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Bioactive peptides (BPs) are protein fragments with beneficial effects on metabolism, physiology, and diseases. This review focuses on proteolytic BPs, which are produced by the action of gut microbiota on proteins in food and have demonstrated to influence the composition of gut microbes. And gut microbiota are candidate targets of BPs to alleviate oxidative stress, enhance immunity, and control diseases, including diabetes, hypertension, obesity, cancer, and immune and neurodegenerative diseases. Despite promising results, further research is needed to understand the mechanisms underlying the interactions between BPs and gut microbes, and to identify and screen more BPs for industrial applications. Overall, BPs offer potential as therapeutic agents for various diseases through their interactions with gut microbes, highlighting the importance of continued research in this area.
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OBJECTIVE: To explore the role of different cells and molecules in the pathogenesis of allergic rhinitis (AR) with positive Artemisia allergen by detecting their expression levels. METHODS: From January 2021 to December 2022,200 AR patients diagnosed in the Otolaryngology Clinic of Ordos Central Hospital were selected as the AR group, and 50 healthy people who underwent physical examination in the hospital during the same period were randomly selected as the healthy control (HC) group. The levels of GATA-3mRNA, RORγtmRNA and FoxP3mRNA in peripheral blood mononuclear cells were detected by real-time fluorescence quantitative PCR (qRT-PCR). The proportions of Th2, Th17 and Treg cells were detected by flow cytometry. The concentrations of IL-4, IL-5, IL-17 and IL-10 in serum were detected by enzyme-linked immunosorbent assay. The differences of transcription gene level, immune cell ratio and cytokine concentration between the two groups were analyzed. RESULTS: There was no difference in age and gender between the two groups. The levels of GATA-3mRNA and RORγtmRNA transcription genes in peripheral blood mononuclear cells, the percentage of Th2, Th17 and Treg immune cells, the levels of eosinophils and basophils in peripheral blood, the concentrations of IL-4, IL-5, IL-17, IL-10 cytokines and IgE in serum of AR patients were significantly higher than those in HC group (P < 0.05). IL-4 and IL-17 were positively correlated with total IgE level. CONCLUSION: The secretion of immune cells and cytokines in peripheral blood of AR patients is abnormal. Th2, Th17, Treg specific transcription factors and related cells and cytokines are involved in the occurrence and development of allergic rhinitis.
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In situ cancer vaccination is an attractive strategy that stimulates protective antitumor immunity. Cytotoxic T lymphocytes (CTLs) are major mediators of the adaptive immune defenses, with critical roles in antitumor immune response and establishing immune memory, and are consequently extremely important for in situ vaccines to generate systemic and lasting antitumor efficacy. However, the dense extracellular matrix and hypoxia in solid tumors severely impede the infiltration and function of CTLs, ultimately compromising the efficacy of in situ cancer vaccines. To address this issue, a robust in situ cancer vaccine, Au@MnO2 nanoparticles (AMOPs), based on a gold nanoparticle core coated with a manganese dioxide shell is developed. The AMOPs modulated the unfavorable tumor microenvironment (TME) to restore CTLs infiltration and function and efficiently induced immunogenic cell death. The Mn2+-mediated stimulator of the interferon genes pathway can be activated to further augment the therapeutic efficacy of the AMOPs. Thus, the AMOPs vaccine successfully elicited long-lasting antitumor immunity to considerably inhibit primary, recurrent, and metastatic tumors. This study not only highlights the importance of revitalizing CTLs efficacy against solid tumors but also makes progress toward overcoming TME barriers for sustained antitumor immunity.
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BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by enhanced TH2 inflammatory response. Fractional exhaled nitric oxide (FeNO) measurement has been used as a valuable tool in predicting the development and management of asthma, another typical TH2 inflammation. However, the clinical significance of FeNO in ABPA remains unclear. OBJECTIVE: To investigate the association between FeNO and the prognosis of patients with ABPA to provide a basis for the use of FeNO in evaluating the efficacy of glucocorticoids in ABPA treatment. METHODS: This study comprised 2 parts; 58 patients were enrolled in the retrospective study. Clinical indexes in patients with different prognoses were compared, and receiver operating characteristic curve analysis was used to determine the threshold value. The prospective observational study involved 61 patients who were regularly followed up at 4 to 6 weeks and 6 months since the initial treatment. Patients were grouped on the basis of baseline FeNO values; correlation analysis was performed in the clinical data. RESULTS: Different prognoses were observed between patients with high and low baseline FeNO values, with a threshold value of 57 parts per billion. The percentage of Aspergillus fumigatus-specific IgE, percentage of positive A fumigatus-specific IgG, and relapse/exacerbation rate differed significantly between the high and low FeNO groups. Patients with higher FeNO needed longer treatment duration and showed shorter interval between glucocorticoid withdrawal and the next relapse/exacerbation. CONCLUSION: Our findings indicate that the level of FeNO is associated with the prognosis of ABPA. It can serve as an independent and valuable biomarker for evaluating the effectiveness of glucocorticoid treatment.
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Aspergilosis Broncopulmonar Alérgica , Aspergillus fumigatus , Biomarcadores , Glucocorticoides , Óxido Nítrico , Humanos , Aspergilosis Broncopulmonar Alérgica/tratamiento farmacológico , Aspergilosis Broncopulmonar Alérgica/diagnóstico , Femenino , Masculino , Glucocorticoides/uso terapéutico , Adulto , Pronóstico , Biomarcadores/análisis , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Aspergillus fumigatus/inmunología , Persona de Mediana Edad , Estudios Retrospectivos , Inmunoglobulina E/sangre , Estudios Prospectivos , Prueba de Óxido Nítrico Exhalado Fraccionado , Inmunoglobulina GRESUMEN
The ball screw pair is a precision drive component that converts rotary motion into linear motion. In practical applications, because the feed system usually has rotational torque and geometric errors, it may increase the contact load of the ball screw pair and reduce the fatigue life. In order to study the influence of different loads and geometric errors on the maximum contact load and fatigue life of ball screw pairs, the following research work was carried out. Firstly, based on the composite load and rotational torque, the ball load distribution model is established, and the accuracy of the model is verified by finite element modeling analysis. Then, the influence of different composite loads, rotation times and geometric errors (including ball size error, lead error and raceway tooth profile error) on the ball load distribution is analyzed. Finally, the influence of compound load, rotating torque and geometric error on the fatigue life of ball screw pairs is studied. The results show that the rotational torque and lead error have a great influence on the load distribution and fatigue life of the ball, and the influence of lead error on load distribution is greater than that of dimension error and tooth profile error. The fatigue life of the ball screw pair with non-uniform load distribution is shorter than that of the ball screw pair with uniform load distribution.
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Fracture propagation with temporary plugging hydraulic fracturing in tight-oil reservoirs is simulated in this study. The research considers dynamic fluid redistribution, with stress differences among multiple fractures. The fracture morphology during temporary plugging staged fracturing (TPSF) is investigated by using a user-defined perforation element combined with a pore-pressure finite-element model. The precision of the integrated model is verified by using the standard finite-element approach. Then, case studies are presented to investigate the influence of cluster spacing, horizontal stress difference coefficients (SDC), injection rates, and barrier tensile strengths. The simulation results show that central cluster fractures are hampered by side-cluster fractures, while TPSF can alleviate the effect and lead to a more uniform propagation of all fractures. Stress interference weakens as cluster spacing increases, and propagation patterns are minimally influenced once spacing reaches 40 m. Higher injection rates can improve the injection pressure, enlarging fracture width, and potentially increasing the risk of fracture penetration. Barrier tensile strength and horizontal SDC can modify fracture geometries and determine the penetration behavior of multiple fractures.
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INTRODUCTION: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear. METHODS: We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21+CD4+T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4+T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-/B-cell co-cultures in vitro were measured. RESULTS: ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T-cells were mainly peripheral T-helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE. CONCLUSION: We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.
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Aspergilosis Broncopulmonar Alérgica , Linfocitos B , Líquido del Lavado Bronquioalveolar , Células Th2 , Humanos , Masculino , Femenino , Aspergilosis Broncopulmonar Alérgica/inmunología , Adulto , Células Th2/inmunología , Persona de Mediana Edad , Estudios de Casos y Controles , Linfocitos B/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/citología , Linfocitos T Reguladores/inmunología , Asma/inmunología , Células Th17/inmunología , Linfocitos T Colaboradores-Inductores/inmunologíaRESUMEN
BACKGROUND: Echinococcosis is prevalent in 9 provinces in Western and Northern China. An epidemiological survey of echinococcosis in 2012 and 2016 showed cases of echinococcosis in Yunnan Province. AIM: To understand the spatial distribution and epidemiological characteristics of echinococcosis in Yunnan for the prevention and control of echinococcosis and to reduce the risk of infection in Yunnan Province. METHODS: Based on the China Information System for Disease Control and Prevention (CISDCP), echinococcosis cases reported from 36 hospitals and 34 Centers for Disease Control were investigated and epidemiologically analyzed from 2021 to 2022. The exclusion criteria included suspected cases, same case only counted once and cases not from Yunnan. A total of 705 cases were investigated, of which 397 cases were suitable for statistical analysis. In these 397 cases, epidemiological investigation was tracked in 187 cases. All data were inputted using double entry in the Excel database, with error correction by double-entry comparison. The data on echinococcosis cases in Yunnan Province were analyzed by ArcGIS 10.1 software to generate a density map of echinococcosis distribution. All statistical analyses were conducted using SPSS 17.0, including the chi-square test, linear regression test and logistic univariate and multivariate regression analyses. RESULTS: A total of 397 cases were found in 89 counties in Yunnan Province. The number of cases in the top three prefectures were Dali (38.1%), Diqing (10.1%), and Kunming (8.3%), and the top five counties were Jianchuan (9.1%), Shangri La (8.3%), Eryuan (7. 6%), Heqing (6.9%), and Dali Districts (5.0%). There were significant differences between the different areas. The case reporting rate by CISDCP (33.8%) was low; the first case was reported by CISDCP in 2002, and the highest number of cases was 50 (2017). Confirmed and clinical cases accounted for 62.5% and 37.5%, respectively. However, 90.9% of the cases of hydatid disease were reported by the hospital system, and only 9.1% of the cases of hydatid disease were found in the community through active screening. The difference between the two methods of case detection was statistically significant. Most of the cases of echinococcosis were found in farmers/herdsmen (75.1%) and students (9.1%). In addition, Han (43.6%) and Bai (26.2%) had a higher incidence of infection than other nationalities, and the liver (87.7%) and lung (6.8%) were the most common sites of cyst formation. Among the analyzed cases, 187 were epidemiologically analyzed and the clinical symptoms were not obvious in the early stage in 47.1% of cases. The results of logistic regression analysis showed that the age group, education level, presence of dogs in the family (either previously or currently), and handwashing (occasionally or not) were factors related to echinococcosis infection. 55.6% of cases were in endemic areas, and 44.4% of cases were in non-endemic areas. Among 83 cases in non-endemic areas, only 4 cases had been to endemic areas and had a history of living, working, travelling, or hunting in echinococcosis epidemic areas. CONCLUSION: Cases of echinococcosis were reported throughout the entire Yunnan province, with the majority distributed in Western Yunnan, suggesting that echinococcosis control should be strengthened in this area. We suggest that an epidemiological investigation should be carried out in the future, based on the clues from newly discovered cases in hospitals or from the CISDCP. The newly discovered cases in the hospital provided clues to comprehensively determine the location of cases and where epidemic spot investigation should be conducted.
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BACKGROUND: Osteosarcoma (OS), with a peak incidence during the adolescent growth spurt, is correlated with poor prognosis for its high malignancy. The tumor microenvironment (TME) is highly complicated, with frequent interactions between tumor and stromal cells. The cancer-associated fibroblasts (CAFs) in the TME have been considered to actively involve in the progression, metastasis, and drug resistance of OS. This study aimed to characterize cellular heterogeneity and molecular characterization in CAFs subtypes and explore the potential targeting therapeutic strategies to improve the prognosis of OS patients. METHODS: The single-cell atlas of human OS tumor lesions were constructed from the GEO database. Then significant marker genes and potential biological functions for each CAFs subtype were identified and explored using the Seurat R package. Next, by performing the survival analyses and constructing the risk scores for CAFs subtypes, we aimed to identify and characterize the prognostic values of specific marker genes and different CAFs subtypes. Furthermore, we explored the therapeutic targets and innovative drugs targeting different CAFs subtypes based on the GDSC database. Finally, prognoses related CAFs subtypes were further validated through immunohistochemistry (IHC) on clinical OS specimens. RESULTS: Overall, nine main cell clusters and five subtypes of CAFs were identified. The differentially expressed marker genes for each CAFs clusters were then identified. Moreover, through Gene Ontology (GO) enrichment analysis, we defined the CAFs_2 (upregulated CXCL14 and C3), which was closely related to leukocyte migration and chemotaxis, as inflammatory CAFs (iCAFs). Likewise, we defined the CAFs_4 (upregulated CD74, HLA-DRA and HLA-DRB1), which was closely related to antigen process and presentation, as antigen-presenting CAFs (apCAFs). Furthermore, Kaplan-Meier analyses showed that CAFs_2 and CAFs_4 were correlated with poor clinical prognosis of OS patients. Meanwhile, therapeutic drugs targeting CAFs_2 and CAFs_4, such as 17-AAG/Docetaxel/Bleomycin and PHA-793887/NG-25/KIN001-102, were also explored, respectively. Finally, IHC assay confirmed the abundant CAFs_2 and CAFs_4 subtypes infiltration in the OS microenvironment compared with adjacent tissues. CONCLUSION: Our study revealed the diversity, complexity, and heterogeneity of CAFs in OS, and complemented the single-cell atlas in OS TME.
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Neoplasias Óseas , Fibroblastos Asociados al Cáncer , Osteosarcoma , Adolescente , Humanos , Osteosarcoma/genética , Perfilación de la Expresión Génica , Expresión Génica , Neoplasias Óseas/genética , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Varicocele is the most prevalent correctable cause of male infertility. Currently, surgical treatment is the primary method to enhance fertility.For many young varicocele patients who have postponed surgery due to time constraints, daytime surgery is especially crucial. Thus, this study aims to investigate the clinical and nursing application value of the Plan-Do-Check-Act (PDCA) cycle in daytime varicocelectomy. METHODS: Retrospective collection of clinical data was conducted on 130 patients undergoing laparoscopic varicocelectomy in the Third Affiliated Hospital of Southern Medical University, Guangzhou,China.Among them, 65 patients who underwent daytime surgery were assigned to the observation group, while 65 patients who underwent routine hospital surgeries were assigned to the control group.The former also implemented PDCA cycle management.A comparison was made between the two groups regarding hospitalization time, hospitalization costs, and patient satisfaction. RESULTS: The observation group exhibited a shorter hospitalization time and lower hospitalization costs compared to the control group, with higher patient satisfaction and pre-discharge visual analog scale (VAS) scores noted (P < 0.05).No significant difference was observed in the incidence of postoperative complications between the two groups during hospitalization (P > 0.05). The implementation of the PDCA cycle in the observation group has demonstrated its effectiveness, ensuring the smooth conduct of the daytime varicocelectomy. CONCLUSION: In conclusion,daytime varicocelectomy can reduce hospitalization time,lower hospitalization costs, improve patient satisfaction. The PDCA Cycle enhances the rationality and efficacy of the daytime varicocelectomy procedure and is highly recommended. Furthermore, it offers valuable reference for the application of the PDCA Cycle in various other diseases and nursing management approaches. TRIAL REGISTRATION: The Trial Registration Number: ChiCTR2300077465;Date of registration: November 9, 2023.
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BACKGROUND: Plasmodium vivax malaria, with the widest geographic distribution, can cause severe disease and death. Primaquine is the main licensed antimalarial drug that can kill hypnozoites. The dose-dependent acute haemolysis in individuals with glucose-6-phospate dehydrogenase (G6PD) deficiency is the main safety concern when using primaquine. The recommended treatment regimen for P. vivax malaria is chloroquine plus primaquine for 14 days (CQPQ14) in Myanmar. The study aimed to evaluate the therapeutic efficacy, safety and adherence for the regimen of artemisinin-naphthoquine plus primaquine for 3 days (ANPQ3) in patients with P. vivax infections compared to those with CQPQ14. METHODS: The patients in the ANPQ3 group were given fixed-dose artemisinin-naphthoquine (a total 24.5 mg/kg bodyweight) plus a lower total primaquine dose (0.9 mg/kg bodyweight) for 3 days. The patients in the CQPQ14 group were given a total chloroquine dose of 30 mg/kg body weight for 3 days plus a total primaquine dose of 4.2 mg/kg bodyweight for 14 days. All patients were followed up for 365 days. RESULTS: A total of 288 patients completed follow-up, 172 in the ANPQ3 group and 116 in the CQPQ14 group. The first recurrence patients were detected by day 58 in both groups. By day 182, 16 recurrences had been recorded: 12 (7.0%) patients in the ANPQ3 group and 4 (3.4%) in the CQPQ14 group. The difference in recurrence-free patients was 3.5 (-8.6 to 1.5) percentage points between ANPQ3 and CQPQ14 group (P = 0.2946). By day 365, the percentage of recurrence-free patients was not significant between the two groups (P = 0.2257). Mean fever and parasite clearance time of ANPQ3 group were shorter than those in CQPQ14 group (P ≤ 0.001). No severe adverse effect was observed in ANPQ3 group, but five (3.9%) patients had acute haemolysis in CQPQ14 group (P = 0.013). Medication percentage of ANPQ3 group was significantly higher than that of CQPQ14 group (P < 0.0001). CONCLUSIONS: Both ANPQ3 and CQPQ14 promised clinical cure efficacy, and the radical cure efficacy was similar between the ANPQ3 and CQPQ14 group. ANPQ3 clears fever and parasites faster than CQPQ14. ANPQ3 is safer and shows better patient adherence to the regimen for treatment of P. vivax malaria along the China-Myanmar border. TRIAL REGISTRATION: ChiCTR-INR-17012523. Registered 31 August 2017, https://www.chictr.org.cn/showproj.html?proj=21352.
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1-Naftilamina/análogos & derivados , Aminoquinolinas , Artemisininas , Malaria Vivax , Humanos , Primaquina/efectos adversos , Malaria Vivax/tratamiento farmacológico , Malaria Vivax/prevención & control , Hemólisis , Artemisininas/efectos adversos , Cloroquina/efectos adversos , FiebreRESUMEN
Cystic fibrosis is a life-shortening genetic disorder, caused by mutations in the gene that encodes cystic fibrosis transmembrane-conductance regulator, a cAMP-activated chloride and bicarbonate channel. Persistent neutrophilic inflammation is a major contributor to cystic fibrosis lung disease. However, how cystic fibrosis transmembrane-conductance regulator loss of function leads to excessive inflammation and its clinical sequela remains incompletely understood. In this study, neutrophils from F508del-CF and healthy control participants were compared for gene transcription. We found that cystic fibrosis circulating neutrophils have a prematurely primed basal state with significantly higher scores for activation, chemotaxis, immune signaling, and pattern recognition. Such an irregular basal state appeared not related to the blood environment and was also observed in neutrophils derived from the F508del-CF HL-60 cell line, indicating an innate characteristic of the phenotype. Lipopolysaccharides (LPS) stimulation drastically shifted the transcriptional landscape of healthy control neutrophils toward a robust immune response; however, cystic fibrosis neutrophils were immune-exhausted, reflected by abnormal cell aging and fate determination in gene programming. Moreover, cystic fibrosis sputum neutrophils differed significantly from cystic fibrosis circulating neutrophils in gene transcription with increased inflammatory response, aging, apoptosis, and necrosis, suggesting additional environmental influences on the neutrophils in cystic fibrosis lungs. Taken together, our data indicate that loss of cystic fibrosis transmembrane-conductance regulator function has intrinsic effects on neutrophil immune programming, leading to premature priming and dysregulated response to challenge.
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Fibrosis Quística , Humanos , Fibrosis Quística/genética , Neutrófilos , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Inmunidad , Inflamación , MutaciónRESUMEN
F-box proteins participate in the regulation of many processes, including cell division, development, and plant hormone responses. Brassinosteroids (BRs) regulate plant growth and development by activating core transcriptional and other multiple factors. In rice, OVATE family proteins (OFPs) participate in BR signalling and regulate grain size. Here we identified an F-box E3 ubiquitin ligase, FBX206, that acts as a negative factor in BR signalling and regulates grain size and yield in rice. Suppressed expression of FBX206 by RNAi leads to promoted plant growth and increased grain yield. Molecular analyses showed that the expression levels of BR biosynthetic genes were up-regulated, whereas those of BR catabolic genes were down-regulated in FBX206-RNAi plants, resulting in the accumulation of 28-homoBL, one of the bioactive BRs. FBX206 interacted with OsOFP8, a positive regulator in BR signalling, and OsOFP19, a negative regulator in BR signalling. SCFFBX206 mediated the degradation of OsOFP8 but suppressed OsOFP19 degradation. OsOFP8 interacted with OsOFP19, and the reciprocal regulation between OsOFP8 and OsOFP19 required the presence of FBX206. FBX206 itself was ubiquitinated and degraded, but interactions of OsOFP8 and OsOFP19 synergistically suppressed the degradation of FBX206. Genetic interactions indicated an additive effect between FBX206 and OsOFP8 and epistatic effects of OsOFP19 on FBX206 and OsOFP8. Our study reveals the regulatory networks of FBX206, OsOFP8, and OsOFP19 in BR signalling that regulate grain size and yield in rice.
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Proteínas F-Box , Oryza , Brasinoesteroides/metabolismo , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Grano Comestible/genética , Grano Comestible/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Rationale: The relationship between symptoms, measured using a validated disease-specific questionnaire, and longitudinal exacerbation risk has not been demonstrated in bronchiectasis. Objectives: The aim of this study is to investigate whether baseline symptoms, assessed using the Quality-of-Life Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and its individual component scores, could predict future exacerbation risk in patients with bronchiectasis. Methods: The study included 436 adults with bronchiectasis from three tertiary hospitals. Symptoms were measured using the QoL-B-RSS, with scores ranging from 0 to 100, where lower scores indicated more severe symptoms. We examined whether symptoms as continuous measures were associated with the risk of exacerbation over 12 months. The analysis was also repeated for individual components of the QoL-B-RSS score. Results: The baseline QoL-B-RSS score was associated with an increased risk of exacerbations (rate ratio, 1.25 for each 10-point decrease; 95% confidence interval [CI], 1.15-1.35; P < 0.001), hospitalizations (rate ratio, 1.24; 95% CI, 1.05-1.43; P = 0.02), and reduced time to the first exacerbation (hazard ratio, 1.12; 95% CI, 1.03-1.21; P = 0.01) over 12 months, even after adjusting for relevant confounders, including exacerbation history. The QoL-B-RSS score was comparable to exacerbation history in its association with future frequent exacerbations (defined as three or more exacerbations per year) and hospitalization (area under the curve, 0.86 vs. 0.84; P = 0.46; and area under the curve, 0.81 vs. 0.83; P = 0.41, respectively). Moreover, patients with more severe symptoms in the majority of individual components of the QoL-B-RSS were more likely to experience exacerbations. Conclusions: Symptoms can serve as useful indicators for identifying patients at increased risk of exacerbation in bronchiectasis. Beyond relying solely on exacerbation history, a comprehensive assessment of symptoms could facilitate timely and cost-effective implementation of interventions for exacerbation prevention.
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Bronquiectasia , Calidad de Vida , Adulto , Humanos , Estudios Prospectivos , Bronquiectasia/complicaciones , Hospitalización , Centros de Atención TerciariaRESUMEN
BACKGROUND: Appropriate malaria treatment-seeking behaviour (TSB) is critical for timely detecting malaria, prompt treatment, and prevention of onward transmission of the disease in a community. This study aimed to compare treatment-seeking behaviours between malaria patients and non-malaria febrile patients, and to analyse the factors associated with appropriate TSB along the China-Myanmar border. METHODS: A cross-sectional study was carried out to investigate the appropriate TSB of microscopy-confirmed malaria patients versus non-malaria febrile (NMF) patients. An unconditional logistic regression analysis (LRA) was used to identify factors associated with appropriate TSB. RESULTS: Among 223 malaria patients and 446 NMF patients, 129 (57.8%) of the malaria patients versus 163 (36.5%) of the NMF patients firstly sought treatment in health facilities without laboratory testing for malaria (P < 0.0001). A total of 85(38.1%) of the malaria patients versus 278 (62.3%) of the NMF patients had appropriate TSB, namely, seeking treatment in health facilities with laboratory testing for malaria within 48 h (P < 0.0001). Multivariate LRA identified that the malaria patients with Chinese nationality had less appropriate TSB compared to those with other nationalities (adjusted odds ratio [AOR]: 0.21, 95% confidence interval CI 0.07-0.68, P = 0.0097), and malaria patients residing in urban areas had more appropriate TSB compared to those living in rural areas (AOR: 2.16, 95%CI 1.06-4.39, P = 0.0337). CONCLUSIONS: TSB was not appropriate in malaria patients. Chinese citizenship and rural residence were two independent factors associated with inappropriate malaria TSB. It is urgently necessary to improve appropriate malaria TSB through effective campaigns of information, education, and communication for malaria control in Myanmar and preventing reestablishment of malaria transmission in Yunnan, China.
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Malaria , Humanos , Estudios Transversales , Mianmar/epidemiología , China/epidemiología , Malaria/prevención & control , Aceptación de la Atención de Salud , Fiebre/diagnósticoRESUMEN
Epithelial ovarian cancer (EOC) is one of the most prevalent gynaecological cancers worldwide. The molecular mechanisms of serous ovarian cancer (SOC) remain unclear and not well understood. SOC cases are primarily diagnosed at the late stage, resulting in a poor prognosis. Advances in molecular biology techniques allow us to obtain a better understanding of precise molecular mechanisms and to identify the chromosome instability region and key driver genes in the carcinogenesis and progression of SOC. Whole-exome sequencing was performed on the normal ovarian cell line IOSE80 and the EOC cell lines SKOV3 and A2780. The single-nucleotide variation burden, distribution, frequency and signature followed the known ovarian mutation profiles, without chromosomal bias. Recurrently mutated ovarian cancer driver genes, including LRP1B, KMT2A, ARID1A, KMT2C and ATRX were also found in two cell lines. The genome distribution of copy number alterations was found by copy number variation (CNV) analysis, including amplification of 17q12 and 4p16.1 and deletion of 10q23.33. The CNVs of MED1, GRB7 and MIEN1 located at 17q12 were found to be correlated with the overall survival of SOC patients (MED1: p = 0.028, GRB7: p = 0.0048, MIEN1: p = 0.0051), and the expression of the three driver genes in the ovarian cell line IOSE80 and EOC cell lines SKOV3 and A2780 was confirmed by western blot and cell immunohistochemistry.
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Neoplasias Ováricas , Humanos , Femenino , Carcinoma Epitelial de Ovario/genética , Neoplasias Ováricas/genética , Línea Celular Tumoral , Variaciones en el Número de Copia de ADN/genética , Inestabilidad Cromosómica/genética , Proteínas de Neoplasias/genética , Péptidos y Proteínas de Señalización Intracelular/genéticaRESUMEN
BACKGROUND: Rodents are the predominant natural hosts of orthohantavirus and the source of human infection, hemorrhagic fever with renal syndrome (HFRS) caused by orthohantavirus is a severe public health problem in the Yichun region, Jiangxi Province, China. However, little information is known about the infection of orthohantavirus in humans and rodents, and the genetic characteristics of the epidemic orthohantavirus in the region. METHODS: The clinical data of HFRS cases in 2016-2021 was analyzed. Virus infection in rodents was analyzed by orthohantavirus antigen detection using immunofluorescent assay, and the species of orthohantaviruses in rodents and patients were identified by real-time RT-PCR and gene sequencing. The S and M segments of orthohantaviruses from rodents and patients were recovered and analyzed. RESULTS: A total of 1,573 HFRS cases were reported in the Yichun region from 2016 to 2021, including 11 death cases. HFRS cases peaked twice each year: in winter from November to January and early summer from May to June. Farmers constituted the predominant population suffering from HFRS. The orthohantavirus antigen was identified in five species of rodents: Apodemus agrarius (A. agrarius), Rattus norvegicus (R. norvegicus), Sorex araneus, Rattus losea (R. losea), and Niviventer confucianus (N. confucianus). The real-time RT-PCR test and genetic analysis results showed that Hantaan orthohantavirus (HTNV), Seoul orthohantavirus (SEOV), and Dabieshan orthohantavirus (DBSV) were circulated in the rodents. HTNV, SEOV, and DBSV from the rodents were distantly related to other known orthohantaviruses and belonged to novel genetic lineages. SEOV and HTNV were found in HFRS patients, but 97.8% (90/92) of the infections were caused by HTNV. Winter and early summer peaks were both caused by HTNV. The HTNV sequences recovered from HFRS cases were closely related to those from A. agrarius. CONCLUSIONS: In the Yichun region, the orthohantaviruses transmitted in rodents include HTNV, SEOV, and DBSV, which have obvious genetic characteristics and high genetic diversity. At the same time, this region is an HFRS mixed epidemic area dominated by HTNV, with two peaks every year, which deserves our high attention.
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Infecciones por Hantavirus , Fiebre Hemorrágica con Síndrome Renal , Orthohantavirus , Virus Seoul , Humanos , Ratas , Animales , Roedores , Fiebre Hemorrágica con Síndrome Renal/epidemiología , Fiebre Hemorrágica con Síndrome Renal/veterinaria , Fiebre Hemorrágica con Síndrome Renal/diagnóstico , Orthohantavirus/genética , Virus Seoul/genética , China/epidemiología , FilogeniaRESUMEN
BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION: Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Asunto(s)
Aspergilosis Broncopulmonar Alérgica , Asma , Humanos , Aspergilosis Broncopulmonar Alérgica/genética , Aspergilosis Broncopulmonar Alérgica/complicaciones , Aspergillus fumigatus/genética , Asma/genética , Aspergillus , Mutación/genética , Proteínas Adaptadoras de Señalización CARD/genéticaRESUMEN
In recent years, immune checkpoint blockades (ICBs) have made great progress in the treatment of cancer. However, most ICBs have not yet been observed to be satisfactory in the treatment of osteosarcoma. Herein, we designed composite nanoparticles (NP-Pt-IDOi) from a reactive oxygen species (ROS) sensitive amphiphilic polymer (PHPM) with thiol-ketal bonds in the main chain to encapsulate a Pt(IV) prodrug (Pt(IV)-C12) and an indoleamine-(2/3)-dioxygenase (IDO) inhibitor (IDOi, NLG919). Once NP-Pt-IDOi enter the cancer cells, the polymeric nanoparticles could dissociate due to the intracellular ROS, and release Pt(IV)-C12 and NLG919. Pt(IV)-C12 induces DNA damage and activates the cGAS-STING pathway, increasing infiltration of CD8+ T cells in the tumor microenvironment. In addition, NLG919 inhibits tryptophan metabolism and enhances CD8+ T cell activity, ultimately activating anti-tumor immunity and enhancing the anti-tumor effects of platinum-based drugs. NP-Pt-IDOi were shown to have superior anti-cancer activity in vitro and in vivo in mouse models of osteosarcoma, providing a new clinical paradigm for combining chemotherapy with immunotherapy for osteosarcoma.
RESUMEN
With the distinct advantages of high resolution, small pixel size, and multi-level pure phase modulation, liquid crystal on silicon (LCoS) devices afford precise and reconfigurable spatial light modulation that enables versatile applications ranging from micro-displays to optical communications. However, LCoS devices suffer from a long-standing problem of polarization-dependent response in that they only perform phase modulation on one linear polarization of light, and polarization-independent phase modulation-essential for most applications-have had to use complicated polarization-diversity optics. We propose and demonstrate, for the first time, an LCoS device that directly achieves high-performance polarization-independent phase modulation at telecommunication wavelengths with 4K resolution and beyond by embedding a polarization-rotating metasurface between the LCoS backplane and the liquid crystal phase-modulating layer. We verify the device with a number of typical polarization-independent application functions including beam steering, holographical display, and in a key optical switching element - wavelength selective switch (WSS), demonstrating the significant benefits in terms of both configuration simplification and performance improvement.