国务院印发《新一代人工智能发展规划》中将人工智能(artificial intelligence,AI)上升为国家战略,将于2030年达到世界领先水平.国家癌症中心发布2017全国癌症统计数据,我国恶性肿瘤新发病例数380. 4万例,相当于平均每天1万人以上被确诊为癌症[1],因此癌症患者的早期诊断和精准治疗极为关键.

目的 探讨直肠孤立性错构瘤性息肉(solitary hamartomatous polyp,SHP)的临床病理学特征、诊断与鉴别诊断.方法 对2例直肠SHP行HE及免疫组化EnVision两步法染色,并复习相关文献.结果 2例患者临床均表现为排便异常,息肉均位于直肠,大小分别为环肠腔一周和占肠腔1/3,质地较软.光镜显示腺上皮及平滑肌组织增生,腺上皮轻～中度异型,腺体间夹杂平滑肌束,腺上皮和平滑肌排列较紊乱.免疫表型:SMA、Calponin、desmin标记平滑肌阳性,平滑肌在腺体之间排列紊乱.结论 直肠SHP属于罕见的胃肠道息肉,依靠病理学检查可确诊,内镜下易误诊为恶性病变.

Intrinsic chemoresistance is the main reason for the failure of human pancreatic ductal adenocarcinoma (PDAC) therapy. To identify the candidate protein, we compared the protein expression profiling of PDAC cells and its distinct surviving cells following primary treatment with gemcitabine (GEM) and 5-fluorouracil (5-FU) by two-dimensional electrophoresis combined with liquid chromatography-mass spectrometry or mass spectrometry. A total of 20 differentially expressed proteins were identified, and annexin A1 (ANXA1) was analyzed for further validation. The functional validation showed that the downregulation of ANXA1 contributes to GEM and 5-FU resistance in PDAC cells through protein kinase C/c-Jun N-terminal kinase/P-glycoprotein signaling pathway. Our findings provide a platform for the further elucidation of the underlying mechanisms of PDAC intrinsic chemoresistance and demonstrated that ANXA1 may be a valid marker for anticancer drug development.

Background: Luteolin (3,4,5,7-tetrahydroxy flavone) is a natural flavonoid abundant in fruits and vegetables. Although luteolin has shown pro-apoptotic activity in hepatocellular carcinoma (HCC) cells, the underlying molecular mechanism has not yet been clarified. Purpose: The aim of this study is to identify novel miRNAs involved in the action of luteolin in HCC cells and to explore the biological roles of these miRNAs. Methods: The effect of luteolin on HCC cell growth was assessed using CCK-8 colony formation assay, flow cytometric analysis in vitro, and a xenograft model in vivo. miRNA expression profiles were assessed using next-generation sequencing. Differentially expressed miRNAs were validated by quantitative PCR. Bioinformatics analysis and luciferase reporter assay were utilized to confirm the binding of miR-6809-5p to the 3'-untranslated region (3'-UTR) of flotillin 1 (FLOT1). Furthermore, the effects of ectopic FLOT1 and miR-6809-5 expression on cell proliferation, colony formation, and cell apoptosis were also assessed. Western blotting analysis was used to detect activation of multiple signaling molecules including Erk1/2, p38, JNK, and NF-kappa B/p65 in the MAPK pathway. Results: It was found that luteolin significantly inhibited HCC growth and caused apoptosis and cell cycle arrest at the G0/G1 phase in Huh7 cells, at the G2/M phase in HepG2 cells in vitro. Tumorigenic studies revealed that luteolin treatment significantly suppressed HCC growth in vivo. miR-6809-5p was upregulated by luteolin. Overexpression of miR-6809-5p suppressed HCC cell growth, while knockdown of miR-6809-5p reversed the anticancer effect of luteolin. With regards to its signaling mechanism, miR-6809-5p directly targets FLOT1 in HCC cells. Enforced expression of FLOT1 prevented miR-6809-5p-mediated growth suppression. Downregulation of FLOT1 exerted growth-suppressive effects on HCC cells. Multiple signaling pathways including Erk1/2, p38, JNK, and NF-kappa B/p65 were inactivated by miR-6809-5p overexpression or FLOT1 downregulation. Conclusion: These findings indicated that miR-6809-5p mediates the growth-suppressive activity of luteolin in HCC, which is causally linked to FLOT1 downregulation. Induction of miR-6809-5p may provide therapeutic benefits in the treatment of HCC.

Artificial intelligence(AI) has become a national strategy in developed countries. AI has been a great success in many scenarios of medicine and health fields, including virtual assistant, medical imaging, drug mining, nutrition, hospital management, health management, mental illness, wearable devices, risk management, pathology and clinical diagnosis and treatment. Here, we reviewed and commented the recent progresses on the application of AI in the pathological diagnosis, ocular diseases, skin disorders, medical imaging, traditional Chinese medicine, electrocardiographic monitoring, medical robots, oncotherapy and translational researches, and summed up and prospected the problems of AI application in medicine and health fields. With the development of technology, AI will lead to a revolutionary progress in medical treatment.

Application of artificial intelligence has made revolutionary advances in many medical scenarios such as diagnosis,drug screening,medical imaging and nursing.Images of pathological sections (2D) are a preliminary breakthrough of artificial intelligence.Abundant medical and pathological resources,and standardization,digitization of pathological section images provide big data for the in-depth study of artificial intelligence.Through a series of research on artificial intelligence in pathologies of breast cancer,gastric cancer,and cholangiocarcinoma,we established a labeling standard of tumor cells and an in-depth learning process,and we also developed an artificial intelligence algorithm for hilar cholangiocarcinoma.However,there are still many problems and we tried to search for the solutions.With the improvement in precision of artificial intelligence diagnosis,pathology of artficial intelligence may be soon applied in future clinical practice.

一、检测非小细胞肺癌（ NSCLC）常见靶向治疗相关基因的意义肺癌是世界范围内发病率及病死率均居于首位的恶性肿瘤［1］，其中NSCLC约占85％左右。随着对其分子途径探索的逐步深入和相对应的靶向药物的不断出现，给其中的部分晚期患者带来了新的希望。

Our previous study has reported that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) regulates the growth and survival of hepatocellular carcinoma (HCC) cells. This study was undertaken to explore the roles of MAP4K4 in the epithelial-mesenchymal transition (EMT) and metastasis in HCC. Effects of overexpression and knockdown of MAP4K4 on the migration, invasion, and EMT of HCC cells were examined. The in vivo role of MAP4K4 in lung metastasis of HCC was determined in nude mice. The relationship between MAP4K4 expression and EMT in human HCC specimens was determined by immunohistochemistry. MAP4K4 overexpression significantly enhanced the migration and invasion of MHCC-97L HCC cells, whereas MAP4K4 silencing hindered the migration and invasion of MHCC-97H HCC cells. MAP4K4-overexpressing cells undergo EMT, which was accompanied by downregulation of E-cadherin and upregulation of vimentin. In contrast, MAP4K4 silencing caused a reversion from a spindle morphology to cobblestone-like morphology and induction of E-cadherin and reduction of vimentin. Pretreatment with chemical inhibitors of JNK and NF-κB abolished MAP4K4-mediated migration, invasion, and regulation of EMT markers in MHCC-97L cells. Ectopic expression of MAP4K4 promoted and knockdown of MAP4K4 inhibited lung metastasis of HCC, which was associated with regulation of JNK and NF-κB signaling and EMT markers. High MAP4K4 immunoreactivity was inversely correlated with E-cadherin and was positively correlated with vimentin, phospho-JNK, and phospho-NF-κB in HCC specimens. Taken together, MAP4K4 promotes the EMT and invasiveness of HCC cells largely via activation of JNK and NF-κB signaling.

Perineural invasion and immunosuppressive tumor microenvironment are the distinct features of pancreatic ductal adenocarcinoma (PDAC). Heterogeneous myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity, posing obstacles for cancer immunotherapy. Increasing evidences have demonstrated the accumulation of MDSCs in PDAC patients. However, the role of MDSCs in perineural invasion of PDAC and the existence of novel MDSC subsets during PDAC remain unclear. This study found that lymphocytic perineural cuffs were frequently present in chronic pancreatitis (CP) tissues and adjacent non-neoplastic pancreatic tissues (ANPTs), but not in PDAC with perineural invasion. Meanwhile, we found that neutrophil-like MDSCs (nMDSCs), but not monocyte-like MDSCs (mMDSCs), were significantly increased in PBMCs and tumor tissues of PDAC patients. Further observation identified two distinct subsets of nMDSCs, CD13hi and CD13low nMDSCs in PDAC patients, which have not been reported previously. Despite a similar morphology, CD13hi nMDSCs expressed higher levels of CD11b, CD33, CD16 and arginase 1 but lower levels of CD66b than CD13low nMDSCs. Importantly, CD13hi MDSCs, compared with CD13low nMDSCs, more effectively suppressed alloreactive T cell responses via an arginase-1-related mechanism. After tumor resection, the circulating CD13hi nMDSCs were decreased markedly. PDAC patients with more CD13hi nMDSCs had a shorter overall survival than those with less CD13hi nMDSCs. To conclude, we identified two novel MDSC subsets with different characteristics and functions in PDAC, demonstrated the association of the two MDSC subsets with cancer progression, and explored their roles in perineural invasion and immune escape of PDAC.

Protein phosphatase 2A (PP2A) is a heterotrimeric protein phosphatase consisting of a 36-kD catalytic C subunit (PP2Ac). This study aimed to explore the prognostic and biological significance of PP2Ac in human hepatocellular carcinoma (HCC). High PP2Ac expression was significantly (P < 0.01) associated with serum hepatitis B surface antigen positivity, serum hepatitis B e antigen positivity, liver cirrhosis, moderate to poor differentiation grade, advanced disease stage, intrahepatic metastasis, and early recurrence in HCC. Multivariate analysis revealed PP2Ac as an independent prognostic factor for overall survival. Enforced expression of hepatitis B virus X protein (HBx) and its carboxyl-terminal truncated isoform induced PP2Ac expression in HCC cells. Co-immunoprecipitation assay revealed a direct interaction between PP2Ac and HBx. Small interfering RNA-mediated knockdown of PP2Ac significantly inhibited in vitro cell proliferation, colony formation, migration, and invasion and reduced tumor growth in an xenograft mouse model. In contrast, overexpression of PP2Ac promoted HCC cell proliferation, colony formation, and tumorigenesis. Additionally, silencing of PP2Ac impaired the growth-promoting effects on HepG2 HCC cells elicited by overexpression of carboxyl-terminal truncated HBx. Gene expression profiling analysis showed that PP2Ac downregulation modulated the expression of numerous genes involved in cell cycle and apoptosis regulation. Collectively, PP2Ac upregulation has a poor prognostic impact on the overall survival of HCC patients and contributes to the aggressiveness of HCC. PP2Ac may represent a potential therapeutic target for HCC.

胰腺为人体最重要的消化腺之一，其解剖位置和组织结构特殊，功能复杂，疾病谱广。胰腺疾病病理包括了内、外分泌两大部分，涉及肿瘤性和非肿瘤性病变两大类，现就我国近十年胰腺疾病病理概况作一回顾。

广义而言,液态活检是指以血液为主的体液标本中细胞及核酸的检测,包括了循环肿瘤细胞和游离DNA两大类.液态活检属于新型的无创性分子病理检测方式,具有广阔的临床应用前景;对于传统病理学而言,液态活检的出现既是机遇也是挑战.本文主要从分子检测技术以及临床应用价值这两方面综合阐述了液态活检作为一种新的非侵入式的检测方法在临床肿瘤早期诊断、筛查等领域的发展前景及面临的挑战.

Objectives The aim of this study was to investigate the effect of the neurotrophic factor Artemin on neuroplasticity and perineural invasion of pancreatic adenocarcinoma.Methods Artemin expressions were detected in human pancreatic adenocarcinoma tissues by Western blot and immunohistochemistry. Artemin overexpression and RNA interference in the pancreatic cancer cell lines were performed to evaluate the effects of Artemin on cell proliferation, invasion, and neurotrophic activity in vitro and in nude orthotopic transplantation tumor models.Results Artemin expression in pancreatic cancer tissues was related to the incidence of lymphatic metastasis and perineural invasion as well as the mean density and total area of nerve fibers. Overexpression of Artemin in pancreatic cancer cell lines improved colony formation, cell migration, matrigel invasion, and neurotrophic activity in vitro. This overexpression also increased the volume of nude orthotopic transplantation tumors; promoted cancer cell invasion of the peripheral organs, nerves, vessels, and lymph nodes; and stimulated the proliferation of peritumoral nerve fibers. Artemin depletion by RNA interference had an inhibitory effect mentioned previously.Conclusions Artemin could promote invasiveness and neurotrophic function of pancreatic adenocarcinoma in vivo and in vitro. Therefore, Artemin could be used as a new therapeutic target of pancreatic carcinoma.

microRNAs (miRNAs) are important regulators of tumor development and progression. In this study, we aimed to explore the expression and role of miR-622 in hepatocellular carcinoma (HCC). We found that miR-622 was significantly downregulated in human HCC specimens compared to adjacent noncancerous liver tissues. miR-622 downregulation was significantly associated with aggressive parameters and poor prognosis in HCC. Enforced expression of miR-622 significantly decreased the proliferation and colony formation and induced apoptosis of HCC cells. In vivo studies demonstrated that miR-622 overexpression retarded the growth of HCC xenograft tumors. Bioinformatic analysis and luciferase reporter assays revealed that miR-622 directly targeted the 3′-untranslated region (UTR) of mitogen-activated protein 4 kinase 4 (MAP4K4) mRNA. Ectopic expression of miR-622 led to a significant reduction of MAP4K4 expression in HCC cells and xenograft tumors. Overexpression of MAP4K4 partially restored cell proliferation and colony formation and reversed the induction of apoptosis in miR-622-overexpressing HCC cells. Inhibition of JNK and NF-κB signaling phenocopied the anticancer effects of miR-622 on HCC cells. Taken together, miR-622 acts as a tumor suppressor in HCC and restoration of miR-622 may provide therapeutic benefits in the treatment of HCC.

Wnt proteins are a group of secreted signaling proteins, which function to regulate cell fate and pattern formation during embryogenesis. Altered expression of Wnt5a has been implicated in human carcinogenesis and tumor progression. A previous study identified that Wnt5a is overexpressed in human pancreatic cancer tissues, and that upregulated expression of Wnt5a promotes tumor cell migration and invasion. The present study investigated the role of Wnt5a in pancreatic cancer cell proliferation in vitro and in an orthotopic nude mouse model. Wnt5a cDNA or small interfering RNA were stably transfected into pancreatic cancer cells to assess cell proliferation-associated behaviors, including cell viability, colony formation and apoptosis in vitro, as well as tumor cell growth in an orthotopic nude mouse model. Western blot analysis was used to analyze the expression of Wnt signaling molecules. The data showed that upregulation of the expression of Wnt5a significantly promoted proliferation of the human pancreatic cells, but inhibited tumor cell apoptosis in vitro and promoted tumor growth in an orthotopic nude mouse model. By contrast, knockdown of the expression of Wnt5a inhibited cell growth and promoted apoptosis of the pancreatic cancer cells. The data also revealed that β-catenin mediated the effects of Wnt5a on the regulation of pancreatic cancer cell apoptosis in vitro. These results suggested that Wnt5a is involved in the modulation of pancreatic cancer cell proliferation, and that Wnt5a may be a potential target for pancreatic cancer therapy.

在器官病理学的基础上，人们早在12世纪前后就开始应用人体组织活检辅助临床疾病的诊断。显微镜问世后，组织病理学成为疾病诊断不可或缺的手段，作为临床病理学家也早已习惯了病理诊断从大体到镜下的病理诊断流程。然而随着生命科学理论和技术的快速发展和进步，近几十年来经典病理学的理论和技术已经经历了许多重大的变革，传统病理学的概念正在不断地延伸和扩展，病理诊断也逐步由宏观向微观世界迈进，形态与功能相结合的病理诊断成为病理学发展的趋势，临床病理的概念已经由常规的组织病理学扩展到免疫病理、分子病理，现代生命科学的理论和技术为病理学这一传统而古老的学科注入了新的生命力，也要求病理学家在适应病理诊断模式转换的同时，更要重视理念／观念的转变。如病理样本的来源除传统的肉眼可见的组织样本外更加多样、复杂，其中近几年发展迅速、临床应用前景广阔的液态活检（ liquid biopsy ）概念的重新提出并越来越受到重视，将是病理学家所面临的新的机遇和挑战，作为临床病理学家应尽快地认识、重视并积极主动地接受这一新技术的应用。