Thromboembolism in Patients with Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease, which has a marked heterogeneity in clinical expression, natural history, and prognosis. HCM is associated with a high prevalence of thromboembolic events (stroke and systemic embolic events), even if taking no account of atrial fibrillation (AF), leading to unexpected disability and death in patients of all ages. Several risk factors of thromboembolism such as AF, greater age, left atrial diameter, heart failure and others have been confirmed in patients with HCM. Conventional thromboembolic predictive models were estimated by several trials in HCM population but it turned out to be unsatisfactory. Based on those previous explorations, researchers tried to modify or develop novel models suitable for HCM population in thromboembolism prediction. In consideration of catastrophic advent events of thromboembolism, current guidelines have recommended life-long anticoagulant therapy after a single short AF.Therefore, early identification of risk factors for thromboembolism, accurate risk stratification, timely preventive measures and aggressive management may help to avoid serious adverse thromboembolic events in HCM population.     

Prediction of lymph node metastasis in rectal cancer: comparison between shear-wave elastography based ultrasomics and MRI

PURPOSEWe aimed to explore the diagnostic efficiency of shear-wave elastography (SWE) ultrasomics in the preoperative prediction of lymph node (LN) metastasis in rectal cancer.METHODSThis study included 87 patients with pathologically confirmed rectal cancer, with data gathered from August 2017 to August 2018. A total of 1044 ultrasomics features of rectal tumor were collected with AK software from the SWE examinations. The least absolute shrinkage and selection operator (LASSO) regression model was used for feature selection and building a SWE ultrasomics signature. The diagnostic performance was evaluated with an area under the receiver operating characteristic curve (AUC) analysis. Then, the diagnostic performance of the SWE ultrasomics signature was compared with magnetic resonance imaging (MRI).RESULTSOf the 87 patients, 40 (46.0%) had LN metastasis. Thirteen ultrasomics features of rectal tumor were selected as the most significant features. The SWE ultrasomics signature correlated with LN metastasis (p < 0.001). Patients with LN metastasis had higher signature than patients without LN metastasis. In terms of diagnostic performance, SWE ultrasomics signature was significantly superior to MRI (AUC, 0.883 vs. 0.760, p = 0.034). The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SWE ultrasomics signature were 82.8%, 87.5%, 78.8%, 77.8%, and 88.1%, respectively, while those of MRI were 75.9%, 77.5%, 74.5%, 72.1%, and 79.6%, respectively.CONCLUSIONSWE ultrasomics is a more accurate predictive method for identifying LN metastasis preoperatively than MRI. Thus, SWE ultrasomics might be used to better guide preoperative individual therapies for patients with rectal cancer.

Colorectal cancer is the third most common cancer and the fourth frequent cause of cancer death worldwide; approximately one-third of these tumors is rectal cancer (1). Accurate identification of lymph node (LN) involvement is important in determining whether rectal cancer patients require preoperative neoadjuvant therapy (2, 3). Therefore, accurate prediction of LN metastasis can provide valuable information and is crucial for treatment decisions and prognosis (4).According to ESGAR guidelines (European Society of Gastrointestinal and Abdominal Radiology) 2016 recommendations, magnetic resonance imaging (MRI) is considered the gold standard for rectal cancer staging (3, 5–7). However, MRI is not perfect for determination of LNs status, and the criteria used to indicate LN metastasis may vary in different institutions (8). A meta-analysis found MRI to be 77% sensitive (95% CI, 69%–84%) and 71% specific (95% CI, 59%–81%) for detection of LN involvement (9). In addition, endoscopic ultrasonography (EUS) is also a widely used method for patients with rectal cancer, but the accuracy of EUS to identify LN involvement is inferior to that of both computed tomography (CT) and MRI because of a lack of visualization of the entire mesorectum and the difficulty in accurately distinguishing benign from malignant nodes based only on the shape, echo feature and size criterion (10–13). Given these limitations, neither MRI nor EUS is an ideal method for diagnosing LN status in rectal cancer.Radiomics, extracted from CT, MRI, or positron emission tomography images, uses a set of quantitative features to describe the geometrical structure, intensity distribution and texture of a region of interest (ROI). These features include shape, edge, and texture metrics, which can provide important insights into the tumor phenotype and the interaction of the tumor with its microenvironment (14, 15). Similarly, we have applied the concept to computing quantitative ultrasound imaging, a term defined as “ultrasomics” (16). Shear-wave elastography (SWE), an ultrasound elastography technique that provides a real-time two-dimensional (2D) quantifiable image of tissue stiffness (17), has emerged as an efficient tool in detection of malignancies. The report of Wang et al. (18) confirmed that the deep learning of elastography showed a better prediction of liver fibrosis staging compared with transient elastography, 2D-SWE, and serological examinations. Therefore, SWE-based ultrasomics has a promising future in staging and prediction.To our knowledge, there has been no study that combines SWE and ultrasomics to predict the LN metastasis. In order to build a robust model, we hypothesized that SWE ultrasomics could be a better option in LN status prediction of colorectal cancer patients. Therefore, the purpose of this study was to evaluate the accuracy of LN metastasis identification before surgical resection using SWE ultrasomics of primary tumor and compare it with MRI.     

牙支持3D导板辅助穿刺卵圆孔射频热凝治疗三叉神经痛的疗效分析

目的:探讨牙支持式3D打印导板辅助穿刺卵圆孔射频热凝治疗三叉神经痛术中术后的疗效分析.方法:对2019年1月～2021年5月收治的三叉神经痛患者40人,根据患者需要随机分成2组:A组(对照组),常规按照Hartel前入路法穿刺卵圆孔,进入卵圆孔后,耳-床线定位确定入颅深度后行射频治疗.B组(导板组),采用3D导板,给患者戴上导板固定后,完成穿刺,耳-床线定位确定入颅深度后行射频治疗.分析2组的术前疼痛评分(VAS)术后即刻及术后1月疼痛消失的有效率,手术时间,穿刺次数,并发症,穿刺的偏移程度.结果:与对照组A组比较在术后即刻有效率、术后1月随访有效率比较无统计学差异(P>0.05).在穿刺次数、穿刺偏移率、手术时间、并发症两组间比较有统计学差异(P<0.05).导板与牙齿紧密贴合率100％.结论:3D打印导板应用于穿刺卵圆孔具有明显的优势,可以减少患者创伤,减少X线辐射,减少穿刺偏移,术后疗效肯定,值得广泛应用.     

重新审视婴幼儿心肺转流中改良超滤的使用

改良超滤(MUF)技术作为心肺转流中节约用血的重要手段之一,具有浓缩血液、清除炎性介质、减轻组织水肿等优点,但随着微小化体外循环技术的应用,MUF在临床应用中的获益性和必要性开始受到各中心的重新审视。本文对近年来MUF的临床使用进展予以综述。     

构建靶向血管内皮生长因子受体2可调控活性的嵌合抗原受体T细胞及其体外功能验证

目的构建靶向血管内皮生长因子受体2(VEGFR2)可调控活性的小分子门控嵌合抗原受体T(smgCAR-T)细胞系统并在体外验证其抗肿瘤和可调节活性。方法采用基因全长合成和磷酸钙转染法构建smgCAR-T及其阳性(CAR+-T)和阴性(CAR--T)对照细胞。同时构建表达VEGFR2的小鼠结直肠癌细胞(MCA38VEGFR2+)。验证并筛选构建成功的细胞后再体外验证CAR-T细胞靶向结合能力。在不同的效靶比下检测白细胞介素-2和肿瘤坏死因子-γ的浓度来评估CAR-T细胞的体外分泌功能,用乳酸脱氢酶浓度评估CAR-T细胞的体外抗肿瘤活性。组间的比较采用t检验或单因素方差分析。结果基因测序和流式细胞术证实CAR-T细胞和靶细胞构建成功。与对照组比较,CAR+-T细胞+MCA38VEGFR2+组具有最强的靶细胞杀伤能力。在smgCAR-T细胞+MCA38VEGFR2+组中,随着C16-(S)-3-甲基吲哚雷帕霉素(Rapalog)滴度升高靶细胞杀伤率逐渐升高;当Rapalog为40 nmol/L时杀伤率达到最大值,为(66.25±13.20)%。分别向smgCAR-T细胞+MCA38VEGFR2+细胞组(A和B组)加入40 nmol/L的Rapalog后,在24 h时可观察到两组杀伤率出现同步升高[(44.25±6.24)%比(49.25±5.56)%,t=1.197,P>0.05],差异无统计学意义。在置换培养基后,再次添加了Rapalog的A组中观察到靶细胞杀伤率升高明显;而未再次添加Rapalog的B组中靶细胞杀伤率升高缓慢;此时,A和B组杀伤率差异有统计学意义[(89.00±3.16)%比(56.50±6.61)%,t=8.873,P<0.01]。结论构建的smgCAR-T细胞在体外展现出一定的抗肿瘤活性,且其活性受小分子化合物Rapalog的可逆调控。     

Nonlinear elasticity of biological basement membrane revealed by rapid inflation and deflation

Basement membrane (BM) is a thin layer of extracellular matrix that surrounds most animal tissues, serving as a physical barrier while allowing nutrient exchange. Although they have important roles in tissue structural integrity, physical properties of BMs remain largely uncharacterized, which limits our understanding of their mechanical functions. Here, we perform pressure-controlled inflation and deflation to directly measure the nonlinear mechanics of BMs in situ. We show that the BMs behave as a permeable, hyperelastic material whose mechanical properties and permeability can be measured in a model-independent manner. Furthermore, we find that BMs exhibit a remarkable nonlinear stiffening behavior, in contrast to the reconstituted Matrigel. This nonlinear stiffening behavior helps the BMs to avoid the snap-through instability (or structural softening) widely observed during the inflation of most elastomeric balloons and thus maintain sufficient confining stress to the enclosed tissues during their growth.

Basement membrane (BM) is a thin layer of fibrous matrix separating cells from the connecting tissues, which functions as a physical barrier and widely exists across multicellular organisms (1). The BM is typically composed of laminins, collagen IV, nidogens, and proteoglycans; laminin and collagen IV are the major components that constitute networks forming the structure of the BM, and nidogen and proteoglycans are associated with the laminin and collagen IV networks. As a physical barrier, the structural and mechanical properties of BM are important in the organization and morphogenesis of tissues and organs as well as in the maintenance of adult functions (2); abnormal BM has been associated with a variety of diseases such as cancer (3). For example, in metastasis, cancer cells must invade through BMs to escape from the primary tumor—a process that causes 90% of cancer-related death (4). Indeed, breaks in BMs can be observed in malignant tumors (5). Thus, mechanical properties of the BM are considered to play important roles in regulating cancer cell invasion (6, 7). Furthermore, as a physical barrier differentiating different parts of tissues, BMs are required to be permeable to small molecules to allow exchange of water and nutrients; the permeability of BM is thus one of the essential kinetic parameters regulating biomolecule exchange and activities of internal cells (8, 9). Given the importance of BMs as a semipermeable barrier maintaining tissue structural integrity, however, their permeability and mechanical properties remain largely unknown, mainly due to the lack of direct measurement methods, especially in situ. This limits our understanding of the physical role of BMs in various physiological and pathological processes such as tumor development and angiogenesis.Determining the mechanical properties of intact BMs in situ is challenging because of their irregular shape, small thickness, and tight connection to the cells inside. Due to these limitations, conventional mechanical tests such as tensile, compression, and bending tests are difficult to be applied to characterize the mechanical behavior of the BM in situ. Instead, previous measurements had been carried out on fragmented BMs isolated from various tissues (e.g., via atomic force microscopy [AFM] indentation) and found that the BM stiffness ranges from ∼kPa to ∼MPa (10–17). In addition, a constitutive relationship is required to extract the material parameters such as elastic modulus and permeability from these experimental measurements. However, like most biological tissues, a reliable constitutive model for the BM is not yet available, causing additional difficulties in obtaining its mechanical parameters from most traditional experiments.In this work, we demonstrate an in situ method to simultaneously measure both the elastic properties and permeability of intact BM in breast cancer spheroid by recording the deflation process of an inflated BM filled with phosphate buffered saline (PBS) by microinjection without requiring complex sample preparation and post-data processing. During the deflation of the BM, its elastic retraction generates a pressure difference to drive the liquid flow through the membrane; the liquid flux can be calculated from the reduction of the intact BM diameter. With the BM thickness measured by transmission electron microscopy (TEM), we can determine the shear modulus, permeability, and diffusivity of the intact BM. Moreover, we find from our measurements that the elasticity of BM is highly nonlinear with a strong strain-stiffening effect. Furthermore, we discuss the possible impact of the strain-stiffening effects of BM on its functions.     

基于数据挖掘的吕英教授治疗自闭症语言障碍的用药规律分析＊

目的 基于中医传承辅助平台软件（TCMISS，V2.5）对吕英教授治疗自闭症语言障碍的处方进行数据挖掘，探索其病因病机及组方规律。方法 收集吕英教授治疗自闭症语言障碍的医案，将其方药信息录入TCMISS，借助该平台集成的关联规则、改进互信息法、复杂系统熵聚类法、无监督熵层次聚类法等分析方法探索吕英教授治疗自闭症语言障碍的药物组方规律。结果 共筛选出120个医案，包含处方共120首，涉及中药89味，其中使用频次前6味中药为桂枝、鸡蛋花、白术、泽泻、石膏、桔梗，药性以寒、温为主，药味以甘、苦居多，归经多属肺、脾、肝经。通过关联规则分析所得的用药模式中，使用频次最高的为桂枝与鸡蛋花、桂枝与泽泻、白术与桂枝，进一步分析得到的核心药物为泽泻、桂枝、白术，为五苓散的药物组成，并基于复杂熵聚类方法演化出6首新处方。结论 吕英教授治疗自闭症语言障碍以阳明“气血津”不足和三焦气化功能失常为主要病机线路，清解阳明伏火、加强阳明本体液津血的生化化生及恢复三焦气化功能正常为主要治法，其核心代表方剂为木防己汤和五苓散。     

中药防治肺动脉高压研究现状及创新药物研发＊

肺动脉高压为恶性肺血管疾病或临床综合征，发病机理涉及复杂的生物学过程和多种分子机制，临床仍缺乏有效治疗药物。尽管单靶点药物的联合应用可有效改善其临床症状，但不能阻止病程进展，且价格昂贵，药物不良反应问题一直未能解决。中药因多成分协同作用、多靶点发挥药效、多途径整合调节疾病的特点，在肺动脉高压的治疗中发挥独特优势，具有良好应用前景和创新药物开发潜力。本文旨在全面系统地梳理近30年中药防治肺动脉高压的研究进展，分析创新药物研发的瓶颈及策略，以期为肺动脉高压的创新药物研发提供有益参考。     

Clinical and Contrast-enhanced Ultrasound Characteristics of Epithelioid and Classic Hepatic Angiomyolipoma: Comparison With Alpha-fetoprotein–negative Hepatocellular Carcinoma

Hepatic angiomyolipoma (HAML) comprises epithelioid angiomyolipoma (EAML) and classic hepatic angiomyolipoma (CAML). The imaging appearance of HAML varies widely, and EAML is more easily misdiagnosed as hepatocellular carcinoma (HCC) than as CAML. The clinical and contrast-enhanced ultrasound (CEUS) features of CAML, EAML and HCC with negative alpha-fetoprotein protein expression (HCC[AFP–]) were retrospectively reviewed. The hyper-vascular type was more commonly found in CAML and EAML lesions than in HCC lesions. Most lesions were hyper-enhanced in the arterial phase. CAMLs showed prolonged hyper-enhancement or iso-enhancement during the portal and late phases on CEUS, making them easily distinguishable from HCC(AFP–). Some EAML lesions (41.7%) were hypo-echoic, similar to HCC(AFP–). However, the hypo-enhancement of EAML lesions occurred later than that of HCC(AFP–) lesions. Thus, our findings may be useful in distinguishing among these lesions to improve diagnostic accuracy.     

关节镜辅助下轴向螺钉内固定术治疗Sanders-2型跟骨骨折疗效观察

目的探讨关节镜辅助下轴向螺钉内固定术治疗Sanders-2型跟骨骨折的临床疗效。方法将50例Sanders-2型跟骨骨折患者按照随机数字表法分为研究组与对照组,各25例。研究组给予关节镜辅助下轴向螺钉内固定术治疗,对照组给予传统切开复位内固定术治疗。术后观察3个月。比较两组手术时间、住院时间、骨折愈合时间、术前与术后3个月末两组Bohler角、Gissane角度数及跟骨高度、宽度,以及两组Maryland足功能评分、手术疗效。结果研究组手术时间、住院时间及骨折愈合时间均显著短于对照组(P<0.05或0.01)。术后3个月末两组Bohler角及Gissane角度数均较术前显著增大(P<0.01),研究组较对照组增大更显著(P<0.05或0.01)。术后3个月末研究组跟骨高度显著>术前(P<0.01),两组跟骨宽度均显著>术前(P<0.01),两组间比较差异无统计学意义(P>0.05)。术后3个月末两组Maryland足功能评分均较术前显著升高(P<0.01),研究组较对照组升高更显著(P<0.01)。研究组手术治疗总有效率显著高于对照组(P<0.05),并发症发生率显著低于对照组(P<0.05)。结论关节镜辅助下轴向螺钉内固定术治疗Sanders-2型跟骨骨折效果显著,能有效促进患者足踝功能恢复,安全性较高,值得临床推广应用。