Determination of proliferating fractions in malignant melanomas by anti-PCNA/cyclin monoclonal antibody

An immunohistochemical study of melanocytic tumours using 19A2, a monoclonal antibody against proliferating cell nuclear antigen (PCNA/cyclin), was performed on tissues routinely processed with formalin fixation and paraffin embedding. In normal skin, keratinocytes of the suprabasal region in epidermis, the papillae and outer root sheath of hair follicles and the basal cells lining the lobules of sebaceous glands were stained in the nucleus. Other skin components, including basal and follicular melanocytes, did not demonstrate nuclear labelling. In addition, expression of PCNA/cyclin in keratinocytes was higher in sun-exposed skin compared with unexposed skin. In melanocytic lesions, PCNA/cyclin positive tumour cells increased in number and staining intensity according to the following progression: common melanocytic naevi; dysplastic naevi; primary melanomas; and metastatic melanomas. Expression of PCNA/cyclin, therefore, provides a useful marker for proliferation and tumour progression in skin.     

三种粪便隐血试验的比较研究

粪便隐血试验是检测消化道微量出血的重要手段。本文用三种隐血试验:血红蛋白定量试验(HQT)、反向间接血球凝集试验(RPHA)和联苯胺试验(BT)对不同消化道疾病患者的粪便进行检测。结果表明隐血的检出用HQT和RPHA较BT更为特异和敏感。     

二维超声心动图对高原婴幼儿右室射血分数的估测

目的：将二维超声测量右室射血分数（RVEF）的方法应用于临床。方法：用心尖四腔观单平面面积－长度法测量43例高原正常婴幼儿RVEF，并与40例患右室扩张肥厚型心肌病（RVDCHM）婴幼儿进行了比较。结果：健康组RVEF均值为58．20％，标准差为7．24％；患儿组均值为36．10％，标准差为7．01％，两组测量的RVEF有非常显著差异（P＜0．001）。结论：心尖四腔观单平面面积－长度法测量RVEF可作为估测右室收缩功能的简单可靠的方法。     

胸腺免疫抑制组分的抗变态反应作用

整体实验表明，胸腺免疫抑制组分肌内注射１ｗｋ对大鼠被动皮肤过敏反应（８、２０、５０和１２５ｍｇ·ｋｇ－１）兔Ａｒｔｈｕｓ反应（４和１２ｍｇ·ｋｇ－１）均有明显的抑制作用。体外实验表明，该药能抑制致敏豚鼠离体回肠平滑肌的过敏性收缩，ＩＣ５０为４４６．７ｍｇ·Ｌ－１。上述结果表明，胸腺免疫抑制组分有抗Ⅰ和Ⅲ型变态反应的作用。     

Effect of a protein binding change on unbound and total plasma concentrations for drugs of intermediate hepatic extraction

For substances eliminated from blood by the liver, the effect of a change in unbound fraction of drug (fu _b )on steady state total (C _b )and unbound (Cu _b )blood concentrations has hitherto only been considered for the two limiting cases, i.e., at the upper and lower extremes of hepatic intrinsic clearance (CL _int ).For a substance of very low CL _int ,if fu _b changes, C _t will change and Cu _b will remain constant, whereas if CL _int isvery high, Cu _b will change and C _b will remain constant.The present study defines the effects of a change in fu _b on C _b and Cu _b over the whole CL _int range. Computer simulations were undertaken which predicted that, for a given change in fu _b ,absolute and relative changes in C _b would decreasenonlinearly with increasing CL _{int, twhile the relative change in} Cu _{b would} increasewith CL _int .The absolute change in Cu_b would be independent of CL _int .Significant changes in C_b and Cu _{b would be observed at intermediate values of} CL _{int not just at the high and low extremes. These theoretical predictions were investigated experimentally in the isolated perfused rat liver by examining the effects of a change in} fu _{b of sodium taurocholate a substance with intermediate} CL _int (such that at fu _b =0.27,hepatic extraction ratio=0.71) induced by concurrent administration of sodium oleate. Sodium 24- ¹⁴ C-taurocholate (specific activity 52 Ci/mmol) was infused into the reservoir in a recycling system at 30 mol/hr for 105 min (n=6). At 45 min a bolus dose of sodium oleate (50 mmol) was administered to the reservoir, followed by a constant infusion of 143 mmol/hr for 1 hr. Following the administration of oleate, taurocholate fu _{b fell promptly by 55% (0.27–0.12). There was a relative increase of taurocholate} C _{b of 22.7% and a relative decrease in} Cu _{b of 45.4%, in accordance with the simulations (p<0.05). We conclude that important changes in unbound steady-state concentration, the pharmacologically active moiety, can occur upon changes in unbound fraction with compounds of intermediate hepatic intrinsic clearance}.This study was supported by the National Health and Medical Research Council of Australia.     

2022年欧洲临床营养与代谢学会和欧洲肥胖研究学会《肌肉减少性肥胖的定义和诊断标准共识》解读及启示

近年来,欧洲临床营养与代谢学会（ESPEN）和欧洲肥胖研究学会（EASO）的专家组成员对肌肉减少性肥胖（SO）的相关研究进行了系统地评价。2022年2月,ESPEN和EASO共同发布了《肌肉减少性肥胖的定义和诊断标准共识》,该共识对SO的定义和诊断进行了详细的阐述,旨在就SO的定义和诊断达成共识,为研究人员和临床工作者提供参考依据,以推进SO预防和治疗的发展。本文主要对《肌肉减少性肥胖的定义和诊断标准共识》中SO的定义,诊断流程包括筛查、诊断和分期标准,拟采用的方法和相关的参数等主要内容进行梳理和解读,旨在为国内医务工作者提供更多参考。     

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