中国肥厚型心肌病患者血栓栓塞事件风险预测模型的构建研究

背景 血栓栓塞（TE）事件是肥厚型心肌病（HCM）的重要并发症。目前针对HCM患者TE事件的风险预测,仅国外学者构建了两个模型：HCM Risk-CVA及French HCM score,然而,现有研究发现HCM Risk-CVA模型对于中国HCM患者的临床价值较为有限。目的 本研究拟构建适合中国HCM患者的TE事件风险预测模型。方法本研究系回顾性队列研究,收集2010—2018年在四川大学华西医院就诊的537例HCM患者的病例资料。本研究通过电话随访或电子病历系统查询患者就诊记录,每6～12个月随访1次,直至出现终点事件或死亡或研究拟定的评估日期（2019-12-31）,终点事件定义为复合性TE事件。采用单因素和多因素Cox回归分析构建风险预测模型,并使用自助重抽样的方法进行内部验证。结果 537例患者中,24例患者有不同程度的数据缺失,最终纳入513例患者。中位随访时间为4.2(1.3,6.2)年,随访过程中42例（8.18%）发生TE事件,年发病率为2.10%[95%CI(1.47%,2.73%)]。根据多因素Cox回归模型构建TE事件风险预测模型,最终纳入年龄、既往TE事件、心...     

芪苈强心胶囊联合尼可地尔对射血分数保留性心力衰竭患者心功能及细胞因子的影响

目的 探讨芪苈强心胶囊联合尼可地尔对射血分数保留性心力衰竭患者心功能及细胞因子的影响。方法 连续入选2019年10月至2020年10月诊断为射血分数保留性心力衰竭的患者共90例,随机分为观察组(45例)与对照组(45例)。对照组给予常规抗心力衰竭药物加芪苈强心胶囊治疗,观察组在对照组治疗基础上,加用尼可地尔治疗。比较两组患者一般临床资料、细胞因子水平、心功能各项指标。随访1年患者心功能情况、细胞因子水平以及不良心脑血管事件(MACCEs)发生情况。结果 两组患者接受治疗1年后脑钠肽(BNP)、左室舒张末期内径、白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)均降低,射血分数(EF)值较治疗前升高,差异有统计学意义(P<0.05)。组间对比发现,两组患者入院时基础BNP、细胞因子、超声心能指标(LVEF、左室舒张末期内径、左房内径)差异无统计学意义(P>0.05);接受治疗1年后观察组IL-1β、IL-6、TNF-α、BNP、左室舒张末期内径低于对照组,EF值高于对照组,差异有统计学意义(P<0.05)。随访1年对照组共有7例发生终点事件,观察组共有4...     

Effective and safe therapy with coenzyme Q10 for cardiomyopathy

Summary Coenzyme Q₁₀ (CoQ₁₀) is indispensable in mitochondrial bioenergetics and for human life to exist. 88/115 patients completed a trial of therapy with CoQ₁₀ for cardiomyopathy. Patients were selected on the basis of clinical criteria,X-rays, electrocardiograms, echocardiography, and coronary angiography. Responses were monitored by ejection fractions, cardiac output, and improvements in functional classifications (NYHA). Of the 88 patients 75%–85% showed statistically significant increases in two monitored cardiac parameters. Patients with the lowest ejection fractions (approx. 10%–30%) showed the highest increases (115%–210%) and those with higher ejection fractions (50%–80%) showed increases of approx. 10%–25% on therapy. By functional classification, 17/21 in class IV, 52/62 in class III, and 4/5 in class II improved to lower classes. Clinical responses appeared over variable times, and are presumably based on mechanisms of DNA-RNA-protein synthesis of apoenzymes which restore levels of CoQ₁₀ enzymes in a deficiency state. 10/21 (48%) of patients in class IV, 26/62 (42%) in class III, and 2/5 (40%) in class II had exceptionally low control blood levels of CoQ₁₀. Clinical responses on therapy with CoQ₁₀ appear maximal with blood levels of approx. 2.5 µg CoQ₁₀/ml and higher during therapy.Abbreviations CHF Congestive heart failure - CO Cardiac output - CoQ₁₀ Coenzyme Q₁₀ - EF Ejection fraction - IC Impedance cardiography - NYHA New York Heart Association - STI Systolic time interval     

Human placentae membrane receptor for IgG—i. Studies on properties and solubilization of the receptor

Characterization of the human placental membrane receptor for human ¹²⁵I-IgG is described. The receptor bound specifically both monomers and aggregates of human IgG. Human colostral IgA, bovine, sheep, pig, and horse IgG were not bound. No effect of pH in the range 6.6–7.4, ionic strength in the range 0.1–0.5, and temperature between 4 and 45°C on the binding was found. A water-soluble fraction containing the active receptor (glycoprotein fraction-PGP) was obtained from the placental membranes using lithium diiodosalicylate. The solubilized receptor interacted with IgG better at 4°C than at 20°C or 37°C. The results on replacement of monomeric IgG by aggregated IgG, and vice versa, suggest that both monomers and aggregates of human IgG, were bound to the same receptor sites. The apparent association constant for monomeric human IgG was 0.86 ± 0.2 × 10⁷ mole^?1, and 2.0 ± 0.16 × 10¹⁵ IgG molecules were bound per l mg of the membrane protein. Formaldehyde (0.1%), 2-mercaptoethanol (50 mM), and periodate (4 mM) showed no effect on the binding properties of the membrane-bound and on the solubilized receptor, as well. Higher concentrations of periodate (10 mM or 20 mM) decreased the binding of IgG to membranes but showed no effect on the water-soluble receptor. Both the membrane-bound and the solubilized receptor were sensitive to papain. Pronose abolished the receptor activity after prolonged proteolysis only. Neuraminidase did not affect the activity of the receptor. The decrease of the binding activity of the membrane-bound receptor by trypsin and phospholipase C was due to a release of a material containing an active receptor. No effect of trypsin or phospholipase C on the activity of solubilized receptor was observed. The results obtained suggest a protein character of the placental Fc receptor. After electrophoresis of ¹²⁵I-labeled solubilized receptor in polyacrylamide gel in the presence of SDS, 2 major protein peaks with molecular weights of 74,000 and 104,000 and 3 minor peaks with molecular weights of 56,000, 144,000, and 163,000 were found.     

Effect of age on cardiac index,stroke index and left ventricular ejection fraction at rest and during exercise as studied by radiocardiography

Radiocardiography was used to measure cardiac output, stroke volume and left ventricular ejection fraction at rest and during muscular exercise in relation with age in 148 healthy subjects (age range: 6–78 years). A clear dependence of these parameters on age was found. The mean annual decrease at rest was 22±9 ml/min/m² for cardiac index, 0.22±0.04 ml/m² for stroke index and 0.0017±0.0003 for left ventricular ejection fraction. Male subjects had significantly (p < 0.001) greater cardiac (9±4%) and stroke indices (11±23%) than females. During submaximal exercise cardiac index increased from 3.5±0.7 l/min/m' to 8.1±1.6 l/min/m² in male subjects (mean age: 32 years) and from 3.1±0.4 l/min/m² to 7.2±1.2 l/min/ m² in female subjects (mean age: 29 years). The corresponding increases in stroke index and left ventricular ejection fraction were: from 52±7 ml/m² to 62±9 ml/m². from 46±7 ml/m² to 51±9 ml/m² and from 0.66±0.08 to 0.79±0.05 and from 0.64±0.10 to 0.72±0.10. In subjects who were 60 years and older the increases of these parameters during exercise were considerably smaller.     

Trabecular Shear Stresses Predict <Emphasis Type="Italic">In Vivo</Emphasis> Linear Microcrack Density but not Diffuse Damage in Human Vertebral Cancellous Bone

Linear microcracks and diffuse damage (staining over a broad region) are two types of microscopic damage known to occur in vivo in human vertebral trabecular bone. These damage types might be associated with vertebral failure. Using microcomputed tomography and finite element analysis for specimens of cancellous bone, we estimated the stresses in the trabeculae of human vertebral tissue for inferosuperior loading. Microdamage was quantified histologically. The density of in vivo linear microcracks was, but the diffuse damage area was not, related to the estimates of von Mises stress distribution in the tissue. In vivo linear microcrack density increased with increasing coefficient of variation of the trabecular von Mises stress and with increasing average trabecular von Mises stress generated per superoinferior apparent axial stress. Nonlinear increase in linear crack density, similar to the increase of the coefficient of variation of trabecular shear stresses, with decreasing bone stiffness and bone volume fraction suggests that damage may accumulate rather rapidly in diseases associated with low bone density due to the dramatic increase of shear stresses in the tissue. © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8719Xx, 8759Ls, 8759Fm, 8710+e     

Differences in protein synthesized in vivo and in vitro by cells associated with the cerebral microvasculature. A protein synthesized in response to trauma?

A protein of molecular weight 71,000 (P₇₁) was synthesized by cells associated with the cerebral microvasculature in telencephalon slices incubated in vitro. This protein, however, was not synthesized in vivo. There was a 30 min delay in the synthesis of P₇₁ by brain slices. During this lag period a new ribonucleic acid species which was required for P₇₁ synthesis was produced in the slices. After this delay P₇₁ became a major product of protein synthesis. P₇₁ was also produced by microvasculature enriched fractions isolated from telencephalon.This protein may be involved in the initial response of the vascular system to injury.     

A method for the accurate determination of anti-hapten cytotoxic T lymphocyte precursors: correction for apparent 'anti-self' reactivity

A method is described for accurately determining the frequency of precursors of hapten specific cytotoxic T cells. The method is based on a standard Poisson analysis of limit dilution cultures, but makes a correction of 'anti-self' reacting clones and for spontaneously arising clones that recognise modified self. These corrections are shown to be especially important when low hapten densities are used, where there may be more than a 10-fold difference between the corrected and uncorrected frequency estimates. Determined levels of antigen specificity and of H-2 restriction are significantly enhanced by application of this method.     

Gm allotypes in blacks with systemic lupus erythematosus

Serum samples were collected from 328 healthy American Blacks and from 61 American Blacks with systemic lupus erythematosus (SLE). Sera were typed for the Gm1,2,3,5,6,13,17, and 21 allotypes as well as for the Km(1) allotype. The frequency of Gm phenotype 1,17;5,6,13 was significantly increased in the SLE patients (p = 0.0001, RR = 3.19, EF = 0.29). Our data suggest the existence of at least two immunoglobulin allotype associated genes that somehow interact to increase susceptibility to SLE in Blacks. To our knowledge, this is the first report of an association of Gm and SLE in Blacks.