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 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

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.

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.

Background and purpose: Magnetic resonance spectroscopy is currently the only non-invasive magnetic resonance imaging technique which can detect metabolite composition of live organ and tissue and also conduct semi-quantitative or quantitative analysis. We analyzed the characteristics of metabolic changes among normal liver, cirrhosis regenerative nodule and liver cancer on the background of cirrhosis by voxel proton MR spectroscopy at 1.5 Tesla. Methods: 20 healthy volunteers (control group), 25 cirrhosis (cirrhosis group) and 23 hepatocellular carcinoma after cirrhosis (HCC group) patients were our candidates. The characteristics of spectra of ~1H-MRS were observed. The height and ratio of choline complex (Cbo) and lipid methylene (Lip2) were recorded and the results were compared among the groups. Results: The success rate of ~1H-MRS was about 88.2% (60/68). There were statistically significant differences among the heights of Lip2 peak of the three groups, and also between that of the control group and the group of liver cancer. But there were no significant differences between that of control group and cirrhosis group, cirrhosis group and liver cancer group. The comparison of the height of Cho peak and the ratio of Cho/Lip2 showed statistically significances both among the three groups and between each other. Conclusion: The metabolic changes of the liver could be shown non-invasively by ~1H-MRS, which could be useful for differential diagnosis or diagnosis of cirrhosis regenerative nodule and HCC.

Objective To observe and compare the efficacy and safety of implantation of tissue expanders adjacent to or under keloid tissues for large keloids on anterior chest. Methods Between Mar 2006 and June 2009, a total of 17 patients with large keloid lesions on anterior chest received treatment with 21 tissue expanders,among which 12 were placed under the normal skin adjacent to keloids, and 9 were inserted under the keloid lesions. The scar size varied from 4.5 cm × 3.0 cm to 15.7 cm × 5.5 cm. The capacity was 70 to 400 ml for expanders adjacent to the keloid tissue, 80 to 500 mi for those beneath the keloid tissues. After tissue expansion for 6 to 8 weeks, the expander was removed and keloid lesions were resected followed by the repair of defect with expanded flaps. Further more, the patients received intraoperative local intradermal injection of betamethasone and postoperative superficial electron beam irradiation with divided doses of 7 Gy in 3 consecutive days within 1 week after the surgery. Follow-up varied from 12 to 50 months. Results Twenty expanders, except 1expander pocket which was removed ahead of time due to infection, were implanted successfully during the whole course of treatment. The main complication was expander exposure in 4 patients, including 1 expander adjacent to the keloids and 3 under keloid lesions, which showed no significant influence on secondary operation. Fifteen patients reported relief of symptoms and achieved satisfactory outcomes, while 2 patients, including 1 treated with expanders adjacent to the keloids and 1 with expanders under the keloid tissue, showed great suture tension and experienced delayed stitch removal followed by the recurrence of keloids after the operation.Conclusions The implantation of tissue expanders under the adjacent normal skin or keloid lesions is an ideal treatment option for large keloids on anterior chest. Regional suture tension is a direct contributor to the recurrence of keloid formation after surgical excision.

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