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1.
Melanoma Res ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847651

ABSTRACT

This meta-analysis aimed to evaluate the comparative diagnostic performance of reflectance confocal microscopy (RCM) and dermoscopy in detecting cutaneous melanoma patients. An extensive search was conducted in the PubMed and Embase databases to identify available publications up to December 2023. Studies were included if they evaluated the diagnostic performance of RCM and dermoscopy in patients with cutaneous melanoma. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. A total of 14 articles involving 2013 patients were included in the meta-analysis. The overall sensitivity of RCM was 0.94 [95% confidence interval (CI), 0.87-0.98], while the overall sensitivity of dermoscopy was 0.84 (95% CI, 0.71-0.95). These results suggested that RCM has a similar level of sensitivity compared with dermoscopy (P = 0.15). In contrast, the overall specificity of RCM was 0.76 (95% CI, 0.67-0.85), while the overall specificity of dermoscopy was 0.47 (95% CI, 0.31-0.63). The results indicated that RCM appears to have a higher specificity in comparison to dermoscopy (P < 0.01). Our meta-analysis indicates that RCM demonstrates superior specificity and similar sensitivity to dermoscopy in detecting cutaneous melanoma patients. The high heterogeneity, however, may impact the evidence of the current study, further larger sample prospective research is required to confirm these findings.

2.
J Infect Public Health ; 17(7): 102456, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38820896

ABSTRACT

BACKGROUND: A. baumannii is an important and common clinical pathogen, especially in the intensive care unit (ICU). This study aimed to characterize one hypervirulent A. baumannii strain in a patient with community-acquired pneumonia and herpes simplex type 1 virus infection. METHODS: Minimum inhibitory concentrations (MICs) were determined using the Kirby-Bauer (K-B) and broth microdilution methods. Galleria mellonella infection model experiment was conducted. Whole-genome sequencing (WGS) was performed using the Illumina and Nanopore platforms. The resistance and virulence determinants were identified using the ABRicate program with ResFinder and the VFDB database. The capsular polysaccharide locus (K locus) and lipooligosaccharide outer core locus (OC locus) were identified using Kleborate with Kaptive. Phylogenetic analyses were conducted using the BacWGSTdb server. RESULTS: A. baumannii XH2146 strain belongs to ST10Pas and ST447Oxf. The strain was resistant to cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole (TMP-SMX). Bautype and Kaptive analyses showed that XH2146 contains OCL2 and KL49. WGS analysis revealed that the strain harbored blaADC-76, blaOXA-68, ant(3'')-IIa, tet(B), and sul2. Notably, tet(B) and sul2, both were located within a 114,700-bp plasmid (designated pXH2146-1). Virulence assay revealed A. baumannii XH2146 possessed higher virulence than A. baumannii AB5075 at 12 h. Comparative genomic analysis showed that A. baumannii ST447 strains were mainly isolated from the USA and exhibited a relatively close genetic relationship. Importantly, 11 strains were observed to carry blaOXA-58; blaOXA-23 was identified in 11 isolates and three ST447 A. baumannii strains harbored blaNDM-1. CONCLUSIONS: Early detection of community-acquired hypervirulent Acinetobacter baumannii strains is recommended to prevent their extensive spread in hospitals.

3.
Ther Adv Hematol ; 15: 20406207241237594, 2024.
Article in English | MEDLINE | ID: mdl-38481949

ABSTRACT

Multiple myeloma (MM) is a hematological cancer characterized by abnormal proliferation of plasma cells in bone marrow. In recent years, autologous stem cell transplantation (ASCT) has become the cornerstone of MM treatment. At the same time, immunotherapy, such as monoclonal antibody therapy and chimeric antigen receptor T cell (CAR-T) has also emerged, in which CAR-T is the most attractive focus. ASCT and its myeloablative preconditioning will turn its immune microenvironment into an inhibited state, which may provide an opportunity for the expansion of CAR-T cells so as to further clear the residual lesions after ASCT and reduce the recurrence rate after ASCT. Meanwhile, the infusion of CAR-T cells can accelerate the cellular immune reconstruction after ASCT of myeloma, thereby improving the antitumor effect. In order to explore the clinic value, this article reviews the progress and prospect of ASCT combined with CAR-T therapy in the treatment of MM.

4.
Mol Neurobiol ; 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38329682

ABSTRACT

This study aimed to identify autophagy-related candidate genes for the early diagnosis of Alzheimer's disease (AD) and elucidate their potential molecular mechanisms. Differentially expressed genes (DEGs) and phenotype-associated significant module genes were obtained using the "limma" package and weighted gene co-expression network analysis (WGCNA) based on hippocampal tissue datasets from AD patients and control samples. The intersection between the list of autophagy-related genes (ATGs), DEGs, and module genes was further investigated to obtain AD-autophagy-related differential expression genes (ATDEGs). Subsequently, the least absolute shrinkage and selection operator (LASSO) algorithm was utilized to identify hub genes, and a second intersection was performed with important module genes from the protein-protein interaction (PPI) network to obtain co-hub genes. Finally, a diagnostic model was constructed by receiver operating characteristic (ROC) analysis to determine the candidate genes with high diagnostic efficacy in the external validation set. Moreover, immune infiltration analysis was performed on AD patient brain tissues and explore the correlation between candidate genes and immune cells. We further analyzed the expression level of candidate genes in the SH-SY5Y cells with Aß25-35 (25 µM). Among the 17 identified AD-ATDEGs, ATP6V1E1 stood out with area under the curve (AUC) values of 0.869, 0.817, and 0.714 in the external validation set, underscoring its high diagnostic efficacy in both hippocampal and peripheral blood contexts for AD patients. Meanwhile, ATP6V1E1 expression was positively correlated with effector memory CD4 + T cells, while negatively correlated with natural killer T cells and activated CD4 + T cells. Results from quantitative PCR (qPCR) and immunofluorescence assays indicated a reduction in ATP6V1E1 expression, aligning with our database analysis findings. In summary, ATP6V1E1 as a candidate gene provides a new perspective for the early identification and pathogenesis of AD.

5.
J Gastroenterol Hepatol ; 38(9): 1520-1529, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37202867

ABSTRACT

BACKGROUND AND AIM: Postoperative complications are important clinical outcomes for colon cancer patients. This study aimed to investigate the predictive value of inflammatory-nutritional indicators combined with computed tomography body composition on postoperative complications in patients with stage II-III colon cancer. METHODS: We retrospectively collected data from patients with stage II-III colon cancer admitted to our hospital from 2017 to 2021, including 198 patients in the training cohort and 50 patients in the validation cohort. Inflammatory-nutritional indicators and body composition were included in the univariate and multivariate analyses. Binary regression was used to develop a nomogram and evaluate its predictive value. RESULTS: In the multivariate analysis, the monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), nutritional risk score (NRS), skeletal muscle index (SMI), and visceral fat index (VFI) were independent risk factors for postoperative complications of stage II-III colon cancer. In the training cohort, the area under the receiver operating characteristic curve of the predictive model was 0.825 (95% confidence interval [CI] 0.764-0.886). In the validation cohort, it was 0.901 (95% CI 0.816-0.986). The calibration curve showed that the prediction results were in good agreement with the observational results. Decision curve analysis showed that colon cancer patients could benefit from the predictive model. CONCLUSIONS: A nomogram combining MLR, SII, NRS, SMI, and VFI with good accuracy and reliability in predicting postoperative complications in patients with stage II-III colon cancer was established, which can help guide treatment decisions.


Subject(s)
Colonic Neoplasms , Humans , Reproducibility of Results , Retrospective Studies , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/surgery , Body Composition , Inflammation/diagnostic imaging , Inflammation/etiology , Nomograms , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Tomography
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(2): 598-601, 2023 Apr.
Article in Chinese | MEDLINE | ID: mdl-37096541

ABSTRACT

Primary myelofibrosis (PMF) is easily confused with cirrhosis, due to its main clinical manifestations of splenomegaly and the blood cytopenia. This review focuses on clinical studies to identify primary myelofibrosis and cirrhosis related portal hypertension, to analyze the differences between the two diseases, in order to distinguish PMF and cirrhosis from the pathogenesis, clinical manifestations, laboratory examinations and treatment principles, and simultaneously improve clinicians' understanding of PMF, which is a reference for exploring the early screening or diagnostic indicators of PMF, also provides a clinical basis for the application of new targeted drugs such as ruxolitinib.


Subject(s)
Anemia , Hypertension, Portal , Primary Myelofibrosis , Humans , Primary Myelofibrosis/drug therapy , Hypertension, Portal/complications , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Splenomegaly/etiology , Splenomegaly/pathology
7.
J Cancer Res Clin Oncol ; 149(7): 2757-2769, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35776199

ABSTRACT

PURPOSE: A barrier to widespread adoption of chimeric antigen receptor (CAR) T-cell therapy is toxicity. To address this, we recently developed a novel antibody-T-cell receptor (AbTCR) platform (trademarked as ARTEMIS®) which was designed to leverage natural immune receptor signaling and regulation. The AbTCR platform includes a gamma/delta (γδ) TCR-based AbTCR construct and a separate co-stimulatory molecule, both engineered to be tumor-specific. Here, we aim to assess the safety and preliminary efficacy of a CD19-directed AbTCR T-cell therapy. METHODS: We generated ET019003 T cells, which are autologous CD19-directed AbTCR T cells. We then conducted an early phase I study to evaluate the safety and preliminary efficacy of ET019003 T cells for the treatment of CD19-positive relapsed/refractory (r/r) B-cell lymphoma. RESULTS: Sixteen patients enrolled in this study and 12 patients were treated. Of the 12 patients treated, 6 patients (50%) achieved a complete response (CR), and 4 (33%) achieved a partial response (PR) (best objective response rate [ORR] of 83%). CRs were durable, including 2 patients with ongoing CRs for 22.7 months and 23.2 months. ET019003 was well-tolerated with an attractive safety profile. No patients experienced severe (grade ≥ 3) cytokine release syndrome (CRS) and only 1 patient experienced immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade. Significant elevations of cytokine levels were not seen, even in patients with marked expansion of ET019003 T cells. CONCLUSION: This study provides initial clinical validation of the AbTCR platform as a novel cancer treatment with the potential to provide durable clinical benefit with low toxicity. TRIAL REGISTRATION: NCT03642496; Date of registration: August 22, 2018.


Subject(s)
Lymphoma, B-Cell , Neurotoxicity Syndromes , Humans , Receptors, Antigen, T-Cell , Lymphoma, B-Cell/therapy , Lymphoma, B-Cell/etiology , Neurotoxicity Syndromes/etiology , Immunotherapy, Adoptive/adverse effects , Antibodies , Antigens, CD19 , Cell- and Tissue-Based Therapy
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(10): 1375-1384, 2022 Oct 28.
Article in English, Chinese | MEDLINE | ID: mdl-36411688

ABSTRACT

OBJECTIVES: Prediabetes is associated with an increased risk of cognitive impairment and neurodegenerative diseases. However, the exact mechanism of prediabetes-related brain diseases has not been fully elucidated. The brain structure of patients with prediabetes has been damaged to varying degrees, and these changes may affect the topological characteristics of large-scale brain networks. The structural covariance of connected gray matter has been demonstrated valuable in inferring large-scale structural brain networks. The alterations of gray matter structural covariance networks in prediabetes remain unclear. This study aims to examine the topological features and robustness of gray matter structural covariance networks in prediabetes. METHODS: A total of 48 subjects were enrolled in this study, including 23 patients with prediabetes (the PD group) and 25 age-and sex-matched healthy controls (the Ctr group). All subjects' high-resolution 3D T1 images of the brain were collected by a 3.0 Tesla MR machine. Mini-mental state examination was used to evaluate the cognitive status of each subject. We calculated the gray matter volume of 116 brain regions with automated anatomical labeling (AAL) template, and constructed gray matter structural covariance networks by thresholding interregional structural correlation matrices as well as graph theoretical analysis. The area under the curve (AUC) in conjunction with permutation testing was employed for testing the differences in network measures, which included small world parameter (Sigma), normalized clustering coefficient (Gamma), normalized path length (Lambda), global efficiency, characteristic path length, local efficiency, mean clustering coefficient, and network robustness parameters. RESULTS: The network in both groups followed small-world characteristics, showing that Sigma was greater than 1, the Lambda was much higher than 1, and Gamma was close to 1. Compared with the Ctr group, the network of the PD group showed increased Sigma, Lambda, and Gamma across a range of network sparsity. The Gamma of the PD group was significantly higher than that in the Ctr group in the network sparsity range of 0.12-0.16, but there was no difference between the 2 groups (all P>0.05). The grey matter network showed an increased characteristic path length and a decreased global efficiency in the PD group, but AUC analysis showed that there was no significant difference between groups (all P>0.05). For the network separation measures, the local efficiency and mean clustering coefficient of the gray matter network in the PD group were significantly increased and AUC analysis also confirmed it (P=0.001 and P=0.004, respectively). In addition, network robustness analysis showed that the grey matter network of the PD group was more vulnerable to random damage (P=0.001). CONCLUSIONS: The prediabetic gray matter network shows an increased average clustering coefficient and local efficiency, and is more vulnerable to random damage than the healthy control, suggesting that the topological characteristics of the prediabetes grey matter covariant network have changed (network separation enhanced and network robustness reduced), which may provide new insights into the brain damage relevant to the disease.


Subject(s)
Gray Matter , Prediabetic State , Humans , Gray Matter/diagnostic imaging , Magnetic Resonance Imaging , Cerebral Cortex , Brain
9.
Sensors (Basel) ; 22(16)2022 Aug 18.
Article in English | MEDLINE | ID: mdl-36015974

ABSTRACT

Blind image deblurring is a challenging problem in computer vision, aiming to restore the sharp image from blurred observation. Due to the incompatibility between the complex unknown degradation and the simple synthetic model, directly training a deep convolutional neural network (CNN) usually cannot sufficiently handle real-world blurry images. An existed generative adversarial network (GAN) can generate more detailed and realistic images, but the game between generator and discriminator is unbalancing, which leads to the training parameters not being able to converge to the ideal Nash equilibrium points. In this paper, we propose a GAN with a dual-branch discriminator using multiple sparse priors for image deblurring (DBSGAN) to overcome this limitation. By adding the multiple sparse priors into the other branch of the discriminator, the task of the discriminator is more complex. It can balance the game between the generator and the discriminator. Extensive experimental results on both synthetic and real-world blurry image datasets demonstrate the superior performance of our method over the state of the art in terms of quantitative metrics and visual quality. Especially for the GOPRO dataset, the averaged PSNR improves 1.7% over others.


Subject(s)
Image Processing, Computer-Assisted , Neural Networks, Computer , Image Processing, Computer-Assisted/methods
10.
Article in English | MEDLINE | ID: mdl-35682018

ABSTRACT

In light of the traffic congestion and traffic environment problems around schools that are caused by students commuting by car, this paper explores an efficient and feasible student commuting travel plan. Based on the ideas of "public-private cooperation" and "parking sharing", combined with the characteristics of the family travel chain during the commuting period, a joint-commuting model of "private car and school bus" is creatively proposed. On the basis of considering the travel cost of parents and the operating cost of school bus, a two-phase commuting travel model for primary and secondary schools is proposed, and an algorithm is designed. The validity of the model is verified by an example and sensitivity analysis. The results show that the total time cost can be reduced by 23.33% when the private-car commuting mode is converted to the joint-commuting model. Among the results, we found that the driving time of a private car in the school commuting phase can be reduced by 23.36%, the dwell time can be reduced by 92.29%, and the driving time in the work and home phase can be reduced by 7.44%. Compared with the school-bus commuting mode, the school-bus time cost of joint commuting can be reduced by 54.88%. In addition, by analyzing the impact of various factors on the objective function and vehicle emissions, it can be seen that staggered commuting to school, regulating regional traffic volume, increasing parking spaces, and improving the utilization of parking spaces can effectively reduce the operating time cost of vehicles and exhaust emissions. The joint-commuting model proposed in this paper considers the balance between service level and resource consumption. While meeting the door-to-door travel needs of students, it can effectively reduce the travel costs of parents and school-bus operation costs, and it can alleviate traffic congestion around schools and reduce the impact on the environment.


Subject(s)
Transportation , Walking , Bicycling , Humans , Motor Vehicles , Schools , Transportation/methods , Vehicle Emissions/analysis
11.
Article in English | MEDLINE | ID: mdl-35682150

ABSTRACT

Student commuting is an important part of urban travel demand and private car commuting plays an important role in urban traffic, especially in areas near schools. Since parents, especially the parents of elementary and junior high school students, prefer to drive rather than take public transport, there will be a negative effect on traffic management. To address the challenge, a simulation model is established based on schools' surrounding regions to analyze traffic status. Specifically, the model focuses on urban construction and transportation near the entrance of schools and neighborhoods. In addition, four variable parameters consisting of the directional hourly volume, the parking demand of delivery vehicles, the distance between the school and intersection, and the average parking time for pick-up vehicles are set as influence factors, while traffic efficiency, energy consumption, and pollutant emissions are considered as the evaluation criteria of our model. Extensive simulated experiments show that comparing different scenarios, the traffic state of schools' surrounding areas can achieve much better performance when the distance between entrances and intersections is 400 m under the 1000 pcu/h condition. This research can provide a scientific basis for school regional traffic management and organization optimization.


Subject(s)
Schools , Transportation , Humans , Students , Walking
12.
Front Immunol ; 12: 724411, 2021.
Article in English | MEDLINE | ID: mdl-34867949

ABSTRACT

The expression level of BCMA in bone marrow of 54 MM patients was detected in this study to explore the relationship between the BCMA expression and the classification, stage, and prognostic factors of MM. The BCMA expression level of the stable group and remission group was lower than that of the newly diagnosed group and relapse group (P=0.001). There was no significant difference in BCMA expression of MM patients in different types and stages (P>0.05), but it was found that for the newly diagnosed MM patients, the BCMA expression level of IgG patients was higher than that of IgA or light-chain patients (rank average 11.20 vs 5.44, P=0.014). There was no significant correlation between the BCMA expression and the age and serum creatinine of MM patients (P>0.05). And there was no significant difference in BCMA expression between patients with different levels of age and serum creatinine (P>0.05). But it was found that the BCMA expression level of the newly diagnosed MM patients was moderately positively correlated with their age (P=0.025, r=0.595). There was no significant correlation between the BCMA expression and serum ß2-microglobulin, serum lactate dehydrogenase, free kap/lam ratio, and urine ß2-microglobulin (P>0.05). But we found that the BCMA expression of patients with high serum ß2-microglobulin was higher than that of patients with low serum ß2-microglobulin (rank average 28.89 vs 17.54, P=0.017). And the BCMA expression of patients with abnormal serum free kap/lam ratio was higher than that of patients with normal ratio (rank average 28.49 vs 13.55, P=0.004). The BCMA expression was strongly positively correlated with 24-h urine protein, was moderately positively correlated with serum M protein and the percentage of plasma cells in bone marrow, was moderately negatively correlated with albumin and hemoglobin count, and was weakly positively correlated with serum corrected calcium (P<0.05). And it was found that the BCMA expression of positive serum immunofixation electrophoresis patients was higher than that of negative patients (rank average 29.94 vs 16.75, P=0.017). And we try to clarify the relationship between the bone marrow BCMA expression and the peripheral blood sBCMA expression. However, we have not found a clear correlation between them so far (P>0.05).


Subject(s)
B-Cell Maturation Antigen/immunology , Bone Marrow/immunology , Multiple Myeloma , Female , Humans , Immunoglobulins/immunology , Immunotherapy, Adoptive , Male , Middle Aged , Multiple Myeloma/classification , Multiple Myeloma/immunology , Multiple Myeloma/pathology , Multiple Myeloma/therapy , Neoplasm Staging , Prognosis , Receptors, Chimeric Antigen
13.
Article in English | MEDLINE | ID: mdl-34795784

ABSTRACT

OBJECTIVE: To explore the diagnostic value of serum heparin binding protein (HBP), blood lactic acid (Lac) combined with high-sensitivity C- reactive protein (hs-CRP) in sepsis and its relationship with prognosis. METHODS: The clinical data of 127 patients with sepsis from March 2019 to March 2021 in our hospital were retrospectively analyzed. 120 outpatients undergoing physical examination in the same period in our hospital were selected as the control group. According to the severity of the disease, 127 sepsis patients were divided into the mild sepsis group (n = 45), severe sepsis group (n = 53), and septic shock group (n = 29). According to the clinical prognosis, the patients were divided into the survival group (n = 96) and death group (n = 31). Serum HBP, Lac, and hs-CRP levels were measured in all subjects. The ROC curves of the subjects were drawn to analyze the predictive value of serum HBP, Lac, and hs-CRP for the prognosis of sepsis patients. RESULTS: The levels of serum HBP, Lac, and hs-CRP in the sepsis group were higher than those in the control group (P < 0.05). With the increase of the severity of sepsis, serum HBP, Lac, and hs-CRP levels of patients gradually increased (P < 0.05). The levels of serum HBP, Lac, and hs-CRP in the death group were higher than those in the survival group (P < 0.05). The AUC of serum HBP, Lac, and hs-CRP for predicting the prognosis of sepsis patients was 0.858 (95% CI: 0.763-0.953), 0.694 (95% CI: 0.589-0.799), and 0.843 (95% CI: 0.759-0.927). The AUC of serum HBP, Lac combined with hs-CRP for predicting the prognosis of sepsis patients was 0.961 (95% CI: 0.000-1.000). CONCLUSION: The levels of serum HBP, Lac, and hs-CRP in patients with sepsis were significantly increased and increased with the severity of sepsis. Serum HBP, Lac, and hs-CRP have a good value in predicting the prognosis of patients with sepsis and worthy of clinical application.

14.
Quant Imaging Med Surg ; 11(10): 4310-4320, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34603986

ABSTRACT

BACKGROUND: Increasing evidence shows that the default mode network (DMN) and cerebellum are prone to structural and functional abnormalities in patients with type 2 diabetes mellitus (T2DM). However, the type of change in the functional connection between the DMN and cerebellum is still unknown. METHODS: In this study, seed-based functional connectivity (FC) analysis was used to examine the intrinsic FC of the cerebellum-DMN between healthy controls (HCs) and T2DM patients. Pearson correlation analysis was used to explore the relationship between clinical variables and changes in FC. RESULTS: Compared with HCs, T2DM patients showed significantly increased FC of the left crus I-left medial superior frontal gyrus, left crus I-right medial superior frontal gyrus, and right crus I-left medial orbitofrontal cortex. Compared with HCs, T2DM patients showed decreased FC of the lobule IX-the right angular gyrus. Moreover, diabetes duration was positively correlated with increased FC of the left crus I-right medial superior frontal gyrus (r=0.438, P=0.007). CONCLUSIONS: Concomitant functional impairment and reorganization in the linkage between the cerebellum and DMN in patients with T2DM may be a biomarker of early brain damage that can help us better understand the pathogenesis of cognitive impairment in T2DM.

15.
Cancer Sci ; 112(7): 2679-2691, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33949040

ABSTRACT

BCR-ABL1 gene fusion associated with additional DNA lesions involves the pathogenesis of chronic myelogenous leukemia (CML) from a chronic phase (CP) to a blast crisis of B lymphoid (CML-LBC) lineage and BCR-ABL1+ acute lymphoblastic leukemia (BCR-ABL1+ ALL). The recombination-activating gene RAG1 and RAG2 (collectively, RAG) proteins that assemble a diverse set of antigen receptor genes during lymphocyte development are abnormally expressed in CML-LBC and BCR-ABL1+ ALL. However, the direct involvement of dysregulated RAG in disease progression remains unclear. Here, we generate human wild-type (WT) RAG and catalytically inactive RAG-expressing BCR-ABL1+ and BCR-ABL1- cell lines, respectively, and demonstrate that BCR-ABL1 specifically collaborates with RAG recombinase to promote cell survival in vitro and in xenograft mice models. WT RAG-expressing BCR-ABL1+ cell lines and primary CD34+ bone marrow cells from CML-LBC samples maintain more double-strand breaks (DSB) compared to catalytically inactive RAG-expressing BCR-ABL1+ cell lines and RAG-deficient CML-CP samples, which are measured by γ-H2AX. WT RAG-expressing BCR-ABL1+ cells are biased to repair RAG-mediated DSB by the alternative non-homologous end joining pathway (a-NHEJ), which could contribute genomic instability through increasing the expression of a-NHEJ-related MRE11 and RAD50 proteins. As a result, RAG-expressing BCR-ABL1+ cells decrease sensitivity to tyrosine kinase inhibitors (TKI) by activating BCR-ABL1 signaling but independent of the levels of BCR-ABL1 expression and mutations in the BCR-ABL1 tyrosine kinase domain. These findings identify a surprising and novel role of RAG in the functional specialization of disease progression in BCR-ABL1+ leukemia through its endonuclease activity.


Subject(s)
DNA-Binding Proteins/metabolism , Endonucleases/metabolism , Fusion Proteins, bcr-abl/metabolism , Homeodomain Proteins/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Nuclear Proteins/metabolism , Acid Anhydride Hydrolases/metabolism , Animals , Blast Crisis/genetics , Blast Crisis/metabolism , Cell Line, Tumor , Cell Proliferation , Cell Survival , DNA Breaks, Double-Stranded , DNA End-Joining Repair , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , Disease Progression , Fusion Proteins, bcr-abl/genetics , Genomic Instability , Heterografts , Histones/analysis , Homeodomain Proteins/genetics , Humans , In Vitro Techniques , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , MRE11 Homologue Protein/metabolism , Mice , Mice, Inbred NOD , Mice, SCID , Nuclear Proteins/deficiency , Nuclear Proteins/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Protein Kinase Inhibitors/therapeutic use
16.
Front Surg ; 8: 646091, 2021.
Article in English | MEDLINE | ID: mdl-33644112

ABSTRACT

Groin hernioplasty is the most performed intervention in the adults worldwide, the minimally invasive inguinal hernia repair techniques widely used by surgeons today are transabdominal preperitoneal patch plasty (TAPP) and total extraperitoneal patch plasty (TEP). We report a 62-year-old man with bowel obstruction caused by the use of self-anchoring barbed suture to close the peritoneum 3 days after TAPP. Surgeons using the barbed suture should be alert to this possibility when encountering this complication of intestinal obstruction, so as to avoid more serious consequences.

17.
RSC Adv ; 11(53): 33481-33489, 2021 Oct 08.
Article in English | MEDLINE | ID: mdl-35497512

ABSTRACT

Natural molybdenite, an inexpensive and naturally abundant material, can be directly used as an anode material for lithium-ion batteries. However, how to release the intrinsic capacity of natural molybdenite to achieve high rate performance and high capacity is still a challenge. Herein, we introduce an innovative, effective, and one-step approach to preparing a type of heterostructure material containing 1T@2H MoS2 crafted from insertion and expansion of natural molybdenite. The metallic 1T phase formed in situ can significantly improve the electronic conductivity of MoS2. At the same time, 1T@2H MoS2 heterostructures can provide an internal electric field (E-field) to accelerate the migration rate of electrons and ions, promote the charge transfer behaviour, and ensure the reaction reversibility and lithium storage kinetics. Such worm-like 1T@2H MoS2 heterostructures also have a large specific surface area and a large number of defects, which will help shorten the lithium-ion transmission distance and provide more ion transmission channels. As a result, it exhibits a discharge capacity of 788 mA h g-1 remarkably at 100 mA g-1 after 485 cycles and stable cycling performance. It also shows excellent magnification performance of 727 mA h g-1 at 1 A g-1, compared to molybdenite concentrate. Briefly, this work's heterostructure architectures open up a new avenue for applying natural molybdenite in lithium-ion batteries, which has the potential to achieve large-scale commercial applications.

18.
Hum Brain Mapp ; 42(2): 329-344, 2021 02 01.
Article in English | MEDLINE | ID: mdl-33064332

ABSTRACT

Antisocial behavior (ASB) is believed to have neural substrates; however, the association between ASB and functional brain networks remains unclear. The temporal variability of the functional connectivity (or dynamic FC) derived from resting-state functional MRI has been suggested as a useful metric for studying abnormal behaviors including ASB. This is the first study using low-frequency fluctuations of the dynamic FC to unravel potential system-level neural correlates with ASB. Specifically, we individually associated the dynamic FC patterns with the ASB scores (measured by Antisocial Process Screening Device) of the male offenders (age: 23.29 ± 3.36 years) based on machine learning. Results showed that the dynamic FCs were associated with individual ASB scores. Moreover, we found that it was mainly the inter-network dynamic FCs that were negatively associated with the ASB severity. Three major high-order cognitive functional networks and the sensorimotor network were found to be more associated with ASB. We further found that impaired behavior in the ASB subjects was mainly associated with decreased FC dynamics in these networks, which may explain why ASB subjects usually have impaired executive control and emotional processing functions. Our study shows that temporal variation of the FC could be a promising tool for ASB assessment, treatment, and prevention.


Subject(s)
Antisocial Personality Disorder/diagnostic imaging , Antisocial Personality Disorder/psychology , Brain/diagnostic imaging , Nerve Net/diagnostic imaging , Adolescent , Adult , Humans , Magnetic Resonance Imaging/methods , Male , Young Adult
19.
Chemosphere ; 263: 127849, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33297003

ABSTRACT

Cyhalofop-butyl is a kind of aromatic phenoxypropionic acid herbicide widely used in agriculture. However, studies on its immunotoxicity to aquatic organisms have not been reported. In this study paper, morphological, immunological, cytological, biochemical and molecular biology methods were used to study the effects of cyhalofop-butyl on the developmental toxicity and immunotoxicity in zebrafish. After cyhalofop-butyl exposed, the results showed that the zebrafish embryos had shorter length, yolk sac edema, significantly reduced number of immune cells, inflammatory response and immunocytes apoptosis. In addition, we found that the expression of immune-related genes and pro-apoptotic genes were up-regulated, and the JAK-STAT signaling pathway mediated the immunotoxicity induced by cyhalofop-butyl. Therefore, our results indicate that cyhalofop-butyl has developmental toxicity and immunotoxicity to zebrafish, and this study offer new contents for the effects of cyhalofop-butyl exposure on aquatic organisms.


Subject(s)
Water Pollutants, Chemical , Zebrafish , Animals , Butanes , Embryo, Nonmammalian , Embryonic Development , Nitriles , Water Pollutants, Chemical/toxicity
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1109-1114, 2020.
Article in English, Chinese | MEDLINE | ID: mdl-33051426

ABSTRACT

OBJECTIVES: To investigate volume changes of subcortical structures in patients with post-hepatitis B cirrhosis. METHODS: Thirty patients with post-hepatitis B cirrhosis (the cirrhosis group) and 24 age- and sex-matched healthy controls (the control group) were enrolled in this prospective study. All subjects underwent neuropsychological tests, blood biochemical determinations, and cerebral MRI. Volumes of 18 selected subcortical structures were automatically segmented and analyzed by the FreeSurfer. In the cirrhosis group, the relationships between abnormal subcortical volumes and clinical index or neurocognitive performance were investigated. The relationships between globus pallidus volumes and pallidal hyperintensity were also examined. RESULTS: Compared with the healthy controls, patients with post-hepatitis B cirrhosis displayed smaller bilateral putamen, amygdala, and nucleus accumbens volumes and larger bilateral globus pallidus volumes (P<0.001 or P=0.001). In the cirrhosis group, the volumes of left putamen and amygdala were negatively correlated with the number connection test-A (NCT-A)(left putamen r=-0.410, P=0.034; left amygdala r=-0.439, P=0.022), and the volumes of bilateral globus pallidus were positively correlated with pallidal index (PI) (left globus pallidus r=0.889, P<0.001; right globus pallidus r=0.900, P<0.001). CONCLUSIONS: Abnormalities of subcortical volumes appear bilaterally symmetrical in patients with post-hepatitis B cirrhosis. Atrophy of left putamen and amygdala might contribute to poor neurocognitive performance, and the manganese deposition might contribute to the increased globus pallidus volumes in patients with post-hepatitis B cirrhosis.


Subject(s)
Hepatitis B , Magnetic Resonance Imaging , Hepatitis B/complications , Hepatitis B/diagnostic imaging , Humans , Liver Cirrhosis/diagnostic imaging , Neuropsychological Tests , Prospective Studies
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