Model for the regulation of size in the wing imaginal disc of Drosophila

For animal development it is necessary that organs stop growing after they reach a certain size. However, it is still largely unknown how this termination of growth is regulated. The wing imaginal disc of Drosophila serves as a commonly used model system to study the regulation of growth. Paradoxically, it has been observed that growth occurs uniformly throughout the disc, even though Decapentaplegic (Dpp), a key inducer of growth, forms a gradient. Here, we present a model for the control of growth in the wing imaginal disc, which can account for the uniform occurrence and termination of growth. A central feature of the model is that net growth is not only regulated by growth factors, but by mechanical forces as well. According to the model, growth factors like Dpp induce growth in the center of the disc, which subsequently causes a tangential stretching of surrounding peripheral regions. Above a certain threshold, this stretching stimulates growth in these peripheral regions. Since the stretching is not completely compensated for by the induced growth, the peripheral regions will compress the center of the disc, leading to an inhibition of growth in the center. The larger the disc, the stronger this compression becomes and hence the stronger the inhibiting effect. Growth ceases when the growth factors can no longer overcome this inhibition. With numerical simulations we show that the model indeed yields uniform growth. Furthermore, the model can also account for other experimental data on growth in the wing disc.     

Serpinb1a suppresses osteoclast formation

Serpinb1a, a serine protease inhibitor family protein, has been implicated in immunoregulation and several metabolic disorders, such as diabetes and obesity; however, its roles in bone remain unknown. Therefore, we herein investigated the physiological functions of Serpinb1a in osteoclastic and osteoblastic differentiation using mouse cell lines. Serpinb1a overexpression markedly reduced the number of tartrate-resistant acid phosphatase (TRAP)- and calcitonin receptor-positive multinucleated cells increased by receptor activator nuclear factor κB ligand (RANKL) in mouse preosteoclastic RAW 264.7 cells. Moreover, it significantly decreased the mRNA levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), TRAP and cathepsin K in these cells. Regarding osteoblasts, Serpinb1a overexpression significantly reduced the mRNA levels of alkaline phosphatase (ALP) and osteocalcin as well as ALP activity induced by bone morphogenetic protein-2 (BMP-2) in mouse mesenchymal ST2 cells, although it did not alter osteoblast differentiation in mouse osteoblastic MC3T3-E1 cells. Concerning the pathophysiological relevance of Serpinb1a, Serpinb1a mRNA levels were decreased in the soleus and gastrocnemius muscles of mice 4 weeks after bilateral sciatic nerve resection. In conclusion, we herein revealed for the first time that Serpinb1a inhibited osteoclast formation induced by RANKL in RAW 264.7 cells and suppressed BMP-2-induced ALP activity in ST2 cells.     

Oxidation sensitizes TRPV2 to chemical and heat stimuli,but not mechanical stimulation

The transient receptor potential vanilloid 2 (TRPV2) ion channel is activated by a chemical ligand (2-aminoethoxydiphenyl borate; 2-APB), noxious heat and mechanical stimulation. In a heterologous mammalian cell expression system, the oxidant chloramine T (ChT) sensitizes TRPV2 activation in response to 2-APB and heat by oxidation of methionine residues at positions 528 and 607 in rat TRPV2. Here, we used a Xenopus oocyte expression system to determine whether ChT-mediated oxidation can also sensitize TRPV2 to mechanical stimulation. In this system, we confirmed that ChT sensitized TRPV2 activation in response to 2-APB and heat, but we detected no sensitization to mechanical stimulation. This result suggests that the activation mechanism of TRPV2 by a chemical ligand and heat differs from that for mechanical stimulation. Further, we demonstrated that two-electrode voltage clamp recording in the Xenopus oocyte expression system is an excellent format for high throughput analysis of oxidization of redox-sensitive TRP channels.     

机械通气患者肺部感染病原菌分布及其影响因素

目的分析机械通气患者肺部感染病原菌分布情况及其感染影响因素,为后续研究提供参考。方法选取2017年2月至2019年2月我院收治的接受机械通气时间大于48 h的115例患者为研究对象,回顾性分析引起肺部感染的病原菌分布和感染相关危险因素。结果 115例患者中,18例经确诊出现肺部感染,占15.65%。感染者中7例死亡,病死率为38.89%。18例肺部感染患者中检出35株病原菌,主要包括6株肺炎克雷伯菌,6株铜绿假单胞菌,5株恶臭假单胞菌,病原菌以革兰阴性菌为主。发生与未发生肺部感染患者的糖尿病史、低白蛋白血症、慢性阻塞性肺疾病史、机械通气时间、插管方式、鼻饲方法、抗生素使用情况、气管切开、定时吸痰和APACHEII评分情况差异有统计学意义(均P0.05)。糖尿病史,低白蛋白血症,慢性阻塞性肺疾病史,机械通气时间,插管方式,鼻饲方法,抗生素使用≥2种,气管切开,定时吸痰,APACHEII评分为影响肺部感染的独立影响因素。结论机械通气患者肺部感染病原菌主要为革兰阴性菌,其次为革兰阳性菌。影响机械通气患者肺部感染的因素较多,应根据患者病史、病情及危险因素采取防护措施。     

Interrelated hypoalgesia,creep, and muscle fatigue following a repetitive trunk flexion exposure

Repetitive trunk flexion can damage spinal tissues, however its association with low back pain in the workplace may be confounded by factors related to pain sensitivity. Muscle fatigue, exercise-induced hypoalgesia, and creep-induced neuromuscular changes following repetitive trunk flexion may all affect this assumed exposure-pain relationship. This study’s purpose was to determine how mechanical pain sensitivity in the low back is affected by a repetitive trunk flexion exposure and identify factors associated with changes in low back pain sensitivity. Pressure pain thresholds, perceptions of sub-threshold stimuli, and muscle fatigue in the trunk and tibia, as well as lumbar spine creep were tracked in 37 young healthy adults before and up to 40 min after a 10-min repetitive trunk flexion exposure. Pressure pain thresholds (p = 0.033), but not perceptions of sub-threshold stimuli (p > 0.102) were associated with approximately a 12.5% reduction in pain sensitivity 10 min after completing the exposure, while creep and local muscle fatigue effects were only observed immediately following the exposure. Creep and fatigue interactions and the corresponding tibial measure co-varied with individual low back pressure pain thresholds. The net hypoalgesic effects of repetitive trunk flexion have the potential to partially mask possibly injurious loads, which could contribute to the severity or incidence of lower back injuries related to these exposures.     

AFM-based dual nano-mechanical phenotypes for cancer metastasis

An enhanced mechanical compliance is considered to be a mechanical indicator for metastatic cancer cells. Our study using atomic force microscopy (AFM) revealed that breast cancer cells agreed well with this hypothesis. However, prostate cancer cells displayed a reverse correlation; less metastatic prostate cancer cells were more mechanically compliant. Two-dimensional AFM force spectroscopy was performed to characterize dual mechanical properties—the cell–substrate adhesion as well as the mechanical compliance. Interestingly, prostate cancer cells displayed a strong positive correlation between the cell–substrate adhesion and metastatic potential. However, there was no clearly observable correlation between the cell–substrate adhesion and the metastatic potential despite variations in mechanical compliance of breast cancer cells. These results suggest that the correlation between the dual mechanical signatures and metastatic potential be uniquely identified for cancer cells originating from different organs. We postulate that this correlation could reveal which step of cancer progression is favorable in terms of physical interaction between cancer cells and micro-environments. We expect that based on the “seed and soil hypothesis”, the identification of the dual mechanical phenotypes, could provide a new insight for understanding how a dominant metastatic site is determined for cancer cells originating from specific organs.     

氨溴索不同给药方式对机械通气大鼠肺内炎性因子水平及肺组织湿/干比值的影响

目的:探讨不同氨溴索给药方式对大鼠机械通气肺部炎性因子释放及肺组织湿/干比值的影响。方法:将45只健康SD雄性大鼠随机分成静脉组、雾化组和对照组,各15只。对照组:大鼠麻醉后行气管切开插管,并行单纯机械通气4h;静脉组:大鼠麻醉后从尾静脉泵入氨溴索,气管切开插管后行机械通气4h;雾化组:大鼠麻醉后行气管切开插管,通过自制装置氧气驱动雾化吸入氨溴索,并行机械通气4 h。各组机械通气后放血处死大鼠,取肺组织,计算肺湿/干重比(W/D)。收集支气管灌洗液(BALF)并检测TNF-α,IL-1β和IL-6浓度。结果:与对照组比较,静脉组和雾化组大鼠支气管灌洗液中TNF-α,IL-1β和IL-6的浓度明显降低(P0.05),但此两组间无显著性差异(P0.05);与对照组比较,静脉组和雾化组大鼠肺组织W/D比也明显降低(P0.05),但雾化组大鼠肺组织W/D比明显低于静脉组大鼠(P0.05)。结论:氨溴索静脉给予和雾化给予都能显著降低大鼠机械通气时肺内炎性因子水平和肺W/D比,而且雾化给予较静脉给予更能减轻大鼠肺组织的W/D比。     

机械通气治疗急性呼吸窘迫综合征的肺复张策略研究

目的:探讨机械通气治疗急性呼吸窘迫综合征(Acute respiratory distress syndrome,ARDS)的肺复张策略的作用。方法:选择2012年1月~2012年12月我院收治的采用机械通气并进行肺复张治疗的ARDS患者94例,根据肺复张方法不同,将所有患者分为对照组和实验组,并比较两组患者的不同时点的氧合指数、肺顺应性及两组出现的并发症。结果:对照组肺复张成功率为72.34%,实验组肺复张成功率为95.75%,X2=38.928,P0.05,两组患者肺复张成功率差异具有统计学意义。两组患者氧合指数、肺顺应性和PaCO2在肺复张实施前比较,差异无统计学意义。肺复张策略实施后24h、48h和72h的氧合指数和PaCO2比较,这三个时点的氧合指数和PaCO2差异具有统计学意义。两组患者肺顺应性在肺复张策略实施后1h、2h和6h比较,t分别=4.939,5.391和5.999,P0.05,此三个时点的肺顺应性差异同样具有统计学意义。对照组气压伤发生率为82.98%,实验组气压伤发生率为59.57%,两组患者气压伤发生率差异具有统计学意义。结论:ARDS的患者在机械通气治疗的过程中上采用肺复张策略,不但可以提高肺复张成功率,改善肺部通气效果,且安全性好,适合临床使用。     

A numerical solution of the mechanical bidomain model

Introduction: The mechanical bidomain model predicts forces on integrin proteins in the membrane. It has been solved analytically for idealized examples, but a numerical algorithm is needed to address realistic problems. Methods: The bidomain equations are approximated using finite differences. An ischemic region is modeled as a circular area having no active tension, surrounded by normal tissue. Results: The membrane force is large in the ischemic border zone, but is small elsewhere. Strain is distributed widely throughout the ischemic region and surrounding tissue. Conclusion: This calculation provides a testable prediction for the mechanism of mechanotransduction and remodeling in cardiac tissue.