2.Challenges and strategies of drug innovation.
Acta Pharmaceutica Sinica 2013;48(7):1031-40
Drug research involves scientific discovery, technological inventions and product development. This multiple dimensional effort embodies both high risk and high reward and is considered one of the most complicated human activities. Prior to the initiation of a program, an in-depth analysis of "what to do" and "how to do it" must be conducted. On the macro level, market prospects, capital required, risk assessment, necessary human resources, etc. need to be evaluated critically. For execution, drug candidates need to be optimized in multiple properties such as potency, selectivity, pharmacokinetics, safety, formulation, etc., all with the constraint of finite amount of time and resources, to maximize the probability of success in clinical development. Drug discovery is enormously complicated, both in terms of technological innovation and organizing capital and other resources. A deep understanding of the complexity of drug research and our competitive edge is critical for success. Our unique government-enterprise-academia system represents a distinct advantage. As a new player, we have not heavily invested in any particular discovery paradigm, which allows us to select the optimal approach with little organizational burden. Virtue R&D model using CROs has gained momentum lately and China is a global leader in CRO market. Essentially all technological support for drug discovery can be found in China, which greatly enables domestic R&D efforts. The information technology revolution ensures the globalization of drug discovery knowledge, which has bridged much of the gap between China and the developed countries. The blockbuster model and the target-centric drug discovery paradigm have overlooked the research in several important fields such as injectable drugs, orphan drugs, and following high quality therapeutic leads, etc. Prejudice against covalent ligands, prodrugs, nondrug-like ligands can also be taken advantage of to find novel medicines. This article will discuss the current challenges and future opportunities for drug innovation in China.
3.Effect of picrosideⅡon expression of myelin basic protein after cerebral ischemia injury in rats
Chinese Journal of Pathophysiology 2014;33(4):584-591
AIM: To verify the neuroprotective effect and optimize the therapeutic dose and time window of picroside Ⅱon cerebral ischemic injury in rats .METHODS:The forebrain ischemia model was established by the method of bilateral common carotid artery occlusion ( BCCAO ) .The successful model rats were randomly divided into 16 groups according to orthogonal design and treated by intraperitoneal injection of picroside Ⅱat different ischemic time poinis and different doses .The changes of the nerve fiber myelin were observed by fast green staining .The immunohistochemical assay and Western blotting were used to quantitatively and qualitatively determine the expression of myelin basic protein (MBP). The mRNA level of MBP in the brain tissues was tested by reverse transcription polymerase chain reaction (RT-PCR).RE-SULTS:Picroside Ⅱ increased the expression of MBP and decreased demyelination after cerebral ischemic injury .The best therapeutic time window and dose were:(1) ischemia for 2.0 h with picrosideⅡat dose of 10 mg/kg according to the results of fast green staining;(2) ischemia for 2.0 h with the dose of 10 mg/kg according to the results of immunohisto-chemical assay;(3) ischemia for 2.0 h with the dose of 10 mg/kg according to the analysis of Western blotting;(4) is-chemia for 1.5 h with the dose of 20 mg/kg according to the detection of RT-PCR.CONCLUSION:Given the principle of the lowest therapeutic dose with the longest time window , the optimized therapeutic dose and time window for rat cerebral ischemic injury is intraperitoneal injection of picroside Ⅱat the doses of 10~20 mg/kg and the time window of ischemia for 1.5~2.0 h.
4.Advance in Relationship between Migraine and Cardiac Right-to-left Shunts (review)
Chinese Journal of Rehabilitation Theory and Practice 2014;(4):344-346
The pathogenesis of migraine is not fully understood as yet. Recently, with the development of ultrasonography, some stud-ies indicated that the prevalence of right-to-left shunt (RLS) seemed to be higher in migraine, especially in migraine with aura. The progress in the relationship between migraine and RLS was reviewed.
5.Percutaneous nucleus pulposus of intervertebral disc under c-arm operation for source of low back pain and disc imaging study
Journal of Chinese Physician 2013;(z1):29-31
Objective To investigate the easement degree of pain after the treatment of low back pain patients in 6 months after the operation.Methods To treat lumbar degenerative osteoarthritis (21cases),lumbar disc herniation(31 cases),Lumbar spinal stenosis assompanied with lumbar disc herniation(1 cases) with percutaneous radiofrequency-ablation,compare the JOA,VAS,Oswestry score of the patients before and at the just after operation,2 weeks,6weeks,3 months,6 months after operation.Results The JOA score of patients after operation rise obviously than that of patients before operation,and VAS and Oswestry score reduce obviously,they all have statiscal significance(P < 0.05).Conclusion The pain of patients who suffered from discogenic low back pain,lumbar disc herniation is relieved by percutaneous radiofrequency-ablation,the quality of patients'life is heightened,all of above indicate that the treatment is an effective method for discogenic low back pain,lumber disc herniation.
6.Thrombospondin-1 in cancer
Journal of International Oncology 2011;38(11):823-826
Thrombospondin-1 expresses in a variety of tumors and induces endothelial cell apoptosis,thus inhibits tumor angiogenesis and prevents tumor growth.It function domain ( Type I sequence):3TSR,retaines the function of inhibit angiogenesis,has the certain practical significance in clinical cancer treatment.
7.VEGF in the treatment and prognosis of lung cancer
Journal of International Oncology 2012;39(4):286-288
Angiogenesis plays a critical role in growth and metastasis of lung cancer.The strongest tumor angiogenesis factor known is the vascular endothelial growth factor (VEGF).Therefore,anti-VEGF therapy which can restrain tumor angiogenesis is an important form of the targeted therapy of lung cancer.The expression of VEGF is also significant to the prognosis of lung cancer.
9.Directional cartilage scaffold for the repair of articular cartilage injury caused by exercise
Chinese Journal of Tissue Engineering Research 2017;21(2):209-214
BACKGROUND:Cartilage scaffold plays an important role in articular cartilage injury, but it is stil restricted in practice, leading to the repair failure using tissue-engineered cartilage. OBJECTIVE:To explore the preparation method of cartilage scaffold with directional structure and its repairing effect in cartilage injury of rabbits. METHODS:Directional cartilage scaffolds were prepared by temperature gradient induced phase separation technique. The cross-linking of cartilage scaffold was completed with genipin. The physical and mechanical properties of scaffolds were determined. Forty-eight white rabbits were modeled into exercised-induced articular cartilage injury and equivalently randomized into two groups, fol owed by implantation of non-directional or directional scaffolds. Samples were col ected at postoperative 6, 12 and 24 weeks to compare the repair effect of two scaffolds on rabbit joint injury. RESULTS AND CONCLUSION:Scanning electron microscope showed that the regular microstructures on the longitudinal section of directional scaffolds were aligned in the same direction, while the longitudinal and transverse planes of the non-directional scaffolds showed porous honeycomb structures. The elastic modulus of the directional scaffold was significantly higher than that of the non-directional scaffold (P<0.05). O’Driscol histological scores in the directional scaffold group were significantly higher than those in the non-directional scaffold group at 6, 12 and 24 weeks postoperatively (P<0.05). At postoperative 24 weeks, in the directional scaffold group, the three-dimensional reconstruction of the rabbit defect region was flat and smooth, and coronal two-dimensional scanning showed the cartilage thickness of the newborn cartilage was very close to that of the normal bone;the cartilage surface in the non-directional rabbits was flat under three-dimensional CT, and coronal two-dimensional scanning showed that the repaired cartilage was almost the same as the normal cartilage. Hematoxylin-eosin staining showed that at 24 weeks postoperatively, the defect site disappeared and the cartilage cel s arranged in the vertical direction in the directional scaffold group. There were typical cartilage lacunae at the defect site in the non-directional scaffold group at 24 weeks postoperatively. Our findings suggest that the directional cartilage scaffold prepared using temperature gradient induced phase separation technique holds good physical and mechanical properties, and its implantation into the rabbit articular cartilage injury induced by exercise can promote the injury repair to obtain ideal mechanical properties.
10.On the Differences of Rational Use of Drugs Policy between China and America and Relevant Reflections
Chinese Medical Ethics 1994;0(05):-
This paper studies the differences of rational use of drugs policy between China and America,mainly focusing on the differences in the policy of clinical pharmacists,the research and development process of substitute for drugs,the guarantee system of medical treatment.In addition,it naturally analyzes the reasons for these kinds of differences from the view of culture and value.At last,it deeply summarizes the humanism positions and justice principles based on which the Rational Use of Drugs was drawn up from the angle of ethics.