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1.
J Neurosurg Spine ; : 1-10, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39303298

RESUMEN

OBJECTIVE: Patients with spinal cord astrocytomas (SCAs) are at high risk for CNS dissemination, yet comprehensive data on characteristics of dissemination are lacking. This study depicts the exact incidence and patterns of dissemination by analyzing data from a large-scale dataset of SCA. METHODS: The authors included 94 patients with SCA based on the 2021 WHO classification from 2011 to 2022, retrospectively collected their clinical and pathological characteristics, and analyzed factors influencing SCA dissemination. RESULTS: CNS dissemination, encompassing leptomeningeal spreading and/or subarachnoid seeding, was evaluated in 94 patients with and without H3 K27 alterations, with an overall dissemination rate reaching 85.0% at 5-year follow-up. Patients with altered H3 K27 had a significantly higher 5-year CNS dissemination rate than patients with H3 K27 wildtype status (95.2% vs 68.0%, p = 0.002). The median dissemination-free survival in H3 K27-altered patients was 14.37 (95% CI 2.84-25.89) months, significantly shorter than those with H3 K27 wildtype (statistics not calculated; p < 0.001). Based on univariate Cox regression analysis, H3 K27M alteration, higher histopathological grade, Ki-67 index (≥ 10%), and tumor length (≥ 4 segments) were identified as potential factors associated with CNS dissemination in SCAs. Multivariate Cox regression analysis revealed that H3 K27M alteration appeared to be a risk factor for this phenomenon (HR 2.089, 95% CI 0.940-4.642, p = 0.070). Following dissemination, H3 K27-altered patients had a median postdissemination survival of 8.83 (95% CI 7.13-10.54) months, which was significantly shorter than the 13.40 (95% CI 3.98-34.26) months in those with H3 K27 wildtype (p = 0.008). CONCLUSIONS: Factors indicative of higher SCA malignancy, such as H3 K27M alteration, higher histopathological grade, Ki-67 index (≥ 10%), and tumor length (≥ 4 segments), were similarly suggestive of higher rates of dissemination. The occurrence of dissemination is closely associated with the outcome events in patients with SCA.

2.
Cancer Lett ; 601: 217154, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39121902

RESUMEN

Spinal cord astrocytoma is a rare and highly debilitating tumor, yet our knowledge of its clinical characteristics, molecular features, and pathogenesis remains limited compared to that of its counterparts in the brain. Current diagnostic and therapeutic approaches for spinal cord astrocytomas are primarily based on established guidelines for brain astrocytomas. However, recent studies have revealed unique clinical and pathological attributes that distinguish spinal cord astrocytomas from their corresponding brain counterparts. These findings underscore the inadequacy of directly applying the clinical guidelines developed for brain astrocytomas to spinal astrocytomas. In this review, we provided an up-to-date overview of the advancements in understanding spinal cord astrocytomas. We also discussed the challenges and future research prospects in this field with the aim of improving the precision of diagnosis and therapy for these tumors. Specifically, we emphasized the importance of enhancing our understanding of the molecular heterogeneity, immune characteristics, and clinical trials of spinal cord astrocytomas.


Asunto(s)
Astrocitoma , Neoplasias de la Médula Espinal , Humanos , Astrocitoma/terapia , Astrocitoma/patología , Astrocitoma/genética , Neoplasias de la Médula Espinal/terapia , Neoplasias de la Médula Espinal/genética , Neoplasias de la Médula Espinal/patología , Biomarcadores de Tumor/genética
3.
Spine J ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39154940

RESUMEN

BACKGROUND CONTEXT: Surgical resection is the preferred treatment in most conus medullaris and cauda equina tumor (CMCET) cases. However, total resection is usually challenging to obtain and has a strong possibility of causing various complications if forcibly attempted. Intraoperative neurophysiological monitoring (IONM) has become a necessary adjunctive tool for CMCET resection. PURPOSE: The current study aimed to evaluate the application value of bulbocavernosus reflex (BCR) monitoring in CMCET surgery. STUDY DESIGN: A retrospective clinical study. PATIENT SAMPLE: The medical records of patients who underwent CMCET resection by the same neurosurgical team at our hospital from September 2020 to June 2022 were retrospectively reviewed. IONM was conducted in all surgeries. According to inclusion criteria and exclusion criteria, ultimately, 105 patients were enrolled in the study. OUTCOME MEASURES: The voiding function was assessed before surgery, 1 month after, and 6 months after surgery using the Neurogenic Bladder Symptom Score (NBSS). If the NBSS obtained 1 month after surgery exceeds 9 points than that before surgery, it can be considered that the patient suffered new-onset postoperative voiding dysfunctions (PVDs). Moreover, if the NBSS could restored (less than 9 points higher than before the surgery) at 6 months after surgery, it was defined as a short-term PVD. Otherwise, it was defined as a long-term PVD. METHODS: The amplitude reduction ratios (ARRs) of bilateral BCR waveforms were calculated and compared between patients with PVDs and those without. The receiver operating characteristic curve analysis was subsequently applied to determine the cut-off value of the maximal and minimal ARRs for predicting PVDs. RESULTS: The maximal and minimal ARRs were significantly correlated with short-term and long-term PVDs (p<.001 for all comparisons, Mann-Whitney U test). The threshold values of maximal ARR for predicting short-term and long-term PVD were 68.80% (AUC=0.996, p<.001) and 72.10% (AUC=0.996, p<.001), respectively. While those of minimal ARR were 50.20% (AUC=0.976, p<.001) and 53.70% AUC=0.999, p<.001). CONCLUSIONS: The amplitude reduction of intraoperative bilateral BCR waveforms showed high predictive value for PVDs.

4.
Chin Neurosurg J ; 10(1): 22, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030604

RESUMEN

BACKGROUND: To assess the clinical effects of hybrid surgery, which includes spinal angiography-assisted microsurgery, in the treatment of spinal dural arteriovenous fistulas (SDAVF). METHODS: We retrospectively reviewed 45 patients who underwent hybrid Spinal dural arteriovenous fistula (SDAVF) resection between September 2019 and June 2022. The hybrid surgery involved intraoperative digital subtraction angiography (DSA) of the spinal vessels to determine the source of the blood-supplying artery, location of the fistula and draining vein, indocyanine green fluorescence (ICG)-assisted microsurgical resection of the fistula, and postoperative DSA to verify therapeutic efficacy. The Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Visual Analog Scale (VAS), Barthel score, modified Rankin Scale (mRS) and modified Aminoff-Logue score (key indicator) were used to assess the clinical effects of SDAVF resection. RESULTS: A series of 45 patients with SDAVF were successfully treated with hybrid surgery without fistula recurrence. There were no intraoperative complications related to spinal angiography, and none of the patients died. Postoperatively, two patients experienced clinical deterioration of spinal cord function, which manifested as bilateral lower extremity paralysis and bladder sphincter dysfunction. Postoperatively, improvement in mALS scores was observed in 16 cases (35.6%) within 1-2 days, 12 cases (26.7%) at 1 week, and 7 cases (15.6%) at 6 months. No SDAVF recurrence was detected in the spinal MRA examination 6 months after surgery. When compared with preoperative mALS scores, 35 cases (77.8%) showed significant improvement in symptoms, 8 cases (17.8%), remained unchanged, and 2 cases (4.4%) deteriorated. Compared with the preoperative scores, the postoperative mALS score was significantly decreased [postoperative vs. preoperative: 2(1,3) vs. 3(2,4)], HAMD score [(12.2 ± 5.5) vs. (19.6 ± 6.3)], HAMA score [(15.6 ± 5.5) vs. (20.5 ± 6.5)], and VAS score [3(2,5) vs. 5(4,8)]. Conversely, Barthel scoresshowed significant increase [(74.6 ± 8.7) vs. (67.8 ± 9.2)] (P < 0.05). However, the mRS scores were lower than preoperatively [1(1,2) vs. 2(1,2.5)], but the difference was not statistically significant (P > 0.05). There was a significant increase in "good" neurological outcomes at follow-up compared with preoperative function (62.2% vs. 33.3%) (P = 0.023). CONCLUSION: Hybrid surgery is a safe and effective treatment for patients with SAVF, which is beneficial for improving anxiety, depression, spinal cord, and neurological function, and relieving pain. However, the treatment of patients with SDAVF is a complex, long-term process requiring further multidisciplinary interventions, including clinical care, psychosocial interventions, and neurorehabilitation.

5.
Plant Sci ; 347: 112204, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39059631

RESUMEN

Adventitious root (AR) formation is a limiting factor in the vegetative propagation of tree peony (Paeonia suffruticosa Andr.). PoARRO-1, which encodes an auxin oxidase involved in AR formation, plays a role in the root development of P. ostii, but its associated molecular regulatory mechanisms are not yet understood. In this study, we examined the role of PoARRO-1 in AR formation in P. ostii. The overexpression of PoARRO-1 in P. ostii test-tube plantlets led to a notable enhancement in both the rooting rate and the average number of ARs in vitro, as well as increased activities of peroxidase (POD), superoxide dismutase (SOD), and indoleacetic acid oxidase (IAAO). PoARRO-1 was involved in the conversion of IAA-Asp and IAA-Glu to OxIAA and promoted IAA oxidation. RNA sequencing analysis revealed that PoARRO-1 overexpression led to upregulation of enzyme activity, auxin metabolism related genes. Further analyses showed that PoARRO-1 interacted with the 1-175 aa position of PoIAA27b to regulate the formation of ARs. We therefore propose that PoARRO-1 interacts with PoIAA27b to promote AR formation, and it may be useful targets for enhancing the in vitro propagation of P. ostii.


Asunto(s)
Ácidos Indolacéticos , Paeonia , Proteínas de Plantas , Raíces de Plantas , Paeonia/genética , Paeonia/metabolismo , Paeonia/crecimiento & desarrollo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Ácidos Indolacéticos/metabolismo , Regulación de la Expresión Génica de las Plantas , Peroxidasas
6.
Spine J ; 24(9): 1704-1711, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38679075

RESUMEN

BACKGROUND CONTEXT: The primary treatment method for intramedullary spinal cord tumor (IMSCT) is surgical resection, but this procedure carries a significant risk of neurological damage. Intraoperative neurophysiological monitoring (IONM) has become a necessary adjunctive tool for IMSCT resection. PURPOSE: The current study aimed to explore the application value of D-wave monitoring in IMSCT surgery, and tried to investigate a tailored criterion for its early warning. STUDY DESIGN: A retrospective clinical study. PATIENT SAMPLE: A retrospective analysis was conducted based on the data of patients who underwent IMSCT surgeries performed by the same neurosurgical team at our hospital. IONM was applied in all surgeries. According to inclusion and exclusion criteria, ultimately 90 patients were enrolled in the study. OUTCOME MEASURES: The McCormick Scale (MMS) was applied to assess the functional outcome through outpatient visits or telephone follow-up at one month and six months postoperatively. Patients with an MMS grade over II one month after surgery were considered to have newly developed postoperative motor dysfunction (PMD). If the MMS grade could be restored to I or II six months after surgery, it was defined as a short-term PMD. Otherwise, it was defined as a long-term PMD. METHODS: The predictive value of different IONM modalities, including somatosensory evoked potential (SEP), muscle motor evoked potential (MEP), and D-wave for PMD, was assessed with sensitivity, specificity, positive predictive value, negative predictive value, and subsequent logistic regression analysis. At last, the cut-off value of the D-wave amplitude reduction ratio for predicting PMD was obtained through the receiver operating characteristic (ROC) curve analysis. RESULTS: SEP showed the worst performance in predicting short-term and long-term PMD. Significant MEP changes were indicated as an independent predictive factor for short-term PMD (OR 5.062, 95% CI 1.947-13.166, p=.001), while D-wave changes were demonstrated as an independent predictor for long-term PMD (OR 339.433, 95% CI 11.337-10770.311, p=.001). The optimum cut-off value of the D-wave amplitude reduction ratio for predicting long-term PMD was 42.18%, with a sensitivity of 100% and a specificity of 93.8% (AUC=0.981, p<.001). CONCLUSIONS: D-wave monitoring showed extremely high specificity in predicting PMD compared to SEP and MEP monitoring. Moreover, the authors suggested that a D-wave amplitude reduction of over 40% during IMSCT surgery generally indicates long-term PMD for patients.


Asunto(s)
Monitorización Neurofisiológica Intraoperatoria , Neoplasias de la Médula Espinal , Humanos , Neoplasias de la Médula Espinal/cirugía , Masculino , Femenino , Persona de Mediana Edad , Adulto , Monitorización Neurofisiológica Intraoperatoria/métodos , Estudios Retrospectivos , Anciano , Potenciales Evocados Somatosensoriales/fisiología , Complicaciones Posoperatorias/etiología , Procedimientos Neuroquirúrgicos/métodos , Potenciales Evocados Motores/fisiología
7.
Expert Opin Biol Ther ; 24(4): 269-284, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38644655

RESUMEN

INTRODUCTION: Colorectal cancer (CRC) is the second most lethal malignancy worldwide. Immune checkpoint inhibitors (ICIs) benefit only 15% of patients with mismatch repair-deficient/microsatellite instability (dMMR/MSI) CRC. The majority of patients are not suitable due to insufficient immune infiltration. Cancer vaccines are a potential approach for inducing tumor-specific immunity within the solid tumor microenvironment. AREA COVERED: In this review, we have provided an overview of the current progress in CRC vaccines over the past three years and briefly depict promising directions for further exploration. EXPERT OPINION: Cancer vaccines are certainly a promising field for the antitumor treatment against CRC. Compared to monotherapy, cancer vaccines are more appropriate as adjuvants to standard treatment, especially in combination with ICI blockade, for microsatellite stable patients. Improved vaccine construction requires neoantigens with sufficient immunogenicity, satisfactory HLA-binding affinity, and an ideal delivery platform with perfect lymph node retention and minimal off-target effects. Prophylactic vaccines that potentially prevent CRC carcinogenesis are also worth investigating. The exploration of appropriate biomarkers for cancer vaccines may benefit prognostic prediction analysis and therapeutic response prediction in patients with CRC. Although many challenges remain, CRC vaccines represent an exciting area of research that may become an effective addition to current guidelines.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/genética , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/inmunología , Animales , Microambiente Tumoral/inmunología
8.
Pain ; 165(9): e96-e105, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38501980

RESUMEN

ABSTRACT: Moderate-to-severe acute postsurgical pain (APSP) can prolong the recovery and worsen the prognosis of patients who undergo spinal surgery. Esketamine and pregabalin may resolve APSP without causing hyperpathia or respiratory depression after surgery. However, there are other risks, such as dissociative symptoms. We designed a randomized controlled trial to investigate the effect of the combination of these 2 drugs on the incidence of APSP in patients who underwent resection of spinal neoplasms. Patients aged 18 to 65 years were randomized to receive esketamine (a bolus dose of 0.5 mg·kg -1 and an infusion dose of 0.12 mg·kg -1 ·h -1 for 48 hours after surgery) combined with oral pregabalin (75-150 mg/day, starting 2 hours before surgery and ending at 2 weeks after surgery) or an identical volume of normal saline and placebo capsules. The primary outcome was the proportion of patients with moderate-to-severe APSP (visual analog scale score ≥ 40) during the first 48 hours after surgery. Secondary outcomes included the incidence of drug-related adverse events. A total of 90 patients were randomized. The incidence of moderate-to-severe APSP in the combined group (27.3%) was lower than that in the control group (60.5%) during the first 48 hours after surgery (odds ratio = 0.25, 95% CI = 0.10-0.61; P = 0.002). The occurrence of mild dissociative symptoms was higher in the combined group than in the control group (18.2% vs 0%). In conclusion, esketamine combined with pregabalin could effectively alleviate APSP after spinal surgery, but an analgesic strategy might increase the risk of mild dissociative symptoms.


Asunto(s)
Analgésicos , Ketamina , Dolor Postoperatorio , Pregabalina , Neoplasias de la Columna Vertebral , Humanos , Pregabalina/uso terapéutico , Pregabalina/administración & dosificación , Ketamina/uso terapéutico , Ketamina/administración & dosificación , Femenino , Persona de Mediana Edad , Masculino , Dolor Postoperatorio/tratamiento farmacológico , Analgésicos/uso terapéutico , Analgésicos/administración & dosificación , Adulto , Neoplasias de la Columna Vertebral/cirugía , Quimioterapia Combinada , Anciano , Dimensión del Dolor/métodos , Método Doble Ciego , Adulto Joven , Resultado del Tratamiento , Adolescente
10.
Mol Cancer ; 23(1): 54, 2024 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-38486218

RESUMEN

BACKGROUND: Phosphoinositide 3-kinases (PI3Ks) are critical regulators of diverse cellular functions and have emerged as promising targets in cancer therapy. Despite significant progress, existing PI3K inhibitors encounter various challenges such as suboptimal bioavailability, potential off-target effects, restricted therapeutic indices, and cancer-acquired resistance. Hence, novel inhibitors that overcome some of these challenges are needed. Here, we describe the characterization of KTC1101, a novel pan-PI3K inhibitor that simultaneously targets tumor cell proliferation and the tumor microenvironment. Our studies demonstrate that KTC1101 significantly increases the anti-PD-1 efficacy in multiple pre-clinical mouse models. METHODS: KTC1101 was synthesized and characterized employing chemical synthesis, molecular modeling, Nuclear Magnetic Resonance (NMR), and mass spectrometry. Its target specificity was confirmed through the kinase assay, JFCR39 COMPARE analysis, and RNA-Seq analysis. Metabolic stability was verified via liver microsome and plasma assays, pharmacokinetics determined by LC-MS/MS, and safety profile established through acute toxicity assays to determine the LD50. The antiproliferative effects of KTC1101 were evaluated in a panel of cancer cell lines and further validated in diverse BALB/c nude mouse xenograft, NSG mouse xenograft and syngeneic mouse models. The KTC1101 treatment effect on the immune response was assessed through comprehensive RNA-Seq, flow cytometry, and immunohistochemistry, with molecular pathways investigated via Western blot, ELISA, and qRT-PCR. RESULTS: KTC1101 demonstrated strong inhibition of cancer cell growth in vitro and significantly impeded tumor progression in vivo. It effectively modulated the Tumor Microenvironment (TME), characterized by increased infiltration of CD8+ T cells and innate immune cells. An intermittent dosing regimen of KTC1101 enhanced these effects. Notably, KTC1101 synergized with anti-PD-1 therapy, significantly boosting antitumor immunity and extending survival in preclinical models. CONCLUSION: KTC1101's dual mechanism of action-directly inhibiting tumor cell growth and dynamically enhancing the immune response- represents a significant advancement in cancer treatment strategies. These findings support incorporating KTC1101 into future oncologic regimens to improve the efficacy of immunotherapy combinations.


Asunto(s)
Linfocitos T CD8-positivos , Fosfatidilinositol 3-Quinasas , Humanos , Animales , Ratones , Cromatografía Liquida , Espectrometría de Masas en Tándem , Inmunoterapia
11.
Mol Cancer ; 23(1): 59, 2024 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-38515149

RESUMEN

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure. METHODS: The whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids (n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335). RESULTS: Anlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels. CONCLUSIONS: CircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.


Asunto(s)
Neoplasias Colorrectales , Indoles , MicroARNs , Quinolinas , Humanos , Animales , Ratones , ARN Circular/genética , Proteína p53 Supresora de Tumor , Estudios Prospectivos , MicroARNs/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Proliferación Celular/genética , Biomarcadores , Ubiquitina Tiolesterasa/metabolismo , Ciclinas/metabolismo
12.
NPJ Precis Oncol ; 8(1): 43, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388726

RESUMEN

Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of sequencing cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) for differential diagnosis of these tumors. Prospectively enrolling 45 patients with intramedullary spinal cord lesions, including diffuse midline glioma (DMG), H3K27-altered (14/45), glioblastoma (1/45), H3-wildtype-astrocytoma (10/45), ependymoma (11/45), and other lesions (9/45), CSF samples were collected via lumbar puncture (41/45), intraoperative extraction (3/45), and Ommaya reservoir (1/45). Then, these samples underwent targeted sequencing along with paired tissue DNA. DMG, H3K27-altered patients exhibited a higher ctDNA positivity (85.7%, 12/14) compared to patients with H3-wildtype-astrocytoma (0/8, P = 0.0003), ependymoma (2/10, P = 0.003), and glioneuronal tumor (0/3, P = 0.009). The histological-grade-IV (P = 0.0027), Ki-67 index ≥10% (P = 0.014), and tumor reaching spinal cord surface (P = 0.012) are also associated with higher ctDNA positivity. Interestingly, for patients with TERT promoter mutant tumors, TERT mutation was detectable in the CSF cfDNA of one DMG case, but not other five cases with histological-grade-II tumors. Shared copy number variants were exclusively observed in DMG, H3K27-altered, and showed a strong correlation (Correlation = 0.95) between CSF and tissue. Finally, H3K27M mutations in CSF exhibited high diagnostic efficiency for DMG, H3K27-altered (Sensitivity = 85.7%, Specificity = 100.0%, AUC = 0.929). Notably, H3K27M was detectable in CSF from patients with recurrent tumors, making it easily applicable for postoperative monitoring. In conclusion, the molecular profile from ctDNA released into CSF of malignant tumors was more frequently detected compared to relatively benign ones. Sequencing of ctDNA in CSF exhibited high efficiency for the differential diagnosis of DMG, H3K27-altered.

13.
J Mater Chem B ; 12(3): 800-813, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38186029

RESUMEN

A multifunctional nanoplatform is obtained by modifying copper hexacyanoferrate (Cu-HCF) nanozyme with hyaluronic acid (HA) and further loading platinum (Pt) nanoparticles. This Cu-HCF-HA@Pt platform shows peroxidase-like and glutathione oxidase-like dual-enzyme catalytic activities and photothermal properties, enabling synergistic chemodynamic and photothermal tumor therapy. HA binds to the CD44 receptor, which is highly expressed on the exterior surface of tumor cells, endowing the nanoplatform with tumor specificity. Cu-HCF-HA@Pt catalyzes the decomposition of H2O2 to produce abundant hydroxyl radicals within tumor cells, increasing intracellular oxidative stress levels and inducing tumor cell apoptosis. Meanwhile, Cu-HCF-HA@Pt catalyzes the conversion of intracellular reduced glutathione (GSH) to oxidized glutathione, resulting in GSH exhaustion. The conversion of CuII to CuI in Cu-HCF via a Fenton-like reaction can improve the peroxidase-like property of Cu-HCF-HA@Pt. After the probe is targeted to the tumor site, irradiation by an 808 nm near-infrared laser causes local heating and brings about photothermal tumor apoptosis when reaching 45 °C. The prepared Cu-HCF-HA@Pt combines nanozyme-catalyzed therapy with photothermal therapy to induce apoptosis in tumor cells.


Asunto(s)
Cobre , Ferrocianuros , Platino (Metal) , Cobre/farmacología , Platino (Metal)/farmacología , Especies Reactivas de Oxígeno , Peróxido de Hidrógeno , Peroxidasa , Peroxidasas , Colorantes
14.
Int J Surg ; 110(1): 183-193, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37800559

RESUMEN

BACKGROUND: Postoperative pain after laminoplasty and laminectomy occurs partially from local trauma of the paraspinal tissue. Finding a multimodal analgesic cocktail to enhance the duration and effect of local infiltration analgesia is crucial. Because of the rapid onset and long duration of action of betamethasone, the authors hypothesized that, a pre-emptive multimodal infiltration regimen of betamethasone and ropivacaine reduces pain scores and opioid demand, and improves patient satisfaction following laminoplasty and laminectomy. MATERIALS AND METHODS: This prospective, randomized, open-label, blinded endpoint study was conducted between 1 September 2021 and 3 June 2022, and included patients between the ages of 18 and 64 scheduled for elective laminoplasty or laminectomy under general anesthesia, with American Society of Anesthesiologists classification I/II. One hundred sixteen patients were randomly assigned to either the BR (Betamethasone-Ropivacaine) group or the R (Ropivacaine) group in a 1:1 ratio. Each group received pre-emptive infiltration of a total of 10 ml study solution into each level. Every 30 ml of study solution composed of 0.5 ml of betamethasone plus 14.5 ml of saline and 15 ml of 1% ropivacaine for the BR group, and 15 ml of 1% ropivacaine added to 15 ml of saline for the R group. Infiltration of epidural space and intrathecal space were avoided and the spinous process, transverse process, facet joints, and lamina were injected, along with paravertebral muscles and subcutaneous tissue. Cumulative 48 h postoperative butorphanol consumption via PCA (Patient-controlled analgesia) was the primary outcome. Intention-to-treat (ITT) principle was used for primary analysis. RESULTS: Baseline characteristics were identical in both groups ( P >0.05). The cumulative 48 h postoperative butorphanol consumption via PCA was 3.0±1.4 mg in the BR group ( n =58), and 7.1±1.2 mg in the R group ( n =58) ( P <0.001). Overall cumulative opioid demand was lower at different time intervals in the BR group ( P <0.001), along with the estimated median time of first analgesia demand via PCA (3.3 h in the BR group and 1.6 h in the R group). The visual analog scale (VAS) score at movement and rest were also significantly lower until 3 months and 6 weeks, respectively. No side effects or adverse events associated with the intervention were observed in this study. CONCLUSIONS: Pre-emptive analgesia with betamethasone and ropivacaine provides better postoperative pain management following laminoplasty and laminectomy, compared to ropivacaine alone. This is an effective technique worthy of further evaluation.


Asunto(s)
Anestésicos Locales , Laminoplastia , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Ropivacaína , Anestésicos Locales/uso terapéutico , Analgésicos Opioides/uso terapéutico , Betametasona/uso terapéutico , Laminectomía/efectos adversos , Butorfanol/uso terapéutico , Laminoplastia/efectos adversos , Estudios Prospectivos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Analgesia Controlada por el Paciente/métodos , Método Doble Ciego , Amidas/uso terapéutico
15.
Neurochirurgie ; 70(1): 101513, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37931654

RESUMEN

BACKGROUND: Spinal hemangioblastomas (HBs) that involving cauda equina are rare. Data on clinical characteristics and long-term intervention outcomes of patients harboring cauda equina HBs remain lacking due to its scarcity. OBJECTIVE: This study aims to present the clinical-radiological features and treatment results of this rare pathology by using cases from a single center. METHODS: A review of demographic data and intervention outcomes of patients harboring cauda equina HBs in our department between 2009 and 2020 was retrospectively carried out. RESULTS: Ten consecutive adult patients were incorporated, with a slight female predominance (n = 6, 60%). The mean age was 39.9 ± 14.7 (range: 18-58) years. Six patients (60%) had von Hippel‒Lindau (VHL) syndrome and showed multiple symptoms and severe neurological deficits, while 4 (40%) were in the sporadic group and only presented pain symptoms. During follow-up, 3 patients (30%) experienced lesion relapse and underwent repeated surgery. Favorable outcomes were achieved in all patients. CONCLUSION: Cauda equina HBs are rare spinal vascular lesions that should be differentiated from other lumbar canal lesions. Total surgical resection is the main treatment modality and can benefit patients, even recurrent patients. The treatment outcome is usually satisfactory, especially in sporadic cases.


Asunto(s)
Cauda Equina , Hemangioblastoma , Neoplasias de la Médula Espinal , Enfermedad de von Hippel-Lindau , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cauda Equina/cirugía , Cauda Equina/patología , Hemangioblastoma/diagnóstico , Hemangioblastoma/cirugía , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Neoplasias de la Médula Espinal/diagnóstico , Neoplasias de la Médula Espinal/cirugía , Neoplasias de la Médula Espinal/patología , Resultado del Tratamiento , Adolescente , Adulto Joven
16.
AJNR Am J Neuroradiol ; 44(12): 1464-1470, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38081676

RESUMEN

BACKGROUND AND PURPOSE: Conventional MR imaging is not sufficient to discern the H3 K27-altered status of spinal cord diffuse midline glioma. This study aimed to develop a radiomics-based model based on preoperative T2WI to determine the H3 K27-altered status of spinal cord diffuse midline glioma. MATERIALS AND METHODS: Ninety-seven patients with confirmed spinal cord diffuse midline gliomas were retrospectively recruited and randomly assigned to the training (n = 67) and test (n = 30) sets. One hundred seven radiomics features were initially extracted from automatically-segmented tumors on T2WI, then 11 features selected by the Pearson correlation coefficient and the Kruskal-Wallis test were used to train and test a logistic regression model for predicting the H3 K27-altered status. Sensitivity analysis was performed using additional random splits of the training and test sets, as well as applying other classifiers for comparison. The performance of the model was evaluated through its accuracy, sensitivity, specificity, and area under the curve. Finally, a prospective set including 28 patients with spinal cord diffuse midline gliomas was used to validate the logistic regression model independently. RESULTS: The logistic regression model accurately predicted the H3 K27-altered status with accuracies of 0.833 and 0.786, sensitivities of 0.813 and 0.750, specificities of 0.857 and 0.833, and areas under the curve of 0.839 and 0.818 in the test and prospective sets, respectively. Sensitivity analysis confirmed the robustness of the model, with predictive accuracies of 0.767-0.833. CONCLUSIONS: Radiomics signatures based on preoperative T2WI could accurately predict the H3 K27-altered status of spinal cord diffuse midline glioma, providing potential benefits for clinical management.


Asunto(s)
Glioma , Humanos , Glioma/diagnóstico por imagen , Glioma/patología , Imagen por Resonancia Magnética/métodos , Estudios Prospectivos , Estudios Retrospectivos , Médula Espinal/diagnóstico por imagen , Médula Espinal/patología
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18.
Int J Surg ; 109(12): 4221-4237, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37988410

RESUMEN

Since the advent of conventional multiport laparoscopic surgery, the prosperity of minimally invasive surgery has been thriving on the advancement of endoscopic techniques. Cosmetic superiority, recovery benefits, and noninferior surgical outcomes weigh single-incision laparoscopic surgery as a promising modality. Although there are surgical challenges posed by steep learning curve and technological difficulties, such as instruments collision, triangulation loss and limited retraction, the establishment of robotic surgical platform as a solution to all is inspiring. Furthermore, with enhanced instrument maneuverability and stability, robotic ergonomic innovations adopt the advantages of single-incision laparoscopic surgery and surmount its recognized barriers by introducing a novel combination, single-incision robotic-assisted surgery. As was gradually diffused in general surgery and other specialties, single-incision robotic-assisted surgery manifests privileges in noninferior clinical outcomes an satisfactory cosmetic effect among strictly selected patients, and has the potential of a preferable surgical option for minimally invasive surgery.


Asunto(s)
Laparoscopía , Procedimientos Quirúrgicos Robotizados , Robótica , Herida Quirúrgica , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Laparoscopía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos
19.
Front Cell Dev Biol ; 11: 1161667, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37745305

RESUMEN

The expression characteristics of non-coding RNA (ncRNA) in colon adenocarcinoma (COAD) are involved in regulating various biological processes. To achieve these functions, ncRNA and a member of the Argonaute protein family form an RNA-induced silencing complex (RISC). The RISC is directed by ncRNA, especially microRNA (miRNA), to bind the target complementary mRNAs and regulate their expression by interfering with mRNA cleavage, degradation, or translation. However, how to identify potential miRNA biomarkers and therapeutic targets remains unclear. Here, we performed differential gene screening based on The Cancer Genome Atlas dataset and annotated meaningful differential genes to enrich related biological processes and regulatory cancer pathways. According to the overlap between the screened differential mRNAs and differential miRNAs, a prognosis model based on a least absolute shrinkage and selection operator-based Cox proportional hazards regression analysis can be established to obtain better prognosis characteristics. To further explore the therapeutic potential of miRNA as a target of mRNA intervention, we conducted an immunohistochemical analysis and evaluated the expression level in the tissue microarray of 100 colorectal cancer patients. The results demonstrated that the expression level of POU4F1, DNASE1L2, and WDR72 in the signature was significantly upregulated in COAD and correlated with poor prognosis. Establishing a prognostic signature based on miRNA target genes will help elucidate the molecular pathogenesis of COAD and provide novel potential targets for RNA therapy.

20.
Plants (Basel) ; 12(16)2023 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-37631175

RESUMEN

Light-emitting diodes (LEDs) can be programmed to provide specialized light sources and spectra for plant growth. UV-A (397.6 nm), blue (460.6 nm), green (520.7 nm), and red (661.9 nm) LED light sources were used to study the effects of different monochromatic lights on the growth, antioxidant system, and photosynthetic characteristics of Spathiphyllum floribundum 'Tian Jiao' (a shade-loving species) and Chrysanthemum morifolium 'Huang Xiu Qiu' (a sun-loving species). This research revealed that green and blue light could enhance the morphological indicators, Chl a/b, photosynthetic electron transfer chain performance, and photosystem activity of S. floribundum, blue and red light could enhance the solution protein, Chl a, and photosynthetic electron transfer chain performance of C. morifolium, red and UV-A light viewed the highest SOD and CAT activities of S. floribundum (275.56 U·min·g-1; 148.33 U·min·g-1) and C. morifolium (587.03 U·min·g-1; 98.33 U·min·g-1), respectively. Blue and green light were more suitable for the growth and development of the shade-loving plant S. floribundum, while red and blue light were more suitable for the sun-loving plant C. morifolium. UV-A light could be used for their stress research. The research revealed the different adaptation mechanism of different plants to light environmental conditions.

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