RESUMEN

Cigarette smoking causes multiple cancers by directly influencing mutation burden of driver mutations. However, the mechanism between somatic mutation caused by cigarette smoking and bladder tumorigenesis remains elusive. Smoking-related mutation profile of bladder cancer was characterized by The Cancer Genome Atlas cohort. Integraticve OncoGenomics database was utilized to detect the smoking-related driver genes, and its biological mechanism predictions were interpreted based on bulk transcriptome and single-cell transcriptome, as well as cell experiments. Cigarette smoking was associated with an increased tumor mutational burden under 65 years old (p = 0.031), and generated specific mutational signatures in smokers. RB1 was identified as a differentially mutated driver gene between smokers and nonsmokers, and the mutation rate of RB1 increased twofold after smoking (p = 0.008). RB1 mutations and the 4-aminobiphenyl interference could significantly decrease the RB1 expression level and thus promote the proliferation, invasion, and migration ability of bladder cancer cells. Enrichment analysis and real-time quantitative PCR (RT-qPCR) data showed that RB1 mutations inhibited cytochrome P450 pathway by reducing expression levels of UGT1A6 and AKR1C2. In addition, we also observed that the component of immunological cells was regulated by RB1 mutations through the stronger cell-to-cell interactions between epithelial scissor+ cells and immune cells in smokers. This study highlighted that RB1 mutations could drive smoking-related bladder tumorigenesis through inhibiting cytochrome P450 pathway and regulating tumor immune microenvironment.

RESUMEN

Intravital microscopy (IVM) is a valuable method for biomedical characterization of dynamic processes, which has been applied to many fields such as neuroscience, oncology, and immunology. During IVM, vibration suppression is a major challenge due to the inevitable respiration and heartbeat from live animals. In this study, taking liver IVM as an example, we have unraveled the vibration inhibition effect of liquid bridges by studying the friction characteristics of a moist surface on the mouse liver. We confirmed the presence of liquid bridges on the liver through fluorescence imaging, which can provide microscale and nondestructive liquid connections between adjacent surfaces. Liquid bridges were constructed to sufficiently stabilize the liver after abdominal dissection by covering it with a polymer film, taking advantage of the high adhesion properties of liquid bridges. We further prototyped a microscope-integrated vibration-damping device with adjustable film tension to simplify the sample preparation procedure, which remarkably decreased the liver vibration. In practical application scenarios, we observed the process of liposome phagocytosis by liver Kupffer cells with significantly improved image and video quality. Collectively, our method not only provided a feasible solution to vibration suppression in the field of IVM, but also has the potential to be applied to vibration damping of precision instruments or other fields that require nondestructive ″soft″ vibration damping.

RESUMEN

BACKGROUND: Delayed neurocognitive recovery (dNCR) can result in unfavorable outcomes in elderly surgical patients. Physical activity (PA) has been shown to improve cognitive function, potentially by reducing systemic inflammatory responses. However, there is a lack of supportive data indicating whether PA has a protective effect against dNCR. AIMS: To examine the correlation between dNCR and PA, and to further analyze if pro-inflammatory cytokines mediate this relationship. METHODS: This study is a prospective nested case-control investigation of elderly patients who had knee replacement surgery. dNCR was defined as a decline in cognitive function compared with baseline by using a battery of neuropsychological tests. PA was assessed with the Physical Activity Scale for the Elderly (PASE). Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum concentrations of IL-6, IL-1ß, and TNF-α. Multivariable logistic regression analysis was conducted to assess the association between PA and dNCR. Mediation analysis was employed to evaluate whether pro-inflammatory cytokines mediate the relationship between them. RESULTS: A cohort of 152 patients was included, resulting in an incidence rate of dNCR of 23.68%. PA was associated with dNCR after full adjustment [OR = 0.199, (95% CI, 0.061; 0.649), P = 0.007]. Mediation analysis showed that the IL-6 mediated the statistical association between PA and dNCR, with mediation proportions (%) of 77.68 (postoperative concentration of IL-6) or 27.58 (the absolute change in IL-6 before and after surgery). CONCLUSIONS: PA serves as a protective factor against dNCR, possibly through the reduction of pro-inflammatory cytokine concentrations. THE CHINESE CLINICAL TRAIL REGISTRY: : www.http://chictr.org.cn , Registration No. ChiCTR2300070834, Registration date: April 24, 2023.

Asunto(s)

Citocinas , Ejercicio Físico , Humanos , Anciano , Masculino , Femenino , Ejercicio Físico/fisiología , Citocinas/sangre , Estudios Prospectivos , Estudios de Casos y Controles , Artroplastia de Reemplazo de Rodilla/rehabilitación , Cognición/fisiología , Análisis de Mediación , Anciano de 80 o más Años , Pruebas Neuropsicológicas

RESUMEN

Enriching microorganisms using a 0.22-µm pore size is a general pretreatment procedure in river microbiome research. However, it remains unclear the extent to which this method loses microbiome information. Here, we conducted a comparative metagenomics-based study on microbiomes with sizes over 0.22 µm (large-sized) and between 0.22 µm and 0.1 µm (small-sized) in a subtropical river. Although the absolute concentration of small-sized microbiome was about two orders of magnitude lower than that of large-sized microbiome, sequencing only large-sized microbiome resulted in a significant loss of microbiome diversity. Specifically, the microbial community was different between two sizes, and 347 genera were only detected in small-sized microbiome. Small-sized microbiome had much more diverse viral community than large-sized fraction. The viruses had abundant ecological functions and were hosted by 825 species of 169 families, including pathogen-related families. Small-sized microbiome had distinct antimicrobial resistance risks from large-sized microbiome, showing an enrichment of eight antibiotic resistance gene (ARG) types as well as the detection of 140 unique ARG subtypes and five enriched risk rank I ARGs. Draft genomes of five major resistant pathogens having diverse ecological and pollutant-degrading functions were only assembled in small-sized microbiome. These findings provide novel insights into river ecosystems, and highlight the overlooked small-sized microbiome in the environment.

Asunto(s)

Ecosistema , Microbiota , Ríos , Ríos/microbiología , Metagenómica , Bacterias/genética

RESUMEN

This research draws on literature review and case analyses revealed that the main reasons for Chinese dating violence's high prevalence are the long-term influence of patriarchy and gender culture and low recognition and awareness of the issue among students. Current Anti-domestic Violence Act does not apply to dating violence rendering victims devoid of preventive skills or relief recourse critiqued. Research exploring the lack of education on intimate partner violence in colleges has made students oblivious to the risks. Finally, the review provides detailed recommendations on expanding the practical scope of the Anti-domestic Violence Act to include dating violence and provide judges with clarification on the relevant elements of a dating relationship and cooperation of the legal system and education system in preventing dating violence.

Asunto(s)

Víctimas de Crimen , Relaciones Interpersonales , Violencia de Pareja , Estudiantes , Humanos , Violencia de Pareja/legislación & jurisprudencia , Femenino , China , Masculino , Víctimas de Crimen/legislación & jurisprudencia , Universidades , Adulto Joven

RESUMEN

Post-traumatic stress disorder (PTSD) is a complex psychological disorder provoked by distressing experiences, and it remains without highly effective intervention strategies. The exploration of PTSD's underlying mechanisms is crucial for advancing diagnostic and therapeutic approaches. Current studies primarily explore PTSD through the lens of the central nervous system, investigating concrete molecular alterations in the cerebral area and neural circuit irregularities. However, the body's response to external stressors, particularly the changes in cardiovascular function, is often pronounced, evidenced by notable cardiac dysfunction. Consequently, examining PTSD with a focus on cardiac function is vital for the early prevention and targeted management of the disorder. This review undertakes a comprehensive literature analysis to detail the alterations in brain and heart structures and functions associated with PTSD. It also synthesizes potential mechanisms of heart-brain axis interactions relevant to the development of PTSD. Ultimately, by considering cardiac function, this review proposes novel perspectives for PTSD's prophylaxis and therapy.

Asunto(s)

Encéfalo , Corazón , Trastornos por Estrés Postraumático , Trastornos por Estrés Postraumático/fisiopatología , Trastornos por Estrés Postraumático/metabolismo , Trastornos por Estrés Postraumático/terapia , Humanos , Corazón/fisiopatología , Encéfalo/metabolismo , Encéfalo/fisiopatología , Animales

RESUMEN

Pharmaceutical plant sites play a significant role in the dissemination of antibiotic resistance genes (ARGs) into the environment. It is imperative to comprehensively monitor of ARGs across various environmental media at these sites. This study focused on three pharmaceutical plants, two located in North China and one in South China. Through metagenomic approaches, we examined the composition, mobility potential, and bacterial hosts of ARGs in diverse media such as process water, groundwater, topsoil, soil cores, and pharmaceutical fermentation residues across diverse environmental matrices, including topsoil, soil cores, process water, groundwater, and pharmaceutical fermentation residues. We identified a wide array of ARGs, comprising 21 types and 740 subtypes, with process water exhibiting the highest abundance and diversity. Treatment processes varied in their efficacy in eliminating ARGs, and the clinically relevant ARGs should also be considered when evaluating wastewater treatment plant efficiency. Geographical distinctions in groundwater ARG distribution between northern and southern regions were observed. Soil samples from the three sites showed minimal impact from pharmaceutical activity, with vancomycin-resistance genes being the most prevalent. High levels of ARGs in pharmaceutical fermentation residues underscore the necessity for improved waste management practices. Metagenomic assembly revealed that plasmid-mediated ARGs were more abundant than chromosome-mediated ARGs. Metagenome-assembled genomes (MAGs) analysis identified 166 MAGs, with 62 harboring multiple ARGs. Certain bacteria tended to carry specific types of ARGs, revealing distinct host-resistance associations. This study enhances our understanding of ARG dissemination across different environmental media within pharmaceutical plants and underscores the importance of implementing strict regulations for effluent and residue discharge to control ARG spread.

Asunto(s)

Bacterias , Farmacorresistencia Microbiana , Metagenómica , China , Bacterias/genética , Bacterias/efectos de los fármacos , Farmacorresistencia Microbiana/genética , Microbiología del Suelo , Monitoreo del Ambiente , Farmacorresistencia Bacteriana/genética , Genes Bacterianos , Antibacterianos/farmacología , Agua Subterránea/microbiología , Agua Subterránea/química , Metagenoma

RESUMEN

The surface of food processing equipment is easily affected by biofilm-forming bacteria, leading to cross-contamination and food safety hazards. The critical issue is how to endow the surface of contact materials with antibacterial and antibiofilm abilities. A sustainable, stable, and antibiofilm coating was prepared by phase transition of glutenin. The disulfide bonds in glutenin were reduced by tris(2-carboxyethyl)phosphine, triggering the phase transition of glutenin. Hydrophobic interactions and intermolecular disulfide bonds may be the primary forces. Furthermore, the phase-transited products formed a nanoscale coating on the surface of stainless steel and glass under their own adhesion force and gravity. The coating exhibited good stability in harsh environments. More importantly, after 3 h of direct contact, the colony of Escherichia coli and Staphylococcus aureus decreased by one logarithm. The amount of biofilm was observed to be significantly decreased through optical microscopy and scanning electron microscopy. This article provides a foundational module for developing novel coatings.

Asunto(s)

Antibacterianos , Biopelículas , Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Adhesión Bacteriana/efectos de los fármacos , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Escherichia coli/efectos de los fármacos , Interacciones Hidrofóbicas e Hidrofílicas , Transición de Fase , Acero Inoxidable/química , Staphylococcus aureus/efectos de los fármacos , Propiedades de Superficie

RESUMEN

Matrix effects limit the application of surface-enhanced Raman scattering (SERS) technology in the field of food safety. This study elucidated it from the perspective of protein corona by employing a model system for melamine SERS detection in milk. Compared with the melamine standard solution, higher detection limits (1 mg/L and 10 mg/L) are observed in milk matrix. The melamine signal exhibits an 80% reduction in whey protein solution, suggesting that protein has a significant impact on SERS signals. The changes in particle size, zeta potential and UV-vis spectra indicate the AuNPs interact with whey protein. Forming protein corona inhibits the melamine-induced AuNPs aggregation, reducing the number of 'hot spot' and the adsorption of melamine on AuNPs (from 0.28 mg/L to 0.07 mg/L), which may be responsible for signal loss. The found matrix effect from protein corona provides new insights for developing strategies about reducing matrix effect in SERS application.

Asunto(s)

Contaminación de Alimentos , Oro , Leche , Corona de Proteínas , Espectrometría Raman , Triazinas , Triazinas/química , Triazinas/análisis , Espectrometría Raman/métodos , Animales , Leche/química , Contaminación de Alimentos/análisis , Corona de Proteínas/química , Corona de Proteínas/análisis , Oro/química , Nanopartículas del Metal/química , Bovinos

RESUMEN

Two candidate International Standards for meningococcal capsular group W and Y (MenW and MenY, respectively) polysaccharides were assessed for their suitability as quantitative standards in various physicochemical assays. The study was designed to evaluate the intended purpose of these standards, namely, to standardize the quantification of the respective polysaccharide content in meningococcal polysaccharide and conjugate vaccines and their intermediate components. Twelve laboratories from eleven different countries participated in the collaborative study of candidate preparations for International Standards for MenW and MenY polysaccharide (coded 16/152 and 16/206, respectively). Unitage was assigned using the Resorcinol assay. Our proposals, on the basis of data from the Resorcinol assay were: 1) candidate standard for MenW polysaccharide (16/152) to be assigned a content of 1.015 ± 0.071 mg MenW polysaccharide per ampoule (expanded uncertainty with coverage factor k = 2.13, corresponding to a 95 % level of confidence) and 2) candidate standard for MenY polysaccharide (16/206) be assigned a content of 0.958 ± 0.076 mg MenY polysaccharide per ampoule (expanded uncertainty with coverage factor k = 2.26, corresponding to a 95 % level of confidence). The amount of polysaccharide per ampoule remained consistent under all stability conditions over a 36-month period.

Asunto(s)

Vacunas Meningococicas , Polisacáridos Bacterianos , Vacunas Meningococicas/normas , Humanos , Estándares de Referencia , Vacunas Conjugadas , Neisseria meningitidis

RESUMEN

Introduction: Intervertebral disc degeneration (IVDD) is a complex disease caused by genetic and environmental factors, but its pathogenesis is still unclear. Although studies of inflammatory cytokines have been used in recent years to unravel the biological mechanisms of a variety of diseases, such analyses have not yet been applied to IVDD. Therefore, we used a Mendelian Randomization approach to explore the potential mechanisms underlying the pathogenesis of IVDD. Methods: We obtained GWAS data from publicly available databases for inflammatory cytokines and IVDD, respectively, and explored the causal relationship between individual inflammatory cytokines and IVDD using instrumental variable (IV) analysis. We primarily used IVW methods to assess causality, while sensitivity, heterogeneity and multidirectionality analyses were performed for positive results (p < 0.05). All analyses were performed using R software. Results: In our study, we performed a two-sample MR analysis of 41 inflammatory cytokines to identify metabolites causally associated with IVDD. Ultimately, 2 serum metabolites associated with IVDD were identified (pval<0.05), IFN-γ and IL-18. sensitivity, heterogeneity, and Pleiotropy test analyses were performed for all results. Conclusion: Our study identified a causal relationship between IFN-γ and IL-18 and IVDD. It is valuable for the monitoring and prevention of IVDD and the exploration of targeted drugs. However, more evidence is needed to validate our study.

RESUMEN

Environmental concentrations of antimicrobials can inhibit Cyanobacteria, but little is known about their effects on Cyanobacteria-blooming freshwater ecosystem. Here, a 21 days' outdoor freshwater mesocosm experiment was established to study effects of single and combined tetracycline, triclocarban and zinc at environmental concentrations on microbial community, microbial function and antimicrobial resistance using amplicon- and metagenomic-based methods. Results showed that three chemicals reshaped the microbial community with magnified effects by chemical combinations. Relative abundance of Cyanobacteria was decreased in all chemical groups, especially from 74.5 to 0.9% in combination of three chemicals. Microbial community networks were more simplified after exposure. Proteobacteria and Bacteroidetes predominated in Cyanobacteria-degraded ecosystems, and their relative abundances were significantly correlated with antibiotic resistome, suggesting that they might host antibiotic resistance genes. Notably, relative abundance (copy per 16 S rRNA gene) of total antibiotic resistome reached five to nine folds higher than the initial abundance in chemical-combined groups. The affected antibiotic resistance genes referred to a wide range of antibiotic classes. However, weak effects were detected on biocide/metal resistance and microbial virulence. Three chemicals posed complicated effects on microbial function, some of which had consistent variations across the groups, while some varied greatly in chemical groups. The findings highlight sensitivity of Cyanobacteria-blooming ecosystem to antimicrobials.

Asunto(s)

Carbanilidas , Cianobacterias , Ecosistema , Agua Dulce , Contaminantes Químicos del Agua , Zinc , Cianobacterias/efectos de los fármacos , Cianobacterias/genética , Zinc/toxicidad , Carbanilidas/toxicidad , Agua Dulce/microbiología , Contaminantes Químicos del Agua/toxicidad , Antibacterianos/toxicidad , Antibacterianos/farmacología , Tetraciclina/farmacología , Tetraciclina/toxicidad , Microbiota/efectos de los fármacos

RESUMEN

An electrochemical gem-difluorination of indeno[1,2-c]furans using commercially available and easy-to-use triethylamine trihydrofluoride as both the electrolyte and fluorinating agent was developed. Remarkably, different reaction pathways of indeno[1,2-c]furans, i.e., paired electrolysis and net oxidation, are operative in a batch reactor and a continuous-flow microreactor to afford the corresponding gem-difluorinated indanones and indenones, respectively.

RESUMEN

This study prepared new helmet-roled molecules (HMs) carrying metronidazole frameworks and a phenyl ring for strengthening adsorption and anticorrosion on mild steel. The adsorption of the HMs on the copper surface was understood by material simulation computation. Furthermore, the surface analysis experiments suggest that the studied molecules could be adsorbed to a mild steel surface through the chemical coordination bonding. The remarkable corrosion resistance of the HMs for mild steel in HCl was surveyed by potentiodynamic polarization and electrochemical impedance spectroscopy at 298 K. The HMs including two metronidazole skeletons displayed the stronger corrosion inhibition effect on mild steel than the HM1 bearing one single metronidazole part (the corrosion inhibition efficiency, HM3, 98.03%, HM2, 95.14%, HM1, 88.72%). The results presented in this study provided an efficient strategy to develop new clinical medicine-based corrosion inhibitors for metal in acid medium through molecular preconstruction.

RESUMEN

BACKGROUND: Hyperkalemia is a common complication of chronic kidney disease (CKD). This study aims to investigate the efficacy and safety of sodium zirconium cyclosilicate and calcium polystyrene sulfonate in reducing potassium in patients with acute and severe hyperkalemia in CKD who are not undergoing dialysis. MATERIALS AND METHODS: A retrospective real-world study was conducted among 73 patients with non-dialysis chronic kidney disease who were hospitalized in the First Affiliated Hospital of Chengdu Medical College from June 2020 to June 2022. 33 patients treated with sodium zirconium cyclosilicate were categorized as SZC group, and the other 40 patients treated with calcium polystyrene sulfonate were categorized as CPS group. Serum potassium, serum sodium, magnesium, calcium, and phosphorus levels were examined. Adverse reactions were recorded during medication. RESULTS: Significantly decreased serum potassium was observed in both groups, whereas the potassium reduction was higher in the SZC group than in the CPS group at 2, 4, 24, and 48 hours after medication while there was no statistically significant difference in the serum potassium level between the two groups at 72 hours. For those people whose initial potassium exceeded 6 mmol/L, the potassium reduction was more obvious in the SZC group than in the CPS group at 2 and 4 hours after medication. The control rate of hyperkalemia in the SZC group was significantly higher than in the CPS group at 4, 24, and 48 hours. No distinct change was observed in serum sodium, calcium, magnesium, and phosphorus before and 72 hours after medication. No severe adverse reactions occurred. CONCLUSION: Sodium zirconium cyclosilicate has a more obvious effect on reducing potassium particularly for those patients with moderate to severe hyperkalemia who need rapid potassium reduction.

RESUMEN

Long-term exposure to microgravity is considered to cause liver lipid accumulation, thereby increasing the risk of non-alcoholic fatty liver disease (NAFLD) among astronauts. However, the reasons for this persistence of symptoms remain insufficiently investigated. In this study, we used tandem mass tag (TMT)-based quantitative proteomics techniques, as well as non-targeted metabolomics techniques based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), to comprehensively analyse the relative expression levels of proteins and the abundance of metabolites associated with lipid accumulation in rat liver tissues under simulated microgravity conditions. The differential analysis revealed 63 proteins and 150 metabolites between the simulated microgravity group and the control group. By integrating differentially expressed proteins and metabolites and performing pathway enrichment analysis, we revealed the dysregulation of major metabolic pathways under simulated microgravity conditions, including the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, steroid hormone biosynthesis and butanoate metabolism, indicating disrupted liver metabolism in rats due to weightlessness. Finally, we examined differentially expressed proteins associated with lipid metabolism in the liver of rats exposed to stimulated microgravity. These findings contribute to identifying the key molecules affected by microgravity and could guide the design of rational nutritional or pharmacological countermeasures for astronauts.

Asunto(s)

Metabolismo de los Lípidos , Hígado , Metabolómica , Proteómica , Simulación de Ingravidez , Animales , Ratas , Hígado/metabolismo , Proteómica/métodos , Masculino , Metabolómica/métodos , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem , Cromatografía Liquida , Trastornos del Metabolismo de los Lípidos/metabolismo

RESUMEN

Lateral flow immunoassay (LFIA), an affordable and rapid paper-based detection technology, is employed extensively in clinical diagnosis, environmental monitoring, and food safety analysis. The COVID-19 pandemic underscored the validity and adoption of LFIA in performing large-scale clinical and public health testing. The unprecedented demand for prompt diagnostic responses and advances in nanotechnology have fueled the rise of next-generation LFIA technologies. The utilization of nanoparticles to amplify signals represents an innovative approach aimed at augmenting LFIA sensitivity. This review probes the nanoparticle-assisted amplification strategies in LFIA applications to secure low detection limits and expedited response rates. Emphasis is placed on comprehending the correlation between the physicochemical properties of nanoparticles and LFIA performance. Lastly, we shed light on the challenges and opportunities in this prolific field.

Asunto(s)

COVID-19 , Nanopartículas , SARS-CoV-2 , Inmunoensayo/métodos , Humanos , Nanopartículas/química , COVID-19/diagnóstico , COVID-19/virología , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación

RESUMEN

This experiment aimed to explore the influence mechanism of external fixator on open fracture. A total of 128 patients with open tibiofibular fractures were included in this study. The patients were randomly divided into external fixator group (n=64) and control group (n=64) according to the order of admission. Double-blind controlled observation was used. The levels of osteocalcin (BGP), ß-CTX, P1 NP, BALP, including haptoglobin (Hp), ceruloplasmin (CER), serum adrenocorticotropic hormone (ACTH), cortisol (COR), C-reactive protein (CRP), white blood cell (WBC) and interleukin-6 (IL-6) were recorded in different groups. The postoperative VAS score and quality of life were recorded. Log-rank was used to analyze the difference in postoperative adverse reaction rates among different groups. External fixation stent treatment increased BGP, PINP, and BALP expression and decreased ß-CTX, Hp, CER, ACTH, COR, CRP, WBC, and IL-6 levels. Patients in the external fixation stent group had significantly lower VAS score quality of life scores and incidence of adverse events than the control group. External fixation stents protect open fracture patients by promoting bone metabolism.

Asunto(s)

Huesos , Proteína C-Reactiva , Fijadores Externos , Osteocalcina , Calidad de Vida , Humanos , Masculino , Femenino , Adulto , Osteocalcina/sangre , Osteocalcina/metabolismo , Persona de Mediana Edad , Huesos/metabolismo , Proteína C-Reactiva/metabolismo , Fracturas Abiertas/cirugía , Fracturas Abiertas/metabolismo , Interleucina-6/sangre , Interleucina-6/metabolismo , Procolágeno/sangre , Procolágeno/metabolismo , Método Doble Ciego , Colágeno Tipo I/metabolismo , Colágeno Tipo I/sangre , Hormona Adrenocorticotrópica/sangre , Hormona Adrenocorticotrópica/metabolismo , Fragmentos de Péptidos/sangre , Extremidades/cirugía , Extremidades/lesiones , Péptidos , Hidrocortisona/sangre

RESUMEN

Objective: Hard-to-heal diabetic foot ulcers (DFUs) are associated with higher mortality rates and an increased medical burden for patients. ON101, a new topical cream, exhibited better healing efficacy than the control dressing in a Phase III trial. In this post hoc analysis, we further identify whether ON101 can improve the healing of ulcers with hard-to-heal risk factors in this cohort of DFU patients. Approach: To compare the efficacy of ON101 with absorbent dressing among various hard-to-heal wounds in patients with DFU, a post hoc analysis of a randomized Phase III trial that included 276 DFU patients was performed by subgrouping those patients based on ulcer depth, location, size, duration, and patients' glycated hemoglobin (HbA1c) levels and body mass index (BMI). Results: In the full analysis set, the proportion of patients achieving healing was 61.7% in the ON101 group and 37.0% in the comparator (p = 0.0001). In subgroup analysis according to risk factors, ON101 demonstrated superior healing capacity on Wagner grade 2 ulcers (p < 0.0001); plantar ulcers (p = 0.0016), ulcer size ≥5 cm2 (p = 0.0122), ulcer duration ≥3 months (p = 0.0043); for patients with HbA1c ≥9% (p = 0.0285); and patients with BMI ≥25 (p = 0.0005). Innovation: ON101, a novel therapeutic drug, can modulate the functions of macrophages and demonstrate superior healing rates to conventional absorbent dressing in patients with hard-to-heal DFUs. Conclusions: The results of this post hoc study suggest that ON101 is a better therapeutic option than conventional dressing used in treatment for DFU patients with higher HbA1c, BMI, or ulcers with complex conditions such as longer duration, deeper wounds, larger size, and plantar location.

RESUMEN

BACKGROUND: The current study presents the effort of a global collaborative group to review the management and outcomes of malignant tumors of the skull base worldwide. PATIENTS AND METHODS: A total of 28 institutions contributed data on 3061 patients. Analysis evaluated clinical variables, survival outcomes, and multivariable factors associated with outcomes. RESULTS: The median age was 56 years (IQR 44-67). The open surgical approach was used in 55% (n = 1680) of cases, endoscopic resection was performed in 36% (n = 1087), and the combined approach in 9.6% (n = 294). With a median follow-up of 7.1 years, the 5-year OS DSS and RFS were 65%, 71.7% and 53%, respectively. On multivariable analysis, older age, comorbidities, histology, dural/intracranial involvement, positive margins, advanced stage, and primary site were independent prognostic factors for OS, DSS, and RFS. Adjuvant RT was a protective prognostic factor. CONCLUSION: The progress across various disciplines may have contributed to improved OS and DSS in this study compared to previous reports.