p38γMAPK蛋白在结肠癌组织中的表达及临床意义

目的探讨人结肠癌中p38γMAPK蛋白的表达及其临床意义。方法应用免疫组织化学法检测54例结肠癌组织、近癌旁组织、癌周正常组织和15例腺瘤息肉组织中p38γ蛋白的表达情况。结果p38γ蛋白的表达主要定位于胞质中,仅少量在胞核中表达。p38γ蛋白在结肠癌组织、癌旁组织、癌周正常组织中的高表达率分别为75.93%、51.85%、37.04%,在结肠腺瘤息肉组织中高表达率为33.33%。p38γ蛋白在结肠癌中的表达明显高于癌旁组织、癌周正常组织和腺瘤息肉组织,有统计学意义（P〈0.01）。p38γ的表达与Duke分期,组织分化程度及有无淋巴结转移有显著差异（P〈0.01）,p38γ的表达与年龄、性别、肿瘤大小、肿瘤位置无明显相关（P〉0.05）。结论结肠癌组织中p38γ蛋白处于过度表达状态,与结肠癌的发生、发展和转移密切相关。     

PPARY2基因Pro12Ala和C1431T多态性及其单倍型与2型糖尿病和肥胖的相关性研究

目的 研究过氧化物体增殖活化受体γ2(peroxisome proliferator activated receptorγ2,PPARγ2)基因Pro12Ala和C1431T多态性及其单倍型与汉族人2型糖尿病、肥胖的关系.方法 应用聚合酶链反应-限制性片段长度多态性的方法,对207例2型糖尿病患者和101名非糖尿病对照者进行PPARγ2基因Pro12Ala和C1431T多态性研究.结果 (1)在非糖尿病对照人群中Aal 12等位基因频率是0.064,T1431等位基因频率是0.252.单倍型分析显示Pro12Ala和C1431T两个位点连锁不平衡(D'=0.63,r2=0.074),组成了3种常见单倍型Pro-C、Pro-T和Ala-T.(2)Pro12Ala和C1431T多态性分布及其单倍型分布频率在2型糖尿病组与对照组组间差异均无统计学意义(P>0.05).(3)Pro12Ala变异与糖尿病患者的血压、血脂相关,地等位基因降低非肥胖糖尿病患者的舒张压(P<0.05),而对肥胖糖尿病患者的血脂水平无保护作用(P<0.05);C1431T多态性与糖尿病患者的超重和肥胖相关,超重和肥胖的糖尿病者T等位基因频率相对较高(P<0.05).结论 Pro12Ala和C1431T多态性可能在汉族人糖尿病发病中不是起主要作用;C1431T多态性与糖尿病患者的超重和肥胖相关.     

2018—2020年参加全国放射性核素γ能谱考核结果分析

目的 保证γ放射性核素实验室活动和结果的有效性,提高实验室γ放射性核素检测的能力。方法 对影响全国γ放射性核素考核结果的相对偏差、准确度、精确度、相对合成不确定度进行统计分析。结果 本实验室2018—2020年全国γ放射性核素考核上报结果均满足合格要求,其中2019年被评为优秀,2018—2020年11个测量结果相对偏差最大为18.01%,2018年|Z_检验|≤1、U_检验≤2.58,2019年|Z_检验|≤1、U_检验≤1,2020年U_检验≤1、U_rel≤20%。结论 本实验室采用的放射性核素γ能谱分析方法正确,检测数据准确、可靠。     

AD治疗新药物——γ-分泌酶抑制剂

家族性阿尔采末病属常染色体显性遗传 ,其中大部分与编码早老素的基因发生突变所导致的γ 分泌酶功能异常有关 ,γ 分泌酶是一包括PS二聚体、Nicastrin、PEN 2等组分的多酶复合体。γ 分泌酶剪切APP、Notch、E cadherin、ErbB 4受体酪氨酸激酶等膜蛋白。目前已发现了许多类型的γ 分泌酶抑制剂 :基于二氟酮、二氟乙醇基团的γ 分泌酶抑制剂 ;脲多肽模拟化合物 ;基于羟乙基二肽电子等配体的化合物 ;具有α 螺旋结构的小肽 ;具有 4 氯 异香豆素基本母核的非肽抑制剂 ;含有丙氨酰基团的化合物。但这些抑制剂目前大多还只是作为一种工具药来研究γ 分泌酶的结构、功能以及作用机制。其中选择性抑制Aβ生成的γ 分泌酶抑制剂很有希望成为一种高效的阿尔采末病治疗药物     

Novel GHB-derived natural products from European mistletoe (Viscum album)

Abstract

Context: The European white-berry mistletoe [Viscum album L. (Loranthaceae)] is among the oldest known medicinal plants. At present the most important application of mistletoe extracts is in the treatment of cancer. However, natural products specific to mistletoe have rarely been encountered in the current literature.

Objective: To discover novel natural products specific to European mistletoe.

Materials and methods: European mistletoe was extracted with methanol, purified to partition against diethyl ether and further purified with XAD-7 column chromatography. Pure compounds were separated by Sephadex column chromatography and preparative HPLC. The structures of the novel compounds were established using a combination of several 2D NMR spectroscopic techniques and mass spectrometry.

Results: A new type of natural product derived from the methyl ester of γ-hydroxybutyric acid (GHB) coupled to hydroxybenzoic acids, namely 3-(3′-carbomethoxypropyl) gallic acid and 3-(3′-carbomethoxypropyl)-7→3″-protocatechoyl galloate were characterized from European white-berry mistletoe. Condensation of the 3-hydroxyl of gallic acid with the 4-hydroxyl of GHB significantly reduced the radical scavenging properties of the former compound.

Discussion and conclusion: The characterized compounds define a novel group of natural products that may be of particular interest because it appears that the two new compounds are not closely related to any known natural product.     

调强放疗射野复杂度对剂量验证的影响

目的:探究针对射野的几何特征提出复杂度的量化方式，分析各个复杂度对γ通过率的影响和ROC曲线，并与其它研究提出的复杂度进行比较。方法:本文提出小子野占比、子野偏离等中心程度、形状不规则度的量化公式。通过放疗计划系统导出临床放疗计划中157个射野的子野MLC位置、跳数等数据，并编写MATLAB程序，代入公式计算相关的复杂度。以各复杂度为自变量，γ通过率为因变量进行线性回归分析。并作出复杂度的ROC曲线以研究复杂度的识别能力。与其它研究提出的跳数利用率（MU/Gy）、小子野评分、以等中心为圆心特定半径圆外面积占比进行比较。结果:线性回归结果显示， x方向偏离度（P<0.001）、y方向偏离度（P<0.001）、形状不规则度（P<0.001）、小子野占比（P=0.026）对γ通过率有显著的影响，ROC曲线下面积较大，识别效果较好。对比以等中心为圆心特定半径圆外面积占比、跳数利用率（Mu/Gy）、小子野评分的量化方式，本研究提出的量化方法与通过率的相关性更高,识别能力更强。结论:基于射野几何复杂度的新的量化方式，其中形状不规则度、偏离等中心程度与通过率的相关性最强，并且前三者对低通过率射野具有一定的识别能力。对计划选择及优化方向提供一定的参考。     

Nanomedicine for acute respiratory distress syndrome: The latest application,targeting strategy,and rational design

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air–blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.     

Role of polymorphic sequences 5′ to the Gγ gene and 5′ to the β gene on the homozygous β thalassemic phenotype

Sixty‐seven homozygous male and female thalassemic patients with different phenotypes, aged between 8 and 33 years, were divided into three groups, according to the severity of their β‐thalassemia (thal) mutations. We investigated whether some co‐inherited genetic factors could influence the phenotype. Patients with milder β‐thal defects, homozygotes or compound heterozygotes for the IVS‐I‐6 (T→C) or ?87 (C→G) mutations had a milder disease. In addition, determination of the co‐inheritance of the ?158 (C→T) ^Gγ polymorphism and the (AT)₉T₅ repeat motif in the region ?540 to ?525, 5′ to the β‐globin gene, showed that in some patients with severe or mild/severe β‐thal mutations, linked to haplotype III, there was higher Hb F expression. We conclude that in homozygous β‐thal patients, the severity of the mutations is the most important factor influencing the phenotype, but some polymorphisms such as the ?158 (C→T) ^Gγ and (AT)₉T₅ repeat motif, increasing the Hb F expression and ameliorate the clinical course of the disease.     

Association between peroxisome proliferator-activated receptor-γ gene polymorphism (Pro12Ala) and Helicobacter pylori infection in gastric carcinogenesis

Abstract

Objective. Helicobacter pylori infection is accompanied by inflammatory processes leading to peptic ulcer and gastric cancer in the minority of infected individuals. The interaction between H. pylori virulence factors, host defense mechanisms and environmental factors determine the outcome of clinical manifestations. One of the host factors involved in the processes of inflammation and carcinogenesis is the peroxisome proliferator-activated receptor-γ (PPAR-γ) molecule. The present case–control study aimed to determine polymorphism of PPAR-γ gene and its association with H. pylori infection and gastrointestinal diseases (peptic ulcer and non-cardia gastric cancer) in Iranian patients. Materials and methods. One hundred and fifty-five patients with upper gastrointestinal diseases (76 peptic ulcer and 79 non-cardia gastric cancer) and 152 matched controls were genotyped for PPAR-γ gene polymorphism (Pro12Ala) by the PCR–RFLP method. Infection with H. pylori was confirmed by histology, the rapid urease test (RUT) and ELISA assay (IgG anti-H. pylori). Results. The frequency of PPAR-γ G (Ala 12) allele was significantly higher in H. pylori positive patients with non-cardia gastric cancer than in controls (22.8% vs. 3.9%, p = 0.027; OR = 3.28; 95% CI = 1.21–8.89), But there was no significant difference without infection (p = 0.7). Moreover, the PPAR-γ polymorphism was not associated with peptic ulcer in the presence or absence of H. pylori infection. Conclusion. Our results indicated PPAR-γ G allele may be an important contributor to non-cardia gastric cancer in Iranian H. pylori infected patients.