Publications by authors named "Yaohui Wang"

128 Publications

Robust Prediction of Immune Checkpoint Inhibition Therapy for Non-Small Cell Lung Cancer.

Front Immunol 2021 13;12:646874. Epub 2021 Apr 13.

Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: The development of immune checkpoint inhibitors (ICIs) is a revolutionary milestone in the field of immune-oncology. However, the low response rate is the major problem of ICI treatment. The recent studies showed that response rate to single-agent programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibition in unselected non-small cell lung cancer (NSCLC) patients is 25% so that researchers defined several biomarkers to predict the response of immunotherapy in ICIs treatment. Common biomarkers like tumor mutational burden (TMB) and PD-L1 expression have several limitations, such as low accuracy and inadequately validated cutoff value.

Methods: Two published and an unpublished ICIs treatment NSCLC cohorts with 129 patients were collected and divided into a training cohort (n = 53), a validation cohort (n = 22), and two independent test cohorts (n = 34 and n = 20). We identified six immune-related pathways whose mutational status was significantly associated with overall survival after ICIs treatment. Then these pathways mutational status combined with TMB, PD-L1 expression and intratumor heterogeneity were incorporated to build a Bayesian-regularization neural networks (BRNN) model to predict the ICIs treatment response.

Results: We firstly proved that TMB, PD-L1, and mutant-allele tumor heterogeneity (MATH) were independent biomarkers. The survival analysis of six immune-related pathways revealed the mutational status could distinguish overall survival after ICIs treatment. When predicting immunotherapy efficacy, the overall accuracy of area under curve (AUC) in validation cohort reaches 0.85, outperforming previous predictors in either sensitivity or specificity. And the AUC in two independent test cohorts reach 0.74 and 0.80.

Conclusion: We developed a pathway-model that could predict the efficacy of ICIs in NSCLC patients. Our study made a significant contribution to solving the low prediction accuracy of immunotherapy of single biomarker. With the accumulation of larger data sets, further studies are warranted to refine the predictive performance of the approach.
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http://dx.doi.org/10.3389/fimmu.2021.646874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076602PMC
April 2021

Imaging, clinical, and pathologic findings of Sertoli-leydig cell tumors.

Sci Prog 2021 Apr-Jun;104(2):368504211009668

Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.

To explore the clinical features, imaging findings, and pathological manifestations of ovarian Sertoli-Leydig cell tumors (SLCTs). The clinical and pathological manifestations, tumor location, size, morphology, vascularity, computed tomography (CT) density, magnetic resonance imaging (MRI) signal intensity, and contrast enhancement patterns in five cases with SLCTs were retrospectively reviewed. SLCTs most commonly occurred in young women. Virilization was observed in three cases (60%). All five tumors were unilateral and oval or round, with a clear boundary. The solid part of the tumor was isoattenuated on the conventional CT scan, and showed isoattenuation or slight hypoattenuation relative to adjacent myometrium on T1 weighted imaging (T1WI) and T2 weighted imaging (T2WI). On contrast-enhanced images, three tumors showed marked enhancement. DICER1 hotspot mutations were commonly seen in SLCTs. A highly vascularized mass with low signal intensity (SI) of the solid part on T2WI and androgen overproduction symptoms may suggest an SLCT.
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http://dx.doi.org/10.1177/00368504211009668DOI Listing
April 2021

Mutation of P-element somatic inhibitor induces male sterility in the diamondback moth, Plutella xylostella.

Pest Manag Sci 2021 Apr 11. Epub 2021 Apr 11.

CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences/Institute of Plant Physiology and Ecology, Shanghai, China.

Background: Genetic manipulation of sex determination pathways in insects provides the basis for a broad range of strategies to benefit agricultural security and human health. The P-element somatic inhibitor (PSI) protein, an exon splicing silencer that promotes male-specific splicing of dsx, plays a critical role in male sexual differentiation and development. The functions of PSI have been characterized in the lepidopteran model species Bombyx mori. However, the molecular mechanism and functions of PSI in Plutella xylostella, a worldwide agricultural pest and taxonomically basal species, are still unknown.

Results: Here we identified PxPSI transcripts and analyzed their spatiotemporal expression pattern in P. xylostella. Multiple sequence alignment revealed that PxPSI contains four KH domains and is highly conserved in lepidopterans. We used the CRISPR-Cas9 system to generate mutations of the PxPSI genomic locus. Disruptions of PxPSI caused male-specific defects in internal and external genitals. In addition, we detected female-specific Pxdsx transcripts in PxPSI male mutants. Mutations also caused changes in expression of several sex-biased genes and induced male sterility.

Conclusion: Our study demonstrates that PxPSI plays a key role in male sex determination in P. xylostella and suggests a potential molecular target for genetic-based pest management in lepidopteran pests.
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http://dx.doi.org/10.1002/ps.6413DOI Listing
April 2021

A volumetric finite-difference method for the design of three-dimensional, arbitrary-structured MRI gradient coil.

Rev Sci Instrum 2021 Mar;92(3):034712

School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, QLD 4072, Australia.

A volumetric finite-difference based method is presented in this paper for the design of three-dimensional (3D), arbitrarily structured gradient coils in magnetic resonance imaging. In the proposed method, the coil space is discretized with quasi-rectangular elements, and the current density of each element is expressed by a finite-difference based numerical approximation of stream functions. The magnetic flux density at target field points can be calculated by those stream function values at all grids of the coil space. The optimization problem is constructed and solved to determine the stream function and coil patterns. This proposed method has been tested on several designs that include a shielded, ultra-short cylindrical coil, a partially shielded biplanar coil, and an asymmetric head coil with 3D geometries. The numerical results show that the proposed method is straightforward to implement and is versatile and suitable for designing complex structured gradient coils with high electromagnetic performance.
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http://dx.doi.org/10.1063/5.0035118DOI Listing
March 2021

[Application of quantitative electroencephalogram monitoring in evaluating thrombolytic effect of acute cerebral infarction].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Feb;33(2):207-210

Department of Emergency, the First Hospital of Qinhuangdao, Qinhuangdao 066000, Hebei, China. Corresponding author: Zhang Chongyang, Email:

Objective: To investigate the value of quantitative electroencephalography (qEEG) in the evaluation of thrombolytic efficacy in acute cerebral infarction.

Methods: A prospective cohort study was conducted. Ninety-four patients with acute cerebral infarction who received intravenous thrombolysis admitted to the department of emergency of Qinhuangdao First Hospital from October 2019 to September 2020 were enrolled. The relative energy values of δ, θ, α and β waves in qEEG before and 2 hours, 24 hours and 7 days after intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis were dynamically monitored, and the power ratio index [DTABR, DTABR = (δ+θ)/(α+β)] was calculated. The National Institutes of Health stroke scale (NIHSS) score was also recorded. The reduction of NIHSS score ≥ 3 or the disappearance of neurological symptoms were regarded as effective thrombolytic therapy. The changes of DTABR before and after thrombolysis in patients with effective and ineffective thrombolysis were analyzed, and the correlation between DTABR and NIHSS score was analyzed by Pearson method.

Results: A total of 94 patients were enrolled, including 64 males and 30 females. The average age was (61.71±10.11) years from 36 to 89 years old. Thrombolysis was effective in 57 cases and ineffective in 37 cases. Compared with before thrombolysis, DTABR of the effective group was significantly decreased at 2 hours, 24 hours and 7 days after thrombolysis (left cerebral infarction: 1.87±1.45, 1.59±0.88, 1.58±0.90 vs. 3.82±2.60; right cerebral infarction: 1.55±0.57, 1.41±0.50, 1.35±0.44 vs. 3.20±1.63, all P < 0.05). DTABR did not change or increase significantly at 2 hours, 24 hours and 7 days after thrombolysis compared with before thrombolysis (left cerebral infarction: 3.56±2.57, 3.48±2.19, 3.54±2.50 vs. 3.11±1.62; right cerebral infarction: 5.29±3.93, 5.33±3.94, 5.19±4.52 vs. 4.73±2.43, all P > 0.05). Pearson correlation analysis showed a significant positive correlation between DTABR and NIHSS score in patients with acute cerebral infarction (r = 0.691, P < 0.01).

Conclusions: The quantitative index of qEEG, DTABR, can accurately and quickly monitor the process of thrombolysis in acute cerebral infarction, and can effectively evaluate the effect of thrombolysis in patients.
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http://dx.doi.org/10.3760/cma.j.cn121430-20201110-00759DOI Listing
February 2021

Rapid Detection of Ractopamine and Salbutamol in Swine Urine by Immunochromatography Based on Selenium Nanoparticles.

Int J Nanomedicine 2021 9;16:2059-2070. Epub 2021 Mar 9.

Joint National Laboratory for Antibody Drug Engineering, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, People's Republic of China.

Purpose: The purpose of this study was to establish a lateral flow immunoassay using selenium nanoparticles (Se-NPs) as a probe to detect ractopamine (RAC) and salbutamol (SAL) in swine urine.

Methods: SDS and PEG were used as templates to prepare Se-NPs; anti-RAC monoclonal antibodies or anti-SAL monoclonal antibodies were labelled with Se-NPs; and rapid detection kits were prepared. The sensitivity, specificity, and stability were measured, and actual samples were analysed.

Results: The Se-NPs were spherical with a diameter of 40.63 ± 5.91 nm, and were conjugated successfully with an anti-RAC antibody to give a total diameter of 82.33 ± 17.91 nm. The detection limit of a RAC kit in swine urine was 1 ng/mL, and that of a SAL kit was 3 ng/mL. Both procedures could be completed within 5 minutes. No cross-reaction occurred with clenbuterol, bambuterol and phenylethanolamine A. Samples were tested consistently across different batches of kits for swine urine. The results of the kits were identical to those of actual clinical samples analysed by ELISA, and the coincidence rate was 100%.

Conclusion: The assay kit does not require any special device for reading the results, and the readout is a simple colour change that can be evaluated with the naked eye. It is easy to operate, sensitive, specific, and stable This kit is suitable for the rapid and real-time detection of RAC and SAL residues in swine urine samples.

Clinical Trial Registration: Swine urines samples were used under approval from the Experimental Animal Ethics committee of the Joint National Laboratory for Antibody Drug Engineering, Henan University.
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http://dx.doi.org/10.2147/IJN.S292648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955707PMC
April 2021

The Sex Determination Cascade in the Silkworm.

Genes (Basel) 2021 Feb 23;12(2). Epub 2021 Feb 23.

Key Laboratory of Insect Developmental and Evolutionary Biology, Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China.

In insects, sex determination pathways involve three levels of master regulators: primary signals, which determine the sex; executors, which control sex-specific differentiation of tissues and organs; and transducers, which link the primary signals to the executors. The primary signals differ widely among insect species. In Diptera alone, several unrelated primary sex determiners have been identified. However, the () gene is highly conserved as the executor component across multiple insect orders. The transducer level shows an intermediate level of conservation. In many, but not all examined insects, a key transducer role is performed by (), which controls sex-specific splicing of . In Lepidoptera, studies of sex determination have focused on the lepidopteran model species (the silkworm). In the primary signal of sex determination cascade starts from , a female-specific PIWI-interacting RNA, and its targeting gene , which is apparently specific to and conserved among Lepidoptera. has not been found in Lepidoptera. Instead, the PSI protein binds directly to pre-mRNA and regulates its alternative splicing to produce male- and female-specific transcripts. Despite this basic understanding of the molecular mechanisms underlying sex determination, the links among the primary signals, transducers and executors remain largely unknown in Lepidoptera. In this review, we focus on the latest findings regarding the functions and working mechanisms of genes involved in feminization and masculinization in Lepidoptera and discuss directions for future research of sex determination in the silkworm.
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http://dx.doi.org/10.3390/genes12020315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926724PMC
February 2021

Local therapy for oligometastatic esophageal squamous cell carcinoma: a prospective, randomized, Phase II clinical trial.

Future Oncol 2021 Apr 25;17(11):1285-1293. Epub 2021 Feb 25.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.

For patients with oligometastatic esophageal squamous cell carcinoma, the efficacy of local therapy is still controversial because of patient selection and lack of adequate controls in most studies. Here the authors design the ESO-Shanghai 13 trial, a prospective, multicenter, randomized, Phase II trial, to assess the impact of combined local therapy and systemic therapy on progression and survival compared with systemic therapy alone for patients with four or less metastases. A total of 102 patients will be recruited over 3 years from approximately five centers and randomized in a 1:1 ratio to receive either systemic therapy alone or systemic therapy and local therapy, such as radiation, surgery and thermal ablation. The primary endpoint is progression-free survival. The secondary endpoints are overall survival, local control, toxicity and quality of life. Clinical trial registration: NCT03904927 (ClinicalTrials.gov).
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http://dx.doi.org/10.2217/fon-2020-0873DOI Listing
April 2021

The pathological significance of LOXL2 in pre-metastatic niche formation of HCC and its related molecular mechanism.

Eur J Cancer 2021 Apr 19;147:63-73. Epub 2021 Feb 19.

Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Feng Lin Road, Shanghai, 200032, PR China. Electronic address:

Objective: The mechanisms underlying the contribution of primary tumour to pre-metastatic niche formation remains largely unknown in hepatocellular carcinoma (HCC). We previously reported that the released LOXL2 from HCC cells under higher stiffness stimulation facilitated the formation of lung pre-metastatic niche. Here, we further clarified the pathological role of LOXL2 in promoting lung pre-metastatic niche formation and lung metastasis occurrence in HCC and its relevant molecular mechanism.

Methods: Using two different animal models and an in vitro system of mechanically tuneable gel mirroring lung tissue stiffness, we explored the underlying mechanism of LOXL2 in pre-metastatic niche formation.

Results: We applied tail vein injection of CM-LV-LOXL2-OEsimulating tumour-released soluble factors to induce lung pre-metastatic niche formation and found that the injected LOXL2 remarkably enhanced CD11b/CD45 bone marrow-derived cells (BMDCs) recruitment and fibronectin expression in lung. Subsequently, LOXL2-overexpressed xenograft HCC models validated that tumour-secreted LOXL2 significantly promoted the occurrence of pulmonary metastasis. In vitro, LOXL2 and LOXL2-caused matrix stiffening not only obviously upregulated the expressions of MMP9 and fibronectin in lung fibroblasts, but also evidently increased the number of adherent HCC cells and the expression of chemokine CXCL12. The activation of PI3K-AKT pathway mediated LOXL2-upregulated fibronectin. HCC patients in High-LOXL2 group had higher ratio of tumour recurrence than HCC patients in Low-LOXL2 group, supporting a significance of LOXL2 in HCC progression and unfavourable outcome.

Conclusion: Primary tumour-released LOXL2 promotes lung pre-metastatic niche formation and lung metastasis occurrence. LOXL2-caused matrix stiffening synergistically regulates lung pre-metastatic niche formation. Targeting LOXL2-induced lung pre-metastatic niche may be a novel intervention approach against HCC metastasis.
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http://dx.doi.org/10.1016/j.ejca.2021.01.011DOI Listing
April 2021

Prognostic factors of non-muscle invasive bladder cancer: a study based on next-generation sequencing.

Cancer Cell Int 2021 Jan 6;21(1):23. Epub 2021 Jan 6.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 37 GuoXueXiang, Chengdu, 610041, People's Republic of China.

Objective: To investigate the genetic prognostic factors for the recurrence of non-muscle invasive bladder cancer.

Materials And Methods: The patients underwent transurethral resection of bladder tumor and received bacillus Calmette-Guérin (BCG) or epirubicin. Next-generation sequencing was performed and alterations of genes, pathways, and tumor mutation burden were recorded. Associations between these clinicopathological and genetic variants were estimated, and prognostic factor identified.

Results: A total of 58 cases were included in our study, and 46 patients underwent treatment with BCG. FGFR3 was the most frequently altered gene (48%), and more commonly detected in intermediate-risk patients. Univariate Cox analysis demonstrated that 10 genes were significantly correlated with BCG failure, while NEB, FGFR1 and SDHC were independent recurrence predictors. Besides, epigenetic-related gene pathway mutations were negatively correlated with recurrence (hazard ratio: 0.198, P = 0.023). DNA damage response and repair gene alterations were positively correlated with tumor burden, while altered TP53 was most frequent among these genes and significant correlated with high tumor burden.

Conclusion: BCG instillation significantly reduced the rate of recurrence compared with epirubicin in this population. Potential biomarkers and therapeutic targets were found with the help of next-generation sequencing; correlations between DDR genes alterations and high tumor mutation burden were also demonstrated.
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http://dx.doi.org/10.1186/s12935-020-01731-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789352PMC
January 2021

MRI-Based Radiomic Model for Preoperative Risk stratification in Stage I Endometrial Cancer.

J Cancer 2021 1;12(3):726-734. Epub 2021 Jan 1.

Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese medicine, Nanjing, Jiangsu Province, China.

Preoperative risk stratification is crucial for clinical treatment of endometrial cancer (EC). This study aimed to establish a model based on magnetic resonance imaging (MRI) and clinical factors for risk classification of EC. A total of 102 patients with pathologically proven Stage I EC were included. Preoperative MRI examinations were performed in all the patients. 720 radiomic features were extracted from T2-weighted images. Least absolute shrinkage and selection operator (LASSO) regression model was performed to reduce irrelevant features. Logistic regression was used to build clinical, radiomic and combined predictive models. A nomogram was developed for clinical application. The radiomic model has a better performance than the model based on clinical and conventional MRI characteristics [AUC of 0.946 (95% CI: 0.882-0.973) vs AUC of 0.756 (95% CI: 0.65, 0.86)]. The combined model consisting of radiomic features and tumor size showed the best predictive performance in the training cohort with AUC of 0.955 in the training and 0.889 in the validation cohorts. MRI-based radiomic model has great potential in prediction of low-risk ECs.
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http://dx.doi.org/10.7150/jca.50872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778535PMC
January 2021

Potential value of guard-wire technology in the interventional treatment for ostial coronary lesions.

BMC Cardiovasc Disord 2020 11 19;20(1):487. Epub 2020 Nov 19.

ICU of Army Special Characteristic Center (Daping Hospital) of PLA, Chongqing, 400000, China.

Background: To explore potential value of guard-wire technology during percutaneous coronary intervention (PCI) in patients with ostial coronary lesions.

Methods: Patients, who underwent PCI, were collected between October 2011 and March 2017. Of the 141 patients, 63 (44.7%) have ostial lesions, and 78 (55.3%) have distal bifurcation sites. They were divided into group A (n = 71) and group B (n = 70). Group A received PCI after guard-wire technology. Group B were given balloon dilation and stent after placing guide wire through target lesion vessel. X-ray exposure time, contrast agent dosage, total PCI duration, pressure incarceration times, cases of malignant arrhythmia and cases of failed PCI of all patients were analyzed, respectively.

Results: The general clinical characteristics includes patients age, sex ratio, the proportion of complications, smoking ratio and left ventricular ejection fraction of both groups was not significantly different. X-ray exposure time, contrast agent dosage, PCI total time, stent positioning time, pressure infestation frequency, arrhythmia frequency and complication number of group B were higher than those of group A. There is no case of malignant arrhythmia and case of failed PCI in group A, while there were five malignant arrhythmia and four failed PCI in group B. Contrast agent dosage and cases of failed PCI increased in group B compared with group A.

Conclusion: The guard wire technology is safer and more feasible to patients with ostial coronary lesions who underwent PCI.
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http://dx.doi.org/10.1186/s12872-020-01779-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678209PMC
November 2020

A novel zinc transporter essential for Arabidopsis zinc and iron-dependent growth.

J Plant Physiol 2021 Jan 2;256:153296. Epub 2020 Nov 2.

Key Laboratory of Forage and Endemic Crop Biotechnology, Ministry of Education, School of Life Sciences, Inner Mongolia University, Hohhot, 010010, PR China; State Key Laboratory of Reproductive Regulatory and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, 010010, PR China. Electronic address:

Zinc (Zn), an essential micronutrient, is absorbed by plant roots and redistributed to leaves. This process must be finely regulated in order to avoid toxic Zn overaccumulation, which can arise due to Zn oversupply or Zn hyperaccumulation induced by Fe deficiency. Although several proteins in Arabidopsis thaliana are essential for retaining Zn in the root and partitioning it from roots to leaves, how Zn homeostasis in leaves is maintained is largely unknown. In this study, we identified a novel Golgi-localized protein named ZINC NUTRIENT ESSENTIAL1 (AtZNE1,At3g08650) in Arabidopsis. AtZNE1 contains 14 putative transmembrane domains. AtZNE1 promoter has strong activity in the root and leaf. Its expression complemented the increased sensitivity of a yeast mutant to excess Zn. The disruption of AtZNE1 in the T-DNA insertion mutant atzne1 caused growth defect under excess-Zn or Fe deficit conditions, but had no effects on the total Zn and Fe contents. We propose that AtZNE1 plays a vital role in plant adaptation to excess Zn or Fe deficiency.
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http://dx.doi.org/10.1016/j.jplph.2020.153296DOI Listing
January 2021

The Predictive Value of Pre-therapeutic Serum Gamma-glutamyl transferase in Efficacy and Adverse Reactions to Neoadjuvant Chemotherapy among Breast Cancer Patients.

J Breast Cancer 2020 Oct 28;23(5):509-520. Epub 2020 Oct 28.

Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Purpose: Gamma-glutamyl transferase (GGT) has been reported as being involved in tumor progression. Previous studies documented a potential relationship between serum GGT level and survival outcome in several types of human malignancies. However, the association between serum GGT levels and response to neoadjuvant chemotherapy (NAC) has not yet been reported. The present study aimed to evaluate the association between pre-therapeutic serum GGT level and the efficacy, long-term survival, and adverse reactions of NAC and to investigate its role in predicting NAC sensitivity in patients with breast cancer.

Methods: A total of 129 patients were recruited and stratified into 2 groups according to serum GGT level (< 29 U/L and ≥ 29 U/L). The association between pre-therapeutic serum GGT levels and clinicopathological parameters was examined. The correlation between pre-therapeutic serum GGT levels and pathological complete response (pCR) was analyzed using univariate and multivariate logistic regression. Survival analyses of relapse-free survival (RFS) and disease-free survival (DFS) were performed. Pearson's χ test and multivariate logistic regression model were used to analyze the correlation between pre-therapeutic serum GGT levels and adverse reactions.

Results: Pre-therapeutic serum GGT levels were associated with pCR among breast cancer patients treated with NAC. Multivariate analysis showed that low-level GGT significantly increased pCR rate. Patients in the high-level GGT group had poorer survival than those in the low-level GGT group. Subgroup analysis demonstrated that serum GGT level was potentially related to RFS and DFS in the hormone receptor-positive group. Low levels of GGT are significantly associated with a higher incidence of neutropenia.

Conclusion: Pre-therapeutic serum GGT level is an independent and novel biomarker for predicting the efficiency, prognosis, and adverse reactions to NAC in breast cancer patients. Patients with low pre-therapeutic serum GGT levels are more likely to have higher pCR rates, better RFS and DFS, and higher hematologic toxicity.

Trial Registration: ClinicalTrials.gov Identifier: NCT02199418, NCT02221999.
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http://dx.doi.org/10.4048/jbc.2020.23.e59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604370PMC
October 2020

Distinct clinicopathological differences between early gastric cardiac and non-cardiac carcinomas: a single-center retrospective study of 329 radical resection cases.

BMC Gastroenterol 2020 Oct 21;20(1):351. Epub 2020 Oct 21.

Department of Pathology, Nanjing Drum Tower Hospital, Nanjing, China.

Background: Early gastric carcinoma is heterogeneous and can be divided into early gastric cardiac carcinoma (EGCC) and early gastric non-cardiac carcinoma (EGNCC) groups. At present, differences in clinicopathology remains obscure between EGCC and EGNCC fundus-corpus and antrum-angularis-pylorus subgroups, especially between EGCC with and without oesophageal invasion.

Methods: In this study, we studied 329 consecutive early gastric carcinoma radical gastrectomies with 70 EGCCs and 259 EGNCCs.

Results: Compared to the EGNCC antrum-angularis-pylorus (n = 181), but not fundus-corpus (n = 78), sub-group, EGCC showed significantly older age, lower prevalence of the grossly depressed pattern, better tumor differentiation, higher percentage of tubular/papillary adenocarcinoma, but lower frequency of mixed poorly cohesive carcinoma with tubular/papillary adenocarcinoma, and absence of lymph node metastasis (LNM) in tumors with invasion up to superficial submucosa (SM1). In contrast, pure poorly cohesive carcinoma was less frequently seen in EGCCs than in EGNCCs, but mixed poorly cohesive carcinoma with tubular/papillary adenocarcinomas was significantly more common in the EGNCC antrum-angularis-pylorus sub-group than in any other group. No significant differences were found between EGCC and EGNCC sub-groups in gender, tumor size, H. pylori infection rate, and lymphovascular/perineural invasion. EGCC with oesophageal invasion (n = 22), compared to EGCC without (n = 48), showed no significant differences in the H. pylori infection rate and oesophageal columnar, intestinal, or pancreatic metaplasia, except for a higher percentage of the former in size > 2 cm and tubular differentiation.

Conclusions: There exist distinct clinicopathologic differences between EGCC and EGNCC sub-groups; EGCC was indeed of gastric origin. Further investigations with larger samples are needed to validate these findings.
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http://dx.doi.org/10.1186/s12876-020-01498-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579997PMC
October 2020

[Current status analysis of bystander cardiopulmonary resuscitation for out-of-hospital cardiac arrest in Qinhuangdao region based on Utstein model].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Sep;32(9):1096-1100

The Health Emergency Dispatch Center of Qinhuangdao City, Qinhuangdao 066000, Hebei, China. Corresponding author: Wang Yaohui, Email:

Objective: To analyze the status quo of bystander cardiopulmonary resuscitation (BCPR) for out-of-hospital cardiac arrest (OHCA) in Qinhuangdao area and its influence on the prognosis of cardiopulmonary resuscitation (CPR).

Methods: Based on the Utstein model CPR database of Qinhuangdao, data of 1 162 OHCA patients admitted to the Health Emergency Dispatch Center of Qinhuangdao City from January 2018 to January 2019 were collected, and they were divided into two groups according to whether BCPR was performed or not. The patients' demographic parameters (gender, age), precardiac arrest parameters (location of cardiac arrest), the parameters of the CPR (first aid response time before hospital, initial diagnosis of causes of cardiac arrest, initial cardiac rhythm) and the parameters of the CPR results [whether to achieve on-site restoration of spontaneous circulation (ROSC) and 30-day survival rate] were collected. Multivariate Logistic regression analysis was performed for the relationship between BCPR and on-site ROSC rate. The social characteristics of bystanders implementing BCPR, including gender, age, occupation, educational background, and acquisition method of CPR knowledge, were analyzed.

Results: Among the 1 162 OHCA patients, the patients witnessed by professional medical personnel in nursing homes, hospitals and other places and pre-hospital emergency personnel were excluded. 852 OHCA patients were enrolled, among which only 24 patients obtained BCPR (2.8%), and the remaining 828 patients did not obtain BCPR (97.2%). There were no statistically significant differences in gender, age, location of cardiac arrest, pre-hospital emergency response time, primary diagnosis of cardiac arrest causes and initial cardiac rhythm between the two groups. Compared with the non-BCPR group, the on-site ROSC rate and the 30-day survival rate of the BCPR group were significantly increased [on-site ROSC rate: 16.7% (4/24) vs. 5.2% (43/828), 30-day survival rate: 8.3% (2/24) vs. 1.3% (11/828), both P < 0.05]. Multivariate Logistic regression analysis showed that BCPR [odds ratio (OR) = 32.132, 95% confidence interval (95%CI) was 11.129-65.471], location of cardiac arrest (OR = 0.080, 95%CI was 1.212-3.125) and response time during pre-hospital emergency treatment (OR = 0.121, 95%CI was 0.174-0.816) were important factors for on-site ROSC of OHCA patients (all P < 0.01). A total of 30 bystanders participated in the implementation of OHCA patients' BCPR, excluding 2 bystanders of lost follow-up, 28 bystanders with effective return visit. The 28 bystanders of BCPR practitioners were mainly male (85.7%), the age was mainly 18-40 years old (57.1%), the occupation was mainly in the tourism service industry (21.5%), students (17.9%), soldiers (14.3%) and bus drivers (10.7%), and the education background was mainly junior college or above (85.7%), the methods of acquiring CPR knowledge mainly included APP and new media (42.9%) and lectures (21.4%).

Conclusions: The BCPR implementation rate of OHCA in Qinhuangdao was only 2.8%. BCPR can improve the success rate of pre-hospital CPR and the 30-day survival rate of OHCA patients. Targeted selection of tourism service industry, students, military personnel and bus drivers as CPR training targets may obtain more significant social benefits.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200714-00520DOI Listing
September 2020

Tumor-Associated Neutrophils Can Predict Lymph Node Metastasis in Early Gastric Cancer.

Front Oncol 2020 21;10:570113. Epub 2020 Sep 21.

Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

The consensus of endoscopic therapy for early gastric cancer (EGC) mainly depends on its clinicopathological features. However, the roles of tumor-associated neutrophils (TANs) in EGC remain uncertain. Here, we explored its predictive role for lymph node metastasis (LNM) in EGC. Three hundred twenty-two patients who underwent radical gastrectomy for EGC were enrolled. Preoperative peripheral blood was used to analyze the neutrophil-to-lymphocyte ratio (NLR), and the different status of TANs was determined by hematoxylin-and-eosin staining (H&E) and immunohistochemistry (IHC). TANs, rather than NLR, were positively associated with tumor size, Lauren classification, lymphovascular invasion (LVI), and LNM. Univariate analysis revealed that TANs were associated with LNM as well as tumor size, depth of invasion, Lauren classification, histological classification, LVI, and perineural invasion. In addition to histological classification and LVI, TANs were found to be an independent risk factor for LNM in EGC ( = 0.013). Stratification analysis by depth of invasion showed LVI in SM1 tumor, and both LVI and TANs ( = 0.042) in SM2 tumor were independent risk factors for LNM. In conclusion, TANs in EGC can predict LNM, and TANs may help to estimate LNM precisely in addition to the current criteria.
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http://dx.doi.org/10.3389/fonc.2020.570113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537418PMC
September 2020

A point-of-care selenium nanoparticle-based test for the combined detection of anti-SARS-CoV-2 IgM and IgG in human serum and blood.

Lab Chip 2020 11;20(22):4255-4261

Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cellular and Molecular Immunology of Henan Province, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China.

COVID-19 is a widespread and highly contagious disease in the human population. COVID-19 is caused by SARS-CoV-2 infection. There is still a great demand for point-of-care tests for detection, epidemic prevention and epidemiological investigation, both now and after the epidemic. We present a lateral flow immunoassay kit based on a selenium nanoparticle-modified SARS-CoV-2 nucleoprotein, which detects anti-SARS-CoV-2 IgM and anti-SARS-CoV-2 IgG in human serum, and the results can be read by the naked eye in 10 minutes. We expressed and purified the SARS-CoV-2 nucleoprotein in HEK293 cells, with a purity of 98.14% and a concentration of 5 mg mL-1. Selenium nanoparticles were synthesized by l-ascorbic acid reduction of seleninic acid at room temperature. After conjugation with the nucleoprotein, a lateral flow kit was successfully prepared. The IgM and IgG detection limits of the lateral flow kit reached 20 ng mL-1 and 5 ng mL-1, respectively, in human serum. A clinical study sample comprising 90 COVID-19-diagnosed patients and 263 non-infected controls was used to demonstrate a sensitivity and specificity of 93.33% and 97.34%, respectively, based on RT-PCR and clinical results. No cross-reactions with rheumatoid factor and positive serum for anti-nuclear antibodies, influenza A, and influenza B were observed. Moreover, the lateral flow kit remained stable after storage for 30 days at 37 °C. Our results demonstrate that the selenium nanoparticle lateral flow kit can conveniently, rapidly, and sensitively detect anti-SARS-CoV-2 IgM and IgG in human serum and blood; it can also be suitable for the epidemiological investigation of COVID-19.
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http://dx.doi.org/10.1039/d0lc00828aDOI Listing
November 2020

Matrix stiffness-mediated effects on macrophages polarization and their LOXL2 expression.

FEBS J 2020 Sep 22. Epub 2020 Sep 22.

Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.

Previously, we reported that the secreted lysyl oxidase like 2 (LOXL2) from hepatocellular carcinoma (HCC) cells under higher stiffness stimulation contributed to the formation of lung premetastatic niche. To further clarify whether matrix stiffness also alters LOXL2 expression in other cells within tumor microenvironment, we developed a gel-based culture system combined with a model of macrophage polarization to evaluate the effects of matrix stiffness on the polarization of M2 macrophages and their LOXL2 expression. THP-1 cells cultured on 6KPa, 10KPa, and 16KPa stiffness substrates were first incubated with 100nM phorbol 12-myristate 13-acetate (PMA) for 24 hours and subsequently treated with 20nM interleukin-4 (IL-4) and 20nM interleukin-13 (IL-13) for 48 hours. The polarization states of M2 macrophages under different stiffness stimulation were comparatively analyzed, and their LOXL2 expressions as well as the underlying molecular mechanism were further explored. Our results demonstrated that increased matrix stiffness remarkably strengthened M2 macrophage polarization and promoted their LOXL2 expression. Activation of integrin β5-FAK-MEK1/2-ERK1/2 pathway participated in matrix stiffness-mediated HIF-1α upregulation, and HIF-1α upregulation resulted in a significant improvement in LOXL2 expression. Additionally, M2 macrophage polarization state and LOXL2 expression in HCC tissues with COL1 /LOX were consistent with the results in vitro, further confirming the regulation roles of matrix stiffness in macrophage polarization and LOXL2 expression. The findings about LOXL2 upregulation in the polarized macrophages under higher stiffness stimulation will be helpful to better understand the underlying mechanism of matrix stiffness-induced premetastatic niche formation in HCC.
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http://dx.doi.org/10.1111/febs.15566DOI Listing
September 2020

The impact of gene polymorphisms on the response and toxicity derived from neoadjuvant chemotherapy for breast cancer.

Gland Surg 2020 Aug;9(4):925-935

Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Background: Neoadjuvant chemotherapy is usually used for treating locally advanced breast cancer. However, not all patients achieve pathologic complete response (pCR). In this study, we selected two epidermal growth factor receptor (EGFR) single nucleotide polymorphism (SNP) sites, rs1468727 and rs845552, to investigate the association between the genotypes and the response and toxicity derived from neoadjuvant chemotherapy for breast cancer.

Methods: All participants took part in clinical trial SHPD001 and SHPD002. For univariate analyses, the association between SNP and pCR or toxicity was analyzed by Chi-square or Fisher's exact test. For multivariate analyses, logistic regression was used instead.

Results: In all, one hundred and eighteen patients were enrolled. We found that the frequency of AA genotype in rs845552 was higher than that of other genotypes in HER2-positive breast cancer (AA AG, P=0.039; AA GG, P=0.005; AA AG+GG, P=0.009). Multivariate logistic regression analyses showed that pCR was more difficult to be achieved in patients with a CT genotype in rs1468727 compared to those with a CC+TT genotype (OR =0.288, 95% CI: 0.109-0.762, P=0.012) or a CC genotype (OR =0.254, 95% CI: 0.076-0.849, P=0.026). Moreover, we demonstrated that both rs1468727 and rs845552 were associated with toxicity that results in complications such as increased total bilirubin, skin rash, peripheral neuropathy, and alopecia (P<0.05).

Conclusions: Our study reported for the first time, that in treating breast cancer with neoadjuvant chemotherapy, EGFR SNP rs1468727 is associated with treatment response, and that both rs1468727 and rs845552 are related to treatment-derived toxicity. In addition, we also found that rs845552 may be related to the status of HER2 in breast cancer.
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http://dx.doi.org/10.21037/gs-20-330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475355PMC
August 2020

A three-dimensional multiscale finite element model of bone coupling mineralized collagen fibril networks and lamellae.

J Biomech 2020 11 9;112:110041. Epub 2020 Sep 9.

Department of Mechanical Engineering, Villanova University, 800 Lancaster Avenue, Villanova, PA, United States. Electronic address:

Despite evidence of contribution of mineralized collagen fibrils (MCF) to both the microscale elastic and fracture response of bone, the extent of influence of MCF orientation and material property variation on the lamellar scale mechanical properties is still not well quantified. To this end, in this study, we developed a three-dimensional multiscale finite element model that linked submicroscale models of MCF networks to microscale models of several lamellae. The developed models evaluated the individual and relative influence of MCF orientation as well as material property variation due to MCF mineral distribution and interaction on the lamellar scale mechanical response of bone. The simulation results showed that the elastic modulus, ultimate strength, and fracture energy at the lamellar scale decreased as the angle between the main axis of MCFs and loading direction increased. The heterogeneity in mineral distribution along MCFs did not lead to a significant difference in the mechanical behavior at the lamellar scale compared to the material property heterogeneity introduced in the models due to MCF orientation variation. Variation in the interaction between MCFs at the submicroscale had a substantial influence on the lamellar scale mechanical properties. In summary, this study established a multiscale model that linked MCFs to lamellae providing the capability of quantifying the relative influence of modifications in material and organizational properties of MCFs due to age, diseases, and treatments on the fracture processes at the lamellar length scale.
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http://dx.doi.org/10.1016/j.jbiomech.2020.110041DOI Listing
November 2020

Integrin αVβ5/Akt/Sp1 pathway participates in matrix stiffness-mediated effects on VEGFR2 upregulation in vascular endothelial cells.

Am J Cancer Res 2020 1;10(8):2635-2648. Epub 2020 Aug 1.

Department of Interventional Radiology, Fudan University Shanghai Cancer Center Shanghai 200032, People's Republic of China.

Our previous study has validated that higher matrix stiffness obviously improves vascular endothelial growth factor (VEGF) expression in HCC cells, highlighting a linkage between matrix stiffness and HCC angiogenesis. However, the effects of matrix stiffness on vascular endothelial cells in HCC and its underlying mechanism remain largely uncharacterized. Here we further analyzed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) in human umbilical vein endothelial cells (HUVECs) grown on different stiffness substrates and explored its regulatory mechanism for better understanding matrix stiffness-regulated angiogenesis in HCC. Our results revealed that increased matrix stiffness significantly upregulated the expression of VEGFR2 in HUVECs, and the expression level of VEGFR2 was positively correlated with the expression levels of COL1 and lysyl oxidase in human HCC tissues and rat HCC tissue, moreover VEGFR2 and CD34 were co-localized at blood vessel of HCC tissues, indicating an obvious regulation role of matrix stiffness in VEGFR2 expression. Simultaneously, increased matrix stiffness also elevated the phosphorylation level of Akt and the expressions of integrin αV/β5 and nuclear Sp1 in HUVECs. Inhibition of integrin αVβ5 remarkably reversed the expression of VEGFR2 and phosphorylation level of Akt in HUVECs grown on higher stiffness substrate. Except that, PI3K inhibitor also suppressed the phosphorylation level of Akt and the expressions of VEGFR2 and nuclear Sp1 evidently. Taken together, higher matrix stiffness increased VEGFR2 expression in HUVECs, and integrin αVβ5/Akt/Sp1 pathway participated in stiffness-mediated effects on VEGFR2 upregulation. This study combining with our previous report discloses a new paradigm in which higher matrix stiffness as an initiator drives HCC angiogenesis via upregulating both VEGFR2 expression in vascular endothelial cells and VEGF expression in HCC cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471346PMC
August 2020

Predictive and prognostic value of EPIC1 in patients with breast cancer receiving neoadjuvant chemotherapy.

Ther Adv Med Oncol 2020 24;12:1758835920940886. Epub 2020 Jul 24.

Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160 Pujian Road, Shanghai 200127, People's Republic of China.

Background: EPIC1 is an oncogenic long non-coding ribonucleic acid (RNA) that promotes cell growth and cell-cycle progression and inhibits apoptosis in several cancer cell lines. However, clinical studies on EPIC1 in breast cancer, specifically in the neoadjuvant setting, are relatively few.

Methods: Patients treated with weekly paclitaxel-cisplatin-based neoadjuvant chemotherapy after core-needle biopsy were included in the study. Real-time quantitative polymerase chain reaction assays were performed to detect EPIC1 expression.

Results: Among all patients included in this study ( = 111), higher EPIC1 expression was associated with estrogen receptor negativity, human epidermal growth factor receptor 2 positivity, higher Ki67 index, and higher histologic grade. Multivariate analysis suggested that EPIC1 expression was an independent predictive factor for pathological complete response, with a significant interaction between EPIC1 expression and age. The Kaplan-Meier Plotter dataset suggested that the EPIC1 high-expression group showed a worse 10-year distant metastasis-free survival and post-progression survival when compared with the EPIC1 low-expression group. The Cancer Genome Atlas dataset suggested that the overall survival in the EPIC1 high-expression group was inferior to that in the EPIC1 low-expression group, specifically in hormone receptor (HorR)-positive patients and patients aged <50 years. Pathway analysis revealed the top pathways that indicated the potential mechanisms of EPIC1 in chemoresistance, including the daunorubicin and doxorubicin metabolic processes.

Conclusions: Our study suggests that EPIC1 may be a promising biomarker for both neoadjuvant chemosensitivity and long-term clinical outcomes in breast cancer, specifically in the HorR-positive premenopausal subgroup. It may also help identify candidate responders and determine treatment strategies.
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http://dx.doi.org/10.1177/1758835920940886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383657PMC
July 2020

The value of the apparent diffusion coefficient in differentiating type II from type I endometrial carcinoma.

Acta Radiol 2020 Jul 29:284185120944913. Epub 2020 Jul 29.

Department of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China.

Background: Diagnostic type II endometrial carcinoma (EC) is considered more aggressive and has a poorer prognosis than type I EC; differentiation between them is helpful for preoperative clinical decision-making. However, the diagnostic value of the apparent diffusion coefficient (ADC) in differentiating them remains unclear.

Purpose: To investigate the value of ADC in differentiating type II EC from type I EC.

Material And Methods: Ninety-four patients with EC who underwent diffusion-weighted imaging (DWI) were retrospectively included and divided into type I and type II subgroups, based on the postoperative pathologic results. We analyzed the clinical characteristics, conventional magnetic resonance imaging manifestations, and ADC mean values (ADC), ADC minimum values (ADC), and ADC max values (ADC). Receiver operating characteristic (ROC) curve analysis was further used to assess the predictive performance.

Results: The ADC, ADC, and tumor size differed significantly between the two subtypes. The area under the ROC curve (AUC) for ADC and ADC was 0.787 (95% confidence interval [CI] = 0.692-0.88) and 0.835 (95% CI = 0.751-0.919) for predicting type II EC, respectively. The optimal cut-off value of ADC for prediction was 0.757 × 10 mm/s with a sensitivity of 91%, a specificity of 58%, and an accuracy of 74%, while for ADC was 0.637 × 10 mm/s with a sensitivity of 82%, a specificity of 73%, and an accuracy of 75%.

Conclusion: EC with lower ADC and ADC values derived from DWI, and a larger size, are indicative of type II EC.
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http://dx.doi.org/10.1177/0284185120944913DOI Listing
July 2020

Evaluation of the Efficacy and Safety of PARP Inhibitors in Advanced-Stage Epithelial Ovarian Cancer.

Front Oncol 2020 3;10:954. Epub 2020 Jul 3.

Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

PARP inhibitors are a novel targeted anti-cancer drug and a large number of clinical studies on PARP inhibitors have been accomplished. This updated meta-analysis was conducted to evaluate the efficacy and safety of PARP inhibitors in advanced-stage epithelial ovarian cancer. Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus were searched to identify the eligible trials up to April 2020. ClinicalTrials.gov was also screened for additional unpublished trials. Data extraction and risk of bias assessment were performed by two independent investigators, respectively. The hazard ratios (HRs) and its 95% confidence intervals (CI) for time-to-event data of progression-free survival (PFS) and overall survival (OS), and the risk ratios (RRs) with 95% CI for dichotomous data of overall response rate (ORR) and occurrence of adverse events (AEs) were calculated by Review Manager 5.3 and Stata 12.0 software. A total of 12 trials with 5,347 patients were included in this meta-analysis. Compared with the control group, PARP inhibitors significantly improved PFS (HR, 0.51; 95% CI, 0.40-0.65; < 0.00001) and ORR (RR, 1.26; 95% CI, 1.11-1.43; = 0.0003). Specifically, PFS was improved regardless of genes mutations and homologous-recombination status. However, no difference was observed in OS between the PARP inhibitors group and the control group (95% CI, 0.73-1.01; = 0.06). PARP inhibitors were associated with a statistically significant higher risk of hematologic events and different PARP inhibitors had different toxicities profiles. PARP inhibitors are an effective and well-tolerated treatment for patients with advanced-stage epithelial ovarian cancer.
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http://dx.doi.org/10.3389/fonc.2020.00954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350528PMC
July 2020

Sentinel node theory helps tracking of primary lesions of cancers of unknown primary.

BMC Cancer 2020 Jul 9;20(1):639. Epub 2020 Jul 9.

Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-an Rd, Shanghai, 200032, China.

Background: Sentinel lymph node is the first stop of lymphatic spreading of cancer with known primary. The lymph node metastasis pattern of cancer of unknown primary (CUP) is unclear and has been presumed to follow the same pathway. To test this hypothesis, data of all 716 patients clinically diagnosed as CUP in our center were collected.

Methods: Diagnoses of lymph node metastasis were established by F-FDG PET-CT and/or biopsy pathology. Three hundred and forty-seven cases meeting the criteria were divided into three groups: pathology-confirmed primary with invasive biopsy or surgery of the suspicious lesion (group A, n = 64), primary still unknown even with invasive biopsy or surgery of the suspicious lesion (group B, n = 204), and others with no suspicious lesion or lesions who had not been sampled due to medical or other reasons (group C, n = 79). We assessed the clinicopathological features between these groups, and the relationship between lymph node metastasis pattern and confirmed primary site.

Results: In group A, the primary sites of 61 cases were compatible with sentinel node theory, resulting in a positive predictive value of 95%. No significant differences in age, sex, bone metastasis, or visceral metastasis observed between group A and group B, except that group A had a higher ratio of differentiated carcinoma (94% vs. 77%, P = 0.003).

Conclusion: To our knowledge, this is the first evidence indicating that the majority of clinical CUP cases follow the sentinel node theory to spread in lymph nodes, which helps tracking the primary, especially for differentiated carcinoma.
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http://dx.doi.org/10.1186/s12885-020-07042-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350562PMC
July 2020

Soluble uric acid induces myocardial damage through activating the NLRP3 inflammasome.

J Cell Mol Med 2020 08 18;24(15):8849-8861. Epub 2020 Jun 18.

Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cellular and Molecular Immunology of Henan Province, School of Basic Medicine, Henan University, Kaifeng, China.

Uric acid crystal is known to activate the NLRP3 inflammasome and to cause tissue damages, which can result in many diseases, such as gout, chronic renal injury and myocardial damage. Meanwhile, soluble uric acid (sUA), before forming crystals, is also related to these diseases. This study was carried out to investigate whether sUA could also activate NLRP3 inflammasome in cardiomyocytes and to analyse the mechanisms. The cardiomyocyte activity was monitored, along with the levels of mature IL-1β and caspase-1 from H9c2 cells following sUA stimulus. We found that sUA was able to activate NLRP3 inflammasome, which was responsible for H9c2 cell apoptosis induced by sUA. By elevating TLR6 levels and then activating NF-κB/p65 signal pathway, sUA promoted NLRP3, pro-caspase 1 and pro-IL-1β production and provided the first signal of NLRP3 inflammasome activation. Meanwhile, ROS production regulated by UCP2 levels also contributed to NLRP3 inflammasome assembly and subsequent caspase 1 activation and mature IL-1β secretion. In addition, the tlr6 knockdown rats suffering from hyperuricemia showed the lower level of IL-1β and an ameliorative cardiac function. These findings suggest that sUA activates NLRP3 inflammasome in cardiomyocytes and they may provide one therapeutic strategy for myocardial damage induced by sUA.
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http://dx.doi.org/10.1111/jcmm.15523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412683PMC
August 2020

Serum miR-222-3p as a Double-Edged Sword in Predicting Efficacy and Trastuzumab-Induced Cardiotoxicity for HER2-Positive Breast Cancer Patients Receiving Neoadjuvant Target Therapy.

Front Oncol 2020 28;10:631. Epub 2020 Apr 28.

Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

We aimed to explore whether the expression of serum miR-222-3p might contribute to early prediction of therapeutic response, clinical outcomes, and adverse events for HER2-positive breast cancer patients receiving neoadjuvant therapy (NAT). A total of 65 HER2-positive breast cancer patients receiving NAT were analyzed. The concentration of serum miR-222-3p was detected by quantitative real-time PCR. Logistic regression analysis was used to identify the association of serum miR-222-3p with pathological complete response (pCR). The relationship of serum miR-222-3p with disease-free survival (DFS) and overall survival (OS) was examined via log-rank test and Cox proportional hazards analysis. The ordered logistic regression was applied to evaluate the association between serum miR-222-3p and adverse events. The miR-222-3p low group was more likely to achieve pCR [odds ratio (OR) = 0.258, = 0.043]. The interaction between miR-222-3p and presenting Ki67 level was also detected for pCR (OR = 49.230, = 0.025). The miR-222-3p low group was correlated with superior DFS ( = 0.029) and OS ( = 0.0037). The expression of serum miR-222-3p was the independent protective factor for trastuzumab-induced cardiotoxicity ( < 0.05) and anemia ( = 0.013). Serum miR-222-3p is the potential factor to predict pCR, survival benefit and trastuzumab-induced cardiotoxicity for HER2-positive breast cancer patients receiving NAT.
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http://dx.doi.org/10.3389/fonc.2020.00631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212359PMC
April 2020

Polysaccharides Improve Testicular Spermatogenic Function in Streptozotocin-Induced Diabetic Rats.

Front Endocrinol (Lausanne) 2020 17;11:164. Epub 2020 Apr 17.

Department of Reproductive Medical Center, The Affiliated Hospital of Guilin Medical University, Guilin, China.

The objective of this study was to investigate the protective effects of polysaccharides (LBP) on testicular spermatogenic function in streptozotocin (STZ)-induced diabetic rats. Compared to the control group, blood glucose levels were significantly increased and the insulin resistance was markedly aggravated in STZ-induced diabetic rats. Further, the weight of testis and epididymis and the sperm number and motility were decreased in diabetic rats. Pathological changes were also observed in the spermatogenic tubules, along with a decreased number of spermatogenic cells, downregulated proliferating cell nuclear antigen (PCNA) expression, and increased cell apoptosis in the testes. Compared to the saline-treated diabetic rat group, metformin and LBP treatment significantly decreased the level of blood glucose and improved insulin resistance and testicular function. After treatment with metformin and LBP, the pathological changes in the spermatogenic tubules improved significantly, with an increase in the number of spermatogenic cells, upregulation of PCNA, and suppression of apoptosis in the testes. The expressions of sirtuin 1 (SIRT1) and hypoxia-inducible factor 1-alpha (HIF-1α) in diabetic testes were also upregulated by metformin or LBP treatment. In summary, LBP exerted protective effects by increasing cell proliferation, inhibiting cell apoptosis, and regulating SIRT1/HIF-1α expression in the testes of diabetic rats.
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http://dx.doi.org/10.3389/fendo.2020.00164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181356PMC
March 2021

Blocking the death checkpoint protein TRAIL improves cardiac function after myocardial infarction in monkeys, pigs, and rats.

Sci Transl Med 2020 04;12(540)

Henan University affiliated Huaihe Hospital, Kaifeng 475004, P.R. China.

Myocardial infarction (MI) is a leading cause of death worldwide for which there is no cure. Although cardiac cell death is a well-recognized pathological mechanism of MI, therapeutic blockade of cell death to treat MI is not straightforward. Death receptor 5 (DR5) and its ligand TRAIL [tumor necrosis factor (TNF)-related apoptosis-inducing ligand] are up-regulated in MI, but their roles in pathological remodeling are unknown. Here, we report that blocking TRAIL with a soluble DR5 immunoglobulin fusion protein diminished MI by preventing cardiac cell death and inflammation in rats, pigs, and monkeys. Mechanistically, TRAIL induced the death of cardiomyocytes and recruited and activated leukocytes, directly and indirectly causing cardiac injury. Transcriptome profiling revealed increased expression of inflammatory cytokines in infarcted heart tissue, which was markedly reduced by TRAIL blockade. Together, our findings indicate that TRAIL mediates MI directly by targeting cardiomyocytes and indirectly by affecting myeloid cells, supporting TRAIL blockade as a potential therapeutic strategy for treating MI.
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http://dx.doi.org/10.1126/scitranslmed.aaw3172DOI Listing
April 2020