RESUMO
Glial activation and dysregulation of adenosine triphosphate (ATP)/adenosine are involved in the neuropathology of several neuropsychiatric illnesses. The ventral hippocampus (vHPC) has attracted considerable attention in relation to its role in emotional regulation. However, it is not yet clear how vHPC glia and their derived adenosine regulate the anxiodepressive-like consequences of chronic pain. Here, we report that chronic cheek pain elevates vHPC extracellular ATP/adenosine in a mouse model resembling trigeminal neuralgia (rTN), which mediates pain-related anxiodepression, through a mechanism that involves synergistic effects of astrocytes and microglia. We found that rTN resulted in robust activation of astrocytes and microglia in the CA1 area of the vHPC (vCA1). Genetic or pharmacological inhibition of astrocytes and connexin 43, a hemichannel mainly distributed in astrocytes, completely attenuated rTN-induced extracellular ATP/adenosine elevation and anxiodepressive-like behaviors. Moreover, inhibiting microglia and CD39, an enzyme primarily expressed in microglia that degrades ATP into adenosine, significantly suppressed the increase in extracellular adenosine and anxiodepressive-like behaviors. Blockade of the adenosine A2A receptor (A2AR) alleviated rTN-induced anxiodepressive-like behaviors. Furthermore, interleukin (IL)-17A, a pro-inflammatory cytokine probably released by activated microglia, markedly increased intracellular calcium in vCA1 astrocytes and triggered ATP/adenosine release. The astrocytic metabolic inhibitor fluorocitrate and the CD39 inhibitor ARL 67156, attenuated IL-17A-induced increases in extracellular ATP and adenosine, respectively. In addition, astrocytes, microglia, CD39, and A2AR inhibitors all reversed rTN-induced hyperexcitability of pyramidal neurons in the vCA1. Taken together, these findings suggest that activation of astrocytes and microglia in the vCA1 increases extracellular adenosine, which leads to pain-related anxiodepression via A2AR activation. Approaches targeting astrocytes, microglia, and adenosine signaling may serve as novel therapies for pain-related anxiety and depression.
Assuntos
Dor Crônica , Neuralgia do Trigêmeo , Animais , Camundongos , Adenosina/farmacologia , Trifosfato de Adenosina/farmacologia , Modelos Animais de Doenças , Hipocampo , MicrogliaRESUMO
BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is acknowledged as an independent risk factor (IRF) for atherosclerotic cardiovascular disease. Nevertheless, studies on the impact of LDL-C on microvasculature are still scarce. The retina, abundant in microvasculature, can now be examined for microvascular alterations through the novel, non-invasive, and quantitative optical coherence tomography angiography (OCTA) technique. METHODS: In this cross-sectional study, 243 patients from the geriatric department were recruited (between December 2022 and December 2023). Individuals were classified into four groups based on their LDL-C levels: Group 1 (≤ 1.8 mmol/L), Group 2 (> 1.8 mmol/L to ≤ 2.6 mmol/L), Group 3 (> 2.6 mmol/L to ≤ 3.4 mmol/L), and Group 4 (> 3.4 mmol/L). The OCTA results including retinal vessel density (VD), foveal avascular zone (FAZ) area, macula thickness, and retinal nerve fiber layer (RNFL) thickness were contrasted across these groups. T-tests, analysis of variance, Welch's tests, or rank-sum tests were employed for statistical comparisons. In cases where significant differences between groups were found, post-hoc multiple comparisons or rank-sum tests were performed for pairwise group comparisons. Spearman's correlation coefficient was employed to perform bivariate correlation analysis to evaluate the relationship between LDL-C levels and various OCTA measurements. Multivariable regression analysis was used to evaluate the association between LDL-C levels and various OCTA measurements. Linear regression analysis or mixed-effects linear models were applied. RESULTS: It was discovered that individuals with LDL-C levels exceeding 2.6 mmol/L (Groups 3 and 4) exhibited reduced VD in the retina, encompassing both the optic disc and macular regions, compared to those with LDL-C levels at or below 2.6 mmol/L (Groups 1 and 2). A negative correlation among LDL-C levels and retinal VD was identified, with r values spanning from - 0.228 to -0.385. Further regression analysis presented ß values between - 0.954 and - 2.378. Additionally, no notable disparities were detected among the groups regarding FAZ area, macular thickness, and RNFL thickness. CONCLUSIONS: The outcomes of this study suggest that elevated LDL-C levels constitute an IRF for decreased VD across the entire retina. TRIAL REGISTRATION: NCT05644548, December 1, 2022.
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LDL-Colesterol , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Masculino , Feminino , Vasos Retinianos/diagnóstico por imagem , LDL-Colesterol/sangue , Idoso , Estudos Transversais , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Macula Lutea/diagnóstico por imagem , Macula Lutea/irrigação sanguínea , Fatores de RiscoRESUMO
BACKGROUND: Several studies have reported on atrial fibrillation (AF) outcomes, including thromboembolism in patients with paroxysmal and non-paroxysmal AF; however the findings still remain controversial on whether risks differ between these clinical subtypes and limited data are available in Asian cohorts. METHODS: We compared the risk of thromboembolism between paroxysmal and persistent AF patients, in a large contemporary Chinese cohort study. A total of 8529 non-valvular atrial fibrillation (NVAF) patients from the Chinese Atrial Fibrillation Registry (CAFR) study were enrolled. The study subjects were divided into two groups: paroxysmal AF (PaAF, defined as AF lasting within 7 days, n = 4642) and persistent AF (PeAF, lasting over 7 days, n = 3887) groups. RESULTS: In non-anticoagulated patients, PeAF group demonstrated a higher risk of stroke, all-cause death, cardiac/ non-cardiac death and composition of stroke/ transient ischemic attack (TIA)/peripheral thromboembolism (PT)/all-cause death, compared to the PaAF group. No significant difference was found in anticoagulated subjects. On multivariate analysis in non-anticoagulated patients, age ≥ 75 years (P = 0.046) and prior stroke/TIA/PT (P = 0.018) but not AF type (P = 0.63) were significantly associated with the risk of stroke/TIA/PT events. CONCLUSIONS: Stroke, all-cause death and cardiac/non-cardiac death in Chinese NVAF population was increased in non-anticoagulated PeAF patients compared with PaAF group, but same between anticoagulated PeAF and PaAF patients. After adjustment, AF type was not an independent predictor of thromboembolism in NVAF patients. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-OCH-13003729. Registered 22 October 2013.
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Povo Asiático , Fibrilação Atrial/etnologia , Acidente Vascular Cerebral/etnologia , Tromboembolia/etnologia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Pequim/epidemiologia , Causas de Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/diagnóstico , Tromboembolia/mortalidade , Tromboembolia/prevenção & controle , Fatores de TempoRESUMO
Cassane-type diterpenes are main bioactive constituents of Caesalpinia minax HANCE. As a part of our ongoing chemical investigation of C. minax, two new degradative cassane-type diterpenes, named caesalpins I (1) and J (2), were isolated from the EtOAc extract of the seeds of C. minax. The structures were elucidated by means of spectroscopic analysis.
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Hidrocarbonetos Aromáticos com Pontes/isolamento & purificação , Caesalpinia/química , Diterpenos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Hidrocarbonetos Aromáticos com Pontes/química , Diterpenos/química , Medicamentos de Ervas Chinesas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Sementes/químicaRESUMO
Background and aims: Most studies have analyzed the relationship between resting heart rate (RHR) measured at only one time point and future clinical events. The current study aims to investigate the impact of long-term RHR changes on future clinical outcomes in a decade-long cohort with type 2 diabetes mellitus (T2DM). Methods: The two-staged follow-up involved 2,513 T2DM participants. The first stage (2008-2014) intended to identify levels and trends in RHR changes, while the second stage (2014-2018) attempted to collect new occurrence records of clinical results. Cox proportional hazards models were applied to predict hazard ratios (HRs), along with 95% confidence interval (CI) for the correlation between RHR changes and future events. Results: There is no significant correlation between baseline RHR levels and long-term clinical events. According to the range of RHR change, compared with the stable RHR group, the adjusted HRs for cardiovascular events and all-cause death in the large increase group were 3.40 (95% CI: 1.33-8.71, p=0.010) and 3.22 (95% CI: 1.07-9.64, p=0.037), respectively. While the adjusted HRs for all-cause death and major adverse cardiac and cerebrovascular events (MACCE) in the moderate decrease group were 0.55 (95% CI: 0.31-0.96, p=0.037) and 0.51 (95% CI: 0.26-0.98, p=0.046). According to the trend of RHR, compared with the normal-normal group, the adjusted HRs for composite endpoint events and cerebrovascular events in the normal-high group were 1.64 (95% CI: 1.00-2.68, p=0.047) and 2.82 (95% CI: 1.03-7.76, p=0.043), respectively. Conclusion: Changes in RHR had predictive value for long-term clinical events in diabetic populations. Individuals with significantly elevated RHR over a particular period of time showed an increased risk of adverse events.
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Diabetes Mellitus Tipo 2 , Frequência Cardíaca , Humanos , Masculino , Feminino , Frequência Cardíaca/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Pessoa de Meia-Idade , Seguimentos , Idoso , Prognóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Descanso/fisiologia , Adulto , Fatores de Risco , Fatores de TempoRESUMO
Anxiety and depression are frequently observed in patients suffering from trigeminal neuralgia (TN), but neural circuits and mechanisms underlying this association are poorly understood. Here, we identified a dedicated neural circuit from the ventral hippocampus (vHPC) to the medial prefrontal cortex (mPFC) that mediates TN-related anxiodepression. We found that TN caused an increase in excitatory synaptic transmission from vHPCCaMK2A neurons to mPFC inhibitory neurons marked by the expression of corticotropin-releasing hormone (CRH). Activation of CRH+ neurons subsequently led to feed-forward inhibition of layer V pyramidal neurons in the mPFC via activation of the CRH receptor 1 (CRHR1). Inhibition of the vHPCCaMK2A-mPFCCRH circuit ameliorated TN-induced anxiodepression, whereas activating this pathway sufficiently produced anxiodepressive-like behaviors. Thus, our studies identified a neural pathway driving pain-related anxiodepression and a molecular target for treating pain-related psychiatric disorders.
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Hormônio Liberador da Corticotropina , Neuralgia do Trigêmeo , Humanos , Hormônio Liberador da Corticotropina/metabolismo , Neuralgia do Trigêmeo/etiologia , Neuralgia do Trigêmeo/metabolismo , Neurônios/metabolismo , Hipocampo/fisiologia , Dor/metabolismoRESUMO
OBJECTIVE: To summary the efficacy and safety of aerosolized iloprost in patients with pulmonary hypertensive crisis. METHODS: On the basis of conventional therapy, aerosolized iloprost (10 µg per time for 10 - 15 min in 2 hours interval, 8 times per day) was administered to four patients with idiopathic pulmonary arterial hypertension and pulmonary hypertensive crisis. Blood pressure, heart rate, systemic artery oxygen saturation, systolic pulmonary arterial pressure (sPAP) measured by echocardiography and the adverse events were analyzed. RESULTS: After aerosolized iloprost therapy, sPAP was significantly decreased and systemic artery oxygen saturation was improved. Adverse events (nausea, vomiting, diarrhea, dry cough) were observed in two patients, and the iloprost use was stopped in one patient due to severe vomiting and diarrhea. CONCLUSION: Aerosolized iloprost could significantly reduce the sPAP and improve the systemic artery oxygen saturation in patients with pulmonary hypertension crisis.
Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Iloprosta/administração & dosagem , Iloprosta/uso terapêutico , Administração por Inalação , Adulto , Pressão Sanguínea , Criança , Hipertensão Pulmonar Primária Familiar , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Myocardial ischemia/reperfusion (I/R) injury is associated with the poor outcome and higher mortality after myocardial infarction. Recent studies have revealed that miR-199a-5p participates in the process of myocardial I/R injury, but the precise roles and molecular mechanisms of miR-199a-5p in myocardial I/R injury remain not well-studied. Ferroptosis has been proposed to promote cardiomyocyte death, closely associated with myocardial I/R injury. Herein, the present study aimed to explore the function and mechanisms by which miR-199a-5p regulates whether miR-199a-5p contributes to ferroptosis-induced cardiomyocyte death responding to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, an in vitro model of myocardial I/R injury focusing on Akt/eNOS signaling pathway. The results found that ferroptosis-induced cardiomyocyte death occurs and is accompanied by an increase in miR-199a-5p level in OGD/R-treated H9c2 cells. MiR-199a-5p inhibitor ameliorated ferroptosis-induced cardiomyocyte death as evidenced by the increased cell viability, the reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) and Fe2+ contents, and the up-regulated glutathione (GSH)/glutathione disulphide (GSSG) ratio as well as glutathione peroxidase 4 (Gpx4) protein expression in H9c2 cells-exposed to OGD/R, while miR-199a-5p mimic had the opposite effects. In addition, OGD/R led to the inhibition of Akt/eNOS signaling pathway, which was also blocked by miR-199a-5p inhibitor and aggravated by miR-199a-5p mimic. Furthermore, LY294002, an inhibitor of Akt/eNOS signaling pathway, abrogated miR-199a-5p inhibitor-induced the reduction of ferroptosis-induced cardiomyocyte death. In summary, our findings demonstrated that miR-199a-5p plays a central role in stimulating ferroptosis-induced cardiomyocyte death during ischemic/hypoxic injury via inhibiting Akt/eNOS signaling pathway.
Assuntos
Ferroptose , MicroRNAs , Traumatismo por Reperfusão Miocárdica , Humanos , Apoptose , Ferroptose/genética , Glucose/metabolismo , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Miócitos Cardíacos/metabolismo , Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Óxido Nítrico Sintase Tipo IIIRESUMO
OBJECTIVE: Programmed cell death 5 (PDCD5) is an apoptosis related gene and plays an important role in the pathogenesis and development of cancer. Whether PDCD5 is present in peripheral blood serum has not been reported. The aim of this study is to determine the contents of PDCD5 protein in peripheral blood serum of cancer patients, as well as normal subjects. METHODS: ELISA was used to detect the serum PDCD5 concentrations in 100 normal persons, 83 patients with breast cancer, 74 patients with gastrointestinal tract cancer and 41 patients with lung cancer. The results were statistically analyzed and discussed. RESULTS: PDCD5 could be detected in peripheral blood serum in both normal subjects and cancer patients. The serum PDCD5 contents in normal persons ranged from 3.8 to 6.1 ng/ml with a median of 4.70±0.68 ng/ml. For cancer patients the PDCD5 levels were 4.59±0.90, 4.79±1.14 and 10.43±22.34 ng/ml for breast cancer, gastrointestinal cancer and lung cancer patients respectively. There was no statistically significant difference between the serum PDCD5 concentrations of normal persons and cancer patients. CONCLUSION: PDCD5 is present in peripheral blood. The PDCD5 levels in cancer patients are not statistically different from that of normal persons, though decreased expression of PDCD5 in malignant tissues has been found.
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BACKGROUND: Post hoc analysis of the landmark atrial fibrillation follow-up investigation of rhythm management trial revealed that amiodarone was associated with higher risks of mortality, intensive care unit admission, and non-cardiovascular death. We aim to evaluate the association between amiodarone use and patient survival under updated medical mode and level using data from the China Atrial Fibrillation (China-AF) Registry study. METHODS: Clinical data of 8161 non-valvular atrial fibrillation (NVAF) patients who were antiarrhythmic drug (AAD)-naive before enrollment into the China-AF Registry, recruited between August 2011 and February 2017, were collected. The primary outcome was all-cause mortality. A Cox proportional hazard regression model was used to evaluate the association between amiodarone use and the outcome. We also calculated the rate of sinus rhythm maintenance at the penultimate follow-up. RESULTS: Compared with 6167 patients of non-AAD group, 689 patients of the amiodarone group were younger (mean age 65.6 vs. 68.6 years), more frequently completed high school education, had fewer comorbidities such as chronic heart failure, prior bleeding, and stroke, and were more likely to be treated in tertiary hospitals while less hospitalization. The proportion of persistent AF was much lower among users of amiodarone, who were also less likely to be taking oral anticoagulants. The patients in the amiodarone group had a statistically insignificant lower incidence of all-cause mortality (2.44 vs. 3.91 per 100 person-years) over a mean follow-up duration of 300.6â±â77.5 days. After adjusting for potential confounders, amiodarone use was not significantly associated with a lower risk of all-cause mortality (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42-1.49). Sub-group analysis revealed the consistent results. The rate of sinus rhythm maintenance at the penultimate follow-up in the amiodarone group was significantly higher than in the non-AAD group. CONCLUSIONS: Our study indicated that amiodarone use was not significantly associated with a lower risk of 1-year all-cause mortality compared with a non-AAD strategy in "real-world" patients with NVAF.
Assuntos
Amiodarona , Fibrilação Atrial , Idoso , Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , China , Humanos , Estudos Prospectivos , Sistema de RegistrosRESUMO
OBJECTIVE: To determine whether the increased level of serum prostate-specific antigen (PSA) could be used as a diagnostic marker of hyperandrogenism in women. METHODS: Forty-five female patients with hyperandrogenism and 50 healthy control women were detected for the levels of serum PSA, testosterone (T), sex hormone binding globulin (SHBG) and dehydroepiandrosterone sulfate (DHEA-S). The results were statistically analyzed. RESULTS: The level of serum PSA was found to be significantly higher in the hyperandrogenism patients than in the healthy controls (9.72 +/- 1.39 pg/ml vs 3.56 +/- 0.44 pg/ml, P < 0.01), and it showed a weak positive correlation with T (r = 0.226, P < 0.05) and DHEA-S (r = 0.255, P < 0.05), and a weak negative correlation with SHBG (r = -0,228, P < 0.05). CONCLUSION: The increased level of PSA could be used as a diagnostic marker of hyperandrogenism in females.
Assuntos
Hiperandrogenismo/sangue , Hiperandrogenismo/diagnóstico , Antígeno Prostático Específico/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Globulina de Ligação a Hormônio Sexual , Adulto JovemRESUMO
OBJECTIVE: To study the effects of salidroside on the function and ultramicro-pathological change of the hypothalamic-pituitary-gonadal (HPG) axis of male rats in experimental navigation and intensive exercise. METHODS: Six-week SD rats were randomized into 3 groups: non-stress control (NC, n = 10), training control (TC, n = 12) and salidroside treatment (ST, n = 12) group. Blood samples were collected from the NC rats that did not receive any stimulus after a 7-day intragastric administration of saline. The TC rats underwent a 10-day running training with increasing load on the treadmill followed by a 7-day intragastric administration of saline. The ST rats were subjected to the same process of running training as the TC group and received intragastric administration of salidroside. Then blood samples were immediately obtained and the levels of testosterone (T), corticosterone (CORT), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) measured by radioimmunoassay. The testis histopathology was observed by HE staining, and the ultrastructural changes of the pituitaries and testes investigated by electron microscopy. RESULTS: The serum T level was significantly lower in the TC than in the NC group, but showed no significant difference between the ST and NC groups. HE staining revealed no significant difference in testis histopathology among the 3 groups. Ultramicro-pathology showed that the secretory granules of the pituitary cells were significantly reduced in the TC rats compared with the NC ones; the number of the granules significantly increased in the ST group compared with the TC rats; and mitochondrial swelling, increase of electron density and decrease/disappearance of mitochondrial cristae were observed in the Leydig cells of the TC rats. But no significant differences were found in the testicular cells between the ST and NC groups. CONCLUSION: Negative psychological stress and intensive exercise can significantly suppress the function of the HPG axis in rats. Salidroside therapy has protective effect on the HPG axis.
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Glucosídeos/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Fenóis/farmacologia , Condicionamento Físico Animal , Hipófise/efeitos dos fármacos , Estresse Psicológico , Animais , Glucosídeos/uso terapêutico , Sistema Hipotálamo-Hipofisário/patologia , Masculino , Fenóis/uso terapêutico , Hipófise/patologia , Ratos , Ratos Sprague-Dawley , Rhodiola/químicaRESUMO
OBJECTIVE: To investigate the effects of schisandra on the function of the pituitary-adrenal cortex, gonadal axis and carbohydrate metabolism in male rats undergoing experimental chronic psychological stress, navigation and strenuous exercise. METHODS: Thirty-four SD rats were randomly allocated into a non-stress group (Group A), a stress control group (Group B) and a schisandra group (Group C). The latter two groups received 10 days of Benford's high-intensity training, followed by 3 hours of wearing floating with psychological stress and another 3 hours of running at the speed of 26.7 m/min. Then blood samples were immediately obtained for the measurement of the levels of testosterone (T), corticosterone (CORT), luteinizing hormone (LH) and blood glucose (Glu). Meanwhile the adrenal gland was excised and its cortex ultrastructure observed under the electron microscope. RESULTS: The Glu level was increased while the T level decreased significantly in Group B as compared with Group A. The CORT level remained unchanged in Group B. Both the Glu and CORT levels were significantly reduced in Group C in comparison with B. However, no significant differences were found in serum LH levels among the three groups. And electron microscopy revealed a reduction of lipid droplets and apoptosis of the adrenal cortex cells in Group B as compared with C. CONCLUSION: Schisandra can reduce the levels of CORT and Glu and protect the structure of the adrenal cortex.
Assuntos
Metabolismo dos Carboidratos , Ciclo-Octanos/farmacologia , Lignanas/farmacologia , Condicionamento Físico Animal , Sistema Hipófise-Suprarrenal/metabolismo , Compostos Policíclicos/farmacologia , Estresse Psicológico/metabolismo , Animais , Glicemia , Corticosterona/sangue , Hipercinese , Masculino , Fitoterapia , Ratos , Ratos Sprague-Dawley , Schisandra/químicaRESUMO
OBJECTIVE: To screen the MYBPC3 gene mutations in Han Chinese patients with hypertrophic cardiomyopathy (HCM). METHODS: Sixty-six patients with HCM were enrolled for the study. The exons in the functional regions of MYBPC3 were amplified with PCR and the products were sequenced. RESULTS: Four novel mutations and four common polymorphisms were identified in this patient cohort. A Lys301fs mutation in exon10 was evidenced in a H30, and when he was 47 years old, he had the chest tightness, shortness of breath with septal hypertrophy of 18.7mm; a Asp463stop mutation in exon17 was detected in a H48, he was 24 years old 24-year-old when a medical examination showed ventricular septal hypertrophy of 15.4 mm; both Gly523Arg mutation in exon18 and Tyr847His mutation in exon26 were found in a H53 with onset age 36 years old, feeling chest tightness after excise and his ventricular septal hypertrophy was 27 mm that time. MYBPC3 mutations occurred in 4.5% patients in this cohort. These mutations were not found in 100 non-HCM control patients. CONCLUSION: MYBPC3 mutation is presented in a small portion of Han Chinese patients with HCM.
Assuntos
Cardiomiopatia Hipertrófica/genética , Proteínas de Transporte/genética , Adulto , Povo Asiático/genética , Análise Mutacional de DNA , Éxons , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , RNA Mensageiro/genéticaRESUMO
OBJECTIVE: To discuss the phenomenon and the possible causes for the skeletal age less than the "real age" in the judicial expertise. METHODS: With referring to the skeletal age verification value provided by the inspection sample pertaining to CHN scoring method, combining with the relevant materials such as "age" and "residence" information provided by the police authority while performing expertise, as well as tracking down and re-visiting some cases, we retrospectively analyzed 829 cases. RESULTS: There were 303 cases for the skeletal age less than "real age" in total, which accounted for 36.6% (303/829), and accounted for 40.8% (303/742) in 742 cases with "age" cases. If the normal age range between both was less than 0.5 year (including 0.5), the numbers of such cases decreased to 190 cases, which accounted for 22.9% (190/829) and 25.6% (190/742), respectively. When the difference was within 0.5, the "age" close to the skeletal age would be more reliable. It was difficult to confirm which one was wrong if the difference was 0.6-2.0 years. However, the error possibility in "age" would increase with increasing the difference value. CONCLUSION: Many uncertain factors may lead to that the skeletal age was less than the "age". The occurring rate for the skeletal age less than "age" is not low. The identification conclusion shall be made with caution after comprehensive assessment.
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Determinação da Idade pelo Esqueleto/métodos , Osso e Ossos/diagnóstico por imagem , Antropologia Forense/métodos , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Punho/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVE: To analyze the clinical, molecular and cytogenetic features of 46, XX (SRY positive) male syndrome. METHODS: The clinical features of 4 patients with 46, XX (SRY positive) male syndrome were analyzed retrospectively. Karyotyping, FISH, PCR amplification of the SRY gene, and Y-chromosome microdeletion were performed to study their molecular cytogenetic features. RESULTS: The Four patients were all sociopsychologically males of short stature and came to hospital for infertility. Physical examination revealed that their testes were small in volume and soft in texture, but their penes were normal. Semen analyses showed complete azoospermia. Detection of serum sexual hormone suggested hypergonadotropic hypogonadism. All were karyotyped as 46, XX. Molecular analyses revealed the presence of the SRY gene and absence of AZFa, b and c of the Y chromosome. FISH analysis showed that SRY genes were translocated to Xp in 3 of the patients. CONCLUSION: Phenotypically 46, XX (SRY positive) male patients are males generally, for the presence of the SRY gene in the whole genome and azoospermia due to the deletion of AZF. The clinical characteristics of the patient include testis dysgenesis, infertility and short stature. The long arm of the Y chromosome might contain the gene associated with body height. Extensive molecular and cytogenetic studies on 46, XX male syndrome may help to elucidate its genotype-phenotype relation.
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Genes sry , Disgenesia Gonadal 46 XX/genética , Adulto , Estatura , Deleção Cromossômica , Cromossomos Humanos Y/genética , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Disgenesia Gonadal 46 XX/sangue , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Hormônio Luteinizante/sangue , Masculino , Reação em Cadeia da Polimerase , Prolactina/sangue , SíndromeRESUMO
Coating a polymeric membrane for gas separation is a feasible approach to fabricate gas sensors with selectivity. In this study, poly(methyl methacrylate)-(PMMA-)membrane-coated palladium (Pd) nanoparticle (NP) films were fabricated for high-performance hydrogen (H2) gas sensing by carrying out gas-phase cluster deposition and PMMA spin coating. No changes were induced by the PMMA spin coating in the electrical transport and H2-sensing mechanisms of the Pd NP films. Measurements of H2 sensing demonstrated that the devices were capable of detecting H2 gas within the concentration range 0-10% at room temperature and showed high selectivity to H2 due to the filtration effect of the PMMA membrane layer. Despite the presence of the PMMA matrix, the lower detection limit of the sensor is less than 50 ppm. A series of PMMA membrane layers with different thicknesses were spin coated onto the surface of Pd NP films for the selective filtration of H2. It was found that the device sensing kinetics were strongly affected by the thickness of the PMMA layer, with the devices with thicker PMMA membrane layers showing a slower response to H2 gas. Three mechanisms slowing down the sensing kinetics of the devices were demonstrated to be present: diffusion of H2 gas in the PMMA matrix, nucleation and growth of the ß phase in the α phase matrix of Pd hydride, and stress relaxation at the interface between Pd NPs and the PMMA matrix. The retardation effect caused by these three mechanisms on the sensing kinetics relied on the phase region of Pd hydride during the sensing reaction. Two simple strategies, minimizing the thickness of the PMMA membrane layer and reducing the size of the Pd NPs, were proposed to compensate for retardation of the sensing response.
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OBJECTIVE: To develop a method of radioimmunoassay for human sperm protein 17(Sp17) determination. METHODS: Anti-recombinant human Sp17 antibody was prepared, the labeling of 125I-rhSp17 performed by chloramine T method, and radioimmunoassay of Sp17 developed. RESULTS: The assay range was 3.3 to approximately 800 microg/L, the sensitivity was 2.0 microg/L, and the intra- and inter-assay coefficients of variation (CV) were 7.5% to approximately 9.8% and 8.2% to approximately 13.2%, respectively. The serum Sp17 level in normal subjects was (15.60 +/- 7.66) microg/L (n = 59). CONCLUSION: This radioimmunoassay of Sp17 fulfills the reasonable requirements of clinical routine and scientific studies in terms of specificity, sensitivity and practicability. Measurement of Sp17 concentration is useful for assessing its native distribution and aberrant expression.
Assuntos
Antígenos de Superfície/sangue , Proteínas de Transporte/sangue , Radioimunoensaio/métodos , Animais , Antígenos de Superfície/imunologia , Proteínas de Ligação a Calmodulina , Proteínas de Transporte/imunologia , Feminino , Humanos , Proteínas de Membrana , Coelhos , Proteínas Recombinantes/imunologia , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: This prospective study was designed to investigate the relationship between lipids levels in both serum and seminal plasma and semen parameters. METHODS: 631 subfertile men were enrolled. Their obesity-associated markers were measured, and semen parameters were analyzed. Also, seminal plasma and serum TC, TG, HDL and LDL and serum FFA, FSH, LH, total testosterone (TT), estradiol (E2) and SHBG levels were detected. RESULTS: Seminal plasma and serum TG, TC and LDL levels were positively related to age. Serum TC, TG and LDL were positively related to obesity-associated markers (P < 0.001), while only seminal plasma TG was positively related to them (P < 0.05). For lipids levels in serum and seminal plasma, only TG level had slightly positive correlation between them (r = 0.081, P = 0.042). There was no significant correlation between serum lipids levels and semen parameters. However, seminal plasma TG, TC, LDL and HDL levels were negatively related to one or several semen parameters, including semen volume (SV), sperm concentration (SC), total sperm count (TSC), sperm motility, progressive motility (PR) and total normal-progressively motile sperm counts (TNPMS). Moreover, seminal plasma TG, TC, LDL and HDL levels in patients with oligospermatism, asthenospermia and teratozoospermia were higher than those with normal sperm concentration, motility or morphology. After adjusting age and serum LH, FSH, TT, E2 and SHBG levels, linear regression analysis showed that SV was still significantly correlated with seminal plasma LDL (P = 0.012), both of SC and TSC with seminal plasma HDL (P = 0.028 and 0.002), and both of PR and sperm motility with seminal plasma TC (P = 0.012 and 0.051). CONCLUSION: The abnormal metabolism of lipids in male reproductive system may contribute to male factor infertility.
Assuntos
Infertilidade Masculina/metabolismo , Lipídeos/análise , Sêmen/química , Adolescente , Adulto , Envelhecimento/metabolismo , China , Estradiol/sangue , Ácidos Graxos não Esterificados/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Infertilidade Masculina/sangue , Infertilidade Masculina/complicações , Lipídeos/sangue , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Estudos Prospectivos , Globulina de Ligação a Hormônio Sexual/análise , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides/anormalidades , Testosterona/sangue , Adulto JovemRESUMO
OBJECTIVE: To observe the effect of pulse wave velocity (PWV) on coronary flow reserve (CFR) in patients with essential hypertension (EH). METHODS: 108 patients with EH were divided into three groups according to the blood pressure (BP) status and antihypertensive drug therapy (ADT): group A (n = 41, with ADT and BP failing to reach the standard), group B (n = 27, with high BP and without ADT), and group C (n = 40, with ADT and BP reaching the standard). Twenty-five sex, age, body mass index, waist/hip ratio, heart rate, fasting glycemia and lipid level-matched healthy persons were used as controls (group D). PWV, CFR, left ventricle mass index (LVMI), E/A ratio, left ventricle isovolumetric relaxation time (IVRT), left ventricular ejection fraction (LVEF) were detected in each group. Correlation analysis was conducted. RESULTS: (1) the PWV values in group A, B, and C were 12.7 m/s +/- 1.3 m/s, 11.9 m/s +/- 2.2 m/s, and 9.6 m/s +/- 0.9 m/s respectively, all significantly higher than that in the group D (8.9 m/s +/- 0.7 m/s, all P < 0.05) and with significant differences between group A and group C and between group B and group C (both P < 0.05). The CFR values in group A, B, and C were 2.56 +/- 0.18, 2.54 +/- 0.19, and 2.97 +/- 0.19 respectively, all significantly lower than that in group D (3.26 +/- 0.26, all P < 0.05), with significant differences between group A and group C and between group B and group C (both P < 0.05). The values of average peak velocity of baseline (APVb) in groups A, B, and C were 38 cm/s +/- 4 cm/s, 36 cm/s +/- 4 cm/s, and 34 cm/s +/- 4 cm/s respectively, significantly higher than that in group D (29 cm/s +/- 4 cm/s, all P < 0.05), without significant difference among group A, B, and C. (2) The values of LVMI in group A, B, and C were 117 g/m(2) +/- 8 g/m(2), 113 g/m(2) +/- 11 g/m(2), and 98 g/m(2) +/- 11 g/m(2) respectively, all significantly higher than that of group D (88 g/m(2) +/- 7 g/m(2), all P < 0.05), with significant differences between group A and group C and between group B and group C. The E/A ratios in groups A and B were 0.76 +/- 0.19 and 0.87 +/- 0.18 respectively, significantly lower than those in group C and D (1.08 +/- 0.18 and 1.19 +/- 0.15 respectively, all P < 0.05). The values of IVRT in group A, B and C were 134 ms +/- 11 ms, 138 ms +/- 11 ms, and 109 ms +/- 12 ms respectively, all significantly higher than that in group D (84 ms +/- 12 ms, all P < 0.05) with a significant difference between group A and group C and between group B and group C (both P < 0.05). There was no significant difference of LVEF among different groups. (3) Stepwise linear regression of PWV showed that the factors significantly influencing PWV were age, LVMI, E/A ratio and SBP, the factors significantly influencing CFR were LVMI and PWV, and PWV was significant negatively correlated to CFR and significant positively correlated to APVb. CONCLUSION: PWV is increased in hypertensive patients. The increase of LVMI and increase of PWV contribute to the decrease of CFR in hypertensive patients. Increase of PWV that attributes to left ventricular hypertrophy and decrease of E/A ratio in patients with hypertension leads to further decrease of CFR. Decrease of CFR in hypertensive patients may cause cardiovascular diseases. Early detection and prevention of increased PWV may decrease the morbidity of cardiovascular diseases.