Compromised dynamic cerebral autoregulation is a hemodynamic marker for predicting poor prognosis even with good recanalization after endovascular thrombectomy.

PURPOSE: In patients undergoing endovascular thrombectomy (EVT) with acute ischemic stroke (AIS), dynamic cerebral autoregulation (dCA) may minimize neurological injury from blood pressure fluctuations. This study set out to investigate the function of dCA in predicting clinical outcomes following EVT. METHODS: 43 AIS of the middle cerebral or internal carotid artery patients underwent with EVT, and 43 healthy individuals (controls) were enrolled in this case control research. The dCA was evaluated using transcranial Doppler 12 h and five days after EVT. The transfer function analysis was used to derive the dCA parameters, such as phase, gain, and coherence. The modified Rankin scale (mRS) at 3 months after EVT was used to assess the clinical outcomes. Thefavorable outcome group was defined with mRS ≤2 and the unfavorable outcome group was defined with mRS score of 3-6. Logistic regression analysis was performed to determine the risk factors of clinical outcomes. RESULTS: A significant impairment in dCA was observed on the ipsilateral side after EVT, particularly in patients with unfavorable outcomes. After 5 days, the ipsilateral phase was associated with poor functional outcomes (adjusted odds ratio [OR] = 0.911, 95% confidence interval [CI]: 0.854-0.972; P = 0.005) and the area under the curve (AUC) (AUC, 0.878, [95% CI: 0.756-1.000] P < 0.001) (optimal cutoff, 35.0°). Phase change was an independent predictor of clinical outcomes from 12 h to 5 days after EVT (adjusted OR = 1.061, 95% CI: 1.016-1.109, P = 0.008). CONCLUSIONS: dCA is impaired in patients with AIS after EVT. Change in dCA could be an independent factor related to the clinical outcomes.

Impact of immediate postrecanalization cooling on outcome in acute ischemic stroke patients with a large ischemic core: prospective cohort study.

BACKGROUND: Patients with large acute ischemic strokes (AIS) often have a poor prognosis despite successful recanalization due to multiple factors including reperfusion injury. The authors aim to describe our preliminary experience of endovascular cooling in patients with a large AIS after recanalization. METHODS: From January 2021 to July 2022, AIS patients presenting with large infarcts (defined as ASPECTS ≤5 on noncontrast CT or ischemic core ≥50 ml on CT perfusion) who achieved successful recanalization after endovascular treatment were analyzed in a prospective registry. Patients were divided into targeted temperature management (TTM) and non-TTM group. Patients in the TTM group received systemic cooling with a targeted core temperature of 33° for at least 48 h. The primary outcome is 90-day favorable outcome [modified Rankin Scale (mRS) 0-2]. The secondary outcomes are 90-day good outcome (mRS 0-3), mortality, intracranial hemorrhage and malignant cerebral edema within 7 days or at discharge. RESULTS: Forty-four AIS patients were recruited (15 cases in the TTM group and 29 cases in the non-TTM group). The median Alberta Stroke Program Early CT Score (ASPECTS) was 3 (2-5). The median time for hypothermia duration was 84 (71.5-147.6) h. The TTM group had a numerically higher proportion of 90-day favorable outcomes than the non-TTM group (46.7 vs. 27.6%, P=0.210), and no significant difference were found regarding secondary outcomes (all P>0.05). The TTM group had a numerically higher rates of pneumonia (66.7 vs. 58.6%, P=0.604) and deep vein thrombosis (33.3 vs. 13.8%, P=0.138). Shivering occurred in 4/15 (26.7%) of the TTM patients and in none of the non-TTM patients (P=0.009). CONCLUSIONS: Postrecanalization cooling is feasible in patients with a large ischemic core. Future randomized clinical trials are warranted to validate its efficacy.

Night shift work was associated with functional outcomes in acute ischemic stroke patients treated with endovascular thrombectomy.

Objective: This study aimed to explore the impact of late night shift work on the functional outcomes of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT). Methods: Consecutive AIS patients who underwent EVT between June 2019 and June 2021 were enrolled and divided into non-night shift work and night shift work groups based on their occupational histories. The primary outcome was the modified Rankin Scale score defined 3-month functional outcome. The secondary outcomes were 3-month mortality, symptomatic intracerebral hemorrhage (sICH), ICH and early recanalization. Results: A total of 285 patients were enrolled, 35 patients (12.3%) were night shift workers, who were younger (P < 0.001) and had a significantly higher prevalence of smoking (P < 0.001), hyperlipidemia (P = 0.002), coronary heart disease (P = 0.031), and atrial fibrillation (P < 0.001). The 3-month favorable outcomes were achieved in 44.8% and 25.7% of patients in the non-night shift work and night shift work groups, respectively (adjusted odds ratio [OR]: 0.24, 95% CI: 0.10-0.57; adjusted P = 0.001). No difference was found in 3-month mortality (adjusted OR: 0.43; 95% CI: 0.14-1.25, adjusted P = 0.121), rates of ICH (adjusted OR: 0.73; 95% CI: 0.33-1.60; adjusted P = 0.430), sICH (adjusted OR: 0.75; 95% CI: 0.34-1.67; adjusted P = 0.487), or early successful recanalization (adjusted OR: 0.42; 95% CI: 0.12-1.56; adjusted P = 0.197). These results were consistent after PSM analysis. Conclusion: Our findings suggest that late night shift work is significantly associated with unfavorable outcomes in patients with AIS after EVT.

HBV promotes its replication by up-regulating RAD51C gene expression.

Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), pegylated-interferon-α(PEG-IFNα) and long-term nucleos(t)ide analogs (NUCs) are mainly drugs used to treat HBV infection, but the effectiveness is unsatisfactory in different populations, the exploration of novel therapeutic approaches is necessary. RAD51C is associated with DNA damage repair and plays an important role in the development and progression of tumors. Early cDNA microarray results showed that RAD51C expression was significantly increased in HBV-infected HCC cells, however, the relationship between HBV infection and abnormal expression of RAD51C has not been reported. Therefore, we conducted RT-PCR, western blot, Co-immunoprecipitation(Co-IP), and immunofluorescence(IF) to detect HBV-RAD51C interaction in RAD51C overexpression or interfering HCC cells. Our results showed that RAD51C and HBV X protein(HBX) produced a direct interaction in the nucleus, the HBV infection of HCC cells promoted RAD51C expression, and the increased expression of RAD51C promoted HBV replication. This indicated that RAD51C is closely related to the occurrence and development of HCC caused by HBV infection, and may bring a breakthrough in the the prevention and treatment study of HCC.

Early venous filling after mechanical thrombectomy in acute ischemic stroke due to large vessel occlusion in anterior circulation.

BACKGROUND: The significance of early venous filling (EVF) after mechanical thrombectomy (MT) in acute ischemic stroke (AIS) is not fully understood. In this study, we aimed to investigate the impact of EVF after MT. METHODS: From January 2019 to May 2022, AIS patients with successful recanalization (modified Thrombolysis in Cerebral Infarction score (mTICI) ≥2b) after MT were retrospectively reviewed. EVF was evaluated on final digital subtraction angiography runs after successful recanalization and was categorized into phase subgroups (arterial phase and capillary phase) and pathway subgroups (cortical veins subgroup and thalamostriate veins subgroup), respectively. The impact of EVF subgroups on functional outcomes after successful recanalization were both investigated. RESULTS: A total of 349 patients achieving successful recanalization after MT were included, including 45 patients in the EVF group and 304 patients in the non-EVF group. Multivariable logistic regression analysis showed the EVF group had a higher rate of intracranial hemorrhage (ICH; 66.7% vs 22%, adjusted odds ratio (aOR) 6.805, 95% CI 3.389 to 13.662, P<0.001), symptomatic ICH (sICH; 28.9% vs 4.9%, aOR 6.011, 95% CI 2.493 to 14.494, P<0.001) and malignant cerebral edema (MCE; 20% vs 6.9%, aOR 2.682, 95% CI 1.086 to 6.624, P=0.032) than the non-EVF group. Furthermore, the cortical veins subgroup of EVF had a higher rate of mortality than the thalamostriate veins subgroup (37.5% vs 10.3%, P=0.029). CONCLUSIONS: EVF is independently associated with ICH, sICH and MCE after successful recanalization of MT, but not with favorable outcome and mortality.

Malignant Middle Cerebral Artery Infarction during Early versus Late Endovascular Treatment in Acute Ischemic Stroke.

INTRODUCTION: Endovascular treatment (EVT) performed in the early time window has been shown to decrease the incidence of malignant middle cerebral artery infarction (MMI). However, the incidence of MMI in patients undergoing EVT during the late time window is unclear. This study aimed to investigate the prevalence of MMI in patients undergoing late EVT and compare it with that in patients undergoing early EVT. METHODS: We retrospectively analyzed consecutive patients with anterior large vessel occlusion stroke who underwent EVT at Xuanwu Hospital between January 2013 and June 2021. Eligible patients were divided into early EVT (within 6 h) and late EVT (6-24 h) groups according to the time from their stroke onset to puncture and compared. The occurrence of MMI post-EVT was the primary outcome. RESULTS: A total of 605 patients were recruited, of whom 300 (50.4%) underwent EVT within 6 h and 305 (49.6%) underwent EVT within 6-24 h. A total of 119 patients (19.7%) developed MMI. 68 patients (22.7%) in the early EVT group and 51 patients (16.7 %) in the late EVT group developed MMI (p = 0.066). After adjusting for covariate variables, late EVT was independently associated with a lower incidence of MMI (odds ratio, 0.404; 95% confidence interval, 0.242-0.675; p = 0.001). CONCLUSION: MMI is not an uncommon phenomenon in the modern thrombectomy era. Compared with the early time window, patients selected by stricter radiological criteria to undergo EVT in the late time window are independently associated with a lower incidence of MMI.

Outcome after endovascular treatment for acute ischemic stroke by underlying etiology: Tertiary experience and meta-analysis.

Objective: To investigate the effect of two major etiologies [intracranial atherosclerotic stenosis (ICAS) and cardioembolism (CE])] on outcomes of acute ischemic stroke (AIS) patients due to large vessel occlusion (LVO) after endovascular thrombectomy (EVT). Methods: Anterior circulation AIS patients receiving EVT were retrospectively analyzed. Clinical and laboratory data were collected. Clinical outcomes including favorable outcome (90-day modified Rankin Scale 0-2), mortality, intracranial hemorrhage (ICH) and symptomatic ICH (sICH) were compared. A systematic review and meta-analysis was also performed. Results: A total of 302 AIS patients were included and divided into the ICAS group (86 patients) and the CE group (216 patients). Patients in the ICAS group were younger (62[18.0] vs. 68[19.0] years, p < 0.001), more likely to have smoking (52.3% vs. 26.9%, p < 0.001) and drinking (52.3% vs. 23.1%, p < 0.001) history, and more frequently required rescue therapy (80.2% vs. 4.6%, p < 0.001) compared to the CE group. However, favorable outcome (aOR 0.722, 95%CI 0.372-1.402, p = 0.336) and mortality (aOR 1.522, 95%CI 0.606-3.831, p = 0.371) were not significantly different between the two groups before and after adjustment. The incidence of sICH and ICH were comparable between the two groups before and after adjustment. Systematic review and meta-analysis consisted of 8 eligible studies (7 previous studies and this current study), incorporating 552 ICAS patients and 1,402 CE patients. Favorable outcome was slightly more likely in the ICAS group compared to the CE group (54.2% vs. 46.3%, OR 1.40, 95%CI 1.00-1.96, I 2 = 53.2%). Moreover, the ICAS group had a lower rate of mortality (14.3% vs. 22.2%, OR 0.63, 95%CI 0.46-0.87, I 2 = 0.0%) and ICH (19.5% vs. 31.9%, OR 0.60, 95%CI 0.42-0.84, I 2 = 0.0%) than the CE group, while the two groups were similar in sICH rate (5.9% vs. 6.7%, OR 0.94, 95%CI 0.55-1.60, I 2 = 6.3%). Conclusion: Etiology was not considered as an important factor in functional outcome, despite the differences in baseline characteristics and technical EVT approach. The current study of anterior circulation AIS-LVO patients supports that outcomes for those with ICAS are not significantly different from those with CE.

Mortality of myasthenia gravis: a national population-based study in China.

OBJECTIVE: As a potentially life-threatening condition, myasthenia gravis (MG) has limited epidemiological studies on mortality. We aim to provide demographic distribution, geographical variation, and temporal trend of MG-related mortality in China. METHODS: The national population-based analysis was conducted based on records derived from the National Mortality Surveillance System of China. All deaths related to MG were identified from 2013 to 2020, and MG-related mortality was evaluated by sex, age, location, and year. RESULTS: A total of 4224 deaths were related to MG during 2013-2020, and the median age at death of MG was 59.45 years, significantly lower than that in the general population (75.47 years, P < 0.05). In 2020, the age-standardized mortality rate of MG was 1.86 per million people and markedly higher in males than in females (2.37 vs. 1.31 per million). The mortality rate per million was lower than 1 in young children, peaking at 2.83 only in males (vs. 0.36 in females) aged 10-19 years, and substantially increased with age, reaching the highest rate of 13.31 for males and 10.58 for females aged 80 years and older. Geographical disparity across China was observed with the highest age-standardized mortality rate in Southwest (2.53 per million). From 2013 to 2020, MG-related mortality rate showed an increasing trend with the average annual percentage change of 3.5% (95% CI, 1.4-5.6). The notable increases occurred in age 10-19 years and over 70 years. INTERPRETATION: In China, MG-related mortality was notably high among adolescent males and the elderly. The increasing death burden due to MG highlight challenges to disease management.

Multimodal CT imaging characteristics may predict post-reperfusion infarct volume in wake-up stroke patients.

Background: Accurate prediction of subsequent infarct volume in acute ischemic stroke (AIS) patients helps determine appropriate interventions and prognosis. The objectives are to assess whether early multimodal CT imaging characteristics of wake-up stroke (WUS) patients could predict post-reperfusion infarct volume and evaluate the accuracy of baseline infarct and penumbra volumes for predicting follow-up infarct volume. Methods: This retrospective study included WUS patients, last seen well (LSW) >6 h, with multimodal CT imaging at baseline. Baseline non-contrast CT (NCCT) and CT perfusion were analyzed using RAPID software, and CT angiography using maximum intensity projection. Post-reperfusion infarct volume was assessed at 24-h following reperfusion on magnetic resonance diffusion-weighted imaging (DWI). Patients were stratified by treatment module for analyses. Results: Of 34 eligible patients, 9 (26.5%) received intravenous recombinant tissue plasminogen activator (r-tPA) alone and 25 (73.5%) received both endovascular thrombectomy (EVT) and r-tPA. All patients had a strong correlation between baseline NCCT alberta stroke program early CT score, clot burden score (CBS), Tan score, infarct volume, penumbra volume with 24-h post-reperfusion infarct volume (respectively, r=0.172, P=0.015; r=0.118, P=0.047; r=0.149, P=0.024; r=0.311, P=0.001 and r=0.120; P=0.045). Among reperfusion therapies, WUS patients who received EVT had a significantly lower 24-h post-reperfusion infarct volume and had a significant difference between baseline infarct volume and 24-h post-reperfusion infarct volume (respectively, 82 vs. 14, P=0.032 and 47 vs. 14, P=0.04). Conclusions: Primarily obtained multimodal CT imaging characteristics may predict post-reperfusion infarct volume in WUS patients, and those who underwent EVT had a significantly lower post-reperfusion infarct volume.

A nomogram for predicting malignant cerebral artery infarction in the modern thrombectomy era.

Objective: This study aimed to develop and validate a nomogram to predict malignant cerebral artery infarction (MMI) after endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) in the modern thrombectomy era. Methods: We retrospectively analyzed data from a prospective cohort of consecutive patients with AIS who underwent EVT at Xuanwu hospital between January 2013 and June 2021. A multivariable logistic regression model was employed to construct the nomogram for predicting MMI after EVT. The discrimination and calibration of the nomogram were assessed both in the derivation and validation cohorts. Results: A total of 605 patients were enrolled in this study, with 425 in the derivation cohort and 180 in the validation cohort. The nomogram was developed based on admission systolic blood pressure (SBP), the National Institute of Health Stroke Score (NIHSS), the Alberta Stroke Program Early Computed Tomography Score (ASPECTS), vessel occlusion site, EVT time window, and recanalization status. The nomogram displayed good discrimination with the area under the receiver operating characteristics (ROCs) curve (AUC) of 0.783 [95% confidence interval (CI), 0.726-0.840] in the derivation cohort and 0.806 (95% CI, 0.738-0.874) in the validation cohort. The calibration of the nomogram was good as well, with the Hosmer-Lemeshow test of p = 0.857 in the derivation cohort and p = 0.275 in the validation cohort. Conclusion: In the modern thrombectomy era, a nomogram containing admission SBP, NIHSS, ASPECTS, vessel occlusion site, EVT time window, and recanalization status may predict the risk of MMI after EVT in patients with AIS.

Analysis of Common Respiratory Infected Pathogens in 3100 Children after the Coronavirus Disease 2019 Pandemic.

OBJECTIVE: To investigate the epidemiological features in children after the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This study collected throat swabs and serum samples from hospitalized pediatric patients of Renmin Hospital of Wuhan University, Wuhan, Hubei province, China before and after the COVID-19 pandemic. Respiratory infected pathogens [adenovirus (ADV), influenza virus A/B (Flu A/B), parainfluenza virus 1/2/3 (PIV1/2/3), respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and Chlamydia pneumoniae (CP)] were detected. The pathogens, age, and gender were used to analyze the epidemiological features in children after the COVID-19 pandemic. RESULTS: The pathogen detection rate was significantly higher in females than in males (P<0.05), and the infection of PIV1 and MP was mainly manifested. After the COVID-19 pandemic, PIV1, PIV3, RSV, and MP had statistically different detection rates among the age groups (P<0.05), and was mainly detected in patients aged 0-6 years, 0-3 years, 0-3 years, and 1-6 years, respectively. When comparing before the COVID-19 pandemic, the total detection rate of common respiratory pathogens was lower (P<0.05). Except for the increase in the detection rate of PIV1 and CP, the infection rate of other pathogens had almost decreased. CONCLUSION: The prevention and control measures for the COVID-19 pandemic effectively changed the epidemiological features of common respiratory tract infectious diseases in pediatric children.

Alterations of inflammatory cytokines in super-acute stroke patients and the potential pathogenesis.

BACKGROUND: Sufficient understanding of the systemic inflammatory response after stroke will make the therapeutic strategy targeting inflammation more feasible. Here, we aimed to identify the globally alterations of circulating cytokines in super-acute ischemic stroke (AIS). METHODS: A broad panel of 65 cytokines was measured in the plasma of twenty-eight AIS patients within 6 h after stroke onset (n = 28), cerebral hemorrhagic patients (n = 28) and healthy controls (n = 18). The diagnostic power of the candidate cytokines and their relationship with the number of lymphocytes and neutrophils were analyzed by receiver operating characteristic (ROC) and spearman rank correlation respectively. RESULTS: The expression level of plasma IL-1beta, IL-2, IL-2R, IL-5, IL-10, CD40L, HGF, MIP-3alpha and MMP-1 were obviously up-regulated, while IL-16 was down-regulated in AIS patients compared to healthy controls. Among them, IL-2R, IL-10, IL-16, MIP-3alpha, and MMP-1 were specially altered in AIS patients, while IL-1beta, IL-2, IL-5, CD40L and HGF were elevated simultaneously in AIS and hemorrhagic stroke patients. Interestingly, IL-6 and TNF-beta were found to be key facytors among the 65 cytokines to distinguish hemorrhage from ischemia. Furthermore, IL-1beta, IL-16, CD40L and HGF were obviously correlated with the number of lymphocytes, and IL-1beta and IL-16 were significantly associated with the number of neutrophils in AIS patients. These results suggest that lymphocytes and neutrophils associated inflammation may play a pivotal role in AIS. CONCLUSIONS: Importantly, except for some mutual pathological processes, AIS and hemorrhage had their own distinctive pathogenesis, and transformation of this knowledge to further research may provide novel treatment strategy for AIS.

TET1s deficiency exacerbates oscillatory shear flow-induced atherosclerosis.

Background: TET1 has been implicated in regulating inflammation and cardiovascular disease, but a newly discovered short isoform of TET1 (termed TET1s) exhibits higher expression in adult tissues than full-length TET1. However, the precise role of TET1 in cardiovascular disease remains undefined. Methods and Results: Based on TET1-/- knockout mice (with deletion of both TET1 and TET1s ) and TET1cs/cs mice (with deletion of only TET1), we found that TET1s deletion in TET1-/- mice resulted in more serious atherosclerotic lesions in the whole aorta than TET1cs/cs in the ApoE-/- background mice fed a high-fat diet. Atherosclerotic lesions with Oil red staining were dramatically localized in the aortic arch, abdominal aorta and ligated LCA, where they were exposed to OSS. Furthermore, the OSS-induced depression of TET1s in vitro and in vivo increased inflammatory cell and red blood cell infiltration into the subendothelial layer by impairing the vascular intimal barrier. TET1s upregulation enhanced vascular endothelial barrier function by increasing gap protein connexin 40 (CX40) expression as measured by RNA-seq and was confirmed by CX40 knockdown. TET1s interaction with Sin3a increased the global and CX40 promoter histone H3K27 acetylation levels, but not DNA methylation, to induce CX40 expression. Conclusions: These data demonstrate the unexpected discovery that laminar shear stress induces TET1s expression to protect the vascular endothelial barrier by increasing CX40 expression in ECs and that TET1s overexpression may be the core step for OSS-induced atherosclerosis therapy.

Temporal trend and attributable risk factors of stroke burden in China, 1990-2019: an analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Understanding the temporal trend of the disease burden of stroke and its attributable risk factors in China, especially at provincial levels, is important for effective prevention strategies and improvement. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is to investigate the disease burden of stroke and its risk factors at national and provincial levels in China from 1990 to 2019. METHODS: Following the methodology in the GBD 2019, the incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of stroke cases in the Chinese population were estimated by sex, age, year, stroke subtypes (ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage), and across 33 provincial administrative units in China from 1990 to 2019. Attributable mortality and DALYs of underlying risk factors were calculated by a comparative risk assessment. FINDINGS: In 2019, there were 3·94 million (95% uncertainty interval 3·43-4·58) new stroke cases in China. The incidence rate of stroke increased by 86·0% (73·2-99·0) from 1990, reaching 276·7 (241·3-322·0) per 100 000 population in 2019. The age-standardised incidence rate declined by 9·3% (3·3-15·5) from 1990 to 2019. Among 28·76 million (25·60-32·21) prevalent cases of stroke in 2019, 24·18 million (20·80-27·87) were ischaemic stroke, 4·36 million (3·69-5·05) were intracerebral haemorrhage, and 1·58 million (1·32-1·91) were subarachnoid haemorrhage. The prevalence rate increased by 106·0% (93·7-118·8) and age-standardised prevalence rate increased by 13·2% (7·7-19·1) from 1990 to 2019. In 2019, there were 2·19 million (1·89-2·51) deaths and 45·9 million (39·8-52·3) DALYs due to stroke. The mortality rate increased by 32·3% (8·6-59·0) from 1990 to 2019. Over the same period, the age-standardised mortality rate decreased by 39·8% (28·6-50·7) and the DALY rate decreased by 41·6% (30·7-50·9). High systolic blood pressure, ambient particulate matter pollution exposure, smoking, and diet high in sodium were four major risk factors for stroke burden in 2019. Moreover, we found marked differences of stroke burden and attributable risk factors across provinces in China from 1990 to 2019. INTERPRETATION: The disease burden of stroke is still severe in China, although the age-standardised incidence and mortality rates have decreased since 1990. The stroke burden in China might be reduced through blood pressure management, lifestyle interventions, and air pollution control. Moreover, because substantial heterogeneity of stroke burden existed in different provinces, improved health care is needed in provinces with heavy stroke burden. FUNDING: National Key Research and Development Program of China and Taikang Yicai Public Health and Epidemic Control Fund.

Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors.

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.

Impact of the COVID-19 pandemic on the process and outcome of thrombectomy for acute ischemic stroke.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic is still spreading across the world. Although the pandemic has an all-round impact on medical work, the degree of its impact on endovascular thrombectomy (EVT) for patients with acute ischemic stroke (AIS) is unclear. METHODS: We continuously included AIS patients with large artery occlusion who underwent EVT in a comprehensive stroke center before and during the Wuhan shutdown. The protected code stroke (PCS) for screening and treating AIS patients was established during the pandemic. The efficacy and safety outcomes including the rate of successful reperfusion (defined as modified Thrombolysis In Cerebral Infarction (mTICI) graded 2b or 3) and time intervals for reperfusion were compared between two groups: pre-pandemic and pandemic. RESULTS: A total of 55 AIS patients who received EVT were included. The baseline characteristics were comparable between the two groups. The time from hospital arrival to puncture (174 vs 125.5 min; p=0.002) and time from hospital arrival to reperfusion (213 vs 172 min; p=0.047) were significantly prolonged in the pandemic group compared with the pre-pandemic group. The rate of successful reperfusion was not significantly different between the two groups (85.7% (n=18) vs 88.2% (n=30); OR 0.971, 95% CI 0.785 to 1.203; p=1.000). CONCLUSION: The results of this study suggest a proper PCS algorithm which combines the COVID-19 screening and protection measures could decrease the impact of the disease on the clinical outcomes of EVT for AIS patients to the lowest extent possible during the pandemic.

Major vault protein plays important roles in viral infection.

Viral replication and related protein expression inside the host cells, and host antiviral immune responses can lead to the occurrence of diverse diseases. With the outbreak of viral infection, a large number of newly diagnosed and died patients infected with various viruses are still reported every year. Viral infection has already been one of the major global public health issues and lead to huge economic and social burdens. Studying of viral pathogenesis is a very important way to find methods for prevention, diagnosis, and cure of viral infection; more evidence has confirmed that major vault protein (MVP) is closely associated with viral infection and pathogenesis, and this review is intended to provide a broad relationship between viruses and MVP to stimulate the interest of related researchers.

The stability of Magoh and Y14 depends on their heterodimer formation and nuclear localization.

Reduced expression of the Y14 gene is a cause of Thrombocytopenia-absent radius (TAR) syndrome. This gene contains a conserved RNA recognition motif (RRM) in the central region and nuclear localization/export sequences (NLS/NES) in the N-terminal. Y14 and Magoh proteins form tight heterodimers and are the core of exon junction complexes (EJCs), which mediate various processes of mRNA metabolism after transcription. In this report, we found that protein expression levels of exogenously expressed Magoh L136R and Y14 L118R (leucine-to-arginine substitution at amino acid residue 136 and 118 respectively, that results in the formation of the complex being lost) are lower than their wild-types. This reduction is likely caused by protein levels, as no difference in mRNA levels was detected. Meanwhile, a cycloheximide chase assay determined that the degradation rates of Magoh L136R and Y14 L118R were faster than their wild-types. Both Y14 L118R and Magoh L136R lost the ability to form heterodimers with corresponding wild-type proteins. However, Y14 L118R is able to still localize in the nucleus which causes the stability of Y14 L118R to be higher than Magoh L136R. These results reveal that the stability of Magoh and Y14 is not only dependent on the heterodimer structure, but also dependent on nuclear localization.