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.

Motor cortex electrical stimulation was first used in the clinical treatment of central pain in 1989.Recently,this technique has been used to treat post-stroke movement disorders and better efficacy has also been obtained.Its mechanisms may include regulating cortex-basal ganglia circuits,exciting the activation of the motor cortex on the affected side but inhibiting the activation of the motor cortex on the contralateral side.regulating the plasticity of brain and resynchronization of electric activity.This article reviews the possible mechanisms,operative methods.clinical efficacy and existing problems.

Objective To establish the quality standard for Ulter Zhuhuang gel.Methods Indirubin,cholic acid and borneol were identified by TLC.The content of indirubin and cholic acid was determined by HPLC.Result The TLC sports developed was fairly clear.The HPLC method showed that the average recovery of indirubin and cholic acid was 100.3% with RSD=2.1% and 98.9% with RSD=1.8% respectively.Conclusion The method is convenient and accurate.It can be used for the quality control of Ulter Zhuhuang gel.

A canine model of sudden coronary death was established by intimal sur-face anodal direct current stimulation of the left circumflex coronary artery (LCX)on 5-8 days after the left anterior descending coronary artery (LAD) infarction. TheLCX intimal injury and subsequent thrombus formation produced ECG ST segment chan-ges at 104?30 minutes (X?SD), followed by premature ventricular beats, ventriculartachycardia (VT), and ventricular fibrillation (VF) in all normal saline (NS) treated dogs(n=6), in procainamide (PA) treated dogs (n=6), ECG ST segment changes appearedat 110?40 minutes, followed by VT and VF in only one dog (P

Objective To discuss the effectiveness of tracer methodology in the training of intern medical record writing. Methods Fifty interns who received medical record writing training in July 2012 were set as control group and were trained by traditional methods. Meanwhile, 58 interns who received medical record writing training in July 2013 were set as investigation group and were trained by tracer methodology. Pre-training questionnaire survey was conducted for interns in investigation group and targeted training was provided. After the training, interns in two groups were surveyed by questionnaire of basic norms of medical record writing. Excel software was used to do data entry and SPSS 21.0 statistical software was used to statistical analysis. P<0.05 signifies statistical differences. Results Final record writing exam after the training demonstrated that there were significant differ-ences in basic requirement of record writing, basic principle of record writing, history taking, record time limit, contents of record writing and correct rate of patients' answer to the document between in-vestigation group and control group with statistical differences(P<0.05). Conclusion Tracer method-ology has obvious effects in intern medical record writing training and is worth popularization and ap-plication in clinical teaching.

Objective To compare the clinical efficacy of endoscopic variceal ligation versus pericardial devascularization in the treatment of portal hypertension.Methods The clinical data of 101 cirrhotic patients with gastroesophageal varices and variceal hemorrhage from January 2010 to January 2012 were analyzed.Fifty-three patients received endoscopic variceal ligation,and forty-eight patients received pericardial devascularization.Postoperative changes in liver function and hypersplenism were compared between the two groups.The rate of rehaemorrhagia and incidence of postoperative complications after surgery were compared as well.Continuous data were expressed as mean ±SD,and categori-cal data were expressed as number of cases or percentage.Comparison of continuous data between the two groups was made by independent-samples t test,and comparison of categorical data was made by chi-square test.Results After surgery,the variceal ligation group showed no significant changes in liver reserve function,while the albumin level was significantly decreased in the pericardial devascularization group (t=2.512,P<0.05).There were no significant changes in the counts of white blood cells and platelets in the endoscopic variceal ligation group after surgery (P>0.05),but significant increases in the counts of white blood cells and platelets were detected in the pericardial devascular-ization group (P<0.05).The rates of postoperative haemorrhage in the two groups were:3 months,7.5%vs 6.2%(χ2 =0.066,P>0.05), 6 months,7.5%vs 8.3%(χ2 =0.021,P>0.05),and 1 year,9.4%vs 8.3%(χ2 =0.038,P>0.05).The incidence rates of postopera-tive complications in the two groups were 24.5%and 50%,respectively (χ2 =7.040,P<0.05).Conclusion Compared with pericardial devascularization,endoscopic variceal ligation causes fewer microlesions,preserves liver function,and leads to a lower incidence of postopera-tive complications.However,if hypersplenism is observed in the cirrhotic patients with gastroesophageal varices and variceal hemorrhage,peri-cardial devascularization can be used to control the hypersplenism and prevent esophageal hemorrhage.

ObjectiveTo observe the effect of low frequency current hydroelectric bath therapy modulated by medium frequency on sequela of sprain of ankle. Methods46 patients with sequela of sprain of ankle were treated with ZM C intellectual faculties intermediate frequency therapeutics instrument. Medium frequency was modulated with full square wave. The frequency of carrying wave was 4KHz. The frequency of modulated wave was 100Hz. The depth of modulation was 80%. The water temperature was 40℃.ResultsAfter treatment, all patients got satisfactory effect and shorter treating course without adverse reactions appearing. Conclusions The low frequency current hydroelectric bath therapy modulated by medium frequency is a simple, safe and better treating method for sequela of sprain of ankle.

Objective To establish a new automatic lung segmentation method in order to deal with the omission of pleural nodules and pulmonary vessels. Methods Lung parenchyma were extracted from chest CT images with the inversed operation of 2D region growing and connected area classification, then the contours and locating the contour points were traced with scan line searching. Finally, the parameters of lung contour points were analyzed to locate the contours distorted by nodules, and curve spline was used to correct distorted contours. Results The experimental results of many sets of CT images verified that the technique proposed was effective. The comparison with other contour correction algorithm verified that line searching contour correction was superior. Conclusion The proposed algorithm includes tumors in the segment results, and confirms the integrality, veracity, real-time quality of this auto-segmentation method.

Objective To observe the effects of chronic arsenic exposure on mRNA expression of estrogen receptor-binding fragment-associated gene 9 (Ebag9) and estrogen-responsive finger protein (efp) in uterus and ovary of female rats.Methods Fifty female Wistar rats were randomly divided into five groups according to arsenic (As2O3) concentrations given through drinking-water:0.00 (control),0.05,0.10,0.20,0.40 mg/L arsenic exposure groups and real-time RCR (RT-PCR) was used to detect the mRNA expression of Ebag9 and efp in uterus and ovary tissue at the 31 weeks of experiment.Results The mRNA expression levels of Ebag9 and efp of the 0.00,0.05,0.10,0.20,0.40 mg/L arsenic exposure groups were respectively as follows:0.761 ± 0.178,0.521 ± 0.130,0.544 ± 0.035,0.525 ± 0.198,0.498 ± 0.240 and 0.795 ± 0.171,0.874 ± 0.077,0.797 ± 0.066,0.796 ± 0.040,0.832 ± 0.096.Compared with control group,a decreased tendency was observed in Ebag9 mRNA level(with P value 0.055 in 0.40 mg/L arsenic exposure group) and increased tendency in efp mRNA level in experimental groups (all P ＞ 0.05).The mRNA expression levels of Ebag9 and efp in ovary of the five groups were by turns:0.702 ± 0.484,0.719 ± 0.336,0.693 ± 0.095,0.706 ± 0.055,0.728 ± 0.073 and 0.924 ± 0.061,1.009 ± 0.034,0.930 ± 0.085,0.929 ± 0.068,1.012 ± 0.101.Compared with control group,the expression level of Ebag9 mRNA showed a increased tendency in 0.05,0.20,0.40 mg/L arsenic exposure groups(all P ＞ 0.05).The efp mRNA level increased in experimental groups,with significant difference in 0.05,0.40 mg/L groups (all P ＜ 0.05).Conclusions The expression of efp mRNA has changed in ovary of female rats exposed to chronic arsenic.Arsenic may act as an environmental endocrine disruptor to exert its effect.

Objective To identify the biomarkers which can be used of estimating the biological behaviors of prostate cancer with osseous metastasis by SELDI-TOF-MS. Methods Screening for potential tumor biomarkers of serum samples from 19 prostate cancer patients and 35 prostate cancer patients with osseous metastasis by using the technology of SELDI-TOF-MS and CM 10 protein chips (Ciphergen Inc. USA).The PBS Ⅱ protein chip reader was used to analyze the CM10 protein chips and transform the protein information into the form of spectra. The protein contents of two groups in the same mass-to-charge ratio (M/Z value) were analyzed and preceded the analysis of variance by Biomarker Wizard software. The proteins whose contents in serum were significantly different, which was distinguished the correctly groups by Biomarker Pattern software. Results The contents of 4 proteins in the two groups were significantly different and the M/Z values of these 6 proteins were from 2000 to 20 000. The relative protein content of prostate cancer patients group was higher than that of Prostate Cancer patients with osseous metastasis group at the M/Z value of 2089,4281, 3507 and 4178 [(4.63±8.03) vs (9.88±10.77), (19.78±21.46) vs (26.73±19.41), (5.46±10.14) vs (8.10±8.74), (38.01 ±26.27) vs (45.25±20.40), (P＜0.05)]. The relative protein content of prostate cancer patients group was lower than that of prostate cancer patients with osseous metastasis group at the M/Z value of 15 900 and 16 081 [(11.52±16.80) vs (4.84±5.83), (8.55±12.64) vs (3.56±3.90), (P＜0.05)]. Conclusion The associated serum protein in prostate cancer with osseous metastasis can be quickly and exactly diagnosed by SELDI-TOF-MS with high sensitivity and specificity. This new method will be widely used in clinical application.