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Organic chemistry serves as a fundamental course in pharmaceutical studies, which is closely associated with medicinal chemistry and innovative drug research. With its multifarious and complex content, certain topics in organic chemistry, such as the theory of chemical bonding relevant to innovative drug design, can be abstract and challenging to comprehend. Integrating case studies from innovative drug research into organic chemistry classroom teaching, along with the use of relevant software to demonstrate the interactions between organic small molecules and biomacromolecules, can make these concepts more vivid, accessible, and engaging for students. Moreover, this approach deepens students' understanding of the relationship between organic chemistry and pharmacy, and ignites their interest and proactivity in learning, which ultimately enhances the overall teaching quality. [ABSTRACT FROM AUTHOR]

Copyright of Journal of East China University of Science & Technology is the property of Journal of East China University of Science & Technology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Computer Engineering & Applications is the property of Beijing Journal of Computer Engineering & Applications Journal Co Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable success in treating hematological malignancies. However, CAR-T therapy for solid tumors is still limited due to the unique solid-tumor microenvironment and heterogeneous target antigen expression, which leads to an urgent need of combining other therapies. At present, nano delivery system has become one of the most promising directions for the development of anti-tumor drugs. Based on the back- ground of CAR-T and tumor treatment, we focus on the research progress of nanomedicine combined with CAR-T therapy, and systematically review the strategies and examples in recent years in the aspects of in vivo delivery of mRNA, regulation of tumor microenvironment, combination with photothermal therapy. And we also look forward to the future direction of this fled. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bile acids are the end products of cholesterol metabolism and are classified as primary bile acids and secondary bile acids. They can promote nutrition absorption and regulate immune response, glucose/lipid/energy metabolism, and microbiota homeostasis by acting on bile acid nuclear receptors and membrane receptors. Cholestatic liver disease (CLD) is a type of liver disease caused by abnormalities of the hepatobiliary system due to cholestasis, with the initial manifestations of hepatocyte and/or bile duct injury, which further leads to abnormal bile acid synthesis, secretion, and excretion. In-depth studies have gradually revealed the role and mechanism of bile acids in CLD, and drugs targeting the action sites of bile acids are under research and development. This article elaborates on the role and mechanism of bile acid metabolism in CLD and summarizes the research and development of drugs for CLD treatment based on bile acid metabolism, so as to provide a reference for future research on the prevention and treatment of CLD. [ABSTRACT FROM AUTHOR]

Cell adhesion plays an important role in most biological processes in human body. Cell adhesion is mainly determined by the binding kinetics of specific molecules (called receptors and ligands) anchored on the cell membrane. Although it is known that the binding relation of specific molecules is affected by various factors such as external forces and cell membrane fluctuations, it is still unclear how the molecular stiffness affects the binding kinetics of the membrane-anchored receptors and ligands. Recent studies on the strong infectivity of the coronavirus reported the importance of specific molecular stiffness to the adhesion between viruses and cells. A coarse-grained model of biomembrane adhesion was developed, and molecular simulation and theoretical analysis were introduced to reveal the role of molecular stiffness in adhesion. The results show that, there is always an optimal membrane spacing and an optimal molecular stiffness value, making the adhesion molecular affinity and the binding kinetic parameters reach the maximum values. This study can not only deepen the understanding of cell adhesion, but also help guide drug design and vaccine development. [ABSTRACT FROM AUTHOR]

In this study, the interactions between the inhibitors and the main protease (Mpro) of SARS-CoV-2 were studied, to understand how the inhibitors influence the dynamics of Mpro of SARS-CoV-2. Firstly, molecular docking was applied to obtain the binding complex of the inhibitors and the main protease, and the binding affinities. The classical molecular dynamics simulations show that, all the tested inhibitors cannot inhibit the dynamics of Mpro’s active pocket. The replica-exchange molecular dynamics simulations show that, the inhibitors influence the shape of the active pocket of Mpro. With the formation of hydrogen bonds between the inhibitors and different sites of the active pocket, the inhibitors affect the length and width of the pocket. The study indicates that the drug design of Mpro should fully consider the importance of the hydrogen network between the potential inhibitors and the active pocket. In this study, the interactions between the inhibitors and the main protease (Mpro) of SARS-CoV-2 were studied, to understand how the inhibitors influence the dynamics of Mpro of SARS-CoV-2. Firstly, molecular docking was applied to obtain the binding complex of the inhibitors and the main protease, and the binding affinities. The classical molecular dynamics simulations show that, all the tested inhibitors cannot inhibit the dynamics of Mpro’s active pocket. The replica-exchange molecular dynamics simulations show that, the inhibitors influence the shape of the active pocket of Mpro. With the formation of hydrogen bonds between the inhibitors and different sites of the active pocket, the inhibitors affect the length and width of the pocket. The study indicates that the drug design of Mpro should fully consider the importance of the hydrogen network between the potential inhibitors and the active pocket. [ABSTRACT FROM AUTHOR]

Objective To find novel lead compounds as p53-MDM2 inhibitors by drug repurposing strategy.Methods The p53-MDM2 inhibitory activities of compounds were determined by FP and western blotting. MTT method was used to determine the in-vitro antitumor activities. The metabolites in human liver microsomes were tested. Results Bepridil showed excellent invitro anti-tumor activity and strong p53-MDM2 protein binding inhibitory activity, which can significantly reduce the expression of MDM2 protein in a dose-dependent manner. The metabolites in human liver microsomes are mainly benzene ring hydroxyl monooxidation metabolites. Conclusion Bepridil can be used as a lead compound for p53-MDM2 protein binding small molecule inhibitors for subsequent structural optimization design studies. [ABSTRACT FROM AUTHOR]

Objective To search for novel potent 3-ester derivatives of arenobufagin and test their antitumor activities in vitro. Methods Target compounds were synthesized by esterification of arenobufagin with acids. CellTiter method was used to assay the in vitro antitumor activities. Results 3-Ester derivatives exhibited excellent antitumor activities against all the cancer cells. Conclusion Among the 3-ester derivatives, compound 2a had the best activities with the IC50 of 4.0−91.7 nmol/L and appeared to be a valuable candidate for further study. [ABSTRACT FROM AUTHOR]

Objectives: To design and synthesize peptide inhibitors targeting transient receptor potential vanilloid 1 (TRPV1) ion channel, and to validate their function., Methods: Based on previous studies on the relation of molecular structure and function of red head toxin (RhTx), a series of peptides were rationally designed and synthesized, with positive charged amino acids linked to the N terminus of RhTx. These Nplus-RhTx peptides were functionally validated by patch-clamp recordings in live cells., Results: Among the 8 synthesized Nplus-RhTx peptides, four inhibited TRPV1 ion channel activated by capsaicin with IC 50 of (188.3±4.7), (193.6±18.0), (282.8±11.9) and (299.5±6.4) µmol/L, respectively., Conclusions: It is feasible to develop TRPV1 peptide inhibitors by using rational design based on N terminal residues of RhTx.

Copyright of Journal of Central China Normal University is the property of Huazhong Normal University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To investigate the anti-skin inflammation effect and mechanism of Angelicae and Borneol from the perspective of blood rheology and inhibition of inflammatory factors. Methods: The 60 SD rats were randomly divided into 6 groups: Normal group, Model group, Positive control group, Borneol group and Angelica-Borneol group. In addition to the Normal group, the rest of the group are established using carrageen glue injection of plantar foot skin, Inflammation model modeling success in each group after 1 h in inflammatory place daub each group separately according to the design of drugs, dosage 4 h after Laser Doppler blood flow imaging system were used to detect each group rats toes blood flow changes, and to measure toes swelling degree, modeling, inflammation tissue after 4 h with Elisa method to detect swollen foot organization of SOD HIS PGE2, MDA PGD2 COX-2 and IL - 6、 IL-1β, IL-8 level. Results: The toe swelling rate of the inflammatory Model group is increased significantly compared to the Normal group. After exposure to different drugs, the rate decreased sharply. And, there are more clear distinctions of the hemorheology between each group, especially the Angelica group which had a dramatic change in the branches of the toes, and the Borneol group had a more significant amelioration on peripheral microcirculation. The combination of two drug improved hemorheology globally .The evaluation of related cytokines showed that, except SOD, the model group showed significant increment of HIS, MDA, PGE2, PGD2, COX-2, Il-6, IL-1β, and IL-8 (P < 0.05). After treatment, Baizhi, Borneol and the combined group eased these indicators in different degrees compared to the model group. Borneol had a weaker effect on SOD and HIS, and Baizhi and the combined group could significantly reduce PGD2, COX-2, IL-6, IL -1β, IL-8 (P＜ 0.05); while they all had no obvious effect on IL-10. Conclusion: Angelica combined with Borneol has obvious anti-inflammatory effect on acute inflammation. Also, this combination group can decrease the side effects of edema and inhibit the increase of hemorheology caused by the expansion of microcirculation. The mechanism may be related to PGE2, COX-2 and A variety of interleukins. [ABSTRACT FROM AUTHOR]

Topomer CoMFA was used to build a three-dimensional quantitative structure-activity relationship (3D-QSAR) model for 18 pyranones in this paper,with key parameters as follows:N= 3, F= 23. 879,r² = 0. 888,q² = 0. 554,r2derr = O. 20,q2derr = 0. 40, SEE= 0. 199,respectively. The results show that this model had a good predictive ability. Topomer search was employed to select in ZINC molecular database,as a results total of 7 new compounds with better activity than template molecules were designed. The interaction mode between the new compounds and the macromolecular protein lEEO was explored by Surflex-dock, the results showed that the ligand molecules acted obviously with B/ ARG274,B/ ARG312,B/ LYS67 and other sites of lEEO. [ABSTRACT FROM AUTHOR]

N6-methyladenosine is one of the most prevalent mRNA modification in eukaryotes. The regulation of this pervasive mark is a dynamic and reversible process. m6A RNA methylation is catalyzed by m6A writers, removed by m A erasers and recognized by m6A readers, thereby regulating multiple RNA processes including alternative splicing, nuclear export, degradation and translation. Accumulated evidence suggests that m6A modification plays a crucial role in the pathogenic mechanism and malignant progression in non-small cell lung cancer (NSCLC), including cell survival, proliferation, migration, invasion, tumor metastasis and drug resistance. Moreover, the expression of m6A and its related proteins are dysregulated in clinical samples and circulating tumor cells (CTCs) of lung cancer patients, indicating that m6A modification may serve as a novel potential biomarker for the diagnosis and prognosis of lung cancer. In this review, by summarizing a great number of recent reports related to m6A's function and its modulators, we aim to provide a new insight on the early diagnosis and drug development in NSCLC therapy. [ABSTRACT FROM AUTHOR]

Copyright of Mycosystema is the property of Mycosystema Editorial Board and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In December 2019, a pneumonia oiiLbreak caused by a human coronavirLis was reporLed in nhan (China). This virus was prcdicLed as a new coronavirus, named Lhc 2019 novel coronavims (2019-nCoV), as iL caused clinical svmpLoms diffcrenL from Severe AcliLc RcspiraLory Syndmmc (SAKS) during Lhe 2003 onLbrcak. CLirrenLlv, mosL of Lhc researchers simply use Lhc complcLe genome or specific sLiucLiiral gene sequences Lo invesLigaLc coronavirus (c. g. phylogcncLic analysis) wiLhonL considering Lhc fLine Lions of Lhc prod Lie Ls from coronavims genes. To overcome Lhis shorLcoming, vve proposed Lhc joinL analysis of Lhe molecular funcLion and phylogcnv, and applied iL in our previous sLiidv of genomes of Be Lac omna virus subgroup B (BB coronavirus). In Lhal sLiidv, wc identified a 22-bp complcmenLcd palindrome； from a highly conserved Coding Sequence； (CDS). BoLh Lhc 22-hp complcmenLcd palindrome (named Wankai complcmenLcd palindrome) and Lhc CDS (named Wankai CDS), cvoluLionarv conserved in BB coronavims genomes, were idenlificd as genomic feaLurcs associated Lo Lhc molecular funcLions of BB coronavirns. In Lhc presenL sLudv, we used these Lwo genomic feaLurcs Lo Lracc lhc origin of 2019-nCoV ((rcnBank； MW908947) and conducL a preliminary sLudv of Lhc mechanisms in Lhc cross-spf；cics infccLion and hosl adaplion of BB coronavims. Our analvLical resuks show LhaL 2019-nCoV wiLh large differences from lhc SAKS coronavirus, may originaLc from BB coronavimscs in baLs. Tli(; mosL imporlanL finding is LhaL Lhc alLcrnaLivc LranslaLion of Nankai CDS could produce more Lhan 17 puLaLivc prolcins, which may be responsible for Lhc hosL adaplion. The genoLvping of 13 viruses using Lhc 17 puLalivc pmLeins revealed Lhc high muLaLion rak; and diversiLy of BB coronavirus. Our sLudv, for Lhc firsL Lime, aimed Lo explain Lhc reason for Lhc high hosL adapLabiliLv of Lhc mulLi-hosL BB coronavims aL Lhc molecular level using large amounLs of genomic daLa. The findings in Lhc presenL sLudv laid fonndaLions for Lhc rapid dcLccLion, genoLvping, vaccine devclopmf；nL and drug design of, bul noL limiLed Lo BB coronavirus. [ABSTRACT FROM AUTHOR]

The 2019 novel Coronavirus (2019-nCoV) has caused Lhc pncLimonia oidbreak in Wuhan (a ciLy of China). In our previous sLiidv, Lhc analvLical rcsiilLs showed LhaL boLh 2019-nCoV and SAKS coronavirus belong Lo Be Lac omna virus subgroup B (BB coronavirus), bnL have large differences, which arc consisLenL wiLh Lhe differences in Lhc clinical svmpLoms of Lwo relaLed diseases. The mosL imporLanL finding was LhaL Lhc alLcrnaLivc LranslaLion of JNankai CDS could produce more Lhan 17 pnLaLive proLeins, which may be responsible for Lhe hosL adapLion. The genoLyping of 13 viruses using Lhc 17 piiLaLivc proLcins revealed Lhe high miiLaLion raLc and divci'siLy of BB corona virus. The presen L sLiidy for Lhc fit's L Lime (on January 21sL, 2020) reporLed a very imporLanL mnLaLion in Lhe Spike (S) proLcins of BcLacoronaviius. By Lhis miiLaLion, 2019-nCoV acquired a cleavage siLe for fiirin enzyme in iLs S pro Lein, which is noL prcscnL in Lhc S proLcins of mosL oLher Be Lac orona virus (c.g. SAKS coronavims). This cleavage siLe may increase Lhe efficiency of virus infee Lion inLo cells, making 2019-nCoV has significanLly sLmngcr LransmissibiliLy Lhan SAKS corona virus. The infccLion mechanism of 2019-nCoV may be changed Lo being more similar Lo Lhosc of M11V, 111V，Ebola vims (EBoV) and some avian inflLienza viruses, oLher Lhan Lhosc of mosL oLher BeLacoronavims (e. g. SAKS coronavims). In addiLion, we LinexpecLedly found LhaL some avian influenza viruses acquired a cleavage siLe for fiirin enzyme by Lhe similar miiLaLion as 2019-nCoV. Therefore，Lhc naLiiral mnLaLion can rcsulL in a shorL inserLion Lo form a cleavage siLe for furin enzyme. The cleavage siLe for furin enzyme in 2019-nCoV conLains Lhc "CGGCGG" sequence encoding Lvvo arginine (R) residues. "CGG"，however, is a rare codon for human. So we concluded LhaL Lhesc Lvvo codons were presenL in Lhc 2019-nCoV - like BeLacomnavirus before Lhev LransmiLLed inLo human and Lhe inLcrmcdiaLc hosL (s) arc mammals vviLh a high rclaLive frequency of "CGG" usage. We provide a relaLivc frequency Lablc of "CGG" usage in mammals Lo help idenLify Lhc inLcrmcdiaLc hosLs of 2019-nCoV. FnLnro sLiidics of Lhis mnLaLion will help Lo reveal Lhe sLronger LransmissibiliLy of 2019-nCoV and lay foundaLions for vaccine devclopmenL and drug design of, biiL noL limiLed Lo 2019-nCoV. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Central China Normal University is the property of Huazhong Normal University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Beijing University of Technology is the property of Journal of Beijing University of Technology, Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of China Surfactant Detergent & Cosmetics (1001-1803) is the property of China Surfactant Detergent & Cosmetics Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To perform the ligand-based computer-aided drug design and construct the pharmacophore model of (1.3)β-D-Glucan Synthase (GS) small molecule inhibitors. Method Six small molecules with diverse structures and good inhibitory activity were selected to construct the training set. The HipHop algorithm in Catalyst pharmacophore generation module was utilized to construct the pharmacophore models. The pharmacophore models were evaluated by constructed Decoy -set 3D database. Results Pharmacophore 02 has a good enrichment factor. sensitivity and specificity parameters. Pharmacophore model validation with Decoyset 3D database proved that the model has good distinguishing capability. Cjonclusion The pharmacophore model of GS small molecule inhibitors was constructed and tested. It will provide valuable information for design and discovery of novel small molecule GS inhibitors. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the rationality of prescriptions from outpatient and emergency departments in 6 hospitals, and promote clinical rational medication. METHODS: On basis of related regulations of “Management Practice of Hospital Prescription Review (on trial)”, stratified equal-ratio sampling method was adopted to extract prescriptions from outpatient and emergency departments in 6 hospitals in Luohe from Oct. 2014 to Sep. 2016, these prescriptions were then analyzed in terms of types of irrational prescriptions, involved clinical departments ol prescriptions with no diagnoses or incomplete diagnoses, distribution of clinical departments, etc. RESULTS: A total ol 169 508 prescriptions Irom inpatient and outpatient departments were extracted, with averagely 2. 89 kinds ol drugs in each prescription, the usage rates ol antibiotics, injection and national essential drugs had met the related criteria, the usage rate ol approved drug name was 100% , the average consumption sum ol each prescription was 1 12. 82 yuan. 3. 68% were irrational prescriptions (6244/169 508) , mainly included types ol non-standard prescriptions (commonly were no diagnoses or incomplete diagnoses) , inappropriate medication and supernormal prescriptions. The top 3 clinical departments ranked in the number ol prescriptions with no diagnoses or incomplete diagnoses were respectively internal medicine, surgery and pediatrics, the number ol prescriptions in the first three quartern were large, and then were gradually reducing. CONCLUSIONS: The inpatient and outpatient prescriptions in 6 hospitals in Luohe are basically rational, however, high attention still needs to be paid in the rational application ol antibiotics, glucocorticoid and other drugs, so as to continuously improved hospital rational medication. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the drug application of outpatient medical orders in reproductive medicine center ol department ol gynecology and obstetrics in the First Affiliated Hospital ol Anhui Medical University (hereinafter referred to as “ our hospital ”) , to discuss the rationality ol off-label medication and related countermeasures, so as lo provide references for clinical rational medication. METHODS: 77 776 outpatients medication orders in reproductive medicine center ol department ol gynecology and obstetrics in our hospital in 2016 were randomly extracted and retrospectively analyzed, oil-label medical orders therein were collected and analyzed on the basis ol dispensatory and relevant regulations in “Prescription Administrant Policy”, and the rationality ol ofl-label medication orders were discussed according to relevant rules ol diagnosis and treatment, clinical guidelines and consensus from specialists, evidence-based medicine or related literatures. RESULTS: Ol 77 776 medication orders, there were 33 239 oil-label medication orders (42.74%); types ol off-label medication orders mainly including overindication, overdose and (or) overlrequeney, oil-route ol administration and oil-contraindication, etc; there were 13 272 oil-label medication orders (39.93%) with application ol progesterone injection, mostly were overdose medication. CONCLUSIONS: Off-label medication in outpatient ol reproductive medicine center ol department ol gynecology and obstetrics is slightly prevalent in our hospital in 2016. According to instructions ol relevant drugs, previous research reports and consensus from related specialists, most off-label medications are basically rational, however, there is still a certain medication risk. Effective measures are suggested to be formulated to ensure clinical rational medication. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate I lie application status of traditional Chinese medicine and combination application with western Medicine in prescriptions from Xiamen the Second Hospital (hereinafter referred to as “our hospital”) , so as to provide reference for the rational drug application in clinic. METHODS: 13 704 prescriptions were extracted from Jul. to Nov. 2015 (except for traditional Chinese medicine) and 16 562 prescriptions were extracted from Jnl. to Nov. 2016 (except for traditional Chinese medicine) in hospital information system, totally 30 266 prescriptions were extracted. And the combination application ol traditional Chinese medicine with western medicine was analyzed. RESULTS: From Jul. to Nov. 2016, the Irequency ol application ol traditional Chinese medicine granules increased significantly compared with the corresponding period ol 2015, vet the Irequency ol application ol traditional Chinese medicine decoction pieces decreased. From Jul. to Nov. 2015, decoction pieces took the most proportion ol the top 10 traditional Chinese medicine ranked by Irequency ol application, yet the formula granules took the most proportion ol the top 10 traditional Chinese medicine ranked by Irequency ol application in the corresponding period ol 2016. The frequency ol application ol traditional Chinese medicine granules was in an increasing tendency, the combination application ol traditional Chinese medicine with western medicine was mainly concentrated on the drug combination ol traditional Chinese medicine granules with western medicine. CONCLUSIONS: The Irequency ol application ol traditional Chinese medicine granules is increasing, and the frequency ol application ol decoction pieces is decreasing. Most combination application ol traditional Chinese medicine with western medicine are rational, vet there are still some irrational drug combination. The clinicians should follow the principle ol traditional Chinese medicine syndrome differentiation and treatment, so as to promote rational drug application. [ABSTRACT FROM AUTHOR]

BJECTIVE; To compare the application of fructose injection in Hunan Cancer Hospital (hereinafter referred to as “our hospital”) before and alter intervention, so as to provide references for rational drug application. METHODS: Retrospective investigation was adopted to collect the total consumption amount ol fructose and the consumption amount in different clinical departments in our hospital in Jan.-Mar. in 2017 (before intervention) and Apr. -Jul. 2017 (alter intervention), each 100 medical records ol before and alter intervention were respectively extracted to be compared and analyzed in terms ol compatibility, indications, course ol treatment and daily consumption amount, etc. RESULTS: The monthly average consumption amount ol fructose injection in our hospital had decreased Irom (5 342 ±743) packages ol before intervention to (3 327 ±208) packages ol alter intervention, vet the difference had no statistical significance (P >0.05); the proportion ol fructose injection for solvent using had decreased from 74% ol before intervention to 26% ol alter intervention, with a decreasing amplitude ol 65%; the species number ol drugs compatible with fructose injection had decreased from 22 types ol before intervention to 13 types ol alter intervention, with a decreasing amplitude ol 41% ; alter intervention, the treatment course, average daily consumption amount and overindication application ol fructose injection had been significantly improved than those ol before intervention, with statistically significant difference^ P <0. 05). CONCLUSIONS: Intervening measures are practicable and effective in improving the rational application ol fructose injection in hospitals. [ABSTRACT FROM AUTHOR]

Research and development of investigational new drugs for nonalcoholic fatty liver disease is now a research hotspot in the field of liver disease. However, there are still great challenges in protocol design and implementation in phase II/III clinical trials. Since there are still controversies over the exact histological definition of nonalcoholic steatohepatitis in the academic world and a lack of long - term large-scale studies on the natural history and clinical pathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, we still face a lot of challenges in the selection and definition of study population, selection of study endpoints, and interpretation of true clinical value. In addition, such clinical trials often have various confounding factors, which should be controller! as much as possible in protocol design and implementation , in order to minimize the bias in research conclusions. [ABSTRACT FROM AUTHOR]

With the advances in medicine, people have deeply understood the complex pathogenesis of diseases. Revealing the mechanism of action and therapeutic effect of drugs from an overall perspective has become the top priority of drug design. However, the traditional drug design methods cannot meet the current needs. In recent years, with the rapid development of systems biology, a variety of new technologies including metabolomics, genomics, and proteomics have been used in drug research and development. As a bridge between traditional pharmaceutical theory and modern science, computer-aided drug design(CADD) can shorten the drug development cycle and improve the success rate of drug design. The application of systems biology and CADD provides a methodological basis and direction for revealing the mechanism and action of drugs from an overall perspective. This paper introduces the research and application of systems biology in CADD from different perspectives and proposes the development direction, providing reference for promoting the application.

As an important membrane protein receptor, G protein-coupled receptor （GPCR） was one of the most important targets in the development of new drugs. Previously, many drugs acting on GPCR were GPCR modulators. With the solution of membrane stability of GPCR, the development of GPCR structural biology and the application of a large number of new drug research methods, the development of new drugs was no longer just limited to traditional high-throughput screening methods. Both structure-based drug design （SBDD） and fragment-based drug discovery （FBDD） have developed rapidly in recent years. The most prominent applications were the screening and verification of novel ligands acting on the β-adrenergic receptor and the adenosine receptor. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the application status of antibiotics in inpatients with alcohol dependence from the Second Affiliated Hospital of Xinxiang Medical University (hereinafter referred to as “our hospital”) , so as to promote the rational application of antibiotics in clinic. METHODS: Medical records of 1 407 patients with alcohol dependence were retrospectively collected from Jan. 2015 to Jun. 2017, and statistical analysis was conducted on the application status of antibiotics in inpatients. RESULTS: Of the 1 407 patients, 216 patients used antibiotics, and the application rate was 15.35%. The application rate of antibiotics in patients complicated with delirium tremens or (and) epilepsy was significantly higher than that of patients without delirium tremens or (and) epilepsy. Of the 216 patients with antibiotics, 191 eases (88.43%) were therapeutic medication, 25 eases (11.57%) were preventive medication; 1 16 eases (53. 70%) were single medication, 99 eases (45. 83%) were double medication and 1 eases (0.46%) was three-drug medication. There were 35 eases had bacterial culture, with bacterial examination rate of 16.20%. CONCLUSIONS: There are still some irrational phenomenon in application of antibiotics in preventive medication and drug combination for inpatients with alcohol dependence, it is necessary to strengthen the train and management of application of antibiotics, so as to improve the level of rational drug application. [ABSTRACT FROM AUTHOR]

Self-assembly refers to the spontaneous process where basic units such as molecules and nanostructured materials form a stable and compact structure. Peptides can self-assemble by non-covalent driving forces to form various morphologies such as nanofibers, nano layered structures, and micelles. Peptide self-assembly technology has become a hot research topic in recent years due to the advantages of definite amino acid sequences, easy synthesis and design of peptides. It has been shown that the self-assembly design of certain peptide drugs or the use of self-assembled peptide materials as carriers for drug delivery can solve the problems such as short half-life, poor water solubility and poor penetration due to physiological barrier. This review summarizes the formation mechanism of self-assembled peptides, self-assembly morphology, influencing factors, self-assembly design methods and major applications in biomedical field, providing a reference for the efficient use of peptides.

Antimicrobial peptides (AMPs) are a class of peptides widely existing in nature with broad-spectrum antimicrobial activity. It is considered as a new alternative to traditional antibiotics because of its unique mechanism of antimicrobial activity. The development and application of natural AMPs are limited due to their drawbacks such as low antimicrobial activity and unstable metabolism. Therefore, the design and optimization of derived peptides based on natural antimicrobial peptides have become recent research hotspots. In this paper, we focus on ribosomal AMPs and summarize the design and optimization strategies of some related derived peptides, which include reasonable primary structure modification, cyclization strategy and computer-aided strategy. We expect to provide ideas for the design and optimization of antimicrobial peptides and the development of anti-infective drugs through analysis and summary in this paper.

Objective To optimize the optimal technology of Angelica dahurica by uniform design,in order to provide experimental basis for processing technology. Methods The U7(76) uniform design was adopted to investigate the softening temperature, softening time and vacuum time to determine the optimal processing technology of Angelica dahurica with the content of imperatorin(Ci6Hi404) as evaluation index. Results The optimal processing technology of Angelica dahurica was with softening temperature of 60 °C,softening time of 60 minutes,vacuum time of 4 minutes and cutting into slices with baking temperature of 60 °C. Conclusion Uniform design provides basis for processing technology of Angelica dahurica,and formulate normative processing technology and technical parameters. [ABSTRACT FROM AUTHOR]

Based on a data set of 143 5-HT6 antagonists, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried Out to aid in the design of 5-HT6 antagonists with potent activity to build 3-dimensional quantitative structure-activity relationship (3D-QSAR) models. The results show that both the optimal CoMFA (Q2 = 0.513, Rnev2 = 864, Rpre2 = 0. 731) and CoMSIA (Q2=0. 515, Rnev2=844, Rpre2 = 0. 777) models have good reliabilities and predictive abilities. Additionally, from the analysis of the contour maps, it can be concluded that bulky R2 substituent with/or without negatively charges, hydrophobic groups both in R3 and R1 substituent at the benzene ring, HB acceptor substituent in R2 and HB donor substituent in R3 will benefit the activity. All the conclusions can supply useful information for better understanding of the mechanism of 5-HT6 antagonism and are also helpful in providing new clues for drug design and synthesis. [ABSTRACT FROM AUTHOR]

Molecular docking plays an important role in computer-aided drug molecular optimal design. A knowledge scoring function for estimating the binding free energy by means of distances between atom pairs is introduced, whose formula is similar to that of potential of mean force (PMF). Based on the knowledge scoring function, and combining an improved multi-population adaptive genetic algorithm based on information entropy, a new docking program KGAsDock is developed. The comparing with famous docking program DOCK6. 1 is given, and the numerical results show that the method can improve the docking accuracy considerably without reducing computing efficiency. [ABSTRACT FROM AUTHOR]

Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.

The effective material basis of Chinese medicine is the key and difficult point in the quality control and modernization research of Chinese medicine. With the increasing application of pharmacophore-based virtual screening in computer-aided drug design, it is possible to employ this technology in the modernization of Chinese medicine. Based on the systematic research method of the pharmacophore model, the present study systematically reviewed the pharmacophore-based technologies and strategies in the identification of active components in Chinese medicine.

Currently available drugs for complex diseases have such limitations as unsatisfactory efficacy, drug resistance, and toxic side effects. Complexity of biological systems is a determinant of drug efficacy. It is not an effective approach to find disturbance strategies for the complicated biological network for complex diseases based on the static topological structures, as biological systems undergo dynamic changes all the time. Supported by profound theoretical basis and rich clinical experience, traditional Chinese medicine(TCM) emphasizes systematic and dynamic treatment depending on changes. Guided by TCM theory in practical treatment, Chinese medicine dynamically and comprehensively regulates the overall state. Therefore, if the dynamic factors are taken into consideration in design, the resultant drugs will be more effective. This study proposes state-regulating(SR) medicine from the perspective of system dynamics, elaborating the concept in terms of the connotations and principle and verifying the feasibility of SR medicine design with the attractor method. Thus, SR medicine is a new concept for drug discovery and design from the aspect of system dynamics, which integrates the TCM focusing on holistic dynamic regulation with biomedicine that features local microscopic research such as molecular mechanisms. The attractor method is a feasible techinical way for SR medicine design.

Cullin-RING E3 ligases (CRLs) are the major components of ubiquitin-proteasome system, responsible for ubiquitylation and subsequent degradation of thousands of cellular proteins. CRLs play vital roles in the regulation of multiple cellular processes, including cell cycle, cell apoptosis, DNA replication, signalling transduction among the others, and are frequently dysregulated in many human cancers. The discovery of specific neddylation inhibitors, represented by MLN4924, has validated CRLs as promising targets for anti-cancer therapies with a growing market. Recent studies have focused on the discovery of the CRLs inhibitors by a variety of approaches, including high through-put screen, virtual screen or structure-based drug design. The field is, however, still facing the major challenging, since CRLs are a large multi-unit protein family without typical active pockets to facilitate the drug design, and enzymatic activity is mainly dependent on undruggable protein-protein interactions and dynamic conformation changes. Up to now, most reported CRLs inhibitors are aiming at targeting the F-box family proteins (e.g., SKP2, β-TrCP and FBXW7), the substrate recognition subunit of SCF E3 ligases. Other studies reported few small molecule inhibitors targeting the UBE2M-DCN1 interaction, which specifically inhibits CRL3/CRL1 by blocking the cullin neddylation. On the other hand, several CRL activators have been reported, such as plant auxin and immunomodulatory imide drugs, thalidomide. Finally, proteolysis-targeting chimeras (PROTACs) has emerged as a new technology in the field of drug discovery, specifically targeting the undruggable protein-protein interaction. The technique connects the small molecule that selectively binds to a target protein to a CRL E3 via a chemical linker to trigger the degradation of target protein. The PROTAC has become a hotspot in the field of E3-ligase-based anti-cancer drug discovery.

According to drug design flattening principle and using podophyllotoxin or 4'-demethylepipodophyllotoxin and aldehydes as starting material,a series of podophyllotoxin derivatives containing an imine structure with low toxicity were highly effective synthesized. Nine target compounds were successfully synthesized,and their structures were confirmed by ~1H-NMR,HR-ESI-MS and melting point data analysis. Using etoposide as positive control drug,nine target compounds were screened for cytotoxicity against He La cells in vitro by MTT method. The antitumor activity screening results showed that compound 6 b,6 d,6 e,6 f,6 g,6 i exhibited higher inhibitory rate against He La cells than those of control drug VP-16. It provides some practical reference value for the further development on the structure modification of podophyllotoxin and study on anti-tumor activity.

To explore potent anticancer agent based on artemisinin scaffold, a series of 10- O -phenyl ethers derivatives containing dihydropyrazolyl or pyrazolyl moiety have been designed and synthesized. Their structures were determined by LC-MS and ¹H-NMR date. Inhibitory effects of the target compounds in human breast cancer MCF-7, MCF/Adr, MDA-MB-231 cells and prostate cell line PC-3 were determined by MTT assay. Those derivatives displayed good antiproliferative activity against the tested cancer cells. Particularly, target compounds exhibited significant cytotoxicity against drug-resistance cells MCF/Adr, which was worthy for further investigation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Telomere plays a crucial role in the physiological and pathological processes of cells. At the end of the telomere, the single-stranded DNA repeat sequence rich in guanine (G) folds in the presence of monovalent metal ions such as Na + or K + to form a G-quadruplex structure. This structure can not be extended by telomerase and inhibits the activity of telomerase, thus becoming a potential anticancer target. Stabilizing the formation of DNA G-quadruplex structures by small molecule ligands has become a new strategy for designing many anticancer drugs, and studying the interaction strength of these small molecule ligands with G-quadruplex is thus of particular importance for screening highly effective anticancer drugs. Single molecule force spectroscopy enables direct measurement of the interaction between small molecule ligands and G-quadruplexes. This review highlights the advances of single-molecule force spectroscopy based on atomic force microscopy in the study of the G quadruplex structure and its interaction with small molecule ligands, and summarizes the application and development trend of single molecule force spectrum technology in G quadruplex.

Based on the anticancer mechanism of biological alkylating agent, we designed and synthesized two alpha pinene derivatives:(1R,5S)-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)methyl benzenesulfonate and (1R,5S)-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)methyl 4-methylbenzenesulfonate, of which structures were confirmed by ¹H-NMR, HPLC and MS date. These two compounds showed a good inhibition of tumor cells' proliferation. Further, the computer siuulation of molecular docking and metabolic kinetics indicated that these two copounds may have stable molecular complexation with protein CDK2, which closely related to the cell cycle., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The pharmacological activities of natural glycosides are closely related to the polyfunctional sugar moieties. Modification of active natural products by glycosylation can change the stereochemical configuration, improve the solubility, tune up the activities and change pharmacokinetic properties for higher efficacy and better selectivity. Compared with the common D-glucose, D-allose, a C-3 epimer of D-glucose rarely exists in nature, but it plays an important role in food, health, medicine, and so on. It is not easily metabolized in the living organisms, but can be used as a safe and low-calorie sweetener. The natural allopyranosides are absolute conjugation forms which are same as other glucopyranosides and rhamnopyranosides with a broad array of biological activities. This article summarizes the major progresses made in phytochemistry and biological activity studies of these compounds. Structure-activity relationship analyses of partial anti-tumor and anti-diabetic allopyranosides were performed regarding the data reported in the literatures. These insights may provide a theoretical and experimental reference for the discovery of new drug and drug design based on allopyranosides.

This study was conducted to design and synthetize highly efficient, specific, non-resistant small MEK inhibitors. Based on active small molecules which have been reported, we studied the action mode with MEK protein using Autodock 4.2, generated innovative and feasible design method, designed novel small MEK protein inhibitors with a reference to molecular modeling and docking. The anti-tumor activities of four kinds of cells including MCF-7, PANC-1, SY5Y, A549 were tested with MTT method in vitro. The structure of 10 new small molecules has been determined with 1H NMR and 13C NMR. The compounds 4, 6, 7, 8, 10 had high antitumor activities, the compounds 1, 3, 5 also showed good activity, and the compounds 2, 9 showed cell selectivity in killing tumor.

In this study, 1-(3-(4-chlorophenyl)-5-methylthio-1H-1,2,4-triazol-1-yl)-butan-1-one discovered previously in our lab was selected as a inhibitor of human dihydroorotate dehydrogenase ( HsDHODH) for structural optimization. The co-crystal of HsDHODH with the hit was obtained and analyzed for guiding the subsequent structural optimization. As a result, a series of novel triazole derivatives were designed and synthesized as potent HsDHODH inhibitors. Among them, compound (3-(4-chlorophenyl)-5-ethylthio-1H- 1,2,4-triazol-1-yl)-furan-2-yl-methanone displayed high potency in the inhibition of HsDHODH with an IC50 value of 1.50 μmol·L−1. Meanwhile, the structure-activity relationships were analyzed based on the biological data and the co-crystal structure. These results provide a valuable reference for optimization of 1H-1,2,4- triazole derivatives as HsDHODH inhibitors in the future.

Twenty phenylpropenamide analogs with structural novelty were designed and synthesized upon pharmacophore-combination strategy. The structures of target compounds were elucidated by IR, 1H NMR, 13C NMR and MS, and all the target compounds were biologically evaluated for the inhibitory activities of platelet aggregation induced by adenosine diphoshate（ADP） and（AA） arachidonic acid via Bron method. As a result, compounds 6b, 9b, 9d and 9h demonstrated potent inhibitory activity against platelet aggregation induced by AA. Meanwhile, compounds 6b, 6d, 6j, 9b and 9g exhibited significant suppression of platelet aggregation induced by ADP.