1. Systematic establishment of allosteric drug design methodology and their applications in drug discovery
Journal of Shanghai Jiaotong University(Medical Science) 2019;39(2):109-112
Allostery, or allosteric regulation, is the phenomenon in which protein functional activity is altered by the binding of an effector at an allosteric site that is topographically distinct from the orthosteric, active site. As one of the most direct and efficient ways to regulate protein function, allostery has played a fundamental role in innumerable biological processes of all living organisms, including enzyme catalysis, signal transduction, cell metabolism, and gene transcription. It is thus considered as "the second secret of life". The abnormality of allosteric communication networks between allosteric and orthosteric sites is associated with the pathogenesis of human diseases. Allosteric modulators, by attaching to structurally diverse allosteric sites, offer the potential for differential selectivity and improved safety compared with orthosteric drugs that bind to conserved orthosteric sites. Harnessing allostery has thus been regarded as a novel strategy for drug discovery. Despite much progress having been made in the repertoire of allostery since the turn of the millennium, the identification of allosteric drugs for therapeutic targets and the elucidation of allosteric mechanisms still present substantial challenges. These challenges are derived from the difficulties in the identification of allosteric sites and mutations, the assessment of allosteric protein-modulator interactions, the screening of allosteric modulators, and the elucidation of allosteric mechanisms in biological systems. To address these issues, we have developed a panel of allosteric services for specific allosteric applications over the past decade, including (i) the creation of the Allosteric Database, with the aim of providing comprehensive allosteric information such as allosteric proteins, modulators, sites, pathways, etc., (ii) the construction of the ASBench benchmark of high-quality allosteric sites for the development of computational methods for predicting allosteric sites, (iii) the development of Allosite and AllositePro for the prediction of the location of allosteric sites in proteins, (iv) the development of the Alloscore scoring function for the evaluation of allosteric protein-modulator interactions, (v) the development of Allosterome for evolutionary analysis of query allosteric sites/modulators within the human proteome, (vi) the development of AlloDriver for the prediction of allosteric mutagenesis, and (vii) the development of AlloFinder for the virtual screening of allosteric modulators and the investigation of allosteric mechanisms. Importantly, we have validated computationally predicted allosteric sites, mutations, and modulators in the real cases of sirtuin 6, casein kinase 2α, phosphodiesterase 10A, and signal transduction and activation of transcription 3. Furthermore, our developed allosteric methods have been widely exploited by other users around the world for allosteric research. Therefore, these allosteric services are expected to expedite the discovery of allosteric drugs and the investigation of allosteric mechanisms.
2.Scheme of Teaching and Training for Sports Rehabilitation Students
Chinese Journal of Rehabilitation Theory and Practice 2010;16(7):696-697
This paper introduced a scheme of teaching and training for sports rehabilitation students, to promote their capability of practices.
3.Laws and Policies of Assistive Technology Service in Canada
Chinese Journal of Rehabilitation Theory and Practice 2011;17(6):589-591
The paper studied legislation, policies, government participation through investigations and internet resources and has a complete cognition of assisitive devices condition in Canada. Canadian Federal Government encourages, guides and participates in assistive technology exploiting based on non-discrimination legislation. Assistive technology service system has been running well in social consciousness,funding, quality and varieties of assistive devices, professional service, necessary social environment and public service.
4.Advance in Assistive Technology for Children with Cerebral Palsy: Functional Features and Typical Products (review)
Chinese Journal of Rehabilitation Theory and Practice 2014;20(11):1053-1056
The assistive devices for children with cerebral palsy are various to meet the special needs, which involve position, mobility,communication, education, career, etc. It tends to be accurate function and a variety of functional integration in position and mobility products.Various series of augmentation alternative communication device have been developed. A large number of assistive technology products have been developed in education, independent live, social skill and therapy fields, and Apps are the important components among them. Various techniques of information and switch have been applied, which may revolutionize the assistive industry.
5.Consideration of Assistive Technology in Individualized Educational Program: Based on SETT Framework
Chinese Journal of Rehabilitation Theory and Practice 2013;19(5):421-425
This article introduced the methods and skill by the procedure about consideration of assistive technology in the individualized educational program (IEP) under the SETT framework, including considering a student's need for assistive technology, gather information of the student, assessing and matching of assistive technology, solution generation, documenting the solution in the IEP, implementation plan. The Quality Indicators for Assistive Technology Services (QIAT) and the people component of the IEP team were also introducd in the article.
6.Assistive Technology under American Acts for People with Disabilities
Chinese Journal of Rehabilitation Theory and Practice 2013;19(11):1082-1086
This paper introduced the key right of people with disabilities for assistive technology under the U.S. laws, including The Rehabilitation Act, Individuals with Disabilities Education Act, Assistive Technology Act and Americans with Disabilities Act. The assistive technology right involved occupation rehabilitation, employment and education and public area. The related agency needs to respond to these requirement. China can learn some from these acts.
7.Comparison between Short- and Long-term Outcome of Rehabilitation for Patients with Severe Traumatic Brain Injury
Chinese Journal of Rehabilitation Theory and Practice 2014;(8):756-759
Objective To compare short- and long-term outcome of rehabilitation in different age patients with severe traumatic brain injury. Methods 116 patients with severe traumatic brain injury aged 18~65 years were divided into 18~44 years old group and 45~65 years old group. They were assessed with Mini-Mental Status Examination (MMSE), simplified Fugl-Meyer Motor Functional Assessment, Fugl-Meyer Balance Assessment, modified Barthel Index (MBI) and Disability Rating Score (DRS) before and 3 months after rehabilitation. And they were followed up with DRS 1 year after discharge. Results All the indexes improved 3 months after rehabilitation (P<0.01). After 1 year of follow-up, the DRS scores continued to decline in both groups, especially in the 18~44 years old group (P<0.05). Conclusion Early rehabilitation can improve the limb function and activities of daily living of adult patients with severe traumatic brain injury, especially in younger people.
9.Discussion on Application of Four Qu-Shi Methods in Treatment of Ulcerative Colitis
World Science and Technology-Modernization of Traditional Chinese Medicine 2014;(5):1153-1155
The pathogenesis of ulcerative colitis (UC) is spleen-stomach weakness with dampness. Therefore, Qu-Shi (QS, eliminating dampness) is the main treatment principle. According to different pathogens, four QS methods in the UC treatment were summarized based on clinical experiences. In the clinic , the application of heat-clearing and dampness-eliminating, warm yang and dampness-eliminating, dampness-eliminating with bitter and pungent, spleen-reinforcing and dampness-eliminating. The indications should be identified for the application of principle-method-prescription-medicine. The flexible application of four methods mentioned above can increase the clinical efficacy.
10.Application analysis of tumor markers CEA,CA125,CA199 in differential diagnosis of malignant pleural effusions
International Journal of Laboratory Medicine 2015;(6):772-773
Objective To explore the difference of serum and pleural effusion CEA ,CA125 and CA199 levels in benign and ma‐lignant pleural effusions to accumulate the practical experience for clinical diagnosis .Methods 125 patients with pleural effusion in this hospital from February 2010 to March 2014 were performed the retrospective analysis and divided into the benign group(49 ca‐ses) and malignant group(76 cases) according to the nature of the fluids .The etiology composition ,pleural effusion and serum tumor markers levels were recorded in the two groups and at the same time the diagnosis efficiency of the tumor markers in pleural effusion was calculated .Results The specificity of the combined detection of CEA ,CA125 and CA199 for diagnosing benign and malignant pleural effusion was 90 .6% ,the sensitivity was 95 .1% ,the positive predictive value was 90 .2% ,negative predictive val‐ue was 95 .3% and accuracy was 92 .7% ,which were higher than those of the single index detection and any 2‐marker combined de‐tection .Conclusion The combined diagnosis of CEA ,CA125 and CA199 in pleural effusion conduces to the assisted diagnosis of be‐nign and malignant pleural effusion .