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Background This study aimed to analyze the effects of ruxolitinib on children with secondary hemophagocytic lymphohistiocytosis (HLH). Methods Eleven pediatric patients diagnosed with HLH and treated with ruxolitinib (ruxolitinib group: group R) between November 2017 and August 2018 were retrospectively analyzed. Eleven age-matched pediatric patients with HLH undergoing conventional treatment (control group: group C) during the same period were also analyzed. Results In group R, three patients who did not respond to methylprednisolone (MP) pulse and intravenous immunoglobulin (IVIG) therapies were treated with Ruxolitinib and their temperature decreased to normal levels. Four patients had normal temperature after conventional treatment (dexamethasone and etoposide, with or without cyclosporine A), but they had severe organ involvement, including obvious yellowing of the skin, increased liver enzyme levels and neuropsychiatric symptoms, and they were all ameliorated with ruxolitinib treatment. Four patients were relieved with ruxolitinib therapy alone. In group C, the body temperatures of eleven patients decreased to normal levels after conventional treatment. The body temperature of group R patients decreased to normal levels more rapidly than that of group C patients. The glucocorticoid dosage in group R was significantly lower than that in group C. Both groups were followed-up for 2–2.5 years. No obvious adverse drug reactions to ruxolitinib were observed during treatment and follow-up. Conclusion Ruxolitinib might be an effective drug in controlling body temperature and reducing inflammation indicators. It might be a potential replacement for glucocorticoid therapy for HLH treatment in children, thereby reducing or avoiding glucocorticoid-related adverse reactions.

BackgroundBrain structural alterations and their clinical significance of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) have not been determined.MethodsWe recruited 35 MOGAD, 38 aquaporin 4 antibody positive neuromyelitis optica spectrum diseases (AQP4+ NMOSD), 37 multiple sclerosis (MS) and 60 healthy controls (HC) who underwent multimodal brain MRI from two centres. Brain lesions, volumes of the whole brain parenchyma, cortical and subcortical grey matter (GM), brainstem, cerebellum and cerebral white matter (WM) and diffusion measures (fractional anisotropy, FA and mean diffusivity, MD) were compared among the groups. Associations between the MRI measurements and the clinical variables were assessed by partial correlations. Logistic regression was performed to differentiate MOGAD from AQP4+ NMOSD and MS.ResultsIn MOGAD, 19 (54%) patients had lesions on MRI, with cortical/juxtacortical (68%) as the most common location. MOGAD and MS showed lower cortical and subcortical GM volumes than HC, while AQP4+ NMOSD only demonstrated a decreased cortical GM volume. MS demonstrated a lower cerebellar volume, a lower FA and an increased MD than MOGAD and HC. The subcortical GM volume was negatively correlated with Expanded Disability Status Scale in MOGAD (R=−0.51; p=0.004). A combination of MRI and clinical measures could achieve an accuracy of 85% and 93% for the classification of MOGAD versus AQP4+ NMOSD and MOGAD versus MS, respectively.ConclusionMOGAD demonstrated cortical and subcortical atrophy without severe WM rarefaction. The subcortical GM volume correlated with clinical disability and a combination of MRI and clinical measures could separate MOGAD from AQP4+ NMOSD and MS.

Background Rituximab (RTX) is a mouse-human chimeric anti-CD20 monoclonal antibody and has been increasingly used for preventing relapses in myasthenia gravis (MG). However, the appropriate dose for maximizing the beneficial effects in refractory MG with acetylcholine receptor (AChR) autoantibody is a long-standing and critical debating question. Methods We performed a meta-analysis to evaluate the efficacy and safety of the different doses of RTX in 260 refractory AChR-MG patients. Results The AChR-MG patients were divided into low or routine RTX dose groups. An overall proportion of 77% (p = 0.000) AChR-MG patients demonstrated improved clinical status as indicated by the Myasthenia Gravis Foundation of America post-intervention scale (MGFA-PIS). There were 77.1% patients showed improved clinical status in lower dose of RTX group (p = 0.000) and 76.8% in routine protocol group (p = 0.000). Although we found there was no significant difference in the proportion of AChR-MG patients with improved clinical status or adverse reactions between the two groups, adverse reactions might be lower in the lower dose RTX group. Conclusion Most of refractory MG patients with anti-AChR autoantibody were well responsive and tolerated to RTX treatment. Repeated application of lower dose of RTX was effective and might be more appropriate for refractory AChR-MG patients with potential lower side effects.

The atmospheric CO2 concentration continues a rapid increase to its current record high value of 416 ppm for the time being. It calls for advanced CO2 capture technologies. One of the attractive technologies is physical adsorption-based separation, which shows easy regeneration and high cycle stability, and thus reduced energy penalties and cost. The extensive research on this topic is evidenced by the growing body of scientific and technical literature. The progress spans from the innovation of novel porous adsorbents to practical separation practices. Major CO2 capture materials include the most widely used industrially relevant porous carbons, zeolites, activated alumina, mesoporous silica, and the newly emerging metal-organic frameworks (MOFs) and covalent-organic framework (COFs). The key intrinsic properties such as pore structure, surface chemistry, preferable adsorption sites, and other structural features that would affect CO2 capture capacity, selectivity, and recyclability are first discussed. The industrial relevant variables such as particle size of adsorbents, the mechanical strength, adsorption heat management, and other technological advances are equally important, even more crucial when scaling up from bench and pilot-scale to demonstration and commercial scale. Therefore, we aim to bring a full picture of the adsorption-based CO2 separation technologies, from adsorbent design, intrinsic property evaluation to performance assessment not only under ideal equilibrium conditions but also in realistic pressure swing adsorption processes.

Traumatic brain injury-induced coagulopathy (TBI-IC) causes life-threatening secondary intracranial bleeding. Its pathogenesis differs mechanistically from that of coagulopathy arising from extracranial injuries and hemorrhagic shock, but it remains poorly understood. We report results of a study designed to test the hypothesis that von Willebrand factor (VWF) released during acute TBI is intrinsically hyperadhesive because its platelet-binding A1-domain is exposed and contributes to TBI-induced vascular leakage and consumptive coagulopathy. This hyperadhesive VWF can be selectively blocked by a VWF A2-domain protein to prevent TBI-IC and to improve neurological function with a minimal risk of bleeding. We demonstrated that A2 given through intraperitoneal injection or IV infusion reduced TBI-induced death by >50% and significantly improved the neurological function of C57BL/6J male mice subjected to severe lateral fluid percussion injury. A2 protected the endothelium from extracellular vesicle-induced injury, reducing TBI-induced platelet activation and microvesiculation, and preventing a TBI-induced hypercoagulable state. A2 achieved this therapeutic efficacy by specifically blocking the A1 domain exposed on the hyperadhesive VWF released during acute TBI. These results suggest that VWF plays a causal role in the development of TBI-IC and is a therapeutic target for this life-threatening complication of TBI.

Recent evidence highlights the role of adiponectin in the pathophysiology of autism spectrum disorder (ASD), yielding conflicting results. The aims of this study were (1) To assess the adiponectin levels of children with ASD and typical developing (TP); (2) To investigate the relationship between adiponectin levels and symptom severity of children with ASD. This is a single-center cross-sectional study from China. From December 2017 to November 2019, first-diagnosis and drug-naive children with ASD were included. Same TP children who were matched with clinical groups by gender and age were included as the control group. The enzyme-linked immunosorbent assay (ELISA) kit was used to determine serum concentrations of adiponectin. We recorded 176 children (88 were ASD and 88 were TP children) and 77.3% (n = 136) were boys and the mean age was 4.3 years (standard deviations [S.D.]: 1.2). The mean (S.D.) levels of adiponectin were 9.01(2.19) and 11.55(2.32) μg/ml for those with ASD and TP subjects. The difference between those two groups was significant (t = 7.169, p

Background and purpose: Subtyping relapsing–remitting multiple sclerosis (RRMS) patients may help predict disease progression and triage patients for treatment. We aimed to subtype RRMS patients by structural MRI and investigate their clinical significances. Methods: 155 relapse-remitting MS (RRMS) and 210 healthy controls (HC) were retrospectively enrolled with structural 3DT1, diffusion tensor imaging (DTI) and resting-state functional MRI. Z scores of cortical and deep gray matter volumes (CGMV and DGMV) and white matter fractional anisotropy (WM-FA) in RRMS patients were calculated based on means and standard deviations of HC. We defined RRMS as “normal” (− 2 < z scores of both GMV and WM-FA), DGM (z scores of DGMV < − 2), and DGM-plus types (z scores of DGMV and [CGMV or WM-FA] < − 2) according to combinations of z scores compared to HC. Expanded disability status scale (EDSS), cognitive and functional MRI measurements, and conversion rate to secondary progressive MS (SPMS) at 5-year follow-up were compared between subtypes. Results: 77 (49.7%) patients were “normal” type, 37 (23.9%) patients were DGM type and 34 (21.9%) patients were DGM-plus type. 7 (4.5%) patients who were not categorized into the above types were excluded. DGM-plus type had the highest EDSS. Both DGM and DGM-plus types had more severe cognitive impairment than “normal” type. Only DGM-plus type showed decreased functional MRI measures compared to HC. A higher conversion ratio to SPMS in DGM-plus type (55%) was identified compared to “normal” type (14%, p < 0.001) and DGM type (20%, p = 0.005). Conclusion: Three MRI-subtypes of RRMS were identified with distinct clinical and imaging features and different prognosis.

The molecular features of hepatitis B virus (HBV) infection, eradication, and pathogenesis are poorly understood, partly due to the lack of an adequate animal model that faithfully reproduces the course of infection. Although Tupaia belangeri were previously recognized as HBV-susceptible animals, the course of infection in adult tupaias remains obscure. Herein, we performed a longitudinal study and demonstrated that adult tupaias were efficiently infected (90% infection rate) with 108 copies of the HBV genome. HBV replicated vigorously, produced high levels of covalently closed circular DNA (cccDNA) in hepatocytes, and released hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAg), and HBV DNA into the serum at day 9 post-inoculation (p.i.), which then decreased on day 15 p.i. The kinetics were consistent with the expression of liver HBsAg and HBeAg, as determined with immunohistochemistry. The viral products in serum at day 9 and 15 p.i. represented de novo synthesized viral products, as treatment with a viral entry inhibitor completely abolished these products from the serum. Viral clearance and serological conversion occurred at day 21 p.i. and were accompanied by elevated alanine transaminase (ALT) levels and liver pathology, such as inflammatory infiltration and hepatocyte ballooning degeneration. Although ALT levels eventually returned to normal levels by day 42 p.i., the liver pathology persisted until at least day 120 p.i. The HBV infection process in tupaia, therefore, exhibits features similar to that of human acute HBV infection, including viral replication, viral eradication, ALT elevation, and liver pathology. Thus, adopting the tupaia model to study host-HBV interactions presents an important advance which could facilitate further investigation and understanding of human HBV infection, especially for features like cccDNA that current small-animal models cannot effectively model.

The challenge for current lithium-ion capacitors (LICs) to obtain high energy density is to improve the energy storage performance at high rates. The key lies in balancing the kinetics mismatch between battery-type anode and capacitor-type cathode as well as ensuring high capacity contribution of electrodes. To this end, graphene aerogel (GA) supported high-capacity silicon (Si) nanoparticles 3D conductive framework is designed as anode for LICs, overcoming the notably volume expansion (300%) of Si and contributing to the high energy density. More importantly, a dominating capacitive mechanism lies in the intercalation process of Si@GA anode, which enables its fast charge–discharge capability. So as to match the high capacity anodes, boron carbonitride nanotubes (BCNNTs) with high-rate pseudocapacitive behavior and desirable capacity are used as cathode to construct a novel LIC with high energy density. Benefiting from high-rate capabilities of both anode and cathode, the rational designed 4.5 V Si@GA//BCNNTs LIC exhibits excellent electrochemical performance, delivering a maximum energy density of 197.3 W h kg−1 at the power density of 225 W kg−1. This strategy may widen the application for materials with volume expansion issues and many other material systems in pseudocapacitive advanced high-rate devices.

The challenge for surgical management of a pancreatic pseudocyst during esophagectomy is not only to preserve the gastric wall, but also to avoid forming a pancreatic fistula. We report a case of a 54-year-old man with an esophageal squamous cell carcinoma who had a synchronous pancreatic pseudocyst. Roux-en-Y cystojejunostomy was performed during a McKeown esophagectomy to enable drainage of the pancreatic pseudocyst through the jejunum. The patient recovered after the operation, and the formation of a pancreatic fistula was avoided successfully.

Aims To compare long‐term efficacy and safety of immunotherapeutic strategies as maintenance to prevent disease relapses of generalized myasthenia gravis (MG) in real‐world settings. Methods This is a retrospective cohort study on generalized MG conducted in seven major neurological centers across China. Eligible participants were patients with generalized MG who were under minimal manifestation status or better. Main outcome measures were probability of patients free of relapses and causes of drug discontinuation. Results Among 1064 patients enrolled, the median (interquartile range) age was 50.3 (37.0‐62.5) years and 641 (60.2%) were women. Disease relapse was significantly lower for rituximab (6.1%) compared with all the other monotherapies (hazard ratio [HR] = 0.18, 95% confidence interval [CI] 0.06 to 0.56, P = .0030). As combination therapies, tacrolimus in combination with corticosteroids reduced risk of disease relapses compared with azathioprine with corticosteroids (HR = 0.45, 95% CI 0.25 to 0.81, P = .0077) or mycophenolate mofetil with corticosteroids (HR = 0.32, 95% CI 0.15 to 0.67, P = .0020). Otherwise, lower‐dose corticosteroids or azathioprine as monotherapy significantly increased risk of disease relapses (HR = 2.78, 95% CI 1.94 to 3.99, P, As monotherapy in patients with generalized myasthenia gravis, rituximab displays higher efficacy to prevent disease relapses compared to other oral immunosupressants.

Background: The impact of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) on brain structure and function is unknown. Objectives: The aim of this study was to study the multimodal brain MRI alterations in MOGAD and to investigate their clinical significance. Methods: A total of 17 MOGAD, 20 aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4 + NMOSD), and 28 healthy controls (HC) were prospectively recruited. Voxel-wise gray matter (GM) volume, fractional anisotropy (FA), mean diffusivity (MD), and degree centrality (DC) were compared between groups. Clinical associations and differential diagnosis were determined using partial correlation and stepwise logistic regression. Results: In comparison with HC, MOGAD had GM atrophy in frontal and temporal lobe, insula, thalamus, and hippocampus, and WM fiber disruption in optic radiation and anterior/posterior corona radiata; DC decreased in cerebellum and increased in temporal lobe. Compared to AQP4 + NMOSD, MOGAD presented lower GM volume in postcentral gyrus and decreased DC in cerebellum. Hippocampus/parahippocampus atrophy associated with Expanded Disability Status Scale ( R = −0.55, p = 0.04) and California Verbal Learning Test ( R = 0.62, p = 0.031). The differentiation of MOGAD from AQP4 + NMOSD achieved an accuracy of 95% using FA in splenium of corpus callosum and DC in occipital gyrus. Conclusion: Distinct structural and functional alterations were identified in MOGAD. Hippocampus/parahippocampus atrophy associated with clinical disability and cognitive impairment.

Lithium-ion capacitors (LICs) have emerged as attractive energy storage devices to bridge the gap between lithium-ion batteries and supercapacitors. While the distinct charge storage kinetics between the anode and the cathode is still a challenge to the widespread application of LICs, the key to improving the energy density of these devices is to widen the operating voltage window and balance the mismatch of the electrode kinetics. To this end, we propose a strategy based on electrostatic attraction by adjusting the B and N atom contents of boron carbonitride (BCN) electrode materials to alter their electronegativities and successfully prepared B-rich and N-rich BCN nanotubes (BCNNTs) via a facile solid-phase synthesis approach. The B-rich BCN (B-BCN) cathode and N-rich BCN (N-BCN) anode noticeably enhance the adsorption of anions and cations, promoting a matching degree between the anode and cathode. In particular, the rationally designed B-BCN//N-BCN LIC achieves a maximum voltage range of 4.8 V, setting a new record for LICs. Furthermore, the energy density reaches up to 200 Wh kg-1 (based on the total mass of cathodic and anodic active materials). Density functional theory calculations provided insight into the mechanism underlying our strategy of widening the voltage range. Our philosophy provides new design guidelines and alternatives for identifying and optimizing high-performance electrodes for energy storage devices.

Background The purpose of this study was to analyze the clinical characteristics and prognostic survival of patients with neuroendocrine tumors of the thymus (NETTs), and to develop and validate a nomogram model for predicting the prognosis of patients. Methods We conducted a retrospective analysis of patients with neuroendocrine tumors of the thymus in the Surveillance, Epidemiology, and End Results (SEER) database in the United States between 1988 and 2016. Cox scale risk regression analysis, the Kaplan‐Meier method and log‐rank test were used to carry out the significance test to determine the independent prognostic factors, from which a nomogram for NETTs was established. C‐index and calibration curve were used to evaluate the prediction accuracy of the model. External validation of the nomogram was performed using data from our center. Results A total of 254 patients with NETTs were collected in the SEER database. In the multivariable analysis, T stage, tumor grade, surgery, and chemotherapy were found to be independent factors affecting the prognosis of patients (all P, The neuroendocrine tumors of the thymus is a rare invasive tumor with a poor prognosis, and visualization models are needed to provide patients with appropriate individualized treatment strategies.In this study, we established and validated a new Nomogram model to predict the survival of patients with neuroendocrine tumors of the thymus.

Background This study investigated the prognostic impact of (neo‐)adjuvant radiation therapies in early stage esophageal cancer. Methods A retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database was conducted from 2004 to 2016. Patients with pathologically staged T1‐4N0M0 esophageal cancer were divided into two treatment groups: (i) neoadjuvant radiotherapy followed by surgery; and (ii) upfront esophagectomy followed by adjuvant radiotherapy. Propensity scored match and Cox proportional hazards model were used to identify covariates associated with overall survival and cancer‐specific survival. Results There were 821 patients selected, of whom 588 (71.6%) received neoadjuvant radiotherapy and 233 (28.4%) received adjuvant radiotherapy. For the entire cohort, neoadjuvant radiotherapy was associated with a significantly benefit in five‐year survival outcomes compared with adjuvant radiotherapy (P, In this population‐based study, we indicated that the addition of neoadjuvant RT for pT3‐4N0 diseases followed by esophagectomy was associated with improved cancer‐specific survival in patients with tumor lengths 5 cm and squamous cell carcinoma. The identification of higher‐risk patients for neoadjuvant therapy would be expected to yield better results than taking a uniform approach to this population, to avoid unnecessary and possibly harmful treatment in node‐negative diseases.

Background The impact of neoadjuvant chemoradiotherapy (nCRT) on early stage esophageal cancer is unknown. Here, we compared the outcomes after esophagectomy alone or nCRT plus surgery for clinically staged node‐negative esophageal cancer. Methods We searched the Surveillance, Epidemiology, and End Results database for patients with clinically node‐negative (cN0) esophageal cancer from 2004 to 2016 who underwent surgery alone or nCRT plus surgery. Propensity score matching and Cox regression analysis were used to identify covariates associated with overall survival and cancer‐specific survival. Results A total of 1587 patients were retrospectively identified, of whom 49.8% (n = 791) received nCRT and 80.2% (n = 1273) were truly node‐negative diseases. For the entire cohort, surgery alone was associated with a statistically significant but modest absolute increase in survival outcomes (P, This study focuses on the use of neoadjuvant chemoradiotherapy to esophageal carcinoma patients with clinically staged node‐negative (cN0) status. Finally, compared with surgery alone, cN0 esophageal cancer with falsely node‐negative (pN+) or localized truly node‐negative (pT3‐4N0) gain a significant survival benefit from neoadjuvant chemoradiation. However, neoadjuvant chemoradiation plus surgery was associated with decreased survival for early‐staged true node‐negative (pT1‐2N0) patients. Despite the inherent limitations, this population‐based study allows for a robust analysis of patients with cN0 esophageal carcinoma and the benefits of neoadjuvant chemoradiation when stratified by nodal and tumor status, and this finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN0 disease.

Background. There is limited evidence of the effects of local anesthesia (LA) on outcomes of non-surgical periodontal treatment (NSPT), in particular among the Chinese. This retrospective cohort study aimed to evaluate the effects of LA on short-term treatment outcomes of NSPT and to determine under what circumstances LA should be prescribed to improve these outcomes. Methods. Data from periodontal examinations of 3980 patients were used. The data were from 3-month re-evaluation records of an electronic periodontal charting record system in the Department of Periodontology of Peking University School and Hospital of Stomatology from June 2008 to January 2015. Descriptive analyses included changes in probing depth (PD) and the Mazza bleeding index (BI). Two-level (patient and tooth) logistic regression models and three-level (patient, tooth, and site) linear regression models were constructed to analyze the influence of LA on PD for all teeth/sites and teeth/sites with an initial PD ≥ 5 mm. Decreases in PD and BI at sites under LA using the initial PD were also compared. Results. A significantly higher mean decrease in PD after NSPT was found in the LA group than in the no local anesthesia (NLA) group (0.98 vs. 0.54 mm, t = 24.12, P 1 and BI > 2) for all teeth (16.7% vs. 13.8%, t = 3.75, P

The 5th International Porto Congress of Multiple Sclerosis took place between the 14th and 16th of February 2019 in Porto, Portugal. Its intensive programme covered a wide-range of themes—including many of the hot topics, challenges, pitfalls and yet unmet needs in the field of multiple sclerosis (MS)—led by a number of well-acknowledged world experts. This meeting review summarizes the talks that took place during the congress, which focussed on issues in MS as diverse as the development and challenges of progressive MS, epidemiology, differential diagnosis, medical management, molecular research and imaging tools.

Coronavirus disease 2019 (COVID-19) has resulted in more than 8.7 million laboratory-confirmed cases and 0.46 million deaths globally (1). Few therapies, if any, have been shown to rapidly ameliorate the respiratory symptoms and prevent against the disease progression. An important mechanism contributing to dyspnea and disease progression in patients with COVID-19 might be the increased work of breathing because of the heightened airway resistance (2). Inhalation of hydrogen/oxygen mixed gas (H2-O2) might have a role in the treatment of COVID-19 given the decreased resistance compared with room air when passing through the airways.

Circulating tumor cells (CTCs), as the precursor of metastases, gain mesenchymal traits through the epithelial‑mesenchymal transition (EMT) process, thereby mediating tumor metastasis. However, the dynamic changes and clinical value of mesenchymal CTCs (MCTCs) in colorectal cancer (CRC) patients remain inconclusive. The aim of the present study was to explore the prognostic value of dynamic changes of MCTCs in CRC patients using our previously developed CTCBIOPSY® device with an immunocytochemistry assay. The results revealed that 74 out of 175 patients were pre‑MCTCs‑positive and 41 out of 127 patients were post‑MCTCs‑positive. Dynamical monitoring revealed that the status of MCTCs remained dynamically changed under the pressure of anticancer therapy, and these dynamic changes were significantly associated with lymphovascular invasion (P

Background and purposeData on the efficacy and safety of alteplase for acute ischaemic stroke (AIS) administered 3–4.5 hours after the onset of stroke symptoms in Chinese patients is limited. We sought to determine whether AIS patients would benefit from thrombolysis with alteplase between 3 and 4.5 hours after the onset of stroke symptoms in a prospective, multicentre, single-arm trial in China.Materials and methodsEligible AIS patients were given 0.9 mg/kg alteplase intravenously. The primary efficacy endpoint was a favourable outcome at 3 months, defined as a score of 0 or 1 on the modified Rankin Scale. Thresholds for the primary efficacy endpoint were determined to be 40% based on the literature review. The primary safety endpoint was symptomatic intracranial haemorrhage (sICH) according to the European Cooperative Acute Stroke Study III (ECASS III) trial definition. Post hoc analysis between this study and the ECASS III trial were compared using the propensity score matching (PSM) method.ResultsA total of 120 eligible AIS patients from 11 sites in China received thrombolysis therapy in this study. The median time from onset of symptoms to needle was 3 hours 54 min. The percentage of patients with a favourable outcome was 63.3% (95% CI 54.4 to 71.4), significantly higher than the predefined threshold (pConclusionsIntravenous alteplase with a standard dose administered between 3 and 4.5 hours after onset of symptoms is effective and safe for Chinese AIS patients.Trial registration numberNCT02930837

Background Glucocorticoid (GC) is the first-line therapy in acute attacks of multiple sclerosis (MS), but its efficacy is individually variable and may be associated with glucocorticoid receptor (GR) gene. Objective To establish the association between GR gene sequence and clinical GC sensitivity in Chinese MS patients. And to investigate the expression differences of serum GRα and FK506 binding protein 5 (FKBP5) in GC responders and non-responders. Materials and methods Coding exons 2–9 of the GR gene from 97 MS patients were sequenced. We performed ELISA to detect serum GRα and FKBP5 before the GC impulse therapy in patients with different GC sensitivities (according to the EDSS changes before and after the GC medication). Results Seven new mutations were located in exon 2, but the presence or absence of mutations was not associated with the response to GC therapy (P = 0.416). The GC-sensitive patients had higher GRα (P = 0.011) but lower FKBP5 (P = 0.025) levels in the serum. Conclusions The GR mutations detected in our study were not associated with the response to GC in Chinese MS patients. Higher GRα and lower FKBP5 levels in the serum might predict the response to GC, which may provide potential therapeutic target for GC-resistant patients with acute MS attack.

ObjectivesWe investigated the predictors of functional outcome in young patients enrolled in a multiethnic study of intracerebral hemorrhage (ICH).MethodsThe Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study is a prospective multicenter study of ICH among adult (age ≥18 years) non-Hispanic white, non-Hispanic black, and Hispanic participants. The study recruited 1,000 participants per racial/ethnic group. The present study utilized the subset of ERICH participants aged ResultsOf the 3,000 patients with ICH enrolled in ERICH, 418 were studied (mean age 43 years, 69% male), of whom 48 (12%) were white, 173 (41%) were black, and 197 (47%) were Hispanic. For supratentorial ICH, black participants (odds ratio [OR], 0.42; p = 0.046) and Hispanic participants (OR, 0.34; p = 0.01) had better outcomes than white participants after adjustment for other factors associated with poor outcome: age, baseline disability, admission blood pressure, admission Glasgow Coma Scale score, ICH volume, deep ICH location, and intraventricular extension.ConclusionsIn young patients with supratentorial ICH, black and Hispanic race/ethnicity is associated with better functional outcomes, compared with white race. Additional studies are needed to identify the biological and social mediators of this association.

As a class of highly stable materials, the application of high dielectric constant materials in the field of energy is hampered by their low electrical conductivity and poor energy storage capacity. To solve these inherent limitations, herein, a useful strategy was developed to improve the energy storage performance of high dielectric constant electrode materials by combining the characteristics of parallel-plate capacitors. A novel sandwich structure with a carbon fiber/metal oxide/metal oxynitride layer (CMM) were used to construct a “mini parallel-plate capacitor” in the electrode, and the capacitance was remarkably enhanced. In this structure, the metal oxides (SnO2, Fe2O3, VO2, and TiO2) with different dielectric constants worked as the dielectric, while the carbon fiber and the metal oxynitride layer worked as the plate electrodes. As expected, the dielectric constant of the metal oxides was directly proportional to the capacitance increase. Specifically, the capacitance of TiO2 was enhanced up to 11.75 times after the construction of this structure. Moreover, the relevant mechanism of the enhanced capacitance was investigated by the parallel-plate capacitor model. This novel strategy can provide new ideas for the study of high dielectric constant materials in the field of energy storage.

Background Guillain-Barre syndrome (GBS) is the most prevalent acute autoimmune polyneuropathy, however, the incidence of GBS across China remains undetermined. We conducted the first nationwide study to extrapolate the incidence and mortality rates of GBS across all age groups at a national scale. Methods This study analyzed patient metrics from the National Hospital Quality Monitoring System, a comprehensive administrative database of which incorporate all 1665 tertiary hospitals in mainland China. For all study patients the "Medical Record Homepage" encompasses 346 distinct variables such as demographic characteristics, diagnoses, procedures, expenses, etc., that are systematically recorded from these hospitals by standard protocol. All GBS diagnoses adhered to the National Institute of Neurologic and Communicative Disorders and Stroke (NINCDS) diagnostic criteria and were identified with ICD-10 code (G61•0). Findings From 2016 to 2019, 75,548 hospital admissions for 38,861 GBS patients were identified. The age- and sex-adjusted incidence per 100,000 person-years is 0•698 (95% confidence interval [CI], 0•691-0•705), 0•233(0•225-0•242) in children and 0•829(0•820-0•837) in adults. The male-to-female ratio is 1•49. Peak disease onset was detected in the 70–74 years age group with an incidence of 1•806/100, 000 (95% CI, 1•741-1•870). Recognizable GBS distribution patterns were recognized in the southeastern coastal areas, where the cases of GBS were concentrated in the summer and autumn seasons. Prevalent comorbidities include hypertension (28•8%) and stroke (14•3%). The median length of hospitalization was 13•0 (8•0–18•0) days with a median hospitalization cost of $2371•60 ($1281•80–5463•60). Covering 69•9% of study patients, the Basic Medical Insurance was the most common payment mechanism. From 2016-2019, 426 adults and 13 children died in this study pool, with a hospital mortality rate of 11•2 per 1,000 person-years. Interpretation For the first time, we obtained a national incidence for GBS at 0•233 in children and 0•829 in adults per 100,000 in China. A differential spatiotemporal incidence is presented most southeast coastal areas in the summer and autumn seasons. Funding National Science Foundation of China (91949208, 91642205, and 81830038); Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing.

As more than two billion people possibly have a latent tuberculosis (LTB) infection, early LTB diagnosis is crucial for the efficient control and elimination of tuberculosis (TB). The aim of this study is to detect the serum antibody responses to dormancy-related DosR regulon antigens of Mycobacterium tuberculosis for the diagnosis of active and latent TB infections. A membrane array with 25 latency antigens detected by silver-enhanced gold nanoparticles was used to determine the corresponding cognate antibody levels in clinical serum samples from healthy controls, TB patients, and individuals with LTB. The array is sized to fit into a 24-well ELISA plate and follows an ELISA-like experimental procedure without expensive instrumentation. Linear discriminant analysis (LDA) of the resulting antibody profiling data set identified a panel of nine DosR antigens with significant discriminatory capability among different subjects with ≥90% sensitivity, specificity, and overall accuracy. Furthermore, the high predictive performance validated by an independent test sample set reflects the robustness and reliability of the LDA classification model. Our current data demonstrate that the nine DosR antigen combination associated with the proposed membrane array platform is a clinically feasible approach for distinguishing different TB infection statuses. The proposed methodology in this study could be further developed for multiple disease serodiagnoses with high sensitivity and specificity.

Esophageal and tracheal foreign body ingestion trigger common pediatric emergencies. In this case report, we describe a pediatric patient with simultaneous tracheal and esophageal obstruction caused by foreign bodies. A child aged 2 years and 1 month swallowed a pair of metallic magnetic beads at the same time; one bead entered the trachea and the other bead entered the esophagus. We suspected that the two magnetic beads were mutually attracted and thus became trapped in their respective lumina. The tracheal foreign body was uneventfully removed; this dislodged the esophageal foreign body, which was then excreted. There were no serious complications in the present case, but parents and medical personnel should be mindful of the potential hazards associated with ingestion of multiple magnetic foreign bodies. A high index of suspicion is appropriate. Investigations must be carefully planned. Treatment should not be delayed; the consequences of delay may be serious.

Stroke, including acute ischaemic stroke and intracerebral haemorrhage, results in neuronal cell death and the release of factors such as damage-associated molecular patterns (DAMPs) that elicit localised inflammation in the injured brain region. Such focal brain inflammation aggravates secondary brain injury by exacerbating blood-brain barrier damage, microvascular failure, brain oedema, oxidative stress, and by directly inducing neuronal cell death. In addition to inflammation localised to the injured brain region, a growing body of evidence suggests that inflammatory responses after a stroke occur and persist throughout the entire brain. Global brain inflammation might continuously shape the evolving pathology after a stroke and affect the patients' long-term neurological outcome. Future efforts towards understanding the mechanisms governing the emergence of so-called global brain inflammation would facilitate modulation of this inflammation as a potential therapeutic strategy for stroke.

A 49-year-old female patient developed chest tightness and shortness of breath without apparent cause and presented to a local hospital. Chest radiography indicated increased thickening of the lung texture, increased multiple patchy densities in the lower lobes of the bilateral lungs and a slightly enlarged thyroid. The patient was treated for pulmonary infection with antibiotics but the symptoms persisted. A repeated CT scan revealed ground-glass attenuation of the bilateral lungs with multiple flaky exudates and visible bronchogenic signs. The symptoms did not improve after broadening anti-microbial coverage. Bronchoscopy and biopsy confirmed cryptogenic organizing pneumonia (COP). Thyroid ultrasound and thyroid function tests jointly confirmed the diagnosis of Hashimoto's thyroiditis (HT). After receiving corticosteroid treatment, the patient's condition improved and she was discharged. This case demonstrates that COP may present in combination with Hashimoto's thyroiditis (HT) and may possibly even be caused by HT. Early confirmation of diagnosis and treatment will help to improve the prognosis of such patients.

Dl-3-n-butylphthalide (NBP) is a synthetic compound that has been approved for the treatment of ischemic stroke in China. The mechanisms underlying the treatment efficacy of NBP have been reported in multiple studies and remain controversial. Here, we show that NBP treatment attenuated ischemic brain injury in mice subjected to transient middle cerebral artery occlusion or photothrombosis-induced permanent cerebral ischemia. NBP induced downregulation of intercellular adhesion molecule 1 and protease-activated receptor 1 in cerebrovascular endothelial cells after cerebral ischemia and reperfusion. This effect was associated with the reduced brain infiltration of myeloid cells and improved cerebral blood flow after reperfusion. The beneficial effects of NBP were diminished in mice subjected to the depletion of Gr1+ myeloid cells before brain ischemia. Therefore, the restriction of neurovascular inflammation is a key mode of action for NBP in ischemic stroke.

Abstract Background: Interleukin 36 (IL-36) cytokines belong to the IL-1 family and play an important role in some autoimmune diseases. However, the relationship between IL-36 and neuromyelitis optica spectrum disorders (NMOSD) remains unclear. Methods: We determined serum IL-36α, IL-36β and IL-36γ levels and assessed correlations with clinical characteristics in 50 NMOSD patients and 30 healthy controls (HC). Results: The concentrations of serum IL-36β and IL-36γ were significantly higher in patients with NMOSD than in HCs and decreased during remission. Serum IL-36β levels were positively correlated with the annual relapse rate (ARR), spinal cord lesion length and Expanded Disability Status Scale (EDSS) scores. Conclusions: Serum IL-36β and IL-36γ levels were related to disease activity in NMOSD patients and may be important biomarkers of NMOSD.

Traumatic brain injury (TBI) is recognized as a global health problem due to its increasing occurrence, challenging treatment, and persistent impacts on brain pathophysiology. Neural cell death in patients with TBI swiftly causes inflammation in the injured brain areas, which is recognized as focal brain inflammation. Focal brain inflammation causes secondary brain injury by exacerbating brain edema and neuronal death, while also exerting divergent beneficial effects, such as sealing the damaged limitans and removing cellular debris. Recent evidence from patients with TBI and studies on animal models suggest that brain inflammation after TBI is not only restricted to the focal lesion but also disseminates to remote areas of the brain. The dissemination of inflammation has been detected within days after the primary injury and persists chronically. This state of inflammation may be related to remote complications of TBI in patients, such as hyperthermia and hypopituitarism, and may lead to progressive neurodegeneration, such as chronic traumatic encephalopathy. Future studies should focus on understanding the mechanisms that govern the initiation and propagation of brain inflammation after TBI and its impacts on post-trauma brain pathology.

Depression and anxiety often co-occur with cardiac diseases. The Shexiang Baoxin pill (SBP) is a proprietary Chinese medicine initially used to treat cardiac conditions. This study explored whether SBP has antidepressant and anxiolytic effects in addition to hormonal and psychotropic mechanisms. Mice underwent 6 weeks of chronic unpredictable mild stress (CUMS) to induce depression- and anxiety-like behavior. During the 6-week experiment, mice received SBP at intragastric doses of 20.25 mg/kg or 40.5 mg/kg daily. Animals were then tested for depression in sucrose preference, forced-swimming, and tail suspension paradigms, and for anxiety in open field and elevated plus maze tests. Both SBP doses significantly reduced anhedonic behavior in the sucrose preference test; the high SBP dose also increased the number of entries into the central zone of the open field. SBP-treated mice had markedly lower blood levels of corticotrophin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) than stressed mice treated with vehicle. Either low- or high-dose SBP reversed stress-induced reductions of norepinephrine (NE) and dopamine (DA) metabolites and the expression levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell-derived neurotrophic factor (GDNF) in related brain regions. These results suggest that SBP could prevent and alleviate prolonged stress-induced anhedonia and anxiety in association with its suppression of the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, modulation of brain monoamine neurotransmitter metabolism and neurotrophins. SBP may be particularly suitable for the management of depressive and anxiety disorders in patients with cardiac conditions. Keywords: Shexiang Baoxin pill (SBP), Depression, Anxiety, HPA axis, BDNF

Tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody, showed its therapeutic efficacy on neuromyelitis optica spectrum disorder (NMOSD). To assess the immunological effects of this drug on B cells, follicular T helper (Tfh) cells, and peripheral T helper (Tph) cells in patients with NMOSD, peripheral B cell and Tfh cell phenotypes were evaluated in 26 patients with NMOSD before and after tocilizumab treatment by nine-color flow cytometry, as well as the expression of costimulatory and co-inhibitory molecules on B cells. Results showed that the frequency of CD27+IgD− switched memory B cells, CD27-IgD- double-negative B cells, and CD27highCD38high antibody-secreting cells was increased in patients with NMOSD. Tocilizumab treatment led to a significant shift of B cells to naïve B cells from memory B cells after 3 months. Three markers on B cells associated with T-cell activation (i.e., CD86 CD69, and HLA-DR) were downregulated after tocilizumab treatment. The frequencies of total Tfh and Tph cells were decreased, whereas that of follicular regulatory T cells tended to increase. Intrinsic increased PD-L1 and PD-L2 expression was characteristic of B cells in patients with NMOSD. Tocilizumab selectively restored PD-L1 on B-cell subsets. These results provided evidence that tocilizumab enhanced B- and T-cell homoeostasis by regulating B-cell differentiation and inhibiting lymphocyte activation in patients with NMOSD.

Ischemic stroke is a common type of cerebrovascular event and also the leading cause of disability. Post-stroke cognitive impairment occurs frequently in stroke survivors. Shexiang Baoxin Pill (SBP) is a proprietary Chinese medicine, initially used to treat cardiovascular diseases. Herein, we aim to explore the effects of SBP on oxygen glucose deprivation and reoxygenation (OGD/R) in neuronal cells (CATH.a) and cerebral ischemia/reperfusion injury induced post-stroke cognitive impairment in middle cerebral artery occlusion (MCAO) rat model. MCAO rats received two doses of oral SBP treatment (28 or 56 mg/kg) after 1 h of operation and once daily for 2 weeks continuously. Behavioral tests, immunoblotting, and immunofluorescence were examined after 14 days. Current data suggest that SBP enhanced cell viability and downregulated apoptosis via activating the PI3K/Akt signaling pathway in CATH. a cells. Furthermore, 14 days of SBP treatment promoted the recovery of learning and locomotor function in the MCAO rats. SBP up-regulated the expression of p-Akt, p-GSK3β, as well as the expression of NMDAR1, PSD-95, and AMPAR. Also, SBP down-regulated the expression of p-CaMKII. These results indicated that long-term SBP treatment might be a potential option for cognitive impairment induced by the ischemic stroke.

Background and ObjectivesTo assess the molecular landscape of B-cell subpopulations across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD).MethodsWe performed B-cell transcriptomic profiles via single-cell RNA sequencing across CSF, blood, and bone marrow in patients with NMOSD.ResultsAcross the tissue types tested, 4 major subpopulations of B cells with distinct signatures were identified: naive B cells, memory B cells, age-associated B cells, and antibody-secreting cells (ASCs). NMOSD B cells show proinflammatory activity and increased expression of chemokine receptor genes (CXCR3 and CXCR4). Circulating B cells display an increase of antigen presentation markers (CD40 and CD83), as well as activation signatures (FOS, CD69, and JUN). In contrast, the bone marrow B-cell population contains a large ASC fraction with increased oxidative and metabolic activity reflected by COX genes and ATP synthase genes. Typically, NMOSD B cells become hyperresponsive to type I interferon, which facilitates B-cell maturation and anti–aquaporin-4 autoantibody production. The pool of ASCs in blood and CSF were significantly elevated in NMOSD. Both CD19− and CD19+ ASCs could be ablated by tocilizumab, but not rituximab treatment in NMOSD.DiscussionB cells are compartmentally fine tuned toward autoreactivity in NMOSD and become hyperreactive to type I interferon. Inhibition of type I interferon pathway may provide a new therapeutic avenue for NMOSD.

With the rapid development of domestic fiber lasers, the output power is constantly improving, resulting that the requirement of active fiber is becoming stricter. YOFC company has proposed a kind of triple cladding active fiber fabrication technology, which combines Plasma Chemical Vapor Deposition (PCVD) platform and Modified Chemical Vapor Deposition (MCVD) platform to make preform which has several characteristics like, large size, high concentration doping, long effective length, high uniformity, Fluorine doped outer cladding and so on. Special fiber drawing technique has been used to match this special preform, finally obtained triple cladding Ytterbium doped fiber (TC YDF) with excellent performance such as, low background loss which is less than 10 dB/km, high doping concentration of rare earth, high uniformity and strong resistance to the photo-darkening; The resonant cavity which consist of this TC YDF can obtained laser power up to 3550w, simultaneously the optical-to optical conversion efficiency is up to 78%, the Raman scattering suppression ratio is larger than 35dB. The fiber laser is continuously monitored for 1500 hours at 3550w, the results show that the output power are nearly stable, which indicates that this TC YDF has an excellent long-term reliability and can be used in industrial processing stably on a large scale.

Background This study aimed to identify variables associated with anastomotic leakage after esophagectomy and established a tool for anastomotic leakage prediction. Methods Twenty-six preoperative and postoperative variables were retrospectively collected from esophageal cancer patients who were treated with radical esophagectomy from January 2018 to June 2020 in the Affiliated Hospital of Qingdao University. SPSS Version 23.0 and Empower Stats software were used for establishing a nomogram after screening relevant variables by univariate and multivariate Logistic regression analyses. The established nomogram was identified by depicting the receiver operating characteristic (ROC) curves and calibration curve, which was verified by 1,000 bootstrap resamples method. Results A total of 604 eligible esophageal cancer patients were included, of which 51 (8.4%) patients had anastomotic leakage. Multivariate Logistic regression analysis showed that smoking, anastomotic location, anastomotic technique, prognostic nutritional index (PNI) and ASA score were independent risks of anastomotic leakage. The area under curve (AUC) of ROC in the established nomogram was 0.764 (95% CI, 0.69-0.83). The internal validation confirmed that the nomogram had a great discrimination ability (AUC =0.766). Depicted calibration curve demonstrated a well-fitted prediction and observation probability. In addition, the decision curve analysis concluded that the newly established nomogram is significant for clinical decision-making. Conclusions This nomogram provided the individual prediction of anastomotic leakage for esophageal cancer patients after surgery, which might benefit treatment results for patients and clinicians, as well as pre-and postoperative intervention strategy-making.

BackgroundInterleukin-6 receptor blockade is effective in reducing the risk of relapses in neuromyelitis optica spectrum disorder (NMOSD). However, its efficacy during acute attacks of NMOSD remains elusive.ObjectiveWe investigated the effects of tocilizumab on disability during acute attacks, as well as its maintenance, in patients with moderate-to-severe myelitis.MethodsNineteen patients with NMOSD received tocilizumab treatment as add-on to high-dose methylprednisolone (HDMP) in acute myelitis and twenty-two patients who only received HDMP were compared. Disease disability was assessed using a multi-level scaling system that included the expanded disability status scale (EDSS), Hauser ambulation index (HAI), modified Rankin scale (mRS), pain numerical rating scale (NRS), functional assessment of chronic illness therapy-fatigue scale (FACIT-F), activity of daily living (ADL), EuroQol five-dimensions-three-level questionnaire (EQ-5D-3L), and sensory function score and bowel and bladder function score in Kurtzke functional systems scores (FSS).ResultsImproved EDSS, HAI, and mRS, as well as increased ADL and EQ-5D-3L were significant in patients on tocilizumab compared with those on steroids as monotherapy at 3 months (p < 0.05). Both groups of patients showed improved pain, fatigue, sensory function, and autonomic function at follow-ups, compared with baseline respectively. The changes in NRS, FACIT-F, and sensory and autonomic FSS showed no significant differences between the two groups. Tocilizumab significantly lowered the risk of relapses (HR = 0.21, 95% CI 0.06–0.76, p = 0.017) and reduced the annualized relapse rate compared with those by steroids (0.1 ± 0.2 vs 0.5 ± 0.6, p = 0.013).ConclusionEarly initiation of tocilizumab provided a safe and effective add-on alternative during attacks, and its maintenance contributed to a significant reduction of relapse rate in NMOSD.

Avian influenza in human, especially the severe type, progresses rapidly and causes multiple complications, such as acute lung injury, acute respiratory distress syndrome (ARDS), pulmonary hemorrhage, pleural effusion, pancytopenia, heart failure, renal failure, multiple organ failure, sepsis, shock, and Reye syndrome. The patients often die from severe pulmonary failure. Compared with adults, children suffering from avian influenza progress more rapidly and are more vulnerable to pneumothorax and secondary infection.

Background: Guillain-Barre syndrome (GBS) is the foremost acute autoimmune polyneuropathy in prevalence, however, the incidence of GBS across China is undetermined. We conducted the first nationwide study to extrapolate the incidence and mortality rate of GBS in all age groups at a national scale. Methods: This study analyzed patient metrics from the National Hospital Quality Monitoring System, a comprehensive administrative database of which incorporate all 1665 tertiary hospitals in mainland China. The “Medical Record Homepage” for all study patients encompass 346 distinct variables such as demographic characteristics, diagnoses, procedures, expenses, etc., which are systematically recorded from these hospitals by standard protocol. All GBS diagnoses adhered to the National Institute of Neurologic and Communicative Disorders and Stroke ( NINCDS ) diagnostic criteria and was identified with ICD-10 code (G 61 ·0).Findings From 2016 to 2019, 75,548 hospital admissions for 38,861 GBS patients were identified. The age- and sex-adjusted incidence per 100,000 person-years is 0·698 (95% confidence interval [CI], 0·691-0·705), with 0·212 (0·202-0·221) in children and 0·796 (0·788-0·804) in adults, respectively. The male-to-female ratio is 1·1.?2. Peak disease onset was detected in the 70–74 years age group with an incidence of 1·806/100, 000 (95% CI, 1·741-1·870). GBS dispersion patterns was recognized in southeast coastal areas who were more likely to develop GBS in the summer and autumn seasons (p< 0·05). Prevalent comorbidities are hypertension (28·8%) and stroke (14·3%). The median length of hospitalization was 13·0 (8·0–18·0) days with a median hospitalization cost of $2371·60 ($1281·80–5463·60). Covering 69·9% of study patients, the Basic Medical Insurance was the most prevalent payment mechanism. From 2016-2019, 434 adults and 5 children died, with a hospital mortality rate of 11·2 per 1,000 person-years. Interpretation: For the first time, we obtained a national incidence for GBS at 0·212 in children and 0·796 in adults per 100,000 in China. A differential spatiotemporal incidence is presented most southeast coastal areas in the summer and autumn seasons. Funding: National Science Foundation of China (91949208, 91642205, and 81830038); Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Beijing Tiantan Hospital affiliated to Capital Medical University, KY2020-013-01.