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Introduction
Brain tumor and neuropathology
Current institution
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January 2000 - present
Publications
Publications (493)
The effectiveness of cancer treatment has been significantly improved through combined therapies that synergistically utilize multiple treatment modalities. While combination strategy mitigates tumor resistance, enhances therapeutic efficacy, and reduces side effects compared to monotherapies, the precise coordination of treatment sequences and tim...
Background
TFE3-rearranged perivascular epithelioid cell tumor (PEComa)-like neoplasm is a recently recognized mesenchymal tumor with melanocytic immunophenotype and TFE3 gene rearrangement, but often lacking smooth muscle differentiation. Herein, we present a case of TFE3-rearranged PEComa-like neoplasm of the kidney to expand its clinicopathologi...
Anorexia nervosa (AN) is a severe psychiatric disorder characterized by substantial heritability and a high mortality rate among psychiatric disorders. While cerebrospinal fluid (CSF) metabolomics has emerged as a novel approach to investigating central nervous system pathologies, its specific causal relationship with anorexia nervosa remains to be...
Purpose
Neoadjuvant immunochemotherapy (NAIC) markedly induces pathologic regression in locally advanced gastric adenocarcinoma. However, specific biomarkers are still lacking to effectively identify the beneficiary patients for NAIC.
Patients and Methods
A prospective, single-arm, phase II study was conducted to treat locally advanced gastric ade...
Dysregulation of the transforming growth factor‐β (TGF‐β) signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug‐resistant CSCs. Through a genome‐wide CRISPR activation screen utilizing stem‐like drug‐resistant properties as a readout...
Hepatocellular carcinoma (HCC) acquires an immunosuppressive microenvironment, leading to unbeneficial therapeutic outcomes. Hyaluronan-mediated motility receptor (HMMR) plays a crucial role in tumor progression. Here, we found that aberrant expression of HMMR could be a predictive biomarker for the immune suppressive microenvironment of HCC, but t...
With the continuous development of informatization, digitalization and artificial intelligence technology, the working mode of the pathology department has gradually changed from the traditional manual check, paper circulation and physical carrier storage to the informatization process and digital storage. The traditional pathology discipline has u...
Background
Anlotinib is a new type of tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors 1/2/3, platelet-derived growth factor receptors α/β, and fibroblast growth factor receptors 1–4 and c-Kit, with a broad spectrum of inhibitory effects on tumor angiogenesis and growth. It has been proven effective in HER2-negati...
Radiotherapy is one of the standard therapeutic regimens for medulloblastoma (MB). Tumor cells utilize DNA damage repair (DDR) mechanisms to survive and develop resistance during radiotherapy. It has been found that targeting DDR sensitizes tumor cells to radiotherapy in several types of cancer, but whether and how DDR pathways are involved in the...
The peptidyl-prolyl cis-trans isomerase Pin1 is a pivotal therapeutic target in cancers, but the regulation of Pin1 protein stability is largely unknown. High Pin1 expression is associated with SUMO1-modified protein hypersumoylation in glioma stem cells (GSCs), but the underlying mechanisms remain elusive. Here we demonstrate that Pin1 is deubiqui...
Background
Mesenchymal stem cells (MSCs) are adult stem cells with self-renewal and multi-directional differentiation potential and possess the functions of immunomodulation, regulation of cell growth, and repair of damage. Over recent years, MSCs have been found to regulate the secretion of inflammatory factors and to exert regulatory effects on v...
The genomic instability (GI) /homologous recombination deficiency (HRD) score, calculated as the sum of the events of loss of heterozygosity (LOH), large-scale state transition (LST) and telomere allele imbalance (TAI), is used to guide the choice of treatment in several cancers, but its relationship with genomic features, clinicopathological chara...
Effective treatment for metastasis, a leading cause of cancer‐associated death, is still lacking. To seed on a distal organ, disseminated cancer cells (DCCs) must adapt to the local tissue microenvironment. However, it remains elusive how DCCs respond the pro‐metastatic niche signals. Here, systemic motif‐enrichment identified myocyte enhancer fact...
PARP (poly(ADP-ribose) polymerase) inhibitors have demonstrated promising clinical activity in multiple homologous recombination (HR) deficiency tumors. However, glioblastoma (GBM) patients have obtained little benefit from PARP inhibitors alone. PARP inhibition shows considerable promise when used together with other therapeutic agents. Thus, nove...
Nanomedicine‐based synergy of chemodynamic therapy (CDT) and radiotherapy (RT) modulated by tumor microenvironment enables rapid tumor ablation, which holds great hope for the refractory and recurrent cancers, such as triple negative breast cancer (TNBC). The clinical translation of hafnium oxide (HfO2), commercially named as NBTXR3, has aroused ne...
Heart dysfunction is one of the most life-threatening organ dysfunctions caused by coronavirus disease 2019 (COVID-19). Myocardial or cardiovascular damage is the most common extrapulmonary organ complication in critically ill patients. Understanding the pathogenesis and pathological characteristics of myocardial and vascular injury is important fo...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-caused coronavirus disease 2019 (COVID-19) is a global crisis with no satisfactory therapies. Vitamin D3 (VD3) is considered a potential candidate for COVID-19 treatment; however, little information is available regarding the exact effects of VD3 on SARS-CoV-2 infection and the...
Gliomas are not only among the most vascular-rich solid tumors, but also the most common primary brain tumors. The vascular morphology and molecular characteristics of gliomas are heterogeneous. Pericytes are one of the important cell components in glioma vascular structure and are highly heterogenies. However, the heterogeneity of pericytes in gli...
Radiotherapy (RT) is one of the important clinical treatments for local control of triple-negative breast cancer (TNBC), but radioresistance still exists. Ferroptosis has been recognized as a natural barrier for cancer progression and represents a significant role of RT-mediated anticancer effects, while the simultaneous activation of ferroptosis d...
Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland-type tumor newly recognized in recent years, with approximately 21 cases reported to date in the English literature, which constitutes a challenge in pathology diagnosis, particularly in small biopsy specimens. Here, we present a case of pulmonary HCCC diagnosed by c...
How does SARS-CoV-2 cause lung microenvironment disturbance and inflammatory storm is still obscure. We here performed the single-cell transcriptome sequencing from lung, blood, and bone marrow of two dead COVID-19 patients and detected the cellular communication among them. Our results demonstrated that SARS-CoV-2 infection increase the frequency...
Background:Mesenchymal stem cells (MSCs) are adult stem cells with self-renewal and multi-directional differentiation potential, and possess the functions of immunomodulation, regulation of cell growth, and repair of damage. Over recent years, MSCs have been found to regulate the secretion of inflammatory factors and to exert regulatory effects on...
Necroptosis plays a double-edged sword role in necroptotic cancer cell death and tumor immune escape. How cancer orchestrates necroptosis with immune escape and tumor progression remains largely unclear. We found that RIP3, the central activator of necroptosis, was methylated by PRMT1 methyltransferase at the amino acid of RIP3 R486 in human and th...
Background: Anlotinib, a novel multi-target tyrosine kinase inhibitor that effectively inhibits VEGFR, PDGFR, FGFR, c-KIT, c-MET, and RET, monotherapy has been proven effective in HER-2 negative metastatic breast cancer, but its efficacy in early-stage triple-negative breast cancer (TNBC) is unknown. This phase 2 study aims to evaluate the efficacy...
Malignant gliomas are largely refractory to immune checkpoint blockade (ICB) therapy. To explore the underlying immune regulators, we examine the microenvironment in glioma and find that tumor-infiltrating T cells are mainly confined to the perivascular cuffs and express high levels of CCR5, CXCR3, and programmed cell death protein 1 (PD-1). Combin...
2021年WHO第5版中枢神经系统肿瘤分类将常见于儿童的胶质瘤分为儿童型弥漫性低级别胶质瘤和高级别胶质瘤。其中儿童型高级别胶质瘤根据分子病理学改变及全基因组DNA甲基化谱聚类分析分为以下4类:弥漫性中线胶质瘤,H3K27变异型;弥漫性半球胶质瘤,H3G34突变型;弥漫性儿童型高级别胶质瘤,H3和IDH野生型;婴儿型半球胶质瘤。本文对其进行详细的解读。.
Only a small proportion of patients with triple-negative breast cancer benefit from immune checkpoint inhibitor (ICI) targeting PD-1/PD-L1 signaling in combination with chemotherapy. Here, we discovered that therapeutic response to ICI plus paclitaxel was associated with subcellular redistribution of PD-L1. In our immunotherapy cohort of ICI in com...
Severe neurological symptoms are associated with Coronavirus disease 2019 (COVID-19). However, the morphologic features, pathological nature and their potential mechanisms in patient brains have not been revealed despite evidence of neurotropic infection. In this study, neuropathological damages and infiltrating inflammatory cells were quantitative...
Glioma is the most aggressive brain tumor having invasive ability and a highly heterogeneous phenotype. Many patients with glioma respond poorly to traditional surgery or temozolomide-based chemotherapy. Over the past few decades, developments in immunotherapeutic strategies have provided newer insights into the treatment of gliomas. Immunotherapy...
Background
Glioblastoma (GB) is the most common and highly malignant brain tumor characterized by aggressive growth and resistance to alkylating chemotherapy. Autophagy induction is one of the hallmark effects of anti-GB therapies with temozolomide (TMZ). However, the non-classical form of autophagy, autophagy-based unconventional secretion, also c...
Current streamline of precision medicine uses histomorphological and molecular information to indicate individual phenotypes and genotypes to achieve optimal outcome of treatment. The knowledge of detected mutations and alteration can hardly describe molecular interaction and biological process which can finally be manifested as a disease. With mol...
Background
Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer.
Methods
The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvan...
Aims
To investigate cardiac pathology in critically ill patients with coronavirus disease 2019 (COVID-19) and identify associations between pathological changes and clinical characteristics.
Methods
The present autopsy cohort study included hearts from 26 deceased patients hospitalized in intensive care units due to COVID-19, and was conducted at...
Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses, but the underlying mechanism remains unclear. In this study, the N proteins of highly pathogenic human coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), middle east respiratory syndrome coronavirus...
Autophagy is a highly conserved process that is vital for tumor progression and treatment response. Although autophagy is proposed to maintain the stemness phenotype in adult diffuse glioma, the molecular basis of the link between autophagy and stemness is poorly understood, which makes it impossible to effectively screen for the population that wi...
Glioblastoma is a lethal primary brain tumor with abundant immune-suppressive glioblastoma-associated macrophage (GAM) infiltration. Skewing immune suppressive GAMs towards an immune-activating phenotype represents a promising immunotherapeutic strategy against glioblastoma. Herein, we reported that genetic deletion of miRNA-processing enzyme Dicer...
Background:
Elucidation of the post-transcriptional modification has led to novel strategies to treat intractable tumors, especially glioblastoma (GBM). The ubiquitin-proteasome system (UPS) mediates a reversible, stringent and stepwise post-translational modification which is closely associated with malignant processes of GBM. To this end, develo...
Glioma progression is accompanied with increased tumor tissue stiffness, yet the underlying mechanisms are unclear. Herein, we employed atomic force microscopy analysis to show that tissue stiffness was higher in isocitrate dehydrogenase (IDH)-wild type gliomas than IDH-mutant gliomas. Bioinformatic analyses revealed that tissue inhibitor of metall...
SARS-CoV-2 is the causative agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19) and poses a significant threat to global health. N protein (NP), which is a major pathogenic protein among betacoronaviruses, binds to the viral RNA genome to allow viral genome packaging and viral particle release. Recent studies showed that NP antagon...
Tumour‐associated macrophages (TAMs) abundantly infiltrate high‐grade gliomas and orchestrate immune response, but their diversity in isocitrate dehydrogenase (IDH)‐differential grade‐4 gliomas remains largely unknown. This study aimed to dissect the transcriptional states, spatial distribution and clinicopathological significance of distinct monoc...
Glioblastoma stem cell (GSC) is the major cause of glioblastoma multiforme (GBM) chemotherapy failure. Hypoxia is one of the determinants of GSC. NF-κB plays a pivotal link between hypoxia and cancer stem cells (CSCs). Disulfiram, an antialcoholism drug, has very strong NF-κB–inhibiting and anti-CSC activity. In this study, the in vitro anti-GSC ac...
Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection driven inflammation is the leading cause of acute cardiac injury associated with coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In thi...
Aims
Sonic hedgehog subtype medulloblastoma is featured with overactivation of hedgehog pathway and can be targeted by SMO‐specific inhibitors. However, the resistance is frequently developed leading to treatment failure of SMO inhibitors. W535L mutation of SMO (SMOW535L) is thought to be an oncogenic driver for Sonic hedgehog subtype MB and confer...
How SARS-CoV-2 causes disturbances of the lung microenvironment and systemic immune response remains a mystery. Here, we first analyze detailedly paired single-cell transcriptome data of the lungs, blood and bone marrow of two patients who died of COVID-19. Second, our results demonstrate that SARS-CoV-2 infection significantly increases the cellul...
With the successful marriage between nanotechnology and oncology, various high‐Z element containing nanoparticles (NPs) are approved as radiosensitizers to overcome radiation resistance for enhanced radiotherapy (RT). Unfortunately, NPs themselves lack specificity to tumors. Due to the inherent tropism nature of malignant cells, mesenchymal stem ce...
Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small population of lung adenocarcinoma (LUAD) cancer cells. A SIRPγhi population displayed CSLC proper...
Medulloblastoma (MB) is one of the most common childhood malignant brain tumors (WHO grade IV), traditionally divided into WNT, SHH, Group 3, and Group 4 subgroups based on the transcription profiles, somatic DNA alterations, and clinical outcomes. Unlike WNT and SHH subgroup MBs, Group 3 and Group 4 MBs have similar transcriptomes and lack clearly...
Invasive growth of glioblastoma makes residual tumor unremovable by surgery and leads to disease relapse. Temozolomide is widely used first-line chemotherapy drug to treat glioma patients, but development of temozolomide resistance is almost inevitable. Ferroptosis, an iron-dependent form of non-apoptotic cell death, is found to be related to temoz...
Background: Our previous study reported a good efficacy and safety of pyrotinib combined with trastuzumab neoadjuvant treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. We further explored the potential biomarkers for the efficacy of pyrotinib combined with trastuzumab neoadjuvant treatment in HER2-positiv...
Platelet-derived growth subunit A (PDGFA) plays critical roles in development of glioblastoma (GBM) with substantial evidence from TCGA database analyses and in vivo mouse models. So far, only platelet-derived growth receptor α (PDGFRA) has been identified as receptor for PDGFA. However, PDGFA and PDGFRA are categorized into different molecular sub...
Although the tumorigenic potential of glioma stem cells (GSCs) is associated with multiple molecular alterations, the gene amplification status of GSCs has not been elucidated. Overexpression of HomeoboxA5 (HOXA5) is associated with increased glioma malignancy. In this study, we identify the gene amplification and protein overexpression of HOXA5 in...
Glioblastoma (GBM) is an aggressive primary brain tumor with unique immunity predominated by myeloid cells. GBM cells have been implicated to evade immune attack through hijacking myeloid-affiliated transcriptional programs to establish an immunosuppressive microenvironment. However, molecular features of immune-evading GBM cells in heterogeneous G...
Tumor vasculature-targeting therapy either using angiogenesis inhibitors or vascular disrupting agents offers an important new avenue for cancer therapy. In this work, a tumor-specific catalytic nanomedicine for enhanced tumor ablation accompanied with tumor vasculature disruption and angiogenesis inhibition was developed through a cascade reaction...
Inflammatory monocytes are key mediators of acute and chronic inflammation; yet, their functional diversity remains obscure. Single-cell transcriptome analyses of human inflammatory monocytes from COVID-19 and rheumatoid arthritis patients revealed a subset of cells positive for CD127, an IL-7 receptor subunit, and such positivity rendered otherwis...
With the technological progresses and applications of human genome sequencing, bioinformatics analysis and data mining, and molecular pathology and artificial intelligence-assisted pathological diagnosis, the development of clinical medicine is moving towards the era of precision diagnosis and treatment. In the context of this era, the traditional...
Rationale: Around 10%-20% patients with glioblastoma (GBM) are diagnosed with more than one tumor lesions or multifocal GBM (mGBM). However, the understanding on genetic, DNA methylomic, and transcriptomic characteristics of mGBM is still limited.
Methods: In this study, we collected nine tumor foci from three mGBM patients followed by whole genome...
Background: The pathological features of severe cardiac injury induced by COVID-19 and relevant clinical features is unknown. This post-mortem study intended to determine the pathological findings of hearts from critically ill COVID-19 cases and explore the association of pathological changes and clinical characteristics.
Methods: This autopsy coho...
Objectives: The pathological features of severe cardiac injury induced by COVID-19 and relevant clinical features is unknown.
Methods: This autopsy cohort study, including hearts from 26 deceased patients hospitalized in intensive care unit due to COVID-19, was conducted at four sites in Wuhan, China. Cases were divided into neutrophil-infiltration...
Glioma stem cells (GSCs) are self-renewing tumor cells with multi-lineage differentiation potential and the capacity of construct glioblastoma (GBM) heterogenicity. Mitochondrial morphology is associated with the metabolic plasticity of GBM cells. Previous studies have revealed distinct mitochondrial morphologies and metabolic phenotypes between GS...
[This corrects the article DOI: 10.1371/journal.pgen.1004873.].
Nitrogen mustard (NM) causes severe vesicating skin injury, which lacks effective targeted therapies. The major limitation is that the specific mechanism of NM-induced skin injury is not well understood. Recently, autophagy has been found to play important roles in physical and chemical exposure-caused cutaneous injuries. However, whether autophagy...
Hypoxia-acquired radioresitance is considered to be a major factor responsible for the clinical failure of radiotherapy. Carbonic anhydrase IX (CA IX), a hypoxia-induced cell-surface enzyme involved in pH regulation of hypoxic solid tumors, has been acknowledged as a desirable target for cancer therapy. Herein, we developed a dual exogenous/endogen...
The lung is the primary organ targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making respiratory failure a leading coronavirus disease 2019 (COVID-19)-related mortality. However, our cellular and molecular understanding of how SARS-CoV-2 infection drives lung pathology is limited. Here we constructed multi-omics and single...
Breast cancer stem-like cells (BCSCs) play vital roles in tumorigenesis and progression. However, the origin and dynamic changes of BCSCs are still to be elucidated. Using the breast cancer mouse model MMTV-PyMT, we constructed a single-cell atlas of 31,778 cells from four distinct stages of tumor progression (hyperplasia, adenoma/MIN, early carcin...
Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)–DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in...
Calcyphosine (CAPS) was initially identified from the canine thyroid. It also exists in many types of tumors, but its expression and function in glioma remain unknown. Here we explored the clinical significance and the functional mechanisms of CAPS in glioma. We found that CAPS was highly expressed in glioma, and high expression of CAPS was correla...
Enhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). Breast tumor-initiating cells (BTICs) are involved in forming VM; however, the specific VM-forming BTIC population and the regulatory mechanisms remain undefined. We find that tumor endothelial marker 8 (TEM8) is...
Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair...
Current conventional treatment strategies for glioblastoma (GBM) have limited efficacy due to the rapid development of resistance to temozolomide (TMZ). It is particularly urgent to develop novel therapeutic strategies that can overcome TMZ resistance and provide patients with better prognoses. Here, a TMZ-resistant GBM cell strain and a mouse mode...
The pathophysiology of coronavirus disease 19 (COVID-19) involves a multitude of host responses, yet how they unfold during the course of disease progression remains unclear. Here, through integrative analysis of clinical laboratory tests, targeted proteomes, and transcriptomes of 963 patients in Shanghai, we delineate the dynamics of multiple circ...
Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic dis...
e12610
Background: Our previous study reported a good efficacy and safety of pyrotinib combined with trastuzumab neoadjuvant treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. We further explored the potential biomarkers for the efficacy of pyrotinib combined with trastuzumab neoadjuvant treatment in HER2-...
Background:
Cardiovascular involvement manifesting as arrhythmias has been confirmed in patients with coronavirus disease 2019 (COVID-19), so we aimed to explore the association between primary tachyarrhythmia and death in critically ill patients with COVID-19 in this retrospective study.
Methods:
A total of 79 critically ill patients with COVID...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-...
Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The...
Nanomaterials with enzyme-like catalytic activity, named as nanozymes, have aroused wide research interest owing to their striking merits bridging nanotechnology and biology. Metal-organic frameworks (MOFs) are a novel class of porous inorganic-organic hybrid materials made from metal ions/clusters and organic ligands, and have shown great prospect...
The physiological homeostasis of gut mucosal barrier is maintained by both genetic and environmental factors and its impairment leads to pathogenesis such as inflammatory bowel disease. A cytokine like molecule, FAM3D (mouse Fam3D), is highly expressed in mouse gastrointestinal tract. Here, we demonstrate that deficiency in Fam3D is associated with...
Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in pa...