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What is known and objective Edaravone is a new antioxidant and hydroxyl radical scavenger. Although there is evidence that it improves clinical outcomes of patients with acute ischaemic stroke (AIS), it is not yet widely accepted for treatment of AIS in Western countries. We further investigated the efficacy and safety of edaravone through this meta‐analysis of randomized controlled clinical trials (RCTs). Method Pubmed, Embase, Web of Science and Cochrane Library were screened up to December 2020 for original articles from SCI journals that published in English. RCTs that compared edaravone versus placebo or no intervention in adult patients and reported the efficacy or safety of edaravone were regarded as eligible. Mortality was regarded as the primary outcome and the improvement of neurological impairment was regarded as the secondary outcome. Safety evaluation was conducted according to the incidence of adverse events. Review Manager 5.3 was employed to perform the assessment of the risk of bias and data synthesis. The Cochrane risk of bias tool for randomized controlled trials was employed to assess the risk of bias. Results and discussion Seven randomized controlled trials with 2069 patients were included. For the incidence of mortality, the pooled RR for studies that evaluated edaravone after three‐month follow‐up was 0.55 (95% Cl, 0.43‐0.7, I2 = 0, P < 0.01). The pooled RR for improvement of neurological impairment at the three months follow‐up was 1.54 (95% CI, 1.27‐1.87, I2 = 0, P < 0.01) in four RCTs. On subgroup analysis of studies that were conducted in Asia, the RR was 1.56 (95% CI, 1.27‐1.90, I2 = 0%; P < 0.01); the pooled RR for studies that conducted in Europe was 1.32 (95% CI, 0.64‐2.72; P = 0.45); the pooled RR for studies that used edaravone for two weeks was 1.42 (95% CI, 1.10 to 1.83, I2 = 0%; P < 0.01); the pooled RR for studies that used edaravone for one week was 1.64 (95% CI, 1.24‐2.16, I2 = 0%; P < 0.01); the pooled RR for studies that conducted in patients with mean age equal to or over 60 years was 1.52 (95% CI, 1.24‐1.87, I2 = 0%; P < 0.01); and the pooled RR for studies that conducted in patients with mean age less than 60 was 1.80 (95% CI, 1.05‐3.08, I2 = 0%; P = 0.03). For the incidence of any treatment‐related adverse events, the pooled RR for studies that evaluated edaravone during treatment was 0.83 (95% CI, 0.51‐1.34, I2 = 0, P = 0.43). The difference of the incidence of any treatment‐related adverse events between two groups was not statistically significant. What is new and conclusion The limited studies indicate that edaravone can improve neurological impairment with a survival benefit at three‐month follow‐up, regardless of the mean age and course of treatment. It is worthy of promotion in the clinical treatment of AIS in Asian countries. More well‐designed RCTs with larger sample sizes are needed to determine the benefits of edaravone in patients from Western countries.

SummaryPrevious studies have demonstrated the association between physical activity and sleep quality. However, there is little evidence regarding different domains of physical activity. This study aimed to examine the associations between domain‐specific physical activities and insomnia symptoms among Chinese men and women. Data of 452 024 Chinese adults aged 30–79 years from the China Kadoorie Biobank Study were analysed. Insomnia symptoms were assessed with self‐reported difficulties in initiating or maintaining sleep, early morning awakening, daytime dysfunction and any insomnia symptoms. Physical activity assessed by questionnaire consisted of four domains, including occupational, commuting‐related, household and leisure‐time activities. Gender‐specific multiple logistic regression models were employed to estimate independent associations of overall and domain‐specific physical activities with insomnia symptoms. Overall, 12.9% of men and 17.8% of women participants reported having insomnia symptoms. After adjustment for potential confounders, a moderate to high level of overall activity was associated with reduced risks of difficulties in initiating or maintaining sleep and daytime dysfunction in both sexes (odds ratios range: 0.87–0.94, P < 0.05). As to each domain of physical activity, similar associations were identified for occupational, household and leisure‐time activities in women but not men (odds ratios range: 0.84–0.94, P < 0.05). Commuting‐related activity, however, was associated with increased risks of difficulties in initiating or maintaining sleep and any insomnia symptoms in both sexes (odds ratios range: 1.07–1.17, P < 0.05). In conclusion, a moderate to high level of physical activity was associated with lower risks of insomnia symptoms among Chinese adults. However, such associations varied hugely in different domains of physical activity and with gender differences, which could help with better policy‐making and clinical practice.

Abstract. The question about how intravenous anesthetic reagents affect the development and function of dendritic cell subsets still has no comprehensive answers. Bone marrow cells differentiated with FMS-like tyrosine kinase 3 ligand in vitro represented the steady-state dendritic cell subsets. The effects of ketamine on the generation and function of dendritic cell subsets were investigated. We found that dendritic cell subsets responded to the anesthetic reagent ketamine in several aspects: 1) The in vitro and in vivo development of plasmacytoid dendritic cells were inhibited by ketamine at high concentrations; 2) The endocytosis of dendritic cells were not influenced by ketamine at concentrations from 50 -200 μM; 3) The maturation markers of conventional dendritic cells were not changed by ketamine upon LPS or CpG stimulation, although the cytokines mRNA profiles were affected; 4) The allogenic-stimulatory activity of dendritic cells was suppressed by ketamine. In conclusion, ketamine hampered plasmacytoid dendritic cell subset development both in vivo and in vitro. The dendritic cells maturation and downstream responses towards different toll-like receptor stimuli were differently regulated by ketamine treatment.

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Background Global developmental delay/intellectual disability (GDD/ID), used to be named as mental retardation (MR), is one of the most common phenotypes in neurogenetic diseases. In this study, we described the diagnostic courses, clinical and genetic characteristics and prenatal diagnosis of a cohort with patients presented GDD/ID with monogenic causes, from the perspective of a tertiary genetic counseling and prenatal diagnostic center. Method We retrospectively analyzed the diagnostic courses, clinical characteristics, and genetic spectrum of patients presented GDD/ID with rare monogenic causes. We also conducted a follow-up study on prenatal diagnosis in these families. Pathogenicity of variants was interpreted by molecular geneticists and clinicians according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). Results Among 81 patients with GDD/ID caused by rare monogenic variants it often took 0.5–4.5 years and 2–8 referrals to obtain genetic diagnoses. Devlopmental delay typically occurred before 3 years of age, and patients usually presented severe to profound GDD/ID. The most common co-existing conditions were epilepsy (58%), microcephaly (21%) and facial anomalies (17%). In total, 111 pathogenic variants were found in 62 different genes among the 81 pedigrees, and 56 variants were novel. The most common inheritance patterns in this outbred Chinese population were autosomal dominant (AD; 47%), following autosomal recessive (AR; 37%), and X-linked (XL; 16%). SCN2A, SHANK3 and STXBP1 were important causal genes. Hot-spot variants were rarely found. By the follow-up, 33 affected families, including 15, 13 and 5 families inherited in AR, AD and XL modes respectively, had undergone prenatal diagnosis. And the recurrence rates are 26.7%, 15.4% and 20% for families inherited in AR, AD, and XL patterns. Conclusion Patients presented with GDD/ID caused by rare single gene variants are characterized by early onset, relatively severe symptoms and great clinical variability and genetic heterogeneity. Timely referrals to genetic counseling and prenatal diagnostic laboratories are important for affected families planning to have additional children.

IntroductionGut microbiota alterations are strongly associated with prescription opioid use (POU) and multisite chronic pain (MCP). However, whether or not these associations are causal remains unknown. Therefore, we aim to explore the causal relationships between them comprehensively.MethodsA two-sample bi-directional Mendelian randomization was conducted to assess the potential associations between gut microbiota and POU/MCP using summary level Genome-wide association studies (GWASs) that were based on predominantly European ancestry.ResultsPotential causal effects were identified between seven host genetic-driven traits of gut microbiota on POU, including Adlercreutzia, Allisonella, Dialister, Anaerofilum, Anaerostipes, ChristensenellaceaeR.7group, and LachnospiraceaeNC2004group at the genus level (p &lt; 0.05) by the Inverse-variance weighted method, with significant causal effects of ChristensenellaceaeR.7group and Allisonella on POU (p &lt; 0.025). A total of five genetically greater abundance of gut microbiota traits were identified to be possibly related to the level of MCP (p &lt; 0.05), including genus ErysipelotrichaceaeUCG003, family Clostridiaceae1, order Gastranaerophilales, order Actinomycetales, and family Actinomycetaceae. In the other direction, no clear evidence was found to support a significant causal relationship between POU and gut microbiota, as well as MCP and gut microbiota. In addition, evidence was also provided for the relationship between triacylglycerols and diacylglycerol elevation, and an increased risk of POU and MCP. No evidence was found across various sensitivity analyses, including reverse causality, pleiotropy, and heterogeneity.ConclusionThe findings from this study provide robust evidence that gut microbiota alterations may be a risk of POU/MCP, but not vice versa.

The study was aimed at exploring the application value of the CT image based on a filtered back projection (FBP) algorithm in the diagnosis of patients with diabetes complicated with tuberculosis and at analyzing the influence of dietary nursing on patients with diabetes complicated with tuberculosis. In this study, the FBP algorithm was used to optimize CT images to effectively obtain reconstructed ROI images. Then, the deviation from measurement values of reconstructed images at different pixel levels was analyzed. 138 patients with diabetes complicated with tuberculosis were selected as research subjects to compare the number of lung segments involved and the CT imaging manifestations at different fasting glucose levels. All patients were divided into the control group (routine drug treatment) and observation group (diet intervention on the basis of drug treatment) by random number table method, and the effect of different nursing methods on the improvement of patients’ clinical symptoms was discussed. The results showed that the distance measurement value decreased with the increase in pixel level, there was no significant difference in the number of lung segments involved in patients with different fasting glucose levels ( P > 0.05 ), and there were statistically significant differences in the incidence of segmental lobar shadow, bronchial air sign, wall-less cavity, thick-walled cavity, pulmonary multiple cavity, and bronchial tuberculosis in patients with different fasting glucose levels ( P < 0.05 ). Compared with the control group, 2 h postprandial blood glucose level in the observation group was significantly improved ( P < 0.05 ), there was a statistical significance in the number with reduced pleural effusion and the number with reduced tuberculosis foci in the two groups ( P < 0.05 ), and the level of hemoglobin in the observation group was 7.1 ± 1.26 , significantly lower than that in the control group ( 8.91 ± 2.03 , P < 0.05 ). It suggested that the changes of CT images based on the FBP reconstruction algorithm were correlated with fasting blood glucose level. Personalized diet nursing intervention can improve the clinical symptoms of patients, which provides a reference for the clinical diagnosis and treatment of patients with diabetes complicated with tuberculosis.