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  • 1
    In: The Lancet, Elsevier BV, Vol. 402, No. 10395 ( 2023-07), p. 27-40
    Type of Medium: Online Resource
    ISSN: 0140-6736
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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    detail.hit.zdb_id: 3306-6
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    SSG: 5,21
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 11 ( 2022-1-26)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2022-1-26)
    Abstract: To develop and validate a radiomics nomogram for the prediction of clinically significant prostate cancer (CsPCa) in Prostate Imaging-Reporting and Data System (PI-RADS) category 3 lesions. Methods We retrospectively enrolled 306 patients within PI-RADS 3 lesion from January 2015 to July 2020 in institution 1; the enrolled patients were randomly divided into the training group (n = 199) and test group (n = 107). Radiomics features were extracted from T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC) imaging, and dynamic contrast-enhanced (DCE) imaging. Synthetic minority oversampling technique (SMOTE) was used to address the class imbalance. The ANOVA and least absolute shrinkage and selection operator (LASSO) regression model were used for feature selection and radiomics signature building. Then, a radiomics score (Rad-score) was acquired. Combined with serum prostate-specific antigen density (PSAD) level, a multivariate logistic regression analysis was used to construct a radiomics nomogram. Receiver operating characteristic (ROC) curve analysis was used to evaluate radiomics signature and nomogram. The radiomics nomogram calibration and clinical usefulness were estimated through calibration curve and decision curve analysis (DCA). External validation was assessed, and the independent validation cohort contained 65 patients within PI-RADS 3 lesion from January 2020 to July 2021 in institution 2. Results A total of 75 (24.5%) and 16 (24.6%) patients had CsPCa in institution 1 and 2, respectively. The radiomics signature with SMOTE augmentation method had a higher area under the ROC curve (AUC) [0.840 (95% CI, 0.776–0.904)] than that without SMOTE method [0.730 (95% CI, 0.624–0.836), p = 0.08] in the test group and significantly increased in the external validation group [0.834 (95% CI, 0.709–0.959) vs. 0.718 (95% CI, 0.562–0.874), p = 0.017]. The radiomics nomogram showed good discrimination and calibration, with an AUC of 0.939 (95% CI, 0.913–0.965), 0.884 (95% CI, 0.831–0.937), and 0.907 (95% CI, 0.814–1) in the training, test, and external validation groups, respectively. The DCA demonstrated the clinical usefulness of radiomics nomogram. Conclusion The radiomics nomogram that incorporates the MRI-based radiomics signature and PSAD can be conveniently used to individually predict CsPCa in patients within PI-RADS 3 lesion.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 3
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 9, No. Suppl 2 ( 2021-11), p. A490-A490
    Abstract: This trail is an open-label, single-arm, phase II study that aims to observe the efficacy and safety of toripalimab combined with anlotinib and platinum-etoposide (EP) chemotherapy as first-line treatment in ES-SCLC (Clinical trial information: NCT04731909 ). The preliminary results of the study have been presented in 2020 ASCO abstract e20570, which demonstrated 100% objective response rate (ORR) and tolerable safety. Here we report PFS analysis results of the study. Methods The study enrolled treatment-naïve ES-SCLC patients (18–75 years, ECOG PS ≤2) who have measurable target lesion evaluated by RECIST v1.1. All enrolled patients received toripalimab (240 mg, d1) combined with etoposide (100 mg/m2, d1–3) plus carboplatin (AUC=5, d1)/cisplatin (75 mg/m2, d1) and anlotinib (12 mg QD, d1–14) of a 21-day cycle. After 4–6 cycles of the treatment, patients who achieved complete response (CR), partial response (PR) or stable disease (SD) could continue to receive maintenance therapy with toripalimab and anlotinib until disease progression. The primary endpoint was overall survival (OS). ORR, disease control rate (DCR), progression-free survival (PFS) and safety were set as secondary endpoints. Results As of July 16, 2021, the median follow-up was 13.7 months. 9 disease progression events occurred of the enrolled 16 treatment-naïve ES-SCLC patients (14 males, 2 females, median age 63). The investigator-assessed median PFS was 13.3 months (95%CI: 5.0–21.6). The PFS rate at 6 months was 81.3% and the PFS rate at 12 months was 31.3%. 15 patients were still alive and the study treatments for 7 patients were still ongoing. At the data cutoff, there was only 1 patient dead with 37.6 months OS and the median OS was not reached. No new unexpected adverse events were observed. Conclusions Combined with preliminary data at 2020 ASCO, toripalimab combined with anlotinib and EP chemotherapy showed excellent ORR and PFS as well as tolerable safety in treatment-naïve ES-SCLC. The combination therapy is expected to provide clinically meaningful OS benefit and become a promising treatment option. Trial Registration This study is registered with ClinicalTrials.gov (National Institutes of Health), number NCT04731909 . Ethics Approval The program was approved by the ethics committee of Army Medical Center (Daping Hospital ).
    Type of Medium: Online Resource
    ISSN: 2051-1426
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2719863-7
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  • 4
    In: Journal of Magnetic Resonance Imaging, Wiley, Vol. 54, No. 6 ( 2021-12), p. 1967-1976
    Abstract: Adjusting abnormal glutamate neurotransmission is a crucial mechanism in the treatment of depression. However, few non‐invasive techniques could effectively detect changes in glutamate neurotransmitters, and no consensus exists on whether glutamate could affect resting‐state function changes in depression. Purpose To study the changes in glutamate chemical exchange saturation transfer (GluCEST) value in the hippocampus of rat model exposed to chronic unpredictable mild stress (CUMS), and to explore the effect of this change on the activity of hippocampal glutamatergic neurons. Study Type Prospective animal study. Animal Model Twenty male Sprague–Dawley rats (200–300 g). Field Strength/Sequence 7. 0 T scanner. Fat rapid acquisition relaxation enhancement sequence for GluCEST , and echo planner imaging sequence for resting‐state functional magnetic resonance imaging (rs_fMRI). Assessment Rats were divided into two groups: CUMS group ( N  = 10) and control group (CTRL, N  = 10). The magnetization transfer ratio asymmetry analysis was used to quantify the GluCEST data, and evaluate the rs_fMRI data through the amplitude of low‐frequency fluctuation (ALFF) and regional homogeneity (ReHo) analysis. Statistical Tests A t ‐test was used to compare the difference in GluCEST or rs_fMRI between CUMS and CTRL groups. Spearman's correlation was applied to explore the correlation between GluCEST values and abnormal fMRI values in hippocampus. Statistical significance was set at P   〈  0.05. Results The GluCEST value in the left hippocampus has changed significantly (3.3 ± 0.3 [CUMS] vs. 3.9 ± 0.4 [CTRL] , P   〈  0.05). In addition, the GluCEST value was significantly positively correlated with the ALFF values ( r  = 0.5, P   〈  0. 05, df = 7) and negatively correlated with the ReHo values ( r  = −0.6, P   〈  0.05, df = 7). Data Conclusion GluCEST technique has the feasibility of mapping glutamate changes in rat depression. Glutamate neurotransmitters are important factors affecting the abnormal function of neural activity. Level of Evidence 2 Technical Efficacy Stage 1
    Type of Medium: Online Resource
    ISSN: 1053-1807 , 1522-2586
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1497154-9
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  • 5
    In: Experimental Dermatology, Wiley, Vol. 33, No. 1 ( 2024-01)
    Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease in which defective T cells, immune complex deposition and other immune system alterations contribute to pathological changes of multiple organ systems. The vitamin D metabolite c is a critical immunomodulator playing pivotal roles in the immune system. Epidemiological evidence indicates that vitamin D deficiency is correlated with the severity of SLE. Our aim is to investigate the effects of 1,25(OH)2D3 (VitD3) on the activation of myeloid dendritic cells (mDCs) by autologous DNA‐containing immune complex (DNA‐ICs), and the effects of VitD3 on immune system balance during SLE. We purified DNA‐ICs from the serum of SLE patients and isolated mDCs from normal subjects. In vitro studies showed that DNA‐ICs were internalized and consumed by mDCs. VitD3 blocked the effects of DNA‐ICs on RelB, IL‐10 and TNF‐α in mDCs. Further analysis indicated that DNA‐ICs stimulated histone acetylation in the RelB promoter region, which was inhibited by VitD3. Knockdown of the histone deacetylase 3 gene (HDAC3) blocked these VitD3‐mediated effects. Co‐culture of mDCs and CD4 + T cells showed that VitD3 inhibited multiple processes mediated by DNA‐ICs, including proliferation, downregulation of IL‐10, TGF‐β and upregulation of TNF‐α. Moreover, VitD3 could also reverse the effects of DNA‐IC‐induced imbalance of CD4 + CD127 − Foxp3 + T cells and CD4 + IL17 + T cells. Taken together, our results indicated that autologous DNA‐ICs stimulate the activation of mDCs in the pathogenesis of SLE, and VitD3 inhibits this stimulatory effects of DNA‐ICs by negative transcriptional regulation of RelB gene and maintaining the Treg/Th17 immune cell balance. These results suggest that vitamin D may have therapeutic value for the treatment of SLE.
    Type of Medium: Online Resource
    ISSN: 0906-6705 , 1600-0625
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2024
    detail.hit.zdb_id: 2026228-0
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  • 6
    In: European Radiology, Springer Science and Business Media LLC, Vol. 33, No. 6 ( 2023-01-04), p. 4214-4222
    Type of Medium: Online Resource
    ISSN: 1432-1084
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1472718-3
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e20570-e20570
    Abstract: e20570 Background: Although the combination of PD-1/PD-L1 immune checkpoint inhibitors (ICIs) with platinum-etoposide chemotherapy (EP) is the preferred first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC), the survival benefit of the addition of ICIs was still modest. Recent studies supported that combination of ICIs and anti-angiogenic agents could be a promising therapeutic strategy for normalization the immunosuppressive microenvironment and overcoming the low efficacy of ICIs. We reported the efficacy and safety of toripalimab combined with anlotinib and EP in treatment-naïve ES-SCLC. Methods: The eligible ES-SCLC patients (18-75 years, ECOG PS ≤2), with measurable target lesion (RECIST v1.1) received toripalimab (240 mg, d1) combined with etoposide (100 mg/m 2 , d1-3) plus carboplatin (AUC = 5, d1)/cisplatin (75 mg/m 2 , d1) and anlotinib (12 mg QD, d1-14) of a 21-day cycle for 4-6 cycles, then patients with CR、PR or SD could continue to receive maintenance therapy with toripalimab and anlotinib until disease progression. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Results: Between 2018 October and 2020 November, 16 treatment-naïve ES-SCLC patients (14 males, 2 females) were enrolled. The median age is 63 (range, 42-74) years. The median follow-up was 7.6 months. 100% (16/16) patients achieved an objective response (1 CR and 15 PR). The DCR was also 100% (16/16). The median DOR had not been reached (range, 4.8+ to 21.9+ month). 37.5% (6/16) patients had disease progression after six months of treatment, while median PFS was not reached. As of Jan 31, 2021, all patients were still alive. The median OS had not been reached. 62.5% (10/16) patients remained on-treatment. The most common adverse events (AEs) were grade 1-2 anemia (75%), decreased appetite (50%) and neutropenia (43.8%). Seven patients had Grade 3 AEs (5 neutropenia; 1 leukopenia, 1 emesis, and 1 ketoacidosis). No Grade 4/5 AEs occurred. Conclusions: Toripalimab combined with anlotinib and etoposide plus carboplatin/cisplatin showed promising anti-tumor activity and tolerable toxicities in treatment-naïve ES-SCLC. Clinical trial information: NCT04731909.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Bioengineering and Biotechnology Vol. 10 ( 2022-2-21)
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-2-21)
    Abstract: With the development of nanotechnology, a theranostics nanoplatform can have broad applications in multimodal image-guided combination treatment in cancer precision medicine. To overcome the limitations of a single diagnostic imaging mode and a single chemotherapeutic approach, we intend to combat tumor growth and provide therapeutic interventions by integrating multimodal imaging capabilities and effective combination therapies on an advanced platform. So, we have constructed IO@MnO 2 @DOX (IMD) hybrid nanoparticles composed of superparamagnetic iron oxide (IO), manganese dioxide (MnO 2 ), and doxorubicin (DOX). The nano-platform could achieve efficient T2-T1 magnetic resonance (MR) imaging, switchable photoacoustic (PA) imaging, and tumor microenvironment (TME)-responsive DOX release and achieve enhanced synergism of magnetic hyperthermia and chemotherapy with PA/MR bimodal imaging. The results show that IMD has excellent heating properties when exposed to an alternating magnetic field (AMF). Therefore, it can be used as an inducer for tumor synergism therapy with chemotherapy and hyperthermia. In the TME, the IMD nanoparticle was degraded, accompanied by DOX release. Moreover, in vivo experimental results show that the smart nanoparticles had excellent T2-T1 MR and PA imaging capabilities and an excellent synergistic effect of magnetic hyperthermia and chemotherapy. IMD nanoparticles could significantly inhibit tumor growth in tumor-bearing mice with negligible side effects. In conclusion, smart IMD nanoparticles have the potential for tumor diagnosis and growth inhibition as integrated diagnostic nanoprobes.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 9
    In: Lupus, SAGE Publications, Vol. 31, No. 12 ( 2022-10), p. 1441-1455
    Abstract: In systemic lupus erythematosus (SLE), immune tolerance is influenced by defects in naturally occurring T cells (Tregs). To investigate the apoptosis rate of Tregs and their suppressive activity in patients with SLE and then to recognize the genes and signaling pathways that cause Treg apoptosis. FACS was used to assess the frequency and apoptosis rates of Tregs in 48 SLE patients and 28 normal controls (NCs). Coculture of Tregs with CD4 + CD25 − CD127 dim/− T cells was used to assess the suppressive activity of Tregs. Microarray analysis was used to generate unstimulated Tregs gene expression profiles from very high activity patients with SLE and NCs. Real-time PCR was used to confirm differential gene expression. In patients with SLE, the frequency of Tregs was substantially reduced compared to Tregs from NCs. Furthermore, Tregs from SLE patients had an elevated rate of apoptosis and a lower suppressing ability than Tregs from NCs. Tregs apoptosis was negatively associated with the total count of Tregs and positively related to disease activity. Unstimulated Tregs gene expression profiles from patients with recent-onset SLE revealed a biological response that can cause apoptosis, partially triggered by stress, DNA damage, and cytokine stimulation. The discovery of pathway-specific expression signatures is a significant step forward in understanding how Tregs defects contribute to the pathogenesis of SLE. Our findings may contribute to the development of new strategies for treating SLE based on abnormal Tregs apoptosis and restoring immune homeostasis in patients with SLE.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    RVK:
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2008035-9
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  • 10
    In: International Journal of Nanomedicine, Informa UK Limited, Vol. Volume 17 ( 2022-09), p. 4619-4638
    Type of Medium: Online Resource
    ISSN: 1178-2013
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2377464-2
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