Publications by authors named "Dong Zhou"

878 Publications

A Omp16 conditional deletion strain is attenuated in BALB/c mice.

J Microbiol Biotechnol 2021 Oct 20;32. Epub 2021 Oct 20.

College of Veterinary Medicine, Northwest A&F University, Yangling, P.R.China.

spp. are facultative intracellular pathogens that invade, survive and proliferate in numerous phagocytic and non-phagocytic cell types, thereby leading to human and animal brucellosis. Outer membrane proteins (Omps) are major immunogenic and protective antigens that are implicated in virulence. A strain deleted of the omp16 gene has not been obtained which suggests that the protein is vital for survival. Nevertheless, we previously constructed an conditional deletion strain of Brucella, ΔOmp16. Here, the virulence and immune response elicted by this strain were assessed in a mouse model of infection. Splenomegaly was significantly reduced at two weeks post-infection in ΔOmp16-infected mice compared to infection with the parental strain. The bacterial load in the spleen also was significantly decreased at this post-infection time point in ΔOmp16-infected mice. Histopathological changes in the spleen were observed via hematoxylin-eosin staining and microscopic examination which showed that infection with the ΔOmp16 strain alleviated spleen histopathological alterations compared to mice infected with the parental strain. Moreover, the levels of humoral and cellular immunity were similar in both ΔOmp16-infected mice and parental strain-infected mice. The results overall show that the virulence of ΔOmp16 is attenuated markedly, but that the immune responses mediated by the deletion and parental strains in mice are indistinguishable. The data provide important insights that illuminate the pathogenic strategies adopted by .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4014/jmb.2110.07016DOI Listing
October 2021

An optimal window of platelet reactivity by LTA assay for patients undergoing percutaneous coronary intervention.

Thromb J 2021 Oct 19;19(1):73. Epub 2021 Oct 19.

Departments of Cardiology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.

Objective: This study was aimed to determine how platelet reactivity (PR) on dual antiplatelet therapy predicts ischemic and bleeding events in patients underwent percutaneous coronary intervention (PCI).

Design: A total of 2768 patients who had received coronary stent implantation and had taken aspirin 100 mg in combination with clopidogrel 75 mg daily for > 5 days were consecutively screened and 1885 were enrolled. The recruited patients were followed-up for 12 months. The primary end-point was the net adverse clinical events (NACE) of cardiovascular death, nonfatal myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST) and any bleeding.

Result: 1709 patients completed the clinical follow-up. By using the receiver operating characteristic (ROC) curve analysis, the optimal cut-off values were found to be 37.5 and 25.5% respectively in predicting ischemic and bleeding events. Patients were classified into 2 groups according to PR: inside the window group (IW) [adenosine diphosphate (ADP) induced platelet aggregation (PL) 25.5-37.4%)] and outside the window group (OW) (PL < 25.5% or ≥ 37.5%). The incidence of NACE was 16.8 and 23.1% respectively in the IW and OW group. The hazard ratio of NACE in IW group was significantly lower [0.69 (95% CI, 0.54-0.89, P = 0.004)] than that in the OW group during 12-month follow-up.

Conclusion: An optimal therapeutic window of 25.5-37.4% for PL predicts the lowest risk of NACE, which could be referred for tailored antiplatelet treatment while using LTA assay.

Trial Registration: Trial registration number: ClinicalTrials.gov NCT01968499 . Registered 18 October 2013 - Retrospectively registered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12959-021-00323-5DOI Listing
October 2021

Formed Li-Ag Alloy Interface Enables LiGePS-Based All-Solid-State Lithium Batteries.

ACS Appl Mater Interfaces 2021 Oct 14. Epub 2021 Oct 14.

Key Laboratory of Material Physics, Ministry of Education, School of Physics and Microelectronics, Zhengzhou University, Zhengzhou 450001, P. R. China.

All-solid-state lithium-metal batteries (ASSLMBs) have received great interest due to their high potential to display both high energy density and safety performance. However, the poor compatibility at the Li/solid electrolyte (SE) interface and penetration of lithium dendrites during cycling strongly impede their successful commercialization. Herein, a thin Ag layer was introduced between Li and LiGePS for the formation of a Li-Ag alloy interface, thus tuning the interfacial chemistry and lithium deposition/dissolution behavior. Superior electrochemical properties and improved interfacial stability were achieved by optimizing the Ag thicknesses. The assembled symmetric cell with [email protected] 1 μm showed a steady voltage evolution up to 1000 h with an areal capacity of 1 mAh cm. Moreover, a high reversible capacity of 106.5 mAh g was achieved in an all-solid-state cell after 100 cycles, demonstrating the validity of the Ag layer. This work highlights the importance of the Li/SE interface re-engineering and provides a new strategy for improving the cycle life of ASSLMBs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c16356DOI Listing
October 2021

Retracted: Expression of Long Non-Coding RNA (lncRNA) Small Nucleolar RNA Host Gene 1 (SNHG1) Exacerbates Hepatocellular Carcinoma Through Suppressing miR-195.

Med Sci Monit 2021 Oct 14;27:e935056. Epub 2021 Oct 14.

Department of Abdominal Surgery, Fujian Provincial Cancer Hospital, Fujian Medical University Teaching Hospital, Fuzhou, Fujian, China (mainland).

Retracted, due to breach of publishing guidelines, following the identification of non-original and manipulated figure images. Reference: Hui Zhang, Dong Zhou, Mingang Ying, Minyong Chen, Peng Chen, Zhaoshuo Chen, Fan Zhang: Expression of Long Non-Coding RNA (lncRNA) Small Nucleolar RNA Host Gene 1 (SNHG1) Exacerbates Hepatocellular Carcinoma Through Suppressing miR-195. Med Sci Monit, 2016; 22: 4820-4829. DOI: 10.12659/MSM.898574.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.935056DOI Listing
October 2021

Complementary Fourier Single-Pixel Imaging.

Sensors (Basel) 2021 Sep 30;21(19). Epub 2021 Sep 30.

Beijing Fisheries Research Institute, Beijing 100068, China.

Single-pixel imaging, with the advantages of a wide spectrum, beyond-visual-field imaging, and robustness to light scattering, has attracted increasing attention in recent years. Fourier single-pixel imaging (FSI) can reconstruct sharp images under sub-Nyquist sampling. However, the conventional FSI has difficulty balancing imaging quality and efficiency. To overcome this issue, we proposed a novel approach called complementary Fourier single-pixel imaging (CFSI) to reduce the number of measurements while retaining its robustness. The complementary nature of Fourier patterns based on a four-step phase-shift algorithm is combined with the complementary nature of a digital micromirror device. CFSI only requires two phase-shifted patterns to obtain one Fourier spectral value. Four light intensity values are obtained by loading the two patterns, and the spectral value is calculated through differential measurement, which has good robustness to noise. The proposed method is verified by simulations and experiments compared with FSI based on two-, three-, and four-step phase shift algorithms. CFSI performed better than the other methods under the condition that the best imaging quality of CFSI is not reached. The reported technique provides an alternative approach to realize real-time and high-quality imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21196544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512370PMC
September 2021

An ArsR Transcriptional Regulator Facilitates sp. Survival via Regulating Self and Outer Membrane Protein.

Int J Mol Sci 2021 Oct 8;22(19). Epub 2021 Oct 8.

College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.

The arsenic acid-resistant (ArsR) family transcriptional regulators are widely distributed in microorganisms, including in the facultative intracellular pathogen spp. ArsR proteins are implicated in numerous biological processes. However, the specific roles of ArsR family members in remain obscure. Here, we show that ArsR6 (BSS2_RS07325) is required for survival both under heat, oxidative, and osmotic stress and in a murine infection model in vivo. RNA-seq and ChIP-seq reveal that 34 potential target genes for ArsR6 protein were identified, among which eight genes were up-regulated and 26 genes were down-regulated, including outer membrane protein 25D (Omp25D). ArsR6 autoregulates its own expression to maintain bacterial intracellular Cu/Ni homeostasis to benefit bacterial survival in hostile environments. Moreover, ArsR6 also regulates the production of virulence factor Omp25D, which is important for the survival of under stress conditions. Significantly, Omp25D deletion strain attenuated in a murine infection model in vivo. Altogether, our findings reveal a unique mechanism in which the ArsR family member ArsR6 autoregulates its expression and also modulates Omp25D expression to maintain metal ion homeostasis and virulence in .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms221910860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509827PMC
October 2021

Trend of Sudden Unexpected Death in Epilepsy Incidence Rate in Rural West China.

Front Neurol 2021 24;12:735201. Epub 2021 Sep 24.

Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.

To explore the trend of sudden unexpected death in epilepsy (SUDEP) incidence rate over time in rural west China. We scanned probable SUDEP patients from the epilepsy program between 2010 and 2019 in rural West China and performed a verbal autopsy for each eligible patient. We calculated the crude and sex-adjusted incidence rate of SUDEP per person-year over a calendar year and the year of follow-up. We calculated the incidence rate ratio with the Poisson model in STATA 12.0 and calculated the annual percentage change (APC) and average annual percentage change in Joinpoint Trend Analysis Software 4.8.0.1 to analyze the trend of SUDEP incidence rate. In 2010-2019, 44 probable SUDEPs were identified from 10,128 patients with a total person-year of 31,347. The crude and sex-adjusted incidence rates of SUDEP were 1.40 and 1.45%0. Twenty-five (56.8%) of the 44 probable SUDEPs had no generalized tonic-clonic seizure 3 months before their death. The incidence of probable SUDEP decreased significantly in the calendar year [APC = -11.7, 95% confidence interval (CI): -21.7 to -0.3] and in time of follow-up (average annual percentage change = -21.2, 95% CI: -34.3 to -5.4). Comparing the first 5 years in follow-up with the subsequent 3 years, the incidence rate of SUDEP decreased significantly (estimated incidence rate ratio = 0.4, 95% CI: 0.2 to 0.8). SUDEP happened to 1.4 cases per thousand patient-years in convulsive epilepsy in rural west China between 2010 and 2019. The incidence rate of SUDEP presented a downward trend over the time of follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.735201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498108PMC
September 2021

The hepatocyte growth factor/c-met pathway is a key determinant of the fibrotic kidney local microenvironment.

iScience 2021 Oct 9;24(10):103112. Epub 2021 Sep 9.

Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT 06030, USA.

The kidney local microenvironment (KLM) plays a critical role in the pathogenesis of kidney fibrosis. However, the composition and regulation of a fibrotic KLM remain unclear. Through a multidisciplinary approach, we investigated the roles of the hepatocyte growth factor/c-met signaling pathway in regulating KLM formation in various chronic kidney disease (CKD) models. We performed a retrospective analysis of single-cell RNA sequencing data and determined that tubular epithelial cells and macrophages are two major cell populations in a fibrotic kidney. We then created a mathematical model that predicted loss of c-met in tubular cells would cause greater responses to injury than loss of c-met in macrophages. By generating c-met conditional knockout mice, we validated that loss of c-met influences epithelial plasticity, myofibroblast activation, and extracellular matrix synthesis/degradation, which ultimately determined the characteristics of the fibrotic KLM. Our findings open the possibility of designing effective therapeutic strategies to retard CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.isci.2021.103112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479790PMC
October 2021

Exploration of alcohol-enhanced Cu-mediated radiofluorination toward practical labeling.

J Labelled Comp Radiopharm 2021 Oct 7. Epub 2021 Oct 7.

Department of Chemistry and Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Champaign, Illinois, USA.

Copper-mediated nucleophilic radiofluorination using boronic precursors is a promising, general method to label aromatic compounds with [ F]fluoride. However, in various reports, large amounts of precursor (60 μmol) were needed to achieve high radiochemical conversions (RCCs), which is neither ideal nor practical for the preparation of F radiopharmaceuticals. To investigate this matter, we studied alcohol-enhanced Cu-mediated nucleophilic radiofluorination using a variety of model reactions in which we varied the concentration of [ F]fluoride (no carrier added or isotope diluted) and the amount of precursor, base, and Cu(OTF) (Py) . We found that lower amounts of precursors (e.g., 15 μmol) could be used and that the amount of base (e.g., K CO or KHCO ) played a critical and limiting role in the labeling reactions. Greater than one-equivalent of base and sufficient amounts of precursors and Cu(OTf) (Py) were required to achieve good to high RCCs. The RCCs were also dependent on the overall concentration of the labeling reactions, with low reaction volumes and high concentrations of reagents being preferred. Our findings will help to improve the design of radiolabeling protocols using alcohol-enhanced copper-mediated radiofluorination of boronic precursors for the preparation of F labeled radiopharmaceuticals and other radiohalogen-labeled compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jlcr.3955DOI Listing
October 2021

Significance of Parkinson Family Genes in the Prognosis and Treatment Outcome Prediction for Lung Adenocarcinoma.

Front Mol Biosci 2021 20;8:735263. Epub 2021 Sep 20.

Department of Thoracic Surgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Epidemiological investigations have shown that patients with Parkinson's disease (PD) have a lower probability of developing lung cancer. Subsequent research revealed that PD and lung cancer share specific genetic alterations. Therefore, the utilisation of PD biomarkers and therapeutic targets may improve lung adenocarcinoma (LUAD) diagnosis and treatment. We aimed to identify a gene-based signature from 25 Parkinson family genes for LUAD prognosis and treatment choice. We analysed Parkinson family gene expression and protein levels in LUAD, utilising multiple databases. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a prognostic model based on the TCGA-LUAD cohort. We validated the model in external GEO cohorts. Immune cell infiltration was compared between risk groups, and GEO data was used to explore the model's predictive ability for LUAD treatment response. Nearly all Parkinson family genes exhibited significant differential expression between LUAD and normal tissues. LASSO regression confirmed that our seven Parkinson family gene-based signature had excellent prognostic performance for LUAD, as validated in three GEO cohorts. The high-risk group was clearly associated with low tumour immune cell infiltration, suggesting that immunotherapy may not be an optimal treatment choice. This is the first Parkinson family gene-based model for the prediction of LUAD prognosis and treatment outcome. The association of these genes with poor prognosis and low immune infiltration requires further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2021.735263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488091PMC
September 2021

A synergistic exploitation to produce high-voltage quasi-solid-state lithium metal batteries.

Nat Commun 2021 Sep 30;12(1):5746. Epub 2021 Sep 30.

Centre for Clean Energy Technology, School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, 2007, Australia.

The current Li-based battery technology is limited in terms of energy contents. Therefore, several approaches are considered to improve the energy density of these energy storage devices. Here, we report the combination of a heteroatom-based gel polymer electrolyte with a hybrid cathode comprising of a Li-rich oxide active material and graphite conductive agent to produce a high-energy "shuttle-relay" Li metal battery, where additional capacity is generated from the electrolyte's anion shuttling at high voltages. The gel polymer electrolyte, prepared via in situ polymerization in an all-fluorinated electrolyte, shows adequate ionic conductivity (around 2 mS cm at 25 °C), oxidation stability (up to 5.5 V vs Li/Li), compatibility with Li metal and safety aspects (i.e., non-flammability). The polymeric electrolyte allows for a reversible insertion of hexafluorophosphate anions into the conductive graphite (i.e., dual-ion mechanism) after the removal of Li ions from Li-rich oxide (i.e., rocking-chair mechanism).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-26073-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484457PMC
September 2021

Serosa-Mimetic Nanoarchitecture Membranes for Highly Efficient Osmotic Energy Generation.

J Am Chem Soc 2021 Oct 27;143(39):16206-16216. Epub 2021 Sep 27.

Centre for Clean Energy Technology, School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia.

Osmotic energy stored between seawater and freshwater is a clean and renewable energy source. However, developing high-efficiency and durable permselective membranes for harvesting osmotic energy remains a longstanding bottleneck. Herein, we report that a nanocomposite membrane with a biological serosa-mimetic structure can achieve high-performance osmotic energy generation through the coupling of two-dimensional (2D) sulfonated covalent organic framework (COF) nanosheets and anion-grafted aramid nanofibers (ANFs). As verified by theoretical calculations and experimental investigations, the 2D COF nanosheets not only provide abundant one-dimensional (1D)/2D nanofluidic channels to synergistically benefit an ultrafast ion migration but also enable high cation permselectivity via the covalently tethered anions. The grafted ANFs increase the mechanical strength of the membrane and further improve the ion diffusion/rectification. When it was applied in an osmotic power generator, the biomimetic membrane delivered a power density of 9.6 W m, far surpassing the commercial benchmark of 5.0 W m. This work could boost the viability of osmotic energy conversion toward a sustainable future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.1c07392DOI Listing
October 2021

Combination of structural MRI, functional MRI and brain PET-CT provide more diagnostic and prognostic value in patients of cerebellar ataxia associated with anti-Tr/DNER: a case report.

BMC Neurol 2021 Sep 24;21(1):368. Epub 2021 Sep 24.

Department of Neurology, West China Hospital, Sichuan University, No. 37 GuoXue Alley, 610041, Chengdu, Sichuan, China.

Background: Brain magnetic resonance imaging (MRI) rarely reveals structural changes in patients with suspected anti-Tr/DNER encephalitis and thus provides very limited information. Here, we combined structural MRI, functional MRI, and positron emission tomography-computed tomography (PET-CT) findings to characterize this rare disorder in a patient.

Case Presentation: A 43-year-old woman presented with progressive cerebellar ataxia, memory impairment, anxiety, and depression. Anti-Tr antibodies were detected in both her serum (1:10) and cerebrospinal fluid (1:10). A diagnosis of anti-Tr-positive autoimmune cerebellar ataxia was established. The patient's symptoms were worse, but her brain MRI was normal. Meanwhile, voxel-based morphometry analysis showed bilateral reduced cerebellar volume, especially in the posterior lobe and uvula of the cerebellum and the middle of the left temporal lobe compared with 6 sex- and age-matched healthy subjects (6 females, 43 ± 2 years; p < 0.05). Using seed-based functional connectivity analysis, decreased connectivity between the posterior cingulate cortex/precuneus and left frontal lobe compared to the control group (p < 0.05) was detected. PET-CT revealed bilateral hypometabolism in the cerebellum and relative hypermetabolism in the cerebellar vermis and bilateral frontal lobe, but no malignant changes.

Conclusions: A combination of structural MRI, functional MRI, and brain PET-CT has higher diagnostic and prognostic value than conventional MRI in patients with suspected anti-Tr/DNER encephalitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12883-021-02403-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461997PMC
September 2021

Potent neutralizing RBD-specific antibody cocktail against SARS-CoV-2 and its mutant.

MedComm (Beijing) 2021 Jun 24. Epub 2021 Jun 24.

Department of Neurology State Key Lab of Biotherapy and Cancer center West China Hospital Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu Sichuan China.

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants has posed a serious global public health emergency. Therapeutic interventions or vaccines are urgently needed to treat and prevent the further dissemination of this contagious virus. This study described the identification of neutralizing receptor-binding domain (RBD)-specific antibodies from mice through vaccination with a recombinant SARS-CoV-2 RBD. RBD-targeted monoclonal antibodies (mAbs) with distinct function and epitope recognition were selected to understand SARS-CoV-2 neutralization. High-affinity RBD-specific antibodies exhibited high potency in neutralizing both live and pseudotype SARS-CoV-2 viruses and the SARS-CoV-2 pseudovirus particle containing the spike protein S-RBD mutant (SARS-CoV-2(V367F)). These results demonstrated that these antibodies recognize four distinct groups (I-IV) of epitopes on the RBD and that mAbs targeting group I epitope can be used in combination with mAbs recognizing groups II and/or IV epitope to make mAb cocktails against SARS-CoV-2 and its mutants. Moreover, structural characterization reveals that groups I, III, and IV epitopes are closely located to an RBD hotspot. The identification of RBD-specific antibodies and cocktails may provide an effective therapeutic and prophylactic intervention against SARS-CoV-2 and its isolates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mco2.79DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441738PMC
June 2021

An integrated analysis of enhancer RNAs in glioma and a validation of their prognostic values.

Am J Transl Res 2021 15;13(8):8611-8631. Epub 2021 Aug 15.

Department of Neurosurgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou 510080, Guangdong Province, P. R. China.

Glioma, a highly aggressive neuroepithelial malignant brain tumor, is associated with high disability and recurrence rates. Enhancer RNA (eRNA) plays a significant role in tumor proliferation and metastasis; however, their functions in gliomas need further evaluation. We used the computational pipeline, PreSTIGE, to predict tissue-specific enhancer-derived RNAs and the underlying regulatory genes. Using data retrieved from the TCGA and CGGA databases, a LASSO regression analysis and multiCox proportional hazards regression analyses were performed to determine the hub eRNAs associated with glioma prognosis. Quantitative reverse transcription PCR was performed on the glioma samples to evaluate the expression characteristics of the identified hub eRNAs. To construct a risk signature, we selected three eRNAs, including CRNDE, MRPS31P5, and LINC00844, for their significant prognostic values. The predictive value of the risk signature was validated using the CGGA and Rembrandt cohorts. Apart from the risk signature, the nomogram performed well at predicting OS in glioma patients. An eRNA-target gene regulatory network was established, which we evaluated using a target gene enrichment analysis. Pathway and gene ontology (GO) analyses demonstrated that the risk signature is associated with mRNA processing and spliceosome in glioma. Furthermore, we found that hub eRNAs potentially regulate the expressions of numerous splicing factors, such as MOV10 and SEC31B, and are correlated with prognosis-associated alteration splicing (AS). In conclusion, we established a risk signature that comprises three eRNAs, which can accurately be utilized as targets to predict prognosis in glioma patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430071PMC
August 2021

Myeloid PTEN deficiency aggravates renal inflammation and fibrosis in angiotensin II-induced hypertension.

J Cell Physiol 2021 Sep 13. Epub 2021 Sep 13.

Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, USA.

Hypertension is a major cause of chronic kidney disease. However, the pathogenesis of hypertensive kidney disease is not fully understood. Recently, we have shown that CXCL16/phosphoinositide-3 kinase γ (PI3Kγ) plays an important role in the development of renal inflammation and fibrosis in angiotensin II (AngII) induced hypertensive nephropathy. In the present study, we examined the role of phosphatase and tensin homolog (PTEN), a major regulator of PI3K signaling, in the pathogenesis of renal inflammation and fibrosis in an experimental model of hypertension induced by AngII. We generated myeloid PTEN conditional knockout mice by crossing PTEN mice with LysM-driven Cre mice. Littermate LysM-Cre PTEN mice were used as a control. Both myeloid PTEN knockout mice and their littermate control mice exhibited similar blood pressure at baseline. AngII treatment resulted in an increase in blood pressure that was comparable between myeloid PTEN knockout mice and littermate control mice. Compared with littermate control mice, myeloid PTEN knockout mice developed more severe kidney dysfunction, proteinuria, and fibrosis following AngII treatment. Furthermore, myeloid PTEN deficiency exacerbated total collagen deposition and extracellular matrix protein production and enhanced myeloid fibroblast accumulation and myofibroblast formation in the kidney following AngII treatment. Finally, myeloid PTEN deficiency markedly augmented infiltration of F4/80 macrophages and CD3 T cells into the kidneys of AngII-treated mice. Taken together, these results indicate that PTEN plays a crucial role in the pathogenesis of renal inflammation and fibrosis through the regulation of infiltration of myeloid fibroblasts, macrophages, and T lymphocytes into the kidney.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.30574DOI Listing
September 2021

Mediastinal Nodular Lymphocyte Predominant Hodgkin Lymphoma Achieved by Endoscopic Transesophageal Cryobiopsy.

Respiration 2021 Sep 1:1-5. Epub 2021 Sep 1.

Department of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

Guidelines have recommended endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine-needle aspiration biopsy as initial sampling approaches of mediastinal lymph nodes for lung cancer staging. However, the small sample volume might restrict the diagnostic utility of needle aspiration in certain mediastinal diseases. We have recently shown that transbronchial mediastinal cryobiopsy, which is capable of providing larger amounts of intact tissue, improves diagnostic yield in rare tumors and benign diseases compared to EBUS-TBNA. Here, we present a case of mediastinal nodular lymphocyte predominant Hodgkin lymphoma successfully diagnosed by endoscopic transesophageal cryobiopsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000518598DOI Listing
September 2021

Pharmacological Inhibition of STAT6 Ameliorates Myeloid Fibroblast Activation and Alternative Macrophage Polarization in Renal Fibrosis.

Front Immunol 2021 26;12:735014. Epub 2021 Aug 26.

Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, United States.

A hallmark of chronic kidney disease is renal fibrosis, which can result in progressive loss of kidney function. Currently, there is no effective therapy for renal fibrosis. Therefore, there is an urgent need to identify potential drug targets for renal fibrosis. In this study, we examined the effect of a selective STAT6 inhibitor, AS1517499, on myeloid fibroblast activation, macrophage polarization, and development of renal fibrosis in two experimental murine models. To investigate the effect of STAT6 inhibition on myeloid fibroblast activation, macrophage polarization, and kidney fibrosis, wild-type mice were subjected to unilateral ureteral obstruction or folic acid administration and treated with AS1517499. Mice treated with vehicle were used as control. At the end of experiments, kidneys were harvested for analysis of myeloid fibroblast activation, macrophage polarization, and renal fibrosis and function. Unilateral ureteral obstruction or folic acid administration induced STAT6 activation in interstitial cells of the kidney, which was significantly abolished by AS1517499 treatment. Mice treated with AS1517499 accumulated fewer myeloid fibroblasts and myofibroblasts in the kidney with ureteral obstruction or folic acid nephropathy compared with vehicle-treated mice. Moreover, AS1517499 significantly suppressed M2 macrophage polarization in the injured kidney. Furthermore, AS1517499 markedly reduced the expression levels of extracellular matrix proteins, and development of kidney fibrosis and dysfunction. These findings suggest that AS1517499 inhibits STAT6 activation, suppresses myeloid fibroblast activation, reduces M2 macrophage polarization, attenuates extracellular matrix protein production, and preserves kidney function. Therefore, targeting STAT6 with AS1517499 is a novel therapeutic approach for chronic kidney disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.735014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426438PMC
August 2021

Epilepsy centers in China: Current status and ways forward.

Epilepsia 2021 Sep 12. Epub 2021 Sep 12.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Objective: China has the largest population of patients with epilepsy worldwide, which imposes a heavy burden on the public and health care systems. Several epidemiological surveys on epilepsy have been performed in China. Although these surveys grossly describe the prevalence and gap in treatment of epilepsy, the status of epilepsy centers is unclear. The number of epilepsy centers has increased substantially in recent decades. Therefore, a nationwide investigation of the scale and distribution, personnel, equipment, and epilepsy care capacity of each epilepsy center is of great value.

Methods: In 2017-2018, a multicenter cross-sectional survey was performed by the Commission on Standardized Development of Epilepsy Centers, China Association Against Epilepsy in 31 provinces, autonomous regions, and municipalities. The survey consisted of 74 questions divided into four sections: (1) overview, (2) personnel, (3) essential equipment and facilities, and (4) epilepsy care service capacity. The questions ranged from January 1, 2016 to December 31, 2016. The data were analyzed using descriptive statistics.

Results: There were 358 epilepsy centers for the 1.38 billion national population in 2016. Three quarters were in the eastern and western regions, and >90% were in tertiary hospitals. There were 9688 doctors engaged in epilepsy care, and 4.8% of doctors and electrophysiological physicians/technicians passed the national test for electroencephalography technical accreditation. A total of 9667 patients underwent resective surgeries in 2016. There were 888 vagus nerve stimulation procedures and 275 deep brain stimulation procedures.

Significance: This study is the first unique survey of epilepsy centers in China. Despite their rapid development, epilepsy centers cannot meet patients' needs at this stage. The results provide data-based evidence for the formulation of policies related to epilepsy service planning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.17058DOI Listing
September 2021

Associations of overweight and obesity with drug-resistant epilepsy.

Seizure 2021 Jul 20;92:94-99. Epub 2021 Jul 20.

Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

Background: Obesity and overweight have been well established as comorbidities of epilepsy in adults. However, the effects of overweight and obesity on the risk of adult drug-resistant epilepsy (DRE) has not been fully assessed. Thus, the objective of this study was to investigate the relationships between categories of body mass index (BMI) and DRE.

Methods: This was a case-control study. Patients with epilepsy hospitalized for Video electroencephalogram were included in the study from 2015 to 2020. Low/normal weight, overweight, and obesity were defined as BMI<23 and 23-24.9 and ≥25 kg/m, respectively. The proportions of patients diagnosed with DRE in each category were calculated.

Results: A total of 1272 patients with drug-responsive epilepsy and 345 patients with DRE were included in this study. More men than women had DRE (P=0.012). Higher proportions of patients with DRE had a history of status epilepticus (P<0.001), CNS infection (P=0.027), developmental delay (P=0.001), and comorbidity (P<0.001). Obesity (BMI≥25 kg/m) was associated with an increased risk of DRE (adjusted OR, 2.339; 95% CI, 1.724-3.171). No significant increase in the risk of DRE was found to be associated with overweight. Further stratified analyses by valproic acid (VPA) treatment attenuated the obesity-DRE relationship, but the associations remained statistically significant (adjusted OR, 1.79; 95% CI, 1.15-2.80).

Conclusion: Obesity, but not overweight, potentially plays a role in DRE, although confounders, such as antiseizure medications (ASMs) use, need to be explored. In the future, well-designed trials are needed to elucidate this issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2021.07.019DOI Listing
July 2021

Purification and comparative study of bioactivities of a natural selenized polysaccharide from Ganoderma Lucidum mycelia.

Int J Biol Macromol 2021 Nov 31;190:101-112. Epub 2021 Aug 31.

College of Food Sciences and Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China; College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, China. Electronic address:

The development of selenized polysaccharides is a promising strategy for the dietary selenium supplementation. The purpose of this research is to determine the influence of selenium on the structure and bioactivity of a polysaccharide fraction (MPN) isolated from Ganoderma lucidum mycelia. After biological selenium enrichment, the selenium content in the selenized polysaccharide (SeMPN) was 18.91 ± 1.8 μg/g. SeMPN had a slightly lower molecular weight than MPN, but the carbohydrate content and monosaccharide composition remained identical. Additionally, the band at 606 cm in MPN changed to 615 cm in SeMPN as revealed by FT-IR spectra. No significant changes were observed in the types and ratios of glycosidic linkages, as determined by NMR spectroscopy. Extracellular and intracellular antioxidant assays demonstrated that SeMPN was more effective than MPN in scavenging free radicals, inhibiting AAPH-induced erythrocyte hemolysis, and protecting catalase (CAT) and glutathione peroxidase (GSH-Px) activity in HO-injured PC12 cells. Additionally, SeMPN had a higher increase effect on RAW 264.7 cells's pinocytic and phagocytic capacity, as well as their production of NO, TNF-α, and IL-6. SeMPN could be as potential functional selenium supplementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.08.189DOI Listing
November 2021

Disrupted functional connectivity in white matter resting-state networks in unilateral temporal lobe epilepsy.

Brain Imaging Behav 2021 Sep 3. Epub 2021 Sep 3.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, Center for Information in Medicine, School of Life Science and Technology, University of Electronic Science and Technology of China, Second North Jianshe Road, Chengdu, 610054, People's Republic of China.

Unilateral temporal lobe epilepsy (TLE) is the most common type of focal epilepsy characterized by foci in the unilateral temporal lobe grey matters of regions such as the hippocampus. However, it remains unclear how the functional features of white matter are altered in TLE. In the current study, resting-state functional magnetic resonance imaging (fMRI) was performed on 71 left TLE (LTLE) patients, 79 right TLE (RTLE) patients and 47 healthy controls (HC). Clustering analysis was used to identify fourteen white matter networks (WMN). The functional connectivity (FC) was calculated among WMNs and between WMNs and grey matter. Furthermore, the FC laterality of hemispheric WMNs was assessed. First, both patient groups showed decreased FCs among WMNs. Specifically, cerebellar white matter illustrated decreased FCs with the cerebral superficial WMNs, implying a dysfunctional interaction between the cerebellum and the cerebral cortex in TLE. Second, the FCs between WMNs and the ipsilateral hippocampus (grey matter foci) were also reduced in patient groups, which may suggest insufficient functional integration in unilateral TLE. Interestingly, RTLE showed more severe abnormalities of white matter FCs, including links to the bilateral hippocampi and temporal white matter, than LTLE. Taken together, these findings provide functional evidence of white matter abnormalities, extending the understanding of the pathological mechanism of white matter impairments in unilateral TLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11682-021-00506-8DOI Listing
September 2021

Regulation of prognosis-related Siglecs in the glioma microenvironment.

J Cancer Res Clin Oncol 2021 Nov 1;147(11):3343-3357. Epub 2021 Sep 1.

School of Medicine, South China University of Technology, Guangzhou, 510006, China.

Purpose: The anti-inflammatory environment of glioma reduces the efficacy of immunotherapies. Therefore, it is vital to transform the immunosuppressive microenvironment of glioma into a pro-inflammatory environment. Sialic acid-binding immunoglobulin-type lectins (Siglecs) can serve as immune checkpoint targets that enhance the anti-tumor immune response. However, the roles of Siglecs in the glioma microenvironment are unknown. This study was conducted to identify targets to inhibit the anti-inflammatory environment to improve therapeutic outcomes in patients with glioma.

Methods: We analyzed the regulatory effect of prognosis-related Siglecs identified from data available in The Cancer Genome Atlas database (TCGA) and China Glioma Genome Atlas Data portal on the immunosuppressive microenvironment of glioma. The effects of prognosis-related Siglecs on the glioma microenvironment were investigated by determining the Pearson correlation coefficients of the Siglecs in transcriptome data from the TCGA database.

Results: Siglec-1, -9, -10, and -14 were closely associated with the prognosis of patients with glioma. The expression of these four Siglecs was significantly increased in the high-risk group and positively correlated with anti-inflammatory cytokine levels in the glioma microenvironment.

Conclusion: Our study provides insights into the effects of prognosis-related Siglecs in glioma immunotherapy, suggesting that targeted prognosis-related Siglecs can modify the microenvironment of glioma and improve the sensitivity of patients with glioma to immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-021-03762-9DOI Listing
November 2021

Ubiquitin specific peptidase 33 promotes cell proliferation and reduces apoptosis through regulation of the SP1/PI3K/AKT pathway in retinoblastoma.

Cell Cycle 2021 Sep 1:1-11. Epub 2021 Sep 1.

Department of Ophthalmology, The Third People's Hospital of Changzhou, Changzhou City, Jiangsu Province, China.

Ubiquitin-specific protease 33 (USP33), a deubiquitinating enzyme (DUB), has been identified to serve as a tumor suppressor or an oncogene in different cancers. However, its role in retinoblastoma (RB) remains unknown. Here, we aimed to uncover USP33 expression profile and function in RB, and disclose the underlying mechanism. USP33 levels in RB tissues and cells were determined using RT-qPCR and western blotting assays. USP33 effects on cell growth, cycle, apoptosis and tumorigenesis were studied using MTT, Edu, cycle and western blotting and assays. The results showed that USP33 expression levels were elevated in RB tissues and cells as compared with normal retinal tissues and cells. Downregulation of USP33 in RB Y79 and WERI-RB1 cells leaded to significant increases in cell apoptosis, G1 phase arrest and tumorigenesis, and reductions in cell growth and G2 and S phase arrest, as well as inhibited the activation of the PI3K/AKT signaling. SP1 overexpression abolished the roles of USP33 downregulation in modulating the activation of PI3K/AKT signaling, cell growth, apoptosis, and cell cycle. This study uncovered that USP33 promoted the progression of RB through regulation of the SP1/PI3K/AKT pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15384101.2021.1970305DOI Listing
September 2021

Typical Radiological Features of a Rare Lateral Ventricular Liponeurocytoma.

Ann Neurol 2021 Nov 4;90(5):851-852. Epub 2021 Sep 4.

Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.26207DOI Listing
November 2021

Regional and remote connectivity patterns in focal extratemporal lobe epilepsy.

Ann Transl Med 2021 Jul;9(14):1128

Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.

Background: Focal epilepsy accounts for most epilepsy cases, and frontal lobe epilepsy (FLE) accounts for the largest proportion of cases of extratemporal epilepsy syndrome. The epileptogenic zone is usually not easy to locate, contributing to a lack of imaging studies. The objective of this study was to evaluate functional connectivity patterns to explore the underlying pathological mechanisms of this disorder.

Methods: Forty-three patients with focal extratemporal epilepsy [mean age ± standard deviation (SD): 29.51±8.04 years, 19 males] and the same number of healthy controls (mean age ± SD: 29.56±8.02 years, 19 males) were recruited to undergo functional magnetic resonance imaging. Mean regional homogeneity (ReHo) was measured, and regions showing significant alterations in ReHo in patients were identified to examine functional connectivity (FC). In particular, FC within the default mode network (DMN) in patients was analyzed.

Results: Patients with extratemporal lobe epilepsy showed significantly higher ReHo in the bilateral precentral gyrus, and lower ReHo in frontal-cerebellum regions than healthy controls [P<0.05, Gaussian random field (GRF)-corrected]. FC analysis based on regions of interest showed significantly higher connectivity in the frontoparietal-insula region and lowered FC in the frontal-cerebellum regions (P<0.05, GRF-corrected). Altered FC within DMN was also demonstrated (P<0.05, GRF-corrected).

Conclusions: Analyses of ReHo and FC based on regions of interest suggest epilepsy-related neural networks are located mainly in frontal regions in extratemporal lobe epilepsy. These findings reveal disruptions of interactions and connectivity of large-scale neural networks and frontotemporal-cerebellar regions, suggesting connectivity-based pathophysiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-21-1374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350670PMC
July 2021

Epilepsy care during the COVID-19 pandemic.

Epilepsia 2021 10 24;62(10):2322-2332. Epub 2021 Aug 24.

Division of Health Outcomes and Knowledge Translation Research, Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

The coronavirus disease 2019 (COVID-19) pandemic has affected the care of all patients around the world. The International League Against Epilepsy (ILAE) COVID-19 and Telemedicine Task Forces examined, through surveys to people with epilepsy (PWE), caregivers, and health care professionals, how the pandemic has affected the well-being, care, and services for PWE. The ILAE included a link on their website whereby PWE and/or their caregivers could fill out a survey (in 11 languages) about the impact of the COVID-19 pandemic, including access to health services and impact on mental health, including the 6-item Kessler Psychological Distress Scale. An anonymous link was also provided whereby health care providers could report cases of new-onset seizures or an exacerbation of seizures in the context of COVID-19. Finally, a separate questionnaire aimed at exploring the utilization of telehealth by health care professionals since the pandemic began was available on the ILAE website and also disseminated to its members. Seventeen case reports were received; data were limited and therefore no firm conclusions could be drawn. Of 590 respondents to the well-being survey (422 PWE, 166 caregivers), 22.8% PWE and 27.5% caregivers reported an increase in seizure frequency, with difficulty in accessing medication and health care professionals reported as barriers to care. Of all respondents, 57.1% PWE and 21.5% caregivers had severe psychological distress (k score >13), which was significantly higher among PWE than caregivers (p<0.01). An increase in telemedicine use during the COVID-19 pandemic was reported by health care professionals, with 40% of consultations conducted by this method. Although 74.9% of health care providers thought that this impacted positively, barriers to care were also identified. As we move forward, there is a need to ensure ongoing support and care for PWE to prevent a parallel pandemic of unmet health care needs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.17045DOI Listing
October 2021

Dysregulated long noncoding RNAs in the brainstem of the DBA/1 mouse model of SUDEP.

BMC Genomics 2021 Aug 17;22(1):621. Epub 2021 Aug 17.

Department of Neurology, West China Hospital, Sichuan University, Wai Nan Guo Xue Lane 37 #, 610041, Chengdu, Sichuan, China.

Background: Long noncoding RNAs (lncRNAs) play an important role in many neurological diseases. This study aimed to investigate differentially expressed lncRNAs and messenger RNAs (mRNAs) in the susceptibility gaining process of primed DBA/1 mice, a sudden unexpected death in epilepsy (SUDEP) model, to illustrate the potential role of lncRNAs in SUDEP.

Methods: The Arraystar mouse lncRNA Microarray V3.0 (Arraystar, Rockville, MD) was applied to identify the aberrantly expressed lncRNAs and mRNAs between primed DBA/1 mice and normal controls. The differences were verified by qRT-PCR. We conducted gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and coexpression analyses to explore the possible function of the dysregulated RNAs.

Results: A total of 502 lncRNAs (126 upregulated and 376 downregulated lncRNAs) and 263 mRNAs (141 upregulated and 122 downregulated mRNAs) were dysregulated with P < 0.05 and a fold change over 1.5, among which Adora3 and Gstt4 were possibly related to SUDEP. GO analysis revealed that chaperone cofactor-dependent protein refolding and misfolded protein binding were among the top ten downregulated terms, which pointed to Hspa1a, Hspa2a and their related lncRNAs. KEGG analysis identified 28 upregulated and 10 downregulated pathways. Coexpression analysis showed fifteen dysregulated long intergenic noncoding RNAs (lincRNAs) and three aberrantly expressed antisense lncRNAs, of which AK012034 and NR_040757 are potentially related to SUDEP by regulating LMNB2 and ITPR1, respectively.

Conclusions: LncRNAs and their coexpression mRNAs are dysregulated in the priming process of DBA/1 in the brainstem. Some of these mRNAs and lncRNAs may be related to SUDEP, including Adora3, Lmnb2, Hspa1a, Hspa1b, Itrp1, Gstt4 and their related lncRNAs. Further study on the mechanism of lncRNAs in SUDEP is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-021-07921-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369804PMC
August 2021

The reinforcement of sludge-recycling enhanced flocculation by the acid activation of settled sludge.

Environ Technol 2021 Sep 9:1-9. Epub 2021 Sep 9.

School of Environment and Energy Engineering, Anhui Jianzhu University, Hefei, People's Republic of China.

Sludge-recycling enhanced flocculation (SEF) is an effective method for enhancing flocculation. In the conventional SEF process, the settled sludge is recirculated into the flocculation process without any further treatment. However, studies have shown that the efficacy of the SEF process could be improved by pre-treating the sludge. In this work, the acid activation of sludge was performed using a range of pH values (1.0-6.0) and charge states, with and without long-chain bridging. The resulting residual turbidities, floc fractal dimensions and floc morphologies were then analyzed, to examine the effects of sludge activation on the efficacy of SEF. In the absence of long-chain bridging, it was found that flocculation was enhanced by pH values between 2.0 and 5.0 in the electrostatic patch (EP) and near charge neutrality (NCN) states. In the EP state, the optimal pH for SEF enhancement was pH = 2.0; in the NCN state, the optimal pH was pH = 3.0. In terms of floc morphology, pH values between 2.0 and 5.0 resulted in larger average floc sizes and lower floc fractal dimensions than conventional SEF. However, in the presence of long-chain bridging, sludge activation did not enhance flocculation; residual turbidity increased with decreases in pH, in both the EP and NCN states. Based on these results, it may be surmised that the acid activation of sludge is suitable for cases without long-chain bridging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09593330.2021.1968956DOI Listing
September 2021

Association of Preoperative Coagulability With Incidence and Extent of Portal Vein Tumor Thrombus and Survival Outcomes in Hepatocellular Carcinoma After Hepatectomy: A Large-Scale, Multicenter Study.

Front Oncol 2021 28;11:697073. Epub 2021 Jul 28.

Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Background: Occurrence of portal vein tumor thrombus (PVTT) worsens the outcomes of hepatocellular carcinoma (HCC) and imparts high economic burden on society. Patients with high risks of having hypercoagulation are more likely to experience thrombosis. Herein, we examined how preoperative international normalized ratio (INR) was related to the incidence and extent of PVTT, and associated with survival outcomes in HCC patients following R0 liver resection (LR).

Methods: Patients with HCC and PVTT were enrolled from six major hospitals in China. The overall survival (OS) and recurrence-free survival (RFS) rates of individuals with different INR levels were assessed with Cox regression analysis as well as Kaplan-Meier method.

Results: This study included 2207 HCC patients, among whom 1005 patients had concurrent PVTT. HCC patients in the Low INR group had a significantly higher incidence of PVTT and more extensive PVTT than the Normal and High INR groups (P<0.005). Of the 592 HCC subjects who had types I/II PVTT following R0 LR, there were 106 (17.9%), 342 (57.8%) and 144 (24.3%) patients in the High, Normal and Low INR groups, respectively. RFS and OS rates were markedly worse in patients in the Low INR group relative to those in the Normal and High INR groups (median RFS, 4.87 versus 10.77 versus 11.40 months, P<0.001; median OS, 6.30 versus 11.83 versus 12.67 months, P<0.001).

Conclusion: Preoperative INR influenced the incidence and extent of PVTT in HCC. Particularly, patients with HCC and PVTT in the Low INR group had worse postoperative prognosis relative to the High and Normal INR groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.697073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356674PMC
July 2021
-->