Network pharmacology and molecular docking analysis reveal insights into the molecular mechanism of Gualou Qumai Wan in clear cell renal cell carcinoma

Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.

A new charging scheme in an emergency department observation unit under Beijing＇s basic medical insurance

Background The new medical insurance policy （JRSYF（2010） No.255） was released by the Beijing Municipal Government and became effective on January 1,2011.Medical expenses incurred during a stay in an emergency department （ED） observation unit can be reimbursed as a hospital admission.The aim of this study was to evaluate the impact of a new charging scheme during stays in ED observation unit under Beijing＇s Basic Medical Insurance.Methods Data for those patients who had stayed in ED observation unit in 2010 （before the implementation of a new charging scheme） and 2012 （after the implementation of this policy） were retrospectively analyzed in terms of length of stay,patients who were observed （PO）,and median medical costs.Results After the implementation of a new charging scheme,compared with the year of 2010,in year of 2012,there were statistically significant longer lengths of stay at the observation unit （6 （4-9） vs.5 （4-7） days; P〈0.001）,more PO （2 257vs.1 783; P〈0.001）,and more median medical costs （RMB 6 026 vs.3 650 Yuan; P〈0.01）.The proportion of elderly patients （≥60 years of age） in 2012 was larger than that in 2010 （70.22% vs.63.71%; P〈0.01）.It was performed on those patients who were admired after the implementation of a new charging scheme.Compared with patients who were not admired had stayed in ED observation units,the patients who were admired had stayed in ED observation units that had a higher proportion for 〉15 days （36.22% vs.5.61%; P〈0.01）; they had higher median medical costs RMB （9 186 vs.5 668Yuan; P〈0.001） and they were more elderly （≥60 years of age） （86.10% vs.66.39%; P〈0.01）.Conclusions The new charging scheme under Beijing＇s Basic Medical Insurance allows patients to get access to inpatient admission more easily.It lowers patients＇ financial burden in ED observation unit.Since more people stay at ED observation unit,it increases ED payments by the insurance system.However,it slows the turnover rate of ED observation unit and causes overcrowding in ED.Hence,the advantages and disadvantages of the new policy are obvious.

Effect of G-CSF and TPO on HIBD in neonatal rats

Objective:To observe effect of granulocyte colony-stimulating factor(G-CSF) and restructure human thrombopoietin on hypoxic-ischemic brain damage(HIBD) in new born rats.Methods:A total of 60 neonatal SD rats were selected and divided into 4 groups,with 15 in each group.Group A served as control group.Rats of Groups B-D were prepared for HIBD model by ligation of left common carotid artery combined with hypoxia method.Rats of Group A were only completed with free left common carotid artery without ligation and hypoxia operation.After HIBD model preparation,Group B was administrated with subcutaneous injection of normal saline for placebo treatment;Group C was administrated with cervical subcutaneous injection of 0.5 μg/10 g granulocyte colony stimulating factor(G-CSF) for 5 d(Once a day);Group D was administrated with intraperitoneal injection of 15 U/10 g recombinant human thromobopoietin(rhTPO) for treatment.After modeling for 7,14 and 21 d,5 rate were sacrificed in each group,respectively.Brain quality damage(%) conditions of experimental animals in each group were compared in different time points,and cerebral histopathological changes of each group were observed.Expression of nestin in rats of each group was detected by immunohistochemical method.Results:After modeling for 7,14 and 21 d,brain quality damages(%) of Groups B,C and D were significant higher than that of in Group A(P<0.05),while brain quality damage(%) degree of Group B was the highest in different time points,followed by Groups D and C,respectively.It was significant different compared among groups(P<0.05).The histopathological observation showed that degrees of brain damages in Groups C and D were significant lower than that of in Group B.After modeling for 7,14 and 21 d,nestin positive cell populations in Groups B,C,and D were significant higher than Group A(P<0.05).Nestin cell populations of Group C in different time points were significant higher than Groups B and D(P<0.05).There was no significant difference in nestin positive cell papulations,in the above time points between Groups B and D(P>0.05).Conclusions:Both G-CSF and TPO can protect the nervous system of HIBD neonatal rats.G-CSF can promote the proliferation and differentiation of neural precursor cells to decrease the degeneration and necrosis of nerve cell.TPO can obviously ameliorate morphology index of HIBD rats.Through regulating ratio of TIMP-1 and MMP-9,TPO can maintain the integrity of blood brain barrier to relieve the occurrence of brain damage.

Long noncoding RNA PPP1R14B-AS1 imitates microRNA-134-3p to facilitate breast cancer progression by upregulating LIM and SH3 protein 1

Long noncoding RNA PPP1R14B antisense RNA 1(PPP1R14B-AS1)has emerged as a critical modulator of liver cancer and lung adenocarcinoma progression.However,the functional importance and biological relevance of PPP1R14B-AS1 in breast cancer remain unclear.Therefore,this study was designed to detect PPP1R14B-AS1 levels in breast cancer cells using qRT–PCR and elucidate the influence of PPP1R14B-AS1 on aggressive phenotypes.Furthermore,molecular events mediating the action of PPP1R14B-AS1 were characterized in detail.Functional experiments addressed the impacts of PPP1R14B-AS1 knockdown on breast cancer cells.In this study,PPP1R14B-AS1 was found to be overexpressed in breast cancer,exhibiting a close correlation with poor patient prognosis.Results also showed that breast cancer cell proliferation and motility were suppressed when PPP1R14B-AS1 was silenced.Mechanistically,PPP1R14B-AS1 acted as a competing endogenous RNA for microRNA-134-3p(miR-134-3p)in breast cancer cells.PPP1R14B-AS1 also increased LIM and SH3 protein 1(LASP1)levels by imitating miR-134-3p in breast cancer cells.Rescue experiments further corroborated that the knockdown of miR-134-3p or an increase in LASP1 restored the aggressive malignant characteristics of breast cancer cells that were weakened by PPP1R14B-AS1 depletion.In summary,PPP1R14B-AS1 facilitated the oncogenicity of breast cancer cells by controlling the miR-134-3p/LASP1 axis.We believe that ourfindings may contribute to the development of precision therapy techniques in thefield of breast cancer treatment.

Long noncoding RNA CCDC183-AS1 depletion represses breast cancer cell proliferation, colony formation, and motility by sponging microRNA-3918

Many studies have illustrated the significance of long noncoding RNAs in oncogenesis and promotion of breast cancer(BC).However,the biological roles of CCDC183 antisense RNA 1(CCDC183-AS1)in BC have rarely been characterized.Thus,we explored whether CCDC183-AS1 is involved in the malignancy of BC and elucidated the possible underlying mechanisms.Our data confirmed elevated CCDC183-AS1 expression in BC,which was associated with poor clinical outcomes.Functionally,knocking down CCDC183-AS1 hampered cell proliferation,colony formation,migration,and invasion in BC.Additionally,the absence of CCDC183-AS1 restrained tumor growth in vivo.Mechanistically,CCDC183-AS1 executed as a competitive endogenous RNA in BC cells by decoying microRNA-3918(miR-3918)and consequently overexpressing fibroblast growth factor receptor 1(FGFR1).Furthermore,functional rescue experiments confirmed that inactivation of the miR-3918/FGFR1 regulatory axis by inhibiting miR-3918 or increasing FGFR1 expression could abrogate the CCDC183-AS1 ablation-mediated repressive effects in BC cells.In summary,CCDC183-AS1 deteriorates the malignancy of BC cells by controlling miR-3918/FGFR1 regulatory axis.We believe that our study can deepen our understanding of BC etiology and contribute to an improvement in treatment choices.

Long noncoding RNA LINC02568 sequesters microRNA-874-3p to facilitate malignancy in breast cancer cells via cyclin E1 overexpression

Increasing numbers of long noncoding RNAs(lncRNAs)are implicated in breast cancer oncogenicity.However,the contribution of LINC02568 toward breast cancer progression remains unclear and requires further investigation.Herein,we evaluated LINC02568 expression in breast cancer and clarified its effect on disease malignancy.We also investigated the mechanisms underlying the pro-oncogenic role of LINC02568.Consequently,LINC02568 was upregulated in breast cancer samples,with a notable association with worse overall survival.Functionally,depleted LINC02568 suppressed cell proliferation,colony formation,and metastasis,whereas LINC02568 overexpression exerted the opposite effects.Our mechanistic investigations suggested that LINC02568 was physically bound to and sequestered microRNA-874-3p(miR-874-3p).Furthermore,miR-874-3p mediated suppressive effects in breast cancer cells by targeting cyclin E1(CCNE1).LINC02568 positively controlled CCNE1 expression by sequestering miR-874-3p.Rescue experiments revealed that increased miR-874-3p or decreased CCNE1 expression recovered cell growth and motility functions induced by LINC02568 in breast cancer cells.In conclusion,the tumor-promoting functions of LINC02568 in breast cancer cells were enhanced by sequestering miR-874-3p and consequently over-expressing CCNE1.Our data may facilitate the identification of novel therapeutic targets in clinical settings.

Influence of clinical pathways used the hospitals of Traditional Chinese Medicine on patients hospitalized with stroke:a systematic review and Meta-analysis

OBJECTIVE:To evaluate the influence of clinical pathways in the hospitals using the Traditional Chinese Medicine in treatment of stroke in terms of postoperative complications, length of stay(LOS),costs incurred during hospitalization, compared with standard medical care.METHODS:Medline, Embase, China National Knowledge Infrastructure(CNKI) platforms, Wanfang databases and the Cochrane Central Register of Controlled Trials were searched.The search was performed up to August 2014.Each study was assessed independently by two reviewers.The assessment of methodological quality of the included studies was based on the Methodological index for non-randomized studies standard.Meta-analyses were performed using Rev Man software, version5.0.RESULTS:Six studies met the study inclusion criteria and were included in the Meta-analysis for a total sample of 710 patients.The aggregate overall results showed that shorter length of stay in the clinical pathway group was observed during hospital stay was associated with the use of the clinical pathways.No significant differences were found in other effects.CONCLUSION:Regardless the possible limitations,our findings show that clinical pathways can significantly reduce LOS.Although there is no clear evidence that clinical pathways can reduce hospital costs, but the cost of hospitalization path group for each included study were lower than the control group.