Publications by authors named "Qi Yan"

723 Publications

Efficacy of Selective Vidian Neurectomy for Allergic Rhinitis Combined with Chronic Rhinosinusitis.

ORL J Otorhinolaryngol Relat Spec 2021 May 5:1-8. Epub 2021 May 5.

Department of Otorhinolaryngology Head and Neck Surgery, XuanWu Hospital, Capital Medical University, Beijing, China.

Objective: The aim of this study was to investigate the efficacy of endoscopic selective vidian neurectomy in the treatment of severe persistent allergic rhinitis (AR) combined with chronic rhinosinusitis (CRS) with nasal polyps (ARwCRSwNP).

Methods: One hundred thirty patients with moderate to severe persistent ARwCRSwNP were enrolled at Xuanwu Hospital, Capital Medical University, from September 2015 to September 2017. Patients were divided into 2 groups. Sixty-one patients (the control group) underwent conventional surgical treatment for CRS with nasal polyps and received conservative treatment for AR. Sixty-nine patients (the experimental group) received conventional surgical treatment for CRS with nasal polyps plus endoscopic selective vidian neurectomy with amputation of the posterior nasal nerve and pharyngeal branch of the vidian nerve. Clinical parameters, including visual analog scale (VAS) score, Lund-Kennedy endoscopic mucosal morphology score, and Lund-Mackay sinus computed tomography (CT) scan lesion range score, were used to analyze and evaluate the preoperative and postoperative data. Comparisons were based on patient scores, and preoperative and postoperative scores obtained at 6, 12, and 24 months were analyzed.

Results: The experimental group had higher therapeutic efficacy in nasal obstruction, nasal itching, rhinorrhea, sneezing, and general symptoms than the control group (p < 0.05). No complications such as tear-secretion disorder or atrophic rhinitis occurred in the experimental group, and no significant difference in complications incidence was observed between the 2 groups (p > 0.05).

Conclusion: Endoscopic selective vidian neurectomy is an effective and safe technique for the management of moderate to severe persistent ARwCRSwNP.
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http://dx.doi.org/10.1159/000512083DOI Listing
May 2021

Case Report: Repeated Low-Dose Rituximab Treatment Is Effective in Relapsing Neuro Behçet's Disease.

Front Neurol 2021 15;12:595984. Epub 2021 Apr 15.

Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Neuro Behçet's disease (NBD) is a rare but most aggressive manifestation of Behçet's disease (BD) with a poor prognosis, and some patients even present a relapsing and treatment-resistant progressive course. In some relapsing NBD cases, traditional corticosteroids and immunosuppressive drugs show limited efficacy, while benefits of biological agents, such as anti-B-lymphocyte CD20 biological agent rituximab (RTX), gradually represent potential therapeutic advantages with clinical rapid remission and long-time maintenance. However, up to now, the optimal dosage of RTX in NBD is still elucidated. Here, we report two patients with relapsing NBD, despite continuous high dose steroids and sufficient azathioprine treatment, still presenting severe and relapsing meningoencephalitis or brainstem involvement. Repeated low-dose RTX (100 mg × 3/1 week apart, 100 mg repeated every 6 months) is then attempted with rapid recovery and sustained remission. The approach in our cases may expand therapeutic options and provide helpful references for relapsing NBD treatment.
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http://dx.doi.org/10.3389/fneur.2021.595984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081882PMC
April 2021

Survival and transcriptomic response of Salmonella enterica on fresh-cut fruits.

Int J Food Microbiol 2021 Apr 20;348:109201. Epub 2021 Apr 20.

Department of Food Science and Nutrition & Institute for Food Safety and Health, Illinois Institute of Technology, Bedford Park, IL, USA.

Salmonella enterica is frequently implicated in foodborne disease outbreaks associated with fresh-cut fruits. In the U.S., more than one third of fruit-related outbreaks have been linked to two S. enterica serotypes Newport and Typhimurium. Approximately 80% of fruit-related human salmonellosis cases were associated with tomatoes, cantaloupes and cucumbers. In this study, we investigated the population dynamics of S. Newport and S. Typhimurium on fresh-cut tomato, cantaloupe, cucumber and apple under short-term storage conditions. We further compared the transcriptomic profiles of a S. Newport strain on fresh-cut tomato and cantaloupe using high-throughput RNA-seq. We demonstrated that both S. enterica Newport and Typhimurium survived well on various fresh-cut fruit items under refrigeration storage conditions, independent of inoculation levels. However, S. enterica displayed variable survival behaviors on different types of fruits. For example, at 7 d storage, the population of S. enterica reduced less than 0.2 log (p > 0.05) on fresh-cut tomato and cantaloupe, in contrast to ~0.5 log (p < 0.05) on cucumber and apple. RNA-seq analysis suggested that S. enterica mediates its survival on fresh-cut fruits through differentially regulating genes involved in specific carbon utilization and metabolic pathways. Several known bacterial virulence factors (e.g., pag gene) were found to be differentially regulated on fresh-cut tomato and cantaloupe, suggesting a link between the events of food contamination and subsequent human infection. Findings from this study contribute to a better understanding of S. enterica survival mechanisms on fresh-cut produce.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2021.109201DOI Listing
April 2021

Impact of Voluntary Folic Acid Fortification of Corn Masa Flour on RBC Folate Concentrations in the U.S. (NHANES 2011-2018).

Nutrients 2021 Apr 16;13(4). Epub 2021 Apr 16.

Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, Atlanta, GA 30341, USA.

Surveillance data have highlighted continued disparities in neural tube defects (NTDs) by race-ethnicity in the United States. Starting in 2016, the Food and Drug Administration (FDA) authorized voluntary folic acid fortification of corn masa flour to reduce the risk of neural tube defects (NTDs) among infants of Hispanic women of reproductive age. To assess the impact of voluntary corn masa fortification, cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 for Hispanic women of reproductive age with available red blood cell (RBC) folate concentrations were analyzed, with additional analyses conducted among Hispanic women whose sole source of folic acid intake was fortified foods (enriched cereal grain products (ECGP) only), excluding ready-to-eat cereals and supplements. RBC folate concentration (adjusted geometric mean) among Hispanic women of reproductive age did not differ between 2011-2016 and 2017-2018, though RBC folate concentration increased significantly among lesser acculturated Hispanic women consuming ECGP only. Concentrations of RBC folate for those born outside the U.S and residing in the U.S <15 years increased from 894 nmol/L (95% CI: 844-946) in 2011-2016 to 1018 nmol/L (95% CI: 982-1162; < 0.001) in 2017-2018. Primarily Spanish-speaking Hispanic women of reproductive age who only consumed ECGP saw an increase from 941 nmol/L (95% CI: 895-990) in 2011-2016 to 1034 nmol/L (95% CI: 966-1107; = 0.03) in 2017-2018. By subpopulation, we observed no significant changes in the proportion at risk of NTDs (<748 nmol/L) and no changes in the model-based estimated NTD rates following voluntary corn masa fortification. This analysis suggests that there is a remaining risk among Hispanics for folate sensitive NTDs, though continued monitoring of folate status in future NHANES data cycles will help inform the long-term efficacy of voluntary fortification of corn masa flour.
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http://dx.doi.org/10.3390/nu13041325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073626PMC
April 2021

Genome-Wide Analysis and Expression Profiles of the Dof Family in under Temperature, Salt and ABA Treatment.

Plants (Basel) 2021 Apr 23;10(5). Epub 2021 Apr 23.

The State Key Laboratory of Grassland Agro-Ecosystems, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China.

The DNA-binding with one zinc finger () family of plant-specific transcription factors has a variety of important functions in gene transcriptional regulation, development, and stress responses. However, the structure and expression patterns of family have not been identified in , which is an important xerophytic and perennial gramineous grass in desert grassland. In this study, 50 genes were identified in and could be classified into four groups. According to genome-wide analysis, 46 of 50 genes were located on 20 chromosomes, and the gene structure and conserved protein motif of these proteins were analyzed. In addition, phylogenetic analysis of genes in , , , and estimated the evolutionary relationships, and these genes were grouped into seven clusters. Moreover, the expression profiles of these genes in were analyzed in response to high/low temperature, salinity, and ABA treatments. These results will provide valuable information for future studies on gene classification, cloning, and functional characterization of this family in .
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http://dx.doi.org/10.3390/plants10050850DOI Listing
April 2021

High-Resolution Metabolomic Assessment of Pesticide Exposure in Central Valley, California.

Chem Res Toxicol 2021 Apr 29. Epub 2021 Apr 29.

Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California 90095, United States.

Pesticides are widely used in the agricultural Central Valley region of California. Historically, this has included organophosphates (OPs), organochlorines (OCs), and pyrethroids (PYRs). This study aimed to identify perturbations of the serum metabolome in response to each class of pesticide and mutual associations between groups of metabolites and multiple pesticides. We conducted high-resolution metabolomic profiling of serum samples from 176 older adults living in the California Central Valley using liquid chromatography with high-resolution mass spectrometry. We estimated chronic pesticide exposure (from 1974 to year of blood draw) to OPs, OCs, and PYRs from ambient sources at homes and workplaces with a geographic information system (GIS)-based model. Based on partial least-squares regression and pathway enrichment analysis, we identified metabolites and metabolic pathways associated with one or multiple pesticide classes, including mitochondrial energy metabolism, fatty acid and lipid metabolism, and amino acid metabolism. Utilizing an integrative network approach, we found that the fatty acid β-oxidation pathway is a common pathway shared across all three pesticide classes. The disruptions of the serum metabolome suggested that chronic pesticide exposure might result in oxidative stress, inflammatory reactions, and mitochondrial dysfunction, all of which have been previously implicated in a wide variety of diseases. Overall, our findings provided a comprehensive view of the molecular mechanisms of chronic pesticide toxicity, and, for the first time, our approach informs exposome research by moving from macrolevel population exposures to microlevel biologic responses.
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http://dx.doi.org/10.1021/acs.chemrestox.0c00523DOI Listing
April 2021

An intracellular nanobody targeting T4SS effector inhibits infection.

Proc Natl Acad Sci U S A 2021 May;118(18)

Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210;

Infection with obligatory intracellular bacteria is difficult to treat, as intracellular targets and delivery methods of therapeutics are not well known. translocated factor-1 (Etf-1), a type IV secretion system (T4SS) effector, is a primary virulence factor for an obligatory intracellular bacterium, In this study, we developed Etf-1-specific nanobodies (Nbs) by immunizing a llama to determine if intracellular Nbs block Etf-1 functions and infection. Of 24 distinct anti-Etf-1 Nbs, NbD7 blocked mitochondrial localization of Etf-1-GFP in cotransfected cells. NbD7 and control Nb (NbD3) bound to different regions of Etf-1. Size-exclusion chromatography showed that the NbD7 and Etf-1 complex was more stable than the NbD3 and Etf-1 complex. Intracellular expression of NbD7 inhibited three activities of Etf-1 and : up-regulation of mitochondrial manganese superoxide dismutase, reduction of intracellular reactive oxygen species, and inhibition of cellular apoptosis. Consequently, intracellular NbD7 inhibited infection, whereas NbD3 did not. To safely and effectively deliver Nbs into the host cell cytoplasm, NbD7 was conjugated to cyclized cell-permeable peptide 12 (CPP12-NbD7). CPP12-NbD7 effectively entered mammalian cells and abrogated the blockade of cellular apoptosis caused by and inhibited infection by in cell culture and in a severe combined-immunodeficiency mouse model. Our results demonstrate the development of an Nb that interferes with T4SS effector functions and intracellular pathogen infection, along with an intracellular delivery method for this Nb. This strategy should overcome current barriers to advance mechanistic research and develop therapies complementary or alternative to the current broad-spectrum antibiotic.
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http://dx.doi.org/10.1073/pnas.2024102118DOI Listing
May 2021

Ang II Promotes SUMO2/3 Modification of RhoGDI1 Through Aos1 and Uba2 Subunits, and then Regulates RhoGDI1 Stability and Cell Proliferation.

Cardiovasc Drugs Ther 2021 Apr 23. Epub 2021 Apr 23.

Department of Pharmacology, School of pharmacy, Nantong University, 19 QiXiu Road, Nantong, 226001, Jiangsu, China.

Purpose: Ang II regulates RhoGDI1 stability and cell proliferation via SUMOylation. However, how Ang II regulates RhoGDI1 SUMOylation remains unknown. In this study, we focused on revealing the effects of E1 subunits (Aos1 and Uba2) on RhoGDI1 SUMOylation in HA-VSMC proliferation.

Methods: The expressions of Aos1, Uba2, and SUMO1 were suppressed by siRNA transfection. HA-VSMCs were treated with Ang II (100 nM) for 24 h. RhoGDI1 SUMOylation and ubiquitination were checked by co-immunoprecipitation. Cell proliferation was detected by EdU assay.

Results: Uba2 or Aos1 suppression significantly inhibited Ang II-induced SUMO2/3 modification of RhoGDI1 and cell proliferation, while not affecting SUMO1 modification of RhoGDI1. In addition, Uba2 or Aos1 suppression promoted RhoGDI1 ubiquitination and degradation. These indicate that both Uba2 and Aos1 are necessary for SUMO2/3 modification of RhoGDI1 that participates in cell proliferation by regulating RhoGDI1 ubiquitination and stability. Moreover, SUMO1 suppression did not affect RhoGDI1 ubiquitination and degradation and cell proliferation in Ang II-induced VSMCs, suggesting that SUMO1 modification does not participate in RhoGDI1 stability and cell proliferation.

Conclusion: This study reveals the differences between SUMO2/3 and SUMO1 modification in regulating RhoGDI1 stability and Ang II-mediated cell proliferation. Schematic summary of roles of SUMO1 and SUMO2/3 modification of RhoGDI1 in regulating RhoGDI1 stability and cell proliferation in Ang II-treated HA-VSMCs.
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http://dx.doi.org/10.1007/s10557-021-07173-3DOI Listing
April 2021

Differential Diagnosis Strategy between Lower Extremity Arterial Occlusive Disease and Lumbar Disc Herniation.

Biomed Res Int 2021 5;2021:6653579. Epub 2021 Apr 5.

Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

Considering the increasingly incidence rate of lower extremity arterial occlusive disease and difficult to distinguish from lumbar disc herniation, it is very necessary to exclude lower extremity arterial occlusive disease resulting in lower limb symptoms from lumbar disc herniation. More importantly, who have a higher risk of combining with lower extremity arterial occlusive disease and misdiagnosed as lumbar disc herniation? Why those patients are easy to be misdiagnosed as lumbar disc herniation? It is worth analyzing and discussing. The risk factors including age, gender, the medical history of high blood pressure, diabetes, smoking and coronary, pulse pressure, lumbar disc herniation segment and type, ankle-brachial index, and straight leg raising test were observed. The Oswestry disability index and the Japanese Orthopedic Association score were collected preoperative, six months after posterior lumbar interbody fusion and six months after vascular interventional treatment to evaluate the symptoms relief and surgical efficacy. There was a statistically significant difference ( < 0.01) in pulse pressure, ankle-brachial index, central disc herniation, and straight leg raising test between two groups. There was a high risk to missed diagnosis of lower extremity arterial occlusive disease and misdiagnosed as lumbar disc herniation when patients are with a mild central lumbar disc herniation, higher pulse pressure, lower ankle-brachial index, and straight leg raising test negative. Therefore, sufficient history-taking and cautious physical examinations contributed to find risk factors and attach importance to such patients and, further, to exclude lower extremity arterial occlusive disease from lumbar disc herniation using lower extremity vascular ultrasound examination.
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http://dx.doi.org/10.1155/2021/6653579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041544PMC
April 2021

Targeted gene panel sequencing for molecular diagnosis of congenital adrenal hyperplasia.

J Steroid Biochem Mol Biol 2021 Apr 14:105899. Epub 2021 Apr 14.

Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai, 200025, PR China. Electronic address:

Context: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive genetic diseases caused by genetic deficiency in nine genes encoding steroidogenesis enzymes and cofactors.

Objective: To establish a targeted next-generation sequencing (NGS) assay for all nine CAH candidate genes.

Methods: We developed a customized targeted NGS assay of CAH candidate genes (CYP21A2, CYP17A1, CYP11B1, StAR, CYP11A1, POR, HSD3B2, H6PD, CYP11B2) and apply this assay plus MLPA of CYP21A2 in a total of 469 patients with CAH like signs and symptoms.

Results: We totally identified 125 variants with seven variant types in eight genes. Variant types included missense variant (46.8%), splicing variant (21.5%), small indel (12.5%), large structure variation (11.8%), nonsense variant (4.1%), UTR variant (2.9%), synonymous variant (0.3%). Successful genotyping, defined as biallelic pathogenic or likely pathogenic variants, was achieved in 98.5% (336/341) of cases, including biallelic variants in CYP21A2 (n = 254), CYP17A1 (n = 45), CYP11B1 (n = 23), StAR (n = 7), HSD3B2 (n = 4), POR (n = 1), CYP11A1 (n = 1) and CYP11B2 (n = 1) gene. Importantly, the assay found one patient with CYP11B1 deficiency, one patient with non-classic POR deficiency and two patients with non-classic CYP17A1 deficiency while clinically diagnosed differently.

Conclusions: Our NGS-based assay plus MLPA of CYP21A2 is a useful tool to genotype all subtypes of CAH. The test successfully achieved genotype in 98.5% of patients with clinically determined CAH. It also efficiently facilitated the diagnosis of CAH in patients with rare subtypes as well as non-classic phenotypes.
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http://dx.doi.org/10.1016/j.jsbmb.2021.105899DOI Listing
April 2021

High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status.

Cell Rep 2021 Apr;35(2):108974

Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address:

Clinical definitions of asthma fail to capture the heterogeneity of immune dysfunction in severe, treatment-refractory disease. Applying mass cytometry and machine learning to bronchoalveolar lavage (BAL) cells, we find that corticosteroid-resistant asthma patients cluster largely into two groups: one enriched in interleukin (IL)-4 innate immune cells and another dominated by interferon (IFN)-γ T cells, including tissue-resident memory cells. In contrast, BAL cells of a healthier population are enriched in IL-10 macrophages. To better understand cellular mediators of severe asthma, we developed the Immune Cell Linkage through Exploratory Matrices (ICLite) algorithm to perform deconvolution of bulk RNA sequencing of mixed-cell populations. Signatures of mitosis and IL-7 signaling in CD206FcεRICD127IL-4 innate cells in one patient group, contrasting with adaptive immune response in T cells in the other, are preserved across technologies. Transcriptional signatures uncovered by ICLite identify T-cell-high and T-cell-poor severe asthma patients in an independent cohort, suggesting broad applicability of our findings.
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http://dx.doi.org/10.1016/j.celrep.2021.108974DOI Listing
April 2021

The role of SYT-SSX fusion gene in tumorigenesis of synovial sarcoma.

Pathol Res Pract 2021 Mar 24;222:153416. Epub 2021 Mar 24.

Department of Pathology, Shihezi University School of Medicine & the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China; Department of Pathology, Central People's Hospital of Zhanjiang and Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, China. Electronic address:

Synovial sarcoma (SS) is an aggressive malignancy of an unknown tissue origin that is characterized by biphasic differentiation. A possible basis of the pathogenesis of SS is pathognomonic t(X;18) (p11.2; q11.2) translocation, leading to the formation and expression of the SYT-SSX fusion gene. More than a quarter of the patients die of SS metastasis within 5 years after the diagnosis, but the pathogenic factors are unknown. Therefore, there is an urgent need to explore the pathogenesis, invasion, metastasis, and clinical treatment options for SS, especially molecular-targeted drug therapy. Recent studies have shown that the SYT-SSX fusion gene associated with SS may be regulated by different signaling pathways, microRNAs, and other molecules, which may produce stem cell characteristics or promote epithelial-mesenchymal transition, resulting in SS invasion and metastasis. This review article aims to show the relationship between the SYT-SSX fusion gene and the related pathway molecules as well as other molecules involved from different perspectives, which may provide a deeper and clearer understanding of the SYT-SSX fusion gene function. Therefore, this review may provide a more innovative and broader perspective of the current research, treatment options, and prognosis assessment of SS.
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http://dx.doi.org/10.1016/j.prp.2021.153416DOI Listing
March 2021

AMD Genetics: Methods and Analyses for Association, Progression, and Prediction.

Adv Exp Med Biol 2021 ;1256:191-200

Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.

Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disease, which is a leading cause of vision loss among the elderly in the developed countries. As one of the most successful examples of genome-wide association study (GWAS), a large number of genetic studies have been conducted to explore the genetic basis for AMD and its progression, of which over 30 loci were identified and confirmed. In this chapter, we review the recent development and findings of GWAS for AMD risk and progression. Then, we present emerging methods and models for predicting AMD development or its progression using large-scale genetic data. Finally, we discuss a set of novel statistical and analytical methods that were recently developed to tackle the challenges such as analyzing bilateral correlated eye-level outcomes that are subject to censoring with high-dimensional genetic data. Future directions for analytical studies of AMD genetics are also proposed.
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http://dx.doi.org/10.1007/978-3-030-66014-7_7DOI Listing
April 2021

Effect of anesthesia on electrocorticography for localization of epileptic focus: Literature review and future directions.

Epilepsy Behav 2021 Apr 1;118:107902. Epub 2021 Apr 1.

Comprehensive Epilepsy Center, Dept. of Neurology, School of Medicine, Yale University, Yale New Haven Hospital, New Haven, CT, United States; Human Brain Mapping Program, University of Pittsburgh Medical Center, Pittsburgh, PA, United States.

Intraoperative electrocorticography (ECoG) is a useful technique to guide resections in epilepsy surgery and is mostly performed under general anesthesia. In this systematic literature review, we seek to investigate the effect of anesthetic agents on the quality and reliability of ECoG for localization of the epileptic focus. We conducted a systematic search using PubMed and EMBASE until January 2019, aiming to review the effects of anesthesia on ECoG yield. Fifty-eight studies were included from 1016 reviewed. There are favorable reports for dexmedetomidine and remifentanil during ECoG recording. There is inadequate, or sometimes conflicting, evidence to support using enflurane, isoflurane, sevoflurane, and propofol. There is evidence to avoid halothane, nitrous oxide, etomidate, ketamine, thiopental, methohexital, midazolam, fentanyl, and alfentanil due to undesired effects. Depth of anesthesia, intraoperative awareness, and surgical outcomes were not consistently evaluated. Available studies provide helpful information about the effect of anesthesia on ECoG to localize the epileptic focus. The proper use of anesthetic agents and careful dose titration, and effective communication between the neurophysiologist and anesthesiologist based on ECoG activity are essential in optimizing recordings. Anesthesia is a crucial variate to consider in the design of studies investigating ECoG and related biomarkers.
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http://dx.doi.org/10.1016/j.yebeh.2021.107902DOI Listing
April 2021

RNF2 Mediates Hepatic Stellate Cells Activation by Regulating ERK/p38 Signaling Pathway in LX-2 Cells.

Front Cell Dev Biol 2021 18;9:634902. Epub 2021 Mar 18.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.

The therapeutic approach of liver fibrosis is still an unsolved clinical problem worldwide. Notably, the accumulation of extracellular matrix (ECM) in the liver is mediated by the production of cytokines and growth factors, such as transforming growth factor-β1 (TGF-β1) in hepatic stellate cells (HSCs). Ring finger protein 2 (RNF2) was identified as the catalytic subunit of polycomb repressive complex 1 (PRC1), mediating the monoubiquitination of histone H2A. In recent years, a growing amount of evidence suggests that RNF2 may play an important role in multiple pathological processes involved in cancer. Here, we explored the role of RNF2 in liver fibrogenesis and its potential mechanisms. The results showed that RNF2 was up-regulated in human fibrotic liver tissue. Knockdown of RNF2 led to a decreasing expression of collagen1 and α-smooth muscle actin (α-SMA) in LX-2 cells, which was upregulated by RNF2 overexpression. Moreover, RNF2 overexpression significantly promoted TGF-β1-induced LX-2 cell proliferation but decreased apoptosis. Furthermore, knockdown of RNF2 inhibited the activation of ERK/p38 signaling pathways induced by TGF-β1. These data suggested that RNF2 is an effective pro-fibrogenic factor for HSC activation via ERK/p38 signaling pathway. RNF2 inhibition might be a promising therapeutic target for liver fibrosis.
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http://dx.doi.org/10.3389/fcell.2021.634902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015948PMC
March 2021

Split-thickness skin graft donor-site morbidity: A systematic literature review.

Burns 2021 Feb 25. Epub 2021 Feb 25.

Shriners Hospital for Children-Boston, 51 Blossom Street, Suite 930, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02114, USA; Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.

The purpose of this systematic literature review is to critically evaluate split-thickness skin graft (STSG) donor-site morbidities. The search of peer-reviewed articles in three databases from January 2009 to July 2019 identified 4271 English-language publications reporting STSG donor-site clinical outcomes, complications, or quality of life. Of these studies, 77 met inclusion criteria for analysis. Mean time to donor-site epithelialization ranged from 4.7 to 35.0 days. Mean pain scores (0-10 scale) ranged from 1.24 to 6.38 on postoperative Day 3. Mean scar scores (0-13 scale) ranged from 0 to 10.9 at Year 1. One study reported 28% of patients had donor-site scar hypertrophy at 8 years. Infection rates were generally low but ranged from 0 to 56%. Less frequently reported outcomes included pruritus, wound exudation, and esthetic dissatisfaction. Donor-site wounds underwent days of wound care and were frequently associated with pain and scarring. Widespread variations were noted in STSG donor-site outcomes likely due to inconsistencies in the definition of outcomes and utilization of various assessment tools. Understanding the true burden of donor sites may drive innovative treatments that would reduce the use of STSGs and address the associated morbidities.
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http://dx.doi.org/10.1016/j.burns.2021.02.014DOI Listing
February 2021

State-Temporal Compression in Reinforcement Learning with the Reward-Restricted Geodesic Metric.

IEEE Trans Pattern Anal Mach Intell 2021 Mar 25;PP. Epub 2021 Mar 25.

It is difficult to solve complex tasks that involve large state spaces and long-term decision processes by reinforcement learning (RL) algorithms. A common and promising method to address this challenge is to compress a large RL problem into a small one. Towards this goal, the compression should be state-temporal and optimality-preserving (i.e., the optimal policy of the compressed problem should correspond to that of the uncompressed problem). In this paper, we propose a reward-restricted geodesic (RRG) metric, which can be learned by a neural network, to perform state-temporal compression in RL. We prove that compression based on the RRG metric is approximately optimality-preserving for the raw RL problem endowed with temporally abstract actions. With this compression, we design an RRG metric-based reinforcement learning (RRG-RL) algorithm to solve complex tasks. Experiments in both discrete (2D Minecraft) and continuous (Doom) environments demonstrated the superiority of our method over existing RL approaches.
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http://dx.doi.org/10.1109/TPAMI.2021.3069005DOI Listing
March 2021

Synergistic Inhibition of Drug-Resistant Colon Cancer Growth with PI3K/mTOR Dual Inhibitor BEZ235 and Nano-Emulsioned Paclitaxel via Reducing Multidrug Resistance and Promoting Apoptosis.

Int J Nanomedicine 2021 15;16:2173-2186. Epub 2021 Mar 15.

Department of Pathology, The First Affiliated Hospital, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases of the Ministry of Education of China, Xinjiang, 832002, People's Republic of China.

Background: Colon cancer is a top lethal cancer in man and women worldwide and drug resistance is the major cause of cancer-related death. Combinational therapy and drug delivery with nanoparticles have been shown to effectively overcome drug resistance in many cancers. We previously reported that nanoemulsion (NE) loaded paclitaxel (PTX) and BEZ235 could synergistically inhibit colon cancer cell growth.

Purpose: To investigate whether NE loaded PTX and BEZ235 can overcome drug resistance and synergistically inhibit drug-resistant colon cancer cell growth in vitro and in vivo.

Methods: The in vitro treatment effect on cell viability was assayed using CCK8 kit, cell morphological change was detected by β-tubulin immunofluorescence staining, drug resistance-related proteins were analyzed by Western blotting, and in vivo tumor growth test was performed in nude mice xeno-transplanted with 2 drug-resistant colon cancer cell lines HCT116-LOHP and HT29-DDP.

Results: Both cell lines were sensitive to PTX but relatively insensitive to BEZ235. PTX combined with BEZ235 synergistically inhibited the proliferation of both cell lines. Nanoemulsion loaded PTX (NE-PTX) reduced the IC50 of PTX to approximately 2/5 of free PTX, indicating a high inhibitory efficacy of NE-PTX. When NE-PTX combined with a low concentration of BEZ235 (50 nM), the IC50 was decreased to approximately 2/3 of free PTX. Moreover, NE-PTX+BEZ235 treatment increased apoptosis, decreased Pgp and ABCC1 expression, and reduced tumor weights compared to the single drug treatment and the control group. These results suggest that nanoemulsion loaded PTX+BEZ235 can overcome drug resistance and improve the inhibitory effect on cancer cell proliferation and tumor growth.

Conclusion: Our study thus provides a possible new approach to treat colon cancer patients with drug resistance.
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http://dx.doi.org/10.2147/IJN.S290731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979685PMC
April 2021

A region-based method for causal mediation analysis of DNA methylation data.

Epigenetics 2021 03 23:1-11. Epub 2021 Mar 23.

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Exposure to environmental factors can affect DNA methylation at a 5'-cytosine-phosphate-guanine-3' (CpG) site or a genomic region, which can then affect an outcome. In other words, environmental effects on an outcome could be mediated by DNA methylation. To date, single CpG-site-based mediation analysis has been employed extensively. More recently, however, there has been considerable interest in studying differentially methylated regions (DMRs), both because DMRs are more likely to have functional effects than single CpG sites and because testing DMRs reduces multiple testing. In this report, we propose a novel causal mediation approach under the counterfactual framework to test the significance of total (TE), direct (DE), and indirect effects (IE) of predictors on response variable with a methylated region (MR) as the mediator (denoted as MR-Mediation). Functional linear transformation is used to reduce the possible high dimension of the CpG sites in a predefined MR and to account for their location information. In our simulation studies, MR-Mediation retained the desired Type I error rates for TE, DE, and IE tests. Furthermore, MR-Mediation had better power performance than testing mean methylation level as the mediator in most considered scenarios, especially for IE (i.e., mediated effect) test, which could be more interesting than the other two effect tests. We further illustrate our proposed method by analysing the methylation mediated effect of exposure to gun violence on total immunoglobulin E or atopic asthma among participants in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study.
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http://dx.doi.org/10.1080/15592294.2021.1900026DOI Listing
March 2021

Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children.

Pediatr Pulmonol 2021 Mar 22. Epub 2021 Mar 22.

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: Exposure to violence (ETV) or chronic stress may influence asthma through unclear mechanisms.

Methods: Epigenome-wide association study (EWAS) of ETV or chronic stress measures and DNA methylation in nasal epithelium from 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed four measures of ETV and chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by p value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA).

Results: Three CpGs (in SNN, PTPRN2, and LINC01164) were associated with maternal perceived stress or gun violence (p = 1.28-3.36 × 10 ), but not with atopic asthma, in EVA-PR. In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence measures in EVA-PR, 12 CpGs (in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4, and ANAPC13) were associated with atopic asthma at FDR-p < .05.

Conclusions: Pending confirmation in longitudinal studies, our findings suggest that nasal epithelial methylation markers associated with measures of ETV and chronic stress may be linked to atopic asthma in children and adolescents.
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http://dx.doi.org/10.1002/ppul.25372DOI Listing
March 2021

Decreased chromobox homologue 7 expression is associated with epithelial-mesenchymal transition and poor prognosis in cervical cancer.

Open Med (Wars) 2021 9;16(1):410-418. Epub 2021 Mar 9.

College of Public Health, Xinjiang Medical University, No. 393, Xinyi Road, Urumqi 830054, Xinjiang, China.

The aim of this study was to evaluate the association of the chromobox homologue 7 (CBX7) expression with the epithelial-mesenchymal transition in cervical cancer (CC), as well as with the disease prognosis. CBX7, E-cadherin (E-cad), and vimentin (VIM) expression levels were detected with immunohistochemistry. The relationship between the expression of CBX7, E-cad, and VIM expression and conventional clinicopathological characteristics of CC were evaluated. The positive expression rates of CBX7 and E-cad in the CC tissues were lower than the adjacent non-tumorous cervical tissues. Moreover, the VIM expression level was higher. The CBX7 expression was positively correlated with the E-cad expression, whereas was negatively correlated with the VIM expression. Furthermore, CBX7 was associated with the disease clinical staging, histological differentiation, lymph node metastasis, and vascular invasion. Patients with negative CBX7 expression showed decreased overall survival rates compared with those with low or high CBX7 expression. Multivariate Cox regression analysis indicated that the decreased CBX7 expression was an independent predictor for the poor prognosis of CC. In conclusion, the absence of CBX7 is associated with the histologic differentiation, lymphatic metastasis, vascular invasion, and poor prognosis of CC. CBX7 may be an independent prognostic factor for the prognosis of CC patients.
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http://dx.doi.org/10.1515/med-2021-0015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957191PMC
March 2021

Weight gain after diagnosis of gestational diabetes mellitus and its association with adverse pregnancy outcomes: a cohort study.

BMC Pregnancy Childbirth 2021 Mar 17;21(1):216. Epub 2021 Mar 17.

Department of Obstetrics, Division of Endocrinology and Metabolism, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No 251, Yaojiayuan Road, Chaoyang District, Beijing, 100026, China.

Background: Gestational diabetes mellitus (GDM) and excessive body weight are two key risk factors for adverse perinatal outcomes. However, it is not clear whether restricted gestational weight gain (GWG) is favorable to reduce the risk for adverse pregnancy and neonatal outcomes in women with GDM. Therefore, this study aimed to assess the association of GWG after an oral glucose tolerance test with maternal and neonatal outcomes.

Methods: This prospective cohort study assessed the association of GWG after an oral glucose tolerance test (OGTT) with pregnancy and neonatal outcomes in 3126 women with GDM, adjusted for age, pre-pregnancy body mass index, height, gravidity, parity, adverse history of pregnancy, GWG before OGTT, blood glucose level at OGTT and late pregnancy. The outcomes included the prevalence of pregnancy-induced hypertension (PIH) and preeclampsia, large for gestational age (LGA), small for gestational age, macrosomia, low birth weight, preterm birth, and birth by cesarean section. GDM was diagnosed according to the criteria established by the International Association of Diabetes and Pregnancy Study Groups.

Results: GWG after OGTT was positively associated with risk for overall adverse pregnancy outcomes (adjusted odds ratio [aOR] = 1.72, 95% confidence interval [CI] = 1.50-1.97), LGA (aOR = 1.29, 95%CI = 1.13-1.47), macrosomia (aOR = 1.24, 95%CI = 1.06-1.46) and birth by cesarean section (aOR = 1.91, 95%CI = 1.67-2.19) in women with GDM. Further analyses revealed that a combination of excessive GWG before OGTT and after OGTT increased the risk of PIH and preeclampsia, LGA, macrosomia, and birth by cesarean section compared with adequate GWG throughout pregnancy. In contrast, GWG below the Institute of Medicine guideline after OGTT did not increase the risk of adverse perinatal outcomes despite GWG before OGTT.

Conclusion: Excessive GWG after OGTT was associated with an elevated risk of adverse pregnancy outcomes, while insufficient GWG after OGTT did not increase the risk of LBW. Restricting GWG after diagnosis of GDM in women with excessive GWG in the first half of pregnancy may be beneficial to prevent PIH and preeclampsia, LGA, macrosomia, and birth by cesarean section.
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http://dx.doi.org/10.1186/s12884-021-03690-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971950PMC
March 2021

Metal-phenolic networks for cancer theranostics.

Biomater Sci 2021 Apr 10;9(8):2825-2849. Epub 2021 Mar 10.

Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, China.

Metal-phenolic networks (MPNs) have shown promising potential in biomedical applications since they provide a rapid, simple and robust way to construct multifunctional nanoplatforms. As a novel nanomaterial self-assembled from metal ions and polyphenols, MPNs can be prepared to assist the theranostics of cancer owing to their bio-adhesiveness, good biocompatibility, versatile drug loading, and stimuli-responsive profile. This Critical Review aims to summarize recent progress in MPN-based nanoplatforms for multimodal tumor therapy and imaging. First, the advantages of MPNs as drug carriers are summarized. Then, various tumor therapeutic modalities based on MPNs are introduced. Next, MPN-based theranostic systems are reviewed. In terms of in vivo applications, specific attention is paid to their biosafety, biodistribution, as well as excretion. Finally, some problems and limitations of MPNs are discussed, along with a future perspective on the field.
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http://dx.doi.org/10.1039/d0bm02064hDOI Listing
April 2021

Protecting China's finless porpoise.

Authors:
Qi Yan Yunhong Hu

Science 2021 Mar;371(6533):1003

School of Landscape Architecture, Nanjing Forestry University, Nanjing, China.

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http://dx.doi.org/10.1126/science.abg9955DOI Listing
March 2021

Exploring the relationship between electronic health records and provider burnout: A systematic review.

J Am Med Inform Assoc 2021 Apr;28(5):1009-1021

Center for Quality, Effectiveness and Outcomes in Cardiovascular Diseases, Division of Vascular and Endovascular Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

Objective: Stress and burnout due to electronic health record (EHR) technology has become a focus for burnout intervention. The aim of this study is to systematically review the relationship between EHR use and provider burnout.

Materials And Methods: A systematic literature search was performed on PubMed, EMBASE, PsychInfo, ACM Digital Library in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Inclusion criterion was original research investigating the association between EHR and provider burnout. Studies that did not measure the association objectively were excluded. Study quality was assessed using the Medical Education Research Study Quality Instrument. Qualitative synthesis was also performed.

Results: Twenty-six studies met inclusion criteria. The median sample size of providers was 810 (total 20 885; 44% male; mean age 53 [range, 34-56] years). Twenty-three (88%) studies were cross-sectional studies and 3 were single-arm cohort studies measuring pre- and postintervention burnout prevalence. Burnout was assessed objectively with various validated instruments. Insufficient time for documentation (odds ratio [OR], 1.40-5.83), high inbox or patient call message volumes (OR, 2.06-6.17), and negative perceptions of EHR by providers (OR, 2.17-2.44) were the 3 most cited EHR-related factors associated with higher rates of provider burnout that was assessed objectively.

Conclusions: The included studies were mostly observational studies; thus, we were not able to determine a causal relationship. Currently, there are few studies that objectively assessed the relationship between EHR use and provider burnout. The 3 most cited EHR factors associated with burnout were confirmed and should be the focus of efforts to improve EHR-related provider burnout.
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http://dx.doi.org/10.1093/jamia/ocab009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068439PMC
April 2021

Digital Footprint of Academic Vascular Surgeons in the Southern United States on Physician Rating Websites: Cross-sectional Evaluation Study.

JMIR Cardio 2021 Feb 24;5(1):e22975. Epub 2021 Feb 24.

Division of Vascular Surgery, Department of Surgery, UT Health San Antonio, San Antonio, TX, United States.

Background: The internet has become a popular platform for patients to obtain information and to review the health care providers they interact with. However, little is known about the digital footprint of vascular surgeons and their interactions with patients on social media.

Objective: This study aims to understand the activity of academic vascular surgeons on physician rating websites.

Methods: Information on attending vascular surgeons affiliated with vascular residency or with fellowships in the Southern Association for Vascular Surgery (SAVS) was collected from public sources. A listing of websites containing physician ratings was obtained via literature reviews and Google search. Open access websites with either qualitative or quantitative evaluations of vascular surgeons were included. Closed access websites were excluded. Ranking scores from each website were converted to a standard 5-point scale for comparison.

Results: A total of 6238 quantitative and 967 qualitative reviews were written for 287 physicians (236 males, 82.2%) across 16 websites that met the inclusion criteria out of the 62 websites screened. The surgeons affiliated with the integrated vascular residency and vascular fellowship programs in SAVS had a median of 8 (IQR 7-10) profiles across 16 websites, with only 1 surgeon having no web presence in any of the websites. The median number of quantitative ratings for each physician was 17 (IQR 6-34, range 1-137) and the median number of narrative reviews was 3 (IQR 2-6, range 1-28). Vitals, WebMD, and Healthgrades were the only 3 websites where over a quarter of the physicians were rated, and those rated had more than 5 ratings on average. The median score for the quantitative reviews was 4.4 (IQR 4.0-4.9). Most narrative reviews (758/967, 78.4%) were positive, but 20.2% (195/967) were considered negative; only 1.4% (14/967) were considered equivocal. No statistical difference was found in the number of quantitative reviews or in the overall average score in the physician ratings between physicians with social media profiles and those without social media profiles (departmental social media profile: median 23 vs 15, respectively, P=.22; personal social media profile: median 19 vs 14, respectively, P=.08).

Conclusions: The representation of vascular surgeons on physician rating websites is varied, with the majority of the vascular surgeons represented only in half of the physician rating websites The number of quantitative and qualitative reviews for academic vascular surgeons is low. No vascular surgeon responded to any of the reviews. The activity of vascular surgeons in this area of social media is low and reflects only a small digital footprint that patients can reach and review.
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http://dx.doi.org/10.2196/22975DOI Listing
February 2021

MiR-506 exerts antineoplastic effects on osteosarcoma cells via inhibition of the Skp2 oncoprotein.

Aging (Albany NY) 2021 02 17;13(5):6724-6739. Epub 2021 Feb 17.

Postdoctoral Research Center on Public Health and Preventive Medicine, Xinjiang Medical University, Xinjiang, China.

S-phase kinase-associated protein 2 (Skp2) performs oncogenic functions in cancers; however, how Skp2 is regulated post-transcriptionally is elusive in osteosarcoma. Therefore, we determined whether miR-506 could directly target Skp2 in osteosarcoma to perform its tumor suppressive functions. Here, we found that miR-506 mimics suppressed cell viability, induced apoptosis, and attenuated migration and invasion in osteosarcoma cells. Moreover, upregulation of Skp2 accelerated cell viability and motility and rescued the tumor suppressive effect of miR-506 in osteosarcoma cells. Moreover, downregulation of Skp2 inhibited cell viability and decreased cell motility, which enhanced the antitumor activity induced by miR-506 mimic transfection in osteosarcoma cells. Our western blotting results implied that miR-506 inhibited Skp2 expression and subsequently upregulated Foxo1 and p57 in OS cells. In summary, miR-506 performs an anticancer activity via directly targeting Skp2 in osteosarcoma cells, indicating that inactivation of Skp2 by miR-506 might be an alternative strategy for treating osteosarcoma.
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http://dx.doi.org/10.18632/aging.202530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993745PMC
February 2021

SR-B1 and CD10 combined immunoprofile for differential diagnosis of metastatic clear cell renal cell carcinoma and clear cell carcinoma of the ovary.

J Mol Histol 2021 Feb 19. Epub 2021 Feb 19.

Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Xinjiang, 832002, China.

Both clear cell renal carcinoma (ccRCC) and clear cell carcinoma of the ovary (CCOC) have a clear cytoplasmic morphological feature, hence it is difficult to identify metastatic ccRCC and CCOC by morphology alone. At present, there are no effective immunohistochemical markers to distinguish between these two tumors. Studies have shown that the clear cytoplasm of ccRCC is mainly caused by cholesterol-rich lipids in the cytoplasm, while that of CCOC is due to the accumulation of cytoplasmic glycogen.

Objective: to hypothesize that the scavenger receptor class B-type 1 (SR-B1) protein responsible for HDL cholesterol uptake may be differentially expressed in ccRCC and CCOC, and high CD10 expression in the renal tubular epithelium may assist in distinguishing between ccRCC and CCOC.

Methods: effective immunohistochemical markers were applied in 90 cases of renal clear cell carcinoma and 31 cases of ovarian cancer to distinguish between the two types of tumors.

Result: SR-B1 and CD10 expression is significantly higher in ccRCC than CCOC. Both SR-B1 and CD10 exhibited focal weak-medium intensity staining in CCOC, and their staining extent and intensity were significantly lower than ccRCC. The sensitivity and specificity of SR-B1 for identifying ccRCC were 74.4% and 83.9%, respectively. The sensitivity and specificity of CD10 for identifying CCOC were 93.3% and 80.6%, respectively. The combined SR-B1( +) CD10( +) immunoprofile supports the diagnosis of ccRCC with a specificity of 93.5%. The combined SR-B1(-) CD10(-) immunoprofile supports the diagnosis of CCOC with a specificity of 93.3%.

Conclusions: our findings demonstrate that the combination of SR-B1 and CD10 immunoprofiling is a valuable tool for differential diagnosis of ccRCC and CCOC.
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http://dx.doi.org/10.1007/s10735-021-09963-3DOI Listing
February 2021

Neoadjuvant therapy of cetuximab combined with chemoradiotherapy in rectal cancer: A single-arm meta-analysis of noncomparative clinical studies and randomized controlled trials.

Medicine (Baltimore) 2021 Feb;100(7):e24649

Department of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

Objective: Preoperative chemoradiotherapy combined with radical resection has reduced local recurrence rates in rectal cancer. Cetuximab shows improvement in rectal cancer treatment. But the role for neoadjuvant therapy of cetuximab combined with chenmoradiotherapy in rectal cancer remains unclear. The present study aimed to use meta-analytical techniques to assess its benefit and risk.

Materials And Methods: We searched PubMed, the Cochrane Library, Embase to identify the correlational non-comparative clinical studies and randomized controlled trials (RCTs). The primary endpoints of interest were pathological complete response (pCR), complete response (CR), partial response (PR), stable disease, progressive disease (PD), R0-resection, R1-resection, and R2-resection. The secondary included any grade of toxicity.

Results: Eleven investigations (9 noncomparative open-label cohort studies and 2 randomized controlled trials) involving 550 patients were ultimately included. The pooled estimates of pCR was 10% (95% confidence interval [CI]: 7%-13%, I2 = 55.9%). Simultaneously, only a small amount of patients achieved CR (11%, 95% CI: 7%-15%, I2 = 44.0%), which was consistent with pCR. Besides, R0 resection (93%, 95% CI: 90%-96%, I2 = 16.5%) seemed to be increased but need further exploration. The safety was also calculated, and most of the toxicities were moderate.

Conclusion: Neoadjuvant therapy of cetuximab combined with chemoradiotherapy could not improve pCR. The raise of R0-resection rate needed to be verified by more high-quality and well-designed RCTs. Meanwhile, the morbidity of toxicity was relatively mild and acceptable.
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http://dx.doi.org/10.1097/MD.0000000000024649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899853PMC
February 2021

Activin A impairs ActRIIA neutrophil recruitment into infected skin of mice.

iScience 2021 Feb 21;24(2):102080. Epub 2021 Jan 21.

Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.

Activin A levels are elevated during multiple severe infections and associated with an increased risk of death. However, the role of activin A in bacterial infection is still unclear. Here, we found that activin A levels were increased during skin infection in mice. Administration of activin A increased the bacterial burden and promoted the spread of bacteria . Moreover, activin A inhibited neutrophil chemotaxis to N-formylmethionine-leucyl-phenylalanine via the type IIA activin receptor (ActRIIA) and impaired ActRIIA neutrophil recruitment to infection foci . Additionally, we identified a novel subpopulation of neutrophils, ActRIIA neutrophils, which exhibit superior phagocytic capacity compared to ActRIIA neutrophils and possess an N2-like immunoregulatory activity via secreting IL-10 and TGF-β. Taken together, these findings indicate that activin A inhibits the recruitment of ActRIIA neutrophils to infected foci, leading to the impairment of bacterial clearance, and thus may hamper early infection control.
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http://dx.doi.org/10.1016/j.isci.2021.102080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873648PMC
February 2021