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.

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.

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.

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.

Objective To study the effects and the mechanism of the ethanol extract of Blueberry(BE) on relaxation vascular endothelium or smooth muscle.Methods To use rat aorta as the specimen,to observe the effects of BE on induced relaxation of the phenylephrine-precontracted aorta.and approach the mechanism on vascular endothelium or smooth muscle.Results BE induced relaxation of the phenylephrine-precontracted(1.0×10~(-5)mol·L~(-1) aorta in a dose-dependent way(P<0.01),which was disappeared by removal of functional endothelium(P<0.01).Pretreatment of the aortic tissues with NG-nitro-L-arginine methyl ester(L-NAME),methylene blue,or 1H[1,2,4]-oxadiazole-[4,3_a]-quinoxalin-1-one (ODQ) inhibited the vascular relaxation induced by BE(P<0.01).BE-induced vascular relaxations were also markedly attenuated by addition of verapamil or diltiazem,while the relaxant effect of BE was not blocked by pretreatment with indomethacine,glibenclamide,tetraethylammonium(TEA),atropine,propranolol(P<0.01).Conclusion These results suggest that BE dilates vascular smooth muscle via endothelium-dependent nitricoxide-cGMP signaling pathway,possible involvement of L-type Ca~(2+) channel.

Objective: To measure serum testosterone level, plasma levels of interleukin-18 (IL-18) and IL-10 and explore their correlation in patients with different types of coronary heart disease (CHD), and their possible role in occurrence and development of CHD. Methods: A total of 96 male CHD patients were divided into acute myocardial infarction (AMI) group (n=35), unstable angina pectoris (UAP) group (n=32) and stable angina pectoris (SAP) group (n=29). Another 30 patients who were excluded for CHD by coronary angiography were enrolled as non CHD control group. Enzyme linked immunosorbent assay (ELISA) was used to measure serum testosterone level and plasma levels of IL-18 and IL-10 in all groups. Results: Compared with non CHD control group, there were significant decreases in serum testosterone level [(13.46±1.99) mmol/L vs. (6.89±1.35) mmol/L vs. (5.02±1.87) mmol/L, t=1.917～2.365, P<0.05 both] in UAP group and AMI group, and that of AMI group was significantly lower than that of UAP group, t=1.034, P<0.05; there were significant increases in IL-18 levels [(146.72±79.36) pg/ml vs. (209.32±80.49) pg/ml vs. (316.78±75.63) pg/ml vs. (457.78±83.21) pg/ml, t=2.016～3.167,P<0.05 all] in SAP group, UAP group and AMI group, and those of UAP group and AMI group were significantly higher than that of SAP group, t=2.173, 2.596, P<0.05; there were significant increases in IL-10 levels [(48.46±18.27) pg/ml vs. (116.45±42.76) pg/ml vs. (85.64±27.33) pg/ml vs. (70.26±18.55) pg/ml, t=2.997～2.018, P<0.05 all] in SAP group, UAP group and AMI group, and those of AMI group and UAP group were significantly lower than that of SAP group (t=2.034, 2.291, P<0.05 both). Pearson linear regression analysis indicated that serum testosterone level was negatively correlated with levels of IL-10 (r=-0.678, P<0.01) and IL-18 (r=-0.579, P<0.01) in CHD group. Conclusion: There are significant changes in serum testosterone level and plasma IL-18, IL-10 levels, and testosterone level is significantly negatively related with IL-18, IL-10 levels, and they can be regard as new indexes assessing coronary atherosclerotic lesion.

Objective To study the relationship between receptor interacting protein (RIP)1 and hepatocyte necropto?sis in isoniazid (INH) induced mouse model. Methods Kunming male mice were randomly divided into three groups. Con?trol group (C) received 0.3 mL of normal saline one time per day. INH group (INH) was injected intraperitoneally INH 100 mg/kg body weight, one time per day. Nec-1+INH group was injected intraperitoneally Nec-1 in 0.1%DMSO and 1 mg/kg body weight one time/12 hours, and INH was injected intraperitoneally at the same dose with that of INH group. All animals were treated for 7 days. Pathological changes of liver tissues were studied by HE staining. RIP1 expression was detected by immunohistochemical, Western blot and real-time PCR analysis. Levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH) and superoxide dismutase (SOD) in liver homogenate were determined by colorimetric method. Re?sults Hepatocytes were arranged orderly in C group. The degeneration and necrosis of hepatocytes were found in Nec-1+INH group, and severe degeneration and necrosis of hepatocytes were found in INH group. Compared with C group, the ex?pression levels of RIP1, ROS and MDA were increased significantly, and the expression levels of GSH and SOD were de?creased significantly in INH group (P<0.05). INH-induced acute liver necroptosis was significantly alleviated after treat?ment with Nec-1. Compared with INH group, the expression levels of RIP1, MDA and ROS were significantly decreased, and the expression levels of GSH and SOD were significantly increased in Nec-1+INH group (P<0.05). Conclusion These re?sults suggest that RIP1 is involved in INH-induced hepatocyte necroptosis in mice. The inhibition of RIP1 expression might be a treatment strategy for prohibition of INH-induced acute liver necroptosis.