Publications by authors named "Yufeng Liu"

344 Publications

Long-Term Effect of Left Atrial Appendage Occlusion in Treating Patients with Previous Ischemic Stroke on the Disease Recurrence.

Comput Math Methods Med 2021 13;2021:6991002. Epub 2021 Oct 13.

Department of Nursing, Tangdu Hospital, Air Force Military Medical University, Xi'an, Shaanxi Province 710038, China.

Methods: A total of 120 patients with IS admitted to Tangdu Hospital from July 2016 to September 2017 were grouped into the control group ( = 60) and the observation group ( = 60). Patients in the control group were only treated with thrombolytics and anticoagulants while those in the observation group were treated with both drugs and LAAO. Transesophageal echocardiography (TEE) was performed to observe the occlusion of LAA in patients in the observation group after 45 d and 6 months, respectively. Clinical outcomes in two groups were compared from the following aspects: recurrence of IS, incidence of systemic embolism, and the 3-year recurrence-free survival (RFS). The 3-year IS recurrence of patients was compared by Fisher's exact test.

Results: No significant differences were observed at baseline levels (age, sex, etc.) between the observation group and control group ( > 0.05). During follow-up visit of 45 d and 6 months, all occluders met the efficacious occludsion criteria. The results of TEE at 45 d after LAAO showed that 50% of patients (30/60) in the observation group had complete occlusion of LAA. The results of TEE at 6 months after LAAO suggested that 58.3% of patients (35/60) had complete occlusion of LAA. IS recurrence in the observation group (3.33%, 2/60) was significantly lower than that in the control group (18.33%, 11/60), with the difference presenting statistical significance ( = 0.008). Incidence of systemic embolism in the observation group (1.67%, 1/60) was markedly lower than that in the control group (13.33%, 11/60) ( = 0.014). The average RFS in the observation group (31.97 months, 95% CI: 27.50~32.31 months) was notably longer than that in the control group (29.91 months, 95% CI: 29.85~32.92 months) ( < 0.05). The 3-year IS recurrence of patients between two groups compared by Fisher's exact test showed significant differences (1 year: = 0.014, 2 year: = 0.008, 3 year: = 0.008).

Conclusion: Regarding patients with previous IS who had poor response to thrombolytics and anticoagulants, LAAO could effectively decrease recurrence of IS and incidence of systemic embolism and prolong RFS of patients. LAAO was, therefore, an alternative for patients with high IS recurrence risk.
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http://dx.doi.org/10.1155/2021/6991002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528575PMC
October 2021

CXCR4 is a Novel Biomarker Correlated With Malignant Transformation and Immune Infiltrates in Gastric Precancerous Lesions.

Front Mol Biosci 2021 5;8:697993. Epub 2021 Oct 5.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

As early gastric cancer (EGC) has a far better prognosis than advanced gastric cancer (GC), early diagnosis and treatment are essential. However, understanding the mechanism of the process from gastric precancerous lesion (GPL) becoming EGC has made little advances. Besides, biomarkers that can monitor the progression of GPL-to-GC are still much insufficient. Key gene modules associated with GPL progression to EGC were identified by integrating two GPL-related data sets, GSE55696 and GSE130823, using the WGCNA method. Combining with the TCGA-STAD cohort, hub genes were identified. Immunofluorescence was conducted to validate the expression. To explore the implication of hub genes in GPL malignant transformation, a correlation test was conducted to identify their co-expression genes, co-expression cytokines, and co-expression immune cells. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to shrink CXCR4-related predictors and construct a prognostic model. Functional enrichment was applied for exploring the potential mechanism. The green module in GSE55696 and the yellow module in GSE130823 were regarded as key gene modules associated with GPL progression to EGC, and 219 intersection genes from them were mainly enriched in critical immune biological processes. Combining with the TCGA-STAD cohort, CXCR4 was identified as a novel biomarker correlated with the malignant transformation of GPL, the positive rate of which was increased with GPL progression according to immunofluorescence. CXCR4 co-expression genes were found mainly involved in regulation of actin. CXCR4 co-expression cytokines were enriched in regulation of chemotaxis, cell chemotaxis, mononuclear cell migration, leukocyte chemotaxis, etc. As for co-expression immune cells, the expression level of CXCR4 was positively correlated with the abundance of macrophages but negatively correlated with that of effector memory T cells and NKT cells during GPL malignant transformation. In addition, the CXCR4-related prognostic model was able to predict the prognosis of GC and serve as an independent predictor for overall survival (OS). CXCR4 was a novel biomarker correlated with malignant transformation of GPL and played a vital role in the control of tumor immunity. CXCR4 is possible to serve as a therapeutic target for malignant transformation of GPL.
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http://dx.doi.org/10.3389/fmolb.2021.697993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523893PMC
October 2021

Ferroptosis Patterns Correlate with Immune Microenvironment Characterization in Gastric Cancer.

Int J Gen Med 2021 12;14:6573-6586. Epub 2021 Oct 12.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.

Objective: We aimed to build a ferroptosis-based classifier to characterize the molecular features of gastric cancers (GC) and investigate the relationship between different ferroptosis patterns and GC tumor microenvironment (TME).

Methods: Based on the genomic and clinical information from TCGA portal and GEO database, non-negative matrix factorization (NMF) was used to identify ferroptosis subtypes in GC patients. In order to estimate the ferroptosis levels, we established ferroptosis subtype score (FSS) to quantify ferroptosis patterns and ferroptosis potential index (FPI) by principal component analysis (PCA). The correlations of different ferroptosis patterns with TME cell-infiltrating characteristics (including immune cell infiltration, immune checkpoints expression levels, tumor mutational burden (TMB) and immunotherapy response) were systematically analyzed.

Results: Two ferroptosis subtypes, C1 (with lower FSS) and C2 (with higher FSS), were determined. C2 displayed a significantly lower FPI than C1. Besides, C2 was associated with diffuse subtype while C1 with intestinal subtype. As for TME characteristics, C2 was in accordance with the immune-excluded phenotype as it showed more active immune and stromal activities but lower TMB, less probability of immunotherapy response and poorer prognosis. C1 was linked to immune-inflamed phenotype as it had lower stromal activities but increased neoantigen load, enhanced response to immunotherapy and relatively better prognosis.

Conclusion: The systematic assessment of ferroptosis patterns and ferroptosis levels presented in our study implied that ferroptosis serves as an important factor in the formation of TME, which may expand the understanding of TME and provide a novel perspective for the development of targeted immunotherapeutic strategies for GC patients.
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http://dx.doi.org/10.2147/IJGM.S331291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520437PMC
October 2021

A PLCB1-PI3K-AKT signaling axis activates EMT to promote cholangiocarcinoma progression.

Cancer Res 2021 Sep 27. Epub 2021 Sep 27.

Department of General surgery, First Affiliated Hospital of Harbin Medical University

As a member of the phospholipase family, phospholipase C beta 1 (PLCB1) is involved in phospholipid hydrolysis and is frequently upregulated in human cancer. However, little is known about the role of PLCB1 in cholangiocarcinoma (CCA). In this study, we uncover a role for PLCB1 in CCA progression and identify the underlying mechanisms. Both human CCA tissues and CCA cell lines expressed high levels of PLCB1. PLCB1 promoted tumor development and growth in various CCA mouse models, including transposon-based tumorigenesis models. PLCB1 activated PI3K/AKT signaling to induce CCA cells to undergo epithelial-to-mesenchymal transition (EMT). Mechanistically, PABPC1 interacted with PLCB1 and PI3K to amplify PLCB1-mediated EMT via PI3K/AKT/GSK-3β/Snail signaling. Ectopic PLCB1 induced resistance to treatment with gemcitabine combined with cisplatin, which could be reversed by the AKT inhibitor MK2206. PLCB1 expression was regulated by miR-26b-5p through direct interaction with PLCB1 3'UTR. Collectively, these data identify a PLCB1-PI3K-AKT signaling axis vital for CCA development and EMT, suggesting that AKT can be used as a therapeutic target to overcome chemotherapy resistance in CCA patients with high PLCB1 expression.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-1538DOI Listing
September 2021

A Novel Red-Emitting NaNbOF:Mn Phosphor with Ultrahigh Color Purity for Warm White Lighting and Wide-Gamut Backlight Displays.

Materials (Basel) 2021 Sep 15;14(18). Epub 2021 Sep 15.

Shanghai Institute of Technology, School of Materials Science and Engineering, Shanghai 201418, China.

In this work, a novel red-emitting oxyfluoride phosphor NaNbOF:Mn with an ultra-intense zero-phonon line (ZPL) was successfully synthesized by hydrothermal method. The phase composition and luminescent properties of NaNbOF:Mn were studied in detail. The photoluminescence excitation spectrum contains two intense excitation bands centered at 369 and 470 nm, which match well with commercial UV and blue light-emitting diode (LED) chips. When excited by 470 nm blue light, NaNbOF:Mn exhibits red light emission dominated by ZPL. Notably, the color purity of the NaNbOF:Mn red phosphor can reach 99.9%. Meanwhile, the NaNbOF:Mn phosphor has a shorter fluorescence decay time than commercial KSiF:Mn, which is conducive to fast switching of images in display applications. Profiting from the intense ZPL, white light-emitting diode (WLED) with high color rendering index of Ra = 86.2 and low correlated color temperature of T = 3133 K is realized using yellow YAG:Ce and red NaNbOF:Mn phosphor. The WLED fabricated using CsPbBr quantum dots (QDs) and red NaNbOF:Mn phosphor shows a wide color gamut of 127.56% NTSC (National Television Standard Committee). The results show that red-emitting NaNbOF:Mn phosphor has potential application prospects in WLED lighting and display backlight.
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http://dx.doi.org/10.3390/ma14185317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467541PMC
September 2021

Adjunctive interleukin-2 for the treatment of drug-susceptible tuberculosis: a randomized control trial in China.

Infection 2021 Sep 25. Epub 2021 Sep 25.

Fuyang No.2 Hospital, Fuyang, China.

Purpose: Evaluation of the efficacy and safety of IL-2 in the treatment of drug-susceptible tuberculosis.

Methods: First, the cases of diagnosed drug-susceptible tuberculosis were randomized into two groups-the control group that received the background regimen of isoniazid, rifampin, pyrazinamide, and ethambutol, and the experimental group that received the background regimen plus IL-2. The efficacy and safety evaluations were performed throughout the therapy process as well as 12 months after the treatment completion.

Results: A total of 1151 patients underwent the randomization, among which 539 (96.2%) of the 560 in the experimental group achieved the sputum culture conversion to negative, compared to the 551 (93.2%) of the 591 in the control group, after 2 months of treatment, with significant difference observed between the groups (P = 0.025). Cavity closure after 2 months in the IL-2 (experimental) group was 60/211 (28.4%) compared to 46/248 (18.5%) in the control group, with a significant difference between the groups (P = 0.001). After treatment completion, the proportion of favorable outcomes was 559/560 (99.8%) in the experimental group and 587/591 (99.3%) in the control group, with no significant difference between the groups. Twelve months after treatment completion, relapse occurred in 15/560 (2.6%) in the IL-2 group and 19/591 (3.2%) in the control group, with no significant difference.

Conclusion: IL-2 may enhance culture conversion and the cavity closure rate in the early treatment phase, although the enhancement may not be significant after treatment completion.
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http://dx.doi.org/10.1007/s15010-021-01698-3DOI Listing
September 2021

Predicting Solvent-Dependent Nucleophilicity Parameter with a Causal Structure Property Relationship.

J Chem Inf Model 2021 Oct 22;61(10):4890-4899. Epub 2021 Sep 22.

Institute of Process Research & Development, School of Chemistry, University of Leeds, Leeds, LS2 9JT, United Kingdom.

Solvent-dependent reactivity is a key aspect of synthetic science, which controls reaction selectivity. The contemporary focus on new, sustainable solvents highlights a need for reactivity predictions in different solvents. Herein, we report the excellent machine learning prediction of the nucleophilicity parameter in the four most-common solvents for nucleophiles in the Mayr's reactivity parameter database ( = 0.93 and 81.6% of predictions within ±2.0 of the experimental values with Extra Trees algorithm). A Causal Structure Property Relationship (CSPR) approach was utilized, with focus on the physicochemical relationships between the descriptors and the predicted parameters, and on rational improvements of the prediction models. The nucleophiles were represented with a series of electronic and steric descriptors and the solvents were represented with principal component analysis (PCA) descriptors based on the ACS Solvent Tool. The models indicated that steric factors do not contribute significantly, because of bias in the experimental database. The most important descriptors are solvent-dependent HOMO energy and Hirshfeld charge of the nucleophilic atom. Replacing DFT descriptors with Parameterization Method 6 (PM6) descriptors for the nucleophiles led to an 8.7-fold decrease in computational time, and an ∼10% decrease in the percentage of predictions within ±2.0 and ±1.0 of the experimental values.
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http://dx.doi.org/10.1021/acs.jcim.1c00610DOI Listing
October 2021

High-Dimensional Precision Medicine From Patient-Derived Xenografts.

J Am Stat Assoc 2021 12;116(535):1140-1154. Epub 2020 Nov 12.

Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

The complexity of human cancer often results in significant heterogeneity in response to treatment. Precision medicine offers the potential to improve patient outcomes by leveraging this heterogeneity. Individualized treatment rules (ITRs) formalize precision medicine as maps from the patient covariate space into the space of allowable treatments. The optimal ITR is that which maximizes the mean of a clinical outcome in a population of interest. Patient-derived xenograft (PDX) studies permit the evaluation of multiple treatments within a single tumor, and thus are ideally suited for estimating optimal ITRs. PDX data are characterized by correlated outcomes, a high-dimensional feature space, and a large number of treatments. Here we explore machine learning methods for estimating optimal ITRs from PDX data. We analyze data from a large PDX study to identify biomarkers that are informative for developing personalized treatment recommendations in multiple cancers. We estimate optimal ITRs using regression-based (Q-learning) and direct-search methods (outcome weighted learning). Finally, we implement a superlearner approach to combine multiple estimated ITRs and show that the resulting ITR performs better than any of the input ITRs, mitigating uncertainty regarding user choice. Our results indicate that PDX data are a valuable resource for developing individualized treatment strategies in oncology. Supplementary materials for this article are available online.
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http://dx.doi.org/10.1080/01621459.2020.1828091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451968PMC
November 2020

Two C═C Bond Participation in Annulation to Pyridines Based on DMF as the Nonadjacent N and C Atom Donors.

J Org Chem 2021 Oct 21;86(19):13446-13453. Epub 2021 Sep 21.

College of Chemistry and Chemical Engineering, Advanced Catalytic Engineering Research Center of the Ministry of Education, Hunan University, Changsha 410082, China.

Two C═C bond participation in annulation to pyridines using ,-dimethylformamide (DMF) as the N1 and C4 synthons has been carried out. In this reaction, DMF contributed one N atom and one C atom to two disconnected positions of pyridine ring, with no need for an additional nitrogen source. Two C═C bonds in two molecules of substituted styrenes offered four carbon atoms in the presence of iodine and persulfate. With the optimized conditions in hand, both symmetric and unsymmetric diaryl-substituted pyridines were obtained in useful yields. On the basis of relevant literature and a series of control experimental results, a possible mechanism was proposed in this work, which may demonstrate how DMF provides both N1 and C4 sources.
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http://dx.doi.org/10.1021/acs.joc.1c01550DOI Listing
October 2021

The covalent Coordination-driven [email protected](Ti)-SH heterojunction with boosting photocatalytic CO reduction and dye degradation performance.

J Colloid Interface Sci 2021 Aug 28;606(Pt 2):1745-1757. Epub 2021 Aug 28.

School of Materials Science and Engineering, Shanghai Institute of Technology, Shanghai 201418, China. Electronic address:

Herein, the optional and controllable growth of BiS onto NH-MIL-125 via covalent conjunction strategy was reported. The experimental results demonstrate that the obtained heterojunction exhibits boosting photocatalytic reduction CO and organic dye degradation. The [email protected] displays the highest yield of 12.46 μmol gh of CO, >13 times that of pure NH-MIL-125. Meanwhile, the reaction kinetic of [email protected] in the degradation of methylene blue is uppermost, which is 160 times than that of the commercial P25. The enhancement of photocatalytic performance could be ascribed to the covalent coordination-driven intimate interfacial interaction in n-scheme heterojunction. Meanwhile, the plausible mechanism was also investigated by UV-vis diffuse reflectance (UV-vis), photoluminescence (PL), electrochemical photocurrent, electron spin resonance (ESR) and electrochemical impedance spectroscopy (EIS).
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http://dx.doi.org/10.1016/j.jcis.2021.08.135DOI Listing
August 2021

The role of miR-199b-3p in regulating Nrf2 pathway by dihydromyricetin to alleviate septic acute kidney injury.

Free Radic Res 2021 Jul 7;55(7):842-852. Epub 2021 Sep 7.

Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

The pathophysiology of septic acute kidney injury (AKI) is very complex and the fatality is high. Nrf2 is crucial for septic AKI, and dihydromyricetin (DMY) has a protective effect on LPS-induced AKI. We aimed to explore whether DMY could affect Nrf2 pathway by regulating miR-199b-3p and played a protective role in septic AKI. The mouse model was induced by cecal ligation and puncture (CLP) and the cell model was stimulated by LPS. Enzyme-linked immunosorbent assay was conducted to examine MDA, SOD, LDH, GSH, TNF-α, kidney injury molecule 1 (KIM-1), and IL-6 levels. The pathological changes were observed by hematoxylin-eosin staining. The targeted relationship between miR-199b-3p and Nrf2 was verified by a dual-luciferase reporter assay. Levels of SOD, GSH, NQO-1, Nrf2, and HO-1 were decreased, MDA, LDH, TNF-α, IL-6, and KIM-1, and miR-199b-3p were increased in the CLP group and LPS-induced HK-2 cells, while the effect was reversed after DMY treatment. There existed renal tubule cell edema and necrosis, inflammatory cell infiltration in the CLP group, the situation was partially improved by DMY. MiR-199b-3p bound to Nrf2. Nrf2 levels were increased, TNF-α, IL-6, and KIM-1 were decreased after transfected with miR-199b-3p inhibitor, these effects were reversed when co-transfected with si-Nrf2. TNF-α, IL-6, KIM-1, and miR-199b-3p levels were increased; Nrf2, NQO-1, and HO-1 levels were decreased in the LPS + DMY + mimics-miR group. MiR-199b-3p was increased in septic AKI models, DMY might alleviate septic AKI by regulating miR-199b-3p to affect the Nrf2 pathway.
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http://dx.doi.org/10.1080/10715762.2021.1962008DOI Listing
July 2021

Prognostic role of DFNA5 in head and neck squamous cell carcinoma revealed by systematic expression analysis.

BMC Cancer 2021 Aug 25;21(1):951. Epub 2021 Aug 25.

Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, China.

Background: The gasdermin E gene (GSDME, also known as DFNA5) is mutated in familial aging-related hearing loss. Recent studies have also revealed that the expression of DFNA5 is suppressed in many cancer types; however, little is known about the function of DFNA5 in head and neck squamous cell carcinoma (HNSCC). Accordingly, the aim of the present study was to evaluate the expression of DFNA5 and explore its prognostic value in HNSCC.

Result: We used a set of bioinformatics tools, including Oncomine, TIMER, TISIDB, cBioPortal, and GEPIA, to analyze the expression of DFNA5 in patients with HNSCC from public databases. Kaplan-Meier plotter was used to evaluate the potential prognostic significance of DFNA5. DFNA5 mRNA levels were significantly higher in HNSCC tissues than in normal tissues, and high DFNA5 expression was correlated with worse survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that DFNA5 expression has a strong positive correlation with cell adhesion and the integrin signaling pathway, whereas its expression was negatively correlated with the levels of infiltrating B cells (cor = - 0.223, P = 8.57e-07) and CD8 T cells (cor = - 0.223, P = 2.99e-07).

Conclusion: This study demonstrates that DFNA5 expression has prognostic value for HNSCC patients. Moreover, these results suggest that regulation of lymphocyte infiltration is the mechanism underlying the function of DFNA5 in HNSCC.
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http://dx.doi.org/10.1186/s12885-021-08692-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390204PMC
August 2021

MODEL FREE ESTIMATION OF GRAPHICAL MODEL USING GENE EXPRESSION DATA.

Ann Appl Stat 2021 Mar 18;15(1):194-207. Epub 2021 Mar 18.

Fred Hutchinson Cancer Research Center.

Graphical model is a powerful and popular approach to study high-dimensional omic data, such as genome-wide gene expression data. Nonlinear relations between genes are widely documented. However, partly due to sparsity of data points in high dimensional space (i.e., curse of dimensionality) and computational challenges, most available methods construct graphical models by testing linear relations. We propose to address this challenge by a two-step approach: first use a model-free approach to prioritize the neighborhood of each gene, then apply a non-parametric conditional independence testing method to refine such neighborhood estimation. Our method, named as "mofreds" (MOdel FRee Estimation of DAG Skeletons), seeks to estimate the skeleton of a directed acyclic graph (DAG) by this two-step approach. We studied the theoretical properties of mofreds, and evaluated its performance in extensive simulation settings. We found mofreds has substantially better performance than the state-of-the art method which is designed to detect linear relations of Gaussian graphical models. We applied mofreds to analyze gene expression data of breast cancer patients from The Cancer Genome Atlas (TCGA). We found that it discovers non-linear relationships among gene pairs that are missed by the Gaussian graphical model methods.
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http://dx.doi.org/10.1214/20-AOAS1380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341558PMC
March 2021

Genome-Wide Characterization of B-Box Gene Family and Its Roles in Responses to Light Quality and Cold Stress in Tomato.

Front Plant Sci 2021 5;12:698525. Epub 2021 Jul 5.

College of Horticulture, Shenyang Agricultural University, Shenyang, China.

Perceiving incoming environmental information is critical for optimizing plant growth and development. Multiple B-box proteins (BBXs) play essential roles in light-dependent developmental processes in plants. However, whether BBXs function as a signal integrator between light and temperature in tomato plants remains elusive. In this study, 31 genes were identified from the newly released tomato () genome sequences and were clustered into five subgroups. Gene structure and protein motif analyses showed relatively high conservation of closely clustered genes within each subgroup; however, genome mapping analysis indicated the uneven distribution of the genes on tomato chromosomes. Promoter -regulatory elements prediction and gene expression indicated that genes were highly responsive to light, hormones, and stress conditions. Reverse genetic approaches revealed that disruption of , and largely suppressed the cold tolerance of tomato plants. Furthermore, the impairment of , and suppressed the photosynthetic response immediately after cold stress. Due to the impairment of non-photochemical quenching (NPQ), the excess photon energy and electron flow excited by low temperature were not consumed in , and silenced plants, leading to the over reduction of electron carriers and damage of the photosystem. Our study emphasized the positive roles of light signaling transcription factors SlBBXs in cold tolerance in tomato plants, which may improve the current understanding of how plants integrate light and temperature signals to adapt to adverse environments.
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http://dx.doi.org/10.3389/fpls.2021.698525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287887PMC
July 2021

A Good Way to Reduce Screening for Retinopathy of Prematurity: Development of the ROP Model in a China Preterm Population.

Front Pediatr 2021 30;9:697690. Epub 2021 Jun 30.

Neonatal Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Retinopathy of prematurity (ROP) is a preventable cause of blindness in children. Without treatment, more than 45% of eyes may suffer permanent vision loss. Current ROP screening guidelines, which include a range of birth weights (BWs) and gestational ages (GAs), may require screening many low-risk preemies who might develop severe ROP. All high-risk infants in the neonatal intensive care unit (NICU) of the First Affiliated Hospital of Zhengzhou University from 2017 to 2021 were included in this retrospective cohort study. Each of the 27 candidate risk factors was evaluated in univariate analysis and adjusted for known risk factors (i.e., GA and BW). The significant results were analyzed in a backward selection multivariate logistic regression model. Receiver operating characteristic (ROC) curves and a nomogram were drawn. The study included 2,040 infants who underwent ROP screening. The weight gain rate [OR, 2.65; 95% confidence interval (CI), 1.49-1.21 ≤ 12 g/d vs. > 18 g/d; = 0.001], blood transfusion (OR, 2.03; 95% CI, 1.14-3.64; = 0.017), invasive mechanical ventilation (OR, 1.74; 95% CI, 1.15-2.66; = 0.009) and N-terminal segment of pro-B-type natriuretic peptide (NT-proBNP) ≥ 25,000 ng/L (OR, 1.51; 95% CI, 1.00-2.28; = 0.048) were four new statistically independent risk factors in addition to GA and BW. The area under the curve (AUC) of the final multivariate model was 0.90 (95% CI, 0.88-0.92; < 0.001). These findings add to our understanding of ROP screening because they include all eligible infants rather than only high-risk infants, as in previous studies. Under the control of BW and GA, low weight gain rate, increased number of blood transfusion, invasive mechanical ventilation and NT-proBNP ≥ 25,000 ng/L were "new" statistically independent risk factors for ROP. The ROP risk can be calculated manually or represented by a nomogram for clinical use.
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http://dx.doi.org/10.3389/fped.2021.697690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278052PMC
June 2021

Risk of having pulmonary tuberculosis in type 2 diabetes: A hospital-based matched case-control study.

Asia Pac J Clin Nutr 2021 Jun;30(2):303-310

School of Public Health, Qingdao University, Qingdao, China. Email:

Background And Objectives: Diabetes mellitus (DM) leads to nearly 3-fold higher risk of pulmonary tuberculosis (TB), indicating an increasing challenge to public health in low-to-middle income countries. Till now, the risk factor is still uncertain. We carried out this study with the main purpose to identify the risk factors of having TB in DM patients.

Methods And Study Design: A hospital-based matched case-control study was conducted in Qingdao, China from March, 2016 to January, 2018. Cases were DM patients with concurrent TB (DM-TB). Each case was matched with two controls, patients with DM only of similar age, sex and DM course. Cox regression of conditional logistic analysis was used to define the risk factors for having TB in DM, and then sensitivity analysis was carried out.

Results: We identified 315 patients, including 105 cases and 210 controls. Smokers had a higher risk of having TB with a multivariable adjusted odds ratio (aOR) of 12.45 than non-smokers. Poor glycemic control (aOR=2.66), frequency of DM re-examination <1 time/year (aOR=3.39), as well as TB contact history was also independently related with higher risk, while BMI ≥24 (aOR=0.42), education level ≥ college (aOR=0.11) showed a negative association.

Conclusions: Poor glycemic control, smoking, low frequency of reexamination was associated with higher risk of having TB in DM, while overweight and obesity, high education levels showed a negative association. These findings provide clues to target DM populations prone to TB, which may be of help to halt the epidemic of TB in high burden countries.
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http://dx.doi.org/10.6133/apjcn.202106_30(2).0015DOI Listing
June 2021

Rejoinder: Learning Optimal Distributionally Robust Individualized Treatment Rules.

J Am Stat Assoc 2021 1;116(534):699-707. Epub 2021 Apr 1.

Department of Statistics and Operations Research, Department of Genetics, Department of Biostatistics, Carolina Center for Genome Science, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC 27599, USA.

We thank the opportunity offered by editors for this discussion and the discussants for their insightful comments and thoughtful contributions. We also want to congratulate Kallus (2020) for his inspiring work in improving the effciency of policy learning by retargeting. Motivated from the discussion in Dukes and Vansteelandt (2020), we first point out interesting connections and distinctions between our work and Kallus (2020) in Section 1. In particular, the assumptions and sources of variation for consideration in these two papers lead to different research problems with different scopes and focuses. In Section 2, following the discussions in Li et al. (2020); Liang and Zhao (2020), we also consider the efficient policy evaluation problem when we have some data from the testing distribution available at the training stage. We show that under the assumption that the sample sizes from training and testing are growing in the same order, efficient value function estimates can deliver competitive performance. We further show some connections of these estimates with existing literature. However, when the growth of testing sample size available for training is in a slower order, efficient value function estimates may not perform well anymore. In contrast, the requirement of the testing sample size for DRITR is not as strong as that of efficient policy evaluation using the combined data. Finally, we highlight the general applicability and usefulness of DRITR in Section 3.
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http://dx.doi.org/10.1080/01621459.2020.1866581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221610PMC
April 2021

Learning Optimal Distributionally Robust Individualized Treatment Rules.

J Am Stat Assoc 2021 15;116(534):659-674. Epub 2020 Sep 15.

Department of Statistics and Operations Research, Department of Genetics, Department of Biostatistics, Carolina Center for Genome Science, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC 27599, USA.

Recent development in the data-driven decision science has seen great advances in individualized decision making. Given data with individual covariates, treatment assignments and outcomes, policy makers best individualized treatment rule (ITR) that maximizes the expected outcome, known as the value function. Many existing methods assume that the training and testing distributions are the same. However, the estimated optimal ITR may have poor generalizability when the training and testing distributions are not identical. In this paper, we consider the problem of finding an optimal ITR from a restricted ITR class where there is some unknown covariate changes between the training and testing distributions. We propose a novel distributionally robust ITR (DR-ITR) framework that maximizes the worst-case value function across the values under a set of underlying distributions that are "close" to the training distribution. The resulting DR-ITR can guarantee the performance among all such distributions reasonably well. We further propose a calibrating procedure that tunes the DR-ITR adaptively to a small amount of calibration data from a target population. In this way, the calibrated DR-ITR can be shown to enjoy better generalizability than the standard ITR based on our numerical studies.
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http://dx.doi.org/10.1080/01621459.2020.1796359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221611PMC
September 2020

Preoperative histogram parameters of dynamic contrast-enhanced MRI as a potential imaging biomarker for assessing the expression of Ki-67 in prostate cancer.

Cancer Med 2021 07 12;10(13):4240-4249. Epub 2021 Jun 12.

Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

Purpose: To investigate whether preoperative histogram parameters of dynamic contrast-enhanced MRI (DCE-MRI) can assess the expression of Ki-67 in prostate cancer (PCa).

Materials And Methods: A consecutive series of 76 patients with pathology-proven PCa who underwent routine DCE-MRI scans were retrospectively recruited. Quantitative parameters including the volume transfer constant (K ), rate contrast (K ), extracellular-extravascular volume fraction (V ), and plasma volume (V ) by outlining the three-dimensional volume of interest (VOI) of all lesions were processed. Then, the histogram analyses of these quantitative parameters were performed. The Spearman rank correlation analysis was used to evaluate the correlation of these parameters and Ki-67 expression of PCa. Receiver operating characteristic (ROC) curve analysis was adopted to evaluate the efficacy of these quantitative histogram parameters in identifying high Ki-67 expression from low Ki-67 expression of PCa.

Results: Eighty-eight PCa lesions were enrolled in this study, including 31 lesions with high Ki-67 expression and 57 lesions with low Ki-67 expression. The median, mean, 75th percentile, and 90th percentile derived from K and K had a moderately positive correlation with Ki-67 expression (r = 0.361-0.450, p < 0.05), in which both the median and mean of K had the highest positive correlation (r = 0.450, p < 0.05). The diagnostic efficacy of the K median, mean, 75th percentile, and 90th percentile, along with the K -based median and mean was assessed by the ROC curve. The area under the curve (AUC) of the mean for K was the highest (0.826). When the cut-off of the mean for K was ≥0.47/min, its Youden index, sensitivity, and specificity were 0.625, 0.871, and 0.754, respectively. The AUC of the median of K was the lowest (0.772).

Conclusion: The histogram of DCE-MRI quantitative parameters is correlated with Ki-67 expression, which has the potential to noninvasively assess the expression of Ki-67 with patients of PCa.
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http://dx.doi.org/10.1002/cam4.3912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267123PMC
July 2021

Design of nanozymes for inflammatory bowel disease therapy.

Sci China Life Sci 2021 Aug 8;64(8):1368-1371. Epub 2021 Jun 8.

Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing National Laboratory of Microstructures, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, 210023, China.

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http://dx.doi.org/10.1007/s11427-020-1937-6DOI Listing
August 2021

Dietary Intake of Vegetables and Cooking Oil Was Associated With Drug-Induced Liver Injury During Tuberculosis Treatment: A Preliminary Cohort Study.

Front Nutr 2021 24;8:652311. Epub 2021 May 24.

Institute of Nutrition and Health, School of Public Health, Qingdao University, Qingdao, China.

Drug-induced liver injury is challenging during tuberculosis treatment. There is no epidemiological data investigating the relation between dietary intake and the risk of drug-induced liver injury during tuberculosis treatment. The aim of this study is to investigate the association of food and nutrient intake with the incidence of tuberculosis-drug-induced liver injury. A cohort study was conducted in two city-level tuberculosis-specialized hospitals in Linyi City and Qingdao City, China from January 2011 to December 2013. The dietary intake was assessed by a 3-day 24-h food recall survey and a standard food-frequency questionnaire. The liver functions including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were monitored throughout the 6-month tuberculosis therapy. Liver injury was defined as ALT or AST higher than two times of the upper limit of normal (ULN). Liver dysfunction was defined as ALT or AST higher than the ULN. The ULN for ALT and AST is 40 U/L. Multivariate logistic regression analyses were performed to determine the dietary factors associated with the incidence of liver injury and liver dysfunction. A total of 605 patients were included in the analysis. During the treatment, 8.1% patients exhibited liver injury and 23.3% patients exhibited liver dysfunction. A lower intake of vegetables was associated with a higher risk of liver injury [OR (95% CI): 3.50 (1.52-8.08), = 0.003) and liver dysfunction [OR (95% CI): 2.37 (1.31-4.29), = 0.004], while a lower intake of cooking oil was associated with a lower risk of liver injury [OR (95% CI): 0.44 (0.20-0.96), = 0.040)] and liver dysfunction [OR (95% CI): 0.51 (0.31-0.85), = 0.009]. The current study indicated that the higher risks of tuberculosis-drug-induced liver injury and liver dysfunction were statistically associated with decreased vegetable intake and increased cooking oil intake.
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http://dx.doi.org/10.3389/fnut.2021.652311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180911PMC
May 2021

Forecasting emergency department hourly occupancy using time series analysis.

Am J Emerg Med 2021 Oct 29;48:177-182. Epub 2021 Apr 29.

Department of Statistics and Operations Research, University of North Carolina at Chapel Hill (UNC), NC, USA. Electronic address:

Study Objective: To develop a novel predictive model for emergency department (ED) hourly occupancy using readily available data at time of prediction with a time series analysis methodology.

Methods: We performed a retrospective analysis of all ED visits from a large academic center during calendar year 2012 to predict ED hourly occupancy. Due to the time-of-day and day-of-week effects, a seasonal autoregressive integrated moving average with external regressor (SARIMAX) model was selected. For each hour of a day, a SARIMAX model was built to predict ED occupancy up to 4-h ahead. We compared the resulting model forecast accuracy and prediction intervals with previously studied time series forecasting methods.

Results: The study population included 65,132 ED visits at a large academic medical center during the year 2012. All adult ED visits during the first 265 days were used as a training dataset, while the remaining ED visits comprised the testing dataset. A SARIMAX model performed best with external regressors of current ED occupancy, average department-wide ESI, and ED boarding total at predicting up to 4-h-ahead ED occupancy (Mean Square Error (MSE) of 16.20, and 64.47 for 1-hr- and 4-h- ahead occupancy, respectively). Our 24-SARIMAX model outperformed other popular time series forecasting techniques, including a 60% improvement in MSE over the commonly used rolling average method, while maintaining similar prediction intervals.

Conclusion: Accounting for current ED occupancy, average department-wide ESI, and boarding total, a 24-SARIMAX model was able to provide up to 4 h ahead predictions of ED occupancy with improved performance characteristics compared to other forecasting methods, including the rolling average. The prediction intervals generated by this method used data readily available in most EDs and suggest a promising new technique to forecast ED occupancy in real time.
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http://dx.doi.org/10.1016/j.ajem.2021.04.075DOI Listing
October 2021

Decreased Treg Cell and TCR Expansion Are Involved in Long-Lasting Graves' Disease.

Front Endocrinol (Lausanne) 2021 12;12:632492. Epub 2021 Apr 12.

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

Graves' disease (GD) is a T cell-mediated organ-specific autoimmune disorder. GD patients who have taken anti-thyroid drugs (ATDs) for more than 5 years with positive anti-thyroid stimulating hormone receptor autoantibodies value were defined as persistent GD (pGD). To develop novel immunotherapies for pGD, we investigated the role of T cells in the long-lasting phase of GD. Clinical characteristics were compared between the pGD and newly diagnosed GD (nGD) (N = 20 respectively). Flow cytometric analysis was utilized to determine the proportions of Treg and Th17 cells (pGD, N = 12; nGD, N = 14). T cell receptor sequencing (TCR-seq) and RNA sequencing (RNA-seq) were also performed (pGD, N = 13; nGD, N = 20). Flow cytometric analysis identified lower proportions of Th17 and Treg cells in pGD than in nGD (P = 0.0306 and P = 0.0223). TCR-seq analysis revealed a lower diversity (P = 0.0025) in pGD. Specifically, marked clonal expansion, represented by an increased percentage of top V-J recombination, was observed in pGD patients. Interestingly, pGD patients showed more public T cell clonotypes than nGD patients (2,741 966). Meanwhile, RNA-seq analysis revealed upregulation of the inflammation and chemotaxis pathways in pGD. Specifically, the expression of pro-inflammatory and chemotactic genes (, , , and ) was increased in pGD, whereas Th17 and Treg cells associated genes (, , , and decreased in pGD. Additionally, TCR diversity was negatively correlated with the expression of pro-inflammatory or chemotactic genes (, , , and ). These results indicated that Treg dysregulation and the expansion of pathogenic T cell clones might be involved in the long-lasting phase of GD upregulating chemotaxis or inflammation response. To improve the treatment of pGD patients, ATDs combined therapies, especially those aimed at improving Treg cell frequencies or targeting specific expanded pathogenic TCR clones, are worth exploring in the future.
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http://dx.doi.org/10.3389/fendo.2021.632492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074859PMC
April 2021

The Effect of Infertility on the Liver Structure, Endocrinology, and Gene Network in Japanese Flounder.

Animals (Basel) 2021 Mar 25;11(4). Epub 2021 Mar 25.

Key Laboratory of Aquatic Genomics, Ministry of Agriculture, Beijing 100141, China.

The liver can synthesize vitellogenin, the precursor of vitellin, which is needed for oocyte development and maturation. Here, we investigated the effects of infertility on liver structure, hormone regulation, and gene and protein networks in Japanese flounder (). Results showed that the liver of infertile fish had fewer vacuoles and significantly lower serum vitellogenin (VTG) level than in liver of fertile fish. Whole transcriptomics analysis between infertile and fertile groups identified 2076 significantly differentially expressed (DE) mRNAs, 431 DE lncRNAs, 265 DE circRNAs, and 53 DE miRNAs. Proteomics analysis identified 838 DE proteins. Integrated analysis of whole transcriptomics and proteomics revealed 60 significantly DE genes and proteins associated with metabolism, immunity, signal transduction, and steroid biosynthesis. Moreover, non-coding RNA (miRNAs, circRNA, and lncRNA) transcripts involved in metabolism, immunity, and signal transduction in infertile liver were identified. In conclusion, this study shows that gonadal infertility is associated with not only changes in histological structure and hormone secretion but also changes in metabolism, immunity, and signal transduction networks in the liver. These results provide valuable information concerning the mechanism underlying infertility in fish.
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http://dx.doi.org/10.3390/ani11040936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066618PMC
March 2021

Preparative separation of five polyphenols from the fruits of Sorbus pohuashanensis Hedl. by high-speed counter-current chromatography.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 May 5;1172:122620. Epub 2021 Mar 5.

School of Pharmaceutical Sciences, Liaoning University, Shenyang 110036, PR China; Natural Products Pharmaceutical Engineering Technology Research Center of Liaoning Province, Shenyang 110036, PR China. Electronic address:

The fruits of Sorbus pohuashanensis Hedl. (S. pohuashanensis) are rich in polyphenols with many beneficial effects such as anti-inflammatory, anti-tussive, anti-asthmatic and anti-cancer. In this study, five polyphenols, including three phenolic acids and two flavonoids, were successfully prepared from the fruits of S. pohuashanensis by high-speed counter-current chromatography (HSCCC) using different solvent systems for the first time. Ethyl acetate-n-butanol-water (3.5:1.5:5, v/v) was screened as the two-phase system to separate neochlorogenic acid (1), chlorogenic acid (2), quercetin 3-O-(6″-α-L-rhamnopyranosyl-4'″-α-L-rhamnopyranosyl)-β-D-glucopyranoside (3) and rutin (5). N-hexane-ethyl acetate-methanol-water (1:3:1:3.5, v/v) was first utilized to isolate 3,5-O-dicaffeoylquinic acid (4). The purities of all these compounds were above 95%. In addition, their chemical structures were identified by mass spectrometer (MS), nuclear magnetic resonance (NMR) or the standards. These results indicated that HSCCC was an effective method to separate polyphenols compounds from the fruits of S. pohuashanensis.
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http://dx.doi.org/10.1016/j.jchromb.2021.122620DOI Listing
May 2021

Inhibition of TGFβ1 accelerates regeneration of fibrotic rat liver elicited by a novel two-staged hepatectomy.

Theranostics 2021 4;11(10):4743-4758. Epub 2021 Mar 4.

Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin 150000, China.

Emerging evidence is demonstrating that rapid regeneration of remnant liver elicited by associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) may be attenuated in fibrotic livers. However, the molecular mechanisms responsible for this process are largely unknown. It is widely acknowledged that the TGFβ1 signaling axis plays a major role in liver fibrosis. Therefore, the aims of this study were to elucidate the underlying mechanism of liver regeneration during ALPPS with or without fibrosis, specifically focusing on TGFβ1 signaling. ALPPS was performed in rat models with -diethylnitrosamine-induced liver fibrosis and no fibrosis. Functional liver remnant regeneration and expression of TGFβ1 were analyzed during the ALPPS procedures. Adeno-associated virus-shTGFβ1 and the small molecule inhibitor LY2157299 (galunisertib) were used separately or in combination to inhibit TGFβ1 signaling in fibrotic rats. Liver regeneration following ALPPS was lower in fibrotic rats than non-fibrotic rats. TGFβ1 was a key mediator of postoperative regeneration in fibrotic liver. Interestingly, AAV-shTGFβ1 accelerated the regeneration of fibrotic functional liver remnant and improved fibrosis, while LY2157299 only enhanced liver regeneration. Moreover, combination treatment elicited a stronger effect. Inhibition of TGFβ1 accelerated regeneration of fibrotic liver, ameliorated liver fibrosis, and improved liver function following ALPPS. Therefore, TGFβ1 is a promising therapeutic target in ALPPS to improve fibrotic liver reserve function and prognosis.
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http://dx.doi.org/10.7150/thno.52102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978300PMC
August 2021

Case Report: Identification of SARS-CoV-2 in Cerebrospinal Fluid by Ultrahigh-Depth Sequencing in a Patient With Coronavirus Disease 2019 and Neurological Dysfunction.

Front Med (Lausanne) 2021 22;8:629828. Epub 2021 Feb 22.

Department of Critical Care Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

We reported that the complete genome sequence of SARS-Coronavirus-2 (SARS-CoV-2) was obtained from a cerebrospinal fluid (CSF) sample by ultrahigh-depth sequencing. Fourteen days after onset, seizures, maxillofacial convulsions, intractable hiccups and a significant increase in intracranial pressure developed in an adult coronavirus disease 2019 patient. The complete genome sequence of SARS-CoV-2 obtained from the cerebrospinal fluid indicates that SARS-CoV-2 can invade the central nervous system. In future, along with nervous system assessment, the pathogen genome detection and other indicators are needed for studying possible nervous system infection of SARS-CoV-2.
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http://dx.doi.org/10.3389/fmed.2021.629828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937706PMC
February 2021

Partial Response to Pyrotinib Plus Capecitabine in an Advanced Breast Cancer Patient with Amplification and Mutation After Anti- Treatment: A Case Report and Literature Review.

Onco Targets Ther 2021 2;14:1581-1588. Epub 2021 Mar 2.

Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.

Human epidermal growth factor receptor2 () overexpression/amplification is associated with high malignancy, rapid disease progression and poor overall survival in breast cancer. The application of anti- drugs has greatly improved the survival of patients with -positive breast cancer, but drug resistance issues affect the long-term efficacy. The mutation is considered to be one of the reasons for resistance to anti- therapy, and there is currently no standard treatment. We report for the first time the detection of amplification with mutation by second-generation sequencing (NGS) in a 57-year-old hormone receptor-negative, -positive woman with advanced breast cancer who was resistant to multi-line anti- therapies. She subsequently received pyrotinib combined with capecitabine treatment and achieved partial response. The small-molecule pan- family irreversible inhibitor pyrotinib combined with capecitabine has shown a promising effect in the treatment of mutation-induced resistance, but the molecular mechanism and efficacy need to be further verified.
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http://dx.doi.org/10.2147/OTT.S289876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936716PMC
March 2021

The ultrafast Kerr effect in anisotropic and dispersive media.

J Chem Phys 2021 Mar;154(9):094202

Department of Chemistry, Columbia University, New York, New York 10027, USA.

The ultrafast optical Kerr effect (OKE) is widely used to investigate the structural dynamics and interactions of liquids, solutions, and solids by observing their intrinsic nonlinear temporal responses through nearly collinear four-wave mixing. Non-degenerate mixing schemes allow for background free detection and can provide information on the interplay between a material's internal degrees of freedom. Here, we show a source of temporal dynamics in the OKE signal that is not reflective of the internal degrees of freedom but arises from a group index and momentum mismatch. It is observed in two-color experiments on condensed media with sizable spectral dispersion, a common property near an optical resonance. In particular, birefringence in crystalline solids is able to entirely change the character of the OKE signal via the off-diagonal tensor elements of the nonlinear susceptibility. We develop a detailed description of the phase-mismatched ultrafast OKE and show how to extract quantitative information on the spectrally resolved birefringence and group index from time-resolved experiments in one and two dimensions.
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http://dx.doi.org/10.1063/5.0037142DOI Listing
March 2021

Plasma Targeted Metabolomics Analysis for Amino Acids and Acylcarnitines in Patients with Prediabetes, Type 2 Diabetes Mellitus, and Diabetic Vascular Complications.

Diabetes Metab J 2021 03 9;45(2):195-208. Epub 2021 Mar 9.

School of Pharmaceutical Sciences, Liaoning University, Shenyang, China.

Background: We hypothesized that specific amino acids or acylcarnitines would have benefits for the differential diagnosis of diabetes. Thus, a targeted metabolomics for amino acids and acylcarnitines in patients with diabetes and its complications was carried out.

Methods: A cohort of 54 normal individuals and 156 patients with type 2 diabetes mellitus and/or diabetic complications enrolled from the First Affiliated Hospital of Jinzhou Medical University was studied. The subjects were divided into five main groups: normal individuals, impaired fasting glucose, overt diabetes, diabetic microvascular complications, and diabetic peripheral vascular disease. The technique of tandem mass spectrometry was applied to obtain the plasma metabolite profiles. Metabolomics multivariate statistics were applied for the metabolic data analysis and the differential metabolites determination.

Results: A total of 10 cross-comparisons within diabetes and its complications were designed to explore the differential metabolites. The results demonstrated that eight comparisons existed and yielded significant metabolic differences. A total number of 24 differential metabolites were determined from six selected comparisons, including up-regulated amino acids, down-regulated medium-chain and long-chain acylcarnitines. Altered differential metabolites provided six panels of biomarkers, which were helpful in distinguishing diabetic patients.

Conclusion: Our results demonstrated that the biomarker panels consisted of specific amino acids and acylcarnitines which could reflect the metabolic variations among the different stages of diabetes and might be useful for the differential diagnosis of prediabetes, overt diabetes and diabetic complications.
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http://dx.doi.org/10.4093/dmj.2019.0209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024149PMC
March 2021
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