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Background: As a marker of the GABAergic system, the expression of glutamate decarboxylase 1 (GAD1) is mainly restricted to the central nervous system. Emerging studies have shown that aberrant expression of GAD1 in tumor tissues may promote tumor cell growth. The role of GAD1 in the development of osteosarcoma (OS) remains unclear, so this study sought to investigate the expression status of GAD1 and the effect of its specific inhibitor 3-mercaptopropionic acid (3-MPA) on OS. Methods: The R2 database was used to analyze the relationship between the expression of GAD1 and clinical prognosis in OS patients. Immunohistochemistry was used to compare the expression profile of GAD1 between OS and matched neighboring tissues. The potential antitumor effects of 3-MPA on cell viability, colony formation and the cell cycle were examined. Moreover, the in vivo effect of 3-MPA on tumor growth was investigated using tumor-bearing nude mice. Results: The expression level of GAD1 was aberrantly upregulated in OS tissues, but almost no expression of GAD1 was found in matched neighboring tissues. Western blotting analyses showed upregulation of GAD1 in OS cells compared to human osteoblast cells. In vitro and in vivo, 3-MPA significantly suppressed the growth of OS. Regarding the mechanism, 3-MPA inhibited ß-catenin and cyclin D1 in OS cells, thereby inactivating the Wnt/ß-catenin pathway. Conclusions: OS displays increased expression of the GABAergic neuronal marker GAD1, and 3-MPA significantly reduces OS growth by inhibiting the Wnt/ß-catenin pathway.
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Osteosarcoma (OS) is a type of tumor. Osteosarcoma stem cells (OSCs) are responsible for drug resistance, recurrence, and immunosuppression in OS. We aimed to determine the heterogeneity of OSCs and the immunosuppression mechanisms underlying the interactions between OSCs and tumor-associated macrophages (TAMs). The cell components, trajectory changes, and cell communication profiles of OS cells were analyzed by transcriptomics at the single-cell level. The intercellular communication patterns of OSCs were verified, and the role of the cell hub genes was revealed. Hub geneS are genes that play important roles in regulating certain biological processes; they are often defined as the genes with the strongest regulatory effect on differentially expressed gene sets. Moreover, various cellular components of the OS microenvironment were identified. Malignant cells were grouped, and OSCs were identified. Further regrouping and communication analysis revealed that the genes in the stemness maintenance and differentiation subgroups were involved in communication with macrophages. Key receptor-ligand pairs and target gene sets for cell communication were obtained. Transcriptome data analysis revealed the key gene RARRES2, which is involved in intercellular communication between OSCs and TAMs. In vitro studies confirmed that macrophages promote RARRES2-mediated stemness maintenance in OSCs via the TAM-secreted cytokine insulin-like growth factor 1. Patient studies confirmed that RARRES2 could be a biomarker of OS. OSCs are highly heterogeneous, and different subgroups are responsible for proliferation and communication with other cells. The IGF-RARRES2 axis plays a key role in maintaining OSC stemness through communication with TAMs.
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Neoplasias Óseas , Osteosarcoma , Humanos , Neoplasias Óseas/patología , Línea Celular Tumoral , Células Madre Neoplásicas/metabolismo , Osteosarcoma/patología , Microambiente Tumoral/genética , Macrófagos Asociados a Tumores/metabolismoRESUMEN
The differentiation fate of bone marrow mesenchymal stem cells (BMSCs) affects the progression of steroid-induced osteonecrosis of the femoral head (SONFH). We find that lncRNA DGCR5 encodes a 102-amino acid polypeptide, RIP (Rac1 inactivated peptide), which promotes the adipogenic differentiation of BMSCs and aggravates the progression of SONFH. RIP, instead of lncRNA DGCR5, binds to the N-terminal motif of RAC1, and inactivates the RAC1/PAK1 cascade, resulting in decreased Ser675 phosphorylation of ß-catenin. Ultimately, the nuclear localization of ß-catenin decreases, and the differentiation balance of BMSCs tilts toward the adipogenesis lineage. In the femoral head of rats, overexpression of RIP causes trabecular bone disorder and adipocyte accumulation, which can be rescued by overexpressing RAC1. This finding expands the regulatory role of lncRNAs in BMSCs and suggests RIP as a potential therapeutic target.
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Células Madre Mesenquimatosas , ARN Largo no Codificante , Ratas , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , beta Catenina/metabolismo , Osteogénesis/genética , Diferenciación Celular/genética , Células Madre Mesenquimatosas/metabolismo , Péptidos/metabolismo , Células CultivadasRESUMEN
Metastasis of osteosarcoma is an important adverse factor affecting patients' survival, and cancer stemness is the crucial cause of distant metastasis. Capsaicin, the main component of pepper, has been proven in our previous work to inhibit osteosarcoma proliferation and enhance its drug sensitivity to cisplatin at low concentrations. This study aims to further explore the anti-osteosarcoma effect of capsaicin at low concentrations (100[Formula: see text][Formula: see text]M, 24[Formula: see text]h) on stemness and metastasis. The stemness of human osteosarcoma (HOS) cells was decreased significantly by capsaicin treatment. Additionally, the capsaicin treatment's inhibition of cancer stem cells (CSCs) was dose-dependent on both sphere formation and sphere size. Meanwhile, capsaicin inhibited invasion and migration, which might be associated with 25 metastasis-related genes. SOX2 and EZH2 were the most two relevant stemness factors for capsaicin's dose-dependent inhibition of osteosarcoma. The mRNAsi score of HOS stemness inhibited by capsaicin was strongly correlated with most metastasis-related genes of osteosarcoma. Capsaicin downregulated six metastasis-promoting genes and up-regulated three metastasis-inhibiting genes, which significantly affected the overall survival and/or disease-free survival of patients. In addition, the CSC re-adhesion scratch assay demonstrated that capsaicin inhibited the migration ability of osteosarcoma by inhibiting its stemness. Overall, capsaicin exerts a significant inhibitory effect on the stemness expression and metastatic ability of osteosarcoma. Moreover, it can inhibit the migratory ability of osteosarcoma by suppressing its stemness via downregulating SOX2 and EZH2. Therefore, capsaicin is expected to be a potential drug against osteosarcoma metastasis due to its ability to inhibit cancer stemness.
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Neoplasias Óseas , Osteosarcoma , Humanos , Capsaicina/farmacología , Capsaicina/uso terapéutico , Capsaicina/metabolismo , Proliferación Celular/genética , Línea Celular Tumoral , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/genética , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Células Madre Neoplásicas/patología , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/farmacología , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción SOXB1/farmacologíaRESUMEN
BACKGROUND: To determine the volume and applicability of local autogenous morselized bone (LAMB) harvested and used during posterior-transforaminal lumbar interbody fusion (P-TLIF) in the lower lumbar spine. METHODS: Clinical and radiographic data of 147 patients (87 males) undergoing P-TLIF from January 2017 to December 2019 for lumbar degenerative diseases were retrospectively analyzed. Computed tomography was used to assess the fusion status (at 6 months, 1 year, and the last follow-up postoperatively), restored disc height, graft fusion area and volume, and the minimum required bone volume (MRBV). Clinical outcomes of P-TLIF were assessed using the Oswestry Disability Index (ODI) and visual analog scale (VAS) for low back pain (LBP) and leg pain (LP). RESULTS: The mean follow-up period was 28.4 ± 4.49 months. The patient's age and diagnosis were correlated to the volume and weight of LAMB (mean volume and weight: 3.50 ± 0.45 mL and 3.88 ± 0.47 g, respectively). The ratio of actual fusion area to the total disc endplate and the ratio of actual fusion volume to the total volume of the disc space were > 40%. MRBV ranged from 1.83 ± 0.48 cm3 to 2.97 ± 0.68 cm3. The proportion of grade 4 or 5 fusions increased from 60.6% at 6 months to 96.6% at the last follow-up. The ODI, VAS-LP, and VAS-LBP scores significantly improved after surgery and remained unchanged during the follow-up. CONCLUSION: When combined with a cage, the volume of LAMB harvested from decompression through the unilateral approach at a single-level is sufficient to achieve a solid interbody fusion in the lower lumbar spine with excellent clinical and radiographic outcomes.
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Dolor de la Región Lumbar , Fusión Vertebral , Masculino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Fusión Vertebral/métodos , Estudios Retrospectivos , Región Lumbosacra/cirugía , Dolor de la Región Lumbar/diagnóstico por imagen , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/cirugía , Descompresión , Resultado del Tratamiento , Procedimientos Quirúrgicos Mínimamente Invasivos/métodosRESUMEN
Ankylosing spondylitis (AS) is a chronic progressive autoimmune disease with insidious onset, high rates of disability among patients, unknown pathogenesis, and no effective treatment. Ferroptosis is a novel type of regulated cell death that is associated with various cancers and diseases. However, its relation to AS is not clear. In the present study, we identified two potential therapeutic targets for AS based on genes associated with ferroptosis and explored their association with immune cells and immune cell infiltration (ICI). We studied gene expression profiles of two cohorts of patients with AS (GSE25101 and GSE41038) derived from the gene expression omnibus database, and ferroptosis-associated genes (FRGs) were obtained from the FerrDb database. LASSO regression analysis was performed to build predictive models for AS based on FRGs, and the ferroptosis level in each sample was assessed via single-sample gene set enrichment analysis. Weighted gene co-expression network and protein-protein interaction network analyses were performed for screening; two key genes, DDIT3 and HSPB1, were identified in patients with AS. The relationship between key genes and ICI levels was assessed using the CIBERSORT algorithm, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, DDIT3 and HSPB1 were identified as diagnostic markers and potential therapeutic targets for AS. DDIT3 was highly positively correlated with the infiltration levels of various immune cells, while HSPB1 was negatively correlated with the infiltration levels of several different types of immune cells. In conclusion, DDIT3 and HSPB1 may induce ferroptosis in the cells of patients with AS via changes in the inflammatory response in the immune microenvironment, and these genes could serve as molecular targets for AS therapy.
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Globally, osteosarcoma (OS) is the most prevalent form of primary bone cancer in children and adolescents. Traditional neoadjuvant chemotherapy regimens have reached a bottleneck; thus, OS survivors have unsatisfactory outcomes. Theaflavin-3,3'-digallate (TF3) exhibits potent anticancer properties against many human cancers. Nevertheless, the biological effects and the underlying molecular mechanism of TF3 in human OS remain unclear. The objective of this study was to investigate the effects of TF3 on human OS cell lines and mouse xenograft models. The results showed that TF3 reduced cell viability, suppressed cell proliferation, and caused G0/G1 cell cycle arrest in both MG63 and HOS cell lines in a concentration-dependent manner. TF3 also altered the homeostatic mechanisms for iron storage in the examined cell lines, resulting in an excess of labile iron. Unsurprisingly, TF3 caused oxidative stress through reduced glutathione (GSH) exhaustion, reactive oxygen species (ROS) accumulation, and the Fenton reaction, which triggered ferroptosis and apoptosis in the cells. TF3 also induced MAPK signalling pathways, including the ERK, JNK, and p38 MAPK pathways. Furthermore, oxidative stress was shown to be the primary reason for TF3-induced proliferation inhibition, programmed cell death, and MAPK pathway activation in vitro. Moreover, TF3 exhibited markedly strong antitumour efficacy in vivo in mouse models. In summary, this study demonstrates that TF3 concomitantly plays dual roles in apoptotic and ferroptotic cell death by triggering the ROS and MAPK signalling pathways in both in vitro and in vivo models.
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Neoplasias Óseas , Ferroptosis , Osteosarcoma , Ratones , Animales , Niño , Humanos , Adolescente , Especies Reactivas de Oxígeno/metabolismo , Xenoinjertos , Línea Celular Tumoral , Apoptosis , Osteosarcoma/tratamiento farmacológico , Proliferación Celular , Antioxidantes/farmacología , Neoplasias Óseas/tratamiento farmacológico , Hierro/farmacologíaAsunto(s)
Fístula del Seno Cavernoso de la Carótida , Seno Cavernoso , Embolización Terapéutica , Laceraciones , Heridas Penetrantes , Humanos , Fístula del Seno Cavernoso de la Carótida/diagnóstico por imagen , Fístula del Seno Cavernoso de la Carótida/etiología , Fístula del Seno Cavernoso de la Carótida/cirugía , Tronco EncefálicoRESUMEN
Background: Severe traumatic cervical spinal cord injury (tcSCI) is a disastrous event for patients and families. Maximizing spinal cord function recovery has become the primary therapeutic goal. This study investigated the effect of early extensive posterior decompression on spinal cord function improvement after severe tcSCI. Methods: A retrospective review of 83 consecutive patients who underwent extensive open-door laminoplasty decompression within 24â h after severe tcSCI (American Spinal Injury Association (ASIA) impairment scale (AIS) grade A to C) between 2009 and 2017 at our institution was performed. The patient clinical and demographic data were collected. Neurological functional recovery was evaluated according to the Japanese Orthopaedic Association (JOA) score system, ASIA motor score (AMS) and AIS grade. Results: Among the 83 patients initially included, the baseline AIS grade was A in 12, B in 28, and C in 43. Twenty-three patients (27.7%) had a high cervical injury. Cervical spinal stenosis (CSS) was identified in 37 patients (44.6%). The mean intramedullary lesion length was 59.6 ± 20.4â mm preoperatively and 34.2 ± 13.3â mm postoperatively (p < 0.0001). At the final follow-up visit, an improvement of at least one and two AIS grades was found in 75 (90.4%) and 41 (49.4%) patients, respectively. 24 (64.9%) patients with an improvement of least two AIS grades had CSS. The mean AMS and JOA score were significantly improved at discharge and the final follow-up visit compared with on admission (p < 0.0001). Conclusions: Our results suggest that early expansive laminoplasty decompression may improve neurological outcomes after severe tcSCI, especially in patients with CSS. Larger and prospective controlled studies are needed to validate these findings.
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Ventriculoperitoneal (VP) shunt disconnection, a VP shunt complication, can be caused by several factors. We report the case of a young man who suffered VP shunt disconnection, and whose entire distal catheter migrated into the abdominal cavity due to a seizure. To our knowledge, risk factors for seizures related to shunt disconnection have not been previously evaluated. We report this rare case to highlight the fact that seizures are not negligible in increasing the probability of disconnection and migration of the entire distal catheter into the abdominal cavity, and the standardized treatment of traumatic seizures is extremely important.
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Elevated intraspinal pressure (ISP) following traumatic spinal cord injury (tSCI) can be an important factor for secondary SCI that may result in greater tissue damage and functional deficits. Our present study aimed to investigate the dynamic changes in ISP after different degrees of acute compression SCI in rabbits with closed canals and explore its influence on spinal cord pathophysiology. Closed balloon compression injuries were induced with different inflated volumes (40 µl, 50 µl or no inflation) at the T7/8 level in rabbits. ISP was monitored by a SOPHYSA probe at the epicenter within 7 days post-SCI. Edema progression, spinal cord perfusion and damage severity were evaluated by serial multisequence MRI scans, somatosensory evoked potentials (SEPs) and behavioral scores. Histological and blood spinal cord barrier (BSCB) permeability results were subsequently analyzed. The results showed that the ISP waveforms comprised three peaks, significantly increased after tSCI, peaked at 72 h (21.86 ± 3.13 mmHg) in the moderate group or 48 h (31.71 ± 6.02 mmHg) in the severe group and exhibited "slow elevated and fast decreased" or "fast elevated and slow decreased" dynamic changes in both injured groups. Elevated ISP after injury was correlated with spinal cord perfusion and edema progression, leading to secondary lesion enlargement. The secondary damage aggravation can be visualized by diffusion tensor tractography (DTT). Moreover, the BSCB permeability was significantly increased at the epicenter and rostrocaudal segments at 72 h after SCI; by 14 days, notable permeability was still observed at the caudal segment in the severely injured rabbits. Our results suggest that the ISP of rabbits with closed canals increased after acute compression SCI and exhibited different dynamic change patterns in moderately and severely injured rabbits. Elevated ISP exacerbated spinal cord perfusion, drove edema progression and led to secondary lesion enlargement that was strongly associated with BSCB disruption. For severe tSCI, early intervention targeting elevated ISP may be an indispensable choice to rescue spinal cord function.
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Traumatismos de la Médula Espinal , Animales , Edema/diagnóstico por imagen , Edema/etiología , Potenciales Evocados Somatosensoriales , Imagen por Resonancia Magnética , Conejos , Médula Espinal/patología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/patologíaRESUMEN
BACKGROUND AND AIMS: This study was designed to explore the effects of Yes-associated protein (YAP) knockdown on human osteosarcoma (HOS) cell sensitivity to Pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT), and to assess how YAP silencing in combination with treatment with the ferroptosis inducer Erastin improves HOS cell sensitivity to MPPa-PDT in an effort to better clarify the molecular mechanisms underlying these phenotypes. METHODS: At 12 h post-MPPa-PDT, Hoechst staining and flow cytometry were conducted to evaluate the apoptotic death of HOS cells. The expression of YAP in these cells at 12 h post-MPPa-PDT treatment was assessed via Western blotting and immunofluorescent staining. BODIPY581/591-C11 was used to evaluate lipid peroxidation. Following shYAP lentiviral transduction, Western blotting was conducted to assess the expression of proteins associated with proliferation, apoptosis, and ferroptosis. EdU assays and clonogenic assays were performed to analyze cellular proliferation. Erastin-treated HOS cells were used to establish a ferroptosis model. Western blotting was used to measure ferroptosis-associated protein levels following shYAP and erastin treatment, while changes in proliferation and MDA levels in each group were examined using an MDA kit. RESULTS: At 12 h post-MPPa-PDT, HOS cells exhibited apoptotic characteristics including nuclear fragmentation and pyknosis, with concomitant increases in apoptosis-associated proteins as detected via Western blotting and apoptotic induction as measured via flow cytometry. Phosphorylated YAP levels fell and non-phosphorylated YAP levels rose following such treatment. Transfection with shYAP was successful as a means of generating stable HOS cell lines, and Western blotting analyses of these cells revealed reductions in proteins associated with cellular proliferation together with the upregulation of apoptosis-related proteins. MDA assays indicated that erastin combined with YAP knockdown enhanced the sensitivity of HOS cells to MPPa-PDT treatment. CONCLUSIONS: These data indicate that ferroptosis and YAP knockdown can enhance osteosarcoma cell sensitivity to MPPa-PDT therapy.
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Neoplasias Óseas , Ferroptosis , Osteosarcoma , Fotoquimioterapia , Porfirinas , Apoptosis , Neoplasias Óseas/tratamiento farmacológico , Línea Celular Tumoral , Ésteres , Humanos , Osteosarcoma/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/farmacologíaRESUMEN
Bone is a dynamic organ that has the ability to repair minor injuries via regeneration. However, large bone defects with limited regeneration are debilitating conditions in patients and cause a substantial clinical burden. Bone tissue engineering (BTE) is an alternative method that mainly involves three factors: scaffolds, biologically active factors, and cells with osteogenic potential. However, active factors such as bone morphogenetic protein-2 (BMP-2) are costly and show an unstable release. Previous studies have shown that compounds of traditional Chinese medicines (TCMs) can effectively promote regeneration of bone defects when administered locally and systemically. However, due to the low bioavailability of these compounds, many recent studies have combined TCM compounds with materials to enhance drug bioavailability and bone regeneration. Hence, the article comprehensively reviewed the local application of TCM compounds to the materials in the bone regeneration in vitro and in vivo. The compounds included icariin, naringin, quercetin, curcumin, berberine, resveratrol, ginsenosides, and salvianolic acids. These findings will contribute to the potential use of TCM compound-loaded materials in BTE.
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The currently recommended management for acute traumatic spinal cord injury aims to reduce the incidence of secondary injury and promote functional recovery. Elevated intraspinal pressure (ISP) likely plays an important role in the processes involved in secondary spinal cord injury, and should not be overlooked. However, the factors and detailed time course contributing to elevated ISP and its impact on pathophysiology after traumatic spinal cord injury have not been reviewed in the literature. Here, we review the etiology and progression of elevated ISP, as well as potential therapeutic measures that target elevated ISP. Elevated ISP is a time-dependent process that is mainly caused by hemorrhage, edema, and blood-spinal cord barrier destruction and peaks at 3 days after traumatic spinal cord injury. Duraplasty and hypertonic saline may be promising treatments for reducing ISP within this time window. Other potential treatments such as decompression, spinal cord incision, hemostasis, and methylprednisolone treatment require further validation.
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BACKGROUND: It remains unclear whether nutritional support can reduce the mortality and infection rate of patients with traumatic brain injury (TBI), improve their gastrointestinal function, and shorten the length of stay in the intensive care unit (ICU). The purpose of this study is to evaluate the effect of nutritional support on the clinical outcome of TBI patients. METHODS: A computer search was conducted of the PubMed, Cochrane Library, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) databases for randomized controlled trials investigating the impact of nutritional support on the clinical outcomes of patients with TBI. The search included the period from the establishment of the database to July 2021. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. RevMan 5.3 statistical software (Cochrane Collaboration) was used to analyze the effect size, and a funnel plot was used to detect publication bias. RESULTS: Seven articles reporting on 260 patients receiving nutritional support therapy compared with 252 standard nutrition control patients were included in the study. Meta-analysis showed that there was no significant difference in mortality between the nutritional support and standard nutrition treatments (RR =0.74; 95% CI: 0.34-1.60; P=0.44). However, there were significant differences in total serum protein levels (MD =2.23; 95% CI: 1.38-3.07; P<0.00001), total infection rates (RR =0.54; 95% CI: 0.41-0.71; P<0.0001), lung infection rates (RR =0.60; 95% CI: 0.45-0.81; P=0.0006), length of stay in ICU (MD =-5.65; 95% CI: -6.18 to -5.13; P<0.00001) and Glasgow Coma Scale scores (MD =2.77; 95% CI: 1.75-3.78; P<0.00001). DISCUSSION: Nutritional support effectively shortens the hospital stay of patients, reduces the infection rate of patients, and has a positive effect on promoting rehabilitation for patients with TBI. However, high-quality, large-sample, multi-center randomized controlled trials are needed to further study the specific implementation standards of nutritional support.
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Lesiones Traumáticas del Encéfalo , Apoyo Nutricional , China , Humanos , Unidades de Cuidados Intensivos , Tiempo de InternaciónRESUMEN
BACKGROUND: Therapeutic hypothermia may need prolonged duration for the patients with severe traumatic brain injury (sTBI). METHODS: The Long-Term Hypothermia trial was a prospective, multicenter, randomized, controlled clinical trial to examine the safety and efficacy in adults with sTBI. Eligible patients were 18-65, Glasgow Coma Scale score at 4 to 8, and initial intracranial pressure (ICP) ≥ 25 mm Hg, randomly assigned to the long-term mild hypothermia group (34-35 °C for 5 days) or normothermia group at 37 °C. The primary outcome was the Glasgow outcome scale (GOS) at 6 months. Secondary outcomes included ICP control, complications and laboratory findings, the length of ICU and hospital stay, and GOS at 6 months in patients with initial ICP ≥ 30 mm Hg. This trial is registered with ClinicalTrials.gov, NCT01886222. FINDINGS: 302 patients were enrolled from June 25, 2013, to December 31, 2018, with 6 months follow-up in 14 hospitals, 156 in hypothermia group and 146 in normothermia group. There was no difference in favorable outcome (OR 1·55, 95%CI 0·91-2·64; P = 0·105) and in mortality (P = 0·111) between groups. In patients with an initial ICP ≥ 30 mm Hg, hypothermic treatment significantly increased favorable outcome over normothermia group (60·82%, 42·71%, respectively; OR 1·861, 95%CI 1·031-3·361; P = 0·039). Long-term mild hypothermia did not increase the incidences of complications. INTERPRETATION: Long-term mild hypothermia did not improve the neurological outcomes. However, it may be a potential option in sTBI patients with initial ICP ≥ 30 mm Hg. FUNDING: : Shanghai municipal government and Shanghai Jiao Tong University/School of Medicine.
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Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. In this study, we employed prenatally exposed to valproic acid (VPA) to establish a validated ASD mouse model and found impaired inhibitory gamma-aminobutyric acid (GABAergic) neurotransmission through a presynaptic mechanism in these model mice, which was accompanied with decreased GABA release and GABA-A and GABA-B receptor subunits expression. And acute administration of individual GABA-A or GABA-B receptor agonists partially reversed autistic-like behaviors in the model mice. Furthermore, acute administration of the combined GABA-A and GABA-B receptor agonists palliated sociability deficits, anxiety and repetitive behaviors in the animal model of autistic-like behaviors, demonstrating the therapeutic potential of above cocktail in the treatment of ASD.
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Trastorno del Espectro Autista/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Agonistas de Receptores de GABA-A/farmacología , Agonistas de Receptores GABA-B/farmacología , Corteza Prefrontal/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/tratamiento farmacológico , Potenciales Sinápticos/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Ácido gamma-Aminobutírico/efectos de los fármacos , Animales , Anticonvulsivantes/farmacología , Trastorno del Espectro Autista/inducido químicamente , Trastorno del Espectro Autista/fisiopatología , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Agonistas de Receptores de GABA-A/administración & dosificación , Agonistas de Receptores GABA-B/administración & dosificación , Masculino , Ratones , Ratones Endogámicos C57BL , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Ácido Valproico/farmacologíaRESUMEN
The treatment of severe traumatic brain injury (TBI) with brain herniation is challenging because outcomes are often associated with high mortality and morbidity. Our aim was to identity factors contributing to decompressive craniectomy (DC) and evaluate treatment outcomes in patients with severe TBI with brain herniation.In this retrospective study, we analyzed medical records of severe TBI with brain herniation from May 2009 to December 2013. We reviewed their demographic data, mechanism of injury, Glasgow Coma Scale (GCS) score, pupil status, computed tomography findings, surgical treatment methods, time interval between brain herniation and surgery, as well as outcomes. GCS and pupil status are clinical parameters for detecting increase intracranial pressure while brain parenchyma bulged above the inner plate of the skull during operation indicated brain swelling as well as increased intracranial pressure on which basis the decision to perform DC or craniotomy was determined intraoperatively.One hundred ninety-four patients were included in the study. We performed DC in 143 of the patients while 51 of them we performed craniotomy. There were no statistically significant differences in the age, gender, or injury mechanism between the 2 groups. GCS, pupillary dilation, midline shift, hematoma type and timing of surgery were associated with DC. Nevertheless, logistic regression analysis revealed that hematoma type and timing of surgery were significantly associated with favorable DC outcomes (Pâ<â.001 and Pâ=â.023). Subdural hematoma and timing of surgery >1âhour were both identified as risk factors for DC. Six months after TBI, 34.0% of patients exhibited favorable outcomes. Overall mortality rate was 30.4%. Age, GCS, pupil dilation, hematoma type, and timing of surgery were all associated with patient outcomes. Further logistic regression analysis revealed that, lower GCS, bilateral pupil dilation, timing of surgery >1âhour, and advanced age were independent risk factors for poor outcomes (Pâ=â.001, Pâ=â.037, Pâ=â.028, and Pâ=â.001, respectively).Our study revealed that, DC is not mandatory for all TBI patients with brain herniation. Nevertheless, DC decreases mortality rate in severe TBI patients with brain herniation. Subdural hematoma and timing of surgery >1âhour are key indicators for DC. Lower GCS, bilateral pupil dilation, delayed timing of surgery and advance age are indicators of poor outcomes.
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Lesiones Traumáticas del Encéfalo/complicaciones , Craneotomía , Encefalocele/etiología , Encefalocele/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Craniectomía Descompresiva , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Retrospective single institution observational study.The aim of the present study was to analyze the influence of early extensive posterior decompression on complications in patients with severe traumatic cervical spinal cord injury (tcSCI).Cervical SCI is associated with a high prevalence of hyponatremia and cardiopulmonary dysfunction. However, very few studies have focused on this exploration to reduce the incidence of SCI early complications.We reviewed the medical records of consecutive patients undergoing extensive posterior decompression within 24âh for severe tcSCI (American Spinal Injury Association Impairment Scale [AIS] A to C) admitted between January 2009 and January 2018. The data collected retrospectively included age, gender, mechanism, and level of SCI, AIS grade, fracture or dislocation, electrolyte, and cardiopulmonary complications.Of the 97 enrolled patients, the baseline AIS grade was AIS A in 14, AIS B in 31, and AIS C in 52. Improvement of at least two AIS grades was found in 26 (26.8%), and improvement of at least one grade was found in 80.4% of patients at discharge. Twenty-nine (29.9%) patients had mild hyponatremia, 8 (8.2%) had moderate hyponatremia, and 3 (3.1%) had severe hyponatremia during hospitalization. The incidences of hyponatremia, hypotension, and tracheotomy were 41.2%, 13.4%, and 6.2%, respectively. The mean forced vital capacity (FVC) on admission and at discharge was 1.34â±â0.46âL and 2.21â±â0.41âL (Pâ<â.0001), respectively. Five patients developed pneumonia.Our results suggest that early expansive posterior decompression significantly reduces the incidence of hyponatremia, hypotension, and tracheotomy by promoting recovery of spinal cord function after severe tcSCI.
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Médula Cervical/fisiopatología , Descompresión Quirúrgica/rehabilitación , Hiponatremia/etiología , Traumatismos de la Médula Espinal/cirugía , Disfunción Ventricular/etiología , Adulto , Médula Cervical/lesiones , Médula Cervical/cirugía , Descompresión Quirúrgica/métodos , Descompresión Quirúrgica/estadística & datos numéricos , Femenino , Humanos , Hiponatremia/sangre , Hiponatremia/fisiopatología , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Traumatismos de la Médula Espinal/sangre , Traumatismos de la Médula Espinal/fisiopatología , Resultado del Tratamiento , Disfunción Ventricular/fisiopatologíaRESUMEN
OBJECTIVE: To evaluate recovering consciousness effect of electroacupuncture (EA) on patients after traumatic brain injury (TBI) surgery. METHODS: A total of 100 patients with traumatic coma were randomly divided into an observation group and a control group, 50 cases in each group. The control group was mainly treated with awakening drugs and neurotrophic drugs; on the basis of treatment in the control group, the observation group was treated with EA at Neiguan (PC 6) and Shuigou (GV 26) with disperse-dense wave, 2 Hz/100 Hz in frequency, 0.1-5 mA in intensity. After 30 min of EA, the needles were stayed 60 min. The treatment was performed once a day for 14 consecutive days. The changes in Glasgow coma score (GCS) was observed in the two groups before treatment and after 7, 14 days of treatment; and the two groups were followed up for 3 months after treatment to evaluate the Glasgow outcome scale (GOS) and Barthel index (BI) scores. RESULTS: After 7, 14 days of treatment, the GCS scores of the two groups were higher than those before treatment (P<0.05), and the increase degree in the observation group was significantly larger than that in the control group (P<0.05). At 3 months of follow-up, the GOS and BI scores of the observation group were better than those of the control group (P<0.05). CONCLUSION: Early electroacupuncture intervention can effectively promote the recovery of consciousness after traumatic brain injury surgery, and has a curative long-term effect.