Publications by authors named "Zhihong Chen"

265 Publications

Gastric Cancer Mesenchymal Stem Cells Inhibit NK Cell Function through mTOR Signalling to Promote Tumour Growth.

Stem Cells Int 2021 29;2021:9989790. Epub 2021 Jun 29.

School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

The dysfunction of natural killer (NK) cells has been increasingly reported in malignancies, especially in solid tumours. Mesenchymal stem cells (MSCs) exhibit pleiotropic functions that include mediating immune cell exhaustion which is implicated in cancer progression. However, the association of MSCs derived from gastric cancer (gastric cancer mesenchymal stem cells: GCMSCs) with the dysfunction of NK cells remains poorly understood. In this study, we demonstrated that GCMSCs effectively contributed to the exhaustion of NK cells through the release of soluble factors. Furthermore, passivation of the antitumour effect in NK cells was closely associated with their dysfunctional state. The GCMSC-conditioned medium prevented the frequency and effector function of infiltrating NK cells in tumour-bearing mouse models, thus promoting tumour growth. Mechanistically, mammalian target of rapamycin (mTOR) signalling, a critical regulator of cellular metabolism that mediates the function of immune cells, was inhibited in NK cells treated with GCMSCs. However, the checkpoint receptor PD-1 was still present at minimal levels with or without GCMSCs. The study results revealed that GCMSCs contributed to dysfunctional NK cells involved at least partially in the inhibition of mTOR signalling, suggesting potential directions for NK cell-based cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/9989790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263240PMC
June 2021

Distribution of COPD Comorbidities and Creation of Acute Exacerbation Risk Score: Results from SCICP.

J Inflamm Res 2021 15;14:3335-3348. Epub 2021 Jul 15.

Department of Respiratory and Critical Care Medicine, Huadong Hospital, Fudan University, Shanghai, People's Republic of China.

Background: Chronic obstructive pulmonary disease (COPD) often coexists with multiple comorbidities which may have a significant impact on acute exacerbations of patients. At present, what kind of comorbidities affects acute exacerbations and how comorbidities lead to poor prognosis are still controversial. The purpose of our study is to determine the impact of comorbidities on COPD exacerbation and establish an acute exacerbation risk assessment system related to comorbidities.

Methods: A total of 742 COPD patients participated in the Shanghai COPD Investigation on Comorbidity Program (SCICP, ChiCTR2000030911). Finally, the baseline information of 415 participants and one-year follow-up data were involved in the analysis. We collected hemogram indices, pulmonary function tests and acute exacerbation of COPD with regular medical follow-up. Q-type cluster analysis was used to determine the clusters of participants. Receiver operating characteristic (ROC) analysis was constructed to assess the ability of indicators in predicting acute exacerbations.

Results: Almost 65% of the population we investigated had at least one comorbidity. The distribution and incidence of comorbidities differed between exacerbation group and non-exacerbation group. Three comorbidity clusters were identified: (1) respiratory, metabolic, immune and psychologic disease (non-severe cases); (2) cardiovascular and neoplastic disease (severe cases); (3) less comorbidity. Different sub-phenotypes of COPD patients showed significant distinction in health status. Anxiety (OR=5.936, =0.001), angina (OR=10.155, =0.025) and hypertension (OR=3.142, =0.001) were found to be independent risk factors of exacerbation in a year. The novel risk score containing BODEx and four diseases showed great prognostic value of COPD exacerbation in developing sample.

Conclusion: Our study detailed the major interaction between comorbidities and exacerbation in COPD. Noteworthily, a novel risk score using comprehensive index - BODEx - and comorbidity parameters can identify patients at high risk of acute exacerbation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/JIR.S315600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289369PMC
July 2021

CD137 and PD-L1 targeting with immunovirotherapy induces a potent and durable antitumor immune response in glioblastoma models.

J Immunother Cancer 2021 Jul;9(7)

Health Research Institute of Navarra (IdiSNA), Pamplona, Spain

Background: Glioblastoma (GBM) is a devastating primary brain tumor with a highly immunosuppressive tumor microenvironment, and treatment with oncolytic viruses (OVs) has emerged as a promising strategy for these tumors. Our group constructed a new OV named Delta-24-ACT, which was based on the Delta-24-RGD platform armed with 4-1BB ligand (4-1BBL). In this study, we evaluated the antitumor effect of Delta-24-ACT alone or in combination with an immune checkpoint inhibitor (ICI) in preclinical models of glioma.

Methods: The in vitro effect of Delta-24-ACT was characterized through analyses of its infectivity, replication and cytotoxicity by flow cytometry, immunofluorescence (IF) and MTS assays, respectively. The antitumor effect and therapeutic mechanism were evaluated in vivo using several immunocompetent murine glioma models. The tumor microenvironment was studied by flow cytometry, immunohistochemistry and IF.

Results: Delta-24-ACT was able to infect and exert a cytotoxic effect on murine and human glioma cell lines. Moreover, Delta-24-ACT expressed functional 4-1BBL that was able to costimulate T lymphocytes in vitro and in vivo. Delta-24-ACT elicited a more potent antitumor effect in GBM murine models than Delta-24-RGD, as demonstrated by significant increases in median survival and the percentage of long-term survivors. Furthermore, Delta-24-ACT modulated the tumor microenvironment, which led to lymphocyte infiltration and alteration of their immune phenotype, as characterized by increases in the expression of Programmed Death 1 (PD-1) on T cells and Programmed Death-ligand 1 (PD-L1) on different myeloid cell populations. Because Delta-24-ACT did not induce an immune memory response in long-term survivors, as indicated by rechallenge experiments, we combined Delta-24-ACT with an anti-PD-L1 antibody. In GL261 tumor-bearing mice, this combination showed superior efficacy compared with either monotherapy. Specifically, this combination not only increased the median survival but also generated immune memory, which allowed long-term survival and thus tumor rejection on rechallenge.

Conclusions: In summary, our data demonstrated the efficacy of Delta-24-ACT combined with a PD-L1 inhibitor in murine glioma models. Moreover, the data underscore the potential to combine local immunovirotherapy with ICIs as an effective therapy for poorly infiltrated tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2021-002644DOI Listing
July 2021

Attention-Guided Discriminative Region Localization and Label Distribution Learning for Bone Age Assessment.

IEEE J Biomed Health Inform 2021 Jul 7;PP. Epub 2021 Jul 7.

Bone age assessment (BAA) is clinically important as it can be used to diagnose endocrine and metabolic disorders during child development. Existing deep learning based methods for classifying bone age use the global image as input, or exploit local information by annotating extra bounding boxes or key points. However, training with the global image underutilizes discriminative local information, while providing extra annotations is expensive and subjective. In this paper, we propose an attention-guided approach to automatically localize the discriminative regions for BAA without any extra annotations. Specifically, we first train a classification model to learn the attention maps of the discriminative regions, finding the hand region, the most discriminative region (the carpal bones), and the next most discriminative region (the metacarpal bones). Guided by those attention maps, we then crop the informative local regions from the original image and aggregate different regions for BAA. Instead of taking BAA as a general regression task, which is suboptimal due to the label ambiguity problem in the age label space, we propose using joint age distribution learning and expectation regression, which makes use of the ordinal relationship among hand images with different individual ages and leads to more robust age estimation. Extensive experiments are conducted on the RSNA pediatric bone age data set. {\color{red} Without using extra manual} annotations, our method achieves competitive results compared with existing state-of-the-art deep learning-based methods that require manual annotation. Code is available at \url{https://github.com/chenchao666/Bone-Age-Assessment}.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/JBHI.2021.3095128DOI Listing
July 2021

Evaluating carbon content in airway macrophages as a biomarker of personal exposure to fine particulate matter and its acute respiratory effects.

Chemosphere 2021 Jun 14;283:131179. Epub 2021 Jun 14.

School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai, 200032, China; Shanghai Typhoon Institute/CMA, Shanghai Key Laboratory of Meteorology and Health, Shanghai, 200030, China. Electronic address:

It remains unclear whether carbon content in airway macrophages (AM) can predict personal short-term exposure to fine particulate matter (PM) air pollution and its respiratory health effects. We aimed to evaluate the pathway from personal PM exposure to adverse respiratory outcomes through AM carbon content. We designed a longitudinal panel study with 3 scheduled follow-ups among 113 non-smoking patients of chronic obstructive pulmonary disease in Shanghai, China, from April 2017 to January 2019. We quantified AM carbon content from induced sputum by image analysis, tested lung function and measured sputum levels of 4 pro-inflammatory cytokines and 2 anti-inflammatory cytokines. We applied the "meet in the middle" approach incorporating linear mixed-effect models to evaluate the associations from external PM exposure to respiratory outcomes through AM carbon content. Our results indicated that personal exposure to PM within 24 h was significantly associated with decreased forced expiratory volume in 1s and anti-inflammatory cytokines, as well as increased macrophages and pro-inflammatory cytokines. These changes were accompanied by increased areas of AM carbon and higher percentage of AM area occupied by carbon, both of which were associated with increased levels of pro-inflammatory cytokines and decreased levels of anti-inflammatory cytokines. Exposure to ambient black carbon and organic carbon in PM within 2 days was significantly associated with increased AM carbon area and percentage of AM area occupied by carbon. Our findings reinforced the causality in respiratory health effects of PM in which increased AM carbon content might serve as a valid exposure biomarker.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.131179DOI Listing
June 2021

Optimization of ultrasonic-assisted extraction of polysaccharides from Hemerocallis citrina and the antioxidant activity study.

J Food Sci 2021 Jul 19;86(7):3082-3096. Epub 2021 Jun 19.

School of Ecological Technology and Engineering, Shanghai Institute of Technology, Shanghai, P.R. China.

The present study discussed the optimization of the ultrasonic-assisted extraction of polysaccharides from daylily polysaccharides (DPs). The extracted crude polysaccharides were further separated and purified, and the antioxidant activities including 1,1-diphenyl-2-111 picrylhydrazyl (DPPH) radical scavenging, 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical scavenging, hydroxyl radical scavenging, and ferric-reducing antioxidant power (FRAP) activities of the obtained fractions were also evaluated. The results showed that the optimal ultrasonic-assisted extraction parameters with DPs yield of 15.25 ± 1.13% were water to powder ratio of 25 ml/g, extraction power of 694 W, extraction temperature of 71°C, extraction time of 38 min, and three times extraction. By DEAE Sepharose Fast Flow column, four water-soluble polysaccharide fractions (DP-1, DP-2, DP-3, and DP-4) were successfully obtained. Monosaccharide component analysis showed that the four obtained fractions were all hetero-polysaccharides that mainly contained rhamnose, arabinose, fructose, galactose, glucose, galacturonic acid, and glucuronic acid in different molar ratios. All the four DP fractions did show obvious antioxidant activities in vitro, and the DP-3 component had relatively high ABTS free radical scavenging activity. Overall, our research showed that DPs could provide cheap raw materials for the development of natural antioxidants in medicines, functional foods, and even cosmetics. PRACTICAL APPLICATION: This article deals with the optimization of the ultrasonic-assisted extraction of polysaccharides from daylily and its antioxidant activities. The results showed that the optimal ultrasonic-assisted extraction yield of DPs was 15.25 ± 1.13%. By DEAE Sepharose Fast Flow column, four water-soluble polysaccharide fractions were successfully obtained, and all the four DP fractions did show obvious antioxidant activities in vitro. Daylily polysaccharides could provide cheap raw materials for the development of natural antioxidants in medicines, functional foods, and even cosmetics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1750-3841.15806DOI Listing
July 2021

Mobility Extraction in 2D Transition Metal Dichalcogenide Devices-Avoiding Contact Resistance Implicated Overestimation.

Small 2021 Jul 10;17(28):e2100940. Epub 2021 Jun 10.

Birck Nanotechnology Center, Department of Electrical and Computer Engineering, Purdue University, 1205 W State St, West Lafayette, IN, 47907, USA.

Schottky barrier (SB) transistors operate distinctly different from conventional metal-oxide semiconductor field-effect transistors, in a unique way that the gate impacts the carrier injection from the metal source/drain contacts into the channel region. While it has been long recognized that this can have severe implications for device characteristics in the subthreshold region, impacts of contact gating of SB in the on-state of the devices, which affects evaluation of intrinsic channel properties, have been yet comprehensively studied. Due to the fact that contact resistance (R ) is always gate-dependent in a typical back-gated device structure, the traditional approach of deriving field-effect mobility from the maximum transconductance (g ) is in principle not correct and can even overestimate the mobility. In addition, an exhibition of two different threshold voltages for the channel and the contact region leads to another layer of complexity in determining the true carrier concentration calculated from Q = C * (V -V ). Through a detailed experimental analysis, the effect of different effective oxide thicknesses, distinct SB heights, and doping-induced reductions in the SB width are carefully evaluated to gain a better understanding of their impact on important device metrics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/smll.202100940DOI Listing
July 2021

Lipopolysaccharide-Activated Bone Marrow-Derived Dendritic Cells Suppress Allergic Airway Inflammation by Ameliorating the Immune Microenvironment.

Front Immunol 2021 19;12:595369. Epub 2021 May 19.

Department of Pulmonary and Critical Care Medicine, Shanghai Institute of Respiratory Disease, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Previous studies have shown that lipopolysaccharide (LPS)-activated bone marrow-derived dendritic cells (DClps) might induce tolerance in autoimmune and cancer models , whereas it remains unclear whether DClps could play a role in allergic disease model. Herein, we aimed to elucidate the potential effects of DClps on OVA-sensitized/challenged airway inflammation in a mouse model, which may help facilitate the application of specific tolerogenic dendritic cells (tolDC) in allergic asthma in the future.

Methods: The phenotype and function of immature DC (DCia), DClps or IL-10-activated-DC (DC10) were determined. OVA-sensitized/challenged mice were treated with OVA-pulsed DCia or DClps or DC10. We assessed the changes of histopathology, serum total IgE level, pulmonary signal transducers and activators of transcription (STAT), pulmonary regulatory T cells (Tregs), and airway recall responses to OVA rechallenge, including proliferation and cytokine secretory function of pulmonary memory CD4 T cells in the treated mice.

Results: DClps exhibited low levels of CD80 and MHCII and increased levels of anti-inflammatory cytokines such as IL-10 and TGF-β. Additionally, DClps treatment dramatically diminished infiltration of inflammatory cells, eosinophilia, serum IgE and STAT6 phosphorylation level, increased the number of pulmonary Tregs. In addition, DClps treatment decreased the proliferation of pulmonary memory CD4 T cells, which further rendered the downregulation of Th2 cytokines .

Conclusion: LPS stimulation may lead to a tolerogenic phenotype on DC, and thereby alleviated the Th2 immune response of asthmatic mice, possibly by secreting anti-inflammatory cytokines, inhibiting pulmonary memory CD4 T cells, downregulating pulmonary STAT6 phosphorylation level and increasing pulmonary Tregs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.595369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171252PMC
June 2021

Macrophage-tumor cell intertwine drives the transition into a mesenchymal-like cellular state of glioblastoma.

Cancer Cell 2021 Jun 3;39(6):743-745. Epub 2021 Jun 3.

Department of Oncological Sciences, The Tisch Cancer Institute, Mount Sinai Icahn School of Medicine, New York City, NY, USA; Department of Neurosurgery, Mount Sinai Icahn School of Medicine, New York City, NY, USA. Electronic address:

Macrophages are the major non-neoplastic infiltrates in the glioblastoma microenvironment. In this issue of Cancer Cell, Hara et al. (2021) demonstrate that macrophages induce a transition of glioblastoma cells into the mesenchymal-like cellular state associated with an increased mesenchymal program in macrophages themselves and enhanced cytotoxicity of T cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ccell.2021.05.003DOI Listing
June 2021

Longitudinal single-cell profiling reveals molecular heterogeneity and tumor-immune evolution in refractory mantle cell lymphoma.

Nat Commun 2021 05 17;12(1):2877. Epub 2021 May 17.

Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and targeting BIRC5 results in marked tumor inhibition in preclinical models. In addition, we discover notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveals diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22872-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128874PMC
May 2021

Cardiac Derived CD51-Positive Mesenchymal Stem Cells Enhance the Cardiac Repair Through SCF-Mediated Angiogenesis in Mice With Myocardial Infarction.

Front Cell Dev Biol 2021 21;9:642533. Epub 2021 Apr 21.

Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Many tissues contained resident mesenchymal stromal/stem cells (MSCs) that facilitated tissue hemostasis and repair. However, there is no typical marker to identify the resident cardiac MSCs. We aimed to determine if CD51 could be an optimal marker of cardiac MSCs and assess their therapeutic potential for mice with acute myocardial infarction (AMI). Cardiac-derived CD51CD31CD45Ter119 cells (named CD51cMSCs) were isolated from C57BL/6 mice(7-day-old) by flow cytometry. The CD51cMSCs were characterized by proliferation capacity, multi-differentiation potential, and expression of typical MSC-related markers. Adult C57BL/6 mice (12-week-old) were utilized for an AMI model via permanently ligating the left anterior descending coronary artery. The therapeutic efficacy of CD51cMSCs was estimated by echocardiography and pathological staining. To determine the underlying mechanism, lentiviruses were utilized to knock down gene (stem cell factor [SCF]) expression of CD51cMSCs. In this study, CD51 was expressed in the entire layers of the cardiac wall in mice, including endocardium, epicardium, and myocardium, and its expression was decreased with age. Importantly, the CD51cMSCs possessed potent self-renewal potential and multi-lineage differentiation capacity and also expressed typical MSC-related surface proteins. Furthermore, CD51cMSC transplantation significantly improved cardiac function and attenuated cardiac fibrosis through pro-angiogenesis activity after myocardial infarction in mice. Moreover, SCF secreted by CD51cMSCs played an important role in angiogenesis both and . Collectively, CD51 is a novel marker of cardiac resident MSCs, and CD51cMSC therapy enhances cardiac repair at least partly through SCF-mediated angiogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.642533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098770PMC
April 2021

Mutations in the sodium channel genes SCN1A, SCN3A, and SCN9A in children with epilepsy with febrile seizures plus(EFS+).

Seizure 2021 May 9;88:146-152. Epub 2021 Apr 9.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China; Department of Pediatrics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China. Electronic address:

Purpose: To explore disease-causing gene mutations of epilepsy with febrile seizures plus (EFS+) in Southern Chinese Han population.

Methods: Blood samples and clinical data were collected from 49 Southern Han Chinese patients with EFS+. Gene screening was performed using whole-exome sequencing and panel sequencing for 485 epilepsy-related genes. The pathogenicity of variants was evaluated based on ACMG scoring and assessment of clinical concordance.

Results: We identified 10 putatively causative sodium channel gene variants in 49 patients with EFS+, including 8 variants in SCN1A (R500Q appeared twice), one in SCN3A and one in SCN9A. All these missense mutations were inherited from maternal or paternal and were evaluated to be of uncertain significance according to ACMG. The clinical features of patients were in concordance with the EFS+ phenotype of the mutated SCN1A, SCN3A and SCN9A gene. The clinical phenotypes of 11 probands with these gene variants included febrile seizures plus (FS+, n=7), Dravet Syndrome (n=3), FS+ with focal seizures (n=1). Three probands with SCN1A variants (R500Q located in the non-voltage areas, or G1711D in the pore-forming domain) developed severe Dravet syndrome. The affected individuals with the other 6 SCN1A variants located outside the pore-forming domain showed mild phenotypes. Novel SCN3A variant ((D1688Y) and SCN9A variant (R185H) were identified in two probands respectively and both of the probands had FS+.

Conclusion: The SCN1A, SCN3A, and SCN9A gene mutations might be a pathogenic cause of EFS+ in Southern Chinese Han population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2021.04.006DOI Listing
May 2021

Improving the charge properties of the WO photoanode using a BiFeO ferroelectric nanolayer.

Phys Chem Chem Phys 2021 Apr 29;23(14):8241-8245. Epub 2021 Mar 29.

Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Guangzhou University, Guangzhou, China.

Tungstic oxide (WO) is a promising visible-light-responsive photoanode material, but it has poor charge transport and collection properties. In this study, a WO/BiFeO core/shell photoanode (WO/BFO) with enhanced photoelectrochemical (PEC) performance was successfully prepared using a facile spin-coating method. The optimal WO/BFO shows an excellently enhanced and stable photocurrent density of ∼2.83 mA cm at 0.6 V vs. Ag/AgCl, which is ∼244% more than WO under AM 1.5 illumination. The results of Mott-Schottky tests, intensity modulated photoelectrochemical spectroscopy and transient photocurrent decay indicated that the BFO ferroelectric nanolayer significantly enhances the charge density of the WO/BFO, and improves its charge transport and separation property and charge lifetime, which could be the reason for the enhanced PEC activity of WO/BFO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cp06214fDOI Listing
April 2021

Clinical Outcome and Cost-Effectiveness Analysis of CSII Versus MDI in Children and Adolescent With Type 1 Diabetes Mellitus in a Public Health Care System of China.

Front Endocrinol (Lausanne) 2021 30;12:604028. Epub 2021 Mar 30.

Paediatric Endocrinology and Metabolism Department, Qingdao Women and Children's Hospital, Qingdao, China.

Objectives: To evaluate the clinical and economic consequences of continuous subcutaneous insulin infusion (CSII) vs. multiple daily injections (MDI) in children and adolescents with type 1 diabetes mellitus (T1DM) from a public health care system in developed areas of developing country, considering changes in glycemic Control, daily insulin requirements, lipid profile, body mass index (BMI), frequency of severe hypoglycemia and Diabetic Ketoacidosis (DKA) and diabetic complications.

Methods: This was a retrospective cohort study of children and adolescents with T1DM. Data were collected at baseline and the end of every year including glycated hemoglobin (HbA1c), insulin dose, lipid profile, blood pressure, and adverse events (severe hypoglycemia and DKA). The Cost-effectiveness analysis was performed using the IQVIA CORE Diabetes Model (CDM) to simulate diabetes progression by utilizing the clinical data obtained from the two groups. The main outcome measures were Life Expectancy, Quality adjusted life years (QALYs), Total Costs and Incremental Costs and Effectiveness Ratio (ICER) of CSII compared with MDI in Chinese pediatric patients with T1DM in Qingdao City (60 years).

Results: Mean HbA1c values and daily insulin doses were significantly lower in those receiving CSII therapy throughout follow-up. Mean direct lifetime costs were ¥ 67,137 higher with CSII treatment than with MDI for pediatric patients. Treatment with CSII was associated with an improvement in life expectancy of 0.41 years for pediatric patients compared with MDI based on CORE diabetes model simulation. The corresponding gains in QALYs were 0.42. These data produced corresponding ICER is ¥ 161,815 per QALY for pediatric T1DM patients in Qingdao. Sensitivity analyses suggested that our base-case assumptions were mostly robust.

Conclusions: CSII is associated with improved long-term clinical outcomes compared with MDI. Based on this model analysis, CSII appears to be more cost-effective for the Qingdao TIDM pediatric population and health care system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.604028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043415PMC
March 2021

Risk Signature Related to Immunotherapy Reaction of Hepatocellular Carcinoma Based on the Immune-Related Genes Associated With CD8 T Cell Infiltration.

Front Mol Biosci 2021 19;8:602227. Epub 2021 Mar 19.

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Hepatocellular carcinoma (HCC) is the most common histological type of liver cancer, with an unsatisfactory long-term survival rate. Despite immune checkpoint inhibitors for HCC have got glories in recent clinical trials, the relatively low response rate is still a thorny problem. Therefore, there is an urgent need to screen biomarkers of HCC to predict the prognosis and efficacy of immunotherapy. Gene expression profiles of HCC were retrieved from TCGA, GEO, and ICGC databases while the immune-related genes (IRGs) were retrieved from the ImmPort database. CIBERSORT and WGCNA algorithms were combined to identify the gene module most related to CD8 T cells in the GEO cohort. Subsequently, the genes in hub modules were subjected to univariate, LASSO, and multivariate Cox regression analyses in the TCGA cohort to develop a risk signature. Afterward, the accuracy of the risk signature was validated by the ICGC cohort, and its relationships with CD8 T cell infiltration and PDL1 expression were explored. Nine IRGs were finally incorporated into a risk signature. Patients in the high-risk group had a poorer prognosis than those in the low-risk group. Confirmed by TCGA and ICGC cohorts, the risk signature possessed a relatively high accuracy. Additionally, the risk signature was demonstrated as an independent prognostic factor and closely related to the CD8 T cell infiltration and PDL1 expression. A risk signature was constructed to predict the prognosis of HCC patients and detect patients who may have a higher positive response rate to immune checkpoint inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2021.602227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017194PMC
March 2021

A dynamic prognostic nomogram to predict the benefit from surgical treatment modality for patients with laryngeal squamous cell carcinoma.

Head Neck 2021 07 30;43(7):2148-2158. Epub 2021 Mar 30.

Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.

Background: Although nonsurgical treatment strategy is increasingly adopted in patients with locoregionally advanced laryngeal squamous cell carcinoma (LSCC), survival disparities were reported between surgical treatment modality and organ preservation protocols, highlighting the great importance for accurate patients' selection.

Method: This secondary analysis used data from the Surveillance, Epidemiology, and End Results database between 2010 and 2015 with follow-up data up to 2018. We developed and validated a dynamic prognostic nomogram for overall survival (OS) in 4237 patients with LSCC and subgroup of 2087 patients with locoregionally advanced laryngeal squamous cell carcinoma (LALSCC). Based on the total risk score derived from the dynamic nomogram, two well-matched risk groups (i.e., low- and high-risk) were created via X-tile software and 1-to-1 propensity score matching (PSM); surgical treatment modality was compared with nonsurgical one in each risk group.

Results: A more accurate and convenient dynamic prognostic nomogram based on age, marital status, T category, N category, M category, tumor size, and tumor differentiation was developed and validated, of which the predictive performance was superior to that of TNM staging system. For high-risk LALSCC selected by the dynamic nomogram, after 1-to-1 PSM, significantly improved OS was observed in patients with receiving surgical treatment compared to those receipt of nonsurgical management (restricted mean survival time at 36-month: 26.6 vs 22.7, p < 0.001; restricted mean survival time at 60-month: 36.7 vs 31.0, p = 0.003).

Conclusion: We establish and validate a more accurate and convenient dynamic prognostic nomogram for patients with LSCC, which may predict the benefit from surgical treatment modality for patients with high-risk LALSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.26683DOI Listing
July 2021

Identification of differential DNA methylation alterations of ovarian cancer in peripheral whole blood based on within-sample relative methylation orderings.

Epigenetics 2021 Mar 22:1-13. Epub 2021 Mar 22.

School of Medical Information Engineering, Gannan Medical University, Ganzhou, China.

Leukocyte cell proportion changes affect the detection of cancer-associated aberrant DNA methylation alterations in peripheral blood samples. We aimed to detect cellular DNA methylation changes in ovarian cancer (OVC) blood samples avoiding the above-mentioned cell-composition effects. Based on the within-sample relative methylation orderings (RMOs) of CpG loci in leukocyte subtypes, we developed the Ref-RMO method to detect aberrant methylation alterations from OVC blood samples. Stable CpG pairs with consistent RMOs in different leukocyte subtypes were determined, more than 99% of which retained their RMO patterns in peripheral whole blood (PWB) in independent datasets. Based on the stable CpG pairs, significantly reversed CpG pairs were detected from OVC PWB samples, which were relative to clinical information such as age, subtype, grade, stage, or CA125 level. Results showed 439 CpG loci were determined to be significant differential DNA methylations between OVC and healthy blood samples. They were mainly enriched in KEGG pathways, such as cytokine-cytokine receptor interaction, apoptosis, proteoglycans in cancer, and immune-associated Gene Ontology terms. STRING analysis showed that they tended to have functional interactions with cancer-associated genes recorded in the COSMIC database. Leukocyte cellular differential DNA methylations could be identified by the proposed RMO-based method from OVC PWB samples, which were cancer-associated aberrant signals against cell-composition effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15592294.2021.1900029DOI Listing
March 2021

Deubiquitinating enzyme inhibitor alleviates cyclin A1-mediated proteasome inhibitor tolerance in mixed-lineage leukemia.

Cancer Sci 2021 Jun 5;112(6):2287-2298. Epub 2021 Apr 5.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Drug resistance is a significant obstacle to effective cancer treatment. Drug resistance develops from initially reversible drug-tolerant cancer cells, which offer therapeutic opportunities to impede cancer relapse. The mechanisms of resistance to proteasome inhibitor (PI) therapy have been investigated intensively, however the ways by which drug-tolerant cancer cells orchestrate their adaptive responses to drug challenges remain largely unknown. Here, we demonstrated that cyclin A1 suppression elicited the development of transient PI tolerance in mixed-lineage leukemia (MLL) cells. This adaptive process involved reversible downregulation of cyclin A1, which promoted PI resistance through cell-cycle arrest. PI-tolerant MLL cells acquired cyclin A1 dependency, regulated directly by MLL protein. Loss of cyclin A1 function resulted in the emergence of drug tolerance, which was associated with patient relapse and reduced survival. Combination treatment with PI and deubiquitinating enzyme (DUB) inhibitors overcame this drug resistance by restoring cyclin A1 expression through chromatin crosstalk between histone H2B monoubiquitination and MLL-mediated histone H3 lysine 4 methylation. These results reveal the importance of cyclin A1-engaged cell-cycle regulation in PI resistance in MLL cells, and suggest that cell-cycle re-entry by DUB inhibitors may represent a promising epigenetic therapeutic strategy to prevent acquired drug resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177811PMC
June 2021

G6PD-NF-κB-HGF Signal in Gastric Cancer-Associated Mesenchymal Stem Cells Promotes the Proliferation and Metastasis of Gastric Cancer Cells by Upregulating the Expression of HK2.

Front Oncol 2021 26;11:648706. Epub 2021 Feb 26.

School of Medicine, Jiangsu University, Zhenjiang, China.

Tumor-associated stromal cells have been widely recognized for their tumor-promoting capability involving paracrine signaling. However, the underlying mechanism and the effects of the molecules in the glycolysis pathway in gastric cancer-associated mesenchymal stem cells (GCMSCs) and gastric cancer cells on tumor progression remain unclear. The expression of hepatocyte growth factor (HGF) in GCMSCs and bone marrow mesenchymal stem cells (BMMSCs) was detected by enzyme-linked immunosorbent assay (ELISA). The effect of HGF derived from GCMSCs on the proliferation, metastasis, and HK2 expression of gastric cancer cells was evaluated and . The effects of G6PD on the production of HGF in mesenchymal stem cells (MSCs) were analyzed by immunoblotting. HGF derived from GCMSCs promoted glycolysis, proliferation, and metastasis of gastric cancer by upregulating c-Myc-HK2 signal. The progression of the disease induced by GCMSCs decelerated in the absence of HK2. The expression of G6PD activated NF-κB signaling and stimulated the production of HGF in GCMSCs. Blocking HGF derived from GCMSCs decreased proliferation, metastasis, and angiogenesis of gastric cancer cells . GCMSCs highly expressed G6PD and facilitated the progression of gastric cancer through the G6PD-NF-κB-HGF axis coordinates. Blocking HGF derived from GCMSCs is a potential new therapeutic target for the treatment of gastric cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.648706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952978PMC
February 2021

Score for predicting overall survival in pancreatic adenocarcinoma patients with positive lymph nodes after surgery: a novel nomogram-based risk assessment.

Gland Surg 2021 Feb;10(2):529-540

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: Pancreatic adenocarcinoma (PaC) patients with positive lymph nodes (PLNs) have a dismal prognosis and lack a specific prognostic stage. This study aimed to construct a nomogram for the prediction of overall survival (OS) in these patients.

Methods: A total of 1,340 patients screened from the Surveillance, Epidemiology, and End Results database were included and randomly divided at a ratio of 7:3 into a training set (n=940) and an internal validation set (n=400). Cox regression analyses were conducted to select independent predictors in the training set, and a nomogram was constructed. The model was verified in the internal validation set and in an external validation set, which comprised 64 patients from a Chinese institute.

Results: Six independent prognostic factors (age at diagnosis, tumor grade, lymph node ratio, T stage, radiotherapy, and chemotherapy) were identified in PaC patients with PLNs and were entered into the nomogram. The final model had a higher C-index for predicting OS than the American Joint Committee on Cancer-8th edition staging system (training set: 0.658 . 0.546; internal validation set: 0.661 . 0.546; external validation set: 0.691 . 0.581). The 1-, 2-, and 3-year area under the receiver operating characteristic curve values indicated better discrimination power for the established nomogram with respect to the prediction of OS in the training, internal validation, and external validation sets than for the American Joint Committee on Cancer-8th edition staging system. Furthermore, the nomogram performed well in both calibration and decision curve analyses (DCA) of clinical applicability. OS in PaC patients with PLNs was significantly distinguished among the three risk groups stratified according to the nomogram score (P<0.001).

Conclusions: The well-calibrated nomogram was determined to be extremely efficient in predicting survival, and defining a high-risk population based on the nomogram score among PaC patients with PLNs after surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/gs-20-597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944054PMC
February 2021

Re-Clustering and Profiling of Digestive System Tumors According to Microenvironment Components.

Front Oncol 2020 10;10:607742. Epub 2021 Feb 10.

Department of Immunology, Basic Medical Institute, Chengde Medical College, Chengde, China.

Background: Immunotherapy has become the most promising therapy in digestive system tumors besides conventional chemotherapy and radiotherapy. But only a few patients can benefit from different types of immunotherapies, such as immune checkpoint blockade (ICB). To identify these ICB-susceptible patients, methods are urgently needed to screen and profile subgroups of patients with different responsiveness to ICB.

Methods: This study carried out analysis on patients with digestive system tumors that were obtained from Cancer Genome Atlas (TCGA) cohorts. The analyses were mainly performed using GraphPad Prism 7 and R language.

Results: We have quantified the microenvironmental components of eight digestive system tumor patients in TCGA cohorts and evaluated their clinical value. We re-clustered patients based on their microenvironment composition and divided these patients into six clusters. The differences between these six clusters were profiled, including survival conditions, enriched biological processes, genomic mutations, and microenvironment traits. Cluster 3 was the most immune-related cluster, exhibiting a high infiltration of non-tumor components and poor survival status, along with an inhibitory immune status, and we found that patients with high stromal score indicated a poor response in ICB cohort.

Conclusions: Our research provides a new strategy based on the microenvironment components for the reclassification of digestive system tumors, which could provide guidance for prognosis judgment and treatment response prediction like ICB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.607742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902780PMC
February 2021

Clinical risk factors for mortality of hospitalized patients with COVID-19: systematic review and meta-analysis.

Ann Palliat Med 2021 Mar 1;10(3):2723-2735. Epub 2021 Feb 1.

Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital Fudan University, Shanghai, China.

Background: New evidence from retrospective cohort studies on risk of death from COVID-19 infection became available. We aimed to systematically review the clinical risk factors for fatal outcome of COVID-19.

Methods: We performed meta-analysis, using PubMed, EMBASE and Cochrane databases from December 1 2019 to June 10 2020. The meta-analysis summarized clinical, laboratory, radiological features, and complications of non-survivors with confirmed COVID-19. In addition, a fixed- or random-effects model was adopted based on the heterogeneity among studies. We also used funnel-plot with Egger's tests to screen potential publication bias.

Results: In total, twenty studies with 15,408 COVID-19 cases were included in our meta-analysis. Male, current smoking, and older age were associated with in-hospital death. Patients aged 60 years or over had the highest pooled ORs [OR 4.94 (2.89, 8.44)]. Non-survivors were more likely to have diabetes, hypertension, cardiovascular disease (CVD), respiratory disease, or chronic kidney disease (CKD). Respiratory disease had the highest pooled ORs [OR 2.55 (2.14, 3.05)]. Dyspnea [OR 3.31 (1.78, 6.16); I2 : 83%] and fatigue [OR 1.36 (1.07, 1.73); I2 : 0%] were associated with increased risk of death. Increased white blood cell count, decreased lymphocyte and platelet counts, were also associated with increased risk of death. Biomarkers of coagulation function, inflammation, liver and kidney function, cardiac and muscle injury were also elevated in nonsurvivors.

Conclusions: Male, current smoking patients aged 60 years or over might face a greater risk of in-hospital death and the comorbidities such as diabetes, hypertension, CVD, respiratory disease, and CKD could also influence the prognosis of the COVID-19. Clinical feature such as dyspnea and fatigue could imply the exacerbation and even death. Our findings highlighted early markers of mortality which were beneficial to identify fatal COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-20-1278DOI Listing
March 2021

Preparation of [email protected] and Solvent Inducing Enhancement Strategy for Raman Determination of Salivary Thiocyanate.

ACS Appl Mater Interfaces 2021 Feb 27;13(5):5966-5974. Epub 2021 Jan 27.

The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors, and Department of Chemistry, Shanghai Normal University, Shanghai 200234, P. R. China.

Making the substrates form highly dense, homogeneous, and stable hotspots regions is important for the sensitive detection of surface-enhanced Raman spectroscopy (SERS). A new strategy based on solvent-induced (SI) SERS substrate to form a stable interval of the hotspot for detection was explored and the enhancement factor (EF) of our SERS substrates could reach about 1.4 × 10. By preferential adsorption of alcohol solutions by Q-Sepharose microsphere (QSS) in mixed water and alcohol solutions, the size of [email protected] was dynamically adjusted and the spacing between gold nanoparticles (AuNPs) was adjusted to keep the substrate in the optimal hotspot mode for the sensitive detection of SERS in the liquid state. As a real application case, such a SI-SERS strategy was employed to determine SCN in saliva and a limit of detection (LOD) of about 10 M could be achieved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c19650DOI Listing
February 2021

Convolutional neural network for accelerating the computation of the extended Tofts model in dynamic contrast-enhanced magnetic resonance imaging.

J Magn Reson Imaging 2021 06 31;53(6):1898-1910. Epub 2020 Dec 31.

Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Run Shaw Hospital and Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China.

Quantitative physiological parameters can be obtained from nonlinear pharmacokinetic models, such as the extended Tofts (eTofts) model, applied to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). However, the computation of such nonlinear models is time consuming. The aim of this study was to develop a convolutional neural network (CNN) for accelerating the computation of fitting eTofts model without sacrificing agreement with conventional nonlinear-least-square (NLLS) fitting. This was a retrospective study, which included 13 patients with brain glioma for training (75%) and validation (25%), and 11 patients (three glioma, four brain metastases, and four lymphoma) for testing. CAIPIRINHA-Dixon-TWIST DCE-MRI and double flip angle T map acquired at 3 T were used. A CNN with both local pathway and global pathway modules was designed to estimate the eTofts model parameters, the volume transfer constant (K ), blood volume fraction (v ), and volume fraction of extracellular extravascular space (v ), from DCE-MRI data of tumor and normal-appearing voxels. The CNN was trained on mixed dataset consisting of synthetic and patient data. The CNN result and computation speed were compared with NLLS fitting. The robustness to noise variations and generalization to brain metastases and lymphoma data were also evaluated. Statistical tests used were Student's t test on mean absolute error, concordance correlation coefficient (CCC), and normalized root mean squared error. Including global pathway modules in the CNN and training the network with mixed data significantly (p < 0.05) improved the CNN performance. Compared with NLLS fitting, CNN yields an average CCC greater than 0.986 for K , greater than 0.965 for v , and greater than 0.948 for v . The CNN accelerated computation speed approximately 2000 times compared to NLLS, showed robustness to noise (signal-to-noise ratio >34.42 dB), and had no significant (p > 0.21) difference applied to brain metastases and lymphoma data. In conclusion, the proposed CNN to estimate eTofts parameters showed comparable result as NLLS fitting while significantly reducing the computation time. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.27495DOI Listing
June 2021

Involvement of a novel regulatory cascade consisting of SET-H3K18ac/H3K27ac-53BP1 in Cr(VI)-induced malignant transformation of 16HBE cells.

Toxicol Lett 2021 Mar 25;339:70-77. Epub 2020 Dec 25.

Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou, China; Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020-2024), Shenzhen Center for Disease Control and Prevention, Shenzhen, China, 518055. Electronic address:

Hexavalent chromium (Cr(VI)) is a well-established human carcinogen with DNA damaging effects. Recently we established a Cr(VI)-induced malignant transformation model from a human bronchial epithelial (16HBE) cell line, and in the transformed (16HBE-T) cells reduced levels of 53BP1 (critical for DNA repair) and the acetylated histone H3K18/27 (H3K18/27ac) were observed. In 16HBE-T cells SET (a multifunctional protein) was elevated by Cr(VI) through quantitative proteomics analysis. In the present study, we further explore the involvement of SET in the H3K18/27ac/53BP1 cascade in the 16HBE-T model, primarily by knockdown of SET. Bioinformatic analysis of the differentially expressed proteins indicated enrichment in histone modifications, in which SET was a major regulator. In 16HBE cells SET expression was enhanced by Cr(VI) in a concentration- and exposure duration-dependent manner. In 16HBE-T cells, SET knockdown showed the following effects: reversal of H3K18/27ac and 53BP1 levels, enhanced enrichment H3K18/27ac in 53BP1's promotor region, increase rate of apoptosis and cell cycle G0/G1 arrest (with or without Cr(VI) treatment), and reduced colony-forming efficiency. Finally, In comparison with benzo(a)pyrene-transformed (malignant, 16HBE-B) cells from 16HBE where no changes in H3K18/27ac, 53BP1 or SET were observed, while the H3K18/27ac/53BP1 cascade was downregulated and SET upregulated in 16HBE-T cells, as compared with the parental 16HBE cells; thus the changes in 16HBE-T might be a specific effect of Cr(VI). In conclusion, our results suggest that SET may be involved in the malignant cell transformation, through inhibiting the H3K18/27ac/53BP1 cascade, at least in the 16HBE cell model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2020.12.017DOI Listing
March 2021

Construction of Nomograms for Predicting Lung and Bone Metastases in Patients with Intrahepatic Cholangiocarcinoma and Identification of Patients Who Can Benefit from Chemotherapy.

J Oncol 2020 2;2020:8889571. Epub 2020 Dec 2.

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Objective: The purpose of our study is to build nomograms for predicting the possibility of lung metastasis (LM) and bone metastasis (BM) in patients with intrahepatic cholangiocarcinoma (ICC).

Methods: 1527 patients diagnosed with ICC between 2010 and 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable logistic regression analyses were used to recognize the predictors of LM and BM, respectively. Then two nomograms were established. We applied the C-index, calibration plot, receiver-operating characteristic (ROC) curve, and decision curve analysis (DCA) to evaluate the novel nomograms. The maximum values of the Youden indexes from the ROC curves were utilized to select the cutoff points of the nomograms. The Kaplan-Meier survival curves were used to evaluate the effect of chemotherapy in different groups. The bootstrap resampling method was chosen for internal validation.

Results: Five predictors for LM and three predictors for BM were identified, and two nomograms were constructed. The nomograms had high values of C-indexes, reaching 0.821 (95% CI 0.772-0.871) for LM and 0.759 (95% CI 0.700-0.818) for BM. C-indexes of 0.814 for LM and 0.749 for BM were also observed in internal validation. The calibration plots, ROC curves, and DCAs exhibited favorable performances for predicting LM and BM. The cutoff points of total points in nomograms were 108 for LM and 144 for BM, which could distinguish between high-risk and low-risk groups for LM and BM. Chemotherapy is suggested to undergo for patients in high-risk groups.

Conclusions: The nomograms could assess the possibility of LM and BM in ICC patients and determine the optimal treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8889571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725572PMC
December 2020

Mixed-lineage leukemia protein modulates the loading of let-7a onto AGO1 by recruiting RAN.

Haematologica 2021 07 1;106(7):1995-1999. Epub 2021 Jul 1.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025.

Not available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2020.268474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252936PMC
July 2021

Sericin inhibits MDA‑MB‑468 cell proliferation via the PI3K/Akt pathway in triple‑negative breast cancer.

Mol Med Rep 2021 02 14;23(2). Epub 2020 Dec 14.

Department of Human Anatomy, Chengde Medical University, Chengde, Hebei 067000, P.R. China.

Triple negative breast cancer (TNBC) is a subtype of breast cancer characterized by an aggressive histology and poor prognosis, with limited treatment options in the clinic. In the present study, the effect of sericin, as an anti‑cancer drug, on TNBC cell proliferation was investigated using a MTT assay, a colony formation assay and immunocytochemistry staining of Ki67. Results from the flow cytometry demonstrated that sericin induced G/G cell cycle arrest and promoted cellular apoptosis. Cell cycle and apoptosis‑related proteins were detected via western blot analysis. Immunocytochemistry staining identified that P21 was translocated into the nucleus. Additionally, several pathways were significantly enriched in TNBC based on the Gene Expression Omnibus database, with the most prominent pathway being the PI3K/Akt signaling pathway. In TNBC MDA‑MB‑468 cells, sericin suppressed the PI3K/Akt pathway. All these findings suggested that sericin served a critical role in suppressing TNBC cell proliferation, inducing cell cycle arrest and promoting cellular apoptosis. The results indicated that the underlying molecular mechanism was, at least partially, via the downregulation of the PI3K/Akt signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2020.11779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751468PMC
February 2021

MOF-derived core/shell C-TiO/CoTiO type II heterojunction for efficient photocatalytic removal of antibiotics.

J Hazard Mater 2021 03 26;406:124675. Epub 2020 Nov 26.

Guangdong Provincial Key Laboratory of Optical Information Materials and Technology & Institute of Electronic Paper Displays, South China Academy of Advanced Optoelectronics, South China Normal University, Guangdong, China. Electronic address:

A novel core/shell C-TiO/CoTiO type II heterojunction was successfully synthesized via a direct calcination method by using MIL-125/Co core-shell nanocakes as a sacrificial template and precursor. In the calcination process, the organic ligand in MIL-125 acts as an in-situ carbon doping source to form a carbon-doped TiO core (C-TiO). At the same time, CoTiO nanoparticles are formed on the surface of C-TiO by an in-situ solid-state reaction between the C-TiO and Co shell of MIL-125/Co. Due to such delicate core/shell structural features, carbon doping and type II heterojunctions, C-TiO/CoTiO core/shell composites can effectively harvest visible light, facilitate the interfacial separation and suppress the recombination of photogenerated electron-hole pairs, leading to the remarkable photocatalytic activity for removal of ciprofloxacin (CIP). In particular, C-TiO/CoTiO-3 exhibits the best photocatalytic degradation activity of CIP with a degradation efficiency of 99.6% and a total carbon content removal percentage of 76% under visible-light illumination for 120 min. In addition, the proposed photocatalytic mechanism study illustrated that the main radical species in the photocatalytic degradation of CIP using C-TiO/CoTiO as the photocatalyst is •OH. This work provides a new approach and insight for synthesizing core/shell heterojunction-based photocatalysts for various applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2020.124675DOI Listing
March 2021

Platelet-derived growth factor beta is a potent inflammatory driver in paediatric high-grade glioma.

Brain 2021 02;144(1):53-69

Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.

Paediatric high-grade gliomas (HGGs) account for the most brain tumour-related deaths in children and have a median survival of 12-15 months. One promising avenue of research is the development of novel therapies targeting the properties of non-neoplastic cell-types within the tumour such as tumour associated macrophages (TAMs). TAMs are immunosuppressive and promote tumour malignancy in adult HGG; however, in paediatric medulloblastoma, TAMs exhibit anti-tumour properties. Much is known about TAMs in adult HGG, yet little is known about them in the paediatric setting. This raises the question of whether paediatric HGGs possess a distinct constituency of TAMs because of their unique genetic landscapes. Using human paediatric HGG tissue samples and murine models of paediatric HGG, we demonstrate diffuse midline gliomas possess a greater inflammatory gene expression profile compared to hemispheric paediatric HGGs. We also show despite possessing sparse T-cell infiltration, human paediatric HGGs possess high infiltration of IBA1+ TAMs. CD31, PDGFRβ, and PDGFB all strongly correlate with IBA1+ TAM infiltration. To investigate the TAM population, we used the RCAS/tv-a system to recapitulate paediatric HGG in newborn immunocompetent mice. Tumours are induced in Nestin-positive brain cells by PDGFA or PDGFB overexpression with Cdkn2a or Tp53 co-mutations. Tumours driven by PDGFB have a significantly lower median survival compared to PDGFA-driven tumours and have increased TAM infiltration. NanoString and quantitative PCR analysis indicates PDGFB-driven tumours have a highly inflammatory microenvironment characterized by high chemokine expression. In vitro bone marrow-derived monocyte and microglial cultures demonstrate bone marrow-derived monocytes are most responsible for the production of inflammatory signals in the tumour microenvironment in response to PDGFB stimulation. Lastly, using knockout mice deficient for individual chemokines, we demonstrate the feasibility of reducing TAM infiltration and prolonging survival in both PDGFA and PDGFB-driven tumours. We identify CCL3 as a potential key chemokine in these processes in both humans and mice. Together, these studies provide evidence for the potent inflammatory effects PDGFB has in paediatric HGGs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awaa382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954387PMC
February 2021
-->