RESUMEN
The subcommissural organ (SCO) is a gland located at the entrance of the aqueduct of Sylvius in the brain. It exists in species as distantly related as amphioxus and humans, but its function is largely unknown. Here, to explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes, Sspo, Car3 and Spdef, that are highly expressed in the SCO. Mouse strains expressing Cre recombinase from endogenous promoter/enhancer elements of these genes were used to genetically ablate SCO cells during embryonic development, resulting in severe hydrocephalus and defects in neuronal migration and development of neuronal axons and dendrites. Unbiased peptidomic analysis revealed enrichment of three SCO-derived peptides, namely, thymosin beta 4, thymosin beta 10 and NP24, and their reintroduction into SCO-ablated brain ventricles substantially rescued developmental defects. Together, these data identify a critical role for the SCO in brain development.
Asunto(s)
Encéfalo , Órgano Subcomisural , Animales , Ratones , Encéfalo/metabolismo , Encéfalo/crecimiento & desarrollo , Encéfalo/embriología , Órgano Subcomisural/metabolismo , Regulación del Desarrollo de la Expresión Génica , Timosina/metabolismo , Timosina/genética , Ratones Transgénicos , Hidrocefalia/genética , Hidrocefalia/metabolismo , Hidrocefalia/patología , Neuronas/metabolismo , Movimiento Celular/fisiología , Péptidos/metabolismo , Ratones Endogámicos C57BLRESUMEN
PURPOSE: To evaluate outcomes of choosing different Roussouly shapes and improving in Schwab modifiers for surgical Roussouly type 1 patients. METHODS: Baseline (BL) and 2-year (2Y) clinical data of adult spinal deformity (ASD) patients presenting with Roussouly type 1 sagittal spinal alignment were isolated in the single-center spine database. Patients were grouped into Roussouly type 1, 2 and 3 with anteverted pelvis (3a) postoperatively. Schwab modifiers at BL and 2Y were categorized as follows: no deformity (0), moderate deformity (+), and severe deformity (++) for pelvic tilt (PT), sagittal vertical axis (SVA), and pelvic incidence and lumbar lordosis mismatch (PI-LL). Improvement in SRS-Schwab was defined as a decrease in the severity of any modifier at 2Y. RESULTS: A total of 96 patients (69.9 years, 72.9% female, 25.2 kg/m2) were included. At 2Y, there were 34 type 1 backs, 60 type 2 backs and only 2 type 3a. Type 1 and type 2 did not differ in rates of reaching 2Y minimal clinically important difference (MCID) for health-related quality of life (HRQOL) scores (all P > 0.05). Two patients who presented with type 3a had poor HRQOL scores. Analysis of Schwab modifiers showed that 41.7% of patients improved in SVA, 45.8% in PI-LL, and 36.5% in PT. At 2Y, patients who improved in SRS-Schwab PT and SVA had lower Oswestry disability index (ODI) scores and significantly more of them reached MCID for ODI (all P < 0.001). Patients who improved in SRS-Schwab SVA and PI-LL had more changes of VAS Back and Short Form-36 (SF-36) outcomes questionnaire physical component summary (SF-36 PCS), and significantly more reached MCID (all P < 0.001). By 2Y, type 2 patients who improved in SRS-Schwab grades reached MCID for VAS back and ODI at the highest rate (P = 0.003, P = 0.001, respectively), and type 1 patients who improved in SRS-Schwab grades reached MCID for SF-36 PCS at the highest rate (P < 0.001). CONCLUSION: For ASD patients classified as Roussouly type 1, postoperative improvement in SRS-Schwab grades reflected superior patient-reported outcomes while type 1 and type 2 did not differ in clinical outcomes at 2Y. However, development of type 3a should be avoided at the risk of poor functional outcomes. Utilizing both classification systems in surgical decision-making can optimize postoperative outcomes.
Asunto(s)
Diferencia Mínima Clínicamente Importante , Humanos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Fusión Vertebral/métodos , Lordosis/cirugía , Lordosis/diagnóstico por imagen , Escoliosis/cirugía , Calidad de VidaRESUMEN
The subcommissural organ (SCO) is a gland located at the entrance of the aqueduct of Sylvius in the brain. It exists in species as distantly related as amphioxus and humans, but its function is largely unknown. To explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes, Sspo, Car3, and Spdef, that are highly expressed in the SCO. Mouse strains expressing Cre recombinase from endogenous promoter/enhancer elements of these genes were used to genetically ablate SCO cells during embryonic development, resulting in severe hydrocephalus and defects in neuronal migration and development of neuronal axons and dendrites. Unbiased peptidomic analysis revealed enrichment of three SCO-derived peptides, namely thymosin beta 4, thymosin beta 10, and NP24, and their reintroduction into SCO-ablated brain ventricles substantially rescued developmental defects. Together, these data identify a critical role for the SCO in brain development.
RESUMEN
Background: Low back pain (LBP) is the main factor of global disease burden. Intervertebral disc degeneration (IVDD) has long been known as the leading reason of LBP. Increasing studies have verified that circular RNAs (circRNAs)-microRNAs (miRNAs)-mRNAs network is widely involved in the pathological processes of IVDD. However, no study was made to demonstrate the circRNAs-mediated ferroptosis, oxidative stress, extracellular matrix metabolism, and immune response in IVDD. Methods: We collected 3 normal and 3 degenerative nucleus pulposus tissues to conduct RNA-sequencing to identify the key circRNAs and miRNAs in IVDD. Bioinformatics analysis was then conducted to construct circRNAs-miRNAs-mRNAs interaction network associated with ferroptosis, oxidative stress, extracellular matrix metabolism, and immune response. We also performed animal experiments to validate the therapeutic effects of key circRNAs in IVDD. Results: We found that circ_0015435 was most obviously upregulated and circ_0071922 was most obviously downregulated in IVDD using RNA-sequencing. Then we observed that hsa-miR-15a-5p was the key downstream of circ_0071922, and hsa-miR-15a-5p was the top upregulated miRNA in IVDD. Bioinformatics analysis was conducted to predict that 56 immunity-related genes, 29 ferroptosis-related genes, 23 oxidative stress-related genes and 8 ECM-related genes are the targets mRNAs of hsa-miR-15a-5p. Then we constructed a ceRNA network encompassing 24 circRNAs, 6 miRNAs, and 101 mRNAs. Additionally, we demonstrated that overexpression of circ_0071922 can alleviate IVDD progression in a rat model. Conclusions: The findings of this study suggested that circ_0071922-miR-15a-5p-mRNA signaling network might affect IVDD by modulating the nucleus pulposus cells ferroptosis, oxidative stress, ECM metabolism, and immune response, which is an effective therapeutic targets of IVDD.
RESUMEN
Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Asunto(s)
Astrocitos , Neuroglía , Ratones , Animales , Neuroglía/fisiología , Diencéfalo , Encéfalo , Neuronas , MamíferosRESUMEN
Natural organisms, such as lobsters, lotus, and humans, exhibit exceptional mechanical properties due to their ordered structures. However, traditional hydrogels have limitations in their mechanical and physical properties due to their disordered molecular structures when compared with natural organisms. Therefore, inspired by nature and the properties of hydrogels similar to those of biological soft tissues, researchers are increasingly focusing on how to investigate bionic ordered structured hydrogels and render them as bioengineering soft materials with unique mechanical properties. In this paper, we systematically introduce the various structure types, design strategies, and optimization mechanisms used to enhance the strength, toughness, and anti-fatigue properties of bionic ordered structured hydrogels in recent years. We further review the potential applications of bionic ordered structured hydrogels in various fields, including sensors, bioremediation materials, actuators, and impact-resistant materials. Finally, we summarize the challenges and future development prospects of bionic ordered structured hydrogels in preparation and applications.
RESUMEN
We report yellow-orange emitting phosphors Sr9-xCaxMg1.5(PO4)7:0.05Eu2+ (SCxMPO:Eu2+, x = 0.5-2.5) and Sr9-yBayMg1.5(PO4)7:0.05Eu2+ (SByMPO:Eu2+, y = 0.5-3.0) with broad emission bands (450-800 nm). All these phosphors can be excited efficiently by blue light and n-UV light. Their crystal structure, photoluminescence spectra, fluorescence decay curves and thermal stability were investigated in detail. As doping concentrations of Ca2+ or Ba2+ increase, Eu2+ emitting centers will selectively occupy different Sr2+ sites, thus leading to the regulation of optical spectra of SCxMPO:Eu2+ and SByMPO:Eu2+. Accordingly, the emission colors of SCxMPO:Eu2+ and SByMPO:Eu2+ samples can gradually turn from yellow to orange when excited using 460 nm blue light. And the emission colors of a given sample can also be varied under different excitations because there are three kinds of emitting centers in SCxMPO:Eu2+ and SByMPO:Eu2+. In addition, introducing Ca2+ and Ba2+ can enhance the thermal stability of the phosphors obviously, and overall, the thermal stability of SByMPO:Eu2+ is better than that of SCxMPO:Eu2+. We chose SB2.5MPO:zEu2+ as an example to further investigate its photoluminescence properties, and found that the optimal doping concentration of Eu2+ is 0.08, and dipole-quadrupole interaction is dominated in the concentration quenching mechanism. Furthermore, high-quality warm white light can be obtained by two ways: (a) 470 nm blue LED chip + SC1.5MPO:Eu2+ [CCT = 3639 K, Ra = 82.21] and (b) 470 nm blue LED chip + SB2.5MPO:Eu2+ and YAG:Ce3+ [CCT = 4284 K, Ra = 86.69]. The excellent performances indicate that SCxMPO:Eu2+ and SByMPO:Eu2+ are attractive candidates for warm WLEDs.
RESUMEN
Cerebral cavernous malformations (CCMs) and spinal cord cavernous malformations (SCCMs) are common vascular abnormalities of the CNS that can lead to seizure, haemorrhage and other neurological deficits. Approximately 85% of patients present with sporadic (versus congenital) CCMs. Somatic mutations in MAP3K3 and PIK3CA were recently reported in patients with sporadic CCM, yet it remains unknown whether MAP3K3 mutation is sufficient to induce CCMs. Here we analysed whole-exome sequencing data for patients with CCM and found that â¼40% of them have a single, specific MAP3K3 mutation [c.1323C>G (p.Ile441Met)] but not any other known mutations in CCM-related genes. We developed a mouse model of CCM with MAP3K3I441M uniquely expressed in the endothelium of the CNS. We detected pathological phenotypes similar to those found in patients with MAP3K3I441M. The combination of in vivo imaging and genetic labelling revealed that CCMs were initiated with endothelial expansion followed by disruption of the blood-brain barrier. Experiments with our MAP3K3I441M mouse model demonstrated that CCM can be alleviated by treatment with rapamycin, the mTOR inhibitor. CCM pathogenesis has usually been attributed to acquisition of two or three distinct genetic mutations involving the genes CCM1/2/3 and/or PIK3CA. However, our results demonstrate that a single genetic hit is sufficient to cause CCMs.
Asunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central , Proteínas Proto-Oncogénicas , Animales , Ratones , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Mutación/genética , Fenotipo , Médula Espinal/patologíaRESUMEN
Novel phosphor exploration and luminescence property regulation are two important strategies in pursing high performance phosphors for white light emitting diodes, and have attracted great attention from the researchers. Herein, novel green phosphors Sr2Ga2SiO7:Eu2+ and Sr2Ga2SiO7:Ce3+,Tb3+ had been obtained by high-temperature solid-state reactions and their luminescence properties had been investigated in detail. Powder X-ray diffraction and Rietveld structure refinement results verified the phase purity and gave the crystal structure of the prepared samples. Due to the electric dipole transition between inter configurations of 4fN and 4fN-15d1, Sr2Ga2SiO7:Eu2+ and Sr2Ga2SiO7:Ce3+ exhibited intense broad excitation and emission bands, giving out green and blue emitting light under UV excitation, respectively. By codoping Tb3+ with Ce3+ in the host and utilizing the energy transfer, tunable blue to green emission had been obtained. The energy transfer mechanism had been determined to be electric dipole-quadrupole interaction through dynamic luminescence analysis using I-H model. The prepared phosphors exhibited good thermal stability with integral emission intensity at 150 °C remaining more than 80 % of the emission intensity at 25 °C. Moreover, by coating Sr2Ga2SiO7:Eu2+ and Sr2Ga2SiO7:Ce3+,Tb3+ on UV chips, green LED devices had been obtained. The investigation results indicated that the Eu2+ singly doped and Ce3+-Tb3+ codoped Sr2Ga2SiO7 might be potential UV excited green phosphors for solid state lighting.
RESUMEN
Psychosis is an abnormal mental condition that can cause patients to lose contact with reality. It is a common symptom of schizophrenia, bipolar disorder, sleep deprivation, and other mental disorders. Clinically, antipsychotic medications, such as olanzapine and clozapine, are very effective in treatment for psychosis. To investigate the neural circuit mechanism that is affected by antipsychotics and identify more selective therapeutic targets, we employed a strategy by using these effective antipsychotics to identify antipsychotic neural substrates. We observed that local injection of antipsychotics into the ventral tegmental area (VTA) could reverse the sensorimotor gating defects induced by MK-801 injection in mice. Using in vivo fiber photometry, electrophysiological techniques, and chemogenetics, we found that antipsychotics could activate VTA gamma-aminobutyric acid (GABA) neurons by blocking GABAA receptors. Moreover, we found that the VTAGABA nucleus accumbens (NAc) projection was crucially involved in such antipsychotic effects. In summary, our study identifies a novel therapeutic target for the treatment of psychosis and underscores the utility of a 'bedside-to-bench' approach for identifying neural circuits that influence psychotic disorders.
RESUMEN
Different segments of the cerebral vascular network may react distinctly to brain ischemia and recanalization. However, there are limited systematic observations of these vascular responses in mice under a physiological state following ischemic stroke. Herein, we aimed to investigate the vasodynamics among several segments along the cerebral vessels in awake mice following cerebral ischemia/recanalization via two-photon imaging. Plasma in the blood vessels were labelled with fluorescein isothiocyanate dextran. Smooth muscle cells and pericytes were labelled via a genetic mouse line (PDGFRß-tdTomato). We observed a no-reflow phenomenon in downstream microcirculation, and the vasodynamics of different segments of larger cerebral vessels varied in the penumbra area following cerebral ischemia-reperfusion. Despite obtaining reperfusion from the middle cerebral artery, there were significant constrictions of the downstream blood vessels in the ischemic penumbra zone. Interestingly, we observed an extensive constriction of the capillaries 3 hours following recanalization, both at the site covered by pericyte soma and by the pericyte process alone. In addition, we did not observe a significant positive correlation between the changed capillary diameter and pericyte coverage along the capillary. Taken together, abnormal constrictions and vasodynamics of cerebral large and small vessels may directly contribute to microcirculation failure following recanalization in ischemic stroke.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Ratones , Animales , Vigilia , Infarto Cerebral/metabolismo , Isquemia/metabolismo , Pericitos/metabolismo , Accidente Cerebrovascular Isquémico/metabolismoRESUMEN
Spinal cord injury (SCI) is a pathological condition that leading to serious nerve damage, disability and even death. Increasing evidence have revealed that circular RNAs (circRNAs) and mRNA are widely involved in the regulation of the pathological process of neurological diseases by sponging microRNAs (miRNAs). Nevertheless, the potential biological functions and regulatory mechanisms of circRNAs in the subacute stage of SCI remain unclear. We analyzed the expression and regulatory patterns of circRNAs and mRNAs in SCI mice models using RNA-sequencing and bioinformatics analysis. A total of 24 circRNAs and 372 mRNAs were identified to be differentially expressed. Then we identifying the immune-related genes (IRGs) from them. The protein-protein interaction network were constructed based on the STRING database and Cytoscape software. Furthermore, Go and KEGG enrichment analysis were conducted to predict the functions of the IRGs and host genes of DECs. These findings will contribute to elucidate the pathophysiology of SCI and provide effective therapeutic targets for SCI patients.
Asunto(s)
ARN Circular , Traumatismos de la Médula Espinal , Ratones , Animales , ARN Circular/genética , Biología Computacional , Análisis de Secuencia de ARN , Traumatismos de la Médula Espinal/genéticaRESUMEN
Study design: Cross-sectional study. Objective: To identify whether Roussouly type 2 could evolve into type 1 as the deterioration progresses. Methods: The study group comprised subjects with a low pelvic incidence (PI). All subjects underwent a standing whole spinal radiograph and sagittal parameters were measured: T1 pelvic angle (TPA), lumbar lordosis (LL), PI, pelvic tilt (PT), L4-S1 angle, thoracolumbar kyphosis (TLK), thoracic kyphosis (TK), lumbar sagittal apex (LSA), lordosis distribution index (LDI) and number of vertebrae included in the lordosis (NVL). All subjects were distributed into two groups; with primary (de novo) degenerative scoliosis (PDS) and without PDS. Subjects without PDS were divided into young adult, adult, middle-aged and elderly groups. The differences in sagittal parameters of each subgroup were compared. Results: In total, 270 subjects were included with a mean age of 58.6 years (range 20-87 years). There was a stepwise increase in the proportion of type 1 with age, whereas type 2 decreased. The TPA, PT, PI-LL, TK, TLK and LDI increased with age in subjects without PDS. The TPA, LDI, TLK and TK increased with age in subjects who displayed type 1, whereas the PT, LL, L4-S1 and PI-LL were unchanged. The TPA, PT, PI-LL and TLK increased with age in subjects who displayed type 2, whereas LL and L4-S1 were decreased, while the LDI and TK remained unchanged. The LSA of subjects without PDS became lower and the NVL decreased with age, with similar phenomena found in the subjects with type 2. There was no statistical difference among the groups for the LSA or NVL distribution of subjects with type 1. The TPA, PT and PI-LL of subjects with PDS were greater than those in Group IV, while the SS, LL and TK were less. The Roussouly-type, NVL and LSA distribution were identical between these two groups. Conclusion: Roussouly type 1 shape may not be an actual individual specific spine type. Rather, type 2 could evolve into the "type 1" shape as deterioration of the sagittal spinal alignment progresses with age. Primary (de novo) degenerative scoliosis had little effect on whether type 2 became type 1. This should be taken into consideration during the assessment and restoration of sagittal balance.
RESUMEN
Lower back pain (LBP) is the primary reason leading to dyskinesia in patients, which can be experienced by people of all ages. Increasing evidence have revealed that paraspinal muscle (PSM) degeneration (PSMD) is a causative contributor to LBP. Current research revealed that fatty infiltration, tissue fibrosis, and muscle atrophy are the characteristic pathological alterations of PSMD, and muscle atrophy is associated with abnormally elevated oxidative stress, reactive oxygen species (ROS) and inflammation. Interestingly, microgravity can induce PSMD and LBP. However, studies on the molecular mechanism of microgravity in the induction of PSMD are strongly limited. This study identified 23 differentially expressed genes (DEGs) in the PSM (longissimus dorsi) of mice which were flown aboard the Bion M1 biosatellite in microgravity by bioinformatics analysis. Then, we performed protein-protein interaction, Gene Ontology function, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for the DEGs. We found that Il6ra, Tnfaip2, Myo5a, Sesn1, Lcn2, Lrg1, and Pik3r1 were inflammatory genes; Fbox32, Cdkn1a, Sesn1, and Mafb were associated with muscle atrophy; Cdkn1a, Sesn1, Lcn2, and Net1 were associated with ROS; and Sesn1 and Net1 were linked to oxidative stress. Furthermore, Lcn2, Fbxo32, Cdkn1a, Pik3r1, Sesn1, Net1, Il6ra, Myo5a, Lrg1, and Pfkfb3 were remarkably upregulated, whereas Tnfaip2 and Mafb were remarkably downregulated in PSMD, suggesting that they might play a significant role in regulating the occurrence and development of PSMD. These findings provide theoretical basis and therapeutic targets for the treatment of PSMD.
Asunto(s)
Ingravidez , Ratones , Animales , Músculos Paraespinales/metabolismo , Músculos Paraespinales/patología , Especies Reactivas de Oxígeno , Atrofia Muscular/genética , Ontología de GenesRESUMEN
Axonal projection conveys neural information. The divergent and diverse projections of individual neurons imply the complexity of information flow. It is necessary to investigate the relationship between the projection and functional information at the single neuron level for understanding the rules of neural circuit assembly, but a gap remains due to a lack of methods to map the function to whole-brain projection. Here an approach is developed to bridge two-photon calcium imaging in vivo with high-resolution whole-brain imaging based on sparse labeling with the genetically encoded calcium indicator GCaMP6. Reliable whole-brain projections are captured by the high-definition fluorescent micro-optical sectioning tomography (HD-fMOST). A cross-modality cell matching is performed and the functional annotation of whole-brain projection at the single-neuron level (FAWPS) is obtained. Applying it to the layer 2/3 (L2/3) neurons in mouse visual cortex, the relationship is investigated between functional preferences and axonal projection features. The functional preference of projection motifs and the correlation between axonal length in MOs and neuronal orientation selectivity, suggest that projection motif-defined neurons form a functionally specific information flow, and the projection strength in specific targets relates to the information clarity. This pipeline provides a new way to understand the principle of neuronal information transmission.
Asunto(s)
Neuronas , Corteza Visual , Animales , Ratones , Neuronas/fisiología , Encéfalo , Corteza Visual/fisiología , Axones/fisiología , Mapeo Encefálico/métodosRESUMEN
Reconstructing neuron morphologies from fluorescence microscope images plays a critical role in neuroscience studies. It relies on image segmentation to produce initial masks either for further processing or final results to represent neuronal morphologies. This has been a challenging step due to the variation and complexity of noisy intensity patterns in neuron images acquired from microscopes. Whereas progresses in deep learning have brought the goal of accurate segmentation much closer to reality, creating training data for producing powerful neural networks is often laborious. To overcome the difficulty of obtaining a vast number of annotated data, we propose a novel strategy of using two-stage generative models to simulate training data with voxel-level labels. Trained upon unlabeled data by optimizing a novel objective function of preserving predefined labels, the models are able to synthesize realistic 3D images with underlying voxel labels. We showed that these synthetic images could train segmentation networks to obtain even better performance than manually labeled data. To demonstrate an immediate impact of our work, we further showed that segmentation results produced by networks trained upon synthetic data could be used to improve existing neuron reconstruction methods.
Asunto(s)
Imagenología Tridimensional , Redes Neurales de la Computación , Imagenología Tridimensional/métodos , Neuronas , Microscopía , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Although frameshift mutations lead to 22% of inherited Mendelian disorders in humans, there is no efficient in vivo gene therapy strategy available to date, particularly in nondividing cells. Here, we show that nonhomologous end-joining (NHEJ)-mediated nonrandom editing profiles compensate the frameshift mutation in the Pcdh15 gene and restore the lost mechanotransduction function in postmitotic hair cells of Pcdh15av-3J mice, an animal model of human nonsyndromic deafness DFNB23. Identified by an ex vivo evaluation system in cultured cochlear explants, the selected guide RNA restores reading frame in approximately 50% of indel products and recovers mechanotransduction in more than 70% of targeted hair cells. In vivo treatment shows that half of the animals gain improvements in auditory responses, and balance function is restored in the majority of injected mutant mice. These results demonstrate that NHEJ-mediated reading-frame restoration is a simple and efficient strategy in postmitotic systems.
Asunto(s)
Proteínas Relacionadas con las Cadherinas , Pérdida Auditiva Sensorineural , Precursores de Proteínas , Animales , Sistemas CRISPR-Cas , Proteínas Relacionadas con las Cadherinas/genética , Modelos Animales de Enfermedad , Edición Génica , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/patología , Humanos , Mecanotransducción Celular , Ratones , Precursores de Proteínas/genéticaRESUMEN
BACKGROUND: Enhanced recovery after surgery (ERAS) for spinal surgery is new; specifically, an ERAS program for elderly patients is lacking. Geriatric patients have special characteristics that result in further harm by surgical stress. ERAS interventions are designed to improve recovery after surgery and can result in substantial benefits in clinical outcomes and cost-effectiveness. We aimed to determine whether ERAS significantly improved satisfaction and outcomes in elderly patients with long-level lumbar fusion. METHODS: Patients >70 years old with lumbar disc herniation or lumbar spinal stenosis who underwent lumbar fusion of ≥3 levels from July 2019 to June 2021 (ERAS group) and from January 2018 to June 2019 (non-ERAS group) were enrolled. Demographic, comorbidity, and surgical data were collected from electronic medical records. ERAS interventions were categorized as preoperative, intraoperative, and postoperative. We also evaluated primary outcome, surgical complications, and length of stay (LOS). RESULTS: The study included 154 patients, 72 in the ERAS group and 82 case-matched patients in the non-ERAS group. Overall, ERAS pathway compliance was 91%. There were no significant differences in readmission and mortality rates at 30-day follow-up between the ERAS and non-ERAS groups. Statistically significant decreases were observed in the ERAS group in complications (6 in ERAS group vs. 19 in non-ERAS group, P = 0.013) and LOS (17.74 ± 5.56 days in ERAS group vs. 22.13 ± 12.21 days in non-ERAS group, P = 0.041). Multivariable linear regression showed that implementation of ERAS (P = 0.002) was correlated with LOS. Multivariable logistic regression showed that implementation of ERAS (P = 0.004) was correlated with complications. CONCLUSIONS: The ERAS protocol used in elderly patients after long-level lumbar fusion surgery was safe and associated with incremental benefits regarding complications and LOS.
Asunto(s)
Recuperación Mejorada Después de la Cirugía , Fusión Vertebral , Anciano , Análisis de Datos , Humanos , Tiempo de Internación , Región Lumbosacra , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Fusión Vertebral/métodosRESUMEN
BACKGROUND: Wound complications are associated with worse satisfaction and additional costs in patients undergoing posterior lumbar fusion (PLF) surgery, and the relationship between enhanced recovery after surgery (ERAS) pathway and wound complications remains poorly characterized. METHODS: In this retrospective single-center study, we compared 530 patients receiving ERAS pathway care with previous 530 patients in non-ERAS group. The primary aim of our study was to identify the relationship between the ERAS program and the incidence of postoperative wound-related complications and other complications following PLF surgery; other outcomes included the length of stay (LOS), 90-day hospital and rehabilitation center readmission. RESULTS: The average patient age was 65 yr. More patients with old cerebral infarction were in ERAS group (p < 0.01), and other demographics and comorbidities were similar between groups. Patients in the ERAS group had a lower incidence of postoperative wound-related complications than the non-ERAS group (12.4 vs. 17.8%, p = 0.02). The non-ERAS group had a significantly higher rate of wound dehiscence or poor wound healing (6% vs. 3%, p = 0.02). ERAS group had a lower incidence of severe postoperative hypoalbuminemia (serum albumin less than 30 g/L) (15.8% vs. 9.0% p < 0.01). Additionally, ERAS patients had shorter postoperative LOS (8.0 ± 1.5 vs. 9.5 ± 1.7, p < 0.01), lower rate of readmission within 90 days (1.9% vs. 6.4%, p < 0.01) and discharge to rehabilitation center (4.2% vs. 1.0%, p < 0.01). CONCLUSION: ERAS pathway might help decrease the rates of postoperative wound complications and severe hypoalbuminemia following PLF surgery; additionally, it demonstrated that ERAS pathway was also associated with shorter LOS and lower rate of readmissions within 90 days.
Asunto(s)
Recuperación Mejorada Después de la Cirugía , Hipoalbuminemia/epidemiología , Región Lumbosacra/diagnóstico por imagen , Complicaciones Posoperatorias/epidemiología , Infección de la Herida Quirúrgica/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipoalbuminemia/complicaciones , Incidencia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Dehiscencia de la Herida Operatoria/epidemiología , Cicatrización de HeridasRESUMEN
Background: Due to the presence of multimorbidity and polypharmacy, patients aged 75 and older are at a higher risk for postoperative adverse events after lumbar fusion surgery. More effective enhanced recovery pathway is needed for these patients. Pain control is a crucial part of perioperative management. The objective of this study is to determine the impact of multimodal pain management on pain control, opioid consumption, and other outcomes. Methods: This is a retrospective review of a prospective collected database. Consecutive patients who underwent elective posterior lumbar fusion surgery (PLF) from October 2017 to April 2021 in our hospital were reviewed. Perioperative multimodal pain management (PMPM) group (from January 2019 to April 2021) in which patients received multimodal analgesia was case-matched to the control group (from October 2017 to December 2018) in which patients were treated under the conventional patient-controlled analgesia (PCA) method. Postoperative visual analogue scale (VAS), opioid consumption, complications within 3 months, and other outcomes were collected and compared between groups. Results: A total of 122 consecutive patients (aged 75 and older) were included in the PMPM group and compared with previous 122 patients. The PMPM group had a lower maximal VAS score (3.0 ± 1.7 vs. 3.7 ± 2.0, p < 0.001) and frequency of additional opioid consumption (6.6% vs. 19.7%, p=0.001) on POD3 than the control group. The rates of postoperative complications were lower in the PMPM group compared with the control group (25% vs. 49%, p=0.006) during a 3-month follow-up period. Conclusions: This study demonstrates that the PMPM protocol is effective in pain control and reducing additional opioid consumption when compared with conventional analgesia, even for patients aged 75 and older. Moreover, these improvements occur with a lower incidence of postoperative complications within three months after PLF surgery.