Silencing of Nesprin‐2 inhibits the differentiation of myofibroblasts from fibroblasts induced by mechanical stretch

Mechanical force plays a pivotal role in the pathogenesis of hypertrophic scar (HTS). Dermal fibroblasts and myofibroblasts are the key cells involved in HTS. Myofibroblasts in HTS possess different biochemical and biophysical characteristics by which myofibroblasts are often distinguished from fibroblasts. The role of mechanotransducers outside the nucleus in the pathogenesis of HTS has been reported in many studies. However, the role of Nesprin‐2 in HTS is not clear. Hence, we aim to construct a cell model of HTS and explore the role of Nesprin‐2 in this process. Myofibroblasts and fibroblasts were isolated from HTS and healthy skin tissues of the same patient. Fibroblasts were exposed to cyclic stretch with 10% magnitude and a frequency of 0.1 Hz for 3 days, 5 days, and 7 days, respectively. After the cell model was confirmed, fibroblasts transfected with siRNA targeting human Nesprin‐2 were exposed to cyclic stretch. The mechanical behaviour and biochemical reaction of the dermal fibroblasts were analysed. The stretched fibroblasts at day 5 showed the same mechanotransductive and biochemical features as unstretched myofibroblasts. Mechanical strain could induce the myofibroblasts differentiation and a cell model of HTS was established successfully at day 5. The expressions of lamin A/C, alpha‐smooth muscle actin, transforming growth factor beta 1, and collagen type I in fibroblasts were reduced by the silencing of Nesprin‐2. Mechanical strain could induce the myofibroblasts differentiation and silencing of Nesprin‐2 could block the mechanical stimulation of terminal myofibroblasts differentiation. Nesprin‐2 might be a potential target to treat the HTS.     

Fatigue Cracking Evolution and Model of Cold Recycled Asphalt Mixtures during Different Curing Times

This paper aims to investigate the fatigue cracking evolution of cold recycled asphalt mixtures with asphalt emulsion (CRME) under different curing times. The fatigue cracking model of CRME based on damage mechanics and fracture mechanics was analyzed according to the fatigue loading curve. Firstly, the fatigue cracking evolution of CRME was studied through an SCB strength test and SCB fatigue test. Then, the fatigue damage mechanics were used to establish a nonlinear fatigue cracking model, and the damage degree of CRME at the initial cracking point was determined. The Paris formula was used to characterize the law of fatigue crack propagation. Finally, the microstructure of CRME was observed by scanning electron microscopy (SEM) with the backscattering method. The results indicate that the initial cracking point appears at around 60% of the fatigue life according to the SCB fatigue test by means of image analysis. The damage variable was obtained through the cracking model, and the value of the damage variable was determined as 0.06–0.17 at the initial cracking point. In addition, the Paris formula showed that the crack growth of CRME can be reflected by the stress intensity factor and correlative parameters. Moreover, cement hydration products were mixed with the asphalt membrane to form a denser spatial structure during the curing process, which may provide higher fatigue performance of CRME. This research may provide a theoretical reference for studying the fatigue cracking behavior of CRME.     

Topology Optimization of Piezoelectric Energy Harvesters for Enhanced Open-Circuit Voltage Subjected to Harmonic Excitations

Energy harvesting devices made of piezoelectric material are highly anticipated energy sources for power wireless sensors. Tremendous efforts have been made to improve the performance of piezoelectric energy harvesters (PEHs). Noticeably, topology optimization has shown an attractive potential to design PEHs with enhanced energy conversion efficiency. In this work, an alternative yet more practical design objective was considered, where the open-circuit voltage of PEHs is enhanced by topologically optimizing the through-thickness piezoelectric material distribution of plate-type PEHs subjected to harmonic excitations. Compared to the conventional efficiency-enhanced designs, the open-circuit voltage of PEHs can be evidently enhanced by the proposed method while with negligible sacrifice on the energy conversion efficiency. Numerical investigations show that the voltage cancellation effect due to inconsistent voltage phases can be effectively ameliorated by optimally distributed piezoelectric materials.     

基于扫描式葡萄糖监测系统的儿童1型糖尿病患者血糖波动的影响因素

目的：经典1型糖尿病(type 1 diabetes mellitus,T1DM)患者由于胰岛β细胞破坏、胰岛素绝对缺乏,需终身依赖外源性胰岛素治疗。中国糖尿病患儿中T1DM约占90%,发病率快速增加且低龄化严重。流行病学研究显示中国患儿平均糖化血红蛋白(glycated haemoglobin,HbA1c)整体偏高、达标率低。良好的血糖管理是糖尿病治疗的重点,维持血糖在目标范围内可阻止或延缓T1DM患者慢性血管并发症。本研究旨在利用扫描式葡萄糖监测系统(flash glucose monitoring system,FGMS)了解湖南省和河南省T1DM患儿的血糖控制情况,分析该群体血糖波动的影响因素。方法：选择2017年8月至2020年8月于两省16所医院内分泌科就诊的T1DM患儿215例,年龄≤14岁,均佩戴FGMS采集血糖数据,分析HbA1c、病程和葡萄糖扫描频率与血糖波动的相关性;根据患儿病程、HbA1c、葡萄糖扫描频率及胰岛素注射方式等因素进行分组比较。结果：HbA1c、病程与平均血糖、血糖标准差、平均血糖波动幅度(mean amplitude of glucose excu...     

印度新专利法的实行对医药企业的影响

印度和我国一样都是发展中国家,人口众多,在医药领域既有很多相似之处,又存在激烈竞争:首先,从地理、人口、经济发展等方面看,中印两国国情比较相近,两国的制药产业也有惊人的相似之处(成本低廉,药品可获得性高);大部分企业仍处于低水平重复仿制阶段;研发力量较为薄弱,仿制药比     

Network pharmacology explores the mechanisms of Eucommia ulmoides cortex against postmenopausal osteoporosis

Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein–protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.     

Extracellular ATP promotes angiogenesis and adhesion of TNBC cells to endothelial cells via upregulation of CTGF

Our previous works have indicated that extracellular ATP is an important prometastasis factor. However, the molecular mechanism involved needs to be further studied. We demonstrated that extracellular ATP treatment could upregulate the expression of connective tissue growth factor (CTGF) in both triple‐negative breast cancer (TNBC) cells and endothelial cells (ECs). Extracellular ATP stimulated the migration of TNBC cells and ECs, and angiogenesis of ECs via the P2Y2––YAP‐CTGF axis. Furthermore, we demonstrated that adenosine triphosphate (ATP) stimulated TNBC cell adhesion to ECs and transmigration through the EC layer via CTGF by upregulation of integrin β1 on TNBC cells and VCAM‐1 on ECs. Both apyrase (ATP‐diphosphohydrolase) and CTGF shRNA treatments could inhibit the metastasis of inoculated tumors to lung and liver in a mouse model, and these treated tumors had fewer blood vessels. Collectively, our data indicated that extracellular ATP promotes tumor angiogenesis and the interactions between TNBC cells and ECs through upregulation of CTGF, thereby stimulating TNBC metastasis. The pleiotropic effects of ATP in angiogenesis and cell adhesion suggest that extracellular ATP or CTGF could be an effective target for TNBC therapy.     

Unusual morphologic features of low‐grade endometrial stromal sarcoma: A case report

BackgroundEndometrial stromal tumours are uncommon tumours of the uterus. They mainly occur in perimenopausal women. Tumours with typical clinicopathological features do not usually pose diagnostic problems. However, rare clinicopathological features can occur, and clinicians without significant experience may have difficulty diagnosing these tumours and managing these patients.MethodsHerein, we report a case of endometrial stromal sarcoma that occurred in a 25‐year‐old woman. The pathological features, immunophenotype, treatment and prognosis were discussed.ResultsThe tumour revealed morphological heterogeneity, and there were similar proliferative‐type endometrial stromal cells, an extensive amount of mature adipose tissue, and prominent rhabdomyoblastic and smooth muscle cells. Histopathological and immunohistochemical studies confirmed low‐grade endometrial stromal sarcoma with smooth muscle, adipocytic and rhabdomyoblastic differentiation (approximately 60% were differentiated tissues). The final treatment of the tumour was total abdominal hysterectomy with bilateral salpingo‐oophorectomy. There was no evidence of recurrence for 109 months postoperatively.ConclusionsWe found that low‐grade endometrial stromal tumours with extensive adipocytic and prominent rhabdomyoblastic differentiation are misdiagnosed because they are infrequent. They must be differentiated from rhabdomyosarcoma with accurate identification of adipocytes, and long‐term follow‐up is needed.     

乳突结节性筋膜炎误诊1例

<正>1病历资料患者,男,64岁,因“自幼左耳流脓,干耳2个月”于2020年3月入院。患者自幼左耳流脓伴听力逐渐下降,无耳鸣,无眩晕、头痛,无鼻塞、流涕、涕中带血等,曾多次在我院门诊使用“氧氟沙星滴耳液1支”滴耳治疗后病情有好转。目前左耳干耳有2个月。既往有高血压病史10年,规律服药,血压控制尚可。1年前因跌伤在我院行左踝关节内侧韧带修补及石膏固定术,当时左耳后有裂伤,清创缝合后治愈。否认家族癌、瘤遗传病史。