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PURPOSE: The treatment with anti-VEGF for Retinopathy of prematurity (ROP) has already been widely applied in clinics even though there are still many concerns about this treatment. In this project we investigated the clinical outcomes of intra-vitreous conbercept (IVC) and ranibizumab (IVR) injection for treating type 1 prethreshold ROP in Zone II. METHODS: The data of ROP infants receiving IVR or IVC from January 2017 to March 2020 who were followed up for at least 12 months in our hospital was studied in the present retrospective study. Regression, reactivation, complications, and ocular biological parameters were evaluated. RESULTS: One hundred twenty-five eyes (64 infants) in IVC group and 229 eyes (117 infants) in IVR group were observed in the study. All infants showed good response to the two anti-VEGF agents. No eyes deteriorated during the observation. No significant difference was found between the two groups as to the regression within one week and one month, the reactivation rate, and the retreatment interval (p > 0.05) whereas retinal complete vascularization rate at 6 mons after the initial treatment and mean completion time of retinal vascularization after initial injection showed significant difference (p < 0.05). At 12 mons PMA the ocular parameters also presented no statistical difference between the two treated groups (p > 0.05). However, the ocular showed slight myopic tendency with the anti-VEGF treatment when compared to the control group (p < 0.05) whereas there was no statistical difference revealed between the two treated groups (p > 0.05). CONCLUSIONS: Both conbercept and ranibizumab for treating type 1 prethreshold ROP in Zone II are safe and effective. They had little effect on the development of ocular whereas there was a slight tendency of myopia after the treatment.
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Inibidores da Angiogênese , Injeções Intravítreas , Ranibizumab , Proteínas Recombinantes de Fusão , Retinopatia da Prematuridade , Humanos , Ranibizumab/uso terapêutico , Ranibizumab/administração & dosagem , Retinopatia da Prematuridade/tratamento farmacológico , Estudos Retrospectivos , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Masculino , Feminino , Recém-Nascido , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Resultado do Tratamento , SeguimentosRESUMO
PURPOSE: To assess the risk of adverse obstetric and perinatal outcomes in subsequent pregnancies among women with a history of recurrent pregnancy loss (RPL). METHODS: Relevant studies were identified by searching the PubMed, Web of Science, and Embase databases. The pooled effect sizes were reported as odds ratios (OR) with their respective 95% confidence intervals (95% CI), and data analysis was performed using the random effects model. RESULTS: A total of 26 studies involving 4,730,728 women were included in this meta-analysis. The results reveal a significant increase in the prevalence of placenta accreta cases after RPL compared to women without RPL (pooled OR 4.04; 95% CI 1.16-14.15; 2 studies; I2 = 94%; P = 0.03). However, no elevated risk of aneuploidies (pooled OR 1.69, 95% CI 0.73-3.90; 5 studies; I2 = 48%; P = 0.22) or congenital anomalies (pooled OR 1.12, 95% CI 0.97-1.30; 7 studies; I2 = 13%; P = 0.12) in subsequent pregnancies of women with RPL was observed. Additionally, a moderate increase in the risk of various other obstetric and perinatal outcomes was found. The magnitude of the elevated risk of these adverse outcomes varied depending on the region. CONCLUSIONS: Women with a history of RPL exhibit a significantly elevated risk of placenta accreta in subsequent pregnancies, along with a moderate increase in the risk of various other adverse obstetric and perinatal outcomes. However, RPL does not signify an increased risk of aneuploidies or congenital anomalies in a consecutive pregnancy.
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Aborto Habitual , Placenta Acreta , Resultado da Gravidez , Humanos , Feminino , Gravidez , Aborto Habitual/epidemiologia , Placenta Acreta/epidemiologia , Resultado da Gravidez/epidemiologia , Estudos de Coortes , Anormalidades Congênitas/epidemiologia , Aneuploidia , Recém-NascidoRESUMO
The integrated satellite-terrestrial network (ISTN) provides a promising solution to achieve high-data-rate and ubiquitous connectivity in next-generation communication networks. Considering the scarce spectrum resources and unevenly distributed traffic demands, we investigate the resource allocation algorithms for ISTNs, where the beam-hopping (BH)-based satellite system and terrestrial systems share the same frequency band. Taking advantage of the scheduling flexibility of BH technology, the dynamical protection zones are constructed to avoid co-channel interference and improve the spectrum efficiency. Since both spectrum efficiency and user fairness are the key optimization indexes in practical systems, two resource allocation problems are formulated to maximize the weighted sum of capacity (MWSC) and maximize the minimum capacity-to-demand ratio (MMCDR) of ISTNs, respectively. By reformulating the problems as mixed-integer linear programming problems, optimal solutions are obtained. To reduce the computational complexity, two greedy suboptimal algorithms are proposed for the MWSC and MMCDR, respectively. The simulation results show that the proposed algorithms achieve higher spectrum efficiency and guarantee fairness between the satellite and terrestrial systems. It is also shown that both the greedy algorithms perform similarly to the optimal algorithms while having much lower complexity.
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BACKGROUND: Because the proportion of elderly individuals and the incidence of cancer worldwide are continually increasing, medical costs for elderly inpatients with cancer are being significantly increasing, which puts tremendous financial pressure on their families and society. The current study described the actual direct medical costs of elderly inpatients with cancer and analyzed the influencing factors for the costs to provide advice on the prevention and control of the high medical costs of elderly patients with cancer. METHOD: A retrospective descriptive analysis was performed on the hospitalization expense data of 11,399 elderly inpatients with cancer at a tier-3 hospital in Dalian between June 2016 and June 2020. The differences between different groups were analyzed using univariate analysis, and the influencing factors of hospitalization expenses were explored by multiple linear regression analysis. RESULTS: The hospitalization cost of elderly cancer patients showed a decreasing trend from 2016 to 2020. Specifically, the top 3 hospitalization costs were material costs, drug costs and surgery costs, which accounted for greater than 10% of all cancers according to the classification: colorectal (23.96%), lung (21.74%), breast (12.34%) and stomach cancer (12.07%). Multiple linear regression analysis indicated that cancer type, surgery, year and length of stay (LOS) had a common impact on the four types of hospitalization costs (P < 0.05). CONCLUSION: There were significant differences in the four types of hospitalization costs for elderly cancer patients according to the LOS, surgery, year and type of cancer. The study results suggest that the health administration department should enhance the supervision of hospital costs and elderly cancer patient treatment. Measures should be taken by relying on the hospital information system to strengthen the cost management of cancer diseases and departments, optimize the internal management system, shorten elderly cancer patients LOS, and reasonably control the costs of disease diagnosis, treatment and department operation to effectively reduce the economic burden of elderly cancer patients.
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Hospitalização , Neoplasias , Centros de Atenção Terciária , Humanos , Estudos Retrospectivos , Idoso , Feminino , Masculino , Neoplasias/economia , Neoplasias/terapia , Neoplasias/epidemiologia , Hospitalização/economia , China/epidemiologia , Centros de Atenção Terciária/economia , Idoso de 80 Anos ou mais , Custos Hospitalares/estatística & dados numéricos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricosRESUMO
Cymbidium mosaic virus (CymMV) and Odontoglossum ringspot virus (ORSV) are among the world's most serious and widespread orchid viruses; they often infect orchids, causing devastating losses to the orchid industry. Therefore, it is critical to establish a method that can rapidly and accurately detect viruses in the field using simple instruments, which will largely reduce the further spread of viruses and improve the quality of the orchid industry and is suitable for mass promotion and application at grassroots agrotechnical service points. In this investigation, we established a rapid amplification method for virus detection at 39 °C for 35 min to detect the presence of CymMV and ORSV simultaneously, sensitively, and specifically in orchids. Primers for the capsid protein (CP)-encoding genes of both viruses were designed and screened, and the reaction conditions were optimized. The experimental amplification process was completed in just 35 min at 39 °C. There were no instances of nonspecific amplification observed when nine other viruses were present. The RPA approach had detection limits of 104 and 103 copies for pMD19T-CymMV and pMD19T-ORSV, respectively. Moreover, the duplex RT-RPA investigation confirmed sensitivity and accuracy via a comparison of detection results from 20 field samples with those of a gene chip. This study presents a precise and reliable detection method for CymMV and ORSV using RT-RPA. The results demonstrate the potential of this method for rapid virus detection. It is evident that this method could have practical applications in virus detection processes.
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Orchidaceae , Doenças das Plantas , Potexvirus , Doenças das Plantas/virologia , Orchidaceae/virologia , Sensibilidade e Especificidade , Proteínas do Capsídeo/genética , Potyvirus/genética , Potyvirus/isolamento & purificação , Potyvirus/classificação , RNA Viral/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Primers do DNA/genéticaRESUMO
Rice straw is burned as a result of agricultural practices and technical limitations, generating significant volumes of ash that might have environmental and ecological consequences; however, the effects on organisms have not been researched. Amphibians depend on their gut and skin microbiomes. Ash exposure may cause inflammation and changes in microbial diversity and function in frogs' skin and gut microbiota due to its chemical composition and physical presence, but the implications remain unclear. Rana dybowskii were exposed to five aqueous extracts of ashes (AEA) concentrations for 30 days to study survival, metal concentrations, and microbial diversity, analyzing the microbiota of the cutaneous and gut microbiota using Illumina sequencing. Dominant elements in ash: K > Ca > Mg > Na > Al > Fe. In AEA, K > Na > Ca > Mg > As > Cu. Increased AEA concentrations significantly reduced frog survival. Skin microbiota alpha diversity varied significantly among all treatment groups, but not gut microbiota. Skin microbiota differed significantly across treatments via Bray-Curtis and weighted UniFrac; gut microbiota was only affected by Bray-Curtis. Skin microbiota varied significantly with AEA levels in Proteobacteria, Bacteroidetes, Actinobacteria, and Firmicutes, while the gut microbiota's dominant phyla, Firmicutes, Bacteroidetes, and Proteobacteria, remained consistent across all groups. Lastly, the functional prediction showed that the skin microbiota had big differences in how it worked and looked, which were linked to different health and environmental adaptation pathways. The gut microbiota, on the other hand, had smaller differences. In conclusion, AEA exposure affects R. dybowskii survival and skin microbiota diversity, indicating potential health and ecological impacts, with less effect on gut microbiota.
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Microbioma Gastrointestinal , Microbiota , Oryza , Animais , Anuros , BactériasRESUMO
Orchids are significant ornamental plants whose viral infection results in substantial economic damage. Cymbidium mosaic virus (CymMV), Odontoglossum ringspot virus (ORSV), and Cymbidium ringspot virus (CymRSV) represent three important and prevalent orchid viruses. The detection system proposed in this study uses a triplex TaqMan quantitative real-time PCR assay to identify CymMV, ORSV, and CymRSV in a simultaneous manner. We designed specific primers and probes for CymMV, ORSV, and CymRSV, with amplified sequences of 156 bp, 148 bp, and 145 bp, respectively. The minimum detection limit of the triplex qRT-PCR assay for CymMV and CymRSV was 1 copy/assay, and the minimum detection limit was 10 copies/assay for ORSV. The minimum stable detection limits for CymMV, ORSV, and CymRSV were 10, 102, and 102 copies/assay, respectively. Therefore, this system exhibited higher sensitivity (approximately 10 to 104-fold) than RT-PCR. The intra-and interassay CVs of Cq values are less than 0.55 and 0.95%, respectively, indicating that the triplex assay is highly reliable and accurate. In addition, 66 samples from five different orchid genera were analyzed using the established assay and gene chip. The detection results demonstrated that the triplex probe qRT-PCR demonstrated higher sensitivity than the gene chip, indicating that the triplex real-time PCR assay could be used for the detection of field samples. Our findings suggest that the triplex real-time RT-PCR detection system represents a rapid, simple, and accurate tool for detecting CymMV, ORSV, and CymRSV on orchids.
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Purpose: Type 1 diabetes is characterized by elevated blood glucose levels, which negatively impacts multiple organs and tissues throughout the body, and its prevalence is on the rise. Prior reports primarily investigated the serum and urine specimen from diabetic patients. However, only a few studies examined the overall metabolic profile of diabetic animals or patients. The current systemic investigation will benefit the knowledge of STZ-based type 1 diabetes pathogenesis. Methods: Male SD rats were arbitrarily separated into control and streptozotocin (STZ)-treated diabetic rats (n = 7). The experimental rats received 50mg/kg STZ intraperitoneal injection daily for 2 consecutive days. Following 6 weeks, metabolites were assessed via gas chromatography-mass spectrometry (GC-MS), and multivariate analysis was employed to screen for differentially expressed (DE) metabolites between the induced diabetic and normal rats. Results: We identified 18, 30, 6, 24, 34, 27, 27 and 12 DE metabolites in the serum, heart, liver, kidney, cortex, renal lipid, hippocampus, and brown fat tissues of STZ-treated diabetic rats, compared to control rats. Based on our analysis, the largest differences were observed in the amino acids (AAs), B-group vitamin, and purine profiles. Using the metabolic pathway analysis, we screened 13 metabolic pathways related to the STZ-exposed diabetes pathogenesis. These pathways were primarily AA metabolism, followed by organic acids, sugars, and lipid metabolism. Conclusion: Based on our GC-MS analysis, we identified potential metabolic alterations within the STZ-exposed diabetic rats, which may aid in the understanding of diabetes pathogenesis.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Complexo Vitamínico B , Ratos , Masculino , Animais , Diabetes Mellitus Experimental/metabolismo , Estreptozocina , Ratos Sprague-Dawley , Metabolômica/métodosRESUMO
Alzheimer's disease (AD) and vascular dementia (VD) are the two most common forms of dementia, share similar symptoms, and are sometimes difficult to distinguish. To investigate the potential mechanisms by which they differ, we identified differentially expressed genes in blood and brain samples from patients with these diseases, and performed weighted gene co-expression network analysis and other bioinformatics analyses. Weighted gene co-expression network analysis resulted in mining of different modules based on differences in gene expression between these two diseases. Enrichment analysis and generation of a protein-protein interaction network were used to identify core pathways for each disease. Modules were significantly involved in cAMP and AMPK signaling pathway, which may be regulated cell death in AD and VD. Genes of cAMP and neurotrophin signaling pathways, including ATP1A3, PP2A, NCEH1, ITPR1, CAMKK2, and HDAC1, were identified as key markers. Using the least absolute shrinkage and selection operator method, a diagnostic model for AD and VD was generated and verified through analysis of gene expression in blood of patients. Furthermore, single sample gene set enrichment analysis was used to characterize immune cell infiltration into brain tissue. That results showed that infiltration of DCs and pDCs cells was increased, and infiltration of B cells and TFH cells was decreased in the brain tissues of patients with AD and VD. In summary, classification based on target genes showed good diagnostic efficiency, and filled the gap in the diagnostic field or optimizes the existing diagnostic model, which could be used to distinguish between AD and VD.
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Objective: At present, there is no early prediction model of left ventricular reverse remodeling (LVRR) for people who are in cardiac arrest with an ejection fraction (EF) of ≤35% at first diagnosis; thus, the purpose of this article is to provide a supplement to existing research. Materials and methods: A total of 109 patients suffering from heart attack with an EF of ≤35% at first diagnosis were involved in this single-center research study. LVRR was defined as an absolute increase in left ventricular ejection fraction (LVEF) from ≥10% to a final value of >35%, with analysis features including demographic characteristics, diseases, biochemical data, echocardiography, and drug therapy. Extreme gradient boosting (XGBoost), random forest, and logistic regression algorithm models were used to distinguish between LVRR and non-LVRR cases and to obtain the most important features. Results: There were 47 cases (42%) of LVRR in patients suffering from heart failure with an EF of ≤35% at first diagnosis after optimal drug therapy. General statistical analysis and machine learning methods were combined to exclude a number of significant feature groups. The median duration of disease in the LVRR group was significantly lower than that in the non-LVRR group (7 vs. 48 months); the mean values of creatine kinase (CK) and MB isoenzyme of creatine kinase (CK-MB) in the LVRR group were lower than those in the non-LVRR group (80.11 vs. 94.23 U/L; 2.61 vs. 2.99 ng/ml; 27.19 vs. 28.54 mm). Moreover, AUC values for our feature combinations ranged from 97 to 94% and to 87% when using the XGBoost, random forest, and logistic regression techniques, respectively. The ablation test revealed that beats per minute (BPM) and disease duration had a greater impact on the model's ability to accurately forecast outcomes. Conclusion: Shorter disease duration, slightly lower CK and CK-MB levels, slightly smaller right and left ventricular and left atrial dimensions, and lower mean heart rates were found to be most strongly predictive of LVRR development (BPM).
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OBJECTS: Caloric restriction (CR) is known to extend lifespan and exert a protective effect on organs, and is thus a low-cost and easily implemented approach to the health maintenance. However, there have been no studies that have systematically evaluated the metabolic changes that occur in the main tissues affected by CR. This study aimed to explore the target tissues metabolomic profile in CR mice. METHODS: Male C57BL/6J mice were randomly allocated to the CR group (n = 7) and control group (n = 7). A non-targeted gas chromatography-mass spectrometry approach and multivariate analysis were used to identify metabolites in the main tissues (serum, heart, liver, kidney, cortex, hippocampus, lung, muscle, and white adipose) in model of CR. RESULTS: We identified 10 metabolites in the heart that showed differential abundance between the 2 groups, along with 9 in kidney, 6 in liver, 6 in lung, 6 in white adipose, 4 in hippocampus, 4 in serum, 3 in cortex, and 2 in muscle. The most significantly altered metabolites were amino acids (AAs) (glycine, aspartic acid, L-isoleucine, L-proline, L-aspartic acid, L-serine, L-hydroxyproline, L-alanine, L-valine, L-threonine, L-glutamic acid, and L-phenylalanine) and fatty acids (FAs) (palmitic acid, 1-monopalmitin, glycerol monostearate, docosahexaenoic acid, 16-octadecenoic acid, oleic acid, stearic acid, and hexanoic acid). These metabolites were associated with 7 different functional pathways related to the metabolism of AAs, lipids, and energy. CONCLUSION: Our results provide insight into the specific metabolic changes that are induced by CR and can serve as a reference for physiologic studies on how CR improves health and extends lifespan.
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Objective: To explore the correlation between characteristics of myocardial energy expenditure (MEE) and the degree of diastolic dysfunction in patients of heart failure with preserved ejection fraction (HFpEF) and its clinical significance. Methods: 125 consecutive patients diagnosed with HFpEF in the Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University from January 2018 to October 2018 were enrolled. According to the degree of diastolic dysfunction, patients were divided into group A (8 ≤ E/e' ≤15) and group B (E/e'> 15), and MEE was calculated, patients finished 1-year clinical follow-up. Results: The level of MEE in group A was significantly lower than that in group B (p < 0.05). During 1-year follow up, MEE over 3145.69 kcal/systole was associated with increased risk of death as compared to patients with MEE less 3145.69 kcal/systole, and in patients with MEE over 101.68 kcal/min than in patients with MEE less than 101.68 kcal/min. Conclusion: There is a significant correlation between MEE and diastolic dysfunction and MEE over 3145.69 kcal/systole as well as MEE over 101.68 kcal/min are linked with increased risk of 1-year mortality in HFpEF.
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Herein, a readily available disilane Me3SiSiMe2(O n Bu) has been developed for the synthesis of diverse silacycles via Brook- and retro-Brook-type rearrangement. This protocol enables the incorporation of a silylene into different starting materials, including acrylamides, alkene-tethered 2-(2-iodophenyl)-1H-indoles, and 2-iodobiaryls, via the cleavage of Si-Si, Si-C, and Si-O bonds, leading to the formation of spirobenzosiloles, fused benzosiloles, and π-conjugated dibenzosiloles in moderate to good yields. Preliminary mechanistic studies indicate that this transformation is realized by successive palladium-catalyzed bis-silylation and Brook- and retro-Brook-type rearrangement of silane-tethered silanols.
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ETHNOPHARMACOLOGICAL RELEVANCE: Herbal polysaccharides have exhibited great immune-enhancing potential. Adjuvants are a key tool for developing efficacious vaccines. In our previous study, a water-soluble polysaccharide extracted from wild Cistanche deserticola Y.C. Ma showed potent immunostimulatory activity. AIM OF STUDY: In this study, the immune profiles and efficacy of aqueous extracts of cultivated Cistanche deserticola Y.C. Ma (AECCD) on ICR mice against ovalbumin (OVA) were investigated. In vitro experiments, the possible DC activation mechanism by AECCD was evaluated. MATERIALS AND METHODS: AECCD were extracted using hot water after which the crude polysaccharides were precipitated by ethanol. Mice were firstly immunized subcutaneously with OVA (10 µg per mouse) alone or OVA (10 µg per mouse) respectively containing different dose of AECCD (200, 400 and 800 µg per mouse) on Days 1 and 14 and the magnitude and kinetics of antibodies and cell-mediated responses were then assessed. RESULTS: AECCD elicited vigorous and long-term IgG responses with mixed Th1/Th2 responses and up-regulated levels of Th-associated cytokines (CD4+IL-4, CD4+IFN-γ and CD8+IFN-γ). Moreover, AECCD induced the strong cellular immune response characterized by increased splenocyte proliferation as well as the activated T cell response. Notably, AECCD significantly enhanced the maturation of dendritic cells (DCs) and inhibited Tregs. In vitro experiments, Preliminary tests indicated that AECCD induced DC activation by promoting phenotypic maturation, cytokine section and allostimulatory activity. Toll-like receptor 4 (TLR4) was an essential receptor for DCs to directly bind AECCD. The inhibitors of NF-κB decreased the expression levels of CD40, CD80, CD86 and MHC-II and the production of IFN-γ, TNF-α and IL-6 through DCs. CONCLUSIONS: Finally, these findings suggested that AECCD could elicit potent and durable antigen specific immune responses through DC activation, which was involved in the regulation of maturation markers and cytokine expression via TLR4-related NF-κB pathway. The study indicates that AECCD is a potential immunomodulator.
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Adjuvantes Imunológicos/farmacologia , Cistanche/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/isolamento & purificação , Animais , Citocinas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Relação Dose-Resposta a Droga , Feminino , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Ovalbumina , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Polissacarídeos/isolamento & purificaçãoRESUMO
BACKGROUND: The structure and composition of the gut microbiota influence patients' response to therapeutic interventions. It is also known that the response to statin treatment can vary greatly from one patient to another, suggesting a possible connection between microbiome composition and response to statins. In the present study, we aim to explore the influence of the microbiome composition on the response to statin treatment among patients with coronary artery disease (CAD). METHODS: A prospective cohort of 836 CAD patients enrolled from January 2016 to December 2017 was used to perform a nested case-control study. We divided 110 CAD patients into two groups according to their response to statins (good response group and poor response group) and compared their gut microbiota. RESULTS: Our analysis reveals no significant difference in microbiome between the two groups. However, significant differences were found in the relative proportion of numerous genera between GR and PR groups. Most remarkably, we could observe that a poor response to statin treatment correlates to a significant decrease in the abundance of beneficial bacteria for the lipid metabolism (Akkermansia muciniphila (A. muciniphila) and Lactobacillus) and a significant increase in the abundance of bacteria (Holdemanella and Facecallibacterium). CONCLUSIONS: Gut microbiota structure is associated with the response to statin. Our results suggest that manipulation of the gut microbiota composition can be an interesting and effective treatment strategy to blood lipid control among CAD patients.
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Doença da Artéria Coronariana , Microbioma Gastrointestinal , Inibidores de Hidroximetilglutaril-CoA Redutases , Estudos de Casos e Controles , Doença da Artéria Coronariana/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos ProspectivosRESUMO
Xuanwei County in Southwest China shows the highest incidence and mortality rate of lung cancer in China. Although studies have reported distinct clinical characteristics of patients from Xuanwei, the molecular features of these patients with non-small cell lung cancer (NSCLC) remain unclear. Here, we comprehensively characterised such cases using next-generation sequencing (NGS). Formalin-fixed, paraffin-embedded tumour samples from 146 patients from Xuanwei with NSCLC were collected for an NGS-based target panel assay; their features were compared with those of reference Chinese and The Cancer Genome Atlas (TCGA) cohorts. Uncommon EGFR mutations, defined as mutations other than L858R, exon 19del, exon 20ins, and T790M, were the predominant type of EGFR mutations in the Xuanwei cohort. Patients harbouring uncommon EGFR mutations were more likely to have a family history of cancer (p = 0.048). A higher frequency of KRAS mutations and lower frequency of rearrangement alterations were observed in the Xuanwei cohort (p < 0.001). Patients from Xuanwei showed a significantly higher tumour mutation burden than the reference Chinese and TCGA cohorts (p < 0.001). Our data indicates that patients from Xuanwei with NSCLC harbouring G719X/S768I co-mutations may benefit from treatment with EGFR-tyrosine kinase inhibitors. Our comprehensive molecular profiling revealed unique genomic features of patients from Xuanwei with NSCLC, highlighting the potential for improvement in targeted therapy and immunotherapy.
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An innovative biosensing assay was developed for simplified, cost-effective, and sensitive detection. By rapid, direct treatment of target proteins with iron porphyrin (TPPFe) in situ, a carboxyl group of amino acid conjugates with an Fe atom of the TPPFe molecule, forming a stable protein complex. We have shown that this complex not only maintains the integrity and functions of original proteins but also acquires peroxidase activity that can turn TMB to a comparably visible signal like that in ELISA. This study is unique since such conversion is difficult to achieve with standard chemical modification or molecular biology methods. In addition, the proposed immunoassay is superior to traditional ELISA as it eliminates an expensive and complicated cross-linking process of an enzyme-labeled antibody. From a practical point of view, we extended this assay to rapid detection of clinically relevant proteins and glucose in blood samples. The results show that this simple immunoassay provides clinical diagnosis, food safety, and environmental monitoring in an easy-to-implement manner.
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Técnicas Biossensoriais , Ensaio de Imunoadsorção Enzimática , Glucose , Imunoensaio , FerroRESUMO
The construction of a seven-membered ring in the polycyclic aromatic hydrocarbon skeleton remains a notoriously difficult but attractive challenge. Herein a novel palladium-catalyzed [4 + 3] decarboxylative annulation of 2-iodobiphenyls with 2-(2-halophenyl)acrylic acids is reported, which provides an efficient approach for assembling various tribenzo[7]annulenes via a C-H activation and decarboxylation process. Moreover, tribenzo[7]annulenes can be also synthesized via a [2 + 2 + 3] decarboxylative annulation strategy by employing readily available 1,2-halobenzenes, phenylboronic acids, and 2-(2-halophenyl)acrylic acids.
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Changes in biothiols, including glutathione (GSH) and cysteine, are closely related to a variety of diseases and cellular functions. Real-time monitoring intracellular GSH and cysteine dynamics in living cells are important for understanding pathophysiological processes. In this study, a stable heterostructure of dual-emission fluorescent gold carbon dots (GCDs) consisting of carbon skeleton and gold nanoclusters was prepared, which emits strong blue fluorescence and weak yellow-orange fluorescence. The blue fluorescence of the as-prepared GCDs has no response to biothiols including GSH and cysteine, but a turn-on yellow-orange fluorescence would be appeared accompanied by the biothiols reacting with the GCDs. Ratiometric fluorescent bioimaging therefore may be established based on the unique GCDs to detect GSH and cysteine levels in living cells. Moreover, real time monitoring GSH and cysteine levels in various cell lines in living cells at different growth stages was realized. The concentration of GSH in cancer cells is higher than that of normal cells, however, the level of cysteine in normal cells is consistently higher than in cancer cells at different stages of cell growth. The fluorescent GCDs probe provides a promising tool for tracking on regulation of GSH and cysteine dynamics by physiological environments due to the capability for real-time quantitation of GSH and cysteine.
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Carbono , Ouro , Cisteína , Corantes Fluorescentes , Glutationa , Espectrometria de FluorescênciaRESUMO
Ferroptosis is an iron-dependent form of regulated cell death. In this study, a ratiometric fluorescent probe, gold carbon dots (GCDs) consisting of carbon skeleton and gold nanoclusters, was used for in situ imaging to monitor redox status in biothiols (glutathione and cysteine) and ferric metabolism of cancer cells in ferroptosis. The as-prepared GCDs can selectively respond to biothiols, interestingly, the fluorescence may be switched to sense ferric ions without interference by biothiols under proper conditions. The robust GCDs-probe exhibits excellent photobleaching resistance and can reversibly respond to intracellular biothiols/ferric ion with high temporal resolution. The 8 h real-time imaging of living cells was employed to track the fluctuation of biothiols, showing the change of redox status in ferroptosis. In addition, release of ferric ions in cells was monitored. The real-time imaging of depletion of biothiols and release of ferric ion in cells indicates the GCDs-probe can monitor how the ferroptosis regulates redox status in biothiols and ferric metabolism.