Publications by authors named "Shen Zhao"

112 Publications

Interaction of Luminescent Defects in Carbon Nanotubes with Covalently Attached Stable Organic Radicals.

ACS Nano 2021 Feb 18. Epub 2021 Feb 18.

Institute for Physical Chemistry, Universität Heidelberg, 69120 Heidelberg, Germany.

The functionalization of single-walled carbon nanotubes (SWCNTs) with luminescent sp defects has greatly improved their performance in applications such as quantum light sources and bioimaging. Here, we report the covalent functionalization of purified semiconducting SWCNTs with stable organic radicals (perchlorotriphenylmethyl, PTM) carrying a net spin. This model system allows us to use the near-infrared photoluminescence arising from the defect-localized exciton as a highly sensitive probe for the short-range interaction between the PTM radical and the SWCNT. Our results point toward an increased triplet exciton population due to radical-enhanced intersystem crossing, which could provide access to the elusive triplet manifold in SWCNTs. Furthermore, this simple synthetic route to spin-labeled defects could enable magnetic resonance studies complementary to fluorescence imaging with functionalized SWCNTs and facilitate the scalable fabrication of spintronic devices with magnetically switchable charge transport.
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http://dx.doi.org/10.1021/acsnano.0c10341DOI Listing
February 2021

Exploring the Dynamic Spatio-Temporal Correlations between PM Emissions from Different Sources and Urban Expansion in Beijing-Tianjin-Hebei Region.

Authors:
Shen Zhao Yong Xu

Int J Environ Res Public Health 2021 Jan 12;18(2). Epub 2021 Jan 12.

Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing 100101, China.

Due to rapid urbanization globally more people live in urban areas and, simultaneously, more people are exposed to the threat of environmental pollution. Taking PM emission data as the intermediate link to explore the correlation between corresponding sectors behind various PM emission sources and urban expansion in the process of urbanization, and formulating effective policies, have become major issues. In this paper, based on long temporal coverage and high-quality nighttime light data seen from the top of the atmosphere and recently compiled PM emissions data from different sources (transportation, residential and commercial, industry, energy production, deforestation and wildfire, and agriculture), we built an advanced Bayesian spatio-temporal autoregressive model and a local regression model to quantitatively analyze the correlation between PM emissions from different sources and urban expansion in the Beijing-Tianjin-Hebei region. Our results suggest that the overall urban expansion in the study area maintained gradual growth from 1995 to 2014, with the fastest growth rate during 2005 to 2010; the urban expansion maintained a significant positive correlation with PM emissions from transportation, energy production, and industry; different anti-haze policies should be designated according to respective local conditions in Beijing, Tianjin, and Hebei provinces; and during the period of rapid urban expansion (2005-2010), the spatial correlations between PM emissions from different sources and urban expansion also changed, with the biggest change coming from the PM emissions from the transport sector.
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http://dx.doi.org/10.3390/ijerph18020608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828208PMC
January 2021

Review of Deep Learning Approaches for the Segmentation of Multiple Sclerosis Lesions on Brain MRI.

Front Neuroinform 2020 20;14:610967. Epub 2020 Nov 20.

School of Intelligent Systems Engineering, Sun Yat-Sen University, Guangzhou, China.

In recent years, there have been multiple works of literature reviewing methods for automatically segmenting multiple sclerosis (MS) lesions. However, there is no literature systematically and individually review deep learning-based MS lesion segmentation methods. Although the previous review also included methods based on deep learning, there are some methods based on deep learning that they did not review. In addition, their review of deep learning methods did not go deep into the specific categories of Convolutional Neural Network (CNN). They only reviewed these methods in a generalized form, such as supervision strategy, input data handling strategy, etc. This paper presents a systematic review of the literature in automated multiple sclerosis lesion segmentation based on deep learning. Algorithms based on deep learning reviewed are classified into two categories through their CNN style, and their strengths and weaknesses will also be given through our investigation and analysis. We give a quantitative comparison of the methods reviewed through two metrics: Dice Similarity Coefficient (DSC) and Positive Predictive Value (PPV). Finally, the future direction of the application of deep learning in MS lesion segmentation will be discussed.
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http://dx.doi.org/10.3389/fninf.2020.610967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714963PMC
November 2020

Corrigendum: Miscarriage Rate Is High With Frozen-Thawed Blastocysts Arising From Poor-Quality Cleavage Stage Embryos.

Front Endocrinol (Lausanne) 2020 26;11:613921. Epub 2020 Nov 26.

Reproductive Medical Center of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

[This corrects the article DOI: 10.3389/fendo.2020.561085.].
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http://dx.doi.org/10.3389/fendo.2020.613921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727598PMC
November 2020

Efficacy and Tolerability of Erlotinib 100 mg/d vs. Gefitinib 250 mg/d in EGFR-Mutated Advanced Non-small Cell Lung Cancer (E100VG250): An Open-Label, Randomized, Phase 2 Study.

Front Oncol 2020 10;10:587849. Epub 2020 Nov 10.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

Erlotinib-based combination therapy leads to increased efficacy but also toxicity for EGFR-mutated NSCLC. Reducing the dose of erlotinib could improve treatment tolerability, but few evidences are available regarding its efficacy at reduced dose. This randomized phase-2 study intends to compare the efficacy and tolerability between lower dose erlotinib (100 mg/d) and standard dose gefitinib (250 mg/d) in EGFR-mutated NSCLC. Patients with EGFR-mutated advanced NSCLC were randomized at 1:1 ratio to receive erlotinib 100 mg/d or gefitinib 250 mg/d until disease progression or unacceptable toxicity. The primary endpoint was disease control rate (DCR). Between April 2013 and September 2018, 171 patients were randomized to receive erlotinib ( = 85) and gefitinib ( = 86); 74 in the erlotinib group and 83 in the gefitinib group were include in analysis. DCR with erlotinib and gefitinib were 91% [95% CI 81.7-95.3] and 93% [85.1-96.6], respectively ( = 0.613). Response rate was 62% [50.8-72.4] in the erlotinib group and 53% [42.4-63.4] in the gefitinib group ( = 0.247). No significant difference was observed between erlotinib and gefitinib in median progression-free survival [10.1 vs. 11.3 months, HR = 1.295 [0.893-1.879], = 0.171] and median overall survival [26.6 vs. 28.7 months, HR = 0.999 [0.637-1.569], = 0.998]. Subgroup analyses by line of treatment, EGFR subtypes and status of central nervous system (CNS) metastasis found similar results. More toxicity [any-grade, 80 [96%] vs. 66 [89]; grade 3-4, 11 [13%] vs. 4 [5%]] and toxicity-related discontinuation [10 [12%] vs. 3 [4%]] occurred with gefitinib compared with erlotinib. But no significant difference was observed. Lower dose erlotinib (100 mg/d) achieved comparable efficacy compared with standard dose gefitinib (250 mg/d) in EGFR-mutated NSCLC. https://clinicaltrials.gov, identifier: NCT01955421.
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http://dx.doi.org/10.3389/fonc.2020.587849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683781PMC
November 2020

Semi-Supervised Learning in Medical Images Through Graph-Embedded Random Forest.

Front Neuroinform 2020 10;14:601829. Epub 2020 Nov 10.

RIKEN AIP, Tokyo, Japan.

One major challenge in medical imaging analysis is the lack of label and annotation which usually requires medical knowledge and training. This issue is particularly serious in the brain image analysis such as the analysis of retinal vasculature, which directly reflects the vascular condition of Central Nervous System (CNS). In this paper, we present a novel semi-supervised learning algorithm to boost the performance of random forest under limited labeled data by exploiting the local structure of unlabeled data. We identify the key bottleneck of random forest to be the information gain calculation and replace it with a graph-embedded entropy which is more reliable for insufficient labeled data scenario. By properly modifying the training process of standard random forest, our algorithm significantly improves the performance while preserving the virtue of random forest such as low computational burden and robustness over over-fitting. Our method has shown a superior performance on both medical imaging analysis and machine learning benchmarks.
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http://dx.doi.org/10.3389/fninf.2020.601829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683389PMC
November 2020

Apatinib combined with paclitaxel-based chemotherapy in patients with taxane-resistant advanced gastric cancer: a single-arm exploratory study.

Ann Transl Med 2020 Oct;8(19):1233

Department of Gastrointestinal Medical Oncology, Fujian Cancer Hospital, Fuzhou, Fujian, China.

Background: Apatinib combined with chemotherapy might be effective and safe for the management of advanced gastric cancer, but the available data are limited. To investigate the efficacy and safety of apatinib in combination with paclitaxel (PTX) alone or POF (PTX, oxaliplatin, and 5-fluorouracil) in patients with taxane-resistant advanced gastric cancer.

Methods: Patients with taxane-resistant advanced gastric cancer were enrolled in the single-center, open-labeled, single-arm, exploratory study (ClinicalTrials.gov #NCT02697838). Apatinib was administered at 850 mg po in combination with weekly PTX or the POF regimen. The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), the time to tumor progression (TTP), and safety.

Results: Twenty participants were recruited from 08/2016 to 01/2018. The duration of the study treatment was 2.07 (0.03-16.2) months. The median follow-up was 24.8 (0.3-26.0) months. The reasons for termination of treatment were disease progression (n=6), adverse events (AEs) (n=5), and patients' will (n=9). The ORR was 11.1% (95% CI: 1.4-34.7%) and the DCR was 77.8% (95% CI: 52.4-93.6%). The median PFS was 3.5 (95% CI: 1.9-5.1) months, the median OS was 4.7 (95% CI: 2.0-7.3) months, and the median TTP was 4.2 (95% CI: 0.562-7.838) months. All 20 (100%) patients had AEs, 17 (85%) had apatinib treatment-emergent AEs (TEAEs), and 18 (90%) had chemotherapy TEAEs. The main grade 3-4 TEAEs were neutropenia, leukopenia, hypertension, and anemia.

Conclusions: This preliminary study suggests that apatinib combined with PTX or POF might be effective and tolerable in patients with chemotherapy-refractory gastric cancer. Studies are necessary to confirm the results.

Trial Registration: ClinicalTrials.gov #NCT02697838.
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http://dx.doi.org/10.21037/atm-20-5841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607108PMC
October 2020

Intermittent PTH Administration Increases Bone-Specific Blood Vessels and Surrounding Stromal Cells in Murine Long Bones.

Calcif Tissue Int 2021 Mar 10;108(3):391-406. Epub 2020 Nov 10.

Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Faculty of Dental Medicine, Hokkaido University, Kita 13 Nishi 7 Kita-ku, Sapporo, 060-8586, Japan.

To verify whether PTH acts on bone-specific blood vessels and on cells surrounding these blood vessels, 6-week-old male mice were subjected to vehicle (control group) or hPTH [1-34] (20 µg/kg/day, PTH group) injections for 2 weeks. Femoral metaphyses were used for histochemical and immunohistochemical studies. In control metaphyses, endomucin-positive blood vessels were abundant, but αSMA-reactive blood vessels were scarce. In the PTH-administered mice, the lumen of endomucin-positive blood vessels was markedly enlarged. Moreover, many αSMA-positive cells were evident near the blood vessels, and seemed to derive from those vessels. These αSMA-positive cells neighboring the blood vessels showed features of mesenchymal stromal cells, such as immunopositivity for c-kit and tissue nonspecific alkaline phosphatase (TNALP). Thus, PTH administration increased the population of perivascular/stromal cells positive for αSMA and c-kit, which were likely committed to the osteoblastic lineage. To understand the cellular events that led to increased numbers and size of bone-specific blood vessels, we performed immunohistochemical studies for PTH/PTHrP receptor and VEGF. After PTH administration, PTH/PTHrP receptor, VEGF and its receptor flk-1 were consistently identified in both osteoblasts and blood vessels (endothelial cells and surrounding perivascular cells). Our findings suggest that exogenous PTH increases the number and size of bone-specific blood vessels while fostering perivascular/stromal cells positive for αSMA/TNALP/c-kit.
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http://dx.doi.org/10.1007/s00223-020-00776-2DOI Listing
March 2021

Corrosion Characteristics of Rolling Oil on the Rolled Copper Foil.

Materials (Basel) 2020 Nov 3;13(21). Epub 2020 Nov 3.

School of Material and Metallurgy, University of Science and Technology Liaoning, Anshan 114051, China.

Static corrosion experiments were carried out to investigate the corrosion of each kind of component in the rolling oil on the rolled copper foil. The surface morphology and chemical composition of corrosion products were detected by a digital camera, scanning electron microscope (SEM), energy dispersive spectrometer (EDS) and X-ray photoelectron spectroscopy (XPS). The results showed that the maximum corrosion rate of rolled copper foil in the base stock and friction modifiers (butyl stearate and dodecanol) was close to zero, while that of rolled copper foil in the N-containing borate, phosphate and the fully formulated rolling oil were 0.17, 1.12 and 0.78 mm/a, respectively. The color of rolled copper foil changing from pink into purple-black when corroded in the N-containing borate. The composition of it was mainly CuO and CuO with some N-containing borate adsorbed on it. However, the color and composition of the corroded copper foil in the phosphate were similar to that of the original copper foil. It was complicated for the corroded copper foil in the fully formulated rolling oil, which showed characteristics both in the N-containing borate and in the phosphate according to different positions. It indicated that there might be little corrosion for the base stock and friction modifiers on the rolled copper foil. It might mainly be extreme pressure additives (N-containing borate and phosphate) that caused the corrosion of rolled copper foil. There might be competition between N-containing borate and phosphate for the corrosion of rolled copper foil in the fully formulated rolling oil, resulting in a lower corrosion rate compared with that in the phosphate.
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http://dx.doi.org/10.3390/ma13214933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662263PMC
November 2020

Molecular features and functional implications of germline variants in triple-negative breast cancer.

J Natl Cancer Inst 2020 Nov 5. Epub 2020 Nov 5.

Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, PR China.

Background: The germline variant spectrum of triple-negative breast cancer (TNBC) is different from that of other subtypes and has demonstrated ethnic differences. However, the germline variants of TNBC among Chinese patients and its clinical significance remain unclear.

Methods: Using our multi-omics TNBC cohort (n = 325), we determined the spectrum of germline variants in TNBC and aimed to illustrate their biological and clinical implications.

Results: Overall, 16.0% (52 of 325) of TNBC patients harbored at least one pathogenic or likely pathogenic germline variant. These germline variants were associated with early-onset of TNBC, the occurrence of contralateral breast cancer, the basal-like immune-suppressed mRNA subtype, and the homologous recombination deficiency (HRD) mutation subtype. Somatic allele-specific imbalance was observed in 54.1% of these germline variants, which was correlated with early-onset of breast cancer and elevated HRD. BRCA1 (7.4%), RAD51D (2.8%) and BRCA2 (2.2%) were the genes most frequently mutated. RAD51D germline variants, especially K91fs, were enriched in Chinese patients with TNBC compared to Caucasian and African American patients. The Chinese-specific RAD51D germline variants were functionally associated with the instability of the RAD51D protein, HRD and sensitivity to PARP inhibitors.

Conclusions: Chinese TNBC patients have a distinct spectrum of germline variants, with a remarkable impact on the clinical and molecular characteristics of the tumor. Integrative germline-somatic analysis may help in identifying TNBC patients who are most likely to be affected by their germline variants and in performing clinical interventions more precisely. The RAD51D variants enriched in our cohort may serve as therapeutic targets and guide precision treatment of TNBC.
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http://dx.doi.org/10.1093/jnci/djaa175DOI Listing
November 2020

Immune-related adverse events of a PD-L1 inhibitor plus chemotherapy versus a PD-L1 inhibitor alone in first-line treatment for advanced non-small cell lung cancer: A meta-analysis of randomized control trials.

Cancer 2021 Mar 29;127(5):777-786. Epub 2020 Oct 29.

Department of Thoracic Surgery and Oncology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: The addition of chemotherapy to a programmed death 1/programmed death ligand 1 (PD-L1) inhibitor is a more effective option as a first-line treatment for advanced non-small cell lung cancer (NSCLC). It might also inhibit an overactive immune response and thereby reduce immune-related adverse events (irAEs). This meta-analysis assessed the rate of irAEs with a PD-(L)1 inhibitor plus chemotherapy (I+C) versus a PD-(L)1 inhibitor alone (I) and evaluated the indirect relative risk (RR) of I+C versus I.

Methods: The protocol of this study was registered with PROSPERO (CRD42020139923). The pooled rates of irAEs at different grades were calculated by a single-arm meta-analysis weighted by sample size, and RRs were determined by direct meta-analysis and indirect treatment comparison.

Results: Overall, I+C had a lower rate of grade 3 or higher irAEs than I (7.1% vs 10.6%; indirect RR, 0.516; 95% confidence interval [CI], 0.291-0.916), although irAEs of any grade were similar. The rate of pneumonitis with I+C was lower than the rate with I for any grade (5.9% vs 7.1%; indirect RR, 0.217; 95% CI, 0.080-0.588) and for grade 3 or higher. In the endocrine system, I+C was associated with a lower overall ratein comparison with I (16.1% vs 20.1%; indirect RR, 0.260; 95% CI, 0.120-0.564), whereas irAEs of the digestive system were similar with I+C and I. In other systems, I+C decreased the rate of skin reactions, including rash, in comparison with I (10.4% vs 12.9%; indirect RR, 0.474; 95% CI, 0.299-0.751). The rate of grade 3 or higher skin reactions (excluding rash) also decreased with I+C versus I (1.1% vs 2.0%) with an indirect RR of 0.158 (95% CI, 0.032-0.765), whereas other included irAEs were similar.

Conclusions: In comparison with a PD-(L)1 inhibitor alone, a combination with chemotherapy for the first-line treatment of NSCLC decreased the rates of most irAEs, such as pneumonitis and endocrine and skin reactions, and the overall rate.

Lay Summary: In the first-line treatment of advanced non-small cell lung cancer (NSCLC), the addition of chemotherapy to a programmed death 1/programmed death ligand 1 (PD-(L)1) inhibitor is a more effective option. Adding chemotherapy might reduce immune-related adverse events (irAEs). Thus, this article assesses the rate of irAEs with a PD-(L)1 inhibitor plus chemotherapy (I+C) in comparison with a PD-(L)1 inhibitor alone (I) and evaluates the indirect relative risk (RR) with I+C versus I. The key finding is that in comparison with a PD-(L)1 inhibitor alone, a combination with chemotherapy for the first-line treatment of NSCLC decreases the rates of most irAEs, such as pneumonitis and endocrine and skin reactions, and the overall rate.
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http://dx.doi.org/10.1002/cncr.33270DOI Listing
March 2021

Automatic vertebrae recognition from arbitrary spine MRI images by a category-Consistent self-calibration detection framework.

Med Image Anal 2021 01 9;67:101826. Epub 2020 Oct 9.

University of Western Ontario, London ON, Canada. Electronic address:

Accurate vertebrae recognition is crucial in spinal disease localization and successive treatment planning. Although vertebrae detection has been studied for years, reliably recognizing vertebrae from arbitrary spine MRI images remains a challenge. The similar appearance of different vertebrae and the pathological deformations of the same vertebrae makes it difficult for classification in images with different fields of view (FOV). In this paper, we propose a Category-consistent Self-calibration Recognition System (Can-See) to accurately classify the labels and precisely predict the bounding boxes of all vertebrae with improved discriminative capabilities for vertebrae categories and self-awareness of false positive detections. Can-See is designed as a two-step detection framework: (1) A hierarchical proposal network (HPN) to perceive the existence of the vertebrae. HPN leverages the correspondence between hierarchical features and multi-scale anchors to detect objects. This correspondence tackles the image scale/resolution challenge. (2) A Category-consistent Self-calibration Recognition (CSRN) Network to classify each vertebra and refine their bounding boxes. CSRN leverages the dictionary learning principle to preserve the most representative features; it imposes a novel category-consistent constraint to force vertebrae with the same label to have similar features. CSRN then innovatively formulates message passing into the deep learning framework, which leverages the label compatibility principle to self-calibrate the wrong pre-recognitions. Can-See is trained and evaluated on a capacious and challenging dataset of 450 MRI scans. The results show that Can-See achieves high performance (testing accuracy reaches 0.955) and outperforms other state-of-the-art methods.
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http://dx.doi.org/10.1016/j.media.2020.101826DOI Listing
January 2021

Miscarriage Rate Is High With Frozen-Thawed Blastocysts Arising From Poor-Quality Cleavage Stage Embryos.

Front Endocrinol (Lausanne) 2020 16;11:561085. Epub 2020 Sep 16.

Reproductive Medical Center of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Embryos with low morphological scores can still develop to the blastocyst stage and result in good clinical outcomes. However, no studies have reported the possible effects of transferring cryopreserved blastocysts developed from poor-quality cleavage stage embryos on pregnancy and perinatal outcomes. In this retrospective study, the clinical value of transferring blastocysts derived from day 3 poor-quality cleavage stage embryos during fertilization and embryo transfer procedures was evaluated. According to the quality of embryos on day 3 from which the transferred blastocyst originated, patients were divided into three groups: poor-quality (111 cycles, group A), good-quality (235 cycles, group B), and top-quality (119 cycles, group C). Group A experienced the highest miscarriage rate (30.2%) which was increased when compared to group C (12.5%) ( = 0.03). The clinical pregnancy rates and live birth rates were not significantly different among the three groups. However, good blastocyst originating from top day 3 embryos resulted in higher live birth rate. Of the 218 live births, no differences in obstetric and perinatal outcomes were noted among the three groups. The results showed that extended culture of poor-quality cleavage stage embryos could resulted in favorable clinical pregnancy rates but at a higher incidence of miscarriages. Meanwhile, the risk of adverse perinatal outcomes was not increased.
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http://dx.doi.org/10.3389/fendo.2020.561085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525122PMC
September 2020

Concomitant Mutations in EGFR 19Del/L858R Mutation and Their Association with Response to EGFR-TKIs in NSCLC Patients.

Cancer Manag Res 2020 18;12:8653-8662. Epub 2020 Sep 18.

Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, People's Republic of China.

Objective: Differences in efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have been observed between non-small cell lung cancer (NSCLC) patients with and mutation. We explored whether the total number or pattern of concomitant mutations of and may explain their different sensitivities.

Patients And Methods: This study contained the mutational profiles of EGFR-mutated NSCLC patients from two cohorts: Guangzhou (G1) and database (G2). Concomitant mutation status and EGFR-TKI response information were retrieved.

Results: A total of 403 patients covered 283 genes in the G1 and 803 patients with a different gene set in the G2 were included. Similar prevalence of total concomitant mutation number was observed in both G1 ( 32.48% vs 30.45%; =0.68) and G2 ( 74.9% vs 73.2%; =0.65) cohorts. Only pathway same more related to mutation. EGFR-TKI response information was recorded for 134 patients in the G2 cohort. showed a higher objective response (OR) rate compared with , regardless of concomitant mutations. Compared to patients with OR, non-OR patients had more concomitant mutations, both in (53.8% vs 83.3%; =0.021) and (51.4% vs 77.8%; =0.029). In particular, total concomitant mutations (OR=0.27; =0.03), sensitive mutations (OR=2.21; =0.04), and (OR=0.244; =0.02) significantly affected the TKI response.

Conclusion: Concomitant mutations were widespread in and and were associated with poorer OR to EGFR-TKIs. However, and had similar numbers and patterns of concomitant mutations, which might not explain the different sensitivity to EGFR-TKI.
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http://dx.doi.org/10.2147/CMAR.S255967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509478PMC
September 2020

Histochemical assessment on the cellular interplay of vascular endothelial cells and septoclasts during endochondral ossification in mice.

Microscopy (Oxf) 2020 Aug 20. Epub 2020 Aug 20.

Developmental Biology of Hard Tissue.

This study was aimed to verify the cellular interplay between vascular endothelial cells and surrounding cells in the chondro-osseous junction of murine tibiae. Many CD31-positive endothelial cells accompanied with Dolichos Biflorus Agglutinin lectin-positive septoclasts invaded into the hypertrophic zone of the tibial epiphyseal cartilage. MMP9 immunoreactive cytoplasmic processes of vascular endothelial cells extended into the transverse partitions of cartilage columns. In contrast, septoclasts included several large lysosomes which indicate the incorporation of extracellular matrices despite no immunopositivity for F4/80 -a hallmark of macrophage/monocyte lineage. In addition, septoclasts were observed in c-fos-/- mice but not in Rankl-/- mice. Unlike c-fos-/- mice, Rankl-/- mice showed markedly-expanded hypertrophic zone and the irregular shape of the chondro-osseous junction. Immunoreactivity of PDGF-bb, which involved in angiogenic roles in the bone, was detected in not only osteoclasts but also septoclasts at the chondro-osseous junction. Therefore, septoclasts appear to assist the synchronous vascular invasion of endothelial cells at the chondro-osseous junction. Vascular endothelial cells adjacent to the chondro-osseous junction possesses endomucin but not EphB4, whereas those slightly distant from the chondro-osseous junction were intensely positive for both endomucin and EphB4, while being accompanied with ephrinB2-positive osteoblasts. Taken together, it is likely that vascular endothelial cells adjacent to the chondro-osseous junction would interplay with septoclasts for synchronous invasion into the epiphyseal cartilage, while those slightly distant from the chondro-osseous junction would cooperate with osteoblastic activities presumably by mediating EphB4/ephrinB2.
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http://dx.doi.org/10.1093/jmicro/dfaa047DOI Listing
August 2020

Nickel-Catalyzed Reductive Aryl Thiocarbonylation of Alkene via Thioester Group Transfer Strategy.

Org Lett 2020 Sep 13;22(17):6734-6738. Epub 2020 Aug 13.

School of Chemistry and Chemical Engineering, Shandong University of Technology, 266 West Xincun Road, Zibo 255049, People's Republic of China.

Herein reported is a nickel-catalyzed reductive aryl thiocarbonylation of alkene via thioester group transfer strategy by using simple and readily available thioesters. In contrast to traditional activation of weaker C(acyl)-S bond, the C(acyl)-C bond of thioester was selectively cleaved to enable this reaction under mild conditions. Furthermore, this approach features operational simplicity and broad substrate scope, providing a complementary and practical route for thioester synthesis without requiring toxic thiol or CO gas.
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http://dx.doi.org/10.1021/acs.orglett.0c02091DOI Listing
September 2020

The perception gap of chemotherapy-induced adverse events between doctors and cancer patients: an observational study in China.

Support Care Cancer 2021 Mar 29;29(3):1543-1548. Epub 2020 Jul 29.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.

Introduction: Patient-reported outcomes (PROs) have been widely accepted in western countries. However, limited attention has been given to PROs in China due to a lack of research on the agreement between doctors' and patients' reports of adverse events. This study aims to reveal the perception gap of chemotherapy-induced adverse events between doctors and cancer patients in China.

Methods: An observational study was administered at Sun Yat-Sen University Cancer Center (SYSUCC). Totally, 200 adult cancer patients undergoing chemotherapy participated. Patient reports were collected by nurses via telephone. Doctor reports were collected by nurses based on their medical records. The agreement between doctors and patients was analyzed by Cohen's κ.

Results: Agreement between doctors and patients varied among different symptoms: 0.26 for nausea/vomiting, 0.49 for constipation, 0.63 for diarrhea, 0.65 for general pain, and 0.76 for rash. Doctors' underreporting rates were 70% for nausea/vomiting, 50% for diarrhea, 38% for rash, 33% for constipation, and 29% for general pain.

Conclusions: The perception gap of chemotherapy-induced adverse events between doctors and patients exists in China, especially regarding subjective symptoms. Introduction of PROs in both clinical trials and routine clinical practice should be considered in China.
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http://dx.doi.org/10.1007/s00520-020-05649-wDOI Listing
March 2021

Regulation of tartary buckwheat-resistant starch on intestinal microflora in mice fed with high-fat diet.

Food Sci Nutr 2020 Jul 12;8(7):3243-3251. Epub 2020 May 12.

Department of School of Perfume and Aroma Technology Shanghai Institute of Technology Shanghai China.

Resistant starch (RS) is closely related to the composition of intestinal flora. Based on many studies on the physiological functions of probiotics and short-chain fatty acids (SCFAs), it is possible that RS can improve the intestinal health of the host. Therefore, we speculated that tartary buckwheat-resistant starch (TBRS) can also regulate the intestinal flora disorder caused by high-fat diet. We randomly divided 36 SPF C57BL/6J mice into low-fat diet, high-fat diet (HF-CS), high-fat diet supplemented with TBRS (HF-BRS), and high-fat diet supplemented with corn-resistant starch (HF-CRS). We analyzed the diversity and richness of gut microbiota based on PCR and Illumina high-throughput sequencing technology. In community abundance, the HF-BRS group was significantly higher than the other three groups ( < .05). TBRS improved the gut microbiota dysbiosis, including decreasing the -to- ratios (F/B) and contributing to the growth of and as well significantly inhibiting the growth of , , and . We also analyzed the production of SCFAs by GC-MS, and the concentration of total SCFAs increased in the HF-CS group. However, TBRS significantly increased the production of SCFAs, especially the propionate concentration compared with the HF-CRS group ( < .05). These results elucidated that TBRS has the potential to improve intestinal health by altering the structure of gut microbiota and increasing the production of SCFAs. Our findings have important implications for TBRS as functional food ingredient to manipulate intestinal microflora.
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http://dx.doi.org/10.1002/fsn3.1601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382121PMC
July 2020

A kinase-interacting protein 1 may serve as a potential biomarker for deteriorative tumor features and poor prognosis in gastric cancer patients.

J Clin Lab Anal 2020 Aug 16;34(8):e23350. Epub 2020 Jul 16.

Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, China.

Objective: This study aimed to explore the association of A kinase-interacting protein 1 (AKIP1) expression with clinicopathological characteristics and prognosis in gastric cancer patients.

Methods: Data of 260 gastric cancer patients were retrospectively reviewed. AKIP1 expression in tumor tissue and non-cancerous tissue specimens was detected by immunohistochemistry and semi-quantitatively scored according to the staining intensity and density. Moreover, the clinicopathological features were retrieved, and disease-free survival (DFS) and overall survival (OS) were calculated.

Results: A kinase-interacting protein 1 expression was increased in tumor tissues compared with non-cancerous tissues (P < .001). In terms of tumor features, tumor AKIP1 high expression correlated with elevated T stage (P < .001) and raised TNM stage (P = .042), while did not correlate with pathological grade (P > .999), tumor size (P = .060), N stage (P = .180), or tumor location (P > .999). Meanwhile, tumor AKIP1 was not associated with the non-tumor features either. Kaplan-Meier curves disclosed that AKIP1 high expression patients had shorter DFS (P = .004) and OS (P = .043) compared with AKIP1 low expression patients. Univariate Cox's regression showed that AKIP1 high expression correlated with shorter DFS (P = .005, hazard ratio [HR] = 1.635) and OS (P = .046, HR = 1.519), whereas multivariate Cox's regression displayed that AKIP1 did not independently predict worse DFS (P = .172, HR = 1.276) or shorter OS (P = .433, HR = 1.183).

Conclusion: A kinase-interacting protein 1 may serve as a potential biomarker for deteriorative tumor features and poor prognosis in gastric cancer patients.
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http://dx.doi.org/10.1002/jcla.23350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439412PMC
August 2020

Hypothermia-Induced Ubiquitination of Voltage-Dependent Anion Channel 3 Protects BV2 Microglia Cells From Cytotoxicity Following Oxygen-Glucose Deprivation/Recovery.

Front Mol Neurosci 2020 5;13:100. Epub 2020 Jun 5.

Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

: Hypothermia attenuates microglial activation and exerts a potential neuroprotective effect against cerebral ischemic-reperfusion (I/R) injury. However, the underlying mechanism remains to be elucidated. In this study, a model of oxygen-glucose deprivation, followed by recovery (OGD/R), was used to investigate whether hypothermia exerts anti-inflammatory and anti-apoptosis properties enhanced ubiquitination and down-regulation of voltage-dependent anion channel 3 (VDAC3) expression. : BV2 microglia were cultured under OGD for 4 h following reperfusion with or without hypothermia for 2, 4, or 8 h. M1 and M2 microglia markers [inducible nitric oxide synthase (iNOS) and arginase (Arg)1] were detected using immunofluorescence. The levels of pro-inflammatory cytokines [tumor necrosis factor (TNF) α, interleukin (IL)-1β], and anti-inflammatory factor (IL-10) were determined using enzyme-linked immunosorbent assay (ELISA). Mitochondrial membrane potential (ΔΨm) was assayed by JC-1 staining using a flow cytometer. Expression of caspase-3, cleaved caspase-3, and VDAC3 were assessed using western blot analysis. The cellular locations and interactions of ubiquitin and VDAC3 were identified using double immunofluorescence staining and immunoprecipitation (IP) assay. Also, the level of the VDAC3 mRNA was determined using a quantitative polymerase chain reaction (qPCR). : Hypothermia inhibited the OGD/R-induced microglia activation and differentiation into the M1 type with pro-inflammatory effect, whereas it promoted differentiation to the M2 type with anti-inflammatory effect. Hypothermia attenuated OGD/R-induced loss of Δψm, as well as the expression of apoptosis-associated proteins. Compared to normothermia, hypothermia increased the level of ubiquitinated VDAC3 in the BV2 microglia at both 2 and 8 h of reperfusion. Furthermore, hypothermia did not attenuate VDAC3 mRNA expression in OGD/R-induced microglia. : Hypothermia treatment during reperfusion, attenuated OGD/R-induced inflammation, and apoptosis in BV2 microglia. This might be due to the promotion of VDAC3 ubiquitination, identifying VDAC3 as a new target of hypothermia.
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http://dx.doi.org/10.3389/fnmol.2020.00100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289978PMC
June 2020

Intrapulmonary inoculation of multicellular spheroids to construct an orthotopic lung cancer xenograft model that mimics four clinical stages of non-small cell lung cancer.

J Pharmacol Toxicol Methods 2020 Jul - Aug;104:106885. Epub 2020 Jun 10.

Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, CA 95211, USA. Electronic address:

Introduction: Lung cancer leads in mortality among all types of cancer in US and Non-small cell lung cancer (NSCLC) is the major type of lung cancer. Mice models of lung cancer based on subcutaneous or orthotopic inoculation of cancer cell suspension do not adequately mimic the progression of lung cancer in clinic.

Methods: A549-iRFP cells (human NSCLC adenocarcinoma) were cultured to form multicellular spheroids (MCS), which were then inoculated intrapulmonarily into male athymic nude mice. The xenograft cancer development was monitored by in vivo fluorescent imaging and validated by open-chest anatomy, ex vivo fluorescent imaging, and histological studies.

Results: The newly developed orthotopic xenograft model of lung cancer simulated all four clinical stages of NSCLC progression over one month: Stage 1) localized tumor at the inoculation site, Stage 2) multiple tumor nodules or larger tumor nodule on the same side of the lung, Stage 3) cancer growth on heart surface, and Stage 4) metastatic cancer on both sides of the lung. The model yielded high rates of postoperative survival (100%) and parenchymal tumor establishment (88.9%). The roughness of the inoculated MCS associated negatively with the time needed to develop metastatic cancer (p = .0299).

Discussion: This new orthotopic xenograft model of NSCLC would facilitate the development of medications to treat lung cancer.
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http://dx.doi.org/10.1016/j.vascn.2020.106885DOI Listing
June 2020

Dual blockade of EGFR and VEGFR pathways: Results from a pilot study evaluating apatinib plus gefitinib as a first-line treatment for advanced EGFR-mutant non-small cell lung cancer.

Clin Transl Med 2020 Jun 4;10(2):e33. Epub 2020 Jun 4.

Department 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, P. R. China.

Background: Dual blockade of both EGFR and VEGFR pathways in EGFR-mutant NSCLC have shown enhanced antitumor efficacy versus EGFR-TKIs alone. Apatinib is an orally effective VEGFR-2 tyrosine kinase inhibitor (TKI). This pilot study aims to evaluate the tolerability, pharmacokinetic profile, and antitumor activity of apatinib plus gefitinib as a therapy for EGFR-mutant advanced NSCLC.

Methods: Advanced non-squamous NSCLC participants harbored with the EGFR 19 deletion or the 21 L858R point mutation were included. There were two cohorts: Cohort A: apatinib 500 mg + gefitinib 250 mg. Cohort B: apatinib 250 mg + gefitinib 250 mg. The primary endpoint was safety profile. Other endpoints consisted of PK analysis, objective response rate (ORR), and progression-free survival (PFS). Exploratory analysis was conducted using next-generation sequencing of plasma circulating-tumor DNA.

Results: Between July 2016 and April 2017, 13 of NSCLC patients were recruited. Six patients were pooled in Cohort A, while seven patients were in Cohort B. Adverse events (AEs) were tolerable (mostly grade 1-2) and the treatment-related AEs were similar in both cohorts: rash (100% vs 71.4%), diarrhea (66.7% vs 71.4%), hypertension (66.7% vs 71.4%), proteinuria (66.7% vs 42.9%), and hand-foot skin reaction (33.3% vs 28.6%). The area under plasma concentration-time curve for the steady state of apatinib was 2864.73 ± 2605.54 ng mL h in Cohort A and 2445.09 ± 1550.89 ng mL h in Cohort B. Of the 11 patients evaluable for efficacy, Cohort A achieved an ORR of 80.0% and reached a median PFS of 19.2 months, while it was 83.3% and 13.4 months in Cohort B. Patients without a concomitant mutation at baseline had a prolonged PFS tendency (20.99 months v 13.21 months, P = .0624). The EGFR-T790M mutation remained the dominant resistance mechanism.

Conclusion: Apatinib (500 mg) plus gefitinib (250 mg) showed a tolerable safety profile and encouraging antitumor activity for advanced EGFR-mutant NSCLC in the first-line setting. Phase III trials of apatinib (500 mg) plus gefitinib (250 mg) are warranted.

Trial Registration: Clinicaltrials.gov, NCT02824458, date of registration June 23, 2016.
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http://dx.doi.org/10.1002/ctm2.33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403827PMC
June 2020

Effects of Different Target Temperatures on Angiogenesis and Neurogenesis Following Resuscitation in a Porcine Model After Cardiac Arrest.

Shock 2021 Jan;55(1):67-73

Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Objective: The optimal effective temperature of targeted temperature management (TTM) used to prevent cerebral injury following cardiopulmonary resuscitation (CPR) is undetermined. In this study, we compared the mortality, neurologic deficits, and cerebral protein levels of two target temperatures.

Methods: Fifty 4-month-old female domestic pigs were randomized to sham, TTM at 33°C ± 0.5°C (T33), TTM at 35°C ± 0.5°C (T35), and normothermic (NT) groups. In the NT and TTM groups, untreated ventricular fibrillation was induced electrically in animals for 10 min, followed by 6 min of CPR. Target core temperatures (Tc) of TTM groups were induced and maintained (6 h) using an endovascular hypothermia device, and rewarmed to 37.5 ± 0.5°C in the next 6 h. Tc of the NT group was maintained at 37.5 ± 0.5°C. The survival outcomes and neurological function were evaluated every 24 h for 72 h.

Results: All animals were successfully resuscitated with no significant differences in baseline characteristics or hemodynamic indexes. Survival rates and neurological outcomes were significantly improved in the TTM groups, with T33 showing the most significant effect. Compared with NT-treated animals, TTM-treated animals had higher expressions of angiopoietin-1, transforming growth factor-alpha , vascular endothelial growth factor, metallopeptidase inhibitor (TIMP)-1, TIMP-2, and platelet-derived growth factor-BB. Macrophage migration inhibitory factor and IL-17F levels were markedly upregulated after resuscitation in the NT group but inhibited in the TTM groups. Neuron-specific enolase staining data was also consistent with our conclusion that hypothermia can reduce reperfusion-induced brain injuries.

Conclusion: Lower target temperature showed greater protective effects against cerebral injuries after CPR, and the improved neurological outcomes after TTM may be associated with decreased expression of pro-inflammatory cytokines and increased expression of blood-brain barrier and neurogenesis regulatory factors in this porcine model of CA following resuscitation.
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http://dx.doi.org/10.1097/SHK.0000000000001559DOI Listing
January 2021

Feasibility and safety of PD-1/L1 inhibitors for non-small cell lung cancer in front-line treatment: a Bayesian network meta-analysis.

Transl Lung Cancer Res 2020 Apr;9(2):188-203

Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.

Background: This Bayesian network meta-analysis (NMA) was conducted to compare efficacy and safety of programmed death 1/ligand 1 (PD-1/L1) inhibitors in previous untreated advanced non-small cell lung cancer (NSCLC) patients.

Methods: Eligible studies evaluating first-line anti-PD-1/L1 based regimens in advanced NSCLC patients were included. Overall survival (OS), progression free survival (PFS), objective response rate (ORR), as well as treatment-related severe adverse events (tr-SAE) were synthesized within the Bayesian framework. Subgroup analysis was conducted according to PD-L1 expression.

Results: Twelve studies including 7,490 patients and 9 treatment strategies were enrolled in this study. For the PD-L1 expression non-selective patients, all chemo-immunotherapies were significantly better than chemotherapy for prolonging OS and PFS, except for caremlizumab plus chemotherapy (HR =0.72) failed to show advantages for OS. In addition, pembrolizumab plus chemotherapy showed better PFS than nivolumab plus ipilimumab (HR =0.66). In PD-L1 ≥50% patients, all immunotherapy was better than chemotherapy for OS, except for nivolumab (HR =0.83) and nivolumab plus ipilimumab (HR =0.70). For PFS, pembrolizumab plus chemotherapy (HR =0.39), atezolizumab plus chemotherapy (HR =0.47) and pembrolizumab (HR =0.67) were significantly better than chemotherapy. In PD-L1 1-49% patients, pembrolizumab plus chemotherapy (HR =0.52) and atezolizumab plus chemotherapy (HR =0.70) were better than chemotherapy for PFS. In the PD-L1 positive or negative group, all included corresponding regimens were equivalence according to OS and PFS.

Conclusions: We conducted a systematic comparison of first line immunotherapy for advanced NSCLC. Chemo-immunotherapies were better than chemotherapy and mono-immunotherapies in most patients. Pembrolizumab might have better efficacy than other PD-1/L1 inhibitors.
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http://dx.doi.org/10.21037/tlcr.2020.02.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225152PMC
April 2020

Molecular Subtyping of Triple-Negative Breast Cancers by Immunohistochemistry: Molecular Basis and Clinical Relevance.

Oncologist 2020 10 1;25(10):e1481-e1491. Epub 2020 Jun 1.

Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.

Background: Molecular subtyping of triple-negative breast cancers (TNBCs) via gene expression profiling is essential for understanding the molecular essence of this heterogeneous disease and for guiding individualized treatment. We aim to devise a clinically practical method based on immunohistochemistry (IHC) for the molecular subtyping of TNBCs.

Materials And Methods: By analyzing the RNA sequencing data on TNBCs from Fudan University Shanghai Cancer Center (FUSCC) (n = 360) and The Cancer Genome Atlas data set (n = 158), we determined markers that can identify specific molecular subtypes. We performed immunohistochemical staining on tumor sections of 210 TNBCs from FUSCC, established an IHC-based classifier, and applied it to another two cohorts (n = 183 and 214).

Results: We selected androgen receptor (AR), CD8, FOXC1, and DCLK1 as immunohistochemical markers and classified TNBCs into five subtypes based on the staining results: (a) IHC-based luminal androgen receptor (IHC-LAR; AR-positive [+]), (b) IHC-based immunomodulatory (IHC-IM; AR-negative [-], CD8+), (c) IHC-based basal-like immune-suppressed (IHC-BLIS; AR-, CD8-, FOXC1+), (d) IHC-based mesenchymal (IHC-MES; AR-, CD8-, FOXC1-, DCLK1+), and (e) IHC-based unclassifiable (AR-, CD8-, FOXC1-, DCLK1-). The κ statistic indicated substantial agreement between the IHC-based classification and mRNA-based classification. Multivariate survival analysis suggested that our IHC-based classification was an independent prognostic factor for relapse-free survival. Transcriptomic data and pathological observations implied potential treatment strategies for different subtypes. The IHC-LAR subtype showed relative activation of HER2 pathway. The IHC-IM subtype tended to exhibit an immune-inflamed phenotype characterized by the infiltration of CD8+ T cells into tumor parenchyma. The IHC-BLIS subtype showed high expression of a VEGF signature. The IHC-MES subtype displayed activation of JAK/STAT3 signaling pathway.

Conclusion: We developed an IHC-based approach to classify TNBCs into molecular subtypes. This IHC-based classification can provide additional information for prognostic evaluation. It allows for subgrouping of TNBC patients in clinical trials and evaluating the efficacy of targeted therapies within certain subtypes.

Implications For Practice: An immunohistochemistry (IHC)-based classification approach was developed for triple-negative breast cancer (TNBC), which exhibited substantial agreement with the mRNA expression-based classification. This IHC-based classification (a) allows for subgrouping of TNBC patients in large clinical trials and evaluating the efficacy of targeted therapies within certain subtypes, (b) will contribute to the practical application of subtype-specific treatment for patients with TNBC, and (c) can provide additional information beyond traditional prognostic factors in relapse prediction.
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http://dx.doi.org/10.1634/theoncologist.2019-0982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543239PMC
October 2020

Anticancer drug R&D landscape in China.

J Hematol Oncol 2020 05 13;13(1):51. Epub 2020 May 13.

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

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http://dx.doi.org/10.1186/s13045-020-00877-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218822PMC
May 2020

Molecular subtypes and precision treatment of triple-negative breast cancer.

Ann Transl Med 2020 Apr;8(7):499

Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Despite the progress made in precision treatment of cancer patients, targeted treatment is still at its early stage in TNBC, and chemotherapy remains the standard treatment. With the advances in next generation sequencing technology, genomic and transcriptomic analyses have provided deeper insight into the inter-tumoral heterogeneity of TNBC. Much effort has been made to classify TNBCs into different molecular subtypes according to genetic aberrations and expression signatures and to uncover novel treatment targets. In this review, we summarized the current knowledge regarding the molecular classification of TNBC and explore the future paradigm for using molecular classification to guide the development of precision treatment and clinical practice.
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http://dx.doi.org/10.21037/atm.2020.03.194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210152PMC
April 2020

Integrated molecular profiling of young and elderly patients with triple-negative breast cancer indicates different biological bases and clinical management strategies.

Cancer 2020 Jul 8;126(14):3209-3218. Epub 2020 May 8.

Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Age at the time of breast cancer diagnosis not only predicts clinical outcome but also indicates distinct molecular characteristics that provide the rationale for appropriate treatment strategies. However, to the authors' knowledge, little is known regarding the molecular profile and biological basis of triple-negative breast cancers (TNBCs) occurring in young and elderly patients.

Methods: Using the study institution's largest, single-center, multiomics TNBC data set, the authors analyzed the clinical and genomic features of young (aged ≤39 years) and elderly (aged ≥65 years) patients with TNBC.

Results: In the current study, a total of 50 patients, 354 patients, and 69 patients, respectively, were grouped as young, intermediate, and elderly patients with TNBC. Young patients with TNBC had worse short-term survival, upregulation of DNA repair, cell cycle and RNA metabolism gene sets, frequent pathogenic germline variants, and predominant homologous recombination deficiency-related mutational signatures. Several copy number alterations also were found to be enriched in young patients with TNBC. Nearly one-half of the TNBC cases in elderly patients were of the luminal androgen receptor subtype. TNBC in elderly patients was identified as being associated with severe fibrosis; a lower Ki-67 index; and somatic mutations in PIK3CA, KMT2D, ERBB2, ERBB3, and their corresponding pathways. Elderly patients with TNBC also were more likely to harbor targetable mutations.

Conclusions: The findings of the current study indicated that young patients with TNBC had an enhanced cell cycle, which may have helped to explain their inferior short-term survival, whereas the homologous recombination deficiency and enriched pathogenic germline variants observed among young patients with TNBC suggested the need for genetic counseling and testing, as well as the potential use of DNA damage agents and poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors. Molecular characteristics of elderly patients with TNBC, although suggesting less response to chemotherapy, provided a rationale for the routine detection of actionable somatic mutations.
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http://dx.doi.org/10.1002/cncr.32922DOI Listing
July 2020

Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation.

Evid Based Complement Alternat Med 2020 22;2020:3789268. Epub 2020 Apr 22.

Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, China.

Objective: To comprehensively evaluate the protective effect of Shenfu injection (SFI) on renal ischaemia/reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) through neutrophil gelatinase-associated lipocalin (NGAL) and to explore effective monitoring of early renal injuries after CPR.

Methods: Thirty healthy minipigs were randomly divided into 3 groups: sham operation (SO) ( = 6), control ( = 12), and SFI ( = 12). The SO group underwent only catheterization, whereas the control and SFI groups were subjected to program-controlled electrical stimulation to establish a cardiac arrest (CA) model due to ventricular fibrillation. After CPR, the return of spontaneous circulation was achieved. Each animal in the SFI group was intravenously injected with SFI after resuscitation. Haemodynamic parameters were monitored at baseline and 2, 6, 12, and 24 hr after CPR. At each time point, venous blood samples were collected for NGAL, creatinine, and ATPase screening.

Results: After CA, the MAP, CPP, and CO of the animals in the control and SFI groups decreased significantly. However, at 6 hr after CPR, the MAP, CPP, and CO of the animals in the SFI group began to recover gradually; the differences between the control and SFI groups were significant ( < 0.005). The renal damage immediately after CPR appeared to be significant in the pathological examinations. However, the degree of renal injury in the SFI group improved significantly, and the apoptosis index was also notably reduced. The blood and urine NGAL levels were clearly elevated after CPR. The greatest increase in NGAL was found in the control group, which was significantly different from that of the SFI group ( < 0.001). SFI can significantly increase the ATPase activity of kidney tissues after CPR and improve abnormal caspase-3 protein expression.

Conclusion: SFI can effectively prevent acute kidney injuries caused by CPR through improving energy metabolism and inhibiting apoptosis.
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http://dx.doi.org/10.1155/2020/3789268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193270PMC
April 2020

Recovery of phosphorus and metallic nickel along with HCl production from electroless nickel plating effluents: The key role of three-compartment photoelectrocatalytic cell system.

J Hazard Mater 2020 07 19;394:122559. Epub 2020 Mar 19.

Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address:

A three-compartment photoelectrocatalytic (PEC) cell system combined with ion exchange and chemical precipitation was proposed to recover phosphorus and nickel from electroless nickel plating effluents containing hypophosphite (HPO) and nickel ions (Ni). Ion exchange was used to concentrate and separate Ni and HPO. As a key unit, the established PEC system consisted of TiO/Ni-Sb-SnO photoanode and Ti cathode. With 25.8 mM NaHPO and 500 mM NiCl, 100 % HPO was oxidized to PO in the anode cell, 78 % Ni was recovered as metallic Ni in the cathode cell, and 900 mM HCl was obtained in the middle cell within 24 h at 3.0 V. Based on quenching experiments and ESR technique, OH radicals were mainly responsible for HPO oxidation. In situ Raman spectroscopy indicated that Ni initially reacted with OH to form α-Ni(OH), which was gradually reduced to metallic Ni. Fortunately, a slight pH decrease in the cathode cell in the three-compartment cell system was beneficial for Ni reduction to Ni°. The obtained PO was recovered by chemical precipitation. Finally, recovery of phosphorus and metallic nickel along with HCl production from an actual electroless nickel plating effluents in terms of efficiency, cost-benefit, and stability assessment were demonstrated.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122559DOI Listing
July 2020