类风湿性关节炎患者下丘脑-垂体-肾上腺轴功能检测及其意义

IL－1、IL－2、IL－3、IL－6、TNF等细胞因子和前列腺素等炎症介质刺激下丘脑分泌促肾上腺皮质激素释放激素（CRH），CRH又可刺激垂体分泌促肾上腺皮质激素（ACTH）和肾上腺分泌皮质类固醇激素，后者抑制炎症和免疫应答，这样就组成一个免疫系统－下丘脑－垂体－肾上腺轴（HPA）的反馈环路。这个环路在RA的发病机制中起重要作用。本文对RA患者HPA功能状况的研究现状作了简要介绍。     

脂联素对脓毒症大鼠白细胞介素-6/信号转导及转录激活因子3通路的影响

目的 研究脂联素（APN）对脓毒症大鼠肺组织白细胞介素-6（IL-6）/信号转导及转录激活因子3（STAT3）通路的影响.方法 盲肠结扎穿孔（CLP）法制作脓毒症动物模型,雄性Wistar大鼠120只,10～ 14周龄,体重250～ 300 g,随机分为对照组（C组）、脓毒症模型组（CLP组）和脂联素预处理组（APN组）,分别于术后2h、6h、12 h、24h、48 h处死,采用酶联免疫吸附法（ELISA）检测肺组织匀浆中IL-6表达水平,半定量逆转录聚合酶链反应（RT-PCR）法检测肺组织匀浆中IL-6 mRNA的表达水平;凝胶阻滞电泳分析技术（EMSA）检测肺组织STAT3的DNA结合活性;同时检测肺组织髓过氧化物酶（MPO）活性;各组剩余10只大鼠观察术后7d的生存率,并绘制生存曲线.结果 与C组比较,CLP组大鼠肺组织IL-6 mRNA及蛋白表达水平升高,STAT3的DNA结合活性表达升高,肺组织匀浆中MPO活性显著升高,死亡率升高（P均＜0.05）;与CLP组比较,APN组大鼠肺组织IL-6 mRNA及蛋白表达水平下降,STAT3的DNA结合活性表达降低,肺组织匀浆中MPO活性显著下降,死亡率明显降低（P均＜0.05）.结论 脂联素可能通过抑制IL-6/STAT3信号转导通路,从而减轻脓毒症性肺损伤.     

基于STAT3信号通路探讨艾司洛尔对脓毒症大鼠急性肝损伤的保护作用

目的探讨艾司洛尔(ES)对脓毒症大鼠急性肝损伤的保护作用及相关信号通路。方法48只雄性SPF级大鼠随机分为假手术(Sham)组、盲肠结扎穿孔(CLP+NS)组和艾司洛尔干预(CLP+ES)组(每组16只)。Sham组采用盲肠探查术,CLP+NS组、CLP+ES组采用CLP法建立脓毒症大鼠模型。CLP+ES组经颈内静脉微量泵入ES稀释液6 h,Sham组和CLP+NS组给予等质量生理盐水。术后6 h、24 h各组分别处死8只大鼠。采用HE染色,观察脓毒症大鼠肝组织形态学变化,生化分析仪检测血清肝功能指标,酶联免疫吸附法(ELISA)检测肝组织中炎性细胞因子水平,Western blot检测肝组织中STAT3信号通路标志蛋白的表达。结果CLP+NS组脓毒症大鼠肝组织炎性细胞浸润明显,而CLP+ES组炎性细胞减少,肝细胞坏死程度好转。术后6 h、24 h,CLP+NS组血清天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)和肝组织匀浆中高迁移率族蛋白B-1(HMGB-1)、白细胞介素-6(IL-6)均升高(P<0.05);而CLP+ES组较CLP+NS组均降低(P<0.05)。术后6 h,与CLP+NS组比较,CLP+ES组脓毒症大鼠肝组织中磷酸化信号转导和转录激活因子3(p-STAT3)表达水平明显下降(P<0.05),细胞因子信号转导抑制因子3(SOCS3)表达明显上升(P<0.05)。术后24 h,CLP+ES组上述蛋白表达与CLP+NS组比较差异无统计学意义(P>0.05)。结论艾司洛尔通过抑制STAT3信号通路,抑制炎性细胞因子释放,从而发挥对脓毒症大鼠急性肝损伤的保护作用。     

有氧运动训练对大鼠下丘脑、垂体IL-1βmRNA、IL-6mRNA的影响

目的：研究长时间运动对老年机体下丘脑、垂体IL-1、IL-6的基因表达的影响。方法：将大鼠随机分为3组：青年安静组（A组）、老年安静对照组（B组）、老年运动训练组（C组）,运动组大鼠在水中进行90d渐进游泳训练,采用PT-PCR的方法检测各组大鼠下丘脑、垂体IL-1、IL-6的基因表达。结果：在下丘脑老年大鼠与青年鼠相比IL-1mRNA和IL-6mRNA表达量显著升高（P〈0.01）,在垂体水平老年大鼠IL-1βmRNA的水平明显高于青年大鼠（P〈0.01）,而IL-6mRNA变化不显著（P〉0.05）。通过3个月的游泳训练老年大鼠下丘脑IL-6mRNA、垂体IL-1βmRNA水平有所下降（P〈0.01）,下丘脑IL-1βmRNA、垂体IL-6mRNA的表达水平变化不显著（P〉0.05）。结论：随着老化机体脑组织中炎性细胞因子的基因表达水平明显升高,运动可以抑制老年大鼠下丘脑、垂体细胞因子的基因表达水平,降低老年期神经细胞对炎症的反应性,有利于下丘脑-垂体-肾上腺轴的正常作用。     

JAK/STAT通路介导脓毒症大鼠肝组织高迁移率族蛋白B1 mRNA表达的研究

目的：探讨Janusk激酶／信号转导和转录激活子（JAK／STAT）通路对盲肠结扎穿孔术（CLP）所致脓毒症大鼠肝组织高迁移率族蛋白B1（HMGB1）mRNA表达和急性肝损害的影响。方法：采用CLP模型，大鼠随机分为正常对照组、CLP脓毒症组、JAK2激酶抑制剂AG490和STAT抑制剂雷帕霉素（RPM）处理组。采用逆转录多聚酶链式反应测定肝HMGB1 mRNA，全自动生化分析仪测定肝功能指标。结果：与正常对照组相比，CLP后6－48h HMGB1 mRNA表达显著升高（P＜0．01）；血清天冬氨酸转氨酶（AST）在6－48h增高明显（P＜0．05），丙氨酸转氨酶（ALT）、AST在24h升高非常显著（P＜0．01）。与CLP组相比，AG490预处理组24h HMGB1 mRNA和ALT水平显著下降（P均＜0．01），24h和48h AST亦明显降低（P均＜0．01）；同样，RPM干预后HMGB1 mRNA表达在6h 和24h显著抑制（P＜0．05和P＜0．01），ALT、AST在24h和48h均不同程度下降（P＜0．01和P＜0．05）。结论：抑制JAK／STAT通路活化可明显下调肝组织HMGB1 mRNA表达，并有助于减轻CLP所致急性肝损伤。     

外源性一氧化碳释放分子对脓毒症大鼠肺组织高迁移率族蛋白B1表达的影响

目的 研究外源性一氧化碳释放分子（CORM-2）对脓毒症大鼠肺组织高迁移率族蛋白B1（HMGB1）表达的影响.方法 盲肠结扎穿孔（CLP）法制备脓毒症动物模型,150只雄性Wistar大鼠,随机分为对照组（C组）、脓毒症模型组（CLP组）和CORM-2组（n=50）,分别于术后6、12、24、48、72 h处死,采用酶联免疫吸附法（ELISA）检测肺组织匀浆中HMGB1表达水平,实时荧光定量聚合酶链反应（real-time PCR）法检测肺组织匀浆中HMGB1 mRNA的表达水平;凝胶阻滞电泳分析技术（EMSA）检测肺组织STAT3的DNA结合活性;同时检测肺组织丙二醛（MDA）含量和湿/干重比（W/D）;流式细胞仪测定细胞凋亡率.结果 与C组比较,CLP、CORM-2组大鼠肺组织HMGB1 mRNA及蛋白表达水平升高,STAT3的DNA结合活性表达升高,肺组织匀浆中MDA含量显著升高,细胞凋亡率和W/D升高;与CLP组比较,CORM-2组大鼠肺组织HMGB1 mRNA及蛋白表达水平下降,STAT3的DNA结合活性表达降低,肺组织匀浆中MDA含量显著下降,细胞凋亡率和W/D降低.结论 CORM-2能够下调肺组织HMGB1表达,减轻脓毒症性肺损伤.     

脓毒症早期大鼠下丘脑-垂体-肾上腺轴超微结构变化与功能的关系

目的 观察脓毒症早期下丘脑-垂体-肾上腺(HPA)轴结构及功能的变化,并探讨其相互关系.方法 雄性SD大鼠30只,按随机数字表法均分为正常对照组、假手术组和脓毒症组.采用盲肠结扎穿孔术(CLP)制作脓毒症大鼠模型,术后6 h取血并处死动物,检测血浆促肾上腺皮质激素(ACTH)、皮质酮(CoRT)以及下丘脑促肾上腺皮质激素释放激素(CRH)水平;透射电镜下观察HPA轴的超微结构改变.结果 脓毒症组血浆ACTH、CORT和下丘脑CRH水平均明显高于正常对照组和假手术组[ACTH(pmol/L):5.78±0.36比1.94±0.31、2.51±0.10;CORT(nmol/L):88.48±4.47比22.02±1.62、34.20±2.51,CRH(μg/L):101.92±6.61比61.65±6.05、66.65±4.03,P＜0.05或P＜0.01].透射电镜下观察:脓毒症组大鼠下丘脑粗面内质网囊状扩张、脱颗粒,高尔基体肿胀,垂体ACTH细胞分泌颗粒增多,肾上腺组织脂滴减少.结论 脓毒症早期大鼠HPA轴处于过度激活状态,血浆ACTH、CORT和下丘脑CRH水平明显升高;HPA轴的超微结构明显改变,且与功能变化有密切联系.

Abstract：

Objective To observe the changes in ultrastructure and function of hypothalamicpituitary-adrenal axis (HPAA), and to approach the relationship between them in early stage of sepsis in rats. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into normal control group,sham group, sepsis group. The sepsis model was reproduced by cecal ligation and puncture (CLP). The rats were sacrificed after collection of blood at 6 hours after CLP, and the levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in the plasma, and the corticotropin release hormone (CRH) in the tissue of hypothalamus were detected. The histopathological changes in HPAA were observed with transmission electron microscopy. Results The levels of ACTH and CORT in plasma, and the CRH in hypothalamus tissue of sepsis group were increased in the early stage of sepsis compared with the normal control group or sham group [ACTH (pmol/L): 5. 78 ± 0. 36 vs. 1.94 ±0.31, 2. 51 ± 0.10; CORT (nmol/L), 88.48±4.47 vs. 22.02±1.62, 34.20±2.51; CRH (μg/L): 101. 92±6. 61 vs. 61.65±6.05,66. 65±4. 03, P＜0. 05 or P＜0. 01]. The changes in ultrastructure of the hypothalamus, pituitary and adrenal were also found. In sepsis group, the ultrastructure of hypothalamus was as follows. Rough endoplasmic reticulum expansion and degranulation of rough endoplasmic reticulum, and swelling of Golgi complex were found. A large number of endocrine granules could be seen in ATCH cells in the pituitary with depletion of adrenal lipid droplets. Conclusion In septic rats, the HPAA was excessively activated, and ACTH and CORT in plasma, and CRH in hypothalamus were significantly increased in early stage of sepsis.The changes in ultrastructure of HPAA were obvious, and the change in function was closely related to the ultrastructural changes.     

腹腔感染性脓毒症可溶性髓样细胞触发受体(sTREM-1)与Janus激酶-信号转导和转录激活因子(JAK/STAT)通路的关系

目的 通过动物脓毒症模型探讨可溶性髓样细胞触发受体(sTREM-1)与Janus激酶-信号转导和转录激活因子(JAK/STAT)通路的关系.方法 采用盲肠结扎穿孔(CLP)法制作大鼠脓毒症模型,大鼠随机(随机数字法)分为正常对照组(n=6)、假手术组(n=24)、CLP组(n=48)、JAK 2抑制剂(AG 490)组(n=48)和STAT3抑制剂(雷帕霉素,RPM)组(n=48).留取外周血行流式细胞仪分析CD4+ CD25+ Treg细胞/CD4+T细胞比值.采用逆转录多聚酶链式反应(RT-PCR)测定肝组织sTREM-1 mRNA表达水平.结果 CLP后6h肝sTREM-1 mRNA表达即高于对照组和假手术组,且随时间变化逐渐升高.AG490组肝组织sTREM-1 mRNA的表达在术后6h、24 h(1.572±0.051,2.063±0.025)较同时间点CLP组(1.592±0.036,2.082±0.021)差异无统计学意义(P＜0.05),而在48 h和72 h AG490组肝组织sTREM-1 mRNA的表达(2.522±0.083,3.153±0.021)低于同时间点CLP组(2.592±0.055,3.204±0.013) (P＜0.05).术后6 h RPM组肝组织sTREM-1mRNA的表达(1.581±0.017)较CLP组差异无统计学意义(P＜0.05),而在术后24、48、72 h RPM组肝组织sTREM-1 mRNA的表达(1.486±0.019,1.263±0.011,1.115±0.022)显著低于同时间点CLP组肝组织sTREM-1 mRNA的表达(P＜0.05).结论 sTREM-1因子与JAK/STAT通路有关,阻断JAK/STAT通路能够抑制sTREM-1 mRNA的表达,减缓脓毒症炎症反应的进展.     

C5a反义肽对脓毒症小鼠心肌中性粒细胞浸润和P－选择素表达的影响

目的：探讨C5a反义肽对脓毒症小鼠心肌中性粒细胞（PMN）浸润的影响。方法盲肠结扎穿孔法（CLP）制备小鼠脓毒症模型,随机分为健康对照组、假手术组、脓毒症组和C5a反义肽治疗组四组。分别在2、4、8、12 h时间点观察心肌组织的病理改变,测心肌组织髓过氧化物酶（ MPO）活性,采用实时定量PCR和免疫印迹法分别检测心肌组织P－选择素mRNA和蛋白表达水平。结果 CLP造模4 h后,脓毒症组心肌病理可见心肌纤维结构疏松,局灶性肌溶解,胞质淡染,间质水肿,伴充血,细胞核肿胀等改变,C5a反义肽治疗组病变程度均较造模组轻;脓毒症组和C5a反义肽治疗组心肌组织MPO活性较对照组明显增高（P＜0．05）,C5a反义肽治疗组低于脓毒症组（P＜0.05）;P－选择素mRNA和蛋白表达量均明显增高（P＜0．05）,且随时间的增加而明显增加（P＜0．05）。与脓毒症组比较,C5a反义肽治疗组各时间点P－选择素mRNA和蛋白表达量明显下降（ P＜0．05）。结论 C5a反义肽可减少脓毒症小鼠心肌组织PMN浸润,C5a反义肽可能是通过减少P－选择素表达来减少PMN浸润的。     

调控骨桥蛋白介导的中性粒细胞浸润减轻脓毒症小鼠肺损伤的研究

目的探讨骨桥蛋白（OPN）中和抗体处理对脓毒症小鼠生存情况的影响及其加剧急性肺损伤的机制。 方法将80只雄性小鼠分成假手术组（Sham组）、脓毒症组[盲肠结扎穿孔术（CLP）组]、阴性对照组[CLP+免疫球蛋白G（IgG）组]及OPN中和抗体组（CLP+ OPN Ab组）,每组各20只。采用CLP制备脓毒症小鼠模型,Sham组除不结扎和穿刺盲肠外,其余手术步骤相同。建模成功即刻,CLP+ IgG组及CLP+ OPN Ab组小鼠分别经颈内静脉注射IgG和OPN单抗,Sham组和CLP组注射等量磷酸盐缓冲液。每组10只用于观察小鼠活动状态及术后7 d存活情况;另外10只分别于术后24 h采集眼眶血及收集肺组织用于OPN及髓过氧化物酶（MPO）检测。比较4组小鼠血清、肺组织OPN信使RNA（mRNA）水平和肺组织中OPN蛋白水平,外周血丙氨酸转氨酶（ALT）、天冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）、白细胞介素6（IL-6）、趋化因子配体2（CXCL-2）和MPO活性。 结果术后第7天,Sham组小鼠10只均存活;CLP组及CLP+ IgG组分别有2只存活,而CLP+ OPN Ab组仍有4只小鼠存活。4组小鼠7 d存活情况比较,差异有统计学意义（χ² = 17.374,P = 0.001）。且与Sham组相比,CLP组、CLP+ IgG组和CLP+ OPN Ab组小鼠存活情况均显著降低（P均< 0.05）;而CLP组、CLP+ IgG组和CLP+ OPN Ab组小鼠存活情况比较,差异均无统计学意义（P均> 0.05）。CLP术后24 h,4组小鼠血清、肺组织OPN mRNA水平和肺组织中OPN蛋白水平,外周血中ALT、AST、LDH、IL-6、CXCL-2、MPO活性比较,差异均有统计学意义（F = 84.227、51.929、41.563、19.558、55.416、75.968、32.824、176.945、119.046,P均< 0.05）。进一步两两比较发现,CLP组、CLP+ IgG组和CLP+ OPN Ab组小鼠血清、肺组织OPN mRNA水平和肺组织中OPN蛋白水平,外周血中ALT、AST、LDH、IL-6、CXCL-2、MPO活性均较Sham组显著增高,且CLP组和CLP+ IgG组更高（P均< 0.05）。 结论OPN单抗中和OPN可调控脓毒症小鼠肺内中性粒细胞浸润,减轻急性损伤,提示OPN可作为脓毒症急性肺损伤的治疗靶点。     

白细胞介素-6/糖蛋白130/转录激活因子3通路在百草枯诱导小鼠急性肺损伤中的作用机制

目的基于肺特异性白细胞介素-6(IL-6)敲除小鼠研究IL-6/糖蛋白130(gp130)/转录激活因子3(STAT3)通路在百草枯(PQ)诱导急性肺损伤(ALI)中的作用。方法野生型C57BL/6J小鼠分为IL-6野生型(IL-6 WT)组、IL-6 WT+PQ组,采用Sftpc(肺表面活性蛋白C基因)-Cre⁺小鼠与IL-6^FLOX/FLOX小鼠交配的方式得到肺特异性IL-6敲除小鼠并分为IL-6 KO组、IL-6 KO+PQ组,单次腹腔注射PQ诱导ALI,比较四组小鼠肺组织病理改变、肺泡动脉氧分压差(PA-aO₂)、肺组织湿/干质量比值(W/D)、IL-6/gp130/STAT3通路、核转录因子-κB(NF-κB) p65、肿瘤坏死因子-α(TNF-α)及白细胞介素-1β(IL-1β)的差异。结果与IL-6 WT组比较,IL-6 WT+PQ组小鼠肺组织出现了典型的ALI病理改变,肺组织胞浆蛋白中IL-6、gp130、p-STAT3、TNF-α、IL-1β表达水平及胞核蛋白中NF-κB p65的表达水平、PA-aO₂、W/D明显增加(P <0.05);与IL-6 WT+PQ组比较,IL-6 KO+PQ组小鼠肺组织病理改变明显改善,肺组织胞浆蛋白中IL-6、gp130、p-STAT3、TNF-α、IL-1β的表达水平及胞核蛋白中NF-κB p65的表达水平、PA-aO₂、W/D明显降低(P <0.05)。结论 IL-6/gp130/STAT3通路激活与PQ诱导ALI有关。     

Effect of omega-3 and ascorbic acid on inflammation markers in depressed shift workers in Shahid Tondgoyan Oil Refinery,Iran: a randomized double-blind placebo-controlled study

The present study aimed to assess the effect of supplementation of omega-3 and/or vitamin C on serum interleukin-6 and high sensitivity C-reactive protein concentration and depression scores among shift workers in Shahid Tondgoyan oil refinery. The study design was randomized, double-blind, placebo-controlled, parallel trial. Totally 136 shift workers with a depression score ≥10 in 21-item Beck Depression Rating Scale were randomly assigned to receive omega-3 (180 mg eicosapentaenoate acid and 120 mg docosahexaenoic acid) or/and vitamin C 250 mg or placebo twice daily (with the same taste and shape as omega-3 and vitamin C) for 60 days in four groups. Depression score, interleukin-6 and high sensitivity C-reactive protein were measured at baseline and after 60 days. This study showed that supplementation of omega-3 plus vitamin C is associated with a decrease in depression score (p<0.05). Supplementation of omega-3 without vitamin C, is associated with a reduction in depression score (p<0.0001) and high sensitivity C-reactive protein concentration (p<0.01). Therefore omega-3 supplementation showed a better effect on reducing depression score and high sensitivity C-reactive protein, but supplementation of vitamin C along with omega-3 did not have significant effect on change in C-reactive protein level compared to omega-3 alone. (Registration number: IRCT201202189056N1)     

Fish oil prevents colon cancer by modulation of structure and function of mitochondria

Cancer cells are more susceptible to metabolic perturbations due to impaired electron transport chain (ETC) that promote uncontrolled proliferation. Mitochondria play a pivotal role in bioenergetics and apoptosis, hence are considered as a promising target in tumor cell eradication. Therefore, the present study is designed to elucidate chemopreventive action of fish oil (FO) in combination with corn oil (CO) on mitochondria in colorectal cancer (CRC). Male Wistar rats were divided into groups depending on dietary regimen—Control group, FO + CO(1:1) and FO + CO(2.5:1). These groups were further subdivided depending on whether these received a weekly intraperitoneal injection of ethylenediamine tetra-acetic acid (EDTA) or N,N-dimethylhydrazine dihydrochloride (DMH) for a period of 4 weeks. The animals sacrificed 48 h and 16 weeks after EDTA/DMH treatment constituted initiation and post-initiation phase respectively. The structural and functional alterations in mitochondria were evaluated using transmission electron microscopy (TEM) and by assaying electron transport chain (ETC) enzymes. Mitochondrial lipid composition and cholesterol levels were also assessed. DMH treatment led to mitochondrial degeneration, disrupted cristae and a significant decrease in ETC complexes suggestive of metabolic reprogramming. Moreover, an increase in cholesterol and cardiolipin (CL) levels in post-initiation phase led to evasion of apoptosis. FO in both the ratios resulted in stabilization and increase in number of mitochondria, however, FO + CO(2.5:1) + DMH group also exhibited mitophagy and crystolysis alongwith altered dynamics in ETC which facilitated apoptosis. It also decreased cholesterol and CL levels to increase apoptosis. Fish oil targets mitochondria in a dose dependent manner that augments apoptosis and hence attenuates carcinogenesis.     

不可分型流感嗜血杆菌外膜蛋白P6基因真核质粒的保护性研究

目的:探讨不可分型流感嗜血杆茵(nontypeable Haemophilus influenzae,NTHi)外膜蛋白P6(outer membrane protein P6,P6)真核质粒的免疫保护性及其可能的保护机制.方法:构建pcDNA3.1/HisA-P6核酸疫苗,转染HeLa细胞;将P6质粒免疫BALB/c小鼠后,ELISA法检测小鼠脾淋巴细胞IFN-γ和IL-4产生水平:CCK-8法分析脾淋巴细胞增殖情况,并建立小鼠NTHi感染模型,检测小鼠鼻咽部灌洗液NTHi数目变化:HE染色法分析鼻黏膜病理变化.结果:pcDNA3.1/HisA-P6在HeLa细胞中有目的蛋白的表达,免疫后pcDNA3.1/HisA-P6组小鼠脾淋巴细胞产生的IFN-γ及刺激指数均高于pcDNA3.1/HisA、PBS对照组(P<0.05).而IL-4的表达无差异;P6组鼻咽部NTHi清除率也显著高于对照组(P<0.01);病理显示P6组小鼠鼻黏膜组织结构基本正常,而时照组鼻黏膜紊乱、脱落.讨论:P6核酸疫苗可诱导小鼠产生明显的抗NTHi保护效应,其可能的保护机制包括细胞免疫、体液免疫及黏膜免疫.     

血小板活化水平与慢性阻塞性肺疾病急性发作相关肺动脉高压的临床研究

目的探究血小板活化标志物在评估慢性阻塞性肺疾病急性发作(AECOPD)患者相关肺动脉高压(PH)病情方面的价值,探索其联合血液学指标评估AECOPD患者合并PH病情的临床应用潜力。方法回顾性筛选2019年1月至2020年12月在太仓市第一人民医院诊断为AECOPD的住院患者,记录患者临床资料及实验室检验结果。根据患者心动超声检查结果计算肺动脉收缩压(PASP),据此判断患者是否合并PH。收集患者入院24 h内血液标本进行流式分析,探索血小板活化指标及联合血液学标志物与AECOPD患者合并PH的相关性及对相关病情的评估价值。结果入组122例患者,分为单纯AECOPD组(n=45)及AECOPD合并PH组(n=77)。按照PASP将入组患者分为无PH组(n=45)、轻度PH组(n=42)、中重度PH组(n=35)。PH组患者患病时间(年:18.3±14.7 vs.11.9±11.4,P<0.05)、炎症指标[C反应蛋白(CRP)、白细胞介素-6(IL-6)]及血小板活化参数CD62P+/CD61+血小板百分比(%:20.7±8.6 vs.7.9±2.8,P<0.01)和荧光强度(48.8±12.9 vs.38.7±10.6,P<0.01)均明显高于单纯AECOPD组患者。Logistic回归分析提示,高CRP、高IL-6浓度及高血小板活化百分比是AECOPD患者合并PH的独立危险因素,该模型拟合优度P=0.984,能正确分类90.2%的研究对象。联合IL-6、CRP及CD62P+/CD61+血小板百分比对AECOPD患者合并PH有一定辅助评估的临床应用价值(AUC=0.972)。血小板活化百分比、PASP与PH严重程度呈正相关(r=0.822,P<0.01)。结论血小板活化参数CD62+/CD61+血小板百分比对AECOPD患者合并PH的病情评估具有一定的临床应用价值及潜力。     

Predictive value of procalcitonin, interleukin-6, and C-reactive protein for survival in postoperative patients with severe sepsis

Purpose

To prospectively evaluate the performance of procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) as percentage of baseline (POB) in predicting hospital survival, we studied 64 consecutive, postoperative patients with severe sepsis.

Materials and Methods

Plasma PCT, IL-6, and CRP were serially measured from day 1 (onset of sepsis) to day 14 in parallel with clinical data until day 28. Multivariate logistic regression and univariate analysis of predictive accuracy of PCT-, IL-6-, and CRP-POB were performed. Newly derived binary prediction rules were evaluated by calculating sensitivity, specificity, positive predictive value, and negative predictive value.

Results

In survivors, PCT and IL-6 significantly decreased from days 1 to 14, whereas CRP did not. In nonsurvivors, the inflammation markers mostly increased within the second week. At day 7, logistic regression analysis revealed PCT-POB as an independent determinant for survival. Especially, PCT-POB not exceeding 50% and PCT-POB not exceeding 25% with CRP-POB not exceeding 75% on day 7 indicated a favorable outcome with a positive predictive value/sensitivity of 75%/97% and 92%/67%, respectively. In comparison, pretest likelihood to survive by day 28 and observed survival rate were 60% and 67%, respectively.

Conclusions

Prediction rules of decrease in PCT-POB on day 7 in combination with CRP-POB may serve to monitor efficacy and guide duration of therapy in critically ill patients.     

类风湿关节炎患者外周血单个核细胞和血浆中人疱疹病毒6型的表达

目的探讨人疱疹病毒6型(HHV6)感染在类风湿关节炎(RA)病因学中的作用。方法采用巢式PCR技术检测62例RA患者(其中3例同时合并干燥综合征)和138名健康献血者外周血单个核细胞和血浆中HHV6DNA表达现状。同期运用美国德灵公司血浆特定蛋白分析仪定量检测RA患者血浆中类风湿因子(rheumatoidfactor,RF)。结果RA患者组外周血单个核细胞(peripheralbloodmononuclearcells,PBMCs)HHV6DNA阳性率与正常对照组比较无差异显著性(P=0.7992);RA患者PBMC中HHV6DNA阳性率与其性别、年龄、病情严重程度等无显著相关性(P>0.05);RA患者组RF阳性(浓度≥20IU/ml)率与PBMC中HHV6DNA阳性率之间无明显一致性(P=0.7502)。RF浓度≥50IU/ml的RA患者组PBMCs中HHV6DNA阳性率明显高于RF浓度<50IU/ml的RA患者组(P=0.0295);部分RA患者血浆中可检出HHV6DNA,而对照组血浆中HHV6DNA阴性。结论HHV6DNA在RA患者PBMCs中有较高检出率,部分RA患者血浆中存在HHV6DNA,提示该组患者中可能存在HHV6活动性感染;HHV6感染可能与RA患者血浆中RF滴度增高有关。     

Flt3配体对培养的树突状细胞免疫表型影响的研究

目的研究早期造血生长因子Flt3配体(Flt3L)对培养的树突状细胞(Dendritic Cell，DC）免疫分子表达的影响。方法分离正常人外周血中单核细胞，以加入细胞因子rhGM-CSF和rhIL-4的培养体系为基础，体外培养树突状细胞。观察加入Flt3L因子后培养的DC的形态变化，并应用流式细胞仪分析DC表面的免疫分子的表达。结果Flt3L能协同GM-CSF、IL-4作用扩增DC。结论Flt3L能使树突状细胞定向分化成为抗原提呈细胞。     

急性白血病患者血清白细胞介素-6白细胞介素-8的变化

目的　探讨血清IL- 6、IL -8水平变化与急性白血病(AL)发生、发展及预后的关系。方法　采用放射免疫法检测5 6例AL患者血清IL- 6、IL- 8水平,2 8例正常健康者血清IL- 6、IL- 8水平。结果　AL患者血清IL- 6、IL -8水平明显增高,完全缓解后,IL- 6、IL -8恢复正常。结论　血清IL- 6、IL- 8的异常升高在急性白血病的发生、发展中可能起一定作用,检测AL患者血清IL- 6、IL- 8水平对判断疗效、估计预后、监测复发有一定意义。     

Homeodomain‐interacting protein kinase phosphorylates the Drosophila Paired box protein 6 (Pax6) homologues Twin of eyeless and Eyeless

Homeodomain‐interacting protein kinase (Hipk), the Drosophila homologue of mammalian HIPK2, plays several important roles in regulating differentiation, proliferation, apoptosis, and stress responses and acts as a mediator for signals of diverse pathways, such as Notch or Wingless signalling. The Paired box protein 6 (Pax6) has two Drosophila homologues, Twin of eyeless (Toy) and Eyeless (Ey). Both stand atop the retinal determination gene network (RDGN), which is essential for proper eye development in Drosophila. Here, we set Hipk and the master regulators Toy and Ey in an enzyme–substrate relationship. Furthermore, we prove a physical interaction between Toy and Hipk in vivo using bimolecular fluorescence complementation. Using in vitro kinase assays with different truncated Toy constructs and mutational analyses, we mapped four Hipk phosphorylation sites of Toy, one in the paired domain (Ser¹²¹) and three in the C‐terminal transactivation domain of Toy (Thr³⁹⁵, Ser⁴¹⁰ and Thr⁴⁵²). The interaction and phosphorylation of the master regulator Toy by Hipk may be important for precise tuning of signalling within the RDGN and therefore for Drosophila eye development.