MiR-124 Reduced Neuroinflammation after Traumatic Brain Injury by Inhibiting TRAF6.

INTRODUCTION: Neuroinflammation contributes to secondary injury after traumatic brain injury (TBI), which has been mainly mediated by the microglia. MiR-124 was reported to play an important role in the polarization of microglia by targeting TLR4 signaling pathway. However, the role and mechanism of miR-124 in neuroinflammation mediated by microglia after TBI is unclear. To clarify this, we performed this research. METHODS: The expression of miR-124 was first measured by RT-PCR in the injured brain at 1/3/7 days post-TBI. Then, miR-124 mimics or inhibitors administration was used to interfere the expression of miR-124 at 24 h post-TBI. Subsequently, the microglia polarization markers were detected by RT-PCR, the expression of inflammatory cytokines was detected by ELISA, the expression of TLR4/MyD88/IRAK1/TRAF6/NF-κB was measured by WB, and the neurological deficit was evaluated by NSS and MWM test. At last, in vitro experiments were performed to explore the exact target molecule of miR-124 on TLR4 signaling pathway. RESULTS: Animal research indicated that the expression of miR-124 was downregulated after TBI. Upregulation of miR-124 promoted the M2 polarization of microglia and inhibited the activity of TLR4 pathway, as well as reduced neuroinflammation and neurological deficit after TBI. In vitro experiments indicated that miR-124 promoted the M2 polarization of microglia and reduced neuroinflammation by inhibiting TRAF6. CONCLUSION: This study demonstrated that upregulation of miR-124 promoted the M2 polarization of microglia and reduced neuroinflammation after TBI by inhibiting TRAF6.

Toll-Like Receptor 2 Attenuates Traumatic Brain Injury-Induced Neural Stem Cell Proliferation in Dentate Gyrus of Rats.

It was not clear how and whether neural stem cells (NSCs) responded to toll-like receptor 2 (TLR2) in the inflammatory environment after traumatic brain injury (TBI). The current study investigated the correlation of TLR2 and NSC proliferation in the dentate gyrus (DG) using the TBI model of rats. Immunofluorescence (IF) was used to observe the expression of BrdU, nestin, and TLR2 in the DG in morphology. Proliferating cells in the DG were labelled by thymidine analog 5-bromo-2-deoxyuridine (BrdU). Three-labelled BrdU, nestin, and DAPI was used for the identification of newly generated NSCs. Western blotting and real-time polymerase chain reaction (PCR) were used to observe the expression of TLR2 from the level of protein and mRNA. We observed that BrdU+/nestin+/DAPI+ cells accounted for 84.30% ± 6.54% among BrdU+ cells; BrdU+ and nestin+ cells in the DG were also TLR2+ cells. BrdU+ cells and the expression of TLR2 (both protein and mRNA levels) both elevated immediately at 6 hours (h), 24 h, 3 days (d), and 7 d posttrauma and peaked in 3 d. Results indicated that TLR2 was expressed on proliferating cells in the DG (NSCs possibly) and there was a potential correlation between increased TLR2 and proliferated NSCs after TBI. Taken together, these findings suggested that TLR2 was involved in endogenous neurogenesis in the DG after TBI.

MiR-124 Enriched Exosomes Promoted the M2 Polarization of Microglia and Enhanced Hippocampus Neurogenesis After Traumatic Brain Injury by Inhibiting TLR4 Pathway.

MicroRNA-124 (miR-124) is a brain specific miRNA that is highly expressed in microglia. The upregulation of miR-124 contributes to M2 polarization of microglia, which is beneficial to neurogenesis. Exosomes are lipid membrane vesicles that can deliver miR-124 into the brain. However, whether miR-124 enriched exosomes (Exo-miR-124) can regulate the polarization of microglia and affect hippocampus neurogenesis after traumatic brain injury (TBI) is unknown. To clarify this, the Exo-miR-124 was first constructed, and then was intravenously administrated into rats via tail vein with the dose of 3 × 109 particles/each rat at 24 h post TBI. The polarization of microglia in hippocampus was evaluated through measuring the signature genes and cytokines of M1/M2 phenotype by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immune sorbent assay (ELISA) at 7/14/21/28 days after TBI. Hippocampus neurogenesis was evaluated through detecting the proliferation marker BrdU/SOX2 and differentiation marker BrdU/NeuN by immunofluorescence (IF) at 7 and 28 days after TBI respectively. Neurological function was evaluated by neurological severity score (NSS) and morris water maze (MWM) at 7/14/21/28 and 24-28 days after TBI respectively. To explore the underlying mechanisms, the mRNA expression of TLR4 pathway molecules in hippocampus were measured by RT-PCR, and the polarization of microglia and the activation of TLR4 pathway in BV2 cells were measured after exosome treatment as well. Results demonstrated that Exo-miR-124 treatment promoted the M2 polarization of microglia, enhanced neurogenesis in hippocampus, and improved function recovery after TBI. The M2 polarization effect of Exo-miR-124 was produced through inhibiting TLR4 pathway, which was verified in hippocampus and BV2 microglia. In conclusion, Exo-miR-124 treatment promoted M2 polarization of microglia and improved hippocampal neurogenesis and functional recovery after brain injury, which might be a strategy to improve the outcome of TBI.

The Effect of SPTLC2 on Promoting Neuronal Apoptosis is Alleviated by MiR-124-3p Through TLR4 Signalling Pathway.

To investigate the role and mechanism of microRNA-124-3p (miR-124-3p) and serine palmitoyltransferase long chain base subunit 2 (SPTLC2) in neuronal apoptosis induced by mechanical injury. Transient transfection was used to modify the expression of miR-124-3p and SPTLC2. After transfection, neuronal apoptosis was evaluated in an in vitro injury model of primary neurons using TUNEL staining and western blot. The correlation between miR-124-3p and SPTLC2 was identified through a dual luciferase reporter assay in HEK293 cells. A rescue experiment in primary neurons was performed to further confirm the result. To explore the downstream mechanisms, co-immunoprecipitation was performed to identify proteins that interact with SPTLC2 in toll-like receptor 4 (TLR4) signalling pathway. Subsequently, the relative expression levels of TLR4 pathway molecules were measured by western blot. Our results showed that increased miR-124-3p can inhibit neuronal apoptosis, which is opposite to the effect of SPTLC2. In addition, miR-124-3p was proved to negatively regulate SPTLC2 expression and suppress the apoptosis-promoting effect of SPTLC2 via the TLR4 signalling pathway.

Acute Traumatic Brain Injury Induces CD4+ and CD8+ T Cell Functional Impairment by Upregulating the Expression of PD-1 via the Activated Sympathetic Nervous System.

OBJECTIVE: Traumatic brain injury (TBI) induces immunosuppression in the acute phase, and the activation of the sympathetic nervous system (SNS) might play a role in this process, but the mechanism involved is unknown. Herein, we explored the impact of acute (a)TBI on the peripheral immune system and its correlation with the SNS and the T cell exhaustion marker, PD-1 (programmed cell death-1). METHODS: Flow cytometry (FCM) was performed to analyze the expression of T cell markers and intracellular cytokines, interferon-γ and tumor necrosis factor-α, and the T cell exhaustion marker, PD-1, in the peripheral blood mononuclear cells (PBMCs) of TBI rats. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the concentration of norepinephrine (NE) in the serum. Propranolol was administrated to block the SNS in vivo and NE stimulation was used to imitate the activation of the SNS in vitro. RESULTS: We found that the concentration of NE was significantly elevated after TBI, and the dysfunction of CD4+ and CD8+ T cells was reversed by the SNS blocker propranolol in vivo and imitated by the SNS neurotransmitter NE in vitro. The expression of PD-1 on CD4+ and CD8+ T cells was upregulated after aTBI, which was reversed by propranolol administration in vivo and imitated by NE stimulation in vitro. Furthermore, the PD-1 blocker reversed the dysfunction of CD4+ and CD8+T cells in vitro. CONCLUSION: Our findings demonstrated that aTBI activated the SNS, and further upregulated the expression of PD-1 on CD4+ and CD8+ T cells, which, in turn, impaired their function and contributed to immunosuppression.

Decomposition behavior and reaction mechanism of Ce0.67Tb0.33MgAl11O19 during Na2CO3 assisted roasting: Toward efficient recycling of Ce and Tb from waste phosphor.

Waste aluminate phosphor is a valuable secondary resource of rare earth elements (REEs). However, Ce and Tb in aluminate green phosphor can hardly be extracted by direct leaching in an inorganic acid. Therefore, Na2CO3 assisted roasting is adopted to decompose the stable spinel structure of Ce0.67Tb0.33MgAl11O19 in the present work and to achieve the transformation of REEs to simple oxides. Based on the thermodynamic calculations, systematic experiments of thermal decomposition have been conducted. The thermal decomposition behavior, phase evolution, valence state change, variations in micro and macro morphology of the green phosphor during Na2CO3 assisted roasting were examined by using TG-DSC/MS, XRD, XPS, SEM/EDS analyses. The results indicated that the green phosphor began to react with solid Na2CO3 at 800 °C, and the reaction was dramatically accelerated with temperature rising above 851 °C. At about 1000 °C, Ce0.67Tb0.33MgAl11O19 could completely decomposed into CeO2, Tb2O3 and MgO by roasting in an equivalent mass of Na2CO3 for 2 h, while α-Al2O3 was hardly attacked in roasting. The decomposition mechanism of Ce0.67Tb0.33MgAl11O19 in molten Na2CO3 could be depicted by the unreacted shrinking core model, and the reaction rate constant was estimated at approximately nanometers per second. The synergistic effect of cation-oxoanion ensures the successful extraction of CeO2 and Tb2O3 from the green phosphor via Na2CO3 assisted roasting method. The converted CeO2 and Tb2O3 can be extracted by using chlorination roasting and separated from non-REE residues. According to these investigations, a new efficient process technology is proposed for sustainable recycling of waste phosphor.

High frequencies of circulating Tfh-Th17 cells in myasthenia gravis patients.

Recent studies show that the frequencies of circulating follicullar helper T (cTfh) cells are significantly higher in myasthenia gravis (MG) patients compared with healthy controls (HC). And, they are positively correlated with levels of serum anti-acetylcholine receptor antibody (anti-AchR Ab). It is unclear whether cTfh cell subset frequencies are altered and what role they play in MG patients. In order to clarify this, we examined the frequencies of cTfh cell counterparts, their subsets, and circulating plasmablasts in MG patients by flow cytometry. We determined the concentrations of serum anti-AChR Ab by enzyme-linked immunosorbent assay (ELISA). We assayed the function of cTfh cell subsets by flow cytometry and real-time polymerase chain reaction (RT-PCR). We found higher frequencies of cTfh cell counterparts, cTfh-Th17 cells, and plasmablasts in MG patients compared with HC. The frequencies of cTfh cell counterparts and cTfh-Th17 cells were positively correlated with the frequencies of plasmablasts and the concentrations of anti-AChR Ab in MG patients. Functional assays showed that activated cTfh-Th17 cells highly expressed key molecular features of Tfh cells including ICOS, PD-1, and IL-21. Results indicate that, just like cTfh cell counterparts, cTfh-Th17 cells may play a role in the immunopathogenesis and the production of anti-AChR Ab of MG.

Activation of Sphingosine 1-Phosphate Receptor 1 Enhances Hippocampus Neurogenesis in a Rat Model of Traumatic Brain Injury: An Involvement of MEK/Erk Signaling Pathway.

Among sphingosine 1-phosphate receptors (S1PRs) family, S1PR1 has been shown to be the most highly expressed subtype in neural stem cells (NSCs) and plays a crucial role in the migratory property of NSCs. Recent studies suggested that S1PR1 was expressed abundantly in the hippocampus, a specific neurogenic region in rodent brain for endogenous neurogenesis throughout life. However, the potential association between S1PR1 and neurogenesis in hippocampus following traumatic brain injury (TBI) remains unknown. In this study, the changes of hippocampal S1PR1 expression after TBI and their effects on neurogenesis and neurocognitive function were investigated, focusing on particularly the extracellular signal-regulated kinase (Erk) signaling pathway which had been found to regulate multiple properties of NSCs. The results showed that a marked upregulation of S1PR1 occurred with a peak at 7 days after trauma, revealing an enhancement of proliferation and neuronal differentiation of NSCs in hippocampus due to S1PR1 activation. More importantly, it was suggested that mitogen-activated protein kinase-Erk kinase (MEK)/Erk cascade was required for S1PR1-meidated neurogenesis and neurocognitive recovery following TBI. This study lays a preliminary foundation for future research on promoting hippocampal neurogenesis and improving TBI outcome.

Quality of life in 188 patients with myasthenia gravis in China.

Myasthenia gravis (MG) is a kind of chronic autoimmune disease which can weaken patients' motor function and, furthermore, produce negative impact on the health-related quality of life (HRQoL). The primary purpose of this research was to evaluate factors that might affect the HRQoL of MG patients. A cross-sectional clinical research was carried out including 188 successive patients with MG. Myasthenia Gravis Foundation of America (MGFA) classification and Quantitative Myasthenia Gravis (QMG) score were applied to assess the severity of the disease. The Medical Outcome Survey 36-Item Short-Form Health Survey (SF-36) was used to estimate the HRQoL. Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were utilized to measure the depression and anxiety symptom. Factors may influence the HRQoL of MG patients include age, educational level, occupation, the situation of the thymus, the type of MG and generalized myasthenia gravis (GMG), the severity of the disease and the psychological disorder. Higher QMG and HARS scores were two significant factors that can prognosticate lower Physical Composite Score (PCS) and Mental Composite Score (MCS), while older age was just a significant factor which has prognostic value for lower PCS. The results of this research may have a potential guiding significance for the clinical treatment strategy and improve the quality of life in patients with MG consequently. In addition to the treatment of physical symptoms, the psychological symptoms such as anxiety and depression should be concerned as well.

A closer look at lithium-ion batteries in E-waste and the potential for a universal hydrometallurgical recycling process.

The demand for lithium-ion batteries (LiBs) is rising, resulting in a growing need to recycle the critical raw materials (CRMs) which they contain. Typically, all spent LiBs from consumer electronics end up in a single waste stream that is processed to produce black mass (BM) for further recovery. It is desired to design a recycling process that can deal with a mixture of LiBs. Hence, this study investigates the structure and composition of battery modules in common appliances such as laptops, power banks, smart watches, wireless earphones and mobile phones. The battery cells in the module were disassembled into cell casing, cathode, anode and separator. Then, the cathode active materials (CAMs) were characterized in detail with XRD-, SEM-, EDX- and ICP-OES-analysis. No direct link was found between the chemistry of the active materials (NMC, LCO, LMO, LFP etc.) and the application. Various BM samples were submitted to a leaching procedure (2 M H2SO4, 50 °C, 2 h, 60 g BM/L) with varying concentration (0-4 vol%) of H2O2 to study the influence of their chemical composition on the dissolution of Li, Ni, Mn and Co. Only a part of the BMs dissolved completely at 4 vol% H2O2, which was attributed to the oxidation state of the transition metals (TMs). Exact determination of H2O2 consumption by redox titration confirmed this hypothesis.

Is cranioplasty the optimal treatment for contralateral subdural effusion after decompressive craniectomy?: a case report.

Introduction and importance: Contralateral subdural effusion (CSDE) is a rare complication secondary to decompressive craniectomy (DC), which can lead to encephalocele and neurologic deterioration. The authors report a case that confirm the existence of unidirectional membrane valve, and cranioplasty is an effective treatment for CSDE. Case presentation: The authors reported a case of 43-year-old female was diagnosed with ruptured intracranial aneurysm and treated with interventional embolization. She underwent DC because of postoperative cerebral infarction subsequently. Her conscious state deteriorated accompanied by encephalocele in postoperative 2 week. A craniocerebral computed tomography (CT) confirmed the diagnosis of CSDE with cerebral hernia. A compression bandaging of the skull defect was applicated, whereas, her conscious state progressive deteriorated. She was transferred to the author's hospital where she underwent burr-hole drainage and clinical symptom has been improved. However, a relapse of CSDE was observed after the removal of drainage tube. Continuous lumbar drainage was employed, and which was ineffective for CSDE in this case. Finally, she underwent cranioplasty, with the help of drainage of subdural effusion, CSDE was completely resolved. Clinical discussion: CSDE is occasionally observed in patients after DC. Intracranial pressure (ICP) gradient and unidirectional membrane valve are the possible mechanisms of CSDE. At present, there is no optimal therapy for CSDE. For symptomatic CSDE patients, one or more treatment measures should be applicated. Conclusion: Cranioplasty is one of the curative and optimal method to treat symptomatic CSDE patients, early cranioplasty combined with burr-hole drainage should be performed for conservative treatment failed and intractable cases.

Recycling as a strategy against rare earth element criticality: a systemic evaluation of the potential yield of NdFeB magnet recycling.

End-of-life recycling is promoted by OECD countries as a promising strategy in the current global supply crisis surrounding rare earth elements (REEs) so that dependence on China, the dominant supplier, can be decreased. So far the feasibility and potential yield of REE recycling has not been systematically evaluated. This paper estimates the annual waste flows of neodymium and dysprosium from permanent magnets, the main deployment of these critical REEs, during the 2011-2030 period. The estimates focus on three key permanent magnet waste flows: wind turbines, hybrid and electric vehicles, and hard disk drives (HDDs) in personal computers (PCs). This is a good indication of the end-of-life recycling of neodymium and dysprosium maximum potential yield. Results show that for some time to come, waste flows from permanent magnets will remain small relative to the rapidly growing global REE demand. Policymakers therefore need to be aware that during the next decade recycling is unlikely to substantially contribute to global REE supply security. In the long term, waste flows will increase sharply and will meet a substantial part of the total demand for these metals. Future REE recycling efforts should, therefore, focus on the development of recycling technology and infrastructure.

A Study on the C, N, and P Contents and Stoichiometric Characteristics of Forage Leaves Based on Fertilizer-Reconstructed Soil in an Alpine Mining Area.

In this study, we analyzed the C, N, and P contents and stoichiometric characteristics of forage leaves of five species (Elymus breviaristatus cv. Tongde, Poa crymophila cv. Qinghai, Puccinellia tenuiflora cv. Qinghai, Festuca sinensis cv. Qinghai, and Poa pratensis cv. Qinghai) in "fertilizer-reconstructed soil" through integrative soil amendment with parched sheep manure and granular organic fertilizer in an alpine mining area. A model is fitted in order to screen out the best forage species suitable for vegetation restoration in the alpine mining area and the most favorable fertilizer dosage to improve the nutrient content of forage leaves. The results showed that (1) increasing the dosages of granular organic fertilizer and sheep manure had little effect on the C content of the five types of forage grasses, but they could significantly increase the N and P contents and N/P of the manually restored grassland in the alpine mining area (p < 0.05). (2) The productivity and stability of the five species were ranked as follows: Elymus breviaristatus cv. Tongde > Puccinellia tenuiflora cv. Qinghai > Festuca sinensis cv. Qinghai > Poa pratensis cv. Qinghai > Poa crymophila cv. Qinghai. (3) According to the fitted least squares model and the willingness to maximize the C, N, and P contents of the leaves, the ranking of the five forage grasses was described by the Prediction Profiler as follows: Elymus breviaristatus cv. Tongde > Puccinellia tenuiflora cv. Qinghai > Festuca sinensis cv. Qinghai > Poa crymophila cv. Qinghai > Poa pratensis cv. Qinghai. (4) The predictive model suggested that the optimal contents of C, N, and P in Elymus breviaristatus cv. Tongde, Festuca sinensis cv. Qinghai, and Poa pratensis cv. Qinghai leaves could be achieved with the application of 3.6 kg/m2 of granular organic fertilizer and 45.0 kg/m2 of sheep manure. For Poa crymophila cv. Qinghai leaves, the ideal content was attained by applying 0 kg/m2 of granular organic fertilizer and 45.0 kg/m2 of sheep manure. Lastly, the optimal C, N, and P contents in Puccinellia tenuiflora cv. Qinghai leaves could be obtained through the application of 3.6 kg/m2 of granular organic fertilizer combined with 0 kg/m2 of sheep manure. In conclusion, the study's results highlight the significant practical value of the fertilizer-reconstructed soil for vegetation restoration in alpine mining regions.

Clinical features of patients with cerebral venous sinus thrombosis at plateau areas.

OBJECTIVE: Cerebral venous sinus thrombosis (CVST) is believed to be associated with high-altitude exposure and has worse clinical prognosis in plateau areas than in plain areas, although this needs to be further verified. This retrospective study aims to compare the clinical differences of patients with CVST in plateau and plain areas and further ascertain the role of high-altitude exposure in the etiology of aggravating predisposition toward CVST. METHODS: Twenty-four symptomatic CVST patients occurring at plateau areas (altitude ≥ 4000 m), in corresponding with 24 CVST patients occurring at plain areas (altitude ≤ 1000 m), were recruited according to the inclusion and exclusion criteria from June 2020 to December 2021. The collected data and compared parameters include clinical features, neuroimaging findings, hematology profile, lipid profile, and coagulation profile within 24 h of hospital admission, as well as the treatment method and final outcome. RESULTS: There were no obvious differences of demographic characteristics, including gender, age, height, and weight between patients with CVST in plateau and plain areas, as well as medical history, neuroimaging findings, treatment protocols, and clinical outcome (all p > .05). Compared to patients with CVST at plain areas, time before hospital admission was longer and heartbeat was slower in patients with CVST at plateau areas (all p < .05). More importantly, elevated red blood cells counts, hemoglobin level, and altered coagulation function were found in patients with CVST at plateau areas (all p < .05). CONCLUSION: CVST patients in plateau areas presented with altered clinical characteristics, altered coagulation function, and aggravated predisposition toward venous thromboembolism compared with CVST patients in plain areas. Future prospective studies will be needed to further elucidate the influences of a high altitude on the pathogenesis of CVST.

Exosomal microRNAs have great potential in the neurorestorative therapy for traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of brain impairment, resulting in acute neural impairment and chronic long-term disability worldwide. Until now, no therapeutics developed can improve the neurological recovery and clinical prognosis of TBI. Latest studies have indicated that the cell-based therapy can improve neurological recovery by promoting intrinsic neurogenesis and neurite growth after TBI in animal experiments and clinical researches. However, subsequent studies have further demonstrated that the benefits of cell-based therapy are mediated by exosomes released from the administered cells, and microRNAs (miRNAs) cargos in exosomes are largely responsible for the therapeutic effects. Moreover, accumulating studies have found that exosomal miRNAs not only play key roles in the pathophysiological process of TBI, but also act as prominent candidates for the neurorestorative therapy for TBI. These evidences indicate that exosomal miRNAs might have great potential in the neurorestorative therapy for TBI. In this review, we will discuss the latest advances about exosomal miRNAs in the brain and the role of exosomal miRNAs in the neurorestorative therapy for TBI. And, we will investigate the possible mechanisms of exosomal miRNAs therapy for TBI, as well as the opportunities and challenges in the translation of exosomal miRNAs therapy to clinical applications for TBI.

The Clinical Differences of Patients With Traumatic Brain Injury in Plateau and Plain Areas.

Objective: Traumatic brain injury (TBI) is a leading cause of death and disability, which tends to have a worse clinical recovery if it occurs in plateau areas than in plain areas. To explore the underlying cause of this outcome preliminarily, this retrospective study was conducted to compare the clinical differences of patients with TBI in plateau and plain areas. Methods: In this study, 32 patients with TBI in plateau areas (altitude ≥ 4,000 m) and 32 in plain areas (altitude ≤ 1,000 m) were recruited according to the inclusion and exclusion criteria from June 2020 to December 2021. The collected data and compared parameters include clinical features, head CT presentations and Marshall classifications, hematology profile, lipid profile, coagulation profile, and multiorgan (cardiac, liver, renal) function within 24 h of hospital admission, as well as the treatment method and final outcome. Results: There were no obvious differences in demographic characteristics, including gender, age, height, and weight, between patients with TBI in plateau and plain areas (all P > 0.05). Compared to patients with TBI in plain areas, the time before hospital admission was longer, heartbeat was slower, systolic blood pressure (SBP) was lower, and hospital stays were longer in patients with TBI in plateau areas (all P < 0.05). More importantly, elevated red blood cells (RBCs) count and hemoglobin (HGB) level, enhanced coagulation function, and higher rates of multiorgan (cardiac, liver, and renal) injury were found in patients with TBI in plateau areas (all P < 0.05). Conclusion: Patients with TBI in plateau areas presented with altered clinical characteristics, enhanced coagulation function, and aggravated predisposition toward multiorgan (cardiac, liver, and renal) injury, compared to patients with TBI in plain areas. Future prospective studies are needed to further elucidate the influences of high altitude on the disease course of TBI.

HBO Alleviates Neural Stem Cell Pyroptosis via lncRNA-H19/miR-423-5p/NLRP3 Axis and Improves Neurogenesis after Oxygen Glucose Deprivation.

Due to the limited neurogenesis capacity, there has been a big challenge in better recovery from neurological dysfunction caused by stroke for a long time. Neural stem cell (NSC) programmed death is one of the unfavorable factors for neural regeneration after stroke. The types of death such as apoptosis and necroptosis have been deeply investigated while the pyroptosis of NSCs is not quite understood. Although it is well accepted that hyperbaric oxygen (HBO) alleviates the oxygen-glucose deprivation (OGD) injury after stroke and reduces programmed death of NSCs, whether NSC pyroptosis is involved in this process is still unknown. Therefore, this study is aimed at studying the potential effect of HBO treatment on NSC pyroptosis following OGD exposure, as well as its influence on NSC proliferation and differentiation in vitro. The results revealed that OGD increased NOD-like receptor protein 3 (NLRP3) expression to induce the pyroptotic death of NSCs, which was rescued by HBO treatment. And the upregulated lncRNA-H19 functioned as a molecular sponge of miR-423-5p to target NLRP3 for NSC pyroptosis following OGD. Most importantly, it was confirmed that HBO exerted protection of NSCs against pyroptosis by inhibiting lncRNA-H19/miR-423-5p/NLRP3 axis. Moreover, HBO restraint of lncRNA-H19-associated pyroptosis benefited the proliferation and neuronal differentiation of NSCs. It was concluded that HBO attenuated NSC pyroptosis via lncRNA-H19/miR-423-5p/NLRP3 axis and enhanced neurogenesis following OGD. The findings provide new insight into NSC programmed death and enlighten therapeutic strategy after stroke.

Impact of high altitude on the incidence of postoperative venous thromboembolism and its genetic susceptibility: A meta-analysis and systematic review.

BACKGROUND: The effect of high-altitude (HA) on venous thromboembolism (VTE) and its mechanism remains ambiguous. To clarify this, we aimed to conduct a meta-analysis and systematic review to evaluate the incidence of VTE at HA and comparatively low altitude (LA) and figure out the intrinsic risk factors such as susceptibility genes of patients with VTE at HA. METHODS: We selected studies that explored the risk factors for HA and VTE by searching PubMed, Embase, and Web of Science to analyze the impact of HA on VTE. All relevant studies before August 2021 were screened using the terms ([high altitude] OR [plateau] OR [mountain]) AND ([venous thromboembolism] OR [deep vein thrombosis] OR [pulmonary embolism]). Latest studies on the gene of HA-VTE patients were also summarized and analyzed. RESULTS: Fifteen studies were eventually assessed, and the overall numbers of subjects with and without VTE were 1475 and 286,926 respectively. The overall incidence of VTE, deep vein thrombosis (DVT) and pulmonary embolism (PE) in the HA group was significantly higher than that in the LA group (P < 0.01). The overall incidence of VTE, DVT and PE in the HA group was significantly higher than that in the LA group at 30 days post operation (P < 0.05, P < 0.05 and P < 0.01, respectively). At 90 days post operation, incidence of VTE and PE in the HA group was higher than that in the LA group (P < 0.01and P < 0.01, respectively), but there was no difference in the incidence of DVT (P = 0.07). Regarding endogenous factors, the analysis of genes in patients with HA-VTE revealed numerous targeted genes such as ANG, ACE, lncRNA-LINC00 659/UXT-AS1 and GP4. CONCLUSIONS: We observed a significant association between HA and the overall incidence of VTE and that at 30/90 days post operation, indicating that HA may be a risk factor for VTE.

Correlation Between Neutrophil to Lymphocyte Ratio and Myocardial Injury in Population Exposed to High Altitude.

Objective: Myocardial injury is a severe complication in population exposed to high altitude. As a new biomarker for inflammatory response, neutrophil to lymphocyte ratio (NLR) has been widely used to predict the prognosis of various diseases. In this study, we intend to explore the risk factors for myocardial injury at high altitude and examine the relationship between NLR level and development of myocardial injury. Methods: Consecutive patients admitted to a secondary general hospital at high altitude from June 2019 to May 2020 were selected into this retrospective study. Clinical and biochemical data were collected. According to the results of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzymes (CK-MB), and aspartate amino transferase (AST), patients were divided into myocardial injury group and normal group. Results: A total of 476 patients were enrolled in this study. Myocardial injury occurred in 158 patients (33.2%). We found that altitude, NLR, hemoglobin, total bilirubin, total cholesterol, and lipoprotein A in myocardial injury group were significantly higher than that in normal group (P < 0.05), while platelet count in myocardial injury group was significantly lower than that in normal group (P < 0.05). Logistic multivariate regression analysis revealed that there was an independent relationship between myocardial injury and smoke, NLR, hemoglobin (P < 0.05). By using Spearman correlation analysis, NLR was proved to have a significant positive correlation with LDH, CK, and CK-MB (P < 0.05) instead of AST. A receiver operating characteristic (ROC) curve was drawn to demonstrate that NLR could significantly predict the occurrence of myocardial injury with an area under the curve (AUC) of 0.594 (95% CI: 0.537-0.650, P < 0.05), and the level of 2.967 (sensitivity = 38.0%, specificity = 83.6%) was optimal cutoff value. Conclusion: The incidence of myocardial injury is high in population at high altitude. Smoke, hemoglobin, and NLR are independent factors related to myocardial injury. As a convenient and efficient marker, NLR is found to be closely associated with myocardial enzymes and have a predict role in the occurrence of myocardial injury. This study will provide a theoretical basis on NLR for the early diagnosis of myocardial injury at high altitude.

Exosomal MicroRNAs as Liquid Biopsy Biomarkers in Hepatocellular Carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) has a high incidence in China and exploring effective ways for early diagnosis is an important method to improve the prognosis of patients with HCC. Additional studies reported that. Some kinds of microRNA (miRNA) in plasma will change accordingly during HCC progress, and this change can be used to diagnose HCC, especially with miRNA-122, miRNA-21 and miRNA-96. We were aiming at investigating the values of the exosomal miRNAs in diagnosis and prognosis for HCC patients. PATIENTS AND METHODS: Blood samples from 50 patients with HCC and 50 patients with hepatic cirrhosis and 50 healthy volunteers were obtained. The diagnostic accuracy of the plasma and exosomal miRNAs and the comparisons among different groups were measured by the area under the curve (AUC) on receiver operating characteristic (ROC) curve analysis. RESULTS: Expression levels of miRNA-21 and miRNA-96 were significantly higher in patients with HCC and of miRNA-122 were significantly lower in HCC compared with cirrhotic patients in both exosomes and plasma. Among different groups, exosomal miRNA-122, miRNA-21 and miRNA-96 were significantly more accurate in diagnosing HCC than those miRNAs in plasma and the alpha-fetoprotein (AFP) level. The miRNA panel had high accuracy in discriminating HCC from the cirrhosis group (AUC 0.924; 95% CI; sensitivity 82%, specificity 92%) and healthy volunteers' group. Exosomal miRNA-21 and miRNA-96 with low expression and miRNA-122 with high expression could be associated with a patient's survival time. However, the miRNA panel could better predict the HCC patient's survival time compared with each miRNA individually. CONCLUSION: This study showed that the expression levels of miRNA-122, miRNA-21 and miRNA-96 in exosomes were more significantly changed than those miRNAs in plasma in patients with HCC compared with cirrhotic patients, and the exosomal miRNA panel containing miRNA-122, miRNA-21 and miRNA-96 could be defined as a diagnostic biomarker for patients with HCC. We also conclude that different expression of exosomal miRNAs, especially the miRNA panel, could predict the HCC patient's prognosis.