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.

The toxic Chinese materia medicia (CMM) has been considered as the combination of active ingredients and toxic ingredients. After reviewing on the theory of traditional Chinese medicine (TCM),combined with clinical and experimental researches,it was found that the two kinds of ingredients have dialectical relationship,they were manifested with "double-side" or "multi-surface" ,even could change into each other. Based on the above understanding,the new research mehods were proposed as follows:Evaluating toxicity of toxic CMM under the physiological and pathological states; Establishing its drug-nature and toxicity under the different pathological states; Focusing on different pathological states to establish the best combination of active and toxic ingredients; Exploring the transitional mechanism of the active and toxic ingredients.

AIM: To investigate the effects of globular adiponectin (gAd) on the expression of adiponectin receptor 1 (AdipoR1) in human umbilical vein endothelial cells (HUVECs), and on the apoptosis induced by advanced glycation end products (AGEs). METHODS: HUVECs were treated with the indicated concentrations of AGEs for 24 h or 48 h in vitro. The cells in gAd treatment group were pretreated with gAd for 24 h, and then were treated with AGEs for another 24 h or 48 h. Cell variability was quantified by MTT assay. Apoptotic cells were detected by flow cytometry with Annexin-FITC/PI double staining. AdipoR1 mRNA in the cells was determined by quantitative real time reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The viability of HUVECs treated with AGEs decreased significantly as compared to the cells treated with HSA (control, P<0.05). Under the same condition of AGEs exposure, the viability of the cells treated with gAd was greatly higher than that of the cells without gAd treatment (P<0.01). The apoptotic rate of HUVECs was significantly elevated by AGEs treatment vs HSA treatment observed by Annexin V-FITC/PI double staining analysis with flow cytometry (P<0.05). Under the condition of AGEs stimulation, the apoptosis of HUVECs was decreased by pretreatment with gAd as compared to that of the cells without gAd treatment (P<0.01). Measured by quantitative real time PCR, AGEs decreased the expression level of AdipoR1 mRNA and gAd increased the expression of AdipoR1 mRNA contrarily (P<0.05). CONCLUSION: AGEs increase the apoptotic rate of HUVECs in a concentration dependent manner and gAd promotes the AdipoR1 mRNA expression.

Objective To explore an easy,safe and effective method for correction of the hypertrophy of mandibulae angle and inferior facial enlargement.Methods Based on the complexion of mandibulae angle hypertrophy,32 patients were treated through an intraoral incision with complete separation of masseter,polish of the diagonal site,camber gonion osteotomy and mandibular marginal plasty under local anaesthesia.Meanwhile,19 patients with masseter hypertrophy were injected with botulinal toxin A three months after the operation,and 2 patients with facio-buccal fullness were treated with removal of the buddal fat pad.Results 12 patients were satisfied with the results after following-up for one to six months.Conclusion This method is easy-doing,safe,reliable and accords with the principle of aesthetics.Osteotomy and grinding of the bone are convenient,which have little damage to patients with less complications and quick recovery.

Objective In this study,we determined whether or not cancer-reactive cytotoxic T-lymphocytes(CTLs)could be induced from peripheral blood mononuclear cells(PBMCs)of colon cancer patients by in vitro stimulation with a PAP peptide.Methods The PBMCs of HLA-A24+ colon cancer patients and healthy donors were stimulated with a PAP213-221 peptide in vitro.The PAP-specific IFN-? was measured by ELISA.The cytotoxicity of CTLs were examined by 51Cr release assay.Results IFN-? produced by the PBMCs of 3 of 5 colon cancer patients and 1 of 8 healthy donors after incubation with PAP213-221 peptide pulsed C1R-A2402 cells were significantly higher then that after incubation with HIV peptide pulsed C1R-A2402 cells(P

With the development of digital hospital construction,the concept of digital hospital has been accepted by lots of hospitals.All sorts of medical information purely facing to medical affairs and its integrated research have become more and more important.Digital management of medical service in hospital has been one of the important field in hospital management,so it has brought a new research orientation on application in the communication standard of medical service.

Objective To evaluate the contrast-enhanced 3D sampling perfection with application-optimized contrasts by using different flip angle evolutions-short TI inversion recovery sequence (SPACE-STIR) for the imaging of the post-ganglionic segments of the brachial plexus.Methods Forty-three patients with suspected brachial plexus lesions were examined with 3D SPACE-STIR and contrast-enhanced 3D SPACE-STIR prospectively.Signal-to-noise ratios (SNR),contrast-to-noise ratios (CNR),and the conspicuousness of roots,trunks,divisions and cords of the brachial plexus of the two 3D sequences were retrospectively compared.Statistical analysis was performed by using student t-test and Wilcoxon rank sum test.Results Compared with 3D SPACE-STIR,contrast-enhanced 3D SPACE-STIR provided the similar SNRs (left,37.41 ±7.34 vs 36.27 ±7.66,t =1.574,P =0.123,right,43.85 ±9.56 vs 42.34 ±9.74,t =1.937,P =0.073),but significantly higher nerve-to-muscle CNRs (left,24.01 ± 6.31 vs 26.39 ± 6.95,right,29.31 ± 7.84 vs 31.77 ± 8.85,t =-3.278,-3.278,both P ＜ 0.01) and nerve-to-lymph gland CNRs(left,-0.84 ± 10.51 vs 15.35 ±8.02,right,-8.47 ± 10.85 vs 19.30 ± 10.35,t =-15.984,-15.651,both P ＜0.01).The conspicuousness of roots and trunks on contrast-enhanced 3D SPACE-STIR was significantly better than that on 3D SPACE-STIR (Z =-3.606,-4.472,P ＜ 0.01),while the conspicuousness of divisions and cords was similar(Z =-1.732,-1.414,P =0.083,0.157).The signal intensity of neoplastic lesions on contrast-enhanced 3D SPACE-STIR tended to decrease rapidly,thus the lesion conspicuousness was worse than that on 3D SPACE-STIR.Conclusions Contrast-enhanced 3D SPACE-STIR has obvious advantages in displaying normal brachial plexus and revealing non-neoplastic lesions of the brachial plexus,but may be insufficient for the diagnosis of neoplastic lesions of the brachial plexus.

Objective To retrospectively analyze CT and MR appearances of hepatic adenoma,and to study the causes of misdiagnosis with review of relative literatures.Methods CT and MRI data of 8 patients with pathologically confirmed hepatic adenoma were retrospectively analyzed.Pre-and post-contrast tri-phase (arterial,portal venous and delayed) CT scans and routine MR .scan were performed in all 8 patients,and proton magnetic resonance spectroscopy (~1H-MRS) was performed in 2 patients.Results Typical demonstrations were found in 4 patients who were correctly diagnosed.Among the others with atypical findings,3 patients were misdiagnosed as liver cancer and 1 as focal nodular hyperplasia (FNH) .The ~1H-MRS curves of 2 adenoma tumor showed that the peak of choline of tumor tissue had no significant difference comparing with that of normal liver tissue around the tumor tissue.Conclusion CT and MRI findings of hepatic adenomas have some characteristics,but atypical manifestations lead to misdiagnose.~1H-MRS may be helpful for the differential diagnosis of hepatic adenoma.

To develop a high-performance liquid chromatographic method for the determination of isoguanosine in Semen Crotonis Tiglii.