Publications by authors named "Lin Liu"

2,440 Publications

  • Page 1 of 1

Neuropsychological Tests in Post-operative Cognitive Dysfunction: Methods and Applications.

Front Psychol 2021 4;12:684307. Epub 2021 Jun 4.

Department of Anesthesiology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China.

Post-operative cognitive dysfunction (POCD) is a neurological complication that relatively frequently occurs in older people after anesthesia/surgery, with varying durations and significant differences in the severity of cognitive impairment. POCD is mainly characterized by memory loss mostly without consciousness disorders, accompanied by abnormal emotions, behaviors, and language, mostly without consciousness disorder. The clinical performance of POCD lacks specificity but can reflect the severity of cognitive impairment in patients. The diagnosis of POCD cannot be separated from the evaluation of perioperative cognitive function of patients, and the more popular and accepted method is neuropsychological tests (NPTs).
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http://dx.doi.org/10.3389/fpsyg.2021.684307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212929PMC
June 2021

Prevalence and molecular characteristics of drug-resistant Mycobacterium tuberculosis in Hainan, China: from 2014 to 2019.

BMC Microbiol 2021 Jun 19;21(1):185. Epub 2021 Jun 19.

NHC Key Laboratory of Control of Tropical diseases, Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, 571199, China.

Background: The emergence of antimicrobial resistance against Mycobacterium tuberculosis (M. tuberculosis) has become the major concern in global tuberculosis control due to its limited therapy options and high mortality. However, the clinical and molecular characteristics of drug-resistant strains vary in different geographical areas. Hainan Island located in southern China, is a high drug-resistant tuberculosis burden area. This study aimed to determine the dynamic changes of drug-resistance patterns and drug-related gene mutation types of M. tuberculosis in Hainan from 2014 to 2019.

Results: A total of 1484 culture-confirmed M. tuberculosis were included in this study. It was found that the proportions of drug resistance to isoniazid and rifampin were 31.3 and 31.1% respectively. Overall the proportion of multidrug resistant M. tuberculosis was 24.9%. Multivariate logistic regression analysis showed that age and the treatment history were independent influencing factors of drug resistant tuberculosis. The proportions of drug-resistant tuberculosis in retreatment patients were considerably higher than those in new patients. The most common mutation types of isoniazid were Ser315 → Thr (66.3%), and the most common mutation types of rifampin were Ser531 → Leu (41.5%).

Conclusions: Our data suggests that the prevalence of drug resistant TB remains high in Hainan, and the risks for developing drug resistance with diversified mutation types increased significantly in retreatment patients. These results contribute to the knowledge of the prevalence of drug resistance in Hainan Province and expand the molecular characteristics of drug resistance in China simultaneously.
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http://dx.doi.org/10.1186/s12866-021-02246-7DOI Listing
June 2021

Role of IL-6-IL-27 Complex in Host Antiviral Immune Response.

J Immunol 2021 Jun 18. Epub 2021 Jun 18.

State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China; and

The IL family of cytokines participates in immune response and regulation. We previously found that soluble IL-6 receptor plays an important role in the host antiviral response. In this study, we detected the IL-6-IL-27 complex in serum and throat swab samples from patients infected with influenza A virus. A plasmid expressing the IL-6-IL-27 complex was constructed to explore its biological function. The results indicated that the IL-6-IL-27 complex has a stronger antiviral effect than the individual subunits of IL-6, IL-27A, and EBV-induced gene 3. Furthermore, the activity of the IL-6-IL-27 complex is mainly mediated by the IL-27A subunit and the IL-27 receptor α. The IL-6-IL-27 complex can positively regulate virus-triggered expression of IFN and IFN-stimulated genes by interacting with adaptor protein mitochondrial antiviral signaling protein, potentiating the ubiquitination of TNF receptor-associated factors 3 and 6 and NF-κB nuclear translocation. The secreted IL-6-IL-27 complex can induce the phosphorylation of STAT1 and STAT3 and shows antiviral activity. Our results demonstrate a previously unrecognized mechanism by which IL-6, IL-27A, and EBV-induced gene 3 form a large complex both intracellularly and extracellularly, and this complex acts in the host antiviral response.
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http://dx.doi.org/10.4049/jimmunol.2100179DOI Listing
June 2021

Home-site fidelity and homing behavior of the big-headed turtle .

Ecol Evol 2021 Jun 2;11(11):5803-5808. Epub 2021 May 2.

Ministry of Education Key Laboratory for Ecology of Tropical Islands Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province College of Life Sciences Hainan Normal University Haikou People's Republic of China.

Site fidelity refers to the restriction of dispersal distance of an animal and its tendency to return to a stationary site. To our knowledge, the homing ability of freshwater turtles and their fidelity is reportedly very low in Asia. We examined mark-recapture data spanning a 4-year period in Diaoluoshan National Nature Reserve, Hainan Province, China, to investigate the site fidelity and homing behavior of big-headed turtles . A total of 11 big-headed turtles were captured, and all individuals were used in this mark-recapture study. The site fidelity results showed that the adult big-headed turtles ( = 4) had a 71.43% recapture rate in the original site after their release at the same site, whereas the juveniles ( = 1) showed lower recapture rates (0%). Moreover, the homing behavior results showed that the adults ( = 5) had an 83.33% homing rate after displacement. Adult big-headed turtles were able to return to their initial capture sites (home) from 150 to 2,400 m away and precisely to their home sites from either upstream or downstream of their capture sites or even from other streams. However, none of the juveniles ( = 4) returned home, despite only being displaced 25-150 m away. These results indicated that the adult big-headed turtles showed high fidelity to their home site and strong homing ability. In contrast, the juvenile turtles may show an opposite trend but further research is needed.
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http://dx.doi.org/10.1002/ece3.7475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207336PMC
June 2021

Oncostatin M Maintains Naïve Pluripotency of mESCs by Tetraploid Embryo Complementation (TEC) Assay.

Front Cell Dev Biol 2021 26;9:675411. Epub 2021 May 26.

State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.

It has been well established that leukemia inhibitory factor (LIF) is essential for maintaining naïve pluripotency of embryonic stem cells (ESCs). Oncostatin M (OSM) is a member of the IL-6 family of cytokines which share gp130 as a receptor subunit, and the OSM-gp130 complex can recruit either LIF receptor β or OSM receptor β. Here we show that OSM can completely replace LIF to maintain naïve pluripotency of ESCs. Mouse ESCs (mESCs) cultured in the presence of LIF or OSM not only express pluripotency genes at similar levels but also exhibit the same developmental pluripotency as evidenced by the generation of germline competent chimeras, supporting previous findings. Moreover, we demonstrate by tetraploid embryo complementation assay, the most stringent functional test of authentic pluripotency that mESCs cultured in OSM produce viable all-ESC pups. Furthermore, telomere length and telomerase activity, which are also crucial for unlimited self-renewal and genomic stability of mESCs, do not differ in mESCs cultured under OSM or LIF. The transcriptome of mESCs cultured in OSM overall is very similar to that of LIF, and OSM activates Stat3 signaling pathway, like LIF. Additionally, OSM upregulates pentose and glucuronate interconversion, ascorbate and aldarate metabolism, and steroid and retinol metabolic pathways. Although the significance of these pathways remains to be determined, our data shows that OSM can maintain naïve pluripotent stem cells in the absence of LIF.
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http://dx.doi.org/10.3389/fcell.2021.675411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189179PMC
May 2021

Humidity-Insensitive NO Sensors Based on SnO/rGO Composites.

Front Chem 2021 28;9:681313. Epub 2021 May 28.

Department of Health and Environmental Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, China.

This study reported a novel humidity-insensitive nitrogen dioxide (NO) gas sensor based on tin dioxide (SnO)/reduced graphene oxide (rGO) composites through the sol-gel method. The sensor demonstrated ppb-level NO detection in p-type sensing behaviors (13.6% response to 750 ppb). Because of the synergistic effect on SnO/rGO p-n heterojunction, the sensing performance was greatly enhanced compared to that of bare rGO. The limit of detection of sensors was as low as 6.7 ppb under dry air. Moreover, benefited from the formed superhydrophobic structure of the SnO/rGO composites (contact angle: 149.0°), the humidity showed a negligible influence on the dynamic response (S) of the sensor to different concentration of NO when increasing the relative humidity (RH) from 0 to 70% at 116°C. The relative conductivity of the sensor to 83% relative humidity was 0.11%. In addition, the response ratio (S/S) between 750 ppb NO and 83% RH was 649.0, indicating the negligible impaction of high-level ambient humidity on the sensor. The as-fabricated humidity-insensitive gas sensor can promise NO detection in real-world applications such as safety alarm, chemical engineering, and so on.
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http://dx.doi.org/10.3389/fchem.2021.681313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193670PMC
May 2021

Mental Health Status of Late-Middle-Aged Adults in China During the Coronavirus Disease 2019 Pandemic.

Front Public Health 2021 26;9:643988. Epub 2021 May 26.

Peking University Sixth Hospital, Peking University Institute of Mental Health, National Health Commission (NHC) Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Chinese Academy of Medical Sciences Research Unit, Peking University, Beijing, China.

The novel coronavirus 2019 (COVID-19) pandemic and related compulsory measures have triggered a wide range of psychological issues. However, the effect of COVID-19 on mental health in late-middle-aged adults remains unclear. This cross-sectional, web-based survey recruited 3,730 participants (≥ 50 years old) between February 28 and March 11 of 2020. The Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Insomnia Severity Index, and Acute Stress Disorder Scale were used to evaluate depression, anxiety, insomnia, and acute stress symptoms. Multivariate logistic regression analysis was fitted to explore risk factors that were associated with the selected outcomes. The mean age of the participants was 54.44 ± 5.99 years, and 2,026 (54.3%) of the participants were female. The prevalence of depression, anxiety, insomnia, and acute stress symptoms among late-middle-aged adults in China during the COVID-19 pandemic was 20.4, 27.1, 27.5, and 21.2%, respectively. Multivariable logistic regression analyses showed that participants who were quarantined had increased odds ratios for the four mental health symptoms, and those with a good understanding of the COVID-19 pandemic displayed a decreased risk for all mental health symptoms among late-middle-aged adults. In addition, participants with a low income and with a risk of COVID-19 exposure at work had a remarkably high risk of depression, anxiety, and acute stress symptoms. Mental health symptoms in late-middle-aged adults in China during the COVID-19 pandemic are prevalent. Population-specific mental health interventions should be developed to improve mental health outcomes in late-middle-aged adults during this public health emergency.
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http://dx.doi.org/10.3389/fpubh.2021.643988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187778PMC
June 2021

Microbial community diversity associated with Tibetan kefir grains and its detoxification of Ochratoxin A during fermentation.

Food Microbiol 2021 Oct 3;99:103803. Epub 2021 Apr 3.

College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China; Laboratory of Quality & Safety Risk Assessment for Agro-products (Yangling), Ministry of Agriculture, Yangling, 712100, China; College of Food Science and Engineering, Northwest University, Xi'an, 710069, China. Electronic address:

Tibetan kefir grains (TKG) are multi-functional starter cultures used in foods and have been applied in various fermentation systems. This study aimed to investigate the microbial community composition of TKG, the detoxification abilities of TKG and their isolates towards common mycotoxins, and the potential for applying TKG and their associated microbial populations to avoid mycotoxin contamination in dairy products. Cultivation-independent high-throughput sequencing of bacterial and fungal rDNA genes indicated that Lactobacillus kefiranofaciens and Kazachstania turicensis were the most abundant bacterial and fungal taxa, respectively. In addition, 27 total isolates were obtained using cultivation methods. TKG removed more than 90% of the Ochratoxin A (OTA) after 24 h, while the isolate Kazachstania unisporus AC-2 exhibited the highest removal capacity (~46.1%). Further, the isolate exhibited good resistance to acid and bile salts environment. Analysis of the OTA detoxification mechanism revealed that both adsorption and degradation activities were exhibited by TKG, with adsorption playing a major detoxification role. Furthermore, the addition of OTA did not affect the microbial community structure of TKG. These results indicate that TKG-fermented products can naturally remove mycotoxin contamination of milk and could potentially be practically applied as probiotics in fermentation products.
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http://dx.doi.org/10.1016/j.fm.2021.103803DOI Listing
October 2021

Age-related differences in corneal nerve regeneration after SMILE and the mechanism revealed by metabolomics.

Exp Eye Res 2021 Jun 9:108665. Epub 2021 Jun 9.

Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. Electronic address:

Purpose: To investigate the effect of age on wound healing after small incision lenticule extraction (SMILE) and the underlying metabolomic mechanisms.

Methods: This prospective study was conducted on 216 patients in four groups: the 18-20 (n = 38, Group I), 21-30 (n = 84, Group Ⅱ), 31-40 (n = 58, Group Ⅲ), and 41-50 (n = 36, Group IV) age groups. The density of corneal epithelial wing cells, basal cells, corneal stromal cells, endothelial cells and corneal nerves were examined with a laser confocal microscope (HRT III-RCM) before and 1 month, 3 month, 6 month and 1 year after SMILE. The central nerve fiber length (CNFL), the central corneal nerve fibre density (CNFD), and the central corneal nerve branch density (CNBD) were analyzed by Nero J. The corneal stroma lenticules were obtained from SMILE to analyze metabolites by high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF-MS).

Results: The density of corneal wing epithelial cells and basal epithelial cells have no significant difference among the four groups. The CNFL was 21.90 ± 1.68 mm/mm in Group Ⅰ and 21.63 ± 2.09 mm/mm in Group Ⅱ after 1 year of SMILE, which represented a return to the preoperative level, whereas the CNFL of Group Ⅲ (19.40 ± 0.98 mm/mm) and Group Ⅳ (18.94 ± 0.72 mm/mm) were lower than that preoperation (P ˂0.01). CNFL repair had a negative correlation with age after surgery (Pearson's R = -0.572, P ˂0.01). The CNFD and the CNBD showed the same trend with the CNFL (Pearson's R = -0.602 and -0.531, P ˂0.05). Through screening the significantly different metabolites between the 18-30 age group (including Group I and Group Ⅱ) and other two groups, 6 common remarkably different metabolites were identified. Meanwhile, 5 unique different metabolites were identified only between the 18-30 age group and the 31-40 age group. Six unique different metabolites were identified only between the 18-30 age group and the 41-50 age group.

Conclusion: Corneal nerve repair after SMILE was significantly affected by age. The identified age-associated differences in metabolites were mainly related to inflammation, oxidation, nerve protection and regeneration.
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http://dx.doi.org/10.1016/j.exer.2021.108665DOI Listing
June 2021

-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report.

Front Immunol 2021 25;12:599493. Epub 2021 May 25.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

MYC/BCL2/BCL6 triple-hit lymphoma (THL) is an uncommon subset of high-grade B-cell lymphoma with aggressive clinical behavior and poor prognosis. TP53 mutation is an independently poor progonistic indicator in patients with THL, hence novel therapeutic strategies are needed for these patients. CD19-directed chimeric antigen receptor(CAR19)-T cell therapy has shown promising efficacy for relapsed/refractory diffuse large B cell lymphoma (RR DLBCL), but the majority of CAR19-T cell products to date have been manufactured using viral vectors. transposon system, with an inclination to memory T cells, offers a more convenient and economical alternative for transgene delivery. We herein report the first case of triple-hit RR DLBCL with TP53 mutation who was treated with generated CAR19-T cells and accompanied by grade 2 cytokine release syndrome. The patient obtained a complete remission (CR) in the 2nd month post-infusion and demanded maintenance therapy. Whether maintenance therapy is favorable and how to administrate it after CAR-T cell infusion remain controversial. Preclinical studies demonstrated that lenalidomide could enhance antitumor activity of CAR19-T cells. Therefore, we pioneered oral lenalidomide after CAR19-T therapy in the patient from the 4th month, and he discontinued after one cycle due to side effects. The patient has still kept sustained CR for over 24 months. Our case have firstly demonstrated the feasibility, preliminary safety and efficacy of -produced CAR19-T cell therapy in triple-hit lymphoma. The innovative combination with lenalidomide warrants further investigation. Our findings shed new light on the possible solutions to improve short-term relapse after CAR19-T cell therapy in RR DLBCL. ChiCTR, number ChiCTR1800018111.
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http://dx.doi.org/10.3389/fimmu.2021.599493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186315PMC
May 2021

Identification of Susceptible Genes for Chronic Obstructive Pulmonary Disease with Lung Adenocarcinoma by Weighted Gene Co-Expression Network Analysis.

Onco Targets Ther 2021 4;14:3625-3634. Epub 2021 Jun 4.

Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.

Purpose: Chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma (LUAD) are common disorders and usually co-exists. However, genetic mechanisms between COPD and LUAD are rarely reported. This study aims to identify susceptible genes of COPD with LUAD.

Methods: Using the published data of GSE106899, co-expression modules were constructed by weighted gene co-expression network analysis (WGCNA). Subsequently, top 50 genes in the most tumor-related module were identified, among which hub genes were selected and validated.

Results: Twenty co-expression modules were constructed on 13,865 genes from 62 lung tissues of COPD patients with or without LUAD, in which one module (blue) was most related to tumorigenesis. Functional enrichment analyses showed that the genes in the blue module were mainly enriched in cell cycle, DNA transcription/replication and cancer pathways, etc. Combined with protein-protein interaction network, MTA1, PKMYT1 and FZR1 genes had the most intramodular connectivity, which were regarded as the hub genes. However, only FZR1 was validated to be overexpressed in lung tissues of COPD with LUAD and cigarette smoke extract-stimulated A549 cells, a human LUAD cell line.

Conclusion: This study suggests overexpression of FZR1 may play a key role in the tumorigenesis of LUAD in patients with COPD.
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http://dx.doi.org/10.2147/OTT.S303544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187107PMC
June 2021

Sea turtle demand in China threatens the survival of wild populations.

iScience 2021 Jun 6;24(6):102517. Epub 2021 May 6.

Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou 571158, China.

Sea turtles are an important umbrella species in marine ecosystems. The populations of all five species of sea turtles in China have dropped sharply due to massive illegal trade and habitat loss. The fast-growing demand for sea turtle displays from Chinese aquariums and private individuals has led to a large-scale illegal trade domestically and internationally. Captive sea turtles are also frequently kept in harsh environments with severe injuries and high mortality rates. Sea turtles have only recently been upgraded from level II to level I on the "List of Wildlife under Special State Protection", this protection level has therefore not matched the real status of sea turtles over the past three decades. The additional collusion between the government and business corporations encourages illegal trade. We argue that the commercial use of sea turtles must be completely prohibited to guarantee their future survival in Chinese waters.
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http://dx.doi.org/10.1016/j.isci.2021.102517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163976PMC
June 2021

High resolution RNA-seq profiling of genes encoding ribosomal proteins across different organs and developmental stages in .

Plant Direct 2021 May 27;5(5):e00320. Epub 2021 May 27.

Guangdong Provincial Key Laboratory for Plant Epigenetics Longhua Bioindustry and Innovation Research Institute College of Life Sciences and Oceanography Shenzhen University Shenzhen China.

In , each ribosomal protein (RP) is encoded by a small gene family consisting of two or more highly homologous paralogues, which results in ribosome heterogeneity. It is largely unknown that how genes from multiple member containing RP families are regulated at transcriptional level to accommodate the needs of different plant organs and developmental stages. In this study, we investigated the transcript accumulation profiles of RP genes and found that the expression levels of RP genes are varied dramatically in different organs and developmental stages. Although most RP genes are found to be ubiquitously transcribed, some are obviously transcribed with spatiotemporal specificity. The hierarchical clustering trees of transcript accumulation intensity of RP genes revealed that different organs and developmental stages have different population of RP gene transcripts. By interrogating of the expression fluctuation trend of RP genes, we found that in spite of the fact that most groups of paralogous RP genes are transcribed in concerted manners, some RPs gene have contrasting expression patterns. When transcripts of paralogous RP genes from the same family are considered together, the expression level of most RP genes are well-matched but some are obviously higher or lower, therefore we speculate that some superfluous RPs may act outside the ribosome and a portion of ribosomes may lack one or even more RP(s). Altogether, our analysis results suggested that functional divergence may exist among heterogeneous ribosomes that resulted from different combination of RP paralogues, and substoichiometry of several RP gene families may lead to another layer of heterogeneous ribosomes which also have divergent functions in plants.
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http://dx.doi.org/10.1002/pld3.320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156134PMC
May 2021

Uncovering the roles of microRNAs/lncRNAs in characterising breast cancer subtypes and prognosis.

BMC Bioinformatics 2021 Jun 4;22(1):300. Epub 2021 Jun 4.

UniSA STEM, University of South Australia, Adelaide, Australia.

Background: Accurate prognosis and identification of cancer subtypes at molecular level are important steps towards effective and personalised treatments of breast cancer. To this end, many computational methods have been developed to use gene (mRNA) expression data for breast cancer subtyping and prognosis. Meanwhile, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been extensively studied in the last 2 decades and their associations with breast cancer subtypes and prognosis have been evidenced. However, it is not clear whether using miRNA and/or lncRNA expression data helps improve the performance of gene expression based subtyping and prognosis methods, and this raises challenges as to how and when to use these data and methods in practice.

Results: In this paper, we conduct a comparative study of 35 methods, including 12 breast cancer subtyping methods and 23 breast cancer prognosis methods, on a collection of 19 independent breast cancer datasets. We aim to uncover the roles of miRNAs and lncRNAs in breast cancer subtyping and prognosis from the systematic comparison. In addition, we created an R package, CancerSubtypesPrognosis, including all the 35 methods to facilitate the reproducibility of the methods and streamline the evaluation.

Conclusions: The experimental results show that integrating miRNA expression data helps improve the performance of the mRNA-based cancer subtyping methods. However, miRNA signatures are not as good as mRNA signatures for breast cancer prognosis. In general, lncRNA expression data does not help improve the mRNA-based methods in both cancer subtyping and cancer prognosis. These results suggest that the prognostic roles of miRNA/lncRNA signatures in the improvement of breast cancer prognosis needs to be further verified.
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http://dx.doi.org/10.1186/s12859-021-04215-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176586PMC
June 2021

A Transfer Learning-Based Active Learning Framework for Brain Tumor Classification.

Front Artif Intell 2021 17;4:635766. Epub 2021 May 17.

Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Brain tumor is one of the leading causes of cancer-related death globally among children and adults. Precise classification of brain tumor grade (low-grade and high-grade glioma) at an early stage plays a key role in successful prognosis and treatment planning. With recent advances in deep learning, artificial intelligence-enabled brain tumor grading systems can assist radiologists in the interpretation of medical images within seconds. The performance of deep learning techniques is, however, highly depended on the size of the annotated dataset. It is extremely challenging to label a large quantity of medical images, given the complexity and volume of medical data. In this work, we propose a novel transfer learning-based active learning framework to reduce the annotation cost while maintaining stability and robustness of the model performance for brain tumor classification. In this retrospective research, we employed a 2D slice-based approach to train and fine-tune our model on the magnetic resonance imaging (MRI) training dataset of 203 patients and a validation dataset of 66 patients which was used as the baseline. With our proposed method, the model achieved area under receiver operating characteristic (ROC) curve (AUC) of 82.89% on a separate test dataset of 66 patients, which was 2.92% higher than the baseline AUC while saving at least 40% of labeling cost. In order to further examine the robustness of our method, we created a balanced dataset, which underwent the same procedure. The model achieved AUC of 82% compared with AUC of 78.48% for the baseline, which reassures the robustness and stability of our proposed transfer learning augmented with active learning framework while significantly reducing the size of training data.
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http://dx.doi.org/10.3389/frai.2021.635766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165261PMC
May 2021

LINC00202 attenuates the progression of gastric cancer via suppressing expression level of KLF2.

J BUON 2021 Mar-Apr;26(2):506-512

Department of Oncology, Tongren People's Hospital, Tongren 554300, China.

Purpose: We aimed to investigate the function of LINC00202 in influencing the malignant progression of gastric cancer (GC).

Methods: The relative level of LINC00202 in GC and adjacent normal tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The difference in LINC00202 level among GC patients with different TNM stages was compared. Subsequently, regulatory effects of LINC00202 on proliferative capacity of AGS and SGC-7901 cells were evaluated. Subcellular distribution of LINC00202 was analyzed. The interaction and correlation between LINC00202 and Krüppel-like factor 2 (KLF2) were analyzed by RNA immunoprecipitation (RIP), Chromatin immunoprecipitation (ChIP) and linear regression test. Finally, the involvement of KLF2 in LINC00202-mediated proliferative ability of GC cells was clarified. LINC00202 was upregulated in GC tissues compared with that in adjacent normal ones. Its level remained higher in GC patients with stage III-IV than those with stage I-II. Silencing LINC00202 markedly attenuated the proliferation of GC cells.

Results: LINC00202 was mainly enriched in nucleus. KLF2 level was negatively correlated to and interacted with LINC00202. Transfection of LINC00202 decreased the recruitment ability of EZH2 on KLF2. Importantly, KLF2 partially reversed the regulatory effect of LINC00202 on the proliferative ability of GC cells.

Conclusions: LINC00202 enhances the proliferative ability of GC cells via negatively regulating KLF2, thus aggravating the progression of GC.
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June 2021

Effect of hemoglobin content on cerebral oxygen saturation during surgery for scoliosis in pediatric patients.

BMC Anesthesiol 2021 Jun 1;21(1):165. Epub 2021 Jun 1.

Department of Transfusion Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Background: Although regional cerebral oxygen saturation (rScO) monitoring has been widely used in clinical practice, the relationship between hemoglobin (dHB) content and rScO is incompletely understood. The aim of this study was to analyze the effect of hemoglobin content on rScO in pediatric patients undergoing general anesthesia for correction of scoliosis.

Methods: Ninety-two pediatric patients aged 3 to 14 years undergoing scoliosis correction surgery were enrolled. Continuous monitoring of bilateral regional cerebral oxygen saturation by near-infrared spectroscopy (NIRS, CASMED, USA) was performed after entering the operation room. rScO was recorded when the patients entered the operating room (T, baseline), after anesthesia induced intubation (T), and after radial artery puncture (T). The lowest value of rScO during surgery was also recorded. The arterial blood pressure (ABP), heart rate (HR), pulse oxygen saturation (SpO), end tidal carbon dioxide partial pressure (PetCO) were continuously recorded. Patients were classified as low rScO or high rScO group according to whether the lowest intraoperative rScO was 15% lower than the baseline value. An analysis and comparison of differences in hemoglobin content in these two groups was carried out.

Results: The preoperative hemoglobin-postoperative hemoglobin of patients in the high rScO group was significantly lower than that in the low rScO group (t = - 7.86, p < 0.01), the amount of bleeding during the operation was also less than that in the low rScO group (t = - 6.05, p < 0.01), and the systolic pressure of patients was higher than that in the low rScO group (t = 4.27, p < 0.01).

Conclusions: The decrease in hemoglobin level which occurs during surgery leads to a decrease in cerebral oxygen saturation. In order to ensure patient safety during surgery, it is necessary to carry out volume management and appropriate transfusion and fluid replacement in a timely manner.

Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800016359 . Registered 28 May 2018.
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http://dx.doi.org/10.1186/s12871-021-01382-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167970PMC
June 2021

Transcriptome Profiling of Embryonic Retinal Pigment Epithelium Reprogramming.

Genes (Basel) 2021 May 29;12(6). Epub 2021 May 29.

Department of Biology and Center for Visual Sciences at Miami University, Miami University, Oxford, OH 45056, USA.

The plasticity of human retinal pigment epithelium (RPE) has been observed during proliferative vitreoretinopathy, a defective repair process during which injured RPE gives rise to fibrosis. In contrast, following injury, the RPE of the embryonic chicken can be reprogrammed to regenerate neural retina in a fibroblast growth factor 2 (FGF2)-dependent manner. To better explore the mechanisms underlying embryonic RPE reprogramming, we used laser capture microdissection to isolate RNA from (1) intact RPE, (2) transiently reprogrammed RPE (t-rRPE) 6 h post-retinectomy, and (3) reprogrammed RPE (rRPE) 6 h post-retinectomy with FGF2 treatment. Using RNA-seq, we observed the acute repression of genes related to cell cycle progression in the injured t-rRPE, as well as up-regulation of genes associated with injury. In contrast, the rRPE was strongly enriched for mitogen-activated protein kinase (MAPK)-responsive genes and retina development factors, confirming that FGF2 and the downstream MAPK cascade are the main drivers of embryonic RPE reprogramming. Clustering and pathway enrichment analysis was used to create an integrated network of the core processes associated with RPE reprogramming, including key terms pertaining to injury response, migration, actin dynamics, and cell cycle progression. Finally, we employed gene set enrichment analysis to suggest a previously uncovered role for epithelial-mesenchymal transition (EMT) machinery in the initiation of embryonic chick RPE reprogramming. The EMT program is accompanied by extensive, coordinated regulation of extracellular matrix (ECM) associated factors, and these observations together suggest an early role for ECM and EMT-like dynamics during reprogramming. Our study provides for the first time an in-depth transcriptomic analysis of embryonic RPE reprogramming and will prove useful in guiding future efforts to understand proliferative disorders of the RPE and to promote retinal regeneration.
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http://dx.doi.org/10.3390/genes12060840DOI Listing
May 2021

Expression Characteristics of microRNA in Pig Umbilical Venous Blood and Umbilical Arterial Blood.

Animals (Basel) 2021 May 27;11(6). Epub 2021 May 27.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

As the medium of material exchange between mother and fetus, umbilical cord blood is closely connected with fetal development. microRNA (miRNA) has a wide range of biological functions and has high flow characteristics. Small RNA sequencing of pig umbilical venous blood (UVB) and umbilical arterial blood (UAB) revealed that a total of 302 miRNAs were identified, and 106 and 22 miRNAs were specifically expressed in the UVB and UAB, respectively. Using the two methods of differential expression multiple and differential expression percentage, it is found that only 35% of the highly expressed miRNAs in the UVB by the two analysis modes overlap, but 56.25% of the enriched signal pathways are the same. Only 20% of the highly expressed miRNAs in the UAB overlap, but 62.07% of the signal pathways are the same. Further analysis revealed that miR-423 can be used as a characteristic miRNA of UVB and has the potential to treat muscle-related diseases. miR-122-5p can be used as a characteristic miRNA of UAB and may help to improve liver- and brain-related diseases. In summary, these results enrich understanding of miRNA in mother-fetal communication and provide a reference for the development and application of porcine cord blood products.
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http://dx.doi.org/10.3390/ani11061563DOI Listing
May 2021

Place Attachment and Household Disaster Preparedness: Examining the Mediation Role of Self-Efficacy.

Int J Environ Res Public Health 2021 May 23;18(11). Epub 2021 May 23.

School of Political Science and Public Administration, Shandong University, Qingdao 266237, China.

Household preparedness is essential for resilience-building and disaster risk reduction. Limited studies have explored the correlations between place attachment, self-efficacy, and disaster preparedness, especially in the east Asian cultural context. This study investigates the mediating role of self-efficacy between place attachment and disaster preparedness based on data from the 2018 Shandong General Social Survey (N = 2181) in China. We categorized the preparedness behaviors into three specific clusters: material, behavioral and awareness preparedness. Multiple linear regressions and the Sobel Goodman tests were employed to estimate the correlations with the control of necessary confounding variables such as disaster experience, socioeconomic and demographic characteristics. The results demonstrate that both the place attachment and self-efficacy are correlated with higher degrees of overall preparedness and all three types of preparedness, and self-efficacy plays a mediating role between place attachment and disaster preparedness. These findings highlight the importance of promoting place attachment and self-efficacy in the advocacies and outreach activities of disaster preparedness.
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http://dx.doi.org/10.3390/ijerph18115565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197108PMC
May 2021

Gene, the GATA Transcription Activator, Regulates the Production of Higher Alcohol during Wheat Beer Fermentation by .

Bioengineering (Basel) 2021 May 8;8(5). Epub 2021 May 8.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Industrial Microbiology Key Laboratory, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.

Uncoordinated carbon-nitrogen ratio in raw materials will lead to excessive contents of higher alcohols in alcoholic beverages. The effect of gene, the GATA transcription activator, on higher alcohol biosynthesis was investigated to clarify the mechanism of regulating higher alcohol metabolism under high concentrations of free amino nitrogen (FAN). The availability of FAN by strain SDT1K with a double-copy deletion was 28.31% lower than that of parent strain S17, and the yield of higher alcohols was 33.91% lower. The transcript levels of the downstream target genes of and higher alcohol production in the double-copy deletion mutant suggested that a part of the effect of deletion on higher alcohol production was the downregulation of , , and . This study shows that GATA factors can effectively regulate the metabolism of higher alcohols in and provides valuable insights into higher alcohol biosynthesis, showing great significance for the wheat beer industry.
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http://dx.doi.org/10.3390/bioengineering8050061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151594PMC
May 2021

A Novel Netrin-1-Derived Peptide Enhances Protection against Neuronal Death and Mitigates of Intracerebral Hemorrhage in Mice.

Int J Mol Sci 2021 May 2;22(9). Epub 2021 May 2.

Institute of Genetics and Cytology, Northeast Normal University, Changchun 130021, China.

It has been reported that Netrin-1 is involved in neuroprotection following injury to the central nervous system. However, the minimal functional domain of Netrin-1 which can preserve the neuroprotection but avoid the major side effects of Netrin remains elusive. Here, we investigated the neuroprotective effect of a peptide E1 derived from Netrin-1's EGF3 domain (residues 407-422). We found that it interacts with deleted colorectal carcinoma (DCC) to activate focal adhesion kinase phosphorylation exhibiting neuroprotection. The administration of the peptide E1 was able to improve functional recovery through reduced apoptosis in an experimental murine model of intracerebral hemorrhage (ICH). In summary, we reveal a functional sequence of Netrin-1 that is involved in the recovery process after ICH and identify a candidate peptide for the treatment of ICH.
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http://dx.doi.org/10.3390/ijms22094829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125294PMC
May 2021

Enterococcus faecium HDRsEf1 inhibits LPS-induced downregulation of ZO-1 expression via TLR2/4-mediated JNK/AP-1 signalling pathways.

J Appl Microbiol 2021 Jun 1. Epub 2021 Jun 1.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.

Aims: ZO-1 is a key regulatory tight junction protein that plays an important role in maintaining gastrointestinal health. In this study, we investigated the protective effect and regulation mechanism of the probiotic Enterococcus faecium HDRsEf1 on tight junction protein ZO-1 at the cellular and molecular levels.

Methods And Results: We established LPS-induced intestinal epithelial cell injury model, and detected the protective effect of HDRsEf1 on ZO-1 in IPEC-J2 cells by Real-time PCR and Western blot. The results showed that HDRsEf1 inhibited the downregulation of ZO-1 expression induced by LPS. HDRsEf1 stabilized the destruction of the ZO-1 structure caused by LPS in an immunofluorescence assay. Through gene overexpression and siRNA interference tests, we found that transcription factor AP-1 inhibited the level of ZO-1 expression. Silencing experiment further supported that the protective effect of HDRSEF1 might mediated by suppression of LPS-provoked activation of ASK1/MKK7/JNK signalling pathways. In addition, HDRsEf1 could stabilize ZO-1 expression by increasing TLR2 expression and competing with LPS for the TLR4 binding site. More interestingly, we also found that HDRsEf1 could stabilize ZO-1 expression through inhibiting the production of TNF-α induced by LPS.

Conclusions: HDRsEf1 could protect the IPEC-J2 cell against LPS induced down-regulation of ZO-1 expression by inhibiting the activation of TLR2/4-mediated JNK-AP-1 and signalling cascade and the production of TNF-α.

Significance And Impact Of The Study: This study can provide a theoretical basis for probiotics to regulate the expression of intestinal tight junction proteins, and supply technical support for probiotics to prevent and treat animal intestinal infectious diseases.
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http://dx.doi.org/10.1111/jam.15167DOI Listing
June 2021

The effect of PCSK9 inhibitors on brain stroke prevention: A systematic review and meta-analysis.

Nutr Metab Cardiovasc Dis 2021 Apr 20. Epub 2021 Apr 20.

Neurology Department, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 05000, China. Electronic address:

Background And Aims: Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes, their effects on brain stroke risk are unclear. The present meta-analysis aimed to evaluate the effects of PCSK9 inhibitors on brain stroke prevention.

Methods And Results: We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov for research published until December 30, 2020, to find randomized controlled trials (RCTs) of PCSK9 inhibitors for brain stroke prevention. Relative risk (RR) and 95% confidence intervals (CIs) were used to represent the outcomes. Seven RCTs with 57,440 participants, including 29,850 patients treated with PCSK9 inhibitors and 27,590 control participants, were included. PCSK9 inhibitors were associated with significant reductions in total brain stroke risk (RR, 0.77; 95% CI, 0.67-0.88; P < 0.001) and ischemic brain stroke risk (RR, 0.76; 95% CI, 0.66, 0.89; P < 0.001) in comparison with the control group. There was no significant difference in cardiovascular mortality (RR, 0.95; 95% CI, 0.84-1.07; P = 0.382) and the risk of hemorrhagic brain stroke (RR, 1.00; 95% CI, 0.66-1.51; P = 0.999) between patients treated with PCSK9 inhibitors and controls. PCSK9 inhibitors did not significantly increase the incidence of neurocognitive adverse events (RR, 1.02; 95% CI, 0.81-1.29; P = 0.85). Moreover, subgroup analysis showed no difference in cognitive function disorder risks among different PCSK9 inhibitors and treatment times.

Conclusions: PCSK9 inhibitors significantly reduced the risk of total brain stroke and ischemic brain stroke without increasing the risk of brain hemorrhage and neurocognitive impairment.
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http://dx.doi.org/10.1016/j.numecd.2021.03.026DOI Listing
April 2021

Regulating Electrocatalytic Oxygen Reduction Activity of Metal Coordination Polymer via d-π Conjugation.

Angew Chem Int Ed Engl 2021 May 29. Epub 2021 May 29.

Nankai University, College of Chemistry, CHINA.

Non-noble transition metal complexes have attracted growing interest as efficient electrocatalysts for oxygen reduction reaction (ORR) while their activities still lack rational and effective regulation. Herein, we propose a d-π conjugation strategy for rough and fine tuning of ORR activity in TM-BTA (TM = Mn/Fe/Co/Ni/Cu, BTA = 1,2,4,5-benzenetetramine) coordination polymers. By first-principle calculations, we elucidate that the strong d-π conjugation elevates the [[EQUATION]] / [[EQUATION]] orbitals of TM centers to enhance intermediate absorption and strengthens the electronic modulation effect from substitute groups on ligands. Based on this strategy, Co-TABQ (tetramino benzoquinone) are found to approach the top of ORR activity volcano. The synthesized Co-TABQ with atomically distributed Co on carbon nanotubes exhibits a half-wave potential of 0.85 V and a specific current of 130 mA mgmetal-1 at 0.8 V, outperforming the benchmark Pt/C. The high activity, low peroxide yield, and considerable durability of Co-BTA and Co-TABQ promise their application in oxygen electrocatalysis. This study provides mechanistic insight into the rational design of transition metal complexes catalysts.
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http://dx.doi.org/10.1002/anie.202104494DOI Listing
May 2021

Contributing factors of fatigue in patients with type 2 diabetes: A systematic review.

Psychoneuroendocrinology 2021 Aug 19;130:105280. Epub 2021 May 19.

School of Nursing, Yangzhou University, Yangzhou, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Jiangsu Key Laboratory of Zoonosis, Yangzhou University, China. Electronic address:

Remarkable evidence supports the link between type 2 diabetes (T2DM) and fatigue. However, a unifying recommendation to identify and prevent fatigue or to prevent its clinical consequences in T2DM is not available at present. Therefore, this study aimed to conduct a systematic review to summarize the definition, measurement tools, and contributing factors of fatigue in T2DM. Nine articles were included for analysis, and results showed that T2DM fatigue was associated with five major factors, including sociodemographic factors, clinical disease factors, inflammatory factors, psychological factors, and behavior and lifestyle. The contributing factors of T2DM fatigue are reviewed, and clinical benefits provide a theoretical basis for further clinical intervention to prevent the occurrence of fatigue and improve the patient's treatment compliance and self-management ability and may be beneficial to their quality of life.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105280DOI Listing
August 2021

Overexpression of the white clover TrSAMDC1 gene enhanced salt and drought resistance in Arabidopsis thaliana.

Plant Physiol Biochem 2021 Aug 19;165:147-160. Epub 2021 May 19.

College of Grassland Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address:

S-adenosylmethionine decarboxylase (SAMDC) mediates the biosynthesis of polyamines (PAs) and plays a positive role in plants' response to adversity stress tolerance. In this study, we isolated a SAMDC gene from white clover, which is located in mitochondria. It was strongly induced when white clover exposed to drought (15% PEG6000), salinity (200 mM NaCl), 20 μM spermidine, 100 μM abscisic acid, and 10 mM HO, especially in leaves. The INVSc1 yeast introduced with TrSAMDC1 had tolerance to drought, salt, and oxidative stress. Overexpression of TrSAMDC1 in Arabidopsis showed higher fresh weight and dry weight under drought and salt treatment and without growth inhibition under normal conditions. Leaf senescence induced by drought and saline was further delayed in transgenic plants, regardless of cultivation in 1/2 MS medium and soil. During drought and salt stress, transgenic plants exhibited a significant increase in relative water content, maximum photosynthesis efficiency (Fv/Fm), performance index on the absorption basis (PI), activities of antioxidant protective enzymes such as SOD, POD, CAT, and APX, and a significant decrease in accumulation of MDA and HO as compared to the WT. The concentrations of total PAs, putrescine, spermidine, and spermidine in transgenic lines were higher in transgenic plants than in WT under normal and drought conditions. These results suggested that TrSAMDC1 could effectively mitigate abiotic stresses without the expense of production and be a potential candidate gene for improving the drought and salt resistance of crops.
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http://dx.doi.org/10.1016/j.plaphy.2021.05.018DOI Listing
August 2021

The patterns of left ventricular alteration by adipose tissue distribution: implication for heart failure prevention.

ESC Heart Fail 2021 May 26. Epub 2021 May 26.

Department of Cardiology, Guangdong Cardiovascular Institute, Hypertension Research Laboratory, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.

Aims: The current study aimed to evaluate the associations between general and abdominal obesity with left ventricular (LV) structure and function and whether these associations differed by sex.

Methods And Results: This is a community-based cross-sectional study, and 971 hypertensive individuals without overt cardiovascular disease were included. General obesity was defined as body mass index (BMI) ≥ 28 kg/m , and abdominal obesity was defined as waist circumference (WC) ≥ 90 cm for men and ≥85 cm for women. The associations between general and abdominal obesity with LV structure and function were examined using linear regression analysis, and the interaction by sex was performed. The mean age was 66.5 ± 11.4 years, and women accounted for 62%. General obese individuals (n = 205) were more likely to have concentric remodelling, LV hypertrophy, and worse diastolic function. Similar differences were observed in abdominal obese individuals (n = 593). General obesity was associated with LV end-diastolic volume, LV mass, left atrial volume, and septal E/e' ratio after adjusting for WC and clinical covariates; and abdominal obesity was associated with septal e' velocity after adjusting for BMI and clinical covariates. The associations between general obesity with LV structure and function did not differ by sex, while the magnitudes of the associations between abdominal obesity with LV mass and septal e' velocity were greater in men.

Conclusions: General and abdominal obesity were associated with different patterns of LV structural and functional alterations, stressing the importance of incorporating BMI and WC measurements into assessing obesity-related LV alterations.
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http://dx.doi.org/10.1002/ehf2.13415DOI Listing
May 2021

Incidental Detection of Sinonasal Inverted Papilloma With 68Ga-FAPI PET/CT in a Patient With Esophageal Cancer.

Clin Nucl Med 2021 May 26. Epub 2021 May 26.

From the Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province; and Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, China.

Abstract: A 68-year-old man with newly diagnosed esophageal cancer was included in a clinical trial of 68Ga-FAPI PET/CT study in tumors (ChiCTR2100044131). Increased tracer uptake was noted in esophageal cancer. In addition, sinonasal inverted papilloma also revealed increased FAPI activity.
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http://dx.doi.org/10.1097/RLU.0000000000003733DOI Listing
May 2021