[目的]探讨β-肾上腺素刺激前后左心室神经型一氧化氮合酶(nNOS)和内皮型一氧化氮合酶(eNOS)对超氧化物水平的调节作用.[方法]取年龄匹配(2～5个月)的eNOS基因敲除(eNOS-/-)和nNOS基因敲除(nNOS-/-)小鼠与年龄相匹配的野生型同胞(eNOS+/++或nNOS+/+)心肌组织,利用单管发光计通过发光素增强化学发光法测量心脏组织中肾上腺素(ISO,10,100 nmol/L)刺激前后超氧化物的生成量.[结果] nNOS-/-和nNOS+/+或eNOS-/-和eNOS+/+小鼠左心室心肌组织中的超氧化物含量闻差异无统计学意义(P＞0.05).给予ISO 100 nmol/L处理可显著增加nNOS-/-小鼠心肌组织超氧化物生成量(P=0.01),但nNOS+/+,eNOS-/-和eNOS+/+小鼠心肌组织中的超氧化物含量未见有明显变化(P＞0.05).用特异性nNOS抑制剂S-甲基-L-硫代瓜氨酸(SMTC,200 nmol/L)抑制nNOS可增加eNOS+/+小鼠心肌组织中的超氧化物含量,在SMTC处理的前提下ISO (100 nmol/L)并未增加nNOS-/-小鼠心肌组织产生超氧化物.[结论] nNOS是调节心肌超氧化物水平的主要一氧化氮合成酶,nNOS的活性可抑制β-肾上腺素刺激下心肌组织生成超氧化物.

目的 研究我国白血病合并结核病的患病率、病死率、临床表现和治疗效果,为今后白血病合并结核病的早期诊断及有效治疗提供依据.方法 以“白血病”“结核”“化疗”以及“leukemia”“tuberculosis”“chemotherapy”为检索词,在中国知网、重庆维普数据库、万方电子期刊数据库以及Pubmed数据库检索,时间截止到2018年7月.结果 符合白血病合并结核病纳入标准的病例共229例,其中肺结核200例,肺外结核29例;急性淋巴细胞白血病64例,急性髓系白血病151例,慢性淋巴细胞白血病4例,慢性髓系白血病10例.男女比例为1.2∶1,平均年龄为43.9岁.临床特点:229例病例中204例(89.1％)以发热为首要临床表现,120例(52.4％)表现为持续高热,表现为低热、盗汗、消瘦的分别有13例(5.7％)、30例(13.1％)、36例(15.7％);184例(80.3％)结核病例通过影像学检查确诊,109例(47.6％)结核菌素(PPD)试验阳性,98例(42.8％)诊断性抗结核治疗有效,24例(10.5％)痰结核菌检查阳性,18例(7.9％)病理活检阳性,3例T细胞斑点(T-spot)试验阳性,2例支气管镜冲洗液涂片阳性,1例结核杆菌PCR测定阳性.135例行抗结核治疗,其中107例治疗有效,有效率79.3％.6例因结核病死亡,归因病死率为2.6％(6/229).结论 白血病患者合并结核病概率较普通人群高,早期临床表现和体征不典型,多方面寻找结核感染证据、早期诊断和规范治疗是降低其病死率的关键.

<span id="ChDivSummary" name="ChDivSummary" class="abstract-text">目的探讨线粒体凋亡通路在棕榈酸诱导的人脐静脉血管内皮细胞（human umbilical vein endothelial cells,HUVECs）凋亡中的作用。方法不同浓度棕榈酸(0.1、0.2、0.4、0.8 mmol·L^-1)作用HUVECs（0、12、24、48 h）,MTT法检测HUVECs增殖能力;免疫荧光法检测HUVECs细胞内活性氧（reactive oxygen species,ROS）的表达水平;免疫印迹法检测HUVECs中AIF、Cyt-C、cleaved caspase-3、Bcl-2、Bax等线粒体凋亡通路蛋白的表达水平;TUNEL法检测细胞内凋亡水平。结果 0.4 mmol·L^-1棕榈酸作用HUVECs 24 h时,细胞增殖率明显降低;AIF、Cyt-C、cleaved caspase-3、Bax/Bcl-2的水平明显升高（P&lt;0.05）,细胞凋亡水平明显增高（P&lt;0.05）;线粒体通透性抑制剂环孢素A （ciclosporine A, CsA）预处理组HUVECs凋亡水平明显下调（P&lt;0.05）。结论棕榈酸所致血管内皮细胞损伤的发病机制可能与线粒体凋亡相关通路密切关联,此研究对脂毒性心肌损伤的防治有重要意义。</span>

冠状动脉粥样硬化性斑块破裂和冠状动脉内血栓形成是急性心肌梗死(AMI)发病的主要病理生理基础[1,3],而炎症反应及氧化应激损伤在急性冠状动脉内血栓形成过程中起关键作用[4-6].炎症是部分心血管疾病及其并发症诊断与治疗的核心,寻求相关特异性炎症因子进行检测,以诊断AMI患者冠状动脉病变严重程度是目前心血管领域研究的热点.研究结果显示,炎症标志物如白细胞介素(IL)-10、转化生长因子(TGF-β)、超敏C反应蛋白(CRP)、血清淀粉样蛋白A(SAA)、血管内皮细胞生长因子(VEGF)及一氧化氮(NO)水平的升高程度可预示一系列心血管疾病的发生,同时心血管疾病亦可导致炎症因子表达水平发生改变.本研究就上述6种炎症因子在AMI的相关病理学中的表达及影响研究进展进行了综述.

Objective To detect the single nucleotide polymorphism (SNP) at locus 1 165 of β1-adrenoceptor (β1-AR) and to investigate the association between the SNP and the infection by enterovirus A71 (EV-A71).Methods Polymerase chain reaction (PCR) amplification technique was used to detect the SNP at locus 1 165 of β1-AR between hand,foot and mouth disease (HFMD) and healthy controls by sanger sequencing method.Results There was a G1165C SNP and three kinds of genotypes (GG,GC,CC) in β1-AR gene in the 77 cases of EV-A71 HFMD patients and 66 cases of healthy controls.For HFMD patients,frequencies of GG,GC and CC genotypes of the G1165C locus were 10％,47％ and 43％,respectively,and alleles frequency of G and C were 34％ and 66％,respectively.But in healthy children,GG,GC,CC genotype frequencies were 7％,41％ and 52％,respectively,and G and C allele frequencies were 28％ and 72％ respectively.Chi-square analysis showed that there were no significant differences in distribution of genotypes (x2 =1.154,df=2,P =0.562) and alleles frequency (x2 =1.091,df=2,P =0.296) between the EV-A71-infected group and the healthy control group.Between mild and severe EV-A71-infected group,there were no significant differences in distribution of genotypes (x2 =3.945,df =2,P =0.139) and alleles frequency (x2 =3.763,df =2,P =0.052).Conclusions The 1 165 SNP in the coding region of β1-AR was not associated with EV-A71 infection and its severity.

Objective To research the diagnostic value of serum neuron specific enolase (NSE) and catecholamine (CA) levels to severe hand foot mouth disease (HFMD) in children,and to provide reference for clinical evaluation of HFMD severity.Methods Totally 110 HFMD childen hospitalized in the Maternal and Child Health Care Hospital of Hainan Province from January 2014 to December 2015 were enrolled in this study.According to the Guide for the Diagnosis and Treatment of HFMD established in 2010 by the ministry of health,110 HFMD children were divided into mild group (44 cases),severe severe group (44 cases) and critical severe group (22 cases).The levels of NSE and CA were tested and compared among three groups.And the relationship between the levels of NSE,CA and the severity of HFMD was analyzed.Results 1)The levels of NSE and epinephrine(E),dopaminel (NE) in severe group were significantly higher than those in the mild group (P＜0.05).2) The levels of NSE and E,NE,DA in critical severe group were significantly higher than those in the severe severe group (P＜0.05).3)The levels of NSE,E,NE,DA levels were positively related to the severity of HFMD (r=0.366,0.590,0.425,0.345,all P＜0.05).Conclusion The levels of NSE and NE would increase with the disease progressing.And the levels of NSE and NE can be used as a reference indicator to assess the severity of HFMD.

系统性红斑狼疮(SLE)是一种能够影响全身器官的自身免疫性疾病,其对抗细胞及组织的异常免疫反应促进了疾病的发展,导致炎症及组织损伤.SLE临床表现复杂,容易反复,预后较差.尽管目前已有不少关于SLE病理生理学的研究,但是其确切的分子机制仍不清楚.近年来有许多关于SLE的表观遗传学机制研究深入分析了SLE的发病机制,且对SEE的早期诊断与治疗提出了新方向.本文就SLE表观遗传学机制的研究进展作一综述,以期为SLE相关研究提供理论依据.

尽管近期心力衰竭在治疗上取得了进步,但心力衰竭仍是导致死亡和发病的主要原因.心力衰竭的特点是心肌能量物质代谢的变化,并且与衰竭的心脏能量缺陷有关.以前的调查显示,从线粒体氧化作用到糖酵解转变以及糖酵解和葡萄糖氧化之间的解耦联作用,均是导致心力衰竭时心脏低效率和功能障碍的主要作用.因此,通过线粒体葡萄糖氧化作用提高能量底物的利用率可能是通过改善心脏的机械做功来降低心衰严重程度的潜在的且可行的方法.一种促进心肌葡萄糖氧化作用的方法是抑制脂肪酸氧化作用.我们将主要概述有关脂肪酸吸收、脂肪酸氧化、脂肪酸氧化转录调节和葡萄糖氧化等靶向酶的药物干预去治疗心力衰竭.

磷酸二酯酶(PDE)是调节环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)活性的重要酶,PDE属于超家族酶系,至少包括11个家族22个亚型,每个家族参与不同的信号传导,是细胞内外信息传递和功能调节的重要环节.PDE3是cAMP的环磷腺苷的水解酶,PDE3抑制剂具有正性肌力、舒张血管、抗血栓及抗增殖作用,是许多药物治疗的新的靶点.本研究就PDE3抑制剂的临床应用研究进展进行了综述.

Aim To explore the role of endoplasmic reticulum stress(ERS)signaling pathway in high fat-induced cell apoptosis in human umbilical vein endo-thelial cells(HUVECs). Methods HUVECs were ex-posed to different concentrations of palmitic acid(0. 1, 0. 2,0. 4,0. 8 mmol·L - 1 )for 24 h and different time points of 0. 4 mmol·L - 1 palmitic acid(0,12, 24,48 h). Cell viability was measured by cell count-ing kit(CCK-8),and the protein expressions of ERS signaling pathway protein such as GRP78,CHOP, PERK,IRE1,ATF6 were determined by Western blot. The level of intracellular apoptosis was detected by immunofluorescence. Results HUVECs exposed to palmitic acid at 0. 4 mmol·L - 1 for 24 h showed a de-crease in their viability and an increase in the expres-sion of ERS signaling pathway proteins (GRP78, CHOP,PERK,IRE1,ATF6)(P < 0. 05);cell ap-optotic levels significantly increased(P < 0. 05). The intracellular apoptosis levels in the vascular endothelial cells of ERS signaling pathway inhibitor 4-phenylbutyr-ic acid (4-PBA,10 mmol · L - 1 )were significantly lower than those of the PA group(P < 0. 05). Conclu-sion Activated ERS signaling pathway might play an important role in the treatment of high fat-induced cell apoptosis in vascular endothelial cells.

Enterovirus 71 (EV71) has a high degree of nerve absorption and which is an important neurotoxic pathogen causing severe hand,foot and mouth disease and central nervous system(CNS) diseases.EV71 infection is at a high incidence in Asia Pacific region.The CNS damage caused by EV71 mainly includes aseptic meningitis,encephalitis,brain stem encephalitis,acute flaccid paralysis,etc,which has a high mortality and poor prognosis,while its injury mechanism is not clear.Now,EV71 related etiology,epidemiology,pathogenesis of CNS damage caused by EV71 infection and EV71 vaccine research progress were summarized,in order to provide theoretical basis for EV71 related studies.

[目的]探讨运动训练对高血压模型大鼠心脏功能的影响.[方法]取健康雄性SD大鼠,随机分为非运动对照组(Sham)、运动组(Sham-ET)、高血压组(Ang-HT)和高血压运动组(Ang-ET).利用血管紧张素Ⅱ诱导建立大鼠高血压模型.采用多动物多通道尾袖套法无创血压系统监测大鼠血压值,心脏超声仪测定左心室射血分数(LVEF).分离心肌细胞,采用IonOptix单细胞收缩检测系统检测心肌细胞收缩性及肌丝钙敏感性.[结果]运动2周末(制作模型4周末)时,Ang-HT与Ang-ET组收缩压和舒张压间差异均有统计学意义(P＜0.05),Sham与Sham-ET组收缩压与舒张压间差异均无统计学意义(P＞0.05),Ang-HT与Ang-ET组LVEF及心肌细胞收缩性间差异均有统计学意义(P＜0.05),Ang-ET组EC50值较Ang-HT组明显缩短(P＜0.05).[结论]运动训练通过恢复心肌细胞肌丝钙离子敏感性而改善心肌细胞收缩性及心功能.

Objective: To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of beta 1 adrenergic receptor G1165C in children with enterovirus 71 (EV71) infection in hand foot and mouth disease (HFMD). Methods: The polymerase chain reaction (PCR) was used to detect the expression of gene polymorphism of (beta 1 adrenergic receptor G1165C in. vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay (ELISA). Results: The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD (P<0.05): however, the levels of plasma adrenalinein in two groups had no statistical differences (P>0.05); There was no significant difference in the distribution of beta 1 adrenergic receptor G1165C genotype and allele between EV71 infection group and healthy control group (P> 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well (p> 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group (P> 0.05). and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups (P> 0.05). Conclusions: As the disease gets worse, the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD. which is an important indicator to evaluate the progress of the disease. However, the gene polymorphism of beta 1 adrenergic receptor G1165C have no significant correlation, not only with the susceptibility and severity of EV71 infection in hand. foot and mouth disease, but also with the levels of catecholamine.

冠心病对人类健康和生命造成了严重的威胁.现除了以往研究的危险因素外,许多研究表明心里因素对冠心病的发病及预后产生重要影响.

目的 探讨外周血中长链酰基辅酶A合成酶(ACSL)1基因高表达是否可能作为急性心肌梗死风险评估的遗传标记及参与急性心肌梗死发病的可能机制.方法 在中国北方汉族人群中,选取急性心肌梗死病人75例为病例组,非冠心病者70例为对照组.详细记录每例研究对象的临床资料.分别采用实时荧光定量PCR及Western印迹检测ACSL1基因在mRNA水平及蛋白水平的表达.结果 在中国北方汉族人群中,急性心肌梗死病人外周血白细胞中ACSL1基因在mRNA 水平以及蛋白水平表达均增高;Logistic回归分析显示:ACSL1基因表达量增高是急性心肌梗死独立危险因素;ACSL1基因的表达量越高,冠状动脉粥样硬化病变程度越重.急性心肌梗死组空腹血糖、总胆固醇、甘油三酯及低密度脂蛋白水平均高于对照组,高密度脂蛋白低于对照组.结论 ACSL1基因在急性心肌梗死病人外周血白细胞中表达显著增高;ACSL1基因表达量增高是急性心肌梗死独立危险因素;外周血中ACSL1的高表达可能作为急性心肌梗死风险评估的分子标记.

急性脊髓炎(acute myelitis,AM)的病因及发病机制尚不清楚,目前多认为是感染或接种疫苗后诱发的一种自身免疫损伤.前驱感染以病毒较为多见,如麻疹病毒、风疹病毒、腮腺炎病毒等,其他病原菌感染导致急性脊髓炎较为少见.检索国内外文献,不乏病毒感染致急性脊髓炎的病例报告,但急性链球菌(Streptococcus, SPP)感染致急性脊髓炎的病例报告罕见.海南省妇幼保健院(海南省儿童医院)重症医学科收治链球菌感染致急性脊髓炎1例患儿.本报道旨在提高临床医师对急性脊髓炎病因及发病机制的认识.

Objective To investigate the changes and roles of nNOS in the plasma of patients with chronic heart failure (CHF).Methods 234 consecutive patients with decomposition CHF who were admitted to Yanbian University Hospital from November 2015 to April 2016 were enrolled.According to the left ventricular ejection fraction(LVEF) values,the patients were divided into 3 groups:group A(EF:20％-29％),group B(EF:30％-49％),group C (EF:≥ 50％).In addition,nNOS concentration was compared between the quinquagenarian group and the elderly group.Results (1)The nNOS concentration of plasma in three groups were statistically significant [(87.7±6.6)U/L vs (178.0± 11.5)U/L vs (142.6±8.8)U/L,P＜0.05],among them,plasma nNOS levels in group A were significantly lower than those in group B[(87.7±6.6)U/L vs (178.0±11.5)U/L,P＜0.01];plasma nNOS levels in group C were lower than those in group B[(178.0±11.5)U/L vs (142.6±8.8)U/L,P＜0.05];plasma nNOS levels in group A were lower than those in group C[(87.7±6.6)U/L vs (142.6±8.8)U/L,P＜0.05].(2)There were significant difference in E peak among the three groups[(0.7±0.05)m/s vs (0.9±0.03)m/s vs (0.8±0.03)m/s,P＜0.05],among them,the value of E peak in group A was lower than that in group B[(0.7±0.05)m/s vs (0.9±0.03)m/s,P＜0.05];the value of E peak in group C was lower than that in group B[(0.8±0.03)m/s vs (0.9±0.03)m/s,P＜0.05];the value of E peak in group A was lower than that in group C [(0.7±0.05)m/s vs (0.8 ±0.03)m/s,P＜0.05].(3)Comparison the nNOS concentration of plasma with between the quinquagenarian group and the elderly group.There was no significant difference (P＞0.05).(4)The nNOS concentration of plasma was positively correlated with ACEI,ARB,digoxin and β-blocker.Conclusion The increase of nNOS in patients with heart failure is to protect the cardiac function through the regulation of E peak.

Aim To explore the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in high fat-induced oxidative stress injury in human umbilical vein endothelial cells (HUVECs).Methods HUVECs were exposed to different concentrations of palmitic acid(0.1,0.2,0.4,0.8 mmol · L-1) for 24 h and different time points of 0.4 mmol · L-1 palmitic acid(0,12,24,48 h).Cell viability was measured by Cell Counting Kit 8,and the protein expression of NADPH oxidase subunits such as p22phox,p47phox,p67phox and gp91phox were determined by Western blot.The expression of reactive oxygen species (ROS) in HUVECs was detected by immunofluorescence.Results Cell proliferation rate of HUVECs stimulated by 0.4 mmol · L-1 palmitic acid for 24 h and 48 h was significantly reduced.In the next experiment,model group was accordingly set as HUVECs stimulated by 0.4 mmol · L-1 palmitic acid for 24 h.The expression of NADPH oxidase subunits such as p22phox,p47phox,p67phox and gp91phox significantly increased at 24 h and 48 h after 0.4 mmol· L-1 palmitic acid stimulation (P ＜ 0.05),and the difference.between the 24 h group and the 48 h group was not significant (P ＞ 0.05).The expression of ROS in HUVECs significantly increased at 24 h and 48 h after O.4 mmol · L-1 palmitic acid stimulation (P ＜ 0.05),and the difference between 24 h group and 48 h group was not significant (P ＜ 0.05).Compared with the model group (0.4 mmol · L-1 palmitic acid stimulation for 24 h),the NADPH oxidase inhibitor diphenyliodonium (DPI,10 μmol · L-1) pretreatment could significantly decrease the expression of ROS in vascular endothelial cells (P ＜ 0.05).Conclusion Activated NADPH oxidase might play an important role in treatment of high fat-induced oxidative stress injury in vascular endothelial cells.

20世纪70年代末期,一氧化氮(Nitric oxide,NO)被认定为一种涉及广泛生物学功能的信号分子[1-3].这一发现使Robert F.Furchgott、 Louis J.Ignarro和FeridMurad在1998年获得了诺贝尔生理学或医学奖.现在已经证实,产生NO的酶,即一氧化氮合酶(NOS)包括三种亚型:神经型一氧化氮合酶(nNOS或NOS1)、诱导型一氧化氮合酶(iNOS或NOS2)和内皮型一氧化氮合酶(eNOS或NOS3).一直以来,eNOS被认定是在心肌中NOS的唯一亚型.它在心脏中的多种功能调控也得到了证实[4,5].