自噬在急性心肌梗死发病中作用的研究进展

自噬是生物细胞内普遍存在且高度保守的一种生理过程,其通过溶酶体融合降解细胞内的大分子组分、受损的细胞器以及侵入胞内的病原菌,以达到维持细胞稳态的目的。自噬在多种疾病的发生发展中也发挥十分重要的作用,尤其是心血管疾病。自噬对其病程的发展可以发挥两种截然不同的作用。适当的自噬作用可以降低炎症反应和氧化应激促进细胞的存活,以及通过减少泡沫细胞的形成而对维持心血管的正常功能起一个保护作用;但过度的自噬作用会对细胞造成不可逆的损伤,诱导细胞发生不依赖于caspase的自噬性细胞死亡,增加局部的炎症反应,从而促进动脉粥样硬化病变的发展。本文就自噬在急性心肌梗死发生发展中作用的研究进展进行了综述,探讨自噬成为预防及治疗心血管疾病新靶标的可能性。     

线粒体自噬在宫颈癌中作用的研究进展

摘要：宫颈癌的发病与高危型人乳头瘤病毒（human papillomavirus, HPV）的持续感染密切相关。线粒体自噬（mitophagy）作为一种细胞质量控制机制,可以选择性地清除功能失调或多余的线粒体,其功能异常与肿瘤发生发展密切相关。近年研究发现,线粒体自噬在宫颈癌中呈现双重调控作用：一方面,适度线粒体自噬可通过清除功能失调的线粒体,维持细胞能量稳态并抑制活性氧（reactive oxygen species, ROS）积累,从而延缓宫颈癌进展;另一方面,过度激活的线粒体自噬可能通过促进肿瘤细胞在缺氧或营养缺乏环境中的存活,增强其侵袭和转移能力。分子机制上,PINK1/Parkin通路是宫颈癌中线粒体自噬的主要调控途径。HPV致癌蛋白E6/E7可通过干扰PINK1/Parkin信号,导致线粒体自噬失调,进而促进宫颈癌细胞增殖。BCL2 相互作用蛋白3（BNIP3）、FUNDC1（FUN14 domain containing 1）等受体介导的线粒体自噬也在宫颈癌转移中发挥重要作用。此外,线粒体自噬直接参与免疫细胞的发育和分化,并直接调节线粒体抗原呈递和免疫细胞稳态。基于HPV相关抗原提供免疫识别靶点以及程序性细胞死亡受体配体 1（PD-L1）/程序性细胞死亡受体1（PD-1）等免疫检查点介导免疫逃逸等的研究,为宫颈癌的免疫治疗提供了更多选择。本文旨在综述线粒体自噬在宫颈癌中作用的研究进展,为开发新型联合治疗策略提供依据。     

综述:老年性痴呆早期的基因变异研究进展

阿尔茨海默病( Alzheimer's disease,AD)又称老年性痴呆,是老年人常见的神经系统变性疾病．AD包括痴呆前阶段和痴呆阶段,年龄老化与遗传因素为目前公认的发病因素．AD的病理生理过程在痴呆诊断前的5～10年就已开始了,这一漫长的AD痴呆前阶段是治疗干预的关键时期,因此目前痴呆前阶段已成为AD相关研究的热点．本文综述了近年来有关AD各主要阶段基因变异的研究进展．     

硫酸软骨素在癌症治疗领域的研究进展

硫酸软骨素是一种硫酸化的糖胺聚糖,其在恶性肿瘤组织中的含量、结构、硫酸化位点等与正常组织存在显著差异,在癌症的迁移,侵袭,血管生成过程中发挥重要调控作用,在癌症的临床研究中具有很大潜力。该文对硫酸软骨素的生物合成进行归类分析,对近几年硫酸软骨素与肿瘤入侵和转移的相关临床研究以及分子机制研究做出综述,以期为开发硫酸软骨素潜在的临床价值和肿瘤治疗靶点研究提供理论依据,为恶性肿瘤的早期诊断和预后评估提供思路。     

程序性细胞死亡在肺炎支原体肺炎中的研究进展

肺炎支原体肺炎（MPP）是一种由肺炎支原体（MP）引起的呼吸系统疾病,其发病机制复杂且多样,涉及多种细胞死亡方式。近年研究显示,程序性细胞死亡（PCD）与MPP有关。PCD包括细胞凋亡、坏死性凋亡、细胞自噬、细胞焦亡、细胞外捕获网化、铁死亡和铜死亡等。因此,深入了解各种PCD机制及其与MMP的关系,分析PCD在MMP发生发展机制中的作用具有重要意义。本文章旨在阐明PCD在MPP研究中的最新进展,分析PCD在疾病进程中的具体作用,并探讨它们作为潜在治疗靶点的可能性。以期为优化MPP的诊断和治疗提供理论基础和实践方向,同时也可为新靶点药物的研发指明方向。     

血小板输注无效与血小板抗原(HPA)多态性的相关性

目的:探讨血小板输注无效(PTR)与血小板抗原(HPA)多态性的相关性.方法:2017年5月到2018年9月选择在首都医科大学附属北京同仁医院输血科进行血小板输注的患者187例,检测所有患者血液的HPA多态性,判断PTR发生情况并进行相关性分析.结果:在187例患者中,发生PTR 32例,发生率为17.1％.PTR患者...     

综述: 癌症免疫治疗临床新进展

肿瘤免疫治疗是一种利用患者自身免疫系统实现抗肿瘤作用的治疗方式,现已成为对抗肿瘤的新型有效疗法．然而,抑制性肿瘤微环境的存在可使肿瘤免疫治疗的效果大打折扣．本文将以肿瘤微环境的组成、分类及其对治疗效果的影响为出发点,探讨通过放化疗、免疫检查点、基因修饰免疫细胞以及多种联合治疗等方式应对抑制性肿瘤微环境,使免疫治疗发挥最大疗效．     

出血性卒中与MTHFR C677T基因多态性的相关性研究

摘要 目的：探讨与分析出血性卒中与亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性的相关性。方法：2020年2月到2021年4月选择在本地区诊治的H型高血压患者220例作为研究对象,检测所有患者的MTHFR C677T基因多态性状况,检测血清同型半胱氨酸、叶酸、维生素B12含量。随访判定患者的出血性卒中状况并进行相关性分析。结果：随访调查1年,220例患者中出现出血性卒中20例（出血性卒中组）,占比9.1 %。出血性卒中组的血清同型半胱氨酸含量明显高于非出血性卒中组,血清维生素B12、叶酸明显低于非出血性卒中组（P<0.05）。两组的MTHFR C677T基因型分布均符合Hardy-Weinberg遗传平衡,出血性卒中组的TT基因型、等位基因T占比分别为70.0 %、80.0 %,都显著高于非出血性卒中组的24.0 %、35.0 %（P<0.05）。Spearman相关系数分析显示H型高血压患者的血清同型半胱氨酸、叶酸、维生素B12含量、TT基因型、等位基因T都与出血性卒中存在相关性（P<0.05）。多元回归分析显示血清同型半胱氨酸、叶酸、维生素B12含量、TT基因型、等位基因T都为导致H型高血压患者出血性卒中发生的重要因素（P<0.05）。结论：H型高血压在随访过程中容易发生出血性卒中,也伴随有血清同型半胱氨酸、维生素B12、叶酸含量异常,MTHFR C677T的T基因型、等位基因T与出血性卒中存在相关性,也是导致出血性卒中发生的重要危险因素。     

白血病融合基因EVI1的多态性与白血病发生风险的相关性

目的:探讨白血病融合基因亲嗜性病毒整合位点1(ecotropic viral integration site-1,EVI1)的多态性与白血病发生风险的相关性。方法:选取本院2017年2月～2019年2月收治的骨刺患儿90例作为研究组,同期选择健康人群83例作为对照组。清晨空腹抽取两组入选者的外周静脉血2 mL,采用PCR方法检测两组入选者EVI1的多态性情况,调查一般资料并进行相关性分析。结果:EVI1 rs17561基因共有CC、CA、AA三种基因型,两组入选者的EVI1 rs17561基因分布均符合Hardy-Weinberg平衡定律,研究对象具有群体代表性。两组入选者EVI1 rs17561基因型分布差异具有统计学意义(P0.05),研究组的EVI1 rs17561基因CC基因型显著高于对照组(90.0%vs. 75.9%, P0.05),研究组的等位基因C频率(显著高于对照组(96.7%vs. 80.7%, P0.05)。在90例骨刺患儿中,6例患儿确诊为白血病,检出率为6.7%,均为CC基因型。研究组患儿EVI1 rs17561基因的CC基因型与血小板计数、危险度分层、诊断分型显著相关(P0.05)。多元Logistic回归分析显示血小板计数、危险度分层、诊断分型为影响EVI1rs17561CC基因型的主要因素(P0.05)。结论:白血病患儿融合基因EVI1多态性比较常见,多表现为rs17561CC等位基因,此等位基因可能与白血病患者的血小板计数、危险度分层、诊断分型显著相关,其中血小板计数、危险度分层、诊断分型为影响EVI1rs17561CC基因型的主要因素。     

邻苯二甲酸二丁酯降低雄激素浓度导致尿道下裂发生机制研究

目的:验证邻苯二甲酸二丁酯(DBP)是通过降低血清雄激素水平导致自噬异常激活,同时探讨DBP致子代大鼠尿道下裂发生的具体机制。方法:将孕鼠随机分为DBP染毒组与对照组,并于妊娠期14-18天通过灌胃的方式,分别用DBP(750 mg/kg/天)饲养DBP染毒,用等量花生油饲养对照组。依照此方法成功构建了子代新生大鼠尿道下裂模型。采集子鼠生殖结节(GT)用福尔马林保存,用免疫组织化学(IHC)染色观察生殖结节组织中自噬水平,即LC3B及Beclin1表达水平;在子鼠麻醉后采集血液标本,用放射免疫分析方法观测子鼠血清睾酮水平。在原代大鼠尿路上皮细胞(PUECs)基础上,用Western印迹方法检测有无双氢睾酮(DHT)对PUECs中LC3I、LC3II及Beclin1表达水平影响。结果:DBP染毒组尿道下裂发生率为42.3%,对照组子代无尿道下裂。DBP染毒组子代GT组织中自噬表达较对照组明显增加。DBP染毒组(n=10)较对照组中血清睾酮水平有明显差异(n=10)(P<0.05)。体外研究表明DHT缺乏组Beclin1及LC3蛋白转化率水平较对照组升高。结论:孕期暴露于DBP可以诱发子代尿道下裂发生,这可能是由于DBP降低子鼠雄激素水平促使自噬发生导致的,然而该疾病的机制仍需要进一步研究。     

Nicotine and apoptosis

Cigarette smoking is associated with a plethora of different diseases. Nicotine is the addictive component of cigarette but also acts onto cells of the non-neuronal system, including immune effector cells. Although nicotine itself is usually not referred to as a carcinogen, there is ongoing debate whether nicotine functions as a ‘tumor enhancer.' By binding to nicotinic acetylcholine receptors, nicotine deregulates essential biological processes like angiogenesis, apoptosis, and cell-mediated immunity. Apoptosis plays critical roles in a wide variety of physiologic processes during fetal development and in adult tissue and is also a fundamental aspect of the biology of malignant diseases. This review provides an overlook how nicotine influences apoptotic processes and is thus directly involved in the etiology of pathological conditions like cancer and obstructive diseases.     

When there’s smoke there’s.....CCN2

There is no treatment for fibrotic disease is a significant cause of mortality. CCN2 Members of the CCN family of matricellular proteins have a characteristic four domain structure. CCN2 (connective tissue growth factor) is believed to play an essential role in fibrogenesis. In a recent paper, data are provided that CCN5 (wisp2), which lacks the carboxy-terminal heparin-binding domain shared by the other CCN proteins, may act as a dominant-negative protein to suppress CCN2-mediated fibrogenesis. These data are consistent with the notion that different CCN proteins may enhance or suppress each other’s action and also suggest that CCN5, may be used as a novel anti-fibrotic therapy.     

Rational design of novel CYP2A6 inhibitors

Inhibition of CYP2A6-mediated nicotine metabolism can reduce cigarette smoking. We sought potent and selective CYP2A6 inhibitors to be used as leads for drugs useful in smoking reduction therapy, by evaluating CYP2A6 inhibitory effect of novel formyl, alkyl amine or carbonitrile substituted aromatic core structures. The most potent CYP2A6 inhibitors were thienopyridine-2-carbaldehyde, benzothienophene-3-ylmethanamine, benzofuran-5-carbaldehyde and indole-5-carbaldehyde, with IC₅₀ values below 0.5 μM for coumarin 7-hydroxylation. Nicotine oxidation was effectively inhibited in vitro by two alkyl amine compounds and benzofuran-5-carbonitrile. Some of these molecules could serve as potential lead molecules when designing CYP2A6 inhibitory drugs for smoking reduction therapy.     

Measurement of nicotine in hair by reversed-phase high-performance liquid chromatography with electrochemical detection

We have developed an assay for nicotine in hair based on reversed-phase HPLC with electrochemical detection. The method uses a low-metal, high-purity silica reversed-phase column. We have investigated the washing, digestion and extraction procedures and discuss the important points in the HPLC method development. The assay is presented as an application in a population of exposed and non-exposed children. Analytical parameters are satisfactory with linearity, recoveries, limit of quantitation and precision all suitable for epidemiological studies involving environmental tobacco smoke exposure assessment.     

Nicotine monitoring in sweat with a sweat patch

In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional samples, such as sweat. In a study conducted with cigarettes smokers and nonsmokers, PharmChek sweat patches were applied to 29 subjects for 72 h. Nicotine was extracted in 5 ml methanol in the presence of 200 ng nicotine-d₄, used as internal standard. After 20 min agitation, the methanolic solution was evaporated to dryness in the presence of 10 μl octanol to ensure nonvolatility of nicotine. Nicotine was determined using gas chromatography coupled to mass spectrometry after separation on a 30-m capillary HP5 MS column. The assay was linear in the range 50–2500 ng/patch, with an extraction recovery of 76±5%. Limit of detection was 10 ng/patch. Nicotine concentrations in sweat were not detected for the nonexposed nonsmokers (n=8), 87 to 266 ng/patch for the passive smokers (n=6) and 150 to 2498 ng/patch for the smokers (n=15). This study demonstrated a useful application of the sweat patch for monitoring tobacco exposure.     

Rapid solid-phase extraction method for automated gas chromatographic–mass spectrometric determination of nicotine in plasma

The aim of this study was to develop a simple, rapid and sensitive assay of nicotine in plasma for automated gas chromatographic–mass spectrometric analysis. Biological samples were extracted using pre-packed Extrelut-1 columns with 5 ml of ethyl acetate. Quantitative analysis was done using deuterium-labelled nicotine as internal standard. The limit of quantitation was 0.5 ng in 1-ml plasma samples. Precision was ranging from 13.3% to 1.64% (R.S.D.) depending on the concentration, while the deviation was 4.16%. This method has been used for determination of nicotine bioavailability from new, low-dosage, nicotine chewing gum strips.