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Background Streptococcus suis (Ss) is a Gram-positive and anaerobic zoonotic pathogen that is susceptible to all populations and can cause meningitis, septicemia, endocarditis and arthritis in humans. Methods In this study, patients with meningitis who were admitted to our hospital with negative blood and cerebrospinal fluid culture were divided into a next-generation sequencing group and a control group. In the next-generation sequencing group, we used the next-generation sequencing method to detect pathogenic bacteria in the patients’ cerebrospinal fluid. In the control group, we used blood and cerebrospinal fluid bacterial culture method to detect pathogenic bacteria in the patients' cerebrospinal fluid. The detection rates of pathogenic bacteria in the cerebrospinal fluid of the two groups were compared and analyzed. Results A total of 18 patients were included in this study, including 8 patients in the next-generation sequencing group and 10 patients in the control group. The mean age (P = 0.613) and mean disease duration (P = 0.294) were similar in both groups. Patients in the next-generation sequencing group had a leukocyte count of 13.13 ± 4.79 × 109, a neutrophil percentage of 83.39 ± 10.36%, and a C-reactive protein level of 134.95 ± 107.69 mg/L. Patients in the control group had a temperature of 38.32 ± 1.07, a leukocyte count of 8.00 ± 2.99 × 109, and a neutrophil percentage of 74.61 ± 8.89%, and C-reactive protein level was 4.75 ± 6.8 mg/L. The statistical results showed that the leukocytes (P = 0.013) and C-reactive protein levels (P = 0.001) were significantly higher in the patients of the next-generation sequencing group than in the control group. No statistically significant differences were seen in body temperature and neutrophil percentage between the two groups (P > 0.05). The incidence of intracranial pressure and meningeal irritation signs were similar in the two groups (P > 0.05). The detection rate of Streptococcus suis in the cerebrospinal fluid of patients in the next-generation sequencing group was 100%, and the detection rate of Streptococcus suis in the cerebrospinal fluid of the control group was 0%. Conclusion The detection rate of Streptococcus suis infection in cerebrospinal fluid by next-generation sequencing was significantly higher than that by blood and cerebrospinal fluid bacterial culture. Therefore, the diagnosis of porcine streptococcal meningitis by next-generation sequencing method is worthy of clinical promotion and application.

Stroke is a fatal disease with high disability and mortality and there is no credible treatment for stroke at present. Studies on stroke are extensively developed to explore the underlying mechanisms of ischemic and reperfusion injuries. Herein, we investigated the functions of microRNA let-7f (also termed let-7f-5p) in vascular endothelial cell dysfunction. The bEnd.3 cells were stimulated with oxygen-glucose deprivation and reoxygenation (OGD/R) to mimic cell injury in vitro. CCK-8 assays, flow cytometry and western blot analyses were conducted to examine the viability and apoptosis of bEnd.3 cells. Reverse transcription quantitative polymerase chain reaction analyses were employed to measure RNA expression. Endothelial cell permeability in vitro assay was employed to assess endothelial permeability of bEnd.3 cells, and expression levels of proteins associated with cell apoptosis or blood-brain barrier (BBB) were detected by western blot analyses. Luciferase reporter assay was conducted to explore the combination between let-7f and HMGA2. We found that OGD/R induced injuries on endothelial cells (bEnd.3) by decreasing cell viability and promoting cell apoptosis. Let-7f exhibited low expression in bEnd.3 cells under OGD/R. Let-7f overexpression increased the viability of bEnd.3 cells and inhibited cell apoptosis. In addition, the endothelial permeability of bEnd.3 cells was increased by OGD/R and reversed by let-7f overexpression. The levels of tight junction proteins (ZO-1 and occludin) were downregulated by OGD/R and then reversed by let-7f overexpression. Mechanistically, HMGA2 is a target gene of let-7f and its expression was negatively regulated by let-7f. Rescue assays revealed that HMGA2 overexpression reversed the effects of let-7f overexpression on cell viability, cell apoptosis, endothelial permeability, and BBB function. In conclusion, let-7f alleviates vascular endothelial cell dysfunction by downregulating HMGA2 expression under OGD/R.

Background An increasing understanding of the genes and molecular pathways of glioblastoma multiforme (GBM) can provide us a useful insight for the development of more effective targeted therapeutic. Methods To investigate the expression and clinical significance of miR-299 and its target genes in GBM, the expression levels of miR-299 and its target gene in human normal brain tissues and GBM were analyzed in silico using genes microarray and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Results Our results show that miR-299 is up-regulated in GBM patients. Moreover, patients with low miR-299 expression had longer overall survival (OS) compared with those with high miR-299 expression. RNA polymerase II elongation factor, ELL2, was identified as a miR-299 direct target. High expression of ELL2 together with miR-299 down-regulation correlated with a shorter median OS. Conclusions Our results provide the first evidence that ELL2 is a direct target of miR-299 and increased ELL2 expression and down-regulation of miR-299 are associated with GBM progression and poor prognosis in patients, suggesting that ELL2 and miR-299 might have potential prognostic value and be used as tumor biomarkers for the diagnosis of patients with GBM.

Glioblastoma stem-like cells (GSCs) are responsible for the initiation and progression of glioblastoma multiforme (GBM), and microRNAs (miRNAs) play an important role in this disease. However, the mechanisms underlying the role of miRNAs in the stemness of GSCs have not been completely elucidated. We previously showed that miR-181a is downregulated in GBM and may predict prognosis in patients with this disease. Here, we demonstrate that the upregulation of miR-181a suppressed GSC formation and inhibited GBM tumorigenesis by targeting the Notch2 oncogene. We found that miR-181a was downregulated in GSCs derived from human glioblastoma U87MG and U373MG cells. The high expression of miR-181a inhibited the levels of stemness-related markers CD133 and BMI1, attenuated sphere proliferation, promoted cell apoptosis, and reduced the tumorigenicity of GSCs. MiR-181a decreased the expression of Notch2 by targeting the 3'-untranslated region of its mRNA. Notch2 overexpression inhibited the effects of miR-181a downregulation on GSCs, and was negatively correlated with miR-181a expression. Moreover, high Notch2 expression together with low miR-181a expression was correlated with a shorter median overall survival for GBM patients. Together, these data show that miR-181a may play an essential role in GSC formation and GBM progression by targeting Notch2, suggesting that Notch2 and miR-181a have potential prognostic value as tumor biomarkers in GBM patients.

Objective: Radiation-induced brachial plexus injury is a devastating complication that occurs after radiotherapy in the vicinity of the brachial plexus. Nasopharyngeal carcinoma, the most common type of cancer in Guangdong Province, is primarily treated with radiotherapy with subsequent side effects. However, radiation-induced brachial plexus injury is rarely reported in nasopharyngeal carcinoma. To draw attention to this correlation, we analyzed the clinical characteristics including the imaging findings of 10 patients suffering from radiation-induced brachial plexus injury for nasopharyngeal carcinoma. Methods: We considered the patients’ medical histories, analyzed their clinical characteristics, and monitored the long-term efficacy of treatment. Results: The total irradiation dose of the nasopharynx ranged from 66.6 to 74 Gy, and that of the supraclavicular fossa ranged from 60 to 70 Gy. The mean latency was 8.2+5.5 years. Seven patients initially complained of bilateral weakness, and three patients complained of isolated pain. The injuries of eight patients reached Grade 3 or worse. Magnetic resonance imaging showed a low signal on T1-weighted images and a high signal on short tau inversion recovery sequences in all cases. Swollen nerve fibers were clearly displayed in magnetic resonance diffusion tensor imaging. Electromyography showed myokymia in three patients. With conservative therapy, only one patient was temporarily relieved of pain, while the conditions of others were not ameliorated. Conclusions: Radiation-induced brachial plexus injury is a late but catastrophic complication in patients with nasopharyngeal carcinoma. Clinicians should be aware of radiation-induced brachial plexus injury when deciding on treatment and should give them regular follow-up post radiotherapy.

Deformation often appears in castings during casting and heat treatment processes, which determines the machining allowance setting and the machining size distribution of product. The paper presents a novel method for integrated simulation of the deformation behavior of castings during casting and heat treatment processes with a unified finite element model. Firstly, analyze the deformation of castings during casting process with the model containing mold and casting, and update the geometry of casting after casting process, then analyze the deformation of castings during heat treatment process and the final geometry shape of casting before machining could be obtained. By the method, investigation on the deformation behavior of a hydro turbine blade casting during casting and heat treatment processes was carried out, and the residual stress distribution and geometry shape of the casting were obtained.

To investigate the expression and clinical significance of miR-181a and its target genes in glioblastoma multiforme (GBM), the expression levels of miR-181a and three target genes in human normal brain tissues and GBM were analyzed in silico using gene microarray, gene ontology, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results show that miR-181a is down-regulated in GBM patients. The three target genes, ANGPT2, ARHGAP18 and LAMC1, are negatively correlated with the expression of miR-181a. Moreover, high expression of ANGPT2 or LAMC1 together with large size of GBM is correlated with a shorter median overall survival. In conclusion, our results showed that miR-181a and it targets ANGPT2 and LAMC1 might be predictors of prognosis in GBM patients.

AIMS: Oxidative stress is frequently implicated in the pathology of neurodegenerative diseases. This study aimed to investigate the effects and their underlying mechanism(s) of edaravone upon hydrogen peroxide (H(2)O(2))–induced oxidative stress and apoptosis in HT22 cells, a murine hippocampal neuronal model. METHODS: HT22 cells were treated with H(2)O(2) in the presence of various concentrations of edaravone or in its absence. A CCK‐8 assay, Hoechst 33342 staining, and flow cytometry were used to detect cytotoxicity and apoptosis. In addition, the levels of reactive oxygen species (ROS) and the expression of Bcl‐2, Bax, p‐ERK 1/2, p‐JNK, and p‐P38 proteins in HT22 cells were examined. RESULTS: Exogenous H(2)O(2) decreased cell viability in a concentration‐dependent manner and was associated with increased apoptosis and ROS production. Moreover, H(2)O(2) significantly activated and upregulated the expression of p‐ERK 1/2, p‐JNK, and p‐P38, while edaravon protected HT22 cells against H(2)O(2)‐induced injury by inhibiting the production of ROS and activating the MAPK signaling pathway. CONCLUSIONS: Our results provide the first evidence that edaravone can protect H(2)O(2)‐induced cell injury in HT22 neurons via its antioxidant action. These findings suggest that edaravone may be useful in the treatment of neurodegenerative disorders in which oxidative stress has been principally implicated.

Acupuncture has been widely practiced in treating vascular cognitive impairment (VCI) in China. A great body of evidence has proved that acupuncture is a promising therapy to coping with VCI: it is effective and safe, and it is simple to operate, thus it is cost-effective. The available experiments have explored several aspects on treating VCI with acupuncture from morphology and molecular biology to electrophysiology in the specific brain areas and structures. The data indicate a series of mechanism for acupuncture to exert its effect, such as promoting the local blood flow and metabolism, alleviating the injury caused by free radicals, and modulating the neurotransmitter activities. On the other side, even though the therapeutic phenomenon has been observed and being applied clinically, the therapy method still needs further validation and verification through large-sample, multicenter, double-blind, and random controlled study. Further molecular and integrated neurobiological research is also warranted to better understand the mechanism. This chapter provides an introduction on the clinical manifestation and characteristics of VCI, the evolution of the definition and diagnosis for VCI, and a systematic literature review of the basic research. Based on it, the application and operation of acupuncture for the clinical treatment of VCI, as well as the possible neurobiological mechanisms, are discussed in details.

To analyze the association of that the polymorphisms and haplotypes of Taq I site in beta fibrinogen gene and the single nucleotide sites -455 G/A, -249 C/T, -148 C/T, +1689T/G, Bsm A I G/C, 448 G/A, Bcl I G/A, Hinf I A/C in beta-fibrinogen gene are linked up with the ischemic stroke(IS).Turbidmetric assay was used to measure the plasma fibrinogen level of one hundred and sixty cases with ischemic stroke and one hundred and thirty healthy individuals from Hainanese Han population. The polymorphisms and genotypes were characterized by PCR-RFLP. Hardy-Weinberg equilibrium and statistical differences of allelic, genotype and haplotype frequencies were obtained by Chi-square test. Pairwise linkage disequilibrium was calculated and haplotypes of nine or four polymorphisms were estimated by the EH + program.There were highly significant differences in genotype frequencies and allelic frequencies of the polymorphisms -455 G/A, -148 C/T, 448 G/A, which happened between the IS group and control subjects (P0.01). However, the significant differences of the allelic frequencies in the other six polymorphisms were not found between the IS group and the control (P0.05). The odds ratio(OR) with the rare alleles of A -455, T -148 and A 448 is 2.46, 2.30 and 2.08 (95% confidence interval 1.153%-3.924%, 1.429%-3.694% and 1.298%-3.329%) respectively. No definite haplotype block was found by linkage disequilibrium analysis in the control group and the IS group. Association of haplotypes constructed from the nine polymorphisms with IS was not found. Among the haplotypes constructed from four polymorphisms including -455 G/A, -148 C/T, 448 G/A alleles, haplotype differences were found between the control group and the IS group. Haplotypes with G -455, C -148, G448 alleles appeared more frequently in control group(Por = 0.01), whereas haplotypes with A -455, T -148, A 448 occurred more frequently in the IS group(P0.01).The results of multi-allele and haplotype analysis indicated that the polymorphisms -455 G/A, -148 C/T, 448 G/A in beta fibrinogen gene were the possible risk factors associated with the occurrence of ischemic stroke in Hainan Han population.