Publications by authors named "Yi Huang"

1,417 Publications

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BCAR1 plays critical roles in the formation and immunoevasion of invasive circulating tumor cells in lung adenocarcinoma.

Int J Biol Sci 2021 11;17(10):2461-2475. Epub 2021 Jun 11.

Thoracic Surgery Department, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing 400042, China.

We investigated the roles of breast cancer anti-estrogen resistance 1 (BCAR1/p130Cas) in the formation and immunoevasion of invasive circulating tumor cells (CTCs) in lung adenocarcinoma (LUAD). Biomarkers of CTCs including BCAR1 and CD274, were evaluated by the CanPatrol method. Proteomics analysis of LUAD cells and exosomes after BCAR1 overexpression (BCAR1-OE) was performed by mass spectrometry. Cell functions and relevant signaling pathways were investigated after BCAR1 knockdown (BCAR1-KO) or BCAR1-OE in LUAD cells. Lastly, and experiments were performed to confirm the roles of BCAR1 in the formation and immunoevasion of CTCs. High expression of BCAR1 by CTCs correlated with CD274 expression and epithelial-to-mesenchymal transition (EMT). RAC1, together with BCAR1, was found to play an important role in the carcinogenesis of LUAD. RAC1 functioned with BCAR1 to induce EMT and to enhance cell proliferation, colony formation, cell invasion and migration, and anoikis resistance in LUAD cells. BCAR1 up-regulated CD274 expression probably by shuttling the short isoform of BRD4 (BRD4-S) into the nucleus. CTCs, as well as tumor formation, were prohibited in nude mice xenografted with BCAR1-KO cells. The co-expression of BCAR1/RAC1 and BCAR1/CD274 was confirmed in LUAD. BCAR1 expression in LUAD is an indicator of poor prognosis, and it associates with immunoevasion. BCAR1, as a new target for the treatment of LUAD, plays roles in the formation and immunoevasion of invasive CTCs. The mechanism includes triggering EMT via RAC1 signaling and up-regulating CD274 expression by shuttling BRD4-S into the nucleus.
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http://dx.doi.org/10.7150/ijbs.61790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315020PMC
June 2021

NLRP3 inflammasome activation and cell death.

Cell Mol Immunol 2021 Jul 28. Epub 2021 Jul 28.

Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.

The NLRP3 inflammasome is a cytosolic multiprotein complex composed of the innate immune receptor protein NLRP3, adapter protein ASC, and inflammatory protease caspase-1 that responds to microbial infection, endogenous danger signals, and environmental stimuli. The assembled NLRP3 inflammasome can activate the protease caspase-1 to induce gasdermin D-dependent pyroptosis and facilitate the release of IL-1β and IL-18, which contribute to innate immune defense and homeostatic maintenance. However, aberrant activation of the NLRP3 inflammasome is associated with the pathogenesis of various inflammatory diseases, such as diabetes, cancer, and Alzheimer's disease. Recent studies have revealed that NLRP3 inflammasome activation contributes to not only pyroptosis but also other types of cell death, including apoptosis, necroptosis, and ferroptosis. In addition, various effectors of cell death have been reported to regulate NLRP3 inflammasome activation, suggesting that cell death is closely related to NLRP3 inflammasome activation. In this review, we summarize the inextricable link between NLRP3 inflammasome activation and cell death and discuss potential therapeutics that target cell death effectors in NLRP3 inflammasome-associated diseases.
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http://dx.doi.org/10.1038/s41423-021-00740-6DOI Listing
July 2021

Anti-F4/80 treatment attenuates Th2 cell responses: Implications for the role of lung interstitial macrophages in the asthmatic mice.

Int Immunopharmacol 2021 Jul 24;99:108009. Epub 2021 Jul 24.

Department of Respiratory & Critical Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China. Electronic address:

Lung interstitial macrophages (IMs) can be polarized towards an alternative activation phenotype in ovalbumin (OVA)-induced asthmatic mice. However, the role of alternative activation of lung IMs in Th2 cell responses in the asthmatic murine is still unclear. Here, we leverage an anti-F4/80 treatment which has been shown to selectively deplete IMs in mice and investigate how this treatment modulates Th2 cell responses in lung and whether the modulation is dependent on lung IMs in murine models of asthma. We show that anti-F4/80 treatment alleviates Th2 cell responses in mice immunized and challenged with OVA or house dust mite (HDM). The anti-F4/80 treatment does not target lung alveolar macrophages (AMs) in OVA-induced asthmatic mice or impact the abundance of other immune cell types, including B cells, T cells, and NK cells in wild-type mice. However, this treatment does inhibit the expression of polarized markers of alternatively activated macrophages, including arginase-1, Ym-1, and Fizz-1 in the lung tissues from OVA-induced asthmatic mice. Furthermore, we find that the inhibitory effects of anti-F4/80 treatment on Th2 cell responses can be reversed upon adoptive transfer of lung IMs. Taken together, our data show that anti-F4/80 treatment attenuates Th2 cell responses, which is at least partially related to depletion of lung IMs in murine models of asthma. This suggests that targeted lung IMs may provide a potential therapeutic protocol for the treatment of asthmatics.
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http://dx.doi.org/10.1016/j.intimp.2021.108009DOI Listing
July 2021

A commentary on "Efficacy and safety of short-term (3 days) enoxaparin in preventing venous thromboembolism after gastric cancer surgery: A single-center, prospective cohort study" (Int J Surg 2021; 89:105946).

Int J Surg 2021 Jul 23:106032. Epub 2021 Jul 23.

Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310009, China. Electronic address:

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http://dx.doi.org/10.1016/j.ijsu.2021.106032DOI Listing
July 2021

Plasma Levels of Heat Shock Protein 90 Alpha Associated With Colorectal Cancer Development.

Front Mol Biosci 2021 8;8:684836. Epub 2021 Jul 8.

Department of Research, Guangxi Medical University Cancer Hospital, Nanning, China.

The role of plasma heat shock protein 90 alpha (HSP90α) in colorectal cancer patients remains unclear. This study aimed to evaluate the relationship between HSP90α and the occurrence and development of colorectal cancer through diagnosis and prognosis value. 635 colorectal cancer patients and 295 healthy controls were recruited. The HSP90α was measured by using the ELISA kit in all objects and the immune cells and common biomarkers as CEA, AFP, CA125, CA153 and CA199 were measured in all colorectal cancer patients. The relationship between plasma HSP90α with clinical features, common tumor markers and immune cells were also conducted. The survival analysis endpoint was progression-free survival (PFS). The levels of plasma HSP90α were significantly higher in colorectal cancer patients compared to healthy controls [51.4 (ng/ml) vs. 43.7 (ng/ml), < 0.001]. In additional, the levels of plasma HSP90α were associated with gender and disease progress as stage, lymphatic and distant metastasis. Furthermore, plasma HSP90α was closed correlation with CEA, CA125, CA199 and percentage of B cells. However, the initial expression level of plasma HSP90α failed to show a prognostic value for progression-free survival in colorectal cancer. The plasma Hsp90α was remarkable higher in colorectal cancer and correlated with common tumor biomarkers and immune cells. Plasma Hsp90α levels were associated with disease progress but a poor diagnosis performance and also failed to show a prognostic value in colorectal cancer.
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http://dx.doi.org/10.3389/fmolb.2021.684836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295900PMC
July 2021

Targeting Glioblastoma Stem Cells: A Review on Biomarkers, Signal Pathways and Targeted Therapy.

Front Oncol 2021 8;11:701291. Epub 2021 Jul 8.

Department of Neurosurgery, University-Town Hospital of Chongqing Medical University, Chongqing, China.

Glioblastoma (GBM) remains the most lethal and common primary brain tumor, even after treatment with multiple therapies, such as surgical resection, chemotherapy, and radiation. Although great advances in medical development and improvements in therapeutic methods of GBM have led to a certain extension of the median survival time of patients, prognosis remains poor. The primary cause of its dismal outcomes is the high rate of tumor recurrence, which is closely related to its resistance to standard therapies. During the last decade, glioblastoma stem cells (GSCs) have been successfully isolated from GBM, and it has been demonstrated that these cells are likely to play an indispensable role in the formation, maintenance, and recurrence of GBM tumors, indicating that GSCs are a crucial target for treatment. Herein, we summarize the current knowledge regarding GSCs, their related signaling pathways, resistance mechanisms, crosstalk linking mechanisms, and microenvironment or niche. Subsequently, we present a framework of targeted therapy for GSCs based on direct strategies, including blockade of the pathways necessary to overcome resistance or prevent their function, promotion of GSC differentiation, virotherapy, and indirect strategies, including targeting the perivascular, hypoxic, and immune niches of the GSCs. In summary, targeting GSCs provides a tremendous opportunity for revolutionary approaches to improve the prognosis and therapy of GBM, despite a variety of challenges.
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http://dx.doi.org/10.3389/fonc.2021.701291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297686PMC
July 2021

Nrf2 Pathway Ameliorates Bladder Dysfunction in Cyclophosphamide-Induced Cystitis via Suppression of Oxidative Stress.

Oxid Med Cell Longev 2021 30;2021:4009308. Epub 2021 Jun 30.

Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.

Objective: To investigate the protective effect and molecular mechanism of nuclear factor E2-related factor 2 (Nrf2) pathway in interstitial cystitis (IC).

Methods: We established a mouse model of IC by cyclophosphamide (CYP) in wild-type mice and Nrf2 gene knockout mice. We examined the histological and functional alterations, the changes of oxidative stress markers, and the expression of the antioxidant genes downstream of Nrf2 pathway.

Results: After CYP administration, the mice showed urinary frequency and urgency, pain sensitization, decreased contractility, bladder edema, and oxidative stress disorder. Notably, the Nrf2 CYP mice had more severe symptoms. The mRNA and protein levels of antioxidant genes downstream of Nrf2 pathway were significantly upregulated in the Nrf2 CYP mice, while there were no significant changes in the Nrf2 CYP mice.

Conclusion: Nrf2 pathway protects bladder injury and ameliorates bladder dysfunction in IC, possibly by upregulating antioxidant genes and inhibiting oxidative stress.
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http://dx.doi.org/10.1155/2021/4009308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279868PMC
June 2021

Imidacloprid induces locomotion impairment of the freshwater crayfish, Procambarus clarkii via neurotoxicity and oxidative stress in digestive system.

Aquat Toxicol 2021 Jul 16;238:105913. Epub 2021 Jul 16.

Key Laboratory of Application of Ecology and Environmental Protection in Plateau Wetland of Sichuan, Xichang University, Xichang 415000, Sichuan Province, China.

Imidacloprid (IMI) is used in integrated farming like the rice-crayfish co-culture system to prevent water weevil. However, the toxic effect of IMI on the freshwater crayfish Procambarus clarkii is unknown. In the current study, the effects of IMI on the locomotion, antioxidative status, digestion and intestinal microbiota of P. clarkii were investigated. The results showed that IMI caused locomotion impairment with reduced crawl velocity, and attenuated their dark preference, aggressiveness and reversal ability. Inhibited AChE in muscle and hepatopancreas indicates the neurotoxicity of IMI which may directly lead their locomotion dysfunction. The increase of antioxidative enzymes activity and MDA level were found after 25 μg/L and 250 μg/L exposure. Significant up-regulation of several antioxidative and immune-related genes, including CZ-SOD, CAT, GPx, GST, AFL, proPO, HSP27 and HSP70 confirmed that oxidative stress was induced in all treatments when exposed to IMI. In addition, there was significant increase of LDH, indicating the different energy allocation during the exposure. Meanwhile, results from DNA damage analysis showed elevated OTM value and 8-OHdG level in hepatopancretic cells. On the other hand, decreases of alpha-amylase, lipase and increase of trypsin in hepatopancreas was observed at 25 and 250 μg/L. In addition, significant changes of composition of intestinal microbiota at both phylum and genus levels were observed according to the 16S rRNA sequencing results. Increase of pathogenic genera and decrease of beneficial bacterial communities revealed the disequilibrium of intestinal flora of crayfish. In summary, results in the present study suggest that IMI at environmentally realistic concentration could induce AChE inhibition and oxidative stress, conjointly leading the locomotion impairment in crayfish. IMI also affected the digestive functions by enzymes inhibition and gut microbiota dysbiosis.
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http://dx.doi.org/10.1016/j.aquatox.2021.105913DOI Listing
July 2021

Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms.

Front Aging Neurosci 2021 6;13:688179. Epub 2021 Jul 6.

Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

DNA methylation at the gene promoter region is reportedly involved in the development of intracranial aneurysm (IA). This study aims to investigate the methylation levels of polypyrimidine tract-binding protein 1 () in IA, as well as its potential to predict IA. Forty-eight patients with IA and 48 age- and sex-matched healthy controls were recruited into this study. Methylation levels of CpG sites were determined via bisulfite pyrosequencing. The levels in the blood were determined using a real-time quantitative reverse transcription-polymerase chain reaction test. Significant differences were found between IAs and controls in CpG1 ( = 0.001), CpG2 ( < 0.001), CpG3 ( = 0.037), CpG4 ( = 0.003), CpG5 ( = 0.006), CpG6 ( = 0.02), and mean methylation ( < 0.001). The mRNA level of in the blood was much lower in IAs compared with controls ( = 0.002), and the expression was significantly associated with DNA methylation promoter levels in individuals ( = -0.73, < 0.0001). In addition, stratification analysis comparing smokers and non-smokers revealed that tobacco smokers had significantly higher levels of DNA methylation in than non-smokers ( = 0.002). However, no statistical difference in methylation was found between ruptured and unruptured IA groups ( > 0.05). The ROC analyses of curves revealed that methylation may be a predictor of IA regardless of sex (both sexes, area under curve (AUC) = 0.78, < 0.0001; male, AUC = 0.76, = 0.002; female, AUC = 0.79, < 0.0001). These findings suggest that long-term tobacco smoke exposure led to DNA methylation in the promoter region of the gene, which further decreased gene expression and participated in the pathogenesis of IA. The methylation of may be a potential predictive marker for the occurrence of IA.
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http://dx.doi.org/10.3389/fnagi.2021.688179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292010PMC
July 2021

Quantifying COVID-19 importation risk in a dynamic network of domestic cities and international countries.

Proc Natl Acad Sci U S A 2021 08;118(31)

Geospatial Data Science Lab, Department of Geography, University of Wisconsin-Madison, Madison, WI 53706.

Since its outbreak in December 2019, the novel coronavirus 2019 (COVID-19) has spread to 191 countries and caused millions of deaths. Many countries have experienced multiple epidemic waves and faced containment pressures from both domestic and international transmission. In this study, we conduct a multiscale geographic analysis of the spread of COVID-19 in a policy-influenced dynamic network to quantify COVID-19 importation risk under different policy scenarios using evidence from China. Our spatial dynamic panel data (SDPD) model explicitly distinguishes the effects of travel flows from the effects of transmissibility within cities, across cities, and across national borders. We find that within-city transmission was the dominant transmission mechanism in China at the beginning of the outbreak and that all domestic transmission mechanisms were muted or significantly weakened before importation posed a threat. We identify effective containment policies by matching the change points of domestic and importation transmissibility parameters to the timing of various interventions. Our simulations suggest that importation risk is limited when domestic transmission is under control, but that cumulative cases would have been almost 13 times higher if domestic transmissibility had resurged to its precontainment level after importation and 32 times higher if domestic transmissibility had remained at its precontainment level since the outbreak. Our findings provide practical insights into infectious disease containment and call for collaborative and coordinated global suppression efforts.
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http://dx.doi.org/10.1073/pnas.2100201118DOI Listing
August 2021

Study on the effect of shikonin on CD36 expression and phagocytic ability of microglia in the isolated cerebral haemorrhage model.

Folia Neuropathol 2021 ;59(2):198-204

Department of Neurosurgery, Yuyao People's Hospital, Yuyao, Zhejiang Province, China.

Aim Of The Study: To investigate the effects of shikonin on CD36 expression and phagocytic ability of microglia, and its protective effect on neurons and the possible mechanism within.

Material And Methods: The effects of shikonin on CD36 expression and phagocytic ability of microglia were detected by Western blot method, and cerebral haemorrhage was isolated by flow cytometry in the experiment. The protective effect of neurons was observed through neuron-microglia co-culture technique. Meanwhile, the effect of hydrogen peroxide on the expression of catalase was detected, and the concentration of hydrogen peroxide was measured in the isolated cerebral haemorrhage model. The t test was used to compare data between 2 groups, and one-way ANOVA was applied to multiple sets of data.

Results: Compared with the control group, the CD36 expression and phagocytic ability of microglia was increased by shikonin in the isolated cerebral haemorrhage model, while inflammatory factors such as tumour necrosis factor a (TNF-a) and interleukin 1b (IL-1b) attenuated the effects of the drug. The amount of neuron apoptosis/necrosis was significantly reduced by the drug, while the expression of catalase in microglia was increased, but the secretion of hydrogen peroxide was decreased in the neuron-microglia co-culture system.

Conclusions: Shikonin can enhance the CD36 expression and the ability to phagocytose erythrocyte of microglia. Simultaneously, shikonin performs protective effects on neuronal cells and promotes the absorption of haematoma. Therefore, shikonin is probably an innovative medicine to treat cerebral haemorrhage.
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http://dx.doi.org/10.5114/fn.2021.107110DOI Listing
January 2021

A single-institution phase I feasibility study of dose-escalated IMRT for non-operative locally advanced esophageal carcinoma.

Clin Transl Radiat Oncol 2021 Sep 29;30:19-25. Epub 2021 Jun 29.

Department of Radiation Oncology, Washington University, St. Louis, MO, United States.

Background And Purpose: Radiation dose escalation to improve poor outcomes with chemoradiation in locally advanced esophageal carcinoma is limited in part by increased toxicity. This Phase I study investigates the use of IMRT to improve tolerability of dose escalation.

Materials And Methods: A single-institution, prospective study was conducted between 2007 and 2013 for individuals with inoperable esophageal carcinoma. Gross disease received 60 Gy in 30 fractions and at-risk sites received 54 Gy with simultaneous integrated boost. Concurrent chemotherapy primarily consisted of cisplatin/5-FU. The primary objective was to assess feasibility (<15% rate of grade 4-5 toxicity). Secondary objectives included assessment of overall survival (OS), progression free survival (PFS), and locoregional (LRR) and distant recurrence.

Results: Twenty-six patients were enrolled with median follow up of 17.6 months (range 0.1 to 152.0). The majority were AJCC 7th edition Stage III (54%), distal esophagus primary (81%), and adenocarcinoma histology (85%). Twenty-one patients (81%) completed their course of radiation therapy, while only 55% received 2 cycles of concurrent cisplatin/5-FU. One grade 5 and one grade 4 cardiac event occurred, both during chemoradiation and before receiving 50 Gy. The 3-year OS was 48.6% (95% CI: 32.5 to 72.2%) and PFS was 28.5% (95% CI: 14.6 to 55.5%). Half developed distant failure with LRR occurring in 10 patients (38%), isolated in 5 patients.

Conclusion: While feasibility was demonstrated, toxicity and compliance remained limiting factors with outcomes similar to historical controls. There remains an uncertain role for dose escalation in definitive management of locally advanced esophageal cancer.
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http://dx.doi.org/10.1016/j.ctro.2021.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267428PMC
September 2021

Hollow-glass-microsphere-assisted half-circle interference for hydrostatic pressure measurement with high sensitivity.

Opt Express 2021 Jul;29(14):21252-21261

We propose and demonstrate a half-circle interferometer using a hollow glass microsphere (HGM) resonator. The half-circle interference is induced by a mismatch between the fundamental mode in the HGM and the modes in the capillary wall. The theoretical model is verified by comparing the simulated and experimental results. The variation in capillary length induced by the axial pressure contributes the most to the half-circle interference, which features a device with a high hydrostatic pressure sensitivity of -1.099 nm/kPa. This device shows potential as a hydrostatic pressure sensor owing to its stability, high sensitivity, and robustness.
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http://dx.doi.org/10.1364/OE.426477DOI Listing
July 2021

A novel risk score system for prognostic evaluation in adenocarcinoma of the oesophagogastric junction: a large population study from the SEER database and our center.

BMC Cancer 2021 Jul 13;21(1):806. Epub 2021 Jul 13.

Department of Gastroenterology Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310000, China.

Background: The incidence rate of adenocarcinoma of the oesophagogastric junction (AEG) has significantly increased over the past decades, with a steady increase in morbidity. The aim of this study was to explore a variety of clinical factors to judge the survival outcomes of AEG patients.

Methods: We first obtained the clinical data of AEG patients from the Surveillance, Epidemiology, and End Results Program (SEER) database. Univariate and least absolute shrinkage and selection operator (LASSO) regression models were used to build a risk score system. Patient survival was analysed using the Kaplan-Meier method and the log-rank test. The specificity and sensitivity of the risk score were determined by receiver operating characteristic (ROC) curves. Finally, the internal validation set from the SEER database and external validation sets from our center were used to validate the prognostic power of this model.

Results: We identified a risk score system consisting of six clinical features that can be a good predictor of AEG patient survival. Patients with high risk scores had a significantly worse prognosis than those with low risk scores (log-rank test, P-value < 0.0001). Furthermore, the areas under ROC for 3-year and 5-year survival were 0.74 and 0.75, respectively. We also found that the benefits of chemotherapy and radiotherapy were limited to stage III/IV AEG patients in the high-risk group. Using the validation sets, our novel risk score system was proven to have strong prognostic value for AEG patients.

Conclusions: Our results may provide new insights into the prognostic evaluation of AEG.
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http://dx.doi.org/10.1186/s12885-021-08558-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278582PMC
July 2021

[A study on KIF1A gene missense variant analysis and its protein expression and structure profiles of an autism spectrum disorder family trio].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jul;38(7):620-625

Mental Health Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.

Objective: To analyze the pathogenic variants of the KIF1A gene and its corresponding protein structure in an autism spectrum disorder (ASD) family trio carrying harmful missense variants in the KIF1A gene.

Methods: The peripheral blood DNA of the patient and his parents was extracted and sequenced using whole exome sequencing (WES) technology and verified by Sanger sequencing. Bioinformatics software SIFT, PolyPhen-2, Mutation Taster, and CADD software were used to analyze the harmfulness and conservation of variants. The Human Brain Transcriptome (HBT) database was used to analyze the expression of the KIF1A gene in the brain. PredictProtein and SWISS-MODEL were further used to predict the secondary structure and tertiary structure of KIF1A wild-type protein and variant protein. PyMOL V2.4 was utilized to investigate the change of hydrogen bond connection after protein variant.

Results: The WES sequencing revealed a missense variant c.664A>C (p.Asn222His) in the child's KIF1A gene, and this variant was a de novo variant. The harmfulness prediction results suggest that this variant is harmful. By analyzing expression level of KIF1A gene in the brain. It is found that KIF1A gene widely expressed in various brain regions during embryonic development. By analyzing the variant protein structure, the missense variant of KIF1A will cause many changes in the secondary structure of protein, such as alpha-helix, beta-strand, and protein binding domain. The connection of hydrogen bond and spatial structure will also change, thereby changing the original biological function.

Conclusion: The KIF1A gene may be a risk gene for ASD.
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http://dx.doi.org/10.3760/cma.j.cn511374-20210120-00060DOI Listing
July 2021

An automated multi-component gas adsorption system (MC GAS).

Rev Sci Instrum 2021 May;92(5):054102

School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.

The knowledge gap on adsorption of complex mixtures in the literature relative to single component data represents a persistent obstacle to developing accurate process models for adsorption separations. The collection of mixed gas adsorption data is an imminent need for improved understanding of the behavior of adsorbent systems in these diverse adsorption applications. Current approaches to understanding mixture adsorption using predictive theories based on pure component adsorption experiments often fail to capture the behavior of more complex, non-ideal systems. In this work, we present an automated volumetric instrument for the measurement of mixed gas adsorption isotherms. This instrument was validated by comparison to other in-house instruments and data available in the literature, and the binary adsorption measurements were found to be thermodynamically consistent. The automation of this instrument allows for rapid collection of high-quality mixture adsorption data.
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http://dx.doi.org/10.1063/5.0031579DOI Listing
May 2021

UNC5B Promotes Vascular Endothelial Cell Senescence via the ROS-Mediated P53 Pathway.

Oxid Med Cell Longev 2021 20;2021:5546711. Epub 2021 Jun 20.

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.

Vascular endothelial cell senescence is involved in human aging and age-related vascular disorders. Guidance receptor UNC5B is implicated in oxidative stress and angiogenesis. Nonetheless, little is known about the role of UNC5B in endothelial cell senescence. Here, we cultured primary human umbilical vein endothelial cells to young and senescent phases. Subsequently, the expression of UNC5B was identified in replicative senescent cells, and then, its effect on endothelial cell senescence was confirmed by UNC5B-overexpressing lentiviral vectors and RNA interference. Overexpression of UNC5B in young endothelial cells significantly increased senescence-associated -galactosidase-positive cells, upregulated the mRNAs expression of the senescence-associated secretory phenotype genes, reduced total cell number, and inhibited the potential for cell proliferation. Furthermore, overexpression of UNC5B promoted the generation of intracellular reactive oxygen species (ROS) and activated the P53 pathway. Besides, overexpression of UNC5B disturbed endothelial function by inhibiting cell migration and tube formation. Nevertheless, silencing UNC5B generated conflicting outcomes. Blocking ROS production or inhibiting the function of P53 rescued endothelial cell senescence induced by UNC5B. These findings suggest that UNC5B promotes endothelial cell senescence, potentially by activating the ROS-P53 pathway. Therefore, inhibiting UNC5B might reduce endothelial cell senescence and hinder age-related vascular disorders.
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http://dx.doi.org/10.1155/2021/5546711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238614PMC
June 2021

The genomic architectures of tumour-adjacent tissues, plasma and saliva reveal evolutionary underpinnings of relapse in head and neck squamous cell carcinoma.

Br J Cancer 2021 Jul 6. Epub 2021 Jul 6.

Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.

Background: Head and neck squamous cell carcinoma (HNSCC) is characterised by a dismal prognosis; nonetheless, limited studies have unveiled the mechanisms underlying HNSCC relapse.

Methods: Next-generation sequencing was performed to identify the somatic mutations in 188 matched samples, including primary tumours, tumour-adjacent tissues (TATs), pre- and post-operative plasma, saliva and peripheral blood lymphocytes (PBLs) from 27 patients. The evolutionary relationship between TATs and tumours were analysed. The dynamic changes of tumour- and TAT-specific mutations in liquid biopsies were monitored together with survival analysis.

Results: Alterations were detected in 27 out of 27 and 19 out of 26 tumours and TATs, respectively. TP53 was the most prevalently mutated gene in TATs. Some TATs shared mutations with primary tumours, while some other TATs were evolutionarily unrelated to tumours. Notably, TP53 mutations in TATs are stringently associated with premalignant transformation and are indicative of worse survival (hazard ratio = 14.01). TAT-specific mutations were also detected in pre- and/or post-operative liquid biopsies and were indicative of disease relapse.

Conclusions: TATs might undergo the processes of premalignant transformation, tumorigenesis and eventually relapse by either inheriting tumorigenic mutations from ancestral clones where the tumour originated or gaining private mutations independent of primary tumours. Detection of tumour- and/or TAT-specific genetic alterations in post-operative biopsies shows profound potential in prognostic use.
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http://dx.doi.org/10.1038/s41416-021-01464-0DOI Listing
July 2021

Kakonein restores diabetes-induced endothelial junction dysfunction via promoting autophagy-mediated NLRP3 inflammasome degradation.

J Cell Mol Med 2021 Jun 27. Epub 2021 Jun 27.

School of Pharmaceutical, Guangzhou University of Chinese Medicine, Guangzhou, China.

In diabetes-induced complications, inflammatory-mediated endothelial dysfunction is the core of disease progression. Evidence shows that kakonein, an isoflavone common in Pueraria, can effectively treat diabetes and its complications. Therefore, we explored whether kakonein protects cardiovascular endothelial function by inhibiting inflammatory responses. In this study, C57BL/6J mice were injected with streptozocin to establish a diabetes model and treated with kakonein or metformin for 7 days. The protective effect of kakonein on cardiovascular endothelial junctions and NLRP3 inflammasome activation was verified through immunofluorescence and ELISA assay. In addition, the regulation of autophagy on the NLRP3 inflammasome was investigated through Western blot, immunofluorescence and RT-qPCR. Results showed that kakonein restored the function of endothelial junctions and inhibited the assembly and activation of the NLRP3 inflammasome. Interestingly, kakonein decreased the expression of NLRP3 inflammasome protein by not reducing the transcriptional levels of NLRP3 and caspase-1. Kakonein activated autophagy in an AMPK-dependent manner, which reduced the activation of the NLRP3 inflammasome. In addition, kakonein inhibited both hyperglycaemia-induced cardiovascular endothelial junction dysfunction and NLRP3 inflammasome activation, similar to autophagy agonist. Our findings indicated that kakonein exerts a protective effect on hyperglycaemia-induced chronic vascular disease by regulating the NLRP3 inflammasome through autophagy.
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http://dx.doi.org/10.1111/jcmm.16747DOI Listing
June 2021

Toxic effects of ammonia on the intestine of the Asian clam (Corbicula fluminea).

Environ Pollut 2021 Jun 19;287:117617. Epub 2021 Jun 19.

Key Laboratory of Pollution Processes and Environmental Criteria, Ministry of Education, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin, 300350, PR China. Electronic address:

Intestines contain a large number of microorganisms that collectively play a vital role in regulating physiological and biochemical processes, including digestion, water balance, and immune function. In this study, we explored the effects of ammonia stress on intestinal inflammation, the antioxidant system, and the microbiome of the Asian clam (Corbicula fluminea). Exposure to varying ammonia concentrations (10 and 25 mg N/L) and exposure times (7 and 14 days) resulted in damage to C. fluminea intestinal tissue, according to histological analysis. Furthermore, intestinal inflammatory responses and damage to the antioxidant system were revealed through qPCR, ELISA, and biochemical analysis experiments. Inflammatory responses were more severe in the treatment group exposed to a lower concentration of ammonia. High-throughput 16S rDNA sequencing showed that ammonia stress under different conditions altered intestinal bacterial diversity and microbial community composition, particularly impacting the dominant phylum Proteobacteria and genus Aeromonas. These results indicate that ammonia stress can activate intestinal inflammatory reactions, damage the intestinal antioxidant system, and alter intestinal microbial composition, thereby impeding intestinal physiological function and seriously threatening the health of C. fluminea.
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http://dx.doi.org/10.1016/j.envpol.2021.117617DOI Listing
June 2021

Chloroquine suppresses proliferation and invasion and induces apoptosis of osteosarcoma cells associated with inhibition of phosphorylation of STAT3.

Aging (Albany NY) 2021 06 24;13(13):17901-17913. Epub 2021 Jun 24.

Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.

Background: Osteosarcoma (OS) is characterized by a high rate of metastasis. It has been found that tumor cells can bypass apoptosis which leads to an uncontrolled proliferation, but chloroquine (CQ) can have an effect on the tumors by inducing apoptosis. We aimed to explore the effects and the hypothetical mechanism of CQ effects on OS.

Methods: We first estimated the CQ effects on proliferation, apoptosis, migration, invasion, and lamellipodia formation of OS cells. Mice bearing xenograft model were used to test the anti-tumor growth and lung metastasis effects of CQ in OS. Western blot and immunohistochemistry were used to explore the mechanism of CQ effects and the association between p-STAT3 expression and lung metastasis of OS patients.

Results: CQ induces the apoptosis and suppressed the viability, proliferation, migration, invasion, and lamellipodia formation of OS cells . experiments demonstrated that CQ inhibited tumor growth and lung metastasis. CQ induced apoptosis was dependent on the lysosomal inhibition and inhibition of protein turnover. The lung metastasis was associated with the p-STAT3 expression in OS patients.

Conclusion: CQ inhibited progression of OS cells , and suppressed tumor growth and lung metastasis . p-STAT3 can be a predictive biomarker for lung metastasis in osteosarcoma patients.
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http://dx.doi.org/10.18632/aging.203196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312460PMC
June 2021

COVID-19 vaccine development from the perspective of cancer patients.

Hum Vaccin Immunother 2021 Jun 25:1-7. Epub 2021 Jun 25.

Department of Radiation Oncology, Rutgers-Cancer Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Currently, many companies around the world are actively developing COVID-19 vaccines. Fourteen vaccines with reliable safety and effectiveness are being successfully distributed to the public. However, there is no specific clinical trial data of the vaccines currently on the market on cancer patients at various stages, so the safety and effectiveness on cancer patients is unknown. This mini-review aims to discuss the impact of COVID-19 on cancer patients, and the urgent need of COVID-19 vaccines for cancer patients. In this review, we described the current status of the COVID-19 vaccine usages in cancer patients, as well as discussed potential problems in the use of vaccine. In addition, we included an original survey of the acceptance of the COVID-19 vaccines in 209 cancer patients and their family members. COVID-19 vaccine can provide cancer patients with social and medical benefits; therefore, clinical trials of vaccines on cancer patients are in great need.
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http://dx.doi.org/10.1080/21645515.2021.1943988DOI Listing
June 2021

Synergistically Assembled Cobalt-Telluride/Graphene Foam with High-Performance Electromagnetic Wave Absorption in Both Gigahertz and Terahertz Band Ranges.

ACS Appl Mater Interfaces 2021 Jul 24;13(26):30967-30979. Epub 2021 Jun 24.

National Institute for Advanced Materials, Tianjin Key Laboratory of Metal and Molecule Based Material Chemistry, Key Laboratory of Functional Polymer Materials, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Materials Science and Engineering, Nankai University, Tianjin 300350, PR China.

Electromagnetic wave (EMW)-absorbing materials have a great impact on civil use and national defense. In this paper, a novel composite, [email protected] (the mass ratio of reduced graphene oxide to CoTe is 1:6, annealed at 300 °C), has been obtained through a facile melt-diffusion method and solvothermal method. The as-prepared samples have shown excellent reflection losses (RL) and effective adsorption bandwidth (EAB) by controlling the loading of CoTe and the annealing temperature. The sample has exhibited a RL of -62.2 dB at 13.04 GHz with the matching thickness of 3.53 mm, and the EAB reaches 8.2 GHz at 2-18 GHz. Moreover, excellent terahertz (THz) absorption property is also obtained at 0.2-2.0 THz. A RL of 54.07 dB is acquired, and the EAB covers 100% of the entire measured bandwidth. Thus, [email protected] can be considered as a promising EMW absorption material in both gigahertz and terahertz band ranges.
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http://dx.doi.org/10.1021/acsami.1c05351DOI Listing
July 2021

Sebaceous carcinoma of the right palate: case report and literature review.

Gland Surg 2021 May;10(5):1819-1825

Department of stomatology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.

Considering the low incidence rates of primary sebaceous carcinoma (SC) of extraorbital sites, let alone those occur in intraoral sites, clinicopathological characteristics and histogenesis are not fully understood. In the present case, a maxillary mass was presented and a low-grade malignant tumor was suspected according to the CT scans, preoperative FNA, and clinical conditions. Other carcinomas, including acinar cell carcinoma (ACC), basaloid cell carcinoma (BCC), SCC, mucoepidermoid carcinoma, and epithelial-myoepithelial carcinoma (EMC), were also considered before surgery. Due to the rare occurrence of SC and no preoperative suspects, a fresh sample was not kept. Sadly, thus cause those special stains (e.g., Oil Red O and Sudan IV) which form the primary basis for a diagnosis of SC in academic circles were missing. A comprehensive literature review identified only 10 cases of intraoral SC, of which the primary sites reported in the English literature were the buccal mucosa, mouth floor, upper labial mucosa, and tongue. Due to an absence of specific biomarkers and simulated characters, histochemistry and immunohistochemistry such as PAS, CK, EMA, p63, p53, S-100, calponin, CD117, Ki-67, a-SMA, and AR form the diagnostic standard of SC. Postoperative immunohistochemistry of our case showed S100(-), Ki-67(-), calponin(-), CD117(-), CK20(-), PAS(-), AR(+), CK(+), CK5/6(+), P53(+), P63(+), a-SMA (+). Thus the diagnosis of SC was finally made. Through discussing the findings of our case and reviewing literature, we present the histological features and discuss possible outstanding biomarkers of this neoplasm.
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http://dx.doi.org/10.21037/gs-21-218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184391PMC
May 2021

Dissolved organic matter (DOM) quality drives biogeographic patterns of soil bacterial communities and their association networks in semi-arid regions.

FEMS Microbiol Ecol 2021 06;97(7)

Department of Microbiology and Plant Biology, University of Oklahoma, Norman, OK 73019, USA.

It is of great interest to elucidate the biogeographic patterns of soil microorganisms and their driving forces, which is fundamental to predicting alterations in microbial-mediated functions arising from environment changes. Although dissolved organic matter (DOM) represents an important resource for soil microorganisms, knowledge of how its quality affects microbial biogeography is limited. Here, we characterized soil bacterial communities and DOM quality in 45 soil samples collected from a 1500-km sampling transect through semi-arid regions in northern China which are currently suffering great pressure from climate change, using Illumina Miseq sequencing and fluorescence spectroscopy, respectively. We found that DOM quality (i.e. the source of DOM and the humification degree of DOM) had profound shaping influence on the biogeographic patterns exhibited by bacterial diversity, community composition and association networks. Specifically, the composition of bacteria community closely associated with DOM quality. Plant-derived DOM sustained higher bacterial diversity relative to microbial-derived DOM. Meanwhile, bacterial diversity linearly increased with increasing humification degree of DOM. Additionally, plant-derived DOM was observed to foster more complex bacterial association networks with less competition. Together, our work contributes to the factors underlying biogeographic patterns not only of bacterial diversity, community composition but also of their association networks and reports previously undocumented important role of DOM quality in shaping these patterns.
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http://dx.doi.org/10.1093/femsec/fiab083DOI Listing
June 2021

Genotype-by-environment interactions for reproduction, body composition, and growth traits in maternal-line pigs based on single-step genomic reaction norms.

Genet Sel Evol 2021 Jun 17;53(1):51. Epub 2021 Jun 17.

Department of Animal Sciences, Purdue University, West Lafayette, IN, 47907, USA.

Background: There is an increasing need to account for genotype-by-environment (G × E) interactions in livestock breeding programs to improve productivity and animal welfare across environmental and management conditions. This is even more relevant for pigs because selection occurs in high-health nucleus farms, while commercial pigs are raised in more challenging environments. In this study, we used single-step homoscedastic and heteroscedastic genomic reaction norm models (RNM) to evaluate G × E interactions in Large White pigs, including 8686 genotyped animals, for reproduction (total number of piglets born, TNB; total number of piglets born alive, NBA; total number of piglets weaned, NW), growth (weaning weight, WW; off-test weight, OW), and body composition (ultrasound muscle depth, MD; ultrasound backfat thickness, BF) traits. Genetic parameter estimation and single-step genome-wide association studies (ssGWAS) were performed for each trait.

Results: The average performance of contemporary groups (CG) was estimated and used as environmental gradient in the reaction norm analyses. We found that the need to consider heterogeneous residual variance in RNM models was trait dependent. Based on estimates of variance components of the RNM slope and of genetic correlations across environmental gradients, G × E interactions clearly existed for TNB and NBA, existed for WW but were of smaller magnitude, and were not detected for NW, OW, MD, and BF. Based on estimates of the genetic variance explained by the markers in sliding genomic windows in ssGWAS, several genomic regions were associated with the RNM slope for TNB, NBA, and WW, indicating specific biological mechanisms underlying environmental sensitivity, and dozens of novel candidate genes were identified. Our results also provided strong evidence that the X chromosome contributed to the intercept and slope of RNM for litter size traits in pigs.

Conclusions: We provide a comprehensive description of G × E interactions in Large White pigs for economically-relevant traits and identified important genomic regions and candidate genes associated with GxE interactions on several autosomes and the X chromosome. Implementation of these findings will contribute to more accurate genomic estimates of breeding values by considering G × E interactions, in order to genetically improve the environmental robustness of maternal-line pigs.
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http://dx.doi.org/10.1186/s12711-021-00645-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212483PMC
June 2021

Highly Stretchable Shape Memory Self-Soldering Conductive Tape with Reversible Adhesion Switched by Temperature.

Nanomicro Lett 2021 May 11;13(1):124. Epub 2021 May 11.

State Key Laboratory and Institute of Elemento-Organic Chemistry, Centre of Nanoscale Science and Technology and Key Laboratory of Functional Polymer Materials, College of Chemistry, Nankai University, Weijin Road 94, Tianjin, 300071, People's Republic of China.

Highlights: Shape memory self-soldering tape used as conductive interconnecting material. Perfect shape and conductivity memory performance and anti-fatigue performance. Reversible strong-to-weak adhesion switched by temperature. With practical interest in the future applications of next-generation electronic devices, it is imperative to develop new conductive interconnecting materials appropriate for modern electronic devices to replace traditional rigid solder tin and silver paste of high melting temperature or corrosive solvent requirements. Herein, we design highly stretchable shape memory self-soldering conductive (SMSC) tape with reversible adhesion switched by temperature, which is composed of silver particles encapsulated by shape memory polymer. SMSC tape has perfect shape and conductivity memory property and anti-fatigue ability even under the strain of 90%. It also exhibits an initial conductivity of 2772 S cm and a maximum tensile strain of ~ 100%. The maximum conductivity could be increased to 5446 S cm by decreasing the strain to 17%. Meanwhile, SMSC tape can easily realize a heating induced reversible strong-to-weak adhesion transition for self-soldering circuit. The combination of stable conductivity, excellent shape memory performance, and temperature-switching reversible adhesion enables SMSC tape to serve two functions of electrode and solder simultaneously. This provides a new way for conductive interconnecting materials to meet requirements of modern electronic devices in the future.
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http://dx.doi.org/10.1007/s40820-021-00652-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113436PMC
May 2021

A Review on Metal-Organic Framework-Derived Porous Carbon-Based Novel Microwave Absorption Materials.

Nanomicro Lett 2021 Jan 12;13(1):56. Epub 2021 Jan 12.

National Institute for Advanced Materials Tianjin Key Laboratory of Metal and Molecule Based Material Chemistry, Key Laboratory of Functional Polymer Materials, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Materials Science and Engineering, Nankai University, Tianjin, 300350, People's Republic of China.

The development of microwave absorption materials (MAMs) is a considerable important topic because our living space is crowed with electromagnetic wave which threatens human's health. And MAMs are also used in radar stealth for protecting the weapons from being detected. Many nanomaterials were studied as MAMs, but not all of them have the satisfactory performance. Recently, metal-organic frameworks (MOFs) have attracted tremendous attention owing to their tunable chemical structures, diverse properties, large specific surface area and uniform pore distribution. MOF can transform to porous carbon (PC) which is decorated with metal species at appropriate pyrolysis temperature. However, the loss mechanism of pure MOF-derived PC is often relatively simple. In order to further improve the MA performance, the MOFs coupled with other loss materials are a widely studied method. In this review, we summarize the theories of MA, the progress of different MOF-derived PC‑based MAMs, tunable chemical structures incorporated with dielectric loss or magnetic loss materials. The different MA performance and mechanisms are discussed in detail. Finally, the shortcomings, challenges and perspectives of MOF-derived PC‑based MAMs are also presented. We hope this review could provide a new insight to design and fabricate MOF-derived PC-based MAMs with better fundamental understanding and practical application.
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http://dx.doi.org/10.1007/s40820-020-00582-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187524PMC
January 2021

Does the sequence of high-dose rate brachytherapy boost and IMRT for prostate cancer impact early toxicity outcomes? Results from a single institution analysis.

Clin Transl Radiat Oncol 2021 Jul 13;29:47-53. Epub 2021 May 13.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, United States.

Background: We present the first report comparing early toxicity outcomes with high-dose rate brachytherapy (HDR-BT) boost upfront versus intensity modulated RT (IMRT) upfront combined with androgen deprivation therapy (ADT) as definitive management for intermediate risk or higher prostate cancer.

Methods And Materials: We reviewed all non-metastatic prostate cancer patients who received HDR-BT boost from 2014 to 2019. HDR-BT boost was offered to patients with intermediate-risk disease or higher. ADT use and IMRT target volume was based on NCCN risk group. IMRT dose was typically 45 Gy in 25 fractions to the prostate and seminal vesicles ± pelvic lymph nodes. HDR-BT dose was 15 Gy in 1 fraction, delivered approximately 3 weeks before after IMRT. The sequence was based on physician preference. Biochemical recurrence was defined per ASTRO definition. Gastrointestinal (GI) and Genitourinary (GU) toxicity was graded per CTCAE v5.0. Pearson Chi-squared test and Wilcoxon tests were used to compare toxicity rates. -value < 0.05 was significant.

Results: Fifty-eight received HDR-BT upfront (majority 2014-2016) and 57 IMRT upfront (majority 2017-2018). Median follow-up was 26.0 months. The two cohorts were well-balanced for baseline patient/disease characteristics and treatment factors. There were differences in treatment sequence based on the year in which patients received treatment. Overall, rates of grade 3 or higher GI or GU toxicity were <1%. There was no significant difference in acute or late GI or GU toxicity between the two groups.

Conclusion: We found no significant difference in GI/GU toxicity in intermediate-risk or higher prostate cancer patients receiving HDR-BT boost upfront versus IMRT upfront combined with ADT. These findings suggest that either approach may be reasonable. Longer follow-up is needed to evaluate late toxicity and long-term disease control.
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http://dx.doi.org/10.1016/j.ctro.2021.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182264PMC
July 2021

Ectopic Pulmonary Goiter Simulating Malignant Tumor Detected on SPECT/CT.

Clin Nucl Med 2021 Jun 16. Epub 2021 Jun 16.

From the Department of Nuclear Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

Abstract: A 46-year-old asymptomatic woman with a newly detected large pulmonary mass was admitted to our hospital. An ultrasonography-guided needle biopsy was performed based on a suspicion of malignancy, and an ectopic goiter was confirmed pathologically. Laboratory findings were unremarkable, except that thyroid function tests suggested subclinical hyperthyroidism. A 131I whole-body scintigraphy and SPECT/CT were further performed and revealed intense radioiodine uptake in the pulmonary mass, the mediastinal nodule, and thyroid gland. A diagnosis of ectopic pulmonary goiter with normally located thyroid was finally made.
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http://dx.doi.org/10.1097/RLU.0000000000003776DOI Listing
June 2021
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