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Liver failure causes blood-brain-barrier (BBB) breakdown leading to central nervous system damage, however the mechanisms whereby the liver influences BBB-integrity remain elusive. One possibility is that the liver secretes an as-yet to be identified molecule(s) that circulate in the serum to directly promote BBB integrity. We developed light-sheet imaging for three-dimensional study of BBB function. We show that liver- or muscle-specific knockout of Hfe2 induces BBB breakdown, leading to accumulation of toxic-blood-derived fibrinogen in the brain, lower cortical neuron numbers, and behavioral deficits. In healthy animals, soluble Hfe2 competes with its homologue RGMa for binding to Neogenin, thereby blocking RGMa-induced downregulation of PDGF-B and Claudin-5 in endothelial cells and the ensuing BBB disruption. Hfe2 administration in an animal model of multiple sclerosis prevented paralysis and immune cell infiltration by inhibiting RGMa-mediated BBB alteration. This study has implications for the pathogenesis and potential treatment of diseases associated with BBB dysfunction such as multiple sclerosis.

Background: Infection with multiple pathogens may play a key role in the pathogenesis of dementia. Whether Helicobacter pylori (H. pylori) infection is associated causally with dementia is controversial. Objective: We conduct a meta-analysis of case-control and cohort studies on the association between H. pylori infection and the risk for all-cause and Alzheimer’s disease (AD) dementia. Methods: Two independent reviewers searched the PubMed, Cochrane Library, and Embase databases with English language restrictions from the date of conception to September 18, 2020. The primary analysis was as follows: the exposure variable was H. pylori infection, and the outcome was incident all-cause and AD dementia. Pooled odds ratios (OR), relative risk (RR), and corresponding 95% confidence intervals (CI) were obtained using the fixed-or random-effect model. Forest plots were generated to summarize the results. Results: Ten studies involving 96,561 participants were included in the meta-analysis: 5 case-control studies and 5 cohort studies. The overall pooled cohort studies showed a significant positive association between H. pylori infection and all-cause dementia with pooled RR of 1.36 (95% CI, 1.11-1.67). There was no association between H. pylori infection and risk for developing AD: RR of 1.33 (95% CI, 0.86-2.05) in cohort studies, and OR of 1.72 (95% CI, 0.97-3.04) in case-control studies. Significant heterogeneity was showed in each comparison group. Conclusion: This meta-analysis supports a positive association between H. pylori infection and the risk of all-cause dementia, but not AD dementia. Due to the interference of confounding factors, randomized controlled trials are needed to prove their causality.

Objective: The purpose of present study was to investigate the effects of condensed molasses fermentation solubles (CMS) on lactation performance, rumen fermentation, nutrient digestibility, and serum parameters of dairy cows.Methods: A total of 75 healthy Holstein cows with the same parity (milk production = 35±2.5 kg, body weight = 570±28 kg) were randomly selected and divided into 5 groups. One group served as control group (CON; no CMS), whereas the other 4 groups were CMS1 (accounted for 1% of the diet), CMS2 (2%), CMS3 (3%), and CMS4 (4%). All cows were fed regularly three times each day at 0800, 1600, and 2400 h. Cows received diet and water ad libitum. The experiment lasted for 60 days.Results: Results showed that the dry matter intake, milk yield, and protein of CMS2 were maximum and higher (p

It is known that nutrition and immunity are connected, but the mechanism is not very clear. Endogenous retroviruses (ERV) account for 8 to 10% of the human and mouse genomes and play an important role in some biological processes of animals. Recent studies indicate that the activation of ERV can affect the expression of the immunity- or inflammation-related genes, and the activities of ERV are subjected to regulation of many factors including nutritional factors. Therefore, we hypothesize that nutritional status can affect the expression of the immunity- or inflammation-related genes via ERV. To verify this hypothesis, the nutritional status of animals was altered by fasting or overfeeding, and the expression of intact ERV (ERVK18P, ERVK25P) and immunity- or inflammation-related genes (DDX41, IFIH1, IFNG, IRF7, STAT3) in the liver was determined by quantitative PCR, followed by overexpressing ERVK25P in goose primary hepatocytes and determining the expression of the immunity- or inflammation-related genes. The data showed that compared with the control group (no fasting), the expression of ERV and the immunity- or inflammation-related genes was increased in the liver of the fasted chickens but decreased in the liver of the fasted geese. Moreover, compared with the control group (routinely fed), the expression of ERV and the immunity- or inflammation-related genes was increased in the liver of the overfed geese. In addition, overexpression of ERVK25P in goose primary hepatocytes can induce the expression of the immunity- or inflammation-related genes. In conclusion, these findings suggest that ERV mediate the effects of fasting and overfeeding on the expression of the immunity- or inflammation-related genes, the mediation varied with poultry species, and ERV and the immunity- or inflammation-related genes may be involved in the development of goose fatty liver. This study provides a potential mechanism for the connection between nutrition and immunity.

Background Neuronal intranuclear inclusion disease (NIID) is an unusual autosomal dominant, chronic progressive neurodegenerative disease. The clinical manifestations of NIID are complex and varied, complicating its clinical diagnosis. To the best of our knowledge, this report is the first to document sporadic adult-onset NIID mimicking acute cerebellitis (AC) that was finally diagnosed by imaging studies, skin biopsy, and genetic testing. Case summary A 63-year-old man presented with fever, gait unsteadiness, dysarthria, and an episode of convulsion. His serum levels of white blood cells and C-reactive protein were significantly elevated. T2-weighted brain magnetic resonance imaging and fluid attenuation inversion recovery sequences showed bilateral high-intensity signals in the medial part of the cerebellar hemisphere beside the vermis. While we initially considered a diagnosis of AC, the patient's symptoms improved significantly without special treatment, prompting our consideration of NIID. Diffusion-weighted imaging showed hyperintensity in the corticomedullary junction. Skin biopsy revealed eosinophilic inclusions positive for anti-p62 in epithelial sweat-gland cells. GGC repeat expansions in the Notch 2 N-terminal like C gene confirmed the diagnosis of NIID. Conclusion For patients with clinical manifestations mimicking AC, the possibility of underlying NIID should be considered along with prompt rigorous examinations.

The neonatal brain is susceptible to hypoxic-ischemic injury due to its developmental characteristics. Hypoxia-ischemia means a decreased perfusion of oxygen and glucose, which can lead to severe encephalopathy. Although early initiation of therapeutic hypothermia was reported to provide neuroprotection for infants after HI, hypothermia administered alone after the acute insult cannot reverse the severe damage that already has occurred or improve the prognosis of severe hypoxic-ischemic encephalopathy. Therefore, exploring new protective mechanisms for treating hypoxic-ischemic brain damage are imperative. Until now, many studies reported the neuroprotective mechanisms of hypoxic/ischemic preconditioning in protecting the hypoxic-ischemic newborn brains. After hypoxia and ischemia, hypoxia-inducible factor signaling pathway is involved in the transcriptional regulation of many genes and is also play a number of different roles in protecting brains during hypoxic/ischemic preconditioning. Hypoxic/ischemic preconditioning could protect neonatal brain by several mechanisms, including vascular regulation, anti-apoptosis, anti-oxidation, suppression of excitotoxicity, immune regulation, hormone levels regulation, and promote cell proliferation. This review focused on the protective mechanisms underlying hypoxic/ischemic preconditioning for neonatal brain after hypoxia-ischemia and emphasized on the important roles of hypoxia inducible factor 1 signaling pathway.

Fat emulsion is an important component of parenteral nutrition in premature infants. However, intravenous fat emulsions (IVFE) was reported to be associated with some serious complications, such as bronchopulmonary dysplasia (BPD). Compared to conventional soybean oil-based IVFE, new-generation IVFE may protect against BPD but the results are conflicting. Relevant literatures search was conducted and the summary effect estimates of odds ratio (OR) and 95% confidence interval (CI) were calculated with fixed-effects models. Of 22 studies involving 3781 infants were selected in this study and BPD was reported as part of the included studies. The pooled estimate for 13 studies, comparing administration of new-generation IVFE with conventional IVFE, indicated that new-generation IVFE was not associated with a reduced risk of BPD in preterm infants, compared with conventional IVFE (OR 0.96; 95% CI 0.80–1.14); the pooled estimate for 18 studies, comparing administration of fish oil-containing IVFE with non-fish oil IVFE, indicated that fish oil-containing IVFE has no protective effect against the occurrence of BPD in preterm infants (OR 0.88; 95% CI 0.71–1.08). There is no evidence to support that the new-generation IVFEs could prevent the incidence of BPD or fish oil-containing IVFEs could show a beneficial effect to BPD in premature infants.

Gonadotropin-releasing hormone (GnRH) is a key neuropeptide of the reproductive system. However, little is known about the role of GnRH in the spotted scat (Scatophagus argus). Here, three GnRH subtypes (cGnRH-II, sGnRH, and sbGnRH) were identified in the spotted scat. cGnRH-II and sGnRH were only expressed in the brains and gonads of both male and female fish, exhibiting a tissue-specific expression pattern, while sbGnRH was expressed at different transcription levels in all examined tissues. During ovarian maturation, hypothalamus-associated sbGnRH was upregulated, while the expression of sGnRH was variable and cGnRH-II first increased and then decreased. In vivo experiments showed that sbGnRH significantly promoted the expression of fsh and lh genes in a dose-dependent manner and exhibited a desensitization effect on lh expression at high concentrations. For sGnRH and cGnRH-II, only high concentrations could induce fsh and lh expression. Furthermore, treatment with highly concentrated sbGnRH peptide also induced fsh and lh expression, whereas the sGnRH and cGnRH-II peptides only induced fsh expression in vitro. 17β-Estradiol (E2) significantly inhibited the expression of sbGnRH mRNA in a dose-dependent manner and did not impact sGnRH and cGnRH-II mRNA levels in vivo or in vitro. The inhibitory effect of E2 on sbGnRH expression was attenuated by the estrogen receptor (ER) broad-spectrum antagonist (fulvestrant) and the ERα-specific antagonist (methyl-piperidinopyrazole), respectively, implying that the feedback regulation on sbGnRH is mediated via ERα. This study provides a theoretical basis for the reproductive endocrinology of the spotted scat by studying GnRH.

Background: Kawasaki Disease (KD) is an acute self-limiting systemic vasculitis syndrome which can result in arterial damage especially in coronary artery. To find possible new biomarkers for the diagnosis of KD by Data independent acquisition (DIA) quantitative proteomics.Methods: Twenty-seven patients with KD were enrolled in the present study, further, gingival crevicular fluid of before IVIG treatment with KD was collected as the experimental group. Meanwhile, 18 healthy volunteers were recruited as the control group.DIA quantitative proteomics mass spectrometry analysis was performed on the GCF samples of each group, and the protein expression profiles of the two groups of GCF were detected. Function enrichment of DEP by KEGG and GO, protein-protein interaction (PPI) analysis for all the DEPs detected, Finally, the multiple reaction monitoring mass spectrometry method was used to verify the selected DEPs.Results:197 DEPs (174 up-regulated and 23 down-regulated) were detected in the CGF between the KD group and the normal control group. Cellular process and metabolic process, binding and catalytic activity are the most altered biological process and molecular function, respectively. NOD−like receptor signaling pathway, Protein processing in endoplasmic reticulum pathway and influenza pathway are most significant pathway. EIF2AK2, B2M and GBP1 are kernel proteins in PPI network. The results of MRM-MS of 12 DEPs including IFIT3, UB2L6, HP, A1AT, HSP90AA1, HNRPC, HSP90AB1, SAA1, MX1, B2M, FKBP4 and TRAP1 were highly consistent with DIA.Conclusions: We suggested that 12 proteins in GCF could be used as new biomarkers for early diagnosis of KD. We also found that KD is closely related to gingival inflammation at the molecular level, which provides new ideas and directions for the diagnosis and treatment of KD.

Background: Kawasaki disease (KD) is an acute self-limiting systemic vasculitis. In study, a randomized controlled trial regarding berberine (main component of Coptidis Rhizoma) function in treating KD was carried out and possible pharmacological mechanisms of Coptidis Rhizoma (CR) on KD therapy were investigated using an integrated network pharmacology approach. Methods: A total of 58 children with KD, younger than 5 years old, were enrolled in the study from October 2018 to May 2019. The patients were randomly divided into control group and BBR treatment group. The therapeutic indicators of the 2 groups before and after treatments were compared. Then, compounds and drug targets of CR from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the SWISS database, the SEA database and the STITCH database were collected, and targeted KD genes were retrieved from the DisGeNET databases, the DrugBank databases and the GeneCards databases. The network pharmacology approach involved network construction, target prediction, and module analysis. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to CR for KD treatments. Results: The berberine group was able to reduce the values of CRP, NLR and PLR significantly. Also, the effect of berberine improved the resistance rate of intravenous injection of gamma globulin significantly. In total, 9 compounds and 369 relative drug targets were collected from TCMSP, SWISS, SEA and STITCH database and 624 KD target genes were collected in DisGeNET, DrugBank and GeneCards database. The network analysis revealed that 41 targets might be the therapeutic targets of CR on KD, among which ATK1, RELA, SRC, CASP3 and MTOR ranked in top 5. Gene ontology enrichment analysis revealed that the reaction to bacteria-derived molecules and to lipopolysaccharide and the apoptosis process were the key biological procedures for CR treating KD. The KEGG pathway enrichment analysis pointed out that the four signaling pathways closely related to CR treating KD including age-rage signaling pathway, fluid shear stress and atherosclerosis, TNF signaling pathway and Toll-like receptor signaling pathway in diabetic complications. Conclusions: we concluded that the introduction of routine treatment combined with berberine in treating KD has advantages than routine treatment and can be considered as a preferred approach in KD. Network pharmacology showed that CR exerted the effect of prevention KD by regulating multi-targets and multi-components.

To analyze value of PDCA circulation mode combined with continuing nursing guided by WeChat on improving the nursing quality of patients with gynecological inflammatory diseases during out-of-hospital treatment. 320 patients with gynecological inflammation were equally divided into control group (routine guidance during out-of-hospital treatment) and observation group (the control group implemented PDCA circulation mode combined with WeChat guidance of continuing care services). Nursing quality score and total nursing efficiency were compared. The patients’ average age, marital status, menopause and disease types showed no difference between two groups. After 3 months of nursing intervention, the scores of nursing quality and total effective rate of nursing in the observation group were better than those in the control group. The improvement degree of mastery rate of gynecological health knowledge and the total nursing satisfaction in the observation group were better than those in the control group. During out-of-hospital treatment of patients with gynecological inflammatory diseases, the implementation of PDCA circulation mode combined with the continuous nursing intervention guided by WeChat is conducive on improving the quality of nursing, improving the grasp of gynecological health knowledge, thus increasing the satisfaction of patients with nursing services, with a high value of promotion and application.

Background: Kawasaki disease (KD) leads to coronary artery damage and the etiology of KD is unknown. The present study was designed to explore the differentially expressed genes (DEGs) in KD serum-induced human coronary artery endothelial cells (HCAECs) by RNA-sequence (RNA-seq). Methods: HCAECs were stimulated with serum (15% (v/v)), which were collected from 20 healthy children and 20 KD patients, for 24 hours. DEGs were then detected and analyzed by RNA-seq and bioinformatics analysis. Results: The expression of SMAD1, SMAD6, CD34, CXCL1, PITX2, and APLN was validated by qPCR. 102 genes, 59 up-regulated and 43 down-regulated genes, were significantly differentially expressed in KD groups. GO enrichment analysis showed that DEGs were enriched in cellular response to cytokines, cytokine-mediated signaling pathway, and regulation of immune cells migration and chemotaxis. KEGG signaling pathway analysis showed that DEGs were mainly involved in cytokine−cytokine receptor interaction, chemokine signaling pathway, and TGF−β signaling pathway. Besides, the mRNA expression levels of SMAD1, SMAD6, CD34, CXCL1, and APLN in the KD group were significantly up-regulated compared with the normal group, while PITX2 was significantly down-regulated. Conclusion: 102 DEGs in KD serum-induced HCAECs were identified, and six new targets may be closely associated with the pathogenesis of KD.

Nemaline myopathy (NEM) is a congenital myopathy that typically presents with proximal muscle weakness and hypotonia. To date, 13 genes have been associated with NEM. The Kelch repeat and BTB domain-containing protein 13 (KBTBD13) gene (KBTBD13)-related NEM is a rarely reported condition, and not a single case has been reported in Asia. Here, we report the case of a mother and daughter in China with NEM caused by a mutation (c.1222C>T) in KBTBD13. Their shared clinical phenotype is symmetrical muscle weakness in the arms and legs with childhood onset. Muscle magnetic resonance imaging showed the unique replacement mode of muscle with fibro-fatty tissue. Histopathological examination revealed the presence of fibers containing rod-shaped structures in the cytoplasm or under the sarcolemma. DNA sequencing analysis detected a heterozygous mutation (c.1222C>T) in KBTBD13 in this family. A founder effect for the variant may exist in the Low Countries of Belgium and the Netherlands, and the mutation may be a hotspot mutation in Europe, as it has not been reported in Asia. Our case study expands the spectrum of KBTBD13-related NEM.

Until recently, the existence of extracellular kinase activity was questioned. Many proteins of the central nervous system are targeted, but it remains unknown whether, or how, extracellular phosphorylation influences brain development. Here we show that the tyrosine kinase vertebrate lonesome kinase (VLK), which is secreted by projecting retinal ganglion cells, phosphorylates the extracellular protein repulsive guidance molecule b (RGMb) in a dorsal-ventral descending gradient. Silencing of VLK or RGMb causes aberrant axonal branching and severe axon misguidance in the chick optic tectum. Mice harboring RGMb with a point mutation in the phosphorylation site also display aberrant axonal pathfinding. Mechanistic analyses show that VLK-mediated RGMb phosphorylation modulates Wnt3a activity by regulating LRP5 protein gradients. Thus, the secretion of VLK by projecting neurons provides crucial signals for the accurate formation of nervous system circuitry. The dramatic effect of VLK on RGMb and Wnt3a signaling implies that extracellular phosphorylation likely has broad and profound effects on brain development, function and disease.

BackgroundNeuronal intranuclear inclusion disease (NIID) is a heterogenous neurodegenerative disorder named after its pathological features. It has long been considered a disease of genetic origin. Recently, the GGC repeated expansion in the 5′-untranslated region (5′UTR) of the NOTCH2NLC gene has been found in adult-onset NIID in Japanese individuals. This study was aimed to investigate the causative mutations of NIID in Chinese patients.MethodsFifteen patients with NIID were identified from five academic neurological centres. Biopsied skin samples were analysed by histological staining, immunostaining and electron microscopic observation. Whole-genome sequencing (WGS) and long-read sequencing (LRS) were initially performed in three patients with NIID. Repeat-primed PCR was conducted to confirm the genetic variations in the three patients and the other 12 cases.ResultsOur patients included 14 adult-onset patients and 1 juvenile-onset patient characterised by degeneration of multiple nervous systems. All patients were identified with intranuclear inclusions in the nuclei of fibroblasts, fat cells and ductal epithelial cells of sweat glands. The WGS failed to find any likely pathogenic variations for NIID. The LRS successfully identified that three patients with adult-onset NIID showed abnormalities of GGC expansion in 5′UTR of the NOTCH2NLC gene. The GGC repeated expansion was further confirmed by repeat-primed PCR in seven familial cases and eight sporadic cases.ConclusionOur findings provided evidence that confirmed the GGC repeated expansion in the 5′UTR of the NOTCH2NLC gene is associated with the pathogenesis of NIID. Additionally, the GGC expansion was not only responsible for adult-onset patients, but also responsible for juvenile-onset patients.

Scatophagus argus is a new emerging aquaculture fish in East and Southeast Asia. To date, research on reproductive development and regulation in S. argus is lacking. Additionally, genetic and genomic information about reproduction, such as gonadal transcriptome data, is also lacking. Herein, we report the first gonadal transcriptomes of S. argus and identify genes potentially involved in reproduction and gonadal development. A total of 136,561 unigenes were obtained by sequencing of testes (n = 3) and ovaries (n = 3) at stage III. Genes upregulated in males and females known to be involved in gonadal development and gametogenesis were identified, including male-biased dmrt1, amh, gsdf, wt1a, sox9b, and nanos2, and female-biased foxl2, gdf9, bmp15, sox3, zar1, and figla. Serum estradiol-17β and 11-ketotestosterone levels were biased in female and male fish, respectively. Sexual dimorphism of serum steroid hormone levels were interpreted after expression analysis of 20 steroidogenesis-related genes, including cyp19a1a and cyp11b2. This gonadal transcript dataset will help investigate functional genes related to reproduction in S. argus.

In ruminants, the ruminal epithelium not only has the function of absorbing nutrients but also is an important tissue to prevent harmful substances in the rumen from entering the blood circulation. Thus, the normal function of ruminal epithelium is critical for ruminants. However, subacute ruminal acidosis induced by high-concentrate diets often damages the barrier function of ruminal epithelium in ruminants. Recently, many studies have shown that dietary supplementation with thiamine is an effective method to alleviate subacute ruminal acidosis. In order to provide theoretical reference for the in-depth study of subacute ruminal acidosis and the application of thiamine in the future, this review introduces the effects of subacute ruminal acidosis on morphological structure, inflammatory response, and tight junction of ruminal epithelium. In addition, this paper summarizes the role of thiamine in maintaining ruminal epithelial function of ruminants during subacute ruminal acidosis challenge.

Background Kawasaki disease (KD) is the main cause of acquired heart disease in children and can lead to coronary artery lesions. This present study was designed to analyze the characteristics of KD peripheral blood mononuclear cells (PBMC) through single-cell RNA sequencing (scRNA-seq) and to explore the potential molecular mechanism of KD. Methods PBMC was collected from one healthy child and one KD patient, and was used to single-cell RNA sequencing for cell clusters identification and differently expressed gene (DEG) determination. GO function enrichment analysis of DEG in B cell and T cells were performed to explore the most active biological function in KD immune cells. Results Twelve cell clusters can be identified in two samples. Compared with healthy child, naive CD8+ T cell, T helper cell and B cell in KD child were decreased, mainly immune-related T cells, and natural killer T (NKT) cell were increased. Cell activation, lymphocyte activation and regulation of immune system process were 3 GO function shared by all four types of T cells and B cell. Conclusions Immune cell disorder appears in the KD patient at single cell level by scRNA-seq.

Sarcotubular myopathy (STM) is a rare autosomal recessive myopathy caused by TRIM32 gene mutations. It is predominantly characterized by the weakness of the proximal limb and mild to moderate elevation of creatine kinase (CK) levels. In this study, we describe a 50‑year‑old Chinese man who exhibited a proximal-to-distal weakness in the muscles of the lower limbs and who had difficulty standing up from a squat position. The symptoms gradually became more severe. He denied a history of cognitive or cardiological problems. The patient's parents and children were healthy. Histopathological examination revealed dystrophic changes and irregular slit-shaped vacuoles containing amorphous materials. Whole-exome sequencing consisting of protein-encoding regions of 19,396 genes was performed, the results of which identified one novel homozygous 2kb deletion chr9.hg19: g.119460021_119461983del (exon2) in the TRIM32 gene. This was confirmed at the homozygous state with quantitative real-time PCR. Here, we present a Chinese case of STM with one novel mutation in TRIM32 and provide a brief summary of all known pathogenic mutations in TRIM32.

Rationale: Neuromyelitis optica spectrum disorders (NMOSDs) are inflammatory demyelinating disorders of the central nervous system; they are characterized by severe optic neuritis and transverse myelitis. Intravenous methylprednisolone pulse (IVMP) therapy is an effective treatment that is administered to patients in the acute phase of NMOSD; this therapy has achieved remarkable results in clinical practice. However, there are no reports on NMOSD patients who have experienced an acute bilateral cerebral infarction while undergoing IVMP treatment. Patient concerns: We report on a 62-yr-old woman who was undergoing IVMP therapy for the primary diagnosis of NMOSD. Unexpectedly, the patient's existing limb weakness worsened, and she developed motor aphasia on the second day of IVMP treatment. Additionally, brain magnetic resonance imaging revealed acute bilateral cerebral infarction. Diagnosis: The patient's clinical manifestations, medical imaging results, and laboratory test results were taken into consideration; the final diagnosis was acute bilateral cerebral infarction in the presence of NMOSD. Interventions: Subsequent to the onset of acute cerebral infarction, the patient was immediately treated with oral aspirin, atorvastatin, and intravenous butylphthalide. The hormone dose was adjusted to an oral 60-mg/d dose for maintenance; this was followed by immunoadsorption plasmapheresis for 3 days, and double-filtration plasmapheresis for 2 days. Outcomes: Following treatment onset, the patient's ocular symptoms significantly improved, and her limb muscle strength gradually recovered. Two months after discharge, the patient's husband reported that she was able to walk with the help of others and take care of herself, and that there was no recurrence. Lessons: Medical professionals must be aware of the possibility of NMOSD patients with cerebrovascular risk factors suffering an acute cerebral infarction while undergoing high-dose IVMP therapy, as this therapy can exacerbate existing problems.

Rationale: GNE myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase(GNE) gene and is clinically characterized by progressive weakness and atrophy of the lower-limb muscles with quadriceps sparing. Nearly all GNE mutations that have been reported thus far in various ethnic populations around the world have been missense or nonsense mutations. Patient concerns: We describe the case of a 32-year-old woman with GNE myopathy. The patient presented with progressive weakness of the lower-limb muscles that had spread to her legs. Her serum creatine kinase level was higher than the normal range. Mild myogenic changes were detected in the tibialis anterior muscles on electromyography, and moderate fatty infiltration was observed in various lower-limb muscles on magnetic resonance imaging. Histopathological examination of a skeletal muscle biopsy specimen revealed variation in muscle fiber size, rimmed vacuoles, and disorganized intermyofibrillar networks. DNA sequencing testing revealed a compound heterozygous mutation consisting of a known mutation (c.620A > T in exon 3) and a novel (exon 1 deletion) mutation. Diagnoses: Taken together, the clinical features, laboratory testing and DNA findings eventually made the diagnosis of GNE myopathy. Interventions and outcomes: Based on the diagnosis of the GNE myopathy, the patient was administered sialic acid 6 g a day for 1 year, and up to now, her symptoms did not progress further. Lessons: We have reported the case of a GNE myopathy patient with compound heterozygous GNE gene mutations. This case expands the genotypic spectrum of GNE myopathy.

Communication between tissues and organs plays an important role in the maintenance of normal physiological functions as well as the occurrence and development of diseases. Communication molecules act as a bridge for interactions between tissues and organs, playing not only a local role in the tissues and organs where they are secreted but also in exerting systemic effects on the whole body via circulation. In this study, blood microRNA-omics analysis of overfed vs. normally fed (control) Landes geese revealed that the content of each of the 21 microRNAs (miRNAs) in the blood of overfed geese was significantly higher than that in the blood of control geese. These miRNAs may have systematic effects in the development of goose fatty liver as well as being candidate markers for the diagnosis of goose fatty liver. We determined the expression of miR-143, miR-455-5p, miR-222a-5p, miR-184, miR-1662, and miR-129-5p using quantitative PCR in goose fatty liver vs. that in normal liver. The expression of these miRNAs, except miR-129-5p, in goose fatty liver was also significantly higher than that in normal liver (P

Background Hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus is characterized by systemic immunopathological injury. Pentraxin-3 is an acute-phase reactant involved in the processes of inflammation and infection. This study aimed to investigate the levels of plasma pentraxin-3 and evaluate its predictive value on disease severity and mortality risk in patients with HFRS. Methods This was a prospective real-world observational study. The concentrations of plasma pentraxin-3 were measured by enzyme linked immunosorbent assay (ELISA) in 105 HFRS patients and 27 healthy controls. We analyzed the clinical relevance between pentraxin-3 and clinical subtyping, hospital stay and conventional laboratory parameters of HFRS patients. Considering the prognosis (death) as the primary endpoint, the levels of pentraxin-3 between survivors and non-survivors were compared, and its association with mortality was assessed by Kaplan-Meier survival analysis. The predictive potency of pentraxin-3 for mortality risk in HFRS patients was evaluated by receiver operating characteristic (ROC) curve analysis. Results The levels of pentraxin-3 during the acute phase were increased with the aggravation of the disease, and showed the highest expression in critical-type patients (P CI: 0.593 ~ 0.914, P = 0.003). Conclusions The detection of plasma pentraxin-3 might be beneficial to the evaluation of disease severity and to the prediction of mortality risk in HFRS patients.

Background Cisplatin resistance (DDP-resistance) remains one of the major causes of poor prognosis in females with ovarian cancer. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of cellular processes, including chemoresistance. The aim of this study was to explore the role of HOX transcript antisense RNA (HOTAIR) in DDP-resistant ovarian cancer cells. Methods DDP-resistant ovarian cancer cell lines (SKOV3/DDP and A2780/DDP) were established. Real-time PCR, western blot, dual-luciferase reporter assay, and flow cytometry were then used to evaluate the effect of HOTAIR/miR-138-5p axis on chemoresistance of DDP-resistant ovarian cancer cells to DDP. Results We found that HOTAIR was upregulated in DDP-resistant cells, while miR-138-5p was downregulated. Knockdown of HOTAIR increased the expression of miR-138-5p in DDP-resistant cells and miR-138-5p is directly bound to HOTAIR. Upregulation of miR-138-5p induced by HOTAIR siRNA or by its mimics enhanced the chemosensitivity of DDP-resistant cells and decreased the expression of EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) and SIRT1 (sirtuin 1). Furthermore, the HOTAIR silencing-induced chemosensitivity of DDP-resistant cells was weakened by miR-138-5p inhibitor. Conclusions These data demonstrate that HOTAIR acts as a sponge of miR-138-5p to prevent its binding to EZH2 and SIRT1, thereby promoting DDP-resistance of ovarian cancer cells. Our work will shed light on the development of therapeutic strategies for ovarian cancer treatment.

The history of brain science is dominated by the study of neurons. However, there are as many glial cells as neurons in the human brain, their complexity increases during evolution, and glial cells play important roles in brain function, behavior, and neurological disorders. Although neurons and glial cells were first described at the same time in the early 19th century, why did the physiological study of glial cells only begin in the 1950s? What are the scientific breakthroughs and conceptual shifts that determined the history of glial cells in relation to that of neurons? What is the impact of the history of glia on the evolution of neuroscience? In order to answer these questions, we reconstructed the history of glial cells, from their first description until the mid-20th century, by examining the relative role of technical developments and scientific interpretations.

To investigate the correlation between the initial prophylactic antibiotic use and the subsequent NEC in high-risk premature infants. We performed a literature search of PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Web of Science, and nine studies with a total of 5207 infants were selected for inclusion in this study. The pooled estimate for the seven studies combined indicating that prophylactic antibiotic usage was associated with a non-significant trend toward increased incidence of NEC [odds ratio (OR) 0.75; 95% confidence interval (CI) 0.26–2.17], and prolonged exposure to prophylactic antibiotics, compared with limited prophylactic antibiotic use, was associated with a significant trend toward the risk of increasing incidence of NEC (OR 1.31; 95% CI 1.08–1.59). Current evidence does not support the use of prophylactic antibiotics to reduce the incidence of NEC for high-risk premature infants.

Estrogen receptors (Er) play a critical role in vitellogenesis. Three ers (erα, erβ1 and erβ2) and vitellogenins (vtg-A, vtg-B and vtg-C) subtypes were isolated in various fish species, while the contribution of each Er to the regulation of vtgs expression was not analyzed in detail. Here, erα, erβ1 and erβ2 were cloned and all were found to be expressed in female liver in Scatophagus argus. During proteic vitellogenesis stage, erα was simultaneously up-regulated, while erβ1 and erβ2 were not, with three vtgs in female liver. The effects of 17β-estradiol (E2) alone or combined with Er antagonists on ers, vtgs mRNA expressions and Vtg protein content in incubated male liver were examined by real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The expressions of erα, erβ1, vtgs mRNA and Vtg protein increased significantly after 24h incubation with E2 (0.1, 1 and 10μM), while Er nonselective antagonist ICI 182 780 (0.01, 0.1 and 1μM) significantly attenuated the up-regulation effects of E2 on ers, vtgs mRNA and Vtg protein in a dose-dependent manner. Erα selective antagonist Methyl-piperidinopyrazole (MPP) (0.01, 0.1 and 1μM) significantly attenuated the up-regulation effects of E2 on erα, vtg-B, vtg-C mRNA and Vtg protein, while promoted the expression of erβ1 and vtg-A. Erβ selective antagonist Cyclofenil (0.01, 0.1 and 1μM) attenuated the up-regulation effects of E2 on erβ1, erβ2, vtg-A, vtg-C mRNA and Vtg protein while promoted the expression of erα and vtg-B. Our results suggest that the regulation of Ers on different vtgs was divergent in S. argus.

Hantaviruses are comprised of tri-segmented negative sense single-stranded RNA, and are members of the Bunyaviridae family. Hantaviruses are distributed worldwide and are important zoonotic pathogens that can have severe adverse effects in humans. They are naturally maintained in specific reservoir hosts without inducing symptomatic infection. In humans, however, hantaviruses often cause two acute febrile diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). In this paper, we review the epidemiology and epizootiology of hantavirus infections worldwide.

Our knowledge of the brain has evolved over millennia in philosophical, experimental and theoretical phases. We suggest that the next phase is simulation neuroscience. The main drivers of simulation neuroscience are big data generated at multiple levels of brain organization and the need to integrate these data to trace the causal chain of interactions within and across all these levels. Simulation neuroscience is currently the only methodology for systematically approaching the multiscale brain. In this review, we attempt to reconstruct the deep historical paths leading to simulation neuroscience, from the first observations of the nerve cell to modern efforts to digitally reconstruct and simulate the brain. Neuroscience began with the identification of the neuron as the fundamental unit of brain structure and function and has evolved towards understanding the role of each cell type in the brain, how brain cells are connected to each other, and how the seemingly infinite networks they form give rise to the vast diversity of brain functions. Neuronal mapping is evolving from subjective descriptions of cell types towards objective classes, subclasses and types. Connectivity mapping is evolving from loose topographic maps between brain regions towards dense anatomical and physiological maps of connections between individual genetically distinct neurons. Functional mapping is evolving from psychological and behavioral stereotypes towards a map of behaviors emerging from structural and functional connectomes. We show how industrialization of neuroscience and the resulting large disconnected datasets are generating demand for integrative neuroscience, how the scale of neuronal and connectivity maps is driving digital atlasing and digital reconstruction to piece together the multiple levels of brain organization, and how the complexity of the interactions between molecules, neurons, microcircuits and brain regions is driving brain simulation to understand the interactions in the multiscale brain.

This chapter describes the clinical symptoms and signs of AECHB and HBV ACLF, classification, grading of HBV ACLF and their features, diagnostic principles and standards in liver pathology, biochemistry, and virology of HBV ACLF. 1. Liver failure is defined as serious damage to the liver cause by a variety of etiologies, leading to liver function disorder or even decompensation, and clinical syndromes with coagulopathy, jaundice, hepatic encephalopathy, and ascites. 2. Severe hepatitis B can be indicated pathologically by apparent hepatocellular necrosis, including extensive multifocal, confluent, bridging, sub-massive or massive necrosis. 3. Laboratory tests during the course of severe exacerbation of chronic hepatitis B can reflect pathological changes and liver function in a timely manner, providing objective and informative reference data for evaluation of disease severity and treatment efficacy. Among the most important laboratory tests are those for prothrombin activity, international normalized ratio, and increases in total bilirubin concentration. 4. Severe hepatitis B is associated with interactions between the virus and host factors. Detection of HBV DNA, HBV genotype, quasispecies and HBV mutation can provide important theoretical bases for the prevention, control or mitigation of the progress of severe hepatitis B. 5. Noninvasive imaging modalities can be used to visualize the entire liver and parts of it. Measuring liver volume to evaluate liver size and liver reserve capacity is regarded as important in diagnosis, surgical approach and prognostic evaluation of patients with severe exacerbation of chronic hepatitis B and liver failure. 6. Model for End-Stage Liver Disease (MELD) is the first quantitative method developed to assess whether a patient with liver failure requires a liver transplant. The predictive value of the MELD model has been improved by the MELD-Na, iMELD, and MESO models. Several other valuable prognostic models have been developed. For example, for patients with HBV-ACLF, the established TPPM scoring system was found to be more predictive than MELD score.

Next-generation sequencing (NGS) technology has led to great advances in understanding the causes of Mendelian and complex neurological diseases. Owing to the complexity of genetic diseases, the genetic factors contributing to many rare and common neurological diseases remain poorly understood. Selecting the correct genetic test based on cost-effectiveness, coverage area, and sequencing range can improve diagnosis, treatments, and prevention. Whole-exome sequencing and whole-genome sequencing are suitable methods for finding new mutations, and gene panels are suitable for exploring the roles of specific genes in neurogenetic diseases. Here, we provide an overview of the classifications, applications, advantages, and limitations of NGS in research on neurological diseases. We further provide examples of NGS-based explorations and insights of the genetic causes of neurogenetic diseases, including Charcot–Marie–Tooth disease, spinocerebellar ataxias, epilepsy, and multiple sclerosis. In addition, we focus on issues related to NGS-based analyses, including interpretations of variants of uncertain significance, de novo mutations, congenital genetic diseases with complex phenotypes, and single-molecule real-time approaches.

Anti-synthetase syndrome (ASS) is a rare autoimmune disorder characterized by the presence of antibodies against aminoacyl-transfer RNA synthetase commonly associated inflammatory myopathy. In this case report, we describe an adult female with NMOSD concurrent with ASS in which the lesion involved the entire length of the spinal cord. Since B-cell mediated molecular pathway is involved in the pathogenesis of NMOSD and ASS, we suggest that the therapeutically targeted killing of B-cells, such as Rituximab, is effective.

Introduction: Gastric adenocarcinoma of the fundic gland type (GA-FG) is a newly described entity that is characterized by well-differentiated neoplasm with unclear etiopathogenesis. Patient concerns: A 60-year-old Chinese man was referred to our hospital for abdominal distension. Diagnosis: Esophagogastroduodenoscopy (EGD) showed a depressed lesion found using in the greater curvature of the stomach. The pathological diagnosis of the biopsy specimens indicated that the tumor was GA-FG (chief cell predominant type, GA-FG-CCP). Interventions: Endoscopic submucosal dissection (ESD) was performed. The histopathological examination of the ESD specimen revealed gastric hyperplasia of the fundic gland type around the adenocarcinoma cells. Outcomes: The surgical outcomes were good. The EGD showed a scar with no recurrence, and no symptoms were observed 1 year postoperatively during the follow-up. Conclusion: We present a rare case of a depressed lesion with a pathogenic expression suggesting gastric hyperplasia of the fundic gland type around the adenocarcinoma cells. Considering the origin of oxyntic mucosa, we consider that it may develop into GA-FG. To understand this issue better, similar cases should be monitored in the future.