11778G>A mutation were designed based on mtDNA complete geneme.Eighty-four patients with LHON were selected from the LHON DNA bank of Molecular Biology Laboratory,Henan Eye Institute,and 40 normal physical examinees aged 18-20 years were from Henan People's Hospital.2 ml of periphery blood was collected from each individual.Based on the double-blindness principle,mtDNA 11778G>A mutation was tested by both Taqman probe and sequencing to check the reliability of real-time Taqman probe.Results The mtDNA 11778G>A mutation was found in 23 out of 84 patients,and 61 showed a negative result by the technique of real-time Taqman probe.The Ct values of 23 patients with mtDNA 11778G>A mutation were 22.993 ±0.708,but those of 5 normal controls were 0.These findings showed a consistent rate of 100% with the sequencing results.In addition,both the false positive rate and the false negative rate were zero.Conclusions Real-time Taqman probe technique is an accurate,convenient,sensitive,specific and intuitionistic method for the diagnosis of mtDNA 11778G>A mutation in LHON patients.It is feasible and suitable to screen the LHON patients with mtDNA 11778G>A mutation in a large scale.
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<p><b>OBJECTIVE</b>To investigate the significance of high sensitivity C-reactive protein (hsCRP) levels in serum for detecting type 2 diabetes mellitus (T2DM) patients at risk of developing nonalcoholic fatty liver (NAFLD).</p><p><b>METHODS</b>Individuals with T2DM (n = 9489) were recruited from the Kailuan Company between 2006 and 2007 for the first phase of this community-based prospective cohort study. For the second phase of the study, the original cohort was recruited for follow-up (at two years from each subject's original enrollment date (baseline)). The total followed-up subjects (n = 2802; 2344 males, 458 females, 22-88 years old) were categorized into quartiles according to baseline measurements of serum hsCRP levels (less than or equal to 0.30, > 0.30-0.60, > 0.60-1.92 and > 1.92 mg/L) and used to determine the relationship between change in incidence rates of NAFLD and predictive value of baseline serum hsCRP levels by logistic regression analysis.</p><p><b>RESULTS</b>Twenty-nine percent (n = 813) of the followed-up subjects developed NAFLD. The incidence (%) of NAFLD at the two-year follow-up had increased in conjunction with the level of serum hsCRP detected at baseline (quartile 1: 22.5%, 2: 27.3%, 3: 32.1%, and 4: 34.3%; all, P less than 0.01). It was found that the subjects in the highest quartile had an increased risk of NAFLD (odds ratio (OR) = 1.80, 95% confidence interval (CI): 1.42-2.28, P less than 0.01), as compared with those in the lowest quartile. Moreover, when the regression model was adjusted for baseline factors of age, sex, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting serum glucose, and body mass index, the risk of NAFLD remained significantly higher for the highest quartile (vs. the lowest quartile; OR = 1.49, 95% CI: 1.16-1.91, P less than 0.01).</p><p><b>CONCLUSION</b>Serum hsCRP levels may be predictive of development of NAFLD in individuals with type 2 diabetes mellitus. The risk of NAFLD increases in parallel with increasing levels of serum hsCRP.</p>
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Humanos , Proteína C-Reativa , Metabolismo , Estudos de Coortes , Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Diagnóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
<p><b>OBJECTIVE</b>To construct the sodium channel gene SCN5A-delQKP1507-1509 mutation associated with congenital long QT syndrome, and its eukaryotic expression vector, and to examine the expression of mutation protein in human embryonic kidney (HEK) 293 cells.</p><p><b>METHODS</b>Eukaryotic expression vector PEGFP-delQKP-hH1 for SCN5A-delQKP1507-1509 mutation was constructed by rapid site-directed mutagenesis. HEK293 cells were transfected with the wild or mutant vector using lipofectamine, and then subjected to confocal microscopy. The transfected cells were immunostained to visualize intracellular expression of the mutant molecules.</p><p><b>RESULTS</b>Direct sequence and electrophoresis analysis revealed 9 basic group absences at position 1507-1509. The delQKP1507-1509 mutation eukaryotic expression vector was expressed in HEK293 cells. Immunostaining of transfected cells showed the expression of both wild type and mutant molecules on the plasma membrane and there was no difference in the amount of protein, which suggested that the mutant delQKP1507-1509 did not impair normal protein expression in HEK293 cells.</p><p><b>CONCLUSIONS</b>Successful construction of mutant SCN5AdelQKP1507-1509 eukaryotic expression vector and expression of SCN5A protein in HEK293 cells provides a basis for further study on the functional effects of congenital long QT syndrome as a cause of SCN5A mutation.</p>
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Humanos , Western Blotting , Células HEK293 , Síndrome do QT Longo , Genética , Mutagênese Sítio-Dirigida , Genética , FisiologiaRESUMO
To investigate the subtype distribution of human immunodeficiency virus-1(HIV-1) infection among men who have sex with men (MSM) in Zhengzhou, Henan Province, forty blood samples were collected from HIV-1 carriers, who acknowledged to have sex with men. The complete gag gene was amplified by RT-PCR and nested-PCR and sequenced. All sequences were edited by BioEdit and subtyped by genotyping software. Phylogenetic analysis of gag gene were then performed using the MEGA 3.1 software, the gene distances were calculated by Distance program. There were three different HIV-1 subtypes including B, CRF01-AE and CRF07-BC present among twenty four MSMs in Zhengzhou. Genotyping results showed that 33.33% (8/24) were B, 41.67% (10/24) were CRF01-AE and 25% (6/24) were CRF07-BC, and subtype CRF01-AE had become the most prevalent HIV-1 subtype in Zhengzhou, Henan province. In conclusion, recombinant HIV-1 strains are circulating in Henan province and the epidemiology is complicated.
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Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , China , HIV-1 , Classificação , Genética , Homossexualidade Masculina , Filogenia , Análise de Sequência de DNA , Produtos do Gene gag do Vírus da Imunodeficiência Humana , GenéticaRESUMO
<p><b>OBJECTIVE</b>This study aimed to investigate the subtype distribution of gp41 gene of human immunodeficiency virus-1 (HIV-1) among men who have sex with men (MSM) in Zhengzhou.</p><p><b>METHODS</b>Thirty blood samples were collected from men who have sex with men infected by HIV. The complete gp41 gene was amplified by RT-PCR and nested-PCR and sequenced. All sequences were edited by Bioedit and subtyped with HIV sequence library US Los Alamos National Laboratory and online genotyping software provided by American National Center of Biotechnology Information. Phylogenetic analysis of gp41 gene was performed using the MEGA 3.1 software, and the genic dispersion rates among subtype of gp41 gene were analyzed.</p><p><b>RESULTS</b>A total of eighteen gene sequences of HIV-1 gp41 gene were obtained from thirty men who have sex with men infected by HIV, which belonged to subtype CRF15-01B (50% (9/18)), CRF01-AE (22% (4/18)), CRF07-B (22% (4/18)) and B (6% (1/18)), respectively. The intersubtype HIV-1 strains aggregate with according reference strains. The genetic distance inter-subtype of subtype CRF15-01B, CRF01-AE and CRF07-B were 0.050 ± 0.007, 0.052 ± 0.009 and 0.082 ± 0.012, respectively.</p><p><b>CONCLUSION</b>The prevalent subtypes of HIV-1 among among MSM in Zhengzhou was complicated and recombinant HIV-1 strains were the most prevalent strains.</p>
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Humanos , Masculino , Genótipo , Proteína gp41 do Envelope de HIV , Genética , Infecções por HIV , Epidemiologia , Virologia , HIV-1 , Genética , Homossexualidade Masculina , Epidemiologia Molecular , Filogenia , Análise de Sequência de DNARESUMO
<p><b>OBJECTIVE</b>To study the Chinese medicine (CM) syndrome laws of patients with pruritic papular eruption (PPE), thus providing reference for its classification and standard diagnosis.</p><p><b>METHODS</b>Using multicenter, prospective trials in 346 PPE patients,the correlations between sex, age, infection route, and CD4 levels and CM syndrome patterns were analyzed. The syndrome laws correlated with PPE was studied from the macroscopic and microscopic aspects.</p><p><b>RESULTS</b>There was no statistical difference in sex, age, or CD4 level among various CM syndrome patterns. There was statistical difference in the infection route among various CM syndrome patterns. Pi-deficiency dampness-accumulation syndrome occurred more in patients infected by blood. Wind production induced by heat in blood syndrome occurred more in those infected by sexual contact. Blood deficiency wind dryness syndrome occurred in those infected by intravenous drug abuse.</p><p><b>CONCLUSIONS</b>Wind production induced by heat in blood syndrome, blood deficiency wind dryness syndrome, and Pi-deficiency dampness-accumulation syndrome exist in CM syndrome types of AIDS. There was statistical difference in different infection routes of the distribution of each syndrome type.</p>
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Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Síndrome da Imunodeficiência Adquirida , Diagnóstico , Exantema , Diagnóstico , Medicina Tradicional Chinesa , Estudos Prospectivos , Prurido , DiagnósticoRESUMO
<p><b>OBJECTIVE</b>To investigate whether mouse-induced pluripotent stem (iPS) cell line IP14D-1 has the potential to differentiate into induced primordial germ cells (iPGCs), and to explore the changes in the expression of iPGCs-differentiation associated genes and their possible mechanisms.</p><p><b>METHODS</b>Undifferentiated IP14D-1 was cultured to proliferate and then differentiated to form 4-, 7- and 9-day-old induced embryoid bodies (iEBs) in vitro, respectively. RT-PCR and immunofluorescence were used to detect the expressions of Lin28, Blimpl, Stra8 and Mvh, as well as the localization of the corresponding protein in iEBs.</p><p><b>RESULTS</b>The expression of Blimpl was higher than that of Lin28 in the undifferentiated IP14D-1 and mouse embryonic stem cells (mESCs). Mvh and Stra8 as well as mESCs and EBs were also expressed in IP14D-1 and iEBs, but with no significant differences. The expression of Lin28 was gradually increased in the IP14D-1-derived iEBs from 4 to 7 days, but decreased at 9 days, and the expression of Blimp1 was gradually reduced with the prolonged growing time of iEBs.</p><p><b>CONCLUSION</b>A stable system was established for the culture and differentiation of IP14D-1 and IP14D-1-derived iEBs. The expressions of Lin28, Blimp1, Mvh and Stra8 were not significantly different between the undifferentiated IP14D-1 and mESCs, nor were the expressions of Mvh and Stra8 between iEBs and EBs. IP14D-1 and iEBs had the potential to differentiate into iPGCs, which increased in number in the 7-day-old iEBs, and the expression of iPGC-differentiation associated Lin28 became lower in the older iEBs.</p>
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Animais , Masculino , Camundongos , Diferenciação Celular , Linhagem Celular , Células-Tronco Embrionárias , Biologia Celular , Células Germinativas , Biologia Celular , Células-Tronco Pluripotentes Induzidas , Biologia Celular , Camundongos Endogâmicos BALB CRESUMO
<p><b>OBJECTIVE</b>The present study performed linkage analysis and gene mapping to find the possible chromosome locus harboring in one family with benign familial infantile convulsions (BFIC) and investigate the possible molecular pathogenesis of BFIC.</p><p><b>METHODS</b>A four-generation family with BFIC was investigated. The family was genotyped using eight hypervariable microsatellite markers covering four loci: D19S245 and D19S250 for the 19q12-13.1 region, D16S3131 and D16S3133 for the 16p12-q12 region, D2S156 and D2S286 for the 2q24 region, and D20S480 and D20S481 for the 20q13.3 region. Polymorphism fragments were amplified using polymerase chain reaction (PCR) method. PCR products for the markers were subjected to electrophoresis on 8% denatured polyacrylamide gel and silver staining for length judgment of amplification fragment. Linkage analysis was performed by use of MLINK in the LINKAGE computer package. Two-point LOD scores were calculated to estimate the linkage relationship.</p><p><b>RESULTS</b>The two-point LOD scores were less than -2.0 for the genetic markers at chromosomes 19q12-13.1, 16p12-q12 and 2q24 at the recombination rate between 0.000 and 0.01. The two-point LOD scores for D20S481 at the 20q13.3 region were 0.3 and 0.25 at the recombination rate of 0.000 and 0.01, respectively.</p><p><b>CONCLUSIONS</b>There is no evidence that this family with BFIC is linked to one of the following loci: 19q12-13.1, 16p12-q12 and 2q24, but a possible linkage with 20q13.3 region cannot be excluded.</p>
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Feminino , Humanos , Masculino , Mapeamento Cromossômico , Epilepsia Neonatal Benigna , Genética , Ligação Genética , Escore Lod , Repetições de MicrossatélitesRESUMO
<p><b>OBJECTIVE</b>To observe the effects of taurine on hemorheology and oxidative stress of diabetic rats.</p><p><b>METHODS</b>40 rats were divided into control group, diabetes group and treatment group at random. Diabetic model was reproduced by intraperitoneal injection of streptozotocin. After having been treated with taurine for 8 weeks, glycosylated hemoglobin (HbA1c) and the serum contents of glucose, superoxide dismutase(SOD), malondialdehyde (MDA) were measured. The changes of hemorheology in different groups were detected respectively.</p><p><b>RESULTS</b>Compared with control group, the content of glucose, MDA and HbA1c in diabetic rats was increased, the activity of SOD was decreased, the levels of whole blood viscosity and the aggregation index of red blood cells and hematocrit were increased and RBC deformability index was decreased in diabetic rats. Moreover, taurine was able to apparently reduce high blood glucose and HbA1c (P < 0.05), markedly elevated the activity of SOD, lowered the content of MDA (P < 0.01); and taurine also could significantly reduce the levels of whole blood viscosity and the aggregation index of red blood cells and hematocrit in the meanwhile, and increase RBC deformability index (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Taurine could enhance the ability of oxidation resistance, improve blood rheology property in diabetic rats, at the same time it could be beneficial to prevent and cure the development of diabetic blood vessel complication.</p>
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Animais , Masculino , Ratos , Glicemia , Diabetes Mellitus Experimental , Sangue , Diabetes Mellitus Tipo 2 , Sangue , Deformação Eritrocítica , Hemoglobinas Glicadas , Metabolismo , Hemorreologia , Malondialdeído , Metabolismo , Estresse Oxidativo , Ratos Wistar , Superóxido Dismutase , Metabolismo , Taurina , FarmacologiaRESUMO
<p><b>OBJECTIVE</b>To investigate the relationship between transforming growth factor beta-1 (TGF-β(1)) gene-509C/T polymorphism and severe chronic periodontitis in Chinese Hans population.</p><p><b>METHODS</b>TGF-β(1)-509C/T genotype polymorphism was analyzed in 102 patients with severe chronic periodontitis (periodontitis group) and 102 healthy controls (control group) by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method.</p><p><b>RESULTS</b>The distributions of TGF-β(1)-509C/T genotype and allele were significantly different between severe chronic periodontitis group and control group (P < 0.05). TGF-β(1)-509CC, CT and TT genotype frequency were 44.1% (45/102), 47.1% (48/102), 8.8% (9/102) in periodontitis group and 29.4% (30/102), 51.0% (52/102), 19.6% (20/102) in control group, respectively. The relative risk analysis found that C allele carriers had higher risk of suffering from severe chronic periodontitis compared with T allele carriers (OR = 1.718, 95%CI: 1.148-2.569).</p><p><b>CONCLUSIONS</b>TGF-β(1)-509C/T polymorphism is associated with severe chronic periodontitis in Chinese Hans population, and C allele may be an important genetic susceptibility gene for severe chronic periodontitis.</p>
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Humanos , Alelos , Periodontite Crônica , Genética , Predisposição Genética para Doença , Genótipo , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Fator de Crescimento Transformador beta , Fator de Crescimento Transformador beta1 , GenéticaRESUMO
<p><b>OBJECTIVE</b>To analyze etiology of hospitalized hypertensive patients in the department of hypertension from 1999 to 2008.</p><p><b>METHODS</b>This retrospective study was performed to analyze the etiology of hospitalized hypertensive patients in department of hypertension and to show the distribution change of hypertension from 1999 to 2008.</p><p><b>RESULTS</b>(1) There were 5867 (75.1%) patients with essential hypertension and 1942 (24.9%) patients with secondary hypertension (SH). (2) The prevalence rate of SH increased significantly during the 10 years (χ(2) = 387.621, P < 0.001) and was higher in 2008 than in 1999 (39.3% vs. 9.5%, P < 0.05). The prevalence of obstructive sleep apnea syndrome (OSAS) and primary aldosteronism (PA) in 2008 increased 38.3 and 1.8 times respectively than in 1999 (χ(2) = 304.025, P < 0.001; χ(2) = 42.845, P < 0.001) and other SH remained unchanged. (3) The prevalence of PA complicated with OSAS increased significantly in recent five years (χ(2) = 26.376, P < 0.001). Incidence of OSAS was 23.9% in PA patients and incidence of PA was 6.7% in OSAS patients.</p><p><b>CONCLUSIONS</b>With the insights gained on hypertension mechanism and the development of new diagnostic technology, percent of diagnosed SH increased remarkably in recent years in hospitalized hypertensive patients in our department of hypertension. OSAS and PA are the leading causes of SH.</p>
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Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Hospitais Especializados , Hipertensão , Epidemiologia , Pacientes Internados , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
Being the primary neurons in the auditory system, spiral ganglion neurons form the afferent synapse with hair cells and play a critical role in the analysis and integration of hearing. Many kinds of neurotransmitters can be found in the cochlear and they have different effects under both physiological and pathological conditions with complicated mechanism. This article reviews the characters of some transmitters in cochlear, such as glutamate, ATP, dopamine and GABA, and their roles in noise-induced hearing loss, hoping to provide more clues for research and therapy of inner ear diseases.
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<p><b>OBJECTIVE</b>The congenital long QT syndrome (LQTs) is a hereditary disorder in which most affected family members have delayed ventricular repolarization manifested on the electrocardiogram (ECG) as QT interval prolongation. The disorder is associated with an increased propensity to arrhythmogenic syncope, polymorphous ventricular tachycardia (torsade de pointes), and sudden arrhythmic death. LQTs is due to mutations involving principally the myocyte ion-channels, and this monogenetic disorder has an autosomal inheritance pattern. This study investigated the gene mutation of a Chinese family of LQTs with multiple phenotypes including dilated cardiomyopathy (DCM) and cardiac conduction defects, thus to understand the molecular pathogenesis of the diseases.</p><p><b>METHODS</b>A three-generation Chinese LQTs family with multiple phenotypes was investigated. Blood sample was collected from the 8 family members and 100 unassociated normal individuals. Polymerase chain reaction (PCR)-DNA direct sequencing was performed to screen all exons and their flanking introns of SCN5A gene for mutation analysis. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to exclude polymorphism.</p><p><b>RESULTS</b>PCR amplification and subsequent direct sequencing of SCN5A from proband revealed a heterozygous deletion of nine base pairs (CAGAAGCCC) in exon 26, corresponding to the three amino acid residues Gln1507-Lys1508-Pro1509 (QKP). This mutation is localized in the linker region between DIII-DIV of SCN5A. The same mutation was found in another patient (her grandmother) and excluded in the remaining living subjects in this family. This mutation was confirmed using SSCP in 100 unassociated healthy individuals. Similar analysis excluded possible mutations that would lead to amino acid changes in KCNQ1, KCNH2 and LAMIN A/C commonly associated with LQTs and DCM with conduction disorders, no new mutations that would lead to amino acid changes was found.</p><p><b>CONCLUSION</b>The result of the present study suggests that SCN5A mutation delQKP1507-1509 exists in patients with LQTs. The delQKP1507-1509 of SCN5A is a novel mutation in Chinese people. The same mutation was previously reported in a French family with only a single LQTs phenotype. Further studies on functional expression of SCN5A mutation delQKP1507-1509 will be helpful to understand the mechanism of the multiple phenotypes.</p>
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Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Povo Asiático , Genética , Análise Mutacional de DNA , Canal de Potássio ERG1 , Canais de Potássio Éter-A-Go-Go , Genética , Canal de Potássio KCNQ1 , Genética , Síndrome do QT Longo , Classificação , Genética , Mutação , Linhagem , Fenótipo , Canais de Sódio , GenéticaRESUMO
Objective To estimate the median survival and the effect of antiretroviral therapy (ART) among HIV-positive former blood donors of Fuyang in Anhui province, China. Methods A retrospective survey was conducted among HIV-positive former blood donors, and data was collected on survivors who had received ART. Weibull function was used to calculate median survival of HIV-positive former blood donors. The effect of ART was estimated through comparing the actual number of deaths after ART with the expected number of deaths in those who did not receive ART. Results The median period of HIV infection was at the end of 1994, with the median survival of HIV-positive former blood donors in Fuyang as 10.8 years. By the end of September 2008, among 159 former blood donors, 74 received ART, with their mean CD4+ T-cell count increased from 247.8/μl to 475.1/μl (P<0.0001). 76 of the 159 former blood donors died. When comparing the expected number of deaths calculated by Weibull function, 31.7% of the total number of deaths was reduced. Conclusion Result from this study was in consistent to the UNAIDS' figures that in the absence of treatment, the net median survival time after infection with HIV was estimated to be 11 years and ART has reduced about one third of the expected deaths.
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<p><b>OBJECTIVE</b>To analyze the etiology of 628 patients with refractory hypertension and to observe the disease distribution with respect to gender and different age groups.</p><p><b>METHODS</b>In this study, clinical data of 628 refractory hypertensives who hospitalized in our hospital from September 1997 to December 2005 were retrospectively analyzed.</p><p><b>RESULTS</b>(1) There were 80.1% (503/628) patients with essential hypertension, 18.9% (119/628) with secondary hypertension (SH) while diagnosis was not clear in 1.0% (6/628) patients. Renovascular hypertension (33.6%) and obstructive sleep apnea syndrome (23.5%) were the major causes of SH. The highest prevalence rate of endocrine hypertension was primary aldosteronism (13.5%). (2) There were significantly more male patients than female patients with essential hypertension, SH, renal hypertension, obstructive sleep apnea syndrome, primary aldosteronism while the incidence of pheochromocytoma in female was significantly higher than that in male patients (all P < 0.05). The incidence of renovascular hypertension was similar between male and female patients. (3) SH occurred more often in young patients (33.1%) than in aged patients (13.8%, P < 0.05).</p><p><b>CONCLUSION</b>Our data from this patient cohort showed that SH, especially renovascular hypertension and obstructive sleep apnea syndrome are major causes for refractory hypertension in young patients and primary aldosteronism was the commonest reason of endocrine hypertension in youth and middle-aged patients with refractory hypertension.</p>
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Distribuição por Idade , China , Epidemiologia , Hiperaldosteronismo , Hipertensão , Epidemiologia , Estudos Retrospectivos , Distribuição por Sexo , Apneia Obstrutiva do SonoRESUMO
Objective To understand the biochemical characteristics and 16S rDNA genetic sequence evolution of strains isolated from diarrhea specimens so as to provide basis for classification and identification of Klebsiella pneumoniae. Methods Specimens were cultured using MacConkey and SS medium. All isolates were identified as K. pneumoniae by automated biochemical tests. DNA was extracted, 1500 bp fragments of the 16S rDNA gene were by amplified PCR and sequenced with K. pneumoniae 16S rDNA primer, after being cut. Fragments of 1000 bp overlapping sequences were analyzed by Blastn to confirm the identity of the isolates. A phylogenetic tree was constructed by PHYLIP process to analyze the 16S rDNA sequence of the isolated strain with other relative bacteria species in the GenBank databases. Results Among 113 specimens of infectious diarrhea, 25 K. pneumoniae strains were identified by biochemical tests, of which 21 subsp, pneumoniae and 4 subsp, ozaenae, no subsp, of rhinoseleroma were isolated. Strains of subsp, pneumoniae were found having nature of resistance. All isolates were resistant to penicillin G and susceptible to polymyxin with some strains were resistant to Nitrofurantoin, Cephalothin, Kanamycin, Tobramycin. After searching in GenBank of 16S rDNA, strains biochemical identified as subsp, ozaenae shared high similarity with Salmonella strains and other intestinal bacteria. 16S rDNA phylogenetie analysis could be used to confirm subsp, pneumoniae, but could not separate other subspecies of K. pneumoniae completely. Conclusion 16S rDNA phylogenetic analysis useful in identifying and classifying K. pneumoniae.