精氨酸代谢对肿瘤生长及肿瘤免疫的影响

氨基酸代谢在疾病发生发展中的重要性逐渐被认知,其中精氨酸代谢与肿瘤的关系已成为研究热点。精氨酸作为条件性必需氨基酸,在肿瘤的发生、生长、转移过程中发挥重要作用。肿瘤免疫抑制性微环境的形成以及髓系免疫细胞的表型变化、成熟程度和功能状态都与精氨酸代谢密不可分。本文针对国内外上述相关研究成果,主要总结了精氨酸代谢在肿瘤生长、抗肿瘤免疫中的作用,归纳了肿瘤免疫微环境中的髓系免疫细胞类型、功能以及靶向精氨酸代谢途径的肿瘤治疗策略。     

地衣芽孢杆菌胶囊联合谷氨酰胺对肝硬化患者免疫功能的影响

目的:探究地衣芽孢杆菌胶囊联合谷氨酰胺对肝硬化患者免疫功能的影响.方法:选取我院102例肝硬化患者(2020年1月至2021年1月),随机分为对照组和研究组,各51例,对照组采用谷氨酰胺治疗,研究组采用地衣芽孢杆菌胶囊联合谷氨酰胺治疗.比较两组疗效、治疗前后肠黏膜屏障功能和免疫功能.结果:研究组总有效率明显高于对照组(P<0.05);治疗后研究组屏障功能指标水平均低于对照组,免疫功能指标均优于对照组高(P<0.05).结论:地衣芽孢杆菌胶囊联合谷氨酰胺治疗肝硬化患者效果显著,可有效改善患者肠黏膜屏障功能,增强机体免疫功能.     

谷氨酰胺在早产儿胃肠道屏障和免疫功能中的评价

通过检测早产儿血浆谷氨酰胺（Gln）、血清分泌型免疫球蛋白A（SIgA）浓度,以此来评估早产儿肠道黏膜屏障和肠道免疫功能。现将结果报告如下。1材料和方法1.1临床资料选取在我院住院治疗,出生体重〈2500g的早产儿60例,采用完全随机对照的方法,随机分为试验组和对照组,其中试验组：口服Gln的患儿35例。     

胃肠道肿瘤的组织化学和免疫组织化学研究

采用组织化学和免疫组织化学方法对胃肠道脾性肿瘤组织及肿瘤周围组织内分泌细胞进行了观察。结果表明:良性腺瘤有腺癌组织中存在内分泌细胞,许多肿瘤组织及胂瘤周围组织中可同时存在2种或2种以上的免疫活性内分泌细胞。这些内分泌细胞的存在可能对肿瘤的发生、发展以及在肿瘤免疫方面起到重要作用。本文研究的结果支持了内分泌细胞内胚层起源说。本试验结果还显示嗜银细胞和免疫活性5—羟色胺(irSer)细胞的分布存在着差异。     

不同麻醉方式对老年腹部肿瘤手术患者术后免疫功能及血清IL-6、TNF-α水平的影响

为探讨不同麻醉方式对老年腹部肿瘤手术患者术后免疫功能及血清IL-6、TNF-α水平的影响,选择老年腹部肿瘤患者94例,按照随机数字表法分为观察组(47例)、对照组(47例)。对照组采用全身麻醉,观察组采用腰硬联合麻醉复合全身麻醉,比较两组患者术前、手术15 min和术毕血流动力学指标,手术时间、拔管时间和苏醒时间,术前和术后3 d免疫功能及血清IL-6和TNF-α水平变化。观察组手术15 min和术毕心率(heart rate,HR)、平均动脉压(mean arterial pressure,MAP)低于同期对照组(P0.05)。两组手术时间比较,差异无统计学意义(P 0.05)。观察组拔管时间和苏醒时间快于对照组(P0.01)。观察组术后3 d CD3~+、CD4~+和CD4~+/CD8~+高于对照组(P0.01)。观察组术后3 d血清IL-6和TNF-α水平低于对照组(P0.001)。腰硬联合麻醉复合全身麻醉对老年腹部肿瘤手术患者效果明显,对血流动力学、免疫功能及炎症反应影响小。     

肿瘤免疫代谢靶向治疗的研究进展

肿瘤免疫疗法的出现改变了许多肿瘤的治疗格局，是肿瘤治疗领域的重大突破。虽然其在一些肿瘤类型中显示出良好疗效，然而，总体反应率仍然偏低，因此需要开发新型的免疫治疗药物及治疗策略。代谢重编程是肿瘤细胞的一大特征，肿瘤微环境中免疫代谢的复杂性是影响肿瘤免疫治疗疗效的重要因素。近年来的研究表明，靶向免疫代谢可以减少免疫抑制，增强抗肿瘤免疫，提高现有肿瘤免疫疗法的疗效甚至克服耐药。文章综述了靶向肿瘤免疫代谢途径治疗的最新进展，包括靶向糖代谢、氨基酸代谢、核苷酸代谢和脂质代谢等，为开发免疫代谢靶向治疗潜力，寻找新靶点提供新思路。     

全身麻醉复合硬膜外麻醉对老年腹部手术患者术后肺部感染及免疫功能的影响

目的:探讨全身麻醉复合硬膜外麻醉对老年腹部手术患者术后肺部感染以及免疫功能的影响.方法:420例行腹部手术的老年患者,根据随机数字表法分为研究组和对照组(各210例),研究组给予全身麻醉复合硬膜外麻醉,对照组单纯全身麻醉.对比两组患者术前和术后第3天发热、咳痰以及肺部感染的发生情况;对比两组患者术前、术后第1天CD3+...     

新菌抗癌剂-Ⅰ号对肿瘤患者免疫功能的影响

36例恶性肿瘤患者,经NBAC-I皮下注射一个疗程后,细胞免疫功能有一定程度的提高,特别是NK细胞活性,从25.4±3.7％提高到28.6±3.7％,差别有显著意义(P<0.05)。无远处转移病灶的肿瘤患者细胞免疫改善更显著。结合浆膜腔给药或瘤体内给药者,效果比单一皮下注射好。     

谷氨酰胺对JAL1杂交瘤细胞生长代谢的影响

为研究不同浓度的谷氨的酰胺对JAL1 杂交瘤细胞生长、葡萄糖消耗、乳酸及氨生成等代谢过程的影响。在细胞培养箱中 ,用含不同浓度谷氨酰胺的培养液培养细胞 ,培养条件为pH 7 0～ 7 5 ,温度 37℃ ,5 %CO2 。实验表明 ,适宜于该株杂交瘤细胞生长的谷氨酰胺浓度为 2mmol/L ,谷氨酰胺浓度与细胞的葡萄糖消耗呈反比 ,与乳酸生成浓度呈反比 ,与氨的生成浓度呈正比     

CD117阴性胃肠道间质瘤的临床病理及免疫组织化学研究

目的 探讨免疫组织化学在形态学典型、免疫组织化学CD117阴性胃肠道间质瘤(GIST)诊断中的意义.方法 对10例CD117阴性、形态学典型的GIST进行c-kit基因第9、11、13、17号外显子及血小板源性生长因子受体α(PDGFRA)基因第12和18号外显子的基因检测,同时所有病例均进行CD117、CD34、平滑肌肌动蛋白(SMA)、结蛋白、S-100蛋白、WT-1、DOG-1 的免疫组织化学染色(EnVision法).结果 10例中8例完成c-kit及PDGFRA基因的检测,仅1例有c-kit基因第9号外显子突变,余未发现基因突变.10例CD117阴性的病例9例CD34阳性,2例SMA局灶阳性.结蛋白和S-100蛋白均阴性.DOG1弥漫阳性者5例,1例弥漫弱阳性,2例局灶阳性,2例阴性.4例WT-1弥漫阳性,2例局灶阳性,1例有散在肿瘤细胞阳性,3例阴性.结论 对胃肠道及胃肠道外形态学典型、但CD117阴性的GIST病例,联合应用多种免疫组织化学标记有助于诊断.DOG-1和WT-1可作为补充加入到CD117阴性GIST的诊断中.

Abstract：

Objective To study the immunophenotype and c-kit or platelet derived growth factor receptor alpha(PDGFRA)gene mutations in CD117-negative gastrointestinal stromal tumors(GISTs).Methods Ten cases of GISTs with typical histologic features but no CD117 expression were retrieved from the archival of Department of Pathology,Peking Union Medical College Hospital,China.The Cages were further evaluated for the presence of c-kit exons 9.11, 13 and 17 mutations and PDGFRA exons 12 and 18mutations.DNA was extracted from the paraffin-embedded tuinor tissue.The PCR products were sequenced directly for the mutations.An immunohistochemical study for CD117,CD34,smooth muscle actin,desmin,S-100 protein.WT-1 and DOC-1 Was also performed.Results Eight of the 10 Cases had the mutation tests completed.C-kit mumfion in exon 9 Wag detected in only one case.Amongst the 10 cases studied, CD34Wag expressed in 9 cases. Smooth muscle actin was focally positive in 2 cases.None of them expressed desmin or S-100 protein.DOG-1 and WT-1 were diffusely positive in 5 and 4 Cages.respectively.In addition.DOG1 Was diffusely but weakly positive in 1 case and focally expressed in 2 cages.Three cases were focally positive for WT-1.Conclusion Pathologic diagnosis of CD117-negative GISTs can be facilitated with the application of a panel of immunohistochemical markers.including DOG-1 and WT-1.     

Effects of glutamine treatment on myocardial damage and cardiac function in rats after severe burn injury

Treatment with glutamine has been shown to reduce myocardial damage associated with ischemia/reperfusion injury. However, the cardioprotective effect of glutamine specifically after burn injury remains unclear. The present study explores the ability of glutamine to protect against myocardial damage in rats that have been severely burned. Seventy-two Wistar rats were randomly divided into three groups: normal controls (C), burned controls (B) and a glutamine-treated group (G). Groups B and G were subjected to full thickness burns comprising 30% of total body surface area. Group G was administered 1.5 g/ (kg•d) glutamine and group B was given the same dose of alanine via intragastric administration for 3 days. Levels of serum creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and blood lactic acid were measured, as well as myocardial ATP and glutathione (GSH) contents. Cardiac function indices and histopathological changes were analyzed at 12, 24, 48 and 72 post-burn hours. In both burned groups, levels of serum CK, LDH, AST and blood lactic acid increased significantly, while myocardial ATP and GSH contents decreased. Compared with group B, CK, LDH, and AST levels were lower and blood lactic acid, myocardial ATP and GSH levels were higher in group G. Moreover, cardiac contractile function inhibition and myocardial histopathological damage were significantly reduced in group G compared to B. Taken together, these results show that glutamine supplementation protects myocardial structure and function after burn injury by improving energy metabolism and by promotedthe synthesis of ATP and GSH in cardiac myocytes.     

Dysregulation of glutamine/glutamate metabolism in COVID-19 patients: A metabolism study in African population and mini meta-analysis

Coronavirus disease 2019 (COVID-19) remains a serious global threat. The metabolic analysis had been successfully applied in the efforts to uncover the pathological mechanisms and biomarkers of disease severity. Here we performed a quasi-targeted metabolomic analysis on 56 COVID-19 patients from Sierra Leone in western Africa, revealing the metabolomic profiles and the association with disease severity, which was confirmed by the targeted metabolomic analysis of 19 pairs of COVID-19 patients. A meta-analysis was performed on published metabolic data of COVID-19 to verify our findings. Of the 596 identified metabolites, 58 showed significant differences between severe and nonsevere groups. The pathway enrichment of these differential metabolites revealed glutamine and glutamate metabolism as the most significant metabolic pathway (Impact = 0.5; −log10P = 1.959). Further targeted metabolic analysis revealed six metabolites with significant intergroup differences, with glutamine/glutamate ratio significantly associated with severe disease, negatively correlated with 10 clinical parameters and positively correlated with SPO₂ (r_s= 0.442, p = 0.005). Mini meta-analysis indicated elevated glutamate was related to increased risk of COVID-19 infection (pooled odd ratio [OR] = 2.02; 95% confidence interval [CI]: 1.17–3.50) and severe COVID-19 (pooled OR = 2.28; 95% CI: 1.14–4.56). In contrast, elevated glutamine related to decreased risk of infection and severe COVID-19, the pooled OR were 0.30 (95% CI: 0.20–0.44), and 0.44 (95% CI: 0.19–0.98), respectively. Glutamine and glutamate metabolism are associated with COVID-19 severity in multiple populations, which might confer potential therapeutic target of COVID-19, especially for severe patients.     

Gastrointestinal autonomic nerve tumors: Immunohistochemical and ultrastructural studies in cases of gastrointestinal stromal tumor

The gastrolntestlnal autonomic nerve tumor (GAN tumor) is an uncommon stromal tumor with a morphological feature resembling the cell processes of the enteric plexus, and was originally teimed a plexoma or plexosarcoma. Light microscoplc studies show the GAN tumor most often consists of spindle-shaped cells indistinguishable from a smooth muscle tumor or Schwann cell tumor. Immunohistochemical and ultrastructural examinations of 18 cases of gastrointestinal stromal tumor (GIST) were performed. During ultrastructural examination, all of the 12 cases which were immunohisto-chemically positive for S-100 protein or neuron-specific eno-lase (NSE) showed synapse-like structures containing dense core neurosecretory granules measuring 100–200 nm, and 40–60 nm endocytoplasmic vesicles. These results suggest that most GIST of neurogenlc origln are tumors derived from the myenteric nerve plexus.     

腹腔镜手术对急性结石性胆囊炎患者 胃肠功能和C反应蛋白的影响

 目的：探讨腹腔镜和开腹胆囊切除术对急性结石性胆囊炎患者胃肠功能和C反应蛋白的影响。方法：回顾性分析50例腹腔镜胆囊切除术(LC组)与50例开腹胆囊切除术(OC组)患者的临床资料,对比两组患者首次肛门排气时间;肠鸣音恢复时间和C反应蛋白水平手术前后的变化。结果：LC组患者术后肛门排气时间及肠鸣音恢复时间均比OC组短,差异有统计学意义（P＜ 0.05）;术后OC组C反应蛋白水平明显高于LC组,两组比较差异有统计学意义（P＜0.05）。结论：LC治疗急性胆囊炎对机体损伤较OC小,胃肠功能恢复快,是一种安全可行的手术方式。     

四磨汤对妇科开腹术后胃肠运动功能的临床效应及安全性研究

目的：探讨四磨汤对妇科开腹术后胃肠运动功能的临床效应及安全性。方法：采用随机、双盲、安慰剂对照进行前瞻性研究，选取妇科开腹术后患者试验组79例，对照组66例。术后第1天，治疗组口服四磨汤口服液，对照组口服模拟四磨汤口服液。记录胃肠运动功能相关指标、生活质量积分、安全性检测指标、不良反应及有无并发症等，然后进行统计学分析。结果：与安慰剂对照组相比：治疗组术后首次肠鸣音恢复时间、首次肛门排气时间、首次排便时间平均分别缩短约9 h、7 h、8 h，治疗组对促进肠道运动的影响优于对照组。治疗组术后第4天生活质量评分明显升高，四磨汤对术后食欲、腹胀、睡眠改善有明显疗效。两组患者在安全性指标、并发症方面均无差异。结论：四磨汤能有效促进妇科开腹术后胃肠运动功能的恢复，减少输液量并改善患者生活质量，在妇科开腹术后患者中使用安全，无明显临床不良反应。     

超声内镜指导下消化道间质瘤诊断及治疗

目的评价超声内镜对消化道间质瘤的诊断及治疗的指导意义。方法常规胃镜及结肠镜检查发现消化道隆起性病变并行超声内镜检查诊断为间质瘤患者92例,其中男性44例,女性48例;年龄18～71岁,平均年龄44岁。根据术前超声内镜检查显示起源层次及大小,分别采取内镜下治疗、手术治疗及随访。结果超声内镜诊断间质瘤共92例,食管39例,胃44例,十二指肠5例,结肠4例。发生于黏膜肌层47例,发生于固有肌层45例。内镜下治疗26例,其中高频电凝电切术6例,内镜下套扎术12例,内镜下黏膜切除术8例,内镜治疗术后出血1例,经内镜下保守治疗止血成功。外科手术治疗8例。内镜下治疗中14例病理检查均为良性间质瘤,手术治疗中3例为交界性间质瘤,5例为良性间质瘤。结论超声内镜对消化道间质瘤定性诊断有较高的特异度及灵敏度,使对消化道间质瘤内镜下治疗成为更快速、损伤更小、更为安全的治疗手段。     

Acute effects of phenylbutyrate on glutamine,branched‐chain amino acid and protein metabolism in skeletal muscles of rats

Phenylbutyrate (PB) acts as chemical chaperone and histone deacetylase inhibitor, which is used to decrease ammonia in urea cycle disorders and has been investigated for use in the treatment of a number of lethal illnesses. We performed in vivo and in vitro experiments to examine the effects of PB on glutamine (GLN), branched‐chain amino acid (BCAA; valine, leucine and isoleucine) and protein metabolism in rats. In the first study, animals were sacrificed one hour after three injections of PB (300mg/kg b.w.) or saline. In the second study, soleus (SOL, slow twitch) and extensor digitorum longus (EDL, fast twitch) muscles were incubated in a medium with or without PB (5 mM). L‐[1‐¹⁴C] leucine was used to estimate protein synthesis and leucine oxidation, and 3‐methylhistidine release was used to evaluate myofibrillar protein breakdown. PB treatment decreased GLN, BCAA and branched‐chain keto acids (BCKAs) in blood plasma, decreased BCAA and increased GLN concentrations in muscles, and increased GLN synthetase activities in muscles. Addition of PB to incubation medium increased leucine oxidation (55% in EDL, 29% in SOL), decreased BCKA and increased GLN in medium of both muscles, increased GLN in muscles, decreased protein synthesis in SOL and increased proteolysis in EDL. It is concluded that PB decreases BCAA, BCKA and GLN in blood plasma, activates BCAA catabolism and GLN synthesis in muscle and exerts adverse effects on protein metabolism. The results indicate that BCAA and GLN supplementation is needed when PB is used therapeutically and that PB may be a useful prospective agent which could be effective in management of maple syrup urine disease.     

胃肠道钙化性纤维性肿瘤分子标志物的研究进展

钙化性纤维性肿瘤(calcifying fibrous tumor,CFT)是一种罕见的良性病变,其临床表现、影像学检查等不具有特异性.发生于胃肠道的CFT,易与其他胃肠道间叶源性肿瘤混淆,如胃肠道间质瘤(gastrointestinal stromal tumor,GIST)和炎性肌纤维母细胞瘤(inflammatory myofibroblastic tumor,IMT),在临床诊断时需进行分子标志物检测才可鉴别.CFT发病原因不明.近年来,越来越多的学者认为胃肠道CFT与IgG4相关性疾病(IgG4-RD)有关.     

重组白细胞介素2促进小鼠胸腺细胞发育及辐射损伤小鼠免疫功能的恢复

经亚致死量照射的BALB/c小鼠胸腺内残留的胸腺干细胞经历与胚胎胸腺发育十分相似的过程,体内给予IL-2(6×10~5u/kg)可明显促进胸腺细胞由CD4~-CD8~-向CD4~+CD8~+再向CD4~+CD8~-/CD4~-CD8~-分化并明显促进胸腺细胞增殖和亚致死量照射小鼠脾细胞对ConA、LPS 的增殖能力,促进同种异型细胞的混合淋巴细胞反应(MLR)和绵羊红细胞(SRBC)的抗体形成细胞数(PFC)等多项免疫功能的恢复。