Summary Severe disease of SARS-CoV-2 is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5–7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Given that every patient is captured at different stages of infection, longitudinal monitoring of the immune response is critical and systems-level analyses are required to capture cellular interactions. Here, we report on a systems-level blood immunomonitoring study of 37 adult patients diagnosed with COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNγ-eosinophil axis activated before lung hyperinflammation and changes in cell-cell co-regulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.

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Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are two most common weight loss procedures; our meta-analysis aims to compare these two in the treatment of morbid obesity and its related comorbidities. An electronic literature research of published studies concerning LRYGB and LSG was performed from inception to October 2013. Percentage of excess weight loss (%EWL), resolution or improvement rate of comorbidities, and adverse events were all pooled and compared by the software Review Manager 5.1. As a result, a total of 21 studies involving 18,766 morbidly obese patients were eventually selected according to the inclusion criteria. No significant difference was found in %EWL during 0.5- to 1.5-year follow-up (P > 0.05), but after that, LRYGB achieved higher %EWL than LSG (P < 0.05). Except for type 2 diabetes mellitus (T2DM) (P < 0.001), the difference between these two procedures in the resolution or improvement rate of other comorbidities did not reach a statistical significance (P > 0.05). There were more adverse events in LRYGB compared with LSG (P < 0.01). In conclusion, LRYGB is superior to LSG in efficacy but inferior to LSG in safety.

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Gestational exposure to nicotine affects brain development, leading to numerous behavioural and physiological deficits in the offspring during adolescence. To analyse the molecular mechanisms underlying these effects, a pathway-focused oligonucleotide microarray was used to determine gene expression profiles in five brain regions (i.e. amygdala, prefrontal cortex, nucleus accumbens, periventricular nucleus of the hypothalamus, and caudate putamen CPu) of adolescent rats that received nicotine or saline during gestation. Following appropriate statistical and Gene Set Enrichment Analyses, 24 cell death/survival-related pathways were found to be significantly modulated by gestational nicotine. On the basis of their biological functions, these pathways can be classified into three categories: growth factor, death receptor, and kinase cascade. We employed a quantitative real-time PCR array to verify the findings by measuring the expression of 29 genes involved in cell death/survival-related pathways. Together, our findings indicate that gestational nicotine exposure has significant effects on gene expression in cell death/survival-related pathways in the brains of adolescent offspring. Such effects appear to be brain region-specific and are realized through regulation of the expression of growth factors and receptors, caspases, kinases, and transcription factors. On the basis of these findings, we offer a hypothetical model to explain how gestational nicotine exposure may affect cell death and survival in the brains of adolescent offspring by regulating the balance between growth-factor and death-receptor pathways.

The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tissue injury to mediate local tissue responses including inflammation and tissue remodeling. We found that in various models of kidney disease, Fn14 expression (mRNA and protein) is upregulated in the kidney. These models include: lupus nephritis mouse models (Nephrotoxic serum Transfer Nephritis and MRL.Faslpr/lpr), acute kidney injury models (Ischemia reperfusion injury and Folic acid injury), and a ZSF-1 diabetic nephropathy rat model. Fn14 expression levels correlate with disease severity as measured by disease histology. We have also shown for the first time the detection of soluble Fn14 (sFn14) in the urine and serum of mice. Importantly, we found the sFn14 levels are markedly increased in the diseased mice and are correlated with disease biomarkers including proteinuria and MCP-1. We have also detected sFn14 in human plasma and urine. Moreover, sFn14 levels, in urine are significantly increased in DN patients and correlated with proteinuria and MCP-1 levels. Thus our data not only confirm the up-regulation of Fn14/TWEAK pathway in kidney diseases, but also suggest a novel mechanism for its regulation by the generation of sFn14. The correlation of sFn14 levels and disease severity suggest that sFn14 may serve as a potential biomarker for both acute and chronic kidney diseases.

Endovascular treatment of giant intracranial aneurysms with coil embolization is often associated with a low complete occlusion rate and a high recanalization rate, and parent artery occlusion remains a practical option in selected patients. Based on our limited experience, the use of an intracranial covered stent appears to be a relatively simple and safe procedure for occluding very large and giant aneurysms while still maintaining the patency of the parent artery.