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1.
Front Bioeng Biotechnol ; 12: 1415617, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39139292

RESUMEN

Introduction: Hallux valgus, a common foot deformity, often necessitates surgical intervention. This study evaluates the biomechanical alterations in patients post-surgery, focusing on the efficacy of an "8" bandage fixation system to promote optimal recovery. Methods: A three-dimensional (3D) model was constructed using CT data from a patient with hallux valgus. A quasi-static finite element analysis (FEA) was conducted in conjunction with gait analysis to evaluate the biomechanical changes at the osteotomy site under "8" shaped bandage fixation following hallux valgus surgery. The effects of the "8" shaped bandage on the stability of the osteotomy site and bone healing were investigated at three load points during the gait cycle. Results: During the Loading Response (LR), Midstance (MSt), and Terminal stance TSt phases, the osteotomy end experienced maximum Von Mises stresses of 0.118, 1.349, and 1.485 MPa, respectively. Correspondingly, the maximum principal stresses, all of which were compressive along the Z-axis, were 0.11662 N, 1.39266 N, and 1.46762 N, respectively. Additionally, these phases showed a maximum relative total displacement of 0.848 mm and a maximum relative shear displacement of 0.872 mm. Conclusion: During the stance phase, the osteotomy end of the first metatarsal is predominantly subjected to compressive stress, with the relative displacement within the safe range to promote healing. The application of an "8" bandage for external fixation after surgery can maintain the dynamic stability of osteotomy sites post-minimally invasive hallux valgus correction during the gait cycle, thereby promoting the healing of the osteotomy ends.

2.
J Chem Phys ; 161(8)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39171709

RESUMEN

Based upon global-minimum searches and first-principles electronic structural calculations, we present the perfectly planar B6O50/-/2- (1-3) systems. Notably, the C2v B6O50/- (1-2) clusters mark a groundbreaking advancement as the first boron oxide clusters to feature a five-membered ring. Both structures exhibit remarkable similarity, each characterized by a central B3O2 ring surrounded by three terminal BO groups. However, a notable difference lies in the bond lengths within the B3O2 core, which are uniform in the former but uneven in the latter. Detailed canonical molecular orbital and AdNDP analyses reveal the delocalized π bonds over the B3O2 ring, affirming the π aromaticity of B6O5-. The Cs B6O52- (3) cluster showcases a chain-like arrangement with three terminal BO groups and a typical OBO group linked to a B2 core, emphasizing the crucial role of electrons in shaping the structure. Detailed chemical bonding analyses reveal the presence of dual three-center four-electron (3c-4e) π hyperbonds in 3, shedding further light on its unique bonding characteristics. Moreover, this study comprehensively extends the B(BO)n0/- (n = 1-5) series and provides valuable perspectives on their structural evolution.

3.
BMC Musculoskelet Disord ; 25(1): 686, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39217326

RESUMEN

BACKGROUND: Previous studies have reported that positive buttress is as effective as anatomical reduction in treating young femoral neck fractures, but whether this effect is related to the Pauwels classification remains unclear. The purpose of this study was to retrospectively analyze the clinical prognosis of positive buttress in young femoral neck fractures with different Pauwels classifications, as well as to assess its biomechanical properties. METHODS: A total of 170 young patients with femoral neck fractures who were treated with three cannulated screws were included in this study. Patients were divided into three groups based on their preoperative Pauwels classification. Each group was divided into three subgroups based on the reduction quality: positive buttress, negative buttress and anatomical reduction. The femoral neck shortening, the incidence of necrosis of the femoral head (AVN) and the Harris hip scores at the last follow-up were compared across the three reduction quality within each Pauwels classification. Subsequently, a volunteer was recruited, CT data of the hip was obtained, and finite element models representing different reduction quality under varying Pauwels classifications were established. The biomechanical properties of each model were then evaluated following the application of strains. RESULTS: In Pauwels type I, there were no significant differences in postoperative femoral neck shortening, incidence of AVN, or Harris score among the three types of reduction quality (P > 0.05). However, positive buttress provided superior biomechanical stability compared to negative buttress and anatomical reduction. In Pauwels type II, the incidence of AVN was similar between the positive buttress and the anatomical reduction groups, and both were significantly lower than that in the negative buttress (P < 0.05). The Harris score of the positive buttress was higher than that of the negative buttress, and there was no significant difference in the occurrence of femoral neck shortening between the three groups (P > 0.05). Finite element analysis showed that the biomechanical stability of positive buttress was equivalent to anatomical reduction, and both were better than negative buttress. In Pauwels type III, the incidence of AVN in the anatomical reduction group was lower than that in both the positive buttress and negative buttress (P < 0.05). There was no significant difference in the occurrence of AVN or femoral neck shortening between positive buttress and negative buttress (P > 0.05). There was also no difference in postoperative Harris scores between the three reduction qualities (P > 0.05). Both positive buttress and negative buttress exhibited identical biomechanical qualities and were inferior to anatomical reduction. CONCLUSIONS: The biomechanical and clinical dominance of positive buttress correlates with Pauwels type. Specifically, Positive buttress is biomechanically stable in Pauwels types I and II. In Pauwels type III, positive buttress is not advantageous. As the Pauwels angle increases, the biomechanical benefit of the positive buttress is lost. Therefore, regardless of the Pauwels classification, negative buttress should be avoided after reduction of femoral neck fractures in young patients.


Asunto(s)
Tornillos Óseos , Fracturas del Cuello Femoral , Análisis de Elementos Finitos , Fijación Interna de Fracturas , Humanos , Fracturas del Cuello Femoral/cirugía , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/clasificación , Estudios Retrospectivos , Femenino , Masculino , Adulto , Fijación Interna de Fracturas/métodos , Adulto Joven , Fenómenos Biomecánicos , Resultado del Tratamiento
4.
J Biopharm Stat ; : 1-22, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39028254

RESUMEN

Dose selection and optimization in early phase of oncology drug development serves as the foundation for the success of late phases drug development. Bivariate Bayesian logistic regression model (BLRM) is a widely utilized model-based algorithm that has been shown to improve the accuracy for identifying recommended phase 2 dose (RP2D) based on dose-limiting-toxicity (DLT) over traditional method such as 3 + 3. However, it remains a challenge to optimize dose selection that strikes a proper balance between safety and efficacy in escalation and expansion phase of phase I trials. In this paper, we first use a phase I clinical trial to demonstrate how the variability of drug exposure related to pharmacokinetic (PK) parameters among trial participants may add to the difficulties of identifying optimal dose. We use simulation to show that concurrently or retrospectively fitting BLRM model for dose/toxicity data from escalation phase with dose-independent PK parameters as covariate lead to improved accuracy of identifying dose level at which DLT rate is within a prespecified toxicity interval. Furthermore, we proposed both model- and rule-based methods to modify dose at patient level in expansion cohorts based on their PK/exposure parameters. Simulation studies show this approach leads to higher likelihood for a dose level with a manageable toxicity and desirable efficacy margin to be advanced to late phase pipeline after being screened at expansion phase of phase I trial.

5.
PLoS Comput Biol ; 20(7): e1012274, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38990982

RESUMEN

Altruistic punishment is key to establishing cooperation and maintaining social order, yet its developmental trends across cultures remain unclear. Using computational reinforcement learning models, we provided the first evidence of how social feedback dynamically influences group-biased altruistic punishment across cultures and the lifespan. Study 1 (n = 371) found that Chinese participants exhibited higher learning rates than Americans when socially incentivized to punish unfair allocations. Additionally, Chinese adults showed slower learning and less exploration when punishing ingroups than outgroups, a pattern absent in American counterparts, potentially reflecting a tendency towards ingroup favoritism that may contribute to reinforcing collectivist values. Study 2 (n = 430, aged 12-52) further showed that such ingroup favoritism develops with age. Chinese participants' learning rates for ingroup punishment decreased from adolescence into adulthood, while outgroup rates stayed constant, implying a process of cultural learning. Our findings highlight cultural and age-related variations in altruistic punishment learning, with implications for social reinforcement learning and culturally sensitive educational practices promoting fairness and altruism.


Asunto(s)
Altruismo , Castigo , Humanos , Castigo/psicología , Adulto , Masculino , Adolescente , Adulto Joven , Femenino , Persona de Mediana Edad , Niño , Refuerzo en Psicología , Estados Unidos , China , Comparación Transcultural , Biología Computacional , Aprendizaje/fisiología
6.
Lancet Microbe ; 5(8): 100846, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38870982

RESUMEN

BACKGROUND: The intensive use of antibiotics has resulted in strong natural selection for the evolution of antimicrobial resistance (AMR), but whether, and under what circumstances, the removal of antibiotics would result in a rapid reduction in AMR has been insufficiently explored. We aimed to test the hypothesis that in the simple, yet common, case of AMR conferred by a single gene, removing antibiotics would quickly reduce the prevalence of resistance if the AMR gene imposes a high fitness cost and costless resistance is extremely rare among its proximal mutants. METHODS: In this genetic study, to test our hypothesis, we used the mcr-1 gene in Escherichia coli, which confers resistance to the last-resort antibiotic colistin, as a model. A high-throughput reverse genetics approach was used to evaluate mcr-1 variants for their fitness cost and resistance levels relative to a non-functional construct, by measuring relative growth rates in colistin-free media and at 2 µg/mL and 4 µg/mL colistin. We identified costless resistant mcr-1 mutants, and examined their properties within the context of the sequential organisation of mcr-1's functional domains as well as the evolutionary accessibility of these mutations. Finally, a simple population genetic model incorporating the measured fitness cost was constructed and tested against previously published real-world data of mcr-1 prevalence in colonised inpatients in China since the 2017 colistin ban in fodder additives. FINDINGS: We estimated the relative growth rates of 14 742 mcr-1 E coli variants (including the wild type), 3449 of which were single-nucleotide mutants. E coli showed 73·8% less growth per 24 h when carrying wild-type mcr-1 compared with the non-functional construct. 6252 (42·4%) of 14 741 mcr-1 mutants showed colistin resistance accompanied by significant fitness costs, when grown under 4 µg/mL colistin selection. 43 (0·3%) mcr-1 mutants exhibited costless resistance, most of which contained multiple mutations. Among the 3449 single mutants of mcr-1, 3433 (99·5%) had a fitness cost when grown in colistin-free media, with a mean relative growth of 0·305 (SD 0·193) compared with the non-functional variant. 3059 (88·7%) and 1833 (53·1%) of 3449 single mutants outgrew the non-functional mcr-1 in the presence of 2 µg/mL and 4 µg/mL colistin, respectively. Single mutations that gave rise to costless mutants were rare in all three domains of mcr-1 (transmembrane domain, flexible linker, and catalytic domain), but the linker domain was enriched with cost-reducing and resistance-enhancing mutations and depleted with cost-increasing mutations. The population genetics model based on the experimental data accurately predicts the rapid decline in mcr-1 prevalence in real-world data. INTERPRETATION: Many identified costless resistant variants that consist of multiple mutations are unlikely to evolve easily in nature. These findings for colistin and mcr-1 might be applicable to other cases in which AMR entails a substantial fitness cost that cannot be mitigated in proximal mutants. FUNDING: National Natural Science Foundation of China, and National Key Research and Development Program of China.


Asunto(s)
Antibacterianos , Colistina , Farmacorresistencia Bacteriana , Proteínas de Escherichia coli , Escherichia coli , Aptitud Genética , Mutación , Colistina/farmacología , Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Farmacorresistencia Bacteriana/genética , Pruebas de Sensibilidad Microbiana , Humanos
7.
Orthop Surg ; 16(6): 1257-1268, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38693601

RESUMEN

The floating toe deformity is classified as a forefoot deformity wherein the distal portion of the toe does not establish touch with the ground, resulting in a suspended or elevated position while the finger is in a relaxed state. At first, it garnered considerable interest as a complication It is worth noting that this condition is particularly common in children under the age of 8, which usually disappears as the individual reaches maturity. Studies have shown that with the aggravation of floating toe deformity, its adverse effects on patients' gait and overall quality of life also increase. Despite the prevalence of floating toe deformity in clinical settings, there is a lack of comprehensive literature investigating its underlying causes and potential preventive strategies. This scope review follows the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) statement guidelines for scope reviews. The literature was obtained from various full-text databases, including China National Knowledge Infrastructure Database (CNKI), Wanfang Database, PubMed, and Web of Science Database. Our search focused on published literature related to floating toes, Weil osteotomy, and distal metatarsal osteotomy, up until March 1, 2023. The literature search and data analysis are conducted by two independent reviewers. If there are any disagreements, a third researcher will participate in the discussion and negotiate a decision. Furthermore, two experienced foot and ankle surgeons conducted a thorough literature analysis for this review. Sixty-two articles were included. Through the clinical analysis of the structural changes of the forefoot before and after operation, the classification of floating toe was described, the causes of pathological floating toe were summarized, and the possible intervention measures for the disease were put forward under the advice of foot and ankle surgery experts. We comprehensively summarize the current knowledge system about the etiology of floating toe and put forward the corresponding intervention strategy. We recommend that future studies will focus on the improvement of surgical procedures, such as the combination of Weil osteotomy, proximal interphalangeal (PIP) arthrodesis and flexor tendon arthrodesis.


Asunto(s)
Osteotomía , Dedos del Pie , Humanos , Osteotomía/métodos , Osteotomía/efectos adversos , Dedos del Pie/cirugía , Complicaciones Posoperatorias
8.
Dev Sci ; 27(4): e13485, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38351606

RESUMEN

Disparities in socioeconomic status (SES) may affect individuals' risk preferences, which have important developmental consequences across the lifespan. Yet, previous research has shown inconsistent associations between SES and risky decision-making, and little is known about how this link develops from a young age. The current research is among the first to examine how SES influences preschoolers' risky decisions in both gain and loss frames. Across two studies, children aged 5 to 6 years (total N = 309, 154 boys) were asked to choose between certain and risky options. The risky option was more advantageous, equal to, or less advantageous than the certain option. Study 1 revealed that in the loss frame, high-SES children (n = 84, 44 boys) chose more risky options and were more sensitive to the expected value compared to low-SES children (n = 78, 42 boys), especially when the risk was more advantageous. However, this SES difference was not significant in the gain frame. Supporting the potential causal link between SES and risky decision-making, Study 2 further found that experimentally increasing low-SES children's (n = 68, 30 boys) status by providing additional resources increased their risk-seeking behavior in the loss frame. Overall, our findings suggest an interaction between environmental cues (gain vs. loss) and early life circumstances (SES) in shaping children's risk preferences. RESEARCH HIGHLIGHTS: This research is among the first to examine how school backgrounds and experimentally manipulated SES influence preschoolers' risk preferences in gain and loss frames. Children were more risk-seeking for losses than for gains; this framing effect was stronger in higher-SES than lower-SES children. Lower-SES children exhibited fewer risk-seeking behaviors and decreased sensitivity to the expected value of options for losses, but not for gains. A temporary boost in SES increased children's risk-seeking behavior, but not sensitivity to expected values.


Asunto(s)
Toma de Decisiones , Asunción de Riesgos , Clase Social , Humanos , Preescolar , Masculino , Femenino , Niño
9.
Adv Sci (Weinh) ; 11(7): e2305495, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38072667

RESUMEN

Magnetic resonance imaging (MRI) demonstrates clear advantages over other imaging modalities in neurosurgery with its ability to delineate critical neurovascular structures and cancerous tissue in high-resolution 3D anatomical roadmaps. However, its application has been limited to interventions performed based on static pre/post-operative imaging, where errors accrue from stereotactic frame setup, image registration, and brain shift. To leverage the powerful intra-operative functions of MRI, e.g., instrument tracking, monitoring of physiological changes and tissue temperature in MRI-guided bilateral stereotactic neurosurgery, a multi-stage robotic positioner is proposed. The system positions cannula/needle instruments using a lightweight (203 g) and compact (Ø97 × 81 mm) skull-mounted structure that fits within most standard imaging head coils. With optimized design in soft robotics, the system operates in two stages: i) manual coarse adjustment performed interactively by the surgeon (workspace of ±30°), ii) automatic fine adjustment with precise (<0.2° orientation error), responsive (1.4 Hz bandwidth), and high-resolution (0.058°) soft robotic positioning. Orientation locking provides sufficient transmission stiffness (4.07 N/mm) for instrument advancement. The system's clinical workflow and accuracy is validated with lab-based (<0.8 mm) and MRI-based testing on skull phantoms (<1.7 mm) and a cadaver subject (<2.2 mm). Custom-made wireless omni-directional tracking markers facilitated robot registration under MRI.


Asunto(s)
Neurocirugia , Robótica , Procedimientos Neuroquirúrgicos/métodos , Encéfalo , Imagen por Resonancia Magnética/métodos
10.
Neural Regen Res ; 18(11): 2357-2364, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37282453

RESUMEN

Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis. Patients with this syndrome produce multiple antibodies, each targeting a different antigen and causing different symptoms and signs. The CV2/collapsin response mediator protein 5 (CRMP5) antibody is a major antibody of this type. It damages the nervous system, which often manifests as limbic encephalitis, chorea, ocular manifestation, cerebellar ataxia, myelopathy, and peripheral neuropathy. Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome, and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis. However, because of the low incidence of this disease, few reports and no reviews have been published about it so far. This article intends to review the research on CV2/CRMP5 antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease. Additionally, this review discusses the current challenges that this disease poses, and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrome, including CV2/CRMP5-associated paraneoplastic neurological syndrome, in recent years.

11.
Front Psychol ; 14: 1053242, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37179861

RESUMEN

Flexible work arrangements (FWA) are becoming increasingly widespread as an efficient means of coping with a dynamic and competitive business environment. Existing studies have primarily examined the impact of FWA as a management system; however, its impact on employee innovation behavior has not been fully explored. Based on the self-determination theory, this study constructed a moderated mediation model that empirically examined the influence of FWA on the innovation behavior of knowledge employees. Our findings are as follows: (1) FWA can activate innovation behavior among knowledge employees; (2) thriving at work plays a partial mediating role; (3) human resource policies that facilitate opportunities have a positive moderating effect. The findings fill a theoretical research gap and provide insights for managers on implementing FWA to promote the innovative behavior of knowledge employees.

12.
Int J Pharm ; 638: 122914, 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37028571

RESUMEN

Cholesterol (CHOL) is essential for developing lipid nanoparticles (LNPs) for gene delivery because it enhances membrane fusion and improves the delivery efficiency of gene cargos. An attractive pDNA carrier, corosolic acid (CA)-modified lipid nanoparticles (CLNPs), was developed by replacing CHOL in LNPs to deliver pDNA at various ratios of nitrogen groups to phosphate groups (N/P). The resultant CLNPs with a higher CHOL/CA ratio exhibited similar mean particle size, zeta potential, and encapsulation efficiency to those of LNPs. In comparison with LNPs, CLNPs (CHOL:CA ratio = 2:1) achieved increased cellular uptake and enhanced transfection efficacy while maintaining low cytotoxicity. In vivo results from chicken experiments demonstrated that CLNPs encapsulating DNA vaccines against avian influenza at a N/P ratio of 3 could elicit similar-level humoral and cellular immune responses compared with those of LNPs at a higher N/P ratio, thereby suggesting the induction of desirable immune effects using less ionizable lipids. Our study provides a reference for further research on the application of CA in LNPs for gene delivery, and the development of novel delivery systems for DNA vaccines against avian influenza.


Asunto(s)
Gripe Aviar , Nanopartículas , Vacunas de ADN , Animales , Gripe Aviar/prevención & control , Lípidos
13.
Front Endocrinol (Lausanne) ; 14: 1115834, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36967762

RESUMEN

Introduction: Previous observational studies have reported that thyroid dysfunction is associated with hallux valgus (HV). However, the causal effect of thyroid dysfunction on hallux valgus is still unknown. To assess whether there is a causal relationship between thyroid dysfunction and hallux valgus, we performed a two-sample Mendelian randomization (MR) study. Methods: The data of the two-sample Mendelian randomization study were obtained from public databases. In this study, hypothyroidism, hyperthyroidism, free thyroxine (FT4), and thyrotropin (TSH) were chosen as exposures. The single nucleotide polymorphisms (SNP) of hypothyroidism and hyperthyroidism were from the genome-wide association studies (GWAS) of the IEU database, including 337,159 subjects. Data for FT4 and TSH (72,167 subjects) were extracted from the ThyroidOmics Consortium. HV was used as the outcome. The SNPs associated with HV were selected from a GWAS of 202,617 individuals in the fignngen database. The inverse variance weighted (IVW) method was used as the primary analysis. Four complementary methods were applied, including MR-presso, MR-Egger, and weighted median. In addition, Cochran's Q test, MR-presso, MR-Egger regression, and the leave-one-out test were used as sensitivity analysis, and the MR-pleiotropy test was performed to examine pleiotropy. Results: According to the results of IVW, we found that there was a causal relationship between hypothyroidism and HV, and hypothyroidism increased the incidence of HV (OR = 2.838 (95% CI: 1.116-7.213); p = 0.028). There were no significant causal effects of hyperthyroidism, FT4, and TSH on HV (p > 0.05). Sensitivity analyses showed that the results were robust and reliable, and no horizontal pleiotropy was detected. Conclusions: Our findings provided genetic support that hypothyroidism might increase the risk of HV. It will predict the occurrence of HV in patients with hypothyroidism and provide suggestions for early prevention and intervention.


Asunto(s)
Hallux Valgus , Hipertiroidismo , Hipotiroidismo , Humanos , Hallux Valgus/epidemiología , Hallux Valgus/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Hipotiroidismo/complicaciones , Hipotiroidismo/epidemiología , Hipotiroidismo/genética , Tirotropina
14.
Foods ; 12(6)2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36981244

RESUMEN

Acrylamide (AA) and ochratoxin A (OTA) are contaminants that co-exist in the same foods, and may create a serious threat to human health. However, the combined effects of AA and OTA on intestinal epithelial cells remain unclear. The purpose of this research was to investigate the effects of AA and OTA individually and collectively on Caco-2 cells. The results showed that AA and OTA significantly inhibited Caco-2 cell viability in a concentration- and time-dependent manner, decreased transepithelial electrical resistance (TEER) values, and increased the lucifer yellow (LY) permeabilization, lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) levels. In addition, the levels of IL-1ß, IL-6, and TNF-α increased, while the levels of IL-10 decreased after AA and OTA treatment. Western blot analysis revealed that AA and OTA damaged the intestinal barrier by reducing the expression of the tight junction (TJ) protein. The collective effects of AA and OTA exhibited enhanced toxicity compared to either single compound and, for most of the intestinal barrier function indicators, AA and OTA combined exposure tended to produce synergistic toxicity to Caco-2 cells. Overall, this research suggests the possibility of toxic reactions arising from the interaction of toxic substances present in foodstuffs with those produced during processing.

15.
Neural Regen Res ; 18(8): 1637-1644, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36751773

RESUMEN

Myasthenia gravis is an acquired, humoral immunity-mediated autoimmune disease characterized by the production of autoantibodies that impair synaptic transmission at the neuromuscular junction. The intervention-mediated clearance of immunoglobulin G (IgG) was shown to be effective in controlling the progression of the disease. The neonatal Fc receptor (FcRn) plays a key role in prolonging the serum half-life of IgG. Antagonizing FcRn to prevent its binding to IgG can accelerate the catabolism of the latter, resulting in decreased levels of IgG, including pathogenic autoantibodies, thereby achieving a therapeutic effect. In this review, we detail the substantial research progress, both basic and clinical, relating to the use of FcRn inhibitors in the treatment of myasthenia gravis.

16.
J Genet Genomics ; 50(5): 330-340, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36414223

RESUMEN

Multiple primary lung cancer (MPLC) is an increasingly prevalent subtype of lung cancer. According to recent genomic studies, the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence. We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found. Using our own and other relevant public data, evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk, indicating evolutionary contingency rather than adaptive convergence. Additionally, tumors from the same MPLC patient are as genetically diverse as those from different patients, while within-tumor genetic heterogeneity is significantly lower. Furthermore, the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor, but not with samples from other tumors or other patients. Overall, there is no evidence of adaptive convergence during the evolution of MPLC. Most importantly, the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient. To fully exploit the strategic value of precision medicine, targeted therapies should be designed and delivered on a per-lesion basis.


Asunto(s)
Neoplasias Pulmonares , Neoplasias Primarias Múltiples , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/cirugía , Mutación
17.
Front Cardiovasc Med ; 9: 976730, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36578835

RESUMEN

Objective: Whether exercise-induced venous-to-systemic shunt (EIS) during cardiopulmonary exercise testing (CPET) has different manifestations or characteristics in idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients remains unknown. We explored the differences in hemodynamics, echocardiography, and prognosis between IPAH and CTEPH patients with and without EIS. Methods: We conducted a retrospective cross-sectional cohort study and included 161 PH patients at Shanghai Pulmonary Hospital. Demographic, echocardiography, pulmonary hemodynamic, and CPET variables were compared between patients with and without EIS stratified by IPAH and CTEPH. EIS was determined by CPET. Binary logistic regression analyses were performed to explore independent influencing factors of EIS. Cox survival analysis was used to quantify the impact of EIS on the prognosis of patients. Results: Exercise-induced venous-to-systemic shunt was found in approximately 17.4% of 86 IPAH patients and 20% of 75 CTEPH patients. All-cause mortality occurred in 43 (26.7%) patients during a median follow-up of 6.5 years. Compared with those without EIS, patients with EIS had higher peak end-tidal O2 and lower VO2/VE and tricuspid annular plane systolic excursion (TAPSE). Among the IPAH patients, EIS was associated with lower cardiac output, cardiac index, mixed venous oxygen saturation, VO2/VE, and TAPSE and higher VE/VCO2 and right ventricular end-diastolic transverse diameter. Logistic regression analysis indicated that VO2/VE was an independent factor influencing whether IPAH patients developed EIS during CPET. Cox logistic regression indicated that female IPAH patients or IPAH patients with higher VO2/VE and EIS had a better prognosis. Female IPAH patients had better 10-year survival. In IPAH patients without EIS, patients with higher VO2/VE had better 10-year survival. However, compared with CTEPH patients without EIS, those with EIS had similar echocardiographic, hemodynamic, CPET parameter results and 10-year survival. Conclusion: Exercise-induced venous-to-systemic shunt exhibits different profiles among IPAH and CTEPH patients. Among IPAH patients, those with EIS had worse peak end-tidal O2, VO2/VE, and TAPSE than those without EIS. VO2/VE was an independent factor of EIS among IPAH patients. IPAH patients with EIS, female sex or higher VO2/VE had better survival. However, the association between EIS and PAH severity or prognosis in CTEPH patients needs to be further explored.

18.
J Appl Biomater Funct Mater ; 19: 22808000211014724, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34210203

RESUMEN

PURPOSE: The effect of flushing at different temperatures on the preparation ability of rotary nickel-titanium files was investigated to provide guideline for clinical application. METHODS: Sixty ProTaper Universal F1 rotary nickel-titanium files were randomly divided into three groups treated by flushing at 6°C, 23°C, and 40°C. Root canal preparation was conducted by step-by-step method on standardized nickel-titanium instrument fracture models. During preparation, the thrust force was set as 10 N, and water was continuously flushed. The motor speed was 350 rpm (rounds per minute), and the torque was 3.0 N cm. When the set torque was reached, the motor automatically rotated in the reverse direction and was pulled out. RESULTS: Root canal preparation was performed using ProTaper Universal F1 rotary nickel-titanium files treated by flushing. The numbers of rotations before the device was fracture were 429.33 ± 214.68, 821.92 ± 410.43, and 1304.92 ± 297.81, respectively. When each root canal was completed, the numbers of instrument rotations were 272.15 ± 88.30, 188.85 ± 34.36, and 163.41 ± 16.18, respectively. Rank sum test and analysis of variance were performed by IBM SPSS Statistics v21.0 software, and both of them were p < 0.01, indicating that the number of cycles to failure (NCF) and the number of instrument rotations for each root tube were statistically different at the three temperatures. CONCLUSIONS: The self-made resin-simulated curved root canal can replace the real root canal to complete the root canal preparation experiment. The group of nickel-titanium files treated by flushing at 23°C can prepare more root canals and prolong the life of nickel-titanium files than at 6°C. When flushing was done at 40°C, the number of root canals prepared by nickel-titanium files was the highest, and it was not easy to damage the instrument, but lateral perforation occurred easily during root canal preparation.


Asunto(s)
Níquel , Titanio , Cavidad Pulpar , Diseño de Equipo , Preparación del Conducto Radicular , Temperatura
19.
Nat Prod Res ; 35(11): 1899-1902, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31328562

RESUMEN

This study was undertaken in order to investigate the antioxidant, anti-inflammatory and antimicrobial activities of various fractions and compounds obtained from the bark of P. hupehensis. The ethyl acetate fraction exhibited strong antioxidant, anti-inflammatory and antimicrobial effects. Six compounds were isolated from this fraction, three of which showed antioxidant activity and anti-inflammatory activity. The biological activities and the active compounds of P. hupehensis were reported for the first time.


Asunto(s)
Juglandaceae/química , Corteza de la Planta/química , Extractos Vegetales/farmacología , Antibacterianos/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Compuestos de Bifenilo/química , Depuradores de Radicales Libres/farmacología , Pruebas de Sensibilidad Microbiana , Picratos/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación
20.
Food Chem ; 321: 126640, 2020 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-32247885

RESUMEN

The oxidation of cold-pressed and commercial refined camellia oil stored at room temperature for one year was comparatively studied by 1H and 31P NMR spectroscopy. The oxidation of extra virgin olive oil (EVOO) under the same conditions was further compared. The 1H NMR showed that no aldehydes were formed in the studied period. Coupled with the changes of unsaturated acyl groups, the oxidation degrees of the three oils could be obtained follow the order: commercial refined camellia oil > cold-pressed camellia oil > EVOO. The 31P NMR showed that the evolution of diacylglycerols (DGs) and ratio D in commercial refined camellia oil was fairly different from other two oils. Besides, the kinetics curves of unsaturated acyl groups and ratio D both fit to an exponential equation with high coefficients which indicated that the oxidation of the studied oils progressed in an exponential way with storage time at room temperature.


Asunto(s)
Camellia/química , Aceites de Plantas/química , Frío , Diglicéridos , Espectroscopía de Resonancia Magnética , Aceite de Oliva/química , Oxidación-Reducción , Presión
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