Publications by authors named "Jiajia Huang"

44 Publications

Single-Crystalline Covalent Organic Frameworks as High-Performance Liquid Chromatographic Stationary Phases for Positional Isomer Separation.

ACS Appl Mater Interfaces 2022 Jan 6. Epub 2022 Jan 6.

Ministry of Education Key Laboratory of Analytical Science for Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China.

Vigorously developing new stationary phases to meet the requirements for the separation of positional isomers that have similar physicochemical properties is still an urgent topic in separation science. Herein, a single-crystalline covalent organic framework (COF-300) packed column for the separation of positional isomers in high-performance liquid chromatography (HPLC) was reported for the first time. Benefitting from its regular shape, excellent chemical and thermal stability, microporous feature, and strong hydrophobicity of single-crystalline COF-300, the single-crystalline COF-300-packed column showed excellent resolution for the separation of positional isomers, including nitroaniline, dichlorobenzene, dibromobenzene, diiodobenzene, diethylbenzene, chloronitrobenzene, bromonitrobenzene, and iodonitrobenzene isomers, which cannot be all separated on commercial columns and a polycrystalline COF-300-packed column. Especially, the resolution values for -/diiodobenzene and -/diiodobenzene were 4.45 and 2.53. Moreover, the alkylbenzene, monosubstituted aromatics, polycyclic aromatic hydrocarbons, and the mixture of ethylbenzene and styrene were also baseline separated on the single-crystalline COF-300-packed column. This successful application not only confirmed the great potential of single-crystalline COFs in HPLC separation of positional isomers but also pioneered the utilization of single-crystalline COFs in separation science.
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http://dx.doi.org/10.1021/acsami.1c20989DOI Listing
January 2022

Establishment and Validation of Prognostic Nomograms Based on Serum Copper Level for Patients With Early-Stage Triple-Negative Breast Cancer.

Front Cell Dev Biol 2021 25;9:770115. Epub 2021 Nov 25.

Departments of Medical Oncology, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Altered copper levels have been observed in several cancers, but studies on the relationship between serum copper and early-stage triple-negative breast cancer (TNBC) remain scare. We sought to establish a predictive model incorporating serum copper levels for individualized survival predictions. We retrospectively analyzed clinicopathological information and baseline peripheric blood samples of patients diagnosed with early-stage TNBC between September 2005 and October 2016 at Sun Yat-sen University Cancer Center. The optimal cut-off point of serum copper level was determined using maximally selected log-rank statistics. Kaplan-Meier curves were used to estimate survival probabilities. Independent prognostic indicators associated with survival were identified using multivariate Cox regression analysis, and subsequently, prognostic nomograms were established to predict individualized disease-free survival (DFS) and overall survival (OS). The nomograms were validated in a separate cohort of 86 patients from the original randomized clinical trial SYSUCC-001 (SYSUCC-001 cohort). 350 patients were eligible in this study, including 264 in the training cohort and 86 in the SYSUCC-001 cohort. An optimal cut-off value of 21.3 μmol/L of serum copper was determined to maximally divide patients into low- and high-copper groups. After a median follow-up of 87.1 months, patients with high copper levels had significantly worse DFS ( = 0.002) and OS ( < 0.001) than those with low copper levels in the training cohort. Multivariate Cox regression analysis revealed that serum copper level was an independent factor for DFS and OS. Further, prognostic models based on serum copper were established for individualized predictions. These models showed excellent discrimination [C-index for DFS: 0.689, 95% confidence interval (CI): 0.621-0.757; C-index for OS: 0.728, 95% CI: 0.654-0.802] and predictive calibration, and were validated in the SYSUCC-001 cohort. Serum copper level is a potential predictive biomarker for patients with early-stage TNBC. Predictive nomograms based on serum copper might be served as a practical tool for individualized prognostication.
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http://dx.doi.org/10.3389/fcell.2021.770115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657150PMC
November 2021

A Novel Prognostic Model Based on the Serum Iron Level for Patients With Early-Stage Triple-Negative Breast Cancer.

Front Cell Dev Biol 2021 4;9:777215. Epub 2021 Nov 4.

Department of Medical Oncology, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

The dysregulation of iron homeostasis has been explored in malignancies. However, studies focusing on the association between the serum iron level and prognosis of patients with early-stage triple-negative breast cancer (TNBC) are scarce. Accordingly, in current study, 272 patients with early-stage TNBC treated at Sun Yat-sen University Cancer Center (SYSUCC) between September 2005 and October 2016 were included as a training cohort, another 86 patients from a previous randomized trial, SYSUCC-001, were analyzed as a validation cohort (SYSUCC-001 cohort). We retrospectively collected their clinicopathological data and tested the serum iron level using blood samples at the diagnosis. In the training cohort, patients were divided into low-iron and high-iron groups according to the serum iron level cut-off of 17.84 μmol/L determined by maximally selected rank statistics. After a median follow-up of 87.10 months, patients with a low iron had a significantly longer median disease-free survival (DFS) of 89.13 [interquartile range (IQR): 66.88-117.38] months and median overall survival (OS) of 92.85 (IQR: 68.83-117.38) months than those in the high-iron group (median DFS: 75.25, IQR: 39.76-105.70 months, = 0.015; median OS: 77.17, IQR: 59.38-110.28 months, = 0.015). Univariate and multivariate Cox analysis demonstrated the serum iron level to be an independent predictor for DFS and OS. Then, a prognostic nomogram incorporating the serum iron level, T stage and N stage was developed for individualized prognosis predictions. It had good discriminative ability with a C-index of DFS (0.729; 95% CI 0.666-0.792) and OS (0.739; 95% CI 0.666-0.812), respectively. Furtherly, we validated the predictive model in the SYSUCC-001 cohort, which also showed excellent predictive performance with a C-index of DFS (0.735; 95% CI 0.614-0.855) and OS (0.722; 95% CI 0.577-0.867), respectively. All these suggested that the serum iron level might be a potential prognostic biomarker for patients with early-stage TNBC, the predictive model based on it might be served as a practical tool for individualized survival predictions.
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http://dx.doi.org/10.3389/fcell.2021.777215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599954PMC
November 2021

Tuning the Ratio of Pt(0)/Pt(II) in Well-Defined Pt Clusters Enables Enhanced Electrocatalytic Reduction/Oxidation of Hydrogen Peroxide for Sensitive Biosensing.

Anal Chem 2021 12 19;93(48):15982-15989. Epub 2021 Nov 19.

Key Laboratory of Pesticides and Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, P.R. China.

Rational design and construction of advanced sensing platforms for sensitive detection of HO released from living cells is one of the challenges in the field of physiology and pathology. Noble metal clusters are a kind of nanomaterials with well-defined chemical composition and special atomic structures, which have been widely explored in catalysis, biosensing, and therapy. Compared with noble metal nanoparticles, noble metal clusters exhibit great potential in electrochemical biosensing due to their high atom utilization efficiency and abundant reactive active sites. Herein, Pt nanoclusters anchored on hollow carbon spheres (Pt/HCS) were successfully prepared for sensitive detection of HO. By tuning the ratio of Pt(0)/Pt(II) at different annealing temperatures, the optimized Pt/HCS-550 showed higher HO reduction and oxidation catalytic activities than other control samples. Density functional theory calculations revealed that HOcan be better activated and dissociated in the Pt model featured with the co-existence of Pt(0)/Pt(II) and the key intermediates OOH*/OH* have a stronger interaction with the Pt model. As a concept application, the electrochemical biosensing platform was successfully applied to sensitive detection of HO released from the cells.
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http://dx.doi.org/10.1021/acs.analchem.1c03362DOI Listing
December 2021

An Aging-Related Gene Signature-Based Model for Risk Stratification and Prognosis Prediction in Breast Cancer.

Int J Womens Health 2021 3;13:1053-1064. Epub 2021 Nov 3.

Departments of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.

Background: Aging, an inevitable process characterized by functional decline over time, is a significant risk factor for various tumors. However, little is known about aging-related genes (ARGs) in breast cancer (BC). We aimed to explore the potential prognostic role of ARGs and to develop an ARG-based prognosis signature for BC.

Methods: RNA-sequencing expression profiles and corresponding clinicopathological data of female patients with BC were obtained from public databases in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). An ARG-based risk signature was constructed in the TCGA cohort based on results of least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis, and its prognostic value was further validated in the GSE20685 cohort.

Results: A six ARG-based signature, including and , was developed in the TCGA cohort and significantly stratified patients into low- and high-risk groups. Patients in the former group showed significantly better prognosis than those in the latter. Multivariate Cox regression analysis demonstrated that the ARG risk score was an independent prognostic factor for BC. A predictive nomogram integrating the ARG risk score and three identified factors (age, N- and M-classification) was established in the TCGA cohort and validated in the GSE20685 cohort. Calibration plots showed good consistency between predicted survival probabilities and actual observations.

Conclusion: A novel ARG-based risk signature was developed for patients with BC, which can be used for individual prognosis prediction and promoting personalized treatment.
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http://dx.doi.org/10.2147/IJWH.S334756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578840PMC
November 2021

Combined tumor-associated macrophages biomarker predicting extremely poor outcome of patients with primary central nervous system lymphoma.

Hematol Oncol 2021 Dec 20;39(5):625-638. Epub 2021 Sep 20.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Primary central nervous system lymphoma (PCNSL) is an aggressive and rare malignancy with poor prognosis. However, there are no reliable prognostic biomarkers for PCNSL in clinical practice. Here, we aimed to identify a reliable prognostic biomarker for predicting the survival of PCNSL patients. In this study, multiplex immunofluorescence and digital imaging analysis were used to characterize tumor-associated macrophages (TAMs) immunophenotypes and the expression of programmed cell death ligand 1 on TAMs, with regard to prognosis from diagnostic tumor tissue samples of 59 PCNSL patients. We found that the M2-to-M1 ratio was a more reliable prognostic biomarker for PCNSL than M1-like or M2-like macrophage infiltration. In addition, the combination of programmed death-ligand 1 (PD-L1) expression on TAMs and the M2-to-M1 ratio in PCNSL demonstrated improved performance in prognostic discrimination than PD-L1-positive TAMs or M2-to-M1 ratio. To validate the prognostic significance of the combined TAMs associated biomarkers, they were integrated into the International Extranodal Lymphoma Study Group (IELSG) index and termed as IELSG-M index. Kaplan-Meier plots showed that the IELSG-M index could discriminate patients into low-, intermediate- or high-risk subgroups, better than IELSG, in terms of prognosis. The areas under the receiver operating characteristic curves of IELSG-M was 0.844 for overall survival; superior to the IELSG model (0.580). Taken together, this study's findings showed that the combination of PD-L1 on TAMs and the M2-to-M1 ratio could be strong prognostic predictive biomarkers for PCNSL and the IELSG-M index had improved prognostic significance than the IELSG index.
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http://dx.doi.org/10.1002/hon.2926DOI Listing
December 2021

Establishment of Prognostic Nomograms for Predicting the Survival of HR-Positive, HER2-Negative Metastatic Breast Cancer Patients Treated with Everolimus.

Drug Des Devel Ther 2021 10;15:3463-3473. Epub 2021 Aug 10.

Departments of Medical Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.

Background: There are no clinically available prognostic models for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer treated with everolimus. We aimed to develop a tool to predict the progression-free survival (PFS) and overall survival (OS) of these patients and to identify optimal candidates who would benefit from everolimus-based treatment in this heterogeneous patient population.

Methods: The clinical data of patients with HR+, HER2- metastatic breast cancer receiving everolimus between May 2012 and January 2018 at Sun Yat-sen University Cancer Center were retrospectively retrieved. Based on potential prognostic factors derived from multivariate Cox analysis, we established predictive nomogram models for PFS and OS and evaluated their predictive values by means of the concordance index (C-index). Calibration curves were used to estimate the consistency between the actual observations and the nomogram-predicted probabilities.

Results: A total of 116 patients with HR+, HER2- metastatic breast cancer were enrolled in this study. Three independent prognostic factors, including the line of everolimus in the metastatic setting, everolimus clinical benefit rate and number of liver metastatic lesions, were identified from the multivariate Cox analysis. Prognostic models for individual survival prediction were established and graphically presented as nomograms. The C-index was 0.738 (95% confidence interval [CI]: 0.710-0.767) for the PFS nomogram and 0.752 (95% CI: 0.717-0.788) for the OS nomogram, which showed favourable discrimination. The calibration curves for the probabilities of 6-, 9-, and 12-month PFS and 1-, 2-, and 3-year OS suggested satisfactory consistency between the actual observations and the predicted probabilities.

Conclusion: We constructed convenient nomogram models for patients with HR+, HER2- metastatic breast cancer to individually predict their potential benefits from everolimus in the metastatic setting. The models showed good performance in terms of accuracy, discrimination capacity and clinical application value.
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http://dx.doi.org/10.2147/DDDT.S314723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364432PMC
January 2022

Immobilizing Enzymes on Noble Metal Hydrogel Nanozymes with Synergistically Enhanced Peroxidase Activity for Ultrasensitive Immunoassays by Cascade Signal Amplification.

ACS Appl Mater Interfaces 2021 Jul 7;13(28):33383-33391. Epub 2021 Jul 7.

Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.

Enzyme immobilization plays an essential role in solving the problems of the inherently fragile nature of enzymes. Although prominent stability and reuse of enzymes can be achieved by enzyme immobilization, their bioactivity and catalytic efficiency will be adversely affected. Herein, PdCu hydrogel nanozymes with a hierarchically porous structure were used to immobilize horseradish peroxidase (HRP) to obtain [email protected] In addition to the improvement of stability and reusability, [email protected] displayed synergistically enhanced activities than native HRP and PdCu hydrogels. Not only the specific interactions between PdCu hydrogel nanozymes and enzymes but also the enrichment of substrates around enzymes by electrostatic adsorption of hydrogels was proposed to expound the enhanced catalytic activity. Accordingly, by taking advantage of the excellent catalytic performance of the [email protected] and the glucose oxidase encapsulated in zeolitic imidazolate framework-8, colorimetric biosensing of the carcinoembryonic antigen via catalytic cascade reactions for achieving signal amplification was performed. The obtained biosensor enhanced the detection sensitivity by approximately 6.1-fold as compared to the conventional HRP-based enzyme-linked immunosorbent assay, demonstrating the promising potential in clinical diagnosis.
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http://dx.doi.org/10.1021/acsami.1c09100DOI Listing
July 2021

Defect-Engineered Nanozyme-Linked Receptors.

Small 2021 08 5;17(33):e2101907. Epub 2021 Jul 5.

Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan, 430079, P. R. China.

Though nanozymes are successfully applied in various areas, the increasing demands facilitate the exploitation of nanozymes possessing higher activity and more functions. Natural enzyme-linked receptors (ELRs) are critical components for signal transductions in vivo by expressing activity variations after binding with ligands. Inspired by this, the defect-engineered carbon nitrides (DCN) are reported to serve as nanozyme-linked receptors (NLRs). For one thing, cyano defects increase the enzyme-like activity by a factor of 109.5. For another, DCN-based NLRs are constructed by employing cyano groups as receptors, and variable outputs are ensued upon the addition of ion ligands. Significantly, both the cascade effect and electronic effect are demonstrated to contribute to this phenomenon. Finally, NLRs are used for pattern recognition of metal ions, indicating the signal transduction ability of NLRs as well. This work not only provides great promise of defect engineering in nanozymes, but also contributes to the design of artificial ELRs.
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http://dx.doi.org/10.1002/smll.202101907DOI Listing
August 2021

Establishing Performance Evaluation for Quality Inspection of Specialty Nurses.

Clin Nurse Spec 2021 Jul-Aug 01;35(4):180-187

Author Affiliations: Clinical Medical Research Center (Ms Cai) and Nursing Department (Mss S. Zheng, Huang, Z. Zheng, Xu, Wu, and Zhou), Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, China.

Purpose: The present study aimed to establish an index system for the performance evaluation of specialty nurses (SNs) in tertiary hospitals.

Background: An objective index system for performance evaluation of SN has not yet been established in China.

Design: A 2-round Delphi survey sought opinions from experts about the index system for SNs' performance evaluation in tertiary hospitals in China.

Methods: Delphi survey was used to inquire approximately 20 experts from the fields of nursing management, nursing education, and clinical nursing. We determined the weight coefficient of each index of performance evaluation based on the opinion. Finally, the index of the quality evaluation was established for SN.

Results: A total of 20 experts from 10 provinces in China reached a consensus on the tertiary indexes of the assessment model. The indexes contained first-level (4), second-level (16), and third-level (24) indicators. The 4 aspects of the performance evaluation, including clinical specialist practice assessment, nursing research, education assessment, medical cooperation recognition, and personal comprehensive ability assessment, reached consensus.

Conclusion: Establishing the performance evaluation for SNs aided the SNs in achieving the best clinical practice after training. The performance evaluation still needed to be continuously improved.
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http://dx.doi.org/10.1097/NUR.0000000000000604DOI Listing
September 2021

Elevated expression of HMGB1 is prognostic of poor survival in patients with relapsed/refractory T/NK-CL.

Ann Hematol 2021 Sep 15;100(9):2293-2302. Epub 2021 May 15.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.

Despite the clinical value of HMGB1 in non-Hodgkin lymphoma (NHL), the impact of HMGB1 protein expression on survival of patients with mature T-cell and NK-cell lymphoma (T/NK-CL) is unknown. Here, we evaluated correlations of HMGB1 expression in tumor tissues with pathophysiological characteristics of disease and determined the prognostic value of HMGB1 expression in relapsed/refractory T/NK-CL. HMGB1 expression was detected by immunohistochemistry (IHC) in 66 cases of relapsed/refractory T/NK-CL, and specimens were classified as high or low HMGB1 expression. Univariate and multivariate Cox regression analyses identified prognostic factors associated with progression-free survival (PFS) and overall survival (OS). High HMGB1 expression was significantly correlated with increased Ki67 levels and progressive lymphoma subtypes. Univariate Cox regression analysis showed that high HMGB1 expression was associated with unfavorable PFS (P = 0.006) and poorer OS (P < 0.001). Prognostic factors identified by univariate analysis were prognostic index for peripheral T-cell lymphoma non-specified (PIT) score ≥ 2, bone marrow involvement, Ki67 ≥ 70%, and high HMGB1 expression. Multivariate Cox regression analysis revealed that high HMGB1 expression was an independent prognostic factor for poorer PFS [hazard ratio (HR) 3.593; 95% confidence interval (CI) 1.171-11.027; P = 0.025] and OS [HR 7.663; 95% CI 2.367-24.803; P = 0.001]. A proposal prognostic model combining HMGB1 and Ki67 expression showed improved prognostic capacity and may help guide treatment planning. High HMGB1 expression may be a promising prognostic predictor and a potential therapeutic target for relapsed/refractory T/NK-CL. Furthermore, to apply HMGB1 as one of the best bio-maker, an external independent control cohort is needed.
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http://dx.doi.org/10.1007/s00277-021-04473-4DOI Listing
September 2021

Nanozyme-Activated Synergistic Amplification for Ultrasensitive Photoelectrochemical Immunoassay.

Anal Chem 2021 05 22;93(17):6881-6888. Epub 2021 Apr 22.

Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.

At present, enzyme-mediated signal amplification strategies have been widely applied in photoelectrochemical (PEC) biosensing systems, while the introduction of natural enzymes onto the surface of photoelectrodes inevitably obstructs the electron transfer due to their insulating properties as proteins, leading to severe damage to photocurrent. In this work, the PdPt bimetallic nanozymes with the efficient peroxidase-like activity were used as alternatives to natural enzymes and amplified PEC biosensing signals via their efficient enzymatic reaction and remarkable enhancement in photocurrent. As a result, photoactive CdS nanorods modified with PdPt bimetallic nanozymes showed a boosted PEC performance compared with the pristine CdS nanorods due to the localized surface plasmon resonance effect and Schottky junction. On the basis of the as-prepared CdS/PdPt photoelectrode, a sensitive split-type glucose oxidase-mediated PEC immunoassay for carcinoembryonic antigen (CEA) detection was successfully constructed. Along with the sandwich immunocomplexing, the subsequently produced hydrogen peroxide (HO) can oxidize 4-chloro-1-naphthol into insoluble precipitates to inhibit photocurrent and simultaneously trigger the bio-etching of CdS to further restrain photocurrent signals due to the excellent peroxidase-mimicking activity of PdPt nanozymes. Owing to the synergistic signal amplification fulfilled by PdPt nanozymes, an ultrasensitive immunoassay of CEA was realized with a wider linear range from 1 to 5000 pg/mL and a low detection limit of 0.21 pg/mL, opening a new avenue for building ultrasensitive PEC biosensors with nanozymes.
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http://dx.doi.org/10.1021/acs.analchem.1c01217DOI Listing
May 2021

Ultrafine MoP Nanoparticle Splotched Nitrogen-Doped Carbon Nanosheets Enabling High-Performance 3D-Printed Potassium-Ion Hybrid Capacitors.

Adv Sci (Weinh) 2021 Apr 2;8(7):2004142. Epub 2021 Feb 2.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Materials Science and Engineering Innovation Center for Textile Science and Technology Donghua University Shanghai 201620 P. R. China.

Size engineering is deemed to be an adoptable method to boost the electrochemical properties of potassium-ion storage; however, it remains a critical challenge to significantly reduce the nanoparticle size without compromising the uniformity. In this work, a series of MoP nanoparticle splotched nitrogen-doped carbon nanosheets ([email protected]) is synthesized. Due to the coordinate and hydrogen bonds in the water-soluble polyacrylamide hydrogel, MoP is uniformly confined in a 3D porous NC to form ultrafine nanoparticles which facilitate the extreme exposure of abundant three-phase boundaries (MoP, NC, and electrolyte) for ionic binding and storage. Consequently, [email protected] delivers an excellent capacity performance (256.1 mAh g at 0.1 A g) and long-term cycling durability (89.9% capacitance retention after 800 cycles). It is further confirmed via density functional theory calculations that the smaller the MoP nanoparticle, the larger the three-phase boundary achieved for favoring competitive binding energy toward potassium ions. Finally, [email protected] is applied as highly electroactive additive for 3D printing ink to fabricate 3D-printed potassium-ion hybrid capacitors, which delivers high gravimetric energy/power density of 69.7 Wh kg/2041.6 W kg, as well as favorable areal energy/power density of 0.34 mWh cm/9.97 mW cm.
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http://dx.doi.org/10.1002/advs.202004142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025015PMC
April 2021

High-dose tamoxifen in high-hormone-receptor-expressing advanced breast cancer patients: a phase II pilot study.

Ther Adv Med Oncol 2021 26;13:1758835921993436. Epub 2021 Feb 26.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510000, China.

Background: Tumor progression following endocrine therapy is considered to indicate resistance to endocrine drugs due to a variety of mechanisms. An insufficient dose of endocrine drugs is one of the causes for treatment failure in some patients with high hormone-receptor (HR)-expressing advanced breast cancer. This study aimed to explore the efficacy of high-dose tamoxifen (TAM) treatment in patients with advanced breast cancer with highly expressed HR.

Materials & Methods: This was a single-arm, phase II pilot study that enrolled patients with advanced breast cancer with high HR expression (estrogen receptor ⩾60% and/or progesterone receptor ⩾60%) following routine endocrine therapy. All enrolled patients received a high-dose of TAM (100 mg/day) until disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety. Exploratory endpoints included the predictive value of α-F-β-fluoroestradiol quantitative positron emission tomography/computed tomography (F-FES PET/CT) for treatment efficacy.

Results: A total of 30 patients were enrolled between September 2017 and February 2019. The median PFS was 6 months [95% confidence interval (CI) 4.9-7.1] and the median OS was 15.6 months (95% CI 8.3-22.9). Five patients experienced a partial response (PR) and none experienced a complete response (CR), with an ORR of 16.7% and CBR of 33.3%. No severe adverse events were observed. Lesions with F-FES maximum standardized uptake value (SUVmax) ⩾4 had a significantly longer PFS [median 9.2 months, (95% CI 6.9-11.6)] compared with lesions with a F-FES SUVmax <4 [median 4.8 months, (95% CI 3.9-5.6);  = 0.022].

Conclusion: A high-dose of TAM is effective and safe for patients with advanced breast cancer with high HR expression. F-FES SUVmax values may predict the local clinical benefits of high-dose TAM .

Trial Registration: [ClinicalTrials.gov identifier: NCT0304565].
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http://dx.doi.org/10.1177/1758835921993436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934038PMC
February 2021

A New Candidate in Polyanionic Compounds for a Potassium-Ion Battery Cathode: KTiOPO.

J Phys Chem Lett 2021 Mar 11;12(11):2721-2726. Epub 2021 Mar 11.

College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, P. R. China.

First-principles computations were performed to investigate the performance of KTiOPO (KTP) as a cathode material for potassium-ion batteries (PIBs), including the stability and electronic properties of depotassiated structures and mechanisms of K deintercalation and diffusion. As depotassiation proceeds, oxygen hole polarons are produced, and there are not peroxides or superoxides formed after deep depotassiation. The anionic oxygen redox in KTP provides a voltage vs K/K over 4 V by the PBE+ method and over 5 V with the more reliable HSE06 hybrid functional. When all K in KTP is removed, the calculated volume compression is only 1.528%. The AIMD simulations at 300 K for TiOPO verify its thermal stability. The PBE+ calculations predict a low ion diffusion barrier of 0.29 eV in bulk KTP, indicating a good charge-discharge rate for KTP as a cathode for PIBs. All of the calculated results indicate that KTP can be a promising cathode material for PIBs.
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http://dx.doi.org/10.1021/acs.jpclett.1c00286DOI Listing
March 2021

Safety, tolerability, and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer: An open-label, dose-escalation, phase I study.

Cancer Commun (Lond) 2021 02 2;41(2):171-182. Epub 2021 Feb 2.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, P. R. China.

Background: The introductions of anti- human epidermal growth factor receptor-2 (HER2) agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer. BAT8001 is a novel antibody-drug conjugate targeting human epidermal growth factor receptor-2 (HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine. This dose-escalation, phase I study was designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.

Methods: This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer (having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1) using a 3 + 3 design of escalating BAT8001 doses. Patients received BAT8001 intravenously in a 21-day cycle, with dose escalation in 5 cohorts: 1.2, 2.4, 3.6, 4.8, and 6.0 mg/kg. The primary objective was to evaluate the safety and tolerability of BAT8001. Preliminary activity of BAT8001 was also assessed as a secondary objective.

Results: Between March 2017 to May 2018, 29 HER2-positive breast cancer patients were enrolled. The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase. The maximum tolerated dose was determined to be 3.6 mg/kg. Grade 3 or greater adverse events (AEs) occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) patients, aspartate aminotransferase increased in 4 (13.8%) patients, γ-glutamyl transferase increased in 2 (6.9%) patients, alanine aminotransferase increased in 2 (6.9%) patients, diarrhea in 2 (6.9%) patients. Objective response was observed in 12 (41.4%; 95% confidence interval [CI] = 23.5%-61.1%) and disease control (including patients achieving objective response and stable disease) was observed in 24 (82.8%; 95% CI = 64.2%-94.2%) patients.

Conclusions: BAT8001 demonstrated favorable safety profiles, with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer. BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.
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http://dx.doi.org/10.1002/cac2.12135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896747PMC
February 2021

The Efficacy and Safety of Traditional Chinese Medicine Tonifying-Shen (Kidney) Principle for Primary Osteoporosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Evid Based Complement Alternat Med 2020 6;2020:5687421. Epub 2020 Oct 6.

The Bao'an District TCM Hospital, The Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Shenzhen 518101, Guangdong, China.

Objective: This study aimed to appraise the efficacy and safety of the tonifying-Shen (kidney) principle (TS (TK) principle) for primary osteoporosis (POP).

Methods: Randomized controlled clinical trials (RCTs) using the TS (TK) principle for POP were searched from eight electronic databases to search for relevant literature that was published from the initiation to September 2019. Two reviewers performed study selection, data extraction, data synthesis, and quality assessment independently. Review Manager 5.3 software was used to assess the risk of bias and conduct the data synthesis. We assessed the quality of evidence for outcomes by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.

Results: Thirty-six studies with 3617 participants were included. Meta-analysis showed a consistently superior effect of the TS (TK) principle combined with conventional Western medicine (CWM) in terms of total effectiveness rates (RR = 1.28; 95% CI (1.23, 1.33); < 0.00001), BMD of the lumbar spine (SMD = 0.71; 95% CI (0.47, 0.95); < 0.00001) and proximal femur (SMD = 0.94; 95% CI (0.49, 1.38); < 0.00001), TCM symptom integral (SMD = -1.23; 95% CI (-1.43, -1.02); < 0.00001), and VAS scores (SMD = -3.88; 95% CI (-5.29, -2.46); < 0.00001), when compared to using CWM alone and with significant differences. Besides, in respect of adverse effects, it showed no significant statistical difference between the experimental and control groups, RR = 0.99 and 95% CI (0.65, 1.51), =0.97.

Conclusion: Our meta-analysis provides promising evidence to suggest that using the TS (TK) principle combined with CWM for POP is more effective than using CWM alone. Also, both of them are safe and reliable for POP.
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http://dx.doi.org/10.1155/2020/5687421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559232PMC
October 2020

[Effects of stachyine on apoptosis in an Aβ-induced PC12 cell model of Alzheimer's disease].

Nan Fang Yi Ke Da Xue Xue Bao 2020 Jul;40(7):1023-1028

Department of Anesthesia, First Affiliated Hospital of Nanchang University, Nanchang 330006, China.

Objective: To investigate the effects of stachydrine (STA) on apoptosis of Aβ-induced PC12 cells mimicking Alzheimer's disease and explore the mechanisms.

Methods: The differential genes of STA were analyzed based on GSE85871 data, and the target genes of STA were identified using STITCH database. PC12 cells were treated with Aβ to establish a cell model of Alzheimer's disease, and the changes in cell viability and cell cycle in response to STA treatment were assessed using MTT assay and flow cytometry, respectively. RT-PCR and Western blotting were used to detect the relevant gene or protein expressions in the treated cells.

Results: GSE85871 data showed 37 up-regulated genes and 48 down-regulated genes in cells following treatment with STA. Analysis of the data from the STITCH database indicated that RPS8 and EED were the target genes of STA. Treatment of PC12 cells with Aβ significantly lowered the cell viability ( < 0.05) and the expressions of RPS8 and EED at both the mRNA and protein levels ( < 0.05), and obviously inhibited the expression of apoptosis-related proteins Bcl-2 and p53 ( < 0.05). STA treatment of the cells significantly reversed the effect of Aβ and induced cell cycle arrest in G2/M phase, causing also significantly increases in the expression levels of RPS8, EED, Bcl-2 and p53 ( < 0.05).

Conclusions: STA plays an important role in inhibiting the apoptosis of PC12 cells induced by Aβ possibly by regulating RPS8 and EED expression to promote the expressions of Bcl-2 and p53.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2020.07.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386225PMC
July 2020

Contingency Nursing Management in Designated Hospitals During COVID-19 Outbreak.

Ann Glob Health 2020 06 29;86(1):70. Epub 2020 Jun 29.

ShanTou Central Hospital, CN.

Background: In December 2019, early cases of COVID-19 were identified in Wuhan, China. By late January 2020, it was evident that COVID-19 was rapidly spreading and represented a national health emergency. In order to contain the spread of COVID-19, China adopted a centralized treatment plan by appointing designated hospitals in each region. Shantou Central Hospital is a Grade A Class A general hospital in Guangdong Province. It was appointed as a provincial COVID-19 designated treatment hospital on January 21, 2020, to provide all COVID-19-related treatments for the city of Shantou. The nursing department at Shantou Central Hospital is fully responsible for hospital nursing administration, nursing human resource management, nursing quality management, and all nursing tasks related to hospital medical care, nursing, teaching, scientific research, preventive healthcare, and so on.

Objective: To summarize the role of nursing management in transforming a general hospital into a designated hospital for treatment of COVID-19 patients.

Methods: We undertook a series of nursing management measures in the strategic phase and the implementation phase.

Findings: Through a series of nursing management measures, all COVID-19 patients admitted to our hospital were cured and discharged. All non-COVID-19 patients and staff hospitalized during the same period were not infected with the virus. During this period, our hospital completed 7,466 operations. Hence, our nursing management measures were effective.

Conclusions: Our efficient nursing management system, first of all, effectively mobilized all available manpower; secondly, up-skilled and trained personnel within a very short period of time; thirdly, provided reliable logistical support for front-line protection equipments; and finally, motivated nurses during this very difficult time to make a significant positive contribution to the fight against COVID-19 pandemic.
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http://dx.doi.org/10.5334/aogh.2918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333556PMC
June 2020

Efficacy of Moxifloxacin plus Treatment of Physician's Choice in Patients with Metastatic Breast Cancer.

Oncologist 2020 10 1;25(10):e1439-e1445. Epub 2020 Jun 1.

Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

Lessons Learned: Moxifloxacin plus continuation of the previous treatment of physician's choice shows promising efficacy in patients with metastatic breast cancer. The addition of moxifloxacin shows well-tolerated toxicities.

Background: Recent studies have confirmed bacterial infection as an important contributor in cancer. Elimination of tumor-associated microbes may lead to a reduction in tumors and improved survival. Moxifloxacin is an orally administrated fourth-generation quinolone with broad-spectrum coverage against tumor-associated bacteria.

Methods: In this study, we assessed the efficacy and safety of moxifloxacin in combination with treatment of physician's choice (TPC) in patients with metastatic breast cancer (MBC). In this single-arm, phase II study, we recruited 30 patients with MBC who had a trend toward disease progression (stable disease [SD] with increased tumor size) during TPC before enrollment at Sun Yat-sen University Cancer Center between January 1 and July 30, 2018. Eligible patients were given moxifloxacin once daily at a dose of 400 mg from days 1 to 7 of a 28-day cycle, in addition to continuing to receive the therapy previously selected by their physicians. Tumor response was determined according to RECIST (version 1.1). Progression-free survival (PFS) was calculated using the Kaplan-Meier method.

Results: The concomitant use of moxifloxacin and previous TPC yielded a median PFS of 6.6 months (95% confidence interval [CI]: 4.0-9.1) and a 1-year PFS of 25.9% (95% CI: 10.0%-41.9%). Objective responses were achieved in seven (23.3%, 95% CI: 7.3%-39.4%) patients. The clinical benefit rate was 46.7% (95% CI: 27.7%-65.6%). No grade 4 adverse events (AEs) and four grade 3 AEs were observed, none of which were considered to have definite relation to moxifloxacin.

Conclusion: The combination of moxifloxacin with previous TPC shows promising efficacy and well-tolerated toxicities in patients with MBC.
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http://dx.doi.org/10.1634/theoncologist.2020-0364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543292PMC
October 2020

A primary neuroendocrine tumor of the left ventricle presenting with diarrhea-an unusual experience and literature review.

Diagn Pathol 2020 Apr 3;15(1):32. Epub 2020 Apr 3.

Department of Pathology, The Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China.

Background: Neuroendocrine tumors (NETs) can secrete bioactive amines in the bloodstream, resulting in the carcinoid syndrome characterized by diarrhea and flushing. The frequency of occurrence of primary cardiac neuroendocrine neoplasms is lesser than that of metastases, and hence, metastases must be adequately ruled out before diagnosis. Cardiac tumors, both primary and metastatic, mainly result in heart-related symptoms, such as heart failure and acquired valvular dysfunction. Here, we report a unique case of a primary left ventricular neuroendocrine tumor presenting with diarrhea.

Case Presentation: A 51-year-old female complaining of intermittent diarrhea for 2 years was admitted to our hospital. Enhancement of total abdominal computed tomography scan, echocardiography, and magnetic resonance imaging indicated a mass in the left ventricle. The indexes of myocardial enzymes were normal. Histologically, round cells with well-differentiated neuroendocrine morphology were arranged in typical pseudo-glandular, trabecular, ribbon-like, and solid nest patterns. Immunohistochemically, the tumor cells were positive for cytokeratin, chromogranin, synaptophysin, and CD56. However, they were negative for caudal type homeobox 2, S100, paired box gene 8, thyroid transcription factor 1, and CD20, which ruled out the origin of gastrointestinal, pancreatic, lung, and Merkel cell carcinomas. The symptoms of diarrhea disappeared after the operation. The patient was asymptomatic at the 9-month follow-up.

Conclusion: Cardiac neuroendocrine tumors with diarrhea are considerably rare and related clinical research is limited. We presented a case and reviewed related articles to improve the identification, diagnosis, and management of patients with cardiac neuroendocrine tumors. The site of origin of a neuroendocrine tumor is clinically vital, and identification of an occult primary tumor using imaging modalities is necessary. Immunohistochemistry is well-suited to indicate the origin of the tumor. Regular follow-up is necessary for both poorly differentiated and well-differentiated cardiac neuroendocrine tumors. It is suggested to detect some neuroendocrinal markers for patients with unexplained reasons of diarrhea.
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http://dx.doi.org/10.1186/s13000-020-00935-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119177PMC
April 2020

The prognostic value of androgen receptor (AR) in HER2-enriched metastatic breast cancer.

Endocr Relat Cancer 2020 04;27(4):199-208

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

The significance of androgen receptor (AR) in metastatic breast cancer (MBC) remains unclear, and it is still largely unknown how AR expression level influences HER2-positive tumors. This study aimed to investigate the prognostic and predictive value of AR in HER2-enriched MBC. Primary and/or paired metastatic tumors of 304 patients with pathologically confirmed HER2-enriched MBC were collected and immunohistochemically assessed for AR expression. The associations of AR and other clinicopathological characteristics were compared using the Chi-square test. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and log-rank test. Cox regression analysis was used to determine independent prognostic factors. AR-positivity with a cut-off value of 10% was observed in 237 (78.0%) cases and was associated with longer PFS, 13.2 months, as compared to that of 8.2 months (P = 0.004) in patients with AR-negativity. Moreover, a significant increase in the 5-year OS rate (65.3% vs 36.2%, P < 0.001) was also observed for patients with AR-positive tumors. Cox regression analysis identified AR-positivity as an independent prognostic factor of both PFS (hazard ratio = 0.71, P = 0.039) and OS (HR = 0.53, P = 0.013). Additionally, for those who received first-line Trastuzumab therapies, prolonged PFS (15.8 months vs 8.2 months, P = 0.005) and 5-year OS rate (66.2% vs 26.2%, P = 0.009) were observed in AR-positive tumors compared to AR-negative ones. In conclusion, AR was identified as an independent prognostic factor for favorable PFS and OS and could also predict the efficacy of first-line Trastuzumab treatment in patients with HER2-enriched MBC.
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http://dx.doi.org/10.1530/ERC-19-0315DOI Listing
April 2020

Safe, Low-Cost, Fast-Kinetics and Low-Strain Inorganic-Open-Framework Anode for Potassium-Ion Batteries.

Angew Chem Int Ed Engl 2019 Nov 25;58(46):16474-16479. Epub 2019 Sep 25.

CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, 350002, P. R. China.

A key challenge for potassium-ion batteries is to explore low-cost electrode materials that allow fast and reversible insertion of large-ionic-size K . Here, we report an inorganic-open-framework anode (KTiOPO ), which achieves a reversible capacity of up to 102 mAh g (307 mAh cm ), flat voltage plateaus at a safe average potential of 0.82 V (vs. K/K ), a long lifespan of over 200 cycles, and K -transport kinetics ≈10 times faster than those of Na-superionic conductors. Combined experimental analysis and first-principles calculations reveal a charge storage mechanism involving biphasic and solid solution reactions and a cell volume change (9.5 %) even smaller than that for Li -insertion into graphite (≈10 %). KTiOPO exhibits quasi-3D lattice expansion on K intercalation, enabling the disintegration of small lattice strain and thus high structural stability. The inorganic open-frameworks may open a new avenue for exploring low-cost, stable and fast-kinetic battery chemistry.
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http://dx.doi.org/10.1002/anie.201909202DOI Listing
November 2019

A novel starch: Characterizations of starches separated from tea (Camellia sinensis (L.) O. Ktze) seed.

Int J Biol Macromol 2019 Oct 7;139:1085-1091. Epub 2019 Aug 7.

State Key Laboratory of Rice Biology and Key Laboratory of the Ministry of Agriculture for the Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou, 310029, PR China. Electronic address:

The physicochemical, thermal and crystal properties of starches isolated from 3 different tea (Camellia sinensis (L.) O. Ktze) seeds were analyzed in this study. The shape of tea starch granules were flat spherical or oval shape, showed unimodal or bimodal distribution with average size of around 9 μm. Tea starch was typical A-type starch. Apparent amylose contents of three tea seed starches ranged from 27.06% to 33.17%. The chains having degree of polymerization (DP) 13-24 were over 50% of the total detectable chains for tea amylopectin. Peak gelatinization temperature of tea starch ranged from 65 to 77 °C and the water solubility reached up to 9.70%. The peak viscosity of tea starches were as high as 5300 cP and final viscosity ranged from 4000 to 6700 cP. The results indicated that tea seed starch had potential as gel reagents and provide some guides for comprehensive utilization of tea starch in food and non-food applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.08.044DOI Listing
October 2019

Novel functional fiber loaded with carbon dots for the deep removal of Cr(VI) by adsorption and photocatalytic reduction.

J Environ Sci (China) 2019 Sep 19;83:195-204. Epub 2019 Apr 19.

School of Chemical Engineering and Energy, Zhengzhou University, Zhengzhou 450001, China. Electronic address:

A novel functional fiber (PAN-CDs) loaded with carbon dots (CDs) with excellent photoreduction and adsorption properties for Cr(VI) was prepared via an amidization reaction between the CDs' carboxyl groups and amine groups on polyacrylonitrile (PAN)-based ion exchange fibers, which could completely preserve the fluorescence properties of the CDs. The photoluminescence (PL), photocatalysis and adsorption properties of PAN-CDs were characterized and analyzed. The PAN-CDs possess high adsorption capacity (297.6 mg/g) and excellent kinetic behavior (attaining adsorption equilibrium in 30 min) for Cr(VI) adsorption. Furthermore, the residual Cr(VI) (approximately 3 mg/L) after adsorption could be removed completely by subsequent photoreduction by the PAN-CDs. The Cr-saturated PAN-CDs could be easily separated by filtering and regenerated, with no observable decay of removal efficiency after five regeneration cycles. In addition, due to the PL quenching action of Cr(VI), the PAN-CDs can also be used as sensor for quantitative detection of trace Cr(VI) in aqueous solution.
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http://dx.doi.org/10.1016/j.jes.2019.04.008DOI Listing
September 2019

The Effects of Ganglioside-Monosialic Acid in Taxane-Induced Peripheral Neurotoxicity in Patients with Breast Cancer: A Randomized Trial.

J Natl Cancer Inst 2020 01;112(1):55-62

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.

Background: Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting adverse effect. Ganglioside-monosialic acid (GM1) functions as a neuroprotective factor. We assessed the effects of GM1 on the prevention of TIPN in breast cancer patients.

Methods: We conducted a randomized, double-blind, placebo-controlled trial including 206 patients with early-stage breast cancer planning to receive taxane-based adjuvant chemotherapy with a follow-up of more than 1 year. Subjects were randomly assigned to receive GM1 (80 mg, day -1 to day 2) or placebo. The primary endpoint was the Functional Assessment of Cancer Treatment Neurotoxicity subscale score after four cycles of chemotherapy. Secondary endpoints included neurotoxicity evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and the Eastern Cooperative Oncology Group neuropathy scale. All statistical tests were two-sided.

Results: In 183 evaluable patients, the GM1 group reported better mean Functional Assessment of Cancer Treatment Neurotoxicity subscale scores than patients in the placebo group after four cycles of chemotherapy (43.27, 95% confidence interval [CI] = 43.05 to 43.49 vs 34.34, 95% CI = 33.78 to 34.89; mean difference = 8.96, 95% CI = 8.38 to 9.54, P < .001). Grade 1 or higher peripheral neurotoxicity in Common Terminology Criteria for Adverse Events v4.0 scale was statistically significantly lower in the GM1 group (14.3% vs 100.0%, P < .001). Additionally, the GM1 group had a statistically significantly lower incidence of grade 1 or higher neurotoxicity assessed by Eastern Cooperative Oncology Group neuropathy scale sensory neuropathy (26.4% vs 97.8%, P < .001) and motor neuropathy subscales (20.9% vs 81.5%, P < .001).

Conclusions: The treatment with GM1 resulted in a reduction in the severity and incidence of TIPN after four cycles of taxane-containing chemotherapy in patients with breast cancer.
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http://dx.doi.org/10.1093/jnci/djz086DOI Listing
January 2020

Propranolol suppresses infantile hemangioma cell proliferation and promotes apoptosis by upregulating miR-125b expression.

Anticancer Drugs 2019 06;30(5):501-507

Department of Pharmacy, Fuwai Central China Cardiovascular Hospital.

Propranolol could repress infantile hemangioma cell growth and induce apoptosis. miR-125b could inhibit cell proliferation in some tumors. However, whether propranolol exerts its proliferation inhibition and apoptosis-promoting effect by regulating the expression of miR-125b needs to be further investigated. In tumor tissue and endothelial cells isolated from infantile hemangioma patients, we found that the expression levels of miR-125b were significantly decreased. In-vitro analysis revealed that propranolol increased the expression of miR-125b in hemangioma cells in a dose-dependent and time-dependent manner. Interestingly, it was observed that regression of miR-125b expression by its inhibitor could abrogate the effect of propranolol on hemangioma cell growth and apoptosis. In addition, our data further identified TFAP4 as a direct target of miR-125b. Collectively, our data provided evidence that propranolol may repress infantile hemangioma cell growth and promote apoptosis through upregulating the miR-125b expression, which exerted its suppression of tumor development by targeting TFAP4.
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http://dx.doi.org/10.1097/CAD.0000000000000762DOI Listing
June 2019

Physicochemical properties of hydroxypropylated and cross-linked rice starches differential in amylose content.

Int J Biol Macromol 2019 May 30;128:775-781. Epub 2019 Jan 30.

State Key Laboratory of Rice Biology, Key Laboratory of the Ministry of Agriculture for Nuclear-Agricultural Sciences, Department of Applied Biosciences, Zhejiang University, Hangzhou 310029, PR China. Electronic address:

Hydroxypropylation and cross-linking were carried out on three rice starches with 6.93%, 19.02% and 48.41% AAC respectively. AAC affected the efficiency of modification, with AAC increased, the molar substitution of hydroxypropylated starch decreased while degree of substitution of cross-linked starch increased. Modifications decreased starch relative crystallinity while the impacts were dependent on rice varieties. Starch granules of high AAC rice were liable to be disrupted by modification. High AAC rice starch had better processability, modifications have more pronounced influences on starch properties of high AAC. Different modifications showed different influences on starch properties, cross-linking decreased AAC content, pasting clarity and swelling power of all three starches, while hydroxypropylation increased pasting clarity and swelling power of high AAC starch. High-degree modifications decreased starch digestibility, higher-CLD crosslinked starch showed constant digestion rate and might be a suitable modification for produce starchy food for equilibrium glucose level.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.01.194DOI Listing
May 2019

Inhibition of chemotherapy resistant breast cancer stem cells by a ROR1 specific antibody.

Proc Natl Acad Sci U S A 2019 01 8;116(4):1370-1377. Epub 2019 Jan 8.

Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Pharmacology, International Cancer Center, Shenzhen University Health Science Center, 518060 Shenzhen, China;

Breast cancers enduring treatment with chemotherapy may be enriched for cancer stem cells or tumor-initiating cells, which have an enhanced capacity for self-renewal, tumor initiation, and/or metastasis. Breast cancer cells that express the type I tyrosine kinaselike orphan receptor ROR1 also may have such features. Here we find that the expression of ROR1 increased in breast cancer cells following treatment with chemotherapy, which also enhanced expression of genes induced by the activation of Rho-GTPases, Hippo-YAP/TAZ, or B lymphoma Mo-MLV insertion region 1 homolog (BMI1). Expression of ROR1 also enhanced the capacity of breast cancer cells to invade Matrigel, form spheroids, engraft in Rag2[Formula: see text] mice, or survive treatment with paclitaxel. Treatment of mice bearing breast cancer patient-derived xenografts (PDXs) with the humanized anti-ROR1 monoclonal antibody cirmtuzumab repressed expression of genes associated with breast cancer stemness, reduced activation of Rho-GTPases, Hippo-YAP/TAZ, or BMI1, and impaired the capacity of breast cancer PDXs to metastasize or reengraft Rag2[Formula: see text] mice. Finally, treatment of PDX-bearing mice with cirmtuzumab and paclitaxel was more effective than treatment with either alone in eradicating breast cancer PDXs. These results indicate that targeting ROR1 may improve the response to chemotherapy of patients with breast cancer.
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http://dx.doi.org/10.1073/pnas.1816262116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347692PMC
January 2019

Pretreatment anti-Mullerian hormone-based nomogram predicts menstruation status after chemotherapy for premenopausal women with hormone receptor-positive early breast cancer.

Breast Cancer Res Treat 2019 Feb 3;173(3):619-628. Epub 2018 Nov 3.

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Dongfeng Road East 651#, Guangzhou, 510060, China.

Purpose: Ovarian function is important for optimizing endocrine treatment in patients with hormone receptor-positive (HR+) early breast cancer (eBC). The aim of the study was to determine whether patients' pretreatment levels of anti-Mullerian hormone (AMH) were associated with menses status after chemotherapy and to build a predictive nomogram model for amenorrhea in women with HR+ eBC.

Methods: Between August 2013 and December 2014, 120 premenopausal patients with HR+ eBC were included retrospectively. The associations among age, prechemotherapy levels of AMH, follicle-stimulating hormone (FSH),and estradiol (E2) and the 2-year postchemotherapy menses status were analyzed. We determined the cutoff values of hormone levels by using the biostatistical tool (Cutoff Finder). A novel nomogram was established to predict the 2-year amenorrhea status based on the logistic analysis. Concordance index (C-index) was used to validate the capacity.

Results: One hundred nine women (90.8%) experienced amenorrhea after chemotherapy. AMH < 0.965 ng/ml predicted amenorrhea at 2 years (AUC 0.84, sensitivity 74% and specificity 81.8%), independent of age. The predictive nomogram based on age and pretreatment AMH and FSH levels was developed to predict the probability of 2-year postchemotherapy amenorrhea with a C-index of 0.88 (95% CI 0.84-0.91).

Conclusions: In premenopausal patients with HR+ eBC, prechemotherapy AMH concentration was associated with the patient's 2-year amenorrhea status, independent of age. The nomogram model based on age and pretreatment AMH and FSH levels accurately predicted the 2-year amenorrhea status.
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http://dx.doi.org/10.1007/s10549-018-4997-2DOI Listing
February 2019
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