Explore the vast range of titles available.

Traumatic brain injury (TBI) has high morbidity and mortality rates. The mechanisms underlying TBI are unclear and may include the change in biological material in exosomes. Circular ribonucleic acids (circRNAs) are enriched and stable in exosomes, which can function as microRNA (miRNA) sponges to regulate gene expression levels. Therefore, we speculated that circRNAs in exosomes might play an important role in regulating gene expression after TBI and then regulate specific signaling pathways, which may protect the brain. We first isolated exosomes from the brain extracellular space in mice with TBI by digestion. We then investigated the alterations in circRNA expression in exosomes by high-throughput whole transcriptome sequencing, analyzed the data by gene ontology (GO) and pathway analysis, and constructed the circRNA-miRNA network. In this study, we identified 231 significantly and differentially expressed circRNAs, including 155 that were upregulated and 76 that were downregulated. GO analysis showed that these differentially expressed circRNAs might be related to the growth and repair of neurons, the development of the nervous system, and the transmission of nerve signals. The most highly correlated pathways that we identified were involved primarily with glutamatergic synapse and the cyclic guanosine monophosphate-protein kinase G signaling pathway. The circRNA-miRNA network predicted the potential roles of these differentially expressed circRNAs and the interaction of circRNAs with miRNAs. Our study broadens the horizon of research on gene regulation in exosomes from the brain extracellular space after TBI and provides novel targets for further research on both the molecular mechanisms of TBI and the potential intervention therapy targets.

Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier (BBB) disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergic receptor agonist that exert protective effects in various central nervous system diseases. The present study was designed to investigate the neuroprotective action of dexmedetomidine in a mouse traumatic brain injury model, and to explore the possible mechanisms. Adult male C57BL/6J mice were subjected to controlled cortical impact. After injury, animals received 3 days of consecutive dexmedetomidine therapy (25 µg/kg per day). The modified neurological severity score was used to assess neurological deficits. The rotarod test was used to evaluate accurate motor coordination and balance. Immunofluorescence was used to determine expression of ionized calcium binding adapter molecule-1, myeloperoxidase, and zonula occluden-1 at the injury site. An enzyme linked immunosorbent assay was used to measure the concentration of interleukin-1β (IL-1β), tumor necrosis factor α, and IL-6. The dry-wet weight method was used to measure brain water content. The Evans blue dye extravasation assay was used to measure BBB disruption. Western blot assay was used to measure protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1 p20, IL-1β, nuclear factor kappa B (NF-κB) p65, occluding, and zonula occluden-1. Flow cytometry was used to measure cellular apoptosis. Results showed that dexmedetomidine treatment attenuated early neurological dysfunction and brain edema. Further, dexmedetomidine attenuated post-traumatic inflammation, up-regulated tight junction protein expression, and reduced secondary BBB damage and apoptosis. These protective effects were accompanied by down-regulation of the NF-κB and NLRP3 inflammasome pathways. These findings suggest that dexmedetomidine exhibits neuroprotective effects against acute (3 days) post-traumatic inflammatory responses, potentially via suppression of NF-κB and NLRP3 inflammasome activation.

Extra-corporeal video telescope operating monitor system provides a necessary instrument to perform high-precision neurosurgical procedures that could substitute or supplement the traditional surgical microscope. The present study was designed to evaluate a compact high-definition two-dimensional exoscope system for assisting in surgical removal of large vestibular schwannoma (VS), as an alternative to a binocular surgical microscope. Patients with Koos grade 3 and grade 4 VS undergoing surgery were enrolled in this prospective cohort study between January 2013 and June 2018. The demographics and tumor characteristics (size, Koos grade, composition [cystic or solid mass]) were matched between the two groups of patients. The following outcome measurements were compared between the two groups: duration of surgery, volume of blood loss, extent of tumor resection, number of operating field adjustments, pre- and post-operative facial and cochlear nerve function evaluated at 3 months post-surgery, complications and surgeons' comfortability. A total of 81 patients received tumor resection through the retrosigmoid approach under either an exoscope (cases, n = 39) or a surgical microscope (control, n = 42). Patients in the two groups had comparable tumor location (P = 0.439), Koos grading (P = 0.867), and composition (P = 0.891). While no significant differences in the duration of surgery (P = 0.172), extent of tumor resection (P = 0.858), facial function (P = 0.838), and hearing ability (P = 1.000), patients operated on under an exoscope had less blood loss (P = 0.036) and a fewer field adjustments (P < 0.001). Both primary and assistant surgeons reported a high level of comfort operating under the exoscope (P = 0.001 and P < 0.001, respectively). The compact high-definition two-dimensional exoscope system provides a safe and efficient means to assist in removing large VSs, as compared to a surgical microscope. After the acquaintance with a visual perception through a dynamic hint and stereoscopically viewing corresponding to the motion parallax, the exoscope system provided a comfortable, high-resolution visualization without compromising operational efficiency and patient safety.

Introduction Subjective chronic tinnitus is a common medical syndrome with a high frequency of cognitive impairment; however, the characteristics of cognitive impairment in chronic tinnitus are poorly understood. Investigating the scope of cognitive impairment across the severity spectrum of tinnitus patients may shed light on the issue. Methods A consecutive series of 207 subjective chronic tinnitus patients were classified into mild tinnitus group (n = 95) and severe tinnitus group (n = 112) by THI score (the cutoff THI scores were 37/38). These patients were assessed using the Cognitive Abilities Screening Instrument (CASI) and P300 event‐related potential. Results Although pure tone averages were not different between mild or severe tinnitus patients, severe tinnitus patients scored lower on the CASI assessment as well as almost all subdomains of CASI, particularly in items such as “short‐term memory,” “concentration or mental manipulation,” “orientation,” “ion and judgment,” “language abilities,” and “visual construction.” Furthermore, compared to mild tinnitus patients, severe tinnitus patients exhibited longer N2 and P3 latencies. Finally, a correlation analysis revealed that tinnitus severity was negatively correlated with CASI score and positively correlated with N2 and P3 latencies. Conclusions This study reveals that tinnitus patients on the severe end of the spectrum may be at risk for serious cognitive deficits, which may not be a secondary response to disease manifestations but a primary feature of the underlying disease. The mild tinnitus group and severe tinnitus group were assessed using the Cognitive Abilities Screening Instrument (CASI) and P300 event‐related potential. Severe tinnitus patients possess distinct cognitive deficits compared to mild tinnitus patients, a difference that could not be accounted for by differences in hearing loss. Our study reveals that tinnitus patients on the severe end of the spectrum may be at risk for serious cognitive deficits, which may not be a secondary response to disease manifestations but a primary feature of the underlying disease.

Sepsis is a leading cause of death in patients with severe infection worldwide. Remifentanil is an ultra-short-acting, potent opioid analgesic. In the study, we aimed to investigate the role and underlying mechanism of remifentanil in lipopolysaccharide- (LPS-) induced inflammation in human aortic endothelial cells (HAECs). HAECs were pretreated with phosphate-buffered saline (PBS) or remifentanil (2.5 μM) for 30 min, then stimulated by LPS (10 μg/ml) for another 24 h. Poly(ADP-ribose) polymerase 1 (PARP-1) was inhibited by small interfering RNA (siRNA). Superoxide anion production and DNA damage were analyzed by dihydroethidium (DHE) staining and comet assay. The inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM-1), PARP-1, poly(ADP-ribose) (PAR), and nuclear factor-kappa B p65 (NF-κB p65) expressions were analyzed by RT-PCR or western blotting analysis. NF-κB p65 nuclear translocation was assessed by immunofluorescence. Compared with the control group, pretreatment with remifentanil significantly reduced superoxide anion production and DNA damage, with downregulation of iNOS, ICAM-1, and PARP-1 expressions as well as PAR expression. Moreover, pretreatment with PARP-1 siRNA or remifentanil inhibited LPS-induced NF-κB p65 expression and nuclear translocation. Remifentanil reduced LPS-induced inflammatory response through PARP-1/NF-κB signaling pathway. Remifentanil might be an optimal choice of analgesia in septic patients.

Low shear stress (LSS) plays a critical role in the site predilection of atherosclerosis through activation of cellular mechanosensors, such as platelet endothelial cell adhesion molecule 1 (PECAM-1). Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that regulates the expression of various inflammatory cytokines. The nuclear enzyme high mobility group box 1 (HMGB1) can induce inflammation response by binding to toll-like receptor 4 (TLR4). In the present study, we aimed to investigate the role and mechanism of HMGB1 in LSS induced inflammation in human umbilical vein endothelial cells (HUVECs). HUVECs were stimulated by undisturbed shear stress (USS, 1 Pa) and LSS (0.4 Pa) in our experiments. Gene expression was inhibited by small interfering RNA (siRNA). ICAM-1 expression was regulated by LSS in a time dependent manner. LSS can induce HMGB1 translocation from nucleus to cytoplasm and release. Compared with the USS, LSS could increase the protein expression of PECAM-1 and PARP-1 as well as the secretion of TNF-α and IL-1β. LSS induced the translocation of HMGB1 from nucleus to cytoplasm. Inhibition of HGMB1 reduced LSS-induced inflammatory response. Inhibition of PARP-1 suppressed inflammatory response through inhibiting TLR4 expression and HMGB1 translocation. PECAM-1 inhibition reduced LSS-induced ICAM-1 expression, TNF-α and IL-1β secretion, and monocytes adhesion. LSS can induce inflammatory response via PECAM-1/PARP-1/HMGB1 pathway. PARP-1 plays a fundamental role in HMGB1 translocation and TLR4 expression. Inhibition of PARP-1 may shed light on the treatment of HMGB1 involved inflammation during atherosclerosis.

Introduction Traumatic brain injury (TBI) remains a leading cause of disability and death among young people in China. Unfortunately, no specific pharmacological agents to block the progression of secondary brain injury have been approved for clinical treatment. Recently, neuroprotective effects of erythropoietin (EPO) have been demonstrated in addition to its principal function in erythropoiesis, and hence it is viewed as a potential drug for TBI. In this study, we have investigated the neuroprotective effects of EPO associated with immune/inflammatory modulation in a mouse experimental TBI model. Methods EPO (5000 U/kg body weight, i.p.) was injected at 1 hr, 1, 2, and 3 days after TBI, and its effect on cognitive function, brain edema, immune/inflammatory cells including regulatory T cells (Tregs), neutrophils, CD3+ T cells, and microglia, cytokines including interleukin‐10 (IL‐10), transforming growth factor‐β (TGF‐β), interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α) were evaluated at different time points after treatment. Results EPO treatment significantly decreased brain edema and improved cognitive function when compared to Saline‐treated mice (p < .05). EPO treatment also significantly increased Tregs level in spleen and injured brain tissue as well as significantly reduced the infiltration and activation of immune/inflammatory cells (neutrophils, CD3+T cells, and microglia) in the injured hemisphere compared to Saline‐treated control animals (p < .05). In addition, ELISA analysis demonstrated that EPO treatment increased the expression of anti‐inflammatory cytokine IL‐10, but decreased the expression of proinflammatory cytokine IL‐1β and TNF‐α in the injured brain tissue (p < .05). Conclusions These findings suggest that EPO could improve neurological and cognitive functional outcomes as well as regulate immune/inflammatory reaction in TBI. EPO attenuated the infiltration and activation of immune/inflammatory cell in the injured brain.

Multi-modal and multi-view imaging is essential for diagnosis and assessment of cervical spondylosis. Deep learning has increasingly been developed to assist in diagnosis and assessment, which can help improve clinical management and provide new ideas for clinical research. To support the development and testing of deep learning models for cervical spondylosis, we have publicly shared a multi-modal and multi-view imaging dataset of cervical spondylosis, named MMCSD. This dataset comprises MRI and CT images from 250 patients. It includes axial bone and soft tissue window CT scans, sagittal T1-weighted and T2-weighted MRI, as well as axial T2-weighted MRI. Neck pain is one of the most common symptoms of cervical spondylosis. We use the MMCSD to develop a deep learning model for predicting postoperative neck pain in patients with cervical spondylosis, thereby validating its usability. We hope that the MMCSD will contribute to the advancement of neural network models for cervical spondylosis and neck pain, further optimizing clinical diagnostic assessments and treatment decision-making for these conditions.

Although previous data showed that remote ischemic preconditioning (RIPC) has beneficial effect on blood pressure (BP) reduction, the efficacy of RIPC-induced decline in BP and the favorable humoral factors in hypertension is elusive. This present study is performed to evaluate whether RIPC reduces BP, improves microvascular endothelial function and increases circulating hSDF-1α generation in hypertension. Fifteen hypertensive patients received 3 periods of 5-min inflation/deflation of the forearm with a cuff on the upper arm daily for 30 days. Clinic and 24-h ambulatory blood pressure monitoring (ABPM) were examined before and after the end of this procedure. Microvascular endothelial function was measured by finger reactive hyperemia index (RHI) using the Endo-PAT 2000 device. The circulating hSDF-1α level was tested by ELISA. RIPC significantly decreased systolic BP (139.13 ± 6.68 versus 131.45 ± 7.45 mmHg) and diastolic BP (89.67 ± 4.98 versus 83.83 ± 6.65 mmHg), meanwhile 24-h ambulatory systolic and diastolic BP dropped from 136.33 ± 9.10 mmHg to 131.33 ± 7.12 mmHg and 87.60 ± 6.22 mmHg to 82.47 ± 4.47 mmHg respectively. RHI was improved (1.95 ± 0.34 versus 2.47 ± 0.44). Plasma hSDF-1α level was markedly increased after RIPC (1585.86 ± 167.17 versus 1719.54 ± 211.17 pg/ml). The increase in hSDF-1α level was associated with the fall in clinic and 24-h ABPM and rise in RHI. The present data suggests that RIPC may be a novel alternative or complementary intervention means to treat hypertension and protect endothelial function.