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OBJECTIVE: Develop a practical scoring system based on radiomics and imaging features, for predicting the malignant potential of incidental indeterminate small solid pulmonary nodules (IISSPNs) smaller than 20 mm. METHODS: A total of 360 patients with malignant IISSPNs (n = 213) and benign IISSPNs (n = 147) confirmed after surgery were retrospectively analyzed. The whole cohort was randomly divided into training and validation groups at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) algorithm was used to debase the dimensions of radiomics features. Multivariate logistic analysis was performed to establish models. The receiver operating characteristic (ROC) curve, area under the curve (AUC), 95% confidence interval (CI), sensitivity and specificity of each model were recorded. Scoring system based on odds ratio was developed. RESULTS: Three radiomics features were selected for further model establishment. After multivariate logistic analysis, the combined model including Mean, age, emphysema, lobulated and size, reached highest AUC of 0.877 (95%CI: 0.830-0.915), accuracy rate of 83.3%, sensitivity of 85.3% and specificity of 80.2% in the training group, followed by radiomics model (AUC: 0.804) and imaging model (AUC: 0.773). A scoring system with a cutoff value greater than 4 points was developed. If the score was larger than 8 points, the possibility of diagnosing malignant IISSPNs could reach at least 92.7%. CONCLUSION: The combined model demonstrated good diagnostic performance in predicting the malignant potential of IISSPNs. A perfect accuracy rate of 100% can be achieved with a score exceeding 12 points in the user-friendly scoring system.
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Neoplasias Pulmonares , Nódulo Pulmonar Solitario , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Neoplasias Pulmonares/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Nódulo Pulmonar Solitario/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Anciano , Curva ROC , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/patología , Hallazgos Incidentales , Sensibilidad y Especificidad , Algoritmos , Adulto , Área Bajo la Curva , RadiómicaRESUMEN
Background: Controversy still exists in the medical community regarding the performance of limited mediastinal lymphadenectomy (LML) in early-stage lung cancer. The objective of this study was to identify predictors of mediastinal lymph node (mLN) status and analyze its role in guiding surgical strategy. Methods: A retrospective cohort study was conducted on 2,834 surgical patients with peripheral cT1N0M0 non-small cell lung cancer between 2016 and 2018. Logistic regression was employed to identify predictors of N2 metastasis. Prognosis was compared between groups and independent prognostic factors were identified using Kaplan-Meier and multivariate Cox analysis. Results: There were 2,126 patients with systematic mLN dissection and 708 with LML. The multivariate analysis showed that N2 metastasis were associated with tumor size and consolidation tumor ratio (CTR). Patients in group A, with CTR >0.5 and tumor size ≤1 cm or CTR ≤0.5, had a significantly lower rate of N2 metastasis compared to those in group B, with CTR >0.5 and tumor size >1 cm (14.2% vs. 0.2%, P<0.001). Additionally, LML demonstrated comparable recurrence-free survival (RFS) and overall survival (OS) in group A, but a worse prognosis in group B compared to systematic lymph node dissection (SND). Furthermore, multivariate Cox regression analysis indicated that SND (vs. LML) was a favorable prognostic predictor for patients in group B [RFS: hazard ratio (HR) =0.71, P=0.005; OS: HR =0.66, P=0.01]. But univariate analysis in group A showed no significant difference in prognosis between SND and LML (RFS: P=0.24; OS: P=0.10). Conclusions: The combination of CTR and tumor size can predict mLN metastasis and procedure-specific outcome (SND vs. LML). This information may assist surgeons in identifying suitable candidates for LML.
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Lower-limb exoskeletons (LLEs) can provide rehabilitation training and walking assistance for individuals with lower-limb dysfunction or those in need of functionality enhancement. Adapting and personalizing the LLEs is crucial for them to form an intelligent human-machine system (HMS). However, numerous LLEs lack thorough consideration of individual differences in motion planning, leading to subpar human performance. Prioritizing human physiological response is a critical objective of trajectory optimization for the HMS. This paper proposes a human-in-the-loop (HITL) motion planning method that utilizes surface electromyography signals as biofeedback for the HITL optimization. The proposed method combines offline trajectory optimization with HITL trajectory selection. Based on the derived hybrid dynamical model of the HMS, the offline trajectory is optimized using a direct collocation method, while HITL trajectory selection is based on Thompson sampling. The direct collocation method optimizes various gait trajectories and constructs a gait library according to the energy optimality law, taking into consideration dynamics and walking constraints. Subsequently, an optimal gait trajectory is selected for the wearer using Thompson sampling. The selected gait trajectory is then implemented on the LLE under a hybrid zero dynamics control strategy. Through the HITL optimization and control experiments, the effectiveness and superiority of the proposed method are verified.
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Electromiografía , Dispositivo Exoesqueleto , Marcha , Extremidad Inferior , Caminata , Humanos , Electromiografía/métodos , Marcha/fisiología , Extremidad Inferior/fisiología , Caminata/fisiología , Algoritmos , Biorretroalimentación Psicológica/métodos , Masculino , Adulto , Fenómenos Biomecánicos/fisiologíaRESUMEN
Objective: The level of mitochondrial DNA copy number (mtDNA-CN) in peripheral blood cells had been identified to be involved in several immune and cardiovascular diseases. Thus, the aim of this study is to evaluate the levels of mtDNA-CN in Kawasaki disease (KD) and to construct a nomogram prediction for coronary artery lesions in children with KD. Methods: One hundred and forty-four children with KD diagnosed from March 2020 to March 2022 were involved in the study. The clinical features and laboratory test parameters of these children were assessed between the KD and normal groups. Univariable and multivariable analyses were performed sequentially to identify the essential risk factors. Subsequently, a nomogram prediction was constructed. Results: A total of 274 children were included in the analysis. Of these, 144 (52.6%) represented the KD group. Peripheral blood DNA mtDNA qPCR showed that the -log value of mtDNA-CN in the KD group (6.67 ± 0.34) was significantly higher than that in the healthy group (6.40 ± 0.18) (P<0.001). The area under the ROC curve for mtDNA-CN in distinguishing KD was 0.757. MtDNA-CN (OR = 13.203, P = 0.009, 95% CI 1.888-92.305), RBC (OR = 5.135, P = 0.014, 95% CI 1.394-18.919), and PA (OR = 0.959, P = 0.014, 95% CI 0.927-0.991) were identified as independent risk factors for coronary artery dilation in children with KD. Finally, the nomogram predictive was established based on the results of multivariable analysis, demonstrating the satisfied prediction and calibration values. Conclusion: The results of this study revealed that mtDNA-CN could be used as a biomarker in predicting the development of KD. Furthermore, the higher the mtDNA-CN was significantly associated with coronary artery dilation in KD.
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Variaciones en el Número de Copia de ADN , ADN Mitocondrial , Síndrome Mucocutáneo Linfonodular , Nomogramas , Humanos , Síndrome Mucocutáneo Linfonodular/genética , Síndrome Mucocutáneo Linfonodular/diagnóstico , Masculino , ADN Mitocondrial/genética , Femenino , Preescolar , Lactante , Vasos Coronarios/patología , Niño , Factores de Riesgo , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/sangre , Curva ROC , Biomarcadores/sangreRESUMEN
OBJECTIVE: To investigate the correlation between morphological typing and monoclonality of bone marrow plasma cells, and explore the diagnostic value of plasma cell morphological typing for high-risk smoldering multiple myeloma(HR-SMM). METHODS: The correlation between the morphological characteristics and the monoclonality of bone marrow plasma cells was analyzed in 84 patients with HR-SMM who treated in our hospital. The consistency of morphologically abnormal bone marrow plasma cells with serum free light chain (sFLC) ratio, next-generation sequencing (NGS) detection results, and its correlation with monoclonal plasma cells detected by flow cytometry (FCM) were further verified. The immunoglobulin types and levels of non-involved immunoglobulins in serum of the patients were detected, and the distribution of plasma cell clusters in patients with different disease was observed. RESULTS: The mean percentage of mature plasma cells were decreased successively in the order of reactive plasmacytosis (RP) group, monoclonal gammopathy of undetermined significance (MGUS) group, smoldering multiple myeloma (SMM) group, HR-SMM group and multiple myeloma (MM) group; while the mean percentage of immature, primitive, reticular and flaming plasma cells were increased successively in the order of RP group, MGUS group, SMM group, and HR-SMM group, and the difference between any two groups was statistically significant (P < 0.05).The average proportion of abnormal plasma cells in the bone marrow of HR-SMM patients was 96.2% of the total plasma cells. The proportion of abnormal plasma cells were in good agreement with the sFLC ratio and the results of NGS detection in HR-SMM patients (kappa=0.879 and kappa=0.891, both >0.75)ï¼and showed good correlation with the monoclonal plasma cells with immunophenotype of CD45-/CD38+/CD138+/CD56+/CD19-( γ=0.825). The levels of non-involved immunoglobulin in IgG, IgA and IgM type HR-SMM patients were all decreased by more than 25% compared with the normal reference range, and the differences were statistically significant (P < 0.05). There was no significant difference in the distribution ratio of plasma cell clusters among different disease groups (P >0.05). CONCLUSION: In HR-SMM patients, the immature, primitive, reticular and flaming plasma cells in bone marrow are considered as abnormal plasma cells, and they are correlated with monoclonal plasma cells. The proportion of abnormal plasma cells in total plasma cells of bone marrow and the reduction extent of non-involved immunoglobulin level in patients have certain reference value for the diagnosis of HR-SMM.
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Mieloma Múltiple , Células Plasmáticas , Humanos , Mieloma Múltiple/patología , Mieloma Múltiple Quiescente/diagnóstico , Médula Ósea/patología , Células de la Médula Ósea , Citometría de Flujo , FumarRESUMEN
BACKGROUND: With the dramatic rise in the number of older cancer patients, the question of whether or not to tell older patients of bad news becomes an urgent and common challenge. However, existing studies concentrated on the three types of disclosure decisions and their reasons, including full disclosure, partial disclosure, and avoidance of disclosure, and the evolution process and factors influencing family members' disclosure decisions are unclear. OBJECTIVE: Explore the experience and factors of the shift between disclosure and concealment among family members of older cancer patients. METHODS: A qualitative study was employed. Semi-structured interviews were conducted with 33 family members at two general hospitals and one community hospital between December 2022 and June 2023. The interview data were analyzed using a content analysis approach. RESULTS: The treatment plan symbolizes the "hope of survival" and it is the fundamental factor for the shift between concealment and disclosure. There are three themes of family members in making decisions during the diagnostic and therapeutic process: (a) When bad news is approaching: Keep calm in the midst of chaos, (b) when a treatment plan is determined: Hope for survival dictates disclosure decisions, and (c) when the patient's disease deteriorated: Finding hope in hopelessness. CONCLUSIONS: Disclosure and concealment are a complex and dynamic process. The factor of the shift lies in the "hope of survival" symbolized by the treatment plan. The key to disclosure by family members is to give patients enough hope to control or cure a patient's disease, or prolong the life of patients and improve their quality of life.
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Familia , Neoplasias , Investigación Cualitativa , Revelación de la Verdad , Humanos , Neoplasias/psicología , Familia/psicología , Anciano , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Depression is a significant global health concern, projected to become the leading disease burden. Vascular burden has been implicated in the pathogenesis of depression. Conversely, whether depression independently influences the process of vascular aging is unknown. This study aims to investigate the mutual relationship between vascular age and depression. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES), the study included 27,764 participants after exclusions. Depression was assessed using the Patient Health Questionnaire (PHQ-9). Vascular aging was assessed by estimated pulse wave velocity (ePWV) and the heart age/vascular age (HVA) based on Framingham Risk Score (FRS). The study employed weighted logistic regression and Cox proportional hazards models to analyze the association between vascular age and depression as well as its mortality risk. Mendelian randomization was utilized to explore the causal associations. RESULTS: Individuals with depression exhibited a higher risk of an advanced vascular age over their chronological age. Mendelian randomization analysis indicated a causal relationship between depression and arterial stiffness. A significant association was found between vascular age and depression incidence with odds ratios ranging from 1.10 to 1.38. As vascular age increased, the risk of mortality in individuals with depression increased by 22 % and 46 %, respectively. LIMITATIONS: The study design limits the exploration of the dynamic relationship between changes in vascular age and depression due to the single timepoint measurement. CONCLUSION: This study highlights the bidirectional relationship between depression and vascular age. Vascular age is a significant biomarker for the risk and prognosis of depression, while depression may contribute to vascular aging, which underscores the importance of integrated strategies for managing both vascular health and depression.
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OBJECTIVE: The aim of this study was to investigate the role and mechanisms of miR-155 in chronic spontaneous urticaria (CSU). METHODS: The expression level of miR-155 in the skin tissues of patients with CSU and experimental rats were detected by RT-qPCR, followed by the measurement of the histamine release rate in the serum through the histamine release test. Besides, hematoxylin & eosin staining was used to observe the pathological changes of the skin tissues; Corresponding detection kits and flow cytometry to measure the changes of immunoglobulins, inflammatory cytokines and T cell subsets in the serum of rats in each group; and western blot to check the expression level of proteins related to JAK/STAT signaling pathway in the skin tissues. RESULTS: Knockdown of miR-155 reduced the number and duration of pruritus, alleviated the skin damage, and decreased the number of eosinophils in CSU rats. Moreover, knockdown of miR-155 elevated the serum levels of IgG and IgM, decreased the levels of IgA and inflammatory cytokines, and reduced the proportion of CD4 + and CD4 + CD25 + T cells, as well as the CD4+/CD8 + ratio in CSU rats. However, Tyr705 intervention could reverse the effects of knockdown of miR-155 on CSU model rats. Furthermore, we found that knockdown of miR-155 significantly reduced the protein expression of IRF-9, as well as the P-JAK2/JAK2 and P-STAT3/STAT3 ratios in the skin tissues of CSU rats. CONCLUSION: Knockdown of miR-155 can alleviate skin damage and inflammatory responses and relieve autoimmunity in CSU rats by inhibiting the JAK/STAT3 signaling pathway.
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BACKGROUND: Conventional five-port laparoscopic surgery, the current standard treatment for colorectal carcinoma (CRC), has many disadvantages. AIM: To assess the influence of reduced-port laparoscopic surgery (RPLS) on perioperative indicators, postoperative recovery, and serum inflammation indexes in patients with CRC. METHODS: The study included 115 patients with CRC admitted between December 2019 and May 2023, 52 of whom underwent conventional five-port laparoscopic surgery (control group) and 63 of whom underwent RPLS (research group). Comparative analyses were performed on the following dimensions: Perioperative indicators [operation time (OT), incision length, intraoperative blood loss (IBL), and rate of conversion to laparotomy], postoperative recovery (first postoperative exhaust, bowel movement and oral food intake, and bowel sound recovery time), serum inflammation indexes [high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)], postoperative complications (anastomotic leakage, incisional infection, bleeding, ileus), and therapeutic efficacy. RESULTS: The two groups had comparable OTs and IBL volumes. However, the research group had a smaller incision length; lower rates of conversion to laparotomy and postoperative total complication; and shorter time of first postoperative exhaust, bowel movement, oral food intake, and bowel sound recovery; all of which were significant. Furthermore, hs-CRP, IL-6, and TNF-α levels in the research group were significantly lower than the baseline and those of the control group, and the total effective rate was higher. CONCLUSION: RPLS exhibited significant therapeutic efficacy in CRC, resulting in a shorter incision length and a lower conversion rate to laparotomy, while also promoting postoperative recovery, effectively inhibiting the inflammatory response, and reducing the risk of postoperative complications.
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Polarization singularities that exist in momentum space have brought new opportunities in various fields such as enhanced optical nonlinearity, structured laser sources, and light field manipulation. However, previous researches have predominantly focused on the polarization singularities above the light line, because they have no leakage and are referred to bound states in the continuum. Here, by extending the polarization fields to Fourier components of the evanescent field on a dielectric metasurface, polarization singularities of different Fourier orders are discovered below the light line. When continuously changing the geometrical parameters of the metasurface, a Fourier order transition process of the polarization singularity is observed through the bandgap closing at the boundary of the Brillouin zone, which finally leads to the annihilation of two singularities with opposite topological charges below the light line. These findings expand the understanding of polarization singularities in the near-field region and may find applications in light field manipulation and light-matter interaction.
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Neuroendocrine carcinoma (NEC) is a rare yet potentially perilous neoplasm. The objective of this study was to develop prognostic models for the survival of NEC patients in the genitourinary system and subsequently validate these models. A total of 7125 neuroendocrine neoplasm (NEN) patients were extracted. Comparison of survival in patients with different types of NEN before and after propensity score-matching (PSM). A total of 3057 patients with NEC, whose information was complete, were extracted. The NEC influencing factors were chosen through the utilization of the least absolute shrinkage and selection operator regression model (LASSO) and the Fine & Gary model (FGM). Furthermore, nomograms were built. To validate the accuracy of the prediction, the efficiency was verified using bootstrap self-sampling techniques and receiver operating characteristic curves. LASSO and FGM were utilized to construct three models. Confirmation of validation was achieved by conducting analyses of the area under the curve and decision curve. Moreover, the FGS (DSS analysis using FGM) model produced higher net benefits. To maximize the advantages for patients, the FGS model disregarded the influence of additional occurrences. Patients are expected to experience advantages in terms of treatment options and survival assessment through the utilization of these models.
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Carcinoma Neuroendocrino , Nomogramas , Humanos , Carcinoma Neuroendocrino/mortalidad , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Neoplasias Urogenitales/mortalidad , Neoplasias Urogenitales/diagnóstico , Neoplasias Urogenitales/patología , Pronóstico , Adulto , Curva ROCRESUMEN
Numerous studies establish a significant correlation between autoimmune disorders (AIDs) and prostate cancer (PCa). Our Mendelian randomization (MR) analysis investigates the potential connection between rheumatoid arthritis (RA) and PCa, aiming to confirm causal links between systemic lupus erythematosus (SLE), hyperthyroidism, and PCa. Summary statistics from genome-wide association studies provided data on PCa and three AIDs. MR analysis, using IVW as the main approach, assessed causal relationships, validated by sensitivity analysis. IVW revealed a correlation between genetically anticipated RA and PCa, notably in Europeans (OR = 1.03; 95% CI 1.01-1.04, p = 2*10-5). Evidence supported a lower PCa risk in individuals with SLE (OR = 0.94; 95% CI 0.91-0.97, p = 2*10-4) and hyperthyroidism (OR = 0.02; 95% CI 0.001-0.2, p = 2*10-3). Weighted mode and median confirmed these findings. No pleiotropic effects were observed, and MR heterogeneity tests indicated dataset homogeneity. Our study establishes a causal link between RA, SLE, hyperthyroidism, and PCa.
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Artritis Reumatoide , Enfermedades Autoinmunes , Estudio de Asociación del Genoma Completo , Lupus Eritematoso Sistémico , Análisis de la Aleatorización Mendeliana , Neoplasias de la Próstata , Humanos , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/epidemiología , Masculino , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/epidemiología , Artritis Reumatoide/genética , Artritis Reumatoide/epidemiología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/epidemiología , Hipertiroidismo/genética , Hipertiroidismo/epidemiología , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , Factores de RiesgoRESUMEN
The pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear. It has been found that interleukin-6 (IL-6) rs1800795 locus and matrix metalloproteinase-3 (MMP-3) rs3025058 locus gene polymorphisms may be associated with AIS susceptibility, which has been controversial and needs to be further confirmed by updated meta-analysis. The aim of the present study was to investigate the association of MMP-3 rs3025058 and IL-6 rs1800795 single nucleotide polymorphisms (SNPs) with susceptibility to AIS. All relevant articles that met the criteria were retrieved and included, and the publication dates were limited from January 2005 to December 2023. The allele frequencies and different genotype frequencies of IL-6 rs1800795 and MMP-3 rs3025058 loci in each study were extracted and statistically analyzed by ReviewManager 5.4 software, and the odds ratio (OR) and 95% confidence interval (95% CI) of different genetic models were calculated. The results of the meta-analysis showed that there was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS. The allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility (5A vs. 6A, OR=1.18; 95% CI, 1.04-1.33; 5A5A vs. 6A6A, OR=1.65; 95% CI, 1.23-2.21; and 5A5A vs. 5A6A + 6A6A, OR=1.54; 95% CI, 1.19-1.99). Results of subgroup analysis revealed that the allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility in the Caucasian population, and the susceptibility of AIS was associated with the genotype 5A5A of MMP-3 rs3025058 SNP in an Asian population. There was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS, while the allele 5A of MMP-3 rs3025058 locus was associated with the susceptibility to AIS, especially in the Caucasian population.
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BACKGROUND: Early referral to palliative care has been viewed as providing opportunity for accomplishing end-of-life care goals of life closure, comfortable dying and effective grieving. However, previous studies have shown that palliative care referrals are being made too late. Healthcare providers play important role in helping terminally ill patients to early access and being referred to palliative care. It is necessary to understand healthcare providers' attitudes on palliative care referral and associated factors regarding referrals. OBJECTIVES: This review aimed to identify and synthesise healthcare providers' attitudes and associated factors on palliative care referrals systematically. DESIGN: A systematic review of qualitative evidence and meta-aggregation was conducted and guided according to PRISMA guideline. DATA SOURCES: PubMed, CINAHL, PsycINFO, EMBASE, Web of Science and Cochrane databases from inception to 24 October 2022. RESULTS: Database searches yielded 5856 references. Twenty-two studies met eligibility criteria and of moderate to high methodological quality were included. Studies occurred in USA, UK, Australia and France with 716 healthcare providers participants were included. A total of 378 codings were finally extracted and integrated into 41 categories, forming three synthesised findings: (1) Healthcare providers' attitudes towards palliative care referrals, (2) the influence of subjective norms on palliative care referral behaviour and (3) perceived behavioural control on palliative care referral behaviour. CONCLUSION: This review demonstrates a series of factors that affect the palliative care referrals, including the attitudes of healthcare providers, the participation of patients and families, the support of colleagues and supervisors, inter-professional collaboration, the availability of hospice resource, disease trajectory and socio-economic factors. Further research that addresses these factors and design relevant trainings on improving healthcare providers' attitudes, enhancing patient and family engagement, strengthening support networks and optimising resource allocation may aid to meet increasing demands of patients. RELEVANCE TO CLINICAL PRACTICE: This review not only guides healthcare providers in making better decisions about patient referrals by identifying and addressing barriers but also aids in the development of effective interventions that facilitate the early initiation of referrals. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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Actitud del Personal de Salud , Personal de Salud , Cuidados Paliativos , Derivación y Consulta , Humanos , Derivación y Consulta/estadística & datos numéricos , Personal de Salud/psicología , Investigación Cualitativa , Masculino , FemeninoRESUMEN
Objective To gain an in-depth understanding of the motivations,patterns,and related factors in family decision-making regarding the referral of terminal patients in tertiary hospitals. Methods Using purposive sampling,terminal patients and their family members from three tertiary hospitals in Beijing were selected as subjects.Semi-structured interviews were conducted,and the interview data were subjected to thematic analysis. Results Following the saturation principle,a total of 11 patients and 15 family members were included.The interview data were organized and analyzed,yielding six major themes:decision premises,decision patterns,family support,support from the referring hospital's medical team,referral channel conditions,and involvement of volunteer teams and social support.Based on these findings,a flowchart illustrating the family decision-making process for the referral of terminal patients was constructed. Conclusions The study provides a comprehensive analysis of various factors influencing family decision-making in the referral of terminal patients in tertiary hospitals.The results underscore the significance of internal and external factors,emphasizing the integrated impact of decision patterns,family support,medical team support,referral channel conditions,and the involvement of volunteer teams and social support.The research offers profound insights into improving the referral process for terminal patients and enhancing the quality of family decision-making.It provides valuable recommendations for future improvements in medical services and decision support.
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Toma de Decisiones , Familia , Derivación y Consulta , Centros de Atención Terciaria , Humanos , Familia/psicología , Femenino , Masculino , Cuidado Terminal/psicología , Persona de Mediana Edad , Apoyo Social , AdultoRESUMEN
Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.
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Modelos Animales de Enfermedad , Exosomas , Células Madre Mesenquimatosas , Muromegalovirus , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Transducción de Señal , Animales , Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , FN-kappa B/metabolismo , Muromegalovirus/fisiología , Ratones Endogámicos C57BL , Macrófagos/inmunología , Infecciones por Citomegalovirus/terapia , Infecciones por Citomegalovirus/virología , Pulmón/virología , Pulmón/patología , Neumonía Viral/terapia , Neumonía Viral/virología , Infecciones por Herpesviridae/terapia , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/inmunología , Neumonía/terapia , Neumonía/virologíaRESUMEN
Renal metastasis of breast angiosarcoma is rare. This article reports the medical records of a patient diagnosed with breast angiosarcoma who underwent radical mastectomy and was found to have multiple lung metastases 3 years after surgery and renal pelvic metastasis 4 years after surgery. The patient underwent robot-assisted laparoscopic radical nephroureterectomy and sleeve resection of the intramural segment of the ureter, and postoperative pathology and immunohistochemical staining confirmed the diagnosis of renal pelvic metastasis of breast angiosarcoma. The patient received anlotinib for lung metastases following surgery and was followed up for 4 months after surgery. Currently, the patient has symptoms of coughing and hemoptysis but no other discomfort. The diagnosis and treatment of this rare malignant tumor remain challenging.
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Glioblastoma (GBM) is the most prevalent primary intracranial tumor. Temozolomide (TMZ) is the first-line chemotherapy for GBM. Nonetheless, the development of TMZ resistance has become a main cause of treatment failure in GBM patients. Evidence suggests that neuropilin-1 (NRP-1) silencing can attenuate GBM cell resistance to TMZ. This study aims to determine potential mechanisms by which NRP-1 affects TMZ resistance in GBM. The parental U251 and LN229 GBM cells were exposed to increasing concentrations of TMZ to construct TMZ-resistant GBM cells (U251/TMZ, LN229/TMZ). BALB/c nude mice were injected with U251/TMZ cells to establish the xenograft mouse model. Functional experiments were carried out to examine NRP-1 functions. Western blotting and real-time quantitative polymerase chain reaction were used to evaluate molecular protein and mRNA expression, respectively. Immunohistochemical staining showed NRP-1 and STAT1 expression in mouse tumors. The results showed that NRP-1 was highly expressed in TMZ-resistant cells. Moreover, knocking down NRP-1 attenuated the TMZ resistance of U251/TMZ cells, while upregulating NRP-1 enhanced TMZ resistance of the parental cells. NRP-1 silencing elevated GBM cell sensitivity to TMZ in tumor-bearing mice. Depleting NRP-1 reduced STAT1, p53, and p21 expression in U251/TMZ cells. STAT1 depletion offset NRP-1 silencing evoked attenuation of GBM cell resistance to TMZ. Collectively, our study reveals that NRP-1 enhances TMZ resistance in GBM possibly by regulating the STAT1/p53/p21 axis.
Asunto(s)
Antineoplásicos Alquilantes , Neoplasias Encefálicas , Resistencia a Antineoplásicos , Glioblastoma , Ratones Endogámicos BALB C , Ratones Desnudos , Neuropilina-1 , Factor de Transcripción STAT1 , Temozolomida , Proteína p53 Supresora de Tumor , Temozolomida/farmacología , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/metabolismo , Glioblastoma/genética , Animales , Resistencia a Antineoplásicos/efectos de los fármacos , Neuropilina-1/metabolismo , Neuropilina-1/genética , Humanos , Factor de Transcripción STAT1/metabolismo , Antineoplásicos Alquilantes/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Línea Celular Tumoral , Ratones , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Creating microenvironments that mimic an enzyme's active site is a critical aspect of supramolecular confined catalysis. In this study, we employ the commonly used chiral 1,1'-bi-2-naphthol (BINOL) phosphates as subcomponents to construct supramolecular hollow nanotube in an aqueous medium through non-covalent intermolecular recognition and arrangement. The hexagonal nanotubular structure is characterized by various techniques, including X-ray, NMR, ESI-MS, AFM, and TEM, and is confirmed to exist in a homogeneous aqueous solution stably. The nanotube's length in solution depends on the concentration of chiral BINOL-phosphate as a monomer. Additionally, the assembled nanotube can accelerate the rate of the 3-aza-Cope rearrangement reaction by up to 85-fold due to the interior confinement effect. Based on the detailed kinetic and thermodynamic analyses, we propose that the chain-like substrates are constrained and pre-organized into a reactive chair-like conformation, which stabilizes the transition state of the reaction in the confined nanospace of the nanotube. Notably, due to the restricted conformer with less degrees of freedom, the entropic barrier is significantly reduced compared to the enthalpic barrier, resulting in a more pronounced acceleration effect.
RESUMEN
Terminally ill patients face multiple difficulties in home care.Home-based palliative care adhering to the concept of whole-person,whole-family,whole-team,and whole-course care is able to meet the needs of terminally ill patients and their families.In this paper,we reported the care history and home-based palliative care process of a patient with end-stage breast tumor and summarized the experience,aiming to provide reference for the future work of home-based palliative care.