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The present study aimed to explore the main active components and potential mechanisms of Panax notoginseng saponins(PNS) and osteopractic total flavone(OTF) in the treatment of osteoporosis(OP) through network pharmacology, molecular docking and in vitro cell experiments, which was expected to provide a theoretical basis for clinical applications. The blood-entering components of PNS and OTF were obtained from literature search and online database, and their potential targets were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The OP targets were obtained by means of searching Online Mendelian Inheritance in Man(OMIM) and GeneCards. The common targets of the drug and disease were screened by Venn. Cytoscape was used to construct a "drug-component-target-disease" network, and the core components were screened according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened according to the node degree. GO and KEGG enrichment analysis of potential therapeutic targets were carried out by R language. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock Vina. Finally, HIF-1 signaling pathway was selected for in vitro experimental verification according to the results of KEGG pathway analysis. Network pharmacology showed that there were 45 active components such as leachianone A, kurarinone, 20(R)-protopanaxatriol, 20(S)-protopanaxatriol, and kaempferol, and 103 therapeutic targets such as IL6, AKT1, TNF, VEGFA and MAPK3 involved. PI3K-AKT, HIF-1, TNF and other signaling pathways were enriched. Molecular docking revealed that the core components had good binding ability to the core targets. In vitro experiments found that PNS-OTF could up-regulate the mRNA expression levels of HIF-1α, VEGFA and Runx2, indicating that the mechanism of PNS-OTF in treating OP may be related to the activation of HIF-1 signaling pathway, and thus PNS-OTF played a role in promoting angiogenesis and osteogenic differentiation. In conclusion, this study predicted the core targets and pathways of PNS-OTF in treating OP based on network pharmacology and carried out in vitro experimental verification, which reflected the characteristics of multi-component, multi-target and multi-pathway synergy of PNS-OTF, and provided new ideas for the future clinical treatment of OP.
Subject(s)
Humans , Molecular Docking Simulation , Network Pharmacology , Osteogenesis , Phosphatidylinositol 3-Kinases , Osteoporosis , Databases, GeneticABSTRACT
OBJECTIVE@#To clarify the epidemiological characteristics and spatial distribution patterns of human norovirus outbreaks in China, identify high-risk areas, and provide guidance for epidemic prevention and control.@*METHODS@#This study analyzed 964 human norovirus outbreaks involving 50,548 cases in 26 provinces reported from 2012 to 2018. Epidemiological analysis and spatiotemporal scanning analysis were conducted to analyze the distribution of norovirus outbreaks in China.@*RESULTS@#The outbreaks showed typical seasonality, with more outbreaks in winter and fewer in summer, and the total number of infected cases increased over time. Schools, especially middle schools and primary schools, are the most common settings of norovirus outbreaks, with the major transmission route being life contact. More outbreaks occurred in southeast coastal areas in China and showed significant spatial aggregation. The highly clustered areas of norovirus outbreaks have expanded northeast over time.@*CONCLUSION@#By identifying the epidemiological characteristics and high-risk areas of norovirus outbreaks, this study provides important scientific support for the development of preventive and control measures for norovirus outbreaks, which is conducive to the administrative management of high-risk settings and reduction of disease burden in susceptible areas.
Subject(s)
Humans , Gastroenteritis/epidemiology , Norovirus , Caliciviridae Infections/epidemiology , Disease Outbreaks , China/epidemiology , GenotypeABSTRACT
Flood disaster is one of the most serious natural disasters in the world, and it could pose an inestimable impact on the affected people. Based on existing laws, regulations, and emergency manuals in China, extensive literature review, epidemiological and related protection evidence, and expert consultation, this study analyzed different health risk factors of flood disaster and proposed a multi-stage, multi-population, and multi-phase comprehensive protection measures for the public in the perspective of pre-event prevention, in-event intervention and post-event rescue strategy, which could provide a scientific basis for improving the level of public health protection against the flood disaster and corresponding health outcomes.
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To explore therapeutic effect of tirofiban‐assisted percutaneous coronary intervention (PCI) on patients with acute ST‐segment elevation myocardial infarction (STEMI) and its influence on serum levels of soluble stromelysin 2 (sST2) and pentraxin (PTX)‐3. Methods : A total of 146 STEMI patients treated in our hospital from 2014 to 2017 were randomly and equally divided into pure PCI group and combined treatment group (received tirofi‐ ban and PCI ) , both groups received aspirin and clopidogrel for 7d after PCI .After treatment , TIMI blood flow grade , serum levels of sST2 and PTX‐3 , LVEDd and LVEF and incidence of major adverse cardiovascular events (MACE) were observed and compared between two groups .Results : After treatment , percentage of TIMI＜grade 3 in combined treatment group was significantly lower than that of pure PCI group (13. 7% vs.34. 2%, P＝0.003 ?).Compared with pure PCI group , there was significant rise in LVEF [ (54.34 ± 6.57 )% vs.(61.42 ± 7.31)%] and significant reductions in LVEDd [ (49. 35 ± 3.13) mm vs.(43.54 ± 3. 44) mm] after six months , ser‐um levels of sST2 [ (57.42 ± 8.93) μg／L vs .(35. 22 ± 8. 53) μg／L] and PTX‐3 [ (0.64 ± 0.11) μg／L vs.(0. 43 ± 0.09) μg／L] after one month in combined treatment group , P＝0. 001 all.During six‐month follow‐up , total inci‐dence rate of MACE in combined treatment group was significantly lower than that of pure PCI group (2. 7% vs. 24.7%, P＝0. 001).Conclusion : Tirofiban‐assisted PCI is beneficial for improving cardiac function , reducing ser‐um sST2 and PTX‐3 levels and incidence rate of MACE in STEMI patients after PCI , which is worth extending .24
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@#【Objective】To investigate the lncRNA expression profile and potential roles in mouse intestinal mucosa after I/R treatment and explore the co-expression relationship between dysregulated lncRNA and apoptotic mRNA at the early stage of reperfusion. 【Methods】 The expression profiles of lncRNA were obtained using microarray and some lncRNA were further validated by quantitative real- time polymerase chain reaction （qRT- PCR）. Gene ontology（GO）analyses were performed to determine closely related biological functions，especially apoptosis-related functions. Finally， the known apoptosis- related mRNA with obviously changes were selected to construct the co-expression network of the dysregulated lncRNA and their correlated apoptotic mRNA， and were analyzed by CNC analysis to calculate the significant correlation of IncRNA-mRNA pairs.【Results】Compared with sham operation group，the expression profile of lncRNA in intestinal epithelium of mice after intestinal I/R was significantly changed ，including 1 503 up- regulated lncRNAs and 2 099 down- regulated lncRNA （Fold change≥2，P<0.05）. At the same time，1 528 mRNA were up- regulated in I/R group，while 1 630 mRNA were down- regulated（fold change≥2.0，P<0.05）. GO enrichment analysis showed that the main functions involved in regulation were lipid metabolism，redox reaction，stress reaction，apoptosis process，programmed cell death，cell cycle，inflammatory response，endothelial cell differentiation and proliferation， tissue remodeling，MAPK，Wnt，vascular endothelial growth factor signaling pathway and so on. Apoptosis-related subitems were enriched in the up- and down-regulated annotations of GO molecular function in different forms ，which were in the forefront. There was a significant co-expression relationship between apoptosis- related mRNA and dysregulated lncRNA. 【Conclusion】 In this study，we established and preliminarily validated the expression profiles of the differentially expressed lncRNA at the early stage of reperfusion in mouse intestinal ischemia injury. Bioinformatics analysis showed that the important biological function of dysregulated lncRNA was the regulation of apoptosis-related processes，and a large number of those lncRNA were indeed highly coexpressed with apoptotic genes ，which would provide a basis and direction for future research.
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AIM:To discuss Daidzein intravitreal injection whether has protective and recovery effects on acute nerve damages. METHODS:After the crush models of acute optic nerve were set up, 72 males SD rats were divided into 4 groups randomly as common group without surgery, FBS negative control group, Daidzein treatment group ( 10μmol/L, 100μmol/L, 1000μmol/L ) and positive control group using rats nerve growth factor ( mNGF, 100ng/mL ). Three days after interference, all experimental animals were executed. HE staining was used to evaluate morphologic change of the retina, immunohisochemical staining and western-blot tests for identifying and quantifying the distinct expression of Caspase-3 and GAP-43 among the groups. RESULTS: Compared with the normal group and negative control group, retinal morphology of different concentrations of each Daidzein treatment group and positive control group was more complete, the expression of Caspase-3 protein was relatively lower, the expression of GAP-43 protein was relatively higher, the differences have statistically significance (P<0. 05).CONCLUSION: Daizein injection in the vitreous cavity has the capacity of protection and restoration in rat's acute nerve damages.
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<p><b>OBJECTIVE</b>To investigate the clinical characteristics and prognostic factors of esophageal carcinosarcoma.</p><p><b>METHODS</b>The clinical data of patients treated by surgery and pathologically diagnosed as esophageal carcinosarcoma between January 1967 and December 2008 were retrospectively reviewed. There were 28 male and 4 female patients aged from 39 to 76 years with a median age of 58 years. All the data were analyzed using SPSS 15.0 software. The overall survival rates were calculated and compared with the Kaplan-Meier method and the Log-rank test. The prognostic factors were identified by Cox hazard regression model.</p><p><b>RESULTS</b>Among all the 32 patients included, 29 patients were polypoid type, 2 patients were fungoid type and 1 patient were medullary type. With regard to the depth of tumor infiltration, 17 patients involved the mucosa or submucosa (pT1), 13 patients involved the muscularis propria (pT2), 2 patients involved the adventitia (pT3). The involvement of local lymph nodes was present in 10 patients, with an incidence of 31.3%, including metastatic carcinoma alone in 7 patients and both carcinomatous and sarcomatous components in 3 patients. According to the most recently published international TNM staging system for esophageal carcinoma (AJCC 2009), 15 patients were in stage I, 13 patients in stage II, 4 patients in stage III. The 1-, 3- and 5-year overall survival rates of the whole group were 90.0%, 72.1% and 57.0%, respectively. Both in single-factor prognostic analysis and in Cox multivariate analysis, pathological N stage was the only prognostic factor (RR = 2.531, 95%CI: 1.055 - 6.070).</p><p><b>CONCLUSIONS</b>Esophageal carcinosarcoma is consisted of both sarcomatous component and carcinomatous component, while the latter one appears more frequently in local lymph node metastasis. In multivariate prognostic analysis, pathological N stage is the only independent prognostic factor. Curative resection of this tumor may achieve good prognosis because of its' lower incidence of lymph node metastasis and less invasive tendency.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Carcinosarcoma , General Surgery , Esophageal Neoplasms , General Surgery , Prognosis , Proportional Hazards Models , Retrospective StudiesABSTRACT
<p><b>OBJECTIVE</b>Since the principles of treatment of primary esophageal small cell carcinoma (PESCC) remain still in controversy, the aim of this study was to investigate the clinical characteristics, treatment modalities and prognostic factors of this malignancy.</p><p><b>METHODS</b>The clinical data of 109 patients treated by surgery in our hospital between October 1989 and April 2009 were retrospectively reviewed and analyzed. According to the most recently published TNM staging system for esophageal cancer (AJCC 2009), there were 17 patients in stage Ib, 31 patients in stage II, 59 patients in stage III, and 2 patients in stage IV. All the data were analyzed using SPSS 15.0 software. The median survival time (MST) and overall survival rate (OS) were calculated and compared by the Kaplan-Meier method and log-rank test. The prognostic factors were calculated by Cox hazard regression model.</p><p><b>RESULTS</b>Among all the 109 patients included, 93 patients were treated by radical esophagectomy, and 11 patients by palliative resection, while 5 patients by exploration. The median survival time (MST) of the whole group was 14.4 months and the 1-, 3- and 5-year overall survival rates (OS) were 56.9%, 17.6%, and 12.0%, respectively. The median survival time (MST) and 5-year overall survival rates (OS) were 18.5 months and 21.4% for pathological N0 cases, 23.5 months and 24.0% for N1 cases, 8.5 months and 0% for N2 cases, and 10.5 months and 0% for N3 cases, respectively (P < 0.001). The MST and 1-, 3- and 5-year OS of patients treated with postoperative chemotherapy were 17.0 months, 60.7%, 19.8%, and 13.0%, respectively, statistically significantly longer than the 7.0 months, 28.5%, 8.9% and 8.9%, respectively, of the patients without chemotherapy (P = 0.005). The pathological N stage and postoperative chemotherapy were independent prognostic factors by Cox multivariate analysis.</p><p><b>CONCLUSIONS</b>Primary esophageal small cell carcinoma is an aggressive systemic disease, characterized by early and wide dissemination of lymph nodes and poor prognosis while treated with surgery or chemotherapy alone. Multimodality treatment based on radical esophagectomy should be recommended for patients in pathological stage I and II.</p>