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  • 1
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    Online Resource
    Purinostat Mesylate Is a Uniquely Potent and Selective Inhibitor of HDACs for the Treatment of BCR-ABL –Induced B-Cell Acute Lymphoblastic Leukemia
    American Association for Cancer Research (AACR) ; 2019
    In:  Clinical Cancer Research Vol. 25, No. 24 ( 2019-12-15), p. 7527-7539
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 25, No. 24 ( 2019-12-15), p. 7527-7539
    Abstract: This study was to perform preclinical evaluation of a novel class I and IIb HDAC-selective inhibitor, purinostat mesylate, for the treatment of Ph+ B-cell acute lymphoblastic leukemia (B-ALL). Experimental Design: Biochemical assays were used to test enzymatic activity inhibition of purinostat mesylate. Ph+ leukemic cell lines and patient cells were used to evaluate purinostat mesylate activity in vitro. BL-2 secondary transplantation Ph+ B-ALL mouse model was used to validate its efficacy, mechanism, and pharmacokinetics properties in vivo. BCR-ABL(T315I)–induced primary B-ALL mouse model and PDX mouse model derived from relapsed Ph+ B-ALL patient post TKI treatment were used to determine the antitumor effect of purinostat mesylate for refractory or relapsed Ph+ B-ALL. Long-term toxicity and hERG blockade assays were used to safety evaluation of purinostat mesylate. Results: Purinostat mesylate, a class I and IIb HDAC highly selective inhibitor, exhibited robust antitumor activity in hematologic cancers. Purinostat mesylate at low nanomolar concentration induced apoptosis, and downregulated BCR-ABL and c-MYC expression in Ph+ leukemia cell lines and primary Ph+ B-ALL cells from relapsed patients. Purinostat mesylate efficiently attenuated Ph+ B-ALL progression and significantly prolonged the survival both in BL-2 secondary transplantation model with clinical patient symptoms of Ph+ B-ALL, BCR-ABL(T315I)–induced primary B-ALL mouse model, and PDX model derived from patients with relapsed Ph+ B-ALL post TKI treatment. In addition, purinostat mesylate possesses favorable pharmacokinetics and low toxicity properties. Conclusions: Purinostat mesylate provides a new therapeutic strategy for patients with Ph+ B-ALL, including those who relapse after TKI treatment.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-19-0516
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 2
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    Targeting glutaminase1 and synergizing with clinical drugs achieved more promising antitumor activity on multiple myeloma
    Impact Journals, LLC ; 2019
    In:  Oncotarget Vol. 10, No. 57 ( 2019-10-15), p. 5993-6005
    Details
    In: Oncotarget, Impact Journals, LLC, Vol. 10, No. 57 ( 2019-10-15), p. 5993-6005
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    URL: Article
    DOI: 10.18632/oncotarget.v10i57
    DOI: 10.18632/oncotarget.27243
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2560162-3
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  • 3
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    Artificial intelligence manages congenital cataract with individualized prediction and telehealth computing
    Springer Science and Business Media LLC ; 2020
    In:  npj Digital Medicine Vol. 3, No. 1 ( 2020-08-28)
    Details
    In: npj Digital Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2020-08-28)
    Abstract: A challenge of chronic diseases that remains to be solved is how to liberate patients and medical resources from the burdens of long-term monitoring and periodic visits. Precise management based on artificial intelligence (AI) holds great promise; however, a clinical application that fully integrates prediction and telehealth computing has not been achieved, and further efforts are required to validate its real-world benefits. Taking congenital cataract as a representative, we used Bayesian and deep-learning algorithms to create CC-Guardian, an AI agent that incorporates individualized prediction and scheduling, and intelligent telehealth follow-up computing. Our agent exhibits high sensitivity and specificity in both internal and multi-resource validation. We integrate our agent with a web-based smartphone app and prototype a prediction-telehealth cloud platform to support our intelligent follow-up system. We then conduct a retrospective self-controlled test validating that our system not only accurately detects and addresses complications at earlier stages, but also reduces the socioeconomic burdens compared to conventional methods. This study represents a pioneering step in applying AI to achieve real medical benefits and demonstrates a novel strategy for the effective management of chronic diseases.
    Type of Medium: Online Resource
    ISSN: 2398-6352
    URL: Article
    DOI: 10.1038/s41746-020-00319-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2925182-5
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  • 4
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    Metagenome-wide association study of the alterations in the intestinal microbiome composition of ankylosing spondylitis patients and the effect of traditional and herbal treatment
    Microbiology Society ; 2020
    In:  Journal of Medical Microbiology Vol. 69, No. 6 ( 2020-06-01), p. 797-805
    Details
    In: Journal of Medical Microbiology, Microbiology Society, Vol. 69, No. 6 ( 2020-06-01), p. 797-805
    Abstract: Introduction . Ankylosing spondylitis (AS) is a systemic progressive disease with an unknown etiology that may be related to the gut microbiome. Therefore, a more thorough understanding of its pathogenesis is necessary for directing future therapy. Aim . We aimed to determine the differences in intestinal microbial composition between healthy individuals and patients with AS who received and who did not receive treatment interventions. In parallel, the pathology of AS in each patient was analysed to better understand the link between AS treatment and the intestinal microbiota of the patients. Methodology . Sixty-six faecal DNA samples, including 37 from healthy controls (HCs), 11 from patients with untreated AS (NM), 7 from patients treated with nonsteroidal anti-inflammatory drugs (e.g. celecoxib; WM) and 11 from patients treated with Chinese herbal medicine (CHM), such as the Bushen–Qiangdu–Zhilv decoction, were collected and used in the drug effect analysis. All samples were sequenced using Illumina HiSeq 4000 and the microbial composition was determined. Results . Four species were enriched in the patients with AS: Flavonifractor plautii , Oscillibacter , Parabacteroides distasonis and Bacteroides nordii (HC vs. NM, P 〈 0.05); only F. plautii was found to be significantly changed in the NM-HC comparison. No additional species were found in the HC vs. CHM analysis, which indicated a beneficial effect of CHM in removing the other three strains. F. plautii was found to be significantly increased in the comparison between the HC and WM groups, along with four other species ( Clostridium bolteae , Clostridiales bacterium 1_7_47FAA, C. asparagiforme and C. hathewayi ). The patients with AS harboured more bacterial species associated with carbohydrate metabolism and glycan biosynthesis in their faeces. They also had bacterial profiles less able to biodegrade xenobiotics or synthesize and transport vitamins. Conclusion . The gut microbiota of the patients with AS varied from that of the HCs, and the treatment had an impact on this divergence. Our data provide insight that could guide improvements in AS treatment.
    Type of Medium: Online Resource
    ISSN: 0022-2615 , 1473-5644
    URL: Article
    DOI: 10.1099/jmm.0.001107
    RVK:
    XA 55020
    Language: English
    Publisher: Microbiology Society
    Publication Date: 2020
    detail.hit.zdb_id: 2083944-3
    SSG: 12
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  • 5
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    Loss-of-function mutations in FREM2 disrupt eye morphogenesis
    Elsevier BV ; 2019
    In:  Experimental Eye Research Vol. 181 ( 2019-04), p. 302-312
    Details
    In: Experimental Eye Research, Elsevier BV, Vol. 181 ( 2019-04), p. 302-312
    Type of Medium: Online Resource
    ISSN: 0014-4835
    URL: Article
    DOI: 10.1016/j.exer.2019.02.013
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 1466924-9
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  • 6
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    Human Adipose-Derived Stem Cells Suppress Elastase-Induced Murine Abdominal Aortic Inflammation and Aneurysm Expansion through Paracrine Factors
    SAGE Publications ; 2017
    In:  Cell Transplantation Vol. 26, No. 2 ( 2017-02), p. 173-189
    Details
    In: Cell Transplantation, SAGE Publications, Vol. 26, No. 2 ( 2017-02), p. 173-189
    Abstract: Abdominal aortic aneurysm (AAA) is a potentially lethal disease associated with immune activation-induced aortic degradation. We hypothesized that xenotransplantation of human adipose-derived stem cells (hADSCs) would reduce aortic inflammation and attenuate expansion in a murine AAA model. Modulatory effects of ADSCs on immune cell subtypes associated with AAA progression were investigated using human peripheral blood mononuclear cells (hPBMNCs) cocultured with ADSCs. Murine AAA was induced through elastase application to the abdominal aorta in C57BL/6 mice. ADSCs were administered intravenously, and aortic changes were determined by ultrasonography and videomicrometry. Circulating monocytes, aortic neutrophils, CD28 − T cells, FoxP3 + regulatory T cells (Tregs), and CD206 + M2 macrophages were assessed at multiple terminal time points. In vitro, ADSCs induced M2 macrophage and Treg phenotypes while inhibiting neutrophil transmigration and lymphocyte activation without cellular contact. Intravenous ADSC delivery reduced aneurysmal expansion starting from day 4 [from baseline: 54.8% (saline) vs. 16.9% (ADSCs), n = 10 at baseline, n = 4 at day 4, p 〈 0.001], and the therapeutic effect persists through day 14 (from baseline: 64.1% saline vs. 24.6% ADSCs, n = 4, p 〈 0.01). ADSC administration increased aortic Tregs by 20-fold ( n = 5, p 〈 0.01), while decreasing CD4 + CD28 − (-28%), CD8 + CD28 − T cells (-61%), and Ly6G/C + neutrophils (-43%, n = 5, p 〈 0.05). Circulating CD115 + CXCR1 − LY6C + -activated monocytes decreased in the ADSC-treated group by day 7 (-60%, n = 10, p 〈 0.05), paralleled by an increase in aortic CD206 + M2 macrophages by 2.4-fold ( n = 5, p 〈 0.05). Intravenously injected ADSCs transiently engrafted in the lung on day 1 without aortic engraftment at any time point. In conclusion, ADSCs exhibit pleiotropic immunomodulatory effects in vitro as well as in vivo during the development of AAA. The temporal evolution of these effects systemically as well as in aortic tissue suggests that ADSCs induce a sequence of anti-inflammatory cellular events mediated by paracrine factors, which leads to amelioration of AAA progression.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    URL: Article
    DOI: 10.3727/096368916X692212
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2020466-8
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  • 7
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    Prevalence of depression and depressive symptoms among outpatients: a systematic review and meta-analysis
    BMJ ; 2017
    In:  BMJ Open Vol. 7, No. 8 ( 2017-08), p. e017173-
    Details
    In: BMJ Open, BMJ, Vol. 7, No. 8 ( 2017-08), p. e017173-
    Abstract: Depression and depressive symptoms are common mental disorders that have a considerable effect on patients’ health-related quality of life and satisfaction with medical care, but the prevalence of these conditions varies substantially between published studies. The aim of this study is to conduct a systematic review and meta-analysis to provide a precise estimate of the prevalence of depression or depressive symptoms among outpatients in different clinical specialties. Design Systematic review and meta-analysis. Data sources and eligibility criteria The PubMed and PsycINFO, EMBASE and Cochrane Library databases were searched to identify observational studies that contained information on the prevalence of depression and depressive symptoms in outpatients. All studies included were published before January 2016. Data characteristics were extracted independently by two investigators. The point prevalence of depression or depressive symptoms was measured using validated self-report questionnaires or structured interviews. Assessments were pooled using a random-effects model. Differences in study-level characteristics were estimated by meta-regression analysis. Heterogeneity was assessed using standard χ 2 tests and the I 2 statistic. The study protocol has been registered with PROSPERO under number CRD42017054738. Results Eighty-three cross-sectional studies involving 41 344 individuals were included in this study. The overall pooled prevalence of depression or depressive symptoms was 27.0% (10 943/41 344 individuals; 95% CI 24.0% to 29.0%), with significant heterogeneity between studies (p 〈 0.0001, τ 2 =0.3742, I 2 =96.7%). Notably, a significantly higher prevalence of depression and depressive symptoms was observed in outpatients than in the healthy controls (OR 3.16, 95% CI 2.66 to 3.76, I 2 =72.0%, χ 2 =25.33). The highest depression/depressive symptom prevalence estimates occurred in studies of outpatients from otolaryngology clinics (53.0%), followed by dermatology clinics (39.0%) and neurology clinics (35.0%). Subgroup analyses showed that the prevalence of depression and depressive symptoms in different specialties varied from 17.0% to 53.0%. The prevalence of depression and depressive symptoms was higher among outpatients in developing countries than in outpatients from developed countries. Moreover, the prevalence of depression and depressive symptoms in outpatients slightly decreased from 1996 to 2010. Regarding screening instruments, the Beck Depression Inventory led to a higher estimate of the prevalence of depression and depressive symptoms (1316/4702, 36.0%, 95% CI 29.0% to 44.0%, I 2 =94.8%) than the Hospital Anxiety and Depression Scale (1003/2025, 22.0%, 95% CI 12.0% to 35.0%, I 2 =96.6%). Conclusion Our study provides evidence that a significant proportion of outpatients experience depression or depressive symptoms, highlighting the importance of developing effective management strategies for the early identification and treatment of these conditions among outpatients in clinical practice. The substantial heterogeneity between studies was not fully explained by the variables examined.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1136/bmjopen-2017-017173
    DOI: 10.1136/bmjopen-2017-017173.supp1
    DOI: 10.1136/bmjopen-2017-017173.supp2
    Language: English
    Publisher: BMJ
    Publication Date: 2017
    detail.hit.zdb_id: 2599832-8
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  • 8
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    Deep learning for automated glaucomatous optic neuropathy detection from ultra-widefield fundus images
    BMJ ; 2021
    In:  British Journal of Ophthalmology Vol. 105, No. 11 ( 2021-11), p. 1548-1554
    Details
    In: British Journal of Ophthalmology, BMJ, Vol. 105, No. 11 ( 2021-11), p. 1548-1554
    Abstract: To develop a deep learning system for automated glaucomatous optic neuropathy (GON) detection using ultra-widefield fundus (UWF) images. Methods We trained, validated and externally evaluated a deep learning system for GON detection based on 22 972 UWF images from 10 590 subjects that were collected at 4 different institutions in China and Japan. The InceptionResNetV2 neural network architecture was used to develop the system. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity were used to assess the performance of detecting GON by the system. The data set from the Zhongshan Ophthalmic Center (ZOC) was selected to compare the performance of the system to that of ophthalmologists who mainly conducted UWF image analysis in clinics. Results The system for GON detection achieved AUCs of 0.983–0.999 with sensitivities of 97.5–98.2% and specificities of 94.3–98.4% in four independent data sets. The most common reasons for false-negative results were confounding optic disc characteristics caused by high myopia or pathological myopia (n=39 (53%)). The leading cause for false-positive results was having other fundus lesions (n=401 (96%)). The performance of the system in the ZOC data set was comparable to that of an experienced ophthalmologist (p 〉 0.05). Conclusion Our deep learning system can accurately detect GON from UWF images in an automated fashion. It may be used as a screening tool to improve the accessibility of screening and promote the early diagnosis and management of glaucoma.
    Type of Medium: Online Resource
    ISSN: 0007-1161 , 1468-2079
    URL: Article
    DOI: 10.1136/bjophthalmol-2020-317327
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 1482974-5
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  • 9
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    Treating Multiple Myeloma in the Context of the Bone Marrow Microenvironment
    MDPI AG ; 2022
    In:  Current Oncology Vol. 29, No. 11 ( 2022-11-21), p. 8975-9005
    Details
    In: Current Oncology, MDPI AG, Vol. 29, No. 11 ( 2022-11-21), p. 8975-9005
    Abstract: The treatment landscape of multiple myeloma (MM) has evolved considerably with the FDA-approval of at least 15 drugs over the past two decades. Together with the use of autologous stem cell transplantation, these novel therapies have resulted in significant survival benefit for patients with MM. In particular, our improved understanding of the BM and immune microenvironment has led to the development of highly effective immunotherapies that have demonstrated unprecedented response rates even in the multiple refractory disease setting. However, MM remains challenging to treat especially in a high-risk setting. A key mediator of therapeutic resistance in MM is the bone marrow (BM) microenvironment; a deeper understanding is necessary to facilitate the development of therapies that target MM in the context of the BM milieu to elicit deeper and more durable responses with the ultimate goal of long-term control or a cure of MM. In this review, we discuss our current understanding of the role the BM microenvironment plays in MM pathogenesis, with a focus on its immunosuppressive nature. We also review FDA-approved immunotherapies currently in clinical use and highlight promising immunotherapeutic approaches on the horizon.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    URL: Article
    DOI: 10.3390/curroncol29110705
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2270777-3
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  • 10
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    Optical Attenuation Coefficient Optimization Algorithm for Deep Tissue Signals in Optical Coherence Tomography Based on Kalman Filter
    MDPI AG ; 2023
    In:  Photonics Vol. 10, No. 4 ( 2023-04-16), p. 460-
    Details
    In: Photonics, MDPI AG, Vol. 10, No. 4 ( 2023-04-16), p. 460-
    Abstract: Optical coherence tomography (OCT) attenuation imaging is a technique that uses the optical attenuation coefficient (OAC) to distinguish the types or pathological states of tissues and has been increasingly used in basic research and clinical diagnosis. With the increasing application of swept-source OCT, scholars are increasingly inclined to explore deep tissues. Unfortunately, the accuracy of OAC calculation when exploring deep tissues has yet to be improved. Existing methods generally have the following problems: overestimation error, underestimation error, severe fluctuation, or stripe artifacts in the OAC calculation of the OCT tail signal. The main reason for this is that the influence of the noise floor on the OCT weak signal at the tail-end is not paid enough attention. The noise floor can change the attenuation pattern of the OCT tail signal, which can lead to severe errors in the OAC. In this paper, we proposed a Kalman filter-based OAC optimal algorithm to solve this problem. This algorithm can not only eliminate the influence of the noise floor, but can also effectively protect the weak signal at the tail-end from being lost. The OAC of deep tissues can be calculated accurately and stably. Numerical simulation, phantom, and in vivo experiments were tested to verify the algorithm’s effectiveness in this paper. This technology is expected to play an essential role in disease diagnosis and in the evaluation of the effectiveness of treatment methods.
    Type of Medium: Online Resource
    ISSN: 2304-6732
    URL: Article
    DOI: 10.3390/photonics10040460
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2770002-1
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