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Background Minimally invasive surgery (MIS), including endoscopic evacuation and minimally invasive catheter (MIC) evacuation, has been widely used in spontaneous cerebellar hemorrhage (SCH) patients. However, the long-term prognosis varies widely. Herein, we aimed to explore the prognostic risk factors of neurological outcome, including peri-operative hematoma and perihematomal edema (PHE), in SCH patients after MIS. Methods Eighty consecutive SCH patients, who underwent MIS between July 2019 and Nov. 2021 from 4 neurosurgical centers were enrolled prospectively. Patients were dichotomized into good (modified Rankin Scale (mRS) score ≤ 3) and poor neurological outcome (mRS score ≥ 4) groups. Peri-operative CT scans were assessed by two independent raters. Hematoma and PHE volume were calculated using 3D Slicer software. Predictors of poor neurological outcome were assessed in logistic regression models. Results Among the enrolled patients, 44 underwent endoscopic evacuation and 36 underwent MIC evacuation. The overall poor neurological outcome rate was 23.8%. Older patients, underwent MIC evacuation, large postoperative PHE, and large preoperative PHE (OR = 1.57, 95% CI: 1.20–1.90) were independently associated with poor neurological outcome. According to the restricted cubic splines analysis, patients were divided into large preoperative PHE subgroup (PHE ≥ 10 ml) and small preoperative PHE subgroup (PHE < 10 ml). In small preoperative PHE subgroup, 1 patient (2.4%) had poor neurological outcome. However, in large preoperative PHE subgroup, 18 patients (47.4%) had poor neurological outcome. Conclusion Large preoperative PHE is an independent risk factor for poor neurological outcome among SCH patients after MIS, especially when the preoperative PHE ≥ 10 ml.

PRRSV and porcine circovirus (PCVs), two of the most significant swine diseases that affect the pig industry. NADC30-like or NADC34-like PRRSV and PCV3 has had a strong in China and could cause clinical disease on pigs. Co-infection of PRRSV and PCVs is frequently observed under field conditions and elicits more severe diseases. However, the endemic status of NADC30-like/NADC34-like PRRSV and PCV3/PCV4 in Jinzhong of Shanxi is unclear under the field condition of immune inactivated vaccines or subunit vaccine (Virus-LikeParticles, VLPs). In this study, we examined 120 weaner dead pigs-lung tissue samples collected from a single PRRSV and PCV positive pig farm in Jinzhong-Shanxi from January to November 2021. Six NADC30-like PRRSV and PCV3 strains were discovered in samples, and PRRSV NSP2 and ORF5 genomes & PCV3 Cap genomes of these strains were sequenced. Phylogenetic analysis indicated that these novel PRRSV and PCV strains belong to NADC30-like PRRSV and PCV3, forming one group in Shanxi, Jinzhong. After NADC30-like PRRSV pregnant sows (African swine fever infection pressure) were immunized with Ch-1a inactivated vaccine for one year, NADC34-like PRRSV was not identified, and NADC30-like PRRSV was still an epidemic strain in the piglet herd. Importantly, PCV2 pregnant sows were immunized with subunit (Cap protein) vaccine for one year, PCV-4 was not detected, and PCV-3 was still an epidemic strain in the piglet herd. Immunization of sows with PRRSV inactivated vaccine and circular VLPs vaccine can reduce viremia and increase the survival rate of piglets, but cannot provide complete virological protection.

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury. Electronic supplementary material The online version of this article (10.1007/s12264-020-00505-7) contains supplementary material, which is available to authorized users.

Background To compare the long-term therapeutic effects of stereotactic aspiration (SA), endoscopic evacuation (EE), and open craniotomy (OC) in the surgical treatment of spontaneous basal ganglia hemorrhage and explore the appropriate clinical indications for each technique. Methods Multiple-treatment inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis was performed to evaluate the therapeutic effects of these techniques. The primary and secondary outcomes were 6-month modified Rankin Scale (mRS) and mortality rates, respectively. Results A total of 703 patients were ultimately enrolled. For the entire cohort, the 6-month mortality rate was significantly higher (OR 2.396, 95% CI: 1.865-3.080), and the 6-month functional outcome was significantly worse (OR 1.359, 95% CI: 1.091-1.692) for SA than that of EE. The 6-month mortality rate for OC was significantly higher (OR 1.395, 95% CI: 1.059-1.837) than that of EE. Further subgroup analysis was stratified by initial hematoma volume and Glasgow Coma Scale (GCS) score. The mortality rate for SA was significantly higher for patients with hematoma volume of 20-40 mL (OR 6.226, 95% CI: 3.848-10.075), 40-80 mL (OR 2.121, 95% CI: 1.492-3.016), and ≥80 mL (OR 5.544, 95% CI: 3.315-9.269) than in the same subgroups of EE. The functional outcomes for SA were significantly worse than that of EE for hematoma volume subgroups of 40-80 mL (OR 1.424, 95% CI: 1.039-1.951) and ≥80 mL (OR 4.224, 95% CI: 1.655-10.776). The mortality rate for SA was significantly higher than that of EE for the GCS score subgroups of 6-8 (OR 2.082, 95% CI: 1.410-3.076) and 3-5 (OR 2.985, 95% CI: 1.904-4.678). The mortality rate for OC was significantly higher for the GCS score of 3-5 subgroup (OR 1.718, 95% CI: 1.115-2.648), and a tendency for a higher mortality rate of 6-8 subgroup (OR 1.442, 95% CI: 0.965-2.156) than that of EE. Conclusions EE can decrease the 6-month mortality rate and improve the 6-month functional outcomes of spontaneous basal ganglia hemorrhage in patients with a hematoma volume ≥40 mL. EE can decrease the 6-month mortality rate of spontaneous basal ganglia hemorrhage in patients with a GCS score of 3-8.

Objectives 20‐hydroxyeicosatetraenoic acid (20‐HETE) is a metabolite of arachidonic acid catalysed by cytochrome P450 enzymes and plays an important role in cell death and proliferation. We hypothesized that 20‐HETE synthesis inhibition may have protective effects in traumatic brain injury (TBI) and investigated possible underlying molecular mechanisms. Materials and methods Neurologic deficits, and lesion volume, reactive oxygen species (ROS) levels and cell death as assessed using immunofluorescence staining, transmission electron microscopy and Western blotting were used to determine post‐TBI effects of HET0016, an inhibitor of 20‐HETE synthesis, and their underlying mechanisms. Results The level of 20‐HETE was found to be increased significantly after TBI in mice. 20‐HETE synthesis inhibition reduced neuronal apoptosis, ROS production and damage to mitochondrial structures after TBI. Mechanistically, HET0016 decreased the Drp1 level and increased the expression of Mfn1 and Mfn2 after TBI, indicating a reversal of the abnormal post‐TBI mitochondrial dynamics. HET0016 also promoted the restoration of SIRT1 and PGC‐1α in vivo, and a SIRT1 activator (SRT1720) reversed the downregulation of SIRT1 and PGC‐1α and the abnormal mitochondrial dynamics induced by 20‐HETE in vitro. Furthermore, plasma 20‐HETE levels were found to be higher in TBI patients with unfavourable neurological outcomes and were correlated with the GOS score. Conclusions The inhibition of 20‐HETE synthesis represents a novel strategy to mitigate TBI‐induced mitochondrial dysfunction and neuronal apoptosis by regulating the SIRT1/PGC‐1α pathway., The mechanism on 20‐HETE–induced alterations of mitochondrial dynamics in neurons. 20‐HETE is synthesized from AA by CYP4A, which is inhibited by HET0016. The alterations of mitochondrial dynamics induced by 20‐HETE activate oxidative stress and subsequently result in neuronal apoptosis mediated by inhibition of the Sirt1/PGC‐1α signalling pathway.

Background Porcine reproductive and respiratory syndrome virus (PRRSV) causes porcine reproductive and respiratory syndrome (PRRS), which is currently insufficiently controlled. From a previous small-scale screen we identified an effective DNA-based short antisense oligonucleotide (AS-ON) targeting viral NSP9, which could inhibit PRRSV replication in both Marc-145 cells and pulmonary alveolar macrophages (PAMs). The objective of this study was to explore the strategy of incorporating locked nucleic acids (LNAs) to achieve better inhibition of PRRSV replication in vitro. Methods The effective DNA-based AS-ON (YN8) was modified with LNAs at both ends as gap-mer (LNA-YN8-A) or as mix-mer (LNA-YN8-B). Marc-145 cells or PAMs were infected with PRRSV and subsequently transfected. Results Compared with the DNA-based YN8 control, the two AS-ONs modified with LNAs were found to be significantly more effective in decreasing the cytopathic effect (CPE) induced by PRRSV and thus in maintaining cell viability. LNA modifications conferred longer lifetimes to the AS-ON in the cell culture model. Viral ORF7 levels were more significantly reduced at both RNA and protein levels as shown by quantitative PCR, western blot and indirect immunofluorescence staining. Moreover, transfection with LNA modified AS-ON reduced the PRRSV titer by 10-fold compared with the YN8 control. Conclusion Taken together, incorporation of LNA into AS-ON technology holds higher therapeutic promise for PRRS control.

The rapid development of social media has accelerated the online rumor propagation, making social conflicts more intense during the development of NIMBY facilities. The “fake news” issue is not new, as the consequences will be amplified when the fakery spreads on social media as online rumors. However, few studies have been undertaken on the online public opinion, especially the rumor propagation on NIMBYism. This study collects data related to the anti-PX demonstration in Maoming city in 2014 on the Weibo platform. To form the rumor text library, qualitative research method is adopted to encode the collected data. Based on the social amplification of risk framework, three sub-frameworks are proposed in this study and statistical method is used to analyze the topics of rumors. Meanwhile, the textual content analysis and impact factor analysis is employed to examine the semantic features of rumor texts and the key role of rumor-mongers respectively. The results show that there are three main propagation lifecycles of rumors while the topics of rumors vary according to the cycle. Rumors belonging to each framework have diverse trend and the assessment framework is dominant throughout the process. “Individuals” and “Elites” are the main force of rumor spreading, and “Media practitioners” are the opinion leaders. These findings are useful for governments to establish a rumor detection system so that official information can be released and rumors can be refuted without delay. Meanwhile, the cooperation with the opinion leaders in online rumor propagation should be strengthened. In addition, a scientific popularization and timely notification of project progress is recommended prior to the development of NIMBY facility.

Ischemic stroke is a severe cerebrovascular disease. Although great progress has been made, the consequent ischemia-reperfusion (I/R) injury is inevitable and affects the therapeutic effect. Adiponectin (APN) is a fat-derived plasma protein that has beneficial actions on cardiovascular disorders. The present study aims to investigate the effect of APN on I/R injury and the potential underlying mechanisms. In step 1, APN were administered for three times (once every 8 h) 24 h before middle cerebral artery occlusion (MCAO). The results indicated that APN treatment reduced infarct volume, neurological deficits and brain water content after I/R injury. Meanwhile, APN was proved to increase the expression of cAMP, PKA, CREB, and BDNF. In step 2, mice were randomly assigned into the Vehicle + I/R, APN + I/R, PKA activator + I/R, PKA inhibitor + APN + I/R groups. PKA activator, PKA inhibitor, as well as APN were administered for three times before MCAO. The results indicated that PKA inhibitor downregulated the expressions of cAMP, PKA, CREB, and BDNF which subsequently weakened the protective effects of APN on cerebral I/R injury. In conclusion, our findings further suggest that APN exerts protective effect against cerebral I/R injury might through the cAMP/PKA-CREB-BDNF signaling pathway. APN is a novel candidate in the treatment of I/R diseases in the future.

Long noncoding RNAs (lncRNAs) have been reported to participate in tumorigenesis and diverse cellular processes in osteosarcoma (OS). However, the role of lncRNA LINC00152 in OS remains elusive. In this study, LINC00152 was highly expressed in osteosarcoma tissues and cell lines. Moreover, MTT and colony formation assays revealed that knockdown of LINC00152 significantly suppressed cell proliferation. The inhibitory effect of LINC00152 knockdown on OS cell migration and invasion was analyzed and demonstrated by transwell assays. Additionally, Chromatin immunoprecipitation (ChIP) and luciferase reporter assays suggested that LINC00152 was transcriptionally activated by the transcription factor TCF3. More importantly, mechanism investigation revealed that LINC00152 was predominantly located in the cytoplasm of OS cells and acted as a competing endogenous RNA (ceRNA) in OS by regulating miR-1182/CDK14 axis. Collectively, LINC00152 was activated by TCF3 and promotes cell proliferation and migration in osteosarcoma via miR-1182-CDK14 axis.

The effects of long non-coding RNAs (lncRNAs) on cellular biological processes and even the tumorigenesis have been widely reported. Small nucleolar RNA host gene 6 (SNHG6) has been reported to participate in regulating biological behaviors of multiple types of cancers. Nevertheless, the functions of SNHG6 in osteosarcoma still remain to be uncovered. This study intended to determine the clinical significance and biological functions of SNHG6 in osteosarcoma. It was confirmed by qRT-PCR that SNHG6 was highly expressed in osteosarcoma tissues and cell lines. Highly expressed SNHG6 predicted poor survival rate and advanced clinical stage for osteosarcoma patients, according to Kaplan-Meier method and Cox regression analysis. Loss-of-function assays were performed to examine the effects of silenced SNHG6 on the progression of osteosarcoma, indicating that silenced SNHG6 suppressed cell proliferation through inducing cell cycle arrest in G0/G1 phase and causing cell apoptosis. In vitro assays exposed the potential oncogenic role of SNHG6 in osteosarcoma, further affirmed by in vivo nude mice assays. Mechanistic assays demonstrated that SNHG6 was negatively correlated with p21 and KLF2 in osteosarcoma. And biological functions of SNHG6 in osteosarcoma were realized through regulating p21 and KLF2. Collectively, SNHG6 was a new type of molecule involving in the progression of osteosarcoma.

Inflammatory markers have been associated with functional outcome and mortality of stroke. We investigated the changes in procalcitonin (PCT) and high-sensitivity C-reactive protein (Hs-CRP) levels during the acute period of ischemic stroke and evaluated the relationship between these levels and the long-term functional outcome and mortality. We prospectively studied 376 patients with acute ischemic stroke (AIS) who were admitted within 24 h after the onset of symptoms. PCT, Hs-CRP, and NIH Stroke Scale (NIHSS) were measured at the time of admission. Long-term functional outcome were measured by modified Rankin scale (mRS) at 1 year after admission. The correlations between the levels of PCT, Hs-CRP, and mortality at 1 year after stroke onset were analyzed. Patients with poor with functional outcome and non-survivors had significantly increased PCT and Hs-CRP levels on admission. Multivariate logistic regression analysis showed that PCT was an independent prognostic marker of 1-year functional outcome and death [odds ratio (OR) 2.33 (95 % CI, 1.33–3.44) and 3.11 (2.02–4.43), respectively, P

Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke, which leads to a high rate of mortality and poor neurological outcomes worldwide. Thrombolytic evacuation with urokinase-type plasminogen activator (uPA) or tissue-type plasminogen activator (tPA) has been showed to be a hopeful treatment for ICH. However, to the best of our knowledge, no clinical trials were reported to compare the efficacy and safety of these two fibrinolytics administrated following minimally invasive stereotactic puncture (MISP) in patients with spontaneous basal ganglia ICH. Therefore, the authors intended here to evaluate the differential impact of uPA and tPA in a retrospective study. In the present study, a total of 86 patients with spontaneous ICH in basal ganglia using MISP received either uPA (uPA group, n = 45) or tPA (tPA group, n = 41), respectively. The clinical baseline characteristics prior to the operation were collected. In addition, therapeutic responses were assessed by the short-term outcomes within 30 days postoperation, as well as long-term outcomes at 1 year postoperation. Our findings showed that, in comparison with tPA, uPA was able to better promote hematoma evacuation and ameliorate perihematomal edema, but the differences were not statistically significant. Moreover, the long-term functional outcomes of both groups were similar, with no statistical difference. In conclusion, these results provide evidence supporting that uPA and tPA are similar in the efficacy and safety for thrombolytic evacuation in combination with MISP in patients with spontaneous basal ganglia ICH.

Hepatoma-derived growth factor (HDGF) regulates various cellular processes involved in the onset and development of tumors. To evaluate the role of HDGF in human gliomas, western blotting analysis, immunohistochemistry staining and reverse transcription-quantitative polymerase chain reaction were performed to detect HDGF protein and mRNA expression levels in glioma and intractable epileptic brain tissue. Various clinicopathological characteristics, including age, gender, World health Organization grade, HDGF expression level, Karnofsky performance Status (KPS) and Ki-67 index were obtained from medical records. The correlation between HDGF expression and these clinicopathological characteristics was statistically evaluated. Following this, multivariate liner regression was used to evaluate their effect on patient survival time. HDGF expression, at the protein and mRNA levels, was observed to be more upregulated in glioma tissues compared with intractable epileptic brain tissue without tumor. Furthermore, the level of HDGF expression was positively associated with the grade of malignancy [grades II~IV, Ki-67 index ≥20% or KPS

Background Porcine reproductive and respiratory syndrome (PRRS) is caused by porcine reproductive and respiratory syndrome virus (PRRSV) and is an economically important disease in swine-producing areas. The objective of this study was to screen for effective antisense oligonucleotides (AS-ONs) which could inhibit PRRSV replication in MARC-145 cells and in pulmonary alveolar macrophages (PAM). Results Nine short AS-ON sequences against the well-conserved regions of PRRSV (5′-UTR, NSP9, ORF5 and ORF7) were selected. When MARC-145 cells or PAM were infected with PRRSV followed by transfection with AS-ONs, four AS-ON sequences targeting 5′-UTR, ORF5 or NSP9 were found to be the most effective oligonucleotides in decreasing the cytopathic effect (CPE) induced by PRRSV infection. Quantitative PCR and indirect immunofluorescence staining confirmed that ORF7 levels were significantly reduced both at RNA and protein levels. The PRRSV titration data furthermore indicated that transfection with AS-ON YN8 could reduce the PRRSV titer by 1000-fold compared with controls. Conclusion The results presented here indicate that DNA-based antisense oligonucleotides can effectively inhibit PRRSV replication in MARC-145 cells and in PAM. Furthermore, comparing with the reported hit rates (approximately 10-30 %), we achieved a higher success rate (44 %). The strategy we took to design the antisense sequences might be applied to select AS-ONs that more efficiently reduce the expression of target genes.

Microglia activation plays an important role in neuroinflammation. Sirtuin1 (SIRT1) has been shown to play a role in regulation of inflammation. Resveratrol, a potent SIRT1 activator, has anti-inflammation property. MicroRNA (miRNA or miR) related to inflammation pathways has been shown to be a promising therapeutic approach for septic encephalopathy (SE). The miR mediated mechanism of regulation of SIRT1 expression in encephalitis. However, the mechanism of was unknown. To address this question, we investigated whether miRNAs and resveratrol regulate the SIRT1 and the functional changes of mice microglia cell lines pre-treated with or without lipopolysaccharide (LPS). The research about direct role of miR-204 and resveratrol on expression of SIRT1 in mice microglia cell lines (N9 and BV2) pre-treated with or without LPS had been performed. Mice microglia cell lines were transfected with miR-204 mimics and inhibitors or treated with resveratrol, and the effects on cell growth, proliferation, and apoptosis of cells were assessed. LPS induced inflammation and activation of mice microglia. Through overexpression of SIRT1, resveratrol, and inhibitor of miR-204 inhibited inflammation process, proliferation of mice microglia cells and promoted its apoptosis. We identified if resveratrol and miR-204 could repress inflammation process and proliferation of mice microglia cell through promoting the expression of SIRT1.