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Recessive congenital methemoglobinemia (RCM) is a hereditary autosomal disorder with an extremely low incidence rate. Here, we report a case of methemoglobinemia type I in a patient with congenital persistent cyanosis. The condition was attributed to a novel compound heterozygous mutation in CYB5R3, characterized by elevated methemoglobin levels (13.4 % of total hemoglobin) and undetectable NADH cytochrome b5 reductase (CYB5R3) activity. Whole-exome sequencing (WES) revealed two heterozygous mutations in CYB5R3: a previously reported pathogenic missense mutation c.611G>A(p.Cys204Tyr) inherited from the father, and a novel stop codon mutation c.906A>G(p.*302Trpext*42) from the mother, the latter mutation assessed as likely pathogenic according to ACMG guidelines. In cells overexpressing the CYB5R3 c.906A>G mutant construct, the CYB5R3 mRNA level was significantly lower than in cells overexpressing the wild-type (WT) CYB5R3 construct. However, there was no significant difference in protein expression levels between the mutant and WT constructs. Notably, an additional protein band of approximately 55 kDa was detected in the mutant cells. Immunofluorescence localization showed that, compared to wild-type CYB5R3, the subcellular localization of the CYB5R3 p.*302Trpext*42 mutant protein did not show significant changes and remained distributed in the endoplasmic reticulum and mitochondria. However, the c.906A>G(p.*302Trpext*42) mutation resulted in increased intracellular reactive oxygen species (ROS) levels and decreased NAD+/NADH ratio, suggesting impaired CYB5R3 function and implicating this novel mutation as likely pathogenic.

Assuntos

Citocromo-B(5) Redutase , Metemoglobinemia , Mutação , Humanos , Masculino , Códon de Terminação/genética , Citocromo-B(5) Redutase/genética , Citocromo-B(5) Redutase/deficiência , Metemoglobinemia/genética , Metemoglobinemia/congênito , Adulto

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JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

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JOURNAL/nrgr/04.03/01300535-202505000-00027/figure1/v/2024-07-28T173839Z/r/image-tiff Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy. Physical exercise enhances neurogenesis and synaptogenesis, and has been widely used for functional rehabilitation after stroke. In this study, we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia. We also examined the role of exercise-induced circulating factors in these effects. Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion. We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area, inhibited gliogenesis, protected synaptic proteins, and improved novel object and spatial memory function. Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise. Agonist activation of adiponectin receptors by AdipoRon mimicked the effects of exercise, while inhibiting receptor activation abolished the exercise effects. In summary, our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

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Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.

Assuntos

Imagem Óptica , Glândulas Paratireoides , Espectroscopia de Luz Próxima ao Infravermelho , Tireoidectomia , Humanos , Glândulas Paratireoides/cirurgia , Glândulas Paratireoides/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Imagem Óptica/métodos , Adulto , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Inclusão em Parafina/métodos , Idoso , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Receptores de Detecção de Cálcio/análise

RESUMO

Background and Aims: The red blood cell distribution width (RDW) to albumin (ALB) ratio (RAR) has been identified as a prognostic indicator for mortality in critically ill patients across various diseases. Nevertheless, the impact of RAR on clinical functional prognosis in Acute ischemic stroke (AIS) remains uncertain. This study aimed to evaluate the prognostic significance of RAR in AIS patients. Methods: A secondary analysis was performed on a cohort study, involving 1906 AIS patients recruited from a South Korean academic hospital. Both univariate and multivariate logistic regression was employed to assess the connections between RAR and negative functional results in AIS. To explore potential non-linear relationships in this association, a generalized additive model (GAM) and smooth curve fitting were utilized. Further, a mediation analysis was performed to identify possible mediators. Results: Out of the 1906 eligible patients, 546 (28.65%) were found to have an unfavorable prognosis. Patients with elevated RAR had a higher likelihood of facing a negative prognosis in AIS (all P<0.001). RAR demonstrated a dose-response relationship with the probability of poor functional prognosis. When analysis of RAR as a continuous variable, an increase in RAR was correlated with a higher risk of adverse prognosis.When RAR was analyzed as quartile variables, the highest RAR remained an independent contributing factor for both 3-month unfavorable outcomes (adjusted OR, 1.4; 95% CI: 1.0-2.1, P=0.046) and 3-month mortality (adjusted OR, 5.2; 95% CI, 2.0-13.9; p<0.001). More interestingly, the presence of a pro-inflammatory state may serve as a mediator in the connections between RAR and adverse functional outcomes. Conclusion: Given its cost-effectiveness and ease of measurement, baseline RAR holds promise as a valuable biomarker for early risk assessment in AIS patients.

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Oxidative stress, or the chronic generation of reactive oxygen species (ROS), is thought to contribute to the progression of aging and aging related diseases. However, low degree of ROS generation has repeatedly been shown to be associated with beneficial outcomes via activation of protective signaling pathways. Berberine, a natural alkaloid isolated from Rhizomacoptidis, has a long history of medicinal use in both Ayurvedic and traditional Chinese medicine, which possesses anti-cancer, anti-inflammatory and anti-neurodegenerative properties. In this study, we utilize Caenorhabditis elegans to examine the mechanisms by which berberine influences healthspan and neurodegenerative diseases. We find that 10 µM berberine significantly extends healthy lifespan in wild type C. elegans. We further show that berberine generates ROS, which is followed by activation of PMK-1/SKN-1 to extend healthspan. Intriguingly, berberine also delays neurodegenerative diseases such as Alzheimer's and polyglutamine diseases in a PMK-1/SKN-1dependent manner. Our work suggests that berberine may be a viable candidate for the prevention and treatment of aging and aging related diseases.

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To address the limitations inherent in both sulfur autotrophic denitrification (SAD) and heterotrophic denitrification (HD) processes, this study introduces a novel approach. Three carbon sources (glucose, methanol, and sodium acetate) were fed into the SAD system to facilitate the transition towards mixotrophic denitrification. Batch experiments were conducted to explore the effects of influencing factors (pH, HRT) on the denitrification performance of the mixotrophic system. Carbon source dosages were varied at 12.5%, 25%, and 50% of the theoretical amounts required for HD (18, 36, and 72 mg/L, respectively). The results showed distinct optimal dosages for each of the three organic carbon sources. The mixotrophic system, initiated with sodium acetate at 25% of the theoretical value, demonstrated the highest denitrification performance, achieving NO3--N removal efficiency of 99.8% and the NRR of 6.25 mg/(L·h). In contrast, the corresponding systems utilizing glucose (at 25% of the theoretical value) and methanol (at 50% of the theoretical value) achieved lower removal efficiency of 77.0% and 88.4%, respectively. The corresponding NRRs were 4.85 mg/(L·h) and 5.65 mg/(L·h). Following the transition from SAD to a mixotrophic system, the abundance of Thiobacillus decreased from 78.5% to 34.4% at the genus level, and the mixotrophic system cultivated a variety of other denitrifying bacteria (Thauera, Aquimonas, Azoarcus, and Pseudomonas), indicating an enhanced microbial community structure diversity. The established artificial neural network (ANN) model accurately predicted the effluent quality of mixotrophic denitrification, which predicted values closely aligning with experimental results (R2 > 0.9). Furthermore, initial pH exerted greater relative importance for COD removal and sulfur conversion, while the relative importance of HRT was more pronounced for NO3--N removal.

RESUMO

This study explores the role of the transcription factor FOXM1 in the initiation and progression of oesophageal squamous cell carcinoma (ESCC). Our findings reveal that FOXM1 is highly expressed in ESCC and correlates with the prognosis of the disease. The relationship between FOXM1 and asparagine synthetase (ASNS) is investigated, and the study demonstrates that FOXM1 activates ASNS, impacting the tumour stemness of ESCC. In this study, we reveal the association between FOXM1 and ESCC development, as well as FOXM1's promotion of migration and proliferation in ESCC cells. The study also highlights FOXM1's regulation of ASNS transcription and the functional role of ASNS in ESCC metastasis and growth. Furthermore, the study explores the impact of FOXM1 and ASNS on ESCC stemness and their potential implications for chemotherapy resistance.

Assuntos

Aspartato-Amônia Ligase , Movimento Celular , Proliferação de Células , Progressão da Doença , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteína Forkhead Box M1 , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Aspartato-Amônia Ligase/genética , Aspartato-Amônia Ligase/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Prognóstico , Animais , Camundongos , Masculino , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Carbono-Nitrogênio Ligases com Glutamina como Doadora de N-Amida

RESUMO

BACKGROUND: From January 2020 to June 2022, strict interventions against COVID-19 were implemented in Guangdong Province, China. However, the evolution of COVID-19 dynamics remained unclear in this period. OBJECTIVES: This study aims to investigate the evolution of within- and between-city COVID-19 dynamics in Guangdong, specifically during the implementation of rigorous prevention and control measures. The intent is to glean valuable lessons that can be applied to refine and optimize targeted interventions for future crises. METHODS: Data of COVID-19 cases and synchronous interventions from January 2020 to June 2022 in Guangdong Province were collected. The epidemiological characteristics were described, and the effective reproduction number (Rt) was estimated using a sequential Bayesian method. Endemic-epidemic multivariate time-series model was employed to quantitatively analyze the spatiotemporal component values and variations, to identify the evolution of within- and between-city COVID-19 dynamics. RESULTS: The incidence of COVID-19 in Guangdong Province was 12.6/100,000 population (15,989 cases) from January 2020 to June 2022. The Rt predominantly remained below 1 and increased to a peak of 1.39 in Stage 5. As for the evolution of variations during the study period, there were more spatiotemporal components in stage 1 and 5. All components were fewer from Stage 2 to Stage 4. Results from the endemic-epidemic multivariate time-series model revealed a strong follow-up impact from previous infections in Dongguan, Guangzhou and Zhanjiang, with autoregressive components of 0.48, 0.45 and 0.36, respectively. Local risk was relatively high in Yunfu, Shanwei and Shenzhen, with endemic components of 1.17, 1.04 and 0.71, respectively. The impact of the epidemic on the neighboring regions was significant in Zhanjiang, Shenzhen and Zhuhai, with epidemic components of 2.14, 1.92, and 1.89, respectively. CONCLUSION: The findings indicate the presence of spatiotemporal variation of COVID-19 in Guangdong Province, even with the implementation of strict interventions. It's significant to prevent transmissions within cities with dense population. Preventing spatial transmissions between cities is necessary when the epidemic is severe. To better cope with future crises, interventions including vaccination, medical resource allocation and coordinated non-pharmaceutical interventions were suggested.

RESUMO

Objective: Circulating microRNAs show cross-sectional associations with overweight and obesity. Few studies provided data to differentiate between a snapshot perspective on these associations versus how microRNAs characterize prodromal risk from disease pathology and complications. This study assessed longitudinal relationships between circulating microRNAs and weight at multiple time-points in the Diabetes Prevention Program trial. Research design and methods: A subset of participants (n=150) from the Diabetes Prevention Program were included. MicroRNAs were measured from banked plasma using a Fireplex Assay. We used generalized linear mixed models to evaluate relationships between microRNAs and changes in weight at baseline, year-1, and year-2. Logistic regression was used to evaluate whether microRNAs at baseline were associated with weight change after 2 years. Results: In fully adjusted models that included relevant covariates, seven miRs (i.e., miR-126, miR-15a, miR-192, miR-23a, and miR-27a) were statistically associated with weight over 2 years. MiR-197 and miR-320a remained significant after adjustment for multiple comparisons. Baseline levels of let-7f, miR-17, and miR-320c were significantly associated with 3% weight loss after 2 years in fully adjusted models. Discussion: This study provided evidence for longitudinal relationships between circulating microRNAs and weight. Because microRNAs characterize the combined effects of genetic determinants and responses to behavioral determinants, they may provide insights about the etiology of overweight and obesity in the context or risk for common, complex diseases. Additional studies are needed to validate the potential genes and biological pathways that might be targeted by these microRNA biomarkers and have mechanistic implications for weight loss and disease prevention.

Assuntos

Diabetes Mellitus Tipo 2 , MicroRNAs , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Longitudinais , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/genética , MicroRNAs/sangue , MicroRNAs/genética , Adulto , Obesidade/genética , Biomarcadores/sangue , Peso Corporal , Sobrepeso/genética , MicroRNA Circulante/sangue , Estudos Transversais , Redução de Peso/genética

RESUMO

BACKGROUND: Vaccination services are increasingly in demand by the public, and mobile apps are an effective tool to meet that demand. However, the characteristics and quality of these apps are unknown. OBJECTIVE: Commonly used vaccination service apps on the market were surveyed with regard to quality, service content, and user experience to evaluate and guide users. METHODS: The Qimai Data mobile app data analytics platform was used to search for common vaccination service apps by keyword, and the WeChat and Alipay platforms were searched for apps. The apps included in the study were independently evaluated by two reviewers using the Mobile Application Rating Scale, and the service content and user experience of the apps were analyzed. The intragroup correlation coefficient between raters was used to measure interrater reliability. RESULTS: In the app stores of the four major Android platforms and the iOS app store, 1092 and 207 apps were found, respectively; 189 WeChat applets and 30 Alipay applets were also found. A total of 29 apps was ultimately included in this study according to the inclusion criteria, including 21 independent apps, 4 WeChat applets, and 4 Alipay applets. Significant differences were found between independent apps and applets in terms of the quality score (t449.57=-5.301; P<.001) and the subjective quality score (z=-4.753; P<.001). No significant differences were found between iOS and Android platforms in terms of the quality score (t1404=-2.55; P=.80) and the subjective quality score (z=-0.137; P=.89). There was good intragroup consistency among the raters. CONCLUSIONS: In this study, independent apps and nonindependent apps that rely on social and payment platforms for implementation were included in the vaccination services category. The overall quality of these apps was acceptable. Nonindependent running apps were found to have slightly lower scores and showed room for improvement, and scores for the participatory apps were found to be generally low overall.

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This study aims to understand the repercussions of the COVID-19 pandemic on hospitalized patients with peripheral arterial disease (PAD) in China, who did not contract SARS-CoV-2. We conducted a multicenter cross-sectional analysis comparing the characteristics and outcomes of hospitalized PAD patients across two distinct periods: Pre-pandemic (P1, from January 2018 to December 2019) and during the pandemic (P2, from January 2020 to December 2021). During P1, 762 hospitalized patients were treated, with an average age of 72.3 years, while 478 patients were treated in P2, with an average age of 65.1 years. Notably, hospitalized patients admitted during the pandemic (P2) exhibited a significantly higher incidence of chronic limb-threatening ischemia (CLTI, 70% vs 54%), diabetic foot infection (47% vs 29%), and infra-popliteal lesions (28% vs 22%). Furthermore, these patients demonstrated a marked deterioration in their Rutherford category and an increased mean score in the Wound, Ischemia, and foot Infection classification system (WIfI). Treatment during the pandemic emerged as a predictor of reduced procedural success and increased major adverse limb events. Factors such as the presence of diabetic foot infection, renal impairment, and deteriorating WIfI scores were identified as independent risk indicators for major adverse limb events. Our results demonstrate that intensive care was provided to severe cases of PAD even during the challenging circumstances of the COVID-19 pandemic. Despite the unprecedented pressures on healthcare systems, patients with severe PAD, particularly those with CLTI, continued to receive necessary in-patient care. The findings underscore the importance of timely medical interventions and extended follow-up for patients exhibiting high-risk factors.

Assuntos

COVID-19 , Doença Arterial Periférica , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Idoso , Doença Arterial Periférica/epidemiologia , Estudos Transversais , Feminino , Masculino , China/epidemiologia , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Pé Diabético/epidemiologia , Hospitalização , Pandemias , Fatores de Risco , Idoso de 80 Anos ou mais

RESUMO

Bacterial biofilm formation is closely associated with persistent infections of medical implants, which can lead to implantation failure. Additionally, the reconstruction of the vascular network is crucial for achieving efficient osseointegration. Herein, an anti-biofilm nanoplatform based on L-arginine (LA)/new indocyanine green (NICG) that is anchored to strontim titanium oxide (SrTiO3) nano-arrays on a titanium (Ti) substrate by introducing polydopamine (PDA) serving as the interlayer is designed and successfully fabricated. Near-infrared light (NIR) is used to excite NICG, generating reactive oxygen species (ROS) that react with LA to release nitric oxide (NO) molecules. Utilizing the concentration-dependent effect of NO, high power density NIR irradiation applied during the early stage after implantation to release a high concentration of NO, which synergized with the photothermal effect of PDA to eliminate bacterial biofilm. Subsequently, the irradiation power density can be finely down-regulated to reduce the NO concentration in subsequent treatment for accelerating the reconstruction of blood vessels. Meanwhile, SrTiO3 nano-arrays improve the hydrophilicity of the implant surface and slowly release strontium (Sr) ions for continuously optimizing the osteogenic microenvironment. Effective biofilm elimination and revascularization alongside the continuous optimization of the osteogenic microenvironment can significantly enhance the osseointegration of the functionalized Ti implant in in vivo animal experiments.

RESUMO

BACKGROUND: Radiomics has become an important tool for distinguishing benign and malignant vertebral compression fractures (VCFs). It is more clinically significant to concentrate on patients who have malignant tumors and differentiate between benign and malignant VCFs. PURPOSE: To explore the value of multiple machine learning (ML) models based on CT radiomics features for differentiating benign and malignant VCFs in patients with malignant tumors. MATERIAL AND METHODS: This study retrospectively analyzed 78 patients with malignant tumors accompanied by VCFs, 45 patients with benign VCFs, and 33 patients with malignant VCFs. A total of 140 lesions (86 benign lesions, 54 malignant lesions) were ultimately included in this study. All patients were divided into training sets (n = 98) and validation sets (n = 42) according to the 7:3 ratio. The radiomics features were screened and dimensioned, and multiple radiomics ML models were constructed. The receiver operating characteristic (ROC) curve was performed to assess the diagnostic performance. RESULTS: Five radiomics features were included in the model. All the ML models built have good diagnostic efficiency, among which the support vector machine (SVM) model performs better. The area under the curve (AUC), sensitivity, specificity, and accuracy in the training set were 0.908, 0.816, 0.883, and 0.857, respectively, while those in the validation set were 0.911, 0.647, 0.92, and 0.81, respectively. CONCLUSION: A variety of ML models built based on CT radiomics features have good value for differentiating benign and malignant VCFs in malignant tumor patients, and the SVM model has a better performance.

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BACKGROUND: Cervical spondylotic myelopathy (CSM) is the most common chronic spinal cord injury with poor surgical and neurologic recovery in the advanced stages of the disease. DTI parameters can serve as important biomarkers for CSM prognosis. The study aimed to investigate the predictive value of dynamic diffusion tensor imaging (DTI) for the postoperative outcomes of CSM. METHODS: One hundred and five patients with CSM who underwent surgery were included in this study. Patients were assessed using the Modified Japanese Orthopedic Association Score (mJOA) before and one year after surgery and then divided into groups with good (≥ 50%) and poor (< 50%) prognoses according to the rate of recovery. All patients underwent preoperative dynamic magnetic resonance imaging of the cervical spine, including T2WI and DTI in natural(N), extension (E), and flexion (F) positions. ROM, Cross-sectional area, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were measured at the narrowest level in three neck positions. Univariate and multivariate logistic regression were used to identify risk factors for poor postoperative recovery based on clinical characteristics, dynamic T2WI, and DTI parameters. Predictive models were developed for three different neck positions. RESULTS: Forty-four (41.9%) patients had a good postoperative prognosis, and 61 (58.1%) had a poor prognosis. Univariate analysis showed statistically significant differences in diabetes, number of compression segments, preoperative mJOA score, cross-sectional area ((Area-N), (Area-E), (Area-F)), ADC((ADC-N), (ADC-E), (ADC-F)) and FA (((FA-N), (FA-E), (FA-F)) (p < 0.05). Multivariable logistic regression showed that natural neck position: Area-N ([OR] 0.226; [CI] 0.069-0.732, p = 0.013),FA-N([OR]3.028;[CI]1.12-8.19,p = 0.029); extension ne-ck position: Area-E([OR]0.248;[CI]0.076-0.814,p = 0.021), FA-E([OR]4.793;[CI]1.737-13.228,p = 0.002);And flextion neck postion: Area-F([OR] 0.288; [CI] 0.095-0.87, p = 0.027),FA-F ([OR] 2.964; [CI] 1.126-7.801, p = 0.028) were independent risk factors for poor prognosis.The area under the curve (AUC) of the prediction models in the natural neck position, extension neck position, and flexion neck positions models were 0.708[(95% CI:0.608∼0.808), P < 0.001]; 0.738 [(95% CI:0.641∼0.835), P < 0.001]; 0.703 [(95% CI:0.602∼0.803), P < 0.001], respectively. CONCLUSION: Dynamic DTI can predict postoperative outcomes in CSM. Reduced FA in the extension position is a valid predictor of poor postoperative neurological recovery in patients with CSM.

Assuntos

Vértebras Cervicais , Imagem de Tensor de Difusão , Espondilose , Humanos , Imagem de Tensor de Difusão/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Espondilose/diagnóstico por imagem , Espondilose/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Idoso , Prognóstico , Valor Preditivo dos Testes , Resultado do Tratamento , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/cirurgia , Adulto

RESUMO

Ethnopharmacological relevance: Danggui Buxue decoction (DBD) is a traditional Chinese herbal formula. According to the theory of traditional Chinese medicine, the combination of Astragali Radix (AR) and Angelica sinensis (AS) is a classic prescription of tonifying qi and enriching blood. DBD has the functions of hematopoietic, immune enhancement and inflammation inhibition, usually used to treat qi and blood deficiency symptoms. Aim of the study: Cyclophosphamide (CY) can inhibit humoral and cellular immunity, leading to the overall immune disorder of the body, resulting in immunosuppressive (IS). Pre-laboratory studies confirmed the immunomodulatory effects of DBD, but its mechanisms have not been thoroughly studied. In this study, the main purpose was to determine the effects of DBD on the immune function and intestinal mucosal barrier function of IS mice induced by CY, and initially explored the immunomodulatory mechanism of DBD. Materials and methods: 100 g of AR and 20 g of AS were accurately weighed and 0.5 g/mL of the DBD was obtained by boiling, filtration and rotary evaporation. Then, mice in the DBD group were administered 5 g/kg of DBD by gavage, positive group were administered 40 mg/kg of levamisole hydrochloride, whereas those in the control and model groups were given the corresponding volume of normal saline by gavage for 1 week. At the end of the experiment, blood, spleen, thymus, ileum and cecum contents of all the experimental mice were collected aseptically. IS mouse model induced by intraperitoneal injection of 80 mg/kg CY for three consecutive days. Pathomorphology was used to observe the physical barrier of the intestine, flow cytometry to detect splenic lymphocytes, immunohistochemistry to determine the content of intestinal barrier-associated proteins, ELISA to measure the secretion of ileal SIgA, qRT-PCR to detect the mRNA expression of immune-related genes in the intestine, and high-throughput sequencing and analysis of cecum contents. Results: DBD alleviated spleen tissue damage and restored impaired immune functions, such as increased thymus index and CD4+/CD8+ subsets of spleen lymphocytes. In addition, DBD could increase ileum villi length and the ratio of villi length to crypt depth (V/C), and decrease crypt depth. Moreover, DBD administration up-regulated the expression of ZO-1, Occludin, Claudin-1, MUC-2 mRNA in ileum. And the secretions of sIgA and ZO-1 in ileum were also significantly improved. Furthermore, the administration of DBD can increase the diversity of gut microbiota, improve the composition of intestinal flora and increase the relative abundance of beneficial genus, such as Bacteroides. Conclusion: DBD alleviated CY-induced immune damage by decreasing the ratio of spleen index to CD4+/CD8+ of T lymphocyte subsets. And the intestinal barrier function of mice was by improves improving the intestinal morphology of the ileum and up-regulating the expression levels of ZO-1, MUC-2 and SIgA. DBD regulates CY-induced gut microbiota dysregulation in mice by increasing species diversity and richness, regulating the phylum, class and order levels of Bacteroidetes.

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Interleukin-12 (IL-12) is a critical cytokine with notable anticancer properties, including enhancing T-cell-mediated cancer cell killing, and curbing tumor angiogenesis. To date, many approaches are evaluated to achieve in situ overexpression of IL-12, minimizing leakage and the ensuing toxicity. Here, it is focused on circular single-stranded DNA (Css DNA), a type of DNA characterized by its unique structure, which could be expressed in mammals. It is discovered that Css DNA can induce sustained luciferase expression for half a year by intramuscular injection and showed effective antitumor results by intratumoral injection. Motivated by these findings, a folate-modified LNP system is now developed for the delivery of Css DNA expressing IL-12 for the therapy of 4T1 triple-negative breast cancer (TNBC). This delivery system effectively activates anti-cancer immune responses, slows tumor growth, significantly prolongs survival in animal models, and prevents tumor recurrence. After 6 months of long-term observation, the elevated level of IL-12 is still detectable in the lymph nodes and serum of the cured mice. This study highlights the long-term sustained expression capacity of Css DNA and its ability to inhibit recurrence, and the potential of tumor-targeted LNPs for Css DNA-based cancer therapy, providing a new insight into gene overexpression strategy.

RESUMO

PURPOSE: To investigate the clinical application of zonally magnified oblique multislice (ZOOM) imaging technology in patients with degenerative cervical myelopathy (DCM) and compare it with T2WI imaging. METHODS: A total of 111 patients diagnosed with DCM were recruited. According to mJOA, patients with DCM were divided into ND + group with neurological dysfunction and ND- group without neurological dysfunction. Routine MRI and ZOOM-DWI were performed on 3.0 T MRI to obtain sagittal T2WI and apparent diffusion coefficient (ADC) diagram. ADC values of the narrow segment and its adjacent upper and lower segments were measured, and compared between the ND + and ND- groups. The correlation between ADC value of cervical spinal cord and mJOA score was analyzed. Additionally, ROC curves were plotted to calculate the AUC values. RESULTS: The comparison between ND + and ND- groups shows that there are significant differences in mJOA score, T2WI, anteroposterior diameter of spinal canal, ADC values of narrow, upper and lower segment (P < 0.05). In ND + group, there is a significant difference between ADC values of the narrow and its upper and lower segments (P < 0.001), while with no significant difference in ADC values of the upper and lower segments (P > 0.05). Results of correlation analysis indicate that in the ND + group, neurological dysfunction evaluated by mJOA scores is correlated with increased ADC values of the narrow segment (r = -0.52, P < 0.001), but not significantly correlated with ADC values of the upper and lower segments. Furthermore, T2WI, anteroposterior diameter of the spinal canal, and cervical cord ADC values all has diagnostic efficacy in evaluating neurological dysfunction in DCM (AUC > 0.5, P < 0.05), with the ADC value of the narrow segment being optimal. CONCLUSION: The ADC value of spinal cord obtained by small-field ZOOM-DWI can be used to evaluate neurological dysfunction in DCM, and is superior to traditional T2WI.