Study on spleen strengthening effects and mechanisms of Atractylodes chinensis and Atractylodes coreana / 中国药理学通报

Aim To analyze the differences in plasma biomarkers and metabolic pathways between Atractylodes chinensis and Atractylodes coreana after intervention in spleen deficiency rats, and discuss the spleen strengthening mechanism of the two from a non targeted metabolomics perspective. Methods A spleen deficiency model was established in SD rats using a composite factor method of improper diet, excessive fatigue, and bitter cold diarrhea. To determine the content of gastrointestinal and immunological indicators, UHPLC-QE-MS technology was used, combined with principal component analysis (PC A) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) methods to search for biomarkers in plasma of spleen deficiency rats, and metabolic pathways were induced using the Pathway database. Results After administration of Atractylodes chinensis and Atractylodes coreana, various indicators in plasma of spleen deficiency rats showed varying degrees of regression. Metabolomics analysis showed that Atractylodes chinensis and Atractylodes coreana respectively recalled 70 and 82 plasma differential metabolites. Atractylodes chinensis mainly regulated two metabolic pathways : "Glycine, serine, and threonine metabolism, and "Thiamine metabolism". Atractylodes coreana mainly regulated five metabolic pathways, "Glycine, serine, and threonine metabolism", "Thiamine metabolism, "Pyrimidine metabolism", "Butanoate metabolism", and "Riboflavin metabolism". Conclusions Both Atractylodes chinensis and Atractylodes coreana have certain regulatory effects on spleen deficiency rats, and their mechanism of action may be related to regulating metabolic pathways such as "Glycine, serine, and threonine metabolism, and "Thiamine metabolism"in spleen deficiency.

Mechanism study of neurofibromin 1 in gallbladder cancer / 中华消化外科杂志

Objective:To investigate the mechanism of neurofibromin 1 (NF1) in gallbla-dder cancer.Methods:The experimental study was conducted. Human gallbladder cancer cell lines, including GBC-SD, NOZ, SGC996, EH-GB1, ZJU0428, human embryonic kidneys cell line 293T and human cervical cancer cell line HELA, were cultured. The recombinant plasmids (mRFP-YAP1 FL-FLAG and eGFP-MYC-NF1 2650?2750-HA) were constructed for co-immunoprecipitation experiment. The truncated Yes associated protein 1(YAP1) and NF1 recombinant proteins were purified in vitro. The interaction between NF1 and YAP1 in vitro or in vivo were verified by isothermal titration calori-metry (ITC) assay, GST pull-down experiment, co-immunoprecipitation, immunofluorescence, laser confocal microscopy, and the expression of NF1 protein in different gallbladder cancer cell lines was verified by Western blot experiments. Observation indicators: (1) interaction between NF1 and YAP1 in vitro; (2) interaction between NF1 and YAP1 in cells; (3) expression of NF1 protein in different human gallbladder cancer cell lines. The dissociation constants were exported from ITC 200 software and represented as Mean± SD. Count data were represented as absolute numbers. Results:(1) Interaction between NF1 and YAP1 in vitro. ① Results of ITC assay showed that there was interac-tion between PPQY and YAP1-WW1, between PPQY and YAP1 (Amino acid residues 162?275), and the dissociation constants between PPQY and YAP1-WW1, between PPQY and YAP1(Amino acid residues 162?275) were (0.42±0.06)mmol/L, (0.69±0.14)mmol/L, respectively. ② GST pull-down results indicated that the target protein His-Sumo-YAP1 WW1 was obviouly observed in protein lane of reaction system between GST-PPQY recombinant protein and His-Sumo-YAP1 WW1, relative to the reaction system between GST protein and His-Sumo-YAP1 WW1. The target protein His-Sumo-YAP1 WW2 was obviouly observed in protein lane of reaction system between GST-PPQY recombinant protein and His-Sumo-YAP1 WW2, relative to the reaction system between GST protein and His-Sumo-YAP1 WW2. (2) Interaction between NF1 and YAP1 in cells. ① Co-immunoprecipitation results indica-ted that NF1 protein was observed in cell lysis solution which was incubated by FLAG gel beads and cotransfected with mRFP-YAP1 FL-FLAG and eGFP-MYC-NF1 2650?2750-HA. ② Immuno-fluorescence and laser confocal microscopy results indicated that YAP1 and NF1 with obvious fluorescence were co-localized in the cytoplasm of human gallbladder cancer NOZ cells. However, YAP1 with obvious fluorescence was localized in the nucleus of human gallbladder SGC996 cells and NF1 showed weak fluorescence. (3) Expression of NF1 protein in different human gallbladder cancer cell lines. Western blot results showed that with the expression level of NF1 protein in HELA cell line as the standard, the relative expression levels of NF1 protein in EH-GB1, GBC-SD, NOZ, SGC996, ZJU0428 cell lines were 1.28, 0, 1.01, 0, 0, respectively. Conclusion:NF1 affects the gallbladder cancer by directly acting on YAP1 protein.

Study on Potential Effective Components and Mechanism of Achyranthes bidentata in the Treatment of Osteoporosis Based on Network Pharmacology / 中国药房

OBJECTIVE： To investigate the potential effective components and mechanism of Achyranthes bidentata in the treatment of osteoporosis （OP）. METHODS： The effective components of A. bidentata were retrieved from the TCMSP database， and corresponding targets of them were collected. The targets related to OP were retrieved from DisGeNET database. TBtools 1.0 mapping software was used to draw the Wayne diagram， and screen the intersecting targets of effective components of A. bidentata and disease OP. Cytoscape 3.6.1 software and STRING database were used to construct and analyze the “drug-component- disease-target” network and protein-protein interaction （PPI） network； KEGG pathway enrichment analysis was conducted by using DAVID bioinformatics resource database. RESULTS： A total of 19 effective components were screened from A. bidentata， and there were 32 intersecting targets between effective components and disease OP. In “drug-component-disease-target” network， there were 45 nodes [1 for A. bidentata， 1 for OP， 11 for effective components （8 of the 19 effective components had no corresponding OP target）， 32 for intersecting targets] and 119 edges between nodes； quercetin， kaempferol， wogonin， baicalein and palmatine were important effective components. In PPI network， there were 31 nodes （1 of 32 intersecting targets was not associated with other proteins） and 212 edges， among which IL6， ESR1， MAPK1， IL8 and MAPK14 were the core targets of the network. There were 67 KEGG enrichment pathways， including rheumatoid arthritis， hepatitis B， Toll-like receptor signaling pathway， PI3K/Akt signaling pathway， JAK/STAT signaling pathway， NF-κB signaling pathway and so on. CONCLUSIONS： The main potential effective components of A. bidentata in the treatment of OP are quercetin， kaempferol， wogonin， baicalein and palmatine， the mechanism of which may be associated with cell differentiation and apoptosis， metabolism， inflammation reaction， etc. It     has multi-component， multi-target and multi-system chara- cteristics.

Advancement of Salvia miltiorrhiza on reversing tumor resistance and chemotherapy sensitization / 中国药理学通报

At present, chemoresistance is one of the leading causes of chemotherapy failure but there is no effective drugs or strategies to reverse the resistance of chemotherapy. In recent years, the anticancer effect of Salvia miltiorrhiza receives wide attention of researchers. The major bioactive constituents in Sal-via miltiorrhiza can be divided into two groups: liposoluble com-ponents ( tanshinoneⅠ, tanshinoneⅡA, dihydrometanoneⅠ and cryptotanshinone, etc. ) and hydrophilic components (salvianol-ic acid A, salvianolic acid B and protocatechualdehyde, etc. ). Recent studies have found that these components not only play different anti-tumor activities, but showed significant reversal re- sistance effects on drug-resistant tumor cells. Besides, with the combination of chemotherapy drugs, they have significant attenu-ated toxicity and synergistic effect. In this paper, we summarize the researches pertaining to the effects of Salvia Miltiorrhiza on the reversal of drug resistance and chemotherapy sensitization in recent years, providing references for the development of Salvia miltiorrhiza as multidrug resistance reversal agents and its ration-al application in clinic.

Advances of studies on effect of drug transporter under hypoxia / 中国药理学通报

Plateau environment has the characteristic of low ox-ygen and low pressure, which leads to a series of physiological changes and affects the process of drug metabolism in the body. Many factors affect the pharmacokinetic parameters, including gastric emptying, blood rheology, cardiopulmonary function, hepatorenal function, cytochrome P450 enzyme and so on. The present study focuses on drug metabolic enzymes, since drug transporter is the key factor that mediates drugs in their entrance to the body through the cell membrane, producing the curative effect. In order to provide the reference to further research on the effect of plateau hypoxia on pharmacokinetics and guide the rational use of drugs, we review in this paper the classification of the transporter, mediated drug substrates, the influence of hypoxia on expression levels of drug transporter substrates and the regulatory mechanism of drug transporter under the condition of hypoxia.

Research progress of reversion molecular targeted drug resistance in non-small cell lung cancer by curcumin / 中国药理学通报

In recent years,molecular biology has rapidly devel-oped,and molecular targeted therapy of non-small cell lung cancer has become a hot spot for the research. Although the tar-geted therapy has a big advantage compared with traditional chemotherapy,it is inevitable to encounter drug resistance in targeted therapy. Therefore,drug resistance has become the sig-nificant obstacle of targeted drugs for the treatment of non-small-cell lung cancer(NSCLC). Curcumin is the main extract of tu-meric rhizome,which harbours a wide range of antitumor activi-ties,and several studies have identified that curcumin exhibits reversion drug resistance against a variety of cancer cells. How-ever,there are few studies on curcumin reversion molecular tar-geted drug resistance. This review summarizes the recent pro-gress in resistance mechanism of targeted drug and the reversion resistance of curcumin.

The psychological mechanism of behavioral intervention and ripple effect in public health / 中华行为医学与脑科学杂志

The development of behavioral medicine is a new and efficient way to improve the level of national health and the behavior intervention is the core content.There are three methods including story-tellingmethod,behavior-image method and patient-centered assessment and counseling for exercise and nutri-tion intervention(PACE)which have been proven to be effective.The psychological theory of homophily,self-regulation and problem solving provide a scientific explanation for the effectiveness of these three kinds of be-havior intervention.Ripple effect amplifies the effect of behavioral intervention and its psychological mecha-nism is self-determinism and self-regulation theory.In the future,the research of behavior intervention and its psychological mechanism needs to make new breakthroughs in aspects of theory,method and technology.

Research progress on role of Wnt signaling pathway in regulation of tumors / 中国药理学通报

Wnt signaling pathway is a highly conservative signal pathway controlling cell growth,differentiation,apoptosis and self-renewal.This signal pathway is often abnormally activated in tumor development and progression,which can cooperate or antagonize with other signal pathways to regulate tumor prolifera-tion,migration and invasion.This paper makes a review of the recent research of Wnt signaling pathway progression and its function in tumor growth regulation.

Overviews and analysis of the U.S. FDA′s new approvals in the 2016 second half year / 国际药学研究杂志

In the second half of 2016,the U.S. Food and Drug Administration(FDA)approved 7 new molecular entities and 3 new Biologic License Application(BLA), the lowest number in recent years. According to the prescription information for profes-sionals,this article introduced the description,mechanism of action and clinical studies and briefly describes the boxed warning,indi-cations and usage,dosage and administration,dosage form and strength,contraindications,warning and precautions,adverse reac-tions,drug interaction and the use in the special population. In addition,the first and critical events in the history of new drug develop-ment and reaserch were emphasized.

Ethical Dilemma and Countermeasure of the Vagrant Mental Patients / 中国医学伦理学

Through investigating the hospital admission and hospital discharge of vagrant mental patients in Xi-aoshan Hospital from January 2011 to December 2015 , the present study found that there existed some ethical di-lemmas including the risk ofdiagnosing mental disorder but actually not, lack of the guarantee of patients' rights and interests and supervision mechanism without guardian, long-term retention in the wards, and so on. It is sug-gested to establish right protection and supervision committee for vagrant mental patients, reduce the misdiagnosis ofdiagnosing mental disorder but actually not through the error correction mechanism, ensure proper treatment and care, create retention way, protect the basic rights of the vagrant mental patients, reduce mental disability, avoid to stray again, so as to perfect the social management system.

Overviews and analysis of the U.S. FDA′s new approvals in the first half year of 2016 / 国际药学研究杂志

In the first half year of 2016,the U.S. food and drug administration(FDA)approved 9 new molecular entities and 8 new biologic license applications. According to the prescription information for professionals,this article introduces the description, mechanism of action and clinical studies;briefly describes the box warning,indications and usage,dosage and administration,dos?age form and strength,contraindications,warning and precautions,adverse reactions,drug interaction and use in special population of these new drugs. In addition,the first and critical events in the history of new drug development and reaserch are emphasized.

New drugs approved by the U.S. FDA(2007-2016):a review / 国际药学研究杂志

The introductions of the new drugs approved by the U.S. FDA have been published in the“Journal of International Pharmaceutical Research”for ten years. However,new problems might emerge with the increasing clinical practice and the cumulative number of patients being treated,such as the indications and purposes change,supplement of the modified efficacy,clinical data and the important new indications,constant improvement of the dosage,form and mode of administration,and the emergence of new,seri?ous and even fatal adverse reactions urge the supplements of contraindications,warnings and precautions,or even the black box warn?ings. In brief,6 entries of the introductions all may be modified,supplemented or canceled. More importantly,ten years of general analyses also find some prominent events,such as the amount of new molecular entity(NME)and new biological products come to an obvious peak in 2015. With regard to this,this paper reviewed the prominent historical events happened in the ten years in order to provide guidance and reference for new drug research and development.

Overviews and analysis of the U.S. FDA′s new approvals in the 2015 second half year / 国际药学研究杂志

In the second half year of 2015,the U.S. Food and Drug Administration(FDA)approved 20 new molecular enti?ties single or compounds and 15 biologics license applications,a total of 35 which record number of approved innovative drugs. Ac?cording to the prescription information for professionals,this article briefly describes the description,mechanism of action and clinical studies,the box warning,indications and usage,dosage and administration,dosage form and strength,contraindications,warning and precautions,adverse reactions,drug interaction and use in special population of these new drugs. In addition,the first and criti?cal events in the history of new drug development and reaserch are emphasized.

A metabolomics study on Shen-Mai decoction’ s protection of myocardial injured rats / 中国药理学通报

Aim With metabolomics method, to study Shen-Mai decoction’ s function on protecting the myo-cardial injured rats caused by doxorubicin for probing into the functioning mechanism of Shen-Mai decoction’ s medical effect. Methods By means of UPLC-TOF-MS, the metabolites of urine of the rats treated by Shen-Mai decoction were analyzed. Then, the differ-ences between each group of the metabolites were sought with PLS-DA ( the partial least square discrimi-nant analysis ) and OPLS-DA ( the orthogonal partial least squares discriminant analysis ) . VIP ( variable importance in projection ) and t test were used to screen out potential biomarkers. Results Fourteen endogenous metabolites such as succinyladenosine, a-denosine 2′, 3′-cyclic phosphate, S-( 3-methylbu-tanoyl )-dihydrolipoamide-E, cis-4-hydroxycyclohexy-lacetic acid, phenylbutyrylglutamine, 3-butyn-1-al, 3-hydroxytetradecanedioic acid, dihydrolipoamide and pyruvic acid, etc. were characterized. Conclusions The results indicate that Shen-Mai decoction can pro-tect the body from myocardial injury by regulating pu-rine metabolism, some acid metabolism, fat metabo-lism and energy metabolism, etc. The study expounds the functioning mechanism for Shen-Mai decoction ’ s medical effect in the body and provides theoretical grounds for the rationality of the two medical herbs ’ compatibility and their combination in clinical treat-ment of diseases.

Overviews and analysis of the U.S. FDA’s new approvals in first half year of 2015 / 国际药学研究杂志

In the first half year of 2015, the U.S. Food and Drug Administration (FDA) approved 11 new molecular entities and 5 new biologic license applications. According to the prescription information for professionals, this article introduces the description, mechanism of action and clinical studies; briefly describes the box warning, indications and usage, dosage and administration, dosage form and strength, contraindications, warning and precautions, adverse reactions, drug interaction and use in special population of these new drugs. In addition, the first and critical events in the history of new drug reaserch and development are emphasized.

Inhibitory effect of isobavachalcone on migration and invasion of Tca8113 cells and its mechanism / 中国药理学通报

Aim To explore the inhibitory effect of isobavachalcone (IBC)on migration and invasion of tongue squamous cell carcinoma Tca81 1 3 cells and its possible mechanism.Methods Tca81 1 3 cells were treated in different concentrations of IBC in vitro.Cell proliferation was detected by MTT;Wound healing as-say and Transwell chamber assay were used to detect the ability of cell migration and invasion;Western blot was applied to detect the expression of Akt,p-Akt, MMP-2 and MMP-9 proteins.Results IBC could in-hibit the proliferation of Tca81 1 3 cells in a concentra-tion-and time-dependent manner.IBC can reduce cell migration and invasion.Western blot showed that IBC could an decrease the expression of p-Akt,MMP-2 and MMP-9 proteins in a concentration-dependent manner. However,the level of Akt was not affected by the con-centration of IBC treatment.Conclusion IBC could inhibit the proliferation, migration and invasion in Tca81 1 3 cells and its mechanism may be associated with the down-regulation of MMP-2 and MMP-9 pro-teins and the inhibition of phosphorylation of upstream Akt.

Overviews and analysis of the U.S. FDA′s new approvals in first half year of 2015 / 国际药学研究杂志

In the first half year of 2015, the U.S. Food and Drug Administration(FDA) approved 11 new molecular entities and 5 new biologic license applications. According to the prescription information for professionals, this article introduces the description, mechanism of action and clinical studies; briefly describes the box warning, indications and usage, dosage and administration, dosage form and strength, contraindications, warning and precautions, adverse reactions, drug interaction and use in special population of these new drugs. In addition, the first and critical events in the history of new drug reaserch and development are emphasized.

Advances in research on molecular mechanisms for the proliferation of pulmonary artery smooth muscle cells and their intervention / 西安交通大学学报(医学版)

Pulmonary artery hypertension (PAH)is a common clinical syndrome.The over-proliferation of pulmonary arterial smooth muscle cells (PASMCs)is a hallmark of pulmonary vascular remodeling which is a critical and fundamental pathogenesis in the development of a variety of pulmonary artery hypertension.Here,we review the advances in studies on signaling transduction pathways mediating the proliferation of PASMCs and also introduce the existing approaches in inhibiting their proliferation and relevant research advances.

Analysis on guarantee mechanisms related to the improvement of community health service modes / 中国卫生政策研究

Objective:To analyze the concerning guarantee mechanisms during the transformation of the com-munity health service mode. Method:Purposive sampling was adopted. Twelve community health service centers in Beijing, Shanghai, Zhengzhou, and Chengdu, where the transformation of the community health service mode was pi-loted earlier and representative, were selected as the field survey sites. The qualitative method was used to collect da-ta accompanied by the quantitative method. Results: The guarantee mechanisms related to the transformation of the community health service mode could be concluded into four main types:collaboration mechanism, health profession-al training mechanism, incentive mechanism, and policy guarantee mechanism. All of the four mechanisms contribu-ted to the improvement of general teamwork, dual referral systems, and the development of contract and appointment services. Conclusion:During the transformation of the community health service mode, priority strategies include top-down design, health professional training mechanisms, and performance-based incentive mechanism, all of which should be implemented in the future.