Necroptosis in inflammatory bowel disease and other intestinal diseases

For a long time, it was believed that apoptosis and necrosis were the main pathways for cell death, but a growing body of research has shown that there are other pathways. Among these, necroptosis, a regulatory caspase-independent, programmed cell death pathway, is supposed to be of importance in the pathogenesis of many diseases. The mechanism of regulating, inducing and blocking necroptosis is a complex process that involves expression and regulation of a series of molecules including receptor interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase like protein. By blocking or downregulating expression of key molecules in the necroptotic pathway, intestinal inflammation can be affected to some extent. In this paper, we introduce the concept of necroptosis, its main pathway, and its impact on the pathogenesis of inflammatory bowel disease (IBD) and other intestinal diseases, to explore new drug targets for intestinal diseases, including IBD.     

清金化痰汤对慢性阻塞性肺疾病急性加重期的临床疗效、炎症反应和气道黏液高分泌的影响

目的:探讨中药方剂清金化痰汤对慢性阻塞性肺疾病急性加重期(AECOPD)的临床疗效、炎症反应和气道黏液高分泌的影响。方法:符合AECOPD入选标准患者80例,随机分为清金化痰汤组(治疗组)和常规治疗组(对照组),每组40例。两组患者均常规给予低流量吸氧、抗感染、祛痰平喘等治疗,清金化痰汤治疗组在此基础上加用中药清金化痰汤口服或鼻饲,两组患者观察时间均为14d。通过评估两组患者抗菌药物使用时间的长短,治疗前后(入院当天和治疗14d)的血气分析及中医证候积分;入院第1d、7d、14d患者外周血中的白细胞计数、中性粒细胞百分比、C-反应蛋白(CRP)、降钙素原、肿瘤坏死因子-α(NF-α)、白介素1β(IL-1β)、白介素8(IL-8)、中性粒细胞弹性蛋白酶(NE)、基质金属蛋白酶-9(MMP-9);痰液中的黏蛋白5AC(MUC5AC)含量来探讨清金化痰汤对AECOPD的临床疗效、炎症反应及气道黏液高分泌的影响。结果:治疗组的抗生素使用时间显著低于对照组,治疗前后的中医证候积分、血气分析结果显著好于对照组,差异有统计学意义(P<0.05);两组患者的炎症指标及NE、MMP-9、MUC5AC的含量均低于入院时,但清金化痰汤组下降水平显著优于对照组,差异具有统计学意义(P<0.05)。结论:在常规西药治疗基础上,配合中药清金化痰汤治疗AECOPD,在改善患者临床症状、控制感染方面比单纯西医常规治疗效果更优,其作用机理可能与该方能够在一定程度上抑制炎症因子、减轻气道黏液高分泌有关。     

二氧化硫对脓毒症大鼠致肺损伤炎性介质的调节

目的 探索内源性二氧化硫(sulfur dioxide,SO2)对脓毒症大鼠所致急性肺损伤过程炎性介质的调节作用.方法 雄性Sprague Dawley大鼠24只随机(随机数字法)被分入假手术对照组(control组),假手术+SO2组(SO2组),脓毒症组(sepsis组),脓毒症+SO2组(sepsis+ SO2组),每组6只.通过肺组织损伤半定量评分(Index of quantitative assessment,IQA)及肺组织湿干质量比(wet/dry weight ratio,W/D)对肺损伤进行评价.检测血浆SO2、白细胞介素6、8及10(interleukins-6,IL 6、interleukins-8,IL 8、interleukins-10,IL 10)及单核细胞趋化蛋白-1(Monocytechemotactic protein-1,MCP-1)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)含量.结果 脓毒症大鼠IQA及W/D与对照组相比显著升高(P均＜0.01),给予SO2干预后显著降低(P均＜0.01).血浆SO2含量在脓毒症组(3.17 ±3.44)μmol/L与对照组(5.87 ±1.96)μmol/L下降,给予SO2干预后显著升高(9.78±3.26) μmol/L,P＜0.01;血浆IL 6、IL 8、IL 10及MCP-1、TNF-α含量在脓毒症组分别为(87.08 ±22.03)、(79.82±19.69)、(66.38 ±21.77)、(157.58 ±42.36)及(65.04±19.42) pg/mg,对照组分别为(47.41 ±9.64)、(42.25±8.16)、(31.96±4.63)、(67.65±10.18)及(33.83 ±5.75)相比显著升高(P均＜0.01);给予SO2干预后分别为(66.01±16.52)、(61.52±18.32)、(45.61 ±16.47)、(117.86 ±34.20)及(61.49±15.33) pg/mg降低(IL 6及IL 8,P均＜0.05,IL 10及MCP-1,P均＜0.01).结论 在脓毒症所致肺损伤的发病过程中,内源性SO2可以通过抑制MCP-1、TNF-α进而减轻炎症因子的表达起到保护作用.     

超短波治疗对脊髓损伤炎症因子和丝裂原活化蛋白激酶通路的影响

目的观察超短波治疗对脊髓损伤(SCI)后炎症因子和丝裂原活化蛋白激酶(MAPK)通路的影响。方法将79只Sprague-Dawley(SD)大鼠随机分成对照组(n=35)、干预组(n=35)和假手术组(n=9)。采用Allen′s法对干预组和对照组大鼠行SCI挫压伤造模, 假手术组仅暴露脊髓组织, 不进行打击。SCI后24 h后, 干预组给予无热量超短波治疗, 每日1次, 每周5次, 每次7 min直至取材前。造模成功1 d后和各组对应的取材时间点(提前1 h), 采用SCI行为学评分(BBB)对3组未取材的大鼠进行运动功能评估。造模成功1 d、3 d、7 d后, 采用免疫荧光和免疫印迹技术观察3组大鼠损伤区域内炎症因子和MAPK通路的动态变化。结果造模成功14 d后, 干预组大鼠的BBB评分为(7.30±1.04)分, 显著优于对照组造模成功14 d后, 差异有统计学意义(P<0.05)。造模成功7 d后, 假手术组大鼠脊髓组织炎症因子NOD样受体热蛋白结构域相关蛋白(NLRP3), 白介素-6(IL-6), 白介素-6受体(IL-6R)和肿瘤坏死因子-α(TNF-α)的含量均...     

Persistent Enhancement on Contrast-Enhanced Ultrasound Studies of Severe Crohn's Disease: Stuck Bubbles?

A small population of patients with severe Crohn's disease (CD) exhibit atypical lack of intensity decline on intestinal contrast-enhanced ultrasound. From a retrospective CD cohort examined with contrast-enhanced ultrasound, 104 patients were identified. Twenty study patients with severe active disease exhibited high peak enhancement (>23 dB) and minimal decline. From the same cohort, 84 control patients also exhibited high peak enhancement >23dB, but with typical intensity decline. Patient outcomes were assessed. Time–intensity curve analysis revealed a significantly higher (p < 0.0001) area under the curve (44.7 ± 1.5 dB·s), washout time and intensities at 60s and 120s in the study population compared with controls (40.0 ± 1.1 dB·s). Study patients had a worse overall outcome with surgery in 30% versus 10% (p?=?0.027) during follow-up. Heightened enhancement with lack of decline on contrast-enhanced ultrasound suggests microbubbles are stuck within the inflamed bowel wall for an extended period. This observation occurs in patients with severe disease and a bad outcome.     

纤维骨性假瘤的影像学诊断

目的分析总结纤维骨性假瘤的影像学表现特点,提高对该病的影像诊断水平。方法回顾性分析5例纤维骨性假瘤的临床影像学资料,包括x线平片检查5例,CT检查4例,MRI检查2例,总结其临床影像学表现特点。结果 5例纤维骨性假瘤均发生于掌指骨旁软组织,其中3例发生于拇指,术前临床x线平片检查均误诊,男1例,女4例,年龄15~36岁。3例X线平片和/或CT表现为指骨旁密度均匀或不均匀的骨性肿块,边缘清楚,邻近骨膜新生骨形成,其中1例MRI示骨性肿块信号类似与肌肉信号;1例X线平片和CT表现为骨皮质侵蚀破坏、骨膜新生骨和软组织肿胀,未见肿块;1例X线平片和CT表现为骨膜新生骨和软组织肿胀,无骨质破坏,MRI示类似于肌肉信号的软组织肿块形成。结论纤维骨性假瘤好发于掌指骨旁软组织,常表现为骨旁边界清楚的骨性肿块,伴有邻近骨膜新生骨,骨质破坏少见,应注意避免误诊为骨旁骨肉瘤、骨软骨瘤或骨髓炎。     

Post-resuscitation intestinal microcirculation: Its relationship with sublingual microcirculation and the severity of post-resuscitation syndrome

Objective

Post-resuscitation syndrome has been recognized as one of the major causes of the poor outcomes of cardiopulmonary resuscitation. The aims of this study were to investigate the intestinal microcirculatory changes following cardiopulmonary resuscitation and relate those changes to sublingual microcirculation and the severity of post-resuscitation syndrome as measured by myocardial function and serum inflammatory cytokine levels.

Methods

Twenty-five rats were randomized into three groups: (1) short duration of cardiac arrest (n = 10): ventricular fibrillation (VF) was untreated for 4 min prior to 6 min of cardiopulmonary resuscitation (CPR); (2) long duration of cardiac arrest (n = 10): VF was untreated for 8 min followed by 8 min of CPR; (3) sham control group (n = 5): a sham operation was performed without VF induction and CPR. Intestinal and sublingual microcirculatory blood flow was visualized by a sidestream dark-field (SDF) imaging device at baseline and 1, 2, 4, 6, 8 h post-resuscitation. Myocardial function was measured by echocardiography and serum cytokine levels (TNF-α and IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).

Results

Both intestinal and sublingual microcirculatory blood flow decreased significantly with increasing duration of cardiac arrest and resuscitation. The decreases in intestinal microcirculatory blood flow were closely correlated with the reductions of sublingual microcirculatory blood flow (perfused small vessels density: r = 0.772, p < 0.01; microcirculatory flow index: r = 0.821, p < 0.01). The decreased microcirculatory blood flow was closely correlated with weakened myocardial function and elevated inflammatory cytokine levels.

Conclusions

The severity of post-resuscitation intestinal microcirculatory dysfunction is closely correlated with that of myocardial function and inflammatory cytokine levels. The measurement of sublingual microcirculation reflects changes of intestinal microcirculation and may therefore provide a new option for post-resuscitation monitoring.     

降钙素原在感染性疾病诊断中应用价值的临床病例分析

目的结合临床病例,分析降钙素原(PCT)在感染性疾病诊断中的应用价值。方法回顾2012年5月至2013年5月首都医科大学附属友谊医院感染内科586例住院患者的血清降钙素原检测结果,并对感染部位及感染病原体进行统计。另外,对其中63例细菌性肺炎患者的血清PCT、PCT评分及其他实验室辅助检查结果进行进一步分析,并计算PSI评分和CURB-65评分。结果多部位感染组PCT、PCT评分大于单一部位感染组;不同部位感染PCT、PCT评分差异有统计学意义,消化系统感染PCT、PCT评分水平高于泌尿系统和呼吸系统感染;在63例细菌性肺炎中,低危组和中高危组PCT、PCT评分无统计学差异;PCT升高组最高体温、C反应蛋白、红细胞沉降率、碱性磷酸酶染色(NAP)阳性率、NAP积分值高于PCT正常组,而病程短于PCT正常组,差异具有统计学意义。结论 PCT作为一种新的感染性炎性标志物,在感染性疾病的诊断中具有重要临床价值。     

血清VCAM-1、FGF2等炎症因子与难愈性糖尿病足的相关性研究

目的探讨血管细胞黏附分子-1(VCAM-1)和成纤维细胞生长因子2(FGF2)等炎症因子与难愈性糖尿病足(DF)发生、发展的关系。方法收集145例难愈性DF患者(DF组)和65例无足部溃疡的2型糖尿病(T2DM)患者(T2DM组)的基本临床资料,采集空腹血检测VCAM-1、FGF2、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA1c)、糖化白蛋白(GA)、C反应蛋白(CRP)、纤维蛋白原(FIB)、白细胞计数(WBC)和中性粒细胞比率(Neu%),并对结果进行统计分析。将DF组参照Wagner分级方法分为WagnerⅢ级(37例)、WagnerⅣ级(92例)和WagnerⅤ级(16例)。结果 DF组和T2DM组之间性别构成、体重指数(BMI)、FBG、2 hPG、HbA1c和GA差异均无统计学意义(P0.05)。DF组VCAM-1、FGF2、TNF-α、IL-6、WBC、Neu%、FIB、CRP、年龄、糖尿病病程和心率均高于T2DM组(P0.01)。TNF-α与VCAM-1呈正相关(r=0.284,P=0.000)。单因素Logistic回归分析表明VCAM-1、FGF2、TNF-α、IL-6、年龄、糖尿病病程、心率、WBC、Neu%、FIB和CRP是DF发生的危险因素。多因素Logistic回归分析显示VCAM-1、TNF-α、FIB和Neu%为DF发生的独立风险因素。WagnerⅤ级组年龄低于WagnerⅢ级组和WagnerⅣ级组(P0.01),而IL-6、CRP、FIB、WBC、Neu%均高于WagnerⅢ级组和WagnerⅣ级组(P0.05、P0.01)。WagnerⅤ级组FGF2和HbA1c高于WagnerⅢ级组(P0.05)。结论血清VCAM-1、FGF2等炎症因子水平升高在DF发生、发展过程中起到重要作用。DF治疗中应注重抗炎治疗。