Helicobacter pylori γ-glutamyl transpeptidase:A formidable virulence factor

Helicobacter pylori(H.pylori)produce an enzyme known asγ-glutamyl transpeptidase(HpGGT)that is highly conserved and common to all strains.HpGGT has been gaining increasing attention as an important virulence factor of the bacterium,having been demonstrated to be an important colonization factor in several animal models and has also recently been strongly associated with the development of peptic ulcer disease.From the results of various independent researcher groups,it is clear that HpGGT acts through several pathways to damage gastric epithelial cells including the induction of apoptosis and cell cycle arrest,production of reactive oxygen species leading to DNA damage,promotion of inflammation by increasing cyclooxygenase-2 and interleukin-8 expression,and upregulation of heparin-binding epidermal growth factor-like growth factor resulting in cell survival and proliferation.In addition,the potential role of HpGGT in promoting gastric carcinogenesis will also be discussed in this review.Apart from affecting the gastric epithelium,HpGGT also has immunomodulatory actions on host immune cells where it displays an antiproliferative effect on T cells by inducing cell cycle arrest and also works with other H.pylori virulence factors to skew dendritic cells towards a tolerogenic phenotype,possibly contributing to the persistence of the pathogen in the gastric mucosa.

Helicobacter pylori gamma-glutamyl transpeptidase and its pathogenic role

Helicobacter pylori(H.pylori)gamma-glutamyl transpeptidase(GGT)is a bacterial virulence factor that converts glutamine into glutamate and ammonia,and converts glutathione into glutamate and cysteinylglycine.H.pylori GGT causes glutamine and glutathione consumption in the host cells,ammonia production and reactive oxygen species generation.These products induce cell-cycle arrest,apoptosis,and necrosis in gastric epithelial cells.H.pylori GGT may also inhibit apoptosis and induce gastric epithelial cell proliferation through the induction of cyclooxygenase-2,epidermal growth factor-related peptides,inducible nitric oxide synthase and interleukin-8.H.pylori GGT induces immune tolerance through the inhibition of T cell-mediated immunity and dendritic cell differentiation.The effect of GGT on H.pylori colonization and gastric persistence are also discussed.

Effect of Glutamine Supplementation on Abilities of Antioxidative and y-glutamyl Transpeptidase Activities in Liver and Intestine of Piglets Fed Diets Containing Raw Soybean

Eighteen male piglets weaned at 28 days age were randomly assigned to one of three treatments (1% glutamate. 1% and 2% glutamine supplementation). The basal diet contained 5% raw soybean. The diets were calculated to be isonitrogenous and isoenergetic. The level of plasma glutahione(GSH) increased markedly in piglets fed glutamine, and the response was related to dose. In treatments I and I , the levels of plasma GSH were significantly higher than that in the control at the 35 days age (P<0.05). The level of plasma GSH in treatment I was significantly higher than that in the control at 42 days age (P<0. 05). At 49 days age, there was no significantly difference of the level of GSH in plasma, liver, spleen, intestine and mes-enteric lymph node. The level of superoxide dismutase (SOD) in liver and spleen was higher than that of the control, however, the difference wasn't significant. Dietary glutamine supplementation decreased γ-glutamyl transpeptidase(γ-GT) activities in liver. The activities of γ-GT of liver protein in treatmentⅡ were significantly lower than that in the control (P<0.05). The activities ofγ-GT of duodenum in treatments I and Ⅱwere also significantly lower than that in the control (P<0.05). But there were no significant differences of the activities of γ-GT in jejunum and ileum. The results showed that dietary glutamine supplementation increased the level of plasma GSH, and decreased γ-GT activities.

Prognostic role of plasma levels ofγ-glutamyl transpeptidase in patients with advanced gastric cancer treated with anti-PD-1 immunotherapy

Objective Antibodies targeting programmed cell death protein 1(PD-1)have become the mainstay of treatment for chemotherapy-refractory gastric cancer,characterized by high levels of programmed cell death ligand-1(PDL-1)expression.However,the routine clinical implementation of PDL-1 testing is currently limited by the lack of robust detection methods.In this regard,the role of plasmaγ-glutamyl transpeptidase(GGT),an N-terminal nucleophilic hydrolase,as an independent predictor of the efficacy of anti-PD-1 therapy remains unknown.In this study,we aimed to assessed the prognostic role of changes in plasma GGT levels(6 weeks vs.baseline)in patients with advanced gastric cancer treated with anti-PD-1 immunotherapy.Methods We retrospectively analyzed data from 57 patients with gastric cancer treated with anti-PD-1 antibodies(camrelizumab,sintilimab,nivolumab,tislelizumab,and toripalimab)at the Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China,from July 2018 to February 2021.Results We found that after 6 weeks of treatment,there were significant differences between responders and non-responders with respect to plasma GGT levels(P<0.001).Multivariate logistic regression analysis revealed that the continuous value of the 6-week difference in GGT levels(OR=1.437,95%CI=1.116-1.849,P=0.005)and 6-week difference in GGT≥0 or<0(OR=53.675,95%CI=6.379-451.669,P<0.001)were independent predictors of disease control.Survival analysis indicated that a reduction in plasma GGT6 levels during treatment was significantly associated with a favorable progression-free survival(PFS)and overall survival(P<0.001).Consistently,univariate and multivariate Cox regression analyses revealed that a reduction in plasma GGT6 levels during treatment was an independent predictor of PFS(HR=1.033,95%CI=1.013-1.053,P=0.001).Conclusion Alterations in plasma GGT levels during treatment can be used as a predictor of disease progression and survival in patients with advanced gastric cancer undergoing treatment with anti-PD-1 antibodies.

Inhibition of Carcinogen Induced Activity of γ-glutamyl Transpeptidase by CertainDietary Constituents in Mouse Skin

Cancer chemoprevention, a desirable and important facet of biomedical research, provides a practical approach to identify potentially useful inhibitors of cancer development, and offers an opporiunity to study the mechanism of carcinogenesis. During the recent Past a number of compounds have been tested for their anticarcinogenic potential specially constituents of our diet. The enzyme γglutamyl transpeptidase (GGT) which catalyses the transfer of glutamyl groups of peptides to other peptides and amino acid and has been proposed as a marker of cell proliferation and neoplasia. It also serves as a tool to evaluate the carcinogenic and cocarcinogenic potential of environmental toxicants. In the present investigations, CGT activity induced by careinogenic polycyclic aromatic hydmiarbons, viz. 7, 12-dimethylbenz(a) anthracene (DMBA) and benzo(a) pyrene (BaP) was significantly inhibited by diallylsulfide (DAS) and indole-3-carbnol (I3C) in mouse skin. DAS and 13C are constituents of garlic and cruciferous vegetables respectively. A significant iIthibition in GGT levels was also observed in a strong mitogen (12-o-tetradecanoyl phorbol-13-acetate) induced activity in mouse skin by pretreatment with DAS/13C. Therefore these dietary constituents seem to be strong modifiers of chemically induced carcinogenesis

急性NSTEMI患者PCI术后血清FAR、γ-GGT、NT-proBNP水平及对预后的预测价值研究

目的探讨并分析急性非ST段抬高心肌梗死(NSTEMI)患者经皮冠状动脉介入治疗(PCI)术后血清纤维蛋白原/白蛋白值(FAR)、γ-谷氨酰转肽酶(γ-GGT),N端脑钠肽前体(NT-proBNP)水平对预后的预测价值。方法回顾性分析2020年2月至2023年2月邯郸市中心医院收治的实施PCI的急性NSTEMI患者93例,根据术后30 d主要不良心血管事件(MACE)发生情况将其分为MACE组(n=21)及无MACE组(n=72)。比较术前、术后30 d MACE组及无MACE组血清FAR、γ-GGT、NT-proBNP水平,采用单因素和多因素Logistic回归分析对影响急性NSTEMI患者术后30 d MACE发生的危险因素进行分析,采用受试者操作特征(ROC)曲线分析血清FAR、γ-GGT、NT-proBNP水平对急性NSTEMI患者术后MACE发生的预测价值。结果MACE组年龄为(65.37±3.46)岁;Killip分级为Ⅰ级2例,Ⅱ级3例,Ⅲ级5例,Ⅳ级11例;病变支数双支5例,3支16例;术后30 d血清FAR、γ-GGT、NT-proBNP水平分别为(2.87±0.55)%、(53.27±3.06)U/L、(914.35±84.35)ng/mL。无MACE组的年龄为(58.71±2.86)岁;Killip分级为Ⅰ级32例,Ⅱ级27例,Ⅲ级7例,Ⅳ级6例;病变支数为双支53例,3支19例;术后30 d血清FAR、γ-GGT、NT-proBNP水平分别为(2.12±0.51)%、(44.33±3.35)U/L、(656.82±75.63)ng/mL。MACE组和无MACE组的年龄、Killip分级、病变支数及术后30 d血清FAR、γ-GGT、NT-proBNP水平比较,差异均有统计学意义(P<0.05),两组性别、吸烟史、高血压史、高血脂史、糖尿病史及术前1 d血清FAR、γ-GGT、NT-proBNP水平比较差异无统计学意义(P>0.05)。多因素Logistic回归分析结果显示,血清FAR、γ-GGT、NT-proBNP升高均为影响急性期NSTEMI患者术后MACE发生的独立危险因素(OR=3.074、2.686、3.340,P均<0.05)。ROC结果显示血清FAR、γ-GGT、NT-proBNP及其联合检测预测急性NSTEMI患者术后MACE发生的曲线下面积(AUC)分别为0.681、0.690、0.733和0.790,联合检测的AUC更高(P<0.05)。结论血清FAR、γ-GGT、NT-proBNP水平升高增加了急性NSTEMI患者PCI术后MACE的发生风险,三者联合检测对患者术后不良预后有一定预测价值。

羊种布鲁氏菌Tat系统底物蛋白ErfK的抗原性和免疫原性研究

为分析羊种布鲁氏菌双精氨酸转运系统(twin-arginine translocation system,Tat system)毒力相关底物蛋白L,D-转肽酶ErfK诱导宿主产生的免疫应答情况,首先对布鲁氏菌M28毒株ErfK基因序列(WP_002963714.1)进行生物信息学分析,参考序列设计引物,构建表达载体pET-30a(+)-ErfK,经IPTG诱导表达、亲和层析和镍柱纯化获得目的蛋白;利用SDS-PAGE和Western blot对重组ErfK(rErfK)蛋白进行抗原性鉴定;将rErfK蛋白免疫小鼠,分别在免疫后15、30和45 d收集血清和脾脏,检测蛋白免疫后小鼠的细胞免疫应答和体液免疫应答情况。生物信息学预测结果显示,ErfK蛋白无跨膜结构,为亲水性蛋白,有多个T细胞和B细胞抗原表位;SDS-PAGE和Western blot均可获得25 kDa的蛋白条带,重组蛋白可与布鲁氏菌阳性血清发生反应,证明rErfK有良好的抗原性;小鼠免疫试验结果显示,rErfK组小鼠脾脏CD8^(+)T细胞含量相比PBS组显著上升(P<0.05),且脾脏Th1型细胞因子IL-2、TNF-α、IFN-γ和Th2型细胞因子IL-4转录水平均显著上升(P<0.05),此外,rErfK免疫也能极显著诱导小鼠血清中总IgG和特异性IgG的产生(P<0.01)。上述结果表明,经大肠杆菌表达的布鲁氏菌rErfK蛋白可诱导小鼠产生良好的体液免疫和细胞免疫应答。本研究为基于ErfK蛋白的布鲁氏菌病诊断试剂和亚单位疫苗研发提供了参考依据。

γ-谷氨酰转肽酶的催化特性及其在食品领域应用研究进展

γ-谷氨酰转肽酶广泛存在于生物体中,可以专一性催化γ-谷氨酰基的转移反应,参与生物体内谷胱甘肽代谢和γ-谷氨酰基循环等生理过程。随着食品酶学、合成生物学技术的发展,γ-谷氨酰转肽酶在生物催化领域的应用也日渐受到重视。基于其水解和转肽催化活性,γ-谷氨酰转肽酶可被应用于茶氨酸等多种γ-谷氨酰化合物的生物催化合成。利用酶工程手段进一步优化γ-谷氨酰转肽酶的催化特性,提高目标产物产率,使得γ-谷氨酰转肽酶在食品功能因子的绿色生物制造领域具有较好的应用前景。文章综述了γ-谷氨酰转肽酶的分子结构、催化机制及其在食品工业中的应用现状,并重点关注γ-谷氨酰转肽酶的分子改造及其在催化合成L-茶氨酸领域的应用,以期为γ-谷氨酰转肽酶在食品领域的研究及应用提供参考。

正常范围内血清谷氨酰基转肽酶与前期高血压的相关性

[目的]观察正常范围内血清谷氨酰基转肽酶(GGT)水平与前期高血压的相关性.[方法]选择自2019年6月至2019年9月间参加健康体格检查的4006例20~60岁非高血压且肝功能正常受检者作为研究对象,分析不同性别人群正常范围内GGT水平与前期高血压的相关性.[结果]与对照组比较,男性前期高血压组年龄、体质量指数(BMI)、血糖(FPG)、总胆固醇(TC)、低密度脂蛋白(LDL)、三酰甘油(TG)、谷草转氨酶(AST)、谷丙转氨酶(ALT)及GGT水平均明显升高(P<0.05);女性前期高血压组年龄、BMI、FPG、TC、LDL、TG、AST、ALT、GGT、尿酸(UA)及肌酐(CREA)水平均明显升高(P<0.05),而高密度脂蛋白(HDL)水平显著降低(P<0.05).男性年龄、BMI、收缩压(SBP)、舒张压(DBP)、FPG、TC、LDL、TG、AST、ALT及UA水平随着GGT水平的升高而升高,而HDL水平随着GGT水平的升高而降低;女性年龄、BMI、SBP、DBP、FPG、TC、LDL、TG、AST、ALT、UA、尿素氮及CREA水平均随着GGT水平的升高而升高.男性未调整时GGT上四分位数组前期高血压的患病风险是下四分位数组的1.881倍(95%CI:1.391~2.544),调整年龄、BMI、FPG、血脂、肝功能等指标后是下四分位数组的1.467倍(95%CI:1.055~2.041);女性未调整时GGT上四分位数组前期高血压的患病风险是下四分位数组的2.295倍(95%CI:1.791~2.939),调整年龄、BMI、FPG、血脂、肝功能及肾功能等指标后上述关系消失.调整年龄、FPG、血脂、肝功能等因素后BMI≥24 kg/m^(2)且GGT水平上四分位数组男性和女性前期高血压患病率分别是BMI<24 kg/m^(2)且GGT水平下四分位数组男性和女性的2.486倍(95%CI:1.634~3.783)和2.027倍(95%CI:1.387~2.962),且男性和女性的前期高血压患病中BMI与GGT水平均有交互作用(P_(交互均)<0.001).[结论]正常范围内GGT水平升高是前期高血压的危险因素,在男性中表现更为突出,且GGT与BMI在前期高血压患病中存在交互作用.

酒精使用障碍严重程度的影响因素及风险预测模型构建

背景酒精使用障碍(AUD)是常见的慢性复发性精神疾病,对于重度AUD,需早期快速识别并及时妥善处理,以避免不可逆的伤害发生。目前,对AUD严重程度的评估主要基于临床医师对患者的精神检查,关于AUD严重程度影响因素及预测模型的研究有限。目的分析AUD患者疾病严重程度的影响因素,构建风险预测模型,为评估AUD患者的疾病严重程度提供参考。方法回顾性选取2017年1月1日—2022年12月31日南宁市第五人民医院收治的、符合《精神障碍诊断与统计手册(第5版)》(DSM-5)AUD诊断标准的1358例首次住院患者为研究对象,收集其基本资料,根据疾病严重程度分为轻中度组(n=330)和重度组(n=1028)。按7∶3将患者分为训练集和测试集,在训练集样本中构建Logistic回归模型,在测试集样本中采用受试者工作特征(ROC)曲线分析该模型对AUD严重程度的预测价值。结果与轻中度组相比,重度组居住地在城市(χ^(2)=7.804)、农民(χ^(2)=17.991)、饮酒频率高于1~2次/天(χ^(2)=35.267)的比例更高,初次饮酒年龄更大(t=-3.858),合并躯体疾病数量更多(Z=-22.782),γ-谷氨酰胺转移酶(χ^(2)=259.940)和总胆红素异常(χ^(2)=148.552)的比例更高(P均<0.01)。在训练集中进行的Logistic分析结果表明,农民(OR=2.024,95%CI:1.352~3.029)、初次饮酒年龄较大(OR=1.075,95%CI:1.025~1.129)、用餐时间外也饮酒(OR=3.988,95%CI:2.408~6.606)、总胆红素水平异常(OR=1.034,95%CI:1.000~1.069)、合并更多的躯体疾病(OR=4.386,95%CI:2.636~7.298)是AUD更严重的危险因素。该模型在测试集中的ROC曲线下面积(AUC)为0.906。结论在精神专科医院中,农民、初次饮酒年龄较大、用餐时间外也饮酒、总胆红素水平异常、合并更多的躯体疾病可能是重度AUD的危险因素。

总胆汁酸与谷氨酰转肽酶对新生儿高胆红素血症发病的影响及交互作用分析

目的研究总胆汁酸与谷氨酰转肽酶的交互作用对新生儿高胆红素血症发病的影响。方法采用回顾性队列研究的方法选择2020年3月至2022年11月于淮南市第一人民医院分娩的267例新生儿为研究对象,根据新生儿是否存有高胆红素血症分为正常组(209例)与高胆红素血症组(58例)。比较两组新生儿一般资料,采用Logistic回归分析影响新生儿高胆红素血症发病的因素,以及总胆汁酸与谷氨酰转肽酶对新生儿高胆红素血症的交互作用。结果高胆红素血症组新生儿感染、胎儿窘迫比例较高,谷草转氨酶、C反应蛋白、碱性磷酸酶、总胆汁酸、谷氨酰转肽酶水平较高,直接胆红素水平较低,差异均有统计学意义(χ^(2)/t值介于5.904~120.928之间,P<0.05);多因素Logistic回归分析结果显示高水平碱性磷酸酶、谷草转氨酶、C反应蛋白、总胆汁酸与谷氨酰转肽酶,低水平直接胆红素,以及新生儿感染、胎儿窘迫均为影响新生儿高胆红素血症发病的危险因素(OR值介于1.364~1.964之间,P<0.05);高总胆汁酸、高谷氨酰转肽酶既具有一定的相加交互作用,又具有相乘交互作用。结论总胆汁酸、谷氨酰转肽酶对新生儿高胆红素血症的影响具有正相加交互作用,临床应及时监测总胆汁酸、谷氨酰转肽酶相关生理水平,保障新生儿健康。

GGT、醛固酮、Hcy在老年重症心力衰竭患者病情及预后评估中的价值探究

目的探究γ-谷氨酰转肽酶(GGT)、醛固酮、同型半胱氨酸(Hcy)在老年重症心力衰竭患者病情及预后评估中的价值。方法选取2022年1月—2023年1月期间于苏州市立医院(南京医科大学附属苏州医院)就诊的100例老年重症心力衰竭患者作为研究组,100例老年非重症心力衰竭患者作为疾病对照组,100例体检的老年健康志愿者作为健康对照组,测定血清GGT、醛固酮、Hcy水平,分析其在3组中的表达差异。评价研究组院内病情变化及预后转归情况,分析不同病情、不同预后老年重症心力衰竭患者血清GGT、醛固酮、Hcy水平表达差异,明确GGT、醛固酮、Hcy对老年重症心力衰竭患者病情和预后的预测价值。结果与健康对照组、疾病对照组比较,研究组GGT、醛固酮、Hcy水平显著升高(P<0.05)。院内病情恶化的老年重症心力衰竭患者血清GGT、醛固酮、Hcy水平高于病情好转患者(P<0.05)。Pearson检验显示,GGT、醛固酮、Hcy与老年重症心力衰竭患者心功能左室射血分数(LVEF)均呈显著负相关(r_(GGT vs.LVEF)=-0.451,r_(醛固酮vs.LVEF)=-0.568,r_(Hcy vs.LVEF)=-0.545,P<0.05)。预后死亡组血清GGT、醛固酮、Hcy水平高于预后存活组(P<0.05)。LVEF、B型利纳钠肽(BNP)、院内病情恶化及GGT、醛固酮、Hcy均是影响患者预后不良的危险因素(P<0.05)。受试者工作特征(ROC)曲线显示,GGT、醛固酮、Hcy三项联合预测老年重症心力衰竭患者病情、预后的效能优于单项预测(P<0.05)。结论GGT、醛固酮、Hcy在老年重症心力衰竭患者外周血中呈高表达,随病情恶化水平升高,与预后生存状况相关,是影响患者预后生存状态的危险因素,可作为临床预测老年重症心力衰竭患者病情和预后的参考指标。

超声弹性成像技术联合血清甲胎蛋白、γ-谷氨酰转肽酶检验诊断肝脏良恶性肿瘤的价值

目的:分析超声弹性成像技术联合血清甲胎蛋白(AFP)、γ-谷氨酰转肽酶(GGT)检验诊断肝脏良恶性肿瘤的应用价值。方法:选取肝脏恶性病变(恶心组)及良性病变(良性组)患者各40例,均进行超声弹性成像检查,测定血清AFP、GGT水平,分析其对肝脏良恶性诊断的价值。结果:恶性组弹性硬度评分及血清AFP、GGT水平均高于良性组(P<0.05)。超声弹性成像弹性硬度评分、S1S2指数联合血清AFP和GGT检验诊断肝脏良恶性肿瘤的敏感度为100.00%,特异度为97.50%,均高于单一指标(P<0.05)。结论:超声弹性成像联合血清AFP、GGT检验诊断肝脏良恶性肿瘤的临床价值高。

扶正固本汤对胆总管结石术后患者胆汁生化指标及肝功能的影响

目的:观察扶正固本汤对胆总管结石术后患者肝功能及胆汁生化指标的影响。方法:选取2019年9月至2023年9月行胆总管探查取石术的患者134例,按照随机数字表法分为对照组和观察组,每组各67例。对照组术后给予常规治疗,观察组则给予扶正固本汤治疗。比较两组患者的临床疗效、不良反应发生率及治疗前后中医证候积分、肝功能指标[谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶(aspartateaminotransferase,AST)、γ-谷氨酰转肽酶(γ-GT)]、胆汁生化指标[总胆红素(total bilirubin,TBIL)、总胆汁酸(total bile acid,TBA)]。结果:两组患者发热、腹痛、黄疸等中医证候积分低于本组治疗前,且治疗后观察组低于对照组(P<0.05)。观察组有效率高于对照组,差异具有统计学意义(P<0.05)。两组患者治疗后AST、ALT以及γ-GT低于本组治疗前,且治疗后观察组低于对照组,差异具有统计学意义(P<0.05)。两组患者治疗后TBA高于本组治疗前,TBIL低于本组治疗前,且治疗后组间比较,差异具有统计学意义(P<0.05)。观察组不良反应发生率低于对照组(P<0.05)。结论:扶正固本汤运用于胆总管结石手术后,能明显提高临床疗效,改善患者肝功能及胆汁生化指标,降低不良反应。

血清铁、CA19-9/GGT比值与肝细胞癌微血管侵犯、术后复发和预后的关系

目的:分析血清铁、癌胚抗原19-9(CA19-9)/γ-谷氨酰转肽酶(GGT)比值与肝细胞癌微血管侵犯(MVI)、术后复发和预后的关系。方法:选择2020年3月至2023年3月我院收治的80例肝细胞癌患者(肝癌组)和53例健康志愿者(对照组),根据是否发生MVI将患者分为MVI组(46例)和非MVI组(34例)。术前检测血清铁、CA19-9/GGT比值,术后定期随访,统计术后复发和总生存(OS)情况,根据复发情况分为复发组(26例)和非复发组(54例)。受试者工作特征(ROC)曲线分析血清铁和CA19-9/GGT诊断术前MVI的价值。分析血清铁、CA19-9/GGT比值与肝细胞癌MVI、术后复发和预后的关系。结果:肝癌组血清铁、CA19-9/GGT比值均高于对照组(P<0.05),肝内转移、TNM分期Ⅲ期、低度分化肝细胞癌患者血清铁、CA19-9/GGT比值高于无肝内转移、TNM分期Ⅰ~Ⅱ期、高中分化患者(P<0.05)。MVI组血清铁、CA19-9/GGT比值均高于非MVI组(P<0.05),复发组血清铁、CA19-9/GGT比值均高于非复发组(P<0.05)。血清铁和CA19-9/GGT诊断术前MVI的截断值分别为56.98μmol/L、2.53,曲线下面积为0.767、0.882,联合诊断为0.934,高于单独诊断(P<0.05)。血清铁高水平、CA19-9/GGT高比值肝细胞癌患者OS生存率低于血清铁低水平、CA19-9/GGT低比值患者(P<0.05)。TNM分期Ⅲ期、高血清铁水平、高CA19-9/GGT比值是肝细胞癌患者不良预后的危险因素(P<0.05)。结论:肝细胞癌患者血清铁水平和CA19-9/GGT比值增高,与术前MVI、术后复发和预后不良有关。

血清HBsAg、HBV RNA、GGT及GPR联合检测对慢性HBV感染自然史的诊断价值

目的探讨慢性乙型肝炎病毒(HBV)感染自然史各期患者血清乙型肝炎病毒表面抗原(HBsAg)、乙型肝炎病毒核糖核酸(HBV RNA)、γ-谷氨酰转肽酶(GGT)、γ-谷氨酰转肽酶/血小板比值(GPR)水平变化及联合检测对慢性HBV感染自然史分期的诊断价值。方法选取2020年11月至2023年12月在昆明市第三人民医院就诊的未经抗病毒治疗的172例慢性HBV感染患者为研究对象,根据HBV感染进程分为HBeAg阳性慢性HBV感染(EPI)组(n=77)、HBeAg阳性CHB(EPH)组(n=42)、HBeAg阴性慢性HBV感染(ENI)组(n=26)、HBeAg阴性CHB(ENH)组(n=27)。比较各组患者血清HBsAg、HBV RNA、GGT、GPR水平差异,绘制受试者工作特征(ROC)曲线探究血清HBsAg、HBV RNA、GGT、GPR联合检测对慢性HBV感染自然史中EPH期和ENH期的诊断价值。结果4组患者血清HBsAg、HBV RNA、GGT、GPR水平比较,差异均有统计学意义(P<0.05)。血清HBsAg、HBV RNA、GGT、GPR联合检测诊断EPH期和ENH期的ROC曲线下面积(AUC)分别为0.869和0.836,敏感度和特异度分别为76.19%、59.26%和84.42%、96.15%。结论血清HBsAg、HBV RNA、GGT、GPR联合检测对慢性HBV感染自然史诊断有较高的准确性和低误诊率,有望取代传统的有创检查,对于慢性HBV感染自然史各期患者的精准诊断及个体化治疗策略的制订发挥着重要的临床意义。

Associations between y-glutamyl transferase, metabolic abnormalities and inflammation in healthy subjects from a population-based cohort: A possible implication for oxidative stress

AIM: To examine the relationships between γ -glutamyltransferase (GGT), alanine-aminotransferase (ALT),aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a population-based sample.METHODS: Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1339subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy).RESULTS: In all patients metabolic parameters and hs-CRP levels linearly increase from the lowest to the highest ALT and GGT tertiles, while in subjects without metabolic abnormalities, there is a significant association between fasting glucose, uric acid, waist circumference,hs-CRP, triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP and glucose levels are associated with GGT levels in a multiple regression model, after adjustments for multiple confounders.In the same model, median NT levels are significantly associated with the increasing GGT tertile (β = 1.06;95%CI 0.67-1.45), but not with the AST and ALT tertiles.In a multiple regression model, after adjusting for age,sex, BMI, waist, smoking, and alcohol consumption, both NT (β = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (β =0.09; 95%CI 0.03-0.15) are significantly associated with fasting glycemia.CONCLUSION: GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals. Prospective studies are needed to establish if GGT could predict future diabetes in these subjects.

Comparing the difference in enhancement of kokumi-tastingγ-glutamyl peptides on basic taste via molecular modeling approaches and sensory evaluation

γ-Glutamyl peptides can enhance basic taste sensations such as saltiness,sweetness,and umaminess,while the molecular mechanism and the difference in taste enhancement remain elusive.Thus,two complex conformations:taste type 1 receptor 1(T1 R1)-MSG and taste type 1 receptor 2(T1 R2)-sucrose were constructed to form binding receptors.These peptides showed affinity for the two receptors,but a higher affi nity scores and more binding amino acid residues for the T1 R1-MSG receptor,implying that they may exhibit a higher umami-enhancing effect.Thereinto,γ-glutamyl alanine(γ-EA)displayed the highest affi nity for the two receptors through mobilizing multiple amino acid residues to form hydrophobic and hydrogen bonds,indicating it had the highest enhancement for umaminess and sweetness among these peptides.Sensory evaluation demonstrated the enhancement ofγ-EA on umaminess was superior to that of sweetness.Generally,γ-glutamyl peptides could enhance basic taste sensation via activating taste receptor,and exhibited a highest umami-enhancing effect.

PT和γ-GT/Alb比值对慢性乙型肝炎患者肝纤维化分期的预测价值

目的:评估凝血酶原时间(PT)、γ-谷氨酰转肽酶/白蛋白(γ-GT/Alb)比值对慢性乙型肝炎(CHB)患者肝纤维化分期的预测价值,并与经典无创模型天冬氨酸氨基转移酶/血小板比值指数(APRI)评分、4因子模型(FIB-4)进行对比。方法:收集2020年4月至2021年5月北京中医药大学东方医院收治的108例CHB肝纤维化患者病例资料作回顾性分析,根据肝活检病理结果将患者分为无或轻度肝纤维化组(S0~S1期,68例)、显著肝纤维化组(≥S2期,40例)。收集患者的血清学指标、APRI、FIB-4等数据,运用单因素分析、多因素logitstic回归分析筛选出独立预测指标并建立综合预测模型,同时采用受试者工作特征曲线(ROC)评价综合模型的预测准确性。结果:单因素分析结果显示,两组患者在γ-GT、Alb、γ-GT/Alb、PT、LN、PLT方面比较,差异具有统计学意义(均P<0.05);多因素logitstic回归分析结果显示,PT和γ-GT/Alb是显著肝纤维化的独立预测指标(P<0.05)。依据logistic回归分析结果建立综合预测模型[logit(P)=-4.926+0.048×γ-GT/Alb+0.147×PT],其ROC曲线下面积(AUC)为0.839,截断值为0.469时,敏感度为78.04%,特异度为97.09%。预测肝纤维化的准确性明显优于APRI及FIB-4,差异有统计学意义(P<0.05)。结论:PT和γ-GT/Alb的综合预测模型对预测CHB导致的显著肝纤维化(≥S2)具有优势,其预测准确性均高于APRI、FIB-4两项指标。

γ-谷氨酰转肽酶/血小板计数比值对接受一线化疗方案的Ⅲ-Ⅳ期胃癌患者的预后价值

目的 探讨γ-谷氨酰转肽酶(γ-gamma-glutamyl transpeptidase, GGT)/血小板计数(Platelet, PLT)比值(γ-glutamyl transpeptidase to platelet ratio index, GPRI)对接受一线化疗方案的Ⅲ-Ⅳ期胃癌患者预后的预测价值。方法 选择138例非手术治疗的Ⅲ-Ⅳ期胃癌患者为研究对象,采集患者化疗前外周静脉血,检测GGT水平及PLT,根据公式GPRI=GGT/PLT(×109/L),计算不同患者的GPRI值。以GPRI>0.39为界值,将患者分为高GPRI组及低GPRI组。对患者进行连续性随访,采用卡方检验分析患者临床病理参数对GPRI比值的影响;利用Kaplan-Meier法及Log-rank检验分析GPRI比值对患者预后的影响。结果 (1)受试者工作特征(Receiver operating characteristic,ROC)曲线分析显示,GPRI、GGT、PLT的最佳临界值分别为0.39、64.68和178.59,ROC曲线下面积(Area under curve,AUC)分别为0.776、0.659和0.705,GPRI判断患者预后的效能明显优于单独检测GGT和血小板。(2)与低GPRI组相比,高GPRI组患者中>1器官转移及腹膜转移发生率、Ⅳ期患者比例、糖苷类肿瘤标志物(CA19-9)>37 U/mL的患者比例均明显较高(P<0.05)。且>1个器官转移(P=0.002)、腹膜转移(P=0.024)、Ⅳ期(P=0.008)、CA19-9水平(P=0.004)和GPRI>0.39(P=0.033)均是影响患者中位无进展生存期(Progression free survival, PFS)和中位总生存期(Overall survival, OS)的独立性危险因素。(3)所有患者的OS及PFS分别为156 d和217 d。低GPRI组、高GPRI组患者的中位PFS分别为202 d、117 d;中位OS分别为269 d、173 d,差异均有统计学意义(P均<0.05)。进一步行亚组分析发现,在转移器官>1个(χ^(2)=18.24,P<0.01)、Ⅳ期(χ^(2)=19.85,P<0.01)和CA19-9水平升高(χ^(2)=12.65,P<0.01)的亚组患者中,低GPRI组患者的OS均明显好于高GPRI组。结论 GPRI对接受一线化疗方案的Ⅲ-Ⅳ期胃癌患者的预后有较高的预测价值,有望作为晚期胃癌患者的一项新的预后指标。