[目的]研究天冬氨酸氨基转移酶/血小板比值指数(APRI)和基于4因子的肝纤维化指数(FIB-4)对判断自身免疫性肝炎(AIH)患者肝纤维化程度的意义,为AIH肝纤维化的早期诊断提供依据.[方法]选取就诊于青岛大学附属医院行肝穿刺活检并诊断为AIH的患者51例,根据肝穿刺病理结果分为F0～F4期共5组,收集研究对象的一般资料、血小板计数(PLT)、谷丙转氨酶(ALT)、谷草转氨酶(AST)等指标,计算APRI、FIB-4.绘制并分析APRI、FIB-4诊断轻度纤维化(≥F1)、显著纤维化(≥F2)、进展期纤维化(≥F3)的受试者工作特征曲线(ROC曲线).[结果]APRI、FIB-4对≥F1缺乏敏感性和特异性;对≥F2的曲线下面积(AUC)分别为0.688、0.809,敏感性分别为58.3％、75.0％,特异性均为74.1％;对≥F3的AUC分别为0.753、0.865,敏感性分别为64.3％、78.6％,特异性分别为81.1％、89.2％.[结论]APRI、FIB-4对≥F1无明确的诊断价值,而对于≥F2及≥F3均有诊断价值,其中FIB-4的诊断效能优于APRI,且二者对于进展期纤维化的诊断效能更高.

[目的]探讨中性粒细胞/淋巴细胞比值(Neutrophil to Lymphocyte Ratio,NLR)与急性胰腺炎(acute pancreatitis,AP)的严重程度及全身并发症之间的关系.[方法]回顾性纳入182例AP患者,根据修订后的亚特兰大分类将AP患者分为轻症、中重症及重症3组.计算入院时NLR值四分位数,并将患者分为4组:NLR≤4.91组、4.92≤NLR＜7.80组、7.81≤NLR≤13.78组、NLR≥13.78组,分别比较修订后的亚特兰大分类、Ranson评分、全身并发症在4组间差异有无统计学意义.采用受试者工作特征(ROC)曲线比较NLR、NLR48 h、白细胞计数及中性粒细胞计数预测AP全身并发症的有效性.[结果]根据修订后的亚特兰大分类,患者入院时NLR水平重症组＞中重症组＞轻症组[15.13(7.86)∶10.07(7.98)∶5.43(4.33),P＜0.001].重症组及中重症组AP患者NLR48 h水平明显高于轻症组患者[8.10(6.74)∶7.62(4.57)∶3.16(2.58),P＜0.001].根据四分位数分组,随着NLR水平升高,Ranson评分重度、修订后亚特兰大分类重症、有全身并发症患者所占比例明显升高(均P＜0.001).计算炎性标志物预测AP全身并发症的ROC曲线下面积,入院时NLR曲线下面积最大,为0.863.当NLR截断值＞10.56时,敏感性为85.7％,特异性为76.2％.[结论]NLR与AP严重程度密切相关,且NLR是预测AP患者全身并发症的重要参数.

消除或缓解胃食管反流症状是GERD临床处理的主要目标之一.临床上,相当比例的GERD患者对规范剂量和疗程的抑酸剂治疗应答不良,常被认为是难治性胃食管反流病( rGERD).rGERD的病因和病理生理学机制复杂,可能包括精神心理因素、胃-食管运动紊乱和食管内脏高敏感等.抗抑郁药常被作为治疗rGERD症状的重要选择.然而,在如何选择适应证,采取何种剂量、疗程,以及判断其疗效如何等方面尚缺乏足以形成共识的循证医学证据.

Long non-coding RNAs (lncRNAs) are a class of more than 200 nucleotides RNA transcripts which have limited protein coding capacity. They regulate numerous biological processes in cancers through diverse molecular mechanisms. Aberrant expression of lncRNAs has been frequently associated with human cancer. Furthermore, the tumor microenvironment (TME) is composed of different cells such as cancer-associated fibroblasts (CAFs), endothelial cells and infiltrated immune cells, and all of which participate in communication with tumor cells affecting the progression of tumor. LncRNAs are directly and indirectly involved in the crosstalk between stromal cells and tumor cells and dysregulated lncRNAs expression in these cells could drive tumorigenesis. In this review, we explore the influence of aberrantly expressed lncRNAs in tumor progression, clarify the critical roles of lncRNAs in the TME, summarize findings on crosstalk between infiltrated immune cells, CAFs, endothelial cells, and tumor cells via lncRNAs, and discuss the promise of lncRNAs as tumor diagnostic markers and therapeutic targets.

目的 探讨不同剂量维生素D(本实验采用VD3)对溃疡性结肠炎(ulcerative colitis,UC)小鼠结肠β-防御素-2的表达及意义.方法 建立C57BL/6小鼠UC模型,并分别给予不同浓度VD3干预,疾病活动指数(DAI)、组织学评分、免疫组化检测小鼠结肠黏膜中β-防御素-2表达.结果 高、低剂量VD3干预组DAI、组织学炎症、β-防御素-2表达明显低于UC组(P＜0.05),高、低剂量VD3组比较差异有统计学意义(P＜0.05),小鼠组间炎症同β-防御素-2表达具有相关性(P＜0.05).结论 维生素D对DSS诱导的急性UC小鼠具有一定的缓解作用,并存在剂量效应关系.

Purpose: The rapidly rising incidence of esophageal adenocarcinoma (EAC), which is usually diagnosed late with a poor prognosis, has become a growing problem. This study investigated the potential transcription factor (TF)-related molecular mechanisms of EAC by using bioinformatics analysis and qRT-PCR validation. Methods: Expression profile datasets for mRNAs (GSE92396, GSE13898, GSE26886 and GSE1420) and miRNAs (GSE16456) were downloaded from the GEO database. Overlapping differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified through integrative analysis. Then, a TF-miRNA-mRNA network was constructed based on bioinformatics data from the TRRUST, TRED and miRTarBase database. Furthermore, overall survival analysis for the mRNAs and miRNAs in the TF-miRNA-mRNA network was performed with data from TCGA, and qRT-PCR was used to validate the results. Results: A total of 294 overlapping DEGs were identified in EAC tissues compared to normal tissues, including 181 downregulated and 113 upregulated genes. Then, 16 TFs that could target the DEGs and were related to cancer were predicted based on public databases, and 41 DEGs that could be targeted were identified as key genes. Additionally, 12 DEMs were predicted through miRTarBase to be associated with the key genes, and TP53-(miR-125b)-ID2 and JUN-(miR-30a)-IL1A from the TF-miRNA-mRNA network were identified to potentially play significant roles in EAC. Furthermore, CCL20, IL1A, ABCC3, hsa-miR-23b, and hsa-miR-191, which are involved in the TF-miRNA-mRNA network, were found to be significantly associated with patient survival in EAC. Finally, the expression of a miRNA-mRNA pair (hsa-miR-30a-5p and IL1A) was revealed to be correlated with prognosis. Conclusion: In this study, a TF-miRNA-mRNA network was constructed to analyze the potential molecular mechanisms of EAC. Key genes and miRNAs associated with patient survival were identified, which may reveal promising approaches for EAC diagnosis and therapy.

巯嘌呤类药物如硫唑嘌呤和6-巯基嘌呤,常用于治疗炎症性肠病(IBD).然而,接受这类药物治疗的患者易出现药物不良反应,其中骨髓抑制最为严重且存在潜在的致命风险.巯嘌呤类药物导致的骨髓抑制具有明显的种族和个体差异.目前,多种遗传标志物被用来鉴定对巯嘌呤类药物敏感的IBD患者.本文就基因检测改善巯嘌呤类药物治疗IBD的安全性作一综述.

目的 探究抗焦虑抑郁药治疗功能性腹痛综合征(FAPS)的临床疗效,验证焦虑抑郁精神心理因素与FAPS的相关性.方法 将67例FAPS患者随机分为试验组(34例)和对照组(33例).两组患者均给予抑酸、促动力等个性化常规治疗,试验组在常规治疗基础上加用盐酸帕罗西汀(赛乐特),随访4周.在治疗0、4周时,分别对两组患者腹痛视觉模拟评分(VAS)、PHQ-9抑郁症筛查量表评分、GAD-7焦虑症筛查量表评分进行比较.结果 治疗后,两组患者的腹痛VAS评分、PHQ-9评分、GAD-7评分均较治疗前下降,且试验组低于对照组(P<0.05).结论 盐酸帕罗西汀对改善伴有焦虑抑郁情绪障碍的FAPS患者的腹痛症状及情绪障碍具有显著疗效.

Although 7,8-dihydroxyflavone (7,8-DHF), a synthetic agonist specific for tyrosine kinase receptor B (TrkB), has been reported to promote intestinal dynamics, its effect on gastric dynamics has not been studied as yet. In this study, we explored how 7,8-DHF affected the carbachol (CCh)-induced contraction of rat gastric muscle by way of measuring the contractile tension of muscular strips. We found that although 7,8-DHF did not directly cause contraction of gastric muscle, it enhanced CCh-induced, instead of substance P- or high K+ -induced, contraction. The enhancing role of 7,8-DHF was partially blocked by ANA-12, a blocker specific for TrkB the activation of which in the gastric strips was evidenced by its phosphorylation. Although 7,8-DHF alone did not activate : phospholipase C (PLC)-γ in gastric muscle, CCh did, and importantly, the combined treatment with CCh + 7,8-DHF activated more PLC-γ. U73122, an antagonist to PLC-γ blocked both the CCh-induced and the 7,8-DHF-enhanced/CCh-induced contraction by ~30%. To pursue how 7,8-DHF could augment CCh-activated PLC-γ phosphorylation, we first examined the effect of 7,8-DHF on the expression of muscarinic receptors in gastric muscle and found that 7,8-DHF specifically increased M3 but not M2 receptor expression possibly through TrkB/Akt (protein kinase B) pathway because the Akt antagonist, LY294002 significantly suppressed the 7,8-DHF-augmemted M3 expression and completely blocked the 7,8-DHF-enhanced cholinergic contraction. Supporting the result, Akt phosphorylation in the gastric muscle was enhanced by 7,8-DHF treatment. The in vivo experiment showed that orally fed 7,8-DHF increased gastric emptying rate. The results imply a possibility that 7,8-DHF may be developed into a drug in the future for enhancing gastric dynamics.

目的 探讨舒肝解郁胶囊治疗伴焦虑抑郁的功能性便秘(FC)的效果.方法 将2017年3-6月来医院消化内科门诊就诊的FC患者80例随机分为试验组和对照组各40例,2组患者均口服双歧三联活菌胶囊、乳果糖口服液,试验组加服舒肝解郁胶囊,疗程为4个周.采用便秘患者症状自评量表(PAC-SYM)、健康问卷抑郁量表(PHQ-9)、广泛性焦虑量表(GAD-7)评分对2组治疗前后进行统计学分析.观察2组治疗效果.结果 治疗前后对照组患者GAD-7评分及PHQ-9评分比较差异无统计学意义(P>0.05);治疗后试验组患者抑郁评分及焦虑评分均低于治疗前及对照组治疗后,差异有统计学意义(P<0.05).治疗后,2组患者便秘症状均有所改善.试验组总有效率85.00％高于对照组的62.50％,差异有统计学意义(χ2=5.23,P=0.041).2组均未出现明显不良反应.结论 舒肝解郁胶囊不仅能显著改善FC患者的焦虑抑郁情绪,而且在便秘症状缓解方面也优于单纯使用益生菌及轻泻剂.

目的 探讨肠道菌益生菌对非酒精性脂肪肝的临床影响.方法 拟针对我院从2015年12月~2016年12月收治的120例非酒精性脂肪肝患者作为研究对象,并随机分为干预组和观察组各60例;两组患者均给予NAFLD患者的传统治疗,干预组患者在此基础上增加肠道益生菌的治疗.对两组患者服药前后的相关肝脏生化指标包括三酰甘油、总胆固醇、尿素氮、以及空腹血糖,肝脏的B超影像.结果 干预组患者在服用药物后的脂肪肝症状较服药前有明显改善(P<0.05).观察组在服用前后各项指标间的比较无统计学差异(P>0.05).观察组在用药前后在尿素氮、三酰甘油、总胆固醇三项检测指标比较具有显著性差异(P<0.05).结论 服用适量的肠道益生菌,有助于缓解非酒精性脂肪肝的临床症状,对于辅助性治疗和病情的预防具有一定的积极作用,值得临床推广.

Objective To investigate the effects of Saccharomyces boulardii ( S. boulardii) on the col-onization of Helicobacter suis ( H. suis) in stomach and the formation of gastric mucosa associated lymphoid tissue (MALT) during H. suis infection. Methods Sixty C57BL/6 wild type mice were randomly divided into six groups. The mice in group A and group B were respectively given sterile distilled water and S. boulardii twice by gavage and then infected with H. suis for one week. The mice in group C and group E were given sterile phos-phate buffer saline by gavage for one week and then respectively given sterile distilled water and S. boulardii by gavage twice a week for 12 weeks. The mice in group D and group F were infected with H. suis for one week and then respectively given sterile distilled water and S. boulardii by gavage twice a week for 12 weeks. Serum and gastric tissue samples were collected from each mouse. Results The bacterial loads of H. suis in the stomachs of mice in group B were significantly lower than those in group A. No significant differences in the levels of se-creted IgA( sIgA) in serum and gastric tissue samples and the expression of IFN-γat mRNA level in gastric mu-cosa samples were found between the two groups. The expression of H. suis 16S RNA and the formation of gastric lymphoid follicles were detected in mice in groups D and F. The levels of sIgA in serum and gastric tissue sam-ples and the expression of IFN-γ and CXCL13 at mRNA level in gastric mucosa samples increased significantly in groups D and F as compared with groups C and E. Compared with the mice in group D, the bacterial loads of H. suis in stomachs, the numbers of MALT per unit length of gastric mucosa and the expression of IFN-γ and CXCL13 at mRNA level in gastric mucosa decreased significantly in mice from group F, but the levels of sIgA in serum and gastric tissue samples increased significantly. Conclusion S. boulardii could inhibit the colonization of H. suis in stomach and suppress the formation of gastric MALT during H. suis infection.

AIM:To investigate the impact of endoscopy nurse involvement during colonoscopy on the polyp detection rate (PDR) and adenoma detection rate (ADR).METHODS:This was a single-center,prospective study.Patients involved were prospectively randomized to a routine colonoscopy group or an endoscopy nurse involvement group.The association of nurse involvement with PDR and ADR was evaluated.RESULTS:A total of 1192 patients were included in the study.The PDR was significantly higher (33.19％ vs 27.81％,P =0.000) among colonoscopies that included an endoscopy nurse compared with those performed by only a physician,as was the left-sided and the right-sided adenomas detected (P =0.017).There was no difference in ADR between the two groups (20.88％ vs 20.55％,P =0.889).Nurse participation was associated with a higher detection rate of small (＜5 mm) polyps (P =0.006).CONCLUSION:Endoscopy nurse involvement in colonoscopies significantly improves the overall PDR.Involvement of a well-trained nurse in screening colonoscopies may be an effective strategy to increase access.

Objective To investigate the effects of high fat diet induced obesity on the formation of gastric mucosa associated lymphoid tissue ( MALT) during Helicobacter suis ( H. suis) infection and its possi-ble mechanism. Methods Forty female C57BL/6 mice were randomly divided into four groups (n=10), including normal control ( NC) group, high fat diet ( HFD) group, H. suis infection ( HS) group and H. suis infection+high fat diet ( HS+HFD) group. The mice of NC group and HS group were given ordinary diet, while the mice of HFD group and HS+HFD group were given high fat diet from the third week after infection. All of the mice were sacrificed to collect their gastric tissues after feeding with different diets for 24 weeks. The number and size of gastric lymphoid follicles were detected by hematoxylin and eosin ( HE) staining. The expression of leptin and its receptor Ob-R, inflammatory cytokine (IFN-γ) and chemokines (CXCL13, CCL-2 ) at mRNA level in the gastric mucosa of each mouse were detected by real - time PCR . Results H. suis infection induced the formation of lymphoid follicles in the gastric mucosa. The number and size of gastric lymphoid follicles and the expression of leptin and its receptor Ob-R, IFN-γ, CXCL13 and CCL-2 at mRNA level in the gastric mucosa samples collected from HS+HFD group were significantly increased as compared with those of the HS group. Conclusion The high fat diet induced obesity could promote the for-mation of gastric MALT during H. suis infection. The mechanism might be associated with the upregulation of leptin, inflammatory cytokines and chemokines.

The definition of gastroesophageal reflux disease ( GERD ) continues to be updated. GERD is now defined as symptoms or complications resulted from the reflux of gastric contents into the esophagus or beyond,into the oral cavity ( including larynx) or lung.GERD is a group of disease syndrome, includes typical symptoms such as acid reflux and heartburn, and atypical symptoms such as chest pain, belching,and extra esophageal symptoms such as cough and asthma.The pathogenesis of GERD includes sliding hiatal hernia, transient lower esophageal sphincter relaxation, acid pocket, decreased ability of esophageal clearance, delayed gastric emptying, duodenogastro-esophageal reflux and so on, anxiety, depression and other stress factors which can lead to increased esophageal sensitivity, which can produce GERD-related symptoms.The effect of stress on esophageal sensitivity is mainly through the peripheral and central mechanisms,namely peripheral sensitization and central sensitization,the latter plays a major role.We should take the principle of individual on the treatment of GERD patients according to the specific circumstances of each patient,while psychological factors should receive attention.

Diabetes mellitus (DM) brings about multiple gastrointestinal complications. Nesfatin-1 is an ingestion regulating peptide which possesses a considerable effect in delaying gastric emptying. We aimed to investigate effects and mechanism of nesfatin-1 application on human gastrointestinal smooth muscle cells (HGSMC). HGSMC were treated with different concentrations of nesfatin-1, and expression of endothelial nitric oxide synthases (eNOS) was confirmed. Besides, HGSMCs were administrated nesfatin-1 along or combination of nesfatin-1 and eNOS inhibitor NG-Nitro L-arginine Methyl Ester (L-NAME). Thereafter, the cell viability, apoptosis, and adhesion were assessed. Western blot analysis was performed to analyze expression of key proteins extracellular regulated protein kinas (ERK) 1/2, p38 mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) on the signaling pathway. The eNOS was significantly upregulated by nesfatin-1 at the optimal concentration of 100 nM (P < 0.05). Nesfatin-1 remarkably suppressed the HGSMC viability and adhesion (P < 0.05) and expedited apoptosis (P < 0.01). Additionally, nesfatin-1 significantly reduced expressions of ERK1/2, p38MAPK and mTOR in HGSMC compared with those in the control group (P < 0.05). However, administration of eNOS inhibitor L-NAME could relieve these effects on HGSMC. Nesfatin-1 inhibited cell viability and adhesion of HGSMC, and promoted cell apoptosis. These effects might be by regulating eNOS-mediated downstream ERK/MAPK/mTOR signaling pathway. It reveals that eNOS inhibitor is praised to be a novel therapeutic strategy and target for DM induced gastrointestinal complications.

目的:探讨下丘脑室旁核(pareventricular,PVN)注射胰高血糖素样肽-1(GLP-1)及其受体拮抗剂Exendin(9-39)后胃组织核组蛋白2(NUCB2)/nesfatin-1表达的影响.方法:选取48只雄性Wistar大鼠,随机分为6组,生理盐水组,四种不同剂量GLP-1组(0.003 nmol/10 μL,0.03 nmol/10 μL,0.3 nmol/l0 μL,3 nmol/10 μL),30 nmol Exendin(9-39)+3 nmol GLP-1 (E+G)组,每组8只.PVN区埋置套管并按每组要求分别经套管给予GLP-1及Exendin(9-39)等药物.给药2小时后处死大鼠并取胃组织,实时荧光定量RT-PCR法检测各组胃组织NUCB2 mRNA表达.另外生理盐水组,3nmoL GLP-1组及E+G组每组分别随机取6只大鼠的部分胃组织,用免疫组织化学法测胃粘膜NUCB2/nesfatin-1蛋白的表达情况.结果:实时荧光定量RT-PCR法发现3 nmoL GLP-1组大鼠胃组织NUCB2 mRNA表达量高于生理盐水组,差异有统计学意义(P＜0.05),而其余各组大鼠胃组织NUCB2 mRNA表达与生理盐水组比较无统计学差异(P＞0.05).免疫组化结果显示3 nmoL GLP-1组胃粘膜NUCB2/nesfatin-1蛋白表达与生理盐水组、E+G组比较有统计学差异(P＜0.05),生理盐水组大鼠胃粘膜NUCB2/nesfatin-1蛋白表达与E+G组比较无明显差异(P＞o.05).结论:PVN注射GLP-1能够促进胃组织NUCB2/nesfatin-1的表达,这一作用可能是通过激活GLP-1受体来完成的.

Reflux esophagitis (RE) is an esophageal mucosal injury, the directly main cause of RE is excessive exposure of gastric contents. This study was aimed to investigate whether miR-133b was involved in hydrochloric acid (Hcl) induced RE. Human esophageal squamous cells Het-1A were employed and were exposed to Hcl, subsequently the expression of miR-133b was detected by quantitative PCR (qPCR). Cells were transfected with miR-133b mimic or inhibitor, and then cell viability, apoptosis and the expression levels of apoptosis related factors were respectively determined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyltetrazolium bromide (MTT), flow cytometry and Western blot. Further, cells were treated with Hcl or transfected with miR-133b mimic or/and inhibitor, Western blot was performed to explore the expression of extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase/ serine/threonine kinase (PI3K/AKT) pathway proteins. Results showed that Hcl exposure significantly inhibited cell viability (P < 0.05) and up-regulated miR-133b (P < 0.001). Overexpression of miR-133b decreased cell viability (P < 0.01), induced apoptosis (P < 0.001), and up-regulated the levels of caspase-3, Fas and p53 (P < 0.01 or P < 0.001). Besides, Hcl exposure and miR-133b overexpression inhibited the phosphorylations of ERK1/2, AKT and PI3K (P < 0.05, P < 0.01 or P < 0.001), However, miR-133b suppression abolished the regulatory effects of miR-133b overexpression on these factors (P < 0.01 or P < 0.001). In conclusion, the expression of miR-133b might be involved in Hcl induced Het-1A cells injury via regulating ERK and PI3K/AKT pathways.

The ingestion of nucleic acids (NAs) as a nutritional supplement or in genetically modified food has attracted the attention of researchers in recent years. Discussions over the fate of NAs led us to study their digestion in the stomach. Interestingly, we found that NAs are digested efficiently by human gastric juice. By performing digests with commercial, recombinant and mutant pepsin, a protein-specific enzyme, we learned that the digestion of NAs could be attributed to pepsin rather than to the acidity of the stomach. Further study showed that pepsin cleaved NAs in a moderately site-specific manner to yield 3′-phosphorylated fragments and the active site to digest NAs is probably the same as that used to digest protein. Our results rectify the misunderstandings that the digestion of NAs in the gastric tract begins in the intestine and that pepsin can only digest protein, shedding new light on NA metabolism and pepsin enzymology.

Objective To investigate the changes of serum levels of ghrelin and obestatin and its clinical significance in patients with diabetic gastroparesis. Methods Fifty patients with obese type 2diabetes who were treated as outpatients or hospitalized in our hospital were enrolled in this study.According to the results of gastric emptying of breath test,the patients were divided into normal gastric emptying of diabetic group(DM group)and diabetic gastroparesis(DGP group).Fifteen healthy volunteers served as normal controls(NC group).Using enzyme-linked immunosorbent assay(ELISA)to detect fasting and postprandial two hours serum ghrelin and obestatin levels. Results Fasting and postprandial 2hours serum ghrelin levels in DM group were higher than that in NC group and DGP group(F=25.13,25.44;q=4.72-10.00;P0.01),and that in DGP were lower than that in NC group(q=3.97,3.05;P0.05).Fasting and postprandial 2hours serum obestatin levels were elevated in proper order of NC group,DM group and DGP group,the differences were significant(F=191.42,80.45;q=8.37-27.37;P0.01). ConclusionThe serum levels of ghrelin and obestatin in patients with type 2diabetes mellitus are associated with gastric emptying,the elevation of serum ghrelin may promote gastric emptying,and elevation of serum obestatin may inhibit gastric emptying.