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Objective: Ferroptosis represents a form of regulated cellular death dependent upon iron and lipid peroxidation derivatives, holding considerable implications for cerebral and neurologic pathologies. In the present study, we endeavored to elucidate the molecular mechanisms governing ferroptosis and appraise the therapeutic value of electrical stimulation of median nerve in addressing cognitive impairments following traumatic brain injury (TBI), employing a rodent model. Methods: In this study, we established a rat model to investigate the cognitive impairments resulting from TBI, followed by the application of median nerve stimulation (MNS). Initially, rats received an intraperitoneal injection of Erastin (2 mg/kg) prior to undergoing MNS. After 24 h of MNS treatment, the rats were subjected to an open field test to evaluate their cognitive and motor functions. Subsequently, we conducted biochemical assays to measure the serum levels of GSH, MDA and SOD. The structural integrity and cellular morphology of hippocampal tissue were examined through H&E staining, Nissl staining and transmission electron microscopy. Additionally, we assessed the expression levels of proteins crucial for neuronal health and function in the hippocampus, including VEGF, SLC7A11, GPX4, Nrf2, α-syn, NEUN and PSD95. Results: Compared to the control group, rats in the stimulation group demonstrated enhanced mobility, reduced levels of tissue damage, a decrease in MDA concentration, and increased levels of GSH and SOD. Additionally, there was a significant upregulation in the expression of proteins critical for cellular defense and neuronal health, including GPX4, SLC7A11, Nrf2, VEGF, α-syn, NEUN, and PSD95 proteins. Conversely, rats in the Erastin group demonstrated decreased mobility, exacerbated pathological tissue damage, elevated MDA concentration, and decreased levels of GSH and SOD. There was also a notable decrease in the expression of GPX4, SLC7CA11, Nrf2, and VEGF proteins. The expression levels of α-syn, NEUN, and PSD95 were similarly diminished in the Erastin group. Each of these findings was statistically significant, indicating that MNS exerts neuroprotective effect in the hippocampal tissue of rats with TBI by inhibiting the ferroptosis pathway. Conclusion: (1) MNS may enhance the cognitive and behavioral performance of rats after TBI; (2) MNS can play a neuroprotective role by promoting the expression of nerve injury-related proteins, alleviating oxidative stress and ferroptosis process; (3) MNS may inhibit ferroptosis of neuronal cells by activating Nrf2/ GPX4 signaling pathway, thereby improving cognitive impairment in TBI rats.

Abstracts Immunotherapy is a revolutionized therapeutic strategy for tumor treatment attributing to the rapid development of genomics and immunology, and immune checkpoint inhibitors have successfully achieved responses in numbers of tumor types, including hematopoietic malignancy. However, acute myeloid leukemia (AML) is a heterogeneous disease and there is still a lack of systematic demonstration to apply immunotherapy in AML based on PD-1/PD-L1 blockage. Thus, the identification of molecules that drive tumor immunosuppression and stratify patients according to the benefit from immune checkpoint inhibitors is urgently needed. Here, we reported that STAT5 was highly expressed in the AML cohort and activated the promoter of glycolytic genes to promote glycolysis in AML cells. As a result, the increased-lactate accumulation promoted E3BP nuclear translocation and facilitated histone lactylation, ultimately inducing PD-L1 transcription. Immune checkpoint inhibitor could block the interaction of PD-1/PD-L1 and reactive CD8+ T cells in the microenvironment when co-culture with STAT5 constitutively activated AML cells. Clinically, lactate accumulation in bone marrow was positively correlated with STAT5 as well as PD-L1 expression in newly diagnosed AML patients. Therefore, we have illustrated a STAT5-lactate-PD-L1 network in AML progression, which demonstrates that AML patients with STAT5 induced-exuberant glycolysis and lactate accumulation may be benefited from PD-1/PD-L-1-based immunotherapy.

ObjectiveThis multi-center cross-sectional study aimed to delineate latent profiles of benefit finding (BF) in individuals undergoing maintenance hemodialysis (MHD) in Shanghai and examine associations between these BF profiles, social support, and coping style.MethodsA total of 384 individuals undergoing MHD (mean age = 57.90, SD = 13.36) were assessed using the Benefit Finding Scale, Simplified Coping Style Questionnaire, and Perceived Social Support Scale. Latent profile analysis (LPA) identified distinct BF categories. Analysis of variance (ANOVA) evaluated the correlation between BF groups and demographic variables, while the relationship between BF, social support, and coping style was tested through correlation and multiple regression analyses.ResultsLPA identified three BF groups: rich BF (54.17%), moderate BF (41.14%), and poor BF (4.69%). Regression analyses indicated that positive coping and social support are protective factors for BF. Additionally, older age and heightened understanding of MHD correlated with higher BF levels.ConclusionThe findings highlighted the importance of recognizing different BF profiles in individuals on MHD and working toward promoting BF levels in the rich BF and moderate BF groups, while helping the poor BF group to identify and address their challenges. Medical professionals should consider interventions tailored to individual psychological profiles to improve mental health and quality of life outcomes in this population.

Abstract Background The hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by persistent eosinophilia and damage to multiple organs. HES can be either primary, secondary or idiopathic. Secondary HES are commonly caused by parasitic infections, allergic reactions or cancer. We described a pediatric case of HES associated with liver damage and multiple thrombi. Case summary A 12-year-old boy with eosinophilia was complicated with severe thrombocytopenia, liver damage, portal vein, splenic vein, and superior mesenteric vein thromboses. The thrombi recanalized after treatment with methylprednisolone succinate and low molecular weight heparin. No side effects appeared after 1-month. Conclusions Corticosteroids should be used at an early stage of HES to prevent further damage to vital organs. Anticoagulants should be recommended only in cases with thrombosis which should be actively screened as a part of evaluation of end organ damage.

Objective Predicting the prognosis of transient ischaemic attack (TIA) is difficult for many frontline clinicians. The purpose of this study was to determine whether subsequent stroke in TIA patients can be predicted via red blood cell distribution width (RDW).Material and methods A total of 360 consecutive patients with new-onset TIA in our stroke centre, were enrolled over the period studied. The patients were divided into three groups: 103 TIA patients, 206 ischaemic stroke (IS) patients and 51 patients with haemorrhagic stroke (HS) within 7 days after TIA. Complete blood count, biochemical parameters and brain imaging were performed on all patients.Results The mean RDW values of patients with IS and HS after TIA were significantly higher than patients with TIA (13.35 ± 1.59 vs 12.84 ± 1.19, 13.32 ± 1.08 vs 12.84 ± 1.19, respectively, all p ≤ .001). In a multivariate model, RDW was independently associated with stroke after TIA (IS: odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.46–3.35, p = .002; HS: OR = 1.511, 95% CI = 1.101–2.074, p = .011). Compared to ABCD2 scores, the diagnostic power of RDW in the differentiation of patients with IS after TIA was better (area under curve (AUC): 0.731 vs 0.613, p = .015). When an RDW cut-off value of 13.95% was accepted for differentiating patients with IS from TIA, the sensitivity and specificity were 73.7% and 74.3%, respectively. However, the AUC for the ability of the RDW to predict HS was 0.653 (95% CI = 0.589–0.716; p

Abstract Background There are remarkable genetic differences between animal major histocompatibility complex (MHC) systems and the human leukocyte antigen (HLA) system. HLA transgenic humanized mouse model systems offer a much better method to study the HLA‐A‐related principal mechanisms for vaccine development and HLA‐A‐restricted responses against infection in human. Methods A recombinant gene encoding the chimeric HLA‐A30 monochain was constructed. This HHD molecule contains the following: α1‐α2 domains of HLA‐A30, α3 and cytoplasmic domains of H‐2Db, linked at its N‐terminus to the C‐terminus of human β2m by a 15‐amino‐acid peptide linker. The recombinant gene encoding the chimeric HLA‐A30 monochain cassette was introduced into bacterial artificial chromosome (BAC) CH502‐67J3 containing the HLA‐A01 gene locus by Red‐mediated homologous recombination. Modified BAC CH502‐67J3 was microinjected into the pronuclei of wild‐type mouse oocytes. This humanized mouse model was further used to assess the immune responses against influenza A virus (H1N1) pdm09 clinically isolated from human patients. Immune cell population, cytokine production, and histopathology in the lung were analyzed. Results We describe a novel human β2m‐HLA‐A30 (α1α2)‐H‐2Db (α3 transmembrane cytoplasmic) (HHD) monochain transgenic mouse strain, which contains the intact HLA‐A01 gene locus including 49 kb 5′‐UTR and 74 kb 3′‐UTR of HLA‐A01*01. Five transgenic lines integrated into the large genomic region of HLA‐A gene locus were obtained, and the robust expression of exogenous transgene was detected in various tissues from A30‐18# and A30‐19# lines encompassing the intact flanking sequences. Flow cytometry revealed that the introduction of a large genomic region in HLA‐A gene locus can influence the immune cell constitution in humanized mice. Pdm09 infection caused a similar immune response among HLA‐A30 Tg humanized mice and wild‐type mice, and induced the rapid increase of cytokines, including IFN‐γ, TNF‐α, and IL‐6, in both HLA‐A30 humanized Tg mice and wild‐type mice. The expression of HLA‐A30 transgene was dramatically promoted in tissues from A30‐9# line at 3 days post‐infection (dpi). Conclusions We established a promising preclinical research animal model of HLA‐A30 Tg humanized mouse, which could accelerate the identification of novel HLA‐A30‐restricted epitopes and vaccine development, and support the study of HLA‐A‐restricted responses against infection in humans.

An asexual fungus, collected from diseased leaves of Paphiopedilum sp. from Guizhou Province, China, and based on the phylogenetic analyses and morphological characters, it was identified as a new species in Curvicladiella. The genus Curvicladiella are recorded for the first time for China.The morphology of Curvicladiella paphiopedili sp. nov. is characterised by penicillate conidiophores with a stipe, dull, tapering towards the apex, the curved stipe extension and cylindrical conidia. In the phylogenetic analyses of combined cmdA, his3, ITS, LSU, tef1 and tub2 sequence data, this taxon was clustered as sister to Curvicladiella cignea within Nectriaceae.

Bovine respiratory disease (BRD) is one of the major health issues in the cattle industry, resulting in significant financial crises globally. There is currently no good treatment, and cattle are made resistant to pneumonia through disease-resistant breeding. The serial blood samples from six Xinjiang brown (XJB) calves were collected for the RNA sequencing (RNA-seq). The obtained six samples were grouped into two groups, in each group as infected with BRD and healthy calves, respectively. In our study, the differential expression mRNAs were detected by using RNA-seq and constructed a protein–protein interaction (PPI) network related to the immunity in cattle. The key genes were identified by protein interaction network analysis, and the results from RNA-seq were verified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 488 differentially expressed (DE) mRNAs were identified. Importantly, the enrichment analysis of these identified DEGs classified them as mainly enriched in the regulation and immune response processes. The 16 hub genes were found to be related to immune pathways categorized by PPIs analysis. Results revealed that many hub genes were related to the immune response to respiratory disease. These results will provide the basis for a better understanding of the molecular mechanism of bovine resistance to BRD.

ObjectiveThe present study aimed to determine whether residual dizziness (RD) after successful repositioning treatment in benign paroxysmal positional vertigo (BPPV) patients could be predicted by red blood cell distribution width (RDW).Materials and methodsIn this study, a total of 303 BBPV patients hospitalized at the neurology department were investigated. The enrolled patients were divided into two groups after successful repositioning treatment: non-RD group included patients who were completely cured, and RD group included patients with RD. We collected data on all subjects, including general information, blood routine examination, blood biochemical examination, and magnetic resonance imaging tests.ResultsThe mean RDW values of patients in the RD group were significantly higher than that in the non-RD group (13.63 ± 1.8 vs. 12.5 ± 0.8; p < 0.001). In subsequent multivariate analysis, elevated RDW levels were a statistically significant risk factor associated with the occurrence of RD [odds ratio = 2.62, 95% confidence interval (CI) 1.88–3.64, p < 0.001]. The area under the ROC curve was 0.723 in terms of its predictive ability to distinguish patients with RD. A cut-off point of 12.95% of RDW predicted RD with a sensitivity of 75.6% and a specificity of 69.5%. Moreover, the AUC for the ability of the RDW to predict recurrence were 0.692 (95% CI = 0.561–0.831; p < 0.014).ConclusionsElevated RDW level was related to increased risk of RD among BPPV patients, requiring further efforts to clarify the actual underlying pathophysiology.

BackgroundGiven that the combination of multiple antibodies in autoimmune encephalitis (AE) is rare and its clinical significance is unclear, this study aimed to investigate the clinical characteristics and significance of overlapping multiple anti-neuronal antibodies in patients with AE.MethodsWe conducted a retrospective analysis of the clinical characteristics, treatment, and prognostic details of 22 patients with multiple coexisting antibodies from multiple clinical centers in China.ResultsAmong the 276 patients who were AE antibody-positive, 22 (7.97%) had two or more antibodies. Among the 22 patients with coexisting AE-related antibodies, 14 patients (63.63%) were combined of cell surface and intracellular antibody, and the remaining 8 patients (36.36%) were detected to be cell surface antibody positive only. The main symptoms of the 22 patients in this cohort included fever, seizures, memory impairment, cognitive decline, and sleep disorders. Five (22.73%) patients had tumors, among whom four had small-cell lung cancers, and one had mediastinal tumors. A total of 20 patients were treated with steroids and intravenous immunoglobulin, and 18 showed varying degrees of symptomatic improvement after first-line immunotherapy. Three patients died of tumor progression or chemotherapy complications.ConclusionThe coexistence of multiple anti-neuronal antibodies in patients with AE may cause a superimposition and diversification of clinical manifestations. Combined paraneoplastic antibody positivity may be suggestive of an underlying malignancy.

Abstract Background Human leukocyte antigen (HLA)‐DP is much less studied than other HLA class II antigens, that is, HLA‐DR and HLA‐DQ, etc. However, the accumulating data have suggested the important roles of DP‐restricted responses in the context of cancer, allergy, and infectious disease. Lack of animal models expressing these genes as authentic cis‐haplotypes blocks our understanding for the role of HLA‐DP haplotypes in immunity. Methods To explore the potential cis‐acting control elements involved in the transcriptional regulation of the HLA‐DPA1/DPB1 gene, we performed the expression analysis using bacterial artificial chromosome (BAC)‐based transgenic humanized mice in the C57BL/6 background, which carried the entire HLA‐DP401 gene locus. We further developed a mouse model of Staphylococcus aureus pneumonia in HLA‐DP401 humanized transgenic mice, and performed the analysis on the expression pattern of HLA‐DP401 and immunological responses in the model. Results In this study, we screened and identified a BAC clone spanning the entire HLA‐DP gene locus. DNA from this clone was analyzed for integrity by pulsed‐field gel electrophoresis and then microinjected into fertilized mouse oocytes to produce transgenic founder animals. Nine sets of PCR primers for regional markers with an average distance of 15 kb between each primer were used to confirm the integrity of the transgene in the five transgenic lines carrying the HLA‐DPA1/DPB1 gene. Transgene copy numbers were determined by real‐time PCR analysis. HLA‐DP401 gene expression was analyzed at the mRNA and protein level. Although infection with S aureus Newman did not alter the percentage of immune cells in the spleen and thymus from the HLA‐DP401‐H2‐Aβ1 humanized mice. Increased expression of HLA‐DP401 was observed in the thymus of the humanized mice infected by S aureus. Conclusions We generated several BAC transgenic mice, and analyzed the expression of HLA‐DPA1/DPB1 in those mice. A model of S aureus‐induced pneumonia in the HLA‐DP401‐H2‐Aβ1−/− humanized mice was further developed, and S aureus infection upregulated the HLA‐DP401 expression in thymus of those humanized mice. These findings demonstrate the potential of those HLA‐DPA1/DPB1 transgenic humanized mice for developing animal models of infectious diseases and MHC‐associated immunological diseases.

Abstract. Atopic dermatitis (AD) is a common disease clinically characterized by chronic recurrent eczematous lesions, dry skin, and pruritus. AD can negatively impact patients’ quality of life. The prevalence of AD in China has been increasing during the past few decades. Based on the most recent advances in the treatment of AD, we updated the 2014 version of the Guidelines for Diagnosis and Treatment of Atopic Dermatitis in China regarding the definition, epidemiology, pathogenesis, clinical classification, diagnosis, prevention, and treatment of AD.

Soil microbes play essential roles in the biogeochemical processes of organic carbon and nutrient cycling. Many studies have reported various short-term effects of fertilization on soil microbes. However, less is known about the effects of longterm fertilization regimes on the rhizosphere. Therefore, the objective of this study was to explore how the soil microbial communities in the rhizosphere respond to different long-term fertilization strategies. Based on a 21-year field treatment experiment in Guizhou, China, we extracted phospholipid fatty acids (PLFAs) to determine the microbial community structure in both the non-rhizosphere (NR) and rhizosphere (R). Six treatments were included: no fertilizer (CK), mineral nitrogen fertilizer (N), N with potassium (NK), phosphorus with K (PK), NPK, and NPK combined with manure (MNPK). The results showed that total PLFAs under unbalanced mineral fertilization (N, NK and PK) were decreased by 45% on average in the NR compared with CK, whereas MNPK increased fungi and G– bacteria abundance significantly in both the NR (by 33 and 23%) and R (by 15 and 20%), respectively. In addition, all microbial groups in the R under these treatments (N, NK and PK) were significantly increased relative to those in the NR, except for the ratio of F/B and G+/G–, which might be due to the high nutrient availability in the R. Soil pH and SOC significantly regulated the soil microbial community and structure, explaining 51 and 20% of the variation in the NR, respectively. However, the rhizosphere microbial community structure was only significantly affected by soil pH (31%). We concluded that the soil microbial community in the NR was more strongly affected by long-term fertilization than that in the R due to the rhizosphere effect in the agricultural ecosystem. Rhizosphere nutrient conditions and buffering capacity could help microbial communities resist the change from the long-term fertilization.

There is an increasing demand for horse milk, but the current domestic performance of the horse milk has not yet conducted a systematic in-depth study. We carried out a pilot study on 13 single nucleotide polymorphisms (SNPs) located within five genes in Kazakh horse using Kompetitive Allele Specific PCR (KASPTM). An association study with average daily milk production of 60 Kazakh mares was performed for 6/13 polymorphic SNPs. The results showed that only two SNPs rs114262445 (NUMB), rs1136347938 (CA8) out of the 6 polymorphic markers were significantly associated with milk production in Kazakh horses. These results indicate the potential of using SNPs for the NUMB and CA8 genes as candidate genes for selection and farm production outputs. This study is relevant for future horse genomic studies.

Abstract Genome-wide association study (GWAS) identified chromosome 12p13 rs12425791 and rs11833579 as susceptibility loci of ischemic stroke (IS) in a European population. However, conflicting results were obtained in subsequent replication analysis. miR-200c, located on chromosome 12p13, was found to have a neuroprotective effect on ischemia. Our aim of this study was to investigate the association of the rs12425791, rs11833579 and rs12904 in the binding site of miR-200c with the risk of IS. The rs12425791, rs11833579, and rs12904 were genotyped using a TaqMan allelic discrimination assay. The results were verified by Sanger sequencing. We found that the rs12904 AG/GG genotypes and G allele were associated with a decreased risk of IS (AG/GG vs. AA: adjusted OR = 0.64; 95% CI, 0.44–0.95; G vs. A: adjusted OR = 0.65; 95% CI, 0.46–0.93). The combined genotypes of the rs11833579AG/AA and rs12904AG/GG were also associated with a reduced risk of IS (OR = 0.65; 95% CI, 0.46–0.93). These findings suggest that the rs12904 may have a jointly protective effect against the risk of IS.

Objective: This study aimed to investigate epidemiological characteristics, clinical manifestations, and long-term outcomes of patients with autoimmune encephalitis (AE) in the east of China.Methods: From January 2015 to December 2019, 226 potential AE patients were recruited from five clinical centers, and a total of 185 patients who met the diagnostic criteria were included in the study. We retrospectively reviewed clinical features, auxiliary examinations, details of treatments, and outcomes of AE, and identified risk factors of poor prognosis. Modified Rankin Scale scores were used to evaluate neurological function, and scores of 3–6 indicated a poor-prognosis.Results: Patients with five main subtypes of AE were enrolled in the study, as follows: anti-NMDAR (79), anti-LGI1 (55), anti-CASPR2 (30), anti-GABABR (16), and anti-AMPAR (5). Among 185 patients, 58.38% (108/185) were male and 41.62% (77/185) were female. The median age at disease onset was 41 years (interquartile range, 17–62). The most common clinical manifestations of AE were seizures (146, 78.92%) and memory deficit (123, 66.49%). A total of 95 (51.35%) patients had abnormal brain magnetic resonance imaging results. Electroencephalographic findings were abnormal in 131 (70.81%) patients, and 168 (90.81%) and 26 (14.05%) patients were treated with first- and second-line immunotherapies, respectively. All surviving patients were followed-up for at least 1 year (range 12–36 months). Good clinical outcomes were achieved in 117 (63.24%), while 68 (36.76%) patients had a poor prognosis. Further, 33 (17.84%) patients relapsed and 10 (5.41%) died within 1 year post-discharge. Older patients tended to have a poorer prognosis, and the occurrence of mental behavioral disorders, movement disorders, disturbance of consciousness, central hypoventilation, and tumors were overrepresented in the poor-prognosis group.Conclusions: AE is a treatable disease, and most patients have a good prognosis. There are differences in the clinical manifestations of patients with different AE subtypes. Some with AE will relapse, and long-term follow-up is of great significance for further research.

Objective: To investigate the roles of serum uric acid (UA), bilirubin (BIL), albumin (ALB), and creatinine (CRE) as major intravascular antioxidants, in benign paroxysmal positional vertigo (BPPV).Methods: The serum levels of UA, BIL, ALB, and CRE were retrospectively analyzed in 70 patients with new-onset idiopathic BPPV and 140 age- and sex-matched healthy controls (HCs).Results: Serum UA, BIL, ALB, and CRE levels were significantly lower in the BPPV group than the HC group. Furthermore, serum levels of BIL and ALB were significantly lower in the BPPV group when compared by sex. Multiple stepwise logistic regression revealed that a reduction in serum ALB was independently related to BPPV (odds ratio = 0.688; 95% confidence interval = 0.607– 0.780). Receiver operating characteristic analyses revealed a cut-off value of 45.15 g/L for ALB with a sensitivity of 74.29% (62.97– 83.07%) and specificity of 73.57% (65.71– 80.18%).Conclusions: Serum levels of UA, BIL, ALB, and CRE were lower in BPPV patients, indicating a lower antioxidant status. Furthermore, a reduction in serum ALB was independently associated with BPPV. These results provide insights into the possible roles of oxidative stress in the pathogenesis of BPPV.

This study was designed to investigate the molecular mechanism of stroke and to explore the effect of miR-224-5p in hypoxic cortical neurons. Firstly, we established a middle cerebral artery occlusion (MCAO) model with Sprague–Dawley rats. Triphenyltetrazolium chloride (TTC) staining showed the brain infarction of an MCAO rat. Longa scores of rats were significantly increased in 12th, 24th, and 48th hours after MCAO. Then, we found that miR-224-5p was increased after MCAO in rats by qRT-PCR. In order to investigate the effect of miR-224-5p in hypoxic neurons, we established an oxygen-glucose deprivation (OGD) model with cortical neurons. MiR-224-5p was also upregulated in neurons after OGD by qRT-PCR. After transfection of the miR-224-5p inhibitor, the number of neurons in the anti-miR-224-5p group significantly increased (P < 0.01) in comparison to the anti-NC group. Furthermore, Tuj1+ (neuronal marker) staining and TUNEL assay (to detect apoptotic cells) were performed in neurons. The survival of neurons in the anti-miR-224-5p group was significantly improved (P < 0.01), while the apoptosis of neurons in the anti-miR-224-5p group was significantly decreased (P < 0.01), when compared with that of the anti-NC group. In addition, we predicted that potential target genes of miR-224-5p were nuclear receptor subfamily 4 group A member 1 (NR4A1), interleukin 1 receptor antagonist (IL1RN), and ring finger protein 38 (RNF38) with bioinformatics databases, such as TargetScan, miRDB, miRmap, and miRanda. The result of qRT-PCR confirmed that NR4A1 was significantly decreased after hypoxic injury (P < 0.01). Meanwhile, luciferase reporter’s assay indicated that NR4A1 was the direct target of miR-224-5p. Compared with the anti-miR-224-5p + siNC group, the number of cortical neurons and the length of the neuron axon in the anti-miR-224-5p + si-NR4A1 group were significantly decreased (P < 0.01), and the number of neuronal apoptosis in the anti-miR-224-5p + si-NR4A1 group was increased (P < 0.01). In conclusion, miR-224-5p played a crucial role in hypoxic neuron injury through NR4A1, which might be an important regulatory mechanism in OGD injury of neurons.

Introduction: Reducing the delay in time to primary percutaneous coronary intervention (PCI) for acute coronary syndrome patients in the non-urban emergency department (ED) is of critical importance. Conventionally, physicians in a non-PCI-capable, non-urban local emergency department (LED) require approval from a tertiary university hospital emergency department (TUH-ED) prior to transferring eligible STEMI patients for PCI procedures. To reduce the ED delay time, this study developed a direct connection between the LED and the cardiac catheterisation laboratory in the TUH (TUH cath lab). Methods: ST-elevation myocardial infarction (STEMI) patients' medical records for 2014 to 2017, from a non-PCI regional hospital located in one of the rural counties in central Taiwan and a TUH-ED in a metropolitan area in the centre of Taiwan, were retrospectively collected and classified into two categories: the LED referral (group A) and the TUH-non-referral (group B). This study compared the ED delay time between TUH non-referral patients in the TUH and LED referral patients in the LED, to determine whether a direct connection reduces current LED delay time. Results: A total of 214 patients (group A, n=62; group B, n=152) who underwent PCI procedures at the TUH were enrolled in the study. ED delay times in the LED were significantly less than the TUH-ED (45.0 v 66.0 min, p

Distoseptispora is one of the sporidesmium-like taxa with great variation in asexual morphology and delineation of species. Phylogenetic analyses of four gene regions LSU, ITS, TEF1α, and RPB2 revealed the placement of several sporidesmium-like species in Distoseptispora (Distoseptisporaceae, Distoseptisporales, Sordariomycetes), collected on submerged decaying twigs from streams in China and Thailand. Based on morphological examination and molecular DNA data, six new species, Distoseptispora amniculi, D. atroviridis, D. effusa, D. fusiformis, D. hyalina, and D. verrucosa, are proposed. Among them, D. hyalina is the first sexual morph confirmed in the genus. A new geographical record is reported for D. lignicola in China. Conidial length proved to be of less taxonomic significance for some Distoseptispora species, whereas the type of conidial septa is informative at species level.

Background: Treatment of myoclonic seizures in myoclonic epilepsy with ragged-red fibers (MERRFs) has been empirical and ineffective. Guideline on this disease is not available. Additional trials must be conducted to find more suitable treatments for it. In this study, the antimyoclonic effects of monotherapies, including levetiracetam (LEV), clonazepam (CZP), valproic acid (VPA), and topiramate (TPM) compared to combination therapy group with LEV and CZP on MERRF, were evaluated to find a more advantageous approach on the treatment of myoclonic seizures. Methods: Treatments of myoclonic seizures with VPA, LEV, CZP, and TPM were reported as monotherapies in 17 MERRF patients from Qilu Hospital between 2003 and 2016, who were diagnosed through clinical data and genetic testing. After 1–4 months of follow-up (mean: 82.9 ± 28.1 days), 12 patients that exhibited poor responses to monotherapy were given a combined treatment consisting of LEV and CZP subsequently. The follow-up period was 4–144 months (mean: 66.3 ± 45.3 months), the effective rates of monotherapy group (17 patients) and combination therapy group (12 patients) were analyzed by Chi-square test. Results: The m.8344 A>G mutation was detected in all patients. There were four patients with partial response (4/17, two in the CZP group and two in the LEV group), ten patients with stable disease (10/17, six in the CZP group, three in the LEV group, and one in the TPM group), and three patients with progressive disease (3/18, two in the VPA group and one in the TPM group). Twelve of the patients with LEV combined with CZP showed a positive effect and good tolerance (12/12), eight of them demonstrated improved cognition and coordination. There was a significant difference between the monotherapy group and combination therapy group in the efficacy of antimyoclonic seizures (χ2 = 13.7, P < 0.001). Conclusions: LEV in combination with CZP is an efficient and safe treatment for myoclonic seizures in patients with this disease exhibiting the m.8344A>G mutation.

Background/Aim: P21, a multifunctional cell cycle-regulatory molecule, regulates apoptotic cell death. In this study we examined the effect of altered p21 expression on the sensitivity of acute myeloid leukemia cells in response to HDAC inhibitor SAHA treatment and investigated the underlying mechanism. Methods: Stably transfected HL60 cell lines were established in RPMI-1640 with supplementation of G-418. Cell viability was measured by MTT assay. Western blot was applied to assess the protein expression levels of target genes. Cell apoptosis was monitored by AnnexinV-PE/7AAD assay. Results: We showed HL60 cells that that didn't up-regulate p21 expression were more sensitive to SAHA-mediated apoptosis than NB4 and U937 cells that had increased p21 level. Enforced expression of p21 in HL60 cells reduced sensitivity to SAHA and blocked TRAIL-mediated apoptosis. Conversely, p21 silencing in NB4 cells enhanced SAHA-mediated apoptosis and lethality. Finally, we found that combined treatment with SAHA and rapamycin down-regulated p21 and enhanced apoptosis in AML cells. Conclusion: We conclude that up-regulated p21 expression mediates resistance to SAHA via inhibition of TRAIL apoptotic pathway. P21 may serve as a candidate biomarker to predict responsiveness or resistance to SAHA-based therapy in AML patients. In addition, rapamycin may be an effective agent to override p21-mediated resistance to SAHA in AML patients.

Isolated torsion of a fallopian tube in the third trimester of pregnancy is an uncommon event. Its common symptoms are lower abdominal pain, vomiting, and nausea. Because these symptoms are nonspecific, isolated torsion of a fallopian tube may be misdiagnosed, delaying treatment and the opportunity to preserve the tube. This is a case report of a primipara in her third trimester, whowas misdiagnosed as having acute appendicitis and ovarian cyst torsion. The ultrasound-assisted examination was useful, but the specific diagnosis was made after laparotomy and histopathology. The patient was managed by simultaneous salpingectomy and cesarean section. This surgical intervention prevented adverse obstetric sequelae. We summarize our experience, provide our conclusions, and review 17 relevant studies from the literature to aid clinicians in understanding, diagnosing, and managing this condition in a timely fashion.

AIM:To evaluate the sensitivity and specificity of one-field non-mydriatic digital fundus photography and direct ophthalmoscopy for diabetic retinopathy(DR)screening, compared with fundus fluorescein angiography( FFA ).METHODS:All 93 patients of type 1 or 2 diabetic who have underwent one-field non-mydriatic digital fundus photography, and direct ophthalmoscopy with dilation of their pupils, and FFA by ophthalmologists. The sensitivity and specificity of one-field non-mydriatic digital fundus photography and direct ophthalmoscopy were calculated respectively, compared with FFA.RESULTS: The sensitivity and specificity of one-field non-mydriatic digital fundus photography for detection of any DR were 80.4% and 94.7%; The sensitivity and specificity of direct ophthalmoscopy for detection of any DR were 64.2% and 84.2%; After the standard for referable DR being lowered down to the moderate non-proliferative diabetic retinopathy(M-NPDR), the sensitivity and specificity of non-mydriatic digital fundus photography for detection were 88.9% and 98.4%, the sensitivity and specificity of direct ophthalmoscopy for detection were 71.5% and 96.7%.CONCLUSION: One-field non-mydriatic digital fundus photography is an effective method for DR screening.

At high levels, copper in grape mash can inhibit yeast activity and cause stuck fermentations. Wine yeast has limited tolerance of copper and can reduce copper levels in wine during fermentation. This study aimed to understand copper tolerance of wine yeast and establish the mechanism by which yeast decreases copper in the must during fermentation. Three strains of Saccharomyces cerevisiae (lab selected strain BH8 and industrial strains AWRI R2 and Freddo) and a simple model fermentation system containing 0 to 1.50 mM Cu2+ were used. ICP-AES determined Cu ion concentration in the must decreasing differently by strains and initial copper levels during fermentation. Fermentation performance was heavily inhibited under copper stress, paralleled a decrease in viable cell numbers. Strain BH8 showed higher copper-tolerance than strain AWRI R2 and higher adsorption than Freddo. Yeast cell surface depression and intracellular structure deformation after copper treatment were observed by scanning electron microscopy and transmission electron microscopy; electronic differential system detected higher surface Cu and no intracellular Cu on 1.50 mM copper treated yeast cells. It is most probably that surface adsorption dominated the biosorption process of Cu2+ for strain BH8, with saturation being accomplished in 24 h. This study demonstrated that Saccharomyces cerevisiae strain BH8 has good tolerance and adsorption of Cu, and reduces Cu2+ concentrations during fermentation in simple model system mainly through surface adsorption. The results indicate that the strain selected from China's stress-tolerant wine grape is copper tolerant and can reduce copper in must when fermenting in a copper rich simple model system, and provided information for studies on mechanisms of heavy metal stress.

Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML) treatment and the underlying mechanism is not fully elucidated. Here, we found that high expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over-expression in leukemic cells induced resistance to chemotherapeutic drugs, enhanced colony formation capacity and inhibited cell differentiation induced by all-trans retinoic acid (ATRA). Meanwhile, inhibition of c-Myc by shRNA or specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs, restrained the colony formation ability and promoted differentiation. RT-PCR and western blotting analysis showed that down-regulation of C/EBPβ contributed to the poor differentiation state of leukemic cells induced by c-Myc over-expression. Importantly, over-expression of C/EBPβ could reverse c-Myc induced drug resistance. In primary AML cells, the c-Myc expression was negatively correlated with C/EBPβ. 10058-F4, displayed anti-proliferative activity and increased cellular differentiation with up-regulation of C/EBPβ in primary AML cells. Thus, our study indicated that c-Myc could be a novel target to overcome drug resistance, providing a new approach in AML therapy.

Background. Polycystic ovarian syndrome (PCOS) women undergoing in vitro fertilization and embryo transfer (IVF-ET) treatment always attain a low cumulative pregnancy rate disaccording with the satisfactory number of oocytes. Objective. We aim to evaluate the status of coagulation and fibrinolytic system in PCOS patients undergoing controlled ovarian hyperstimulation (COH) process. Method. Of the 97 women, 30 patients with PCOS composed the study group; 67 women of child-bearing age with normal endocrine function composed the control group. All participants underwent GnRH agonist standard long protocol, and plasma HCY, FVIII, FX, and D-dimer levels as well as hormone parameters were measured at day of full downregulation, hCG priming, and embryos transfer. Results. On day of full downregulation, FX levels were significantly higher in PCOS group (P

The title thiacalix[4]arene derivative, C36H34Br2O8S4, adopts an unusual pinched cone conformation with the propoxy-substituted benzene rings inclined inward [forming a dihedral angle of 33.4 (1)°] and with the brominated benzene rings bent outward, making a dihedral angle of 66.1 (1)°. In the crystal, the molecules form chains along [001] via C—H...S hydrogen bonds and S...S contacts [S...S = 3.492 (3) Å]. The chains are associated into bilayers through C—H...O hydrogen bonds, generating an R22(10) motif.

In the title compound, C11H13N3O2, the 1,2,3-triazole ring and the phenol ring form a dihedral angle of 55.46 (5)°. In the crystal, inversion-related molecules associate through pairs of hydroxy–phenol O—H...O hydrogen bonds, giving centrosymmetric cyclic dimers [graph set R22(18)]. These dimers are linked into infinite chains along [001], giving an overall two-dimensional network structure parallel to the bc plane through hydroxy O—H...N and triazole C—H...N hydrogen bonds.

In the title compound, C30H26Br2O4S4, the thiacalix[4]arene unit adopts a pinched cone conformation, with one of the ether-substituted rings bent towards the calix cavity and the two phenolic rings bent outwards. The phenyl rings make dihedral angles of 27.12 (9), 36.71 (10), 75.04 (8), and 76.01 (7)° with the virtual plane defined by the four bridging S atoms. The two opposite ether-substituted rings are almost parallel to each other, with an interplanar anagle of 2.99 (12)°, while the two phenolic rings are nearly perpendicular to each other, making a dihedral angle of 74.52 (11)° and a Br...Br distance of 13.17 (2) Å. Two intramolecular O—H...O hydrogen bonds between the OH groups and the same ether O atom stabilize the cone conformation. In the crystal, two different chains of molecules, one with alternating and the other with tail-to-tail orientations, are formed by intermolecular offset-face-to-face π–π stacking interactions with distances of 3.606 (3) to 4.488 (4) Å between the centroids of the aromatic rings.