Publications by authors named "Jin Dai"

232 Publications

Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer.

EBioMedicine 2021 Nov 21;74:103714. Epub 2021 Nov 21.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address:

Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management.

Methods: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280-473 days), and an independent case-control study from Beijing (n = 99).

Findings: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78-0.99) vs. 0.56 (0.36-0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins.

Interpretation: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention.

Funding: The funders are listed in the Acknowledgement.
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http://dx.doi.org/10.1016/j.ebiom.2021.103714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617343PMC
November 2021

CDDO-Im ameliorates osteoarthritis and inhibits chondrocyte apoptosis in mice via enhancing Nrf2-dependent autophagy.

Acta Pharmacol Sin 2021 Nov 9. Epub 2021 Nov 9.

Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.

Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease with few treatment options. The pathogenesis of OA is characterized by sustained inflammation, oxidative stress and chondrocyte apoptosis that eventually lead to cartilage degradation and joint dysfunction. In the present study, we identified a synthetic triterpenoid CDDO-Im(1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole) as an activator of Nrf2 (nuclear factor erythroid 2-related factor 2) that displayed strong anti-OA effects. We showed that CDDO-Im (20 nM) significantly alleviated TNF-α-induced apoptosis of primary human chondrocytes and extracellular matrix degradation. In a mouse OA model incurred by DMM (destabilization of medial meniscus), administration of CDDO-Im (2.5 mg/kg, ip, every other day for 8 weeks) effectively reduced knee joint cartilage erosion and serum levels of inflammatory cytokines IL-1β and IL-6. We revealed that CDDO-Im (20 nM) significantly enhanced autophagy activities in chondrocytes, whereas the autophagy inhibition by chloroquine (CQ, 50 μM) or 3-methyladenine (3-MA, 5 mM) abrogated the anti-apoptosis and chondroprotective effects of CDDO-Im in TNF-α-treated chondrocytes. Moreover, we confirmed that CDDO-Im (1-20 nM) dose-dependently activated Nrf2 pathway in TNF-α-treated chondrocytes, and its chondroprotective and autophagy-enhancing effects were significantly diminished when Nrf2 signaling was blocked by Nrf2 inhibitor ML385 (20 μM) or siRNA-mediated Nrf2 knockdown. Together, our results demonstrate that CDDO-Im exhibits prominent chondroprotective and anti-OA activities owing to its Nrf2 activation and autophagy-enhancing properties, which might provide new insights into the strategies of OA clinical prevention and treatment.
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http://dx.doi.org/10.1038/s41401-021-00782-6DOI Listing
November 2021

Analysis of right ventricular flow with 4-dimensional flow cardiovascular magnetic resonance imaging in patients with pulmonary arterial hypertension.

Quant Imaging Med Surg 2021 Aug;11(8):3655-3665

Siemens Shenzhen Magnetic Resonance Ltd., Shenzhen, China.

Background: Cardiac flow closely interact with function, however, the correlation of right ventricular (RV) flow and function remains unknown, thus our objective is to observe right ventricular flow with four-dimensional phase-contrast cardiovascular magnetic resonance imaging (4D flow CMR) in patients with pulmonary arterial hypertension (PAH) and to analyze flow components with RV function and hemodynamics.

Methods: This study retrospectively enrolled 30 patients with PAH (mean age: 49±13 years, 16 females) and 14 age- and sex-matched healthy volunteers as controls (mean age: 44±12 years, 9 females). All patients who underwent CMR and right heart catheterization (RHC) within 1 week between January 2019 and July 2020 were included. Hemodynamics were measured with RHC. RV flow components, including the percentages of direct flow (RVPDF), retained inflow (RVPRI), delayed ejection flow (RVPDEF) and residual volume (RVPRVo) were quantified using 4D flow CMR. The associations between RV flow components and other CMR metrics, clinical data, and hemodynamics were analyzed by Spearman's correlation analysis.

Results: In patients with PAH, RVPDF was decreased and RVPRVo was increased compared with the normal control group. The sum of RVPDF and RVPDEF RV was significantly correlated with RV ejection fraction (RVEF) (r=0.802, P<0.001), and there was no notable difference between RVEF and the sum of RVPDF and RVPDEF (t=0.251, P=0.831). Both RVPDF and RVPRVo were correlated (in opposite directions) with the RV end-diastolic volume index, RV end-systolic volume index, RV global longitudinal strain, and RVEF. RVPDF was negatively correlated with pulmonary vascular resistance (PVR), and positively correlated with cardiac output and cardiac index. RVPRVo was positively correlated with PVR and negatively correlated with cardiac output and cardiac index.

Conclusions: RV blood flow components qualified with 4D flow CMR is a valuable noninvasive method for the assessment of RV function and hemodynamics in patients with PAH.
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http://dx.doi.org/10.21037/qims-20-1267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245951PMC
August 2021

Revisiting social MPE: an integration of molecular pathological epidemiology and social science in the new era of precision medicine.

Expert Rev Mol Diagn 2021 Sep 26;21(9):869-886. Epub 2021 Jul 26.

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States.

Introduction: Molecular pathological epidemiology (MPE) is an integrative transdisciplinary area examining the relationships between various exposures and pathogenic signatures of diseases. In line with the accelerating advancements in MPE, social science and its health-related interdisciplinary areas have also developed rapidly. Accumulating evidence indicates the pathological role of social-demographic factors. We therefore initially proposed social MPE in 2015, which aims to elucidate etiological roles of social-demographic factors and address health inequalities globally. With the ubiquity of molecular diagnosis, there are ample opportunities for researchers to utilize and develop the social MPE framework.

Areas Covered: Molecular subtypes of breast cancer have been investigated rigorously for understanding its etiologies rooted from social factors. Emerging evidence indicates pathogenic heterogeneity of neurological disorders such as Alzheimer's disease. Presenting specific patterns of social-demographic factors across different molecular subtypes should be promising for advancing the screening, prevention, and treatment strategies of those heterogeneous diseases. This article rigorously reviewed literatures investigating differences of race/ethnicity and socioeconomic status across molecular subtypes of breast cancer and Alzheimer's disease to date.

Expert Opinion: With advancements of the multi-omics technologies, we foresee a blooming of social MPE studies, which can address health disparities, advance personalized molecular medicine, and enhance public health.
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http://dx.doi.org/10.1080/14737159.2021.1952073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478868PMC
September 2021

High-Throughput Drug Screening and Multi-Omic Analysis to Guide Individualized Treatment for Multiple Myeloma.

JCO Precis Oncol 2021 6;5. Epub 2021 Apr 6.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Multiple myeloma (MM) is a genetically heterogeneous malignancy characterized by variable treatment responses. Although numerous drugs have been approved in recent years, the ability to predict treatment response and tailor individual therapy is limited by the absence of robust predictive biomarkers. The goal of this clinical trial was to use ex vivo, high-throughput screening (HTS) of 170 compounds to predict response among patients with relapsed or refractory MM and inform the next treatment decisions. Additionally, we integrated HTS with multi-omic analysis to uncover novel associations between in vitro drug sensitivity and gene expression and mutation profiles.

Materials And Methods: Twenty-five patients with relapsed or refractory MM underwent a screening bone marrow or soft tissue biopsy. Sixteen patients were found to have sufficient plasma cells for HTS. Targeted next-generation sequencing was performed on plasma cell-free DNA from all patients who underwent HTS. RNA and whole-exome sequencing of bone marrow plasma cells were performed on eight and seven patients, respectively.

Results: Results of HTS testing were made available to treating physicians within a median of 5 days from the biopsy. An actionable treatment result was identified in all 16 patients examined. Among the 13 patients who received assay-guided therapy, 92% achieved stable disease or better. The expression of 105 genes and mutations in 12 genes correlated with in vitro cytotoxicity.

Conclusion: In patients with relapsed or refractory MM, we demonstrate the feasibility of ex vivo drug sensitivity testing on isolated plasma cells from patient bone marrow biopsies or extramedullary plasmacytomas to inform the next line of therapy.
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http://dx.doi.org/10.1200/PO.20.00442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232547PMC
April 2021

DNA methylation signatures associated with prognosis of gastric cancer.

BMC Cancer 2021 May 25;21(1):610. Epub 2021 May 25.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Haidian District, Beijing, 100142, People's Republic of China.

Background: Few studies have examined prognostic outcomes-associated molecular signatures other than overall survival (OS) for gastric cancer (GC). We aimed to identify DNA methylation biomarkers associated with multiple prognostic outcomes of GC in an epigenome-wide association study.

Methods: Based on the Cancer Genome Atlas (TCGA), DNA methylation loci associated with OS (n = 381), disease-specific survival (DSS, n = 372), and progression-free interval (PFI, n = 383) were discovered in training set subjects (false discovery rates < 0.05) randomly selected for each prognostic outcome and were then validated in remaining subjects (P-values < 0.05). Key CpGs simultaneously validated for OS, DSS, and PFI were further assessed for disease-free interval (DFI, n = 247). Gene set enrichment analyses were conducted to explore the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways simultaneously enriched for multiple GC prognostic outcomes. Methylation correlated blocks (MCBs) were identified for co-methylation patterns associated with GC prognosis. Based on key CpGs, risk score models were established to predict four prognostic outcomes. Spearman correlation analyses were performed between key CpG sites and their host gene mRNA expression.

Results: We newly identified DNA methylation of seven CpGs significantly associated with OS, DSS, and PFI of GC, including cg10399824 (GRK5), cg05275153 (RGS12), cg24406668 (MMP9), cg14719951(DSC3), and cg25117092 (MED12L), and two in intergenic regions (cg11348188 and cg11671115). Except cg10399824 and cg24406668, five of them were also significantly associated with DFI of GC. Neuroactive ligand-receptor interaction pathway was suggested to play a key role in the effect of DNA methylation on GC prognosis. Consistent with individual CpG-level association, three MCBs involving cg11671115, cg14719951, and cg24406668 were significantly associated with multiple prognostic outcomes of GC. Integrating key CpG loci, two risk score models performed well in predicting GC prognosis. Gene body DNA methylation of cg14719951, cg10399824, and cg25117092 was associated with their host gene expression, whereas no significant associations between their host gene expression and four clinical prognostic outcomes of GC were observed.

Conclusions: We newly identified seven CpGs associated with OS, DSS, and PFI of GC, with five of them also associated with DFI, which might inform patient stratification in clinical practices.
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http://dx.doi.org/10.1186/s12885-021-08389-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152126PMC
May 2021

miR-143 is implicated in growth plate injury by targeting IHH in precartilaginous stem cells.

Int J Med Sci 2021 3;18(9):1999-2007. Epub 2021 Mar 3.

Department of Orthopaedics, Children's Hospital of Soochow University, Suzhou, 215000, China.

Precartilaginous stem cells (PCSCs) are able to initiate chondrocyte and bone development. The present study aimed to investigate the role of and the underlying mechanisms involved in PCSC proliferation. In a rat growth plate injury model, tissue from the injury site was collected and the expression of and its potential targets was determined. PCSCs were isolated from the rabbits' distal epiphyseal growth plate. Cell viability, DNA synthesis, and apoptosis were determined with MTT, BrdU, and flow cytometric analysis, respectively. Real time PCR and western blot were performed to detect the mRNA and protein expression of the indicated genes. Indian hedgehog () was identified as a target gene for with luciferase reporter assay. Decreased expression of and increased expression of gene were observed in the growth plate after injury. mimics decreased cell viability and DNA synthesis and promoted apoptosis of PCSCs. Conversely, siRNA-mediated inhibition of led to increased growth and suppressed apoptosis of PCSCs. Transfection of decreased luciferase activity of wild-type but had no effect when the 3'-UTR of was mutated. Furthermore, the effect of overexpression was neutralized by overexpression of IHH. Our study showed that is involved in growth plate behavior and regulates PCSC growth by targeting , suggesting that may serve as a novel target for PCSC-related diseases.
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http://dx.doi.org/10.7150/ijms.46474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040405PMC
November 2021

Effects of continuous positive airway pressure treatment in obstructive sleep apnea patients with atrial fibrillation: A meta-analysis.

Medicine (Baltimore) 2021 Apr;100(15):e25438

Department of Cardiology, First Affiliated Hospital of Zhejiang Chinese Medical University.

Background: Obstructive sleep apnea (OSA) is correlated with atrial fibrillation (AF). Over the past decade, there has been an increasing interest in the relationship between OSA with continuous positive airway pressure (CPAP) and progression or recurrence of AF.

Methods: This investigation was an analysis of studies searched in the Cochrane Library, PubMed, EMBASE, EBSCO, OVID, and Web of Science databases from inception to July 2020 to evaluate the recurrence or progression of AF in CPAP users, CPAP nonusers, and patients without OSA.

Results: Nine studies with 14,812 patients were recruited. CPAP therapy reduced the risk of AF recurrence or progression by 63% in a random-effects model (24.8% vs 40.5%, risk ratio [RR] = 0.70, 95% confidence interval [CI] = 0.57-0.85, P = .035). Compared with non-OSA patients, AF recurrence or progression was much higher in CPAP nonusers (40.6% vs 21.1%, RR = 1.70, 95% CI = 1.19-2.43, P = .000). However, AF recurrence or progression in the CPAP group was similar to that in the non-OSA group (24.0% vs 21.1%, RR = 1.13, 95% CI = 0.87-1.47, P = .001). Begg correlation test and Egger regression test revealed no publication bias in this analysis.

Conclusions: OSA is a salient factor in the progression or recurrence of AF. CPAP therapy for OSA may contribute to reduction of AF in patients for whom radiofrequency ablation or direct current cardioversion is not performed.

Trial Registration: The protocol for this meta-analysis was registered on PROSPERO with a registration No. CRD42019135229.
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http://dx.doi.org/10.1097/MD.0000000000025438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051983PMC
April 2021

Hair color and risk of keratinocyte carcinoma in US women and men.

J Am Acad Dermatol 2021 Mar 11. Epub 2021 Mar 11.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China; Department of Dermatology, Warren Alpert Medical School, Brown University, Providence, Rhode Island; Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.01.099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433260PMC
March 2021

Load-induced regulation of tendon homeostasis by SPARC, a genetic predisposition factor for tendon and ligament injuries.

Sci Transl Med 2021 02;13(582)

Institute of Tendon and Bone Regeneration, Paracelsus Medical University-Spinal Cord Injury and Tissue Regeneration Center Salzburg, 5020 Salzburg, Austria.

Tendons and tendon interfaces have a very limited regenerative capacity, rendering their injuries clinically challenging to resolve. Tendons sense muscle-mediated load; however, our knowledge on how loading affects tendon structure and functional adaption remains fragmentary. Here, we provide evidence that the matricellular protein secreted protein acidic and rich in cysteine (SPARC) is critically involved in the mechanobiology of tendons and is required for tissue maturation, homeostasis, and enthesis development. We show that tendon loading at the early postnatal stage leads to tissue hypotrophy and impaired maturation of Achilles tendon enthesis in mice. Treadmill training revealed a higher prevalence of spontaneous tendon ruptures and a net catabolic adaptation in mice. Tendon hypoplasia was attenuated in mice in response to muscle unloading with botulinum toxin A. In vitro culture of three-dimensional tendon constructs showed load-dependent impairment of ribosomal S6 kinase activation, resulting in reduced type I collagen synthesis. Further, functional calcium imaging revealed that lower stresses were required to trigger mechanically induced responses in tendon fascicles. To underscore the clinical relevance of the findings, we further demonstrate that a missense mutation (p.Cys130Gln) in the follistatin-like domain of , which causes impaired protein secretion and type I collagen fibrillogenesis, is associated with tendon and ligament injuries in patients. Together, our results demonstrate that SPARC is a key extracellular matrix protein essential for load-induced tendon tissue maturation and homeostasis.
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http://dx.doi.org/10.1126/scitranslmed.abe5738DOI Listing
February 2021

Open reduction and Herbert screw fixation of Pipkin type IV femoral head fracture in an adolescent: A case report.

World J Clin Cases 2021 Feb;9(4):898-903

Department of Orthopaedics, Children's Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China.

Background: Femoral head fracture is extremely rare in children. This may be the youngest patient with femoral head fracture ever reported in the literature. There are few pediatric studies that focus on cases treated with open reduction the modified Hardinge approach.

Case Summary: A 14-year-old female adolescent suffered a serious traffic accident when she was sitting on the back seat of a motorcycle. A pelvic radiograph and computed tomography revealed a proximal femoral fracture and slight acetabular rim fracture. This was diagnosed as a Pipkin type IV femoral head fracture. An open reduction and Herbert screw fixation was performed a modified Hardinge approach. After 1-year follow-up, the patient could walk without aid and participate in physical activities. The X-ray results showed that the fractures healed well with no evidence of complications.

Conclusion: Open reduction and Herbert screw fixation is an available therapy to treat Pipkin type IV femoral head fractures in children.
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http://dx.doi.org/10.12998/wjcc.v9.i4.898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852633PMC
February 2021

Effect of biofeedback combined with high-quality nursing in treatment of functional constipation.

World J Clin Cases 2021 Feb;9(4):784-791

Department of Anorectal Disease, Shenyang Hospital of Traditional Chinese Medicine, Shenyang 110000, Liaoning Province, China.

Background: Functional constipation (FC) is a common functional gastrointestinal disease with various clinical manifestations. It is a physical and mental disease, which seriously affects patient physical and mental health and quality of life. Biofeedback therapy is the treatment of choice for FC, especially outlet obstructive constipation caused by pelvic floor dysfunction. High-quality nursing is a new nursing model in modern clinical work and a new concept of modern nursing service.

Aim: To explore the effect of biofeedback combined with high-quality nursing in the treatment of FC.

Methods: A total of 100 patients with FC admitted to our hospital from March 2015 to July 2019 were selected for clinical observation. These patients were randomly divided into two groups of 50: Experimental group (biofeedback combined with high-quality nursing treatment group) and control group (biofeedback group).

Results: The constipation symptom score of the experimental group was significantly lower than that of the control group, and the difference was statistically significant ( < 0.05). The anal canal resting pressure and initial defecation threshold of the experimental group were significantly lower than those of the control group, and the maximum squeeze systolic pressure of the anal canal of the experimental group was significantly higher than that of the control group ( < 0.05). The Self-Rating Anxiety Scale and Zung's Self-Rating Depression Scale scores of the two groups were significantly lower than before treatment. The Self-Rating Anxiety Scale and Self-Rating Depression Scale scores of the experimental group were significantly lower than those of the control group ( < 0.05). The patient satisfaction score of the experimental group was significantly higher than that of the control group ( < 0.05).

Conclusion: The application of biofeedback combined with high-quality nursing in the treatment of FC has significant advantages over pure biofeedback treatment, and it is worthy of promotion in clinical work.
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http://dx.doi.org/10.12998/wjcc.v9.i4.784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852631PMC
February 2021

Restoring RUNX1 deficiency in RUNX1 familial platelet disorder by inhibiting its degradation.

Blood Adv 2021 02;5(3):687-699

Department of Pathology, University of Washington School of Medicine, Seattle, WA.

RUNX1 familial platelet disorder (RUNX1-FPD) is an autosomal dominant disorder caused by a monoallelic mutation of RUNX1, initially resulting in approximately half-normal RUNX1 activity. Clinical features include thrombocytopenia, platelet functional defects, and a predisposition to leukemia. RUNX1 is rapidly degraded through the ubiquitin-proteasome pathway. Moreover, it may autoregulate its expression. A predicted kinetic property of autoregulatory circuits is that transient perturbations of steady-state levels result in continued maintenance of expression at adjusted levels, even after inhibitors of degradation or inducers of transcription are withdrawn, suggesting that transient inhibition of RUNX1 degradation may have prolonged effects. We hypothesized that pharmacological inhibition of RUNX1 protein degradation could normalize RUNX1 protein levels, restore the number of platelets and their function, and potentially delay or prevent malignant transformation. In this study, we evaluated cell lines, induced pluripotent stem cells derived from patients with RUNX1-FPD, RUNX1-FPD primary bone marrow cells, and acute myeloid leukemia blood cells from patients with RUNX1 mutations. The results showed that, in some circumstances, transient expression of exogenous RUNX1 or inhibition of steps leading to RUNX1 ubiquitylation and proteasomal degradation restored RUNX1 levels, thereby advancing megakaryocytic differentiation in vitro. Thus, drugs retarding RUNX1 proteolytic degradation may represent a therapeutic avenue for treating bleeding complications and preventing leukemia in RUNX1-FPD.
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http://dx.doi.org/10.1182/bloodadvances.2020002709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876894PMC
February 2021

SARS-CoV-2 serological cross-reactivity with autoantibodies - Authors' reply.

Authors:
Jialin Teng Jin Dai

Lancet Rheumatol 2021 Jan 24;3(1):e16. Epub 2020 Dec 24.

Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

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http://dx.doi.org/10.1016/S2665-9913(20)30359-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758717PMC
January 2021

Preoperative Combined Prediction Models Have Superior Capability in Predicting Survival as the Child-Pugh Grade in Patients with HCC after Interventional Embolotherapy.

Cancer Manag Res 2020 7;12:12537-12547. Epub 2020 Dec 7.

Department of Gastroenterology, Suzhou Hospital of Anhui Medical University, Suzhou, Anhui 234000, People's Republic of China.

Background: It is of important clinical significance for hepatocellular carcinoma (HCC) patients to evaluate prognosis before interventional embolotherapy.

Methods: A total of 106 patients with HCC after interventional embolotherapy who had complete data with follow-up information until September 2019 were included in this study. These data were analyzed using SPSS Version 22.0 and R (version 3.6.1) statistical software.

Results: 1) The diameter of the tumor, ascites, FIT, AFP, ALT, AST, GGT, and Child-Pugh score had the ability to predict the prognosis and survival of patients with HCC. Among these molecules, the predictive effectiveness (or the area under the receiver operating characteristic [ROC] curve) of GGT was the highest, although it was slightly lower than the predictive effectiveness of the Child-Pugh score, which is the gold standard for survival analysis. 2) Among survival analyses combining five molecular indicators, the predictive postoperative viability for combination 1 was the strongest with an area under the ROC curve (AUC) of 0.856 (0.779, 0.932), similar to the all-molecular combination (combination 16) with an AUC of 0.872 (0.798, 0.945), but much higher than that of the Child-Pugh score of 0.720 (0.616, 0.823) for HCC patients (all p<0.05). 3) Kaplan-Meier analyses showed that the 3-year cumulative survival rates were 55.3% for low-risk patients and 2.6% for high-risk patients.

Conclusion: A combined prediction model can determine the optimal combination of preoperative routine detection indices in patients with HCC intervention, and ROC curve analysis can quantify the efficacy of these indices in the survival and prognosis of HCC. Interestingly, combination 1 showed stronger predictive capability than the Child-Pugh score in predicting death risks for postoperative patients with HCC. When combination 1 has several missing clinical data, these combination prediction models (12, 3, 7, 13, 16) are also a replaceable choice. These findings may have important clinical significance in the formulation of individualized medical programs.
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http://dx.doi.org/10.2147/CMAR.S274970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732159PMC
December 2020

LINC00210 exerts oncogenic roles in glioma by sponging miR-328.

Exp Ther Med 2020 Dec 2;20(6):137. Epub 2020 Oct 2.

Department of Neurosurgery, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.

Long non-coding RNAs (lncRNAs) have been reported to serve key roles in human cancer types, including glioma. However, to the best of our knowledge, the expression and function of lncRNA LINC00210 in glioma have not previously been investigated. The present study was conducted to explore the regulatory role of LINC00210 in glioma cells. The present study demonstrated that LINC00210 was significantly upregulated in glioma tissues, and high expression of LINC00210 was significantly associated with advanced clinical stage and poor prognosis in patients with glioma. It was found that LINC00210 knockdown significantly inhibited the proliferation and migration of U251 and T98G cells. The results of luciferase reporter assays indicated that LINC00210 could directly target microRNA (miR)-328 in glioma cells, and miR-328 expression was negatively correlated with LINC00210 expression in glioma tissues. LINC00210 knockdown significantly promoted the expression of miR-328 in U251 and T98G cells. Moreover, silencing miR-328 impaired the inhibitory effects of LINC00210 knockdown on the proliferation and migration of U251 and T98G cells. Therefore, the present results suggested that LINC00210 may exert an oncogenic role in glioma via sponging miR-328.
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http://dx.doi.org/10.3892/etm.2020.9266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581018PMC
December 2020

Dieulafoy disease with gastric MALT lymphoma: A case report.

Medicine (Baltimore) 2020 Oct;99(41):e22651

Department of Gastroenterology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Shangcheng District, Hangzhou, Zhejiang Province, China.

Rationale: Dieulafoy lesion (DL), a rare cause of gastrointestinal bleeding, is easily covered by blood scab formation on the mucous membrane for its small size, which makes it difficult to be identified under endoscope. In clinical practice, it is also very easy to miss gastric mucosa-associated lymphoid tissue (MALT) lymphoma that exhibits atypical early manifestations under gastroendoscope and is difficult to be diagnosed by routine superficial biopsy. Most patients only experience nonspecific dyspepsia symptoms.

Patient Concerns: A 68-year-old man suffering from repeated melena for 6 years arrived at our hospital. The patient had undergone gastroscopy and capsule endoscopy at other hospitals for several times and received symptomatic treatment, but his melena still continued to recur. At our hospital, the capsule endoscopy displayed that there existed large hemorrhage in the stomach, after which a gastrointestinal decompression tube was placed, so the bright red blood was drained. Subsequently, a sunken vascular malformation tissue in the anterior wall of the gastric fundus was observed under emergency endoscope. Pulsating blood flow appeared immediately after biopsy, and over-the-scope clip (OTSC) was quickly applied to stop the bleeding. Near the bleeding point, scar-like tissue that was surrounded by interrupted mucosa was discovered, and biopsy was performed at this site.

Diagnosis: The diagnosis of DL and gastric MALT were determined by the digestive endoscopy and biopsy pathology.

Interventions: With the diagnosis of DL and gastric MALT, the hemorrhagic spot was treated by OTSC. After the patient's condition was stable, anti-Helicobacter pylori treatment was performed.

Outcomes: After the corresponding treatment, the 6-month follow-up revealed that the lymphoma was not completely cured, but no further bleeding occurred. There was no bleeding in the epigastric region and the patient was in good condition.

Lessons: From endoscopy, it is easy to miss DL. When the hemostatic equipment is fully prepared, biopsy can be performed. After biopsy, pulsatile bleeding is convincing evidence for Dieulafoy disease. OTSC represents an effective and low-risk method for DL and it could replace surgery. Moreover, the mucosa surrounding Dieulafoy disease should be carefully observed to exclude coexisting diseases such as lymphoma or gastric cancer.
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http://dx.doi.org/10.1097/MD.0000000000022651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544426PMC
October 2020

Comparative efficacy and safety of catheter ablation interventions for atrial fibrillation: comprehensive network meta-analysis of randomized controlled trials.

J Interv Card Electrophysiol 2021 Oct 4;62(1):199-211. Epub 2020 Oct 4.

Department of Cardiology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China.

Purpose: Point-by-point radiofrequency (RF) ablation has been the cornerstone of pulmonary vein isolation (PVI) for patients with atrial fibrillation (AF); however, it remains a complex and time-consuming procedure. Many novel AF catheter ablation (CA) techniques have been introduced, but whether they represent valuable alternatives remains controversial. Thus, we conducted a network meta-analysis to comprehensively evaluate the efficacy and safety of different CA interventions.

Methods: We systematically searched several databases (Embase, PubMed, the Cochrane Library, and ClinicalTrials.gov ) from inception to March, 2020. The primary outcomes of interest were freedom from atrial tachyarrhythmia (AT) and procedure-related complications; secondary outcomes included procedure time and fluoroscopy time.

Results: Finally, 33 randomized controlled trials (RCTs) with a total of 4801 patients were enrolled. No significant differences were found among the different interventions in terms of primary efficacy or safety outcomes. PVAC was most likely to have the shortest procedure time (Prbest = 61.5%) and nMARQ the shortest fluoroscopy time (Prbest = 60.6%); compared with conventional irrigated RF (IRF) ablation, cryoballoon ablation (CBA) showed comparable clinical efficacy and safety; CBA with second-generation CB (CB2) had a significantly shorter procedure time than IRF with contact force technology (CF-IRF) (WMD = - 20.75; p = 0.00).

Conclusion: There is insufficient evidence to suggest that one CA technique is superior to another. However, PVAC may be associated with a shorter procedural duration, and the CB2 catheters also seemed to reduce the procedure time compared with that of CF-IRF. Further large-scale studies are warranted to compare the available CA techniques and provide an up-to-date optimum recommendation.
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http://dx.doi.org/10.1007/s10840-020-00878-9DOI Listing
October 2021

NK6 Homeobox 2 Regulated Gastrokin-2 Suppresses Gastric Cancer Cell Proliferation and Invasion via Akt Signaling Pathway.

Cell Biochem Biophys 2021 Mar 3;79(1):123-131. Epub 2020 Oct 3.

Department of Anesthesiology, Guizhou Provincial People's Hospital, Guiyang, 550003, Guizhou, China.

This study aims to explore the role of Gastrokin-2 (GKN2) in gastric cancer and its function in the progression and metastasis of gastric cancer. The expression of GKN2 in the patient samples was examined by qRT-PCR and western blot. The transcription factor NK6 Homeobox 2 (NKX6-2), which binds to the GKN2 promoter, was predicted by cBioportal and JSPAR. Binding between NKX6-2 and the GKN2 promoter was analyzed by dual-luciferase assay. MTT assay and transwell assay were used to detect changes in gastric cancer cell viability and migration after GKN2 overexpression, which was achieved by transfection of GKN2 overexpression vector. Akt signaling pathway markers were assessed by western blot. GKN2 is downregulated in gastric cancer and low GKN2 expression is correlated to poor survival, metastasis, and higher clinical stages. NKX6-2 binds the promoter region of GKN2 and regulate its expression. GKN2 overexpression inhibits the proliferation, migration, and invasion of gastric cancer cells, which was mediated by Akt signaling pathway. NKX6-2 regulated GKN2 inhibits the proliferation and invasion of gastric cancer cells by inhibiting Akt signaling pathway. GKN2 can be used as a potential diagnostic and therapeutic target for patients with clinical gastric cancer.
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http://dx.doi.org/10.1007/s12013-020-00948-9DOI Listing
March 2021

P-doped WO flowers fixed on a TiO nanofibrous membrane for enhanced electroreduction of N.

Chem Commun (Camb) 2020 Oct;56(85):12937-12940

Key Laboratory of High Performance Fibers & Products (Ministry of Education), College of Materials Science and Engineering, Donghua University, Shanghai 201620, China. and Innovation Center for Textile Science and Technology, Donghua University, Shanghai 200051, China.

Herein, nanoneedle-constructed WO3 flowers are prepared by hydrothermal synthesis, which are characterized by a large surface area leading to abundant active sites. Additionally, P doping is employed as an effective way to generate charge imbalance and induce more empty d-orbitals around W6+, thus facilitating the adsorption of N2 molecules. Moreover, a flexible TiO2 nanofibrous membrane is used as an electrocatalytically active matrix to fix the P-doped, nanoneedle-constructed WO3 flowers. The hierarchically structured [email protected] nanofibrous membrane acts as a self-supported electrocatalyst, presenting an enhanced ammonia yield (6.54 × 10-10 mol s-1 cm-2) and faradaic efficiency (17.5%) compared to the undoped counterpart.
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http://dx.doi.org/10.1039/d0cc05854hDOI Listing
October 2020

Thymosin‑β 4 induces angiogenesis in critical limb ischemia mice via regulating Notch/NF‑κB pathway.

Int J Mol Med 2020 Oct 11;46(4):1347-1358. Epub 2020 Aug 11.

Department of Emergency Internal Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.

Thymosin‑β 4 (Tβ4) has been reported to exert a pro‑angogenic effect on endothelial cells. However, little is known on the role and underlying mechanisms of Tβ4 on critical limb ischemia (CLI). The present study aimed therefore to investigate the mechanisms and pro‑angiogenic effects of Tβ4 in CLI mice. Tβ4 overexpression lentiviral vector was first transfected into HUVEC and CLI mice model, and inhibitors of Notch pathway (DAPT) and NF‑κB pathway (BMS) were also applied to HUVEC and CLI mice. Subsequently, MTT, tube formation and wound healing assays were used to determine the cell viability, angiogenesis and migratory ablity of HUVEC, respectively. Western blotting, reverse transcription, quantitative PCR, immunofluorescence and immunohistochemistry were used to detect the expression of the angiogenesis‑related factors angiopoietin‑2 (Ang2), TEK receptor tyrosine kinase 2 (tie2), vascular endothelial growth factor A (VEGFA), CD31 and α‑smooth muscle actin (α‑SMA) and the Notch/NF‑κB pathways‑related factors NOTCH1 intracellular domain (N1ICD), Notch receptor 3 (Notch3), NF‑κB and p65 in HUVEC or CLI mice muscle tissues. The results demonstrated that Tβ4 not only enhanced the cell viability, angiogenesis and migratory ability of HUVEC but also promoted the expression of Ang2, tie2, VEGFA, N1ICD, Notch3, NF‑κB, and phosphorylated (p)‑p65 in HUVEC. In addition, Tβ4 promoted the expression of CD31, α‑SMA Ang2, tie2, VEGFA, N1ICD and p‑p65 in CLI mice muscle tissues. Treatment with DAPT and BMS had opposite effects of Tβ4, whereas Tβ4 reversed the effect of DAPT and BMS. The findings from the present study suggested that Tβ4 may promote angiogenesis in CLI mice via regulation of Notch/NF‑κB pathways.
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http://dx.doi.org/10.3892/ijmm.2020.4701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447324PMC
October 2020

Concurrent ipsilateral Tillaux fracture and medial malleolar fracture in adolescents: management and outcome.

J Orthop Surg Res 2020 Sep 17;15(1):423. Epub 2020 Sep 17.

Children's Hospital of Soochow University, No. 92 Zhongnan street, Suzhou, Industrial Park, Jiangsu, China.

Background: The concurrent ipsilateral Tillaux fracture with medial malleolar fracture in adolescents commonly suffer from high-energy injury, making treatment more difficult. The aim of this study was to discuss the mechanism on injury, diagnosis, and treatment of this complex fracture pattern.

Methods: The charts and radiographs of six patients were reviewed. The function was assessed by the American Orthopedic Foot and Ankle Society ankle-hindfoot scores.

Results: The mean age at operation was 12.8 years. The mean interval from injury to operation was 7.7 days. Five Tillaux fractures and all medial malleolar fractures were shown on AP plain radiographs. One Tillaux fracture and two cases with avulsion of posterolateral tibial aspect were confirmed in axial computerized tomography. There was talar subluxation laterally with medial space widening in three and syndesmotic disruption in one. There were five patients sustaining ipsilateral distal fibular fractures. All fractures, except nonunion in two medial malleolar fractures and in one Tillaux fracture, healed within 6-8 weeks. There was one case of osteoarthritis of ankle joint. The average AOFAS score was 88.7.

Conclusions: Computerized tomography is helpful in identifying the fracture pattern. Anatomic reduction and internal fixation of Tillaux and medial malleolar fracture was recommended to restore the articular surface congruity and ankle stability.
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http://dx.doi.org/10.1186/s13018-020-01961-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499953PMC
September 2020

Autonomous topological time crystals and knotty molecular motors.

J Phys Condens Matter 2021 Jan;33(1):015702

Nordita, Stockholm University, Roslagstullsbacken 23, SE-106 91 Stockholm, Sweden.

We show that topology is a very effective tool, to construct classical Hamiltonian time crystals. For this we numerically analyze a general class of time crystalline Hamiltonians that are designed to model the dynamics of molecular closed strings. We demonstrate how the time crystalline qualities of a closed string are greatly enhanced when the string becomes knotted. The Hamiltonians that we investigate include a generalized Kratky-Porod wormlike chain model in combination with long range Coulomb and Lennard-Jones interactions. Such energy functions are commonplace in coarse grained molecular modeling. Thus we expect that physical realizations of Hamiltonian time crystals can be constructed in terms of knotted ring molecules.
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http://dx.doi.org/10.1088/1361-648X/abb682DOI Listing
January 2021

Simplified Reverse Genetics Method to Recover Recombinant Rotaviruses Expressing Reporter Proteins.

J Vis Exp 2020 04 17(158). Epub 2020 Apr 17.

Department of Biology, Indiana University;

Rotaviruses are a large and evolving population of segmented double-stranded RNA viruses that cause severe gastroenteritis in the young of many mammalian and avian host species, including humans. With the recent advent of rotavirus reverse genetics systems, it has become possible to use directed mutagenesis to explore rotavirus biology, modify and optimize existing rotavirus vaccines, and develop rotavirus multitarget vaccine vectors. In this report, we describe a simplified reverse genetics system that allows the efficient and reliable recovery of recombinant rotaviruses. The system is based on co-transfection of T7 transcription vectors expressing full-length rotavirus (+)RNAs and a CMV vector encoding an RNA capping enzyme into BHK cells constitutively producing T7 RNA polymerase (BHK-T7). Recombinant rotaviruses are amplified by overseeding the transfected BHK-T7 cells with MA104 cells, a monkey kidney cell line that is highly permissive for virus growth. In this report, we also describe an approach for generating recombinant rotaviruses that express a separate fluorescent reporter protein through the introduction of a 2A translational stop-restart element into genome segment 7 (NSP3). This approach avoids deleting or modifying any of the viral open reading frames, thus allowing the production of recombinant rotaviruses that retain fully functional viral proteins while expressing a fluorescent protein.
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http://dx.doi.org/10.3791/61039DOI Listing
April 2020

Promoted Electrocatalytic Nitrogen Fixation in Fe-Ni Layered Double Hydroxide Arrays Coupled to Carbon Nanofibers: The Role of Phosphorus Doping.

Angew Chem Int Ed Engl 2020 Aug 26;59(32):13623-13627. Epub 2020 May 26.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Innovation Center for Textile Science and Technology, Donghua University, Shanghai, 200051, China.

The key to bringing the electrocatalytic nitrogen fixation from conception to application lies in the development of high-efficiency, cost-effective electrocatalysts. Layered double hydroxides (LDHs), also known as hydrotalcites, are promising electrocatalysts for water splitting due to multiple metal centers and large surface areas. However, their activities in the electrocatalytic nitrogen fixation are unsatisfactory. Now, a simple and effective way of phosphorus doping is presented to regulate the charge distribution in LDHs, thus promoting the nitrogen adsorption and activation. The P-doped LDHs are further coupled to a self-supported, conductive matrix, that is, a carbon nanofibrous membrane, which prevents their aggregation as well as ensuring rapid charge transfer at the interface. By this strategy, decent ammonia yield (1.72×10  mol s  cm ) and Faradaic efficiency (23 %) are delivered at -0.5 V vs. RHE in 0.1 m Na SO .
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http://dx.doi.org/10.1002/anie.202005579DOI Listing
August 2020

MiR-132/212 promotes the growth of precartilaginous stem cells (PCSCs) by regulating Ihh/PTHrP signaling pathway.

Biosci Rep 2020 05;40(5)

Department of Orthopaedics, Children's Hospital of Soochow University, Suzhou 215000, China.

Precartilaginous stem cells (PCSCs) are adult stem cells that can initiate chondrocytes and bone development. In the present study, we explored whether miR-132/212 was involved in the proliferation of PCSCs via Hedgehog signaling pathway. PCSCs were isolated and purified with the fibroblast growth factor receptor-3 (FGFR-3) antibody. Cell viability, DNA synthesis and apoptosis were measured using MTT, BrdU and flow cytometric analysis. The mRNA and protein expression were detected by real-time PCR and Western blot, respectively. The target gene for miR-132/212 was validated by luciferase reporter assay. Results showed that transfection with miR-132/212 mimic significantly increased cell viability and DNA synthesis, and inhibited apoptosis of PCSCs. By contrast, miR-132/212 inhibitor could suppress growth and promote apoptosis of PCSCs. Luciferase reporter assays indicated that transfection of miR-132/212 led to a marked reduction of luciferase activity, but had no effect on PTCH1 3'-UTR mutated fragment, suggesting that Patched1 (PTCH1) is a target of miR-132/212. Furthermore, treatment with miR-132/212 mimics obviously increased the protein expression of Indian hedgehog (Ihh) and parathyroid hormone related protein (PTHrP), which was decreased after treatment with Hedgehog signaling inhibitor, cyclopamine. We also found that inhibition of Ihh/PTHrP signaling by cyclopamine significantly suppressed growth and DNA synthesis, and induced apoptosis in PCSCs. These findings demonstrate that miR-132/212 promotes growth and inhibits apoptosis in PCSCs by regulating PTCH1-mediated Ihh/PTHrP pathway, suggesting that miR-132/212 cluster might serve as a novel target for bone diseases.
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http://dx.doi.org/10.1042/BSR20191654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214394PMC
May 2020

Surprising simplicities and syntheses in limbless self-propulsion in sand.

J Exp Biol 2020 02 28;223(Pt 5). Epub 2020 Feb 28.

Department of Physics, Georgia Institute of Technology, Atlanta, GA 30332, USA.

Animals moving on and in fluids and solids move their bodies in diverse ways to generate propulsion and lift forces. In fluids, animals can wiggle, stroke, paddle or slap, whereas on hard frictional terrain, animals largely engage their appendages with the substrate to avoid slip. Granular substrates, such as desert sand, can display complex responses to animal interactions. This complexity has led to locomotor strategies that make use of fluid-like or solid-like features of this substrate, or combinations of the two. Here, we use examples from our work to demonstrate the diverse array of methods used and insights gained in the study of both surface and subsurface limbless locomotion in these habitats. Counterintuitively, these seemingly complex granular environments offer certain experimental, theoretical, robotic and computational advantages for studying terrestrial movement, with the potential for providing broad insights into morphology and locomotor control in fluids and solids, including neuromechanical control templates and morphological and behavioral evolution. In particular, granular media provide an excellent testbed for a locomotion framework called geometric mechanics, which was introduced by particle physicists and control engineers in the last century, and which allows quantitative analysis of alternative locomotor patterns and morphology to test for control templates, optimality and evolutionary alternatives. Thus, we posit that insights gained from movement in granular environments can be translated into principles that have broader applications across taxa, habitats and movement patterns, including those at microscopic scales.
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http://dx.doi.org/10.1242/jeb.103564DOI Listing
February 2020

Prevalence and Risk Factors of Preoperative Deep Vein Thrombosis in Patients with End-Stage Knee Osteoarthritis.

Ann Vasc Surg 2020 Apr 15;64:175-180. Epub 2019 Oct 15.

State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, PR China; Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing, Jiangsu, PR China. Electronic address:

Background: The purpose of this study is to determine the prevalence and the risk factors of DVT in end-stage OA patients.

Methods: From March 2015 to June 2017, 521 patients with knee degenerative osteoarthritis undergoing knee arthroplasty were enrolled; 458 patients (87.9%) were admitted for primary total knee arthroplasty and 63 patients (12.1%) were admitted for unicompartmental knee arthroplasty. Parameters were compared using χ or t-test for both the groups. Binary logistic regression analysis was used to determine risk factors.

Results: The incidence of preoperative DVT was 6.7% (n = 35). Age in preoperative DVT group was significantly more than the non-DVT group (72.54 ± 6.53 vs. 68.65 ± 7.35, P = 0.002). Preoperative D-dimer >0.5 μg/mL (P < 0.001) was also associated with preoperative DVT in knee osteoarthritis patients. The incidence increased with age significantly (2.17% in <65 years, 6.86% in ≥65 <75 years, and 12.26% in ≥75 years) (P = 0.008). Thus, age (P = 0.041, OR 1.075, 95% CI [1.002-1.110]) and D-dimer >0.5 μg/mL (P < 0.001, OR 4.441, 95% CI [1.942-10.153]) were the independent risk factors for preoperative DVT in knee osteoarthritis patients.

Conclusions: The incidence of DVT in end-stage osteoarthritis was 6.7%. The results suggest that older people aged over 75 and D-dimer > 0.5 μg/mL were risk factors for DVT among patients admitted to the hospital for total knee arthroplasty. Instrumental screening should be encouraged, especially in subgroups at higher risk for preoperative DVT.
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http://dx.doi.org/10.1016/j.avsg.2019.08.089DOI Listing
April 2020
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