Publications by authors named "Haiqing Li"

139 Publications

Molecular and Clinical Features of Hospital Admissions in Patients with Thoracic Malignancies on Immune Checkpoint Inhibitors.

Cancers (Basel) 2021 May 28;13(11). Epub 2021 May 28.

Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010-3000, USA.

Lung cancer patients undergoing systemic treatment with immune checkpoint inhibitors (ICIs) can lead to severe immune-related adverse events (irAEs) that may warrant immediate hospitalization. Patients with thoracic malignancies hospitalized at City of Hope while undergoing treatment with ICIs were identified. Pathology and available next-generation sequencing (NGS) data, including the programmed death-ligand 1 (PD-L1) status and clinical information, including hospitalizations, invasive procedures, and the occurrence of irAEs, were collected. Unpaired T-tests, Chi-square/Fisher's exact test, and logistic regression were used to analyze our cohort. The overall survival (OS) was calculated and compared using univariate and multivariate COX models. Ninety patients with stage IV lung cancer were admitted after ICI treatment. Of those patients, 28 (31.1%) had documented irAEs. Genomic analyses showed an enrichment of mutations ( = 5/6 vs. = 7/26, 83.3% vs. 26.9%; odds ratio (OR) (95% confidence interval (CI): 13.5 (1.7-166.1); < 0.05) and mutations ( = 4/6, 66.7% vs. = 5/26, 19.2%; OR (95% CI): 8.4 (1.3-49.3), < 0.05) in patients with irAE occurrences. Patients with somatic genomic alterations (GAs) in (median OS of 2.7 vs. 7.2 months; HR (95% CI): 3.1 (0.57-17.1); < 0.05) or (median OS of 3.0 vs. 12.4 months; HR (95% CI): 3.1 (0.70-13.8); < 0.05) demonstrated a significantly shorter OS. Patients with irAEs showed a trend toward improved OS (median OS 16.4 vs. 6.8 months, = 0.19) compared to hospitalized patients without documented irAEs. Lung cancer patients who required treatment discontinuance or interruption due to irAEs ( = 19) had significantly longer OS (median OS 18.5 vs. 6.2 months; HR (95% CI): 0.47 (0.28-0.79); < 0.05). Our results showed a significant survival benefit in lung cancer patients hospitalized due to irAEs that necessitated a treatment interruption. Patients with positive somatic GAs in and were associated with significantly worse OS compared to patients with negative GAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13112653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198372PMC
May 2021

Microglial Exosomes in Neurodegenerative Disease.

Front Mol Neurosci 2021 11;14:630808. Epub 2021 May 11.

Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.

Microglia play an important role in neurodegenerative disease [i.e., Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS)]. These diseases share some similar pathological changes and several microglia-associated processes, including immune response, neuroinflammation, phagocytosis, elimination of synapses et al. Microglia in the central nervous system (CNS) has been described as having both destructive and protective effects in neurological disorders. Besides, considerable evidence also indicates that microglia play a significant role in neurogenesis, neuronal cell death, and synaptic interactions. The communication between microglia and neurons is of vital role in regulating complex functions which are key to appropriate the activity of the brain. Accumulating studies have also demonstrated that exosomes with sizes ranging from 40-100 nm, released by microglia, could serve as key mediators in intercellular signaling. These exosomes, identified in terms of cellular origin in many kinds of biological fluids, exert their effects by delivering specific cargos such as proteins, microRNAs (miRNAs), and mRNAs. It was shown that microglial exosomes could transport to and be uptake by neurons, which may either be beneficial or instead, detrimental to CNS diseases. The focus of this review is to summarize the involvement of microglial exosomes in critical pathologies associated with neurodegenerative disease and how they contribute to these disorders, including PD, AD, and ALS. We also review the application of microglia exosomes as potential biomarkers in monitoring disease progression, as well as focusing on their roles as drug delivery vehicles in treating neurodegenerative disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnmol.2021.630808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148341PMC
May 2021

Teaching NeuroImages: Symmetric Deep Cerebellar White Matter T2 and SWI Hypointense Lesions in a Case of Cerebrotendinous Xanthomatosis.

Neurology 2021 May 4. Epub 2021 May 4.

Yue Zhang, Huashan Hospital, Fudan University, Department of Neurology, Shanghai, China; Yimin Sun, Huashan Hospital, Fudan University, Department of Neurology, Shanghai, China; Haiqing Li, Huashan Hospital, Fudan University, Department of Radiology, Shanghai, China;

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000012154DOI Listing
May 2021

Pulmonary tuberculosis as a risk factor for chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Ann Transl Med 2021 Mar;9(5):390

State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Prior pulmonary tuberculosis (TB) can cause permanent changes in lung anatomy and is associated with lung function loss. However, it remains unclear whether pulmonary function impairment owing to TB is associated with airflow obstruction, the hallmark of chronic obstructive pulmonary disease (COPD). The aim of this systematic review and meta-analysis was to assess the association and quantify the magnitudes of association between pulmonary TB and COPD, and to evaluate the prevalence of COPD in patients with prior pulmonary TB.

Methods: We searched the PubMed, Embase, and Web of Science databases for studies published from inception to January 1, 2020. Pooled effect sizes were calculated according to a random effects model or fixed effect model depending on heterogeneity. Specific subgroups (different diagnostic criteria, smoking status, income level) were examined.

Results: A total of 23 articles were included in this study. Compared with controls, patients with pulmonary TB had an odds ratios (ORs) of 2.59 [95% confidence interval (CI): 2.12-3.15; P<0.001] for developing COPD. In jackknife sensitivity analyses, the increased risk of prior pulmonary TB remained consistent for COPD; when the meta-analysis was repeated and one study was omitted each time, the ORs and corresponding 95% CIs were greater than 2. Funnel plots of ORs with Egger's linear regression (t=2.00, P=0.058) and Begg's rank correlation (Z=0.75, P=0.455) showing no significant publication bias. Subgroup analysis showed that the same conclusion was still present in never smokers (ORs 2.41; 95% CI: 1.74-3.32; P<0.001), patients with pulmonary TB diagnosed using chest X-ray (ORs 2.47; 95% CI: 1.23-4.97; P<0.001), and low- and middle-income country (LMIC) settings (ORs 2.70; 95% CI: 2.08-3.51; P<0.001). The pooled prevalence of COPD in patients with prior pulmonary TB was 21% (95% CI: 16-25%; P<0.001).

Conclusions: Individuals with prior pulmonary TB have an increased risk and high prevalence of COPD. Future studies identifying the underlying mechanisms for TB-associated COPD and therapeutic strategies are required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-4576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033376PMC
March 2021

Serum Neurofilament Light and GFAP Are Associated With Disease Severity in Inflammatory Disorders With Aquaporin-4 or Myelin Oligodendrocyte Glycoprotein Antibodies.

Front Immunol 2021 16;12:647618. Epub 2021 Mar 16.

Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

To evaluate the potential of serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP) as disease biomarkers in neuromyelitis optica spectrum disorder (NMOSD) with aquaporin-4 antibody (AQP4-ab) or myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD). Patients with AQP4-ab-positive NMOSD ( = 51), MOGAD ( = 42), and relapsing-remitting multiple sclerosis (RRMS) ( = 31 for sNfL and = 22 for sGFAP testing), as well as healthy controls (HCs) ( = 28), were enrolled prospectively. We assessed sNfL and sGFAP levels using ultrasensitive single-molecule array assays. Correlations of sNfL and sGFAP levels with clinical parameters were further examined in AQP4-ab-positive NMOSD and MOGAD patients. sNfL levels were significantly higher in patients with AQP4-ab-positive NMOSD (median 17.6 pg/mL), MOGAD (27.2 pg/mL), and RRMS (24.5 pg/mL) than in HCs (7.4 pg/mL, all < 0.001). sGFAP levels were remarkably increased in patients with AQP4-ab-positive NMOSD (274.1 pg/mL) and MOGAD (136.7 pg/mL) than in HCs (61.4 pg/mL, both < 0.001). Besides, sGFAP levels were also significantly higher in patients with AQP4-ab-positive NMOSD compared to those in RRMS patients (66.5 pg/mL, < 0.001). The sGFAP/sNfL ratio exhibited good discrimination among the three disease groups. sNfL levels increased during relapse in patients with MOGAD ( = 0.049) and RRMS ( < 0.001), while sGFAP levels increased during relapse in all three of the disease groups (all < 0.05). Both sNfL and sGFAP concentrations correlated positively with Expanded Disability Status Scale scores in AQP4-ab-positive NMOSD (β = 1.88, = 0.018 and β = 2.04, = 0.032) and MOGAD patients (β = 1.98, = 0.013 and β = 1.52, = 0.008). sNfL and sGFAP levels are associated with disease severity in AQP4-ab-positive NMOSD and MOGAD patients, and the sGFAP/sNfL ratio may reflect distinct disease pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.647618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008082PMC
March 2021

Deep Learning for Automatic Differential Diagnosis of Primary Central Nervous System Lymphoma and Glioblastoma: Multi-Parametric Magnetic Resonance Imaging Based Convolutional Neural Network Model.

J Magn Reson Imaging 2021 Mar 11. Epub 2021 Mar 11.

Academy for Engineering and Technology, Fudan University, Shanghai, China.

Background: Differential diagnosis of primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is useful to guide treatment strategies.

Purpose: To investigate the use of a convolutional neural network (CNN) model for differentiation of PCNSL and GBM without tumor delineation.

Study Type: Retrospective.

Population: A total of 289 patients with PCNSL (136) or GBM (153) were included, the average age of the cohort was 54 years, and there were 173 men and 116 women.

Field Strength/sequence: 3.0 T Axial contrast-enhanced T -weighted spin-echo inversion recovery sequence (CE-T WI), T -weighted fluid-attenuation inversion recovery sequence (FLAIR), and diffusion weighted imaging (DWI, b = 0 second/mm , 1000 seconds/mm ).

Assessment: A single-parametric CNN model was built using CE-T WI, FLAIR, and the apparent diffusion coefficient (ADC) map derived from DWI, respectively. A decision-level fusion based multi-parametric CNN model (DF-CNN) was built by combining the predictions of single-parametric CNN models through logistic regression. An image-level fusion based multi-parametric CNN model (IF-CNN) was built using the integrated multi-parametric MR images. The radiomics models were developed. The diagnoses by three radiologists with 6 years (junior radiologist Y.Y.), 11 years (intermediate-level radiologist Y.T.), and 21 years (senior radiologist Y.L.) of experience were obtained.

Statistical Analysis: The 5-fold cross validation was used for model evaluation. The Pearson's chi-squared test was used to compare the accuracies. U-test and Fisher's exact test were used to compare clinical characteristics.

Results: The CE-T WI, FLAIR, and ADC based single-parametric CNN model had accuracy of 0.884, 0.782, and 0.700, respectively. The DF-CNN model had an accuracy of 0.899 which was higher than the IF-CNN model (0.830, P = 0.021), but had no significant difference in accuracy compared to the radiomics model (0.865, P = 0.255), and the senior radiologist (0.906, P = 0.886).

Data Conclusion: A CNN model can differentiate PCNSL from GBM without tumor delineation, and comparable to the radiomics models and radiologists.

Level Of Evidence: 4 TECHNICAL EFFICACY: Stage 2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.27592DOI Listing
March 2021

Brain structural alterations in MOG antibody diseases: a comparative study with AQP4 seropositive NMOSD and MS.

J Neurol Neurosurg Psychiatry 2021 Jul 9;92(7):709-716. Epub 2021 Mar 9.

Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Background: Brain structural alterations and their clinical significance of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) have not been determined.

Methods: We recruited 35 MOGAD, 38 aquaporin 4 antibody positive neuromyelitis optica spectrum diseases (AQP4+ NMOSD), 37 multiple sclerosis (MS) and 60 healthy controls (HC) who underwent multimodal brain MRI from two centres. Brain lesions, volumes of the whole brain parenchyma, cortical and subcortical grey matter (GM), brainstem, cerebellum and cerebral white matter (WM) and diffusion measures (fractional anisotropy, FA and mean diffusivity, MD) were compared among the groups. Associations between the MRI measurements and the clinical variables were assessed by partial correlations. Logistic regression was performed to differentiate MOGAD from AQP4+ NMOSD and MS.

Results: In MOGAD, 19 (54%) patients had lesions on MRI, with cortical/juxtacortical (68%) as the most common location. MOGAD and MS showed lower cortical and subcortical GM volumes than HC, while AQP4+ NMOSD only demonstrated a decreased cortical GM volume. MS demonstrated a lower cerebellar volume, a lower FA and an increased MD than MOGAD and HC. The subcortical GM volume was negatively correlated with Expanded Disability Status Scale in MOGAD (R=-0.51; p=0.004). A combination of MRI and clinical measures could achieve an accuracy of 85% and 93% for the classification of MOGAD versus AQP4+ NMOSD and MOGAD versus MS, respectively.

Conclusion: MOGAD demonstrated cortical and subcortical atrophy without severe WM rarefaction. The subcortical GM volume correlated with clinical disability and a combination of MRI and clinical measures could separate MOGAD from AQP4+ NMOSD and MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2020-324826DOI Listing
July 2021

Tumor Epigenetic Signature and Survival in Resected Gastric Cancer Patients.

J Am Coll Surg 2021 Apr 17;232(4):483-491.e1. Epub 2021 Jan 17.

Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Beckman Research Institute of City of Hope, Duarte, CA.

Background: Precision oncology can identify patient-specific molecular signatures to better inform the prognosis and management of surgical cancer patients. Specifically, microRNAs (miRs) hold promise as prognostic biomarkers because dysregulation of individual miRs is implicated in tumorigenesis, progression, and metastases of various malignancies, including gastric adenocarcinoma (GC).

Study Design: To identify miRs prognostic of survival after radical gastrectomy, we studied GC patients within The Cancer Genome Atlas (TCGA) who had undergone R0 or R1 resection and had data on clinical characteristics, overall survival (OS), and tumor miR expression. The miRs expressed by at least 15% of tumors were eligible for study. From 10 replicate samples, each with 80% of patients, miRs were selected using age-adjusted proportional hazards regression with stepwise selection. Cross-validated miRs (selected by multiple replicates) were retained if they optimized an accelerated failure-time model of OS using all patients.

Results: In this GC cohort (n = 270), half (916/1,870) of miRs screened met our criteria for evaluation. Cross-validation identified 20 miRs as prognostic, of which 14 (miR-129-1, miR-373, miR-490, miR-597, miR-1185-2, miR-3943, miR-4756, miR-5683, miR-6510, miR-6733, miR-6808, miR-6855, miR-6882, miR-8072) were independently informative. The age-adjusted 14-miRNA panel remained significantly associated with OS after adjustment for pathologic prognostic factors (number of lymph nodes examined, number of positive lymph nodes) and other clinical covariates (TNM stage, residual tumor, tumor microsatellite instability, targeted molecular therapy, sex, race, ethnicity). Panel-predicted survival estimates below the upper tertile cut-off were associated with worse outcome (30% vs 74% OS at 3 years, p < 0.0001).

Conclusions: In surgically resected GC patients, an epigenetic signature of miRs associated with survival has the potential to improve prognostication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jamcollsurg.2020.12.023DOI Listing
April 2021

Subtyping relapsing-remitting multiple sclerosis using structural MRI.

J Neurol 2021 May 2;268(5):1808-1817. Epub 2021 Jan 2.

Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, No.119, The West Southern 4th Ring Road, Fengtai District, Beijing, 100070, China.

Background And Purpose: Subtyping relapsing-remitting multiple sclerosis (RRMS) patients may help predict disease progression and triage patients for treatment. We aimed to subtype RRMS patients by structural MRI and investigate their clinical significances.

Methods: 155 relapse-remitting MS (RRMS) and 210 healthy controls (HC) were retrospectively enrolled with structural 3DT1, diffusion tensor imaging (DTI) and resting-state functional MRI. Z scores of cortical and deep gray matter volumes (CGMV and DGMV) and white matter fractional anisotropy (WM-FA) in RRMS patients were calculated based on means and standard deviations of HC. We defined RRMS as "normal" (- 2 < z scores of both GMV and WM-FA), DGM (z scores of DGMV < - 2), and DGM-plus types (z scores of DGMV and [CGMV or WM-FA] < - 2) according to combinations of z scores compared to HC. Expanded disability status scale (EDSS), cognitive and functional MRI measurements, and conversion rate to secondary progressive MS (SPMS) at 5-year follow-up were compared between subtypes.

Results: 77 (49.7%) patients were "normal" type, 37 (23.9%) patients were DGM type and 34 (21.9%) patients were DGM-plus type. 7 (4.5%) patients who were not categorized into the above types were excluded. DGM-plus type had the highest EDSS. Both DGM and DGM-plus types had more severe cognitive impairment than "normal" type. Only DGM-plus type showed decreased functional MRI measures compared to HC. A higher conversion ratio to SPMS in DGM-plus type (55%) was identified compared to "normal" type (14%, p < 0.001) and DGM type (20%, p = 0.005).

Conclusion: Three MRI-subtypes of RRMS were identified with distinct clinical and imaging features and different prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-020-10376-7DOI Listing
May 2021

Brain MRI characteristics in neuromyelitis optica spectrum disorders: A large multi-center retrospective study in China.

Mult Scler Relat Disord 2020 Nov 30;46:102475. Epub 2020 Aug 30.

Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Electronic address:

Purpose: To investigate the brain MRI features in neuromyelitis optica spectrum disorders (NMOSD) and its clinical relevance in a large multi-center cohort in China.

Methods: 270 NMOSD patients were recruited from seven centers. The brain MRI were classified as normal, NMOSD-specific lesions, multiple sclerosis-like, nonspecific white matter changes. Brain volumes including whole brain, white, gray matter, cortex and subcortex gray matter volume were measured. The relationship between MRI measures, clinical disability and cognitive impairment were investigated.

Results: 98 patients (36.3%) had normal brain MRI; 48 patients (17.7%) had NMOSD-specific lesions located in dorsal brainstem, corticospinal tract corpus, callosum and periependymal lesions surrounding the ventricular system; 16 patients (6%) had multiple sclerosis-like lesions; and 108 patients (40%) had nonspecific white matter changes. NMOSD patients with brain lesions had a trend of lower subcortex gray matter volume compared to patients without lesions. 52.5% patients with normal brain MRI and 50.8% patients with abnormal brain MRI showed cognitive impairment. No significant differences were identified in brain volume between cognitive impairment and cognitive preserved groups.

Conclusion: In this large multicenter NMOSD cohort, nonspecific white matter changes were the most common findings (40%). NMOSD patients with brain lesions demonstrated a trend of having lower brain volume than patients without lesions. Approximately 50% NMOSD patients presented cognitive impairment independent of brain lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2020.102475DOI Listing
November 2020

Multiparametric-MRI-Based Radiomics Model for Differentiating Primary Central Nervous System Lymphoma From Glioblastoma: Development and Cross-Vendor Validation.

J Magn Reson Imaging 2021 01 31;53(1):242-250. Epub 2020 Aug 31.

Academy for Engineering and Technology, Fudan University, Shanghai, China.

Background: Preoperative differentiation of primary central nervous system lymphoma (PCNSL) from glioblastoma (GBM) is important to guide neurosurgical decision-making.

Purpose: To validate the generalization ability of radiomics models based on multiparametric-MRI (MP-MRI) for differentiating PCNSL from GBM.

Study Type: Retrospective.

Population: In all, 240 patients with GBM (n = 129) or PCNSL (n = 111).

Field Strength/sequence: 3.0T scanners (two vendors). Sequences: fluid-attenuation inversion recovery, diffusion-weighted imaging (DWI), and contrast-enhanced T -weighted imaging (CE-T WI). Apparent diffusion coefficients (ADCs) were derived from DWI.

Assessment: Cross-vendor and mixed-vendor validation were conducted. In cross-vendor validation, the training set was 149 patients' data from vendor 1, and test set was 91 patients' data from vendor 2. In mixed-vendor validation, a training set was 80% of data from both vendors, and the test set remained at 20% of data. Single and multisequence radiomics models were built. The diagnoses by radiologists with 5, 10, and 20 years' experience were obtained. The integrated models were built combining the diagnoses by the best-performing radiomics model and each radiologist. Model performance was validated in the test set using area under the ROC curve (AUC). Histological results were used as the reference standard.

Statistical Tests: DeLong test: differences between AUCs. U-test: differences of numerical variables. Fisher's exact test: differences of categorical variables.

Results: In cross-vendor and mixed-vendor validation, the combination of CE-T WI and ADC produced the best-performing radiomics model, with AUC of 0.943 vs. 0.935, P = 0.854. The integrated models had higher AUCs than radiologists, with 5 (0.975 vs. 0.891, P = 0.002 and 0.995 vs. 0.885, P = 0.007), 10 (0.975 vs. 0.913, P = 0.029 and 0.995 vs. 0.900, P = 0.030), and 20 (0.975 vs. 0.945, P = 0.179 and 0.995 vs. 0.923, P = 0.046) years' experiences.

Data Conclusion: Radiomics for differentiating PCNSL from GBM was generalizable. The model combining MP-MRI and radiologists' diagnoses had superior performance compared to the radiologists alone.

Level Of Evidence: 4 TECHNICAL EFFICACY STAGE: 2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.27344DOI Listing
January 2021

α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer.

Nat Cancer 2020 Mar 20;1(3):345-358. Epub 2020 Mar 20.

Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA.

Genetic-driven deregulation of the Wnt pathway is crucial but not sufficient for colorectal cancer (CRC) tumourigenesis. Here, we show that environmental glutamine restriction further augments Wnt signaling in APC mutant intestinal organoids to promote stemness and leads to adenocarcinoma formation via decreasing intracellular alpha-ketoglutarate (aKG) levels. aKG supplementation is sufficient to rescue low-glutamine induced stemness and Wnt hyperactivation. Mechanistically, we found that aKG promotes hypomethylation of DNA and histone H3K4me3, leading to an upregulation of differentiation-associated genes and downregulation of Wnt target genes, respectively. Using CRC patient-derived organoids and several CRC tumour models, we show that aKG supplementation suppresses Wnt signaling and promotes cellular differentiation, thereby significantly restricting tumour growth and extending survival. Together, our results reveal how metabolic microenvironment impacts Wnt signaling and identify aKG as a potent antineoplastic metabolite for potential differentiation therapy for CRC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s43018-020-0035-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442208PMC
March 2020

Tanshinone IIA Ameliorates Progression of CAD Through Regulating Cardiac H9c2 Cells Proliferation and Apoptosis by miR-133a-3p/EGFR Axis.

Drug Des Devel Ther 2020 20;14:2853-2863. Epub 2020 Jul 20.

Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, People's Republic of China.

Background: Coronary artery disease (CAD) leads to the highest mortality worldwide, seriously threatening human health. Tanshinone IIA (Tan IIA), which could be extracted from Danshen, is applied in the treatment of cardiovascular and cerebrovascular diseases. MicroRNAs (miRNAs, miRs) play pivotal roles in cell proliferation and cell apoptosis of the cardiovascular system. The aim of the present study was to explore the role of Tan IIA in CAD in vitro and the underlying molecular mechanism.

Methods: Real-time polymerase chain reaction (RT-PCR) and Western blot were used for the detection of miRNA/mRNA and protein, respectively. Target genes of miR-133a-3p were searched in TargetScan, and the targeting relationship was verified by dual-luciferase reporter assay. Cell proliferation was determined using a Cell Counting Kit-8 (CCK-8) and EdU labeling. Cell apoptosis was detected by flow cytometry and TUNEL staining.

Results: In the present study, lower miR-133a-3p level and higher epidermal growth factor receptor (EGFR; the target of miR-133a-3p) level were found in HO-induced H9c2 cells. In addition, Tan IIA upregulated miR-133a-3p and downregulated EGFR expression. Moreover, Tan IIA promoted cell proliferation and suppressed apoptosis and enhanced G0/G1, which was reversed by miR-133a-3p inhibitor, while siRNA-EGFR abolished the effects induced by miR-133a-3p in HO-induced H9c2 cells.

Conclusion: Tan IIA reversed HO-induced cell proliferation reduction, cell apoptosis induction, and G0/G1 arrest reduction in H9c2 cells by miR-133a-3p/EGFR axis. The findings suggested a potential molecular basis of Tan IIA in treating patients with CAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S245970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381819PMC
July 2020

Thermal bleaching of photodarkening and heat-induced loss and spectral broadening in Tm-doped fibers.

Opt Express 2020 Jul;28(15):21845-21853

We demonstrate the thermal bleaching effect on a photodarkened thulium-doped fiber (TDF) in detail. The bleaching effect on visible transmission initiates at 250 °C and a complete recovery is achieved at 550 °C. Prior to the recovery, a post-irradiation heat-induced spectral loss is observed. It indicates that an intermediate energy state is generated in the TDF under exposure to near-infrared (NIR) radiation, exhibiting the spectral attenuation in visible (VIS) and NIR region as driven by color center after thermal activation. And, with thermal treatment, the bleached TDF shows a partial photodarkening (PD) resistance when it is subject to photoirradiation again. In addition, the temperature-dependent spectral broadening and red shift that may distort the measured decay curve of excess loss is observed and discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.397356DOI Listing
July 2020

Disparate and Alarming Impact of Gastrointestinal Cancers in Young Adult Patients.

Ann Surg Oncol 2021 Feb 1;28(2):785-796. Epub 2020 Aug 1.

Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA.

Background: The rise in the incidence of gastric cancer (GC) and colorectal cancer (CRC) in young adults (YA) remains unexplained. We aim to identify differences in these malignancies between YA and older patients.

Patients And Methods: We retrospectively analyzed the California Cancer Registry for all GC and CRC cases from 2000 to 2012. Pearson's Chi square analysis and stepwise regression model with backward elimination were used to analyze differences in demographic, clinical, and histopathologic features, and log-rank test to compare survival between young (≤ 40 years) and older adults (41-90 years) with GC or CRC, separately.

Results: We analyzed 19,368 cases of GC and 117,415 cases of CRC. YA accounted for 4.6% of GC (n = 883) and 2.8% of CRC (n = 3273) patients. Compared with older patients, YA were more likely to be Hispanic (P < 0.0001) and have poorly differentiated (P < 0.0001), higher histologic grade (P < 0.0001), and signet ring features (P < 0.0001). Synchronous peritoneal metastases were more common in YA patients (32.1% vs. 14.1% GC, 8.8% vs. 5.4% CRC, P < 0.0001). The 5-year overall survival (OS) of YA with CRC or GC was longer than that of older patients with the same stage of malignancy; except YA with stage I GC, who demonstrated poor OS and disease-specific survival (DSS) (65.1% and 67.9%, respectively) which were significantly worse than those of adults aged 41-49 years (70.7% and 76.2%, respectively) and 50-64 years (69.1% and 78.1%, respectively).

Conclusions: YA with GC or CRC have distinctly worse clinical and histopathologic features compared with older patients and are disproportionately of Hispanic ethnicity. These results contribute to improving understanding of younger versus older GI cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-020-08969-7DOI Listing
February 2021

Dietary glutamine supplementation suppresses epigenetically-activated oncogenic pathways to inhibit melanoma tumour growth.

Nat Commun 2020 07 3;11(1):3326. Epub 2020 Jul 3.

Department of Molecular Biology and Biochemistry; School of Biological Sciences, University of California, Irvine, Irvine, CA, 92697, USA.

Tumour cells adapt to nutrient deprivation in vivo, yet strategies targeting the nutrient poor microenvironment remain unexplored. In melanoma, tumour cells often experience low glutamine levels, which promote cell dedifferentiation. Here, we show that dietary glutamine supplementation significantly inhibits melanoma tumour growth, prolongs survival in a transgenic melanoma mouse model, and increases sensitivity to a BRAF inhibitor. Metabolomic analysis reveals that dietary uptake of glutamine effectively increases the concentration of glutamine in tumours and its downstream metabolite, αKG, without increasing biosynthetic intermediates necessary for cell proliferation. Mechanistically, we find that glutamine supplementation uniformly alters the transcriptome in tumours. Our data further demonstrate that increase in intra-tumoural αKG concentration drives hypomethylation of H3K4me3, thereby suppressing epigenetically-activated oncogenic pathways in melanoma. Therefore, our findings provide evidence that glutamine supplementation can serve as a potential dietary intervention to block melanoma tumour growth and sensitize tumours to targeted therapy via epigenetic reprogramming.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-17181-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335172PMC
July 2020

Association of molecular characteristics with survival in advanced non-small cell lung cancer patients treated with checkpoint inhibitors.

Lung Cancer 2020 08 24;146:174-181. Epub 2020 May 24.

Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA; Division of Medical Oncology, Cedars-Sinai Medical Center, USA. Electronic address:

Objectives: Immune checkpoint inhibitors (ICIs) have changed the landscape of lung cancer therapy. However significant proportions of patients have primary or acquired resistance to ICIs. Molecular characterization is critical for patient selection and overcoming resistance to checkpoint inhibitors. The purpose of this study is to investigate the molecular characteristics associated with ICIs outcomes in advanced non-small cell lung cancer (NSCLC) patients.

Materials And Methods: All advanced stage NSCLC patients at City of Hope who received ICIs (pembrolizumab, nivolumab, atezolizumab, and durvalumab) were identified retrospectively. Overall survival (OS, from the start of the ICIs), Pathology and information on genomic alterations (GAs) including next-generation sequencing (NGS) data, tumor mutation burden (TMB), and Programmed death-ligand 1 (PD-L1) levels were collected. Chi-square and Fisher's exact test, Log-rank test were used for comparison of demographics, and survival curves respectively. Univariate and multivariate COX proportional hazards model was used for survival analysis.

Results: 346 NSCLC patients were identified. Univariate and multivariate analysis found the association of OS with PD-L1 level ≥50% (Hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.06-0.59; P < 0.01), EGFR (HR 7.38; 95% CI, 1.15-47.42; P < 0.05), and TET2 (HR 0.15; 95% CI, 0.03-0.90; P < 0.05). The median OS was not reached [NR] for the 12 patients who had genomic alterations (GAs) in TET2 (12/108, 11%) versus (vs) 11.5 months in TET2 negative patients (98/108, 89%). Interestingly, GAs in TET2 and FANCA were mutually exclusive and patients who had GAs in FANCA gene (6%) had shorter OS (5.5 months vs 14.5 months, Log-rank test, P < 0.05).

Conclusions: We described the clinical and molecular features of NSCLC patients treated with ICIs. The association of GAs in TET2 with longer OS and its mutual exclusivity with FANCA GAs were insightful for developing novel therapeutic strategies to improve ICIs outcomes in NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2020.05.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158847PMC
August 2020

Brain MRI features of Chinese Han patients with MOG-antibody disease.

Mult Scler Relat Disord 2020 Aug 15;43:102167. Epub 2020 May 15.

Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China; Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai, China. Electronic address:

Background The spectrum of imaging features of patients with MOG antibody disease (MOGAD) remains unclear. We aimed to determine the brain MRI features of MOGAD in a Chinese Han cohort and to assess differences in brain MRI features between MOGAD and neuromyelitis optica spectrum disorders (NMOSDs). Methods We retrospectively reviewed the MRI images of 43 patients with MOGAD. As a routine diagnostic approach, all patients underwent serum aquaporin 4 IgG (AQP4-IgG) and MOG-IgG detection via cell-based assays. The topographies and features of brain lesions were independently assessed by two raters. As a comparison, topographies and features of brain lesions were also assessed using neuroimaging characteristics of NMOSDs recommended by the international panel for NMO diagnosis (IPND) in 2015. Results Thirty-five (81.4%) patients were found to have brain lesions. These brain lesions were classified into the following three patterns according to their distributions: (I) lesions involving midline structures and deep gray matte; (II) supratentorial white matter lesions; and (III) cortical gray matter lesions. There were 17 patients whose brain lesions did not fulfill the neuroimaging characteristics of NMOSDs recommended by the 2015 IPND, in which 11 patients had cortical gray matter lesions and/or juxtacortical white matter lesions, four patients had middle cerebral peduncles lesions, and two patients had gray matter lesions and juxtacortical white matter lesions, as well as middle cerebral peduncles lesions. Conclusion MOGAD in this Chinese Han cohort exhibited distinct brain MRI features, especially in terms of cortical gray matter lesions, juxtacortical white matter lesions, and middle cerebral peduncles lesions, which may help to further identify and diagnose patients with MOGAD while they are waiting for serological antibody results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2020.102167DOI Listing
August 2020

Promotion of pulse peak power by halving the repetition rate based on a vector soliton.

Opt Lett 2020 Apr;45(7):1635-1638

We report on an all-fiber mode-locked repetition-rate-switch pulse operation in a Yb-doped fiber laser based on a polarization rotation vector soliton. The polarization controller (PC) in a fiber loop and a polarization-dependent isolator at the output port are incorporated into the laser resonator at the switch of the repetition rate. By adjusting the PC in the cavity, the mode locking can be switched between the fundamental repetition rate and half of it with a tiny pulse width change. Also, the halved pulse exhibits unique properties: a huge promotion in energy and peak power. To the best of our knowledge, this is the first all-fiber seed source with a passive switch of the repetition rate based on a vector soliton.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.384348DOI Listing
April 2020

Pericardial fluid levels of growth differentiation factor 15 in patients with or without coronary artery disease: a prospective study.

Ann Transl Med 2020 Feb;8(4):113

Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

Background: Growth differentiation factor 15 (GDF15) has already been reported as a novel efficient biomarker in patients with coronary artery diseases (CAD). However, very little is demonstrated about the potential impact of pericardial fluid GDF-15 accumulation on CAD. The aim of this study was to evaluate pericardial fluid and plasma GDF15 levels in patients with ischemic heart disease.

Methods: In this study, 42 consecutive patients (21 patients with significant CAD; 21 patients without CAD) undergoing open heart surgery were recruited in this study. Pericardial fluid were obtained at the time of surgery, and GDF15 levels in the samples were measured by enzyme-linked immunosorbent assay. Plasma glucose, creatinine, CK-MB, cTnI and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements were performed.

Results: The plasma GDF15 levels were markedly higher than the pericardial fluid levels both in the CAD group and non-CAD group (1,174.0±148.7 . 677.8±77.2 pg/mL, P<0.01; 925.8±127.4 . 617.4±76.2 pg/mL, P<0.01). The levels of pericardial fluid GDF15, was not statistically different between the CAD and non-CAD groups (P>0.05). An obvious correlation was observed between plasma and pericardial fluid GDF15 concentration both in the CAD group and non-CAD group (R=0.53, P<0.01; R=0.54, P<0.01). An obvious positive correlation was found between pericardial fluid GDF15 and plasma creatinine levels in CAD patients but not in non-CAD patients (R=0.65, P<0.01). In the CAD group, an obvious correlation was also observed between pericardial fluid GDF15 levels and NT-ProBNP (R=0.63, P<0.01), while no relationship was found in non-CAD group. There was a positive correlation between pericardial fluid GDF15 and LVEF in non-CAD group but not in CAD group patients (R=-0.44, P<0.05).

Conclusions: Our study first revealed an association between pericardial fluid GDF15 and baseline characteristics. Pericardial fluid GDF15 levels are associated with cardiac and kidney function in patients with coronary artery disease and may be a valuable marker for assessing CAD severity and predicting its complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd.2019.12.92DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048982PMC
February 2020

Uncovering Differently Expressed Markers and Heterogeneity on Human Pancreatic Cancer.

Transl Oncol 2020 Mar 3;13(3):100749. Epub 2020 Mar 3.

Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, California, 91010, USA. Electronic address:

Discovery of biomarkers is critical to understand tumor heterogeneity and microenvironment. To determine differently expressed makers on cancer tissue for comprehensive profiling, the multiplexed tissue imaging mass cytometer (IMC) which uniquely combines time-of-flight mass spectrometry with metal-labeling technology to enable breakthrough discovery on single cell level was employed to investigate the expression of seven markers related to the epithelial-to-mesenchymal transition [α-smooth muscle actin (α-SMA), vimentin, collagen I, cytokeratin 7, pan-keratin], tumor proliferation (Ki-67), and human leucocyte antigen (HLA-DR) on human pancreatic cancer tissue. The difference was analyzed using bioinformatic tools. We observed the high expression of α-SMA, vimentin, collagen I, and Ki-67 on grade I but not on grade III. HLA-DR was highly expressed on grade I/III but not on grade II. Overall, the expression of markers has elucidated the heterogeneity intratumors. Additionally, to identify biomarkers on pancreatic cancer cells by blind systematic evolution of ligands by exponential enrichment (SELEX), aptamer pull-down assay and liquid chromatography-tandem mass spectrometry were used. Mortalin was identified as a potential a prognostic marker of pancreatic cancer. Our studies demonstrate that the IMC and blind SELEX might be implemented to discover biomarkers which can be used to better understand tumor biology and biomedical research applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tranon.2020.100749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056725PMC
March 2020

Prognostic Role of NT-proBNP for in-Hospital and 1-Year Mortality in Patients with Acute Exacerbations of COPD.

Int J Chron Obstruct Pulmon Dis 2020 8;15:57-67. Epub 2020 Jan 8.

Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.

Background And Objective: The association between N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations and in-hospital and 1-year mortality in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients is largely unknown. Our objective was to explore the usefulness of NT-proBNP concentrations in AECOPD patients as a prognostic marker for in-hospital and 1-year mortality.

Methods: NT-proBNP levels were measured in patients upon admission and laboratory and clinical data were also recorded. The cut-point for the NT-proBNP concentration level for in-hospital death was obtained using the receiver operating characteristic (ROC) curve. Univariate and multivariate logistic regression and Cox regression were used in the analyses of factors of in-hospital and 1-year mortality.

Results: A total of 429 patients were enrolled. Twenty-nine patients died during hospitalization and 59 patients died during the 1-year follow-up. Patients who died in-hospital compared with those in-hospital survivors were older (80.14±6.56 vs 75.93±9.45 years, p=0.003), had a higher percentage of congestive heart failure (65.52% vs 33.75%, p<0.001), had higher NT-proBNP levels (5767.00 (1372.50-12,887.00) vs 236.25 (80.03-1074.75) ng/L, p<0.001), higher neutrophil counts (10.52±5.82 vs 7.70±4.31, p=0.016), higher D-dimer levels (1231.62±1921.29 vs 490.11±830.19, p=0.048), higher blood urea nitrogen levels (9.91±6.33 vs 6.51±4.01 mmol/L, p=0.001), a lower body mass index (19.49±3.57 vs 22.19±4.76, p=0.003), and higher hemoglobin levels (122.34±25.36 vs 130.57±19.63, p=0.034). The area under the ROC curve (AUC) for NT-proBNP concentration was 0.88 (95% confidence interval [CI], 0.84-0.93). NT-proBNP concentrations ≥551.35 ng/L were an independent prognostic factor for both in-hospital and 1-year mortality after adjustment for relative risk (RR) (RR=29.54, 95% CI 3.04-286.63, p=0.004 for the multivariate logistic regression analysis) and hazard ratio (HR) (HR=4.47, 95% CI, 2.38-8.41, p <0.001 for the multivariate cox regression analysis).

Conclusion: NT-proBNP was a strong and independent predictor of in-hospital and 1-year mortality in AECOPD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/COPD.S231808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955621PMC
February 2021

Preparation, characterization, and application of magnetic activated carbon for treatment of biologically treated papermaking wastewater.

Sci Total Environ 2020 Apr 3;713:136423. Epub 2020 Jan 3.

Beijing Key Laboratory of Resource-oriented Treatment of Industrial Pollutants, School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing 100083, China. Electronic address:

In view of the urgent need for tertiary treatment of papermaking wastewater and the difficulty in separating powdered activated carbon (PAC) from water, the magnetic activated carbon (33%-MPAC, 50%-MPAC and 67%-MPAC) were prepared by chemical coprecipitation method for adsorption of biologically treated papermaking wastewater (BTPW). A series of characterization of MPAC and PAC were carried out and show that the content of iron oxides is negatively related to the proportion of micropores in MPAC. The loaded iron oxides is mainly the mixture of magnetite and maghemite, and the maximum saturation magnetization of MPAC can reach 29.68 emu/g. Batch mode experiments were performed, and found that the adsorption effect of MPAC is slightly worse than that of PAC, the adsorption capacity of COD in MPAC can reach about 65 mg/g, and pH = 2 and 10 °C are more favorable for adsorption. The adsorption isotherms and kinetics were well fitted by the Freundlich model and pseudo-second-order kinetic model, respectively. The selective adsorption was studied by using the excitation emission matrix (EEM) fluorescence spectrum and high-performance size exclusion chromatography (HPSEC). It is concluded that all adsorbents are preferred to adsorb humic acid-like substances (HA). And all adsorbents are preferred to adsorb low apparent molecular weight substances (LAMW, AMW < 1500 Da), with the increase of iron oxides content, the phenomenon of MPAC preferentially adsorbed LAMW became less obvious.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2019.136423DOI Listing
April 2020

High coupling efficiency technology of large core hollow-core fiber with single mode fiber.

Opt Express 2019 Nov;27(23):33135-33142

With the research of hollow-core fiber with large core diameter, the coupling efficiency from hollow-core fiber with large core diameter to single-mode fiber is difficult to increase through the traditional technology, we proposed a novel coupling method to improve the coupling efficiency by attaching a pure silica small ball at the front end of single-mode fiber, the coupling efficiency of 50% from hollow-core fiber with a large core diameter of 110 µm to single-mode fiber can be achieved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.27.033135DOI Listing
November 2019

Localized Electrical Induction Heating for Highly Efficient Synthesis and Regeneration of Metal-Organic Frameworks.

ACS Appl Mater Interfaces 2020 Jan 8;12(3):4097-4104. Epub 2020 Jan 8.

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering , Nanjing Tech University , Nanjing 211816 , China.

Based on carbon fibers (CFs) delivered localized electrical induction heat, a novel electrical induction framework synthesis (EIFS) strategy has been developed to in-situ grow versatile metal-organic frameworks (MOFs) on CFs, resulting in the production of a set of MOF-coated CF ([email protected]) fibers. Detailed studies on the production of [email protected] indicate that the use of EIFS leads to dramatically accelerated MOF growth at dozen times higher reaction rate than that of the conventional solvothermal reaction. By periodically switching anodes during EIFS reactions, uniform [email protected] fibers with well-controlled MOF loadings have been achieved depending on the reaction conditions. Mediated by the embedded CFs in the resulting [email protected], [email protected] exhibit well-regulated electrical induction heating capacities depending on MOF loadings and the applied voltages. Driven by such localized heat, up to 100% of the adsorbed CO in [email protected] can be rapidly released, demonstrating an electrical induction framework regeneration (EIFR) process for highly efficient regeneration of MOFs. As CFs enable to rapidly deliver localized electrical induction with over 90% of electrothermal conversion efficiency and at rather low operation voltage, currently developed EIFS and EIFR process provide a highly efficient, low-energy, low operation cost, and safe way to highly efficient synthesis and regeneration of MOF materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.9b19216DOI Listing
January 2020

Quantitative brain lesion distribution may distinguish MOG-ab and AQP4-ab neuromyelitis optica spectrum disorders.

Eur Radiol 2020 Mar 20;30(3):1470-1479. Epub 2019 Nov 20.

Department of Radiology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.

Objectives: Antibodies to myelin oligodendrocyte glycoprotein (MOG-ab) and antibodies to aquaporin-4 (AQP4-ab) have been suggested to play roles in commonly separated subsets of patients with neuromyelitis optica spectrum disorder (NMOSD) phenotypes. The aim of this study is to quantitatively delineate and compare the brain lesion distributions of AQP4-ab-positive and MOG-ab-positive patients.

Methods: Fifty-seven and twenty-eight clinical MRI scans were collected from fifty-two AQP4-ab-positive and twenty-four MOG-ab-positive patients, respectively. T2 lesions were segmented manually on each axial FLAIR image. Probabilistic lesion distribution maps were created for each group after spatial normalization. Lobe-wise and voxel-wise quantitative comparisons of the two distributions were performed. A classification model based on the lesion distribution features was constructed to differentiate the two patient groups.

Results: Infratentorial and supratentorial brain lesions were found in both AQP4-ab-positive and MOG-ab-positive patients, with large inter-group overlap mainly in deep white matter (WM). In comparison with those in the AQP4 group, the brain lesions of the MOG-ab-positive patients had a larger size, dispersed distribution, and higher probabilities in the cerebellum, pons, midbrain, and GM and juxtacortical WM in temporal, sublobar, frontal, and parietal lobes. The area under the receiver operating characteristic curve of the lesion-distribution-based classification model was 0.951.

Conclusions: MOG-ab-positive and AQP4-ab-positive groups showed similar but quantitatively different brain lesion distributions. These results may help clinicians in considering MOG versus AQP4 in initial diagnosis, and add rationale for sending corresponding serologic testing.

Key Points: • Brain lesion distributions of AQP-ab-positive and MOG-ab-positive NMOSD patients • Larger size, dispersed distribution, higher lesion probabilities in the cerebellum, pons, midbrain, and GM and juxtacortical WM in the MOG group • The lesion-distribution-based classification model differentiates the two groups with AUC = 0.951.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-019-06506-zDOI Listing
March 2020

532 nm pump induced photo-darkening inhibition and photo-bleaching in high power Yb-doped fiber amplifiers.

Opt Express 2019 Sep;27(19):26523-26531

A novel method for mitigating photo-darkening and the effective photo-bleaching phenomenon by 532 nm cladding pump in Yb-doped fiber were herein reported. Compared with the pristine fiber, beyond 30% of photo-darkening induced excess loss was suppressed by 532 nm pretreatment. Moreover, the excess loss in the photo-darkened fiber was completely bleached with 532 nm pump. Additionally, the bleached fiber exhibited better photo-darkening resistance. Therefore, for high power application, a 20/400 gamma irradiated fiber was bleached in situ by 532 nm pump and the laser properties were explored. The output power restored to 421W accounting for 82% of the pristine fiber, with the mode instability threshold rising to over 2.6 times and the efficiency increasing from 37% to 63%. The results indicate 532 nm pump has bright prospects for the stable operation of high power fiber lasers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.27.026523DOI Listing
September 2019

Phenotypic Switching of Naïve T Cells to Immune-Suppressive Treg-Like Cells by Mutant KRAS.

J Clin Med 2019 Oct 18;8(10). Epub 2019 Oct 18.

Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA.

Oncogenic (mutant) Ras protein Kirsten rat sarcoma viral oncogene homolog (KRAS) promotes uncontrolled proliferation, altered metabolism, and loss of genome integrity in a cell-intrinsic manner. Here, we demonstrate that CD4 T cells when incubated with tumor-derived exosomes from mutant (MT) KRAS non-small-cell lung cancer (NSCLC) cells, patient sera, or a mouse xenograft model, induce phenotypic conversion to FOXP3 Treg-like cells that are immune-suppressive. Furthermore, transfecting T cells with MT KRAS cDNA alone induced phenotypic switching and mathematical modeling supported this conclusion. Single-cell sequencing identified the interferon pathway as the mechanism underlying the phenotypic switch. These observations highlight a novel cytokine-independent, cell-extrinsic role for KRAS in T cell phenotypic switching. Thus, targeting this new class of Tregs represents a unique therapeutic approach for NSCLC. Since KRAS is the most frequently mutated oncogene in a wide variety of cancers, the findings of this investigation are likely to be of broad interest and have a large scientific impact.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8101726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832522PMC
October 2019

Monitoring and Determining Mitochondrial Network Parameters in Live Lung Cancer Cells.

J Clin Med 2019 Oct 18;8(10). Epub 2019 Oct 18.

Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA.

Mitochondria are dynamic organelles that constantly fuse and divide, forming dynamic tubular networks. Abnormalities in mitochondrial dynamics and morphology are linked to diverse pathological states, including cancer. Thus, alterations in mitochondrial parameters could indicate early events of disease manifestation or progression. However, finding reliable and quantitative tools for monitoring mitochondria and determining the network parameters, particularly in live cells, has proven challenging. Here, we present a 2D confocal imaging-based approach that combines automatic mitochondrial morphology and dynamics analysis with fractal analysis in live small cell lung cancer (SCLC) cells. We chose SCLC cells as a test case since they typically have very little cytoplasm, but an abundance of smaller mitochondria compared to many of the commonly used cell types. The 2D confocal images provide a robust approach to quantitatively measure mitochondrial dynamics and morphology in live cells. Furthermore, we performed 3D reconstruction of electron microscopic images and show that the 3D reconstruction of the electron microscopic images complements this approach to yield better resolution. The data also suggest that the parameters of mitochondrial dynamics and fractal dimensions are sensitive indicators of cellular response to subtle perturbations, and hence, may serve as potential markers of drug response in lung cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8101723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832496PMC
October 2019

Mitigation of mode instability in laser oscillators based on deuterium loading.

Opt Express 2019 Sep;27(18):25964-25973

Ytterbium-doped fiber (YDF) loaded with deuterium is used herein to mitigate mode instability. Experimental results reveal that this method can increase the mode instability threshold in a laser oscillator. Specifically, when the YDF was loaded with deuterium over two- and four-week periods, the mode instability threshold power increased from ∼459 W to ∼533 W (16%) and to ∼622 W (35%), respectively, but the respective laser efficiencies were almost unaffected (71.5% vs. 72.9% and 75.4%). In conclusion, deuterium loading is effective in the mitigation of mode instability. It is envisaged to be applied in the power scaling of high-power fiber lasers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.27.025964DOI Listing
September 2019