Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions

BACKGROUND Study shows that signal transducer and activator of transcription 3(STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2(PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats.AIM To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats.METHODS A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with Nmethyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen(PCNA), STAT3,and PKM2 were examined by Western blot and immunofluorescence.RESULTS We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liverprecancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression,PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells.Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2.CONCLUSION The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.

Diagnostic performance of narrow-band imaging international colorectal endoscopic and Japanese narrow-band imaging expert team classification systems for colorectal cancer and precancerous lesions

BACKGROUND In recent years,two new narrow-band imaging(NBI)classifications have been proposed:The NBI international colorectal endoscopic(NICE)classification and Japanese NBI expert team(JNET)classification.Most validation studies of the two new NBI classifications were conducted in classification setting units by experienced endoscopists,and the application of use in different centers among endoscopists with different endoscopy skills remains unknown.AIM To evaluate clinical application and possible problems of NICE and JNET classification for the differential diagnosis of colorectal cancer and precancerous lesions.METHODS Six endoscopists with varying levels of experience participated in this study.Eighty-seven consecutive patients with a total of 125 lesions were photographed during non-magnifying conventional white-light colonoscopy,non-magnifying NBI,and magnifying NBI.The three groups of endoscopic pictures of each lesion were evaluated by the six endoscopists in randomized order using the NICE and JENT classifications separately.Then we calculated the six endoscopists’sensitivity,specificity,accuracy,positive predictive value,and negative predictive value for each category of the two classifications.RESULTS The sensitivity,specificity,and accuracy of JNET classification type 1 and 3 were similar to NICE classification type 1 and 3 in both the highly experienced endoscopist(HEE)and less-experienced endoscopist(LEE)groups.The specificity of JNET classification type 1 and 3 and NICE classification type 3 in both the HEE and LEE groups was>95%,and the overall interobserver agreement was good in both groups.The sensitivity of NICE classification type 3 lesions for diagnosis of SM-d carcinoma in the HEE group was significantly superior to that in the LEE group(91.7%vs 83.3%;P=0.042).The sensitivity of JNET classification type 2B lesions for the diagnosis of high-grade dysplasia or superficial submucosal invasive carcinoma in the HEE and LEE groups was 53.8%and 51.3%,respectively.Compared with other types of JNET classification,the diagnostic ability of type 2B was the weakest.CONCLUSION The treatment strategy of the two classification type 1 and 3 lesions can be based on the results of endoscopic examination.JNET type 2B lesions need further examination.

Focal liver lesions in cirrhosis:Role of contrast-enhanced ultrasonography

Contrast-enhanced ultrasound(CEUS)represents a great innovation for the evaluation of focal liver lesions(FLLs).The main advantage of CEUS is the realtime imaging examination and the very low toxicity in patients with renal failure.Liver cirrhosis has been recognized as a major risk factor for the onset of hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(ICC).HCC in liver cirrhosis develops as the last step of a complex that leads to the gradual transformation from regenerative nodule through dysplastic nodule to HCC.In patients with liver cirrhosis,a surveillance program is recommended consisting of ultrasound(US)for detecting small focal lesions.A wide spectrum of benign and malignant lesions other than HCC may be found in the cirrhotic liver and their differentiation is important to avoid errors in staging diseases that may preclude potentially curative therapies.Several published studies have explored the value of CEUS in liver cirrhosis and they have been shown to have excellent diagnostic and prognostic performances for the evaluation of non-invasive and efficient diagnosis of FLLs in patients at high risk for liver malignancies.The purpose of this article is to describe and discuss CEUS imaging findings of FLLs including HCC and ICC,all of which occur in cirrhotic livers with varying prevalence.

Therapeutic mechanisms of integrated traditional Chinese and conventional medicine underlying its treatment of precancerous lesions of gastric cancer

China has a high incidence of gastric cancer. Secondary prevention of gastric cancer is a major public health problem that must be solved urgently. Modern medicine focuses on the pathogenesis of precancerous lesions of gastric cancer(PLGC), and it has been found that there are a variety of abnormal gene expression patterns in PLGC. This study summarizes recent advances in our understanding of the therapeutic mechanisms of PLGC from various clinical studies;this will provide a reference for studying the therapeutic mechanisms of Traditional Chinese Medicine in the treatment of PLGC from the combined points of view of Traditional Chinese and Conventional medicine.

Expression of glutathione S-transferase placental mRNA in hepatic preneoplastic lesions in rats

IM To detect glutathione Stransferase placental (GSTP) mRNA expression in hepatic preneoplastic lesions in rats.METHODS Using SolitFarber model, the GSTP mRNA expression was observed in hepatic preneoplastic lesions induced by diethylnitrosamine (DEN) in rats and normal and regenerated hepatic tissues in the control group by in situ hybridization.RESULTS GSTP mRNA was mainly expressed in altered hepatic foci (AHF) and some of the oval cells in hepatic preneoplastic lesions and the extent of its expression was different among various foci or/and positive cells in the same focus whereas no expression was observed in normal and regenerated hepatic tissues.CONCLUSION Cells in AHF and oval cells may be the preneoplastic cells in the experimental hepatocellular carcinoma at the molecular level and heterogeneity exists in GSTP transcription levels..

Dynamic role of myofibroblasts in oral lesions

Fibroblasts are the most abundant cellular components of connective tissue. They possess phenotypical heterogenicity and may be present in the form of smooth muscle cells or myofibroblasts(MFs). MFs are spindle-shaped cells with stress fibres and welldeveloped fibronexus,and they display α-smooth muscle actin immunohistochemically and smoothmuscle myofilaments ultrastructurally. MFs play a crucial role in physiological and pathological processes. Derived from various sources,they play pivotal roles not only by synthesizing and producing extracellular matrix components,such as other connective tissue cells,but also are involved in force production. In the tissue remodelling phase of wound closure,integrinmediated interactions between MFs and type I collagen result in scar tissue formation. The tumour stroma in oral cancer actively recruits various cell types into the tumour mass,where they act as different sources of MFs. This article reviews the importance of MFs and its role in pathological processes such as wound healing,odontogenic cysts and tumours,salivary gland tumours,oral preneoplasia,and oral squamous cell carcinoma. Research oriented on blocking the transdifferentiation of fibroblasts into MFs can facilitate the development of noninvasive therapeutic strategies for the treatment of fibrosis and/or cancer.

内镜治疗肝硬化患者上消化道早癌的风险及处理策略

肝硬化患者患上消化道肿瘤风险增加,尤其是酒精性肝硬化患者.随着内镜检查的推广及普及,越来越多的上消化道早癌得以早期发现及治疗.内镜治疗已成为上消化道早癌的首选治疗方式,肝硬化患者由于可能存在血小板减少、凝血功能障碍、合并食管胃静脉曲张等情况,内镜治疗过程中出血、感染等风险较大.近年来国内外已有部分研究探讨内镜治疗肝硬化伴上消化道早癌的安全性及有效性.本文总结了近年来发表的内镜治疗肝硬化伴上消化道早癌的研究结果,简要综述其风险及防治策略,为临床提供指导.

ADCY7、GPR86、GRIN2D、RGS4对胃癌前病变进展的预测价值

背景:目前临床上尚无有效预测胃癌前病变进展或筛查早期胃癌的生物学标志物。目的:研究腺苷酸环化酶7(ADCY7)、G蛋白偶联受体GPR86、N⁃甲基⁃D⁃天冬氨酸离子能谷氨酸受体2D(GRIN2D)、G蛋白信号调节因子4(RGS4)在不同胃黏膜病变中的表达及其对胃癌前病变进展的预测价值。方法:应用免疫组化法、real-time PCR和蛋白质印迹法检测ADCY7、GPR86、GRIN2D、RGS4在Correa级联各阶段(包括慢性非萎缩性胃炎、慢性萎缩性胃炎、低级别和高级别上皮内瘤变、黏膜层和黏膜下层早期胃癌)以及胃癌与相应癌旁组织间的表达差异。结果:ADCY7、GPR86、GRIN2D、RGS4在胃炎、上皮内瘤变、早期胃癌中的表达呈递增趋势,除GRIN2D在上皮内瘤变与早期胃癌中的表达无明显差异外,两两比较差异均有统计学意义(P均<0.001)。GPR86、GRIN2D mRNA和蛋白在胃癌组织中的表达显著高于癌旁>5 cm组织(P均<0.05);RGS4蛋白在胃癌组织中的表达高于癌旁>5 cm组织,其mRNA表达趋势则相反(P均<0.05);ADCY7仅蛋白表达在胃癌与癌旁>5 cm组织间差异显著(P<0.05)。结论:ADCY7、GPR86、GRIN2D、RGS4在Correa级联各阶段以及胃癌与相应癌旁组织间的表达变化提示其参与了胃癌前病变的发生、发展,可能具有预测胃癌前病变进展的价值。

益脾养肝方对肝癌前病变大鼠肝星状细胞活化的影响

目的探讨益脾养肝方对二乙基亚硝胺(Diethylnitrosamine,DEN)诱导的肝癌前病变中肝星状细胞活化及胶原沉积的影响。方法将26只雄性Sprague-Dawley大鼠随机分为空白组、模型组、益脾养肝方组和护肝片组,空白组5只,其余3组各7只。腹腔注射DEN诱导肝癌前病变模型,给药14 w后处死。取肝组织观察并记录其大小、外观等变化,计算肝重比(肝脏指数),通过HE染色观察大鼠肝组织病理形态学改变,天狼星红染色观察各组胶原沉积表达,免疫组化检测α-平滑肌动蛋白(alpha smooth muscle actin,α-SMA)的表达,实时定量PCR(Real Time PCR,RT-PCR)检测Ⅰ型胶原蛋白(typeⅠcollagen,CollagenⅠ)的表达,以研究益脾养肝方对大鼠肝癌前病变模型的影响。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果与模型组相比,益脾养肝方组和护肝片组肝脏病理形态显著改善,肝脏指数、CollagenⅠ和α-SMA表达均降低(P值均<0.05);与护肝片组相比,益脾养肝方组对肝脏的保护作用更显著,其肝脏指数、CollagenⅠ和α-SMA表达均显著降低(P值均<0.05)。结论益脾养肝方可有效改善DEN诱导的大鼠肝癌前病变,其机制可能与抑制肝星状细胞活化,减少胶原沉积有关。

胰腺导管内乳头状黏液性肿瘤的病理诊断进展

胰腺导管内乳头状黏液性肿瘤(intraductal papillary mucinous neoplasm, IPMN)是胰腺导管腺癌重要的癌前病变。IPMN诊疗决策的制定首先基于对IPMN相关病理学的深刻理解。本文围绕IPMN宏观检查、微观检查、分子检测及鉴别诊断四个方面进行系统的文献综述。本综述详细阐述了IPMN大体类型分类、组织学分级与分化亚型、IPMN伴浸润性癌的组成模式和组织学类型、IPMN分子研究的新进展以及重要的鉴别诊断等。该分析肯定IPMN特殊的异质性和异时性的特点,为寻找新的方法帮助临床医师制定适宜的诊疗方案奠定基础。

大黄素干预PI3K/Akt/mTOR信号通路影响肝癌前病变大鼠铁死亡的作用机制

目的 探究大黄素对二乙基亚硝胺(diethylnitrosamine, DEN)诱导的肝癌前病变大鼠磷脂酰肌醇3-激酶(phosphoinositide 3-kinase, PI3K)/蛋白激酶B(protein kinase B, Akt)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)信号转导通路的调控作用及对铁死亡的影响。方法 采用DEN诱发大鼠肝癌前病变进行肝癌前病变造模。随机将50只雄性SD大鼠分为对照组[未造模+10ml/(kg·d)生理盐水灌胃)]、DEN模型组[肝癌前病变造模+10 ml/(kg·d)生理盐水灌胃]、DEN+大黄素组[肝癌前病变造模+80 mg/(kg·d)大黄素浓缩液灌胃]、DEN+护肝片组[肝癌前病变造模+900 mg/kg护肝片灌服]和DEN+大黄素+护肝片组[肝癌前病变造模+80 mg/(kg·d)大黄素浓缩液灌胃+900 mg/kg护肝片灌服],每组各10只大鼠。各组大鼠连续干预治疗12周。生化分析法检测各组大鼠血清丙氨酸氨基转移酶(alanine aminotransferase, ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase, AST)、白蛋白(albumin, ALB)水平;比较各组大鼠的肝脏指数。酶联免疫吸附试验(enzyme-linked immunosorbent assay, ELISA)法检测各组大鼠血清白细胞介素1β(interleukin 1 beta, IL-1β)、肿瘤坏死因子α(tumor necrosis factor alpha, TNF-α)、IL-10含量。苏木精-伊红(hematoxylin-eosin, HE)染色法观察各组大鼠肝组织病理形态学改变;脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling, TUNEL)分析各组大鼠肝组织细胞凋亡情况。免疫组织化学法检测各组大鼠肝组织中铁死亡中心调节因子谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)蛋白表达。马松三色染色(Masson′s trichrome staining, MASSON)法分析各组大鼠肝组织病理改变。逆转录聚合酶链反应(reverse transcription polymerase chain reaction, RT-PCR)法检测各组大鼠肝组织中PIK3、Akt、mTOR的mRNA水平。结果 与对照组比较,DEN模型组大鼠ALT水平、AST水平、肝脏指数显著升高,ALB水平显著降低(P均<0.05),血清IL-1β、TNF-α、IL-10含量明显升高(P均<0.05);肝细胞明显炎性浸润,细胞免疫应答增加,肝细胞形态畸变并出现变性死亡;肝组织中GPX4蛋白表达量明显下降(P<0.05),PI3K、Akt、mTOR的mRNA表达量明显上升(P均<0.05)。与DEN模型组比较,DEN+大黄素组、DEN+护肝片组、DEN+大黄素+护肝片组大鼠ALT水平、AST水平、肝脏指数显著降低,ALB显著升高(P均<0.05),血清IL-1β、TNF-α、IL-10含量明显降低(P均<0.05);肝细胞排列趋向正常,炎性浸润减轻,肝细胞弥漫性纤维化病变减弱,血管及胆管周围肝细胞形态逐渐好转,蓝色胶原纤维组织减少;肝组织中GPX4蛋白表达量明显上升(P均<0.05),PI3K、Akt、mTOR的mRNA表达量明显下降(P均<0.05),且上述变化DEN+大黄素+护肝片组改善效果明显优于DEN+大黄素组和DEN+护肝片组(P均<0.05)。结论 大黄素可通过促进组织中铁死亡相关蛋白GPX4表达来改善大鼠肝癌前病变,其作用机制可能与大黄素调控PI3K/Akt/mTOR信号通路有关。

基于M1型巨噬细胞极化-慢性炎症-肝细胞恶变探究益脾养肝方治疗肝癌前病变作用机制

目的基于M1型巨噬细胞极化-慢性炎症-肝细胞恶变发展过程探究益脾养肝方治疗肝癌前病变大鼠的作用机制。方法90只Wistar大鼠随机分为空白组、模型组、护肝片组和益脾养肝方高、中、低剂量组,每组15只。空白组予蒸馏水腹腔注射,其余各组予二乙基亚硝胺腹腔注射诱导肝癌前病变模型,每周2次(50 mg/kg),连续16周。造模第2日起,益脾养肝方高、中、低剂量组分别予1.2、0.6、0.3 g/mL益脾养肝方灌胃,护肝片组予护肝片溶液921 mg/kg灌胃,空白组和模型组予等量生理盐水灌胃,连续16周。观察肝脏外观,ELISA检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转氨酶(AST)、碱性磷酸酶(ALP)、α-L-岩藻糖苷酶(AFU)及肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、诱导型一氧化氮合酶(iNOS)、单核细胞趋化蛋白-1(MCP-1)含量,HE染色、Masson染色观察肝组织形态,免疫组化检测肝细胞恶变标志物OV6、细胞角蛋白19(CK19)、CD133和上皮细胞黏附分子(EpCAM)表达,qPCR检测肝组织CK19、CD133、EpCAM mRNA表达,免疫荧光共定位检测M1型巨噬细胞标志物CD68与IL-6和TNF-α共表达。结果与空白组比较,模型组大鼠肝脏质硬,表面粗糙、边缘变钝,可见大量结节,血清ALT、AST、ALP、AFU、TNF-α、IL-6、i NOS、MCP-1含量明显升高(P<0.01),肝组织有大面积异型增生结节、炎性细胞浸润,胶原纤维增多,肝组织OV6、CK19、CD133、EpCAM表达显著升高,CD68与IL-6和TNF-α共表达显著升高(P<0.01);与模型组比较,各给药组大鼠肝脏结节减少且较小,血清ALT、AST、ALP、AFU、TNF-α、IL-6、iNOS、MCP-1含量均显著降低(P<0.01),肝细胞异型增生及炎性细胞浸润显著改善,胶原纤维减少,肝组织OV6、CK19、CD133、EpCAM表达显著降低,CD68与IL-6和TNF-α共表达显著降低(P<0.05,P<0.01)。结论益脾养肝方可能通过抑制M1型巨噬细胞极化减轻炎症反应,改善肝细胞恶变,对二乙基亚硝胺诱导的肝癌前病变大鼠发挥治疗作用。

芪术化积方治疗肝细胞癌癌前病变患者的随机对照研究

背景肝细胞癌(HCC)存在发病率高、死亡率高的特点,在癌前病变阶段进行早期诊断及时干预可有效降低HCC的发生率,对其防治具有显著意义。现代医学对于HCC癌前病变的治疗存在干预时机难以把握、治疗手段单一等问题,中医药防治HCC癌前病变或许是一种简单有效的新途径。目的观察芪术化积方治疗HCC癌前病变(肝郁脾虚、痰瘀互结证)的临床疗效及安全性。方法纳入2019年10月—2020年3月在山东中医药大学附属医院、威海市中医院、泰安市中医院肝病科门诊就医且符合中医证型“肝郁脾虚、痰瘀互结证”的HCC癌前病变初诊患者为研究对象。收集患者的一般资料[性别、年龄、乙型病毒性肝炎(HBV)后肝硬化史、HCC家族史、10年以上饮酒史],患者的中医证候积分、肝功能指标[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、白蛋白(ALB)、谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)]、肿瘤标志物指标[甲胎蛋白(AFP)、甲胎蛋白异质体(AFP-L3)、异常凝血酶原(DCP)]、影像学指标(病灶类型、病灶性质、病灶长径)、安全性指标、不良反应。采用随机数字表法将符合纳入标准且完成研究的64例患者分为观察组(n=34)和对照组(n=30),对照组予以抗病毒、抗炎保肝等常规治疗;观察组予以常规治疗联合芪术化积方治疗。疗程为48周,停药后随访48周,观察两组患者治疗周期及随访周期中HCC发生率及并发症的发生情况,比较两组患者治疗前后中医证候改善指标(中医证候积分、总有效率)、肝功能指标、肿瘤标志物指标、影像学指标(病灶长径、病灶稳定率、病灶改善率)、安全性指标(安全率)的差异。结果治疗后两组中医证候积分、ALT、AST、TBIL、GGT、ALP、AFP-L3均低于治疗前,ALB水平高于治疗前(P<0.05);观察组患者治疗后的DCP值、病灶长径均低于治疗前(P<0.05)。组间比较结果显示,观察组中医证候积分、AST、ALP水平低于对照组,ALB水平高于对照组(P<0.05)。治疗周期结束后观察组的中医证候总有效率(91.2%)高于对照组(63.3%)(P<0.05);观察组病灶改善率(35.3%)和病灶稳定率(50.0%)与对照组(20.0%,43.3%)比较,差异无统计学意义(P>0.05)。随访周期结束后观察组HCC发生率(8.8%)与对照组(16.7%)比较,差异无统计学意义(P>0.05);并发症发生率(8.8%)低于对照组(30.0%)(P<0.05)。安全性指标方面,观察组2例出现轻度不良反应,对照组3例出现轻度不良反应,两组均未出现安全性指标异常,观察组安全率(94.1%)与对照组(90.0%)比较,差异无统计学意义(P>0.05)。结论芪术化积方治疗HCC癌前病变(肝郁脾虚、痰瘀互结证),在改善中医证候、改善肝功能、缩小病灶结节、降低远期HCC发生率及减少肝硬化并发症等方面有较好的临床疗效及安全性。

近10年中医辨治胃癌前病变的研究进展

对近10年来有关中医辨治胃癌前病变(precancerous lesions of gastric cancer,PLGC)的研究进行综述。PLGC是指在慢性萎缩性胃炎基础上出现的胃黏膜肠上皮化生和异型增生,作为慢性萎缩性胃炎与胃癌的中间阶段,PLGC的病程较缓慢。中医辨治PLGC具有一定的优势。PLGC主要可分为脾胃虚弱证、脾胃湿热证、肝胃气滞证、胃络瘀阻证、胃阴不足证5种证型。胃镜技术的普及促进了胃病微观辨证的发展,微观辨证与宏观辨证的结合为PLGC的中医辨证论治提供了更加丰富的理论支持。PLGC根本病机为脾胃虚弱,脾胃气机不畅,兼有湿热、瘀毒、痰湿等病理因素蕴结,日久胃阴亏耗。中药治疗PLGC的临床研究开展较多,治疗主要采用以益气健脾为主,兼以疏肝活血、化湿消瘀、化瘀解毒、养阴益胃,从而防止PLGC向胃癌进一步发展。针灸治疗胃癌前病变的研究开展较少。今后需开展更多严格且规范的多中心、大样本的临床随机对照试验,深入研究针灸治疗胃癌前病变机制,以期为中医辨治PLGC提供更多高级别的循证依据。

激光共聚焦显微内镜在上消化道早癌和癌前病变中的应用进展

上消化道癌主要包括食管癌和胃癌,其发病率和死亡率高,早期发现可极大改善患者预后,提高5年生存率和生活质量。激光共聚焦显微内镜在上消化道早癌和癌前病变诊断方面有独特优势,可以实时诊断和光学活检,通过观察黏膜微观结构、细胞、亚细胞、微血管形态等进行体内组织学诊断。本文就激光共聚焦显微内镜在早期食管癌、胃癌和癌前病变中的应用进行系统阐述,以评价其临床应用价值和前景。

Hp、RASAL2、CDH1及TP53对胃癌前病变与早期胃癌的鉴别诊断价值

目的探讨幽门螺杆菌(Hp)、RAS蛋白激活样因子2(RASAL2)、钙黏蛋白1(CDH1)及肿瘤抑制基因P53(TP53)对胃癌前病变与早期胃癌的鉴别诊断价值。方法选取2021年6月至2023年6月收治的早期胃癌52例,根据1:1选例原则另选取同期胃癌前病变52例、胃炎52例,分别纳入胃癌组、癌前组、胃炎组。比较3组及不同病理特征的早期胃癌患者Hp、RASAL2、CDH1、TP53阳性表达率,比较胃癌组Hp阳性、阴性患者RASAL2、CDH1、TP53阳性表达率,采用Spearman相关分析探讨各指标阳性表达与早期胃癌患者部分病理特征的相关性,采用受试者工作特征(ROC)曲线分析联合检测对早期胃癌及胃癌前病变的鉴别诊断价值。结果3组Hp、CDH1、TP53阳性表达率胃癌组>癌前组>胃炎组,RASAL2阳性表达率胃癌组<癌前组<胃炎组,差异有统计学意义(P<0.05,P<0.01)。胃癌组Hp阳性患者CDH1、TP53阳性表达率高于Hp阴性患者,RASAL2阳性表达率低于Hp阴性患者(P<0.05,P<0.01);早期胃癌患者Hp、RASAL2、CDH1、TP53阳性表达率在肿瘤浸润深度及淋巴结转移方面比较差异有统计学意义(P<0.05,P<0.01)。Hp、CDH1、TP53阳性表达与早期胃癌肿瘤浸润深度、淋巴结转移均呈正相关,RASAL2阳性表达与之呈负相关(P<0.01)。ROC曲线分析结果显示,Hp、RASAL2、CDH1、TP53联合诊断胃癌前病变的曲线下面积(AUC)为0.904(95%CI:0.846,0.945),联合诊断早期胃癌的AUC为0.894(95%CI:0.819,0.946)。结论Hp、CDH1、TP53在早期胃癌组织中阳性表达率较高,RASAL2阳性表达率较低,联合检测对胃癌前病变及早期胃癌具有一定鉴别诊断价值,可作为临床鉴别诊断胃癌前病变、早期胃癌的辅助指标。

内镜黏膜下剥离术在早期胃癌及癌前病变治疗中的价值

目的评价内镜黏膜下剥离术(endoscopic submucosal dissection,ESD)治疗早期胃癌及癌前病变的安全性、有效性,为早期胃癌及癌前病变的内镜治疗提供依据。方法回顾性分析2012年10月到2014年8月在第二军医大学长海医院消化内镜中心接受ESD治疗的214例胃黏膜病变患者的临床资料,分析术前评估、病理特征、ESD治疗及术后随访等情况。结果214例患者术前评估中,接受内镜窄带成像(narrow band imaging,NBI)检查者67例(31.3%),NBI联合放大内镜(magnifying endoscopy,ME)检查者39例(18.2%),超声内镜(endoscopic ultrasonography,EUS)检查者50例(23.4%),CT检查者50例(23.4%),活组织检查者192例(89.7%)。214例病灶术后病理中,低级别上皮内瘤变84例(39.2%)、高级别上皮内瘤变55例(25.7%)、高分化癌45例(21.0%)、中分化癌19例(8.9%)、低分化癌11例(5.1%)。ESD整块切除率为96.3%,完整切除率为92.1%;ESD手术时间为14~290min,平均(59.9±49.6)min;术中大出血2例(0.9%),术中穿孔2例(0.9%);术后延迟出血5例(2.3%),术后复发5例(2.3%),无患者发生术后延迟性穿孔。结论 ESD是治疗早期胃癌及癌前病变的有效手段,但应进行完善的术前评估以避免不必要或过度的ESD治疗,术后定期随访是监测术后病灶残留与复发的有效手段。

癌基因蛋白ras p21、甲胎蛋白在实验性大鼠肛癌前病变中的表达

应用免疫组化技术，检测了ｒａｓｐ２１、ＡＦＰ在二乙基亚硝胺（ＤＥＮＡ）诱发的大鼠肝癌前病变中的表达。结果显示：诱癌早期肝小叶周边区即出现ｐ２１、ＡＦＰ表达阳性细胞，随诱癌过程进行，阳性细胞增多并主要分布在变异肝细胞灶和结节中，且常见两者同时表达的现象。由此提示，两者与大鼠肝癌发生有密切关系，ｐ２１过度表达直接参与了大鼠肝癌的启动和演进。同时表达ＡＦＰ、ｐ２１的细胞和病变是较具特异性的癌前病变。ｐ２ｌ与ＡＦＰ的联合表达可为人类肝癌提供一个参考诊断标志。

正肝方治疗肝硬化伴高甲胎蛋白血症的近期疗效观察

目的观察中药正肝方治疗肝硬化伴高甲胎蛋白(AFP)患者的临床疗效,并探讨其疗效机理。方法64例肝硬化伴高AFP患者,随机分为正肝方治疗组和对照组。对照组给予常规西药综合治疗,正肝方治疗组在常规西药综合治疗基础上,加用中药正肝方,每天1剂,每天2次口服,疗程6个月。观察两组患者治疗前后肝功能(ALT、GGT、TBIL、ALB)、AFP值、CD4、CD4/CD8值及肝脏影像学检查情况,比较各组治疗效果。结果正肝方能有效降低患者AFP水平(P<0·01),升高患者CD4、CD4/CD8值(P<0·01或P<0·05)。结论正肝方能有效降低AFP水平,其机理可能与提高患者的细胞免疫功能有关。

河南食管癌高发区居民食管色素镜检查及手术标本碘染色结果分析

目的 :评价色素镜 (纤维内镜下行粘膜碘染 )对提高食管癌高发区无症状人群食管癌各级癌前病变检出率的意义以及碘染对获取手术切除大体标本癌旁各级病变组织的影响。方法 :常规食管纤维内镜观察后 ,在食管表面喷洒体积分数为 2 %的卢戈液染色 ,根据染色情况分别取活检组织进行组织病理学检查。采取同样的卢戈溶液对手术切除的食管标本作碘染色 ,并根据染色结果 ,分别取材作进一步的组织病理学分析。结果 :纤维内镜下碘染后 ,可观察到清晰的片状不染区 ,以及花斑状 ,点状和条状不染区。手术切除标本碘染后也出现相似的变化。对染色区和不染区分别取材 ,发现手术切除标本碘染区的各级癌前病变检出率明显高于不染区 (P <0 .0 5 ) ,特别是间变和原位癌病灶。 2 35例无症状人群色素镜检查组 (碘染组 )基底细胞过度增生和间变的检出率分别为 6 4 % (114 /179)和 74 % (14 /19) ,均明显高于非碘染组 36 % (6 5 /179)和 2 6 % (5 /19) (P <0 .0 5 )。但无症状人群碘染组染色区取材仍发现 4 %的间变检出率。结论 :色素镜 (碘染色 )能明显提高无症状人群食管癌前病变的检出率。手术切除标本行碘染色是获取各级癌前病变的有效手段。