Characteristics and risk factor analyses of high-grade intraepithelial neoplasia in older patients with colorectal polyps

BACKGROUND According to the degree of intradermal neoplasia in the colorectal exhalation,it can be divided into two grades:Low-grade intraepithelial neoplasia(LGIN)and high-grade intraepithelial neoplasia(HGIN).Currently,it is difficult to accurately diagnose LGIN and HGIN through imaging,and clinical diagnosis depends on postoperative histopathological diagnosis.A more accurate method for evaluating HGIN preoperatively is urgently needed in the surgical treatment and nursing intervention of colorectal polyps.AIM To explore the characteristics and risk factors of HGIN in older patients with colorectal polyps.METHODS We selected 84 older patients diagnosed with HGIN as the HGIN group(n=95 colonic polyps)and 112 older patients diagnosed with LGIN as the LGIN group(n=132 colonic polyps)from Shandong Provincial Hospital Affiliated to Shandong First Medical University.The endoscopic features,demographic characteristics,and clinical manifestations of the two patient groups were compared,and a logistic regression model was used to analyze the risk factors for HGIN in these patients.RESULTS The HGIN group was older and had a higher number of sigmoid colon polyps,rectal polyps,pedunculated polyps,polyps≥1.0 cm in size,polyps with surface congestion,polyps with surface depression,and polyps with villous/tubular adenomas,a higher proportion of patients with diabetes and a family history of colorectal cancer,patients who experienced rectal bleeding or occult blood,patients with elevated carcinoembryonic antigen(CEA)and cancer antigen 199(CA199),and lower nutritional levels and higher frailty levels.The polyp location(in the sigmoid colon or rectum),polyp diameter(≥1.0 cm),pathological diagnosis of(villous/tubular adenoma),family history of colorectal cancer,rectal bleeding or occult blood,elevated serum CEA and CA199 levels,lower nutritional levels and higher frailty levels also are independent risk factors for HGIN.CONCLUSION The occurrence of high-grade neoplastic transformation in colorectal polyps is closely associated with their location,size,villous/tubular characteristics,family history,elevated levels of tumor markers,and lower nutritional levels and higher frailty levels.

Missed diagnosis of early gastric cancer or high-grade intraepithelial neoplasia

AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenos-copy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89,23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.

Prediction value of high-grade prostatic intraepithelial neoplasia for prostate cancer on repeat biopsies

Objective: The significance of isolated high-grade prostatic intraepithelial neoplasia in initial biopsy as an predic-tor for prostate cancer has been extensively research, and the true relationship remnant is no clear till now. The aim of this study is to evaluate prediction value of cancer on repeat biopsy in patients with high-grade prostatic intraepithelial neoplasia, using multivariate analysis. Methods: Thirty-eight men with a diagnosis of isolated high-grade prostatic intraepithelial neo-plasia in initial needle biopsy were studies, in the Fist Affiliated Hospital of Medical School of Xi'an Jiaotong University, from January 2003 to March 2009. These samples were using immunostaining of p63 and 34βE12 and P504s, with a median fol-low-up of 525 (range, 7 to 1650) days, and to researched the incidence of subsequent prostate cancer, and to predicted the risk of prostate cancer in clinicopathological parameters of isolated high-grade prostatic intraepithelial neoplasia on repeat biopsies by logistic regression analysis. Results: There were 10 of 38 (26.3%) men with prostate cancer on repeat biopsies after diagnosis isolated high-grade prostatic intraepithelial neoplasia in initial biopsy, of the rates of prostate cancer were 80% for micropapillary and 75% for cribriform high-grade prostatic intraepithelial neoplasia (P < 0.05), respectively. The positive cores of isolated high-grade prostatic intraepithelial neoplasia was the important for the risk of prostate cancer using Multi-factor logistic regression analysis. The time range in 30 to 690 days was stronger risk for prostate cancer detection after diagnosis isolated HGPIN in initial biopsy. p63 and 34βE12 were disrupted positive expression, and P504S was weak posi-tive expression in the 61% isolated high-grade prostatic intraepithelial neoplasia. Conclusion: Isolated high-grade prostatic intraepithelial neoplasia on repeat biopsy conferred a 26.3% risk of prostate cancer, and this risk level is lower than the previ-ously reported risk of 24% to 58%. The number of positive cores and the histopathological pattern with high-grade prostatic intraepithelial neoplasia on initial biopsy was significantly associated with the risk of cancer.

Treatment strategy for gastric non-invasive intraepithelial neoplasia diagnosed by endoscopic biopsy

Treatment strategies,whether as follow-up or"total incisional biopsy"for gastric noninvasive intraepithelial neoplasia diagnosed by examination of an endoscopic forceps biopsy specimen,are controversial due to problems associated with the diagnostic accuracy of endoscopic forceps biopsy and questions about the safety and efficacy of endoscopic treatment.Based on the histological findings of the biopsy specimen,it is difficult to differentiate between reactive or regenerative changes,inflammation and neoplastic changes,intraepithelial and invasive tumors.Therefore,gastric neoplasia diagnosed as noninvasive intraepithelial often develop into invasive carcinoma during follow-up.Recent advances in endoscopic modalities and treatment devices,such as image-enhanced endoscopy and highfrequency generators,may make endoscopic treatment,such as endoscopic submucosal dissection(ESD),a therapeutic option for gastric intraepithelial neoplasia,including low-grade neoplasms.Future studies are required to evaluate whether ESD is a valid strategy for gastric intraepithelial neoplasm with regard to safety and cost effectiveness.

Diagnosis of gastric intraepithelial neoplasia by narrow-band imaging and confocal laser endomicroscopy

AIM:To evaluate the diagnosis of different differentiated gastric intraepithelial neoplasia (IN) by magnifica-tion endoscopy combined with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE). METHODS:Eligible patients with suspected gastric IN lesions previously diagnosed by endoscopy in secondary hospitals and scheduled for further diagnosis and tratment were recruited for this study. Excluded from the study were patients who had liver cirrhosis, impaired renal function, acute gastrointestinal (GI) bleeding, coagulopathy, esophageal varices, jaundice, and GI post-surgery. Also excluded were those who were pregnant, breastfeeding, were younger than 18 years old, or were unable to provide informed consent. All patients had all mucus and bile cleared from their stom-achs. They then received upper GI endoscopy. When a mucosal lesion is found during observation with whitelight imaging, the lesion is visualized using maximal magnification, employing gradual movement of the tip of the endoscope to bring the image into focus. Saved images are analyzed. Confocal images were evaluated by two endoscopists (Huang J and Li MY), who were familiar with CLE, blinded to the related information about the lesions, and asked to classify each lesion as either a low grade dysplasia (LGD) or high grade dysplasia (HGD) according to given criteria. The results were compared with the final histopathologic diagnosis. ME-NBI images were evaluated by two endoscopists (Lu ZS and Ling-Hu EQ) who were familiar with NBI, blinded to the related information about the lesions and CLE images, and were asked to classify each lesion as a LGD or HGD according to the "microvascular pattern and surface pattern" classification system. The results were compared with the final histopathologic diagnosis. RESULTS: The study included 32 pathology-proven low grade gastric IN and 26 pathology-proven high grade gastric IN that were detected with any of the modalities. CLE and ME-NBI enabled clear visualization of the vascular microsurface patterns and microvascular structures of the gastric mucosa. The accuracy of the CLE and the ME-NBI diagnosis was 88% (95% CI:78%-98%) and 81% (95% CI: 69%-93%), respectively. The kappa coefficient of agreement between the histopathology and the in vivo CLE imaging was 0.755; between the histopathology and the in vivo CLE imaging was 0.615. McNemar's test (binomial distribution used) indicated that the agreement was significant (P < 0.05). When patients were diagnosed by MENBI with CLE, the overall accuracy of the diagnosis was 86.21% (95% CI:73%-96%), and the kappa coefficient of agreement was 0.713, according to McNemar's test (P < 0.05). CONCLUSION:Higher diagnostic accuracy, sensitivityand specificity of CLE over ME-NBI indicate the feasibility of these two techniques for the efficacious diagnostic classification of gastric IN.

Differential gene expression profiling of gastric intraepithelial neoplasia and early-stage adenocarcinoma

AIM: To investigate the differentiated whole genome expression profiling of gastric high- and low-grade intraepithelial neoplasia and early-stage adenocarcinoma.

Clinical efficacy and prognostic risk factors of endoscopic radiofrequency ablation for gastric low-grade intraepithelial neoplasia

BACKGROUND The use of radiofrequency ablation(RFA)has been reported in the treatment of gastric low-grade intraepithelial neoplasia(LGIN).However,its efficacy and prognostic risk factors have not been well analyzed.AIM To explore the efficacy and prognostic risk factors of RFA for gastric LGIN in a large,long-term follow-up clinical study.METHODS The clinical data of 271 consecutive cases from 198 patients who received RFA for treatment of gastric LGIN at the Chinese PLA General Hospital from October 2014 to October 2020 were reviewed in this retrospective study.Data on operative parameters,complications,and follow-up outcomes including curative rates were recorded and analyzed.RESULTS The curative rates of endoscopic RFA for gastric LGIN at 3 mo,6 mo,and 1-5 years after the operation were 93.3%,92.8%,91.5%,90.3%,88.5%,85.7%,and 83.3%,respectively.Multivariate analyses revealed that Helicobacter pylori(H.pylori)infection and disease duration>1 year had a significant effect on the curative rate(P<0.001 and P=0.013,respectively).None of patients had bleeding,perforation,infection,or other serious complications after RFA,and the main discomfort was postoperative abdominal pain.CONCLUSION RFA was safe and effective for gastric LGIN during long-term follow-up.H.pylori infection and disease course>1 year may be the main risk factors for relapse of LGIN after RFA.

INDUCTION OF GASTRIC INTRAEPITHELIAL NEOPLASIA OF GLANDULAR STOMACH OF MONGOLIAN GERBILS BY ELICOBACTER PYLORI

Objective： To setup an animal model of gastric carcinogenesis by Helicobacter pylori （Hp） for basic, prevention and therapeutic research of Hp-related diseases. Methods： 22 young male Mongolian gerbils were administrated with suspension of Hp strain TN2 by intragastric garage for 5 consecutive times （4×10^8 CFU/time, 1 time/4 days）. 10 male gerbils were used as negative control. Two infected gerbils were killed at 10, 20, and 30 weeks, respectively, after inoculation to monitor the development of gastric lesions. Other animals were killed at 40 experimental weeks. Pathological changes of glandular stomach were examined histologically. Results： Gastric intraepithelial neoplasias （GIN） and low-grade dysplasias were observed only in the pyloric antrum of Hp-treated gerbils （3 and 2 ones, respectively）, but not in control group （5/13 vs. 0/10, P〈0.04）. High incidence of chronic active gastritis and chronic atrophic gastritis were observed in Hp-treated animals （10/13, 76.9%）. Low incidence of chronic atrophic gastritis was also detected in negative control gerbils （3/10, 30%; P〈0.04）. Conclusion： Hp inoculation could induce chronic inflammation and malignant lesions of the glandular stomach of Mongolian gerbils conveniently.

Diagnosis and therapies for gastric non-invasive neoplasia

There has been a great discrepancy of pathological diagnosis for gastric non-invasive neoplasia/dysplasia between Japanese and western pathologists. In Japan, lesions that most western pathologists diagnose as dysplasia are often considered adenocarcinoma based on nuclear and structural atypia regardless of the presence of invasion. In the Vienna classification, gastric non-invasive intraepithelial neoplasia(NIN) weredivided into low grade and high grade(including intramucosal cancer of Japanese criteria). The diagnosis by both endoscopy and pathology of biopsy specimen is difficult. Recent advances of diagnostic modality such as magnified endoscopy and imaged enhanced endoscopy is expected to improve the diagnostic yield for NIN. There are two treatment strategies for NIN, observation and diagnostic therapy by endoscopic resection(ER). ER is acceptable because of its less invasiveness and high local control rate, on the other hand, cancer-developing rate of low-grade NIN is reported to be low. Therefore there is controversy for the treatment of gastric NIN. Prospective study based on unified pathological definition is required in the future.

Determination of an Appropriate Endoscopic Monitoring Interval for Patients with Gastric Precancerous Conditions in China

Objective Gastric precancerous conditions such as atrophic gastritis(AG)and intestinal metaplasia(IM)are considered independent risk factors for gastric cancer(GC).The suitable endoscopic monitoring interval is unclear when we attempt to prevent GC development.This study investigated the appropriate monitoring interval for AG/IM patients.Methods Totally,957 AG/IM patients who satisfied the criteria for evaluation between 2010 and 2020 were included in the study.Univariate and multivariate analyses were used to determine the risk factors for progression to high-grade intraepithelial neoplasia(HGIN)/GC in AG/IM patients,and to determine an appropriate endoscopic monitoring scheme.Results During follow-up,28 AG/IM patients developed gastric neoplasia lesions including gastric low-grade intraepithelial neoplasia(LGIN)(0.7%),HGIN(0.9%),and GC(1.3%).Multivariate analysis identified H.pylori infection(P=0.022)and extensive AG/IM lesions(P=0.002)as risk factors for HGIN/GC progression(P=0.025).Conclusion In our study,HGIN/GC was present in 2.2%of AG/IM patients.In AG/IM patients with extensive lesions,a 1–2-year surveillance interval is recommended for early detection of HIGN/GC in AG/IM patients with extensive lesions.

内镜热损伤术治疗胃低级别上皮内瘤变的临床疗效及术后病理升级的影响因素

目的探讨内镜热损伤术治疗胃低级别上皮内瘤变(LGIN)的临床疗效以及术后病理升级的影响因素。方法选取胃黏膜LGIN患者共98例,所有患者均接受内镜热损伤术治疗,并分析术后1年内的疗效情况;根据术后病理差异分为病理升级组和病理未升级组,采用多因素Logistic回归分析内镜热损伤术后LGIN患者出现病理升级的影响因素。结果98例患者治愈率术后12个月(82.65%)低于术后3个月(95.92%)、复发率(2.04%)高于术后3个月(11.11%)(P<0.05)。单因素结果分析显示,年龄、性别、幽门螺旋杆菌感染、病灶颜色、病变部位与内镜热损伤术后病理升级无关(P>0.05);病变直径、病灶形态、表面溃疡、自发性出血与内镜热损伤术后病理升级有关(P<0.05)。多因素Logistic回归分析结果显示,病变直径≥2 cm、凹陷型、有表面溃疡以及有自发性出血是LGIN患者内镜热损伤术后病理升级的独立危险因素(P<0.05)。结论内镜热损伤术治疗胃低级别上皮内瘤变的临床疗效较好,但患者在术后出现病理升级的概率较高,病变直径≥2 cm、凹陷型、有表面溃疡以及有自发性出血是术后病理升级的独立危险因素,临床中需针对高危人群给予积极干预,以减少疾病出现进展的几率。

窄带成像技术联合放大内镜在胃上皮内瘤变及早期胃癌中的应用价值

目的:探讨窄带成像技术(NBI)联合放大内镜(ME)在胃上皮内瘤变及早期胃癌(EGC)中的应用价值。方法:选取就诊的疑似胃上皮内瘤变及EGC患者108例为研究对象,均接受常规白光内镜检查与NBI-ME检查。比较常规白光内镜与NBI-ME的图像质量评分。以组织病理学结果为金标准,比较白光内镜和NBI-ME诊断胃上皮内瘤变及EGC的准确率。比较胃上皮内瘤变及EGC在NBI-ME下的特征。结果:NBI-ME在病灶轮廓、胃黏膜表层形态、微血管形态方面的图像质量评分均高于常规白光内镜(均P<0.05)。组织病理学检查结果,胃上皮内瘤变60例,EGC48例。白光内镜诊断胃上皮内瘤变46例,EGC 35例,其诊断胃上皮内瘤变准确率为76.67%,诊断EGC准确率为72.92%。NBI-ME诊断胃上皮内瘤变56例,EGC 44例,其诊断胃上皮内瘤变准确率为93.33%,诊断EGC准确率为91.67%。NBI-ME诊断胃上皮内瘤变及EGC的准确率高于白光内镜(均P<0.05)。胃上皮内瘤变与EGC在边界线、不规则表面微结构和黏膜微血管、腺管密度、黏膜微血管密度方面比较差异有统计学意义(均P<0.05)。结论:NBI-ME在胃上皮内瘤变和EGC的诊断中具有较高的应用价值。

组蛋白H3K27me3沉默子重塑上调胃黏膜高级别上皮内瘤变磷酸甘油醛激酶1表达

目的 绘制胃黏膜高级别上皮内瘤变(High-Grade Intraepithelial Neoplasia, HGIN)组织的组蛋白H3K27me3沉默子图谱,寻找沉默子调控的重要靶基因。方法 从本院内镜中心收集HGIN与正常胃黏膜组织各24例,采用H3K27me3染色体靶向切割和标签化(Cleavage Under Target&Tagmentation, CUT&Tag)测序技术捕获基因组修饰区域。通过生物信息学分析比较两类组织的沉默子信号特征以及差异;整合RNA测序数据及高通量染色体构象捕获技术(Hi-C)公共数据,分析沉默子重塑调控的靶基因及调控的潜在生物学过程。结果 与正常胃黏膜相比,HGIN组织H3K27me3修饰数量减少,信号强度全局性降低,呈现H3K27me3信号峰重塑现象;转录组差异分析结果显示,与正常胃黏膜组织相比,HGIN共有8 887个差异表达基因,其中表达上调基因4 335个,表达下调基因4 552个,其中CTNNB1等肿瘤发生相关基因显著上调;整合分析表观组学和转录组学数据,发现沉默子丢失可能在转录水平上调氨基酸生物合成、精氨酸与脯氨酸代谢和糖酵解等关键代谢基因,如糖酵解关键酶磷酸甘油醛激酶1(phosphoglycerate kinase1,PGK1)表达,进而促进胃黏膜上皮内瘤变。结论 组蛋白H3K27me3沉默子信号丢失是HGIN表观重塑特征之一,沉默子丢失可能与PGK1等糖酵解和氨基酸代谢基因表达紊乱相关。

基于GEO基因芯片联合网络药理学及分子对接技术探讨参苓脾喜汤治疗慢性胃炎、胃黏膜上皮内瘤变、胃早期癌作用机制

目的 基于GEO基因芯片、网络药理学及分子对接技术探讨参苓脾喜汤防治慢性胃炎(CG)、胃黏膜上皮内瘤变(GIN)、胃早期癌(EGC)的作用机制。方法 从GEO数据库下载含CG、GIN、EGC基因芯片GSE130823,使用R4.1.1筛选共同差异表达基因。利用TCMSP数据库筛选参苓脾喜汤活性成分及对应靶点,使用R4.1.1对共同表达基因与药物靶点取交集,通过Cytoscape3.9.1软件构建中药-活性成分-靶点网络,并通过STRING数据库构建蛋白相互作用(PPI)网络并进行拓扑分析,以筛选核心靶点,使用R4.1.1对交集基因进行GO功能和KEGG通路富集分析。最后将排名靠前的药物活性成分与核心靶点蛋白进行分子对接验证。结果 共筛选出1 115个差异表达基因,参苓脾喜汤活性成分119种,靶点247个,主要活性成分包括槲皮素、豆甾醇、木犀草素等。预测得到参苓脾喜汤治疗CG、GIN、EGC潜在作用靶点22个,包括CHRM3、AR、ADRB2、DPP4等。GO功能和KEGG富集分析结果显示,参苓脾喜汤治疗CG、GIN、EGC主要涉及对cAMP、IL-17、TNF、离子跨膜转运蛋白活性的调节、钙信号通路等方面。分子对接结果显示,木犀草素与ALB、AR、DPP4有较强结合能力,槲皮素与ALB、DPP4有较强结合能力,豆甾醇与AR有较强结合能力。结论 参苓脾喜汤中多种活性成分可能通过cAMP、IL-17、TNF等信号通路,调控ALB、AR、DPP4、CYP3A4等靶点治疗CG、GIN、EGC。

不伴幽门螺旋杆菌感染的胃黏膜低级别上皮内瘤变降级因素分析

目的:分析胃黏膜低级别上皮内瘤变(LGIN)患者的临床资料,探究不伴幽门螺旋杆菌感染(H.pylori)的LGIN降级的相关因素。方法:经纳排标准收集2012年1月至2022年12月于石河子大学第一附属医院内镜中心复诊、内镜活检并经病理回报为LGIN患者95例与病理降级患者289例的临床和病理资料。采用秩和检验、卡方检验分析基线资料,通过多因素二元Logistic回归分析筛选独立影响因素,构建预测方程并采用受试者工作特征曲线(ROC)与Hosmer-Lemeshow检验验证。结果:纳入研究的384例患者中男、女比例为1.29:1;单因素分析显示:维持LGIN组与降级组在性别、发红、粗糙、巴黎分型Ⅱa、Ⅱc与Ⅱa+Ⅱc均存在统计学差异(均P<0.05)。多因素回归分析显示:黏膜表面粗糙是LGIN降级的保护因素(OR=0.479,95%CI 0.268~0.857),巴黎分型Ⅱa型是LGIN降级的危险因素(OR=2.799,95%CI 1.685-4.650)。根据多因素结果构建预测LGIN病理降级方程P=ex/(1+ex),e为自然对数的底,x=0.530-0.736×黏膜表面粗糙+1.029×巴黎分型Ⅱa型;绘制的ROC曲线下面积为0.638 (95%CI 0.570~0.705);Hosmer-Lemeshow拟合度检验结果显示有较好的拟合度(χ^(2)=0.069,P=0.966)。结论:对于不伴H.pylori感染的LGIN患者存在黏膜表面粗糙与巴黎分型为非Ⅱa型病变时,LGIN复诊诊断为病理降级的可能性小。

骆云丰基于“五行立极”思想辨治胃低级别上皮内瘤变经验

“五行立极”思想是以传统中医五行生克制化学说为基础的进一步灵变,其是指以主要病变一行为核心,其余四行根据与之生克制化关系进行排序,从而主治病变一行,兼调四行,从而恢复五行之稳态。骆云丰主任从“五行立极”思想辨治胃低级别上皮内瘤变时以土为极,认为其以土行虚衰为本,加之肝火乘袭、肺金亏虚、肾水泛溢,命火不暖、君火失煦,以致五脏皆病,痰湿、瘀血、热毒等病理产物相互胶着而成。基于此认识,骆主任在临床上常以健运土行为治疗核心,兼调四行(抑木、补金、制水、益火),从而复其形质,常获佳效。

早期胃癌和上皮内瘤变在放大内镜窄带成像技术下的表现

目的研究放大内镜窄带成像技术(ME-NBI)在早期胃癌和上皮内瘤变中的诊断效能,以及相关病变的ME-NBI下表现。方法回顾性分析131例早期胃癌和上皮内瘤变病例的临床资料。分析病变的ME-NBI下表现,比较ME-NBI和白光内镜(WLI)+活检两种方法在早期胃癌和上皮内瘤变中的诊断效能。研究不同程度病变的ME-NBI下表现。结果ME-NBI诊断早期胃癌、高级别上皮内瘤变(HGIN)和低级别上皮内瘤变(LGIN)的诊断准确率分别为77.96%、77.96%和77.96%;WLI+活检诊断以上病变的准确率分别为60.53%、58.47%和69.70%,两种检查方法诊断LGIN的准确率比较,差异无统计学意义(P>0.05),两种检查方法诊断早期胃癌和HGIN的准确率比较,差异有统计学意义(P<0.05)。在LGIN中,脑回样腺管出现率最高,为60.46%。乳头状腺管和绒毛状腺管在LGIN和早期胃癌中出现率较高,分别为57.14%和52.00%。结论ME-NBI诊断早期胃癌准确率较WLI+活检高。边界线在分化型早期胃癌和上皮内瘤变中有较高的敏感性。绒毛状和乳头状微腺管结构在早期胃癌中出现率更高。脑回状微腺管在LGIN中出现率明显高于其他病变组。

中药分期治疗脾胃湿热型慢性萎缩性胃炎伴低级别上皮内瘤变患者的疗效观察

目的探讨中药分期治疗脾胃湿热型慢性萎缩性胃炎(Chronic atrophic gastritis,CAG)伴低级别上皮内瘤变(Low-grade gastric intraepithelial neoplasia,LGIN)患者的临床疗效。方法选取2021年3月—2023年5月期间河北省中医院收治的脾胃湿热型CAG伴LGIN患者120例,按照随机数字表法分为对照组和研究组,每组各60例。对照组给予CAG伴LGIN常规治疗,研究组采用清热化湿通络方治疗4周,随后采用健脾益气和胃化湿方治疗4周,两组患者均治疗8周。观察比较两组患者治疗前后中医证候积分、胃黏膜病理学评分、血清b胃蛋白酶原Ⅰ(PepsinogenⅠ,PGⅠ)、b胃蛋白酶原Ⅱ(PepsinogenⅡ,PGⅡ)水平、PGⅠ/PGⅡ、血清炎症因子[白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-8(Interleukin-8,IL-8)、白细胞介素-10(Interleukin-10,IL-10)、肿瘤坏死因子α(Tumor necrosis factor-α,TNF-α)]水平、血清肿瘤标志物[血清癌胚抗原(Carcinoembryonic antigen,CEA)、糖类抗原724(Carbohydrate antigen 724,CA724)、糖类抗原199(Carbohydrate antigen 199,CA199)、糖类抗原125(Carbohydrate antigen 125,CA125)]水平、免疫功能指标[免疫球蛋白A(Immunoglobulin A,IgA)、免疫球蛋白M(Immunoglobulin M,IgM)、免疫球蛋白G(Immunoglobulin G,IgG)、白细胞介素-2(Interleukin-2,IL-2)、干扰素γ(Interferon-γ,IFN-γ)、抑制性T细胞(Inhibitory T cells,CD8^(+))、成熟T淋巴细胞(Mature T lymphocytes,CD3^(+))、诱导性T细胞(Induced T cells,CD4^(+))、CD4^(+)/CD8^(+)]、临床疗效及不良反应情况。结果治疗后研究组临床总有效率96.67%(58/60)明显高于对照组85.00%(51/60),差异有统计学意义(P<0.05)。治疗后两组患者各项中医证候积分及总积分均较治疗前降低,差异有统计学意义(P<0.05);且研究组各项中医证候积分及总积分均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者胃黏膜病理学评分均较治疗前降低,差异有统计学意义(P<0.05);且研究组胃黏膜病理学评分明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者PGⅠ、PGⅡ水平及PGⅠ/PGⅡ均较治疗前升高,差异有统计学意义(P<0.05);且研究组PGⅠ、PGⅡ水平及PGⅠ/PGⅡ均明显高于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清TNF-α、IL-8、IL-6、IL-10水平均较治疗前降低,差异有统计学意义(P<0.05);且研究组血清炎症因子水平明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者CA199、CEA、CA724、CA125水平均较治疗前降低,差异有统计学意义(P<0.05);且研究组血清肿瘤标志物水平明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)、IgA、IgM、IgG、IL-2、IFN-γ指标均较治疗前升高,CD8^(+)均较治疗前降低,差异有统计学意义(P<0.05);且研究组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)、IgA、IgM、IgG、IL-2、IFN-γ指标均明显高于对照组,CD8^(+)明显低于对照组,差异有统计学意义(P<0.05)。治疗期间,两组患者不良反应发生率比较,差异无统计学意义(P>0.05)。结论中药分期治疗脾胃湿热型CAG伴LGIN疗效确切,可通过抑制炎症反应,提升免疫功能,减轻临床症状及胃黏膜损伤,阻断疾病进展,降低胃癌发生风险。

基于阴阳与基因调控关系辨治胃黏膜上皮内瘤变

胃黏膜上皮内瘤变是胃癌前病变,具有发展为胃癌的危险。阳主动,阴主静,文章基于阴阳理论,衷中参西,微观辨证与宏观辨证结合,以阴阳消长失调和基因调控紊乱的关系为出发点,认为胃黏膜上皮内瘤变发生时胃黏膜细胞凋亡周期紊乱和细胞异常增殖分化是阴阳消长失衡在细胞基因调控水平上的体现,进而探讨胃黏膜上皮内瘤变的病因病机以及辨证论治过程,为中医药治疗胃黏膜上皮内瘤变提供更多的理论依据,丰富治疗该病的临床手段。

基于GEO芯片联合网络药理学探讨胃复春治疗胃低级别上皮内瘤变机制

目的基于胃低级别上皮内瘤变(LGIN)患者GEO芯片及网络药理学,探究胃复春治疗胃LGIN的作用机制。方法从GEO数据库下载LGIN芯片,以logFoldChange=1、adjust P=0.05为标准筛选差异表达基因作为疾病靶点,检索文献收集胃复春入血成分并预测得到药物靶点,疾病靶点与药物靶点交集得到潜在作用靶点,采用蛋白互作网络及构建“入血成分-疾病”筛选核心靶点及化合物。通过ClusterProfiler包对交集靶点进行GO富集分析、KEGG通路富集分析并构建核心通路-靶点关系。核心靶点及核心通路共有靶点整合得到药效靶点,构建药效团模型预测核心化合物对药效靶点作用,采用分子对接进一步验证。结果基于数据集GSE130823/GSE55696筛选得到差异表达基因2871个,文献整理分析得到入血成分75个,对应靶点663个,潜在作用靶点131个,蛋白互作网络分析显示,白细胞介素6、表皮生长因子受体、JUN、细胞色素P4503A4酶、肝细胞核因子4α、肾上腺素受体等为核心靶点,药材-入血成分-靶点网络分析显示,槲皮素、香茶菜素O、线纹香茶菜酸、异橙黄酮、桔皮素、蓝萼甲素、蓝萼乙素为核心化合物。网络药理学分析结果显示,神经活性配体-受体相互作用、化学致癌作用、Rap1信号通路、类固醇激素生物合成、HIF-1、FoxO信号通路等为胃复春治疗慢性胃炎进展性LGIN病变的核心通路,药效团及分子对接显示核心化合物可调节药效靶点表达,发挥抗炎、调节能量代谢及癌症形成、调节黏膜血流量及黏膜损伤修复等作用。结论胃复春通过作用于神经活性受体-配体互作、钙离子、化学致癌、胆碱能、Rap1、药物代谢酶、HIF-1、FoxO等信号通路干预胃LGIN进程。