ABSTRACT
The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.
ABSTRACT
Objective@#To evaluate the effect of vaccine and provide scientific evidence for prevention and control of influenza virus, this study aims to analyze the characteristics of genomic variation of influenza A (H1N1) pdm09 viruses in Inner Mongolia.@*Methods@#The 16 viral strains were selected randomly according to the influenza A (H1N1) pdm09 viruses isolated from network laboratories in Inner Mongolia, 2013-2017. The hemagglutinin(HA) and neuraminidase(NA) genomic sequences were obtained by using RT-PCR and sequencing, and genomic characteristics were analyzed via bioinformatics.@*Results@#Compared to the A/California/07/2009 vaccine strain, the relatively obvious variation of antigen of influenza A (H1N1) pdm09 viruses in Inner Mongolia since 2014, and the vaccine provided a poor protection to influenza A (H1N1) pdm09 virus infection, while the A/Michigan/45/2015 vaccine strain recommended by WHO recently has a satisfactory protective effects. Several viral isolates from Inner Mongolia increased the binding force of virus in human upper respiratory tract because of D222N and D222G substitution within HA. E119K and H275Y substitution within NA gene of viral strains, suggesting that the viruses were resistant to NA inhibitors.@*Conclusions@#The influenza A (H1N1) pdm09 viruses had gradual variations as time went on, and the WHO recommended vaccine was relatively lagging. Virulent strains and drug-resistant strains appeared in the population, and the genetic characteristics of influenza virus surveillance should be strengthened to find the new mutants of virus in time, which provide evidence for the prevention and control of influenza.
ABSTRACT
<p><b>OBJECTIVE</b>The aim of this study was to determine the repeatability and reproducibility of optical coherence tomography angiography (OCTA) based on optical microangiography (OMAG) measurements of macular vessels in normal eyes.</p><p><b>METHODS</b>In this prospective cohort study, 40 eyes of 40 healthy volunteers underwent repeated OCTA (Cirrus HD-OCT 5000 angiography system, Carl Zeiss Meditec, Inc.) scans on two separate visit days. On each visit day, the eyes were scanned three times. The following parameters were used to quantitatively describe the OCTA images of the superficial vascular network: vessel area density (VAD), vessel skeleton density (VSD), vessel diameter index (VDI), vessel perimeter index (VPI), vessel complexity index (VCI), flux, and foveal avascular zone (FAZ). Coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for evaluating intravisit and intervisit repeatability, as well as interobserver reproducibility.</p><p><b>RESULTS</b>The measurements showed high repeatability [CVs ⪕ 4.2% (intravisit) and ⪕ 4.6% (intervisit)] and interobserver reproducibility (ICCs ⪖ 0.923) for all parameters.</p><p><b>CONCLUSION</b>This study demonstrated good repeatability and reproducibility of OCTA based on OMAG for the measurement of superficial vessel parameters in normal eyes.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Cohort Studies , Evaluation Studies as Topic , Fluorescein Angiography , Reference Standards , Healthy Volunteers , Image Processing, Computer-Assisted , Microvessels , Diagnostic Imaging , Prospective Studies , Reproducibility of Results , Retina , Diagnostic Imaging , Retinal Vessels , Diagnostic Imaging , Tomography, Optical Coherence , Reference StandardsABSTRACT
Many studies have reported the relationship between CXCL12 G801A polymorphism and cancer risk, with conflicting results. In this study, we tried to clarify the possibility that this polymorphism may increase cancer risk by conducting an updated meta-analysis. PubMed and EMbase were searched for case-control studies regarding the association of the gene polymorphism and cancer risk. Data were extracted and odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of the association. Heterogeneity among articles and publication bias was also assessed. Significantly increased risk for cancer was found (A vs. G: OR=1.26, 95% CI=1.13-1.40, P<0.01; AA+AG vs. GG: OR=1.33, 95% CI=1.16-1.52, P<0.01). In subgroup analysis, statistically elevated cancer risk was found in both Asian and Caucasian populations (for Asian, AA+AG vs. GG: OR=1.74, 95% CI=1.22-2.47, P<0.01; for Caucasian, AA+AG vs. GG: OR=1.24, 95% CI=1.09-1.42, P<0.01). Our result indicated that CXCL12 G801A polymorphism is a risk factor for cancer. To validate the finding, further large-size case-control studies are warranted.
ABSTRACT
Many studies have reported the relationship between CXCL12 G801A polymorphism and cancer risk, with conflicting results. In this study, we tried to clarify the possibility that this polymorphism may increase cancer risk by conducting an updated meta-analysis. PubMed and EMbase were searched for case-control studies regarding the association of the gene polymorphism and cancer risk. Data were extracted and odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of the association. Heterogeneity among articles and publication bias was also assessed. Significantly increased risk for cancer was found (A vs. G: OR=1.26, 95% CI=1.13-1.40, P<0.01; AA+AG vs. GG: OR=1.33, 95% CI=1.16-1.52, P<0.01). In subgroup analysis, statistically elevated cancer risk was found in both Asian and Caucasian populations (for Asian, AA+AG vs. GG: OR=1.74, 95% CI=1.22-2.47, P<0.01; for Caucasian, AA+AG vs. GG: OR=1.24, 95% CI=1.09-1.42, P<0.01). Our result indicated that CXCL12 G801A polymorphism is a risk factor for cancer. To validate the finding, further large-size case-control studies are warranted.