Publications by authors named "H Qiu"

3,994 Publications

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[Role of different cells derived extracellular vesicles in acute respiratory distress syndrome].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Mar;33(3):373-376

Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China. Corresponding author: Qiu Haibo, Email:

Acute respiratory distress syndrome (ARDS) is a common clinical critical condition of the respiratory system, with a high fatality rate and lack of effective drug treatment, hence it is a global medical problem to be solved urgently. Recently, with the in-depth research on extracellular vesicles (EVs) at home and abroad, more and more evidences suggest that EVs play a critical role in the initiation, development and progression of ARDS and have potential clinical application value. The role of different cells derived EVs in ARDS will be reviewed in this paper.
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http://dx.doi.org/10.3760/cma.j.cn121430-20201126-00730DOI Listing
March 2021

The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance.

BMC Biol 2021 Apr 8;19(1):67. Epub 2021 Apr 8.

Department of Biochemistry and Molecular Biology, School of Pre-Clinical Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China.

Background: Trachypithecus leucocephalus, the white-headed langur, is a critically endangered primate that is endemic to the karst mountains in the southern Guangxi province of China. Studying the genomic and transcriptomic mechanisms underlying its local adaptation could help explain its persistence within a highly specialized ecological niche.

Results: In this study, we used PacBio sequencing and optical assembly and Hi-C analysis to create a high-quality de novo assembly of the T. leucocephalus genome. Annotation and functional enrichment revealed many genes involved in metabolism, transport, and homeostasis, and almost all of the positively selected genes were related to mineral ion binding. The transcriptomes of 12 tissues from three T. leucocephalus individuals showed that the great majority of genes involved in mineral absorption and calcium signaling were expressed, and their gene families were significantly expanded. For example, FTH1 primarily functions in iron storage and had 20 expanded copies.

Conclusions: These results increase our understanding of the evolution of alkali tolerance and other traits necessary for the persistence of T. leucocephalus within an ecologically unique limestone karst environment.
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http://dx.doi.org/10.1186/s12915-021-00998-2DOI Listing
April 2021

Allogeneic Hematopoietic Stem Cell Transplantation Improved Survival for Adult Core Binding Factor Acute Myelogenous Leukemia Patients with Intermediate- and Adverse-Risk Genetics in the 2017 European LeukemiaNet.

Transplant Cell Ther 2021 Feb 11;27(2):173.e1-173.e9. Epub 2020 Dec 11.

Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. Electronic address:

The use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for consolidation therapy in patients with core binding factor (CBF) acute myelogenous leukemia (AML) with intermediate- and adverse-risk genetics remains controversial. We retrospectively analyzed the clinical outcomes of 286 CBF-AML patients with intermediate- and adverse-risk genetics in first complete remission following consolidation with chemotherapy (n = 122), auto-HSCT (n = 27), or allo-HSCT (n = 137) between January 2009 and December 2018 at our center. Patients with allo-HSCT showed superior 5-year overall survival (OS; 74% versus 38% or 49%; P < .001) and progression-free survival (PFS; 74% versus 26% or 49%; P < .001) and lower cumulative incidence of relapse (CIR; 9% versus 69% or 31%; P < .001) compared with chemotherapy alone or auto-HSCT. In the allo-HSCT group, minimal residual disease (MRD) at the second and third months after allo-HSCT could predict relapse in t(8;21) patients (2 months: P = .002; 3 months: P < .001) but not in inv(16) patients. Moreover, positive MRD after 2 courses of consolidation chemotherapy before allo-HSCT was an independent risk factor for survival in CBF-AML patients with intermediate- and adverse-risk genetics, whereas haploidentical donor (haplo-) HSCT could overcome the adverse prognosis (5-year OS, 87%; 5-year PFS, 81%; 5-year CIR, 7%). Allo-HSCT could be the optimal first-line consolidation therapy for patients with intermediate- and adverse-risk genetics, and haplo-HSCT could improve survival for patients with positive MRD after 2 courses of consolidation chemotherapy.
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http://dx.doi.org/10.1016/j.jtct.2020.10.010DOI Listing
February 2021

Long-term Outcomes with Nonmyeloablative HLA-Identical Related Hematopoietic Cell Transplantation Using Tacrolimus and Mycophenolate Mofetil for Graft-versus-Host Disease Prophylaxis.

Transplant Cell Ther 2021 Feb 11;27(2):163.e1-163.e7. Epub 2020 Dec 11.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Washington.

Nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) from HLA-identical related donors using cyclosporine (CSP) and mycophenolate mofetil (MMF) for postgrafting immunosuppression is effective therapy for hematologic cancers. However, graft-versus-host-disease (GVHD) remains a major cause of morbidity and mortality. Pilot data suggested lower acute GVHD incidence with tacrolimus/MMF compared to historical experience using CSP/MMF after nonmyeloablative HCT. In a phase II multicenter trial, we evaluated the effect of tacrolimus/MMF for GVHD prophylaxis after HLA-identical related donor peripheral blood HCT in patients with hematologic malignancies (n = 150) using conditioning with 2 Gy total body irradiation (TBI) for patients with a preceding (within 6 months) planned autologous HCT (n = 50) or combined with 90 mg/m fludarabine for those without recent autologous HCT (n = 100). Oral tacrolimus was given from days -3 to 56 (tapered by day +180 if no GVHD). Oral MMF was given from days 0 to 27. Patient median age was 57 (range, 20 to 74) years. The cumulative incidences (CI) of day 100 grade II to IV and III to IV acute GVHD were 27% and 4%, respectively. With median follow-up of 10.3 (range, 3.1 to 14.5) years, the 5-year CI of chronic extensive GVHD was 48%. One-year and 5-year estimates of nonrelapse mortality, relapse/progression, survival, and progression-free survival were 9% and 13%, 35% and 50%, 73% and 53%, and 56% and 37%, respectively. GVHD prophylaxis with tacrolimus/MMF resulted in a low risk of acute GVHD and compared favorably with results from a concurrent trial using CSP/MMF. A randomized phase III trial to investigate tacrolimus/MMF versus CSP/MMF in nonmyeloablative HCT is warranted.
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http://dx.doi.org/10.1016/j.jtct.2020.10.016DOI Listing
February 2021

Cyclometalated iridium(III) complexes as mitochondria-targeted anticancer and antibacterial agents to induce both autophagy and apoptosis.

J Inorg Biochem 2021 Mar 29;219:111450. Epub 2021 Mar 29.

School of Pharmacy, Guangdong Medical University, Dongguan 523808, China. Electronic address:

Mitochondrial damage will hinder the energy production of cells and produce excessive ROS (reactive oxygen species), resulting in cell death through autophagy or apoptosis. In this paper, four cyclometalated iridium(III) complexes (Ir1: [Ir(piq)L]PF; Ir2: [Ir(bzq)L]PF; Ir3: [Ir(dfppy)L]PF; Ir4: [Ir(thpy)L]PF; piq = 1-phenylisoquinoline; bzq = benzo[h]quinoline; dfppy = 2-(2,4-difluorophenyl)pyridine;thpy = 2-(2-thienyl)pyridine; L = 1,10-phenanthroline-5-amine) were synthesized and characterized. Cytotoxicity tests show that these complexes have excellent cytotoxicity to cancer cells, and mechanism studies indicatethat these complexes can specifically target mitochondria. Complexes Ir1 and Ir2 can damage the function of mitochondria, subsequently increasing intracellular levels of ROS, decreasing MMP (mitochondrial membrane potential), and interfering with ATP energy production, which leads to autophagy and apoptosis. Furthermore, autophagy induced by Ir1 and Ir2 can promote cell death in coordination with apoptosis. Surprisingly, these four complexes also showed moderate antibacterial activity to S. aureusand P. aeruginosa.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111450DOI Listing
March 2021

Using Urban Landscape Pattern to Understand and Evaluate Infectious Disease Risk: A Case Study of COVID-19 in Wuhan.

Authors:
Yang Ye Hongfei Qiu

Urban For Urban Green 2021 Apr 2:127126. Epub 2021 Apr 2.

Department of Landscape Architecture, College of Horticulture and Forest, Huazhong Agricultural University, No. 1, Shizishan Street Hongshan District, Wuhan, Hubei Province, 430070, China.

COVID-19 case numbers in 161 sub-districts of Wuhan were investigated based on landscape epidemiology, and their landscape metrics were calculated based on land use/land cover (LULC). Initially, a mediation model verified a partially mediated population role in the relationship between landscape pattern and infection number. Adjusted incidence rate (AIR) and community safety index (CSI), two indicators for infection risk in sub-districts, were 25.82∼63.56 ‱ and 3.00∼15.87 respectively, and central urban sub-districts were at higher infection risk. Geographically weighted regression (GWR) performed better than OLS regression with AICc differences of 7.951∼181.261. The adjusted R in GWR models of class-level index and infection risk were 0.697 to 0.817, while for the landscape-level index they were 0.668 to 0.835. Secondly, 16 key landscape metrics were identified based on GWR, and then a prediction model for infection risk in sub-districts and communities was developed. Using principal component analysis (PCA), development intensity, landscape level, and urban blue-green space were considered to be principal components affecting disease infection risk, explaining 73.1% of the total variance. Cropland (PLAND and LSI), urban land (NP, LPI, and LSI) and unused land (NP) represent development intensity, greatly affecting infection risk in urban areas. Landscape level CONTAG, DIVISION, SHDI, and SHEI represent mobility and connectivity, having a profound impact on infection risk in both urban and suburban areas. Water (PLAND, NP, LPI, and LSI) and woodland (NP, and LSI) represent urban blue-green spaces, and were particularly important for infection risk in suburban areas. Based on urban landscape pattern, we proposed a framework to understand and evaluate infection risk. These findings provide a basis for risk evaluation and policy-making of urban infectious disease, which is significant for community management and urban planning for infectious disease worldwide.
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http://dx.doi.org/10.1016/j.ufug.2021.127126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017915PMC
April 2021

Do essential elements (P and Fe) have mitigation roles in the toxicity of individual and binary mixture of yttrium and cerium to Triticum aestivum?

J Hazard Mater 2021 Mar 27;416:125761. Epub 2021 Mar 27.

School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Essential elements can affect the bioavailability, uptake, and toxicity of metals. However, hardly any research has focused on the roles of essential elements on the toxicity of rare earth metals. Here we examined how P and Fe modified the individual and binary toxicity of Y and Ce to Triticum aestivum, respectively. Standard root elongation tests were used to quantify the toxicity of both single and binary mixtures at three levels of P addition (1, 5, and 10 μM) and Fe addition (0.1, 1, and 5 mM). Our results showed that both P and Fe can alleviate individual toxicity of Y or Ce irrespective of the dose indicators as suggested by the enhanced EC50 values. Both P and Fe might mitigate Y/Ce toxicity by limiting Y/Ce uptake into roots and improving nutritional status of wheats, whereas P can also decrease free Y/Ce ion activities in the exposure media. As for the mixture toxicity of Y and Ce, only improved P, but not Fe can exhibit approximately additive mixture toxicity, which can be adequately predicted by the simple Concentration Addition model. Our results suggested the important roles of P and Fe in assessing Y and Ce toxicity accurately.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125761DOI Listing
March 2021

Microglial Polarization: Novel Therapeutic Strategy against Ischemic Stroke.

Aging Dis 2021 Apr 1;12(2):466-479. Epub 2021 Apr 1.

1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Ischemic stroke, which is the second highest cause of death and the leading cause of disability, represents ~71% of all strokes globally. Some studies have found that the key elements of the pathobiology of stroke is immunity and inflammation. Microglia are the first line of defense in the nervous system. After stroke, the activated microglia become a double-edged sword, with distinct phenotypic changes to the deleterious M1 types and neuroprotective M2 types. Therefore, ways to promote microglial polarization toward M2 phenotype after stroke have become the focus of attention in recent years. In this review, we discuss the process of microglial polarization, summarize the alternation of signaling pathways and epigenetic regulation that control microglial polarization in ischemic stroke, aiming to find the potential mechanisms by which microglia can be transformed into the M2 polarized phenotype.
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http://dx.doi.org/10.14336/AD.2020.0701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990355PMC
April 2021

Dynamic Change of Intracellular Metabolism of Microglia Evaluated by Transcriptomics in an Alzheimer's Mouse Model.

J Alzheimers Dis 2021 Mar 30. Epub 2021 Mar 30.

Department of Neurology, Zhongshan Hospital; State Key Laboratory of Medical Neurobiology; Institutes of Brain Science; Fudan University, Shanghai, China.

Background: Microglia play diverse roles in Alzheimer's disease (AD). Intracellular metabolism has been indicated an important factor in modulating the function of microglia. However, it is not clear whether the intracellular metabolism of microglia changes dynamically in different stages of AD.

Objective: To determine whether microglia intracellular metabolism changes dynamically in different stages of AD.

Methods: Microglia were extracted from APPSwe/PS1dE9 (APP/PS1) mice and wild-type littermates at 2, 4, and 8 months old by fluorescence-activated cell sorting and used for RNA-sequencing analysis and quantitative PCR. Morphologies of amyloid plaques and microglia were detected by immunofluorescence staining.

Results: Compared with control littermates, the microglia of APP/PS1 mice exhibited significant transcriptional changes at 2-month-old before microglia morphological alterations and the plaque formation. The changes continued drastically following age with defined morphological shift of microglia and amyloid plaque enhancement in brains. Further analysis of those genotype and age dependent transcriptomic changes revealed that differentially expressed genes enriched in pathways related to energy metabolism. Compared with wild-type mice, there were changes of some vital genes related to glucose metabolism and lipid metabolism pathways in APP/PS1 mice at different ages. Glucose metabolism may play a major role in early activation of microglia, and lipid metabolism may be more important in later activation period.

Conclusion: Our results showed that microglia actively participate in the pathological progress of AD. The intracellular metabolism of microglia changed significantly in different stages of AD, even preceding amyloid-β deposition.
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http://dx.doi.org/10.3233/JAD-210213DOI Listing
March 2021

Crop straw retention influenced crop yield and greenhouse gas emissions under various external conditions.

Environ Sci Pollut Res Int 2021 Apr 4. Epub 2021 Apr 4.

College of Resources and Environment, Qingdao Agricultural University, Qingdao, 266109, China.

Crop straw retention is a strongly recommended practice for sustainable agricultural production in China. However, a comprehensive analysis of straw retention effects on crop yield, NO and CH emissions, net greenhouse gas (NGHG), and net greenhouse gas intensity (NGHGI) and their response to various external influence factors, including location/climatic conditions, soil properties, and field management practices, in a national scale were easily ignored. Based on the collected published literatures, we found that straw retention improved crop yield and NO and CH emissions by 4.7% (-4.6 to 25.8%), 18.3% (-26.6 to 57.6%), and 21.0% (-49.0 to 214.5%) in contrast with no-straw retention. For different external conditions, crop yield was increased by 15.9% in temperate zone and 10.7% in upland soils with straw retention. NO emissions which correspond to the above conditions were enhanced by 42.2% and 18.8%, while CH emissions were restrained by 49.0% in temperate zone. Negligible changes in crop yield and NO emissions were observed for subtropical zone or paddy soils, but with increase in CH emissions. Additionally, straw retention enhanced NGHG and NGHGI by 20.7% and 15.4% on average regardless of various external conditions, respectively. However, NGHG was reduced under conditions of straw retention in temperature or mulching to field. Straw retention under appropriate site-specially conditions simultaneously safeguard food security and slightly increase environmental effects.
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http://dx.doi.org/10.1007/s11356-021-13698-9DOI Listing
April 2021

Overweight, obesity and coronary artery lesions among Kawasaki disease patients.

Nutr Metab Cardiovasc Dis 2021 Jan 28. Epub 2021 Jan 28.

Children's Heart Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 3250002, Zhejiang, China. Electronic address:

Background And Aims: Overweight is associated with increased cardiovascular disease in general populations. However, a similar relationship among Kawasaki Disease (KD) patients was unclear. The study aimed to investigate the relation between weight-for-height and coronary artery lesions (CAL) among KD patients, and whether laboratory indices modified this relation.

Methods And Results: All consecutive KD patients from January 2009 to December 2014 in a city in China were reviewed, and classified into overweight/obese and control groups. All patients were followed to assess the occurrence of CAL by echocardiography for two months from disease onset. The independent effect of overweight/obesity on CAL was evaluated after adjustment for confounders. The interaction effect between overweight and laboratory indices was examined. The prevalence of overweight/obesity among KD patients was 18.5% (95%CI: 16.0%, 21.0%). The proportion of male patients and the proportion of non-standard IVIG treatment were significantly higher in overweight/obese children in comparison with their counterparts. Overweight/obesity was associated with increased odds of total CAL (aOR = 1.69, 95%CI: 1.16, 2.45) and also increased odds of CAL after treatment (aOR = 1.96, 95%CI: 1.09, 3.51); after adjustment for age, gender, KD type, change of medical departments, number of days before admission, treatment regimen and laboratory index. Similar results were found using stratification analysis. In addition, patients at risk of overweight were also associated with significantly increased risk of CAL. There was interaction between weight-for-height and platelet, WBC, and albumin.

Conclusions: Overweight/obesity may be an independent risk factor for CAL among KD patients. Some laboratory indicators may modify this association.
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http://dx.doi.org/10.1016/j.numecd.2021.01.015DOI Listing
January 2021

Ductile-to-Brittle Transition and Brittle Fracture Stress of Ultrafine-Grained Low-Carbon Steel.

Materials (Basel) 2021 Mar 26;14(7). Epub 2021 Mar 26.

National Institute for Materials Science, 1-2-1, Sengen, Tsukuba 305-0047, Japan.

Ductile-to-brittle transition (DBT) temperature and brittle fracture stress, , are important toughness criteria for structural materials. In this paper, low-carbon steels with an ultrafine elongated grain (UFEG) structure (transverse grain size 1.2 μm) and with two ferrite ()-pearlite structure with grain sizes 10 µm and 18 µm were prepared. The UFEG steel was fabricated using multipass warm biaxial rolling. The tensile tests with a cylindrical specimen and three-point bending tests with a single-edge-notched specimen were performed at -196 °C. The local stress near the notch was quantitatively calculated via finite element analysis (FEA). The for each sample was quantified based on the experimental results and FEA. The relationship between and in the wide range of 1.0 μm to 138 μm was plotted, including data from past literature. Finally, the conditions of grain size and temperature that cause DBT fracture in low-carbon steel were shown via the stress- map. The results quantitatively showed the superiority of grain size for brittle fracture.
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http://dx.doi.org/10.3390/ma14071634DOI Listing
March 2021

The Effect of Void Arrangement on the Pattern Transformation of Porous Soft Solids under Biaxial Loading.

Materials (Basel) 2021 Mar 4;14(5). Epub 2021 Mar 4.

State Key Laboratory of Structural Analysis for Industrial Equipment, International Research Center for Computational Mechanics, Department of Engineering Mechanics, Dalian University of Technology, Dalian 116024, China.

Structural topology and loading condition have important influences on the mechanical behaviors of porous soft solids. The porous solids are usually set to be under uniaxial tension or compression. Only a few studies have considered the biaxial loads, especially the combined loads of tension and compression. In this study, porous soft solids with oblique and square lattices of circular voids under biaxial loadings were studied through integrated experiments and numerical simulations. For the soft solids with oblique lattices of circular voids, we found a new pattern transformation under biaxial compression, which has alternating elliptic voids with an inclined angle. This kind of pattern transformation is rarely reported under uniaxial compression. Introducing tensile deformation in one direction can hamper this kind of pattern transformation under biaxial loading. For the soft solids with square lattices of voids, the number of voids cannot change their deformation behaviors qualitatively, but quantitatively. In general, our present results demonstrate that void morphology and biaxial loading can be harnessed to tune the pattern transformations of porous soft solids under large deformation. This discovery offers a new avenue for designing the void morphology of soft solids for controlling their deformation patterns under a specific biaxial stress-state.
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http://dx.doi.org/10.3390/ma14051205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961720PMC
March 2021

The Progress of Advanced Ultrasonography in Assessing Aortic Stiffness and the Application Discrepancy between Humans and Rodents.

Diagnostics (Basel) 2021 Mar 6;11(3). Epub 2021 Mar 6.

Center for Molecular and Translational Medicine, Institute of Biomedical Science, Georgia State University, Atlanta, GA 30303, USA.

Aortic stiffening is a fundamental pathological alteration of atherosclerosis and other various aging-associated vascular diseases, and it is also an independent risk factor of cardiovascular morbidity and mortality. Ultrasonography is a critical non-invasive method widely used in assessing aortic structure, function, and hemodynamics in humans, playing a crucial role in predicting the pathogenesis and adverse outcomes of vascular diseases. However, its applications in rodent models remain relatively limited, hindering the progress of the research. Here, we summarized the progress of the advanced ultrasonographic techniques applied in evaluating aortic stiffness. With multiple illustrative images, we mainly characterized various ultrasound techniques in assessing aortic stiffness based on the alterations of aortic structure, hemodynamics, and tissue motion. We also discussed the discrepancy of their applications in humans and rodents and explored the potential optimized strategies in the experimental research with animal models. This updated information would help to better understand the nature of ultrasound techniques and provide a valuable prospect for their applications in assessing aortic stiffness in basic science research, particularly with small animals.
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http://dx.doi.org/10.3390/diagnostics11030454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001300PMC
March 2021

Simple and efficient registration of 3D point cloud and image data for an indoor mobile mapping system.

J Opt Soc Am A Opt Image Sci Vis 2021 Apr;38(4):579-586

Registration of 3D lidar point clouds with optical images is critical in the combination of multisource data. Geometric misalignment originally exists in the pose data between lidar point clouds and optical images. To improve the accuracy of the initial pose and the applicability of the integration of 3D points and image data, we develop a simple but efficient registration method. We first extract point features from lidar point clouds and images: point features are extracted from single-frame lidar and point features are extracted from images using a classical Canny operator. The cost map is subsequently built based on Canny image edge detection. The optimization direction is guided by the cost map, where low cost represents the desired direction, and loss function is also considered to improve the robustness of the proposed method. Experiments show positive results.
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http://dx.doi.org/10.1364/JOSAA.414042DOI Listing
April 2021

A machine learning-based pulmonary venous obstruction prediction model using clinical data and CT image.

Int J Comput Assist Radiol Surg 2021 Mar 31. Epub 2021 Mar 31.

Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Dongchuan Rd 96, Guangzhou, 510080, China.

Purpose: In this study, we try to consider the most common type of total anomalous pulmonary venous connection and established a machine learning-based prediction model for postoperative pulmonary venous obstruction by using clinical data and CT images jointly.

Method: Patients diagnosed with supracardiac TPAVC from January 1, 2009, to December 31, 2018, in Guangdong Province People's Hospital were enrolled. Logistic regression were applied for clinical data features selection, while a convolutional neural network was used to extract CT images features. The prediction model was established by integrating the above two kinds of features for PVO prediction. And the proposed methods were evaluated using fourfold cross-validation.

Result: Finally, 131 patients were enrolled in our study. Results show that compared with traditional approaches, the machine learning-based joint method using clinical data and CT image achieved the highest average AUC score of 0.943. In addition, the joint method also achieved a higher sensitivity of 0.828 and a higher positive prediction value of 0.864.

Conclusion: Using clinical data and CT images jointly can improve the performance significantly compared with other methods that using only clinical data or CT images. The proposed machine learning-based joint method demonstrates the practicability of fully using multi-modality clinical data.
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http://dx.doi.org/10.1007/s11548-021-02335-yDOI Listing
March 2021

Donepezil Ameliorates Pulmonary Arterial Hypertension by Inhibiting M2-Macrophage Activation.

Front Cardiovasc Med 2021 15;8:639541. Epub 2021 Mar 15.

Department of Cardiovascular Medicine, The Affiliated Zhuzhou Hospital Xiangya Medical College, Central South University, Zhuzhou, China.

The beneficial effects of parasympathetic stimulation in pulmonary arterial hypertension (PAH) have been reported. However, the specific mechanism has not been completely clarified. Donepezil, an oral cholinesterase inhibitor, enhances parasympathetic activity by inhibiting acetylcholinesterase, whose therapeutic effects in PAH and its mechanism deserve to be investigated. The PAH model was established by a single intraperitoneal injection of monocrotaline (MCT, 50 mg/kg) in adult male Sprague-Dawley rats. Donepezil was administered via intraperitoneal injection daily after 1 week of MCT administration. At the end of the study, PAH status was confirmed by echocardiography and hemodynamic measurement. Testing for acetylcholinesterase activity and cholinergic receptor expression was used to evaluate parasympathetic activity. Indicators of pulmonary arterial remodeling and right ventricular (RV) dysfunction were assayed. The proliferative and apoptotic ability of pulmonary arterial smooth muscle cells (PASMCs), inflammatory reaction, macrophage infiltration in the lung, and activation of bone marrow-derived macrophages (BMDMs) were also tested. PASMCs from the MCT-treated rats were co-cultured with the supernatant of BMDMs treated with donepezil, and then, the proliferation and apoptosis of PASMCs were evaluated. Donepezil treatment effectively enhanced parasympathetic activity. Furthermore, it markedly reduced mean pulmonary arterial pressure and RV systolic pressure in the MCT-treated rats, as well as reversed pulmonary arterial remodeling and RV dysfunction. Donepezil also reduced the proliferation and promoted the apoptosis of PASMCs in the MCT-treated rats. In addition, it suppressed the inflammatory response and macrophage activation in both lung tissue and BMDMs in the model rats. More importantly, donepezil reduced the proliferation and promoted the apoptosis of PASMCs by suppressing M2-macrophage activation. Donepezil could prevent pulmonary vascular and RV remodeling, thereby reversing PAH progression. Moreover, enhancement of the parasympathetic activity could reduce the proliferation and promote the apoptosis of PASMCs in PAH by suppressing M2-macrophage activation.
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http://dx.doi.org/10.3389/fcvm.2021.639541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005547PMC
March 2021

Early T-Cell Precursor Acute Lymphoblastic Leukemia and T/Myeloid Mixed Phenotype Acute Leukemia Possess Overlapping Characteristics and Both Benefit From CAG-Like Regimens and Allogeneic Hematopoietic Stem Cell Transplantation.

Transplant Cell Ther 2021 Feb 28. Epub 2021 Feb 28.

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. Electronic address:

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) and T-lymphoid/myeloid mixed phenotype acute leukemia (T/M-MPAL) are closely related entities and remain a therapeutic challenge. In this study, we characterized the clinical features of 43 ETP-ALL and 41 T/M-MPAL patients and compared clinical outcomes and safety between cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CAG)-like regimens in 34 patients and conventional ALL regimens in 50 patients. In our series, ETP-ALL and T/M-MPAL showed similar biological characteristics, immunophenotypes, genomic alterations, and outcomes. The complete remission (CR) rate and minimal residual disease (MRD)-negative CR rate of CAG-like regimens were significantly higher compared with conventional ALL regimens (CAG-like: 80.0% and 59.7%, respectively; P = .039; ALL: 51.4% and 31.3%, respectively; P = .048). Overall, 90.0% of cases (18/20) achieved CR using combined decitabine and CAG-like regimens. Additionally, CAG-like regimens had lower rates of grade 3 or 4 infection (18.8% vs. 38.2%; P = .059) and grade 1 or 2 hepatotoxicity (37.5% vs. 60.0%; P = .043) than conventional ALL regimens. The 38 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the first CR (CR1) had better overall survival (OS) and leukemia-free survival (LFS) than the 11 patients who underwent allo-HSCT in the second CR (CR2) or in no remission (median OS not reached vs. 7.6 months, P = .0004; median LFS not reached vs. 11.6 months, P = .0008). There was a significant difference in 3-year OS (95.7% vs. 52.5%; P = .0039) and LFS (95.8% vs. 43.5%; P = .0003) after allo-HSCT between pre-transplant MRD-negative and MRD-positive patients. The median OS for patients without allo-HSCT was 32.1 months in the CAG-like group compared with 12.1 months in the non-CAG-like group (P = .019). These findings suggest that ETP-ALL and T/M-MPAL possess overlapping characteristics and CAG-like regimens improve their clinical outcomes.
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http://dx.doi.org/10.1016/j.jtct.2021.02.032DOI Listing
February 2021

Asymmetric Total Synthesis of Sarpagine and Koumine Alkaloids.

Angew Chem Int Ed Engl 2021 Mar 29. Epub 2021 Mar 29.

Chongqing University, School of Pharmaceutical Sciences, CHINA.

We report here a concise, collective, and asymmetric total synthesis of sarpagine alkaloids and biogenetically related koumine alkaloids, which structurally feature a rigid cage scaffold, with L-tryptophan as the starting material. Two key bridged skeleton-forming reactions, namely tandem sequential oxidative cyclopropanol ring-opening cyclization and ketone α-allenylation, ensure concurrent assembly of the caged sarpagine scaffold and installation of requisite derivative handles. With a common caged intermediate as the branch point, by taking advantage of ketone and allene groups therein, total synthesis of five sarpagine alkaloids (affinisine, normacusine B, trinervine, Na-methyl-16-epipericyclivine, and vellosimine) with various substituents and three koumine alkaloids (koumine, koumimine, and N-demethylkoumine) with more complex cage scaffolds has been accomplished.
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http://dx.doi.org/10.1002/anie.202102416DOI Listing
March 2021

Activation of ephrinb1/EPHB2/MAP-2/NMDAR Mediates Hippocampal Neurogenesis Promoted by Transcranial Direct Current Stimulation in Cerebral-Ischemic Mice.

Neuromolecular Med 2021 Mar 29. Epub 2021 Mar 29.

Department of Pharmacology, College of Pharmacy, Chongqing Key Lab of Biochemistry and Molecular Pharmacology, Chongqing Key Lab Drug Metabolism, Chongqing Medical University, No. 1 Yixueyuan Road, Chongqing, 400016, China.

tDCS, a new, safe, non-invasive physical therapy method, is often used in motor dysfunction rehabilitation. However, the effects and underlying mechanisms of tDCS on hippocampal neurogenesis after cerebral ischemia (CI) are still unclear. This study aimed to investigate the promotive effect and mechanism of repetitive anodal-tDCS on hippocampal neurogenesis after CI in mice. The CI model in mice was established using bilateral common carotid artery occlusion (BCCAO). The pathological changes in the hippocampal CA1 region and cognitive function were assessed by hematoxylin and eosin staining and Morris water maze test, respectively. Hippocampal neurogenesis was observed by immunofluorescence staining. The levels of expression of ephrinb1, EPHB2, MAP-2, and NMDAR in the hippocampi were analyzed by qRT-PCR and Western blotting. Compared with the sham mice, the model mice showed significant neuronal damage in the hippocampal CA1 region (P < 0.01), cognitive dysfunction (P < 0.01), and endogenous hippocampal neurogenesis (P < 0.01). These results suggested that the CI model was successfully established, and that CI could promote endogenous hippocampal neurogenesis, but this hippocampal neurogenesis was unable to recover cognitive dysfunction. Compared with the model mice, the tDCS mice had ameliorated pathological damage in the CA1 region (P < 0.01), improved cognitive function (P < 0.01), increased hippocampal neurogenesis (P < 0.01), and increased mRNA and protein expression of ephrinb1, EPHB2, MAP-2, and NMDAR (P < 0.05). Repetitive anodal-tDCS can promote hippocampal neurogenesis and improve cognitive function in CI mice. The effect may be related to the activation of the ephrinb1/EPHB2/MAP-2/NMDAR signaling pathway.
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http://dx.doi.org/10.1007/s12017-021-08654-2DOI Listing
March 2021

A Novel Intergenic Region Between KLHL31 and LRRC1-ALK Exon 20 Fusion Variant in Advanced Lung Adenocarcinoma and its Remarkable Response to ALK Inhibitor.

J Thorac Oncol 2021 Apr;16(4):e21-e23

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2020.12.016DOI Listing
April 2021

miR-30b-5p inhibits cancer progression and enhances cisplatin sensitivity in lung cancer through targeting LRP8.

Apoptosis 2021 Mar 29. Epub 2021 Mar 29.

State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, China.

Accumulated evidence has demonstrated that miRNAs are closely implicated in lung carcinogenesis. Herein, we explored the expression pattern of miR-30b-5p in lung cancer, and aimed to uncover miR-30b-5p roles in lung cancer progression and drug resistance. miR-30b-5p expression profiles in lung cancer tissues and the matched non-tumor tissues were determined by using qPCR. Cell viability, migration, invasion and in vivo tumorigenesis were determined by using the CCK-8, colony formation, wound healing, transwell chambers experiments and tumor xenograft models. RNA immunoprecipitation (RIP) and dual luciferase reporter experiments were applied to evaluate the relationship between miR-30b-5p and LRP8. The results demonstrated that miR-30b-5p showed a low expression profile in lung cancer tissues and cells, and closely linked to poor prognosis and malignant clinical process. Cell viability, migration, invasiveness and tumorigenesis were significantly weakened following miR-30b-5p overexpression in A549 and NCI-H1299 cells, while cell apoptosis rates were increased. In addition, miR-30b-5p was lowly expressed in A549/DDP (a cisplatin drug resistant cell line) as compared with A549 cells, and miR-30b-5p increased A549/DDP cell sensitivity to DDP. However, these above roles of miR-30b-5p were all significantly impaired following the overexpression of LRP8 which was overexpressed in lung cancer tissues. Collectively, this study demonstrated that miR-30b-5p functions as a tumor suppressor in lung cancer, and re-sensitizes lung cancer cells to DDP by targeting LRP8.
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http://dx.doi.org/10.1007/s10495-021-01665-1DOI Listing
March 2021

Ion therapy of pulmonary fibrosis by inhalation of ionic solution derived from silicate bioceramics.

Bioact Mater 2021 Oct 10;6(10):3194-3206. Epub 2021 Mar 10.

Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.

Pulmonary fibrosis (PF) is a chronic and progressively fatal disease, but clinically available therapeutic drugs are limited due to efficacy and side effects. The possible mechanism of pulmonary fibrosis includes the damage of alveolar epithelial cells II (AEC2), and activation of immune cells such as macrophages. The ions released from bioceramics have shown the activity in stimulating soft tissue derived cells such as fibroblasts, endothelia cells and epithelia cells, and regulating macrophage polarization. Therefore, this study proposes an "ion therapy" approach based on the active ions of bioceramic materials, and investigates the therapeutic effect of bioactive ions derived from calcium silicate (CS) bioceramics on mouse models of pulmonary fibrosis. We demonstrate that silicate ions significantly reduce pulmonary fibrosis by simultaneously regulating the functions of AEC2 and macrophages. This result suggests potential clinical applications of ion therapy for lung fibrosis.
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http://dx.doi.org/10.1016/j.bioactmat.2021.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966967PMC
October 2021

Addition of Astatine-211-Labeled Anti-CD45 Antibody to TBI as Conditioning for DLA-Identical Marrow Transplantation: A Novel Strategy to Overcome Graft Rejection in a Canine Presensitization Model: "Radioimmunotherapy to Overcome Transfusion-Induced Sensitization".

Transplant Cell Ther 2021 Feb 25. Epub 2021 Feb 25.

Clinical Research Division, Fred Hutchinson Cancer research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington. Electronic address:

In a canine model of presensitization using donor blood transfusions, 100% of historical control dogs receiving 9.2 Gy total body irradiation (TBI) conditioning before dog leukocyte antigen (DLA)-identical marrow grafts had graft rejection. In this presensitization model, we investigated whether the addition of monoclonal antibody (mAb)-based targeted radioimmunotherapy (RIT) with astatine-211 (At) to TBI could overcome graft rejection. At is an alpha-particle-emitting isotope that has a short path length, very high energy, and a short t½ of 7.2 hours, which allowed targeting radiation to the T cells responsible for graft rejection. Normal canine recipients were given three preceding transfusions of unirradiated whole blood on days -24, -17, and -10 before transplant from their DLA-identical marrow donors. At-anti-CD45 mAb was administered on day -3, and TBI followed by marrow grafts on day 0. Six of the 7 dogs (86%) achieved sustained engraftment as assessed by 100% donor chimerism in mononuclear cells, granulocytes, and CD3 T cells. One dog receiving the lowest CD34 cell content (0.35 × 10 cells/kg) rejected the graft. There were no late rejections in dogs followed up to 1 year. Graft-versus-host disease was seen in one dog. At-anti-CD45 mAb in combination with TBI as conditioning was successful in abrogating graft rejection in 86% of dogs in this presensitization model. At-anti-CD45 mAb conditioning with TBI may serve as a novel promising strategy to overcome graft rejection in heavily transfused patients with red cell disorders.
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http://dx.doi.org/10.1016/j.jtct.2021.02.018DOI Listing
February 2021

Si Miao Formula attenuates non-alcoholic fatty liver disease by modulating hepatic lipid metabolism and gut microbiota.

Phytomedicine 2021 Mar 10;85:153544. Epub 2021 Mar 10.

Functional Metabolomics and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Biomedical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address:

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with few therapeutic options available currently. Traditional Chinese Medicine (TCM) has been practiced for thousands of years in China and Asian countries, and regarded as an important source for identifying novel medicines for diseases. Si Miao Formula (SMF) is a classical TCM formula for the treatment of gout disease by reducing serum uric acid concentrations, while high concentration of uric acid is also an independent risk factor for NAFLD.

Purpose: To investigate the protective effect of SMF on NAFLD in a mouse model induced by a high fat/high sucrose (HFHS) diet.

Methods: Mice received a HFHS diet over a 16-week period to induce NAFLD with or without SMF intervention. Lipid levels were measured in both the liver and serum. Histopathological staining was used to evaluate the extent of hepatic lipid accumulation. Liver transcriptomics was used to enrich differentially expressed genes and to predict regulatory pathways after gene set enrichment analysis. 16S rRNA gene sequencing was used to determine the microbial composition. Genes of liver lipid metabolism, inflammation and intestinal tight junctions were detected by qRT-PCR analysis.

Results: SMF attenuated hepatic steatosis, reduced body weight gain and lipid concentrations, improved sensitivity to insulin and also tolerance to glucose, in mice fed an HFHS diet. Hepatic transcriptomics showed that SMF downregulated the biosynthesis of fatty acids and stimulated the insulin secretion pathway. SMF significantly altered the gut microbiota composition and in particular increased the proportion of Akkermansia muciniphila. In agreement with liver transcriptomics, SMF downregulated the expression of genes implicated in the metabolism of lipids (Acly, Fas, Acc, Scd-1) and pro-inflammatory cytokines (Il-1β, Nlrp-3) in the livers.

Conclusion: The results indicate that SMF attenuates HFHS diet-induced NAFLD and regulates hepatic lipid metabolism pathways. The anti-NAFLD effect of SMF was linked to modulation of the gut microbiota composition and in particular an increased relative abundance of Akkermansia muciniphila.
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http://dx.doi.org/10.1016/j.phymed.2021.153544DOI Listing
March 2021

Novel heterozygous mutation of SLC12A3 gene in Gitelman syndrome.

QJM 2021 Mar 27. Epub 2021 Mar 27.

Department of Nephrology, West China Hospital, Sichuan University, Guoxue Alley No.37, Chengdu, Sichuan Province, 610041, China.

Background: Gitelman syndrome (GS) is an autosomal recessive disease primarily caused by mutations in the SLC12A3 gene, characterized by the hypokalaemic metabolic alkalosis with hypomagnesemia. Here, we investigated the mutation of SLC12A3 gene in a Chinese pedigree with GS and analyzed the clinical manifestations.

Case Presentation: We present the case of a 17-year-old boy diagnosed of GS due to persistent hypokalaemia. To confirm the diagnosis of the proband and to screen for the SLC12A3 gene mutation in this pedigree, we performed SLC12A3 gene mutation tests in the 5 family members. A novel compound heterozygous mutation SLC12A3 (c.976 (exon8) de1G and c.506-1G>A (IVS3)) was identified by genetic testing in the proband. His mother is a carrier of a variant (c.506-1G>A (IVS3)), and his grandmother, father, and younger sister are the carriers of the other mutation (c.976 (exon8) de1G; p. A322_V326delinsDRNFF). His pedigree members had no GS- related symptoms.

Conclusion: This is the first study to report the novel pathogenic compound heterozygous mutation of SLC12A3 gene in GS, which could extend the spectrum of known SLC12A3 gene mutations and provide further insight into the heterogeneity of GS.
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http://dx.doi.org/10.1093/qjmed/hcab066DOI Listing
March 2021

The Effect of Different Diameter of Fat Converters on Adipose Tissue and Its Cellular Components: Selection for Preparation of Nanofat.

Aesthet Surg J 2021 Mar 26. Epub 2021 Mar 26.

Department of Oral and Maxillofacial Surgery, and the Chief Director, Department of Cosmetic Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Background: Nanofat is an autologous product that is prepared mechanically from harvested fat. In nanofat grafting, converters are used for mechanical emulsification to facilitate fat injection. To date, the study of different converters has received scant attention whether these affect the characteristics of nanofat, so as the practical applications and indications.

Objectives: This study set out to investigate the influence of different internal diameter of converters on biological functionality of nanofat during shuffling.

Methods: Three-dimensional finite element method was used to simulate the process of mechanical emulsification of fat,and also for researching the stress with five different converters (3.76mm、 2.00mm、 1.20mm 、1.00mm 、0.80mm). Assessment of morphology of emulsified fat was conducted. Isolated stromal vascular fraction was analyzed for cellular components, number and viability through flowcytometry and Live/ Dead staining. Adipocytic and angiogenic differentiation assay allowed assessment of differentiation capacity of stromal vascular fraction.

Results: The smaller the aperture of the converter, the greater the mechanical force on adipose tissue during mechanical emulsification, showing the different macroscopic and microscopic structure of the emulsified fat. No difference in viability, ration of endothelial progenitor cells and other cells was found. Angiogenic and adipogenic differentiation capacity of the stromal vascular fraction did show a significant change in five different converters.

Conclusions: The mechanical emulsification from different aperture of converters does exert different effects of adipose tissue structure, cell content and multipotency differentiation while not its viability. Converters with different apertures can be selected according to clinical needs.
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http://dx.doi.org/10.1093/asj/sjab146DOI Listing
March 2021