Publications by authors named "Hui Cai"

573 Publications

SERPINB10 contributes to asthma by inhibiting the apoptosis of allergenic Th2 cells.

Respir Res 2021 Jun 14;22(1):178. Epub 2021 Jun 14.

Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.

Background: Serine peptidase inhibitor, clade B, member 10 (SERPINB10) contributes to allergic inflammation in asthma. However, its role in the T-helper type 2 (Th2) response of allergic asthma is not known. The goal of this study was to unveil the function of SERPINB10 in the Th2 response of allergic asthma and the mechanism by which SERPINB10 affects the viability of Th2 cells.

Methods: Th2 cytokines and serum levels of house dust mite (HDM)-specific IgE in bronchoalveolar lavage fluid were examined by ELISA in an HDM-induced asthma model. The number and apoptosis of Th1 and Th2 cells in mouse lungs were measured by flow cytometry. Naïve CD4 T cells from patients with asthma were cultured under appropriate polarizing conditions to generate Th1 and Th2 cells. SERPINB10 expression in polarized Th1 and Th2 cells was quantified by real-time reverse transcription-quantitative polymerase chain reaction. SERPINB10 expression was knocked down in human CD4 T cells with lentivirus.

Results: Knockdown of SERPINB10 expression significantly diminished HDM-induced Th2 cytokine secretion and level of HDM-specific IgE. After HDM exposure, SERPINB10-knockdown mice had diminished numbers of Th2 cells, but similar numbers of Th1 cells, compared with those in negative-control mice. Th2 cells of SERPINB10-knockdown mice were more susceptible to apoptosis than that of control mice. Stimulating T-cell receptors (TCRs) with anti-CD3 antibody caused upregulation of SERPINB10 expression in polarized Th2 cells, but not polarized Th1 cells. Knockdown of SERPINB10 expression resulted in fewer numbers and greater apoptosis of polarized Th2 cells.

Conclusion: Our results suggest that SERPINB10 may contribute to allergic inflammation and the Th2 response of asthma by inhibiting the apoptosis of Th2 cells.
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http://dx.doi.org/10.1186/s12931-021-01757-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201873PMC
June 2021

BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants.

Nature 2021 Jun 10. Epub 2021 Jun 10.

Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve around the world, generating new variants that are of concern based on their potential for altered transmissibility, pathogenicity, and coverage by vaccines and therapeutics. Here we report that 20 human sera, drawn 2 or 4 weeks after two doses of BNT162b2, neutralize engineered SARS-CoV-2 with a USA-WA1/2020 genetic background (a virus strain isolated in January 2020) and spike glycoproteins from the newly emerged B.1.617.1, B.1.617.2, B.1.618 (all first identified in India) or B.1.525 (first identified in Nigeria) lineages. Geometric mean plaque reduction neutralization titers against the variant viruses, particularly the B.1.617.1 variant, appear lower than the titer against USA-WA1/2020 virus, but all sera tested neutralize the variant viruses at titers of at least 40. The susceptibility of these newly emerged variants to BNT162b2 vaccine-elicited neutralization supports mass immunization as a central strategy to end the coronavirus disease 2019 (COVID-19) pandemic across geographies.
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http://dx.doi.org/10.1038/s41586-021-03693-yDOI Listing
June 2021

Responses and coping methods of different testicular cell types to heat stress: overview and perspectives.

Biosci Rep 2021 Jun;41(6)

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.

To facilitate temperature adjustments, the testicles are located outside the body cavity. In most mammals, the temperature of the testes is lower than the body temperature to ensure the normal progression of spermatogenesis. Rising temperatures affect spermatogenesis and eventually lead to a decline in male fertility or even infertility. However, the testes are composed of different cell types, including spermatogonial stem cells (SSCs), spermatocytes, spermatozoa, Leydig cells, and Sertoli cells, which have different cellular responses to heat stress. Recent studies have shown that using different drugs can relieve heat stress-induced reproductive damage by regulating different signaling pathways. Here, we review the mechanisms by which heat stress damages different cells in testes and possible treatments.
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http://dx.doi.org/10.1042/BSR20210443DOI Listing
June 2021

Development and Validation of a CD8+ T Cell Infiltration-Related Signature for Melanoma Patients.

Front Immunol 2021 10;12:659444. Epub 2021 May 10.

Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, China.

Aim: Immunotherapy shows efficacy in only a subset of melanoma patients. Here, we intended to construct a risk score model to predict melanoma patients' sensitivity to immunotherapy.

Methods: Integration analyses were performed on melanoma patients from high-dimensional public datasets. The CD8+ T cell infiltration related genes (TIRGs) were selected TIMER and CIBERSORT algorithm. LASSO Cox regression was performed to screen for the crucial TIRGs. Single sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithm were used to evaluate the immune activity. The prognostic value of the risk score was determined by univariate and multivariate Cox regression analysis.

Results: 184 candidate TIRGs were identified in melanoma patients. Based on the candidate TIRGs, melanoma patients were classified into three clusters which were characterized by different immune activity. Six signature genes were further screened out of 184 TIRGs and a representative risk score for patient survival was constructed based on these six signature genes. The risk score served as an indicator for the level of CD8+ T cell infiltration and acted as an independent prognostic factor for the survival of melanoma patients. By using the risk score, we achieved a good predicting result for the response of cancer patients to immunotherapy. Moreover, pan-cancer analysis revealed the risk score could be used in a wide range of non-hematologic tumors.

Conclusions: Our results showed the potential of using signature gene-based risk score as an indicator to predict melanoma patients' sensitivity to immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2021.659444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141567PMC
May 2021

Associations of circulating choline and its related metabolites with cardiometabolic biomarkers: an international pooled analysis.

Am J Clin Nutr 2021 May 21. Epub 2021 May 21.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Choline is an essential nutrient; however, the associations of choline and its related metabolites with cardiometabolic risk remain unclear.

Objective: We examined the associations of circulating choline, betaine, carnitine, and dimethylglycine (DMG) with cardiometabolic biomarkers and their potential dietary and nondietary determinants.

Methods: The cross-sectional analyses included 32,853 participants from 17 studies, who were free of cancer, cardiovascular diseases, chronic kidney diseases, and inflammatory bowel disease. In each study, metabolites and biomarkers were log-transformed and standardized by means and SDs, and linear regression coefficients (β) and 95% CIs were estimated with adjustments for potential confounders. Study-specific results were combined by random-effects meta-analyses. A false discovery rate <0.05 was considered significant.

Results: We observed moderate positive associations of circulating choline, carnitine, and DMG with creatinine [β (95% CI): 0.136 (0.084, 0.188), 0.106 (0.045, 0.168), and 0.128 (0.087, 0.169), respectively, for each SD increase in biomarkers on the log scale], carnitine with triglycerides (β = 0.076; 95% CI: 0.042, 0.109), homocysteine (β = 0.064; 95% CI: 0.033, 0.095), and LDL cholesterol (β = 0.055; 95% CI: 0.013, 0.096), DMG with homocysteine (β = 0.068; 95% CI: 0.023, 0.114), insulin (β = 0.068; 95% CI: 0.043, 0.093), and IL-6 (β = 0.060; 95% CI: 0.027, 0.094), but moderate inverse associations of betaine with triglycerides (β = -0.146; 95% CI: -0.188, -0.104), insulin (β = -0.106; 95% CI: -0.130, -0.082), homocysteine (β = -0.097; 95% CI: -0.149, -0.045), and total cholesterol (β = -0.074; 95% CI: -0.102, -0.047). In the whole pooled population, no dietary factor was associated with circulating choline; red meat intake was associated with circulating carnitine [β = 0.092 (0.042, 0.142) for a 1 serving/d increase], whereas plant protein was associated with circulating betaine [β = 0.249 (0.110, 0.388) for a 5% energy increase]. Demographics, lifestyle, and metabolic disease history showed differential associations with these metabolites.

Conclusions: Circulating choline, carnitine, and DMG were associated with unfavorable cardiometabolic risk profiles, whereas circulating betaine was associated with a favorable cardiometabolic risk profile. Future prospective studies are needed to examine the associations of these metabolites with incident cardiovascular events.
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http://dx.doi.org/10.1093/ajcn/nqab152DOI Listing
May 2021

Bosonic condensation of exciton-polaritons in an atomically thin crystal.

Nat Mater 2021 May 6. Epub 2021 May 6.

Institute of Physics, Carl von Ossietzky University, Oldenburg, Germany.

The emergence of two-dimensional crystals has revolutionized modern solid-state physics. From a fundamental point of view, the enhancement of charge carrier correlations has sparked much research activity in the transport and quantum optics communities. One of the most intriguing effects, in this regard, is the bosonic condensation and spontaneous coherence of many-particle complexes. Here we find compelling evidence of bosonic condensation of exciton-polaritons emerging from an atomically thin crystal of MoSe embedded in a dielectric microcavity under optical pumping at cryogenic temperatures. The formation of the condensate manifests itself in a sudden increase of luminescence intensity in a threshold-like manner, and a notable spin-polarizability in an externally applied magnetic field. Spatial coherence is mapped out via highly resolved real-space interferometry, revealing a spatially extended condensate. Our device represents a decisive step towards the implementation of coherent light-sources based on atomically thin crystals, as well as non-linear, valleytronic coherent devices.
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http://dx.doi.org/10.1038/s41563-021-01000-8DOI Listing
May 2021

Long-term Diet Quality and Gut Microbiome Functionality: A Prospective, Shotgun Metagenomic Study among Urban Chinese Adults.

Curr Dev Nutr 2021 Apr 2;5(4):nzab026. Epub 2021 Apr 2.

Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Diet is known to affect human gut microbiome composition; yet, how diet affects gut microbiome functionality remains unclear.

Objective: We compared the diversity and abundance/presence of fecal microbiome metabolic pathways among individuals according to their long-term diet quality.

Methods: In 2 longitudinal cohorts, we assessed participants' usual diets via repeated surveys during 1996-2011 and collected a stool sample in 2015-2018. Participants who maintained a healthy or unhealthy diet (i.e., stayed in the highest or lowest quintile of a healthy diet score throughout follow-up) were selected. Participants were excluded if they reported a history of cancer, cardiovascular disease, diabetes, or hypertension; had diarrhea or constipation in the last 7 d; or used antibiotics in the last 6 mo before stool collection. Functional profiling of shotgun metagenomics was performed using HUMAnN2. Associations of dietary variables and 420 microbial metabolic pathways were evaluated via multivariable-adjusted linear or logistic regression models.

Results: We included 144 adults (mean age = 64 y; 55% female); 66 had an unhealthy diet and 78 maintained a healthy diet. The healthy diet group had higher Shannon α-diversity indexes of microbial gene families and metabolic pathways (both < 0.02), whereas β-diversity, as evaluated by Bray-Curtis distance, did not differ between groups (both > 0.50). At < 0.01 [false discovery rate (FDR) <0.15], the healthy diet group showed enriched pathways for vitamin and carrier biosynthesis (e.g., tetrahydrofolate, acetyl-CoA, and l-methionine) and tricarboxylic acid (TCA) cycle, and increased degradation (or reduced biosynthesis) of certain sugars [e.g., cytidine monophosphate (CMP)-legionaminate, deoxythymidine diphosphate (dTDP)-l-rhamnose, and sucrose], nucleotides, 4-aminobutanoate, methylglyoxal, sulfate, and aromatic compounds (e.g., catechol and toluene). Meanwhile, several food groups were associated with the CMP-legionaminate biosynthesis pathway at FDR <0.05.

Conclusions: In a small longitudinal study of generally healthy, older Chinese adults, we found long-term healthy eating was associated with increased α-diversity of microbial gene families and metabolic pathways and altered symbiotic functions relevant to human nutrition and health.
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http://dx.doi.org/10.1093/cdn/nzab026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068758PMC
April 2021

Altered transcriptome and disease-related phenotype emerge only after fibroblasts harvested from patients with age-related macular degeneration are differentiated into retinal pigment epithelium.

Exp Eye Res 2021 Jun 22;207:108576. Epub 2021 Apr 22.

Department of Ophthalmology and Visual Science, Yale University School of Medicine, 300 George St., Suite 8100, New Haven, CT, 06510, USA. Electronic address:

We have reported previously that retinal pigment epithelium (RPE) differentiated from induced pluripotent stem cells (iPSC) generated from fibroblasts of patients with age-related macular degeneration (AMD) exhibit a retinal degenerative disease phenotype and a distinct transcriptome compared to age-matched controls. Since the genetic composition of the iPSC and RPE are inherited from fibroblasts, we investigated whether differential behavior was present in the parental fibroblasts and iPSC prior to differentiation of the cell lines into RPE. Principal component analyses revealed significant overlap (essentially no differences) in the transcriptome of fibroblasts between AMD and controls. After reprogramming, there was no significant difference in the transcriptome of iPSC generated from AMD versus normal donors. In contrast, the transcriptome of RPE derived from iPSC segregated into two distinct clusters of AMD-derived cells versus controls. Interestingly, mitochondrial dysfunction in AMD-derived RPE was evident after approximately two months in culture. Moreover, these differences in mitochondrial dysfunction were not evident in the parental fibroblasts and iPSC. This study demonstrates an altered transcriptome and impaired mitochondrial function in RPE derived from AMD patients versus controls, and demonstrates these differences are not present in the original fibroblasts or iPSC. These results suggest that pathology in AMD is triggered upon differentiation of parent cells into RPE. More study of this phenomenon could advance the current understandings of the etiology of AMD and the development of novel therapeutic targets.
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http://dx.doi.org/10.1016/j.exer.2021.108576DOI Listing
June 2021

Circulating trimethylamine N-oxide in association with diet and cardiometabolic biomarkers: an international pooled analysis.

Am J Clin Nutr 2021 05;113(5):1145-1156

Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Trimethylamine N-oxide (TMAO), a diet-derived, gut microbial-host cometabolite, has been linked to cardiometabolic diseases. However, the relations remain unclear between diet, TMAO, and cardiometabolic health in general populations from different regions and ethnicities.

Objectives: To examine associations of circulating TMAO with dietary and cardiometabolic factors in a pooled analysis of 16 population-based studies from the United States, Europe, and Asia.

Methods: Included were 32,166 adults (16,269 white, 13,293 Asian, 1247 Hispanic/Latino, 1236 black, and 121 others) without cardiovascular disease, cancer, chronic kidney disease, or inflammatory bowel disease. Linear regression coefficients (β) were computed for standardized TMAO with harmonized variables. Study-specific results were combined by random-effects meta-analysis. A false discovery rate <0.10 was considered significant.

Results: After adjustment for potential confounders, circulating TMAO was associated with intakes of animal protein and saturated fat (β = 0.124 and 0.058, respectively, for a 5% energy increase) and with shellfish, total fish, eggs, and red meat (β = 0.370, 0.151, 0.081, and 0.056, respectively, for a 1 serving/d increase). Plant protein and nuts showed inverse associations (β = -0.126 for a 5% energy increase from plant protein and -0.123 for a 1 serving/d increase of nuts). Although the animal protein-TMAO association was consistent across populations, fish and shellfish associations were stronger in Asians (β = 0.285 and 0.578), and egg and red meat associations were more prominent in Americans (β = 0.153 and 0.093). Besides, circulating TMAO was positively associated with creatinine (β = 0.131 SD increase in log-TMAO), homocysteine (β = 0.065), insulin (β = 0.048), glycated hemoglobin (β = 0.048), and glucose (β = 0.023), whereas it was inversely associated with HDL cholesterol (β = -0.047) and blood pressure (β = -0.030). Each TMAO-biomarker association remained significant after further adjusting for creatinine and was robust in subgroup/sensitivity analyses.

Conclusions: In an international, consortium-based study, animal protein was consistently associated with increased circulating TMAO, whereas TMAO associations with fish, shellfish, eggs, and red meat varied among populations. The adverse associations of TMAO with certain cardiometabolic biomarkers, independent of renal function, warrant further investigation.
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http://dx.doi.org/10.1093/ajcn/nqaa430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106754PMC
May 2021

A Prospective Investigation of Circulating Metabolome Identifies Potential Biomarkers for Gastric Cancer Risk.

Cancer Epidemiol Biomarkers Prev 2021 Apr 1. Epub 2021 Apr 1.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.

Background: Metabolomics is widely used to identify potential novel biomarkers for cancer risk. No investigation, however, has been conducted to prospectively evaluate the role of perturbation of metabolome in gastric cancer development.

Methods: 250 incident cases diagnosed with primary gastric cancer were selected from the Shanghai Women's Health and the Shanghai Men's Health Study, and each was individually matched to one control by incidence density sampling. An untargeted global profiling platform was used to measure approximately 1,000 metabolites in prediagnostic plasma. Conditional logistic regression was utilized to generate ORs and values.

Results: Eighteen metabolites were associated with gastric cancer risk at < 0.01. Among them, 11 metabolites were lysophospholipids or lipids of other classes; for example, 1-(1-enyl-palmitoyl)-GPE (P-16:0) (OR = 1.56; = 1.89 × 10). Levels of methylmalonate, a suggested biomarker of vitamin B12 deficiency, was correlated with increased gastric cancer risk (OR = 1.42; = 0.004). Inverse associations were found for three biomarkers for coffee/tea consumption (3-hydroxypyridine sulfate, quinate and N-(2-furoyl) glycine), although the associations were only significant when comparing cases that were diagnosed within 5 years after the blood collection to matched controls. Most of the identified associations were more profound in women and never smokers than their male or ever smoking counterparts and some with notable significant interactions.

Conclusions: Our study identified multiple potential risk biomarkers for gastric cancer independent of infection and other major risk factors.

Impact: New risk-assessment tools to identify high-risk population could be developed to improve prevention of gastric cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1633DOI Listing
April 2021

Prediction models for breast cancer prognosis among Asian women.

Cancer 2021 Jun 11;127(11):1758-1769. Epub 2021 Mar 11.

Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: Robust and reliable prognosis prediction models have not been developed and validated for Asian patients with breast cancer, a rapidly growing yet understudied population in the United States.

Methods: We used longitudinal data from the Shanghai Breast Cancer Survival Study, a population-based prospective cohort study (n = 5042), to develop prediction models for 5- and 10-year disease-free survival (DFS) and overall survival (OS). The initial models considered age at diagnosis, tumor grade, tumor size, number of positive nodes, TNM stage, chemotherapy, tamoxifen therapy, and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status. We then evaluated whether the addition of modifiable lifestyle factors (physical activity, soy isoflavones intake, and postdiagnostic weight change) improved the models. All final models have been validated internally and externally in the National Cancer Database when applicable.

Results: Our final models included age at diagnosis, tumor grade, tumor size, number of positive nodes, TNM stage, chemotherapy, tamoxifen therapy, ER status, PR status, 6-month postdiagnostic weight change, interaction between ER status and tamoxifen therapy, and interaction between age and TNM stage. The internal validation yielded C-statistics of 0.76, 0.74, 0.78, and 0.75 for 5-year DFS, 10-year DFS, 5-year OS, and 10-year OS, respectively. The external validation yielded C-statistics of 5- and 10-year OS both at 0.78 for Chinese ethnicity, 0.79 for East Asian ethnicity, and 0.75 and 0.76 for all ethnic groups combined.

Conclusion: We developed prediction models for breast cancer prognosis from a large prospective study. Our prognostic models performed very well in women from the United States-particularly in Asian American women-and demonstrated high prediction accuracy and generalizability.
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http://dx.doi.org/10.1002/cncr.33425DOI Listing
June 2021

[Clinical features of neurogenic bladder with vesicoureteral reflux in children].

Zhongguo Dang Dai Er Ke Za Zhi 2021 Mar;23(3):279-282

Department of Nephrology, Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.

Objective: To study the clinical features of vesicoureteral reflux (VUR) in children with neurogenic bladder (NB), and to provide a reference for its early diagnosis and treatment.

Methods: Clinical data were collected from 26 children with NB and urinary tract infection who were admitted to the Department of Pediatric Nephrology from January 2014 to December 2019. According to the presence or absence of VUR, the children were divided into a VUR group with 11 children and a non-VUR group with 15 children. Clinical features were compared between the two groups.

Results: Compared with the non-VUR group, the VUR group had a significantly higher proportion of children with non- urinary tract infection, hydronephrosis (the severity of hydronephrosis increased with the grade of VUR), abnormal Tc-DMSA renal scanning findings, elevated ratios of urinary albumin, urinary IgG and urinary transferrin to creatinine, increased residual urine volume, and increased detrusor leak point pressure ( < 0.05).

Conclusions: When NB children have the clinical manifestations of non- urinary tract infection, hydronephrosis, abnormal Tc-DMSA renal scanning findings, glomerular proteinuria, increased bladder residual urine volume, and high detrusor leak point pressure, such children may already have VUR, and so diagnosis and intervention should be performed as early as possible.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969185PMC
March 2021

Identification of Triterpene Acids in Extract as Bile Acid Uptake Transporter Inhibitors.

Drug Metab Dispos 2021 May 3;49(5):353-360. Epub 2021 Mar 3.

Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, China (H.C., Y.C., D.K., X.C., Y.L.) and Department of Membrane Transport and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, Japan (H.C., Q.Z., I.T., Y.L.)

Literature reports that reduces blood lipid levels; however, the underlying mechanism remains unclear. Blood lipid levels are closely related to the enterohepatic circulation of bile acids, where uptake transporters playing a significant role. extract is commonly used in traditional prescriptions and food supplements in China. We investigated the effects of and its five triterpene acids on bile acid uptake transporters, including intestinal apical sodium-dependent bile acid transporter (ASBT) and hepatic sodium/taurocholate cotransporting polypeptide (NTCP). Triterpene acids were fingerprinted by high-performance liquid chromatography-TripleTOF and quantified by ultraperformance liquid chromatography/tandem mass spectrometry. The inhibitory effect of and its five major representative triterpene acids on ASBT and NTCP was investigated by in vitro assays using oocytes expressing ASBT and NTCP. extract exhibited significant inhibitory effects with half-maximum inhibition constants of 5.89 µg/ml and 14.6 µg/ml for NTCP and ASBT, respectively. Among five triterpene acids, poricoic acid A, poricoic acid B, and polyporenic acid C significantly inhibited NTCP function. Poricoic acid A, poricoic acid B, and dehydrotumulosic acid significantly inhibited ASBT function. The representative triterpene acid, poricoic acid A, was identified as a competitive inhibitor of NTCP with an inhibitory constant of 63.4 ± 18.7 µM. In conclusion, our results indicate that both extract and its major triterpenes are competitive inhibitors of ASBT and NTCP. Accordingly, it was suggested that competitive inhibition of these bile acid transporters is one of the underlying mechanisms for the hypolipidemic effect of SIGNIFICANCE STATEMENT: , a commonly used Chinese herbal medicine and food supplement, demonstrates significantly inhibitory effects on the function of apical sodium-dependent bile acid transporter and sodium/taurocholate cotransporting polypeptide. has potential to reduce the blood lipid through inhibition of these uptake transporters in enterohepatic circulation of bile acid.
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http://dx.doi.org/10.1124/dmd.120.000308DOI Listing
May 2021

A novel DNA methylation-based model that effectively predicts prognosis in hepatocellular carcinoma.

Biosci Rep 2021 Mar;41(3)

Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China.

Purpose: To build a novel predictive model for hepatocellular carcinoma (HCC) patients based on DNA methylation data.

Methods: Four independent DNA methylation datasets for HCC were used to screen for common differentially methylated genes (CDMGs). Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to explore the biological roles of CDMGs in HCC. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis were performed to identify survival-related CDMGs (SR-CDMGs) and to build a predictive model. The importance of this model was assessed using Cox regression analysis, propensity score-matched (PSM) analysis and stratification analysis. A validation group from the Cancer Genome Atlas (TCGA) was constructed to further validate the model.

Results: Four SR-CDMGs were identified and used to build the predictive model. The risk score of this model was calculated as follows: risk score = (0.01489826 × methylation level of WDR69) + (0.15868618 × methylation level of HOXB4) + (0.16674959 × methylation level of CDKL2) + (0.16689301 × methylation level of HOXA10). Kaplan-Meier analysis demonstrated that patients in the low-risk group had a significantly longer overall survival (OS; log-rank P-value =0.00071). The Cox model multivariate analysis and PSM analysis identified the risk score as an independent prognostic factor (P<0.05). Stratified analysis results further confirmed this model performed well. By analyzing the validation group, the results of receiver operating characteristic (ROC) curve analysis and survival analysis further validated this model.

Conclusion: Our DNA methylation-based prognosis predictive model is effective and reliable in predicting prognosis for patients with HCC.
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http://dx.doi.org/10.1042/BSR20203945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955104PMC
March 2021

Calcineurin A-α suppression drives nuclear factor-κB-mediated NADPH oxidase-2 upregulation.

Am J Physiol Renal Physiol 2021 05 22;320(5):F789-F798. Epub 2021 Feb 22.

Division of Nephrology, Department of Medicine, and Department of Physiology, Emory University, Atlanta, Georgia.

Calcineurin inhibitors (CNIs) are vital immunosuppressive therapies in the management of inflammatory conditions. A long-term consequence is nephrotoxicity. In the kidneys, the primary, catalytic calcineurin (CnA) isoforms are CnAα and CnAβ. Although the renal phenotype of CnAα mice substantially mirrors CNI-induced nephrotoxicity, the mechanisms downstream of CnAα are poorly understood. Since NADPH oxidase-2 (Nox2)-derived oxidative damage has been implicated in CNI-induced nephrotoxicity, we hypothesized that CnAα inhibition drives Nox2 upregulation and promotes oxidative stress. To test the hypothesis, Nox2 regulation was investigated in kidneys from CnAα, CnAβ, and wild-type (WT) littermate mice. To identify the downstream mediator of CnAα, nuclear factor of activated T cells (NFAT) and NF-κB regulation was examined. To test if Nox2 is transcriptionally regulated via a NF-κB pathway, CnAα and WT renal fibroblasts were treated with the NF-κB inhibitor caffeic acid phenethyl ester. Our findings showed that cyclosporine A treatment induced Nox2 upregulation and oxidative stress. Furthermore, Nox2 upregulation and elevated ROS generation occurred only in CnAα mice. In these mice, NF-κB but not NFAT activity was increased. In CnAα renal fibroblasts, NF-κB inhibition prevented Nox2 upregulation and reactive oxygen species (ROS) generation. In conclusion, these findings indicate that ) CnAα loss stimulates Nox2 upregulation, ) NF-κB is a novel CnAα-regulated transcription factor, and ) NF-κB mediates CnAα-induced Nox2 and ROS regulation. Our results demonstrate that CnAα plays a key role in Nox2 and ROS generation. Furthermore, these novel findings provide evidence of divergent CnA isoform signaling pathways. Finally, this study advocates for CnAα-sparing CNIs, ultimately circumventing the CNI nephrotoxicity. A long-term consequence of calcineurin inhibitors (CNIs) is oxidative damage and nephrotoxicity. This study indicates that NF-κB is a novel calcineurin-regulated transcription factor that is activated with calcineurin inhibition, thereby driving oxidative damage in CNI nephropathy. These findings provide additional evidence of divergent calcineurin signaling pathways and suggest that selective CNIs could improve the long-term outcomes of patients by mitigating renal side effects.
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http://dx.doi.org/10.1152/ajprenal.00254.2020DOI Listing
May 2021

Carotid Intraplaque Neovascularization Predicts Ischemic Stroke Recurrence in Patients with Carotid Atherosclerosis.

Gerontology 2021 12;67(2):144-151. Epub 2021 Feb 12.

Department of Ultrasound, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China,

Introduction: This study aimed to examine whether intraplaque neovascularization (IPN) of carotid plaques, as characterized by contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke recurrence in patients with carotid atherosclerosis.

Methods: We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the carotid artery on the side consistent with symptoms. All patients underwent CEUS after their first admission. IPN was graded on the basis of the presence and location of microbubbles within each plaque.

Results: We eventually included 155 patients, all of whom underwent IPN analysis. After a follow-up of 24 months, we recorded 25 (16.1%) stroke recurrences in the whole population. All the recurrences occurred in patients presenting IPN. There was significant difference in the IPN between the 2 groups (p = 0.002). In the final Cox proportional-hazards multivariable models, IPN of grade 2 was independently associated with the risk of stroke recurrence (HR = 4.535; 95% CI: 1.892-10.870; p = 0.001). This association remained after adjusting for the degree of carotid stenosis (HR = 3.491; 95% CI: 1.410-8.646; p = 0.007).

Conclusions: IPN was an independent predictor of stroke recurrence in patients with a recent ischemic stroke and carotid atherosclerosis. In predicting stroke recurrence, IPN may be an earlier indicator than carotid stenosis and may help stratify the risk of stroke recurrence.
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http://dx.doi.org/10.1159/000511360DOI Listing
February 2021

Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression.

J Exp Clin Cancer Res 2021 Feb 1;40(1):54. Epub 2021 Feb 1.

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.

Background: Accumulating evidence has highlighted the importance of negative elongation factor complex member E (NELFE) in tumorigenesis. However, the relationship between NELFE and gastric cancer (GC) remains unclear. This study aimed to explore the expression pattern and specific function of NELFE in GC.

Methods: NELFE expression was evaluated by immunohistochemistry and qRT-PCR in GC tissues, respectively. Cell proliferation, migration and invasion were measured by CCK-8, colony formation, transwell assays, and nude mice model. Bioinformatics analysis was performed to search potential target genes of NELFE, and a Cignal Finder 10-Pathway Reporter Array was used to explore potential signaling pathways regulated by NELFE. Dual-luciferase reporter assays, qRT-PCR and western blotting were conducted to verify their regulatory relationship. The expression correlations among NELFE, β-catenin and CSNK2B were further explored by immunohistochemistry on consecutive resections.

Results: NELFE was significantly overexpressed in GC tissues both in protein and mRNA level and negatively correlated with the prognosis of GC patients. Gain- and loss-of-function experiments showed that NELFE potentiated GC cell proliferation and metastasis in vitro and in vivo. CSNK2B was identified as a downstream effector of NELFE. Wnt/β-catenin signaling may mediate the regulation of CSNK2B by NELFE. In addition, NELFE, β-catenin and CSNK2B were all remarkably upregulated in tumor tissues compared with adjacent normal tissues, and their expression levels in GC were positively correlated with each other.

Conclusion: Our findings reveal a new NELFE-Wnt/β-catenin-CSNK2B axis to promote GC progression and provide new candidate targets against this disease.
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http://dx.doi.org/10.1186/s13046-021-01848-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851912PMC
February 2021

Effects of FeO nanoparticles on extracellular polymeric substances and nonylphenol degradation in river sediment.

Sci Total Environ 2021 May 22;770:145210. Epub 2021 Jan 22.

Department of Agriculture and Biotechnology, Wenzhou Vocational College of Science and Technology, Wenzhou 325006, China. Electronic address:

In this study, the impact of FeO nanoparticles (nFeO) on microbial extracellular polymeric substances (EPS) and nonylphenol (NP) degradation in sediment were investigated. The results showed that the addition of nFeO lowered the degree of EPS overproduction and the amount of polysaccharides and proteins secreted in NP contaminated sediment. Particularly, the secretion of colloidal EPS (C-EPS) lowered significantly (P < 0.05), and the content of tyrosine-like, tryptophan-like, and soluble microbial by-product-like substances in C-EPS also decreased, leading to a lower aromaticity, humification, and hydrophobicity of C-EPS. Furthermore, with lower C-EPS content in water, NP was adsorbed to sediment more easily, and the weakened toxic effect of NP to bacteria as well as a higher proportion of organic matter degrading microbes stimulated NP degradation. These findings revealed the vital role of nFeO in alleviating NP toxicity to microbes and reducing NP ecological risk in aquatic environments.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145210DOI Listing
May 2021

Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera.

Science 2021 03 29;371(6534):1152-1153. Epub 2021 Jan 29.

BioNTech, An der Goldgrube 12, 55131 Mainz, Germany.

Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage called B.1.1.7 (variant of concern: VOC 202012/01), which is reported to spread more efficiently and faster than other strains, emerged in the United Kingdom. This variant has an unusually large number of mutations, with 10 amino acid changes in the spike (S) protein, raising concerns that its recognition by neutralizing antibodies may be affected. In this study, we tested SARS-CoV-2-S pseudoviruses bearing either the Wuhan reference strain or the B.1.1.7 lineage spike protein with sera of 40 participants who were vaccinated in a previously reported trial with the messenger RNA-based COVID-19 vaccine BNT162b2. The immune sera had slightly reduced but overall largely preserved neutralizing titers against the B.1.1.7 lineage pseudovirus. These data indicate that the B.1.1.7 lineage will not escape BNT162b2-mediated protection.
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http://dx.doi.org/10.1126/science.abg6105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971771PMC
March 2021

Efficacy and safety of intraoperative radiotherapy in rectal cancer: A systematic review and meta-analysis.

World J Gastrointest Oncol 2021 Jan;13(1):69-86

General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China.

Background: In recent years, intraoperative radiotherapy (IORT) has been increasingly used for the treatment of rectal cancer. However, the efficacy and safety of IORT for the treatment of rectal cancer are still controversial.

Aim: To evaluate the value of IORT for patients with rectal cancer.

Methods: We searched PubMed, Embase, Cochrane Library, Web of Science databases, and conference abstracts and included randomized controlled trials and observational studies on IORT non-IORT for rectal cancer. Dichotomous variables were evaluated by odds ratio (OR) and 95% confidence interval (CI), hazard ratio (HR) and 95%CI was used as a summary statistic of survival outcomes. Statistical analyses were performed using Stata V.15.0 and Review Manager 5.3 software.

Results: In this study, 3 randomized controlled studies and 12 observational studies were included with a total of 1460 patients, who are mainly residents of Europe, the United States, and Asia. Our results did not show significant differences in 5-year overall survival (HR = 0.80, 95%CI = 0.60-1.06; = 0.126); 5-year disease-free survival (HR = 0.94, 95%CI = 0.73-1.22; = 0.650); abscess (OR = 1.10, 95%CI = 0.67-1.80; = 0.713), fistulae (OR = 0.79, 95%CI = 0.33-1.89; = 0.600); wound complication (OR = 1.21, 95%CI = 0.62-2.36; = 0.575); anastomotic leakage (OR = 1.09, 95%CI = 0.59-2.02; = 0.775); and neurogenic bladder dysfunction (OR = 0.69, 95%CI = 0.31-1.55; = 0.369). However, the meta-analysis of 5-year local control was significantly different (OR = 3.07, 95%CI = 1.66-5.66; = 0.000).

Conclusion: The advantage of IORT is mainly reflected in 5-year local control, but it is not statistically significant for 5-year overall survival, 5-year disease-free survival, and complications.
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http://dx.doi.org/10.4251/wjgo.v13.i1.69DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805273PMC
January 2021

Long-term diet quality is associated with gut microbiome diversity and composition among urban Chinese adults.

Am J Clin Nutr 2021 03;113(3):684-694

Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Few population-based studies have evaluated the influence of long-term diet on the gut microbiome, and data among Asian populations are lacking.

Objective: We examined the association of long-term diet quality, comprising 8 food groups (fruit, vegetables, dairy, fish/seafood, nuts/legumes, refined grains, red meat, and processed meat), with gut microbiome among Chinese adults.

Methods: Included were 1920 men and women, enrolled in 2 prospective cohorts (baseline 1996-2006), who remained free of cardiovascular diseases, diabetes, and cancer at stool collection (2015-2018) and had no diarrhea or antibiotic use in the last 7 d before stool collection. Microbiome was profiled by 16S rRNA sequencing. Long-term diet was assessed by repeated surveys at baseline and follow-ups (1996-2011), with intervals of 5.2 to 20.5 y between dietary surveys and stool collection. Associations of dietary variables with microbiome diversity and composition were evaluated by linear or negative binomial hurdle models, adjusting for potential confounders. False discovery rate (FDR) <0.1 was considered significant.

Results: The mean ± SD age at stool collection was 68 ± 1.5 y. Diet quality was positively associated with microbiome α-diversity (P = 0.03) and abundance of Firmicutes, Actinobacteria, Tenericutes, and genera/species within these phyla, including Coprococcus, Faecalibacterium/Faecalibacterium prausnitzii, Bifidobacterium / Bifidobacterium adolescentis, and order RF39 (all FDRs <0.1). Significant associations were also observed for intakes of dairy, fish/seafood, nuts/legumes, refined grains, and processed meat, including a positive association of dairy with Bifidobacterium and inverse associations of processed meat with Roseburia /Roseburia faecis. Most associations were similar, with or without adjustment for BMI and hypertension status or excluding participants with antibiotic use in the past 6 mo.

Conclusion: Among apparently healthy Chinese adults, long-term diet quality is positively associated with fecal microbiome diversity and abundance of fiber-fermenting bacteria, although magnitudes are generally small. Future studies are needed to examine if these bacteria may mediate or modify diet-disease relations.
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http://dx.doi.org/10.1093/ajcn/nqaa350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948864PMC
March 2021

Oxidative stress activates NORAD expression by H3K27ac and promotes oxaliplatin resistance in gastric cancer by enhancing autophagy flux via targeting the miR-433-3p.

Cell Death Dis 2021 01 18;12(1):90. Epub 2021 Jan 18.

Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Oxaliplatin resistance undermines its curative effects on cancer and usually leads to local recurrence. The oxidative stress induced DNA damage repair response is an important mechanism for inducing oxaliplatin resistance by activating autophagy. ELISA is used to detect target genes expression. TMT-based quantitative proteomic analysis was used to investigate the potential mechanisms involved in NORAD interactions based on GO analysis. Transwell assays and apoptosis flow cytometry were used for biological function analysis. CCK-8 was used to calculate IC50 and resistance index (RI) values. Dual-luciferase reporter gene assay, RIP and ChIP assays, and RNA pull-down were used to detect the interaction. Autophagy flux was evaluated using electron microscope and western blotting. Oxidative stress was enhanced by oxaliplatin; and oxaliplatin resistance gastric cancer cell showed lower oxidative stress. TMT labeling showed that NORAD may regulate autophagy flux. NORAD was highly expressed in oxaliplatin-resistant tissues. In vitro experiments indicate that NORAD knockdown decreases the RI (Resistance Index). Oxaliplatin induces oxidative stress and upregulates the expression of NORAD. SGC-7901 shows enhanced oxidative stress than oxaliplatin-resistant cells (SGC-7901-R). NORAD, activated by H3K27ac and CREBBP, enhanced the autophagy flux in SGC-7901-R to suppress the oxidative stress. NORAD binds to miR-433-3p and thereby stabilize the ATG5- ATG12 complex. Our findings illustrate that NORAD, activated by the oxidative stress, can positively regulate ATG5 and ATG12 and enhance the autophagy flux by sponging miR-433-3p. NORAD may be a potential biomarker for predicting oxaliplatin resistance and mediating oxidative stress, and provides therapeutic targets for reversing oxaliplatin resistance.
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http://dx.doi.org/10.1038/s41419-020-03368-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814071PMC
January 2021

Tongxinluo promotes axonal plasticity and functional recovery after stroke.

Transl Neurosci 2020 25;11(1):428-438. Epub 2020 Nov 25.

Department of Neurology, the First Affiliated Hospital of Guangxi Medical University , Nanning, Guangxi Zhuang Autonomous Region, 530021, China.

Background: The aim of this study was to investigate the neural plasticity in contralesional cortex and the effects of tongxinluo (TXL) in cerebral ischemic rats.

Methodology: We used stroke-prone renovascular hypertensive (RHRSP) cerebral ischemia rat models to study the effect of TXL and the underlying mechanisms. We performed foot-fault and beam-walking tests to evaluate the motor function of rats after cortical infarction. Biotinylated dextran amine (BDA) was used to track axonal sprouting and neural connections.

Results: TXL enhanced the recovery of motor function in cerebral infarction rats. TXL increased axonal sprouting in the peri-infarcted area but not in the corpus callosum, indicating in situ origination instead of crossing between cortical hemispheres through the corpus callosum. TXL promoted the sprouting of corticospinal axons into the denervated side of spinal gray matter. The synaptophysin (SYN)-positive intensity in the peri-infarcted area of TXL-treated group was greater than that in the vehicle group. We observed co-localization of SYN with BDA-positive fibers in the denervated spinal cord gray matter in the TXL group, suggesting that axonal remodeling and synaptic connections were promoted by TXL.

Conclusion: TXL may promote the recovery of neurological function by promoting the axonal remodeling and synapse formation of motor neuronal fibers after focal cortical infarction in hypertensive rats.
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http://dx.doi.org/10.1515/tnsci-2020-0127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718613PMC
November 2020

Iatrogenic femoral artery pseudoaneurysm surgically repaired with combined bovine pericardial roll and autologous great saphenous vein grafts.

Chin J Traumatol 2021 Mar 11;24(2):75-78. Epub 2020 Nov 11.

Department of Vascular Surgery, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address:

Iatrogenic femoral artery pseudoaneurysm caused by invasive procedures is one of the common complications for endovascular interventions. We present a case of a young male with a complex iatrogenic femoral artery pseudoaneurysm as a result of iatrogenic femoral artery puncture. The defective femoral artery was repaired with combined bovine pericardial tube and autologous great saphenous vein grafts. Computed tomography angiography showed the grafts were still patent one year after the surgery.
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http://dx.doi.org/10.1016/j.cjtee.2020.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071716PMC
March 2021

Interactions of iron-based nanoparticles with soil dissolved organic matter: adsorption, aging, and effects on hexavalent chromium removal.

J Hazard Mater 2021 03 28;406:124650. Epub 2020 Nov 28.

Institute of Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

The interactions and mechanisms between soil dissolved organic matter (DOM) and three types of iron-based nanoparticles (NPs), i.e., nanoscale zero-valent iron (nZVI) particles, FeO NPs, and FeO NPs, were investigated in short-term exposure experiments. The adsorption results showed that soil DOM was rapidly adsorbed on the surface of the iron-based NPs with the adsorption rate varying according to FeO > FeO > nZVI. Spectral analysis results revealed that aromatic DOM fractions with high-molecular-weights were preferentially adsorbed. The binding mechanism was determined as hydrogen bonding and ligand exchange via Fourier transform infrared spectroscopy (FT-IR) analysis. Scanning electron microscopy, FT-IR, X-ray photoelectron spectroscopy, and X-ray diffraction were used to identify the corrosion products of the three iron-based NPs at the adsorption equilibrium. The results suggest that FeO and/or γ-FeO and α-FeOOH were the main corrosion products of nZVIs and α-FeOOH was obtained as an aged product of FeO NPs. Results of Cr(VI) removal tests suggest that the aged nZVI achieved 79.87% of Cr(VI) removal and the Cr(VI) removal efficiency was significantly improved by coating DOM onto FeO NPs. The overall data indicate the fate and transformation of iron-based NPs and the enhancement for Cr(VI) removal after interactions between DOM and NPs.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124650DOI Listing
March 2021

Association between lincRNA expression and overall survival for patients with triple-negative breast cancer.

Breast Cancer Res Treat 2021 Apr 27;186(3):769-777. Epub 2020 Nov 27.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 800, Nashville, TN, 37203, USA.

Purpose: Long intergenic non-coding RNAs (lincRNAs) are increasingly recognized as important regulators for pathogenesis and/or prognosis of breast cancer, including triple-negative breast cancer (TNBC) subtype. However, few previous studies used RNA-sequencing (RNA-Seq) technology, and none included an independent replication.

Methods: To systematically evaluate the association between expression of lincRNAs and TNBC survival, we examined lincRNA expression profiles in TNBC tissues using RNA-Seq data for 200 TNBC patients from the Shanghai Breast Cancer Survival Study (SBCSS) and Southern Community Cohort Study (SCCS).

Results: Twenty-five lincRNAs were found to be associated with overall survival (P < 0.05 and no significant heterogeneity across studies at Q statistic P > 0.1), and 61 lincRNAs were associated with disease-free survival (DFS). Among these, two lincRNAs (LINC01270 and LINC00449) were significantly associated with both worse overall survival and DFS and were expressed at significantly higher levels in tumor tissues compared with adjacent normal breast tissues (log[Fold Change] > 0.5 and FDR < 0.05). We further evaluated the potential functions of LINC01270 and LINC00449 using in vitro functional experiments and found that siRNA-mediated knockdown of LINC01270 and LINC00449 expression significantly decreased cell viability, colony formation and cell migration ability in TNBC cells (P < 0.05).

Conclusions: Evidence from observational studies and in vitro experiments indicates that LINC00449 and LINC01270 may be prognostic biomarkers for TNBC.
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http://dx.doi.org/10.1007/s10549-020-06021-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088339PMC
April 2021

Mortality for Robotic- vs Video-Assisted Lobectomy-Treated Stage I Non-Small Cell Lung Cancer Patients.

JNCI Cancer Spectr 2020 Oct 15;4(5):pkaa028. Epub 2020 Apr 15.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.

Background: To address the US Food and Drug Administration's recent safety concern on robotic surgery procedures, we compared short- and long-term mortality for stage I non-small cell lung cancer (NSCLC) patients treated by robotic-assisted thoracoscopic surgical lobectomy (RATS-L) vs video-assisted thoracoscopic surgical lobectomy (VATS-L).

Methods: From the National Cancer Database, we identified 18 908 stage I NSCLC patients who underwent RATS-L or VATS-L as the primary operation from 2010 to 2014. Cox proportional hazards models were used to estimate hazard ratios (HRs) for short- and long-term mortality using unmatched and propensity score-matched analyses. All statistical tests were 2-sided.

Results: Patients treated by RATS-L had higher 90-day mortality than those with VATS-L (6.6% vs 3.8%, = .03) if conversion to open thoracotomy occurred. After excluding first-year observation, multiple regression analyses showed RATS-L was associated with increased long-term mortality, compared with VATS-L, in cases with tumor size 20 mm or less: hazard ratio (HR) = 1.33 (95% confidence interval [CI] = 1.15 to 1.55), HR = 1.36 (95% CI = 1.17 to 1.58), and HR = 1.33 (95% CI = 1.11 to 1.61) for unmatched, N:1 matched, and 1:1 matched analyses, respectively, in the intention-to-treat analysis. Among patients without conversion to an open thoracotomy, the respective hazard ratios were 1.19 (95% CI = 1.10 to 1.29), 1.19 (95% CI = 1.10 to 1.29), and 1.17 (95% CI = 1.06 to 1.29). Similar associations were observed when follow-up time started 18 or 24 months postsurgery. No statistically significant mortality difference was found for patients with tumor size of greater than 20 mm. These associations were not related to case volume of VATS-L or RATS-L performed at treatment institutes.

Conclusions: Patients with small (≤20 mm) stage I NSCLC treated with RATS-L had statistically significantly higher long-term mortality risk than VATS-L after 1 year postsurgery.
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http://dx.doi.org/10.1093/jncics/pkaa028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660043PMC
October 2020