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The spatial transcriptomic landscape of human gingiva in health and periodontitis

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Science China(Life Sciences) 2024年第4期67卷 720-732页

作者： Zongshan Shen Ran Zhang Yunjia Huang Jiayao Chen Mengjun Yu Chunhua Li Yong Zhang Lingling Chen Xin Huang Jichen Yang Zhengmei Lin Songlin Wang Bin Cheng Hospital of Stomatology Guangdong Provincial Key Laboratory of StomatologyGuanghua School of StomatologySun Yat-sen UniversityGuangzhou 510055China Beijing Laboratory of Oral Health Capital Medical UniversityBeijing 100050China Department of Oral pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100050China Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical SciencesBeijing 100050China BGI-Qingdao BGI-ShenzhenQingdao 266555China

The gingiva is a key oral barrier that protects oral tissues from various stimuli.A loss of gingival tissue homeostasis causes periodontitis,one of the most prevalent inflammatory diseases in humans.The human gingiva exists as a complex cell network comprising specialized structures.To understand the tissue-specific pathophysiology of the gingiva,we applied a recently developed spatial enhanced resolution omics-sequencing(Stereo-seq)technique to obtain a spatial transcriptome(ST)atlas of the gingiva in healthy individuals and periodontitis patients.By utilizing Stereo-seq,we identified the major cell types present in the gingiva,which included epithelial cells,fibroblasts,endothelial cells,and immune cells,as well as subgroups of epithelial cells and immune cells.We further observed that inflammation-related signalling pathways,such as the JAK-STAT and NF-κB signalling pathways,were significantly upregulated in the endothelial cells of the gingiva of periodontitis patients compared with those of healthy individuals.Additionally,we characterized the spatial distribution of periodontitis risk genes in the gingiva and found that the expression of IFI16 was significantly increased in endothelial cells of inflamed gingiva.In conclusion,our Stereo-seq findings may facilitate the development of innovative therapeutic strategies for periodontitis by mapping periodontitis-relevant genes and pathways and effector cells.

关键词： spatial transcriptomics gingiva periodontal disease periodontitis risk genes

Classificatory updates in verrucous and cuniculatum carcinomas:Insights from the 5^(th) edition of WHO-IARC head and neck tumor classification

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World Journal of clinical Oncology 2024年第4期15卷 464-467页

作者： Felipe Martins Silveira Lauren Frenzel Schuch Ronell Bologna-Molina Department of Diagnostics in Oral pathology and Oral Medicine Faculty of DentistryUniversidad de la RepúblicaMontevideo 1600Uruguay Department of Oral pathology Universidad Juarez del Estado de DurangoDurango 13400Mexico

The International Agency for Research on Cancer(IARC)and World Health Organization(WHO)collaboratively produce the'WHO Blue Books'essential tools standardizing the diagnostic process for human cancers.Regular updates in this classification accommodate emerging molecular discoveries,advances in immunohistochemical techniques,and evolving clinical insights.The 5th edition of the WHO/IARC classification of head and neck tumors refines the'Oral Cavity and Mobile Tongue'chapter,including sections for non-neoplastic lesions,epithelial tumors,and tumors of uncertain histogenesis.Notably,the epithelial tumors section is rearranged by tumor behavior,starting with benign squamous papillomas and progressing through potentially malignant oral disorders to oral squamous cell carcinoma(OSCC).The section on OSCC reflects recent information on epidemiology,pathogenesis,and histological prognostic factors.Noteworthy is the specific categorization of verrucous carcinoma(VC)and carcinoma cuniculatum(CC),both associated with the oral cavity and distinct in clinical and histologic characteristics.This classification adjustment emphasizes the oral cavity as their predominant site in the head and neck.Designating specific sections for VC and CC aims to provide comprehensive insights into these unique subtypes,elucidating their clinical features,distinct histological characteristics,prevalence,significance,and clinical relevance.By categorizing these subtypes into specific sections,the 5th edition of the WHO classification aims to provide a more nuanced and detailed account,enhancing our understanding of these specific variants within the broader spectrum of head and neck tumors.

关键词： World Health Organization Squamous cell carcinoma of head and neck Verrucous carcinoma Mouth neoplasms

Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

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Chinese Journal of Cancer Research 2024年第2期36卷 124-137页

作者： Jialin Zhang Gengshen Yin Chunmiao Ye Man Feng Changhua Ji Wenzhong Zhou Fei Wang Lixiang Yu Shuya Huang Zhigang Yu Department of Breast Surgery the Second Hospital of Shandong UniversityJinan 250033China Institute of Translational Medicine of Breast Disease Prevention and Treatment Shandong UniversityJinan 250033China Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease Jinan 250033China Department of pathology the Third Affiliated Hospital of Shandong First Medical University(Affiliated Hospital of Shandong Academy of Medical Sciences)Jinan 250031China Department of pathology the Second Hospital of Shandong UniversityJinan 250033China

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical

关键词： Breast cancer HER2 pyrotinib trastuzumab primary resistance pertuzumab

Epidemiological and histopathological characteristics of thyroid carcinoma in a Tunisian health care center

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 37-42页

作者： Maissa Ben Thayer Fatma Khanchel Imen Helal Dorra Chiboub Hedhli Raoueh Ehsen Ben Brahim Raja Jouini Aschraf Chadli-Debbiche Faculty of Medicine of Tunis Tunis El Manar UniversityTunisTunisia Depatment of pathology Habib Thameur's HospitalTunisTunisia Department of Otorhinolaryngology-Head and Neck surgery Habib Thameur's HospitalTunisTunisia

Background:Thyroid carcinoma(TC)accounts for almost 0.5%–1%of total malignancies.Its incidence is increasing rapidly worldwide.Several studies have drawn up the epidemiological profile of TC and its clinical and pathological features.However,to date,no similar studies have been conducted in Tunisia.Aims:To establish an epidemiological profile of TC in a Tunisian health care institute and to analyze its clinical and histopathological characteristics in our institute.Materials and Methods:We present a retrospective study reviewing the cases of TC diagnosed in our institution in a 4-year period.Results:We collected a sample of 192 cases of TC.It consisted of 31 males and 161 females(83.8%)with a sex-ratio M/F of 0.19.The mean age was 46.4 years.Papillary thyroid carcinoma was the most frequent histological subtype.The multifocality rate was 33.8%.The mean size of TC was 2.2±1.9 cm.60.9%of TC were staged pT1 and 20.3%had nodal involvement.Papillary thyroid microcarcinomas were noted in 37.5%of cases.Conclusion:Our results were consistent with those of the literature.A high proportion of pT1 and pN0 tumors were noted in our series,suggesting that TC's diagnosis and management was performed at an early stage of the disease in our institution.In addition,our study enabled us to notice the impact of the Coronavirus disease 19 crisis on the management of TC in our institution.Further studies are needed to establish the epidemiological profile of TC in Tunisia and to assess its clinical and pathological features.

关键词： coronavirus disease 19 epidemiology papillary thyroid carcinoma papillary thyroid microcarcinoma pathology thyroid carcinoma

New strategies in the diagnosis and treatment of immune-checkpoint inhibitor-mediated colitis

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World Journal of clinical Cases 2024年第6期12卷 1050-1062页

作者： Tsvetelina Velikova Boris Krastev Milena Gulinac Miroslav Zashev Vasko Graklanov Milena Peruhova Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria Medical Center Nadezhda Medical Center NadezhdaSofia 1407Bulgaria General and clinical pathology Medical University of PlovdivPlovdiv 4002Bulgaria Department of General Surgery University Hospital“Heart and Brain”Burgas 8000Bulgaria First Department of Internal Diseases Medical University of PlovdivPlovdiv 4000Bulgaria Department of Hematology University Hospital“St.George”Plovdiv 4000Bulgaria Division of Gastroenterology University Hospital“Heart and Brain”Burgas 1000Bulgaria

Immune-checkpoint inhibitor-mediated colitis(IMC)is an increasingly recognized adverse event in cancer immunotherapy,particularly associated with immune checkpoint inhibitors(ICIs)such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 antibodies.As this revolutionary immunotherapy gains prominence in cancer treatment,understanding,diagnosing,and effectively managing IMC becomes paramount.IMC represents a unique challenge due to its immune-mediated nature and potential for severe complications.However,a precise picture of IMC pathophysiology is currently unavailable.Therefore,we aimed to summarize the existing data while acknowledging the need for further research.This comprehensive review explores the mechanisms underlying ICIs,gastrointestinal adverse effects,and,in particular,IMC’s incidence,prevalence,and features.Our review also emphasizes the importance of recognizing IMC’s distinct clinical and histopathological features to differentiate it from other forms of colitis.Furthermore,this paper highlights the urgentneed for evolving diagnostic methods,therapeutic strategies,and a multidisciplinary approach to effectively manage IMC.

关键词： Immune-checkpoint inhibitors Immune-checkpoint inhibitor-mediated colitis Inhibitor-mediated colitis management Immunotherapy-associated colitis Checkpoint inhibitor-induced colitis Gastrointestinal adverse effects Checkpoint inhibitor toxicity Inhibitor-mediated colitis therapy

Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

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Military Medical Research 2024年第2期11卷 180-205页

作者： Hong Weng Kang-Ping Xiong Wang Wang Kai-Yu Qian Shuai Yuan Gang Wang Fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu Xing Huang Hang Zheng Xing-Huan Wang Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence‑Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Key Laboratory of Tumor Biological Behaviors Wuhan 430071China Department of pathology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for pathology and Molecular Diagnostics Wuhan UniversityWuhan 430071China Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of PCa.Methods:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University.The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa.The expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques.To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa.The Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical significance.Results:ASPA was identified as a novel inhibitor of PCa progression.The expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,migration,and invasion,respectively.The inhibitory

关键词： Prostate cancer Aspartoacylase LYN JNK AP-1 C-Jun Phosphorylation

A novel saliva-based miRNA profile to diagnose and predict oral cancer

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International Journal of Oral Science 2024年第1期16卷 97-109页

作者： Jaikrishna Balakittnen Chameera Ekanayake Weeramange Daniel F.Wallace Pascal H.G.Duijf Alexandre S.Cristino Gunter Hartel Roberto A.Barrero Touraj Taheri Liz Kenny Sarju Vasani Martin Batstone Omar Breik Chamindie Punyadeera Saliva&Liquid Biopsy Translational Laboratory Griffith Institute for Drug DiscoveryGriffith UniversityNathanQLDAustralia Department of Medical Laboratory Sciences Faculty of Allied Health SciencesUniversity of JaffnaJaffnaSri Lanka Menzies Health Institute Griffith UniversityGold CoastQLDAustralia School of Biomedical Sciences Faculty of HealthQueensland University of TechnologyBrisbaneQLDAustralia Centre for Cancer Biology Clinical and Health SciencesUniversity of South Australia&SA PathologyAdelaideSAAustralia Institute of clinical Medicine Faculty of MedicineUniversity of OsloOsloNorway Department of Medical Genetics Oslo University HospitalOsloNorway Griffith Institute for Drug Discovery Griffith UniversityNathanQLDAustralia QIMR Berghofer Medical Research Institute Statistics UnitBrisbaneQLDAustralia School of Public Health The University of QueenslandBrisbaneQLDAustralia School of Nursing Queensland University of TechnologyBrisbaneQLDAustralia eResearch Research InfrastructureAcademic DivisionQueensland University of TechnologyBrisbaneQLDAustralia Department of Anatomical pathology Royal Brisbane and Women’s HospitalHerstonQLDAustralia Faculty of Medicine The University of QueenslandBrisbaneQLDAustralia Royal Brisbane and Women’s Hospital Cancer Care ServicesHerstonQLDAustralia Department of Otolaryngology Royal Brisbane and Women’s HospitalHerstonQLDAustralia Department of Oral and Maxillofacial Surgery Royal Brisbane and Women’s HospitalHerstonQLDAustralia

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p,miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.

关键词： specificity salivary diagnosis

Two cases on primary bone marrow lymphoma

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Cancer Pathogenesis and Therapy 2024年第1期2卷 58-61页

作者： Zining Wang Lu Sun Yue Wang Haoran Chen Hongbin Pu Bo Yang Xuechun Lu Medical School of Chinese PLA Beijing 100853China Department of Hematology The Second Medical Center&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China Department of pathology The First Medical CenterChinese PLA General HospitalBeijing 100853China National Institutes for Food and Drug Control Beijing 102629China Management School Shanxi Medical UniversityTaiyuanShanxi 030604China

Managing Editor:Peng Lyu Primary bone marrow lymphoma(PBML)is a rare lymphoma accounting for 1.23%of non-Hodgkin lymphoma(NHL)cases.It is characterized by tumor cells invading only the bone marrow without systemic lymphadenopathy or extranodal organ involvement.Owing to the lack of standardized treatment regimens,most patients are treated using rituximab with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)regimens;however,their efficacy needs to be further investigated.

关键词： lymphoma cases involvement

AN UPTODATE ON NUCLEAR CARDIOLOGY

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湖南医学院学报 1980年第3期 216-218页

作者： Wei-PingLoh F.A.C.P. F.R.C.P. President American Center for Chinese Medical Sciences clinical Professor of pathology Indiana University School of Medicine Indiana University School of Medicine

Nuclear medicine has developed rapidly over the past 20 years.In recent eight years nuclear cardiology has become a new discipline as a result of major advances in instrumentation,newly developed radiOactive tracers and the applicatiOn of computer technology.The nuclear cardiology methods offer the advantages of non-invasive introduction and safety without alteration of measurable hemodynamic

关键词： AN UPTODATE ON NUCLEAR CARDIOLOGY