Geometric Confinement Guides the Expression of Cancer Stem Cell Molecular Markers CD44 via Cell Traction Forces.

Cancer stem cells (CSCs) play a critical role in the cancer metastasis and account for tumor heterogeneity. Growing evidence indicates that the CSC phenotypes are related to the tumor microenvironment. In this study, we report that the gradient of mechanical stresses guides the spatial patterning of the expression of CD44 and Yes-associated protein (YAP) in the geometrically confined multicellular sheets. Our study shows that the cytoskeletal contraction regulates the expression of CD44 through the translocation of YAP into the nucleus. The results demonstrate that geometric confinement and mechanical stresses are the regulators in the spatial patterning of CSC. It may help to understand the relationship between the tumor microenvironment and oncogenesis.

[High-risk Active Implantable Medical Devices Standards].

Objective: Comprehensive standards of active implantable medical devices with high risks are required by China's current industrial development, and standard problems and ideas are discussed in this paper. Methods: Analysis of the status of China's active implantable medical device standards and international standards. For the booming field for active implantable medical devices with high risks, international standard's problems, ideas and trends are analyzed. Results: Bottleneck of the development of China's active implantable medical device standards is the lack of Chinese medical devices industry actual independent research and development capability. China's independent standard research on the basis of independent core technology of active implantable medical devices is the opportunity to promote the internationalization of China standard. Conclusion: Improving the standards of active implantable medical devices based on independent core technology, combined with problems of existing international standards, to further improve and develop international standards and lead high level international technical standards.

Fatigue test of helical nervous electrodes and weak point analysis of helical nervous electrodes design.

Due to the increasing number of both implantation and removal of the helical nervous electrodes, the safety and the reliability of the electrode becomes an important issue in its clinical application-particularly its fatigue failure caused by body movement. Utilizing fatigue testing, we evaluated the weak points of the helical electrode. Our data analysis for fatigue cycles recorded by the fatigue test equipment showed that the adhesive strength between the silicone and suture, and the load of the electrode were essential for the mechanical durability of the electrode. The locations of the weak points and improvements for helical electrode design were given. The suggestions of decreasing damages to the nerves in clinical use will be helpful to the surgeons.

Responsive neurostimulation for the treatment of medically intractable epilepsy.

With an annual incidence of 50/100,000 people, nearly 1% of the population suffers from epilepsy. Treatment with antiepileptic medication fails to achieve seizure remission in 20-30% of patients. One treatment option for refractory epilepsy patients who would not otherwise be surgical candidates is electrical stimulation of the brain, which is a rapidly evolving and reversible adjunctive therapy. Therapeutic stimulation can involve direct stimulation of the brain nuclei or indirect stimulation of peripheral nerves. There are three stimulation modalities that have class I evidence supporting their uses: vagus nerve stimulation (VNS), stimulation of the anterior nuclei of the thalamus (ANT), and, the most recently developed, responsive neurostimulation (RNS). While the other treatment modalities outlined deliver stimulation regardless of neuronal activity, the RNS administers stimulation only if triggered by seizure activity. The lower doses of stimulation provided by such responsive devices can not only reduce power consumption, but also prevent adverse reactions caused by continuous stimulation, which include the possibility of habituation to long-term stimulation. RNS, as an investigational treatment for medically refractory epilepsy, is currently under review by the FDA. Eventually systems may be developed to enable activation by neurochemical triggers or to wirelessly transmit any information gathered. We review the mechanisms, the current status, the target options, and the prospects of RNS for the treatment of medically intractable epilepsy.

Study on DBS device for small animals.

Although deep brain stimulation (DBS) therapy has been achieved, fine tuning on the operational parameters and the equipment are needed in order to make the stimulation treatment more applicable. Thus, the purpose of this study is to design and produce a deep brain stimulation device for DBS experiments for small animals (e.g. rats). Physical size, durability, cost of device and convenience of operation are the major focuses in this study. The designed pulse generator can produce pulses with adjustable frequencies, pulse widths and amplitudes. Telemetry and remote control of the system reduced the physical size of the implant component. Battery voltage measurement and electrode impedance measurement justified the values of parameters applied for stimulation. Power consumption is low enough and test results show it is expected to work for more than three months when using typical pulse parameters. Finally, we use the device on the DBS experiment of rats. The results prove that the design of the device can fulfill the requirements for deep brain stimulation in animal experiments.