心脏再生的研究新进展

心肌梗死后容易发生心衰、恶性心律失常甚至猝死等而威胁患者生命,有效改善心梗患者心功能促进心肌再生已经成为研究的热点。目前促进心肌再生的方法可大体概括为干细胞法诱导心肌增殖,微小核糖核酸诱导心肌再生,调控心肌细胞增殖有关的通路及细胞周期因子诱导心肌增殖,调节心肌细胞微环境诱导心肌增殖。虽然这些方法的研究都取得了一定的进展,但许多机制并未明确,也有诸多问题没有解决,还需要更深入的研究,随着心脏再生的研究,这一领域必将带来振奋人心的结果。     

An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide

Background and aim: Microscopic colitis (MC) is an inflammatory disease of the bowel, hypothetically induced by an immunologic response to a luminal microbial agent. We aimed to characterize the microbiome composition in MC and subtypes collagenous colitis (CC) and lymphocytic colitis (LC) and to identify a possible microbial effect of treatment.

Method: Stool samples were collected from MC patients prior to treatment, at 8 weeks (during treatment) and at 16 weeks (after treatment), and from healthy controls, not receiving treatment, at matched time-points. Microbiome composition was analyzed by sequencing of the 16S and 18S genes. Differences between patients and controls were analyzed by Shannon’s diversity index (mean, standard deviation (SD)) and principal coordinate analysis (PCoA) complemented with a permanova test of UniFrac distances.

Results: Ten LC patients, 10?CC patients and 10 controls were included. By PCoA, the bacterial composition in MC patients differed from controls at baseline (p?=?.02), but not during and after treatment (p?=?.09 and p?=?.33, respectively). At baseline, bacterial diversity was lower in MC patients compared to controls (2.5, SD: 0.5 vs 3.5, SD: 0.3, p?<?.05). Diversity in MC patients increased during (3.0, SD: 0.6) and after treatment and (2.9, SD: 0.5) compared with baseline (p?<?.01). Eukaryotes were detected in fewer samples from MC patients compared with controls (11/20 (55%) vs. 9/10 (90%), p?=?.06) with no effect of treatment.

Conclusion: Microbiome composition is altered in MC patients. During and after treatment with budesonide the microbiome composition in MC patients was driven towards the composition in healthy controls.     

Comparative analysis of Bayer wide-range C-reactive protein (wr-CRP) and the Dade-Behring high sensitivity C-reactive protein (hs-CRP) in patients with inflammatory bowel disease

OBJECTIVE: The recently introduced Bayer wide‐range C‐reactive protein (wr‐CRP) assay might be relevant for the real‐time low‐cost and online determination of inflammatory bowel disease (IBD) activity. Our aim was to examine whether wr‐CRP can substitute for the Dade Behring high sensitivity C‐reactive protein (hs‐CRP) assay in IBD patients. METHODS: A total of 71 patients with IBD, of whom 48 had Crohn's disease CD and 23 had ulcerative colitis (UC) with various intensities of disease activity participated in the study. The CRP of patients who were under treatment at the Department of Gastroenterology and Liver Diseases were measured using both wr‐CRP and the hs‐CRP. RESULTS: A significant (r = 0.995; P < 0.001) correlation was noted between the hs‐CRP and wr‐CRP measurements for the whole sample as well as for the two diseases, CD (r = 0.994; P < 0.001) and UC (r = 0.997; P < 0.001), which were analyzed separately. CONCLUSION: The Bayer wr‐CRP assay might be a useful low‐cost and real‐time inflammation‐sensitive biomarker in patients with IBD.     

吲哒帕胺对高血压高危患者血清肌酐、尿酸、血钾及左室肥厚的长期影响

目的　观察吲哒帕胺 (寿比山 )在高血压高危患者中长期应用时SCr、UA、血钾的变化 ,以及合用血管紧张素转换酶抑制剂 (ACEI)能否减轻这些变化。方法　吲哒帕胺组 (Ⅰ组 ) 182例 ,给予吲哒帕胺 2 .5mg/d口服 ,如 2～ 4周后未达到目标血压 (<14 0 / 90mmHg)则加用ACEI苯那普利 (10mg/d)或卡托普利 (2 5～ 75mg/d)。对照组 (C组 )2 10例 ,给予钙拮抗剂 (硝苯地平 30mg/d或非洛地平 5mg/d)或 /和ACEI(苯那普利 10mg/d或卡托普利 2 5～ 75mg/d) ,治疗前后测定SCr、UA、血钾、血脂和血糖并做心超测定左室重量指数。结果　Ⅰ组SCr、UA明显升高 ;Ⅰ组有 7例SCr>2 5 0 μmol/L(而C组为 3例 ,3.8%vs 1.4 % ,P <0 0 5 ) ;7例因UA明显升高而诱发痛风 ;血钾明显降低 (P <0 0 0 1) ,低血钾发生率 14 .8% (C组仅 1.4 % ,P <0 0 0 1)。在Ⅰ组中 ,吲哒帕胺与ACEI合用者与单用吲哒帕胺者相比 ,SCr和UA升高的幅度及血钾降低的幅度明显降低 (P <0 0 1) ,低血钾的发生率亦明显减少 (5 .8%vs 2 5 .3% ,P<0 0 1)。Ⅰ组和C组伴LVH者的LVMI分别减轻 10 8%和 11.5 %。Ⅰ组单用吲哒帕胺的有效降压 (BP <14 0 / 90mmHg)率为 4 9.2 % ,加用ACEI后提高到 85 .3%。结论　吲哒帕胺降压作用肯定 ,长期服用能减轻高血压左室肥厚 ,对     

Dicarbonyl Electrophiles Mediate Inflammation-Induced Gastrointestinal Carcinogenesis

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急性脑血管病患者应激性高血糖、血清钾、钠、氯的变化及其与中风类型、病情轻重、预后关系

目的探讨急性脑血管病患者应激性高血糖、血清钾、钠、氯的变化及其与中风类型、病情轻重、预后关系。方法本文对我院神经内科2004年6月～2005年6月住院急性脑血管病患者248例进行研究，其中出血性中风89例，缺血性中风159例，于入院次日晨检测空腹血糖、血清钾、钠、氯，观察血糖、血钠、血氯、血钾值的变化及其与脑卒中类型、病情轻重、预后关系。结果（1）急性脑血管病患者易出现应激性高血糖、低钠血症、低氯血症、低钾血症；（2）出血性中风血糖明显高于缺血性中风；高血糖组死亡率明显高于非高血糖组；死亡组的血糖均值亦显著高于存活组；统计学上差异有显著性。（3）出血性中风低血钠、低血氯的发生率明显高于缺血性中风，统计学上差异有显著性；低血钠、低血氯组中的中、重度患者显著多于正常血钠、血氯组；与正常血钠、血氯组相比，高血钠、高血氯组患者在中风类型、病情轻重及预后方面差异均无显著性，但血钠、血氯显著升高时，死亡率明显增加。与正常血钾组相比，低血钾组中患者在中风类型、病情及预后方面差异无显著性，但血钾明显降低时，病死率增加。高血钾组患者在中风类型、病情轻重和正常血钾组相比差异无显著性，但病死率则明显高于正常血钾组。结论急性脑血管病患者存在应激反应，急性脑血管病患者应激性高血糖、低钠血症、低氯血症可以作为判断急性脑血管病病情、预后评估的指标之一。高钠血症、高氯血症、高钾血症、低钾血症与中风类型、病情及预后方面差异无显著性，但当出现严重的高钠血症、高氯血症、高钾血症、低钾血症时，病死率明显增加。     

Biomarkers of Vascular Inflammation for Cardiovascular Risk Prognostication: A Meta-Analysis

ObjectivesThe purpose of this study was to systematically explore the added value of biomarkers of vascular inflammation for cardiovascular prognostication on top of clinical risk factors.BackgroundMeasurement of biomarkers of vascular inflammation is advocated for the risk stratification for coronary heart disease (CHD).MethodsWe systematically explored published reports in MEDLINE for cohort studies on the prognostic value of common biomarkers of vascular inflammation in stable patients without known CHD. These included common circulating inflammatory biomarkers (ie, C-reactive protein, interleukin-6 and tumor necrosis factor-a, arterial positron emission tomography/computed tomography and coronary computed tomography angiography–derived biomarkers of vascular inflammation, including anatomical high-risk plaque features and perivascular fat imaging. The main endpoint was the difference in c-index (Δ[c-index]) with the use of inflammatory biomarkers for major adverse cardiovascular events (MACEs) and mortality. We calculated I² to test heterogeneity. This study is registered with PROSPERO (CRD42020181158).ResultsA total of 104,826 relevant studies were screened and a final of 39 independent studies (175,778 individuals) were included in the quantitative synthesis. Biomarkers of vascular inflammation provided added prognostic value for the composite endpoint and for MACEs only (pooled estimate for Δ[c-index]% 2.9, 95% CI: 1.7-4.1 and 3.1, 95% CI: 1.8-4.5, respectively). Coronary computed tomography angiography–related biomarkers were associated with the highest added prognostic value for MACEs: high-risk plaques 5.8%, 95% CI: 0.6 to 11.0, and perivascular adipose tissue (on top of coronary atherosclerosis extent and high-risk plaques): 8.2%, 95% CI: 4.0 to 12.5). In meta-regression analysis, the prognostic value of inflammatory biomarkers was independent of other confounders including study size, length of follow-up, population event incidence, the performance of the baseline model, and the level of statistical adjustment. Limitations in the published literature include the lack of reporting of other metrics of improvement of risk stratification, the net clinical benefit, or the cost-effectiveness of such biomarkers in clinical practice.ConclusionsThe use of biomarkers of vascular inflammation enhances risk discrimination for cardiovascular events.     

Innate immune system plays a critical role in determining the progression and severity of acetaminophen hepatotoxicity

BACKGROUND & AIMS: Inflammatory mediators released by nonparenchymal inflammatory cells in the liver have been implicated in the progression of acetaminophen (APAP) hepatotoxicity. Among hepatic nonparenchymal inflammatory cells, we examined the role of the abundant natural killer (NK) cells and NK cells with T-cell receptors (NKT cells) in APAP-induced liver injury. METHODS: C57BL/6 mice were administered a toxic dose of APAP intraperitoneally to cause liver injury with or without depletion of NK and NKT cells by anti-NK1.1 monoclonal antibody (MAb). Serum alanine transaminase (ALT) levels, liver histology, hepatic leukocyte accumulation, and cytokine/chemokine expression were assessed. RESULTS: Compared with APAP-treated control mice, depletion of both NK and NKT cells by anti-NK1.1 significantly protected mice from APAP-induced liver injury, as evidenced by decreased serum ALT level, improved survival of mice, decreased hepatic necrosis, inhibition of messenger RNA (mRNA) expression for interferon-gamma (IFN-gamma), Fas ligand (FasL), and chemokines including KC (Keratinocyte-derived chemokine); MIP-1 alpha (macrophage inflammatory protein-1 alpha); MCP-1 (monocyte chemoattractant protein-1); IP-10 (interferon-inducible protein); Mig (monokine induced by IFN-gamma) and decreased neutrophil accumulation in the liver. Hepatic NK and NKT cells were identified as the major source of IFN-gamma by intracellular cytokine staining. APAP induced much less liver injury in Fas-deficient (lpr) and FasL-deficient (gld) mice compared with that in wild-type mice. CONCLUSIONS: NK and NKT cells play a critical role in the progression of APAP-induced liver injury by secreting IFN-gamma, modulating chemokine production and accumulation of neutrophils, and up-regulating FasL expression in the liver, all of which may promote the inflammatory response of liver innate immune system, thus contributing to the severity and progression of liver injury downstream of the metabolism of APAP and depletion of reduced glutathione (GSH) in hepatocytes.