基于多层次集成学习的骨质疏松辅助诊断研究

目的 原发性骨质疏松是一种起病隐匿、病程较长,在中老年人中高发的疾病,其可引起包括骨折在内的一系列严重症状,是我国中老年人致残致死的主要原因之一。与骨质疏松相关的生理检验指标有很多,如何筛选利用这些指标为诊断服务、建立诊断模型,尚未有成熟、统一的方法。方法 利用人工智能相关技术,对临床骨质疏松患者指标使用多种特征相关性算法进行特征选择,并在此基础上提出了一种多层次的集成学习框架：SAB-SVMKNN算法,其通过将内部同质学习器集成和外部异质学习器集成结合,将集成学习中的Boosting算法和Bagging算法使用Stacking进行集成,构建性能更强,适应性更好地诊断预测模型。结果 使用特征选择从原始数据中的31项临床指标中筛选了对于骨质疏松最重要的8种相关特征,通过这种方式使各模型准确率平均提高了9.2%,且该研究对应的模型准确率提升18.6%,最终达到了94.8%的准确率。结论 特征选择对于临床诊断和骨质疏松疾病的研究具有重要意义,该研究构建的预测模型可以有助于提高医生的诊断准确率。     

1992—2010年 N-花生四烯酰乙醇胺研究文献计量分析

摘 要：通过文献计量学方法分析内源性大麻素 N-花生四烯酰乙醇胺（anandamide,AEA）的研究现状。以 anandamide 为关键词在 ISI Web of Knowledge 数据库中检索相关文献,对其发表时间、语种、作者、期刊来源、学科类别和被引用次数等进行分析。共检索相关文献3 015篇,主要作者、国家、期刊、学科类别、发表时间依次为：Di Marzo V（220篇）、美国（1 254篇）、Br J Pharmacol（189篇）、生物化学与分子生物学类（2 631篇）、2009年（318篇）。AEA 领域的研究正逐渐受到世界各国研究者的重视,但其产业化、规模化发展还需要很长的发展过程。     

胃镜活检组织P53和C-erbB-2同步检测的意义

目的 分析P53和C-erbB-2在胃癌和肠化生组织中表达的差异，以期有助于筛检胃癌高危人群及临床早期诊断。方法 以免疫组化ABC法对15例正常黏膜、16例轻度肠化生、15例中度肠化生、13例重度肠化生和14例胃癌组织进行同步检测。结果 P53和C-erbB-2免疫组化阳性在胃癌组织中分别是8／14(57．1％)和7／14(50％)。胃癌组中P53和C-erbB-2双重表达免疫组化阳性的敏感性是28．6％，特异性是100％；P53和(或)C-erbB-2(合并表达)表达免疫组化阳性的敏感性是84．6％，特异性是88．1％。结论 C-erbB-2特异性高，临床上可用作胃癌肿瘤诊断的标记物。P53和C-erbB02双重表达在胃癌早期诊断中可作为一种辅助手段，合并表达能在临床活检筛检高危人群中起作用。     

脓毒症患者肝功能变化与病情严重度及预后的关系

目的探讨脓毒症患者肝功能变化与病情严重度及预后的相关性。方法将2009年5月~2012年5月入住我院有完整临床资料的脓毒症患者126例分成死亡组(A组,n=35)和存活组(B组,n=91),分析比较两组患者主要肝功能指标的差异及主要肝功能指标异常与病情严重度(APACHE-Ⅲ评分)的关系。同时,根据APACHE-Ⅲ评分的三分位数分为Ⅰ组(n=16)、Ⅱ组(n=83)和Ⅲ组(n=27),分析比较不同分值组间肝功能主要指标的差异性。结果①死亡组患者与肝功能相关的主要指标:死亡组的总胆红素(TBIL)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆汁酸(TBA)明显高于存活组(P<0.01),而白蛋白(ALB)、胆碱酯酶(CHE)明显低于存活组(P<0.01)。②APACHE-Ⅲ评分Ⅲ组的TBIL、ALT、AST、TBA高于Ⅰ、Ⅱ组(P<0.01),而Ⅲ组的ALB、CHE低于Ⅰ、Ⅱ组(P<0.01)。③APACHE-Ⅲ评分与TBIL、ALT、AST、TBA呈正相关(P<0.01),与ALB、CHE呈负相关(P<0.01)。结论与肝功能相关的主要指标ALB、TBIL、ALT、AST、CHE和TBA的检测对判断脓毒症患者的预后及评估病情严重度有一定指导意义。     

脾动脉瘤的临床特征与腔内治疗：附30例报告

背景与目的:脾动脉瘤(SAA)是一类少见、具有潜在致命破裂风险的内脏动脉瘤疾病。SAA的传统手术方式为开腹切除动脉瘤及脾脏。近年来,随着介入技术和材料的发展,SAA的腔内治疗越来越普及。相比于开放手术,腔内治疗具有微创、简便、术后快速康复的优势。本文探讨SAA腔内治疗的有效性和安全性。方法:回顾性分析2012年1月—2019年12月在中南大学湘雅医院血管外科治疗的30例SAA患者资料,并介绍了我科治疗SAA的3种介入手术方式。结果:患者30例均行腹部CTA明确SAA诊断,其中近脾门型17例,中间型9例,远脾门型4例;囊状动脉瘤19例,梭形动脉瘤11例。30例均采取腔内治疗方法,其中21例行SAA栓塞术,6例行脾动脉支架置入术,3例行脾动脉裸支架置入+栓塞术。患者术后平均住院时间4 d,平均住院费用5万元,术后发生腹痛、呕吐、发热等症状10例,症状均在3 d以内缓解,无后遗症发生。发生穿刺点出血1例,保守治疗好转后出院。住院期间无急性脾梗死发生,没有发生需再次手术的并发症。22例患者术后随访3～6个月,CT复查示动脉瘤完全血栓化,未见造影剂进入;出现无症状局灶性脾梗死5例。结论:介入腔内手术可在保留脾脏的情况下治疗SAA,治疗效果确切,且创伤小,术后恢复快,并发症发生概率低,住院时间短,费用相比开放手术无明显增加。腔内治疗可作为绝大部分SAA的首选治疗,具体手术方式需根据术前CTA显示的SAA形态及位置来决定。     

Sea-blue histiocyte syndrome in bone marrow secondary to total parenteral nutrition including fat-emulsion sources: a clinicopathologic study of seven cases

Bone marrow examination revealed a lipid-laden histiocytosis in seven patients undergoing long-term total parenteral nutrition necessitated by extensive short-bowel surgical resection. Clinical abnormalities occurred during this treatment which required bone marrow examination. These included hepatosplenomegaly and peripheral blood cytopenia; the median time to the detection of these abnormalities was 64 months.   The most striking change within the bone marrow was the presence of many pigment-laden histiocytes which had the typical morphology of sea-blue histiocytes seen in the so-called idiopathic sea-blue histiocyte syndrome. The occurrence of sea-blue histiocytosis in the bone marrow in association with long-term parenteral nutrition for short-bowel syndrome has not, to our knowledge, been reported previously and should now be considered in the differential diagnosis of bone marrow sea-blue histiocytosis.     

Further delineation of the KBG syndrome caused by ANKRD11 aberrations

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases.     

In vivo treatment with recombinant IL-12 protects C57BL/6J mice against secondary alveolar echinococcosis

Using an experimental model of hepatic Echinococcus multilocularis infection in C57BL/6J mice, intraperitoneal administration of 0.8 μg of recombinant IL-12 to mice with an established infection was shown to reduce the parasite burden as soon as two weeks after the end of treatment. At that time, in vitro Echinococcus multilocularis -induced spleen T cell proliferative responses as well as IFN-γ and IL-5 production were higher in IL-12 treated mice than in untreated mice. Administration of 0.8 μg of IL-12 at the time of infection was shown to be without effect on the parasite establishment. However, this treatment greatly inhibited the subsequent metacestode development. Indeed, ten weeks after infection, it induced a complete healing in 37.5% of mice. At that time, the development of metastases was inhibited in 68.75% of IL-12-treated mice. This reduction of parasite burden was mainly associated with a strong proliferation of spleen cells to E. multilocularis antigen and with a high IFN-γ production. Altogether, our results show that IL-12 is of crucial importance in inhibiting the larval growth after the metacestode establishment in the liver and suggest that this cytokine could be of potential value in the treatment of human alveolar echinococcosis .     

RP-HPLC法测定β-司他夫定的有关物质

目的:建立了β-司他夫定原料有关物质的RP-HPLC测定方法和水解破坏制备系统适用性试验溶液方法。方法:采用Agilent 1100型高效液相色谱仪,使用SUPELCOSIL LC-18-DB(4.6 mm×250 mm,5μm)色谱柱,以0.01 mol·L-1醋酸铵溶液-乙腈(96.5∶3.5)和0.01 mol·L-1醋酸铵溶液-乙腈(75∶25)为流动相,梯度洗脱,检测波长254 nm,柱温25℃。结果:β-司他夫定和4种已知杂质及其他未知杂质均能达到有效分离;经水解破坏产生的α-司他夫定与β-司他夫定的分离度均达2.8;β-司他夫定、胸腺嘧啶、β-胸苷与5-O’-苯甲酰-司他夫定线性范围分别为0.51~26μg·m L-1(r=1.000)、0.13~27μg·m L-1(r=1.000)、0.50~25μg·m L-1(r=1.000)、1.7~6.3μg·m L-1(r=1.000),已知杂质胸腺嘧啶、β-胸苷与5-O’-苯甲酰-司他夫定的平均加样回收率(n=9)分别为102.8%(RSD=1.5%)、100.6%(RSD=0.9%)、101.9%(RSD=2.1%);β-司他夫定与3种已知杂质的最小检出量均在2.5 ng以下;经水解破坏制备的系统适用性溶液的重复性良好;供试品溶液在4℃下的30 h内基本稳定。结论:本方法灵敏、准确、可靠,专属性强,可用于β-司他夫定原料的有关物质测定。