Publications by authors named "XuDong Xie"

47 Publications

Nomogram for Predicting Deep Venous Thrombosis in Lower Extremity Fractures.

Biomed Res Int 2021 22;2021:9930524. Epub 2021 Jun 22.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road. 1277#, Wuhan, 430022 Hubei, China.

Deep venous thrombosis (DVT) is a common complication in patients with lower extremity fractures, causing delays in recovery short-term and possible impacts on quality of life long-term. Early prediction and prevention of thrombosis can effectively reduce patient pain while improving outcomes. Although research on the risk factors for thrombosis is prevalent, there is a stark lack of clinical predictive models for DVT occurrence specifically in patients with lower limb fractures. In this study, we aim to propose a new thrombus prediction model for lower extremity fracture patients. Data from 3300 patients with lower limb fractures were collected from Wuhan Union Hospital and Hebei Third Hospital, China. Patients who met our inclusion criteria were divided into a thrombosis and a nonthrombosis group. A multivariate logistic regression analysis was carried out to identify predictors with obvious effects, and the corresponding formulas were used to establish the model. Model performance was evaluated using a discrimination and correction curve. 2662 patients were included in the regression analysis, with 1666 in the thrombosis group and 996 in the nonthrombosis group. Predictive factors included age, Body Mass Index (BMI), fracture-fixation types, energy of impact at the time of injury, blood transfusion during hospitalization, and use of anticoagulant drugs. The discriminative ability of the model was verified using the C-statistic (0.676). For the convenience of clinical use, a score table and nomogram were compiled. Data from two centers were used to establish a novel thrombus prediction model specific for patients with lower limb fractures, with verified predictive ability.
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http://dx.doi.org/10.1155/2021/9930524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245242PMC
June 2021

A Novel Prediction Model of COVID-19 Progression: A Retrospective Cohort Study.

Infect Dis Ther 2021 Jun 14. Epub 2021 Jun 14.

Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.

Introduction: Estimating the risk of disease progression is of utmost importance for planning appropriate setting of care and treatment for patients with coronavirus disease 2019 (COVID-19). This study aimed to develop and validate a novel prediction model of COVID-19 progression.

Methods: In total, 814 patients in the training set were included to develop a novel scoring system; and 420 patients in the validation set were included to validate the model.

Results: A prediction score, called ACCCDL, was developed on the basis of six risk factors associated with COVID-19 progression: age, comorbidity, CD4 T cell count, C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH). For predicting COVID-19 progression, the ACCCDL score yielded a significantly higher area under the receiver operating characteristic curve (AUROC) compared with the CALL score, CoLACD score, PH-COVID-19 score, neutrophil-lymphocyte ratio, and lymphocyte-monocyte ratio both in the training set (0.92, 0.84, 0.83, 0.83, 0.76, and 0.65, respectively) and in the validation set (0.97, 0.83, 0.83, 0.78, 0.74, and 0.60, respectively). Over 99% of patients with the ACCCDL score < 12 points will not progress to severe cases, and over 30% of patients with the ACCCDL score > 20 points will progress to severe cases.

Conclusion: The ACCCDL score could stratify patients with at risk of COVID-19 progression, and was useful in regulating the large flow of patients with COVID-19 between primary health care and tertiary centers.
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http://dx.doi.org/10.1007/s40121-021-00460-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202540PMC
June 2021

Deep learning for predicting COVID-19 malignant progression.

Med Image Anal 2021 Aug 12;72:102096. Epub 2021 May 12.

Department of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, United Kingdom.

As COVID-19 is highly infectious, many patients can simultaneously flood into hospitals for diagnosis and treatment, which has greatly challenged public medical systems. Treatment priority is often determined by the symptom severity based on first assessment. However, clinical observation suggests that some patients with mild symptoms may quickly deteriorate. Hence, it is crucial to identify patient early deterioration to optimize treatment strategy. To this end, we develop an early-warning system with deep learning techniques to predict COVID-19 malignant progression. Our method leverages CT scans and the clinical data of outpatients and achieves an AUC of 0.920 in the single-center study. We also propose a domain adaptation approach to improve the generalization of our model and achieve an average AUC of 0.874 in the multicenter study. Moreover, our model automatically identifies crucial indicators that contribute to the malignant progression, including Troponin, Brain natriuretic peptide, White cell count, Aspartate aminotransferase, Creatinine, and Hypersensitive C-reactive protein.
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http://dx.doi.org/10.1016/j.media.2021.102096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112895PMC
August 2021

Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis.

J Nanobiotechnology 2021 May 21;19(1):150. Epub 2021 May 21.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: Enhanced angiogenesis can promote diabetic wound healing. Mesenchymal stem cells (MSCs)-derived exosomes, which are cell-free therapeutics, are promising candidates for the treatment of diabetic wound healing. The present study aimed to investigate the effect of exosomes derived from MSCs pretreated with pioglitazone (PGZ-Exos) on diabetic wound healing.

Results: We isolated PGZ-Exos from the supernatants of pioglitazone-treated BMSCs and found that PGZ-Exos significantly promote the cell viability and proliferation of Human Umbilical Vein Vascular Endothelial Cells (HUVECs) injured by high glucose (HG). PGZ-Exos enhanced the biological functions of HUVECs, including migration, tube formation, wound repair and VEGF expression in vitro. In addition, PGZ-Exos promoted the protein expression of p-AKT, p-PI3K and p-eNOS and suppressed that of PTEN. LY294002 inhibited the biological function of HUVECs through inhibition of the PI3K/AKT/eNOS pathway. In vivo modeling in diabetic rat wounds showed that pioglitazone pretreatment enhanced the therapeutic efficacy of MSCs-derived exosomes and accelerated diabetic wound healing via enhanced angiogenesis. In addition, PGZ-Exos promoted collagen deposition, ECM remodeling and VEGF and CD31 expression, indicating adequate angiogenesis in diabetic wound healing.

Conclusions: PGZ-Exos accelerated diabetic wound healing by promoting the angiogenic function of HUVECs through activation of the PI3K/AKT/eNOS pathway. This offers a promising novel cell-free therapy for treating diabetic wound healing.
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http://dx.doi.org/10.1186/s12951-021-00894-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139165PMC
May 2021

Efficacy Evaluation of Thymosin Alpha 1 in Non-severe Patients With COVID-19: A Retrospective Cohort Study Based on Propensity Score Matching.

Front Med (Lausanne) 2021 23;8:664776. Epub 2021 Apr 23.

Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Thymosin alpha 1 (Thymosin-α1) is a potential treatment for patients with COVID-19. We aimed to determine the effect of Thymosin-α1 in non-severe patients with COVID-19. We retrospectively enrolled 1,388 non-severe patients with COVID-19. The primary and secondary clinical outcomes were evaluated with comparisons between patients treated with or without Thymosin-α1 therapy. Among 1,388 enrolled patients, 232 patients (16.7%) received both Thymosin-α1 therapy and standard therapy (Thymosin-α1 group), and 1,156 patients (83.3%) received standard therapy (control group). After propensity score matching (1:1 ratio), baseline characteristics were well-balanced between the Thymosin-α1 group and control group. The proportion of patients that progressed to severe COVID-19 is 2.17% for the Thymosin-α1 group and 2.71% for the control group ( = 0.736). The COVID-19-related mortality is 0.54% for the Thymosin-α1 group and 0 for the control group ( = 0.317). Compared with the control group, the Thymosin-α1 group had significantly shorter SARS-CoV-2 RNA shedding duration (13 vs. 16 days, = 0.025) and hospital stay (14 vs. 18 days, < 0.001). No statistically significant difference was found between the Thymosin-α1 group and control group in duration of symptoms (median, 4 vs. 3 days, = 0.843) and antibiotic utilization rate (14.1% vs. 15.2%, = 0.768). For non-severe patients with COVID-19, Thymosin-α1 can shorten viral RNA shedding duration and hospital stay but did not prevent COVID-19 progression and reduce COVID-19-related mortality rate.
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http://dx.doi.org/10.3389/fmed.2021.664776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102900PMC
April 2021

Germline Saturation Mutagenesis Induces Skeletal Phenotypes in Mice.

J Bone Miner Res 2021 Apr 27. Epub 2021 Apr 27.

Center for Genetics of Host Defense, UT Southwestern Medical Center, Dallas, TX, USA.

Proper embryonic and postnatal skeletal development require coordination of myriad complex molecular mechanisms. Disruption of these processes, through genetic mutation, contributes to variation in skeletal development. We developed a high-throughput N-ethyl-N-nitrosourea (ENU)-induced saturation mutagenesis skeletal screening approach in mice to identify genes required for proper skeletal development. Here, we report initial results from live-animal X-ray and dual-energy X-ray absorptiometry (DXA) imaging of 27,607 G3 mice from 806 pedigrees, testing the effects of 32,198 coding/splicing mutations in 13,020 genes. A total of 39.7% of all autosomal genes were severely damaged or destroyed by mutations tested twice or more in the homozygous state. Results from our study demonstrate the feasibility of in vivo mutagenesis to identify mouse models of skeletal disease. Furthermore, our study demonstrates how ENU mutagenesis provides opportunities to create and characterize putative hypomorphic mutations in developmentally essential genes. Finally, we present a viable mouse model and case report of recessive skeletal disease caused by mutations in FAM20B. Results from this study, including engineered mouse models, are made publicly available via the online Mutagenetix database. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4323DOI Listing
April 2021

miRNA-92a-3p regulates osteoblast differentiation in patients with concomitant limb fractures and TBI via IBSP/PI3K-AKT inhibition.

Mol Ther Nucleic Acids 2021 Mar 15;23:1345-1359. Epub 2021 Feb 15.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Patients who sustain concomitant fractures and traumatic brain injury (TBI) are known to have significantly quicker fracture-healing rates than patients with isolated fractures. The mechanisms underlying this phenomenon have yet to be identified. In the present study, we found that the upregulation of microRNA-92a-3p (miRNA-92a-3p) induced by TBI correlated with a decrease in integrin binding sialoprotein (IBSP) expression in callus formation. , overexpressing miRNA-92a-3p inhibited IBSP expression and accelerated osteoblast differentiation, whereas silencing of miRNA-92a-3p inhibited osteoblast activity. A decrease in IBSP facilitated osteoblast differentiation via the Phosphatidylinositol 3-kinase/threonine kinase 1 (PI3K/AKT) signaling pathway. Through luciferase assays, we found evidence that IBSP is a miRNA-92a-3p target gene that negatively regulates osteoblast differentiation. Moreover, the present study confirmed that pre-injection of agomiR-92a-3p leads to increased bone formation. Collectively, these results indicate that miRNA-92a-3p overexpression may be a key factor underlying the improved fracture healing observed in TBI patients. Upregulation of miRNA-92a-3p may therefore be a promising therapeutic strategy for promoting fracture healing and preventing nonunion.
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http://dx.doi.org/10.1016/j.omtn.2021.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920808PMC
March 2021

The vital role of Gli1 mesenchymal stem cells in tissue development and homeostasis.

J Cell Physiol 2021 Sep 2;236(9):6077-6089. Epub 2021 Feb 2.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Periodontics, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

The hedgehog (Hh) signaling pathway plays an essential role in both tissue development and homeostasis. Glioma-associated oncogene homolog 1 (Gli1) is one of the vital transcriptional factors as well as the direct target gene in the Hh signaling pathway. The cells expressing the Gli1 gene (Gli1 cells) have been identified as mesenchymal stem cells (MSCs) that are responsible for various tissue developments, homeostasis, and injury repair. This review outlines some recent discoveries on the crucial roles of Gli1 MSCs in the development and homeostasis of varieties of hard and soft tissues.
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http://dx.doi.org/10.1002/jcp.30310DOI Listing
September 2021

Efficacy evaluation of intravenous immunoglobulin in non-severe patients with COVID-19: A retrospective cohort study based on propensity score matching.

Int J Infect Dis 2021 Apr 9;105:525-531. Epub 2021 Jan 9.

Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address:

Objectives: At the present time, there is an absence of any proven effective antiviral therapy for patients with coronavirus disease 2019 (COVID-19). The aim of this study was to assess the efficacy of intravenous immunoglobulin (IVIG) in non-severe patients with COVID-19.

Methods: A retrospective study based on propensity score matching (PSM) was designed. Primary outcomes included the severity and mortality rates. Secondary outcomes included the duration of fever, virus clearance time, length of hospital stay, and use of antibiotics.

Results: A total of 639 non-severe patients with COVID-19 were enrolled. Forty-five patients received IVIG therapy and 594 received non-IVIG therapy. After PSM (1:2 ratio), the baseline characteristics were well balanced between the IVIG group (n = 45) and control group (n = 90). No statistically significant difference was found between the IVIG group and control group in the duration of fever (median 3 vs 3 days, p = 0.667), virus clearance time (median 11 vs 10 days, p = 0.288), length of hospital stay (median 14 vs 13 days, p = 0.469), or use of antibiotics (40% vs 38.9%, p = 0.901). Meanwhile, compared to the IVIG group, no more patients in the control group progressed to severe disease (3.3% vs 6.6%, p = 0.376) or died (0 vs 2.2%, p = 0.156).

Conclusions: In non-severe patients with COVID-19, no benefit was observed with IVIG therapy beyond standard therapy.
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http://dx.doi.org/10.1016/j.ijid.2021.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833031PMC
April 2021

A Novel Instant 3-Dimensional Printing System for Postoperative Fracture Patients: A Comparative Cohort Study.

Med Sci Monit 2021 Jan 1;27:e928240. Epub 2021 Jan 1.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).

BACKGROUND Traditional plaster (TP) is a widely used auxiliary fixation (AF) approach for postoperative fracture patients. However, patient discomfort and inconvenience to clinicians has limited its application. We introduce a novel instant 3-dimensional printing appliance system (3D-AS) to address such issues. MATERIAL AND METHODS Twenty-seven postoperative fracture patients were divided randomly between a TP group and a 3D-AS group, and analyzed retrospectively. Radiographic images during follow-up were evaluated for fracture healing and fracture reduction quality. The range of motion (ROM) was recorded to assess motor performance. Patient pain was assessed using the Visual Analogue Scale (VAS). Complications were also compared between the 2 groups. RESULTS The patients comprised 17 men and 10 women with ages ranging from 21 to 69 years (mean age: 47.35). All patients completed a follow-up visit (range: 14-19 months, mean: 13.59 months). Although no significant difference was found between general characteristics (P>0.05) and the time of fracture union (P>0.05), significant differences between groups were seen in complications (P<0.05), VAS (P<0.01), patient satisfaction (P<0.05), and ROM for the upper joints (P<0.05). CONCLUSIONS Our study suggests that 3D-AS provides better upper-limb ROM and more comfortable healing for postoperative fracture patients, indicating that it can be recommended for use in such patients.
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http://dx.doi.org/10.12659/MSM.928240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784143PMC
January 2021

MAGGIC Risk Model Predicts Adverse Events and Left Ventricular Remodeling in Non-Ischemic Dilated Cardiomyopathy.

Int J Gen Med 2020 10;13:1477-1486. Epub 2020 Dec 10.

Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China.

Purpose: We aimed to study the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) risk model's prognostic value and relationship with left ventricular remodeling in dilated cardiomyopathy.

Patients And Methods: Dilated cardiomyopathy patients were prospectively recruited and underwent clinical assessments. MAGGIC risk score was calculated. Patients were followed up for adverse events and echocardiography. Primary endpoints were all-cause mortality and first rehospitalization due to heart failure. Secondary endpoint was left ventricular remodeling defined as a decline in left ventricular ejection fraction >10% or an increase in left ventricular end-diastolic diameter >10%. Survival status was examined using Cox regression analysis. The model's ability to discriminate adverse events and left ventricular remodeling was calculated using a receiver operating characteristics curve.

Results: In total, 114 patients were included (median follow-up time = 31 months). The risk score was independently related to adverse events (2-year all-cause mortality: hazard ratio [HR] = 1.122; 95% confidence interval [CI], 1.043-1.208; 1-year first rehospitalization due to heart failure: HR = 1.094; 95% CI, 1.032-1.158; 2-year first rehospitalization due to heart failure: HR = 1.088; 95% CI, 1.033-1.147, all P < 0.05). One-year change in left ventricular end-diastolic diameter was correlated with the risk score (r = 0.305, P = 0.002). The model demonstrated modest ability in discriminating adverse events and left ventricular remodeling (all areas under the curve were 0.6-0.7).

Conclusion: The MAGGIC risk score was related to adverse events and left ventricular remodeling in dilated cardiomyopathy.
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http://dx.doi.org/10.2147/IJGM.S288732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736706PMC
December 2020

Percutaneous transmyocardial ablation of a metastatic adrenocortical carcinoma invading the interventricular septum.

Eur Heart J 2021 05;42(20):2023

Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang, China.

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http://dx.doi.org/10.1093/eurheartj/ehaa911DOI Listing
May 2021

The identification of critical time windows of postnatal root elongation in response to Wnt/β-catenin signaling.

Oral Dis 2020 Dec 12. Epub 2020 Dec 12.

Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX, USA.

Objectives: In this study, we attempted to define the precise window of time for molar root elongation using a gain-of-function mutation of β-catenin model.

Materials And Methods: Both the control and constitutively activated β-catenin (CA-β-cat) mice received a one-time tamoxifen administration (for activation of β-catenin at newborn, postnatal day 3, or 5, or 7, or 9) and were harvested at the same stage of P21. Multiple approaches were used to define the window of time of postnatal tooth root formation.

Results: In the early activation groups (tamoxifen induction at newborn, or P3 or P5), there was a lack of molar root elongation in the CA-β-cat mice. When induced at P7, the root length was slightly reduced at P21. However, the root length was essentially the same as that in the control when β-cat activated at P9. This study indicates that root elongation occurs in a narrow time of window, which is highly sensitive to a change of β-catenin levels. Molecular studies showed a drastic decrease in the levels of nuclear factor I-C (NFIC) and osterix (OSX), plus sharp reductions of odontoblast differentiation markers, including Nestin, dentin sialoprotein (DSP), and dentin matrix protein 1 (DMP1) at both mRNA and protein levels.

Conclusions: Murine molar root elongation is precisely regulated by the Wnt/β-catenin signaling within a narrow window of time (newborn to day 5).
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http://dx.doi.org/10.1111/odi.13753DOI Listing
December 2020

Exosomes as a Novel Approach to Reverse Osteoporosis: A Review of the Literature.

Front Bioeng Biotechnol 2020 23;8:594247. Epub 2020 Oct 23.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Osteoporosis is a chronic disease requiring long-term, sometimes lifelong, management. With the aging population, the prevalence of osteoporosis is increasing, and with it so is the risk of hip fracture and subsequent poor quality of life and higher mortality. Current therapies for osteoporosis have various significant side effects limiting patient compliance and use. Recent evidence has demonstrated the significant role of exosomes in osteoporosis both and . In this review, we summarize the pathogenesis of senile osteoporosis, highlight the properties and advantages of exosomes, and explore the recent literature on the use of exosomes in osteogenesis regulation. This is a very helpful review as several exosomes-based therapeutics have recently entered clinical trials for non-skeletal applications, such as pancreatic cancer, renal transplantation, and therefore it is urgent for bone researchers to explore whether exosomes can become the next class of orthobiologics for the treatment of osteoporosis.
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http://dx.doi.org/10.3389/fbioe.2020.594247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644826PMC
October 2020

Proteinase bone morphogenetic protein 1, but not tolloid-like 1, plays a dominant role in maintaining periodontal homeostasis.

J Periodontol 2021 Jul 9;92(7):1018-1029. Epub 2020 Nov 9.

Biomedical Sciences, Texas A&M College of Dentistry, Dallas, TX, USA.

Background: Periodontitis is caused by multiple factors involving a bacterial challenge and a susceptible host, although there is no report on gene mutation directly linked to this common disease. Mutations in the proteinase bone morphogenetic protein 1 (BMP1) were identified in patients with osteogenesis imperfecta, who display some dentin defects and alveolar bone loss. We previously reported essential roles of BMP1 and tolloid-like 1 (TLL1), two closely related extracellular proteinases with overlapping functions, in mouse periodontium growth by simultaneous knockout (KO) of both genes, although the separate roles of BMP1 and TLL1 have remained unclear. Here, we have investigated whether and how BMP1 and TLL1 separately maintain periodontal homeostasis by comparing single Bmp1 KO and Tll1 KO with double KO (dKO) phenotypes.

Methods: Floxed Bmp1 and/or Tll1 alleles were deleted in transgenic mice via ubiquitously expressed Cre induced by tamoxifen treatment starting at 4-weeks of age (harvested at 18-weeks of age). Multiple approaches, including X-ray, micro-CT, calcein and alizarin red double-labeling, scanning electron microscopy, and histological and immunostaining assays, were used to analyze periodontal phenotypes and molecular mechanisms.

Results: Both Bmp1 KO and double KO mice exhibited severe periodontal defects, characterized by periodontal ligament (PDL) fiber loss and ectopic ossification in the expanded PDL area, and drastic reductions in alveolar bone and cementum volumes, whereas Tll1 KO mice displayed very mild phenotypes. Mechanistic studies revealed a sharp increase in the uncleaved precursor of type I collagen (procollagen I), leading to defective extracellular matrices.

Conclusions: BMP1, but not TLL1, is essential for maintaining periodontal homeostasis. This occurs at least partly via biosynthetic processing of procollagen I, thereby maintaining appropriate levels of procollagen I and its activated products such as mature collagen I.
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http://dx.doi.org/10.1002/JPER.20-0354DOI Listing
July 2021

Prognostic Value of Cardiac Magnetic Resonance-Derived Right Ventricular Remodeling Parameters in Pulmonary Hypertension: A Systematic Review and Meta-Analysis.

Circ Cardiovasc Imaging 2020 07 16;13(7):e010568. Epub 2020 Jul 16.

Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine (Y.D., Z.P., D.W., J.L., J.F., R.X., J.D., X.C., X.X., X.W., X.G.).

Background Cardiac right ventricular remodeling plays a substantial role in pathogenesis, progression, and prognosis of pulmonary hypertension. Cardiac magnetic resonance is considered an excellent tool for evaluation of right ventricle. However, value of right ventricular remodeling parameters derived from cardiac magnetic resonance in predicting adverse events is controversial. Methods The Pubmed (MEDLINE), Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure platform (CNKI), China Science and Technology Journal Database (VIP), and Wanfang databases were systematically searched until November 2019. Studies reporting hazard ratios (HRs) for all-cause death and composite end point of pulmonary hypertension were included. Univariate HRs were extracted from the included studies to calculate pooled HRs of each right ventricular remodeling parameter. Results Eight studies with 1120 patients examining all-cause death (female: 44%-92%, age: 40-67 years old, follow-up time: 27-48 months) and 10 studies with 604 patients examining composite end point (female: 60%-83%, age: 29-57 years old, follow-up time: 10-68 months) met the criteria. Right ventricular ejection fraction was the only parameter which could predict both all-cause death (pooled HR=0.95; =0.014) and composite end point (pooled HR=0.95; <0.001), although right ventricular end-diastolic volume index (pooled HR=1.01; <0.001), right ventricular end-systolic volume index (pooled HR=1.01, =0.045), and right ventricular mass index (pooled HR=1.03, =0.032) only predicted composite outcome. Similar results were observed when we conducted the meta-analysis among patients with World Health Organization type I of pulmonary hypertension. Conclusions Cardiac magnetic resonance-derived right ventricular remodeling parameters have independent prognostic value for all-cause death and composite end point of patients with pulmonary hypertension. Right ventricular ejection fraction was the strongest prognostic factor among all the right ventricular remodeling parameters. Right ventricular mass index, right ventricular end-diastolic volume index, and right ventricular end-systolic volume index also demonstrated prognostic value.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.010568DOI Listing
July 2020

Multiple Non-coding ANRIL Transcripts Are Associated with Risk of Coronary Artery Disease: a Promising Circulating Biomarker.

J Cardiovasc Transl Res 2021 Apr 22;14(2):229-237. Epub 2020 Jun 22.

Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.

Multiple ANRIL transcriptional isoforms, such as lncANRIL and circANRIL have been identified. We sought to explore their diagnostic value in patients with coronary artery disease (CAD). First, we selected six target ANRIL isoforms and measured their expression in CAD patients and controls in the peripheral blood. Their diagnostic values were evaluated. circANRIL(exon14-4) was identified as the best potential biomarker. Afterwards, we validated its diagnostic value and evaluated its prognostic value in a larger clinical cohort. Among six tested ANRILs, lncANRIL(exon1) and lncANRIL(exon4-6) in the CAD patients were significantly increased, while circANRIL(exon14-4) was downregulated. circANRIL(exon14-4) had the highest diagnostic value among the three isoforms. The combination of circANRIL(exon14-4) and other factors resulted in a more accurate differentiation of CAD patients. Moreover, lower expression of circANRIL(exon14-4) was associated with higher incidence of MACE. circANRIL(exon14-4) is closely associated with CAD risk and severity, which provides a promising circulating biomarker for CAD diagnosis and prognosis.
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http://dx.doi.org/10.1007/s12265-020-10053-0DOI Listing
April 2021

Spatiotemporal impacts of climate change on food production: case study of Shaanxi Province, China.

Environ Sci Pollut Res Int 2020 Jun 28;27(16):19826-19835. Epub 2020 Mar 28.

Chang'an University, Xi'an, 710127, China.

The climate change on the impact of grain production potential has significant regional differences. Researchers have studied the grain production potential of various crop combinations or focused on single crop types in a typical area; however, the regional differences of the climate change on the impact of grain production potential were neglected. This paper used the Global Agro-Ecological Zone (GAEZ 3.0) model to focus on the analysis what is the climate change on the impact of grain production potential in different geographic units (Northern Shaanxi Plateau, Guanzhong Basin, Qinba Mountain) in Shaanxi Province of China. The case showed that the precipitation (Pre) what made changes of grain production potential was the most important factor in different geographic units. The increase of Pre had a positive impact on the grain production potential in Northern Shaanxi Plateau and Guanzhong Basin. However, in Qinba Mountain, due to excessive Pre in the Qinba Mountains, the decrease of Pre had a certain positive impact on the grain production potential. The precipitation was less in the Northern Shaanxi Plateau; therefore, its major factors leading to changes of crop production were precipitation and rainfall days. The increase of the mean maximum temperature (Tmx) and the mean minimum temperature (Tmn) had a positive impact of the grain production potential in the Northern Shaanxi Plateau and Guanzhong Basin. The higher temperature had a negative impact on the grain production potential. In Qinba Mountain, the increase of the temperature has a certain negative impact on the grain production potential. It has more influence of Tmx in the Guanzhong Basin and Qinba Mountain rather than that in the Northern Shaanxi Plateau. Generally speaking, the major climatic factors leading grain production potential were Pre and Tmx in Guanzhong Basin and Qinba Mountain.
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http://dx.doi.org/10.1007/s11356-020-08447-3DOI Listing
June 2020

Anti-oral Squamous Cell Carcinoma Effects of a Potent TAZ Inhibitor AR-42.

J Cancer 2020 1;11(2):364-373. Epub 2020 Jan 1.

College of Stomatology, Chongqing Medical University, Chongqing, China.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide. Although great progress has been made in diagnosis and treatment strategies in recent years, the 5-year survival rate of OSCC patients is still disappointingly low. Hence, there is still an unmet medical need for sufferers with OSCC. As a downstream effector of Hippo pathway, TAZ was up-regulated in multiple cancers including OSCC, and considered as an effective therapeutic target. In this study, we constructed a stable transfected cell line HEK293-TAZ to screen TAZ inhibitor using dual-luciferase reporter assay, and found a potential TAZ inhibitor AR-42. The results showed that AR-42 effectively suppressed the viability and proliferation of OSCC cells, and induced cellular apoptosis and cell cycle arrest in G2/M phase. Moreover, AR-42 potently inhibited cell invasion and the capacity of sphere-forming, as well as the expression of EMT and cancer stem cell related proteins in OSCC cells, exhibiting potential efficacy against OSCC metastasis and self-renewal of oral cancer stem cell. Further mechanism studies showed that AR-42 inhibited the total amount of TAZ and its paralog YAP mainly through blockade of TAZ/YAP transcription and promotion of TAZ/YAP protein degradation. Additionally, the inhibitory effect of AR-42 against TAZ, as well as its anti-OSCC activity could be also observed in SCC9 xenograft model. Taken together, AR-42 deserves to be further studied as a TAZ inhibitor, and is worthy to be further assessed as a potential drug candidate for OSCC treatment.
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http://dx.doi.org/10.7150/jca.32436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930442PMC
January 2020

Association between chymase gene polymorphisms and atrial fibrillation in Chinese Han population.

BMC Cardiovasc Disord 2019 12 30;19(1):321. Epub 2019 Dec 30.

Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Chymase is the major angiotensin II (Ang II)-forming enzyme in cardiovascular tissue, with an important role in atrial remodeling. This study aimed to examine the association between chymase 1 gene (CMA1) polymorphisms and atrial fibrillation (AF) in a Chinese Han population.

Methods: This case-control study enrolled 126 patients with lone AF and 120 age- and sex-matched healthy controls, all from a Chinese Han population. Five CMA1 polymorphisms were genotyped.

Results: The CMA1 polymorphism rs1800875 (G-1903A) was associated with AF. The frequency of the GG genotype was significantly higher in AF patients compared with controls (p = 0.009). Haplotype analysis further demonstrated an increased risk of AF associated with the rs1800875-G haplotype (Hap8 TGTTG, odds ratio (OR) = 1.668, 95% CI 1.132-2.458, p = 0.009), and a decreased risk for the rs1800875-A haplotype (Hap5 TATTG, OR = 0.178, 95% CI 0.042-0.749, p = 0.008).

Conclusions: CMA1 polymorphisms may be associated with AF, and the rs1800875 GG genotype might be a susceptibility factor for AF in the Chinese Han population.
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http://dx.doi.org/10.1186/s12872-019-01300-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936049PMC
December 2019

Diode-side-pumped joule-level square-rod Nd:glass amplifier with 1 Hz repetition rate and ultrahigh gain.

Opt Express 2019 Nov;27(23):32912-32923

An effective diode-side-pumped joule-level square-rod Nd:glass multipass amplifier with 1 Hz repetition rate is developed. A Pockels cell is used to extend the amplification-pass to twelve-pass. The linear depolarization compensation method and adaptive optics based wavefront aberration correction method are used to minimize the thermal effects. Combined with the relay-imaging technology and beam-shaping method, good beam quality is obtained. Under the small-signal gain of 3.23 and the input energy of 50 µJ, the output energy of 1 J and the net gain of 2×10 are realized. The effective energy-extraction efficiency in the whole aperture of Nd:glass rod is 12%. The total wavefront aberration is 1.1 µm (peak valley). The Strehl Ratio is 0.62, and 90% of far-field energy is concentrated in 3 times the diffraction limit. The near-field modulation index of twelve-pass amplification at 1 J is 1.4.
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http://dx.doi.org/10.1364/OE.27.032912DOI Listing
November 2019

Enhanced effects of electrospun collagen-chitosan nanofiber membranes on guided bone regeneration.

J Biomater Sci Polym Ed 2020 02 11;31(2):155-168. Epub 2019 Nov 11.

Department of Periodontics, West China College of Stomatology, Sichuan University, Chengdu, Sichuan, China.

It was aim to study the physicochemical features and biocompatibility of electrospun collagen-chitosan membranes, and its potential in guided bone regeneration. Electrospinning technology was applied in the fabrication of electrospun collagen membranes and electrospun collagen-chitosan membranes following observation of scanning electron microscope. Physicochemical properties including tensile strength, elongation rate, porosity, degradation rate, and biocompatibility of membranes were measured then. , calvarial bone defects created on rats were covered with two kinds of membranes respectively. In the 4th and 8th week, enzyme-linked immunosorbent assay testing bone alkaline phosphatase and osteocalcin, Micro CT analyzing bone volume, bone volume/total volume, trabecular number and trabecular spacing values, and histological staining were carried out for evaluating the potentials of the membranes on bone regeneration. We found that regular and highly-porous structure favoring the adhesion and proliferation of periodontal ligament cells was observed in all electrospinning groups. Compared with electrospun collagen membranes, electrospun collagen-chitosan membranes performed better physiochemical features including higher tensile strength and more stable degradation rate. In the animal model, compared with the other groups, higher levels of bone alkaline phosphatase in the 4th week and osteocalcin in the 8th week were observed in the electrospun collagen-chitosan membrane. Meanwhile, both of the radiographical and histological results further confirmed that the new bone formation (with higher bone volume, bone volume/total volume, Trabecular number, and lower Trabecular spacing) were more active in the electrospun collagen-chitosan membrane. In conclusion, Electrospun collagen-chitosan membranes perform excellent physicochemical properties, biocompatibility, and great effects on guided bone regeneration, which as the membrane has good application prospect in tissue regeneration.
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http://dx.doi.org/10.1080/09205063.2019.1680927DOI Listing
February 2020

Association Between Toothbrushing and Behavioral Risk Factors of Non-communicable Diseases: A population Based Survey of 4500 adults in China.

Sci Rep 2019 06 11;9(1):8498. Epub 2019 Jun 11.

Department of Maxillofacial Surgery, College of Stomatology, Chongqing Medical University, Chongqing, China.

Non-communicable Disease (NCD) related behavioral risk factors (BRF) plays a crucial role in NCD prevention, as does oral hygiene behavior in oral health promotion. We examined the association between NCD BRF and toothbrushing using data from a population-based survey, which recruited 4485 adults aged 18+ years, in Chongqing city, China. Prevalence of five NDC BRF and their clustering within individual were determined by toothbrushing frequency. Ordinal logistic regression examined the association between toothbrushing and BRF clustering. Prevalence of current smoking, insufficient intake of vegetable and fruit, and harmful use of alcohol increased significantly with toothbrushing frequency. Respondents who brushed teeth ≥2 times daily consumed more red meat than those with less frequent toothbrushing. Relative to those with no BRF, the adjusted cumulative odds ratio of brushing teeth less frequently was 2.1 (95% CI: 1.4-3.1) for respondents with 3+ BRF. The adjusted cumulative odds ratio was 1.5 (1.1-2.1) and 1.4 (1.0-1.8) for those who had two BRF and those who had one, respectively. Significant correlation between toothbrushing and NCD BRF implied that integrated intervention strategy involving the both may be beneficial in public health programs targeting at either oral health or NCDs, or both.
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http://dx.doi.org/10.1038/s41598-019-44662-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560131PMC
June 2019

DMP1 Ablation in the Rabbit Results in Mineralization Defects and Abnormalities in Haversian Canal/Osteon Microarchitecture.

J Bone Miner Res 2019 06 3;34(6):1115-1128. Epub 2019 Mar 3.

Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX, USA.

DMP1 (dentin matrix protein 1) is an extracellular matrix protein highly expressed in bones. Studies of Dmp1 knockout (KO) mice led to the discovery of a rare autosomal recessive form of hypophosphatemic rickets (ARHR) caused by DMP1 mutations. However, there are limitations for using this mouse model to study ARHR, including a lack of Haversian canals and osteons (that occurs only in large mammalian bones), high levels of fibroblast growth factor 23 (FGF23), and PTH, in comparison with a moderate elevation of FGF23 and unchanged PTH in human ARHR patients. To better understand this rare disease, we deleted the DMP1 gene in rabbit using CRISPR/Cas9. This rabbit model recapitulated many features of human ARHR, such as the rachitic rosary (expansion of the anterior rib ends at the costochondral junctions), moderately increased FGF23, and normal PTH levels, as well as severe defects in bone mineralization. Unexpectedly, all DMP1 KO rabbits died by postnatal week 8. They developed a severe bone microarchitecture defect: a major increase in the central canal areas of osteons, concurrent with massive accumulation of osteoid throughout all bone matrix (a defect in mineralization), suggesting a new paradigm, where rickets is caused by a combination of a defect in bone microarchitecture and a failure in mineralization. Furthermore, a study of DMP1 KO bones found accelerated chondrogenesis, whereas ARHR has commonly been thought to be involved in reduced chondrogenesis. Our findings with newly developed DMP1 KO rabbits suggest a revised understanding of the mechanism underlying ARHR. © 2019 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3683DOI Listing
June 2019

Progress in the application of exosomes as therapeutic vectors in tumor-targeted therapy.

Cytotherapy 2019 05 25;21(5):509-524. Epub 2019 Jan 25.

Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People's Republic of China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong,Jiangsu, People's Republic of China. Electronic address:

Cancer is the second leading cause of death in the world with a high annual incidence level. Researchers have been working on developing treatments for cancer. Targeted therapy is an emerging treatment modality that is more novel than surgery, radiotherapy and chemotherapy. In targeted therapy, exogenous nanoscale microparticles are applied as carriers for drugs or genes. However, conventional particles have certain limitations attributed to non-specific cytotoxicity, biocompatibility and low delivery efficacy in individual therapeutic vector systems. Exosomes are small vesicles secreted by various cells that consist of lipid bilayer membranes without organelles. Due to their excellent biocompatibility, exosomes have received increased attention in recent years for targeted therapy applications. This review briefly introduces the current status of targeted therapy, and exosomes are introduced by their structural characteristics, physiological effects and separation methods. This review also discusses the applications of engineered exosomes derived from different cells in the field of targeted therapies and compares the two-way regulation of mesenchymal stromal cell-derived exosomes in tumor therapy.
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http://dx.doi.org/10.1016/j.jcyt.2019.01.001DOI Listing
May 2019

Off-axis eight-pass neodymium glass laser amplifier with high efficiency and excellent energy stability.

Appl Opt 2018 Oct;57(29):8727-8732

A new relay-imaged off-axial eight-pass laser amplifier with several joules energy and 1 Hz repetition rate was demonstrated. The extraction efficiency and pulse-to-pulse energy stability were greatly improved. Under the single-pass small-signal gain of 3.6, a net gain of 900 and an effective extraction efficiency of 42.4% in the beam aperture were realized. Pulse-to-pulse energy stability of 0.83% (peak-valley) and 0.17% (root-mean-square) was achieved by the significant saturation of eight-pass amplification, which, to the best of our knowledge, is the best energy stability in several-joules-class amplifiers. The far-field quality was 2.52 times the diffraction limit, and the near-field modulation of the 90% beam aperture was 1.28. No parasitic oscillations or pencil beams were observed. Moreover, another key feature of the proposed amplifier was the ability to remarkably improve the pulse contrast with a unique design.
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http://dx.doi.org/10.1364/AO.57.008727DOI Listing
October 2018

Dynamic Electrocardiography is Useful in the Diagnosis of Persistent Atrial Fibrillation Accompanied with Second-Degree Atrioventricular Block.

Acta Cardiol Sin 2018 Sep;34(5):409-416

Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Background: Periodic electrocardiography (ECG) at every clinical visit is generally performed for heart rhythm surveillance, and 24-h Holter ECG is usually used as the gold standard. We aimed to investigate the electrocardiographic features of persistent atrial fibrillation (AF) accompanied with second-degree atrioventricular block (AVB).

Methods: From October 2012 to November 2015, 204 patients with an RR interval > 2.0 s before radiofrequency ablation were included. Dynamic ECG (DCG) was performed before and after the radiofrequency ablation. The patients were divided into two groups based on changes in DCG after radiofrequency ablation: group A (non-second-degree AVB group) and group B (second-degree AVB group). An RR interval > 2.0 s, the distribution of escape rhythm, mean heart rate and the long RR interval in the two groups were analyzed.

Results: After radiofrequency ablation, all 204 patients who had persistent AF converted to sinus rhythm successfully. In group A (n = 193), the distribution of an RR interval > 2.0 s and escape rhythm were significantly correlated with sleep or rest, while no correlation was observed in group B (n = 11). The average RR interval prolongation and escape rhythm were significantly higher in group B than in group A (p < 0.05). The average number of long RR intervals > 3.0 s and average number of escape rhythm episodes (< 35 bpm) were significant predictive factors of second-degree AVB after radiofrequency ablation.

Conclusions: DCG is a useful tool for the diagnosis of persistent AF accompanied with second-degree AVB.
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http://dx.doi.org/10.6515/ACS.201809_34(5).20180326EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160510PMC
September 2018

General memristor with applications in multilayer neural networks.

Neural Netw 2018 Jul 3;103:142-149. Epub 2018 Apr 3.

School of Automation, Huazhong University of Science and Technology, Wuhan 430074, China; Department of Automation, Huazhong University of Science and Technology, Wuhan 430074, China.

Memristor describes the relationship between charge and flux. Although several window functions for memristors based on the HP linear and nonlinear dopant drift models have been studied, most of them are inadequate to capture the full characteristics of memristors. To address this issue, this paper proposes a unified window function to describe a general memristor with restrictions of its parameters given. Compared with other window functions, the proposed function demonstrates high validity and accuracy. In order to make the simulation results have high consistency with the results of actual circuit, we apply the new window function to the simulation of a memristor-based multilayer neural network (MNN) circuit. The overall accuracy will vary with the change of control parameters in the window function. It implies that the proposed model can guide the design of actual memristor-based circuits.
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http://dx.doi.org/10.1016/j.neunet.2018.03.015DOI Listing
July 2018

Eosinophils in patients with lone atrial fibrillation.

Pacing Clin Electrophysiol 2017 Aug 21;40(8):955-958. Epub 2017 Jul 21.

Department of Cardiology, Biomedical Research (Therapy) Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Background: Inflammation has been evidenced as a critical contributable mechanism for the atrial fibrillation (AF) onset and development. As the consistent inflammatory and oxidative marker, the effects of white blood cell (WBC) and its differential on lone atrial fibrillation (LAF) were investigated in the study.

Methods: A total of 126 patients with paroxysmal LAF who scheduled for rhythm control drug therapy and 120 age- and gender-matched subjects in sinus rhythm were included sequentially. Peripheral blood sample and clinic data were collected during the first evaluation. Recurrence of AF was evaluated by outpatient clinics and telephone visits for the following 12 months.

Results: Peripheral eosinophil count, neutrophil count, and left atrial diameter (LAD) were significantly higher in LAF than control. Within a follow-up of 12 months, 56 patients (44.4%) had developed AF recurrence. Patients with AF recurrence had higher eosinophil count and LAD. Univariable analyses showed a statistically significant relationship between eosinophil count (P = 0.042), LAD (P = 0.030), and AF recurrence. Multivariate logistic regression analysis showed that LAD (OR: 1.090 per 1 mm increase; 95% CI: 1.007-1.180; P = 0.032) and eosinophil (OR: 1.643 per 1 × 10 /L increase; 95% CI: 1.047-2.578; P = 0.031) were independent predictors of AF recurrence during antiarrhythmic drug therapy.

Conclusion: Our results support the association of the WBC response and its components with the LAF. Especially, the peripheral eosinophil and LAD may play important roles in mediating inflammation and atrial remodeling in AF.
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http://dx.doi.org/10.1111/pace.13146DOI Listing
August 2017

Process-oriented adaptive optics control method in the multi-pass amplifiers.

Opt Express 2017 May;25(9):9848-9859

In this talk, we propose and demonstrate the process-oriented adaptive optics (AO) wavefront control method, for optimizing the beam quality in the multi-pass amplifiers. Different from the conventional target-oriented wavefront control approach, the novel method divides the aberration correction process into several steps, to optimize the wavefront quality in time during the courses of the beam's transport and amplification. The experimental results show that the proposed method can effectively prevent the beam quality from worsening and ensure the successful reality of multi-pass amplification, so it has obvious advantages both in efficiency and accuracy over the traditional target-oriented method.
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http://dx.doi.org/10.1364/OE.25.009848DOI Listing
May 2017
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