Publications by authors named "Tian Chen"

432 Publications

Single molecule, full-length transcript sequencing provides insight into the gene family in .

PeerJ 2021 15;9:e11808. Epub 2021 Jul 15.

College of Horticulture and Plant Protection, Yangzhou University, Yangzhou, China.

Background: The tree peony ( section DC), one of the traditional famous flowers with both ornamental and medicinal value, was widely used in China. Surprisingly little is known about the full-length transcriptome sequencing in tree peony, limiting the research on its gene function and molecular mechanism. The trehalose phosphate phosphatase () family genes has been found to affect plant growth and development and the function of genes in is unknown.

Methods: In our study, we performed single molecule, full-length transcript sequencing in . 10 family members were identified from PacBio sequencing for bioinformatics analysis and transcriptional expression analysis.

Results: A total of 230,736 reads of insert (ROI) sequences and 114,215 full-Length non-chimeric reads (FLNC) were obtained for further ORFs and transcription factors prediction, SSR analysis and lncRNA identification. NR, Swissprot, GO, COG, KOG, Pfam and KEGG databases were used to obtain annotation information of transcripts. 10 family members were identified with molecular weights between 48.0 to 108.5 kD and isoelectric point between 5.61 to 6.37. Furthermore, we found that family members contain conserved TPP or TPS domain. Based on phylogenetic tree analysis, PoTPS1 protein was highly similar to AtTPS1 protein in . Finally, we analyzed the expression levels of all genes in and found expressed at the highest level. In conclusion, this study combined the results of the transcriptome to systematically analyze the 10 family members, and sets a framework for further research of this important gene family in development of tree peony.
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http://dx.doi.org/10.7717/peerj.11808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286706PMC
July 2021

Crosstalk between RNA-Binding Proteins and Immune Microenvironment Revealed Two RBP Regulatory Patterns with Distinct Immunophenotypes in Periodontitis.

J Immunol Res 2021 5;2021:5588429. Epub 2021 Jul 5.

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

Periodontitis is an inflammatory disease whose pathogenesis is closely related with immunology. RNA-binding proteins (RBPs) were found to play crucial roles in immunity. Therefore, we aimed to investigate the potential impact of RBPs in the immune microenvironment in periodontitis. The differential expressions of RBPs in periodontitis and healthy samples were determined and were used to construct an RBP-based classifier for periodontitis using logistic regression. The correlations between RBPs and immune characteristics were investigated by the Spearman correlation. Unsupervised clustering was conducted to identify the RBP regulatory patterns. RBP-related genes were identified by WGCNA, while biological distinctions were revealed by GSVA and GO. 24 dysregulated RBPs were identified, from which a 12-RBP classifier was established to distinguish periodontitis with AUC of 0.942. Close protein-protein interactions and expression correlations were observed especially between SPATS2 and ISG20. ISG20 and ESRP1 were found to be highly correlated with immunocyte infiltration, immune signaling activation, and HLA expressions in periodontitis. Two distinct RBP regulatory patterns were identified with different immune and other biological characteristics in periodontitis. Our findings indicate a significant impact of RBPs in shaping the immune microenvironment in periodontitis, which might bring new insights into the understanding of immune mechanisms in the pathogenesis of periodontitis.
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http://dx.doi.org/10.1155/2021/5588429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275429PMC
July 2021

The novel hybrid polycarbonate polyurethane / polyester three-layered large-diameter artificial blood vessel.

J Biomater Appl 2021 Jul 20:8853282211033415. Epub 2021 Jul 20.

Department of Vascular, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: The most common materials of artificial blood vessels are polyethylene terephthalate and polytetrafluoroethylene. But polycarbonate polyurethane (PCU) is an ideal material for vascular prostheses because of their excellent characteristics. As far as we know, our artificial blood vessel is the first type of hybrid PCU/polyester three-layered large-diameter artificial blood vessel in the world.

Objective: The purpose of this preclinical animal experiment is to evaluate the hemocompatibility, histocompatibility, effectiveness, and safety of the three-layered large-diameter artificial blood vessel in sheep.

Methods: The artificial blood vessels took place of the initial segments of the sheep's thoracic aorta by end-to-end anastomosis.

Results: All of the 14 sheep are male, their average body weight (BW) was 30.57 ± 3.95 kg. All 14 artificial blood vessels successfully replaced the thoracic aortas. 5 sheep did not survive to the end of the experiment, while the remaining 9 sheep did. After the surgery, the blood biochemical and blood routine indicators fluctuate slightly within the normal range. The angiography showed that the implanted artificial blood vessels were unobstructed without obvious stenosis or expansion. 24 weeks after surgery, the lumen surfaces of the artificial blood vessels were covered by endothelia in different degrees, and the average endothelialization rate was 69.44% (range: 20% to 100%).

Conclusions: This artificial blood vessel is the first to use PCU in large-diameter artificial vascular grafts. It has excellent blood compatibility, wonderful biocompatibility, high endothelialization rate, and 100% patency.
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http://dx.doi.org/10.1177/08853282211033415DOI Listing
July 2021

A comparative study on the circadian rhythm of the electrical signals of and .

Plant Signal Behav 2021 Jul 6:1950899. Epub 2021 Jul 6.

State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang, China.

The circadian clock regulates a wide range of physiological processes in plants. Here we showed the circadian variations of the electrical signals in L. and L. in a natural state, which were analyzed using the day-night cycle method. The circadian characteristics of different plant electrical signals were compared by constructing a coupling model for the circadian rhythm of plant electrical signals. The electrical signal sensor had two electrode plates, which were fixed on the two ends of the splint, leaves could then be clamped and measured. The clamping force between the two electrode plates was uniform, which enabled continuous and nondestructive measurements. The results showed that an electric cyclic behavior was observed (circadian cycle) with the circadian variation in the plants within 24 h. Both the resistance (R) and the impedance (Z) increased firstly in the early morning and then decreased subsequently, while the capacitance (C) showed an opposite variation. Under different weather conditions, plant electrical signals showed periodic changes when the temperature and light intensity in the environment slightly changed within the physiological tolerance of plant. This indicated that the circadian clock of plant electrical signals could be maintained endogenously. The variation curves of plant electrical signals as time increased were fitted using the sine equation. The characteristic parameters of circadian rhythm of plant electrical signals were obtained. We found that although all plant electrical signals exhibited electric cyclic behavior, but the characteristics of circadian rhythms of electrical signals were different. This study provided a scientific basic for precisely monitoring plant electrical signals, and a reference for revealing circadian rhythms of plant electrical signals and their occurrence rules.
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http://dx.doi.org/10.1080/15592324.2021.1950899DOI Listing
July 2021

A methylotrophic origin of methanogenesis and early divergence of anaerobic multicarbon alkane metabolism.

Sci Adv 2021 Jul 2;7(27). Epub 2021 Jul 2.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

Methanogens are considered as one of the earliest life forms on Earth, and together with anaerobic methane-oxidizing archaea, they have crucial effects on climate stability. However, the origin and evolution of anaerobic alkane metabolism in the domain Archaea remain controversial. Here, we present evidence that methylotrophic methanogenesis was the ancestral form of this metabolism. Carbon dioxide-reducing methanogenesis developed later through the evolution of tetrahydromethanopterin -methyltransferase, which linked methanogenesis to the Wood-Ljungdahl pathway for energy conservation. Anaerobic multicarbon alkane metabolisms in Archaea also originated early, with genes coding for the activation of short-chain or even long-chain alkanes likely evolving from an ethane-metabolizing ancestor. These genes were likely horizontally transferred to multiple archaeal clades including () Bathyarchaeia, Lokiarchaeia, Hadarchaeia, and the methanogenic Methanoliparia.
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http://dx.doi.org/10.1126/sciadv.abj1453DOI Listing
July 2021

Analysis and Functional Verification of Gene Associated with Oil Accumulation Process in .

Int J Mol Sci 2021 Jun 29;22(13). Epub 2021 Jun 29.

College of Horticulture and Plant Protection, Yangzhou University, Yangzhou 225009, China.

The plant transcription factor (), a member of , is involved in the regulation of glycolysis and the expression of genes related to the de novo synthesis of fatty acids in plastids. In this study, the key regulator of seed oil synthesis and accumulation transcription factor gene was identified and cloned, having a complete open reading frame of 1269 bp and encoding 422 amino acids. Subcellular localization analysis showed that is located at the nucleus. After the expression vector of was constructed and transformed into wild-type , it was found that the overexpression of increased the expression level of downstream target genes such as , , and . As a result, the seeds of transgenic plants became larger, the oil content increased significantly, and the unsaturated fatty acid content increased, which provide a scientific theoretical basis for the subsequent use of genetic engineering methods to improve the fatty acid composition and content of plant seeds.
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http://dx.doi.org/10.3390/ijms22136996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267616PMC
June 2021

Rationale and Design of Assessing the Effectiveness of Short-Term Low-Dose Lithium Therapy in Averting Cardiac Surgery-Associated Acute Kidney Injury: A Randomized, Double Blinded, Placebo Controlled Pilot Trial.

Front Med (Lausanne) 2021 14;8:639402. Epub 2021 Jun 14.

Division of Kidney Disease and Hypertension, Department of Medicine, Rhode Island Hospital, Brown University School of Medicine, Providence, RI, United States.

Burgeoning pre-clinical evidence suggests that therapeutic targeting of glycogen synthase kinase 3β (GSK3β), a convergence point of multiple cellular protective signaling pathways, confers a beneficial effect on acute kidney injury (AKI) in experimental models. However, it remains unknown if GSK3β inhibition likewise mitigates AKI in humans. Cardiac surgery associated acute kidney injury (CSA-AKI) poses a significant challenge for clinicians and currently the only treatment available is general supportive measures. Lithium, an FDA approved mood stabilizer, is the best-known GSK3β inhibitor and has been safely used for over half a century as the first line regimen to treat bipolar affective disorders. This study attempts to examine the effectiveness of short term low dose lithium on CSA-AKI in human patients. This is a single center, prospective, randomized, double blinded, placebo controlled pilot study on patients undergoing cardiac surgery with cardiopulmonary bypass. Patients will be randomized to receive a small dose of lithium or placebo treatment for three consecutive days. Renal function will be measured via creatinine as well as novel AKI biomarkers. The primary outcome is incidence of AKI according to Acute Kidney Injury Network (AKIN) criteria, and secondary outcomes include receipt of new dialysis, days on dialysis, days on mechanical ventilation, infections within 1 month of surgery, and death within 90 days of surgery. As a standard selective inhibitor of GSK3β, lithium has been shown to exert a beneficial effect on tissue repair and regeneration upon acute injury in multiple organ systems, including the central nervous system and hematopoietic system. In experimental AKI, lithium at small doses is able to ameliorate AKI and promote kidney repair. Successful completion of this study will help to assess the effectiveness of lithium in CSA-AKI and could potentially pave the way for large-scale randomized trials to thoroughly evaluate the efficacy of this novel regimen for preventing AKI after cardiac surgery. This study was registered prospectively on the 17th February 2017 at ClinicalTrials.gov (NCT03056248, https://clinicaltrials.gov/ct2/show/NCT03056248?term=NCT03056248&draw=2&rank=1).
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http://dx.doi.org/10.3389/fmed.2021.639402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236527PMC
June 2021

Associations of low level of fluoride exposure with dental fluorosis among U.S. children and adolescents, NHANES 2015-2016.

Ecotoxicol Environ Saf 2021 Sep 22;221:112439. Epub 2021 Jun 22.

School of Public Health and Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address:

Drinking water fluoridation was a mid-twentieth century innovation based on the medical hypothesis that consuming low doses of fluoride at the teeth forming years provided protection against dental decays. Numerous studies showed that high level exposure to fluoride could cause dental and skeleton fluorosis. However, there was limited study focusing on the fluorosis effect of low levels of exposure to fluoride. Therefore, our study aimed to examine whether the low level of fluoride exposure (measured in blood plasma and household tap water) was associated with the risk of dental fluorosis based on data of the National Health and Nutrition Examination Survey (NHANES) 2015-2016. We analyzed data in 2098 children and adolescents who had Dean's Index scores, and water and plasma fluoride measures. The Dean's Index score was measured by calibrated dental examiners using the modified Dean's fluorosis classification system. Fluoride was measured in plasma and household tap water. In this study, we found that the rate of fluoride concentration in water above the recommended level of 0.7 mg/L was 25%, but the prevalence of dental fluorosis was 70%. Binary logistic regression adjusted for covariates showed that higher water fluoride concentrations (0.31-0.50, 0.51-0.70, > 0.70 compared 0.00-0.30) were associated with higher odds of dental fluorosis (OR = 1.48, 95% CI: 1.13-1.96, p = 0.005; OR = 1.92, 95% CI: 1.44-2.58, p < 0.001, and OR = 2.30, 95% CI: 1.75-3.07, p < 0.001, respectively). The pattern of regression between plasma fluoride and dental fluorosis was similar. Inclusion, our study showed that even low level of water or plasma fluoride exposure was associated with increased the risk of dental fluorosis. The safety of public health approach of drinking water fluoridation for global dental caries reduction are urgently needed further research.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112439DOI Listing
September 2021

Linear Hyperkeratotic Papules and Comedo-like Plugs on the Extremities: A Quiz.

Acta Derm Venereol 2021 Jul 7;101(7):adv00492. Epub 2021 Jul 7.

Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Skin and Immune Diseases, 100730 Beijing, China.

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http://dx.doi.org/10.2340/00015555-3851DOI Listing
July 2021

Aerobic granular sludge treating low-strength municipal wastewater: Efficient carbon, nitrogen and phosphorus removal with hydrolysis-acidification pretreatment.

Sci Total Environ 2021 Jun 5;792:148297. Epub 2021 Jun 5.

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, PR China.

Low organic load while high fraction of particulates still challenging the application of aerobic granular sludge process in low-strength municipal wastewater treatment. The feasibility of adopting short cycle length to increase organic load and hydrolysis-acidification pretreatment to enhance anaerobic COD uptake was evaluated. As the cycle length decreased from 4 h to 2 h, the organic loading rate increased from 0.98 to 1.3 g L d and granulation appeared after two weeks. Moreover, with the hydrolysis-acidification pretreatment, the average effluent TN and TP concentrations decreased respectively from 17.8 to 13.7 mg L and 0.76 to 0.41 mg L, meeting the Grade IA of the effluent standards in China. Furthermore, cycle tests were conducted to reveal the underlying mechanism of the pretreatment effects. The results showed that the hydrolysis-acidification pretreatment enhanced the COD storage and phosphorus release in anaerobic phase, and improved the simultaneous nitrification-denitrification process, as well as the phosphorus uptake in aeration phase.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148297DOI Listing
June 2021

Analysis of serum metabolome of workers occupationally exposed to hexavalent chromium: A preliminary study.

Toxicol Lett 2021 Oct 19;349:92-100. Epub 2021 Jun 19.

Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, 100191, China. Electronic address:

Hexavalent chromium (Cr(VI)) compound is considered as a common environmental and occupational pollutant due to widespread application in industry and agriculture. Cr(VI) as a carcinogen poses a serious threat to human health and the underlying mechanisms need further investigation. Previous studies had demonstrated the characteristic expression profiling after Cr(VI) treatment in vitro and in vivo at the levels of gene and protein. The comprehensive metabolic signatures were also conducive to discover potential biomarkers for effects assessment of Cr(VI) toxicity. In the current study, Ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) non-targeted metabolomics was applied to analyze serum metabolic changes in 77 chromate exposure workers and 62 controls. Thirteen metabolites were found significantly decreased and 41 metabolites were increased, which were involved in arginine and proline metabolism, and glycerophospholipid metabolism by bioinformatic analysis. Furthermore, there were significant negative correlations between blood Cr level and Arginine, PC(18:2/24:4) and PC(14:0/16:0), subgroup analyses indicated that these correlations were observed in male-only subgroups, and were not found among chromate workers and controls separately. Diet could be a potential confounder which was not controlled rigorously in this study. These findings provided preliminary clues to investigate the underlying mechanisms of Cr(VI)-induced toxicity and were required to be further verified in future researches.
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http://dx.doi.org/10.1016/j.toxlet.2021.06.007DOI Listing
October 2021

Integrated analysis identifies S100A16 as a potential prognostic marker for pancreatic cancer.

Am J Transl Res 2021 15;13(5):5720-5730. Epub 2021 May 15.

Department of Laboratory Diagnostics, Changhai Hospital, Navy Medical University Shanghai, China.

Background: The new S100 protein family member S100A16 is functionally expressed in various cancers. This study explored the prognostic value and potential role of S100A16 in pancreatic cancer (PC).

Methods: RNA-seq and clinical data were obtained from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA-PAAD) dataset to compare the expression level of S100A16 between groups. The genes co-expressed with S100A16 in TCGA-PAAD were analyzed using cBioPortal. Gene Ontology and Kyoto Encyclopedia of Genes and genomes enrichment analyses were also performed on these genes. Pathways related to S100A16 expression dysregulation were explored using gene set enrichment analysis. The Tumor Immune Estimation Resource was used to analyze the correlation between S100A16 and infiltrating immune cells. The Kaplan-Meier method and Cox analyses were used to assess the prognostic significance of S100A16 for PC.

Results: The S100A16 expression level was high in PC and increased with the degree of malignancy. The S100A16 functions in PC were mainly enriched in the immune modules, but negatively correlated with the immune activity (T-cell, cytokine, immune, co-receptor, signaling adaptor, cell adhesion molecule, chemokine, and JAK/STAT signaling) and infiltration level (T cells and macrophages). The strongest negative correlation was observed between the expression of CD8 T cells and S100A16. Furthermore, high S100A16 expression also indicated worse overall survival and, therefore, worse prognosis of PC.

Conclusion: S100A16 is a potential independent prognostic marker and immunotherapy target for PC. Mechanistically, S100A16 potentially affects prognosis by extensive immunosuppression, including the inhibition of the anti-tumor immune response of CD8 T cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205789PMC
May 2021

Development and validation of an individualized immune prognostic model in stage I-III lung squamous cell carcinoma.

Sci Rep 2021 Jun 16;11(1):12727. Epub 2021 Jun 16.

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

Lung squamous cell carcinoma (LUSC) possesses a poor prognosis even for stages I-III resected patients. Reliable prognostic biomarkers that can stratify and predict clinical outcomes for stage I-III resected LUSC patients are urgently needed. Based on gene expression of LUSC tissue samples from five public datasets, consisting of 687 cases, we developed an immune-related prognostic model (IPM) according to immune genes from ImmPort database. Then, we comprehensively analyzed the immune microenvironment and mutation burden that are significantly associated with this model. According to the IPM, patients were stratified into high- and low-risk groups with markedly distinct survival benefits. We found that patients with high immune risk possessed a higher proportion of immunosuppressive cells such as macrophages M0, and presented higher expression of CD47, CD73, SIRPA, and TIM-3. Moreover, When further stratified based on the tumor mutation burden (TMB) and risk score, patients with high TMB and low immune risk had a remarkable prolonged overall survival compared to patients with low TMB and high immune risk. Finally, a nomogram combing the IPM with clinical factors was established to provide a more precise evaluation of prognosis. The proposed immune relevant model is a promising biomarker for predicting overall survival in stage I-III LUSC. Thus, it may shed light on identifying patient subset at high risk of adverse prognosis from an immunological perspective.
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http://dx.doi.org/10.1038/s41598-021-92115-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209222PMC
June 2021

Immobilizing of palladium on melamine functionalized magnetic chitosan beads: A versatile catalyst for p-nitrophenol reduction and Suzuki reaction in aqueous medium.

Int J Biol Macromol 2021 Aug 11;184:358-368. Epub 2021 Jun 11.

Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang 110819, PR China. Electronic address:

In this study, an environmental-friendly palladium catalyst with high efficiency, magnetic, recoverability, reusability, and excellent stability was prepared and thoroughly characterized by the Fourier transform infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM), X-ray diffraction (XRD), Elemental mapping, Thermogravimetric analysis (TGA) and Energy-dispersive X-ray spectroscopy (EDX). Results demonstrates that melamine provides a coordination point on the surface of chitosan microspheres, which provides a platform for the uniform distribution of palladium (II) and combines with palladium (II) firmly to avoid unnecessary leaching of nanoparticles. Besides, FeO/[email protected] microcapsules exhibited high catalytic performance in reducing p-NP in water at room temperature (150-300 s). This composite was also effective in the Suzuki-Miyaura coupling reaction under mild conditions with high catalytic performance (TON = 3.8 × 10, TOF = 7.6 × 10). Reproducibility experiments also showed that FeO/[email protected] microcapsules have high recovery efficiency and can work at least six times during these two catalytic reactions. The hot filtration test indicated that the catalyst has heterogeneous nature.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.055DOI Listing
August 2021

Comprehensive Profiling Reveals Distinct Microenvironment and Metabolism Characterization of Lung Adenocarcinoma.

Front Genet 2021 28;12:619821. Epub 2021 May 28.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Lung adenocarcinoma has entered into an era of immunotherapy with the development of immune checkpoint inhibitors (ICIs). The identification of immune subtype is crucial to prolonging survival in patients. The tumor microenvironment (TME) and metabolism have a profound impact on prognosis and therapy. The majority of previous studies focused on only one aspect, while both of them are essential to the understanding of tumorigenesis and development. We hypothesized that lung adenocarcinoma can be stratified into immune subgroups with alterations in the TME infiltration. We aimed to explore the "TME-Metabolism-Risk" patterns in each subtypes and the mechanism behind. Glycolysis and cholesterol were selected for the analysis of metabolic states based on the first half of the study. Bioinformatic analysis was performed to investigate the transcriptomic and clinical data integrated by three lung adenocarcinoma cohorts (GSE30219, GSE31210, GSE37745, = 415). The results were validated in an independent cohort (GSE50081, = 127). In total, 415 lung adenocarcinoma samples were integrated and analyzed. Four major immune subtypes were indentified using bioinformatic analysis. Subtype NC1, characterized by a high level of glycolysis, with extremely low microenvironment cell infiltration. Subtype NC2, characterized by the "Silence" and "Cholesterol biosynthesis Predominant" metabolic states, with a middle degree infiltration of microenvironment cell. Subtype NC3, characterized by the lack of "Cholesterol biosynthesis Predominant" metabolic state, with abundant microenvironment cell infiltration. Subtype NC4, characterized by "Mixed" metabolic state, with a relatively low microenvironment cell infiltration. Least absolute shrinkage and selection operator (LASSO) regression and multivariate analyses were performed to calculate the risk of each sample, and we attempted to find out the potential immune escape mechanism in different subtypes. The result revealed that the lack of immune cells infiltration might contribute to the immune escape in subtypes NC1 and NC4. NC3 was characterized by the high expression of immune checkpoint molecules and fibroblasts. NC2 had defects in activation of innate immune cells. There existed an obviously survival advantage in subtype NC2. Gene set enrichment analysis (GSEA) and Gene Ontology analysis indicated that the PI3K-AKT-mTOR, TGF-β, MYC-related pathways might be correlated with this phenomenon. In addition, some differentially expressed genes (DEGs) were indentified in subtype NC3, which might be potential targets for survival phenotype transformation.
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http://dx.doi.org/10.3389/fgene.2021.619821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193848PMC
May 2021

Bending Response of a Book with Internal Friction.

Phys Rev Lett 2021 May;126(21):218004

Flexible Structures Laboratory, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.

We study the bending of a booklike system, comprising a stack of elastic plates coupled through friction. The behavior of this layered system is rich and nontrivial, with a nonadditive enhancement of the apparent stiffness and a significant hysteretic response. A dimension reduction procedure is employed to develop a centerline-based theory describing the stack as a nonlinear planar rod with internal shear. We consider the coupling between the nonlinear geometry and the elasticity of the stacked plates, treating the interlayer friction perturbatively. This model yields predictions for the stack's mechanical response in three-point bending that are in excellent agreement with our experiments. Remarkably, we find that the energy dissipated during deformation can be rationalized over 3 orders of magnitude, including the regimes of a thick stack with large deflection. This robust dissipative mechanism could be harnessed to design new classes of low-cost and efficient damping devices.
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http://dx.doi.org/10.1103/PhysRevLett.126.218004DOI Listing
May 2021

[Genetic Diagnosis of Thalassemia in Baise, Guangxi Zhuang Autonomous Region].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):865-868

Genetic Laboratory of Baise Maternal and Child Health Hospital;Baise 533000, Guangxi Zhuang Autonomous Region, China,E-mail:

Objective: To understand the genotypes and distribution characteristics of thalassemia in Baise, Guangxi Zhuang Autonomous Region, to provide references for the prevention and diagnosis of thalassemia in the region and improve the quality of eugenics.

Methods: 3 482 pregnant women and their spouses from January 2019 to August 2019 in Baise Maternal and Child Health Hospital for prenatal genetic diagnosis were selected, α, β- thalassemia genes were detected by Gap-PCR, PCR and DNA reverse dot hybridization, cases carrying thalassemia gene were confirmed and statistical analyzed.

Results: 2 260 samples (64.90%) carrying thalassemia gene were found, among which 1 459 cases (64.56%) were diagnosed as α- thalassemia, 617 cases (27.30%) as β- thalassemia, 184 cases (8.14%) as α complex β- thalassemia. Among 1 459 α- thalassemia genes, --SEA /αα(637 cases, 43.66%), -α3.7 /αα (306 cases, 20.97%), -αCS /αα(143 cases, 9.80%), -α4.2 /αα(124 cases, 8.50%) and -αWS /αα(77 cases, 5.27%) were the most common, while among 617 β- thalassemia genes, CD17 (229 cases, 37.12%), CD41-42 (213 cases, 34.52%), IVS-I-1 (41 cases, 6.65%), βE (38 cases, 6.16%) and CD71-72 (34 cases, 5.51%) were the most common. And --SEA /αα/ CD17 (24 cases, 13.04%), -α4.2 /αα/ CD17 (13 cases, 7.07%), -α3.7 /αα/ CD41-42 (12 cases, 6.52% ) and --SEA /αα/ CD41-42 (12 cases, 6.52%) were mainly found in 184 cases of α complex β - thalassemia.

Conclusion: Genotyes of thalassemia in Baise, Guangxi Zhuang Autonomous Region are complex and diverse. The prenatal screening and diagnosis of thalassemia in the region should be strengthened in accordance with the characteristics of genetypes in the region, in order to reduce birth defects and improve eugenics quality.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.033DOI Listing
June 2021

Neoadjuvant nivolumab for patients with resectable HPV-positive and HPV-negative squamous cell carcinomas of the head and neck in the CheckMate 358 trial.

J Immunother Cancer 2021 Jun;9(6)

Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.

Background: Head and neck squamous cell carcinomas (HNSCCs) are common malignancies caused by carcinogens, including tobacco and alcohol, or infection with human papillomavirus (HPV). Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) pathway are effective against unresectable recurrent/metastatic HNSCC. Here, we explored the safety and efficacy of anti-PD-1 therapy in at-risk resectable HPV-positive and HPV-negative HNSCC in the neoadjuvant setting.

Methods: The phase I/II CheckMate 358 trial in virus-associated cancers assessed neoadjuvant nivolumab in patients with previously untreated, resectable HPV-positive or HPV-negative HNSCC. Patients received nivolumab 240 mg intravenously on days 1 and 15, with surgery planned by day 29. Safety/tolerability (primary endpoint) was assessed by monitoring adverse events (AEs) and surgical delays. Radiographic response was measured before surgery using RECIST v1.1, adapted for a single post-nivolumab evaluation. Pathologic specimens were examined for treatment response using immune-based criteria.

Results: From November 2015 to December 2017, 52 patients with AJCC (seventh edition) stage III-IV resectable HNSCC received neoadjuvant nivolumab (26 HPV-positive, 26 HPV-negative). Any-grade treatment-related AEs (TRAEs) occurred in 19 patients (73.1%) and 14 patients (53.8%) in the HPV-positive and HPV-negative cohorts, respectively; grade 3-4 TRAEs occurred in five (19.2%) and three patients (11.5%), respectively. No patient had a protocol-defined TRAE-related surgical delay (>4 weeks). Thirty-eight patients were reported as undergoing complete surgical resection, 10 had a planned post-nivolumab biopsy instead of definitive surgery due to a protocol misinterpretation, and four did not undergo surgery or biopsy, including two with tumor progression. Radiographic response rates in 49 evaluable patients were 12.0% and 8.3% in the HPV-positive and HPV-negative cohorts, respectively. There were no complete pathologic responses by site or central review in operated patients. Among 17 centrally evaluable HPV-positive tumors, one (5.9%) achieved major pathological response and three (17.6%) achieved partial pathologic response (pPR); among 17 centrally evaluable HPV-negative tumors, one (5.9%) achieved pPR.

Conclusions: Neoadjuvant nivolumab was generally safe and induced pathologic regressions in HPV-positive (23.5%) and HPV-negative (5.9%) tumors. Combinatorial neoadjuvant treatment regimens, and continued postoperative therapy for high-risk tumors, are warranted in future trials to enhance the efficacy of this approach.

Trial Registration Number: ClinicalTrials.gov NCT02488759; https://clinicaltrials.gov/ct2/show/NCT02488759.
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http://dx.doi.org/10.1136/jitc-2021-002568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183204PMC
June 2021

Extracellular vesicles derived from T-cell acute lymphoblastic leukemia inhibit osteogenic differentiation of bone marrow mesenchymal stem cells via miR-34a-5p.

Endocr J 2021 May 25. Epub 2021 May 25.

Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China.

Reduced bone formation in patients with T-cell acute lymphoblastic leukemia (T-ALL) may be related to the interaction between tumour cells and bone marrow stromal cells (BMSCs). The miRNAs in extracellular vesicles derived from leukemia cells play an essential role in regulating the function of BMSCs; however, the regulatory mechanisms remain unclear. The expression of miR-34a-5p in T-ALL patients and cells was measured by quantitative real-time PCR. BMSCs were co-cultured with extracellular vesicles isolated from T-ALL cells in mineralization medium. The osteogenic differentiation of BMSCs was evaluated by Alizarin Red S staining, alkaline phosphatase (ALP) staining, and detection of osteogenic differentiation markers. A dual-luciferase reporter assay was performed to confirm the targeting relationship between miR-34a-5p and Wnt family member 1 (WNT1). MiR-34a-5p expression was upregulated in T-ALL patients and Jurkat cells. After BMSCs were co-cultured with extracellular vesicles derived from T-ALL cells, osteogenic differentiation of BMSCs was inhibited, and bone mineralization and ALP activity were decreased compared to those of control cells. MiR-34a-5p knockdown in T-ALL cells restored osteogenic differentiation of BMSCs co-cultured with extracellular vesicles. In addition, miR-34a-5p targets and negatively regulates WNT1 expression. In conclusion, our results demonstrated that knockdown of miR-34a-5p in extracellular vesicles derived from T-ALL cells promoted osteogenic differentiation of BMSCs by regulating WNT1.
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http://dx.doi.org/10.1507/endocrj.EJ21-0005DOI Listing
May 2021

Development of a Sensitive Diagnostic Assay for Parkinson Disease Quantifying α-Synuclein-Containing Extracellular Vesicles.

Neurology 2021 05 23;96(18):e2332-e2345. Epub 2021 Mar 23.

From the Departments of Pathology (Z.H., T.S., P.A., D.S., M.B., L.S., K.B., T.K., C.P., M.S., J.Z.), Neurology (C.P.Z.), and Psychiatry and Behavioral Sciences (E.R.P.), University of Washington School of Medicine, Seattle; Department of Neurology (Z.H.), West China Medical School, Sichuan University, Chengdu; Department of Pathology (C.T., J.Z.), Central Laboratory (J.Z.), The First Affiliated Hospital and School of Medicine, and National Health and Disease Human Brain Tissue Resource Center (J.Z.), Zhejiang University, Hangzhou; Geriatric Research, Education, and Clinical Center (C.P.Z.) and Mental Illness Research, Education, and Clinical Centre (E.R.P.), Veterans Affairs Puget Sound Health Care System, Seattle, WA; Parkinson's Disease Research, Education, and Clinical Care Center (J.F.Q.), Portland VA Medical Center; Department of Neurology (J.F.Q.), Oregon Health and Science University, Portland; Department of Pathology (T.J.M.), Stanford University School of Medicine, Palo Alto, CA; and Department of Neurology (J.A.), St. Olav's Hospital, Trondheim, Norway.

Objective: To develop a reliable and fast assay to quantify the α-synuclein (α-syn)-containing extracellular vesicles (EVs) in CSF and to assess their diagnostic potential for Parkinson disease (PD).

Methods: A cross-sectional, multicenter study was designed, including 170 patients with PD and 131 healthy controls (HCs) with a similar distribution of age and sex recruited from existing center studies at the University of Washington and Oregon Health and Science University. CSF EVs carrying α-syn or aggregated α-syn were quantified using antibodies against total or aggregated α-syn, respectively, and highly specific, sensitive, and rapid assays based on the novel Apogee nanoscale flow cytometry technology.

Results: No significant differences in the number and size distribution of total EVs between patients with PD and HCs in CSF were observed. When examining the total α-syn-positive and aggregated α-syn-positive EV subpopulations, the proportions of both among all detected CSF EVs were significantly lower in patients with PD compared to HCs ( < 0.0001). While each EV subpopulation showed better diagnostic sensitivity and specificity than total CSF α-syn measured directly with an immunoassay, a combination of the 2 EV subpopulations demonstrated a diagnostic accuracy that attained clinical relevance (area under curve 0.819, sensitivity 80%, specificity 71%).

Conclusion: Using newly established, sensitive nanoscale flow cytometry assays, we have demonstrated that total α-syn-positive and aggregated α-syn-positive EVs in CSF may serve as a helpful tool in PD diagnosis.

Classification Of Evidence: This study provides Class III evidence that total and aggregated α-syn-positive EVs in CSF identify patients with PD.
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http://dx.doi.org/10.1212/WNL.0000000000011853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166433PMC
May 2021

Physicochemical properties and digestive kinetics of whey protein gels filled with potato and whey protein mixture emulsified oil droplets: effect of protein ratios.

Food Funct 2021 Jul;12(13):5927-5939

School of Food and Biological Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China. and Institute of Food Physical Processing, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China. and Jiangsu Provincial Key Laboratory for Food Physical Processing, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China.

Incorporating protein emulsified droplets into protein gels as active fillers have attracted much attention. However, using animal and plant protein mixtures emulsified droplets as the filler is lacking. We investigated the effect of emulsified droplets covered by potato protein (PP) and whey protein (WP) mixtures of different ratios (10/0, 9/1, 7/3, 5/5, 3/7, 1/9, 0/10) on mechanical, microstructural characteristics and digestion of emulsion-filled WP gels (EFWG). The results showed that the particle size of emulsified droplets increased with the enhancement of PP ratio, whereas their ζ-potential value decreased. Increasing the PP ratio improved the elastic moduli (G'), fracture stress and hardness of EFWG, while lowered the water holding capacity and swelling ratios of EFWG. Confocal laser scanning microscopy revealed that a higher PP ratio leads to a thicker gel skeleton and fine network. Although the enhancement of the PP ratio decreased disulfide bond content in EFWG, it improved the hydrogen bond and total non-covalent interactions in EFWG. Increased PP in filling emulsions delayed the release rate of the free amino group and free fatty acid during digestion. Moreover, the presence of NaCl improved the gel properties and digestion of EFWG. The findings of this study may provide information for developing new WP gel products with specific digestion rates.
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http://dx.doi.org/10.1039/d1fo00653cDOI Listing
July 2021

Multiplex ligation-dependent probe amplification identifies copy number changes in normal and undetectable karyotype MDS patients.

Ann Hematol 2021 May 15. Epub 2021 May 15.

Department of Hematology and Blood and Marrow Transplantation, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huan-Hu-Xi Road, Ti-Yuan-Bei, Hexi District, Tianjin, 300060, China.

Chromosomal abnormalities play an important role in classification and prognostication of myelodysplastic syndrome (MDS) patients. However, more than 50% of low-risk MDS patients harbor a normal karyotype. Recently, multiplex ligation-dependent probe amplification (MLPA) has emerged as an effective and robust method for the detection of cytogenetic aberrations in MDS patients. To characterize the subset of MDS with normal karyotype or failed chromosome banding analysis, we analyzed 144 patient samples with normal karyotype or undetectable through regular chromosome banding analysis, which were subjected to parallel comparison via fluorescence in situ hybridization (FISH) and MLPA. MLPA identifies copy number changes in 16.7% of 144 MDS patients, and we observed a significant difference in overall survival (OS) (median OS: undefined vs 27 months, p=0.0071) in patients with normal karyotype proved by MLPA versus aberrant karyotype cohort as determined by MLPA. Interestingly, patients with undetectable karyotype via regular chromosome banding indicated inferior outcome. Collectively, MDS patients with normal or undetectable karyotype via chromosome banding analysis can be further clarified by MLPA, providing more prognostic information that benefit for individualized therapy.
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http://dx.doi.org/10.1007/s00277-021-04550-8DOI Listing
May 2021

NIR-absorbing Prussian blue nanoparticles for transarterial infusion photothermal therapy of VX2 tumors implanted in rabbits.

Nanoscale 2021 May 29;13(18):8490-8497. Epub 2021 Apr 29.

Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.

Nanomaterial-related photothermal therapy has been intensively investigated for treatment of hepatocellular carcinoma (HCC). However, owing to the low specificity to tumors and easy excretion from the systemic circulation, the low dose of photoactive nanomaterials in solid tumors severely hinders the photothermal therapy applications for HCC. Herein, an innovative strategy for transarterial infusion photothermal therapy (TAIPPT) of VX2 tumors implanted in rabbits is reported. NIR-absorbing Prussian blue nanoparticles were prepared by microemulsion methods, which demonstrate excellent photothermal therapy capacity and satisfactory biocompatibility. Prussian blue nanoparticles are transarterially infused into VX2 tumors and irradiated for photothermal therapy. TAIPPT achieves fast and efficient delivery of nanoparticles into tumors and complete ablation by one-time transarterial infusion treatment. Furthermore, TAIPPT could activate the immune cells in rabbits and inhibit distant tumors. Our findings describe a promising strategy for tumor eradication and may benefit future clinical HCC patients.
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http://dx.doi.org/10.1039/d1nr01394gDOI Listing
May 2021

Improving source inversion performance of airborne pollutant emissions by modifying atmospheric dispersion scheme through sensitivity analysis combined with optimization model.

Environ Pollut 2021 Sep 19;284:117186. Epub 2021 Apr 19.

Key Laboratory of Beijing on Regional Air Pollution Control, College of Environmental & Energy Engineering, Beijing University of Technology, Beijing, 100124, China.

Estimating accurately airborne pollutant emissions source information (source strength and location) is important for achieving effective air pollution management or adequate emergency responses to accidents. Inversion method is one of the useful tools to identify the source parameters. The atmospheric dispersion scheme has been proven to be the key to determining the source inversion performance by influencing the accuracy of the dispersion models. Modifying the atmospheric dispersion scheme is an important potential method to improve the inversion performance, but this has not been studied previously. To fill this gap, a novel approach for parameter sensitivity analysis combined with an optimization method was proposed to improve the source inversion performance by optimizing empirical scheme. The dispersion coefficients σ and σ of the typical BRIGGS scheme under different atmospheric dispersion conditions were optimized and used for air pollutant dispersion and source inversion. The results showed that the prediction performance of the air pollutant concentrations was greatly improved with statistical indices |FB| and NMSE decreased by 0.22 and 2.07, respectively; FAC2 and R increased by 0.10, and 0.08, respectively. For source inversion, the results of the significance analysis suggested that the accuracy in the source strength and location parameter (x0) were both significantly improved by ∼271% (relative deviation reduced from 60.0% to 16.2%) and ∼121% (absolute deviation reduced from 27.6 to 12.5 m). The improvement of source strength inversion accuracy was more significant under unstable atmospheric conditions (stability class A, B, and C); the mean absolute relative deviation was reduced by 97.5%. These results can help to obtain more accurate source information and to provide reliable reference for air pollution managements or emergency response to accidents. This study provides a novel and versatile approach to improve estimation performance of pollutant emission sources and enhances our understanding of source inversion.
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http://dx.doi.org/10.1016/j.envpol.2021.117186DOI Listing
September 2021

B-Lymphoblastic Leukemia With Aberrant CD5 Expression.

Am J Clin Pathol 2021 Apr 5. Epub 2021 Apr 5.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Objectives: B-acute lymphoblastic leukemia (B-ALL) is a neoplasm of precursor lymphoid cells committed to the B-lineage. Expression of CD5 is rare in B-ALL.

Methods: We studied the clinicopathologic, immunophenotypic, and molecular genetic features of 10 cases of B-ALL with aberrant CD5 expression, and compared with CD5-B-ALL.

Results: B-ALL with aberrant CD5 expression is rare and predominantly affects men. Patients with CD5+ B-ALL had shorter median overall survival (21 vs 45 months, P = .0003). Expression of CD5 imposed a challenge in the differential diagnoses between B-ALL and other CD5+ B-cell lymphomas with blastic morphology. Dim CD20 and CD45, lack of surface immunoglobulin, expression of CD34 and TdT, negative immunostain for cyclin D1, and absence of t(11;14)(q13;q32) support a diagnosis of B-ALL.

Conclusions: CD5 expression is rare in B-ALL and associated with poor clinical outcome. CD5+ B-ALL represents a distinct entity that needs to be considered in the differential diagnoses of CD5+ B-cell lymphoproliferative disorders.
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http://dx.doi.org/10.1093/ajcp/aqaa269DOI Listing
April 2021

[Clinical Analysis of B-Cell Non-Hodgkin Lymphoma Treated with Modified Conditioning Regimen].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Apr;29(2):469-473

Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China,E-mail:

Objective: To investigate the efficacy, safety and prognosis of auto-HSCT between classical and modified conditioning regimen in patients with B-cell non-Hodgkin lymphoma.

Methods: 36 patients diagnosed as B-cell non-Hodgkin lymphoma treated with autologous hematopoietic stem cell transplantation from January 2015 to June 2018 in Tianjin Cancer Hospital were retrospectively analyzed. The patients were divided into two groups: Idarubicin group and non-Idarubicin group. The overall survival (OS), progression-free survival (PFS), adverse reactions and hematopoietic reconstitution time between the two groups were compared. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison between groups, and Cox regression was used for multivariate analysis.

Results: The median follow-up time was 29 months. Among these 36 patients with B-cell non-Hodgkin lymphoma before transplantation, 21 patients achieved CR and 15 patients achieved PR. The reconstitution time of neutrophil (P>0.05) and platelet (P>0.05) was not significantly different between Idarubicin and non-Idarubicin group. Also, the adverse reactions were not significantly different between two groups. The addition of idarubicin showed not aggravate the adverse reactions of patients. The OS and PFS of patients with idarubicin was longer than that of patients without idarubicin. The multivariate analysis showed that, the modified conditioning regimen and the remission state before transplantation were closely associated with prognosis.

Conclusion: The above-mentioned results indicated that the combination of modified conditioning regimen with idarubicin can lengthen the OS and PFS of the patients significantly, and show not aggravate of bone marrow inhibition, moreover, the hematopoietic reconsititution time show not lengthen, which means that it can be a safe and effective choice for autologous HSCT in the patients with B cell non-Hodgkin lymphoma.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.02.026DOI Listing
April 2021

Is Treating Patients With Stage 4 Pressure Ulcers With Vitamins A and C, Zinc, and Arginine Justified?

Wounds 2021 Mar;33(3):77-80

Wright State University School of Medicine, Dayton, Ohio; Jobst Vascular Institute/ProMedica Health system, Toledo, Ohio.

Introduction: Management of patients with pressure wounds often may entail the administration of vitamins A and C, zinc, and arginine. Supplementing these nutrients as part of a standard wound care protocol may increase the risk for toxicity and unnecessarily increase the cost of health care.

Objective: This study aimed to correlate the nutritional status represented by albumin and prealbumin levels with aforementioned nutrient levels. This understanding would determine whether albumin and prealbumin levels have good predictive value in identifying patients with vitamin deficiencies in this population.

Materials And Methods: Twenty patients aged 18 to 90 years were included, patients had to be admitted in the acute hospital setting with stage 4 pressure ulcers on their sacrum, hips, or heels. Patients already on vitamin supplements were excluded from the study. An odds ratio (OR) was used to assess the association between vitamin deficiency and albumin/prealbumin status. Fisher exact test was performed to test the significance of the association.

Results: The OR of vitamin A deficiency vs albumin deficiency was 0.27, but the association was not significant (95% CI, 0.004-3.68; P = .34). The OR of zinc deficiency vs albumin deficiency was 25.67 (95% CI, 1.2-568.9), and the association was significant (P = .01). The odds of a patient with vitamin C deficiency also having albumin deficiency was 0.62 times greater than that for patients without vitamin C deficiency. Vitamin A deficiency was more likely to be associated with prealbumin deficiency. Zinc deficiency was more likely to be associated with albumin deficiency. While arginine deficiency was more likely to be associated with albumin deficiency, and less likely to be associated with prealbumin deficiency, the results were not statistically significant.

Conclusions: This study showed that routine treatment with vitamins A and C, zinc, and arginine in patients with stage 4 pressure ulcers is not justified.
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March 2021

OTUD1 Regulates Antifungal Innate Immunity through Deubiquitination of CARD9.

J Immunol 2021 Apr 31;206(8):1832-1843. Epub 2021 Mar 31.

Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, 250012 Jinan, Shandong, People's Republic of China;

CARD9 is an essential adaptor protein in antifungal innate immunity mediated by C-type lectin receptors. The activity of CARD9 is critically regulated by ubiquitination; however, the deubiquitinases involved in CARD9 regulation remain incompletely understood. In this study, we identified ovarian tumor deubiquitinase 1 (OTUD1) as an essential regulator of CARD9. OTUD1 directly interacted with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-κB and MAPK pathway. OTUD1 deficiency impaired CARD9-mediated signaling and inhibited the proinflammatory cytokine production following fungal stimulation. Importantly, mice were more susceptible to fungal infection than wild-type mice in vivo. Collectively, our results identify OTUD1 as an essential regulatory component for the CARD9 signaling pathway and antifungal innate immunity through deubiquitinating CARD9.
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http://dx.doi.org/10.4049/jimmunol.2001253DOI Listing
April 2021

Study on the characteristics of intestinal motility of constipation in patients with Parkinson's disease.

World J Gastroenterol 2021 Mar;27(11):1055-1063

Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

Background: Constipation is one of the most important nonmotor symptoms in Parkinson's disease (PD) patients, and constipation of different severities is closely related to the pathogenesis of PD. PD with constipation (PDC) is considered a unique type of constipation, but its mechanism of formation and factors affecting its severity have been less reported. Understanding the gastrointestinal motility characteristics and constipation classification of PDC patients is essential to guide the treatment of PDC. In this study, the colonic transit test and high-resolution anorectal manometry were used to identify the intestinal motility of PDC to provide a basis for the treatment of PDC.

Aim: To investigate the clinical classification of PDC, to clarify its characteristics of colonic motility and rectal anal canal pressure, and to provide a basis for further research on the pathogenesis of PDC.

Methods: Twenty PDC patients and 20 patients with functional constipation (FC) who were treated at Xuanwu Hospital of Capital Medical University from August 6, 2018 to December 2, 2019 were included. A colonic transit test and high-resolution anorectal manometry were performed to compare the differences in colonic transit time, rectal anal canal pressure, and constipation classification between the two groups.

Results: There were no statistically significant differences in sex, age, body mass index, or duration of constipation between the two groups. It was found that more patients in the PDC group exhibited difficulty in defecating than in the FC group, and the difference was statistically significant. The rectal resting pressure, anal sphincter resting pressure, intrarectal pressure, and anal relaxation rate in the PDC group were significantly lower than those in the FC group. The proportion of paradoxical contractions in the PDC group was significantly higher than that in the FC group. There was a statistically significant difference in the type composition ratio of defecatory disorders between the two groups ( < 0.05). The left colonic transit time, rectosigmoid colonic transit time (RSCTT), and total colonic transit time were prolonged in PDC and FC patients compared to normal values. The patients with FC had a significantly longer right colonic transit time and a significantly shorter RSCTT than patients with PDC ( < 0.05). Mixed constipation predominated in PDC patients and FC patients, and no significant difference was observed.

Conclusion: Patients with PDC and FC have severe functional dysmotility of the colon and rectum, but there are certain differences in segmental colonic transit time and rectal anal canal pressure between the two groups.
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http://dx.doi.org/10.3748/wjg.v27.i11.1055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985734PMC
March 2021

The Efficacy of First-Generation EGFR-TKI Combined With Brain Radiotherapy as the First-Line Treatment for Lung Adenocarcinoma Patients With Brain Metastases and EGFR Sensitive Mutations: A Retrospective study.

Technol Cancer Res Treat 2021 Jan-Dec;20:1533033821997819

Cancer Center, Union Hospital, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China.

Background: It was controversial that whether LUAD patients with brain metastases (BMs) and EGFR sensitive mutations should be conducted using brain radiotherapy when treated with first-generation EGFR-TKI. Herein, a retrospective study was designed to compare the efficacy of first-generation EGFR-TKI combined with brain radiotherapy and EGFR-TKI alone as first-line treatment for these LUAD patients.

Patients And Methods: We retrospectively analyzed the status of patients with advanced LUAD carrying EGFR sensitive mutations who received first-generation EGFR-TKI treatment in our center. iPFS was the first time of intracranial progression or death from the diagnosis of BMs, PFS was the time of progression of any site or death from the diagnosis of BMs, and OS was the time of confirmed BMs to death or the last follow-up time. Differences in characteristics between groups were compared using the Chi-square test. The Kaplan-Meier method was used to calculate the iPFS, PFS, and OS. Univariate analysis, multivariate analysis, and subgroup analysis were conducted by Cox regression model.

Results: There were 77 patients (77/134, 57.5%) in the TKI + RT group and 57 patients (57/134, 42.5%) in the TKI group. TKI + RT group had a significant higher intracranial ORR and DCR, and the combination therapy was independently significantly associated with a longer iPFS (18.9 10.5 months, = 0.0009), systematic PFS (12.5 8.4 months, = 0.0071) and OS (30.8 . 22.7 months, = 0.0183). Females, non-smokers, and younger patients benefited more from the combination therapy. Subgroup analysis demonstrated that the combination therapy could improve the iPFS in patients with more than 3 BMs ( = 0.005); however, it couldn't improve the OS for these patients.

Conclusion: Our study confirmed the effect of the combination of EGFR-TKI and brain radiotherapy as first-line treatment for LUAD patients with BMs and EGFR sensitive mutations.
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http://dx.doi.org/10.1177/1533033821997819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958186PMC
March 2021
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