目的:评价液基薄层细胞制片在荧光原位杂交（FISH）技术检测尿路上皮癌中的应用价值。方法:收集解放军第八一医院2016年8月至2018年12月就诊的42例尿路上皮癌患者的新鲜晨尿。应用荧光标记的第3、7、17号染色体着丝粒探针及p16位点探针，用液基薄层细胞制片及传统离心滴片两种预处理方式对尿液进行富集。比较两种处理方式的FISH结果。结果:液基薄层细胞富集方法收集细胞数多于传统离心滴片方法，差异有统计学意义[（312.0±28.6）个比（283.0±36.8）个， t=1.86， P=0.035]；传统离心滴片方法预处理FISH制片合格率为90.5%（38/42），液基细胞学预处理制片合格率为95.2%（40/42），两组比较差异无统计学意义（ χ2=0.02， P=0.90）。 结论:液基薄层细胞制片的细胞富集效果好，操作判读简单，耗时短，成本低，结果可靠，可用于尿路上皮癌临床FISH检测。

The structure and performance of nuclear cytoplasmic autophagosomes was explored. Seventeen cases of hepatocellular carcinoma and liver cells with other diseases from liver tissues were selected. The nuclear cytoplasm were isolated and degraded by the nuclear membrane. Damaged cytoplasm had damaged its own membrane and the surrounding nuclear tissues other than the nuclear membrane, leading to specific nucleolysis and cell death of liver cancer cells and liver cells.

Objective To study the manufacture and clinical application of the fixed?removable prostheses for hereditary opalescent dentin. Methods The pedigree of a patient suffered from hereditary opalescent dentin found in Nanjing was tracked, and the heredi?tary features were assessed. The most appropriate jaw position was established by try?in and occlusal adjustment of the temporary pros?theses for three months, where the fixed?removable prostheses were designed and manufactured. The patient was followed up regularly for five years, and the fixed?removable prostheses were evaluated from safety, strength and fitness. The assessment was referred to the improved prostheses evaluation standards by United States Public Health Service. Results Three sequential generations with hereditary opalescent dentin were found in this family, and the prevalence of later generation was 50%, the findings were compatible with an auto?somal dominant inheritance. According to the follow?up, the patient was satisfied with the masticatory function, fitness, facial form, aesthetics and comfortableness of temporomandibular joint. Clinical examination showed the marginal fitness, gingival health, color sta?bility and strength of crowns was satisfactory, and no complications such as fracture, exfoliation, dropping or abutment crown fracture were found. Conclusion The occlusal reconstruction of the fixed?removable prostheses for hereditary opalescent dentin is satisfactory.

Objective To investigate and analyze the expression of miR-21 in hepatocarcinoma cell strains and the relation-ship with PTEN. Methods The quantitative reverse transcription-PCR were used to detect the expression of miR-122 and PTEN in hepatocarcinoma cell strains, PTEN and p-Akt expression was detected in tumor-bearing nude mice treated with miR-21 inhibitor. Re-sults The relative expression of miR-21 was 2?97±0?79,137?66±23?60 and 11?21±1?14 in WRL-68, MHCC97-H and SMMC-7721strains respectively, while that was 1?29 ± 0?33, 36?90 ± 11?84 and 6?22 ± 0?85 respectively when miR-21 inhibitor was transfected. The relative expression of PTEN was 2?88 ± 0?93, 0?19 ± 0?07 and 0?62 ± 0?06 in WRL-68, MHCC97-H and SMMC-7721strains respectively, while that was 6?11±1?07, 2?65±0?66 and 4?32±0?84 respectively when miR-21 inhibitor was transfected. The expression of PTEN was positive and p-Akt was down regulated when tumor-bearing nude mice was treated with miR-21 inhibitor. Conclusion MiR-21 is an upstream regulation factor of PTEN, it can affect PTEN expression.

将代价敏感方法引入肺癌细胞图像识别,建立基于代价敏感图像层的肺癌细胞病理诊断系统(Cost-sensitive Image-level Lung Cancer Diagnosis System,CILCDS),并研究其临床应用价值.与既往方法比较,CILCDS在癌与正常细胞的判断以及癌细胞的分类识别诊断过程中取得了最低的错误分类代价0.37％以及更高的组织病理结果符合率97.61％.基于代价敏感图像层技术能够有效减少肺癌细胞病理诊断过程中的假阳性结果,有可能为肺癌细胞病理诊断提供一个更为有效的检测手段.

Objective The tumor tissues used in molecular pathological detection are usually got after surgery,which causes trauma and is not suitable for the terminal cancer patients or the recurrent and metastasis patients.The aim of this study was to explore significance of non small cell lung cancer(NSCLC) pleural effusion cell blocks in molecular pathological detection as tumor tissues replacement materials.Methods Tumor cells from the pleural effusion in 30 NSCLC patients were got to make cell blocks through stratified centrifugal.Immunohistochemistry,fluorescence in situ hybridization(FISH) and gene sequencing methods were used in this study.Results The tumor cells of cell block section were rich and could keep part of histological structure.Immunohistochemistry staining could assist diagnosis and tumor parting.The FISH positive detection rate of epidermal growth factor receptor(EGFR) was 33.33%(10 /30 cases) including 6 cases of high polysomy in 4 cases of amplification.The mutation rate of EGFR gene was 26.67%(8 /30).6 cases were detected in the exon 19.2 cases were detected in the exon 21.Conclusion The NSCLC pleural effusion cell blocks are useful for the diagnosis,which are helpful for the determination of the primary source of tumor,and may instruct the molecular targeted therapy.

Objective To investigate the expression of miR-122 in hepatocellular carcinoma cells and its relationship with cell cycle regulation.Methods The in situ hybridization and quantitative reverse transcription —PCR(qRT-PCR) were used to detect the expression of miR-122 in 50 cases of primary hepatocellular carcinoma and corresponding adjacent normal tissues,and flow cytometry was used to detect the cell cycle.The correlation between the expression of miR-122 and the cell cycle was analyzed.Results The expression of miR-122 in hepatocellular carcinoma tissues was(17.74 ± 9.20) % of adjacent normal tissues,while it was(19.89 ± 8.80) % in well and moderately differentiated hepatocellular carcinoma and(9.16 ± 4.77) % in poorly differentiated hepatocellular carcinoma;The positive rate of miR-122 was 80.0%(40 /50) in adjacent normal tissues,and 30.0%(15 /50) in hepatocellular carcinoma(P < 0.05).The percentage of S-phase cells was increased and the percentage of G 1 / G 0 phase cells was decreased in hepatocellular carcinoma compared with the adjacent normal tissues(P < 0.05).In the miR-122 negative expressed hepatocellular carcinoma,the percentage of S phase cells was increased and the percentage of G 1 / G 0 phase cells was significantly decreased(P < 0.05),compared with the miR-122 positive expressed hepatocellular carcinoma.Conclusion Downregulation of miR-122 in hepatocellular carcinoma provokes the division and proliferation of cancer cells.

Objective To evaluate the value of malignant serous cavity effusion cell blocks in the application of molecular pathological diagnosis.Methods Tumor cells were collected and embedded into cell blocks through stratified centrifugal from 85 cancer patients with malignant serous cavity effusion,then were detected by immunohistochemistry,fluorescence in situ hybridisation(FISH) and gene sequencing methods.Results The tumor cells of cell block section were rich and remained histological structures.Immunohistochemistry staining could assist diagnosis and tumor parting.FISH and gene sequencing could provide gene amplification and mutation situation.Ten caces of EGFR gene amplification and 8 caces of EGFR gene mutation were observed in 30 non-small cell lung cancer samples.Conclusion Malignant serous cavity effusion cell blocks are useful for the diagnosis and determing the primary source of tumor,which can instruct targeted therapy.

Objective The cost-sensitive classification strategy can effectively improve the rate of identification at the lowest cost of misdiagnosis.The aim of this study is to propose a novel cost-sensitive image-level lung cancer diagnosis system(CILCDS) for computer-aided pathological analysis of needle biopsy specimens.Methods CILCDS mainly incorporated the model of latent Dirichlet allocation(LDA),a cost-sensitive support vector machine(CSSVM) and a multi-class support vector machine(mcSVM).Using CILCDS,we conducted differential diagnoses on 271 needle biopsy specimens of the lungs,240 of them with postoperative histopathological results for comparison.Results We achieved obviously lower cost of misdiagnosis and higher precision of normal/cancerous identification based on the results of comparisons made with multi-instance learning algorithms such as axis-parallel rectangles,citation K-nearest neighbors and ensemble of diversity density,as well as our previous multi-class multi-instance adaptive boosting(MCMI-AdaBoost).Conclusion CILCDS affords a high accuracy and reduces false positive results in the cytopathological diagnosis of lung cancer.

Objective To explore the clinicopathological characteristics and differential diagnosis of sarcomatoid thyroid carcinoma(STC).Methods One case of oral soft tissue metastasis from STC without thyroid focus was reported and the relevant literatures were reviewed.Results The patient was a 63 years old woman.A polypoid mass with peduncle was located in the right upper jaw.Histopathologically,STC was a widely invasive tumour composed of an admixture of spindle cells,pleomorphic giant cells and epithelioid cells.The nuclei were bizarre and single or multiple.They revealed prominent nucleoli.Mitotic figures could be numerous.Extensive coagulative necrosis with accompanying polymorphonuclear leukocytes was often seen.Immunohistochemically,tumour cells expressed TTF-1,Vimentin,CKpan,SMA and Ki-67.CK7 was only positive in a few tumour cells.Tg,CD68,LCA,Myogenin,MG,HMB45 and S-100 were negative.Conclusion Oral soft tissue metastasis of STC is rare.It is a highly malignant tumour with poor prognosis.The diagnosis of STC should be based on clinical history,histopathological changes and immunohistochemical tests.It should be distinguished from other tumours.

一、病史摘要 患者,男性,60岁,江苏东台人,农民,因"发现乙肝表面抗原阳性20余年,肝占位4 d"于2010年7月17日入院.患者于20余年前即发现乙型肝炎病毒表面抗原(HBsAg)阳性,长期未注意监测乙型肝炎病毒学指标及肝功能等的变化.近1年来轻度间断乏力,无畏寒、发热,无明显恶心、呕吐、厌油,无腹痛、腹胀、腹泻、便血,无尿黄异常加深.

目的探讨牙源性鳞状细胞瘤的临床病理特征、诊断及鉴别诊断。方法光镜观察及免疫组化法对1例牙源性鳞状细胞瘤进行临床病理分析,并复习文献。结果肿瘤位于右下颌骨,病灶为多房囊性,表面骨质菲薄,内容物为灰白色凝胶样,骨质破坏。光镜下可见肿瘤组织由形态大小不等、分化良好的鳞状上皮岛和纤维间质构成,具有局部浸润性。免疫组化:K i-67和p53均阴性。结论牙源性鳞状细胞瘤是一种罕见的良性上皮性肿瘤,组织学形态特点是其诊断的主要依据,需与成釉细胞瘤、高分化鳞状细胞癌、牙源性钙化上皮瘤或成釉细胞纤维瘤相鉴别。

Objective To study the ultrastructural characteristics of pulmonary cryptococcosis(PC).Methods Tissues obtained from 17 patients with PC were observed by light microscope and electron microscope.Results Microscopically,the cryptococcosis granuloma formation was observed.Vacuolar cryptococcus spore could be seen in plasma of multinuclear giant cell,macrophage and mesenchyma,which stained in red color with PAS and mucicarmine.Electron microscopy revealed that most of cryptococcus neoformans(CN) had a simple structure with a few organelles.The capsule was seen in all organisms.Gemmation of CN could be observed.Conclusion PC is an infrequent fungal disease in lung.The clinical manifestation and imaging of PC are nonspecific.It can be differentiated from other diseases based on histopathological features and ultrastrual observation.

Purpose To study the clinicopathological features and differential diagnosis of pulmonary cryptococcosis(PC) to increase clinicians and pathologists awareness of it.Methods Seventeen cases of PC were reviewed and investigated by light and electron microscopy and histochemical staining.Results The patients consisted of 12 males and 5 females,with age of 5～67 years.The main symptoms were cough,plegm,fever,chestache and headache.Microscopically,the non-caseating granuloma formation was observed in these cases.Vascuolar cryptococcus spore could be seen in cytoplasma of multinuclear giant cell,macrophage and mesenchyma.It is red by stained with PAS.Electron microscopy revealed that most of cryptococcus neoformans(CN) had a simple structure with a few organelles.The capsule was seen in all organisms.Conclusions PC is an infrequent fungal disease in lung.The clinical manifestation and imaging of PC are nonspecific.It can be differentiated from other diseases based on histopathological features,histochemical staining and ultrastructural observation.

目的探讨肺隐球菌病（PC）的临床特点、影像学表现、诊断和治疗,提高对该病的认识。方法回顾性分析解放军第八一医院、上海长海医院和上海长征医院2000年1月至2009年1月收治的34例PC的临床资料。结果34例PC中,男24例,女10例;年龄3～72岁,平均（40.6±13.5）岁;有基础疾病12例（35.3%）;有症状28例（82.4%）,主要为发热（20例）,咳嗽、咳痰（22例）,胸痛（8例）,胸闷（5例）,咯血（4例）。全身播散性PC 7例（20.6%）,其中合并隐球菌脑膜炎3例,同时合并隐球菌脑膜炎、败血症3例,合并第三胸椎隐球菌病1例。影像学表现呈多样性与非特异性,分为肺结节、肿块型（17例）,肺炎型（10例）,混合型（6例）,弥漫性粟粒影（1例）。组织病理确诊27例,隐球菌培养或涂片检查阳性10例。单纯手术治疗6例,单纯药物治疗21例,手术+药物治疗6例,放弃治疗1例。抗真菌药物疗程2周～2年,住院死亡1例。随访25例治愈,8例失访。结论PC的临床和影像学表现不典型,临床常易误诊,诊断依赖于病理学及微生物学检查。

目的通过对川崎病(KD)的临床、病理、免疫学特征的研究,结合文献复习,探讨其临床病理改变和免疫表型与诊断的关系。方法采用常规病理学和免疫组化检测,回顾性分析1例川崎病患者的临床病理和免疫组化标记特点,并复习相关文献。结果KD的病理学特征是非特异性的,其主要改变为坏死性血管炎,小血管腔内可见纤维素性血栓,血管内皮细胞肿胀,血管壁中层平滑肌细胞水肿、分离,炎细胞浸润,主要为CD4+T细胞、富含IgA的浆细胞、巨噬细胞。结论川崎病是免疫相关性血管炎性综合征,需与中毒性休克综合征相鉴别。

病人 男,29岁.前胸壁隐痛4个月,1个月前扪及胸骨中段隆起,无发热、咳嗽及其他不适.查体:第3前肋平胸骨处扪及略高出胸骨的肿块,约3.0 cm× 3.0 cm,质地硬,轻度压痛.胸骨侧位片(图1)及胸部CT(图2)检查示胸骨体中部左、前方1.5 cm×1.0 cm骨质破坏,边缘欠光整,前缘骨皮质破坏中断.全身核素骨扫描检查未见明确异常放射性浓聚影.胸骨病灶穿刺活检涂片病理检查:见较多淋巴细胞、浆细胞、中性粒细胞、嗜酸性粒细胞及散在的组织细胞浸润,考虑炎性病变,不排除嗜酸性肉芽肿可能。

目的:运用强化学习、多分类器集成、降维方法等最新计算机技术,结合细胞病理知识,设计制作"智能化肺癌细胞病理图像诊断系统"。方法:采集细胞图像,运用基于强化学习的图像分割法将细胞区域从背景中分离出来;运用基于B样条和改进deBoor-Cox方法对重叠细胞进行分离和重构;提取40个细胞特征用于贝叶斯、支持向量机、K紧邻和决策树4种分类器,集成产生肺癌细胞分类结果;建立肺癌细胞病理图库,运用基于LDA等降维方法对细胞进行比对,给予未定型癌细胞分类。结果:"智能化肺癌细胞病理诊断系统"应用于临床随机1200例肺部病灶穿刺细胞学涂片,肺癌识别诊断率94.80%,假阳性率1.85%,假阴性率3.35%,肺癌分类识别率82.90%,核异型细胞识别率74.20%。结论:"智能化肺癌早期细胞病理诊断系统"对肺癌细胞涂片诊断率高,克服了肺癌细胞病理诊断过程中取检细胞数量少,重叠细胞识别率低,涂片背景及染色差异等干扰因素,可辅助临床肺部病灶的穿刺细胞病理诊断。

Objective To study a new technique (lung cancer diagnossing system, LCDS) based on the computer imaging and artificial neural network for early diagnosis of lung cancer, and evaluate it's value in early cytopathological diagnosis of lung cancer. Methods The cytological smears from the specimens obtained by Percutaneous Aspiration Lung Biopsy (PALB) in 512 cases were synthetically analyzed by LCDS. Among them, 362 cases received operations. The diagnoses by LCDS were compared with postoperative histopathological diagnosis. Results In cytopathological diagnoses for the 512 specimens, LCDS can judge between cancer cells and non-cancer cells from lung lesions with its image analysis and expert system. Moreover, it can distinguish squamous carcinoma, adenocarcinoma and small cell carcinoma in cytopathological diagnosis with built-in neural network. The total coincident rate of LCDS diagnosis was 91.80% compared with the pathological diagnosis. In the 362 cases, the sensitivity of LCDS diagnosis was 94.79% (291/307), the specificity was 90.91%(50/55), and the consistent rate was 94.20%(341/362). Conclusion The diagnostic pattern of LCDS was practical and effective. It has applicable value in cytopathological diagnosis of lung cancer and may be an efficient means for early diagnosis of lung cancer.

1 病案摘要 患者女,28岁.因颈部包块于2003年10月10日入我院.患者3 个月前曾因左甲状腺肿瘤在外院手术切除,术后病理诊断;左甲状腺滤泡性腺瘤.