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Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

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International Journal of Oral Science 2024年第2期16卷 349-358页

作者： xinjia cai Heyu Zhang Yanjin Wang Jianyun Zhang Tiejun Li 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 DevicesBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina Department of Oral Pathology Shanghai Stomatological Hospital&School of StomatologyFudan UniversityShanghaiChina Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence *** combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin ***,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw *** of the different prognosis,differential diagnosis of several cysts can contribute to clinical *** collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of *** Inception_v3 neural network was utilized to train and test models developed from patch-level ***,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning *** AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of *** advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide ***,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the ***,we have developed the robust diagnostic and prognostic models for *** AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

关键词： diagnosis pathology prognosis

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CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression

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International Journal of Oral Science 2024年第1期16卷 134-144页

作者： Xuan Zhou xinjia cai Fengyang Jing Xuefen Li Jianyun Zhang Heyu Zhang Tiejun Li Department of Oral Pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina

Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force ***, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

关键词： CD97 osteoclast inhibited

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Genomic alterations in oral multiple primary cancers

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International Journal of Oral Science 2024年第1期16卷 145-153页

作者： Wen Wang Qian Wang Shiying Sun Pengfei Zhang Yuyu Li Weimin Lin Qiwen Li Xiao Zhang Zhe Ma Haiyan Lu Hebei Key Laboratory of Stomatology Hebei Clinical Research Center for Oral DiseasesHebei Medical UniversityShijiazhuangChina Department of Orthodontics School and Hospital of StomatologyHebei Medical UniversityShijiazhuangChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina Department of Preventive Dentistry School and Hospital of StomatologyHebei Medical UniversityShijiazhuangHebeiChina

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in ***, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

关键词： alterations metastasis oral

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Biomarkers of malignant transformation in oral leukoplakia:from bench to bedside

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第10期24卷 868-882页

作者： xinjia cai Jianyun ZHANG Heyu ZHANG Tiejun LI 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 100081China Central Laboratory Peking University School and Hospital of StomatologyBeijing 100081China Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)Beijing 100081China

Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma,which indicates a high potential of *** malignant transformation of oral leukoplakia seriously affects patient survival and quality of life;however,it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical *** a major problem in the field of head and neck pathologies,it is imperative to identify biomarkers of malignant transformation in oral *** this review,we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to *** no single biomarker has yet been applied in the clinical setting,profiling for genomic instability might be a promising adjunct.

关键词： Oral leukoplakia Oral squamous cell carcinoma Malignant transformation Biomarker Prognosis

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Role of DKK4 in Tumorigenesis and Tumor Progression

Role of DKK4 in Tumorigenesis and Tumor Progression

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2018口腔病理年会暨第十二次全国口腔病理学术会议

作者： xinjia cai Zhigang Yao Long Li Junhui Huang Department of Oral Pathology Xiangya Stomatological Hospital Central South University

Tumor is the most public health problem. The Wnt signal pathway extensively participates in diverse progresses containing embryonic development, maintenance of homeostasis and tumor pathogenesis. The Wnt signal pathway consists of canonical signal pathway, noncanonical Wnt/PCP pathway and noncanonical Wnt/Ca2+ pathway. The deletion of the ligand of Wnts results in cytoplasmic β-catenin phosphorylation, stopping entry of β-catenin to nuclear in canonical Wnt signaling. Instead, binding of Wnts to frizzled(FZ/FZD) as well as LRP5/6 causes activation of Wnt signal pathways. This facilitates entry of β-catenin to nuclear. The Dickkopf proteins(DKKs) have been known as the antagonist of Wnt signal pathway. A number of research of DKK1, 2, 3 have been reported, however, the effect of DKK4 on tumor process is still mysterious. A more distinct comprehension about the effect of DKK4 on tumorigenesis and tumor process will shed light on biomedical research of DKK4 and tumor research. This review summarizes the current knowledge of DKK4 in various kinds of tumors.

关键词： Tumor Wnt signal pathway β-catenin DKK4

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口腔白斑致病因素的研究进展

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中华口腔医学研究杂志（电子版） 2017年第2期11卷 111-114页

作者：蔡鑫嘉姚志刚李龙刘桂刘君杰黄俊辉中南大学湘雅口腔医院口腔病理科长沙410078

虽然学者们对口腔白斑(OLK)进行了大量研究,也发表了大量相关论文,但对于OLK病因的认识并不一致。为了探究OLK的致病因素,本研究搜集了相关的文献进行综述与分析,以便明确OLK发病的主要原因。本研究按系统评价要求制定相应的纳入与排除... 详细信息

虽然学者们对口腔白斑(OLK)进行了大量研究,也发表了大量相关论文,但对于OLK病因的认识并不一致。为了探究OLK的致病因素,本研究搜集了相关的文献进行综述与分析,以便明确OLK发病的主要原因。本研究按系统评价要求制定相应的纳入与排除标准。从Pub Med、CNKI(中国知识基础设施工程)、万方数据知识服务平台等数据库中检索出2012年1月至2016年7月共406篇OLK相关文献。检索部分文献中的引用参考文献,下载阅读并分析103篇与本研究内容要求一致的文献。使用的检索式:"口腔白斑"AND"致病因素"。研究显示吸烟持续时间、日吸烟数量和日饮酒量与OLK的发生有关,局部刺激可引起口腔黏膜损伤,引发慢性炎症从而导致OLK。假丝酵母菌感染与人乳头瘤病毒(HPV)感染可能导致OLK从而引起上皮异常增生。全身因素如唾液菌群、微量元素、放射线、微循环改变和遗传因素等均可提高OLK患病率。

关键词：白斑,口腔致病因素病例分析口腔黏膜

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Wnt5a基因在乳腺癌细胞株MCF-7中的表达及其与E-钙黏蛋白、波形蛋白基因的关系

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肿瘤研究与临床 2016年第10期28卷 649-653页

作者：邱霞杨国荣刘利黄勇曾若兰姚晓艺石静吴至佛汪灵刘桂蔡鑫嘉黄俊辉长沙市第二社会福利院老年科 410007 中南大学湘雅医院肿瘤科长沙410008 中南大学湘雅口腔医院病理科长沙410000

目的：探讨Wnt5a基因在人乳腺癌细胞株MCF-7中的表达及其与E-钙黏蛋白、波形蛋白基因表达的相关性。方法采用反转录聚合酶链反应（RT-PCR）检测Wnt5a、E-钙黏蛋白mRNA和波形蛋白mRNA在MCF-7细胞和人正常乳腺上皮细胞株MCF-10A中的表达... 详细信息

目的：探讨Wnt5a基因在人乳腺癌细胞株MCF-7中的表达及其与E-钙黏蛋白、波形蛋白基因表达的相关性。方法采用反转录聚合酶链反应（RT-PCR）检测Wnt5a、E-钙黏蛋白mRNA和波形蛋白mRNA在MCF-7细胞和人正常乳腺上皮细胞株MCF-10A中的表达，分析Wnt5a表达与E-钙黏蛋白mRNA、波形蛋白mRNA的关系。结果 MCF-7细胞中，Wnt5a、E-钙黏蛋白mRNA水平均低于MCF-10A细胞[（16.93±2.97）%比（27.47±2.76）%，（12.97±1.35）%比（20.43±2.60）%，均P＜0.05]，波形蛋白mRNA水平高于MCF-10A细胞[（16.53±0.85）%比（6.33±2.08）%，P＜0.05]。在MCF-7细胞中，Wnt5a与E-钙黏蛋白mRNA的表达呈正相关（r＝0.997，P＜0.05），与波形蛋白mRNA的表达呈负相关（r＝-0.998， P＜0.05）。结论 Wnt5a在人乳腺癌细胞株MCF-7中的表达低于人正常乳腺上皮细胞株MCF-10A，其在乳腺癌的发生与发展中可能发挥抑癌基因的作用。 Wnt5a在乳腺癌细胞中的表达与E-钙黏蛋白mRNA的表达呈正相关，与波形蛋白mRNA的表达呈负相关。 Wnt5a可能通过影响乳腺癌上皮细胞的转化导致乳腺癌的侵袭和转移。

关键词：乳腺肿瘤 E-钙黏蛋白波形蛋白上皮间质转化

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丹参联合曲安奈德局部注射治疗口腔黏膜下纤维性变的meta分析

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口腔疾病防治 2018年第6期26卷 374-378页

作者：蔡鑫嘉黄俊辉姚志刚李龙刘桂刘君杰李慧玲崔琳中南大学湘雅口腔医院口腔病理科湖南长沙410078

目的评价丹参联合曲安奈德局部注射治疗口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是否比单独应用曲安奈德局部注射治疗OSF有效。方法通过检索相关文献进行meta分析,最后有3篇文献符合纳入标准并均属于随机对照试验。视觉模拟评... 详细信息

目的评价丹参联合曲安奈德局部注射治疗口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是否比单独应用曲安奈德局部注射治疗OSF有效。方法通过检索相关文献进行meta分析,最后有3篇文献符合纳入标准并均属于随机对照试验。视觉模拟评分法(Visual Analogue Scale/Score,VAS)分值、张口度改变各纳入172例病例(实验组86例,对照组86例),口腔黏膜病损面积变化纳入152例病例(实验组76例,对照组76例)。分别比较丹参联合曲安奈德局部注射与单独应用曲安奈德局部注射治疗OSF前后患者口腔灼痛感VAS值、张口度和口腔黏膜病损面积变化。结果丹参联合曲安奈德局部注射组的VAS减少量与单独应用曲安奈德局部注射组差异无统计学意义(P>0.05);丹参联合曲安奈德局部注射组的张口度增加量高于单独应用曲安奈德局部注射组(P=0.05);丹参联合曲安奈德局部注射组的口腔黏膜病损面积减小量高于单独应用曲安奈德局部注射组(P<0.05)。结论丹参联合曲安奈德治疗OSF比单独应用曲安奈德的疗效更好。

关键词：口腔粘膜下纤维性变 meta分析丹参曲安奈德

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依据冷机性能调整运行策略节能分析

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制冷 2012年第1期31卷 74-77页

作者：于鑫家高兴蔡建平袁杰大连海洋大学大连116023 大连盛和自控技术有限公司大连116023

由于冷机的水温和流量运行参数的变化,会导致变风量空调系统风量调节失灵,最后当成定风量系统去使用。这样既增加了初投资,又没有得到后期的节能效果。调查发现,运行多年的冷机设备,冷冻水温差小、流量偏大。利用公式COP=Q/W求出冷机性... 详细信息

由于冷机的水温和流量运行参数的变化,会导致变风量空调系统风量调节失灵,最后当成定风量系统去使用。这样既增加了初投资,又没有得到后期的节能效果。调查发现,运行多年的冷机设备,冷冻水温差小、流量偏大。利用公式COP=Q/W求出冷机性能指数。分析发现冷机在实际运行过程中的COP波动很大,平均COP偏低。随着冷负荷增大,冷机COP与系统整体COP有所提高,同时用电量也增大。通过调整冷机的运行策略使系统重新恢复为变风量系统运行。

关键词： COP 能耗分析节能

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补肾活血法促进卵泡发育障碍模型大鼠卵巢颗粒细胞增殖的实验研究

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北京中医药大学学报 2014年第4期37卷 231-235,I0001页

作者：蔡竞吴克明熊婷婷黄丽廖凤娇陕西中医学院附属医院陕西712000 成都中医药大学

目的以颗粒细胞增殖为切入点探讨补肾活血中药复方新加归肾丸促卵泡发育的分子机制。方法采用雷公藤多苷致卵泡发育障碍大鼠模型,分别给予高、中、低剂量新加归肾丸灌胃治疗2周,处死大鼠,摘取双侧卵巢,计算卵巢指数;卵巢组织HE染色,光... 详细信息

目的以颗粒细胞增殖为切入点探讨补肾活血中药复方新加归肾丸促卵泡发育的分子机制。方法采用雷公藤多苷致卵泡发育障碍大鼠模型,分别给予高、中、低剂量新加归肾丸灌胃治疗2周,处死大鼠,摘取双侧卵巢,计算卵巢指数;卵巢组织HE染色,光学显微镜下测量颗粒细胞厚度;Taqman实时荧光定量PCR法、免疫组化法检测卵巢兔抗细胞周期蛋白D2(CyclinD2)mRNA和颗粒细胞CyclinD2蛋白的表达。结果模型对照组大鼠卵巢指数、颗粒细胞厚度、CyclinD2 mRNA表达以及CyclinD2蛋白表达均较常对照组降低(P<0.05或者P<0.01);经不同剂量的新加归肾丸治疗后,以上指标均不同程度的升高,以中药高、中剂量组效果最为明显(P<0.05或P<0.01)。结论补肾活血中药复方新加归肾丸可能通过上调CyclinD2的表达,加速细胞周期进程,促使颗粒细胞的增殖,从而进一步促进卵泡发育。

关键词：补肾活血新加归肾丸颗粒细胞厚度兔抗细胞周期蛋白D2 卵泡发育障碍大鼠 CyclinD2

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