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1.
Artículo en Inglés | MEDLINE | ID: mdl-38994612

RESUMEN

INTRODUCTION: Chronic diabetic wounds pose a significant threat to the health of diabetic patients, representing severe and enduring complications. Globally, an estimated 2.5% to 15% of the annual health budget is associated with diabetes, with diabetic wounds accounting for a substantial share. Exploring new therapeutic agents and approaches to address delayed and impaired wound healing in diabetes becomes imperative. Traditional Chinese medicine (TCM) has a long history and remarkable efficacy in treating chronic wound healing. In this study, all topically applied proprietary Chinese medicines (pCMs) for wound healing officially approved by the National Medical Products Administration (NMPA) were collected from the NMPA TCM database. Data mining was employed to obtain a high-frequency TCM ingredients pair, Pearl-Borneol (1:1). METHOD: This study investigated the effect and molecular mechanism of the Pearl-Borneol pair on the healing of diabetic wounds by animal experiments and metabolomics. The results from animal experiments showed that the Pearl-Borneol pair significantly accelerated diabetic wound healing, exhibiting a more potent effect than the Pearl or Borneol treatment alone. Meanwhile, the metabolomics analysis identified significant differences in metabolic profiles in wounds between the model and normal groups, indicating that diabetic wounds had distinct metabolic characteristics from normal wounds. Moreover, Vaseline-treated wounds exhibited similar metabolic profiles to the wounds from the model group, suggesting that Vaseline might have a negligible impact on diabetic wound metabolism. In addition, wounds treated with Pearl, Borneol, and Pearl-Borneol pair displayed significantly different metabolic profiles from Vaseline-treated wounds, signifying the influence of these treatments on wound metabolism. Subsequent enrichment analysis of the metabolic pathway highlighted the involvement of the arginine metabolic pathway, closely associated with diabetic wounds, in the healing process under Pearl- Borneol pair treatment. Further analysis revealed elevated levels of arginine and citrulline, coupled with reduced nitric oxide (NO) in both the model and Vaseline-treated wounds compared to normal wounds, pointing to impaired arginine utilization in diabetic wounds. Interestingly, treatment with Pearl and Pearl-Borneol pair lowered arginine and citrulline levels while increasing NO content, suggesting that these treatments may promote the catabolism of arginine to generate NO, thereby facilitating faster wound closure. Additionally, borneol alone significantly elevated NO content in wounds, potentially due to its ability to directly reduce nitrates/nitrites to NO. Oxidative stress is a defining characteristic of impaired metabolism in diabetic wounds. RESULTS: The result showed that both Pearl and Pearl-Borneol pair decreased the oxidative stress biomarker methionine sulfoxide level in diabetic wounds compared to those treated with Vaseline, indicating that Pearl alone or combined with Borneol may enhance the oxidative stress microenvironment in diabetic wounds. CONCLUSION: In summary, the findings validate the effectiveness of the Pearl-Borneol pair in accelerating the healing of diabetic wounds, with effects on reducing oxidative stress, enhancing arginine metabolism, and increasing NO generation, providing a mechanistic basis for this therapeutic approach.

2.
Int J Mol Sci ; 25(13)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-39000115

RESUMEN

Selenium (Se) is an essential trace element for humans. Low concentrations of Se can promote plant growth and development. Enhancing grain yield and crop Se content is significant, as major food crops generally have low Se content. Studies have shown that Se biofortification can significantly increase Se content in plant tissues. In this study, the genetic transformation of wheat was conducted to evaluate the agronomic traits of non-transgenic control and transgenic wheat before and after Se application. Se content, speciation, and transfer coefficients in wheat grains were detected. Molecular docking simulations and transcriptome data were utilized to explore the effects of selenium-binding protein-A TaSBP-A on wheat growth and grain Se accumulation and transport. The results showed that TaSBP-A gene overexpression significantly increased plant height (by 18.50%), number of spikelets (by 11.74%), and number of grains in a spike (by 35.66%) in wheat. Under normal growth conditions, Se content in transgenic wheat grains did not change significantly, but after applying sodium selenite, Se content in transgenic wheat grains significantly increased. Analysis of Se speciation revealed that organic forms of selenomethionine (SeMet) and selenocysteine (SeCys) predominated in both W48 and transgenic wheat grains. Moreover, TaSBP-A significantly increased the transfer coefficients of Se from solution to roots and from flag leaves to grains. Additionally, it was found that with the increase in TaSBP-A gene overexpression levels in transgenic wheat, the transfer coefficient of Se from flag leaves to grains also increased.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Plantas Modificadas Genéticamente , Proteínas de Unión al Selenio , Selenio , Selenito de Sodio , Triticum , Triticum/genética , Triticum/metabolismo , Triticum/crecimiento & desarrollo , Proteínas de Unión al Selenio/metabolismo , Proteínas de Unión al Selenio/genética , Selenio/metabolismo , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Selenito de Sodio/metabolismo , Grano Comestible/metabolismo , Grano Comestible/genética , Grano Comestible/crecimiento & desarrollo , Simulación del Acoplamiento Molecular , Semillas/crecimiento & desarrollo , Semillas/metabolismo , Semillas/genética , Semillas/efectos de los fármacos
3.
Int J Biol Macromol ; 275(Pt 2): 133686, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38972653

RESUMEN

Eucommia ulmoides Oliv. (tu-chung), as a famous nature medical and edible plant, has the effect of tonifying liver and kidney, strengthening the function of the muscles and bones, and miscarriage prevention. Accumulating evidence has demonstrated that the polysaccharides from Eucommia ulmoides Oliv. (EUPs) are a kind of vital and representative biologically active macromolecules and have various health-promoting biological activities in vivo and in vitro, such as antioxidant activity, immunomodulatory activity, hypolipidemic and hypoglycemic activities, anti-inflammatory activities, anti-tumor activity, and among others. The review aims to comprehensively and systematically collate the recent research progress on extraction and purification methods, structural characteristics, biological activities, mechanism of action, structural modification, and toxicity of EUPs to support their therapeutic potential and health-care functions. New valuable insights for future research with EUPs were also proposed in the areas of structural characterization and pharmacological activities to promoting the development of therapeutic agents and functional foods.

5.
Diabetes Metab ; 50(5): 101560, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38950855

RESUMEN

AIM: To explore the relationships of multiple reproductive factors with type 2 diabetes mellitus (T2DM) risk and the joint effects of reproductive factors and genetic susceptibility. METHODS: We included 262,368 women without prevalent T2DM from the UK biobank. Cox proportional hazards regression models were employed to estimate the relationships of reproductive factors with T2DM risk and the joint effects of reproductive factors and genetic susceptibility. RESULTS: During a mean follow-up of 12.2 years, 8,996 T2DM cases were identified. Early menarche (<12 years, hazard ratio (HR) 1.08 [95 % confidence interval (CI) 1.02;1.13]), late menarche (≥15 years, HR 1.11 [1.04;1.17]), early menopause (<45 years, HR 1.20 [1.12;1.29]), short reproductive lifespan (<30 years, HR 1.25 [1.16;1.35]), hysterectomy (1.31, HR [1.23;1.40]), oophorectomy (HR 1.28 [1.20;1.36]), high parity (≥4, HR 1.25 [1.17;1.34]), early age at first live birth (<20 years, HR 1.23 [1.16;1.31]), miscarriage (HR 1.13 [1.07;1.19]), stillbirth (HR 1.14 [1.03;1.27]), and ever used hormonal replacement therapy (HR 1.19 [1.14;1.24]) were related to a higher T2DM risk, while ever used oral contraceptives (HR 0.93 [0.89;0.98]) was related to a lower T2DM risk. Furthermore, women with reproductive risk factors and high genetic risk had the highest T2DM risk compared to those with low genetic risk and without reproductive risk factors. CONCLUSION: Our findings show that multiple reproductive factors are related to T2DM risk, particularly in women with high genetic risk.

6.
Front Psychol ; 15: 1281207, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38899122

RESUMEN

Anthropomorphism, the attribution of human-like qualities (e.g., mental states) to nonhuman entities, is a universal but variable psychological experience. Adults with professionally diagnosed autism or high levels of subclinical autistic traits consistently show greater tendencies to anthropomorphize, which has been hypothesized to reflect 1) a compensatory mechanism for lack of social connectedness and 2) a persistence of childhood anthropomorphism into adulthood. Here, we directly tested these hypotheses in a general population sample consisting of both adults (N=685, 17-58 years old) and early adolescents (N=145, 12-14 years old) using the refined 9-item Anthropomorphism Questionnaire (AnthQ9), which measures both present and childhood anthropomorphic tendencies. We found that adults with heightened autistic traits reported increased present anthropomorphism (e.g., tend more to perceive computers as having minds), which held even after controlling for social connectedness. In contrast, adolescents with heightened autistic traits did not show increased present anthropomorphism, but rather reported reduced childhood anthropomorphism (e.g., less likely to perceive toys as having feelings) after controlling for social connectedness. We also found evidence that the present and childhood subscales of the AnthQ9 may tap into fundamentally different aspects of anthropomorphism. The results suggest that increased anthropomorphic tendencies in adults with heightened autistic traits cannot be explained solely by increased sociality motivation, but may be due to delayed development of anthropomorphism, although alternative possibilities of measurement problems cannot be ruled out. Implications for the measurement of anthropomorphism and its relation with theory of mind were also discussed.

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124672, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38905899

RESUMEN

Nitroxyl (HNO), a reactive nitrogen species (RNS), is essential for plant growth. However, the action of HNO in plants has been difficult to understand due to the lack of highly sensitive and real-time in-situ monitoring tools. Herein, we presented a near-infrared fluorescent probe, DCI-HNO, based on dicyanoisophorone fluorophore, for real-time mapping HNO in plants. The introduction of a phosphine moiety as a specific HNO recognition unit can inhibit the intramolecular charge transfer (ICT) of probe DCI-HNO. However, in the presence of HNO, the ICT process occurred, leading to the emission at 665 nm. Probe DCI-HNO exhibited high sensitivity (97 nM), rapid response time (8 min), large Stokes shift (135 nm) for detection of HNO in plants. The novel developed probe has successfully imaged endogenous HNO produced during NO/H2S cross-talk in plant tissues. Additionally, the up-regulated in HNO levels during tobacco aging and in response to stress has been confirmed. Therefore, probe DCI-HNO has provided a reliable method for monitoring the NO/H2S cross-talk and revealing the role of HNO in plants.

8.
Bone Joint J ; 106-B(7): 720-727, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38945537

RESUMEN

Aims: This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients. Methods: A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts. Results: Of these patients, 264 (25.2%) had negative cultures. Patients with a culture-negative compared with a culture-positive status were more likely to have the following characteristics: younger age (≤ 40 years) (113/264 (42.8%) vs 257/783 (32.8%); p = 0.004), a haematogenous aetiology (75/264 (28.4%) vs 150/783 (19.2%); p = 0.002), Cierny-Mader host A (79/264 (29.9%) vs 142/783 (18.1%); p < 0.001), antibiotic use before sampling (34/264 (12.9%) vs 41/783 (5.2%); p<0.001), fewer taken samples (n<3) (48/264 (18.2%) vs 60/783 (7.7%); p<0.001), and less frequent presentation with a sinus (156/264 (59.1%) vs 665/783 (84.9%); p < 0.001). After initial treatments of first-debridement and antimicrobial, infection eradication was inferior in culture-positive osteomyelitis patients, with a 2.24-fold increase (odds ratio 2.24 (95% confidence interval 1.42 to 3.52)) in the redebridement rate following multivariate analysis. No statistically significant differences were found in long-term recurrence and complications within the two-year follow-up. Conclusion: We identified several factors being associated with the culture-negative result in osteomyelitis patients. In addition, the data also indicate that culture negativity is a positive prognostic factor in early infection eradication. These results constitute the basis of optimizing clinical management and patient consultations.


Asunto(s)
Desbridamiento , Osteomielitis , Humanos , Osteomielitis/microbiología , Osteomielitis/terapia , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Antibacterianos/uso terapéutico , Resultado del Tratamiento , Adulto Joven , Adolescente
9.
BMC Public Health ; 24(1): 1550, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38853276

RESUMEN

BACKGROUND: Obesity is characterized by excessive fat accumulation in the body. Physical activity (PA) is an effective intervention to combat obesity, but the effectiveness of different PA patterns on controlling obesity is unclear. Lipid accumulation product (LAP), derived from waist circumference and triglycerides, is a novel indicator for obesity evaluation. However, the association between PA patterns (i.e., weekend warriors and regularly active) and LAP remains unexplored. This study aims to elucidate the relationship between PA patterns and LAP in US adult population. METHODS: Adult individuals with complete data on LAP, PA patterns, and other covariates from the National Health and Nutrition Examination Survey (NHANES) database (2007-2018) were included in this study. Multivariate linear regression models were utilized to explore the association between PA patterns and LAP. Subgroup analyses, interaction tests, restricted cubic spline (RCS) regression analyses, and threshold and saturation effect analyses were also performed to investigate the stability and nonlinearity of PA-LAP association, respectively. RESULTS: A total of 11,212 participants were included in this study. After adjusting for all potential covariates, being regularly active (RA) (ß=-8.85, P < 0.05) obtained significantly higher LAP reduction as opposed to being weekend warriors (WWs) (ß=-4.70, P = 0.3841). Furthermore, subgroup analyses and interaction tests indicated that the PA-LAP association was more pronounced in individuals with higher education levels (P interaction = 0.0084) and diabetes (P interaction = 0.0062). Additionally, a significant, non-linear, and negative correlation between weekly total PA and LAP in non-inactive individuals was identified by RCS analysis (P for overall < 0.001, P for nonlinearity = 0.009). A threshold of 440 min in weekly total PA was found to arouse favorable LAP reduction. CONCLUSIONS: Being regularly active obtained better LAP reduction as opposed to being WWs. For non-inactive adults, engaging in more than 440 min of PA per week helps to reduce LAP effectively.


Asunto(s)
Ejercicio Físico , Actividades Recreativas , Encuestas Nutricionales , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Ejercicio Físico/fisiología , Estados Unidos , Producto de la Acumulación de Lípidos , Obesidad/prevención & control , Adulto Joven , Circunferencia de la Cintura
10.
J Asthma Allergy ; 17: 517-537, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855058

RESUMEN

Purpose: Cough variant asthma (CVA) is a chronic inflammatory disease characterized by recurrent coughing, a prevalent cause of chronic cough in children and adults. As a unique form of asthma, researchers have recently become increasingly interested in developing effective diagnostic and treatment methods. Currently, there has been no bibliometric analysis in CVA. Therefore, this study aims to enrich this knowledge network by examining the current development status, research focal points, and emerging trends in this field. Methods: Articles and reviews on CVA published between 1993 and 2022 were collected from the Web of Science Core Collection (WoSCC) database. Relevant data from the reports were extracted, and collaborative network analysis was performed using CiteSpace and VOSviewer software. Results: 772 articles were included in this study, indicating a significant increase since 2019. The countries with the highest output are China, Japan. The Journal of Asthma and Pulmonary Pharmacology Therapeutics emerged as the most prolific journals in this field. Keyword analysis revealed 22 clusters, highlighting airway inflammation, airway hyperresponsiveness, and eosinophil as the main focus and frontier of research on CVA. Conclusion: From the visual analysis results, the research of CVA is still in the development stage, and there is no unified definition of pathogenesis, diagnostic criteria and treatment strategies. Therefore, researchers and teams should actively carry out cross-institutional and cross-regional cooperation, expand cooperation areas, and carry out high-quality clinical research in the future.

11.
Sci Rep ; 14(1): 13954, 2024 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886537

RESUMEN

China, is characterized by its remarkable ethnical diversity, which necessitates whole genome variation data from multiple populations as crucial tools for advancing population genetics and precision medical research. However, there has been a scarcity of research concentrating on the whole genome of ethnic minority groups. To fill this gap, we developed the Guizhou Multi-ethnic Genome Database (GMGD). It comprises whole genome sequencing data from 476 healthy unrelated individuals spanning 11 ethnic minorities groups in Guizhou Province, Southwest China, including Bouyei, Dong, Miao, Yi, Bai, Gelo, Zhuang, Tujia, Yao, Hui, and Sui. The GMGD database comprises more than 16.33 million variants in GRCh38 and 16.20 million variants in GRCh37. Among these, approximately 11.9% (1,956,322) of the variants in GRCh38 and 18.5% (3,009,431) of the variants in GRCh37 are entirely new and do not exist in the dbSNP database. These novel variants shed light on the genetic diversity landscape across these populations, providing valuable insights with an average coverage of 5.5 ×. This makes GMGD the largest genome-wide database encompassing the most diverse ethnic groups to date. The GMGD interactive interface facilitates researchers with multi-dimensional mutation search methods and displays population frequency differences among global populations. Furthermore, GMGD is equipped with a genotype-imputation function, enabling enhanced capabilities for low-depth genomic research or targeted region capture studies. GMGD offers unique insights into the genomic variation landscape of different ethnic groups, which are freely accessible at https://db.cngb.org/pop/gmgd/ .


Asunto(s)
Bases de Datos Genéticas , Etnicidad , Genoma Humano , Humanos , Etnicidad/genética , China/etnología , Genética de Población/métodos , Secuenciación Completa del Genoma/métodos , Variación Genética , Grupos Minoritarios , Polimorfismo de Nucleótido Simple
12.
World J Nucl Med ; 23(2): 73-78, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38933075

RESUMEN

Objective Our objective was to investigate the basic information of the personnel and facilities of nuclear medicine in Beijing. Methods This survey was performed by the Beijing Quality Control Center in 2018. The investigation included personnel, equipment, and clinical applications, and data were then compared with previous surveys. The paper questionnaires were used for the survey, which required information about the personnel, devices, and clinical applications. Results About 38 nuclear medicine departments in Beijing were involved in the survey. The number of nuclear medicine staff was 531 in 2018, showing an increase of 58.7% over the past decade. Positron emission tomography/computed tomography (PET/CT), single-photon emission computed tomography (SPECT), and single-photon emission computed tomography/computed tomography (SPECT/CT) represented the main nuclear medicine facilities, and the total number of surveyed departments was 18, 24, and 34, respectively. The quality control results showed significant improvement from the 2005 levels. The total number of scintigraphy procedures was estimated at 199,607 (153,185 SPECT and 46,422 PET/CT). The estimated annual number of scintigraphy images was 8.9 per 1,000 population for SPECT and 2.7 per 1,000 population for PET/CT during 2018. The most frequent radioiodine-targeted therapy was 131 I-targeted therapy for hyperthyroidism in 2018. Conclusion Nuclear medicine has experienced rapid growth in the past 10 years in Beijing, either in personnel, equipment, and scintigraphy. Future efforts will focus on the use of new isotopes in the diagnosis, implementing quality strategy, and enhancing training.

13.
Sci Total Environ ; 944: 173954, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-38876334

RESUMEN

BACKGROUND: Previous studies have linked single metal to hemoglobin levels in children and adolescents; however, studies with regards to metal mixtures are still limited. OBJECTIVE: We aimed to investigate the associations of single metal and metal mixtures with hemoglobin levels in children and adolescents. METHODS: We conducted a cross-sectional study of 2064 children and adolescents aged 6 to 19 years in Liuzhou, China in 2018. The concentrations of 15 metals in urine were determined by inductively coupled plasma mass spectrometry. Generalized linear regression and weighted quantile sum (WQS) regression were used to estimate the associations of single metal and metal mixtures with hemoglobin levels, respectively. RESULTS: The multivariable-adjusted ß-values for the highest versus the first quartiles of urinary metal concentrations were - 1.57 (95 % confidence interval [CI]: -3.01, -0.13) for chromium, -2.47 (95 % CI: -3.90, -1.05) for nickel and 1.88 (95 % CI: 0.49, 3.28) for copper. In addition, we found a significant negative association between the WQS index and hemoglobin levels (adjusted ß = -0.93, 95 % CI: -1.69, -0.19), with nickel contributing the most to the WQS index at 59.0 %. Subgroup analyses showed that exposure to urinary nickel or metal mixtures were associated with decreased hemoglobin levels in adolescents, but not in children (all Pinteration < 0.001). CONCLUSION: Among children and adolescents, urinary chromium and nickel concentrations were associated with decreased hemoglobin levels, while copper showed a positive relationship. Moreover, a negative association was observed between exposure to metal mixtures and hemoglobin levels. These findings need to be further validated in prospective studies.


Asunto(s)
Exposición a Riesgos Ambientales , Contaminantes Ambientales , Hemoglobinas , Humanos , Adolescente , Niño , China , Hemoglobinas/análisis , Masculino , Estudios Transversales , Femenino , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales/sangre , Contaminantes Ambientales/orina , Metales/orina , Metales/sangre , Adulto Joven , Pueblos del Este de Asia
15.
Sci Rep ; 14(1): 12587, 2024 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-38821992

RESUMEN

This study was desinged to evaluate the efficacy and safety of activated allograft combined with the induced membrane technique for reconstruction of infected segment bone defects of lower limbs. A retrospective analysis was conducted on 19 patients from May 2015 to February 2017. After debridements, the bone defects were filled with antibiotic bone cement to form the induced membrane. Autologous mesenchymal stem cells were seeded onto allografts to construct activated allograft, which was implanted into the induced membrane after infection was controlled. The clinical efficacy and complications were observed. 19 patients with 20 infected segment bone defect were evaluated. The average deficit size was 11.08 (4-17) cm in length. After a mean follow-up of 71.84 (61-82) months, bone union was achieved in 16 patients (17 sites), resulting in a final union rate of 84.21% (16/19 patients). The average bone union time was 10.18 (5-28) months. There were 2 patients with recurrence of infection, 3 patients with graft absorption, and 1 patient with malunion due to implant breakage. There were no graft-related complications. This study provides clinical significance for the treatment of patients with insufficient autologous bone.


Asunto(s)
Aloinjertos , Trasplante Óseo , Procedimientos de Cirugía Plástica , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Trasplante Óseo/métodos , Procedimientos de Cirugía Plástica/métodos , Cementos para Huesos , Resultado del Tratamiento , Anciano , Adulto Joven , Trasplante de Células Madre Mesenquimatosas/métodos , Osteomielitis/cirugía , Osteomielitis/terapia , Desbridamiento/métodos , Trasplante Homólogo/métodos
16.
Bone Joint J ; 106-B(6): 613-622, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38821512

RESUMEN

Aims: The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes. Methods: Between May 2012 and December 2020, 203 patients with infected segmental bone defects treated with the IMT were enrolled. The digital medical records of these patients were retrospectively analyzed. Factors associated with unfavourable outcomes were identified through logistic regression analysis. Results: Among the 203 enrolled patients, infection recurred in 27 patients (13.3%) after bone grafting. The union rate was 75.9% (154 patients) after second-stage surgery without additional procedures, and final union was achieved in 173 patients (85.2%) after second-stage surgery with or without additional procedures. The mean healing time was 9.3 months (3 to 37). Multivariate logistic regression analysis of 203 patients showed that the number (≥ two) of debridements (first stage) was an independent risk factor for infection recurrence and nonunion. Larger defect sizes were associated with higher odds of nonunion. After excluding 27 patients with infection recurrence, multivariate analysis of the remaining 176 patients suggested that intramedullary nail plus plate internal fixation, smoking, and an allograft-to-autograft ratio exceeding 1:3 adversely affected healing time. Conclusion: The IMT is an effective method to achieve infection eradication and union in the management of infected segmental bone defects. Our study identified several risk factors associated with unfavourable outcomes. Some of these factors are modifiable, and the risk of adverse outcomes can be reduced by adopting targeted interventions or strategies. Surgeons can fully inform patients with non-modifiable risk factors preoperatively, and may even use other methods for bone defect reconstruction.


Asunto(s)
Trasplante Óseo , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Óseo/métodos , Adulto , Anciano , Desbridamiento/métodos , Adolescente , Factores de Riesgo , Recurrencia , Adulto Joven , Osteomielitis/cirugía , Curación de Fractura
17.
J Exp Clin Cancer Res ; 43(1): 141, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745192

RESUMEN

BACKGROUND: Neuroblastoma (NB) patients with amplified MYCN often face a grim prognosis and are resistant to existing therapies, yet MYCN protein is considered undruggable. KAP1 (also named TRIM28) plays a crucial role in multiple biological activities. This study aimed to investigate the relationship between KAP1 and MYCN in NB. METHODS: Transcriptome analyses and luciferase reporter assay identified that KAP1 was a downstream target of MYCN. The effects of KAP1 on cancer cell proliferation and colony formation were explored using the loss-of-function assays in vitro and in vivo. RNA stability detection was used to examine the influence of KAP1 on MYCN expression. The mechanisms of KAP1 to maintain MYCN mRNA stabilization were mainly investigated by mass spectrum, immunoprecipitation, RIP-qPCR, and western blotting. In addition, a xenograft mouse model was used to reveal the antitumor effect of STM2457 on NB. RESULTS: Here we identified KAP1 as a critical regulator of MYCN mRNA stability by protecting the RNA N6-methyladenosine (m6A) reader YTHDC1 protein degradation. KAP1 was highly expressed in clinical MYCN-amplified NB and was upregulated by MYCN. Reciprocally, KAP1 knockdown reduced MYCN mRNA stability and inhibited MYCN-amplified NB progression. Mechanistically, KAP1 regulated the stability of MYCN mRNA in an m6A-dependent manner. KAP1 formed a complex with YTHDC1 and RNA m6A writer METTL3 to regulate m6A-modified MYCN mRNA stability. KAP1 depletion decreased YTHDC1 protein stability and promoted MYCN mRNA degradation. Inhibiting MYCN mRNA m6A modification synergized with chemotherapy to restrain tumor progression in MYCN-amplified NB. CONCLUSIONS: Our research demonstrates that KAP1, transcriptionally activated by MYCN, forms a complex with YTHDC1 and METTL3, which in turn maintain the stabilization of MYCN mRNA in an m6A-dependent manner. Targeting m6A modification by STM2457, a small-molecule inhibitor of METTL3, could downregulate MYCN expression and attenuate tumor proliferation. This finding provides a new alternative putative therapeutic strategy for MYCN-amplified NB.


Asunto(s)
Proteína Proto-Oncogénica N-Myc , Neuroblastoma , Proteína 28 que Contiene Motivos Tripartito , Humanos , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neuroblastoma/patología , Ratones , Animales , Proteína Proto-Oncogénica N-Myc/genética , Proteína Proto-Oncogénica N-Myc/metabolismo , Proteína 28 que Contiene Motivos Tripartito/metabolismo , Proteína 28 que Contiene Motivos Tripartito/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Estabilidad del ARN , Línea Celular Tumoral , Factores de Empalme de ARN/metabolismo , Factores de Empalme de ARN/genética , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Adenosina/análogos & derivados , Adenosina/metabolismo
18.
Eur Spine J ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38809439

RESUMEN

OBJECTIVE: This study was designed to investigate the clinical features, treatment modalities, and risk factors influencing neurological recovery in patients who underwent scoliosis correction with delayed postoperative neurological deficit (DPND). METHODS: Three patients with DPND were identified from 2 central databases for descriptive analysis. Furthermore, all DPND cases were retrieved from the PubMed and Embase databases. Neurological function recovery was categorized into complete and incomplete recovery groups based on the American Spinal Injury Association (ASIA) impairment scale. RESULTS: Two patients were classified as type 3, and one was classified as type 2 based on the MRI spinal cord classification. Intraoperative neurophysiological monitoring (IONM) was consistently negative throughout the corrective procedure, and intraoperative wake-up tests were normal. The average time to DPND development was 11.8 h (range, 4-18 h), and all three patients achieved complete recovery of neurological function after undergoing revision surgery. A total of 14 articles involving 31 patients were included in the literature review. The mean time to onset of DPND was found to be 25.2 h, and 85.3% (29/34) of patients experienced DPND within the first 48 h postoperatively, with the most common initial symptoms being decreased muscle strength and sensation (26 patients, 83.9%). Regarding neurological function recovery, 14 patients were able to reach ASIA grade E, while 14 patients were not able to reach ASIA grade E. Univariate analysis revealed that preoperative diagnosis (p = 0.004), operative duration (p = 0.017), intraoperative osteotomy method (p = 0.033), level of neurological deficit (p = 0.037) and deficit source (p = 0.0358) were significantly associated with neurological outcomes. Furthermore, multivariate regression analysis indicated a strong correlation between preoperative diagnosis (p = 0.003, OR, 68.633; 95% CI 4.299-1095.657) and neurological prognosis. CONCLUSION: Our findings indicate that spinal cord ischemic injury was a significant factor for patients experiencing DPND and distraction after corrective surgery may be a predisposing factor for spinal cord ischemia. Additionally, it is important to consider the possibility of DPND when limb numbness and decreased muscle strength occur within 48 h after corrective scoliosis surgery. Moreover, emergency surgical intervention is highly recommended for DPND caused by mechanical compression factors with a promising prognosis for neurological function, emphasizing the importance of taking into account preoperative orthopedic diagnoses when evaluating the potential for neurological recovery.

19.
Br J Nutr ; : 1-34, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38772904

RESUMEN

Epilepsy ranks fourth among neurological diseases, featuring spontaneous seizures and behavioral and cognitive impairments. Although anti-epileptic drugs are currently available clinically, 30% of epilepsy patients are still ineffective in treatment, and 52% of patients experience serious adverse reactions. In this work, the neuroprotective effect of α-linolenic acid (ALA, a nutrient) in mice and its potential molecular mechanisms exposed to pentylenetetrazol was assessed. The mice were injected with pentetrazol 37 mg/kg, and ALA was intra-gastrically administered for 40 days. The treatment with ALA significantly reduced the overall frequency of epileptic seizures and improved the behavior impairment and cognitive disorder caused by pentetrazol toxicity. In addition, ALA can not only reduce the apoptosis rate of brain neurons in epileptic mice, but also significantly reduce the content of brain inflammatory factors (IL-6, IL-1, and TNF-α). Furthermore, we predicted that the possible targets of ALA in the treatment of epilepsy were JAK2 and STAT3 through molecular docking. Finally, through molecular docking and Western Blot studies, we revealed the potential mechanism of ALA ameliorates pentylenetetrazol-induced neuron apoptosis and neurological impairment in mice with seizures by downregulating the JAK2/STAT3 pathway. This study aimed to investigate the antiepileptic and neuroprotective effects of ALA, as well as explore its potential mechanisms, through the construction of a chronic ignition mouse model via intraperitoneal PTZ injection. The findings of this research provide crucial scientific support for subsequent clinical application studies in this field.

20.
Small ; : e2401308, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773889

RESUMEN

Incorporating ultralow loading of nanoparticles into polymers has realized increases in dielectric constant and breakdown strength for excellent energy storage. However, there are still a series of tough issues to be dealt with, such as organic solvent uses, which face enormous challenges in scalable preparation. Here, a new strategy of dual in situ synthesis is proposed, namely polymerization of polyethylene terephthalate (PET) synchronizes with growth of calcium borate nanoparticles, making polyester nanocomposites from monomers directly. Importantly, this route is free of organic solvents and surface modification of nanoparticles, which is readily accessible to scalable synthesis of polyester nanocomposites. Meanwhile, uniform dispersion of as ultralow as 0.1 wt% nanoparticles and intense bonding at interfaces have been observed. Furthermore, the PET-based nanocomposite displays obvious increases in both dielectric constant and breakdown strength as compared to the neat PET. Its maximum discharged energy density reaches 15 J cm-3 at 690 MV m-1 and power density attains 218 MW cm-3 under 150 Ω resistance at 300 MV m-1, which is far superior to the current dielectric polymers that can be produced at large scales. This work presents a scalable, safe, low-cost, and environment-friendly route toward polymer nanocomposites with superior capacitive performance.

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