RESUMO
Objective: While the pain threshold index (PTI) holds potential as a tool for monitoring analgesia-pain equilibrium, its precision in forecasting postoperative pain in children remains unconfirmed. This study's primary aim was to assess the PTI's predictive precision for postoperative pain. Methods: Children (aged 2-16 years) undergoing general surgery under general anesthesia were included. Within 5â min prior to the patient's emergence from surgery, data including PTI, wavelet index (WLI), heart rates (HR) and mean arterial pressure (MAP) were collected. Subsequently, a 15-min pain assessment was conducted following the patient's awakening. The accuracy of these indicators in discerning between mild and moderate to severe postoperative pain was evaluated through receiver operating characteristic (ROC) analysis. Results: The analysis encompassed data from 90 children. ROC analysis showed that PTI was slightly better than HR, MAP and WLI in predicting postoperative pain, but its predictive value was limited. The area under the curve (AUC) was 0.659 [0.537â¼0.780] and the optimal threshold was 65[64-67]. Sensitivity and specificity were determined at 0.90 and 0.50, respectively. In a multivariable logistic regression model, a higher predictive accuracy was found for a multivariable predictor combining PTI values with gender, BMI, HR and MAP (AUC, 0.768; 95%CI, 0.669-0.866). Upon further scrutinizing the age groups, PTI's AUC was 0.796 for children aged 9-16, 0.656 for those aged 4-8, and 0.601 for younger individuals. Conclusions: PTI, when used alone, lacks acceptable accuracy in predicting postoperative pain in children aged 2 to 16 years. However, when combined with other factors, it shows improved predictive accuracy. Notably, PTI appears to be more accurate in older children.
RESUMO
As vastly modified on secreted proteins, N-glycosylation is found on milk proteins and undergo dynamic changes during lactation, characterizing milk protein glycosylation would benefit the elucidation of glycosylation pattern differences between samples. However, their low abundance required specific enrichment. Herein, through rational design and controllable synthesis, we developed a novel multi-functional polymer for the isolation of protein glycosylation. It efficiently separated glycopeptides from complex background inferences with mutual efforts of hydrophilic interaction chromatography (HILIC), metal ion affinity and ion exchange. By fine-tuning Ca2+ as regulators of aldehyde hyaluronic acid (HA) conformation, the grafting density of HA was remarkably improved. Moreover, grafting Ti4+ further enhanced the enrichment performance. Application of this material to characterize bovine milk and colostrum proteins yields 479 and 611 intact glycopeptides, respectively. Comparative analysis unraveled the distinct glycosylation pattern as well the different distribution of glycoprotein abundances between the two samples, offering insights for functional food development.
RESUMO
The primary aim of this research was to explore the functions of Wtap and Ythdf1 in regulating neuronal Lipocalin-2 (Lcn2) through m6A modification in traumatic brain injury (TBI). By employing transcriptome sequencing and enrichment analysis, we identified the Wtap/Ythdf1-mediated Lcn2 m6A modification pathway as crucial in TBI. In our in vitro experiments using primary cortical neurons, knockout of Wtap and Ythdf1 led to the inhibition of Lcn2 m6A modification, resulting in reduced neuronal death and inflammation. Furthermore, overexpression of Lcn2 in cortical neurons induced the activation of reactive astrocytes and M1-like microglial cells, causing neuronal apoptosis. In vivo experiments confirmed the activation of reactive astrocytes and microglial cells in TBI and importantly demonstrated that Wtap knockdown improved neuroinflammation and functional impairment. These findings underscore the significance of Wtap/Ythdf1-mediated Lcn2 regulation in TBI secondary injury and suggest potential therapeutic implications for combating TBI-induced neuroinflammation and neuronal damage.
Assuntos
Lesões Encefálicas Traumáticas , Lipocalina-2 , Neurônios , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Lipocalina-2/metabolismo , Lipocalina-2/genética , Animais , Neurônios/metabolismo , Neurônios/patologia , Camundongos , Microglia/metabolismo , Microglia/patologia , Astrócitos/metabolismo , Astrócitos/patologia , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Masculino , Camundongos Endogâmicos C57BL , Apoptose , Camundongos Knockout , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologiaRESUMO
Nonfunctioning pituitary adenoma (NFPA) is one of the major subtypes of pituitary adenomas (PA) and its primary treatment is surgical resection. However, normal surgery fails to remove lesions completely and there remains in lack of frontline treatment, so the development of new drugs for NFPA is no doubt urgent. Oridonin (ORI) has been reported to have antitumor effects on a variety of tumors, but whether it could exhibit the same effect on NFPA requires to be further investigated. The effects of ORI on pituitary-derived folliculostellate cell line (PDFS) cell viability, colony formation, proliferation ability, migration, and invasion were examined by Cell Counting Kit-8, colony formation assay, 5Ethynyl2'deoxyuridine proliferation assay, wound-healing assay, and Transwell assay. The differentially expressed genes in the control and ORI-treated groups were screened by transcriptome sequencing analysis and analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. Cell cycle analysis was performed to detect changes in cell cycle. Annexin V-fluorescein isothiocyanate/propidium iodide staining was performed to detect apoptosis in ORI-treated cells. Western blot assay was performed to detect Bax, Bcl-2, and cleaved Caspase-3 protein expression. ORI inhibited PDFS cell viability and significantly suppressed cell proliferation, migration, and invasion. GO and KEGG results showed that ORI was associated with signaling pathways such as cell cycle and apoptosis in PDFS cells. In addition, ORI blocked cells in G2/M phase and induced apoptosis in PDFS cells. ORI can trigger cell cycle disruption and apoptosis collaboratively in PDFS cells, making it a promising and effective agent for NFPA therapy.
Assuntos
Apoptose , Proliferação de Células , Diterpenos do Tipo Caurano , Neoplasias Hipofisárias , Diterpenos do Tipo Caurano/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Adenoma/tratamento farmacológico , Adenoma/patologiaRESUMO
BACKGROUND: Percutaneous balloon compression (PBC) is an effective, low-cost, and simple treatment for primary trigeminal neuralgia (TN). However, PBC has poor efficacy and no better solution for the third branch (V3) of TN. METHODS: Clinical data of 52 patients with trigeminal neuralgia treated with PBC were retrospectively analyzed. Postoperative numbness of the patient was evaluated by facial numbness at the Barrow Neurological Institute (BNI-N). The main observation was the incidence of higher numbness in the V3 than in the other two branches or equally strong numbness in the three branches in the immediate postoperative period. RESULTS: The efficacy values in the pear-shaped balloon group at the first postoperative day (T1), the first month (T2), in the third month (T3), and the sixth month (T4) were 96.7%, 93.3%, 93.3%, and 90%, respectively, and 1 patient (3.3%) had recurrence. The efficacy value for the extracapsular capsule group was 95.5% at all times and there were no patients with recurrence within 6 months after surgery. In the immediate postoperative period, the effective compression rate of V3 in the pear-shaped balloon group was 43.3%, and 86.4% in the extracapsular capsule group (P = 0.020). At six months of follow-up, the effective compression rate of V3 was higher in the extracapsular capsule group than in the pear-shaped balloon group. CONCLUSIONS: The riveted structure of the extracapsular capsule can effectively compress V3, thus performing PBC with a balloon shaped as an extracapsular capsule is a new, effective, and safe treatment option for TN V3. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2300067313.
Assuntos
Neuralgia do Trigêmeo , Humanos , Feminino , Neuralgia do Trigêmeo/cirurgia , Neuralgia do Trigêmeo/terapia , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Adulto , Nervo Trigêmeo/cirurgiaRESUMO
Catalytic ozone (O3) decomposition is a promising technology for curbing indoor O3 pollution, whereas its application is limited by the stability and moisture resistance of heterogeneous catalysts. Ag-Hollandite is a capable solution, but its facile synthesis still lacks systematic investigation. In this study, Ag-Hollandite catalysts were prepared using AgMnO4 as the precursor by reflux (AMO-Re), hydrothermal (AMO-HT), and homogeneous (AMO-HR) methods, respectively. The as-prepared samples showed excellent stability under moisture conditions, with the optimal one maintaining an O3 conversion rate of 99.19 % after 100 h. In the characterization results, Ramsdellite (R-MnO2) was identified as an intermediate species in the synthesis. AMO-HR exhibits higher activity due to enhanced active site exposure and weakened adsorption towards *OO species, while reduced surface hydroxyl content was a crucial factor for moisture resistance. This study aims to contribute insights for preparing catalysts by a facile method.
RESUMO
Moxibustion has a long history of use as a traditional Chinese medicine therapy. Infrared radiation is an important and effective factor in moxibustion. Instead of the time-consuming and laborious process of holding moxa sticks in the hand, moxibustion devices are commonly used as moxibustion methods and tools in modern times. With the publication of the international standard of moxibustion devices (ISO18666:2021, Traditional Chinese Medicine - General requirements of moxibustion devices) published, moxibustion devices of various materials are now sold in the pharmacies and online stores. However, the influence of moxibustion devices on the therapeutic effect of moxibustion has not been studied. Therefore, this research was aimed to evaluate the infrared radiation of moxibustion devices, in order to select the moxibustion device that delivered infrared radiation closest to that of moxa stick combustion. The combination of combustion stability and infrared radiation intensity showed that cardboard tubes and silicone were better materials for moxibustion devices. In the mid-far infrared wave band, the moxibustion devices made from cardboard tubes and silica gels can better maintain the thermal effect generated by moxibustion and enable it to be more easily absorbed by the human body. The infrared radiation intensity of the cardboard moxibustion devices increased rapidly and steadily and could be maintained for the longest time. In conclusion, cardboard tubes are the better material for moxibustion devices with respect to infrared radiation.
RESUMO
Background: Thyroid cancer (TC) is a common endocrine cancer with a favourable prognosis. However, poor patient prognosis due to TC dedifferentiation is becoming an urgent challenge. Recently, methyltransferase-like 3 (METTL3)-mediated N6 -methyladenosine (m6A) modification has been demonstrated to play an important role in the occurrence and progression of various cancers and a tumour suppressor role in TC. However, the mechanism of METTL3 in TC remains unclear. Methods: The correlation between METTL3 and prognosis in TC patients was evaluated by immunohistochemistry. Mettl3fl/flBrafV600ETPO-cre TC mouse models and RNA-seq were used to investigate the underlying molecular mechanism, which was further validated by in vitro experiments. The target gene of METTL3 was identified, and the complete m6A modification process was described. The phenomenon of low expression of METTL3 in TC was explained by identifying miRNAs that regulate METTL3. Results: We observed that METTL3 expression was negatively associated with tumour progression and poor prognosis in TC. Mechanistically, silencing METTL3 promoted the progression and dedifferentiation of papillary thyroid carcinoma (PTC) both in vivo and in vitro. Moreover, overexpressing METTL3 promoted the sensitivity of PTC and anaplastic thyroid cancer (ATC) cells to chemotherapeutic drugs and iodine-131 (131I) administration. Overall, the METTL3/PAX8/YTHDC1 axis has been revealed to play a pivotal role in repressing tumour occurrence, and is antagonized by miR-493-5p.
Assuntos
Diferenciação Celular , Metiltransferases , Fator de Transcrição PAX8 , Neoplasias da Glândula Tireoide , Animais , Feminino , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Metiltransferases/metabolismo , Metiltransferases/genética , MicroRNAs/metabolismo , MicroRNAs/genética , Fator de Transcrição PAX8/metabolismo , Fator de Transcrição PAX8/genética , Prognóstico , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genéticaRESUMO
Photodynamic therapy has been regarded as a noninvasive treatment for cancer with spatiotemporal control over drug activation. Bis-terpyridyl Ru(II) complexes exhibit a promising achiral structure but suffer from low photoreactivity due to deviation from the ideal octahedral geometry. Herein, we introduce the donor-acceptor-donor motif to construct a dinuclear bis-terpyridyl Ru(II) complex (Ru2). Ru2 exhibits superior light absorption properties compared with mononuclear complex Ru1. Importantly, upon 595 nm light excitation, Ru2 shows promising synergetic type I/II photosensitization and photocatalytic activity, while Ru1 is inactive. Anticancer mechanistic studies reflect that Ru2 induces intracellular redox imbalance and affects the biosynthetic and metabolic processes, leading to cell apoptosis. Overall, this work provides a simple strategy to rouse the PDT efficiency of bis-terpyridyl Ru(II) complexes.
Assuntos
Antineoplásicos , Complexos de Coordenação , Fotoquimioterapia , Fármacos Fotossensibilizantes , Rutênio , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Rutênio/química , Rutênio/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Piridinas/farmacologia , Piridinas/química , Piridinas/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Perovskite light-emitting diodes (PeLEDs) that can be air-processed promises the development of displaying optoelectronic device, while is challenged by technical difficulty on both the active layer and hole transport layer (HTL) caused by the unavoidable humidity interference. Here, we propose and validate that, planting the polymer brush with tailored functional groups in inorganic HTL, provides unique bilateral embedded anchoring that is capable of simultaneously addressing the n phases crystallization rates in the active layer as well as the deteriorated particulate surface defects in HTL. Exemplified by zwitterionic polyethyleneimine-sulfonate (PEIS) in present study, its implanting in NiOx HTL offers abundant nuclei sites of amino and sulfonate groups that balance the growth rate of different n phases in quasi-2D perovskite films. Moreover, the PEIS effectively nailed the interfacial contact between perovskite and NiOx, and reduced the particulate surface defects in HTL, leading to the enhanced PLQY and stability of large-area blue perovskite film in ambient air. By virtue of these merits, present work achieves the first demonstration of the air-processed blue PeLEDs in large emitting area of 1.0 cm2 with peak external quantum efficiency (EQE) of 2.09 %, which is comparable to the similar pure-bromide blue PeLEDs fabricated in glovebox.
RESUMO
Cancer cells undergo metabolic adaptation to promote their survival and growth under energy stress conditions, yet the underlying mechanisms remain largely unclear. Here, we report that tripartite motif-containing protein 2 (TRIM2) is upregulated in response to glutamine deprivation by the transcription factor cyclic AMP-dependent transcription factor (ATF4). TRIM2 is shown to specifically interact with carnitine O-palmitoyltransferase 1 (CPT1A), a rate-limiting enzyme of fatty acid oxidation. Via this interaction, TRIM2 enhances the enzymatic activity of CPT1A, thereby regulating intracellular lipid levels and protecting cells from glutamine deprivation-induced apoptosis. Furthermore, TRIM2 is able to promote both in vitro cell proliferation and in vivo xenograft tumor growth via CPT1A. Together, these findings establish TRIM2 as an important regulator of the metabolic adaptation of cancer cells to glutamine deprivation and implicate TRIM2 as a potential therapeutic target for cancer.
RESUMO
Dysregulation of protein core-fucosylation plays a pivotal role in the onset, progression, and immunosuppression of cancer. However, analyzing core-fucosylation, especially the accurate determination of the core-fucosylation (CF) site occupancy ratio, remains challenging. To address these problems, we developed a truncation strategy that efficiently converts intact glycopeptides with hundreds of different glycans into two truncated forms, i.e., a monosaccharide HexNAc and a disaccharide HexNAc+core-fucose. Further combination with data-independent analysis to form an integrated platform allowed the measurement of site-specific core-fucosylation abundances and the determination of the CF occupancy ratio with high reproducibility. Notably, three times CF sites were identified using this strategy compared to conventional methods based on intact glycopeptides. Application of this platform to characterize protein core-fucosylation in two breast cancer cell lines, i.e., MDA-MB-231 and MCF7, yields a total of 1615 unique glycosites and about 900 CF sites from one single LC-MS/MS analysis. Differential analysis unraveled the distinct glycosylation pattern for over 201 cell surface drug targets between breast cancer subtypes and provides insights into developing new therapeutic strategies to aid precision medicine. Given the robust performance of this platform, it would have broad application in discovering novel biomarkers based on the CF glycosylation pattern, investigating cancer mechanisms, as well as detecting new intervention targets.
Assuntos
Fucose , Polissacarídeos , Humanos , Polissacarídeos/química , Polissacarídeos/metabolismo , Polissacarídeos/análise , Fucose/química , Fucose/metabolismo , Glicosilação , Espectrometria de Massas em Tandem , Linhagem Celular Tumoral , Glicopeptídeos/química , Glicopeptídeos/análise , Glicopeptídeos/metabolismoRESUMO
Background: Aurora kinase A (AURKA) and tumor-infiltrating lymphocytes (TILs) are both known to play an essential role in tumorigenesis. However, the expression and prognostic value of the AURKA and TILs in medullary thyroid carcinoma (MTC) have not yet been investigated. Patients and methods: Surgical specimens and clinical data of 137 patients diagnosed with MTC were collected. AURKA expression and TILs infiltration were quantified by immunohistochemistry and hematoxylin-eosin staining. Subsequently, the prognostic value of AURKA expression and TIL infiltration in MTC was evaluated. Results: AURKA was highly expressed in patients with multifocal tumor, cervical lymph node metastasis, and an advanced TNM stage, indicating a high probability of recurrence. AURKA further exhibited a positive correlation with TILs (R = 0.44, P < 0.001). High expression of AURKA combined with a low numbers of TILs (AURKAhigh/TILslow) was identified as an independent prognostic factor for biochemical recurrence (odds ratio: 4.57, 95% confidence interval: 1.54-14.66, P < 0.01) and recurrence-free survival (hazard ratio: 3.64, 95% confidence interval: 1.52-8.71, P < 0.001). The combination of AURKA and TILs apparently improves the prognostic value for biochemical recurrence (area under the curve: 0.751) and structural recurrence (area under the curve: 0.836) of MTC. Notably, AURKAhigh/TILslow demonstrated a high value for prediction of distant or unresectable locoregional recurrence, with an overall accuracy of 86.9%. Conclusion: AURKAhigh is associated with the MTC malignancy. The combination of AURKAhigh/TILslow was identified as novel independent prognostic marker in MTC, predicting incurable disease recurrence with high accuracy.
RESUMO
Sleep is crucial for human health, insufficient sleep or poor sleep quality may negatively affect sleep function and lead to a state of sleep deprivation. Sleep deprivation can result in various health problems, including chronic pain. The intricate relationship between sleep and pain is complex and intertwined, with daytime pain affecting sleep quality and poor sleep increasing pain intensity. The article first describes the influence of sleep on the onset and development of pain, and then explores the impact of daytime pain intensity on nighttime sleep quality and subsequent pain thresholds. However, the primary emphasis is placed on the pivotal role of oxidative stress in this bidirectional relationship. Although the exact mechanisms underlying sleep and chronic pain are unclear, this review focuses on the role of oxidative stress. Numerous studies on sleep deprivation have demonstrated that it can lead to varying degrees of increased pain sensitivity, while chronic pain leads to sleep deprivation and further exacerbates pain. Further research on the role of oxidative stress in the mechanism of sleep deprivation-induced pain sensitization seems reasonable. This article comprehensively reviews the current research on the interrelationship between sleep deprivation, pain and the crucial role of oxidative stress.
RESUMO
OBJECTIVE: Considering fluid stimulation is one of the essential biomechanical signals for periodontal tissues, this study aims to characterizing fluid mechanics response during occlusal loading by a hydro-mechanical coupling model for periodontal ligament. DESIGN: Models simulating periodontium with normal bone height and with intraosseous defects were built with three mechanical modules: tooth, periodontal ligament and alveolar bone. Tooth was modeled as linear elastic, and periodontal ligament and alveolar bone as a hydro-mechanical coupling model. Transient analyses under dynamic occlusal loading were performed. Fluid dynamics within periodontal ligament space was simulated and visualized by post-processing module. RESULTS: Reciprocating oscillatory flow occurred within the periodontal ligament under occlusal loading. Higher pore pressure and fluid velocity were observed in furcation and apical regions compared to mid-root and cervical regions. Intraosseous defects increased pore pressure and fluid velocity within the periodontal ligament, most significantly near the defect. CONCLUSION: Based on the results of the hydro-mechanical coupling model, significant oscillatory fluid motion is observed within the periodontal ligament under occlusal loading. Particularly, higher fluid velocity is evident in the furcation and apical areas. Additionally, Intraosseous defects significantly enhance fluid motion within the periodontal ligament.
Assuntos
Análise de Elementos Finitos , Ligamento Periodontal , Ligamento Periodontal/fisiologia , Humanos , Fenômenos Biomecânicos , Processo Alveolar/fisiologia , Hidrodinâmica , Modelos Biológicos , Simulação por Computador , Força de MordidaRESUMO
This study explored the use of biochar to accelerate the establishment of anaerobic ammonium oxidation (anammox) reactors operating at 15 ± 1â. Incorporating 10 g/L bamboo charcoal in S1 accelerated the start-up of anammox in 87 days, which was significantly shorter than 103 days in S0 (without biochar). After 140 days, S1 exhibited a 10.9 % increase in nitrogen removal efficiency due to a 28.9 % elevation in extracellular polymeric substances, bolstering anammox bacterial resilience. Predominant anammox bacteria (Cadidatus Brocadia and Cadidatus Jettenia) showed relative abundances of 3.19 % and 0.38 % in S1, respectively, which were significantly higher than 0.40 % and 0.05 % in S0. Biochar provides favorable habitats for the enrichment of anammox bacteria and accelerates the establishment of anammox at low temperatures. This finding holds promise for enhancing the efficiency of anammox in cold climates and advancing sustainable wastewater nitrogen removal.
Assuntos
Reatores Biológicos , Carvão Vegetal , Nitrogênio , Oxirredução , Carvão Vegetal/química , Temperatura Baixa , Anaerobiose , Compostos de Amônio/metabolismo , Bactérias/metabolismo , Purificação da Água/métodos , Águas Residuárias/químicaRESUMO
BACKGROUND: Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated. METHODS: A retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated. RESULTS: The 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13-0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42-0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15-12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29-4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17-27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45-6.65; P = 0.004) were independent predictor of DFS. CONCLUSION: Early changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly.
Assuntos
Calcitonina , Carcinoma Neuroendócrino , Recidiva Local de Neoplasia , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Calcitonina/sangue , Pessoa de Meia-Idade , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Prognóstico , Adulto , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Seguimentos , Tireoidectomia/métodos , Idoso , Taxa de Sobrevida , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Adulto Jovem , Adolescente , Fatores de Risco , Fatores de TempoRESUMO
Photodynamic therapy (PDT) is a promising modality for cancer treatment. However, limited tissue penetration of external radiation and complicated tumor microenvironments (TMEs) restrict the antitumor efficiency of PDT. Herein, we report an energy-storing DNA-based hydrogel, which enables tumor-selective PDT without external radiation and regulates TMEs to achieve boosted PDT-mediated tumor immunotherapy. The system is constructed with two ultralong single-stranded DNA chains, which programmed partial complementary sequences and repeated G-quadruplex forming AS1411 aptamer for photosensitizer loading via hydrophobic interactions and π-π stacking. Then, energy-storing persistent luminescent nanoparticles are incorporated to sensitize PDT selectively at tumor site without external irradiation, generating tumor antigen to agitate antitumor immune response. The system catalytically generates O2 to alleviate hypoxia and releases inhibitors to reverse the IDO-related immunosuppression, synergistically remodeling the TMEs. In the mouse model of breast cancer, this hydrogel shows a remarkable tumor suppression rate of 78.3 %. Our study represents a new paradigm of photodynamic immunotherapy against cancer by combining laser-free fashion and TMEs remodeling.
Assuntos
DNA , Hidrogéis , Imunoterapia , Fotoquimioterapia , Fármacos Fotossensibilizantes , Microambiente Tumoral , Animais , Fotoquimioterapia/métodos , Microambiente Tumoral/efeitos dos fármacos , Hidrogéis/química , Imunoterapia/métodos , Feminino , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Camundongos Endogâmicos BALB C , Humanos , Linhagem Celular Tumoral , LasersRESUMO
Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients. Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.