ABSTRACT
Objective: To explore the application of manual screening collaborated with the Artificial Intelligence TPS-Assisted Cytologic Screening System in urinary exfoliative cytology and its clinical values. Methods: A total of 3 033 urine exfoliated cytology samples were collected at the Henan People's Hospital, Capital Medical University, Beijing, China. Liquid-based thin-layer cytology was prepared. The slides were manually read under the microscope and digitally presented using a scanner. The intelligent identification and analysis were carried out using an artificial intelligence TPS assisted screening system. The Paris Report Classification System of Urinary Exfoliated Cytology 2022 was used as the evaluation standard. Atypical urothelial cells and even higher grade lesions were considered as positive when evaluating the recognition sensitivity, specificity, and diagnostic accuracy of artificial intelligence-assisted screening systems and human-machine collaborative cytologic screening methods in urine exfoliative cytology. Among the collected cases, there were also 1 100 pathological tissue controls. Results: The accuracy, sensitivity and specificity of the AI-assisted cytologic screening system were 77.18%, 90.79% and 69.49%; those of human-machine coordination method were 92.89%, 99.63% and 89.09%, respectively. Compared with the histopathological results, the accuracy, sensitivity and specificity of manual reading were 79.82%, 74.20% and 95.80%, respectively, while those of AI-assisted cytologic screening system were 93.45%, 93.73% and 92.66%, respectively. The accuracy, sensitivity and specificity of human-machine coordination method were 95.36%, 95.21% and 95.80%, respectively. Both cytological and histological controls showed that human-machine coordination review method had higher diagnostic accuracy and sensitivity, and lower false negative rates. Conclusions: The artificial intelligence TPS assisted cytologic screening system has achieved acceptable accuracy in urine exfoliation cytologic screening. The combination of manual screening and artificial intelligence TPS assisted screening system can effectively improve the sensitivity and accuracy of cytologic screening and reduce the risk of misdiagnosis.
Subject(s)
Artificial Intelligence , Urologic Neoplasms , Humans , Urothelium/pathology , Cytodiagnosis , Epithelial Cells/pathology , Sensitivity and Specificity , Urologic Neoplasms/diagnosis , Urologic Neoplasms/pathology , Urologic Neoplasms/urineABSTRACT
Talaromycosis (TSM) is an opportunistic deep mycosis prevalent in southeast Asia and southern China, affecting HIV-positive, anti-interferon-gamma autoantibody-positive and other immunodeficiency hosts. These hosts are often co-infected with mycobacterium tuberculosis, non-tuberculosis mycobacteria, bacteria, fungi, viruses and other opportunistic infections. The clinical characteristics and the pathogenic spectrum of TSM with opportunistic infections vary with different immune states. The rates of misdiagnosis, missed diagnosis and mortality are high. This review summarized the clinical characteristics of TSM with opportunistic infections in order to improve the level of clinical diagnosis and treatment.
Subject(s)
Mycoses , Opportunistic Infections , Humans , Mycoses/diagnosis , Opportunistic Infections/diagnosis , Interferon-gamma/therapeutic use , ChinaABSTRACT
The prolongation of patient's overall survival is the accepted as gold standard to prove clinical values of anti-cancer drugs. However, if overall survival is taken as the primary endpoint in clinical trials for cancer types with a relatively good prognosis in the process of new anti-cancer drug research and development, the time to market the drugs will be prolonged due to the long follow-up time. In addition, overall survival is often interfered by confounding factors such as follow-up treatment. Therefore, regulatory agencies have established an accelerated review model using surrogate endpoints for the approval of new anti-cancer drugs, but there are still some problems in the use of surrogate endpoints in cancer clinical trials. From the perspective of new drug review, the authors expounds the key points of confirming and rationally using surrogate endpoints in clinical trials of anti-cancer drugs, which will improve the level of clinical trials of new anti-cancer drugs and accelerate the development of anti-tumor drugs.
Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Neoplasms/therapy , Antineoplastic Agents/therapeutic use , BiomarkersABSTRACT
Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.
Subject(s)
Antineoplastic Agents , Neoplasms , Antineoplastic Agents/therapeutic use , Clinical Trials as Topic , Humans , Marketing , Neoplasms/drug therapy , Research Design , United States , United States Food and Drug AdministrationABSTRACT
OBJECTIVE: The present study is to characterize the role of long intergenic non-coding RNA, regulator of reprogramming (linc-ROR) in bone marrow mesenchymal stem cell (BMSCs) chondrogenesis, cartilage formation and OA development. METHODS: Linc-ROR expression pattern in articular cartilage tissue sample from OA patients were studied by real-time PCR. Linc-ROR lentivirus mediated BMSCs were constructed. In vitro micromass cultured BMSCs chondrogenesis or in vivo MeHA hydrogel encapsulated BMSCs cartilage formation activity were studied. Linc-ROR associating miRNAs which repressed SOX9 expression were characterized by luciferase assay, real-time PCR and Western blot. Linc-ROR was co-transfected with miRNAs into BMSCs to study its rescue effect on SOX9 expression and chondrogenesis activity. RESULTS: Linc-ROR was down-regulated in articular cartilage tissue from OA patients and was positively correlated with the expression level of SOX9 (R2 = 0.43). Linc-ROR expression was upregulated during BMSCs chondrogenesis. Linc-ROR ectopic expression significantly promoted in vitro BMSCs chondrogenesis and in vivo cartilage formation activities as revealed by safranin O, alcian blue and COL II staining. The mRNA expression level of chondrogenesis markers including COL II, SOX9 and ACAN were increased, and the hypertrophy markers MMP13 and COL X were decreased upon linc-ROR overexpression in BMSCs. Linc-ROR functioned as a miRNA sponge for miR-138 and miR-145. Both miR-138 and miR-145 suppressed BMSCs chondrogenesis activity and SOX9 expression, while co-expression of linc-ROR displayed a rescuing effect. CONCLUSIONS: Taken together, linc-ROR modulated BMSCs chondrogenesis differentiation and cartilage formation by acting as a competing endogenous RNA for miR-138 and miR-145 and activating SOX9 expression. Linc-ROR could be considered as a new diagnostic and therapeutic target for OA treatment.
Subject(s)
Cartilage, Articular/metabolism , Chondrogenesis/genetics , Mesenchymal Stem Cells/metabolism , Osteoarthritis, Knee/genetics , RNA, Long Noncoding/genetics , SOX9 Transcription Factor/genetics , Aged , Aged, 80 and over , Aggrecans/metabolism , Blotting, Western , Collagen Type X/metabolism , Female , Humans , In Vitro Techniques , Male , Matrix Metalloproteinase 13/metabolism , MicroRNAs/metabolism , Middle Aged , Osteoarthritis, Knee/metabolism , RNA, Long Noncoding/metabolism , Real-Time Polymerase Chain Reaction , SOX9 Transcription Factor/metabolism , Up-RegulationABSTRACT
Ecdysteroids, as the key growth hormones, regulate moulting, metamorphosis and reproduction in arthropods. Ecdysteroid biosynthesis is catalysed by a series of cytochrome P450 monooxygenases (CYP450s) encoded by Halloween genes, including spook (spo), phantom (phm), disembodied (dib), shadow (sad) and shade (shd). The ecdysteroid biosynthesis in insects is clear with 20-hydroxyecdysone (20E) as the main ecdysteroid. However, the information on the major ecdysteroids in arachnids is limited. In this study, Halloween genes spo, dib, sad and shd, but not phm, were identified in the pond wolf spider, Pardosa pseudoannulata. Phylogenetic analysis grouped arachnid and insect Halloween gene products into two CYP450 clades, the CYP2 clan (spo and phm) and the mitochondrial clan (dib, sad, and shd). In P. pseudoannulata, the temporal expression profile of the four Halloween genes in concurrence with spiderling moulting with steady increase in the course of the 2nd instar followed by a rapid dropdown once moulting was completed. Spatially, the four Halloween genes were highly expressed in spiderling abdomen and in the ovaries of female adults. In parallel, ponasterone A (PA), but not 20E, was detected by LC-MS/MS analysis in P. pseudoannulata, and it was demonstrated as a functional ecdysteroid in the spider by accelerating of moulting with PA addition. The present study revealed the different ecdysteroid biosynthesis pathways in spiders and insects.
Subject(s)
Ecdysteroids/biosynthesis , Spiders , Animals , Chromatography, Liquid , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Ecdysone , Ecdysterone/analogs & derivatives , Ecdysterone/metabolism , Female , Gene Expression Regulation, Developmental , Genes, Insect , Insect Proteins/metabolism , Metamorphosis, Biological , Molting , Ovary/metabolism , Phylogeny , RNA Interference , Spiders/genetics , Spiders/metabolism , Spiders/physiology , Tandem Mass SpectrometryABSTRACT
Objective: To analyze the association between high density lipoprotein cholesterol (HDL-C) and the risk of cardiovascular disease mortality. Methods: A total of 71 618 residents aged over 18 years with complete baseline data, who were filed on the health information big data platform of Yinzhou district, Ningbo city, Zhejiang Province from 2009 to 2014, were selected as the research population. The research population were divided into four groups according to the level of HDL-C: low-level group (HDL-C<1.0 mmol/L), intermediate-level group (1.0 mmol/L≤HDL-C<1.5 mmol/L), medium-high-level group (1.5 mmol/L≤HDL-C<2.0 mmol/L) and high-level group (HDL-C≥2.0 mmol/L). Cox proportional hazard model was used to calculate the risk ratio of cardiovascular diseases mortality in different groups. Results: The study population was followed up for a total of 427 989.4 person-years, follow-up time of (5.98±1.04)years. During the follow-up period, there were 799 deaths due to cardiovascular diseases. After adjusting for confounding factors, compared with the medium-high-level group as the reference group, the HR (95%CI) for cardiovascular diseases mortality was 1.43 (1.13-1.82) in the low-level group and 1.22 (1.02-1.46) in the high-level group. Conclusion: The low level of HDL-C (<1.5 mmol/L) is associated with a higher risk of cardiovascular disease deaths. The level of HDL-C can be used as a biological indicator to monitor the development of cardiovascular diseases and guide treatment.
Subject(s)
Cardiovascular Diseases , Adult , Cholesterol, HDL , Humans , Middle Aged , Proportional Hazards Models , Risk FactorsABSTRACT
Maintenance of a suitable uterine milieu is important for embryo development and subsequent implantation during early pregnancy. High estrogen level in proestrous and estrous stages is essential for uterine anti-bacterial activity during preimplantation period. Lipocalin-2 is an essential molecule which prevents bacterial infection by sequestering iron. In this study, the highest expression of lipocalin-2 is observed in the endometrial epithelium on day 1 of normal pregnancy and pseudopregnancy, which exhibit a similar hormone scenario. By injecting the agonists for estrogen receptor α and estrogen receptor ß in ovariectomized mice, we found estrogen receptor α is the dominant member for estrogen regulation on lipocalin-2 expression. Estrogen treatment in estrogen receptor α-knockout mice further confirmed the role of estrogen receptor α. Using published data from whole-genome estrogen receptor α binding site assay, significant estrogen receptor α recruitment peaks are found at the downstream of lipocalin-2 gene after estrogen treatment. Furthermore, to study the anti-bacterial activity of lipocalin-2 in uterus, Escherichia coli is injected to mimic bacterial infection. Our results showed an obvious induction of lipocalin-2 in Escherichia coli-treated group. Taken together, this study indicates estrogen regulation of lipocalin-2 in uterine epithelium is mediated by estrogen receptor α, and lipocalin-2 may have anti-bacterial activity during early pregnancy.
Subject(s)
Estrogen Receptor alpha/metabolism , Lipocalin-2/metabolism , Pregnancy, Animal/metabolism , Uterus/metabolism , Animals , Epithelium/metabolism , Escherichia coli , Female , Lipopolysaccharides , Mice , Mice, Knockout , Pregnancy , Pseudopregnancy/metabolismABSTRACT
Lung cancer is the most frequently diagnosed cancer and the most common cause of cancer mortality in China. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers. The mutation rate of epidermal growth factor receptor (EGFR) gene is relatively high, accounts for 32%~38% of all NSCLC. During the last decade, the application of EGFR specific tyrosine kinase inhibitors (TKI) significantly improved prognosis of NSCLC patients with sensitive EGFR mutations. Thus, the research and development of third generation EGFR-TKI have entered the period of rapid development. The fourth generation EGFR-TKI which targeting EGFR C797S has even begun clinical development in China. This review will discuss the clinical research and drug review of EGFR-TKI from the perspective of drug review.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Carcinoma, Non-Small-Cell Lung/enzymology , Carcinoma, Non-Small-Cell Lung/genetics , China , Drug Resistance, Neoplasm , ErbB Receptors/genetics , ErbB Receptors/metabolism , Humans , Lung Neoplasms/enzymology , Lung Neoplasms/genetics , MutationABSTRACT
AIM: To investigate the differential diagnosis value of preoperative computed tomography (CT) features between pre/minimally invasive and invasive adenocarcinoma in pulmonary mixed ground glass nodules (mGGNs). MATERIALS AND METHODS: The histopathological data and CT images of 146 mGGNs in 141 patients were reviewed retrospectively. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to identify the CT features differentiating between pre/minimally invasive and invasive adenocarcinoma and to evaluate their accuracy. RESULTS: In univariate analysis, there were significant differences (p<0.05) in the nodule diameter, volume, density, mass, solid portion volume, shape, margin, air bronchogram, and pleural retraction between pre/minimally invasive and invasive adenocarcinoma. Multivariate logistic regression analyses revealed that nodule mass and volume were statistically significant independent differentiators. ROC curve analysis was performed to evaluate the differentiators. According to the corresponding ROC curve, the optimal cut-off mass to differentiate pre/minimally invasive adenocarcinoma from invasive adenocarcinoma was 254.87 mg, with a sensitivity of 84.52%, a specificity of 88.71%, and an accuracy of 86.30%. Compared with the area under the ROC curve (AUC) for mass, volume, and diameter, the differential diagnosis value of mass was higher than those of volume and diameter. CONCLUSION: Nodule mass and volume were significant differentiators of pre/minimally invasive adenocarcinoma from invasive adenocarcinoma in mGGN, and mass had a higher differential diagnosis value.
Subject(s)
Adenocarcinoma in Situ/pathology , Adenocarcinoma of Lung/pathology , Lung Neoplasms/pathology , Adenocarcinoma in Situ/diagnostic imaging , Adenocarcinoma of Lung/diagnostic imaging , Adult , Aged , Aged, 80 and over , Female , Humans , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Neoplasm Invasiveness , Preoperative Care/methods , ROC Curve , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
Single arm trial (SAT) was widely used for new drug application (NDA) of novel anti-cancer drugs in recent years. The listing time was greatly shortened by SAT while comparing with randomized controlled trials (RCT). Thus, the companies intended to get NDA through SAT. To encourage innovation and accelerate the developments of anti-cancer agents, we summarize the background and key issues of SAT, discuss the conditions of accepting SAT for NDA, and systematically elaborate the design and principles of SAT in this review.
Subject(s)
Antineoplastic Agents/administration & dosage , Neoplasms/drug therapy , Humans , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVE: To explore the potential of autologous dendritic cells (DCs) pulsed with caner/testis antigen NY-ESO-1 peptides in inducing specific cytotoxic T lymphocyte (CTLs) response and antineoplastic immune function of specific CTLs. METHODS: Fifteen patients with II to III stage positive HLA -A0201+ and NY-ESO-1+ were enrolled in the Cancer Hospital Chinese Academy of Medical Sciences on the basis of preclinical experiments from November 2014 to October 2015, and their peripheral blood mononuclear cells (PBMCs) and peripheral blood lymphocytes (PBLs) were isolated. The PBMCs were induced into DCs and pulsed with NY-ESO-1 peptide. The phenotypes of DCs were stained with antibodies against HLA-DR+CD11c+,CD80+,CD83+ and CD86+, and subsequently analyzed by multichannel flow cytometry (FCM). The killing effects of CTLs pulsed with HLA-A0201-binding peptide NY-ESO-1 and the potential of autologous DCs pulsed with NY-ESO-1 peptides in inducing specific cytotoxic T lymphocytes (CTLs) responses were determined. The patients were administered two infusions of auto-logous CTLs for 1 time every two weeks. The total infusion was with 2 times. The immunological responses and clinical responses were examined in 1 week after the final administration. RESULTS: The immunophenotype of DCs pulsed with NY-ESO-1 peptide was analyzed, HLA-DR+CD11c+ cells (93.6%±1.2%), CD80+ cells (87.3%±3.6%), CD83+ cells (82.8%±2.5%) and CD86+ cells (93.4%±6.4%). PBLs isolated from patients primed by DCs pulsed with NY-ESO-1 peptide proliferated continuously and the proliferation index (PI) of the PBLs were analyzed. There was significant difference between the DCs loaded with polypeptides and those unloaded, though it could promote the proliferation of PBLs, but the PI was significantly lower than that of the DCs loaded with NY-ESO-1 peptide (P<0.05). The average percentage of special CTLs primed by DCs pulsed with NY-ESO-1 peptides was significantly higher than that in the control group (5.2%±1.2% vs. 0.4%±0.1%). CTLs induced by NY-ESO-1 pulsed DCs exerted a stronger killing effect on T2 cell line pulsed with NY-ESO-1 peptide than that in the control group at the ratio of E (effect) to T (target) as 30:1, P<0.05. The cytokine levels in the patients'sera such as IFN-γ, IL-2 and IL-12 were increased after treatments [(132.9±10.2) µg/L vs. (46.4±3.1) µg/L; (101.3±6.4) µg/L vs. (26.7±1.2) µg/L; (51.3±2.6) µg/L vs. (26.4±1.1) µg/L; all P<0.05], and the percentages of antigen-specific CD8+IFN-γ+ increased in these patients (P<0.01). CONCLUSION: Auto-DCs pulsed with NY-ESO-1 peptides can induce the proliferation of allogenic CTLs, which elicit specific immune responses ex vivo or in vivo, and boost anticancer immunity markedly.
Subject(s)
Antigens, Neoplasm , Dendritic Cells , Membrane Proteins , Peptides , T-Lymphocytes, Cytotoxic , CD8-Positive T-Lymphocytes , Dendritic Cells/immunology , Humans , Leukocytes, Mononuclear , Male , T-Lymphocytes, Cytotoxic/immunologyABSTRACT
Objective: To explore the role and related mechanisms of angiotensin-(1-7)(Ang-(1-7)) on Toll-like receptor 4 (TLR4) mediated oxidized low-density lipoprotein(ox-LDL)-induced oxidative stress in human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were cultured in vitro and divided into six groups: the control group (normal medium), the ox-LDL group(treated with 75 mg/L ox-LDL), the ox-LDL+ Ang-(1-7) group (1 µmol/L Ang-(1-7) pretreated for 30 minutes, then intervened with 75 mg/L ox-LDL), the ox-LDL+ Ang-(1-7)+ A-779 group(1 µmol/L A-779 (Mas receptor) pretreated for 30 minutes, 1 µmol/L Ang-(1-7) pretreated for 30 minutes, then intervened with 75 mg/L ox-LDL), the ox-LDL+ A-779 group (1 µmol/L A-779 pretreated for 30 minutes, then intervened with 75 mg/L ox-LDL), the ox-LDL+ HTA125 group (10 µg/L HTA125 (TLR4-blocking antibody) pretreated for 30 minutes, then intervened with 75 mg/L ox-LDL ). The corresponding index was detected after 24 hours after intervention. Apoptosis of cells were detected by Annexin V-FITC/PI double staining flow cytometry and transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL). The generation of reactive oxygen species (ROS), products in oxidative stress, were detected by DCFH-DA staining. The mRNA and protein expression levels of NADPH oxidase 4(NOX4) and TLR4 were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis respectively. Results: (1) The results of Annexin V-FITC/PI double staining flow cytometry showed that the proportion of apoptotic cells was higher in ox-LDL group than in control group ((21.18±1.40)% vs. (1.59±0.26)%, P<0.01), lower in ox-LDL+ Ang-(1-7) group((7.42±1.07)%) and ox-LDL+ HTA125 group((9.19±1.01)%) than in ox-LDL group (both P<0.01), higher in ox-LDL+ Ang-(1-7)+ A-779 group ((19.91±1.30)%) and ox-LDL+ A-779 group((20.47±0.95)%) than in ox-LDL+ Ang-(1-7) group (both P<0.01). (2) The TUNEL results showed that the proportion of apoptotic cells was higher in ox-LDL group than in control group((10.83±0.77)% vs. (2.83±0.82)%, P<0.01), lower in ox-LDL+ Ang-(1-7) group ((3.66±0.54)%)and ox-LDL+ HTA125 group((4.97±0.60)%) than in ox-LDL group(both P<0.01), higher in ox-LDL+ Ang-(1-7)+ A-779 group((10.69±0.62)%) and ox-LDL+ A-779 group((11.43±0.42)%) than in ox-LDL+ Ang-(1-7) group (both P<0.01). (3) ROS level was higher in ox-LDL group than in control group(0.093±0.014 vs. 0.053±0.011, P<0.01), lower in ox-LDL+ Ang-(1-7) group (0.063±0.011, P<0.01)and ox-LDL+ HTA125 group(0.070±0.010, P<0.05)than in ox-LDL group, higher in ox-LDL+ Ang-(1-7)+ A-779 group(0.088±0.003) and ox-LDL+ A-779 group(0.095±0.005) than in ox-LDL+ Ang-(1-7) group (both P<0.01). (4) The mRNA expression level of NOX4 was higher in ox-LDL group than in control group(11.74±0.65 vs. 1.00±0.00, P<0.01), lower in ox-LDL+ Ang-(1-7) group (2.85±0.75)and ox-LDL+ HTA125 group(5.57±0.52) than in ox-LDL group(both P<0.01), higher in ox-LDL+ Ang-(1-7)+ A-779 group(10.51±0.54) and ox-LDL+ A-779 group (11.04±1.01) than in ox-LDL+ Ang-(1-7) group (both P<0.01), higher in ox-LDL group than in control group(27.60±1.86 vs. 1.00±0.00, P<0.01), lower in ox-LDL+ Ang-(1-7) group (8.00±1.03)and ox-LDL+ HTA125 group(14.83±0.97)than in ox-LDL group(both P<0.01), higher in ox-LDL+ Ang-(1-7)+ A-779 group(24.81±2.19) and ox-LDL+ A-779 group (26.64±0.65)than in ox-LDL+ Ang-(1-7) group (both P<0.01). (5)The protein expression level of NOX4 was higher in ox-LDL group than in control group (0.61±0.09 vs. 0.23±0.02, P<0.01), lower in ox-LDL+ Ang-(1-7) group(0.27±0.03) and ox-LDL+ HTA125 group(0.22±0.02) than in ox-LDL group(both P<0.01), higher in ox-LDL+ Ang-(1-7)+ A-779 group (0.58±0.06)and ox-LDL+ A-779 group(0.61±0.03) than in ox-LDL+ Ang-(1-7) group (both P<0.01). The protein expression level of TLR4 was higher in ox-LDL group than in control group(0.18±0.02 vs. 0.08±0.01, P<0.01), lower in ox-LDL+ Ang-(1-7) group(0.07±0.01) and ox-LDL+ HTA125 group(0.09±0.01) than in ox-LDL group(both P<0.01), higher in ox-LDL+ Ang-(1-7)+ A-779 group(0.18±0.02) and ox-LDL+ A-779 group(0.20±0.02) than in ox-LDL+ Ang-(1-7) group (both P<0.01). Conclusion: TLR4 mediated the ox-LDL induced injury in HUVECs, and Ang-(1-7) could attenuate ox-LDL induced injury in HUVECs by modulating the specific Mas receptors.
Subject(s)
Angiotensin I , Human Umbilical Vein Endothelial Cells , Oxidative Stress , Peptide Fragments , Toll-Like Receptor 4 , Angiotensin II/analogs & derivatives , Apoptosis , Cells, Cultured , Fluoresceins , Humans , Lipoproteins, LDL , Reactive Oxygen SpeciesABSTRACT
The article "Fas/FasL induces myocardial cell apoptosis in myocardial ischemia-reperfusion rat model", by X.-M. Liu, Z.-M. Yang, X.-K. Liu, published in Eur Rev Med Pharmacol Sci 2017; 21 (12): 2913-2918- PMID: 28682425 has been retracted by the Editor in Chief. Following some concerns raised on PubPeer (link: https://pubpeer.com/publications/29CE1A59A8180E414855FA3871BCAC), the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The authors were informed about the journal's investigation but remained unresponsive and have not provided the manuscript's raw data. The journal's investigation revealed a figure overlap between panels 10 U/mL and 100 U/mL in Figure 1. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/12953.
ABSTRACT
Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.
Subject(s)
Infant, Newborn, Diseases , Infant, Premature, Diseases , Infant , Infant, Newborn , Male , Humans , Female , Pregnancy , Infant, Extremely Premature , Gestational Age , Magnesium Sulfate/therapeutic use , Cross-Sectional Studies , Infant, Premature, Diseases/epidemiology , Steroids , Intensive Care Units, Neonatal , China/epidemiologyABSTRACT
Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Subject(s)
Bronchopulmonary Dysplasia , Retinopathy of Prematurity , Sepsis , Infant , Infant, Newborn , Humans , Birth Weight , Intensive Care Units, Neonatal , Retrospective Studies , Tertiary Care Centers , Infant, Extremely Low Birth Weight , Gestational Age , Infant, Extremely Premature , Sepsis/epidemiology , Retinopathy of Prematurity/epidemiology , Bronchopulmonary Dysplasia/epidemiologySubject(s)
Atherosclerosis , Kruppel-Like Transcription Factors , Macrophages , Monocytes , Humans , InflammationABSTRACT
The aim of this study was to better understand posterior oral cavity cancer (POCC) and its surgical treatment. This was a retrospective study of 76 patients who were diagnosed with POCC and underwent surgical treatment. Twenty-eight patients were treated with anatomical unit resection surgery (AURS) and 48 patients with conventional surgery. After initial treatment with curative intent, the patients were followed-up regularly with clinical examinations and imaging; the median duration of follow-up was 30.9 months (range 2-67 months). The 3-year overall survival was 64.3% in the experimental AURS group and 39.6% in the conventional surgery control group (hazard ratio 0.49, 95% confidence interval 0.26-0.93; P=0.031). The 3-year disease-free survival was 64.3% in the experimental group and 37.5% in the control group (hazard ratio 0.53, 95% confidence interval 0.27-1.02; P=0.114). In conclusion, AURS is an effective surgical treatment for POCC that can considerably improve patient survival rates.
Subject(s)
Mouth Neoplasms , Disease-Free Survival , Humans , Mouth Neoplasms/surgery , Neoplasm Recurrence, Local , Retrospective Studies , Skull Base , Treatment OutcomeABSTRACT
Objective: To investigate ferroptosis in laryngeal squamous cell carcinoma (LSCC) and its regulation by M2 macrophage-derived exosomes. Methods: LSCC and adjacent noncancerous tissue samples were collected from 32 patients treated in the Department of Otorhinolaryngology, Head and Neck Surgery of the Second Affiliated Hospital of Harbin between September 2018 and April 2021, including 26 males and 6 females, aged 43-79 years. The expressions of ferroptosis marker glutathione peroxidase 4(GPX4) in LSCC and adjacent noncancerous tissues were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR). The correlations between GPX4 expression and clinicopathological factors in LSCC were analyzed. Biological changes of TU212 cells after treated with ferroptosis-induced agent erastin were detected by transmission electron microscope, cell counting kit-8(CCK-8), clone test, reactive oxygen species(ROS), malondialdehyde(MDA), glutathione(GSH), JC-1, RT-PCR and western blot. Exosomes were isolated from the supernatant of M0/M2 macrophages (M0-exos/M2-exos) and co-incubated with erastin-treated TU212 cells to detect the change of ferroptosis in cells of each group. The data were analyzed by SPSS software of version19.0. Results: GPX4 expression in LSCC tissues was significantly higher than that in adjacent noncancerous tissues (2.04±0.65 vs. 0.99±0.09, F=30.36, P<0.001), and was closely related to T stage and clinical stage (â -â ¡vs.â ¢-â £: 1.75±0.39 vs. 2.18±0.71, F=2.25, P<0.05; T1-2 vs. T3-4: 1.71±0.42 vs. 2.20±0.69, F=2.06, P<0.05). In TU212 cells treated with erastin, mitochondrial crest became smaller, membrane density increased, proliferation rate decreased, intracellular ROS level increased, mitochondrial membrane potential depolarized, GSH content decreased, intracellular MDA level increased and expressions of GPX4 mRNA and protein decreased. Change of M0 into M2 macrophages was induced by IL-4 stimulation. When erastin-treated TU212 cells were incubated with M2-exos, cell proliferation was partially restored and GPX4 expression was enhanced, and also with the recoveries of levels of ROS, MDA and GSH (all P<0.05). Conclusions: Ferroptosis is one of the cell death ways of LSCC. M2-exos may inhibit ferroptosis of LSCC cells.