Allergens induce upregulated IL-18 and IL-18Rα expression in blood Th2 and Th17 cells of patients with allergic asthma.

Allergic asthma (AA) is closely associated with the polarization of T helper (Th)2 and Th17 cells. Interleukin (IL)-18 acts as an inducer of Th2 and Th17 cell responses. However, expressions of IL-18 and IL-18 receptor alpha (IL-18Rα) in blood Th2 and Th17 cells of patients with AA remain unclear. We therefore investigated their expressions in Th2 and Th17 cells using flow cytometric analysis, quantitative real-time PCR (qPCR), and murine AA model. We observed increased proportions of Th2, Th17, IL-18+, IL-18+ Th2, and IL-18+ Th17 cells in blood CD4+ T cells of patients with AA. Additionally, house dust mite seemed to upregulate further IL-18 expression in Th2 and Th17, and upregulate IL-18Rα expression in CD4+ T, Th2, and Th17 cells of AA patients. It was also found that the plasma levels of IL-4, IL-17A, and IL-18 in AA patients were elevated, and they were correlated between each other. In ovalbumin (OVA)-induced asthma mouse (AM), we observed that the percentages of blood CD4+ T, Th2, and Th17 cells were increased. Moreover, OVA-induced AM expressed higher level of IL-18Rα in blood Th2 cells, which was downregulated by IL-18. Increased IL-18Rα expression was also observed in blood Th2 cells of OVA-induced FcεRIα-/- mice. Collectively, our findings suggest the involvement of Th2 cells in AA by expressing excessive IL-18 and IL-18Rα in response to allergen, and that IL-18 and IL-18Rα expressing Th2 cells are likely to be the potential targets for AA therapy.

Lattice QCD Calculation of Electroweak Box Contributions to Superallowed Nuclear and Neutron Beta Decays.

We present the first lattice QCD calculation of the universal axial γW-box contribution □_{γW}^{VA} to both superallowed nuclear and neutron beta decays. This contribution emerges as a significant component within the theoretical uncertainties surrounding the extraction of |V_{ud}| from superallowed decays. Our calculation is conducted using two domain wall fermion ensembles at the physical pion mass. To construct the nucleon four-point correlation functions, we employ the random sparsening field technique. Furthermore, we incorporate long-distance contributions to the hadronic function using the infinite-volume reconstruction method. Upon performing the continuum extrapolation, we arrive at □_{γW}^{VA}=3.65(7)_{lat}(1)_{PT}×10^{-3}. Consequently, this yields a slightly higher value of |V_{ud}|=0.973 86(11)_{exp}(9)_{RC}(27)_{NS}, reducing the previous 2.1σ tension with the CKM unitarity to 1.8σ. Additionally, we calculate the vector γW-box contribution to the axial charge g_{A}, denoted as □_{γW}^{VV}, and explore its potential implications.

ACSL4 promotes microglia-mediated neuroinflammation by regulating lipid metabolism and VGLL4 expression.

Acyl-CoA synthetase long-chain family member 4 (ACSL4) is an important isozyme in polyunsaturated fatty acid (PUFA) metabolism. The role of ACSL4 in the lipopolysaccharide (LPS)-induced inflammation of microglia, and the effects of ACSL4-mediated inflammation on the progression of Parkinson's disease (PD) are unknown. In this study, we found that ACSL4 expression was increased after LPS stimulation. Knocking down ACSL4 in microglia decreased proinflammatory cytokine production. Mechanistically, ACSL4 reduced vestigial-like family member 4(VGLL4) expression to promote NF-κB signal transduction; and ACSL4 regulated lipid composition after LPS stimulation. In addition, knocking down ACSL4 alleviated neuroinflammation in a systemic LPS model and acute l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) model. These data revealed ACSL4 to be a novel regulator that promotes microglia-mediated neuroinflammation by regulating VGLL4 expression and lipid metabolism.

Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression.

BACKGROUND: Many neurological diseases involve neuroinflammation, during which overproduction of cytokines by immune cells, especially microglia, can aggregate neuronal death. Ferroptosis is a recently discovered cell metabolism-related form of cell death and RSL3 is a well-known inducer of cell ferroptosis. Here, we aimed to investigate the effects of RSL3 in neuroinflammation and sensitivity of different type of microglia and macrophage to ferroptosis. METHODS: Here, we used quantitative RT-PCR analysis and ELISA analysis to analyze the production of proinflammatory cytokine production of microglia and macrophages after lipopolysaccharides (LPS) stimulation. We used CCK8, LDH, and flow cytometry analysis to evaluate the sensitivity of different microglia and macrophages to RSL3-induced ferroptosis. Western blot was used to test the activation of inflammatory signaling pathway and knockdown efficiency. SiRNA-mediated interference was conducted to knockdown GPX4 or Nrf2 in BV2 microglia. Intraperitoneal injection of LPS was performed to evaluate systemic inflammation and neuroinflammation severity in in vivo conditions. RESULTS: We found that ferroptosis inducer RSL3 inhibited lipopolysaccharides (LPS)-induced inflammation of microglia and peritoneal macrophages (PMs) in a cell ferroptosis-independent manner, whereas cell ferroptosis-conditioned medium significantly triggered inflammation of microglia and PMs. Different type of microglia and macrophages showed varied sensitivity to RSL3-induced ferroptosis. Mechanistically, RSL3 induced Nrf2 protein expression to inhibit RNA Polymerase II recruitment to transcription start site of proinflammatory cytokine genes to repress cytokine transcription, and protect cells from ferroptosis. Furthermore, simultaneously injection of RSL3 and Fer-1 ameliorated LPS-induced neuroinflammation in in vivo conditions. CONCLUSIONS: These data revealed the proinflammatory role of ferroptosis in microglia and macrophages, identified RSL3 as a novel inhibitor of LPS-induced inflammation, and uncovered the molecular regulation of microglia and macrophage sensitivity to ferroptosis. Thus, targeting ferroptosis in diseases by using RSL3 should consider both the pro-ferroptosis effect and the anti-inflammation effect to achieve optimal outcome.

ACSL4 exacerbates ischemic stroke by promoting ferroptosis-induced brain injury and neuroinflammation.

Acyl-CoA synthetase long-chain family member 4 (ACSL4) is an important isozyme for polyunsaturated fatty acids (PUFAs) metabolism that dictates ferroptosis sensitivity. The role of ACSL4 in the progression of ischemic stroke is unclear. Here, we found that ACSL4 expression was suppressed in the early phase of ischemic stroke and this suppression was induced by HIF-1α. Knockdown of ACSL4 protected mice against brain ischemia, whereas, forced overexpression of ACSL4 exacerbated ischemic brain injury. ACSL4 promoted neuronal death via enhancing lipid peroxidation, a marker of ferroptosis. Moreover, knockdown of ACSL4 inhibited proinflammatory cytokine production in microglia. These data identify ACSL4 as a novel regulator of neuronal death and neuroinflammation, and interventions of ACSL4 expression may provide a potential therapeutic target in ischemic stroke.

Development and full validation of an LC-MS/MS methodology to quantify capmatinib (INC280) following intragastric administration to rats.

A highly sensitive, specific and simple LC-MS/MS method for quantification of capmatinib (INC280) in rat plasma was presented. The LC-MS/MS method was validated in terms of specificity and selectivity, linearity, accuracy and precision, matrix effect, extraction recovery, dilution integrity, carryover and stability as per the US Food and Drug Administration's bioanalytical method validation guideline. The validated assay was applied for quantification of capmatinib from a pharmacokinetic study in rats following oral administration at the doses of 1.0, 3.0 and 9.0 mg/kg. The calibration curve ranges from 1 to 2000 ng/ml with desirable linearity and r2 > 0.99. The intra- and inter-batch accuracies were within 99.24-103.59 and 97.76-102.83% with coefficients of variation 5.08-7.36 and 3.18-4.99%, respectively. No significant interference was observed by endogenous peak at the retention time of capmatinib and IS. The assay was free from any matrix effect and showed precise recovery across the calibration curve range, and samples were stable under all experimental conditions. The validated assay was successfully applied to analyze plasma samples of pharmacokinetic study in rat to determine the concentration of capmatinib. In summary, a novel method for analyzing capmatinib in rat plasma has been successfully validated and is now being utilized for quantification of capmatinib from pre-clinical studies.

Stepwise stent deployment technique for tandem intracranial aneurysms: a review of 21 cases.

OBJECTIVES: We performed this study to report our experience using a stepwise stent deployment technique for the treatment of tandem intracranial aneurysms. METHODS: Patients with intracranial tandem aneurysms that were treated with a stepwise stent deployment technique between May 2009 and June 2013 were retrospectively reviewed. RESULTS: Twenty-one patients with 42 tandem aneurysms were identified (11 men, 10 women), with a mean age of 53.7 years (range, 17-82 years). Subarachnoid haemorrhage was confirmed in 12 patients using computed tomography at onset. Complete occlusion was achieved in 20 of the aneurysms (47.6%) after the procedure, neck remnant in 9 (21.4%), and aneurysm remnant in 13 (31.0%). The perioperative complications included in-stent thrombosis in one case and vasospasm in two cases, none of which left a permanent neurological deficit. The modified Rankin Scale (mRS) score at discharge was 0-2 in 20 cases and 3 in one case. The follow-up angiograms available for 17 patients showed complete occlusion in 26 aneurysms, improved in 4, and stable in 4. All of the patients had mRS scores of 0-1 during the clinical follow-up period. CONCLUSIONS: The stepwise stent deployment technique is feasible and helpful in the treatment of intracranial tandem aneurysms. KEY POINTS: • Treating wide-necked intracranial aneurysms with stent-assisted coiling is preferable. • Tandem wide-necked intracranial aneurysms can be treated with a single stent. • Stepwise stent deployment is technically feasible for embolizing tandem intracranial aneurysms.

Biphasic influence of dexamethasone exposure on embryonic vertebrate skeleton development.

Dexamethasone (Dex) has anti-inflammatory and immunomodulatory properties against many conditions. There is a potential teratogenic risk, however, for pregnant women receiving Dex treatment. It has been claimed that Dex exposure during pregnancy could affect osteogenesis in the developing embryo, which still remains highly controversial. In this study, we employed chick embryos to investigate the effects of Dex exposure on skeletal development using combined in vivo and in vitro approach. First, we demonstrated that Dex (10(-8)-10(-6)µmol/egg) exposure resulted in a shortening of the developing long bones of chick embryos, and it accelerated the deposition of calcium salts. Secondly, histological analysis of chick embryo phalanxes exhibited Dex exposure inhibited the proliferation of chondrocytes, increased apoptosis of chondrocytes and osteocytes, and led to atypical arranged hypertrophic chondrocytes. The expression of genes related to skeletogenesis was also analyzed by semi-quantitative RT-PCR. The expression of ALP, Col1a2 and Col2a1 was decreased in the Dex treated phalanxes. A detectable increase was observed in Runx-2 and Mmp-13 expression. We next examined how Dex affected the different stages of skeletogenesis in vitro. Utilizing limb bud mesenchyme micromass cultures, we determined that Dex exposure exerted no effect on apoptosis but impaired chondrogenic cell proliferation. Interestingly, low dose of Dex moderately prompted nodule formation as revealed by alcian blue staining, but higher doses of Dex significantly inhibited similar chondrogenic differentiation. Dex exposure did not induce apoptosis when the chondrogenic precursors were still at the mesenchymal stage, however, cell viability was suppressed when the mesenchyme differentiated into chondrocytes. Alizarin red staining revealed that the capacity to form mineralized bone nodules was correspondingly enhanced as Dex concentrations increased. The mRNA level of Sox-9 was slightly increased in mesenchymal cell mass treated by low concentration of Dex. Mmp-13 expression was obviously up-regulated by Dex in both mesenchymal cells and primary chondrocyte cultures. And Col10a1 expression was also increased by Dex exposure in chondrocyte. In summary, we have revealed that different concentrations of Dex exposure during early gestation could exert a biphasic effect on vertebrate skeletal development.

[Research progress of ICU-acquired weakness].

ICU-acquired weakness (ICU-AW) is a common complication in the intensive care unit (ICU). The occurrence of ICU-AW directly leads to prolonged ICU stays for critically ill patients, and in severe cases, it continues to affect their quality of life even after discharge. This article provides a comprehensive review of the research progress on ICU-AW based on domestic and foreign studies, aiming to provide a scientific overview of ICU-AW, including its definition, pathophysiology, diagnosis, screening tools, influencing factors, and potential intervention strategies, so as to promote timely planning and implementation of relevant screening and intervention measures.

Multifunctionalized Supramolecular Cyclodextrin Additives Boosting the Durability of Aqueous Zinc-Ion Batteries.

The poor cycling stability of aqueous zinc-ion batteries hinders their application in large-scale energy storage due to uncontrollable dendrite growth and harmful hydrogen evolution reactions. Here, we designed and synthesized an electrolyte additive, N-methylimidazolium-ß-cyclodextrin p-toluenesulfonate (NMI-CDOTS). The cations of NMI-CD+ are more easily adsorbed on the abrupt Zn surface to regulate the deposition of Zn2+ and reduce dendrite generation under the combined action of the unique cavity structure with abundant hydroxyl groups and the electrostatic force. Meanwhile, p-toluenesulfonate (OTS-) is able to change the Zn2+ solvation structure and suppress the hydrogen evolution reaction by the strong interaction of Zn2+ and OTS-. Benefiting from the synergistic role of NMI-CD+ and OTS-, the Zn||Zn symmetric cell exhibits superior cycling performance as high as 3800 h under 1 mA cm-2 and 1 mA h cm-2. The Zn||V2O5 full battery also shows a high specific capacity (198.3 mA h g-1) under 2.0 A g-1 even after 1500 cycles, and its Coulomb efficiency is nearly 100% during the charging and discharging procedure. These multifunctional composite strategies open up possibilities for the commercial application of aqueous zinc-ion batteries.

Transcatheter mitral valve-in-valve for pregnancy with anti-phospholipid syndrome: a case report.

BACKGROUND: Perioperative management and cardiac surgery in pregnant women with anti-phospholipid syndrome combined with heart valve disease have been rarely reported. CASE PRESENTATION: We describe a case of transcatheter mitral valve-in-valve replacement in a pregnant woman with bioprosthetic valve failure and anti-phospholipid syndrome at 18 weeks' gestation. The patient underwent a cesarean section delivery at 34 weeks of gestation, resulting in the birth of a healthy baby. CONCLUSIONS: Transapical mitral valve-in-valve surgery resulted in safe maternal and infant outcomes in a pregnant woman with anti-phospholipid syndrome combined with mitral bioprosthetic valve failure. The success of this procedure underscored the importance of multidisciplinary teamwork.

Chromatin target of protein arginine methyltransferases alleviates cerebral ischemia/reperfusion-induced injury by regulating RNA alternative splicing.

RNA splicing is a post-transcriptional event that regulates many physiological and pathological events. However, whether RNA splicing regulates cerebral I/R-induced brain injury remains largely unknown. In this study, we found that the chromatin target of Prmts (CHTOP) was highly expressed in neurons, and anti-inflammatory cytokine interleukin-10 (IL-10) upregulates its expression after ischemia. In addition, overexpression or knockdown of CHTOP alleviated or exacerbated neuronal death in both experimental stroke mice and cultured neurons. Mechanistically, RNA alternative splicing is altered early after oxygen and glucose deprivation/reoxygenation (OGD/R). CHTOP interacted with nuclear speckle-related proteins to regulate alternative mRNA splicing of neuronal survival-related genes after OGD/R. In addition, I/R injury-induced cytokines IL-10 regulate CHTOP-mediated RNA splicing to alleviate ischemic brain injury. Taken together, this study reveals the alteration of RNA splicing after OGD/R and identifies the IL-10-CHTOP-RNA splicing axis as a modulator of brain injury, which may be promising therapeutic targets for ischemic stroke.

Dexmedetomidine suppressed the biological behavior of RAW264.7 cells treated with LPS by down-regulating HOTAIR.

Background: Previous studies have revealed dexmedetomidine have potential protective effects on vital organs by inhibiting the release of inflammatory cytokines. To investigate the effects of dexmedetomidine on sepsis, especially in the initial inflammatory stage of sepsis. RAW264.7 cells were used as the cell model in this study to elucidate the underlying mechanisms. Methods: In this study, we conducted several assays to investigate the mechanisms of dexmedetomidine and HOTAIR in sepsis. Cell viability was assessed using the CCK-8 kit, while inflammation responses were measured using ELISA for IL-1ß, IL-6, and TNF-α. Additionally, we employed qPCR, MeRIP, and RIP to further explore the underlying mechanisms. Results: Our findings indicate that dexmedetomidine treatment enhanced cell viability and reduced the production of inflammatory cytokines in LPS-treated RAW264.7 cells. Furthermore, we observed that the expression of HOTAIR was increased in LPS-treated RAW264.7 cells, which was then decreased upon dexmedetomidine pre-treatment. Further investigation demonstrated that HOTAIR could counteract the beneficial effects of dexmedetomidine on cell viability and cytokine production. Interestingly, we discovered that YTHDF1 targeted HOTAIR and was upregulated in LPS-treated RAW264.7 cells, but reduced in dexmedetomidine treatment. We also found that YTHDF1 increased HOTAIR and HOTAIR m6A levels. Conclusions: Collectively, our results suggest that dexmedetomidine downregulates HOTAIR and YTHDF1 expression, which in turn inhibits the biological behavior of LPS-treated RAW264.7 cells. This finding has potential implications for the prevention and treatment of sepsis-induced kidney injury.

Farrerol Alleviates Cerebral Ischemia-Reperfusion Injury by Promoting Neuronal Survival and Reducing Neuroinflammation.

Ischemia-reperfusion (I/R) injury is a key influencing factor in the outcome of stroke. Inflammatory response, oxidative stress, and neuronal apoptosis are among the main factors that affect the progression of I/R injury. Farrerol (FAR) is a natural compound that can effectively inhibit the inflammatory response and oxidative stress. However, the role of FAR in cerebral I/R injury remains unknown. In this study, we found that FAR reduced brain injury and neuronal viability after cerebral I/R injury. Meanwhile, administration of FAR also reduced the inflammatory response of microglia after brain injury. Mechanistically, FAR treatment directly reduced neuronal death after oxygen glucose deprivation/re-oxygenation (OGD/R) through enhancing cAMP-response element binding protein (CREB) activation to increase the expression of downstream neurotrophic factors and anti-apoptotic genes. Moreover, FAR decreased the activation of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, inhibited microglia activation, and reduced the production of inflammatory cytokines in microglia after OGD/R treatment or LPS stimulation. The compromised inflammatory response by FAR directly promoted the survival of neurons after OGD/R. In conclusion, FAR exerted a protective effect on cerebral I/R injury by directly decreasing neuronal death through upregulating CREB expression and attenuating neuroinflammation. Therefore, FAR could be a potentially effective drug for the treatment of cerebral I/R injury.

CD8+ T cells in brain injury and neurodegeneration.

The interaction between the peripheral immune system and the brain is increasingly being recognized as an important layer of neuroimmune regulation and plays vital roles in brain homeostasis as well as neurological disorders. As an important population of T-cell lymphocytes, the roles of CD8+ T cells in infectious diseases and tumor immunity have been well established. Recently, increasing number of complex functions of CD8+ T cells in brain disorders have been revealed. However, an advanced summary and discussion of the functions and mechanisms of CD8+ T cells in brain injury and neurodegeneration are still lacking. Here, we described the differentiation and function of CD8+ T cells, reviewed the involvement of CD8+ T cells in the regulation of brain injury including stroke and traumatic brain injury and neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), and discussed therapeutic prospects and future study goals. Understanding these processes will promote the investigation of T-cell immunity in brain disorders and provide new intervention strategies for the treatment of brain injury and neurodegeneration.

Unconventional T cells in brain homeostasis, injury and neurodegeneration.

The interaction between peripheral immune cells and the brain is an important component of the neuroimmune axis. Unconventional T cells, which include natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, γδ T cells, and other poorly defined subsets, are a special group of T lymphocytes that recognize a wide range of nonpolymorphic ligands and are the connection between adaptive and innate immunity. Recently, an increasing number of complex functions of these unconventional T cells in brain homeostasis and various brain disorders have been revealed. In this review, we describe the classification and effector function of unconventional T cells, review the evidence for the involvement of unconventional T cells in the regulation of brain homeostasis, summarize the roles and mechanisms of unconventional T cells in the regulation of brain injury and neurodegeneration, and discuss immunotherapeutic potential as well as future research goals. Insight of these processes can shed light on the regulation of T cell immunity on brain homeostasis and diseases and provide new clues for therapeutic approaches targeting brain injury and neurodegeneration.

Serum Cholinesterase, C-reactive Protein, Interleukin 6, and Procalcitonin Levels as Predictors of Mortality in Patients in the Intensive Care Unit.

Objective: The prognostic utility of inflammatory markers in survival has been suggested in patients with cancer; however, evidence on their prognostic value in severely ill patients is very limited. We aimed to explore the prognostic value of cholinesterase (ChE), C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) in predicting mortality in patients from the intensive care unit (ICU). Methods: Serum levels of ChE, CRP, IL-6 and PCT were measured in ICU patients from December 13th, 2019 to June 28th, 2022. We assessed the predictive power of ChE, CRP, IL-6, and PCT using the receiver operating characteristic (ROC) curves. Furthermore, we evaluated their diagnostic accuracy by comparing the areas under the ROC curve (AUCs) along with their corresponding 95% confidence intervals (CIs). The cut-off values were determined to dichotomise these biomarkers, which were then included in multivariable logistic regression models to examine their relationship with ICU mortality. Results: Among 253 ICU patients included in the study, 66 (26%) died during the ICU stay. The AUCs to predict ICU mortality were 0.643 (95% CI, 0.566-0.719), 0.648 (95% CI, 0.633-0.735), 0.643 (95% CI, 0.563-0.723) and 0.735 (95% CI, 0.664-0.807) for ChE, CRP, IL-6 and PCT, respectively. After adjusting for age, sex and disease severity, lower ChE level (<3.668 × 103 U L-1) and higher levels of CRP (>10.546 mg dL-1), IL-6 (>986.245 pg mL-1) and PCT (>0.505 µg L-1) were associated with higher mortality risk, with odd ratios of 2.70 (95% CI, 1.32-5.54), 4.99 (95% CI, 2.41-10.38), 3.24 (95% CI, 1.54-6.78) and 3.67 (95% CI, 1.45-9.95), respectively. Conclusion: ChE, CRP, IL-6 and PCT were independent ICU mortality risk factors in severely ill patients. Elevated PCT levels exhibited better predictive value than the other three biomarkers that were evaluated.

Stochastic cooling notch filter developments for the high-precision spectrometer ring in the high intensity heavy-ion accelerator facility project.

Stochastic cooling of the high-precision spectrometer ring (SRing) at the High Intensity Heavy-Ion Accelerator Facility (HIAF) project in China, which is used mainly for experiments with radioactive fragment beams, is applied to speed up the cooling process of a stored ion beam. In this article, a new coaxial-type notch filter with an amplitude equalizer in the long branch and an optical-type notch filter with phase-stabilized optical fiber are discussed and evaluated for the SRing stochastic cooling system. Both prototypes of coaxial and optical notch filters are fabricated and tested. The minimum notch depth of coaxial and optical notch filters reaches to 26 and 40 dB, respectively. The performance of both coaxial notch filter and optical fiber notch filter is presented in this work. These developments will be used not only for the longitudinal stochastic cooling system but also have potential for the beam feedback system.

The roles of methylprednisolone treatment in patients with COVID-19: A systematic review and meta-analysis.

The roles of methylprednisolone in treatment of patients with COVID-19 remain unclear. The aim of this study was to evaluate the efficacy and safety of methylprednisolone in treatment of COVID-19 patients. PubMed, Cochrane and Web of Science were searched for studies comparing methylprednisolone and no glucocorticoids treatment in patients with COVID-19. Statistical pooling was reported as risk ratio (RR) or mean difference (MD) with corresponding 95 % confidence interval (CI). Thirty-three studies were eligible, including 5 randomized trials and 28 observational studies. Meta-analysis showed that compared with no glucocorticoids, methylprednisolone in treatment of COVID-19 patients was associated with reduced short-term mortality (RR 0.73; 95% CI 0.60-0.89), less need for ICU admission (RR 0.77; 95% CI 0.66-0.91) and mechanical ventilation (RR 0.69; 95% CI 0.57-0.84), increased 28-day ventilator-free days (MD 2.81; 95% CI 2.64-2.97), without increasing risk of secondary infections (RR 1.04; 95% CI 0.82-1.32), but could prolong duration of viral shedding (MD 1.03; 95% CI 0.25-1.82). Subgroup analyses revealed that low-dose (≤2mg/kg/day) methylprednisolone treatment for ≤ 7 days in severe COVID-19 patients was associated with relatively better clinical outcomes, without increasing duration of viral shedding. Compared with no glucocorticoids, methylprednisolone treatment in COVID-19 patients is associated with reduced short-term mortality and better clinical outcomes, without increasing secondary infections, but could slightly prolong duration of viral shedding. Patients with severe COVID-19 are more likely to benefit from short-term low-dose methylprednisolone treatment (1-2 mg/kg/day for ≤ 7 days).

Roles of peripheral immune cells in the recovery of neurological function after ischemic stroke.

Stroke is a leading cause of mortality and long-term disability worldwide, with limited spontaneous repair processes occurring after injury. Immune cells are involved in multiple aspects of ischemic stroke, from early damage processes to late recovery-related events. Compared with the substantial advances that have been made in elucidating how immune cells modulate acute ischemic injury, the understanding of the impact of the immune system on functional recovery is limited. In this review, we summarized the mechanisms of brain repair after ischemic stroke from both the neuronal and non-neuronal perspectives, and we review advances in understanding of the effects on functional recovery after ischemic stroke mediated by infiltrated peripheral innate and adaptive immune cells, immune cell-released cytokines and cell-cell interactions. We also highlight studies that advance our understanding of the mechanisms underlying functional recovery mediated by peripheral immune cells after ischemia. Insights into these processes will shed light on the double-edged role of infiltrated peripheral immune cells in functional recovery after ischemic stroke and provide clues for new therapies for improving neurological function.