Publications by authors named "Yifan Xu"

145 Publications

Genome-Wide Identification of Tannase Genes and Their Function of Wound Response and Astringent Substances Accumulation in Juglandaceae.

Front Plant Sci 2021 17;12:664470. Epub 2021 May 17.

State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou, China.

Tannins are important polyphenol compounds with different component proportions in different plant species. The plants in the Juglandaceae are rich in tannins, including condensed tannins and hydrolyzable tannins. In this study, we identified seven tannase genes () responsible for the tannin metabolism from walnut, pecan, and Chinese hickory, and three nut tree species in the Juglandaceae, which were divided into two groups. The phylogenetic and sequence analysis showed that genes and neighboring clade genes ( genes) had similar sequences compared with other carboxylesterase genes, which may be the origin of genes produced by tandem repeat. genes also indicated higher expressions in leaf than other tissues and were quickly up-regulated at 3 h after leaf injury. During the development of the seed coat, the expression of the synthesis-related gene and the hydrolase gene was continuously decreased, resulting in the decrease of tannin content in the dry sample of the seed coat of Chinese hickory. However, due to the reduction in water content during the ripening process, the tannin content in fresh sample increased, so the astringent taste was obvious at the mature stage. In addition, the ' expression was higher than in the initiation of development, but continued to be down-regulated while and were up-regulated, which may bring about the significant differences in tannin content and astringent taste between Chinese hickory and pecan. These results suggested the crucial role of in wound stress of leaves and astringent ingredient accumulation in seed coats of two nut tree species in the Juglandaceae.
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http://dx.doi.org/10.3389/fpls.2021.664470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165273PMC
May 2021

Integrated study of circRNA, lncRNA, miRNA, and mRNA networks in mediating the effects of testicular heat exposure.

Cell Tissue Res 2021 May 20. Epub 2021 May 20.

School of Life Science, Bengbu Medical College, Bengbu, Anhui, China.

The World Health Organization has recognized that testicular function is temperature dependent. Testicular heat exposure caused by occupational factors, lifestyle, and clinical diseases can lead to different degrees of reproductive problems. The aim of this study was to reveal the transcriptional regulatory network and its potential crucial roles in mediating the effects of testicular heat exposure. Testicular tissue was collected from a group of mice subjected to scrotal heat exposure as well as a control group. RNA was isolated from both groups and used for high-throughput sequencing. Using differential transcriptome expression analysis, 172 circRNAs, 279 miRNAs, 465 lncRNAs, and 2721 mRNAs were identified as significantly differentially expressed in mouse testicular tissue after heat exposure compared with the control group. Through Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, differentially expressed lncRNAs and mRNAs were found to have potentially important functions in meiotic cell cycle (GO:0051321), cytoplasm (GO:0005737), membrane raft (GO:0045121), MAPK signaling (mmu04010), purine metabolism (mmu00230), and homologous recombination (mmu03440). Some of the most upregulated and downregulated lncRNAs and circRNAs were predicted to be associated with numerous miRNAs and mRNAs through competing endogenous RNA regulatory network analysis, which were validated with molecular biology experiments. This research provides high-throughput sequencing data of a testicular heat exposure model and lays the foundation for further study on circRNAs, miRNAs, and lncRNAs that are involved in male reproductive diseases related to elevated testicular temperature.
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http://dx.doi.org/10.1007/s00441-021-03474-zDOI Listing
May 2021

Susceptibility of patients with chronic obstructive pulmonary disease to heart rate difference associated with the short-term exposure to metals in ambient fine particles: A panel study in Beijing, China.

Sci China Life Sci 2021 May 13. Epub 2021 May 13.

State Key Joint Laboratory for Environmental Simulation and Pollution Control and Beijing Innovation Center for Engineering Science and Advanced Technology, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China.

Susceptibility of patients with chronic obstructive pulmonary disease (COPD) to cardiovascular autonomic dysfunction associated with exposure to metals in ambient fine particles (PM, particulate matter with aerodynamic diameter ≤2.5 µm) remains poorly evidenced. Based on the COPDB (COPD in Beijing) panel study, we aimed to compare the associations of heart rate (HR, an indicator of cardiovascular autonomic function) and exposure to metals in PM between 53 patients with COPD and 82 healthy controls by using linear mixed-effects models. In all participants, the HR levels were significantly associated with interquartile range increases in the average concentrations of Cr, Zn, and Pb, but the strength of the associations differed by exposure time (from 1.4% for an average 9 days (d) Cr exposure to 3.5% for an average 9 d Zn exposure). HR was positively associated with the average concentrations of PM and certain metals only in patients with COPD. Associations between HR and exposure to PM, K, Cr, Mn, Ni, Cu, Zn, As, and Se in patients with COPD significantly differed from those in health controls. Furthermore, association between HR and Cr exposure was robust in COPD patients. In conclusion, our findings indicate that COPD could exacerbate difference in HR following exposure to metals in PM.
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http://dx.doi.org/10.1007/s11427-020-1912-4DOI Listing
May 2021

CDK4 Amplification in Esophageal Squamous Cell Carcinoma Associated With Better Patient Outcome.

Front Genet 2021 29;12:616110. Epub 2021 Apr 29.

Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.

In the present study, we aimed to investigate the clinical and prognostic values of amplification and improve the risk stratification in patients with esophageal squamous cell carcinoma. amplification was analyzed by fluorescence hybridization using tissue microarray consisting of representative tissues of 520 patients with esophageal squamous cell carcinoma, and its correlation with clinicopathological features and clinical outcomes were evaluated. amplification was found in 8.5% (44/520) of patients with esophageal squamous cell carcinoma. amplification was negatively correlated with disease progression ( = 0.003) and death ( = 0.006). Patients with amplification showed a significantly better disease-free survival ( = 0.016) and overall survival ( = 0.023) compared with those patients without amplification. When patients were further stratified into I-II stage groups and III-IV stage groups, amplification was significantly associated with both better disease-free survival ( = 0.023) and overall survival ( = 0.025) in the I-II stage group rather than the III-IV stage group. On univariate and multivariate analysis, invasive depth and amplification were associated with disease-free survival and overall survival. Taken together, amplification was identified as an independent prognostic factor for survival, which could be incorporated into the tumor-node-metastasis staging system to refine risk stratification of patients with esophageal squamous cell carcinoma.
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http://dx.doi.org/10.3389/fgene.2021.616110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116700PMC
April 2021

Kidney Transplant List Status and Outcomes in the ISCHEMIA-CKD Trial.

J Am Coll Cardiol 2021 May 4. Epub 2021 May 4.

NYU Grossman School of Medicine, New York, NY, USA.

Background: Patients with chronic kidney disease (CKD) and coronary artery disease frequently undergo preemptive revascularization before kidney transplant listing.

Objectives: In this post-hoc analysis from ISCHEMIA-CKD, we compared outcomes of patients not listed versus those listed according to management strategy.

Methods: In ISCHEMIA-CKD (n=777), 194 patients (25%) with chronic coronary syndromes and at least moderate ischemia were listed for transplant. The primary (all-cause mortality or nonfatal myocardial infarction [MI]) and secondary (death, nonfatal MI, hospitalization for unstable angina, heart failure, resuscitated cardiac arrest, or stroke) outcomes were analyzed using Cox multivariable modeling. Heterogeneity of randomized treatment effect between listed versus not listed groups was assessed.

Results: Compared with those not listed, listed patients were younger (60 versus 65 years), less likely of Asian race (15% versus 29%), more likely on dialysis (83% versus 44%), had fewer anginal symptoms, and more likely to have coronary angiography and coronary revascularization irrespective of treatment assignment. Among patients assigned to an invasive strategy versus conservative strategy, the adjusted hazard ratios (aHR) (95% confidence interval [CI]) for the primary outcome were 0.91 (0.54-1.54) and 1.03 (0.78-1.37) for those listed and not listed, respectively (pinteraction=0.68). Adjusted HR for secondary outcomes were 0.89 (0.55-1.46) in listed and 1.17 (0.89-1.53) in those not listed (pinteraction=0.35).

Conclusions: In ISCHEMIA-CKD, an invasive strategy in kidney transplant candidates did not improve outcomes compared with conservative management. These data do not support routine coronary angiography or revascularization in patients with advanced CKD and chronic coronary syndromes listed for transplant.
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http://dx.doi.org/10.1016/j.jacc.2021.05.001DOI Listing
May 2021

Electrospun heparin-loaded nano-fiber sutures for the amelioration of achilles tendon rupture regeneration: evaluation.

J Mater Chem B 2021 05;9(20):4154-4168

Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.

Peritendinous blood circulation improvement is a challenge to promote the healing of ruptured tendons in clinical treatment. Although electrospun membranes or scaffolds enable the reduction of complications such as adhesion, however, low efficiency, toxicity issues, the loss of biological activity, and complex electrospinning techniques are all bottlenecks of these systems. Improving the blood supply is crucial for their successful use, which involves promoting the metabolism and nutrient absorption in tendons. Here, a multifunctional, structurally simple strategy involving heparin-loaded sutures (PPH) that are clinically applicable is reported, in the form of electrospun core-shell nanofibers, with the ability to perform sustained release of anticoagulants heparin (verified in our previous publication) for the improvement of the healing of Achilles tendon. The morphology and diameter distribution of the collagen fiber in the PPH group are closely related to the health of the Achilles tendon than those of commercial sutures (CS). The in vivo results of the total collagen content and the expression of collagen type I in the PPH group are more than those of the CS group. After 6 weeks of culture, the tensile strength of the PPH group shows no significant difference compared to the healthy group. The data obtained in this study improves the current understanding on the regeneration of ruptured tendons and presents a promising strategy for clinical treatment.
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http://dx.doi.org/10.1039/d1tb00162kDOI Listing
May 2021

Physiological functions and therapeutic applications of neutral sphingomyelinase and acid sphingomyelinase.

Biomed Pharmacother 2021 Jul 3;139:111610. Epub 2021 May 3.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address:

Sphingomyelin (SM) can be converted into ceramide (Cer) by neutral sphingomyelinase (NSM) and acid sphingomyelinase (ASM). Cer is a second messenger of lipids and can regulate cell growth and apoptosis. Increasing evidence shows that NSM and ASM play key roles in many processes, such as apoptosis, immune function and inflammation. Therefore, NSM and ASM have broad prospects in clinical treatments, especially in cancer, cardiovascular diseases (such as atherosclerosis), nervous system diseases (such as Alzheimer's disease), respiratory diseases (such as chronic obstructive pulmonary disease) and the phenotype of dwarfisms in adolescents, playing a complex regulatory role. This review focuses on the physiological functions of NSM and ASM and summarizes their roles in certain diseases and their potential applications in therapy.
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http://dx.doi.org/10.1016/j.biopha.2021.111610DOI Listing
July 2021

Analysis of the Australia and New Zealand referral criteria for transfer to a liver unit for paracetamol overdose.

Emerg Med Australas 2021 May 4. Epub 2021 May 4.

Department of Critical Care, The University of Melbourne, Melbourne, Victoria, Australia.

Objectives: Paracetamol overdose is common and can lead to fulminant hepatic failure. In cases that are not improving with standard medical therapy with N-acetylcysteine, some patients may require liver transplant. The Australia and New Zealand (ANZ) referral criteria for transfer to a liver unit have not been extensively studied for its predictive value. The aim of this study was to evaluate the ANZ referral criteria for predicting mortality in paracetamol overdose.

Methods: This study involves a retrospective analysis of patients who developed hepatotoxicity post-paracetamol overdose presenting to an Australian health service with a liver transplant unit between 2010 and 2019 and were treated with N-acetylcysteine. The primary outcome was death or transplant.

Results: Out of 983 paracetamol overdose presentations, 81 (8.2%) cases developed hepatotoxicity. Of these, 17 cases (21%) met the composite endpoint of death or transplant. The ANZ referral criteria is highly sensitive at predicting the primary endpoint of death or transplant at time of referral 100% (95% confidence interval 81-100) but had low specificity at 30% (95% confidence interval 19-42).

Conclusions: The ANZ referral criteria were highly sensitive for predicting the outcome of mortality and transplant. This is important for screening patients who may become unstable and difficult to transfer at a later stage of their admission.
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http://dx.doi.org/10.1111/1742-6723.13795DOI Listing
May 2021

Long non-coding RNA XIST promotes retinoblastoma cell proliferation, migration, and invasion by modulating microRNA-191-5p/brain derived neurotrophic factor.

Bioengineered 2021 Dec;12(1):1587-1598

Department of ophtalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is oncogenic in multiple cancers. Herein, the present study is aimed at delving into how XIST functions in retinoblastoma (RB) and investigating its underlying mechanism. In this study, XIST, miR-191-5p, BDNF mRNA, and BDNF expression levels in RB tissues or cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. The models of gain-of-function and loss-of-function were established by the transfection of pcDNA3.1-XIST, XIST siRNA, and miR-191-5p mimics and inhibitors into SO-Rb50 and Y79 cells, respectively. RB cell proliferation, migration, invasion, and apoptosis were detected employing cell counting kit-8 (CCK-8), Transwell, and terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) assays. The regulatory relationships among XIST, miR-191-5p, and BDNF were affirmed utilizing bioinformatics analysis, luciferase reporter assay, qRT-PCR, as well as Western blot. We reported that, XIST expression was markedly elevated in RB tissue and RB cells. XIST overexpression accelerated RB cell proliferation, migration, and invasion, and attenuated RB cell apoptosis but miR-191-5p exerted the opposite effects. Besides, BDNF expression was inhibited by miR-191-5p in both mRNA and protein levels. XIST indirectly improved BDNF expression by repressing miR-191-5p expression as a competitive endogenous RNA. In conclusion, XIST expression is abnormally elevated in RB tissues and XIST can modulate proliferation, migration, invasion, and apoptosis of RB cells by regulating miR-191-5p/BDNF axis.
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http://dx.doi.org/10.1080/21655979.2021.1918991DOI Listing
December 2021

The Efficacy of Computerized Cognitive Behavioral Therapy for Depressive and Anxiety Symptoms in Patients With COVID-19: Randomized Controlled Trial.

J Med Internet Res 2021 05 14;23(5):e26883. Epub 2021 May 14.

Department of Psychiatry, The First Hospital of Shanxi Medical University, Taiyuan, China.

Background: The prevalence of depressive and anxiety symptoms in patients with COVID-19 is higher than usual. Previous studies have shown that there are drug-to-drug interactions between antiretroviral drugs and antidepressants. Therefore, an effective and safe treatment method was needed. Cognitive behavioral therapy (CBT) is the first-line psychological therapy in clinical treatment. Computerized CBT (cCBT) was proven to be an effective alternative to CBT and does not require face-to-face therapy between a therapist and the patient, which suited the COVID-19 pandemic response.

Objective: This study aims to evaluate the efficacy of the cCBT program we developed in improving depressive and anxiety symptoms among patients with COVID-19.

Methods: We customized a cCBT program focused on improving depressive and anxiety symptoms among patients with COVID-19, and then, we assessed its effectiveness. Screening was based on symptoms of depression or anxiety for patients who scored ≥7 on the Hamilton Depression Rating Scale (HAMD) or the Hamilton Anxiety Scale (HAMA). A total of 252 patients with COVID-19 at five sites were randomized into two groups: cCBT + treatment as usual (TAU; n=126) and TAU without cCBT (n=126). The cCBT + TAU group received the cCBT intervention program for 1 week. The primary efficacy measures were the HAMD and HAMA scores. The secondary outcome measures were the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Athens Insomnia Scale (AIS). Assessments were carried out pre- and postintervention. The patients' symptoms of anxiety and depression in one of the centers were assessed again within 1 month after the postintervention assessment.

Results: The cCBT + TAU group displayed a significantly decreased score on the HAMD, HAMA, SDS, SAS, and AIS after the intervention compared to the TAU group (all P<.001). A mixed-effects repeated measures model revealed significant improvement in symptoms of depression (HAMD and SDS scores, both P<.001), anxiety (HAMA and SAS scores, both P<.001), and insomnia (AIS score, P=.002) during the postintervention and follow-up periods in the cCBT + TAU group. Additionally, the improvement of insomnia among females (P=.14) and those with middle school education (P=.48) in the cCBT + TAU group showed no significant differences when compared to the TAU group.

Conclusions: The findings of this study suggest that the cCBT program we developed was an effective nonpharmacological treatment for symptoms of anxiety, depression, and insomnia among patients with COVID-19. Further research is warranted to investigate the long-term effects of cCBT for symptoms of anxiety, depression, and insomnia in patients with COVID-19.

Trial Registration: Chinese Clinical Trial Registry ChiCTR2000030084; http://www.chictr.org.cn/showprojen.aspx?proj=49952.
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http://dx.doi.org/10.2196/26883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128049PMC
May 2021

High circulating insulin-like growth factor-1 reduces the risk of renal cell carcinoma: a Mendelian randomization study.

Carcinogenesis 2021 Jun;42(6):826-830

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

Insulin and insulin-like growth factors play important roles in carcinogenesis. Circulating insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have been linked to cancer susceptibility. The associations of circulating IGF-1 and IGFBP-3 with the risk of renal cell carcinoma (RCC) are inconsistent. Recent large genome-wide association studies have identified 413 single nucleotide polymorphisms (SNPs) associated with IGF-1 and 4 SNPs associated with IGFBP-3. In this large case-control study consisting of 2069 RCC patients and 2052 healthy controls of European ancestry, we used a two-sample Mendelian randomization (MR) approach to investigate the associations of genetically predicted circulating IGF-1 and IGFBP-3 with RCC risk. We used an individual level data-based genetic risk score (GRS) and a summary statistics-based inverse-variance weighting (IVW) method in MR analyses. We found that genetically predicted IGF-1 was significantly associated with RCC risk in both the GRS analysis [odds ratio (OR) = 0.43 per SD increase, 95% confidence interval (CI), 0.34-0.53] and the IVW analysis (OR = 0.46 per SD increase, 95% CI, 0.37-0.57). Dichotomized at the median GRS value of IGF-1 in controls, individuals with high GRS had a 45% reduced RCC risk (OR = 0.55, 95% CI, 0.48-0.62) compared with those with low GRS. Genetically predicted circulating IGFBP-3 was not associated with RCC risk. This is the largest RCC study of circulating IGF-1 and IGFBP-3 to date and our data suggest a strong inverse relationship between circulating IGF-1 level and RCC risk.
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http://dx.doi.org/10.1093/carcin/bgab031DOI Listing
June 2021

Phase flicker minimisation for crosstalk suppression in optical switches based on digital liquid crystal on silicon devices.

Opt Express 2021 Mar;29(7):10556-10567

The phase flicker in digital liquid crystal on silicon (LCOS) device introduces temporal phase noise to the phase pattern displayed on the device. Such temporal phase noise could elevate the power of unwanted diffraction orders and ultimately cause crosstalk in optical switches based on the LCOS technology. Building on our previous work, this paper demonstrated an automated phase flicker optimisation process by using the genetic algorithm. The method developed in this work further shortened the optimisation process by 10x. It was also demonstrated that the optimised digital driving waveform set was able to reduce the crosstalk level in the optical switches by at least 3 dB.
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http://dx.doi.org/10.1364/OE.415800DOI Listing
March 2021

Genome-wide DNA methylation profiling of leukocytes identifies CpG methylation signatures of aggressive prostate cancer.

Am J Cancer Res 2021 1;11(3):968-978. Epub 2021 Mar 1.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center Houston, TX 77030, USA.

Most of screening-detected prostate cancer (PCa) are indolent and not lethal. Biomarkers that can predict aggressive diseases independently of clinical features are needed to improve risk stratification of localized PCa patients and reduce overtreatment. We aimed to identify leukocyte DNA methylation differences between clinically defined aggressive and non-aggressive PCa. We performed whole genome DNA methylation profiling in leukocyte DNA from 287 PCa patients with Gleason Score (GS) 6 and ≥8 using Illumina 450k methylation arrays. We observed a global hypomethylation in GS≥8 patients compared to GS=6 PCa patients; in contrast, the methylation level in core promoter and exon 1 region was significantly higher in GS≥8 patients than GS=6 PCa. We then performed 5-fold cross validated random forest model training on 1,459 differentially methylated CpG Probes (DMPs) with false discovery rate (FDR) <0.01 between GS=6 and GS≥8 groups. The power of the predictive model was further reinforced by ranking the DMPs with Decreased Gini and re-train the model with the top 97 DMPs (Testing AUC=0.920, predict accuracy =0.847). In conclusion, we identified a CpG methylation signature in leukocyte DNA that is associated with aggressive clinical features of PCa at diagnosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994169PMC
March 2021

Distinct progenitor behavior underlying neocortical gliogenesis related to tumorigenesis.

Cell Rep 2021 Mar;34(11):108853

IDG/McGovern Institute for Brain Research, Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center of Biological Structure, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Neuroscience Graduate Program, Feil Family Brain & Mind Research Institute, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address:

Radial glial progenitors (RGPs) give rise to the vast majority of neurons and glia in the neocortex. Although RGP behavior and progressive generation of neocortical neurons have been delineated, the exact process of neocortical gliogenesis remains elusive. Here, we report the precise progenitor behavior and gliogenesis program at single-cell resolution in the mouse neocortex. Fractions of dorsal RGPs transition from neurogenesis to gliogenesis progressively, producing astrocytes, oligodendrocytes, or both in well-defined propensities of ∼60%, 15%, and 25%, respectively, by fate-restricted "intermediate" precursor cells (IPCs). Although the total number of IPCs generated by individual RGPs appears stochastic, the output of individual IPCs exhibit clear patterns in number and subtype and form discrete local subclusters. Clonal loss of tumor suppressor Neurofibromatosis type 1 leads to excessive production of glia selectively, especially oligodendrocyte precursor cells. These results quantitatively delineate the cellular program of neocortical gliogenesis and suggest the cellular and lineage origin of primary brain tumor.
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http://dx.doi.org/10.1016/j.celrep.2021.108853DOI Listing
March 2021

Distinct progenitor behavior underlying neocortical gliogenesis related to tumorigenesis.

Cell Rep 2021 Mar;34(11):108853

IDG/McGovern Institute for Brain Research, Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center of Biological Structure, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Neuroscience Graduate Program, Feil Family Brain & Mind Research Institute, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address:

Radial glial progenitors (RGPs) give rise to the vast majority of neurons and glia in the neocortex. Although RGP behavior and progressive generation of neocortical neurons have been delineated, the exact process of neocortical gliogenesis remains elusive. Here, we report the precise progenitor behavior and gliogenesis program at single-cell resolution in the mouse neocortex. Fractions of dorsal RGPs transition from neurogenesis to gliogenesis progressively, producing astrocytes, oligodendrocytes, or both in well-defined propensities of ∼60%, 15%, and 25%, respectively, by fate-restricted "intermediate" precursor cells (IPCs). Although the total number of IPCs generated by individual RGPs appears stochastic, the output of individual IPCs exhibit clear patterns in number and subtype and form discrete local subclusters. Clonal loss of tumor suppressor Neurofibromatosis type 1 leads to excessive production of glia selectively, especially oligodendrocyte precursor cells. These results quantitatively delineate the cellular program of neocortical gliogenesis and suggest the cellular and lineage origin of primary brain tumor.
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http://dx.doi.org/10.1016/j.celrep.2021.108853DOI Listing
March 2021

Dietary Assessment Methods to Estimate (Poly)phenol Intake in Epidemiological Studies: A Systematic Review.

Adv Nutr 2021 Mar 3. Epub 2021 Mar 3.

Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.

Nutritional epidemiological studies have frequently reported associations between higher (poly)phenol intake and a decrease in the risk or incidence of noncommunicable diseases. However, the assessment methods that have been used to quantify the intakes of these compounds in large-population samples are highly variable. This systematic review aims to characterize the methods used to assess dietary (poly)phenol intake in observational studies, report the validation status of the methods, and give recommendations on method selection and data reporting. Three databases were searched for publications that have used dietary assessment methods to measure (poly)phenol intake and 549 eligible full texts were identified. Food-frequency questionnaires were found to be the most commonly used tool to assess dietary (poly)phenol intake (73%). Published data from peer-reviewed journals were the major source of (poly)phenol content data (25%). An increasing number of studies used open-access databases such as Phenol-Explorer and USDA databases on flavonoid content since their inception, which accounted for 11% and 23% of the data sources, respectively. Only 16% of the studies reported a method that had been validated for measuring the target (poly)phenols. For future research we recommend: 1) selecting a validated dietary assessment tool according to the target compounds and target period of measurement; 2) applying and combining comprehensive (poly)phenol content databases such as USDA and Phenol-Explorer; 3) detailing the methods used to assess (poly)phenol intake, including dietary assessment method, (poly)phenol content data source; 4) follow the Strengthening the Reporting of Observational Studies in Epidemiology-Nutritional Epidemiology (STROBE-nut) framework; and 5) complementing dietary intake assessment based on questionnaires with measurement of (poly)phenols in biofluids using appropriate and validated analytical methods.
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http://dx.doi.org/10.1093/advances/nmab017DOI Listing
March 2021

Biomolecular Modeling and Simulation: A Prospering Multidisciplinary Field.

Annu Rev Biophys 2021 05 19;50:267-301. Epub 2021 Feb 19.

College of Arts and Science, New York University, New York, New York 10003, USA.

We reassess progress in the field of biomolecular modeling and simulation, following up on our perspective published in 2011. By reviewing metrics for the field's productivity and providing examples of success, we underscore the productive phase of the field, whose short-term expectations were overestimated and long-term effects underestimated. Such successes include prediction of structures and mechanisms; generation of new insights into biomolecular activity; and thriving collaborations between modeling and experimentation, including experiments driven by modeling. We also discuss the impact of field exercises and web games on the field's progress. Overall, we note tremendous success by the biomolecular modeling community in utilization of computer power; improvement in force fields; and development and application of new algorithms, notably machine learning and artificial intelligence. The combined advances are enhancing the accuracy andscope of modeling and simulation, establishing an exemplary discipline where experiment and theory or simulations are full partners.
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http://dx.doi.org/10.1146/annurev-biophys-091720-102019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105287PMC
May 2021

Effects of metformin on the osteogenesis of alveolar BMSCs from diabetic patients and implant osseointegration in rats.

Oral Dis 2021 Feb 19. Epub 2021 Feb 19.

Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.

Objectives: This study aimed to explore the effects of metformin on osteogenic differentiation of alveolar bone marrow mesenchymal stem cells (BMSCs) from type-2 diabetes mellitus (T2DM) patients (DM-BMSCs) and implant osseointegration in rats, screen the optimal concentration, and investigate whether metformin could protect against the adverse impact of T2DM on BMSC osteogenic capacity.

Subjects And Methods: Different concentrations of metformin were administered to human-derived BMSCs and Wistar rats receiving implants. ALP detection, alizarin red staining, real-time RT-PCR and Western blotting were performed to detect osteogenesis and investigate the mechanism. Toluidine blue staining was performed to analyse bone-implant contact in rats.

Results: Metformin increased implant osseointegration in a rat model and promoted the osteogenic capacity of DM-BMSCs via the AMPK/BMP/Smad signalling pathway, and 125 μM was the optimal concentration; however, concentrations over 200 µM, metformin showed an inhibitory effect on DM-BMSCs. Additionally, metformin at the optimal concentration (125 µM) identified in this study could compensate for the negative impacts of T2DM on the osteogenic differentiation of BMSCs.

Conclusions: Metformin can promote the osteogenesis of BMSCs from T2DM patients and osseointegration in rats, and it might be an effective drug for increasing the success rate of T2DM-associated implants.
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http://dx.doi.org/10.1111/odi.13808DOI Listing
February 2021

Anesthetic Management of Asleep and Awake Craniotomy for Supratentorial Tumor Resection.

Anesthesiol Clin 2021 Mar;39(1):71-92

Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Mail Code UH2, Portland, OR 97239, USA.

Understanding how anesthetics impact cerebral physiology, cerebral blood flow, brain metabolism, brain relaxation, and neurologic recovery is crucial for optimizing anesthesia during supratentorial craniotomies. Intraoperative goals for supratentorial tumor resection include maintaining cerebral perfusion pressure and cerebral autoregulation, optimizing surgical access and neuromonitoring, and facilitating rapid, cooperative emergence. Evidence-based studies increasingly expand the impact of anesthetic care beyond immediate perioperative care into both preoperative optimization and minimizing postoperative consequences. New evidence is needed for neuroanesthesia's role in neurooncology, in preventing conversion from acute to chronic pain, and in decreasing risk of intraoperative ischemia and postoperative delirium.
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http://dx.doi.org/10.1016/j.anclin.2020.11.007DOI Listing
March 2021

Pain Management in Neurosurgery: Back and Lower Extremity Pain, Trigeminal Neuralgia.

Anesthesiol Clin 2021 Mar;39(1):179-194

Anesthesiology, Medical College of Wisconsin, Milwaukee, 959 North Mayfair Road, Wauwatosa, WI 53226, USA.

Interventional anesthetic techniques are an integral component of a biopsychosocial approach and multidisciplinary treatment. Injection techniques are often used to diagnose disorders, decrease the need for surgery, or increase the time to surgery. The role of neural blockade techniques using local anesthetics and steroids in the assessment and treatment of pain continues to be refined. With the current opioid crisis and an aging population with increasing medical comorbidities, there is an emphasis on the use of nonopioid, nonsurgical, and multimodal therapies to treat chronic pain. This article reviews indications, goals, and methods of common injection techniques.
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http://dx.doi.org/10.1016/j.anclin.2020.11.004DOI Listing
March 2021

Self-Catalyzed Surface Reaction-Induced Fluorescence Resonance Energy Transfer on Cysteine-Stabilized MnO Quantum Dots for Selective Detection of Dopamine.

Anal Chem 2021 02 5;93(7):3586-3593. Epub 2021 Feb 5.

Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education, China), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, PR China.

A simple one-step ultrasonic method was developed for the synthesis of luminescent MnO quantum dots (MnO QDs) in the presence of cysteine, in which cysteine acted as the exfoliating agent and stabilization ligand. The cysteine-stabilized MnO QDs (Cys-MnO QDs) possess a fluorescence quantum yield of 4.7%, and the fluorescence intensity of Cys-MnO QDs is sensitive to dopamine (DA). The mechanism by which the Cys-MnO QDs catalyzed the self-polymerization of DA to form polydopamine nanoparticles (PDA NPs) and caused the fluorescence resonance energy transfer (FRET) between MnO QDs and PDA NPs was revealed. The sensing platform displayed a wide detection range (0.1-200 μM) with a low detection limit of 28 nM for the detection of DA. Moreover, the Michael addition/Schiff base reaction between the PDA NPs and cysteine on MnO QDs was demonstrated to facilitate the excellent selectivity toward DA detection in the presence of various interferences. This work not only develops a robust method for the preparation of highly luminescent MnO QDs but also provides a universal strategy on the basis of surface chemical reaction-induced FRET for the detection of DA with high sensitivity and selectivity, which is promising in the application of clinical diagnosis, drug delivery, and fluorescence-guided cancer therapy.
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http://dx.doi.org/10.1021/acs.analchem.0c05102DOI Listing
February 2021

Green light extends Drosophila longevity.

Exp Gerontol 2021 05 1;147:111268. Epub 2021 Feb 1.

College of Life Information Science & Instrument Engineering, Hangzhou Dianzi University, Hangzhou 310018, China.

The role of visible light on longevity is incompletely understood. Here we show the effect of visible light in Drosophila melanogaster is wavelength specific. Life span was significantly extended by green light, whereas blue light reduced longevity dramatically, and minor impact was observed with red light. While oxidative stress, heat stress, or caloric restriction does not contribute to the beneficial effect of green light, our study found that the life span extension effect of green light might be mediated by microbiota or photosensitive micronutrients in food medium. In conclusion, we report that green light can extend longevity and present the potential of light as a noninvasive therapy for aging-related diseases.
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http://dx.doi.org/10.1016/j.exger.2021.111268DOI Listing
May 2021

Krebs von den Lungen-6 and surfactant protein-A in interstitial pneumonia with autoimmune features.

Medicine (Baltimore) 2021 Jan;100(4):e24260

Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou.

Abstract: Interstitial pneumonia with autoimmune features (IPAF) is a special subtype of interstitial lung disease that has received worldwide attention. Krebs von den Lungen-6 (KL-6) and surfactant protein-A (SP-A) can be used as an important biomarker of interstitial lung disease, but its exact relationship with IPAF is poorly understood.A total of 65 IPAF patients were included in the study and were followed up for 52 weeks. The KL-6 and SP-A were evaluated by chemiluminescence enzyme immunoassay. The above indicators were tested at 2 time points, baseline (the first admission of patients) and 52 weeks. We also collected the indicators of antinuclear antibodies and rheumatoid factor. Based on high-resolution computed tomography evaluations, patients were divided into: aggravation, stable, and improvement group. At same time, 30 age-matched normal people as normal control were recruited, the same information was collected. Correlations among the groups were compared and analyzed.The KL-6 and SP-A level in IPAF patients were significantly higher than normal controls (fold increase = 11.35 and 1.39, both P < .001) and differed significantly at baseline and 52 weeks in IPAF (difference ratio = 37.7% and 21.3%, P < .05, both). There were significant differences at baseline and 52 weeks (r values of aggravation, improvement, and stable groups for KL-6 were 0.705, 0.770, and 0.344, P = .001, .001, and .163, and for SP-A the r value were 0.672, 0.375, and 0.316, P = .001, .126, and .152). In aggravation group, KL-6 and SP-A were correlated with CT scores (both P < .05). Diffusing capacity of the lung for carbon monoxide (DLCO) and forced vital capacity (FVC), % predicted showed a progressive downward trend, with a significant difference at baseline and 52 weeks in IPAF patients (difference ratio = 23.8% and 20.6%, both P < .05). There was a significant correlation between KL-6 and FVC % predicted and DLCO (both P < .05), SP-A showed negatively correlated with DLCO, but not significantly correlated with FVC % predicted (P < .05 and .47).This study demonstrated that KL-6 and SP-A can reflect disease progression, and both 2 play a key role at reflection of lung epithelial cell injury and fibrosis degree in IPAF.
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http://dx.doi.org/10.1097/MD.0000000000024260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850699PMC
January 2021

A powerful arsenite-oxidizing biofilm bioreactor derived from a single chemoautotrophic bacterial strain: Bioreactor construction, long-term operations and kinetic analysis.

Chemosphere 2021 Jun 18;273:129672. Epub 2021 Jan 18.

State Key Laboratory of Biogeology and Environmental Geology & School of Environmental Studies, China University of Geosciences (Wuhan), Wuhan, 430070, People's Republic of China.

Microbial oxidation of As(III) by biofilm bioreactors followed by adsorption is a promising and environment friendly approach to remediate As(III) contaminated groundwater; however, poor activity, stability and expandability of the bioreactors hampered their industrious applications. To resolve this issue, we constructed a new biofilm bioreactor using a powerful chemoautotrophic As(III)-oxidizing bacterium Rhizobium sp. A219. This strain has strong ability to form biofilms and possesses very high As(III)-oxidizing activities in both planktonic and biofilm forms. Perlites were used as the biofilm carriers. Long-term operations suggest that the bioreactor has very high efficiency, stability and scalability under different geochemical conditions, and it is cheap and easy to construct and operate. During the operations, it is only required to supply air, nothing else. All the common contaminants in groundwater slightly affected the bioreactor As(III)-oxidizing activity. The common contaminants in groundwater can be largely removed through assimilation by the bacterial cells as nutrition. The bioreactor completely oxidize 1.0, 5.0, 10.0, 20.0 and 30.0 mg/L As(III) in 12, 18, 20, 25 and 30 min, respectively. Approximately 18, 18, 12, 12 and 21 min were needed to oxidize 1.1 mg/L As(III) at 20, 25, 30, 35 and 40 °C, respectively. The bioreactor works well under the pH values of 5-8, and the most optimal was 7.0. The data suggest that this bioreactor possesses the highest efficiency and stability, and thus has the great potential for industrial applications among all the described As(III)-oxidizing bioreactors derived from a single bacterium.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129672DOI Listing
June 2021

Cadmium induced skeletal underdevelopment, liver cell apoptosis and hepatic energy metabolism disorder in Bufo gargarizans larvae by disrupting thyroid hormone signaling.

Ecotoxicol Environ Saf 2021 Mar 25;211:111957. Epub 2021 Jan 25.

College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China. Electronic address:

Cadmium (Cd) is hazardous to human health and it is also highly detrimental to amphibian life. In this study, Bufo gargarizans larvae were exposed to environmentally relevant Cd concentrations of 5, 100 and 200 μg L from Gosner stage (Gs) 26 to Gs 42 of metamorphic climax about 6 weeks. The results showed thyroid structural injuries and thyroid signaling disruption were induced by high Cd exposure (100 and 200 μg L). Moreover, tadpole skeleton including whole body, vertebrata, forelimb and hindlimb was developmentally delayed by high Cd exposure through downregulating the mRNA expressions of genes involved with skeletal ossification and growth pathway. Moreover, liver histopathological injuries were caused by high Cd exposure featured by hepatocytes malformation, nuclear degeneration and increasing melanomacrophage centers. Meanwhile, liver apoptosis rate showed on the rise in a dose-dependent way and Cd stimulated liver apoptosis by upregulating mRNA expressions of genes related to extrinsic and intrinsic apoptosis pathways. Furthermore, high Cd caused hepatic glucometabolism disorder by decreasing the genetic expressions associated with glycolysis and mitochondrial oxidative phosphorylation. In addition, liver lipid metabolism was disrupted by high Cd exposure through downregulating mRNA levels of genes related to fatty oxidation and upregulating mRNA levels of genes related to fatty acid synthesis. We suggested that Cd did great harm to tadpole health by disturbing thyroid function, skeletal growth, liver cell apoptosis signaling and hepatic energy metabolism pathway.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111957DOI Listing
March 2021

Mesenchymal stem cells as a double-edged sword in tumor growth: focusing on MSC-derived cytokines.

Cell Mol Biol Lett 2021 Jan 20;26(1). Epub 2021 Jan 20.

Department of Orthopaedics, Shaoxing People's Hospital, The First Affiliated Hospital of Shaoxing University, Shaoxing, 312000, Zhejiang, People's Republic of China.

Mesenchymal stem cells (MSCs) show homing capacity towards tumor sites. Numerous reports indicate that they are involved in multiple tumor-promoting processes through several mechanisms, including immunosuppression; stimulation of angiogenesis; transition to cancer-associated fibroblasts; inhibition of cancer cell apoptosis; induction of epithelial-mesenchymal transition (EMT); and increase metastasis and chemoresistance. However, other studies have shown that MSCs suppress tumor growth by suppressing angiogenesis, incrementing inflammatory infiltration, apoptosis and cell cycle arrest, and inhibiting the AKT and Wnt signaling pathways. In this review, we discuss the supportive and suppressive impacts of MSCs on tumor progression and metastasis. We also discuss MSC-based therapeutic strategies for cancer based on their potential for homing to tumor sites.
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http://dx.doi.org/10.1186/s11658-020-00246-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818947PMC
January 2021

Mesenchymal stem cells as a double-edged sword in tumor growth: focusing on MSC-derived cytokines.

Cell Mol Biol Lett 2021 Jan 20;26(1). Epub 2021 Jan 20.

Department of Orthopaedics, Shaoxing People's Hospital, The First Affiliated Hospital of Shaoxing University, Shaoxing, 312000, Zhejiang, People's Republic of China.

Mesenchymal stem cells (MSCs) show homing capacity towards tumor sites. Numerous reports indicate that they are involved in multiple tumor-promoting processes through several mechanisms, including immunosuppression; stimulation of angiogenesis; transition to cancer-associated fibroblasts; inhibition of cancer cell apoptosis; induction of epithelial-mesenchymal transition (EMT); and increase metastasis and chemoresistance. However, other studies have shown that MSCs suppress tumor growth by suppressing angiogenesis, incrementing inflammatory infiltration, apoptosis and cell cycle arrest, and inhibiting the AKT and Wnt signaling pathways. In this review, we discuss the supportive and suppressive impacts of MSCs on tumor progression and metastasis. We also discuss MSC-based therapeutic strategies for cancer based on their potential for homing to tumor sites.
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http://dx.doi.org/10.1186/s11658-020-00246-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818947PMC
January 2021

Quantitative Assessment of Dietary (Poly)phenol Intake: A High-Throughput Targeted Metabolomics Method for Blood and Urine Samples.

J Agric Food Chem 2021 Jan 29;69(1):537-554. Epub 2020 Dec 29.

Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Science and Medicine, King's College London, London SE1 9NH, U.K.

Many studies have associated the consumption of (poly)phenol-rich diets with health benefits. However, accurate high-throughput quantitative methods for estimating exposure covering a broad spectrum of (poly)phenols are lacking. We have developed and validated a high-throughput method for the simultaneous quantification of 119 (poly)phenol metabolites in plasma and urine using ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry, with a very fast sample treatment and a single run time of 16 min. This method is highly sensitive, precise, accurate, and shows good linearity for all compounds ( > 0.992). This novel method will allow a quantitative assessment of habitual (poly)phenol intake in large epidemiological studies as well as clinical studies investigating the health benefits of dietary (poly)phenols.
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http://dx.doi.org/10.1021/acs.jafc.0c07055DOI Listing
January 2021

Changes in bioactive lipid mediators in response to short-term exposure to ambient air particulate matter: A targeted lipidomic analysis of oxylipin signaling pathways.

Environ Int 2021 02 14;147:106314. Epub 2020 Dec 14.

BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. Electronic address:

Background: Exposure to ambient air particulate matter (PM) is a risk factor for cardiometabolic diseases. The knowledge of the underlying mechanisms is still evolving, but systemic inflammation and oxidative stress are central to the ability of PM to induce cardiometabolic effects. Oxylipins derived from polyunsaturated fatty acids (PUFAs) are bioactive lipid mediators that have fundamental roles in the signaling of inflammatory events. However, the associations between oxylipins and short-term exposure to PM in humans are unknown.

Methods: Using targeted lipidomic analyses, we measured 16 oxylipins derived from lipoxygenase (LOX), cytochrome P450 (CYP), and cyclooxygenase (COX) pathways and their parent PUFAs in serum samples of 110 adults enrolled in a panel study in Beijing, China. Each participant completed 2-7 clinical visits from 2013 to 2015. PM with aerodynamic diameter ≤ 2.5 μm (PM) and ≤ 0.1 μm (ultrafine particles, UFPs) were continuously monitored at a station. Linear mixed-effects models were applied to examine the associations between changes in lipid mediators and exposure to ambient PM during the preceding 1 to 3 days before the clinical visit.

Results: Serum concentrations of PUFAs, including omega-6 arachidonic acid (ARA) and omega-3 eicosapentaenoic acid (EPA), were significantly increased in association with interquartile range (IQR) increases in PM with different exposure windows (i.e., 1-3 days). Regarding oxylipins, significant PM-associated changes included increases in LOX-derived leukotriene B4 (LTB4), 12(S)-, 15(S)-hydroxyeicosatetraenoic acid (HETE), 12-hydroxyeicosapentaenoic acid (HEPE), and 17-hydroxydocosahexaenoic acid (HDHA); an increase in CYP-derived 5,6-dihydroxyeicosatrienoic acid (DHET); and a decrease in COX-derived prostaglandin E2.

Conclusions: Short-term exposure to PM was associated with PUFAs and oxylipins derived from LOX, CYP, and COX pathways in humans. Our findings provide mechanistic insight suggesting bioactive oxylipins might be used as biomarkers and have important implications as mediators of PM-associated systemic cardiometabolic effects.
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http://dx.doi.org/10.1016/j.envint.2020.106314DOI Listing
February 2021

Risk factors related to intracranial infections after transsphenoidal pituitary adenomectomy under endoscope.

Ideggyogy Sz 2020 Nov;73(11-12):399-403

Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Department of Neurosurgery, Nanjing 210000, Jiangsu Province, P. R. China.

Background And Purpose: Background - Up to now, the risk factors related to intracranial infections after transsphenoidal pituitary adenomectomy remain controversial. Purpose - To analyze the risk factors related to intracranial infections after transsphenoidal pituitary adenomectomy under an endoscope, and to provide evidence for preventing and controlling the occurrence and development of infections.

Methods: A total of 370 patients receiving endoscopic transsphenoidal pituitary adenomectomy in our hospital from January 2014 to October 2017 were selected. The risk factors related to postoperative intracranial infections were analyzed. The hospitalization lengths and expenditures of patients with and without intracranial infections were compared.

Results: Of the 370 patients, 18 underwent postoperative intracranial infections, with the infection rate of 4.86%. Intraoperative blood loss >120 mL, cerebrospinal leakage, diabetes, preoperative use of hormones, macroadenoma as well as surgical time >4 h all significantly increased the infection rate (P<0.05). Preoperative use of antibacterial agents prevented intracranial infection. Compared with patients without intracranial infections, the infected ones had significantly prolonged hospitalization length and increased expenditure (P<0.05). Discussion - It is of great clinical significance to analyze the risk factors related to intracranial infection after endoscopic transsphenoidal pituitary adenomectomy, aiming to prevent and to control the onset and progression of infection.

Conclusion: Intracranial infections after endoscopic transsphenoidal pituitary adenomectomy were affected by many risk factors, also influencing the prognosis of patients and the economic burden.
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http://dx.doi.org/10.18071/isz.73.0399DOI Listing
November 2020