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BACKGROUND: The function of kallistatin in airway inflammation, particularly chronic rhinosinusitis with nasal polyps (CRSwNP), has not been elucidated. OBJECTIVE: We sought to investigate the role of kallistatin in airway inflammation. METHODS: Kallistatin and proinflammatory cytokine expression levels were detected in nasal polyps. For the in vivo studies, we constructed the kallistatin-overexpressing transgenic mice to elucidate the role of kallistatin in airway inflammation. Furthermore, the levels of plasma IgE and proinflammatory cytokines in the airways were evaluated in the kallistatin-/- rat in vivo model under a type 2 inflammatory background. Finally, the Notch signaling pathway was explored to understand the role of kallistatin in CRSwNP. RESULTS: We showed that the expression of kallistatin was significantly higher in nasal polyps than in the normal nasal mucosa and correlated with IL-4 expression. We also discovered that the nasal mucosa of kallistatin-overexpressing transgenic mice expressed higher levels of IL-4 expression, associating to TH2-type inflammation. Interestingly, we observed lower IL-4 levels in the nasal mucosa and lower total plasma IgE of the kallistatin-/- group treated with house dust mite allergen compared with the wild-type house dust mite group. Finally, we observed a significant increase in the expression of Jagged2 in the nasal epithelium cells transduced with adenovirus-kallistatin. This heightened expression correlated with increased secretion of IL-4, attributed to the augmented population of CD4+CD45+Notch1+ T cells. These findings collectively may contribute to the induction of TH2-type inflammation. CONCLUSIONS: Kallistatin was demonstrated to be involved in the CRSwNP pathogenesis by enhancing the TH2 inflammation, which was found to be associated with more expression of IL-4, potentially facilitated through Jagged2-Notch1 signaling in CD4+ T cells.
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Linfocitos T CD4-Positivos , Mucosa Nasal , Rinosinusitis , Serpinas , Células Th2 , Animales , Femenino , Humanos , Masculino , Ratones , Ratas , Linfocitos T CD4-Positivos/inmunología , Quimiotaxis de Leucocito/inmunología , Enfermedad Crónica , Citocinas/metabolismo , Inmunoglobulina E/inmunología , Inmunoglobulina E/sangre , Inflamación/inmunología , Interleucina-4/inmunología , Interleucina-4/metabolismo , Ratones Transgénicos , Mucosa Nasal/inmunología , Mucosa Nasal/metabolismo , Pólipos Nasales/inmunología , Rinosinusitis/inmunología , Serpinas/inmunología , Serpinas/genética , Serpinas/metabolismo , Transducción de Señal , Células Th2/inmunologíaRESUMEN
Obstruction is inevitable and will significantly impact the actual output performance of photovoltaic modules, even jeopardize their operational safety. We introduced a layer of bubbles into photovoltaic glass. These bubbles can alter the path of incident light, while the internal reflection at the glass/air interface enables the redirected light rays to have longer lateral propagation distance, circumventing the obstructions. The optimized photovoltaic glass with a bubble diameter of 1.8 mm and a surface density of 16â cm-2 enables the light intensity underneath a 6.6 × 6.6 cm2 obstruction to reach 21.83% of the incident light intensity. This enhancement permits a partial shading of the photovoltaic module, increasing its output power by â¼20.8% and decreasing the reverse bias voltage on the shaded cell by â¼1.4â V.
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OBJECTIVES: To explore the effect of intranasal administration of recombinant human basic fibroblast growth factor (rh-bFGF) on postoperative chronic rhinosinusitis with nasal polyps (CRSwNP) patients. DESIGN: A prospective, randomised, controlled, single-blinded trial. SETTING AND PARTICIPANTS: Seventy-five hospitalised patients who met the criteria of primary bilateral CRSwNP were enrolled from March 2020 to January 2021. MAIN OUTCOME MEASURES: Visual analogue scale, 22-item Sino-Nasal Outcome Test, Lund-Kennedy (L-K) system and scanning electron microscopy and quantitative real-time polymerase chain reaction. RESULTS: Seventy-five patients with CRSwNP were randomly assigned to three groups, and 72 patients completed the 1-month medication regimen and 1-year follow-up. Rh-bFGF nasal-spray and drop application reduced general nasal VAS scores within 2 weeks after endoscopic sinus surgery (ESS) compared to the control group. In contrast, only rh-bFGF nasal-drops reduced SNOT-22 scores at 2 weeks and 1 year compared with the control group. A significant reduction in the endoscopic L-K score was observed in the rh-bFGF nasal-spray and drop group compared with the control group. This is primarily because rh-bFGF promotes cilia growth in the nasal mucosal epithelium after the operation, as illustrated by scanning electron microscopy and expression of CP110, Tap73 and Foxj1 mRNA. For eosinophilic CRSwNP, the general VAS score of rh-bFGF nasal-drops was more obviously reduced compared to the control group after ESS. A similar trend was observed for L-K score. CONCLUSIONS: Rh-bFGF nasal-drops and sprays can quickly and effectively relieve postoperative symptoms and improve long-term prognosis of patients with CRSwNP. Moreover, rh-bFGF nasal-drops is also an effective method for postoperative patients with eosinophilic CRSwNP.
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Pólipos Nasales , Rinitis , Sinusitis , Humanos , Pólipos Nasales/complicaciones , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/cirugía , Estudios Prospectivos , Rinitis/complicaciones , Rinitis/tratamiento farmacológico , Rinitis/cirugía , Sinusitis/complicaciones , Sinusitis/tratamiento farmacológico , Sinusitis/cirugía , Mucosa Nasal , Rociadores Nasales , Enfermedad Crónica , EndoscopíaRESUMEN
BACKGROUND: Deep neck space abscess (DNSA) is a serious infection in the head and neck. Antibiotic therapy is an important treatment in patients with DNSA. However, the results of bacterial culture need at least 48 h, and the positive rate is only 30-50%, indicating that the use of empiric antibiotic treatment for most patients with DNSA should at least 48 h or even throughout the whole course of treatment. Thus, how to use empiric antibiotics has always been a problem for clinicians. This study analyzed the distribution of bacteria based on disease severity and clinical characteristics of DNSA patients, and provides bacteriological guidance for the empiric use of antibiotics. METHODS: We analyzed 433 patients with DNSA who were diagnosed and treated at nine medical centers in Guangdong Province between January 1, 2015, and December 31, 2020. A nomogram for disease severity (mild/severe) was constructed using least absolute shrinkage and selection operator-logistic regression analysis. Clinical characteristics for the Gram reaction of the strain were identified using multivariate analyses. RESULTS: 92 (21.2%) patients developed life-threatening complications. The nomogram for disease severity comprised of seven predictors. The area under the receiver operating characteristic curves of the nomogram in the training and validation cohorts were 0.951 and 0.931, respectively. In the mild cases, 43.2% (101/234) had positive culture results (49% for Gram-positive and 51% for Gram-negative strains). The positive rate of cultures in the patients with severe disease was 63% (58/92, 37.9% for Gram-positive, and 62.1% for Gram-negative strains). Diabetes mellitus was an independent predictor of Gram-negative strains in the mild disease group, whereas gas formation and trismus were independent predictors of Gram-positive strains in the severe disease group. The positivity rate of multidrug-resistant strains was higher in the severe disease group (12.1%) than in the mild disease group (1.0%) (P < 0.001). Metagenomic sequencing was helpful for the bacteriological diagnosis of DNSA by identifying anaerobic strains (83.3%). CONCLUSION: We established a DNSA clinical severity prediction model and found some predictors for the type of Gram-staining strains in different disease severity cases. These results can help clinicians in effectively choosing an empiric antibiotic treatment.
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Absceso , Cuello , Absceso/tratamiento farmacológico , Absceso/microbiología , Antibacterianos/uso terapéutico , Humanos , Metagenómica , Cuello/microbiología , Índice de Severidad de la EnfermedadRESUMEN
Subhani et al. found that Sm-doping in CsPbIBr2 decreased its bandgap from 2.05 eV to 1.8 eV; thus, the efficiency of CsPbIBr2 solar cells was improved by â¼30%. However, Sm is a vital strategic resource with high costs. Metal Sn is much more abundant and cheaper than Sm; meanwhile, it has been proven that Sn can adjust the bandgap of CsPbIBr2 in a broader range, 2.05 eV to 1.64 eV. Therefore, Sn-doping in CsPbIBr2 may improve the efficiency of CsPbIBr2 solar cells, even to a greater extent. In this work, we established the TiO2/CsPbIBr2 interface model by gradient Sn-doping in CsPbIBr2 and investigated the impacts of such gradient doping on the carrier separation behaviors at the TiO2/CsPbIBr2 interface from the aspects of the cross-interface electric field, bandgap, and band matching, based on first-principles calculations. It is found that gradient Sn-doping can transfer more electrons from TiO2 to perovskites, thus creating an enhanced cross-interface electric field conducive to the separation of carriers at the TiO2/CsPbIBr2 interface. Affected by the existence of the interface, the bandgap of each perovskite layer gradually increases as it moves away from the interface; in addition, due to the gradient Sn-doping, the steps between the bandgaps of adjacent perovskite layers become smaller and more uniform, which is favorable for the separation of electrons. In summary, gradient Sn-doping can improve the carrier separation at the TiO2/CsPbIBr2 interface.
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PURPOSE: An investigation of arthroscopic surgery combined with coverage of the microfractured wound surface with platelet-rich plasma (PRP) and fibrin gels (FG) to treat knee cartilage defects. METHODS: Between February 2017 and February 2020, 145 patients with knee cartilage defects were treated. Only isolated full-thickness cartilage defects were included, and 28 patients (12 men and 16 women) were included in this study. They were all treated with arthroscopic surgery on subchondral bones, filled with PRP and thrombin, and sealed with FG. The knee pain visual analogue scale (VAS) scores were measured after the patients climbed ten stairs up and down, and the Western Ontario and McMaster Universities osteoarthritis index and the area of cartilage defects were measured through the pre-operative and post-operative follow-up. The complication incidences were also observed. RESULTS: All patients were followed up for ten to 15 months (median 12 months). The knee pain VAS scores decreased from 6.57 ± 1.07 pre-operatively to 2.09 ± 1.35 at the last follow-up. The WOMAC osteoarthritis index decreased from 44.32 ± 3.95 (mean ± sd) pre-operatively to 16.57 ± 2.20 by the last follow-up. The cartilage defect decreased from 2.93 ± 0.65 cm2 pre-operatively to 1.09 ± 0.69 cm2 at the last follow-up. All scores showed statistically significant improvements after surgery (p < 0.05). No complications were observed. CONCLUSION: The combination therapy of arthroscopic surgery and covering the microfractured wound surface with PRP and FG can repair knee cartilage defects, relieve pain, and improve function, and is a safe and effective treatment.
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Enfermedades de los Cartílagos , Cartílago Articular , Fracturas por Estrés , Osteoartritis de la Rodilla , Plasma Rico en Plaquetas , Artroscopía , Enfermedades de los Cartílagos/cirugía , Cartílago Articular/cirugía , Femenino , Fibrina , Geles , Humanos , Imagen por Resonancia Magnética , Masculino , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/terapia , Dolor , Resultado del TratamientoRESUMEN
OBJECTIVES: To assess the impact of risk factors on the disease control among chronic rhinosinusitis (CRS) patients, following 1 year of functional endoscopic sinus surgery (FESS), and combining the risk factors to formulate a convenient, visualised prediction model. DESIGN: A retrospective and nonconcurrent cohort study. SETTING AND PARTICIPANTS: A total of 325 patients with CRS from June 2018 to July 2020 at the First Affiliated Hospital of Sun Yat-sen University, the Third Affliated Hospital of Sun Yat-sen University, the Seventh Affiliated Hospital of Sun Yat-sen University. MAIN OUTCOMES MEASURES: Outcomes were time to event measures: the disease control of CRS after surgery 1 year. The presence of nasal polyps, smoking habits, allergic rhinitis (AR), the ratio of tissue eosinophil (TER) and peripheral blood eosinophil count (PBEC) and asthma was assessed. The logistic regression models were used to conduct multivariate and univariate analyses. Asthma, TER, AR, PBEC were also included in the nomogram. The calibration curve and area under curve (AUC) were used to evaluate the forecast performance of the model. RESULTS: In univariate analyses, most of the covariates had significant associations with the endpoints, except for age, gender and smoking. The nomogram showed the highest accuracy with an AUC of 0.760 (95% CI, 0.688-0.830) in the training cohort. CONCLUSIONS: In this cohort study that included the asthma, AR, TER, PBEC, which had significantly affected the disease control of CRS after surgery. The model provided relatively accurate prediction in the disease control of CRS after FESS and served as a visualised reference for daily diagnosis and treatment.
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Asma , Pólipos Nasales , Rinitis Alérgica , Rinitis , Sinusitis , Asma/complicaciones , Enfermedad Crónica , Estudios de Cohortes , Humanos , Pólipos Nasales/complicaciones , Pólipos Nasales/diagnóstico , Pólipos Nasales/cirugía , Estudios Retrospectivos , Rinitis/complicaciones , Rinitis/diagnóstico , Rinitis/cirugía , Rinitis Alérgica/complicaciones , Factores de Riesgo , Sinusitis/diagnóstico , Sinusitis/etiología , Sinusitis/cirugíaRESUMEN
BACKGROUND: Increasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established. METHODS: This study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were included. The Pearson's chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p-value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram. RESULTS: The c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups. CONCLUSIONS: The nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.
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Estesioneuroblastoma Olfatorio/mortalidad , Nomogramas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de SupervivenciaRESUMEN
Pulmonary arterial hypertension (PAH) is characterized by persistent pulmonary vasoconstriction and pulmonary vascular remodeling. The pathogenic mechanisms of PAH remain to be fully clarified and measures of effective prevention are lacking. Recent studies; however, have indicated that epigenetic processes may exert pivotal influences on PAH pathogenesis. In this review, we summarize the latest research findings regarding epigenetic regulation in PAH, focusing on the roles of non-coding RNAs, histone modifications, ATP-dependent chromatin remodeling and DNA methylation, and discuss the potential of epigenetic-based therapies for PAH.
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Epigénesis Genética , Hipertensión Pulmonar/genética , Animales , Ensamble y Desensamble de Cromatina , Metilación de ADN , Código de Histonas , Humanos , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , ARN no Traducido/genética , ARN no Traducido/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Recent studies suggest that epithelial cell (EC)-derived cytokines contribute to allergic airway disease exacerbation. OBJECTIVE: To confirm our hypothesis that atopic dendritic cells (DCs) are activated to up-regulate the receptors of cytokines that mainly derived from ECs and enhance TH2 responses. METHODS: The expressions of interleukin 17 receptor B (IL-17RB) (IL-25 receptor), membrane-bound ST2 (IL-33 receptor), thymic stromal lymphopoietin receptor (TSLPR), granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR), and several functional markers on CD1c+ monocyte-derived DCs (mo-DCs) were detected by flow cytometry. Lipopolysaccharide (LPS)-activated mo-DCs were cocultured with autologous CD4+ T cells, and cytokine production by these T cells was determined by intracellular flow cytometry. RESULTS: LPS activated both nonatopic and atopic mo-DCs to express a higher level of GM-CSFR but only activated atopic mo-DCs to express increased IL-17RB, which was subsequently activated by IL-25 involved with signal transducer and activator of transcription 5 phosphorylation. In addition, LPS increased the expression of the OX40 ligand (OX40L) but decreased inducible costimulator ligand on atopic CD86+ mo-DCs. More importantly, IL-25 further up-regulated OX40L on atopic CD86+ mo-DCs. After coculturing with LPS-activated mo-DCs from atopic individuals, CD4+ T cells had enhanced inflammatory responses by increased production of IL-4, IL-5, IL-13, and interferon γ (IFN-γ). In contrast, further addition of IL-25 led CD4+ T cells to produce higher level of IL-4 but lower level of IFN-γ. CONCLUSION: Atopic IL-17RB+ DCs can be up-regulated by LPS and promote a TH2-type response, implying that the IL-25/IL-17RB pathway may represent a potential molecular mechanism underlying the regulation of ECs on DCs in allergic airway disease.
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Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Hipersensibilidad Inmediata/inmunología , Hipersensibilidad Inmediata/metabolismo , Lipopolisacáridos/inmunología , Receptores de Interleucina-17/metabolismo , Células Th2/inmunología , Adulto , Alérgenos , Biomarcadores , Estudios de Casos y Controles , Citocinas/metabolismo , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Inmunofenotipificación , Activación de Linfocitos/inmunología , Masculino , Monocitos/inmunología , Monocitos/metabolismo , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Células Th2/metabolismo , Adulto JovenRESUMEN
Adult mesenchymal stem cells (MSCs) are immunoprivileged cells due to the low expression of major histocompatibility complex (MHC) II molecules. However, the expression of MHC molecules in human-induced pluripotent stem cells (iPSCs)-derived MSCs has not been investigated. Here, we examined the expression of human leukocyte antigen (HLA) in human MSCs derived from iPSCs, fetuses, and adult bone marrow (BM) after stimulation with interferon-γ (IFN-γ), compared their repair efficacy, cell retention, inflammation, and HLA II expression in immune humanized NOD Scid gamma (NSG) mice of hind limb ischemia. In the absence of IFN-γ stimulation, HLA-II was expressed only in BM-MSCs after 7 days. Two and seven days after stimulation, high levels of HLA-II were observed in BM-MSCs, intermediate levels were found in fetal-MSCs, and very low levels in iPSC-MSCs. The levels of p-STAT1, interferon regulatory factor 1, and class II transactivator exhibited similar phenomena. Moreover, p-STAT1 antagonist significantly reversed the high expression of HLA-II in BM-MSCs. Compared to adult BM-MSCs, transplanting iPSC-MSCs into hu-PBMNC NSG mice revealed markedly more survival iPSC-MSCs, less inflammatory cell accumulations, and better recovery of hind limb ischemia. The expression of HLA-II in MSCs in the ischemia limbs was detected in BM-MSCs group but not in iPSC-MSCs group at 7 and 21 days after transplantation. Our results demonstrate that, compared to adult MSCs, human iPSC-MSCs are insensitive to proinflammatory IFN-γ-induced HLA-II expression and iPSC-MSCs have a stronger immune privilege after transplantation. It may attribute to a better therapeutic efficacy in allogeneic transplantation.
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Miembro Posterior/irrigación sanguínea , Antígenos de Histocompatibilidad Clase II/biosíntesis , Células Madre Pluripotentes Inducidas/metabolismo , Interferón gamma/farmacología , Isquemia/terapia , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Animales , Xenoinjertos , Humanos , Isquemia/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones SCIDRESUMEN
BACKGROUND: Chronic rhinosinusitis (CRS) is defined as a condition of inflammation in the paranasal sinus mucosa persisting for more than 12 weeks. We previously reported that the prevalence of CRS was about 8 % in China. Here, we aim to investigate the occupational and environmental risk factors associated with CRS. METHODS: Data were collected from seven Chinese cities: Urumqi, Changchun, Beijing, Wuhan, Chengdu, Huaian and Guangzhou. CRS was diagnosed according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EP(3)OS) document. Participants were asked to complete a standardized questionnaire, which was developed by the Global Allergy and Asthma European Network (GA(2)LEN) project and covered sociodemographic characteristics, CRS-related symptoms and occupational and environmental exposures. We evaluated the association between CRS and various occupational and environmental factors using odds ratios (ORs) and 95 % confidence intervals (95 % CIs). RESULTS: The total study population consisted of 10,633 subjects, 850 (7.99 %) of whom were defined as having CRS according to the EP(3)OS criteria. We found that there were significant associations between occupational and environmental factors and CRS. Specifically, having a clearance-related job, occupational exposure to dust, occupational exposure to poisonous gas, a pet at home or carpet at home or at the workplace were risk factors for CRS. Additionally, the method used to keep warm in winter, the duration of time spent using air conditioning in summer and the frequency of exposure to mouldy or damp environments were significantly different in subjects with and without CRS. CONCLUSIONS: Our data showed that some occupational and environmental exposures are strongly associated with CRS, which aids in understanding the epidemiology of CRS.
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Contaminación del Aire Interior , Exposición por Inhalación/efectos adversos , Pólipos Nasales/epidemiología , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Salud Laboral , Rinitis/epidemiología , Sinusitis/epidemiología , Adolescente , Adulto , Distribución de Chi-Cuadrado , Niño , Preescolar , China/epidemiología , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pólipos Nasales/diagnóstico , Enfermedades Profesionales/diagnóstico , Oportunidad Relativa , Prevalencia , Rinitis/diagnóstico , Factores de Riesgo , Sinusitis/diagnóstico , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Chronic mountain sickness (CMS), originally characterized by excess hemoglobin (Hb), is currently diagnosed using score-based diagnostic criteria combined with excessive erythrocytosis and clinical symptoms. However, the current criteria have limited applicability. We applied these criteria to 1,029 Chinese Han males migrated to and have been stayed at the Qinghai-Tibet plateau (3,700-5,000 m) for 2-96 months to investigate the prevalence of CMS and its correlations with Hb concentration, altitude, and the length of residence. METHODS: Subjects were screened for CMS using the latest approved diagnostic criteria combined with excessive erythrocytosis and clinical symptoms. Hb concentrations were measured, and a cut-off point was determined with k-means clustering. Predisposing factors were evaluated with binary logistic analysis and curve fitting analysis. RESULTS: (1) The prevalence of CMS at the Qinghai-Tibetan plateau was 17.8% (183/1029 subjects, with CMS score ≥ 6, and Hb ≥ 210 g/L), which is higher than that previously reported. (2) While individuals were identified into two Hb clusters with a cut-off point of 200 g/L, in the low-Hb cluster (Hb < 200 g/L), the oxygen saturation remained stable as the Hb increased; in the high-Hb cluster (Hb ≥ 200 g/L), the oxygen saturation decreased as the Hb increased. (3) Two critical factors associated with CMS development were residence at an altitude of 4,500 m and a 60-month length of residence. CONCLUSIONS: Our presenting scoring system is more sensitive than previous diagnostic criteria and favors early screening and treatment of patients with CMS. Our finding suggests that an adjusted Hb threshold of 200 g/L (instead of 210 g/L) is more adaptable in Han individuals at all altitudes. The weight of Hb level should score ≥ 6 points using the CMS scoring system because of the pathophysiologic role of excessive erythrocytosis in patients with CMS. In addition, our data suggest the importance of early screening of CMS via regular medical examinations within the first 60 months of residence at high altitudes, especially >4500 m.
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Adaptación Fisiológica , Mal de Altura/diagnóstico , Altitud , Hemoglobinas/metabolismo , Oxígeno/sangre , Adulto , Mal de Altura/sangre , Pueblo Asiatico , China/epidemiología , Enfermedad Crónica , Etnicidad , Humanos , Hipoxia , Masculino , Tamizaje Masivo , Enfermedades Profesionales , Policitemia/diagnóstico , Policitemia/etiología , Prevalencia , Valores de Referencia , Tibet/epidemiología , Migrantes , Adulto JovenAsunto(s)
Corticoesteroides/administración & dosificación , Interleucina-17/metabolismo , Pólipos Nasales/tratamiento farmacológico , Nariz/efectos de los fármacos , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Adulto , Enfermedad Crónica , Femenino , Humanos , Masculino , Pólipos Nasales/metabolismo , Rinitis/metabolismo , Sinusitis/metabolismoRESUMEN
N-Succinyl amino acids (N-Suc-AAs) are garnering attention for their potential as taste-active compounds. The intricate variety of N-Suc-AAs presented considerable challenges in identifying those with taste-active properties. Consequently, we employed structure-based virtual screening to pinpoint taste-active N-Suc-AAs, revealing N-succinyl-L-tryptophan (ST) as a compound with high affinity for different taste receptors. Following this discovery, ST was synthesized through an enzymatic process, achieving a yield of 40.2%, with its structure verified via NMR spectroscopy. Sensory evaluation alongside electronic tongue assessments indicated that ST at a concentration of 1 mg/L significantly enhances umami, kokumi, and saltiness intensities, while concurrently mitigating bitterness from various bitter compounds, whilst itself remaining tasteless. Additionally, time-intensity (TI) results elucidated a marked augmentation in umami duration and a notable diminution in bitterness duration for solutions imbued with 1 mg/L ST. Molecular docking study suggested ST interacted with diverse taste receptors as an agonist or antagonist, primarily through hydrogen bonds and hydrophobic interactions. This study marked the inaugural report on the enzymatic synthesis of ST and its efficacy in improving taste characteristics, underscoring the importance of ST in improving sensory qualities of food products and fostering innovation within the seasoning industry.
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Simulación del Acoplamiento Molecular , Gusto , Triptófano , Humanos , Triptófano/química , Aromatizantes/química , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Adulto , Masculino , Papilas Gustativas/química , FemeninoRESUMEN
N-lauroyl-L-tryptophan (LT), which has the strongest potential flavor-presenting activity, was skillfully screened from numerous N-Lau-AAs docked to different taste receptors by molecular simulation techniques. Subsequently, LT was synthesized employing food-grade commercial enzymes and structurally characterized, the optimized yields of LT could reach 69.08%, 76.16%, and 50.40%, respectively. Sensory and E-tongue evaluations showed that LT at 1 mg/L significantly benefited the performance of different taste sensations and exhibited different bitter taste masking effects: L-Ile (68.42%), L-Trp (68.18%), D-salicylic acid (48.48%) and quinine (35.00%). The molecular docking results illustrated that LT had a high affinity for various taste receptors, dominated by hydrogen bonding and hydrophobic interactions. This work provided a rare systematic elucidation of the potential and mechanism of enzymatically synthesized LT in enhancing taste properties. It provides novel insights into the directions and strategies for the excavation and innovation of flavor enhancers and food flavors.
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Aromatizantes , Simulación del Acoplamiento Molecular , Gusto , Triptófano , Humanos , Aromatizantes/química , Triptófano/química , Adulto , Masculino , FemeninoRESUMEN
In this study, food-grade glutamine transaminase (TGase) was utilized for the green-catalyzed preparation of N-butyryl amino acids. For improving the reusability of the enzyme preparation, immobilized TG enzyme (94.23% immobilization rate) was prepared. Furthermore, the yield of N-butyryl phenylalanine (BP) synthesized by TGase was obtained as 20.73% by one-factor experiment. The BP synthesis yield of immobilized TGase was 95.03% of that of TGase and remained above 60% of the initial enzyme activity after five runs. The sensory evaluation and E-tongue results showed that the addition of BP significantly increased the umami, saltiness, and richness intensities of the samples, and decreased the intensities of sourness, bitterness, and aftertaste-B. The molecular docking results indicated that hydrogen bonding dominated the binding of BP to taste receptors in the taste presentation mechanism of BP. These results confirmed the potential of BP as a flavor enhancer with promising applications in the food industry.
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Enzimas Inmovilizadas , Aromatizantes , Fenilalanina , Gusto , Fenilalanina/química , Humanos , Aromatizantes/química , Aromatizantes/metabolismo , Enzimas Inmovilizadas/química , Simulación del Acoplamiento Molecular , Biocatálisis , Transaminasas/química , Transaminasas/metabolismo , MasculinoRESUMEN
To satisfy the demands of the food industry, innovative flavor enhancers need to be developed urgently to increase the food flavor. In our work, N-lauroyl phenylalanine (LP) was prepared from phenylalanine (l-Phe) and lauric acid (Lau) in water through the use of commercial enzymes (Promatex, Sumizyme FP-G, and Trypsin), and its flavor-presenting properties and mechanism were investigated. The highest LP yields obtained under one-factor optimized conditions were 61.28, 63.43, and 77.58%, respectively. Sensory assessment and an e-tongue test revealed that 1 mg/L LP enhanced the kokumi, saltiness, and umami of the simulated chicken broth solution and attenuated the bitterness of the l-isoleucine solution. The molecular simulation results suggested that the mechanisms of LP enhancement of kokumi and umami were related to hCaSR and hT1R1-hT1R3, and that hydrophobic forces and hydrogen bonds were involved in the binding of LP to taste receptors. The results implied that LP is a potential flavor enhancer for food applications.
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Aromatizantes , Fenilalanina , Gusto , Fenilalanina/química , Aromatizantes/química , Aromatizantes/metabolismo , Humanos , Ácidos Láuricos/química , Masculino , Animales , Biocatálisis , Adulto , Pollos , Femenino , Adulto JovenRESUMEN
BACKGROUNDS: A deep neck space abscess (DNSA) is a critical condition resulting from infection of deep neck fascia and soft issue, leading to high morbidity and mortality. Therefore, intensive care can be very significant for patients with DNSA. This study aimed to develop models to predict the need for postoperative intensive care in patients with DNSA. METHODS: We retrospectively analyzed the records of 332 patients with DNSA who received drainage operation between 2015 and 2020. Multivariate logistic regression analysis and the eXtrem Gradient Boosting (XGBoost) algorithm were used to develop predictive models. RESULTS: We developed two predictive models, the nomogram and the XGBoost model. The area under the curve (AUC) of the nomogram was 0.911 and of the XGBoost model was 0.935. CONCLUSION: We developed two predictive models for guiding clinical decision making for postoperative ICU admission for DNSA patients, which may help improve prognosis and optimize intensive care resource allocation.
RESUMEN
BACKGROUND: The role of genetics in determining an individual's susceptibility to high altitude pulmonary edema (HAPE) is unclear. However a number of genetic polymorphisms have recently been found to be overrepresented in patients with HAPE. Changes at the mitochondrial level may play an important role in the human body's adaptation to hypoxia. Polymorphisms of mitochondrial DNA (mtDNA) have been shown to be responsible for differences in organelle function. Therefore, the frequency of mtDNA 3397A/G and 3552T/A polymorphisms were studied to determine their potential role in HAPE. OBJECTIVES: To further study the role of mtDNA 3397A/G and 3552T/A variations of reduced nicotinamide adenosine dinucleotide dehydrogenase 1 in HAPE susceptibility. METHODS: The single-nucleotide polymorphisms of mtDNA 3397 and 3552 in patients with HAPE (n = 132) and their matched control subjects (n = 233) were studied using polymerase chain reaction sequencing. RESULTS: The frequency of mtDNA 3397G in the HAPE group (2.3%) was significantly higher than that of the control group (0%; P = .021; odds ratio, 2.806; 95% confidence interval, 2.443 to 3.223). The frequency of mtDNA 3552A in the HAPE group (6.8%) also was significantly higher than in the control group (1.7%; P = .012; odds ratio, 4.198; 95% confidence interval, 1.264 to 13.880). CONCLUSIONS: In this study, we present the first evidence of differences in mtDNA polymorphism frequencies between HAPE victims and healthy Han Chinese. Genotypes of mtDNA 3397G and 3552A were correlated with HAPE susceptibility. This result could contribute to defining the role of the mitochondrial genome in the pathogenesis of HAPE.