To determine the prevalence and risk factors for diabetic retinopathy (DR) and sight-threatening diabetic retinopathy (STDR) in a multi-hospital-based DR screening programme among patients with ...diabetes in China, the Lifeline Express Diabetic Retinopathy Screening Program.
Patients with diabetes in eight hospitals across mainland China (both southern and northern) from January 2014 to July 2016 were recruited in this programme. All participants underwent a standardised interview and examinations and received digital fundus photography. DR severity was graded from retinal fundus photographs by retina specialists in the reading centre of Joint Shantou International Eye Center, according to the grading standards of the English National Screening Programme. STDR was defined as the presence of preproliferative DR (R2), proliferative DR (R3) and/or maculopathy (M1).
16 305 patients with diabetes were screened for DR in total. Fundus photographs were gradable for 15 078 patients (92.5%). The age-gender-standardised prevalence of any DR and STDR was 27.9% (95% CI, 27.2% to 28.6%) and 12.6% (95% CI, 12.1% to 13.1%), respectively. In the multiple logistic regression analysis, younger age (OR, 0.967), longer duration of diabetes (OR, 1.093), higher haemoglobin A1c (OR, 1.115), higher fasting plasma glucose (OR, 1.074), higher systolic blood pressure (OR, 1.014), faster heart rate (OR, 1.010), higher low-density lipoprotein (OR, 1.149), lower triglycerides (OR, 0.975), higher blood urea nitrogen (BUN) (OR, 1.012) and elevated serum creatinine level (OR, 1.003) were associated with the presence of DR. Similar risk factors, except for BUN and triglycerides, were found for STDR.
The prevalence of DR and STDR in diabetes was 27.9% and 12.6%, respectively in this multi-hospital-based population across China. Compared with Western population with diabetes, similar risk factors for DR and STDR were found in Chinese patients with diabetes.
The peak of Internet searches and social media data about the coronavirus disease 2019 (COVID-19) outbreak occurred 10-14 days earlier than the peak of daily incidences in China. Internet searches ...and social media data had high correlation with daily incidences, with the maximum r > 0.89 in all correlations. The lag correlations also showed a maximum correlation at 8-12 days for laboratory-confirmed cases and 6-8 days for suspected cases.
The ability to accurately identify and isolate cells is the cornerstone of precise disease diagnosis and therapies. A single-step cell identification method based on logic analysis of multiple ...surface markers will have unique advantages because of its accuracy and efficacy. Herein, using multiple DNA aptamers for cancer biomarker recognition and associative toehold activation for signal integration and amplification as two molecular keys, we have successfully operated a cell-surface device that can perform AND Boolean logic analysis of multiple biomarkers and precisely label the target cell subtype in large populations of similar cells via the presence or absence of different biomarkers. Our approach can achieve single-step cancer cell identification and isolation with excellent sensitivity and accuracy and thus will have broad applications in biological science, biomedical engineering, and personalized medicine.
More and more targeted agents become available for B cell malignancies with increasing precision and potency. The first-in-class Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, has been in ...clinical use for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. More selective BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being explored. Acalabrutinib (ACP-196) is a novel irreversible second-generation BTK inhibitor that was shown to be more potent and selective than ibrutinib. This review summarized the preclinical research and clinical data of acalabrutinib.
Owing to the prevalence and high mortality rates of cardiac diseases, a more detailed characterization of the human heart is necessary; however, this has been largely impeded by the cellular ...diversity of cardiac tissue and limited access to samples. Here, we show transcriptome profiling of 21,422 single cells-including cardiomyocytes (CMs) and non-CMs (NCMs)-from normal, failed and partially recovered (left ventricular assist device treatment) adult human hearts. Comparative analysis of atrial and ventricular cells revealed pronounced inter- and intracompartmental CM heterogeneity as well as compartment-specific utilization of NCM cell types as major cell-communication hubs. Systematic analysis of cellular compositions and cell-cell interaction networks showed that CM contractility and metabolism are the most prominent aspects that are correlated with changes in heart function. We also uncovered active engagement of NCMs in regulating the behaviour of CMs, exemplified by ACKR1
-endothelial cells, injection of which preserved cardiac function after injury. Beyond serving as a rich resource, our study provides insights into cell-type-targeted intervention of heart diseases.
The development of chimeric antigen receptor T (CAR-T) cell therapy, a specific type of immunotherapy, in recent decades was a fantastic breakthrough for the treatment of hematological malignancies. ...However, difficulties in collecting normal T cells from patients and the time cost of manufacturing CAR-T cells have limited the application of CAR-T-cell therapy. In addition, the termination of related clinical trials on universal CAR-T cell therapy has made further research more difficult. Natural killer (NK) cells have drawn great attention in recent years. Chimeric antigen receptor-NK (CAR-NK) cell therapy is a promising strategy in the treatment of malignant tumors because of its lack of potential for causing graft-versus-host disease (GVHD). In this review, we will address the advances in and achievements of CAR-NK cell therapy.
As a typical representative of all-inorganic lead halide perovskites, cesium lead bromide (CsPbBr3) has attracted significant attention in the context of photovoltaics and other optoelectronic ...applications in recent years. In this paper, CsPbBr3 single crystal growth was conducted by a creative electronic dynamic gradient (EDG) method. The crystal structure was systematically investigated using scientific instruments and equipment. X-ray diffraction techniques, including X-ray diffraction (XRD), temperature-dependent X-ray powder diffraction and the X-ray rocking curve, were used to identify the phase and to investigate phase transition rules. Electron diffraction techniques, including high-resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED) and electron backscatter diffraction (EBSD), were used to investigate the crystal micro-structure. The final results indicated that the grown CsPbBr3 crystal was a perfect single crystal preferentially orienting in the (110) direction and met the basic demand of its applications.
PD-1-PD-L1 interaction is known to drive T cell dysfunction, which can be blocked by anti-PD-1/PD-L1 antibodies. However, studies have also shown that the function of the PD-1-PD-L1 axis is affected ...by the complex immunologic regulation network, and some CD8
T cells can enter an irreversible dysfunctional state that cannot be rescued by PD-1/PD-L1 blockade. In most advanced cancers, except Hodgkin lymphoma (which has high PD-L1/L2 expression) and melanoma (which has high tumor mutational burden), the objective response rate with anti-PD-1/PD-L1 monotherapy is only ~20%, and immune-related toxicities and hyperprogression can occur in a small subset of patients during PD-1/PD-L1 blockade therapy. The lack of efficacy in up to 80% of patients was not necessarily associated with negative PD-1 and PD-L1 expression, suggesting that the roles of PD-1/PD-L1 in immune suppression and the mechanisms of action of antibodies remain to be better defined. In addition, important immune regulatory mechanisms within or outside of the PD-1/PD-L1 network need to be discovered and targeted to increase the response rate and to reduce the toxicities of immune checkpoint blockade therapies. This paper reviews the major functional and clinical studies of PD-1/PD-L1, including those with discrepancies in the pathologic and biomarker role of PD-1 and PD-L1 and the effectiveness of PD-1/PD-L1 blockade. The goal is to improve understanding of the efficacy of PD-1/PD-L1 blockade immunotherapy, as well as enhance the development of therapeutic strategies to overcome the resistance mechanisms and unleash the antitumor immune response to combat cancer.
Cutaneous T-cell lymphomas (CTCLs) comprise a group of heterogeneous diseases involving malignant T cells. The pathogenesis and etiology of CTCL are still unclear, although a large number of genetic ...and epidemiological studies on CTCL have been conducted. Most CTCLs have an indolent course, making early diagnosis difficult. Once large-cell transformation occurs, CTCL progresses to more aggressive types, resulting in an overall survival of less than five years. Epigenetic drugs, which have shown certain curative effects, have been selected as third-line drugs in patients with relapsing and refractory CTCL. Many studies have also identified epigenetic biomarkers from tissues and peripheral blood of patients with CTCL and suggested that epigenetic changes play a role in malignant transformation and histone deacetylase inhibitor (HDACi) resistance in CTCL. Single-cell sequencing has been applied in CTCL studies, revealing heterogeneity in CTCL malignant T cells. The mechanisms of HDACi resistance have also been described, further facilitating the discovery of novel HDACi targets. Despite the heterogeneity of CTCL disease and its obscure pathogenesis, more epigenetic abnormalities have been gradually discovered recently, which not only enables us to understand CTCL disease further but also improves our understanding of the specific role of epigenetics in the pathogenesis and treatment. In this review, we discuss the recent discoveries concerning the pathological roles of epigenetics and epigenetic therapy in CTCL.
Retinal fundus diseases can lead to irreversible visual impairment without timely diagnoses and appropriate treatments. Single disease-based deep learning algorithms had been developed for the ...detection of diabetic retinopathy, age-related macular degeneration, and glaucoma. Here, we developed a deep learning platform (DLP) capable of detecting multiple common referable fundus diseases and conditions (39 classes) by using 249,620 fundus images marked with 275,543 labels from heterogenous sources. Our DLP achieved a frequency-weighted average F1 score of 0.923, sensitivity of 0.978, specificity of 0.996 and area under the receiver operating characteristic curve (AUC) of 0.9984 for multi-label classification in the primary test dataset and reached the average level of retina specialists. External multihospital test, public data test and tele-reading application also showed high efficiency for multiple retinal diseases and conditions detection. These results indicate that our DLP can be applied for retinal fundus disease triage, especially in remote areas around the world.
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