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OBJECTIVE: The present study aimed to characterize three-dimensional (3D) long-term quantitative condyle change including positional, surface, and volumetric alterations in patients with skeletal class III malocclusion treated with bimaxillary orthognathic surgery. MATERIAL AND METHODS: Twenty-three eligible patients (9 males, 14 females, mean age: 28.28 years old) treated from Jan. 2013 to Dec. 2016 with postoperative follow-up over 5 years were retrospectively enrolled. Cone-beam computed tomography scan for each patient was conducted at 4 stages: 1 week preoperatively (T0), immediately after surgery (T1), 12 months postoperatively (T2), and 5-year postoperatively (T3). Positional changes, surface, and volumetric remodeling of condyle were measured in segmented visual 3D models and statistically compared between stages. RESULTS: Our 3D quantitative calibrations revealed that the condylar center shifted in anterior (0.23 ± 1.50 mm), medial (0.34 ± 0.99), and superior (1.11 ± 1.10 mm) directions and rotated outward (1.58 ± 3.11°), superior (1.83 ± 5.08°), and backward (4.79 ± 13.75°) from T1 to T3. With regard to condylar surface remodeling, bone formation was frequently observed in the anteromedial areas, while bone resorption was commonly detected in the anterolateral area. Moreover, condylar volume remained largely stable with a minimal reduction during the follow-up. CONCLUSION: Collectively, although condyle undergoes positional changes and bone remodeling after bimaxillary surgery in patients with mandibular prognathism, these changes largely fall in the range of physical adaptations in the long run. CLINICAL RELEVANCE: These findings advance the current understanding of long-term condylar remodeling after bimaxillary orthognathic surgery in skeletal class III patients.
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6-Thioguanine (6-TG) is a purine analog anticancer drug used to treat childhood acute leukemia and inflammatory bowel disease; however, the over-dosage use of 6-TG can cause serious adverse effects. Therefore, monitoring the free 6-TG concentration in the human body is critical during drug therapy. In this work, a highly sensitive and rapid fluorescent nanoprobe based on Cu/Ag nanoclusters (NCs) for the detection of 6-TG was developed. The maximum emission wavelength of Cu/Ag NCs was observed at 563 nm with an excitation wavelength of 330 nm. A selective fluorescence quenching effect of 6-TG on the Cu/Ag NCs was found. Under optimum conditions for the determination of 6-TG, a wide linear concentration range from 2.5 to 100 µmol L-1 was observed with a limit of detection (LOD) of 1.57 µmol L-1. The characteristics of simple operation, high sensitivity and selectivity make this fluorescent nanoprobe a promising candidate for the detection of 6-TG in biological samples, as demonstrated by the application in spiked human serum with recoveries of 97.6 to 104.8%. In general, this proposed method has good potential for the detection of 6-TG in biological samples.
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Nanopartículas Metálicas , Humanos , Criança , Tioguanina , Cobre , Prata , Corantes FluorescentesRESUMO
The ability of dendritic cells (DCs) to initiate and regulate adaptive immune responses is fundamental for maintaining immune homeostasis upon exposure to self or foreign antigens. The immune regulatory function of DCs is strictly controlled by their distribution as well as by cytokines, chemokines, and transcriptional programming. These factors work in conjunction to determine whether DCs exert an immunosuppressive or immune-activating function. Therefore, understanding the molecular signals involved in DC-dependent immunoregulation is crucial in providing insight into the generation of organismal immunity and revealing potential clinical applications of DCs. Considering the many breakthroughs in DC research in recent years, in this review we focused on three basic lines of research directly related to the biological functions of DCs and summarized new immunotherapeutic strategies involving DCs. First, we reviewed recent findings on DC subsets and identified lineage-restricted transcription factors that guide the development of different DC subsets. Second, we discussed the recognition and processing of antigens by DCs through pattern recognition receptors, endogenous/exogenous pathways, and the presentation of antigens through peptide/major histocompatibility complexes. Third, we reviewed how interactions between DCs and T cells coordinate immune homeostasis in vivo via multiple pathways. Finally, we summarized the application of DC-based immunotherapy for autoimmune diseases and tumors and highlighted potential research prospects for immunotherapy that targets DCs. This review provides a useful resource to better understand the immunomodulatory signals involved in different subsets of DCs and the manipulation of these immune signals can facilitate DC-based immunotherapy.
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Naïve B cells become activated and differentiate into antibody-secreting plasma cells (PCs) when encountering antigens. Here, we reveal that the WW domain-containing adapter protein with coiled-coil (Wac), which is important for histone H2B ubiquitination (ubH2B), is essential for PC differentiation. We demonstrate that B cell-specific Wac knockout mice have severely compromised T cell-dependent and -independent antibody responses. PC differentiation is drastically compromised despite undisturbed germinal center B cell response in the mutant mice. We also observe a significant reduction in global ubH2B in Wac-deficient B cells, which is correlated with downregulated expression of some genes critical for cell metabolism. Thus, our findings demonstrate an essential role of Wac-mediated ubH2B in PC differentiation and shed light on the epigenetic mechanisms underlying this process.
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Background: Professional identity is crucial for the development of pharmacy students' professional confidence, learning motivation and future career choices. However, how to develop students' professional identity in pharmacy education is an underdeveloped field of research. The critical component of professional identity has been considered formed as a result of stepwise socialization. Therefore, pharmacy professional identity might be influenced by associations with other health care professionals, such as physicians and nurses, who are involved in health care collaboration with pharmacists. Objectives: This work aimed to investigate the effect of a student-led interview intervention called "Pharmacy from the perspectives of other health professions" as an intervention on pharmacy freshmen's perceptions and positivity toward the pharmacy profession. Methods: In this prospective pre/postintervention study, the effect of the interview intervention on students' job preferences as well as attitudes toward the pharmacy profession and pharmacists' role in health care was evaluated among 70 first-year pharmacy undergraduates equally divided into intervention and control groups using a self-developed questionnaire. Results: Compared with the controls, the numbers of respondents reporting no specific reasons for selecting the pharmacy profession and stating that they were unclear about their preferred post-graduation work sector were significantly reduced after the intervention. Participating in the intervention increased the number of students who agreed or strongly agreed that they would have a fulfilling and socially respectable career. Significantly more students in the intervention group agreed with the pharmacists' role in health care as well as the current situation of pharmacy human resources than in the control group. Conclusion: This student-led interview intervention could be applied as an effective tool for improving students' professional identity and positivity in pharmacy education.
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This study provides a novel method of preparing lotus seed starch nanocrystals (LS-SNCs) using acid hydrolysis combined with ultrasonic-assisted acid hydrolysis (U-LS-SNCs) and evaluates the structural characteristics of starch nanocrystals using scanning electron microscopy; analysis of particle size, molecular weight, and X-ray diffraction patterns; and FT-IR spectroscopy. The results showed that the preparation time of U-LS-SNCs could be reduced to 2 days less than that for LS-SNCs. The smallest particle size and molecular weight were obtained after a 30 min treatment with 200 W of ultrasonic power and 5 days of acid hydrolysis. The particle size was 147 nm, the weight-average molecular weight was 3.42 × 104 Da, and the number-average molecular weight was 1.59 × 104 Da. When the applied ultrasonic power was 150 W for 30 min and acid hydrolysis was applied for 3 days, the highest relative crystallinity of the starch nanocrystals was 52.8%. The modified nanocrystals can be more widely used in various applications such as food-packaging materials, fillers, pharmaceuticals, etc.
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Mulberry (Morus alba), a widely distributed economic plant, can withstand long-term flooding stress. However, the regulatory gene network underlying this tolerance is unknown. In the present study, mulberry plants were subjected to submergence stress. Subsequently, mulberry leaves were collected to perform quantitative reverse-transcription PCR (qRT-PCR) and transcriptome analysis. Genes encoding ascorbate peroxidase and glutathione S-transferase were significantly upregulated after submergence stress, indicating that they could protect the mulberry plant from flood damage by mediating ROS homeostasis. Genes that regulate starch and sucrose metabolism; genes encoding pyruvate kinase, alcohol dehydrogenase, and pyruvate decarboxylase (enzymes involved in glycolysis and ethanol fermentation); and genes encoding malate dehydrogenase and ATPase (enzymes involved in the TCA cycle) were also obviously upregulated. Hence, these genes likely played a key role in mitigating energy shortage during flooding stress. In addition, genes associated with ethylene, cytokinin, abscisic acid, and MAPK signaling; genes involved in phenylpropanoid biosynthesis; and transcription factor genes also showed upregulation under flooding stress in mulberry plants. These results provide further insights into the adaptation mechanisms and genetics of submergence tolerance in mulberry plants and could aid in the molecular breeding of these plants.
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Background: A sharp rise in household consumption of disinfectants triggered by COVID-19 pandemic has generated tremendous environmental burden and risks of disinfectant emissions in the post-pandemic period. To address this emerging challenge, replacing highly hazardous disinfectants with more environmental friendly alternatives has been accepted as an inherently effective solution to environment issues posed by disinfectant emerging contaminants. However, no study has yet been done to explore the potential customers' attitudes and the market prospect of environmental friendly disinfectants until now. Methods: This cross-sectional questionnaire-based survey was conducted from January to March, 2022, among resident volunteers in China, to explore the practices, knowledge and attitudes of the public regarding environmental friendly disinfectants for household use. Results: Among a total of 1,861 Chinese residents finally included in the analyses, 18% agreed or strongly agreed that they paid special attention to the environmental certification label on the product, and only bought the environmental certified disinfectant products; 16% and 10% were using environmental friendly disinfectants for hand sanitization and environmental disinfection, respectively. The mean self-assessed and actual knowledge scores were 2.42 ± 1.74 and 2.12 ± 1.97, respectively, out of a total of 5. Participants having good practices of consuming environmental friendly disinfectants achieved higher knowledge scores. Residents' overall attitudes toward the development, consumption and application of environmental friendly disinfectants were very positive. "Possible conflict between disinfection effectiveness and environmental factor of disinfectants in a context of severe COVID-19 pandemic" was considered as the most important barrier jeopardizing the participants' usage intention for environmental friendly disinfectants. Conclusions: These data suggested most residents of China had a positive attitude, poor knowledge and practices toward environmental friendly disinfectants. More should be done to enhance the residents' environmental knowledge levels about disinfectants, and to further develop and promote disinfectant products with both excellent disinfection activity and environmentally friendly attributes.
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COVID-19 , Desinfetantes , Humanos , COVID-19/prevenção & controle , Pandemias , Conhecimentos, Atitudes e Prática em Saúde , Estudos Transversais , ChinaRESUMO
Our current knowledge regarding soil organic matter (SOM) turnover during vegetation succession is often limited to conventional C decomposition models. However, microbial enzyme-mediated SOM degradation and nutrient cycling are mainly reflected in the kinetic parameters of these enzymes. Changes in the composition and structure of plant communities are typically accompanied by alterations in soil ecological functions. Therefore, it is important to clarify the kinetic parameters of soil enzymes and their temperature sensitivity in response to vegetation succession, especially under the current trend of climate change-related global warming; however, these are still understudied. Here, we examined the kinetic parameters of soil enzymes, their temperature sensitivity, and their associations with environmental variables over long-term (approximately 160 years) vegetation succession on the Loess Plateau using a space-for-time substitution method. We found that the kinetic parameters of soil enzymes changed significantly during vegetation succession. Specific response characteristics varied depending on the enzyme. Overall, the temperature sensitivity (Q10, 0.79-1.87) and activation energy (Ea, 8.69-41.49 kJ·mol-1) remained stable during long-term succession. Compared with N-acetyl-glucosaminidase and alkaline phosphatase, ß-glucosidase was more sensitive to extreme temperatures. In particular, two kinetic parameters (i.e., maximum reaction rate, Vmax; half-saturation constant, Km) of ß-glucosidase were decoupled at low (5 °C) and high (35 °C) temperatures. Overall, Vmax was the primary determinant of variations of enzyme catalytic efficiency (Kcat) during succession, and soil total nutrients had a greater impact on Kcat than available nutrients. Our results suggested that soil ecosystems played an increasingly important role as a C source during long-term vegetation succession, as indicated by the positive responses of the C cycling enzyme Kcat, while the factors related to soil N and P cycling remained relatively stable.
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A synchronous crystal- and microstructure-dependent strategy was implemented to synthesize the organic hybrid antimoniotungstate layered ionic crystal Na5.5H6.5[(SbW9O33)2{WO2(OH)}2{WO2}RuC7H3NO4]·36H2O, and the layered structure was constructed through the Na+ bridged sheet and the hydrogen-bonded layers. It displayed an effective proton conductivity of 2.97 × 10-2 S cm-1 at 348 K and 75% RH, owing to the complete interlayer confined hydrogen-bond network formed by the hydrogens of interlayer crystal waters, organic ligands ({RuC7H3NO4}2+, {C7H3NO4} is formed by the hydrolysis of pyridine 2,5-dicarboxylic acid (C7H5NO4)), and acidic protons (H+), along with the interlayer domain as a transport channel. Furthermore, the hydrogen-bond network originating from interlayer organic ligands and acidic protons was more stable at a higher temperature of 423 K, preserving a high conductivity of 1.99 × 10-2 S cm-1.
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A growing body of research recently suggested the association between vestibular dysfunction and cognitive impairment. Meniere's disease (MD), a common clinical vestibular disorder, is usually accompanied by hearing loss and emotional stress, both of which may mediate the relationship between vestibule dysfunction and cognition. It is currently unknown whether the cognitive decline in MD patients could improve through treatment and how it relates to multiple clinical characteristics, particularly the severity of vertigo. Therefore, in the present study, the MD patients were followed up for 3, 6, and 12 months after treatment, and the cognitive functions, vertigo symptoms, and related physical, functional, and emotional effects of the patients were assessed using the Montreal Cognitive Assessment (MoCA) and Dizziness Handicap Inventory (DHI), aiming to explore the change in cognition before and after therapy and the correlation with various clinical features. It was found that cognitive decline in MD patients compared to healthy controls before therapy. Importantly, this cognitive impairment could improve after effective therapy, which was related to the severity of vertigo, especially in functional and physical impacts. Our results support the view that vestibular dysfunction is a potentially modifiable risk factor for cognitive decline.
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BACKGROUND: Orthognathic surgery has been performed with increasing frequency for the treatment of severe malocclusion, yet the postsurgical neuromuscular recovery of patients has been inadequately studied. OBJECTIVE: To investigate the effect of short-term and simple jaw motor training on accuracy and precision of jaw motor control in patients following orthodontic treatment and orthognathic surgery. METHODS: Twenty patients who had completed preoperative orthodontics, 20 patients who had undergone bimaxillary orthognathic surgery and 20 age-and-gender-matched healthy controls participated in the study. Participants were asked to perform 10 continuous jaw opening and finger lifting movements before and after a 30-min motor training session. The variability in the amplitude of these simple movements was expressed as percentage in relation to the target position (accuracy - Daccu ) and as coefficient of variation (precision - CVprec ) to describe the motor performance. Furthermore, the changes in amplitude before and after training were measured in percentage. RESULTS: Daccu and CVprec of simple jaw and finger movements significantly decreased after motor training (p ≤ .018) in all groups. The relative changes in finger movements were higher than jaw movements (p < .001) but with no differences among the groups (p ≥ .247). CONCLUSION: Both accuracy and precision of simple jaw and finger movements improved after short-term motor training in all three groups, demonstrating the inherent potential for optimization of novel motor tasks. Finger movements improved more than jaw movements but with no differences between groups, suggesting that changes in occlusion and craniofacial morphology are not associated with impaired neuroplasticity or physiological adaptability of jaw motor function.
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AIMS: To investigate whether recurrent gestational diabetes mellitus (GDM) is associated with an increased risk of preterm birth. METHODS: We conducted a prospective population-based cohort study covering all live singleton births born to nulliparous and multiparous mothers aged 20 years and older in Qingdao, from 2018 to 2020 (n = 105,528). Preterm birth (<37 gestational weeks) was classified into moderate preterm birth (32-36 weeks of gestation) and very preterm birth (<32 weeks). Logistic regression analysis was performed to estimate the risk and severity of prematurity in relation to parity among mothers with previous GDM, current GDM, and recurrent GDM (previous and current GDM), using mothers without GDM as the reference group. Z-test and ratio of odds ratios (ROR) were used to determine subgroup differences. RESULTS: Maternal GDM increased the risk of preterm birth in both nullipara (ORadj = 1.28, 95 %CI: 1.14-1.45) and multipara (ORadj = 1.26, 95 %CI: 1.14-1.40). However, the risk of premature delivery in multiparous mothers with recurrent GDM and those with current GDM did not differ significantly, with a ROR of 0.89 (95 %CI: 0.71-1.12). The risk of recurrent GDM on preterm birth was most pronounced among multiparous mothers with pre-pregnancy BMI above 30 kg/m2 (ORadj = 2.18, 95 %CI: 1.25-3.82) as compared with those with current GDM alone (ROR = 2.20, 95 %CI: 1.07-4.52). The risk of GDM for moderate preterm birth was similar to that of overall preterm birth. In contrast, GDM was not associated with very preterm birth irrespective of parity (all P values > 0.05). CONCLUSIONS: Maternal GDM increased the risk of preterm birth in nullipara and multipara, whereas recurrent GDM was not associated with a further increase in the risk of prematurity in multiparous mothers. Maternal GDM did not contribute to very preterm birth irrespective of parity. Our findings can be useful for facilitating more targeted preventive strategies for adverse pregnancy outcomes.
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Diabetes Gestacional , Doenças do Recém-Nascido , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/etiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos de Coortes , Estudos Prospectivos , Resultado da GravidezRESUMO
Objective: Adenoid hypertrophy (AH) and otitis media with effusion (OME) are common pediatric otolaryngological diseases and often occur concurrently. The purpose of this study was to comprehensively analyze the factors that influence the occurrence of OME pediatric patients with AH. Methods: Patients younger than 12 years with AH, who were hospitalized for treatment at Beijing Tsinghua Changgung Hospital in Beijing, China, between March 2018 and February 2022 were enrolled. The patients were divided into an AH group and an AH + OME group based on the presence of OME. The authors collected the following clinical data for univariable analysis: sex; age; body mass index (BMI); comorbid nasal congestion/rhinorrhea, recurrent tonsillitis, or allergic rhinitis (AR); adenoid and tonsil grade; tonsillar hypertrophy; food/drug allergy; history of adenoidectomy and congenital diseases; breastfeeding status; preterm birth; exposure to environmental tobacco smoke (ETS); family history of adenotonsillectomy, otitis media, and AR; main data of polysomnography and oropharyngeal conditional pathogen culture data of some patients. Univariate analysis was performed as a basis for logistic regression analysis. Results: A total of 511 children (329 boys and 182 girls) were included, their mean age was 5.37 ± 2.10 years. Of them, 407 (79.6%) were in the AH group and 104 (20.4%) in the AH + OME group. Univariate analysis revealed statistically significant differences in age, BMI, adenoid grade, AR, breastfeeding status, and ETS exposure between the two groups. Multivariate stepwise logistic regression analysis showed that age, adenoid grade, AR, breastfeeding status, and ETS influenced the occurrence of OME in pediatric patients with AH. The risk of OME decreased with increasing age. High adenoid grade, ETS exposure, and comorbid AR were risk factors for OME in pediatric patients with AH, but breastfeeding was a protective factor. The final analytical results of the oropharyngeal conditional pathogen culture data showed that Streptococcus pneumoniae positivity was associated with OME in AH. Conclusion: The pathogenesis of AH with OME is complex. Young age, high adenoid grade, ETS exposure, non-breastfed status, comorbid AR, and the presence of S. pneumoniae in the oropharynx are risk factors for OME in pediatric patients with AH.
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Background: The issue of whether a stroke is causally related to gastrointestinal disorders was still not satisfactorily understood. Therefore, we investigated if there is a connection between stroke and the most prevalent gastrointestinal disorders, including peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Methods: We applied two-sample Mendelian randomization to investigate relationships with gastrointestinal disorders. We obtained genome-wide association study (GWAS) summary data of any stroke, ischemic stroke, and its subtypes from the MEGASTROKE consortium. From the International Stroke Genetics Consortium (ISGC) meta-analysis, we acquired GWAS summary information on intracerebral hemorrhage (ICH), including all ICH, deep ICH, and lobar ICH. Several sensitivity studies were performed to identify heterogeneity and pleiotropy, while inverse-variance weighted (IVW) was utilized as the most dominant estimate. Results: No evidence for an effect of genetic predisposition to ischemic stroke and its subtypes on gastrointestinal disorders were found in IVW. The complications of deep ICH are a higher risk for PUD and GERD. Meanwhile, lobar ICH has a higher risk of complications for PUD. Conclusion: This study provides proof of the presence of a brain-gut axis. Among the complications of ICH, PUD and GERD were more common and associated with the site of hemorrhage.
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OBJECTIVE: Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. METHODOLOGY: We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. RESULTS: We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. CONCLUSION: We found that PAX9 variants commonly lead to loss of the second molars.
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Anodontia , População do Leste Asiático , Humanos , Anodontia/genética , Mutação de Sentido Incorreto , Fenótipo , Genótipo , Fator de Transcrição PAX9/genética , LinhagemRESUMO
The T cell-dependent (TD) antibody response involves the generation of high affinity, immunoglobulin heavy chain class-switched antibodies that are generated through germinal center (GC) response. This process is controlled by coordinated transcriptional and post-transcriptional gene regulatory mechanisms. RNA-binding proteins (RBPs) have emerged as critical players in post-transcriptional gene regulation. Here we demonstrate that B cell-specific deletion of RBP hnRNP F leads to diminished production of class-switched antibodies with high affinities in response to a TD antigen challenge. B cells deficient in hnRNP F are characterized by defective proliferation and c-Myc upregulation upon antigenic stimulation. Mechanistically, hnRNP F directly binds to the G-tracts of Cd40 pre-mRNA to promote the inclusion of Cd40 exon 6 that encodes its transmembrane domain, thus enabling appropriate CD40 cell surface expression. Furthermore, we find that hnRNP A1 and A2B1 can bind to the same region of Cd40 pre-mRNA but suppress exon 6 inclusion, suggesting that these hnRNPs and hnRNP F might antagonize each-other's effects on Cd40 splicing. In summary, our study uncovers an important posttranscriptional mechanism regulating the GC response.
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Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B , Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H , Sequência de Bases , Centro Germinativo/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Íntrons , Precursores de RNA/genética , Precursores de RNA/metabolismo , Linfócitos BRESUMO
Targeted therapy attempts are needed to enhance esophageal squamous cell carcinoma (ESCC) patients' overall survival and satisfaction of life. Nuclear factor erythroid 2-related factor 2 (NRF2), as a high-confidence cancer driver gene, controls the antioxidant response, metabolic balance and redox homeostasis in cancer and is regarded as a potent molecular target for cancer treatment. Here, we attempted to find a new NRF2 inhibitor and study the underlying molecular mechanism in ESCC. We found that up-regulated NRF2 protein was negatively correlated with patient prognosis and promoted tumor proliferation in ESCC. Moreover, Pizotifen malate (PZM), a FDA-approved medication, bound to the Neh1 domain of NRF2 and prevented NRF2 protein binding to the ARE motif of target genes, suppressing transcription activity of NRF2. PZM treatment suppressed tumor development in ESCC PDX model by inducing ferroptosis via down-regulating the transcription of GPX4, GCLC, ME1 and G6PD. Our study illustrates that the over expression of NRF2 indicates poor prognosis and promotes tumor proliferation in ESCC. PZM, as a novel NRF2 inhibitor, inhibits the tumor growth by inducing ferroptosis and elucidates a potent NRF2-based therapy strategy for patients with ESCC.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Ferroptose , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/genética , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Malatos/uso terapêutico , Pizotilina/uso terapêutico , Carcinoma de Células Escamosas/patologia , Ferroptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão GênicaRESUMO
PURPOSE: Readmission is one of the measures of quality of care and potential costs. This study aimed to determine whether lactate dehydrogenase (LDH) is associated with an increased risk of 30-day readmission in gastric cancer. METHODS: We performed a retrospective study of patients who underwent radical gastrectomy for gastric cancer at our institution between July 2014 and May 2018. Balanced cohorts were created by propensity score matching (PSM) with a 1:1 ratio to generate the elevated LDH (ELDH) group (n = 151) and the low LDH group (Control) (n = 302). To determine the incidence, causes, and risk factors of 30-day readmission, subgroup analyzes were performed and used to develop an efficient prediction model. RESULTS: A total of 788 patients met the criteria to be included in the study. The cutoff value for serum LDH was 215.5. After PSM, a total of 302 patients were matched in pairs (ELDH group, n = 151, Control group, n = 151). ELDH levels had a higher risk of readmission (p = 0.005, Odds ratio 3.768, 95% confidence interval 1.493-9.510). The pre-match 30-day readmission rate was 7.2 percent, and common causes of post-match readmission included infection-related symptoms, gastrointestinal symptoms, and gastrointestinal bleeding. CONCLUSIONS: Patients with preoperative ELDH levels, postoperative complications, and high preoperative American Society of Anesthesiologists Scores had a higher risk of readmission 30 days after surgery.
