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Non-tuberculous mycobacteria (NTM) infection is common in bronchiectasis, with rising incidence globally. However, investigation into NTM in bronchiectasis patients in China remains relatively limited. This work aimed to identify and understand the features of NTM in bronchiectasis patient in Fuzhou district of China. The pulmonary samples were collected from 281 bronchiectasis patients with suspected NTM infection in Fuzhou, 2018-2022. MPB64 antigen detection was employed for the preliminary evaluation of NTM. Further NTM identification was realized using gene chip and gene sequencing. Among 281 patients, 172 (61.21%) patients were NTM-positive (58.72%) according to MPB64 antigen detection, with females (58.72%) outnumbering males (41.28%) and the highest prevalence in the age group of 46-65 years. In total, 47 NTM single infections and 3 mixed infections (1 Mycobacterium tuberculosis complex-M. intracellulare, 1 M. avium-M. intracellulare, and 1 M. abscessus-M. intracellulare) were identified through multicolor melting curve analysis (MMCA), which was compared with gene sequencing results. Both methods suggested Mycobacterium (M.) intracellulare, M. abscessus, and M. avium as the primary NTM species affecting bronchiectasis patients. M. intracellulare and M. abscessus were more frequent in females than males with the highest prevalence in the age group of 46-65 years according to MMCA. This research provides novel insights into the epidemiological and clinical features of NTM in bronchiectasis patients in Southeastern China. Significantly, M. intracellulare, M. abscessus, and M. avium were identified as the major NTM species, contributing to a better understanding and management of bronchiectasis accompanied by NTM infection.
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Bronquiectasia , Infecções por Mycobacterium não Tuberculosas , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Micobactérias não Tuberculosas/genética , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/complicações , Bronquiectasia/diagnóstico , Bronquiectasia/epidemiologia , Bronquiectasia/complicações , Complexo Mycobacterium avium/genética , Hospitais , China/epidemiologiaRESUMO
The Wnt/ß-catenin pathway is critical to maintaining cell fate decisions. Recent study showed that liquid-liquid-phase separation (LLPS) of Axin organized the ß-catenin destruction complex condensates in a normal cellular state. Mutations inactivating the APC gene are found in approximately 80% of all human colorectal cancer (CRC). However, the molecular mechanism of the formation of ß-catenin destruction complex condensates organized by Axin phase separation and how APC mutations impact the condensates are still unclear. Here, we report that the ß-catenin destruction complex, which is constructed by Axin, was assembled condensates via a phase separation process in CRC cells. The key role of wild-type APC is to stabilize destruction complex condensates. Surprisingly, truncated APC did not affect the formation of condensates, and GSK 3ß and CK1α were unsuccessfully recruited, preventing ß-catenin phosphorylation and resulting in accumulation in the cytoplasm of CRCs. Besides, we propose that the phase separation ability of Axin participates in the nucleus translocation of ß-catenin and be incorporated and concentrated into transcriptional condensates, affecting the transcriptional activity of Wnt signaling pathway.
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Complexo de Sinalização da Axina , beta Catenina , Humanos , Complexo de Sinalização da Axina/genética , Proteína Axina/genética , Proteína Axina/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Separação de Fases , Mutação/genética , Via de Sinalização Wnt/genética , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismoRESUMO
Flexible sensors are highly flexible, malleable, and capable of adapting todifferent shapes, surfaces, and environments, which opens a wide range ofpotential applications in the field of human-machine interface (HMI). Inparticular, flexible pressure sensors as a crucial member of the flexiblesensor family, are widely used in wearable devices, health monitoringinstruments, robots and other fields because they can achieve accuratemeasurement and convert the pressure into electrical signals. The mostintuitive feeling that flexible sensors bring to people is the change ofhuman-machine interface interaction, from the previous rigid interaction suchas keyboard and mouse to flexible interaction such as smart gloves, more inline with people's natural control habits. Many advanced flexible pressuresensors have emerged through extensive research and development, and to adaptto various fields of application. Researchers have been seeking to enhanceperformance of flexible pressure sensors through improving materials, sensingmechanisms, fabrication methods, and microstructures. This paper reviews the flexible pressure sensors in HMI in recent years, mainlyincluding the following aspects: current cutting-edge flexible pressuresensors; sensing mechanisms, substrate materials and active materials; sensorfabrication, performances, and their optimization methods; the flexiblepressure sensors for various HMI applications and their prospects.
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Eletricidade , Dispositivos Eletrônicos Vestíveis , HumanosRESUMO
OBJECTIVE: Inflammatory bowel disease (IBD) is listed by the World Health Organization as one of the modern intractable diseases. High mobility histone box 1 (HMGB1), originally described as a non-histone nucleoprotein involved in transcriptional regulation, was later identified as a pro-inflammatory cytokine that may contribute to the pathogenesis of inflammatory diseases such as IBD. Neutrophil extracellular traps (NETs) play an important role in the pathophysiology of IBD The aim of this study was to investigate the role of HMGB1 in experimental colitis mice and its potential mechanisms of action. METHODS: We first constructed the experimental colitis mouse model. Intervention of mice by rhHMGB1 supplementation or HMGB1 inhibition. The pathological morphology of the colon was observed using HE staining. Apoptosis of colonic tissue intestinal epithelial cells was evaluated using Tunel assay. The expression of HMGB1, ZO-1 and occludin in colon tissue was detected by immunohistochemistry, ELISA and western-blot. We also assessed the effects of HMGB1 on colonic injury, NETs content, macrophage polarization and inflammatory cells in mice. The regulatory effect of HMGB1 inhibition on NETs was assessed by combining DNase I. RESULTS: Inhibition of HMGB1 significantly reduced the inflammatory model in experimental colitis mice, as evidenced by reduced body weight, increased colonic length, reduced DAI scores and apoptosis, reduced inflammatory response, and improved colonic histopathological morphology and intestinal mucosal barrier function. Meanwhile, inhibition of HMGB1 was able to reduce the expression of CD86, citH3 and MPO and increase the expression of CD206 in the colonic tissue of mice. In addition, DNase I intervention was also able to improve colonic inflammation in mice. And the best effect was observed when DNase I and inhibition of HMGB1 were intervened together. CONCLUSION: Inhibition of HMGB1 ameliorates IBD by mediating NETs and macrophage polarization.
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Colite , Armadilhas Extracelulares , Proteína HMGB1 , Doenças Inflamatórias Intestinais , Animais , Camundongos , Proteína HMGB1/metabolismo , Armadilhas Extracelulares/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Doenças Inflamatórias Intestinais/patologia , Modelos Animais de Doenças , Macrófagos/metabolismo , Desoxirribonuclease I , Camundongos Endogâmicos C57BL , Sulfato de DextranaRESUMO
We report the oxidative dimerization reaction of siloxydienes derived from simple enones that creates a new gamma-gamma (γ-γ) C-C bond using catalytic iron and benzoyl peroxide as the terminal oxidant in acetonitrile solvent at ambient temperature. The reaction shows a broad substrate scope including cyclic and acyclic siloxydienes derived from ketones, aldehydes, and esters, which are converted to 1,8-dicarbonyl compounds under mild catalytic reaction conditions in 19-89 % yield across 30 examples. The method is suitable for the coupling of sterically demanding carbon centers, including the formation of vicinal quaternary centers. Conceptually, the dienol ether serves as a precursor to a conjugated radical cation, which undergoes highly site selective γ-dimerization reactions. The γ-γ dimerization strategy is applied to the synthesis of a bioactive analogue of honokiol.
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OBJECTIVE: Inflammation, malnutrition, and cancer are intricately interconnected. Despite this, only a few studies have delved into the relationship between inflammatory malnutrition and the risk of death among cancer survivors. This study aimed to specifically investigate the association between the categorically defined Naples prognostic score (NPS) and the prognosis of cancer survivors. METHODS: Data from 42,582 participants in the National Health and Nutrition Examination Survey (NHANES, 1999-2018) were subjected to analysis. Naples prognostic scores (NPS) were computed based on serum albumin (ALB), total cholesterol (TC), neutrophil to lymphocyte ratio (NLR), and lymphocyte to monocyte ratio (LMR), and participants were stratified into three groups accordingly. Cancer status was ascertained through a self-administered questionnaire, while mortality data were sourced from the National Death Index up to December 31, 2019. Multiple logistic regression was employed to estimate the odds ratio (OR) with a 95% confidence interval (CI) between NPS and cancer prevalence within the U.S. community population. Kaplan-Meier survival analysis and the Log-rank test were utilized to compare survival disparities among the three groups. Additionally, Cox proportional regression was utilized to estimate the hazard ratio (HR) with a 95% CI. RESULTS: The incidence of cancers was 9.86%. Among the participants, 8140 individuals (19.1%) were classified into Group 0 (NPS 0), 29,433 participants (69.1%) into Group 1 (NPS 1 or 2), and 5009 participants (11.8%) into Group 2 (NPS 3 or 4). After adjusting for confounding factors, the cancer prevalence for the highest NPS score yielded an odds ratio (OR) of 1.64 (95% CI: 1.36, 1.97) (P(for trend) < 0.05). In comparison to cancer survivors in Group 0, those with the highest NPS had adjusted hazard ratios (HRs) of 2.57 (95% CI: 1.73, 3.84) for all-cause mortality, 3.44 (95% CI: 1.64, 7.21) for cardiovascular mortality, 1.60 (95% CI: 1.01, 2.56) for cancer mortality, and 3.15 (95% CI: 1.74, 5.69) for other causes of mortality (All P(for trend) < 0.05). These associations remained consistent when stratified by age, sex, race, and body mass index. CONCLUSIONS: This study indicates that the Naples prognostic score (NPS), serving as a novel prognostic metric integrating inflammation and nutritional status, is closely linked to cancer prognosis within the general population.
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Sobreviventes de Câncer , Neoplasias , Inquéritos Nutricionais , Humanos , Feminino , Masculino , Sobreviventes de Câncer/estatística & dados numéricos , Prognóstico , Pessoa de Meia-Idade , Neoplasias/mortalidade , Idoso , Adulto , Inflamação , Neutrófilos , Desnutrição/epidemiologia , Colesterol/sangue , Estados Unidos/epidemiologia , Albumina Sérica/análise , Albumina Sérica/metabolismo , Monócitos/metabolismo , Linfócitos/metabolismoRESUMO
Glaucoma is the leading cause of irreversible blindness worldwide. Previous observational studies have suggested a relationship between central corneal thickness (CCT) and glaucoma; however, the results are inconsistent. This study aimed to investigate whether CCT is associated with a risk for developing open-angle glaucoma (OAG). We employed two-sample Mendelian randomization to assess the relationship between CCT and OAG, namely, primary open-angle glaucoma (POAG) and suspected glaucoma. Genetic instruments composed of variants associated with CCT at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies from Iglesias et al. for discovery and Bonnemaijer et al. for replication. Summary-level statistics for these instruments for the OAG were obtained from the FinnGen Project (Release 10). Inverse-variance-weighted regression of genetic susceptibility predicted that increased CCT was positively associated with an increased risk for POAG (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.008; P = 0.001) and suspected glaucoma (OR, 1.006; 95% CI, 1.003-1.009; P < 0.001). In the replication sample of CCT, increased CCT was also positively associated with an increased risk for POAG (OR, 1.004; 95% CI, 1.000-1.008; P = 0.029) and suspected glaucoma (OR, 1.005; 95% CI, 1.001-1.008; P = 0.013). We found genetic evidence supporting a potential causal association between increased CCT and the risk of POAG and suspected glaucoma in the European population. This findings indicates the clinical significance of CCT in the diagnosis and treatment of glaucoma. Further studies are needed to elucidate the underlying mechanisms of this causal relationship.
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Córnea , Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Aberto , Análise da Randomização Mendeliana , Glaucoma de Ângulo Aberto/genética , Humanos , Córnea/patologia , Polimorfismo de Nucleotídeo Único , Pressão Intraocular/fisiologia , Fatores de Risco , Predisposição Genética para Doença , Paquimetria Corneana , Masculino , FemininoRESUMO
BACKGROUND: Inflammation and nutrition and depression are interrelated, and both are related to changes in mortality rates. We investigated the association of nutritional and inflammation index or depressive symptoms with the risk of all-cause mortality or cause-specific mortality among cancer survivors. METHODS: A prospective cohort of a nationally representative sample of cancer survivors, aged 40 years or older (n = 2331; weighted population, 15 248 255; 67.6 ± 11.0 years; 50.6 % males), were recruited from the US National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Advanced lung cancer inflammation index (ALI) reflected inflammation and nutritional status and Patient Health Questionnaire 9 (PHQ-9) demonstrated depressive symptoms. The independent and joint associations of ALI and PHQ-9 score with mortality outcomes were examined among cancer survivors and Cox regression analysis based on weights was used to calculate the relative risk. RESULTS: We identified 605 all-cause deaths (cancer, 204; non-cancer, 401) over a median of 6.2 years of follow-up (15,385 person-years; interquartile range, 3.3-9.8 years). High ALI was observed to be consistently associated with lower risks of all-cause (hazard ratio [HR], 0.516; 95 % CI, 0.400-0.667) and non-cancer (HR, 0.414; 95 % CI, 0.291-0.588) mortality compared with low ALI in a series of adjusted models. Meanwhile, lower PHQ-9 score (0-4) was associated with lower risks of all-cause (HR, 0.686; 95 % CI, 0.521-0.903) and non-cancer (HR, 0.686; 95 % CI, 0.474-0.992) mortality compared with higher PHQ-9 score (≥10). Furthermore, joint analyses showed that high ALI was associated with a decreased risk of death among cancer survivors who were not depressive. Specifically, survivors with high ALI but not depressive symptoms had the lowest overall (HR, 0.404; 95 % CI, 0.228-0.715) risks. CONCLUSION: In this cohort study, we observed impact of nutritional and inflammatory status and depressive symptoms on mortality among cancer survivors, with the lowest risks of death from both all causes and non-cancer being noted among the combination of high level ALI with no depression.
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Sobreviventes de Câncer , Neoplasias , Masculino , Humanos , Feminino , Estudos de Coortes , Depressão/complicações , Inquéritos Nutricionais , Estudos Prospectivos , InflamaçãoRESUMO
BACKGROUND: International migration has accelerated the HIV-1 spread across national borders, gradually reducing the restrictions on the geographical distribution of HIV-1 subtypes. Subtypes A and G are globally recognized as the third and sixth most dominant HIV-1 genotypes, mainly prevalent in Africa, but rarely detected in China. Here we reported an imported HIV-1 recombinant which was composed of sub-subtypes A1 and A7 of subtype A and subtype G genes in a Chinese female. This virus was the first HIV-1 recombinant including A7 genes reported in the world. CASE PRESENTATION: The near full-length genome (NFLG) was obtained from the plasma sample of the female in an HIV-1 molecular epidemiological survey with 853 participants in China. Phylogenetic analyses showed that this NFLG sequence contains three A7 segments, four G segments and one A1 segment with seven breakpoints, and all these segments were closely related to HIV-1 references circulating in Africa. The evidence from epidemiological investigation indicated that this female participant had a more-than-two-years heterosexual contact history with a fixed partner from Nigeria, a country in west Africa, which further supported the results of phylogenetic analyses. By the Bayesian phylogenetic analyses, the times of most recent common ancestors (tMRCA) of the partial pol gene (nt2308-3284, A7 region) and full-length vpr-vpu plus partial env gene (nt5534-6858, G region) were estimated around 1989 and 1984, respectively. CONCLUSIONS: In this study, by using the NFLG sequencing, we identified an imported HIV-1 A1/A7/G recombinant which was estimated to originate around 1980s in Africa and introduced into China with international migration. This study highlighted the complexity of the global HIV-1 epidemic, the necessity of using genome sequences to determine HIV-1 genotypes and the importance of real-time monitoring of HIV-1 infection among international migrants and travelers.
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Soropositividade para HIV , HIV-1 , Humanos , Feminino , HIV-1/genética , Filogenia , Teorema de Bayes , China/epidemiologia , NigériaRESUMO
Precisely modulating the synergistic release behavior of multiple bioactive substances has emerged as a formidable challenge in recent years. In this work, we successfully prepared core-sheath nanofibers, where a thin cellulose acetate (CA) coating enrobed the core. Curcumin (Cur) was encapsulated in the core layer as a model drug, while zinc oxide (ZnO) nanoparticles were loaded on the sheath layer. The prepared fiber exhibited a straight cylindrical morphology containing nanoparticles, and the distinct core-sheath nanostructure was demonstrated through transmission electron microscopy (TEM). X-ray diffraction (XRD) and Fourier transform infrared (FTIR) were conducted to study the physical state and compatibility among CA, Cur, and ZnO. Drug release data indicated that core-sheath nanofibers were able to decelerate the rate of drug release, and the thickness of the sheath layer increased in the presence of ZnO particles. Most remarkably, these core-sheath nanofibers exhibited the remarkable ability to sustain the release of drugs and zinc ion (Zn2+), the two-day synergistically release behavior leading to a significant increase in cell proliferation. This material preparation strategy for the synergistic and controlled release of two bioactive substances is instructive for the exploration of innovative and versatile drug delivery systems.
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Nanofibras , Óxido de Zinco , Preparações Farmacêuticas , Nanofibras/química , ZincoRESUMO
BACKGROUD: The recurrence rate of chronic rhinosinusitis with nasal polyps (CRSwNP) is positively correlated with eosinophil infiltration. Increased interleukin (IL)-19 and eosinophil chemokine RANTES levels have been reported in patients with CRSwNP. This study aimed to clarify the role of IL-19 in mediating RANTES expression and eosinophilic infiltration in eosinophilic CRSwNP (Eos CRSwNP). METHODS: Nasal tissue samples were obtained from patients with CRSwNP and controls. The expression of IL-19, its receptors, ECP, and RANTES in tissues was investigated. Primary human nasal epithelial cells (HNECs) and nasal polyp tissue blocks were cultured, then stimulated by IL-19; ERK phosphorylation, NF-κB pathway activation, RANTES level, eosinophils migration and infiltration were detected using RT-qPCR, ELISA, western blotting, HE, immunohistochemistry, immunofluorescence staining, confocal microscopy, and transwell migration assay. RESULTS: The expression of IL-19 and its receptors (IL-20R1/IL-20R2), eosinophil cationic protein, and RANTES in nasal tissues from patients with Eos CRSwNP was significantly increased compared to that in non-Eos CRSwNP and control subjects. IL-19 co-localized with RANTES in nasal tissues and significantly elevated RANTES expression in HNECs. IL-19-blocking antibody and siRNA knockdown of IL-20R1 ameliorated the effect of IL-19 on RANTES secretion in HNECs. Moreover, IL-19-induced RANTES upregulation was associated with the activation of the ERK and NF-κB pathways. NF-κB activation was mediated by the ERK pathway in IL-19-treated HNECs, and IL-19 enhanced eosinophil infiltration in nasal polyp tissue blocks. CONCLUSIONS: Our findings indicate that IL-19 promotes RANTES expression via the ERK/NF-κB pathway in HNECs and is implicated in eosinophil infiltration in patients with Eos CRSwNP.
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Pólipos Nasais , Rinite , Sinusite , Humanos , NF-kappa B/metabolismo , Eosinófilos , Regulação para Cima , Sistema de Sinalização das MAP Quinases , Interleucinas/genética , Interleucinas/metabolismo , Epitélio , Doença CrônicaRESUMO
C-O bond formation via C-H alkoxylation remains a challenge, especially coupling with a secondary alcohol, due to its low activity and sterically encumbered property. Here, we report a general and effective cobalt-catalyzed oxidative cross-coupling of benzamides with secondary alcohols via C-H alkoxylation reaction under solvothermal conditions, enabled by a salicylaldehyde/cobalt complex. The protocol features easy operation without additives, broad substrate scope, and excellent functional tolerance. The applicability is proven by the gram-scale synthesis and modification of natural products.
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A straight and efficient protocol for the synthesis of hindered indole-ethers via C-H alkoxylation of indoles was developed by a cobalt-catalyzed cross-dehydrogenative coupling reaction with secondary alcohols. The selection of the salicylaldehyde-Co(II) catalyst enables the reaction to proceed under conditions without acid or base addition in the presence of limited alcohols. The protocol has broad substrate scope for both indole and secondary alcohols and exhibits good functional tolerance. The synthetic applications are proven by gram-scale reaction and further diversification of the product. Preliminary mechanistic investigations indicate that the activation of C-H bonds is not the rate-determining step of the reaction.
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Myocardial ischemia/reperfusion (MI/R) injury is a detrimental disease with high mortality worldwide. We aimed to explore the role of G protein-coupled receptor 4 (GPR4) and lysophosphatidic acid receptor 1 (LPAR1) in MI/R injury in vitro. H9c2 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to simulate the MI/R injury and GPR4 expression was detected. Then, GPR4 was knocked down and cell viability was examined with a CCK-8 assay. The activities of LDH, CK and CK-MB were detected to evaluate the damage of OGD/R-induced H9c2 cells. ELISA kits and TUNEL staining were used to examine the inflammation and apoptosis of H9c2 cells exposed to OGD/R conditions. Western blot was employed to detect the expression of proteins related to apoptosis and NLRP3 inflammasome signaling. Additionally, Co-IP analyzed the binding between GPR4 and LPAR1. Finally, LPAR1 was overexpressed to conduct the rescue experiments. Results revealed that GPR4 was upregulated in OGD/R-treated H9c2 cells and GPR4 knockdown attenuated the damage of H9c2 cells. OGD/R induced inflammation and apoptosis were markedly inhibited by GPR4 silencing, as evidenced by the decreased TNF-α, IL-6 and IL-8 levels as well as the elevated Bcl-2 expression and reduced Bax and cleaved caspase3 expression. Moreover, GPR4 bound to LPAR1 and upregulated LPAR1 expression. Interference with GPR4 inactivated the NLRP3 inflammasome signaling. Besides, LPAR1 overexpression abrogated the effects of GPR4 silencing on the damage, inflammation and apoptosis of H9c2 cells induced by OGD/R. Particularly, LPAR1 upregulation promoted the activation of NLRP3 inflammasome signaling in GPR4-silenced H9c2 cells induced by OGD/R. To be concluded, GPR4 deficiency inactivates NLRP3 inflammasome signaling by inhibiting LPAR1 expression to ameliorate OGD/R -induced inflammation and apoptosis of cardiomyocytes.
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PURPOSE: This study aimed to develop a multisequence MRI-based volumetric histogram metrics model for predicting pathological complete response (pCR) in advanced head and neck squamous cell carcinoma (HNSCC) patients undergoing neoadjuvant chemo-immunotherapy (NCIT) and compare its predictive performance with AJCC staging and RECIST 1.1 criteria. METHODS: Twenty-four patients with locally advanced HNSCC from a prospective phase II trial were enrolled for analysis. All patients underwent pre- and post-NCIT MRI examinations from which whole-tumor histogram features were extracted, including T1WI, T2WI, enhanced T1WI (T1Gd), diffusion-weighted imaging (DWI) sequences, and their corresponding apparent diffusion coefficient (ADC) maps. The pathological results divided the patients into pathological complete response (pCR) and non-pCR (N-pCR) groups. Delta features were calculated as the percentage change in histogram features from pre- to post-treatment. After data reduction and feature selection, logistic regression was used to build prediction models. ROC analysis was performed to assess the diagnostic performance. RESULTS: Eleven of 24 patients achieved pCR. Pre_T2_original_firstorder_Minimum, Post_ADC_original_firstorder_MeanAbsoluteDeviation, and Delta_T1Gd_original_firstorder_Skewness were associated with achieving pCR after NCIT. The Combined_Model demonstrated the best predictive performance (AUC 0.95), outperforming AJCC staging (AUC 0.52) and RECIST 1.1 (AUC 0.72). The Pre_Model (AUC 0.83) or Post-Model (AUC 0.83) had a better predictive ability than AJCC staging. CONCLUSION: Multisequence MRI-based volumetric histogram analysis can non-invasively predict the pCR status of HNSCC patients undergoing NCIT. The use of histogram features extracted from pre- and post-treatment MRI exhibits promising predictive performance and offers a novel quantitative assessment method for evaluating pCR in HNSCC patients receiving NCIT.
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Neoplasias de Cabeça e Pescoço , Terapia Neoadjuvante , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/patologia , Idoso , Imageamento por Ressonância Magnética/métodos , Estadiamento de Neoplasias , Adulto , Resultado do Tratamento , Valor Preditivo dos Testes , Imunoterapia/métodos , Imagem de Difusão por Ressonância Magnética/métodosRESUMO
Cell division cycle associated 5 (CDCA5) is correlated with the development and progression of many malignant tumors. However, little is known about its role in epithelial ovarian cancer (EOC) progression. In this study, the clinical value, biological function and underlying mechanisms of CDCA5 in EOC were evaluated. CDCA5 mRNA and protein levels were substantially upregulated in EOC and had a significant positive correlation with adverse clinicopathological characteristics and a poor prognosis. CDCA5 facilitated proliferation, invasion, and metastasis and disrupted mitochondrial-mediated endogenous apoptosis by activating the cell cycle pathway and inhibiting the P53 pathway in EOC cells. Conversely, knockdown of CDCA5 expression blocked the malignant activities of EOC cells and suppressed the growth of xenograft tumors in vivo. Mechanistically, the transcription factor KLF5 bound to a specific site in the CDCA5 promoter and promoted CDCA5 expression. Moreover, KLF5 overexpression rescued the negative regulation of inhibited CDCA5 expression on EOC cell proliferation. In conclusion, our findings revealed that CDCA5 promoted tumor progression of EOC via the KLF5/CDCA5/cell cycle and P53 axes, which might provide new insights into the roles of CDCA5 in EOC.
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Neoplasias Ovarianas , Proteína Supressora de Tumor p53 , Feminino , Humanos , Carcinoma Epitelial do Ovário/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Ciclo Celular/genética , Proliferação de Células/genética , Neoplasias Ovarianas/patologia , Regulação Neoplásica da Expressão Gênica/genética , Movimento Celular/genética , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismoRESUMO
We aimed to establish the prevalence of atypical masturbation in the general population and explore the association between atypical masturbation and male sexual dysfunction in heterosexual males. Atypical masturbation refers to stimulation significantly distinct from that encountered during partnered sexual activity. We posted questionnaires that contained the abridged International Index of Erectile Function (IIEF-6) and the premature ejaculation diagnostic tool on social media in China. We collected 2743 valid questionnaires from December 9, 2020, to April 18, 2021. We found that the prevalence of atypical masturbation in the general population was 10.97%. Men with atypical masturbation had lower IIEF-6 scores and higher rates of erectile dysfunction (ED) than men with typical masturbation. The prevalence of premature ejaculation and estimated intravaginal ejaculatory latency time were not significantly different among men with different patterns of masturbation. Our study demonstrated that atypical masturbation is associated with ED, and a clinician dealing with sexual issues should inquire more fully about masturbation patterns than has been done to date.
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Disfunção Erétil , Heterossexualidade , Masturbação , Ejaculação Precoce , Humanos , Masculino , Masturbação/epidemiologia , Masturbação/psicologia , Heterossexualidade/estatística & dados numéricos , Heterossexualidade/psicologia , Adulto , Pessoa de Meia-Idade , Inquéritos e Questionários , China/epidemiologia , Ejaculação Precoce/epidemiologia , Ejaculação Precoce/psicologia , Disfunção Erétil/epidemiologia , Prevalência , Disfunções Sexuais Fisiológicas/epidemiologia , Parceiros Sexuais/psicologia , Adulto JovemRESUMO
Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment, and the increase in number and survival of premature infants may inflate its burden globally. We aimed to comprehensively assess the trends and inequalities in the burden of ROP-related visual impairment and to identify improvement gaps to facilitate appropriate actions in neonatal care systems. We obtained ROP data from the Global Burden of Disease 2019 study. We employed joinpoint regression analysis to assess the trends of the burden of ROP-related visual impairment, measured by age-standardised prevalence rates, health equity analysis methods to evaluate cross-country burden inequalities, and data envelopment and stochastic frontier analyses to identify improvement gaps based on the development status, i.e., sociodemographic index (SDI). Between 1990 and 2019, the age-standardised prevalence rates of ROP-related visual impairment significantly increased worldwide (average annual percentage change: 0.23 [95% confidence interval, 0.21-0.26] among males and 0.26 [0.25-0.27] among females), primarily in developed regions. Although significant SDI-related cross-country inequalities were identified, these reduced over time (slope index of inequality: -57.74 [-66.22 to -49.25] in 1990 to -29.68 [-38.39 to -20.97] in 2019; health concentration index: -0.11 [-0.13 to -0.09] in 1990 to -0.07 [-0.09 to -0.06] in 2019). Notably, some less-developed countries exhibited superior performance despite limited resources, whereas others with a higher SDI delivered lagging performance. Conclusion: The global burden of ROP-related visual impairment has steadily increased between 1990 and 2019, with disproportionate burden concentration among less-developed countries, requiring appropriate preventive and intervention measures. What is Known: ⢠Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment. ⢠The prevalence of ROP is anticipated to increase due to the growing number of extremely premature infants. What is New: ⢠The prevalence of ROP-related visual impairment has increased worldwide, primarily in developed regions, with declining but persisting cross-country inequalities. ⢠The increasing burden of ROP-related visual impairment should be considered as part of global and national health agendas, requiring interventions with proven efficacy.
Assuntos
Doenças do Recém-Nascido , Retinopatia da Prematuridade , Recém-Nascido , Masculino , Lactente , Feminino , Humanos , Criança , Retinopatia da Prematuridade/complicações , Retinopatia da Prematuridade/epidemiologia , Países em Desenvolvimento , Lactente Extremamente Prematuro , Prevalência , Transtornos da Visão/epidemiologia , Transtornos da Visão/etiologia , Idade GestacionalRESUMO
BACKGROUND: The presence of sensory impairment among older age cohorts exerts a significant impact on both individuals and society generally. Although the impact of dietary patterns on health is vital across all stages of life, there still a paucity of comprehensive research on the association between dietary variety and sensory impairments. OBJECTIVE: To investigate the potential relationship between dietary diversity and the prevalence of visual and hearing impairment or dual sensory impairments (visual and hearing impairment) among the oldest old population. METHODS: This is a cross-sectional study relied on data obtained from the 2018 survey conducted by the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Subjects aged 80 and older with complete vision and hearing data were included in the study. Multivariate logistic regression models were developed to examine the association between dietary components and visual and hearing impairment while controlling for age, gender, socioeconomic demographic factors, living habits, other food habits, and general health status. RESULTS: The study included 10,093 participants, with an average age of 92.29 ± 7.75 years. Vision and hearing function were assessed based on the ability to distinguish the direction of the break in the circle and the requirement for hearing aids, respectively. Upon controlling for confounding variables, individuals with a greater Dietary Diversity Score (DDS, the number of food groups, range: 1-11) had a reduced likelihood of experiencing visual impairment (odds ratio [OR] = 0.944, 95% confidence interval [CI], 0.915-0.974) and dual sensory impairment (OR = 0.930, 95% CI, 0.905-0.955). In comparison to the low dietary variety group (insufficient dietary diversity, DDS < 4), the high dietary diversity group (sufficient dietary diversity, DDS ≥ 4) exhibited a decreased risk of visual impairment (OR = 0.820, 95% CI, 0.713-0.944) and dual sensory impairment (OR = 0.751, 95% CI, 0.667-0.846). However, no statistically significant correlation was observed between dietary diversity and the presence of only hearing impairment (OR = 0.924, 95% CI, 0.815-1.047) (P < 0.05). CONCLUSIONS AND IMPLICATIONS: The synthesis of research findings suggests that following diverse dietary patterns and healthy nutritional practices may be an effective and affordable way to prevent age-related decline in visual impairment and dual sensory impairment.
Assuntos
Dieta , Perda Auditiva , Transtornos da Visão , Humanos , Feminino , Masculino , China/epidemiologia , Estudos Transversais , Perda Auditiva/epidemiologia , Transtornos da Visão/epidemiologia , Idoso de 80 Anos ou mais , Estudos Longitudinais , Dieta/estatística & dados numéricos , Longevidade , Prevalência , População do Leste AsiáticoRESUMO
NUDT2 is an enzyme important for maintaining the intracellular level of the diadenosine tetraphosphate (Ap4A). Bi-allelic loss of function variants in NUDT2 has recently been reported as a rare cause of intellectual disability (ID). Herein, we describe a Chinese girl with ID, attention deficit hyperactivity disorder (ADHD), and motor delays with abnormal walking posture and difficulty climbing stairs, who bears compound heterozygous variants c.34 C > T (p.R12*) and c.194T > G (p.I65R) in NUDT2. Homozygous variants c.34 C > T (p.R12*) or c.186del (p.A63Qfs*3) in NUDT2 were previously reported to cause ID. This is the first patient with ID due to compound heterozygous variants in NUDT2 and p.I65R is a novel missense variant. This study enriched the genotype and phenotype of NUDT2-related ID and supported the critical developmental involvement of NUDT2.