Background An Increasing number of studies in the literature have shown that microRNAs (miRNAs) can be used as early diagnostic markers for esophageal carcinoma (EC), but their conclusions remain controversial. Hence, we performed this meta-analysis to evaluate the diagnostic accuracy of using miRNAs in EC and to provide an experimental basis for early diagnosis of the disease. Methods This meta-analysis included 39 Asian studies from 18 articles, which covered 3,708 EC patients and 2,689 healthy controls. We used a bivariate random-effects model, the chi-square test and the I 2 test to assess sensitivity and heterogeneity. Results Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of miRNAs for diagnosis of EC in Asians reached 0.798, 0.785, 3.705, 0.257 and 14.391, respectively. Additionally, the area under the summary receiver operating characteristic curve was 0.86. Subgroup analysis based on research country (China vs. Japan), sample types (plasma vs. serum) and miRNAs (single vs. multiple; singly reported miRNAs vs. repeatedly reported miRNAs) showed no significant difference in accuracy of diagnosis for each subgroup. Conclusions MiRNAs can distinguish EC patients from healthy controls. Blood-based miRNAs have better diagnostic value in detecting EC than saliva-based miRNAs, whereas both serum and plasma are recommended for clinical specimens for miRNA detection.
To investigate the remission rate of all-transretinoic acid (ATRA) combined with arsenics acid(ATO) on acute promyelocytic leukemia, and the efficacy and safety of sequential consolidation therapy with idarubicin, all-trans retinoic acid and arsenic trioxide/compound Huangdai tablet.Between January 2011 and January 2016 years 22 patients with newly diagnosed acute promyelocytic leukemia who received ATRA combined with ATO till complete remission in our hospital were retrospectively analyzed. Rates of CR, early mortality, complications and duration of induction were analyzed. The low/intermediate risk patients received 1-2 courses of idarubicin (IDA) single-agent chemotherapy, ATRA and compound Huangdai tablet /ATO alternative treatment of 4 cycles after complete remission; the high-risk patients received idarubicin and cytarabine chemotherapy, ATRA and compound Huangdai tablet /ATO alternative treatment of a total of 4 cycles for double-induction group.Double-induction achieved a 100% CR rates after 28.23±1.6 days induction. During induction, the infection rate was 50%, 36.4% of patients had differentiation syndrome and 27.3% suffered from bleeding in different locations. The 5-year overall survival was 100% and relapse-free survival was 95.4%.This protocol has a good antileukemic effect. The combination of ATRA and ATO achieves extremely high complete reminssion rate and reduces coagulopathy to cut down early mortality. Sequential therapy with IDA, ATRA, and ATO as a consolidation regimen results in satisfactory clinical outcomes with tolerable side effects.
Abstract Background: The role of the tumor microenvironment (TME) in fostering the development of malignancies is prompting the pursuit of anticancer therapies that target its components as to opposed to the tumor itself. As part of their immune surveillance duties, immune cells form part of this microenvironment, and yet, cancer cells have devised means to downplay their tumoricidal capabilities. Colony stimulating factor 1 receptor (CSF-1R) may offer such a means of controlling tumor associated macrophages in the tumor microenvironment. Methods: The IC50 of CBT-102 against CSF1R was evaluated in both cell free system and cell based assays, where enzyme activity was evaluated with radiometric assay format, and cell growth inhibition was evaluated in the Ba/F3 hCSF1R cell line by the CellTiter-Glo (CTG) method. Further evaluation of CBT-102 IC50 was undertaken in M-NFS-60 syngeneic cell lines and human monocytes. In vivo studies of CBT-102 in combination with anti-PD1 antibody were performed in H22 and MC38 syngeneic models. Results: CBT-102 demonstrated a reproducible activity against CSF1R in a radiometric enzyme activity assay. Using engineered BaF3 hCSF1R cell lines, we demonstrated the IC50 value of CBT-102 was 0.588 µM compared to 1.333 µM of sulfatinib, a similar multi-kinase inhibitor, and 0.279 µM of GW2580, a more specific CSF1R kinase inhibitor. Similar studies conducted in M-NFS-60 cell lines and human monocyte also showed sub-micromolar activities of CBT-102. In vivo study combining CBT-102 with anti-PD1 antibody in syngeneic models demonstrated a favorable combination effect compared to each of the single agents. Conclusions: We demonstrated previously that CBT-102 effectively inhibits VEGFR and angiogenesis. The newly revealed mechanism of CBT-102, inhibiting CSF1R and macrophages, offers a promising dual mechanism of action in addition to targeting VEGFR and angiogenesis. Rational combination with check-point inhibitors (CPIs) may improve the efficacy of CBT-102 and broaden the impact of CPIs. Further studies may be needed to delineate the interplay among CBT-102’s different mechanisms and its impact in combination with CPIs. Citation Format: Elaine Liu, Lan Yang, Gavin Choy, Xiaoling Zhang, Tillman Pearce, Mamatha Reddy, Sanjeev Redkar, Qian Shi. CBT-102, an oral small molecule multi-kinase inhibitor, demonstrates favorable CSF-1R activity, offering means of controlling tumor associated macrophages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2205.
with the advent of the era of knowledge economy, colleges and universities of human resources management is facing new challenges, only to constantly innovation,can improve their strength.This paper first introduces the background and necessity of the university human resources management mechanism innovation.Then, from recruitment configuration of human resource management, training development, performance management, etc to explore management mechanism innovation.
Oxidative stress and inflammation are key pathological features of atherosclerotic plaques. Numerous nanomedicines have been developed to alleviate oxidative stress and reduce inflammation within plaques. However, nonbioactive carrier materials reduce the bioavailability of nanomedicines and may pose potential biological toxicity. In this study, we utilized the unique amphiphilic chemical structure of lipoic acid (LA) to prepare LA nanoparticles (LA NPs) via a self-assembly method. Leveraging the inherent anti-inflammatory and antioxidant properties of LA, these NPs were used for the treatment of atherosclerosis. In an inflammatory macrophage model, LA NPs exhibited superior anti-inflammatory activity compared to free LA. Through ultrasound imaging and pathological methods, we discovered that LA NPs demonstrated nice antiatherosclerotic effects in an atherosclerotic mice model. Immunofluorescence analysis further indicated that the antiatherosclerotic effects of LA were associated with the alleviation of oxidative stress within the plaques, reduced macrophage infiltration, and downregulation of inflammatory cytokine levels. Therefore, LA NPs offer a promising therapeutic strategy for the treatment of atherosclerosis.
Gualou Guizhi decoction (GLGZD) is effective for the clinical treatment of limb spasms caused by ischemic stroke, but its underlying mechanism is unclear. Propidium iodide (PI) fluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), immunohistochemistry, western blot, and real-time qPCR were used to observe the axonal regeneration and neuroprotective effects of GLGZD aqueous extract on organotypic cortical slices exposed to oxygen-glucose deprivation (OGD) and further elucidate the potential mechanisms. Compared with the OGD group, the GLGZD aqueous extract decreased the red PI fluorescence intensity; inhibited neuronal apoptosis; improved the growth of slice axons; upregulated the protein expression of tau and growth-associated protein-43; and decreased protein and mRNA expression of neurite outgrowth inhibitor protein-A (Nogo-A), Nogo receptor 1 (NgR1), ras homolog gene family A (RhoA), rho-associated coiled-coil-containing protein kinase (ROCK), and phosphorylation of collapsin response mediator protein 2 (CRMP2). Our study found that GLGZD had a strong neuroprotective effect on brain slices after OGD injury. GLGZD plays a vital role in promoting axonal remodeling and functional remodeling, which may be related to regulation of the expression of Nogo-A and its receptor NgR1, near the injured axons, inhibition of the Rho-ROCK pathway, and reduction of CRMP2 phosphorylation.
AIM:To explore the oral health status of middle aged people in Gansu Province and get scientific information for the oral health prevention.METHODS:An equal-sized stratified multi-stage random sampling design was applied in the investigation.According to the standard and method used in the third national oral health epidemiologic investigation,the oral health investigation was made to 791 people aged from 35-44 in Gansu.RESULTS:The caries prevalence rate was 62.58%.There was no difference between urban and rural samples(P0.05).But the caries prevalence rate of femal was higher than male(P0.05).The mean dental crown caries was 1.89 and root caries was 1.01 respectively.The detection rates of gingival bleeding,dental calculus,periodontal pocket and periodontal attachment loss were 93.55%,99.37%,60.93% and 38.18% respectively.All the detection rates were higher than the results of the third national oral health epidemiologic investigation.The detection rate of diseases of oral macosa was 6.70%.The dentition defection rate was 36.41% and the repaired rate was 35.42%.The main denture-prosthesis was removable partial dentures and irregular fixed bridge.The rate of removable partial dentures was higher in female and rural than in male and urban.CONCLUSION: In general,the oral healthy status of middle aged people in Gansu province is not ideal.The prevalence of caries and periodontal disease is serious.It is essential to strengthen the oral health education and guide them to have good oral healthy habit and correct medical treatment behavior,so as to prevent oral diseases and improve their life quality.
Orphan nuclear receptors share sequence homology with members of the nuclear receptor superfamily, but ligands are unknown or unnecessary. A novel orphan receptor, estrogen receptor-related protein 3 (ERR3), was identified by yeast two-hybrid screening, using the transcriptional coactivator glucocorticoid receptor interacting protein 1 (GRIP1) as bait. The putative full-length mouse ERR3 contains 458 amino acids and is closely related to two known orphan receptors ERR1 and ERR2. All the ERR family members share an almost identical DNA-binding domain, which has 68% amino acid identity with that of estrogen receptor. ERR3 bound specifically to an estrogen response element and activated reporter genes controlled by estrogen response elements, both in yeast and in mammalian cells, in the absence of any added ligand. A conserved AF-2 activation domain located in the hormone-binding domain of ERR3 was primarily responsible for transcriptional activation. The ERR3 AF-2 domain bound GRIP1 in a ligand-independent manner both in vitro and in vivo, through the LXXLL motifs of GRIP1, and GRIP1 functioned as a transcriptional coactivator for ERR3 in both yeast and mammalian cells. Expression of ERR3 in adult mouse was restricted; highest expression was observed in heart, kidney, and brain. In the mouse embryo no expression was observed at day 7, and highest expression occurred around the 11-15 day stages. Although ERR3 is much more closely related to ERR2 than to ERR1, the expression pattern for ERR3 was similar to that of ERR1 and distinct from that for ERR2, suggesting a unique role for ERR3 in development.
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