Multi-target drugs can simultaneously adjust multiple links of the disease network. Despite the higher efficacy and lower toxicity caused by single targets, multi-target drugs become ideal drugs for treating complicated diseases as well the main direction of drug R & D. By virtue of their structural diversity, higher multi-target activity and lower toxicity, natural products become an important source for developing multi-target drugs. Computer-aided drug design (CADD) is a commonly used multi-target drug R&D method, which mainly includes virtual screening and pharmacophore design. In this paper, the authors made a systematical analysis and discussed the prospects and advantages of various methods for multi-target drug R&D with natural products.
Biological Products ; chemical synthesis ; pharmacology ; Biomedical Research ; instrumentation ; Computer-Aided Design ; Drug Design ; Humans ; Molecular Targeted Therapy

To study the quantitative structure-activity relationship (QSAR) between the stuctures of 29 flavonoids and the inhibitory activity of their multidrug resistance-associated protein (MRP) 1 and 2 by using the comparative molecular similarity index analysis (CoMSIA). By studying the impact of the combination of different molecular force fields, researchers obtained the molecular force fields that played an important role in inhibiting the activity of MRP1 and MRP2, built the optimized QSAR model, and discussed the structural modification method for flavonoids' multidrug resistance-associated protein inhibitor. The results of the study could not only provide the guidance for new drug R&D, but also help partially discuss the synergy mechanism between MRP1 and MRP2 receptors and traditional Chinese medicines containing flavonoids.
Drugs, Chinese Herbal ; chemistry ; pharmacology ; Flavonoids ; chemistry ; pharmacology ; Humans ; Models, Molecular ; Multidrug Resistance-Associated Proteins ; antagonists & inhibitors ; chemistry ; Quantitative Structure-Activity Relationship

In clinical teaching practice of over 30 years, professor LIAN Yu-lin combines physiological, pathological and anatomic knowledge with TCM treatment based on syndrome differentiation, forming own unique theoretical system. This paper introduces LIAN's experience on treatment of cervical spondylosis in detail, and location of cervical vertebra three lines and determination of needling depth and reinforcing-reducing manipulation based on clinical manifestations of various types of cervical spondylosis, and combination of long needle with short needle, deep needling with superficially needling, stressing the main point and having a definite object. This is an effective pathway for treatment of cervical spondylosis.
Acupuncture Therapy ; Adult ; Cervical Vertebrae ; Female ; Humans ; Male ; Middle Aged ; Spinal Osteophytosis ; classification ; therapy

Objective To compare clinical outcome of intracytoplasmic sperm injection(ICSI)cycle by using fresh and cryopreserved-thawed testicular and epididymal spermatozoa in azoospermic patients.Methods Between September 2006 and May 2007,208 azoospermic patients underwent in vitro fertilization(IVF)were treated in Center of Reproductive Medicine,Peking University Third Hospital.Those couples were divided into two groups based on their wishes,including 171 cases in fresh group and 37 cases in cryopreserved-thawed group.The cryopreserved testicular or epididymal spermatozoa were thawed and recovered before ICSI procedure iu thawed group.The outcomes of ICSI in each group were compared.including clinical outcomes(two pronuclear fertilization,high quality embryo,clinical pregnancy and embryo implantation)and pregnancy outcomes(spontaneous miscarriage,gestational weeks and neonatal birth weight).Results (1),The utilization rate were 92%(23/25)in cryopreserved-thawed testicular spermatozoa and 100%(12/12)in epididymal spermatozoa.(2)Between fresh and cryopreserved-thawed groups,no statistical difference was observed in two pronuclear fertilization rate[62.25%(973/1563)vs.64.53%(282/437),P=0.960],high quality embryo rate[78.9%(768/973)vs.79.1%(223/282),P=0.985],clinical pregnancy rate per embryo transfer[44.4%(60/135)vs.46.9%(15/32),P:0.688]and embryo implantation rate[29.3%(84/287)vs.33.3%(23/69),P=0.508].(3)No significant difference between flesh and cryopreserved group was found in spontaneous miscarriage rate (11%vs.7%,P＝1.000),gestational weeks(single birth:39.0 weeks vs.38.7 weeks,P:0.538;twins:36.8 weeks vs.36.3 weeks,P=0.571)and birth weight(single birth:3409 g vs.3350 g,P=0.699;twins:2584 g vs.2635 g,P=0.703).Conclusion It suggested that tissue from the azoospermic patients who underwent diagnostic testieular and epididymal biopsy should be eryopreseved for IVF-ET.

The combined application of statins that inhibit HMG-CoA reductase and fibrates that activate PPAR-α can produce a better lipid-lowering effect than the simple application, but with stronger adverse reactions at the same time. In the treatment of hyperlipidemia, the combined administration of TCMs and HMG-CoA reductase inhibitor in treating hyperlipidemia shows stable efficacy and less adverse reactions, and provides a new option for the combined application of drugs. In this article, the pharmacophore technology was used to search chemical components of TCMs, trace their source herbs, and determine the potential common TCMs that could activate PPAR-α. Because there is no hyperlipidemia-related medication reference in modern TCM classics, to ensure the high safety and efficacy of all selected TCMs, we selected TCMs that are proved to be combined with statins in the World Traditional/Natural Medicine Patent Database, analyzed corresponding drugs in pharmacophore results based on that, and finally obtained common TCMs that can be applied in PPAR-α and combined with statins. Specifically, the pharmacophore model was based on eight receptor-ligand complexes of PPAR-α. The Receptor-Ligand Pharmacophore Generation module in the DS program was used to build the model, optimize with the Screen Library module, and get the best sub-pharmacophore, which consisted of two hydrogen bond acceptor, three hydrophobic groups and 19 excluded volumes, with the identification effectiveness index value N of 2. 82 and the comprehensive evaluation index CAI value of 1. 84. The model was used to screen the TCMD database, hit 5,235 kinds of chemical components and 1 193 natural animals and plants, and finally determine 62 TCMs. Through patent retrieval, we found 38 TCMs; After comparing with the virtual screening results, we finally got seven TCMs.
Acyl Coenzyme A ; metabolism ; Animals ; Databases, Factual ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Hydrophobic and Hydrophilic Interactions ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; chemistry ; pharmacology ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Medicine, Chinese Traditional ; Models, Molecular ; Quantitative Structure-Activity Relationship ; Technology

Objective To investigate the clinical efficacy of She medicine therapy in rehabilitation after endoscopic surgery for lumbar intervertebral disc herniation.Methods Sixty patients with lumbar intervertebral disc herniation were allocated, using random number table method following registration order, to treatment and control groups, 30 cases each. The treatment group received She medicine therapy and the control group, oral administration of conventional drugs. The excellent and good rate was observed in the two groups after treatment. Post-treatment active straight leg raising times and analgesic dosages were compared between the two groups.Results Active straight leg raising time was significantly advanced (P<0.01) and the number of potent analgesic uses was significantly decreased (P<0.01) in the treatment group after endoscopic surgery for lumbar intervertebral disc herniation. The excellent and good rate was 93.3％ in the treatment group and 80.0％ in the control group; there was a statistically significant difference between the two groups (P<0.05).Conclusion She medicine therapy can help rapid rehabilitation after endoscopic surgery for lumbar intervertebral disc herniation.

OBJECTIVETo observe the effect of gastric dynamics by transcutaneous electrical acupoint stimulation (TEAS) combined general anesthesia when controlled hypotension dropped to 60% of the mean arterial prenssure (MAP) baseline, and to provide experimental evidence for organ protection in clinical controlled hypotension.

METHODSEighteen male beagles were randomly divided into three groups, the general anesthesia group (blank), the general anesthesia induced controlled hypotension group (control), and the general anesthesia combined TEAS induced controlled hypotension group (experiment), 6 in each group. Controlled hypotension was performed in the latter two groups with isoflurane inhalation and intravenous injection of sodium nitroprusside (SNP). The mean arterial pressure (MAP) was lowered to 60% of the MAP baseline and kept for 60 min. Controlled hypotension was not performed in Beagles of the control group. For Beagles in the experiment group, TEAS [2/100 Hz, (4 ± 1) mA] was applied to bilateral Hegu (LI4), Quchi (LI11), Zusanli (ST36), and Sanyinjiao (SP6) from stable physiological conditions to the end of maintaining stages. Changes of EGG frequencies and EGG amplitudes were monitored. Serum levels of gastrin (GAS) and motilin (MTL) were also detected at corresponding time points during and after experiment.

RESULTSAs for the pressure control effect of TEAS combined general anesthesia in the controlled hypotension, during the process of controlled hypotension (T1-T4), MAP levels of two controlled pressure groups remained relatively stable, and were kept at 60% of the MAP baseline. When the blood pressure dropped to the target low MAP and maintained at 60 min (T1-T4), EGG amplitudes of Beagles in all the three groups showed decreasing tendency. But it was more obviously lower than its basic level in the control group (P <0.05), while it was not obviously decreased in the experiment group (P < 0.05). EGG frequencies of Beagles in all the three groups showed no obvious change during this stage. By the end of the MAP rising stage (T8), the EGG amplitude of the experimental group was significantly higher than that of the control group and the blank group (P < 0.05), while it didn' t show any obvious increase in the control group. During this period, EGG frequencies of the two controlled hypotension groups decreased more than those of the blank group. Two h after rising blood pressure (at T9), EGG amplitudes and frequencies in the two controlled hypotension groups basically restored to their respective baselines and levels of the blank group at T9. At 2 h (T9) after controlled hypotension, serum levels of GAS and MTL were lower than those of basic levels in the two controlled hypotension groups (P <0.05). However, serum levels of GAS and MTL had an increasing trend in the two controlled hypotension groups at 24-72 h (T10-T12). Besides, the increasing speed and amplitude was better in experiment group than in the control group at T10-T12. However, there was no statistical difference between the two groups (P > 0.05). At 72 h (T12) serum levels of GAS and MTL had basically restored to their basic levels in the two controlled hypotension groups and that of the blank control group.

CONCLUSIONEGG amplitudes could be effectively improved in TEAS combined general anesthesia for controlled hypotension at 60% of the MAP baseline, the recovery of the serum GAS level accelerated, gastric power improved and stomach protected.

Acupuncture Points ; Anesthesia ; methods ; Anesthesia, General ; Animals ; Arteries ; Dogs ; Gastrins ; Hypotension, Controlled ; Male ; Motilin ; Nitroprusside ; Transcutaneous Electric Nerve Stimulation

Cholesterol ester transfer protein (CETP) is a key regulator of high density lipoprotein (HDL). Owing to its important role in the reverse of cholesterol transport, CETP has become a hotspot target in modulating lipid drug design. In this paper, structure based pharmacophore (SBP) models for CETP inhibitors were built based on the protein structure 4F2A from Protein Database (PDB). The best pharmacophore contained six hydrophobic features, one hydrogen bond acceptor feature and nine excluded volume features, with the N and CAI value was 3.33 and 2.31 respectively. Then the model was used to search the traditional Chinese medicine database (TCMD) and 629 compounds originated from 315 TCM herbs were obtained. Molecular docking was also used to validate SBP by analyzing the critical amino acid residue and the interaction between potential active compounds and receptor. In this study, several TCM herbs, like Lycii Frutus and Schisandrae chinensis fructus, which contained more optimal SBP based screening results, have been reported hypolipidemic effect, and need to be studied deeply in a more focused research on herbal active constituents. Therefore, this study could provide reliable fundamental data for exploring the action mechanisms of TCM, and be applicable to identify lead candidates, which can be utilized as starting scaffolds for natural CETP inhibitors.
Cholesterol Ester Transfer Proteins ; antagonists & inhibitors ; Drug Evaluation, Preclinical ; methods ; Medicine, Chinese Traditional ; Molecular Docking Simulation

Objective To observe the clinical efficacy of acupuncture of She Medicine in treating acute lumbar sprain.Method Eighty patients with acute lumbar sprain were randomized into a treatment group and a control group,40 cases each.The treatment group was intervened by acupuncture of She medicine,while the control group received conventional medication.After successive 3-day treatment,the changes in Visual Analogue Scale (VAS) and Modified-Modified Schober (MMS) scores were observed,and the clinical efficacies were compared between the two groups.Result After the intervention,the VAS and MMS scores were significant changed in both groups (P＜0.01).The VAS and MMS scores of the treatment group were significantly different from those of the control group after the intervention (P＜0.01).The total effective rate and recovery rate were respectively 92.5％ and 70.0％ in the treatment group,versus 77.5％ and 40.0％ in the control group,and the between-group differences were statistically significant (P＜0.01).Conclusion Acupuncture of She medicine is effective in treating acute lumbar sprain,with advantages of swift action in releasing symptoms and high recovery rate.

0.01),which were significantly different from group Ⅲ(P