Publications by authors named "Yingying Xu"

262 Publications

RNA demethylation increases the yield and biomass of rice and potato plants in field trials.

Nat Biotechnol 2021 Jul 22. Epub 2021 Jul 22.

Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.

RNA N-methyladenosine (mA) modifications are essential in plants. Here, we show that transgenic expression of the human RNA demethylase FTO in rice caused a more than threefold increase in grain yield under greenhouse conditions. In field trials, transgenic expression of FTO in rice and potato caused ~50% increases in yield and biomass. We demonstrate that the presence of FTO stimulates root meristem cell proliferation and tiller bud formation and promotes photosynthetic efficiency and drought tolerance but has no effect on mature cell size, shoot meristem cell proliferation, root diameter, plant height or ploidy. FTO mediates substantial mA demethylation (around 7% of demethylation in poly(A) RNA and around 35% decrease of mA in non-ribosomal nuclear RNA) in plant RNA, inducing chromatin openness and transcriptional activation. Therefore, modulation of plant RNA mA methylation is a promising strategy to dramatically improve plant growth and crop yield.
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http://dx.doi.org/10.1038/s41587-021-00982-9DOI Listing
July 2021

Multi-omic analysis of altered transcriptome and epigenetic signatures in the UV-induced DNA damage response.

DNA Repair (Amst) 2021 Jul 15;106:103172. Epub 2021 Jul 15.

Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou 510260, China; Key Laboratory of Neurological Function and Health, School of Basic Medical Science, Guangzhou Medical University, Guangzhou 511436, China. Electronic address:

The transcription-related DNA damage response was visualized on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a small proportion of mature RNA transcripts undergo changes, with significant activation of DNA repair factors. Notably, an increase of chromatin accessibility is observed at the immediate early recovery phase and serves as binding sites for selective stage-specific transcription factors. Whole genome analysis of DNA methylation (5mC) delineates pervasive dynamics during DNA repair process, and hypomethylation at gene bodies and 3'UTR is accompanied by induction of DNA damage response genes. Furthermore, temporal-specific mA RNA methylation has been defined and appears to affect DNA repair by modulation of translation. These findings provide a resource for identifying players required for transcription-coupled nucleotide excision repair and reveal insights into the epigenetic regulation of the transcriptional programs in response to genotoxic stress.
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http://dx.doi.org/10.1016/j.dnarep.2021.103172DOI Listing
July 2021

Safety, efficacy, and serum concentration monitoring of bedaquiline in Chinese patients with multidrug-resistant tuberculosis.

Int J Infect Dis 2021 Jul 19. Epub 2021 Jul 19.

Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China. Electronic address:

Objectives: To determine the safety and efficacy of bedaquiline for Chinese multidrug-resistant tuberculosis patients based on serum concentration monitoring and identify factors associated with QTc prolongation occurring during treatment.

Methods: We collected data from 35 patients who received treatment regimens containing bedaquiline for multidrug-resistant tuberculosis (MDR-TB) from May 2018 to December 2020. Blood samples were collected, and serum concentrations of bedaquiline were measured using high-performance liquid chromatography-mass spectrometry.

Results: After completing the 24-week bedaquiline treatment course, 80.0% of the patients' sputum cultures turned negative. The median time to sputum culture conversion was 75.5 days (interquartile range, 52-126). The median serum concentration of bedaquiline was 0.586 ± 0.288 µg/ml during treatment and 0.205 ± 0.145 µg/ml 16 weeks after bedaquiline discontinuation. Bedaquiline remained detectable 52 weeks after discontinuation. Combination with clofazimine (CFZ) during bedaquiline treatment significantly increased cardiac QTc prolongation. When QTc prolongation occurred, serum potassium levels decreased by 10.71% from baseline, while serum sodium levels increased by 1.07% from baseline.

Conclusions: Bedaquiline had good treatment outcomes for Chinese MDR-TB patients. Combination with clofazimine increased the risk of QTc prolongation. Serum electrolytes (potassium and sodium) should be measured regularly during treatment of MDR-TB with regimens containing bedaquiline.
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http://dx.doi.org/10.1016/j.ijid.2021.07.038DOI Listing
July 2021

Ethical dilemmas faced by frontline support nurses fighting COVID-19.

Nurs Ethics 2021 Jul 13:9697330211015284. Epub 2021 Jul 13.

Linfield College, USA.

Background: In 2019, an outbreak of COVID-19 broke out in Hubei, China. Medical workers from all over the country rushed to Hubei and participated in the treatment and care of COVID-19 patients. These nurses, dedicated to their professional practice, volunteered to provide compassion and expert clinical care during the pandemic. As with other acts of heroism, the ethical dilemmas associated with working on the front line must be considered for future practice.

Purpose: To explore the ethical dilemmas of frontline nurses of Jiangsu Province in China during deployment to Wuhan to fight the novel coronavirus pneumonia, and to provide a basis for developing strategies to help nursing staff address personal and practice concerns in order to work more effectively during this pandemic and other disasters in the future.

Research Design And Method: Using the phenomenological research method and the purpose sampling method, semi-structured interviews were conducted with 10 nurses, post-deployment to Wuhan, who had worked on the front line to fight the novel coronavirus.

Ethical Considerations: The research proposal was approved by the Research Ethic Committee of Yangzhou University, China.

Findings: From the analysis of the interviews of the 10 participants, three main themes were identified: ethical dilemmas in clinical nursing, ethical dilemmas in interpersonal relationships, and ethical dilemmas in nursing management.

Conclusion: During a quick response to public health emergencies, where nurses are deployed immediately as a call to action, the issues surrounding ethical dilemmas from several perspectives must be considered. This research suggests that a team approach to proactive planning and open communication during the emergency is an efficient and productive strategy to improve the nurses' experience and sense of well-being.
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http://dx.doi.org/10.1177/09697330211015284DOI Listing
July 2021

Treatment of axillary bromhidrosis in adolescents by combining electrocauterization with ultrasound-guided botulinum toxin type A injection.

J Plast Reconstr Aesthet Surg 2021 Apr 18. Epub 2021 Apr 18.

Department of Ultrasound, The Third Hospital of Jilin University, No.126, Xiantai Street, Erdao District, Changchun, Jilin 130000, China. Electronic address:

The aim of this study is to investigate the efficacy of treatment-combined electrocauterization after removal of apocrine sweat glands with ultrasound-guided (BOTOX) injection for adolescents with axillary bromhidrosis. From January 2015 to January 2018, 90 adolescents with axillary bromhidrosis were recruited and randomly divided into three groups (group A, B, and C). Patients in group A underwent electrocauterization after removal of apocrine sweat glands, patients in group B received ultrasound-guided BOTOX injection, and patients in group C had electrocauterization after the removal of apocrine sweat glands followed by ultrasound-guided BOTOX administration after two weeks. All patients were followed up for one year. The percentages of axillary malodor score at twelve months after treatments compared with pre-operation for group A, group B, and group C were 20.2%, 27.5%, and 12.5%, respectively. Significant statistical differences were observed in changes of axillary malodor score among the three groups at three, six, nine and twelve months postoperatively. Satisfaction rates of group A, group B, and group C were 90.0%, 93.3%, and 96.7%, respectively. The side effects after surgery in group A were similar to group C, and no side effect was observed in group B. One-year postoperative scar formation rate of group A was 16.7%, which was significantly higher than that of group B (0) and group C (6.66%). Combination of electrocauterization after removal of apocrine sweat glands with ultrasound-guided BOTOX injection showed better treatment effects.
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http://dx.doi.org/10.1016/j.bjps.2021.03.089DOI Listing
April 2021

New dihydro-β-agarofuran sesquiterpenoids from Tripterygium wilfordii and their anti-inflammatory activity.

Bioorg Chem 2021 Jun 29;114:105140. Epub 2021 Jun 29.

Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, People's Republic of China. Electronic address:

Twenty seven dihydro-β-agarofuran sesquiterpenoids, including fifteen new congeners, wilforsinines I-W (1-9, 12-13, 24-27), and twelve known compounds were isolated from the dried root of Tripterygium wilfordii. The structures of the new sesquiterpenoids, wilforsinines I-W, were elucidated by extensive spectroscopic data analysis. The anti-inflammatory activity of isolates 1-27 were evaluated by examining their inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 macrophage cells. Among them, wilforsinine K (3) and angulatin M (16) exerted optimal inhibitory effects on the production of NO in LPS-induced RAW 264.7 cells. Moreover, Western blot results revealed that their anti-inflammatory activities were correlated with the suppression of the expression of nitric oxide synthase (iNOS) and down-regulation of the level of NF-κB p65 phosphorylation.
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http://dx.doi.org/10.1016/j.bioorg.2021.105140DOI Listing
June 2021

Tumor chemical suffocation therapy by dual respiratory inhibitions.

Chem Sci 2021 Apr 28;12(22):7763-7769. Epub 2021 Apr 28.

The State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences 1295 Ding-xi Road Shanghai 200050 P. R. China.

The extraordinarily rapid growth of malignant tumors depends heavily on the glucose metabolism by the pathways of glycolysis and mitochondrial oxidative phosphorylation to generate adenosine 5'-triphosphate (ATP) for maintaining cell proliferation and tumor growth. This study reports a tumor chemical suffocation therapeutic strategy by concurrently suppressing both glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) the co-deliveries of EDTA and rotenone into a glutathione (GSH)-overexpressed tumor microenvironment. EDTA is to block the glycolytic pathway through inhibiting the activity of glycolytic enzymes the chelation of magnesium ion, a co-worker of glycolytic enzymes, despite the presence of Ca. Meanwhile rotenone is to inhibit the mitochondrial OXPHOS. This work provides a novel tumor suffocation strategy by the co-deliveries of glucose metabolism inhibitors, especially by de-functioning glycolytic enzymes eliminating their co-worker magnesium.
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http://dx.doi.org/10.1039/d1sc00929jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188586PMC
April 2021

DeepRecS: From RECIST Diameters to Precise Liver Tumor Segmentation.

IEEE J Biomed Health Inform 2021 Jun 23;PP. Epub 2021 Jun 23.

Liver tumor segmentation (LiTS) is of primary importance in diagnosis and treatment of hepatocellular carcinoma. Known automated LiTS methods could not yield satisfactory results for clinical use since they were hard to model flexible tumor shapes and locations. In clinical practice, radiologists usually estimate tumor shape and size by a Response Evaluation Criteria in Solid Tumor (RECIST) mark. Inspired by this, in this paper, we explore a deep learning (DL) based interactive LiTS method, which incorporates guidance from user-provided RECIST marks. Our method takes a three-step framework to predict liver tumor boundaries. Under this architecture, we develop a RECIST mark propagation network (RMP-Net) to estimate RECIST-like marks in off-RECIST slices. We also devise a context-guided boundary-sensitive network (CGBS-Net) to distill tumors contextual and boundary information from corresponding RECIST(-like) marks, and then predict tumor maps. To further refine the segmentation results, we process the tumor maps using a 3D conditional random field (CRF) algorithm and a morphology hole-filling operation. Verified on two clinical contrast-enhanced abdomen computed tomography (CT) image datasets, our proposed approach can produce promising segmentation results, and outperforms the state-of-the-art interactive segmentation methods.
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http://dx.doi.org/10.1109/JBHI.2021.3091900DOI Listing
June 2021

Prognostic value of inflammatory and nutritional markers for hepatocellular carcinoma.

Medicine (Baltimore) 2021 Jun;100(25):e26506

Central Laboratory.

Abstract: Many clinical studies have demonstrated that the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and Onodera's prognostic nutritional index (OPNI) are visibly involved in the prognosis of a variety of tumors. In our research, we aim to determin the prognostic impact of NLR, PLR, and OPNI for hepatocellular carcinoma (HCC).Data of hepatocellular carcinoma patients undergoing treatment in Changzhi People's Hospital between 2011 and 2017 were reviewed. 270 patients with HCC were under inclusion criteria. The optimal cut-off points of OPNI, NLR and PLR were determined by using the X-tile program. The overall survival (OS) was analyzed by Kaplan-Meier method. Multivariate analysis was performed using Cox Proportional Hazard Regression model to determine independent prognostic indicators for HCC.As revealed by Univariate and multivariate analysis, OPNI, Treatment, PLR, and BCLC Stage can be used as independent prognostic indicators for HCC. Comparing the P values and hazard ratios, we found out that the OPNI has greatest influence on prognosis in these indexes. The appropriate cut-off points of NLR, PLR, and OPNI were 2.5, 133.3, and 39.5, respectively. High score OPNI group had a better OS. In the analysis between OPNI and clinicopathological characteristics, there were differences in treatment, postoperative therapy, AST, ALBI grade, NLR and PLR between the high OPNI group and the low OPNI group, while others did not.OPNI is a straightforward and effective independent prognostic indicator for HCC.
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http://dx.doi.org/10.1097/MD.0000000000026506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238303PMC
June 2021

HIF-1-induced mitochondrial ribosome protein L52: a mechanism for breast cancer cellular adaptation and metastatic initiation in response to hypoxia.

Theranostics 2021 25;11(15):7337-7359. Epub 2021 May 25.

Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

Hypoxia is a hallmark of the physical microenvironment of solid tumors. As a key factor that regulates tumor development and progression, hypoxia can reprogram the expression of multiple genes, whose biological function and molecular mechanism in cancer remain largely unclear. The mitochondrial ribosome protein family consists of nuclear-encoded mitochondrial proteins that are responsible for protein synthesis in the mitochondria. A high-throughput RNA sequencing assay was carried out to identify differentially expressed mRNAs between breast cancer tissues and adjacent normal tissues as well as breast tumors with metastasis and those without metastasis. Our clinical samples and TCGA database were analyzed to observe the clinical value of mitochondrial ribosome protein L52 (MRPL52) in human breast cancer. Potent hypoxia response elements in the promoter region of MRPL52 were identified and validated by chromatin immunoprecipitation and luciferase reporter assays. Functional experiments were performed using breast cancer cell lines with MRPL52 ectopic expression and knockdown cultured in a 20% or 1% O environment. MRPL52 expression was upregulated in human breast cancer and was significantly associated with aggressive clinicopathological characteristics and a higher metastatic risk of breast cancer patients. We found that the overexpression of MRPL52 in breast cancer is induced by hypoxia-inducible factor-1 in response to hypoxic exposure. The role of MRPL52 in suppressing apoptosis and promoting migration and invasion of hypoxic breast cancer cells was demonstrated by our experimental evidence. Mechanistically, MRPL52 promoted PTEN-induced putative kinase 1 /Parkin-dependent mitophagy to remove oxidatively damaged mitochondria and prevent uncontrolled reactive oxygen species (ROS) generation, thus repressing activation of the mitochondrial apoptotic cascade. Additionally, MRPL52 augmented epithelial-mesenchymal transition, migration and invasion of hypoxic breast cancer cells by activating the ROS-Notch1-Snail signaling pathway. Benefited from this bidirectional regulatory mechanism, MRPL52 is responsible for maintaining ROS levels in a window that can induce tumorigenic signal transduction without causing cytotoxicity in hypoxic breast cancer cells. This work elucidates the molecular mechanism by which MRPL52 mediates hypoxia-induced apoptotic resistance and metastatic initiation of breast cancer, and provides new insights into the interplay between cancer and the tumor microenvironment.
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http://dx.doi.org/10.7150/thno.57804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210597PMC
May 2021

SAA1/TLR2 axis directs chemotactic migration of hepatic stellate cells responding to injury.

iScience 2021 May 29;24(5):102483. Epub 2021 Apr 29.

Institute of Public Health, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Science Park, Guangzhou, Guangdong 510530, China.

Hepatic stellate cells (HSCs) are crucial for liver injury repair and cirrhosis. However, the mechanism of chemotactic recruitment of HSCs into injury loci is still largely unknown. Here, we demonstrate that serum amyloid A1 (SAA1) acts as a chemokine recruiting HSCs toward injury loci signaling via TLR2, a finding proven by gene manipulation studies in cell and mice models. The mechanistic investigations revealed that SAA1/TLR2 axis stimulates the Rac GTPases through PI3K-dependent pathways and induces phosphorylation of MLC (pSer19). Genetic deletion of TLR2 and pharmacological inhibition of PI3K diminished the phosphorylation of MLCpSer19 and migration of HSCs. In brief, SAA1 serves as a hepatic endogenous chemokine for the TLR2 receptor on HSCs, thereby initiating PI3K-dependent signaling and its effector, Rac GTPases, which consequently regulates actin filament remodeling and cell directional migration. Our findings provide novel targets for anti-fibrosis drug development.
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http://dx.doi.org/10.1016/j.isci.2021.102483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169952PMC
May 2021

Extended-release of therapeutic microRNA via a host-guest supramolecular hydrogel to locally alleviate renal interstitial fibrosis.

Biomaterials 2021 May 27;275:120902. Epub 2021 May 27.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China. Electronic address:

Activated fibroblasts are critical contributors to renal interstitial fibrosis thus becoming the cellular target for fibrosis treatment. Previously, microRNA 29 b (miR-29 b) is shown to be down-regulated in various animal models of renal fibrosis. Herein, we describe a facile strategy to achieve localized and sustained delivery of therapeutic microRNA to the kidney via a host-guest supramolecular hydrogel. Specifically, cationic bovine serum albumin is used to complex with miR-29 b to afford nanocomplexes (cBSA/miR-29 b), which is proven to specifically inhibit fibroblast activation in a dose-dependent manner in vitro. Following unilateral ureteral obstruction in mice, a single injection of the hydrogel loaded with cBSA/miR-29 b in vivo, significantly down-regulated proteins and genes related to fibrosis for up to 21 days without affecting the normal liver or kidney functions. Overall, the localized delivery of cBSA/miR-29 b via a host-guest supramolecular hydrogel represents a safe and effective intervention strategy to delay and reverse the progression of interstitial renal fibrosis.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120902DOI Listing
May 2021

An Immune Model to Predict Prognosis of Breast Cancer Patients Receiving Neoadjuvant Chemotherapy Based on Support Vector Machine.

Front Oncol 2021 27;11:651809. Epub 2021 Apr 27.

Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.

Tumor microenvironment has been increasingly proved to be crucial during the development of breast cancer. The theory about the conversion of cold and hot tumor attracted the attention to the influences of traditional therapeutic strategies on immune system. Various genetic models have been constructed, although the relation between immune system and local microenvironment still remains unclear. In this study, we tested and collected the immune index of 262 breast cancer patients before and after neoadjuvant chemotherapy. Five indexes were selected and analyzed to form the prediction model, including the ratio values between after and before neoadjuvant chemotherapy of CD4/CD8 T cell ratio; lymphosum of T, B, and natural killer (NK) cells; CD3CD8 cytotoxic T cell percent; CD16CD56 NK cell absolute value; and CD3CD4 helper T cell percent. Interestingly, these characters are both the ratio value of immune status after neoadjuvant chemotherapy to the baseline. Then the prediction model was constructed by support vector machine (accuracy rate = 75.71%, area under curve = 0.793). Beyond the prognostic effect and prediction significance, the study instead emphasized the importance of immune status in traditional systemic therapies. The result provided new evidence that the dynamic change of immune status during neoadjuvant chemotherapy should be paid more attention.
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http://dx.doi.org/10.3389/fonc.2021.651809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111218PMC
April 2021

PA-ResSeg: A phase attention residual network for liver tumor segmentation from multiphase CT images.

Med Phys 2021 Jul 30;48(7):3752-3766. Epub 2021 May 30.

College of Computer Science and Technology, Zhejiang University, Hangzhou, Zhejiang, China.

Purpose: Liver tumor segmentation is a crucial prerequisite for computer-aided diagnosis of liver tumors. In the clinical diagnosis of liver tumors, radiologists usually examine multiphase CT images as these images provide abundant and complementary information of tumors. However, most known automatic segmentation methods extract tumor features from CT images merely of a single phase, in which valuable multiphase information is ignored. Therefore, it is highly demanded to develop a method effectively incorporating multiphase information for automatic and accurate liver tumor segmentation.

Methods: In this paper, we propose a phase attention residual network (PA-ResSeg) to model multiphase features for accurate liver tumor segmentation. A phase attention (PA) is newly proposed to additionally exploit the images of arterial (ART) phase to facilitate the segmentation of portal venous (PV) phase. The PA block consists of an intraphase attention (intra-PA) module and an interphase attention (inter-PA) module to capture channel-wise self-dependencies and cross-phase interdependencies, respectively. Thus, it enables the network to learn more representative multiphase features by refining the PV features according to the channel dependencies and recalibrating the ART features based on the learned interdependencies between phases. We propose a PA-based multiscale fusion (MSF) architecture to embed the PA blocks in the network at multiple levels along the encoding path to fuse multiscale features from multiphase images. Moreover, a 3D boundary-enhanced loss (BE-loss) is proposed for training to make the network more sensitive to boundaries.

Results: To evaluate the performance of our proposed PA-ResSeg, we conducted experiments on a multiphase CT dataset of focal liver lesions (MPCT-FLLs). Experimental results show the effectiveness of the proposed method by achieving a dice per case (DPC) of 0.7787, a dice global (DG) of 0.8682, a volumetric overlap error (VOE) of 0.3328, and a relative volume difference (RVD) of 0.0443 on the MPCT-FLLs. Furthermore, to validate the effectiveness and robustness of PA-ResSeg, we conducted extra experiments on another multiphase liver tumor dataset and obtained a DPC of 0.8290, a DG of 0.9132, a VOE of 0.2637, and a RVD of 0.0163. The proposed method shows its robustness and generalization capability in different datasets and different backbones.

Conclusions: The study demonstrates that our method can effectively model information from multiphase CT images to segment liver tumors and outperforms other state-of-the-art methods. The PA-based MSF method can learn more representative multiphase features at multiple scales and thereby improve the segmentation performance. Besides, the proposed 3D BE-loss is conducive to tumor boundary segmentation by enforcing the network focus on boundary regions and marginal slices. Experimental results evaluated by quantitative metrics demonstrate the superiority of our PA-ResSeg over the best-known methods.
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http://dx.doi.org/10.1002/mp.14922DOI Listing
July 2021

Electrical and visible light dual-responsive ZnO nanocomposite with multiple wound healing capability.

Mater Sci Eng C Mater Biol Appl 2021 May 26;124:112066. Epub 2021 Mar 26.

College of Chemistry, Nanchang University, Nanchang, Jiangxi 330088, PR China; The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330088, PR China. Electronic address:

The healing process of open wounds is a competition between cells and bacteria. Therefore, a strategy that can quickly remove bacteria and promote cell proliferation to accelerate wound healing is urgently needed. Inspired by photoelectric synergy tactics, we improved both the optical and electrical response of zinc oxide (ZnO) through the modification of polydopamine (PDA) and reduced graphene oxide (rGO), thus obtaining a ZnO composite named PDA-rGO-ZnO (PrZ). Combined with the photoelectric double stimulation, the sterilization target could be completed from multiple physical levels simultaneously. More importantly, the band gap of ZnO was considerably narrowed by PDA encapsulation. The encapsulated ZnO thus could be effectively excited by pure yellow light (YL) with a moderate long wavelength, which fundamentally improved its safety in exerting photocatalytic antibacterial properties. In addition, we found that electrical stimulation (ES) could not only help to clear bacteria, but also facilitate the formation of new blood vessels. Animal experiments further showed that PrZ efficaciously regulated the immune response around the wound surface, promoted cell proliferation and the formation of collagen fibers, thereby accelerating wound healing.
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http://dx.doi.org/10.1016/j.msec.2021.112066DOI Listing
May 2021

Phase I study of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive advanced solid tumors.

Gastric Cancer 2021 Jul 4;24(4):913-925. Epub 2021 May 4.

Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Hai-Dian District, Fu-Cheng Road 52, Beijing, 100142, China.

Purpose: RC48 contains the novel humanized anti-HER2 antibody hertuzumab conjugated to MMAE via a cleavable linker. A phase I study was initiated to evaluate the toxicity, MTD, PK, and antitumor activity of RC48 in patients with HER2-overexpressing locally advanced or metastatic solid carcinomas, particularly gastric cancer.

Patients And Methods: This was a 2-part phase I study. Successive cohorts of patients received escalating doses of RC48 (0.1 mg/kg, 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 2.5 mg/kg, and 3.0 mg/kg). Dose expansion proceeded at the dose of 2.0 mg/kg Q2W. The efficacy and safety set included all patients who received at least one dose of RC48.

Results: Fifty-seven patients were enrolled, the MTD was unavailable due to termination of 3.0 mg/kg cohort; 2.5 mg/kg Q2W was declared the RP2D. RC48 was well tolerated, the most frequent grade 3 or worse TRAEs included neutropenia (19.3%), leukopenia (17.5%), hypoesthesia (14.0%), and increased conjugated blood bilirubin (8.8%). Four deaths occurred during the whole study, three of which were believed to be related to RC48. Overall, ORR and DCR were 21.0% (12/57) and 49.1% (28/57). Notably, patients who were HER2 IHC2+/FISH- responded similarly to those who were IHC2+/FISH+ and IHC3+, with ORRs of 35.7% (5/14), 20% (2/10), and 13.6% (3/22), respectively. In patients who were pretreated with HER2-targeted drugs, RC48 also showed promising efficacy, with ORR of 15.0% (3/20) and DCR of 45.0% (9/20).

Conclusion: RC48 was well tolerated and showed promising antitumor activity in HER2-positive solid tumors, including gastric cancer with HER2 IHC 2+/FISH- status.

Clinical Trial Information: NCT02881190.
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http://dx.doi.org/10.1007/s10120-021-01168-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205919PMC
July 2021

Loss of polarity protein Par3, via transcription factor Snail, promotes bladder cancer metastasis.

Cancer Sci 2021 Jul 1;112(7):2625-2641. Epub 2021 May 1.

NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Bladder cancer (BLCA) remains the leading cause of cancer-related mortality among genitourinary malignancies worldwide. BLCA metastasis represents the primary reason for its poor prognosis. In this study, we report that decreased expression of partitioning defective 3 (Par3), a polarity protein (encoded by PARD3), is associated with tumor aggressive phenotypes and poor prognosis in BLCA patients. Consistently, ablation of Par3 promotes the metastasis and invasion of BLCA cells in vitro and in vivo. Further studies reveal that zinc finger protein Snail represses the expression of Par3 by binding to E2-box (CAGGTG) of PARD3 promoter-proximal. Inhibition of GSK-3β promotes the expression and nuclear localization of Snail and then reduces the expression of Par3, resulting in the metastasis and invasion of BLCA cells. Moreover, we detected the interaction between Par3 (936-1356 aa) and ZO-1 (1372-1748 aa), which is involved in the maintenance of tight junction. Together, our results demonstrate that the GSK-3β/Snail/Par3/ZO-1 axis regulates BLCA metastasis, and Snail is a major regulator for Par3 protein expression in BLCA.
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http://dx.doi.org/10.1111/cas.14920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253273PMC
July 2021

Mild Magnetic Hyperthermia-Activated Innate Immunity for Liver Cancer Therapy.

J Am Chem Soc 2021 Jun 30;143(21):8116-8128. Epub 2021 Apr 30.

State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China.

Magnetic hyperthermia therapy (MHT) is noninvasive and features excellent tissue penetration for deep-seated tumors, but unfortunately, it suffers the low therapeutic efficacy due to the limited magneto-thermal efficiency and insufficient intratumor accumulation of conventional intravenous-injected magnetic nanoparticles, which are actually mostly sequestered by the mononuclear phagocyte system, especially the liver. Such a disadvantageous characteristic of preferential liver uptake is here exploited, for the first time as far as we know, to treat orthotopic liver cancer by mild MHT using specially designed composite magnetic nanoparticles. A kind of core-shell-structured and Zn-doped [email protected] superparamagnetic nanoparticles (ZCMF) has been synthesized which exhibits excellent and highly controllable magnetic hyperthermia performance owing to an exchange-coupled magnetism between the core and shell, and Zn doping. The controllable mild MHT at 43-44 °C based on ZCMF demonstrates almost complete inhibition of liver cancer cell proliferation and tumor growth, which is associated with the suppression of heat shock protein 70 (HSP70) expression. More importantly, the mild MHT-treated liver cancer cells are capable of activating natural killer (NK) cells by dramatically upregulating the expression of UL16-binding proteins (ULBPs), ligands of natural killer group 2 member D (NKG2D). As a result, the growth of both xenograft tumors and orthotopic liver tumors were almost completely suppressed under mild MHT via induced NK-cell-related antitumor immunity . This work not only evidences the great potential of mild MHT but also reveals the underlying immunity activation mechanism in liver cancer treatment by mild MHT.
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http://dx.doi.org/10.1021/jacs.1c02537DOI Listing
June 2021

The transcriptional coactivator AF9 simultaneously sustains hypoxia tolerance and metabolic advantages in liver cancer.

Hepatology 2021 Apr 30. Epub 2021 Apr 30.

Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, 510006, China.

Proteins that recognize the epigenetic modifications function as mediators to interpret the epigenetic codes. Hypoxia response and metabolic rewiring are two major events during cancer progression. However, it's still unclear whether and how epigenetic regulator integrates hypoxia response and metabolism together. We data mined the clinical association of 33 histone Kac reader proteins with liver cancer and that AF9 is upregulated in cancer and correlates with tumor stage and poor prognosis. Conditional deletion of Af9 in mouse liver resulted in decreased tumor formation induced by c-Met/β-catenin. Loss of AF9 heavily impaired cell proliferation and completely blocked solid tumor formation. We further discovered AF9 formed a positive feedback circuit with HIF1α and also stabilized cMyc. Mechanically, AF9 interacted with HIF1α and targeted HIF1A promoter while AF9 recognized cMyc acetylation at K148, protected cMyc phosphorylation at S62 and then stabilized the cMyc which in turn upregulates PFKP expression. Otherwise, knockout of Af9 in mouse hepatocyte increased the infiltration of CD8+ T cells which is linked to the downregulation of LDHA. In conclusions, AF9 is upregulated to promote gene expression of hypoxia tolerance and glycolysis by simultaneously forming a complex with HIF1α and recognizing acetylated cMyc. Our results establish the oncogenic role of AF9 in human liver cancer, which could be a potential target for designing novel drugs against liver cancer.
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http://dx.doi.org/10.1002/hep.31870DOI Listing
April 2021

Modeling the Population Health Impact of ENDS in the U.S.

Am J Health Behav 2021 05;45(3):588-610

Research Economist, Juul Labs Inc, Washington, DC, United States.

Our objective was to improve understanding of the population health impact of electronic nicotine delivery systems (ENDS) availability in the US via computational modeling. We present an agent-based population health model (PHM) that simulates annual smoking, ENDS use, and associated mortality for individual agents representing the US population, both adults and youth, between 2000 and 2100. Model transitions were derived from key population surveys and a large longitudinal study of JUUL purchasers. The mortality impact of ENDS is modeled as excess risk relative to smoking. Outcomes are compared between a cigarettes-only Base Case and a Modified Case where ENDS are introduced in 2010. Model validation demonstrates that the PHM simulates population-level behavior and outcomes realistically. The availability of ENDS in the US is projected to reduce smoking and prevent 2.5 million premature deaths by 2100 in the Modified Case. Sensitivity analyses show that a significant population health benefit occurs under all plausible scenarios. Our results suggest the availability of ENDS is likely to result in a significant health benefit to the US population as a whole, after accounting for both beneficial and harmful uses.
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http://dx.doi.org/10.5993/AJHB.45.3.12DOI Listing
May 2021

Transitions in Smoking among Adults Newly Purchasing the JUUL System.

Am J Health Behav 2021 05;45(3):546-562

Senior Scientific Advisor, PinneyAssociates Inc, Pittsburgh, PA, United States.

In this study, we prospectively assessed changes in smoking a year after US adults' first-time purchase of a JUUL Starter Kit (JSK). Descriptive analyses assessed transitions in smoking status at 12 months among adult (age ≥21) JSK purchasers providing baseline and 12-month follow-up data (N = 27,164 [49.0% of baseline]), stratified by baseline smoking status. Baseline regular use of other ENDS was also considered. Purchasers included baseline past 30-day smokers (65.2%), former smokers (12.0%), and never smokers (9.7%); over 90% were ever-smokers. One year later, the majority (58%) of those smoking at baseline reported no longer smoking. Former smokers or never smokers who were smoking at 12 months represented less than 2% of respondents. Former and current smokers who were regularly using other ENDS at baseline were less likely to report smoking at 12 months. Past 30-day smoking prevalence in a large longitudinal study of first-time JSK purchasers fell by more than half over 12 months. Analyzing the sample composition at purchase and transitions within subgroups defined by smoking status allows for a detailed understanding to help inform assessments of the population health impact of ENDS.
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http://dx.doi.org/10.5993/AJHB.45.3.9DOI Listing
May 2021

The Triglyceride-Glucose Index is Associated with Diabetic Retinopathy in Chinese Patients with Type 2 Diabetes: A Hospital-Based, Nested, Case-Control Study.

Diabetes Metab Syndr Obes 2021 9;14:1547-1555. Epub 2021 Apr 9.

Department of Ophthalmology, First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China.

Background: This study aimed to investigate the association between the triglyceride-glucose (TyG) index and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes.

Methods: In this nested case-control study, all diabetic participants were registered hospitalizations during 2012-2018, including 596 with DR as cases and three matching controls per case. DR was assessed using Early Treatment Diabetic Retinopathy Study criteria. The TyG index was calculated: Ln (fasting blood glucose [mg/dL] × fasting triglycerides [mg/dL] ÷ 2). Multivariate logistic regression, a receiver-operating characteristic (ROC) curve, linear regression models, and mediation analysis were used to explore associations.

Results: The TyG index was lower in DR and decreased as its severity advanced among 2,112 subjects (=0.005). After confounders (sex, duration of diabetes, use of antidiabetic agents, heart rate, systolic blood pressure, pulse pressure, height, weight, body-mass index, and glycated hemoglobin) had been accounted for, there were significant associations between the TyG index and any-severity DR (OR 0.83, 95% CI 0.73-0.95; =0.006), as well as vision-threatening DR (VTDR; OR 0.53, 95% CI 0.36-0.76; =0.001). ROC analysis indicated that the TyG index showed significant discriminatory ability in any-severity DR (area under curve [AUC] 0.534, =0.015) and VTDR (AUC 0.624, =0.001).

Conclusion: The TyG index was associated with the presence and severity of DR. Our findings suggest that the TyG index may become a useful biomarker in evaluating and following the presence of DR and VTDR.
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http://dx.doi.org/10.2147/DMSO.S294408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043781PMC
April 2021

A novel chondroitin sulfate E from Dosidicus gigas cartilage and its antitumor metastatic activity.

Carbohydr Polym 2021 Jun 20;262:117971. Epub 2021 Mar 20.

National Glycoengineering Research Center and Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, 72 Binhai Rd, Qingdao, 266237, People's Republic of China. Electronic address:

Chondroitin sulfate (CS) chains containing GlcUAβ1-3GalNAc(4S,6S) (E unit) have been shown to be involved in various physiological and pathological processes. However, commercial E unit-rich CS (CS-E) is difficult to produce on a large scale due to expensive and limited squid cartilage resources. In this study, a novel CS-E (CS-nE) was isolated from the cheap and abundant cartilage of the giant squid Dosidicus gigas. The CS-nE has a surprisingly large molecular mass of 696 kDa and a relatively high E unit proportion (44.5 %). It can interact with various growth factors, including HGF, bFGF, pleiotrophin, and HB-EGF, with high affinity, and exhibits dose-dependent anti-metastatic activity. Furthermore, the E unit-rich decasaccharide selectively prepared from CS-nE has been shown to be the minimal functional domain with the strongest antitumor metastatic activity. Taken together, CS-nE will be a very promising candidate for the development of CS-E-based pharmaceutical products.
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http://dx.doi.org/10.1016/j.carbpol.2021.117971DOI Listing
June 2021

Assessment of CPS + EG, Neo-Bioscore and Modified Neo-Bioscore in Breast Cancer Patients Treated With Preoperative Systemic Therapy: A Multicenter Cohort Study.

Front Oncol 2021 16;11:606477. Epub 2021 Mar 16.

Institute of Mental Health, Peking University, Beijing, China.

This study was to assess the prognosis stratification of the clinical-pathologic staging system incorporating estrogen receptor (ER)-negative disease, the nuclear grade 3 tumor pathology (CPS + EG), Neo-Bioscore, and a modified Neo-Bioscore system in breast cancer patients after preoperative systemic therapy (PST). A retrospective multicenter cohort study was conducted from 12 participating hospitals' databases from 2006 to 2015. Five-year disease free survival (DFS), disease specific survival (DSS), and overall survival (OS) were calculated using Kaplan-Meier Method. Area under the curve (AUC) of the three staging systems was compared. Wald test and maximum likelihood estimates in Cox proportional hazards model were used for multivariate analysis. A total of 1,077 patients were enrolled. The CPS + EG, Neo-Bioscore, and modified Neo-Bioscore could all stratify the DFS, DSS, and OS (all P < 0.001). While in the same stratum of Neo-Bioscore scores 2 and 3, the HER2-positive patients without trastuzumab therapy had much poorer DSS (P = 0.013 and P values < 0.01, respectively) as compared to HER2-positive patients with trastuzumab therapy and HER2-negative patients. Only the modified Neo-Bioscore had a significantly higher stratification of 5-year DSS than PS (AUC 0.79 . 0.65, P = 0.03). So, the modified Neo-Bioscore could circumvent the limitation of CPS + EG or Neo-Bioscore.

Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03437837.
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http://dx.doi.org/10.3389/fonc.2021.606477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009183PMC
March 2021

Maternal Urinary Organophosphate Esters and Alterations in Maternal and Neonatal Thyroid Hormones.

Am J Epidemiol 2021 Mar 29. Epub 2021 Mar 29.

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Production of organophosphate esters (OPEs), which represent a major flame retardant class present in consumer goods, has risen over the past two decades. Experimental studies suggest that OPEs may be associated with thyroid hormone disruption, but few human studies have examined this association. We quantified OPE metabolites in the urine of 298 pregnant women in the Health Outcomes and Measures of the Environment Study from Cincinnati, Ohio (enrolled 2003-2006) at three time points (16 and 26 weeks' gestation, delivery), and thyroid hormones in 16-week maternal and newborn cord sera. Urinary bis(1,3-dichloro-2-propyl)-phosphate concentrations were generally associated with decreased triiodothyronine and thyroxine and increased thyroid stimulating hormone in maternal and newborn thyroid hormones in quartile dose-response analyses and multiple informant models. There was weaker evidence for thyroid hormone alterations in association with diphenyl-phosphate and di-n-butyl-phosphate. Bis-2-chloroethyl-phosphate was not associated with alterations in thyroid hormones in any analyses. We did not observe any evidence of effect modification by infant sex. These results suggest that gestational exposure to some OPEs may influence maternal and neonatal thyroid function, although replication in other cohorts is needed.
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http://dx.doi.org/10.1093/aje/kwab086DOI Listing
March 2021

An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis.

Acta Pharm Sin B 2021 Mar 18;11(3):835-847. Epub 2020 Oct 18.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

Localized delivery, comparing to systemic drug administration, offers a unique alternative to enhance efficacy, lower dosage, and minimize systemic tissue toxicity by releasing therapeutics locally and specifically to the site of interests. Herein, a localized drug delivery platform ("plum‒pudding" structure) with controlled release and long-acting features is developed through an injectable hydrogel ("pudding") crosslinked self-assembled triblock polymeric micelles ("plum") to help reduce renal interstitial fibrosis. This strategy achieves controlled and prolonged release of model therapeutics in the kidney for up to three weeks in mice. Following a single injection, local treatments containing either anti-inflammatory small molecule celastrol or anti-TGF antibody effectively minimize inflammation while alleviating fibrosis inhibiting NF-B signaling pathway or neutralizing TGF-1 locally. Importantly, the micelle-hydrogel hybrid based localized therapy shows enhanced efficacy without local or systemic toxicity, which may represent a clinically relevant delivery platform in the management of renal interstitial fibrosis.
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http://dx.doi.org/10.1016/j.apsb.2020.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982499PMC
March 2021

Generation of WAe001-A-58 human embryonic stem cell line with inducible expression of the SARS-CoV-2 nucleocapsid protein.

Stem Cell Res 2021 05 26;53:102197. Epub 2021 Jan 26.

Institute of Public Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. Electronic address:

Excessive prostaglandin E (PGE) is the key pathological basis for COVID-19 and a Celebrex treatment of hospitalized COVID-19 patients with comorbidities led to 100% discharged rate and zero death (Hong et al. 2020). It is also suggested that SARS-CoV-2 infected multiple organs and the SARS-CoV nucleocapsid (N) protein transcriptionally drives the expression of the host COX-2 gene. In order to test whether SARS-CoV-2 N protein activates COX-2 transcription in multiple human relevant cell types, an expression inducible human embryonic stem cell line was generated by piggyBac transposon system. This cell line maintained its pluripotency, differentiation potentials, normal morphology and karyotype.
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http://dx.doi.org/10.1016/j.scr.2021.102197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835078PMC
May 2021

Calcitriol promotes the maturation of hepatocyte-like cells derived from human pluripotent stem cells.

J Steroid Biochem Mol Biol 2021 Jul 22;211:105881. Epub 2021 Mar 22.

Institute of Public Health, Guangzhou Institutes of Biomedicine and Health, Chinese, Academy of Sciences, 510530, Guangzhou, China; Key Laboratory of Regenerative Biology, South China Institute for Stem Cell, Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 510530, Guangzhou, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 510530, Guangzhou, China. Electronic address:

Human hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) represent a promising cell source for the assessment of hepatotoxicity and pharmaceutical safety testing. However, the hepatic functionality of HLCs remains significantly inferior to primary human hepatocytes. The bioactive vitamin D (VD), calcitriol, promotes the differentiation of many types of cells, and its deficiency is correlated to the severity of liver diseases. Whether calcitriol contributes to the differentiation of HLCs needs to be explored. Here, we found that the supplementation of calcitriol improved the functionalities of hPSCs-derived HLCs in P450 activities, urea production, and albumin secretion. Moreover, calcitriol also enhanced mitochondrial respiratory function with increased protein expression levels of the subunit of respiratory enzyme complexes in HLCs. Further analyses showed that the mitochondrial biogenesis regulators and mitophagy were increased by calcitriol, thus improving the mitochondrial quality. These improvements in functionality and mitochondrial condition were dependent on vitamin D receptor (VDR) because the improvements were abolished under VDR-deficient conditions. Our finding provides a cost-effective chemical process for HLC maturation to meet the demand for basic research and potential clinic applications.
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http://dx.doi.org/10.1016/j.jsbmb.2021.105881DOI Listing
July 2021

Association of Symptoms of Attention Deficit and Hyperactivity with Problematic Internet Use among University Students in Wuhan, China During the COVID-19 Pandemic.

J Affect Disord 2021 05 5;286:220-227. Epub 2021 Mar 5.

National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, China. Electronic address:

Background: COVID-19 is still spreading worldwide and posing a threat to individuals' physical and mental health including problematic internet use (PIU). A potentially high-risk group for PIU are those with symptoms of attention deficit and hyperactivity (ADHD symptoms), because of restrictions in their physical activity levels and engagement in computer diversions requiring only short attention spans.

Methods: We used convenience sampling in a cross-sectional survey of university students from 30 universities in Wuhan, Hubei Province, China. We assessed PIU using the Internet Addiction Test and ADHD symptoms using the WHO Adult ADHD Self-Report Screening Scale. Using logistic regression and linear regression analyses we adjusted for demographic, epidemic-related and psychological covariates in models of the association between ADHD symptoms and PIU.

Results: Among 11,254 participants, we found a 28.4% (95% CI, 27.5%-29.2%) prevalence of PIU, relatively higher than before the pandemic. In our final logistic regression model, participants with ADHD symptoms had approximately two times the risk for PIU (OR: 2.31, 95% CI: 1.89-2.83). Similarly, individuals with depression, anxiety, insomnia, PTSD symptoms and feeling stress during the pandemic had a higher risk of PIU, while those exercising regularly during the pandemic had a lower risk.

Limitations: The cross-sectional design and reliance on internet based self-reports for ADHD symptoms and PIU assessments, without direct structured interviews for validation, are limitations.

Conclusions: The prevalence of PIU was high during COVID-19, and those people with ADHD symptoms and other mental illness symptoms appear to be at higher risk of PIU. Regular exercise may reduce that PIU risk and hence should be recommended during the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.jad.2021.02.078DOI Listing
May 2021

Comparison of three lymph node staging methods for predicting outcome in breast cancer patients with mastectomy.

Ann Transl Med 2021 Feb;9(4):300

Department of Breast Surgery, the First Affiliated Hospital of China Medical University, Shenyang, China.

Background: Axillary lymph node (ALN) staging is essential in predicting the clinical outcome of breast cancer (BC) patients. Traditionally, it follows the tumor-node-metastasis (TNM) staging, but its accuracy needs further improvement.

Methods: A total of 9,616 BC patients from the Surveillance, Epidemiology, and End Results (SEER) database and 675 patients from the First Affiliated Hospital of China Medical University underwent mastectomy together with ALN dissection were reviewed. Univariate and multivariate logistic analyses were conducted to find the most meaningful factors relevant to prognosis.

Results: After univariate and multivariate analyses, age, race, primary site, radiation, chemotherapy, grade, T-stage, estrogen receptor (ER), progesterone receptor (PR), total number of positive lymph nodes (pN), positive lymph node ratio (LNR) and log odds of positive LNs (LODDS) were found to be significantly associated with overall survival (OS). Using these non-LN risk factors, we further compared the efficacy of three different ALN staging methods in prognosis via nomograms. Harrell's concordance index (C-index) and Akaike Information Criterion (AIC) were used to measure nomogram performance of the ALN staging methods: pN: C-index=0.687 (95% CI: 0.678-0.696), AIC =61,398.24; LNR: C-index =0.691 (95% CI: 0.683-0.701), AIC =61,313.56; and LODDS: C-index =0.691 (95% CI: 0.682-0.700), AIC =61,315.60. We found that the nomogram incorporating LODDS had better predictive ability compared with other two methods. Furthermore, an external validation revealed a C-index of 0.753 (95% CI: 0.690-0.816) for the Asian population, which indicates the nomogram based on LODDS may have universality for both Western and Asian populations.

Conclusions: Compared with pN and LNR, LODDS showed higher homeostasis in LN evaluation, and showed marked efficacy in evaluating survival differences among patients with negative LN staging. We constructed a BC prognosis model by incorporating highly relevant clinical pathological factors and a new method of LN staging, which may greatly aid in guiding postoperative treatment.
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http://dx.doi.org/10.21037/atm-20-4856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944312PMC
February 2021
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