人海绵状血管瘤内皮细胞特性的体外研究

目的 研究人海绵状血管瘤内皮细胞在形态、表型和功能方面的改变。方法 从人海绵状血管瘤组织分离、纯化血管内皮细胞,并应用透射电子显微镜、流式细胞术、逆转录聚合酶链反应（RT-PCR）、明胶酶谱法和激光共聚焦显微镜等技术与人正常人肝窦内皮细胞进行比较分析。结果 与正常人肝窦内皮细胞相比,人海绵状血管瘤内皮细胞的超微结构上,具有异常膨大的内质网和空泡样结构;表型上,高表达整合素αvβ3;功能上,体外形成血管样网络结构异常,并可能与其高表达的内源性血管内皮细胞生长因子、血管生成素1以及基质金属蛋白酶2有关。结论 人海绵状血管瘤内皮细胞在形态、表型和功能特性上都不同于正常肝窦内皮细胞。     

Intra-operative frozen section diagnosis of breast lesions: a retrospective analysis of 13 243 Chinese patients

Background Although cytological methods for breast oncology have been used in recent decades, intra-operative frozen section has been playing a vital role in making therapeutic decisions. We analyzed a large series of frozen section diagnoses for Chinese cases of breast lesion within the last 15 years. The experience was expected to increase the diagnostic accuracy of cases with breast lesions. Methods The data from consecutive 13243 cases of breast lesions diagnosed with intra-operative frozen sections between 1988 to 2002 were compared with paraffin sections in a case by case manner. The causes of false negative and positive diagnoses as well as delayed diagnoses were analyzed. Results One hundred and seventeen cases （0.9%） were falsely diagnosed, with one false positive case and 116 false negative cases. The diagnosis of 47 cases （0.4%） was delayed. The proportion of several lesions had the features of the patients＇ ages. Six types （false invasion, peri-papUloma, adenoma of nipple duct, florid adenosis, sclerosing adenosis, and granulose cell tumor） of lesions may lead to false positive, and four types （morphological changes responding chemotherapy, well differentiated papillary carcinoma, invasive Iobular carcinoma, and tubular carcinoma） to a false negative. Gross and microscopic findings may be inconsistent in two types of lesions （radial scar and florid adenosis） microscopic and clinical findings in three types （ganulomatous mastitis mammary, duct ectasia, and fat necrosis）, and three types （abundant fat or sclerous tissues; borderline lesions and changes of post-chemotherapy） were likely wrongly classified. Conclusions Intra-operative frozen section can accurately identify breast lesions in many instances, leading to fewer errors on account of more diaanostic experience and understandina of diaanostic limitations.     

Optimized cardiac resynchronization therapy in patients with congestive heart failure

Heart failure was a major and increasing public health problem, with an almost ＂epidemic＂ increase in the number of patients. Despite recent advances in pharmacotherapy, the prognosis remains poor. Cardiac resynchronization therapy （CRT）, by pacing right and left ventricles, has been proved to improve symptoms and reduce mortality for heart failure patients with cardiac dyssynchrony, However, 20% to 30% of patients did not respond to CRT. The good cardiac synchronicity before CRT and the remaining atrioventficular, inter- and intra-ventricular dyssynchrony after CRT may explain the non-response. New echocardiographic techniques, and in particular tissue Doppler imaging （TDI） analysis, has been proved to be a helpful tool in evaluating cardiac dyssynchrony, as well as in assessing the degree of cardiac resynchronization after biventricular device implantation. So, in this study, we optimized the pacing parameters to determine whether echo-guided optimizing of AV/VV delays would enhance the effect of CRT on cardiac function and synchronicity.     

北方汉族人群醛固酮合成酶基因多态性与高血压的关系

目的 探讨北方汉族人群醛固酮合成酶基因（CYP11B2）启动子区C-344T和第三外显子K173R多态性位点与原发性高血压的关系。方法在哈尔滨报社人群中分别选取182例原发性高血压患者和189例正常对照者进行病例．对照研究,采用多聚酶链式反应／限制性片段长度多态性（PCR—RFLP）及直接测序技术检测C-344T和K173R的基因型。结果各位点基因型分布在男性和女性组中均符合Hardy—Weinberg遗传平衡定律。C-344T位点的基因型和等位基因频率以及K173R的等位基因频率在整个群体和按性别分组后亚群体的分布在高血压组和对照组间差异均没有显著性（P≥0．05）。而K173R位点的基因型频率在整个群体中具有边缘统计学意义（P=0．0500）,且在女性组中更为明显（P=0．0038）,并以显性方式遗传,这种遗传方式在对混杂因素进行校正后更加明显。同时K173R与女性的收缩压显著相关。结论 在北方汉族人群中,CYP11B2K173R多态性位点与女性高血压的易感相关联。     

Finite element models of rib as an inhomogeneous beam structure under high-speed impacts

Fracture of ribs commonly occurs during blunt impacts and can lead to serious injuries or even fatality. The finite element (FE) modeling of ribs under impacts, however, is difficult due to the complex geometry, the difficulty in determining material parameters, and the amount of the computational time required. This study develops a method of modeling ribs as inhomogeneous beam structures. The geometries are reconstructed from images acquired with X-ray computed tomography. Bone material properties, orthotropic or isotropic, are determined from the CT pixel values. From the material distribution inside the cross-section, generalized classical beam formulations use to determine the local homogenized stiffness of the nodes along the rib. To compare the accuracy and efficiency of the method, detailed three-dimensional (3D) FE models of ribs are also developed. Simulations of three benchmark problems that represent different loading or impact conditions demonstrate that the beam FE model is very efficient and is at least as accurate as a very finely meshed 3D FE model. Finally, the rib FE model is used to study blunt trauma injury of animal tests under high-speed impacts. The consistency between predictions and experimental results shows that the developed rib model is a great value to study of blunt trauma caused by high-speed impacts.     

The online case-crossover study is a novel approach to study triggers for recurrent disease flares

OBJECTIVES: To evaluate the feasibility of conducting an online case-crossover study of triggers for recurrent disease flares. METHODS: We conducted an online case-crossover study of triggers for recurrent flares using gout as a paradigm. We constructed a Web site and recruited individuals with history of gout via the Internet. We confirmed gout diagnosis by reviewing each subject's medical records. We collected via the Internet exposure information during the intercritical period using a scheduled Control-period Questionnaire, and prior to recurrent gout attacks using a Hazard-period Questionnaire. RESULTS: Over 10 months we recruited 197 subjects with a history of gout from 41 states and the District of Columbia. We obtained medical records from 172 subjects. All participants had experienced at least one recurrent attack and filled out required questionnaires. The median time between the date of an attack and the date of logging on to the Web site was 2 days. The incidence rate of recurrent gout attacks was 1.03 per person-year. Longer disease duration and presence of comorbidities appeared to increase the risk of recurrent flares. CONCLUSION: The results of this study demonstrate that a case-crossover study can be successfully conducted through the Internet. This approach has broad applicability to other diseases typified by recurrent attacks.     

Next-generation sequencing-based identification of EGFR and NOTCH2 complementary mutations in non-small cell lung cancer

Although targeted therapy has emerged as an effective treatment strategy for non-small cell lung cancer (NSCLC), some patients cannot benefit from such therapy due to the limited number of therapeutic targets. The present study aimed to identify mutated genes associated with clinicopathological characteristics and prognosis and to screen for mutations that are not concurrent with applicable drug target sites in patients with NSCLC. Tumor tissue and blood samples were obtained from 97 patients with NSCLC. A lung cancer-specific panel of 55 genes was established and analyzed using next-generation sequencing (NGS). The results obtained from the clinical cohort were compared with the NSCLC dataset from The Cancer Genome Atlas (TCGA). Subsequently, 25 driver genes were identified by taking the intersection of the 55 lung-cancer-specific genes with three databases, namely, the Catalog of Somatic Mutations in Cancer database, the Network of Cancer Genes database and Vogelstein''s list. Functional annotation and protein-protein interaction analysis were conducted on these 25 driver genes. The χ² test and logistic regression were used to evaluate the association between mutations in the 25 driver genes and the clinicopathological characteristics of 97 patients, and phosphatase and tensin homolog (PTEN) and kirsten rat sarcoma viral oncogene homolog (KRAS) were associated with stage at diagnosis and sex, respectively, while epidermal growth factor receptor (EGFR) was associated with sex, stage at diagnosis, metastasis, CEA and CYFRA21-1. Moreover, the association between the 25 driver gene mutations and overall survival were examined using Cox regression analysis. Age and Notch homolog 2 (NOTCH2) mutations were independent prognostic factors in TCGA dataset. The correlations between statistically significant mutations in EGFR, KRAS, PTEN and NOTCH2 were further examined, both in the clinical data and TCGA dataset. There was a negative correlation between EGFR and NOTCH2 mutations (correlation coefficient, −0.078; P=0.027). Thus, the present study highlights the importance of NOTCH2 mutations and might provide novel therapeutic options for patients with NSCLC who do not harbor EGFR mutations.     

Future of targeted therapy for gastrointestinal cancer: Claudin 18.2

The treatment of gastrointestinal cancer has always been a crucial research area, and targeted therapy has been receiving increasing attention. At present, the effect of targeted therapy is unsatisfactory for gastric cancer. Thus, the discovery of new targets is crucial. Claudin 18.2 (CLDN18.2), a member of the claudin family, belongs to the tight junction protein family that controls the flow of molecules between cell layers. CLDN18.2 expression has been discussed in many studies. In recent years, there have been many studies on targeted therapy with CLDN18.2-ideal monoclonal antibody 362. Furthermore, CLDN18.2-specific chimeric antigen receptor T therapy has been used for CLDN18.2-positive tumors, such as gastric and pancreatic cancers. Considerable research has been focused on CLDN18.2. CLDN18.2, a newly discovered marker for precise targeted therapy of gastric cancer, could offer new hope for the treatment of gastric cancer.     

Exceeding 30 ELNs is strongly recommended for pT3-4N0 patients with gastric cancer: A multicenter study of survival,recurrence, and prediction model

The argument concerning the exact minimum number of examined lymph nodes (ELNs) has continued for a long time among various regions, and no consensus has been reached for stratified pathological T stages for data to date. Data from 4607 pN0 patients with gastric cancer were analyzed. Kaplan-Meier analysis showed the similar overall survival (OS) outcomes among the 3 groups (ELNs ≤ 15, 16 ≤ ELNs ≤ 29 and ELNs ≥ 30, P = .171). However, the ELNs ≥ 30 group had a better disease-free survival (DFS) outcome compared with the others (all P < .05). An increased ELN group (ELNs ≥ 30) showed an improved OS only for pT3 patients (hazard ratio [HR] = 0.397, 95% confidence interval (CI): 0.182-0.866, P = .020), while an improved DFS for pT3 patients (HR = 0.362, 95%CI: 0.152-0.860, P = .021) and pT4 patients (HR = 0.484, 95%CI: 0.277-0.844, P = .011) in the multivariate analysis. A well discriminated and calibrated nomogram was constructed to predict the probability of the OS and DFS, with the C-index for OS and DFS prediction of 0.782 (95%CI: 0.735 to 0.829) and 0.738 (95%CI: 0.685 to 0.791), respectively. This study provides new and useful insights into the impact of ELN count on reducing stage migration and postoperative recurrence of pN0 patients with gastric cancer in 2000-2017. In conclusion, a larger number of ELNs is suggested for surgeons to prolong the prognosis of pN0 gastric cancer, especially for pT3 patients.