结核分枝杆菌多表位诊断抗原的制备

将结核分枝杆菌(Mycobacterium tuberculosis,Mtb)多个B细胞预测表位串联表达(命名为B102),并初步评价其作为诊断抗原的血清学诊断价值。将MtbPstS1、ESAT6、CFP10、Ag85B、Ag85A及PPE54等6个蛋白的11个B细胞预测表位串联,加入合适的连接臂后全基因合成;将多表位片段插入带有TRX标签的表达质粒中,在大肠杆菌BL21(DE3)中诱导表达,并利用Ni~(2+)-Chelating亲和层析和DEAE阴离子交换层析纯化目的蛋白;利用Western blotting (WB)技术对目的蛋白抗原性进行鉴定,并建立Mtb抗体检测竞争法ELISA技术,初步评价此方法对阴阳血清样本的鉴别能力。目的蛋白以包涵体形式存在,其表达量约占菌体总蛋白的31.25%,经纯化及复性后蛋白B102可溶性存在,浓度为3.124mg/mL,纯度为96.71%;WB实验表明目的蛋白能与Mtb阳性血清相应抗体发生反应。对60份Mtb阳性血清及60份Mtb阴性血清进行检测得出其灵敏度为90.00%,特异性为93.33%,阳性预测值为93.10%,阴性预测值为90.32%,符合率为91.67%,McNemer检验的结果提示与"金标准"诊断结果无差异,Kappa=0.833,提示两种方法诊断结果一致性优异。原核表达与层析纯化可以获取抗原性优异的Mtb多表位诊断抗原,作为诊断抗原可以应用于Mtb的血清学检测中。     

Distinguishing structural features between Crohn's disease and gastrointestinal luminal tuberculosis using Mueller matrix derived parameters

Recently, the incidence of inflammatory bowel diseases, especially the Crohn's disease (CD) and gastrointestinal luminal tuberculosis (ITB), has grown rapidly worldwide. Currently there is no general gold standard to distinguish between CD and ITB tissues, which both have tuberculosis and surrounding fibrous structures. Mueller matrix imaging technique is suitable for describing the location, density and distribution behavior of such fibrous structures. In this study, we apply the Mueller matrix microscopic imaging to the CD and ITB tissue samples. The 2D Mueller matrix images of the CD and ITB tissue slices are measured using the Mueller matrix microscope developed in our previous study, then the Mueller matrix polar decomposition and Mueller matrix transformation parameters are calculated. To evaluate the distribution features of the fibrous structures surrounding the tuberculosis areas more quantitatively and precisely, we analyze the retardance related Mueller matrix derived parameters, which show clear different distribution behaviors between the CD and ITB tissues, using the Tamura image processing method. It is demonstrated that the Mueller matrix derived parameters can reveal the structural features of tuberculosis areas and be used as quantitative indicators to distinguish between CD and ITB tissues, which may be useful for the clinical diagnosis.      

Detection of dental plaque and its potential pathogenicity using quantitative light‐induced fluorescence

Quantitative light‐induced fluorescence (QLF) technology can detect some dental plaque as red fluorescence. This in vivo study aimed to identify the microbial characteristics of red fluorescent (RF) dental plaque using 16S rRNA gene sequencing and evaluate the correlations between RF plaque and the clinical symptoms of dental diseases. Paired supragingival plaque samples collected from each 10 subjects and consisted of RF and non‐RF dental plaques as observed by QLF technology using a 405 nm blue light source for excitation. The characteristics of the bacterial communities in the RF and non‐RF plaque samples were compared by sequencing analysis. An increase in microbial diversity was observed in RF plaque compared with the non‐RF plaque. There were significant differences in the community compositions between the 2 types of dental plaque. Periodontopathic bacteria were significantly more abundant in the RF plaque than non‐RF plaque. The fluorescence intensity of RF plaque was significantly related to the proportion of the periodontopathic bacterial community and the presence of gingival inflammation. In conclusion, the plaque red fluorescence is associated with changes in the microbial composition and enrichment of periodontopathic pathogens, which suggests that RF plaque detected by QLF technology could be used as a risk indicator for gingival inflammation.      

miRNA在心肌梗死中的作用及其机制研究进展

急性心肌梗死（AMI）是最常见的心血管事件,具有高发病率和高死亡率,严重威胁人类生命健康。微小RNA（miRNA）通过调节心肌细胞炎症、纤维化、细胞自噬及新生血管形成的表型机制发挥功能。本综述探讨了心肌梗死后miRNA上调及下调的分子机制,以及miRNA对心肌梗死早期诊断中的价值。     

Incremental hospital charges associated with obesity as a secondary diagnosis in children

Objective: The objective was to evaluate the association of obesity as a comorbidity with hospital charges, by comparing charges for pediatric hospitalizations with vs. without obesity as a secondary diagnosis. Methods: Using the 2000 Healthcare Cost and Utilization Project (HCUP) Kids’ Inpatient Database (KID), a nationally representative sample of pediatric hospital discharges, we identified the most common non‐pregnancy‐related principal diagnoses for children 2 to 18 years of age: asthma, pneumonia, affective disorders, and appendicitis. For each we compared mean charges and mean length of stay for hospitalizations with vs. without obesity as a secondary diagnosis, adjusting for relevant socio‐demographics and hospital type. Results: Among children's discharges in 2000, 1.1% listed obesity as a secondary diagnosis. These had a disproportionate likelihood of being older, black, Medicaid beneficiaries, and hospitalized at a general hospital. Adjusted mean hospital charges were significantly higher for discharges with obesity as a secondary diagnosis vs. those without: appendicitis ($14,134 vs. $11,049; p < 0.01), asthma ($7766 vs. $6043; p < 0.05), pneumonia ($12,228 vs. $9688; p < 0.05), and affective disorders ($8292 vs. $7769; p < 0.01). Whereas obesity as a secondary diagnosis was associated with a pattern of increased adjusted mean length of stay, only asthma and affective disorders had statistically significant differences (0.6 days) (p < 0.01). Conclusion: This national analysis suggests obesity as a secondary diagnosis is associated with significantly higher charges for the most common reasons for pediatric hospitalizations. This presents a financial imperative for further research to evaluate factors that contribute to higher inpatient charges related to obesity as a comorbidity and underscores the need for obesity prevention initiatives.     

糖尿病性视网膜病变早期mfERG的研究

目的:探讨糖尿病患者糖尿病性视网膜病变早期多焦视网膜电图(multifocal electroretinogram,mfERG)的特点。方法:应用德国ROLAND公司RETIscan系统对24例40眼糖尿病患者,同时对27例40眼正常对照眼记录mfERG。按机器的默认值一阶反应进行记录。整个记录过程中可以分为12个时段,每个时段记录为时间47秒。结果:mERG测得的糖尿病患者组1～5环所在位置的P1波的振幅密度随离心度的增加而降低,P1波和N1波幅值降低和潜伏时延迟。各象限的P1、N1波振幅密度、波幅值降低,潜伏时延迟。结论:糖尿病性视网膜病变受累的区域多发生在黄斑部,功能上的改变早于形态学的变化;病变的早期功能改变最先出现于视网膜的后极偏颞上方;糖尿病患者在未出现眼底改变时各个象限视网膜的外层已经严重受累。     

The concept of mental disorder: diagnostic implications of the harmful dysfunction analysis

What do we mean when we say that a mental condition is a medical disorder rather than a normal form of human suffering or a problem in living? The status of psychiatry as a medical discipline depends on a persuasive answer to this question. The answers tend to range from value accounts that see disorder as a sociopolitical concept, used for social control purposes, to scientific accounts that see the concept as strictly factual. I have proposed a hybrid account, the harmful dysfunction (HD) analysis, that incorporates both value and scientific components as essential elements of the medical concept of disorder, applying to both physical and mental conditions. According to the HD analysis, a condition is a disorder if it is negatively valued ("harmful") and it is in fact due to a failure of some internal mechanism to perform a function for which it was biologically designed (i.e., naturally selected). The implications of this analysis for the validity of symptom-based diagnostic criteria and for challenges in cross-cultural use of diagnostic criteria are explored, using a comparison of the application of DSM diagnostic criteria in the U.S. and Taiwan.     

Drugging the undruggable proteins in cancer: A systems biology approach

In recent years, the research community has, with comprehensive systems biology approaches and related technologies, gained insight into the vast complexity of numerous cancers. These approaches allow an in-depth exploration that cannot be achieved solely using conventional low-throughput methods, which do not closely mimic the natural cellular environment. In this review, we discuss recent integrative multiple omics approaches for understanding and modulating previously identified ‘undruggable’ targets such as members of the RAS family, MYC, TP53, and various E3 ligases and deubiquitinases. We describe how these technologies have revolutionized drug discovery by overcoming an array of biological and technological challenges and how, in the future, they will be pivotal in assessing cancer states in individual patients, allowing for the prediction and application of personalized disease treatments.     

胃炎性纤维性息肉的临床特征及内镜下诊治

摘要 目的：研究胃炎性纤维性息肉（IFP）的临床特征及内镜下诊断和治疗情况。方法：收集2010.1.1~2021.1.1陕西省人民医院确诊的11例IFP,重点分析其超声内镜表现及临床特征,探索其内镜下治疗价值。结果：IFP多发生在胃窦,均发生于40岁以上人群,男女比例无明显差别,平均直径1.2 cm,大部分临床无症状,有时可引起出血或腹痛。超声内镜示其为粘膜下隆起,孤立、界清,表面多光滑,均起源于粘膜下层,呈低回声,界清,类圆形;内镜下粘膜挖除术治疗IFP,手术时间短,恢复快,并获得完整的标本,术后病理有助确诊。结论：胃炎性纤维性息肉多发生40岁以上人群,多为胃窦孤立的粘膜下病变,多无症状,超声内镜有助于IFP的术前精确评估,内镜下粘膜挖除术是治疗IFP一项安全有效的方法,术后病理最终确诊。