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81.
Ceramide synthases (CerS) synthesise ceramides of defined acyl chain lengths, which are thought to mediate cellular processes in a chain length-dependent manner. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed a significant elevation of CerS2 and its products, C24-ceramides, in CD11b+ cells (monocytes and neutrophils) isolated from blood. This result correlates with the clinical finding that CerS2 mRNA expression and C24-ceramide levels were significantly increased by 2.2- and 1.5-fold, respectively, in white blood cells of MS patients. The increased CerS2 mRNA/C24-ceramide expression in neutrophils/monocytes seems to mediate pro-inflammatory effects, since a specific genetic deletion of CerS2 in blood cells or a total genetic deletion of CerS2 significantly delayed the onset of clinical symptoms, due to a reduced infiltration of immune cells, in particular neutrophils, into the central nervous system. CXCR2 chemokine receptors, expressed on neutrophils, promote the migration of neutrophils into the central nervous system, which is a prerequisite for the recruitment of further immune cells and the inflammatory process that leads to the development of MS. Interestingly, neutrophils isolated from CerS2 null EAE mice, as opposed to WT EAE mice, were characterised by significantly lower CXCR2 receptor mRNA expression resulting in their reduced migratory capacity towards CXCL2. Most importantly, G-CSF-induced CXCR2 expression was significantly reduced in CerS2 null neutrophils and their migratory capacity was significantly impaired. In conclusion, our data strongly indicate that G-CSF-induced CXCR2 expression is regulated in a CerS2-dependent manner and that CerS2 thereby promotes the migration of neutrophils, thus, contributing to inflammation and the development of EAE and MS. 相似文献
82.
目的:探讨老年人桡骨远端C型骨折的手术治疗与非手术治疗的疗效差异,评价两种方法的优缺点。方法回顾性分析2009-12—2011-12收治的老年桡骨远端C型骨折68例,按照治疗方法分为A组(手术组)及B组(非手术组),统计分析两组患者的临床资料。结果 A组33例, B组35例,平均随访21.5个月。两组患者的年龄、骨折类型均无差异(P>0.05);术后影像学指标A组优于B组,骨折愈合时间B组优于A组,治疗成本A组大于B组(P<0.05);Cooney评分早期A组优于B组,1年后两组无差异,两组的并发症无差异(P>0.05)。结论老年人桡骨远端C型骨折手术治疗较非手术治疗可获得更好的复位及早期功能,但远期功能恢复无差异。 相似文献
83.
冠状病毒(coronavirus,CoVs)感染主要累及肺部,但对心血管系统损伤作用也不容忽视。CoVs感染引起的心脏损伤并非罕见,其发生与病情的严重程度密切相关。本文首先从CoVs引起心血管损伤的证据入手,进一步探讨了CoVs对心肌的直接损伤,以及肾素血管紧张素(RAS)系统激活和细胞因子风暴与炎症反应对心血管损伤的可能作用机制。相关心血管损伤的可能机制包括,(1)病毒直接作用:CoVs在心肌细胞复制,损伤心肌;(2)RAS系统激活:感染CoVs后,心脏血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)的表达下调,激活RAS系统,使得血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)收缩血管功能增强,Ang1-7保护心脏效应减弱;(3)诱发细胞因子风暴:循环细胞因子和全身炎症反应引起心脏损伤;(4)其他:包括低氧血症和儿茶酚胺心脏毒性。本文就相关内容作一综述,为后续的详尽机制和治疗策略研究提供思路。 相似文献
84.
《Anales de pediatría (Barcelona, Spain : 2003)》2020,92(4):241.e1-241.e11
On 31 December 2019, the Wuhan Municipal Committee of Health and Healthcare (Hubei Province, China) reported that there were 27 cases of pneumonia of unknown origin with symptoms starting on the 8 December. There were 7 serious cases with common exposure in market with shellfish, fish, and live animals, in the city of Wuhan. On 7 January 2020, the Chinese authorities identified that the agent causing the outbreak was a new type of virus of the Coronaviridae family, temporarily called «new coronavirus», 2019-nCoV. On January 30th, 2020, the World Health Organisation (WHO) declared the outbreak an International Emergency. On 11 February 2020 the WHO assigned it the name of SARS-CoV2 and COVID-19 (SARS-CoV2 and COVID-19).The Ministry of Health summoned the Specialties Societies to prepare a clinical protocol for the management of COVID-19. The Spanish Paediatric Association appointed a Working Group of the Societies of Paediatric Infectious Diseases and Paediatric Intensive Care to prepare the present recommendations with the evidence available at the time of preparing them. 相似文献
85.
目的:观察PCR仪与测序仪在丙型肝炎病毒(HCV)基因型检测中的应用。方法:选择2018年1月~2018年12月收治的134例HCV感染患者为研究对象,给予患者PCR仪检测、测序仪检测。结果:测序仪检测134例均可分型,PCR仪检测130例患者可分型,4例未能分型。PCR检测结果:134例HCV感染患者中,1b型59例,2a型47例,3a型6例,3b型15例,6a型3例,4例为分出型别。基因测序结果:134例均可分型:1型59例,2a型40例,2i型7例,3a型6例,3b型15例,6a型3例,6n型4例。PCR仪检测法检测符合率97.0%。结论:PCR仪测序仪检测用于丙型肝炎病毒基因型检测,操作便捷,但其只能检测探针覆盖的型别,个别罕见型别不能分型。 相似文献
86.
87.
《Mayo Clinic proceedings. Mayo Clinic》2022,97(12):2271-2281
ObjectiveTo investigate the association between type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) with risk of sudden cardiac arrest (SCA).MethodsIn a prospective community-based study of SCA from February 1, 2002, through November 30, 2019, we ascertained 2771 cases age 18 years of age or older and matched them to 8313 controls based on geography, age, sex, and race/ethnicity. We used logistic regression to evaluate the independent association between diabetes, T1D, T2D, and SCA.ResultsPatients had a mean age of 64.5±15.9 years, were 33.3% female and 23.9% non-White race. Overall, 36.7% (n=1016) of cases and 23.8% (n=1981) of controls had diabetes. Among individuals with diabetes, the proportion of T1D was 6.5% (n=66) among cases and 2.0% among controls (n=40). Diabetes was associated with 1.5-times higher odds of SCA. Compared with those without diabetes, the odds ratio and 95% CI for SCA was 4.36 (95% CI, 2.81 to 6.75; P<.001) in T1D and 1.45 (95% CI, 1.30 to 1.63; P<.001) in T2D after multivariable adjustment. Among those with diabetes, the odds of having SCA were 2.41 times higher in T1D than in T2D (95% CI, 1.53 to 3.80; P<.001). Cases of SCA with T1D were more likely to have an unwitnessed arrest, less likely to receive resuscitation, and less likely to survive compared with those with T2D.ConclusionType 1 diabetes was more strongly associated with SCA compared with T2D and had less favorable outcomes following resuscitation. Diabetes type could influence the approach to risk stratification and prevention of SCA. 相似文献
88.
Ngai-Yin Chan Chi-Chung Choy Ho-Chuen Yuen Hoi-Fan Chow Ho-Fai Fong 《The Canadian journal of cardiology》2019,35(4):396-404
Background
Persistent iatrogenic atrial septal defect (iASD) is a common but poorly characterized complication after cryoballoon (CB) pulmonary vein isolation (PVI) procedures. We therefore investigate its prevalence, evolution, risk factors, and clinical outcomes in a prospective longitudinal study.Methods
A total of 108 patients (41 women, mean age 57 ± 11.3) underwent CB PVI for AF. Serial transesophageal echocardiography (TEE) was performed 9 months and then annually until 6 years after the procedure to study the characteristics of persistent iASD.Results
Persistent iASD occurred in 33 (30.6%) patients 9 months after CB PVI. Spontaneous closure of iASD was found in 6 (22.2%) and 3 (15.8%) patients 2 and 3 years after the procedures, respectively. No spontaneous closure was observed on 4, 5, and 6-year TEE follow-up. The projected long-term persistence rate of iASD after CB PVI was therefore 20% (30.6% × 0.778 × 0.842). Using multivariate logistic regression, a higher number of cryoapplications (≥ 2 minutes) was the only independent predictor of persistent iASD 9 months after CB PVI (odds ratio [OR] 1.207; 95% confidence interval [CI], 1.033-1.411, P = 0.018). Two (1.9%) patients with significantly larger iASD size than the others (long diameter 12.6 ± 0.8 vs 3.7 ± 1.5 mm, P < 0.001; short diameter 10.9 ± 0.2 vs 3 ± 1.1 mm, P < 0.001) required percutaneous closure because of exertional dyspnea and right ventricular enlargement. Over 129.7 patient-years follow-up, during which iASD persisted, there was no occurrence of neurologic events.Conclusions
Approximately one fifth of patients undergoing CB PVI will have permanently persistent iASD. Patients with defect sizes of greater than 10 mm may need percutaneous closure due to significant left-to-right shunting. 相似文献89.
Dominique Trudel Luminita-Mihaela Avarvarei Michèle Orain Stéphane Turcotte Marie Plante Jean Grégoire Reinhild Kappelhoff David P. Labbé Dimcho Bachvarov Bernard Têtu Christopher M. Overall Isabelle Bairati 《Pathology, research and practice》2019,215(6):152369
Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance. 相似文献
90.
《Vaccine》2021,39(45):6601-6613
AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain. 相似文献