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CD19嵌合抗原受体T细胞疗法是治疗B细胞血液肿瘤的新兴免疫疗法,并取得了较好的疗效。随着其使用的增加,免疫效应细胞相关细胞因子释放综合征的发生率也相应升高,迫切需要对其精确机制和治疗进行进一步的临床研究。文章总结了细胞因子释放综合征的机制、临床表现、分级系统、治疗以及管理策略。  相似文献   
3.
Our knowledge of the radiological spectrum of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is growing rapidly. An update on the radiological features of the disease, and its evolution is thus necessary. Magnetic resonance imaging (MRI) has an increasingly important role in the differential diagnosis of MOGAD particularly from aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and multiple sclerosis (MS). Differentiating these conditions is of prime importance because the management is different between the three inflammatory diseases, and thus could prevent further attack-related disability. Therefore, identifying the MRI features suggestive of MOGAD has diagnostic and prognostic implications. We herein review optic nerve, spinal cord and the brain MRI findings from MOGAD adult patients, and compare them to AQP4-NMOSD and MS.  相似文献   
4.

Background

Epidemiology of patients with worsening heart failure and reduced ejection fraction (HFrEF) in the real-world setting is not well described.

Objectives

The purpose of this study was to describe incidence, clinical characteristics, treatment, and outcomes of patients with HFrEF who develop worsening heart failure (HF) in the real-world setting.

Methods

Data on patients with incident HFrEF from the National Cardiovascular Data Registry PINNACLE were linked to pharmacy, private practitioner, and hospital claims databases. Incidence, clinical characteristics, treatment (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist) and outcomes of patients with worsening HF, defined as ≥90 days of stable HF with subsequent worsening requiring intravenous diuretic agents, were assessed.

Results

Of 11,064 HFrEF patients, 1,851 (17%) developed worsening HF on average 1.5 years following initial HF diagnosis. Patients who developed worsening HF were more likely to be African American, be octogenarians, and have higher comorbidity burden (p < 0.001). At the onset of worsening HF, 42.4% of patients were on monotherapy, 43.4% were on dual therapy, and 14.1% were on triple therapy. A total of 48%, 61%, and 98% of patients were on >50% target dose for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist, respectively. The 2-year mortality rate was 22.5%, and 56% of patients were rehospitalized within 30 days of the worsening HF event.

Conclusions

In the real-world setting, 1 in 6 patients with HFrEF develop worsening HF within 18 months of HF diagnosis. These patients have a high risk for 2-year mortality and recurrent HF hospitalizations. The use of standard-of-care therapies both before and after the onset of worsening HF is low. With high unmet medical need, patients with worsening HF require novel treatment strategies as well as greater optimization of existing guideline-directed therapy.  相似文献   
5.

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
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《Cancer cell》2021,39(9):1279-1291.e3
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9.
While the beneficial impact of physical activity has been ascertained in a variety of pathological scenarios, including diabetes and low-grade systemic inflammation, its potential remains still putative for periodontal health. Periodontal disease has been associated with inflammatory systemic alterations, which share a common denominator with type 2 diabetes mellitus and cardiovascular disease. Physical exercise, along with nutritional counseling, is a cornerstone in the treatment and prevention of type 2 diabetes, also able to reduce the prevalence of periodontal disease and cardiovascular risk. In addition, considering the higher incidence of periodontitis in patients with type 2 diabetes compared to healthy controls, the fascinating research question would be whether physical activity could relieve the inflammatory pressure exerted by the combination of these two diseases. This multi-disciplinary viewpoint discusses available literature in order to argument the hypothesis of a “three–way relationship” linking diabetes, periodontitis, and physical activity.  相似文献   
10.
Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia, but the underlying mechanism has not yet been fully elucidated. Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment, and the phosphoinositide 3-kinase(PI3 K)/Akt signaling pathway plays an important role in autophagy regulation. To investigate the role played by the PI3 K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models, we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method. Starting at 2 hours after modeling, electroacupuncture was delivered at the Shenting(GV24) and Baihui(GV20) acupoints, with a dilatational wave(1–20 Hz frequency, 2 mA intensity, 6 V peak voltage), for 30 minutes/day over 8 consecutive days. Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury, increased the mRNA expression levels of the PI3 K/Akt signaling pathwayrelated factors Beclin-1, mammalian target of rapamycin(mTOR), and PI3 K, increased the protein expression levels of phosphorylated Akt, Beclin-1, PI3 K, and mTOR in the ischemic cerebral cortex, and simultaneously reduced p53 mRNA and protein expression levels. In the Morris water maze test, the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. In the spatial probe test, the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. Electroacupuncture stimulation applied to the Shenting(GV24) and Baihui(GV20) acupoints activated the PI3 K/Akt signaling pathway and improved rat learning and memory impairment. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, China(approval No. 8150150901) on March 10, 2016.  相似文献   
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