RESUMO
This study examined differences in middle-aged adults' preferred features of their current versus future residential environments and how these differences varied by health and social characteristics. A sample of 1,651 Korean middle-aged adults (aged 49-64) rated their preferences for each of 12 features (e.g., proximity to family/relatives, house price) regarding current and future residential environments, separately. Respondents considered "accessibility to health services" and "opportunity for leisure activities" more important for future residential environments than for current ones. Respondents with poorer health considered features that help them compensate for health decline more important, while those who contacted friends/neighbors more frequently and participated in more cultural activities considered features that help them maintain their social interactions more important for future residential environments than the past. Our findings identified middle-aged adults' various demands for residential features after retirement, which reflect their strategic reactions to future needs for successful adaptation in later years.
RESUMO
BACKGROUND: Breathlessness shares aging mechanisms of frailty and sarcopenia. RESEARCH QUESTION: Are frailty and sarcopenia associated with breathlessness itself? STUDY DESIGN AND METHODS: We analyzed data from a population-based, prospective cohort study of 780 community-dwelling older adults. Breathlessness was defined using the modified Medical Research Council Dyspnea Scale (≥2 points) and the Chronic Obstructive Pulmonary Disease Assessment Test (≥10 points). Frailty was defined by frailty index (FI), frailty phenotype, and FRAIL questionnaire. Sarcopenia was defined by the Asian Working Group for Sarcopenia 2019. Sarcopenia phenotype score quantifies the number of criteria met. The associations of frailty and sarcopenia with breathlessness was evaluated by logistic regression analyses. Adjusted odds ratio (aOR) were calculated, accounting for age, sex, chronic airway disease, smoking status, body mass index, lung functions, socioeconomic status (living alone, income, education), comorbid conditions (hypertension, diabetes, malignancy, myocardial infarction, heart failure), and other geriatric contributors (cognitive dysfunction, depression, malnutrition, polypharmacy, fall history in the past year). Institutionalization-free survival was compared by log-rank test. RESULTS: The prevalence of frailty is higher in the breathlessness group compared to non-breathlessness group (42.6% vs. 10.5% by FI, 26.1% vs. 8.9% by frailty phenotype, and 23.0% vs. 4.2% by FRAIL) and sarcopenia (38.3% vs. 26.9%), with P < 0.01 for all comparisons. The multivariable logistic regression analyses showed that frailty (FI [aOR: 9.29], FRAIL questionnaire [aOR: 5.21], and frailty phenotype [aOR: 3.09]) and sarcopenia phenotype score (score 2 [aOR: 2.00] and score 3 [aOR: 2.04] compared to score 0) were associated with breathlessness. The cumulative incidence of institutionalization-free survival was higher in the breathlessness group than counterparts (P = 0.02). INTERPRETATION: The findings suggest that frailty and sarcopenia strongly contribute to breathlessness in community-dwelling older adults. Measuring sarcopenia and frailty in older adults may offer opportunities to prevent age-related breathlessness.
RESUMO
Metastatic gastric cancer (GC) presents significant clinical challenges due to its poor prognosis and limited treatment options. To address this, we conducted a targeted protein biomarker discovery study to identify markers predictive of metastasis in advanced GC (AGC). Serum samples from 176 AGC patients (T stage 3 or higher) were analyzed using the Olink Proteomics Target panels. Patients were retrospectively categorized into nonmetastatic, metastatic, and recurrence groups, and differential protein expression was assessed. Machine learning and gene set enrichment analysis (GSEA) methods were applied to discover biomarkers and predict prognosis. Four proteins (MUC16, CAIX, 5'-NT, and CD8A) were significantly elevated in metastatic GC patients compared to the control group. Additionally, GSEA indicated that the response to interleukin-4 and hypoxia-related pathways were enriched in metastatic patients. Random forest classification and decision-tree modeling showed that MUC16 could be a predictive marker for metastasis in GC patients. Additionally, ELISA validation confirmed elevated MUC16 levels in metastatic patients. Notably, high MUC16 levels were independently associated with metastatic progression in T3 or higher GC. These findings suggest the potential of MUC16 as a clinically relevant biomarker for identifying GC patients at high risk of metastasis.
Assuntos
Biomarcadores Tumorais , Antígeno Ca-125 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/sangue , Masculino , Feminino , Biomarcadores Tumorais/sangue , Pessoa de Meia-Idade , Antígeno Ca-125/sangue , Prognóstico , Idoso , Proteínas de Membrana/sangue , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Metástase Neoplásica , Estudos Retrospectivos , AdultoRESUMO
PURPOSE: Peritoneal carcinomatosis (PC) presents a major challenge in the treatment of late-stage, solid tumors, with traditional therapies limited by poor drug penetration. We evaluated a novel hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) system using a human abdominal cavity model for its efficacy against AGS gastric cancer cells. MATERIALS AND METHODS: A model simulating the human abdominal cavity and AGS gastric cancer cell line cultured dishes were used to assess the efficacy of the HPIPAC system. Cell viability was measured to evaluate the impact of HPIPAC under 6 different conditions: heat alone, PIPAC with paclitaxel (PTX), PTX alone, normal saline (NS) alone, heat with NS, and HPIPAC with PTX. RESULTS: Results showed a significant reduction in cell viability with HPIPAC combined with PTX, indicating enhanced cytotoxic effects. Immediately after treatment, the average cell viability was 66.6%, which decreased to 49.2% after 48 hours and to a further 19.6% after 120 hours of incubation, demonstrating the sustained efficacy of the treatment. In contrast, control groups exhibited a recovery in cell viability; heat alone showed cell viability increasing from 90.8% to 94.4%, PIPAC with PTX from 82.7% to 89.7%, PTX only from 73.3% to 74.8%, NS only from 90.9% to 98.3%, and heat with NS from 74.4% to 84.7%. CONCLUSIONS: The HPIPAC system with PTX exhibits a promising approach in the treatment of PC in gastric cancer, significantly reducing cell viability. Despite certain limitations, this study highlights the system's potential to enhance treatment outcomes. Future efforts should focus on refining HPIPAC and validating its effectiveness in clinical settings.
Assuntos
Aerossóis , Sobrevivência Celular , Quimioterapia Intraperitoneal Hipertérmica , Paclitaxel , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Paclitaxel/farmacologia , Paclitaxel/administração & dosagem , Quimioterapia Intraperitoneal Hipertérmica/métodos , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Hipertermia Induzida/métodos , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologiaRESUMO
BACKGROUND: Pain assessment and patient education are essential for successful postoperative pain management. However, the provision of personnel for performing these tasks is often insufficient. Recently, attempts have been made to implement smartphone applications for educating and monitoring surgical patients. We developed a smartphone application (app) for postoperative pain management, and conducted a feasibility study. METHODS: This single-center prospective observational study included 60 patients aged < 70 years who underwent elective surgery. This study evaluated the SmartAPS application, which offers tools for postoperative pain assessment and educational materials for pain management. The primary outcome was the active usage rate, defined as responding at least twice daily on postoperative days (PODs) 1 and 2. Additionally, we investigated patient satisfaction with the app and educational videos as well as any challenges encountered during use. RESULTS: Sixty patients were enrolled in the study and active app use was achieved in 56.7% of them. Response rates peaked at 85.0% for pain intensity and 83.3% for opioid-related side effects at 14:00 on POD 1 but dropped to 56.7% and 58.3%, respectively, at 18:00 on POD 2. Among the patients who responded to the survey regarding the app usage, 84.0% reported satisfaction with the app and 80% found it beneficial for managing postoperative pain. Furthermore, 92.0% did not encounter difficulties using the app, indicating a generally positive user experience. CONCLUSIONS: Our findings support the utility of the SmartAPS application in acute pain services, highlighting its potential for improving postoperative pain management.
RESUMO
PURPOSE: External ear reconstruction has been a challenging subject for plastic surgeons for decades. Popular methods using autologous costal cartilage or polyethylene still have their drawbacks. With the advance of three-dimensional (3D) printing technique, bioscaffold engineering using synthetic polymer draws attention as an alternative. This is a clinical trial of ear reconstruction using 3D printed scaffold, presented with clinical results after 1 year. MATERIALS AND METHODS: From 2021 to 2022, five adult patients with unilateral microtia underwent two-staged total ear reconstruction using 3D printed implants. For each patient, a patient-specific 3D printed scaffold was designed and produced with polycaprolactone (PCL) based on computed tomography images, using fused deposition modeling. Computed tomography scan was obtained preoperatively, within 2 weeks following the surgery and after 1 year, to compare the volume of the normal side and the reconstructed ear. At 1-year visit, clinical photo was taken for scoring by two surgeons and patients themselves. RESULTS: All five patients had completely healed reconstructed ear at 1-year follow-up. On average, the volume of reconstructed ear was 161.54% of that of the normal side ear. In a range of 0 to 10, objective assessors gave scores 3 to 6, whereas patients gave scores 8 to 10. CONCLUSION: External ear reconstruction using 3D printed PCL implant showed durable, safe results reflected by excellent volume restoration and patient satisfaction at 1 year postoperatively. Further clinical follow-up with more cases and refinement of scaffold with advancing bioprinting technique is anticipated. The study's plan and results have been registered with the Clinical Research Information Service (CRIS No. 3-2019-0306) and the Ministry of Food and Drug Safety (MFDS No. 1182).
Assuntos
Microtia Congênita , Procedimentos de Cirurgia Plástica , Impressão Tridimensional , Humanos , Procedimentos de Cirurgia Plástica/métodos , Masculino , Adulto , Feminino , Microtia Congênita/cirurgia , Poliésteres , Próteses e Implantes , Adulto Jovem , Orelha Externa/cirurgia , Orelha Externa/anormalidades , Tomografia Computadorizada por Raios X , Alicerces Teciduais , Resultado do Tratamento , AdolescenteRESUMO
In this study, magnetic biochar was synthesized by doping Fe3O4 onto the biochar surface followed by analysis of its properties. The efficiency of methylene blue (MB) removal through the combined processes of adsorption and photolysis was assessed. The presence of Fe3O4 on the biochar surface was confirmed using Raman spectroscopy and X-ray photoelectron spectroscopy. The magnetic biochar, after MB adsorption, showed a magnetism of 39.50 emu/g leading to a 97.07 % recovery rate. The specific surface area of biochar was higher (380.68 m2/g) than that of magnetic biochar (234.46 m2/g), and the maximum adsorption capacity of MB was higher in the biochar (0.03 mg/g) than that in magnetic biochar (0.02 mg/g) under the optimal conditions for MB adsorption. The MB adsorption experiments using biochar or magnetic biochar were optimally conducted under 10-20 mg/L MB concentration, 1 g biochar dosage, pH 12, 200 rpm rotation speed, 25 °C temperature, and 30 min duration. Under dark conditions, biochar had a higher MB removal rate, at 83.91 %, compared to magnetic biochar, at 78.30 %. Under visible light (λ > 425 nm), magnetic biochar effectively removed MB within 10 min, highlighting the synergistic effect of adsorption and photolysis. MB is physically and chemically adsorbed by the monolayer on the surface of EB and EMB according to adsorption behavior.
Assuntos
Carvão Vegetal , Lignina , Azul de Metileno , Fotólise , Azul de Metileno/química , Carvão Vegetal/química , Adsorção , Lignina/química , Biomassa , Concentração de Íons de Hidrogênio , Poluentes Químicos da Água/química , Espectroscopia FotoeletrônicaRESUMO
BACKGROUND: The technical challenges and safety concerns of single-incision laparoscopic gastrectomy for overweight and obese gastric cancer patients remain unclear. This study aimed to evaluate the safety and feasibility of single-incision laparoscopic distal gastrectomy (SIDG) compared to multiport laparoscopic distal gastrectomy (MLDG) in overweight and obese gastric cancer patients. METHODS: This study retrospectively analyzed overweight and obese patients (body mass index ≥ 25 kg/m2) and pathologic stage T1 primary gastric adenocarcinoma treated with either SIDG or MLDG. The SIDG and MLDG groups were propensity score matched at a 1:2 ratio using age, sex, height, body weight, American Society of Anesthesiologists classification, year of surgery, pathologic N stage, and anastomosis method as covariates. RESULTS: After 1:2 matching, the study included patients who underwent SIDG (n = 179) and MLDG (n = 358). No significant difference in the number of retrieved lymph nodes was found between the SIDG and MLDG groups (52.8 ± 19.3 vs. 53.9 ± 21.0, P = 0.56). Operation times were significantly shorter in the SIDG group (170.8 ± 60.0 min vs. 186.1 ± 52.6 min, P = 0.004). The postoperative hospital length of stay was comparable between the 2 groups (SIDG: 5.9 ± 3.4 days vs. MLDG: 6.3 ± 5.1 days, P = 0.23), as was postoperative complication rate (SIDG: 13.4% vs. MLDG: 12.8%, P = 0.89). CONCLUSIONS: SIDG was shown to be as safe and feasible as MLDG for overweight and obese gastric cancer patients, with comparable early postoperative complication rates without compromising operation time compared to MLDG.
Assuntos
Estudos de Viabilidade , Gastrectomia , Laparoscopia , Obesidade , Sobrepeso , Pontuação de Propensão , Neoplasias Gástricas , Humanos , Gastrectomia/métodos , Masculino , Feminino , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/complicações , Laparoscopia/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sobrepeso/complicações , Obesidade/complicações , Obesidade/cirurgia , Idoso , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma/complicações , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Tempo de Internação , Adulto , Duração da CirurgiaRESUMO
A virtual-reality-simulation-based nursing education program incorporating an information processing model helps nursing students develop their learned knowledge as nursing behavior and develop their ability to cope with complex clinical challenges. The purpose of this study is to develop a nursing education program using an immersive virtual reality simulation app for clinical situations based on an information processing model and identify the effects. A non-quantitative control group pretest-post-test design was employed. The programs were developed using the ADDIE model and an information processing model. In order to verify the effectiveness of the program, six adult nursing learning issues were taught to the experimental group over 6 weeks. The nursing education program in this study provides comprehensive experiential learning through advanced virtual simulation, significantly enhancing nursing students' performance confidence, critical-thinking abilities, and problem-solving skills across a wide range of clinical scenarios. By repeatedly engaging with diverse learning topics related to adult nursing, this program not only equips students with essential practical skills but also contributes to the overall improvement of patient safety and the quality of medical care.
RESUMO
Gastro-oEsophageal Cancers (GECs) are severe diseases whose management is rapidly evolving. The European Society of Surgical Oncology (ESSO) is committed to the generation and spread of knowledge, and promotes the multidisciplinary management of cancer patients through its core curriculum. The present work discusses the approach to GECs, including the management of oligometastatic oesophagogastric cancers (OMEC), the diagnosis and management of peritoneal metastases from gastric cancer (GC), the management of Siewert Type II tumors, the importance of mesogastric excision, the role of robotic surgery, textbook outcomes, organ preserving options, the use of molecular markers and immune check-point inhibitors in the management of patients with GECs, as well as the improvement of current clinical practice guidelines for the management of patients with GECs. The aim of the present review is to provide a concise overview of the state-of-the-art on the management of patients with GECs and, at the same time, to share the latest advancements in the field and to foster the debate between surgical oncologists treating GECs worldwide. We are sure that our work will, at the same time, give an update to the advanced surgical oncologists and help the training surgical oncologists to settle down the foundations for their future practice.
Assuntos
Neoplasias Esofágicas , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Procedimentos Cirúrgicos Robóticos/educação , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Oncologia Cirúrgica/educação , Currículo , Inibidores de Checkpoint Imunológico/uso terapêutico , Europa (Continente) , Tratamentos com Preservação do Órgão , Sociedades MédicasRESUMO
Introduction: Bicortical screw fixation, which penetrates and fixes the near and far cortex of bone, has been conventionally used to achieve compressive fixation for fracture using screws. Open reduction and internal fixation using the locking plate are widely used for treating proximal humerus fractures. However, minimal contact between the bone and the locking plate can lead to an insufficient reduction. Theoretically, a dual-lead locking screw with different leads for the screw head and body could enhance the reduction and fixation stability of fragments in proximal humeral fractures without bicortical fixation, and achieve additional compression at the bone-plate-screw interface. This study assessed the insertion mechanics of the lead ratio of the dual-lead locking screw and its effect on the fixation stability of the proximal humerus fracture. Methods: A Multi-Fix® locking plating system composed of ∅ 3.5â mm locking screws and a locking plate was used to make a locked plating for Sawbone bone blocks and fourth-generation composite humeri. Two different types of Sawbone bone blocks were used to simulate the osteoporotic (10 PCF) and normal cancellous (20 PCF) bones. The lead of the screw head thread (Lhead) was 0.8â mm, and that of the screw body (Lbody) was 0.8, 1.25, 1.6, 2.0, and 2.4â mm, whose lead ratios (Rlead=Lbody/Lhead) were 1.0, 1.56, 2.0, 2.5, and 3.0, respectively. Results: The dual-lead locking screw elevated the compression between the locking plate and the bone. The elevation in the compression due to the dual-lead thread became weaker for the cancellous bone when the lead of the screw body was more than twice that of the screw head. The plate/humerus compression with strong bone quality withstood higher dual-lead-driven compression. Discussion: A dual-lead locking screw of Lbody=1.25mm (Rlead=1.56) is recommended for maximum rotational stability for the locked humerus plating. The screws with over Lbody=1.6mm (Rlead=2) have no advantage in terms of the failure torque and maximum torsional deformation. Any locking dual-lead screw with a body thread lead of <1.6â mm (Rlead=2) can be used without the risk of bone crush when surgeons require additional compression to the locked cancellous bone plating.
RESUMO
This study examined the concordance in spouses' intention to move after retirement among midlife couples and its association with couples' marital characteristics (i.e., marital satisfaction and dyadic coping). Using a sample of 1,285 middle-aged couples in Korea (aged 49-64), we conducted logistic/multinomial regression controlling for individual and household characteristics. The majority of couples (83%) were concordant in their moving desires-by either agreeing to move (29%) or to stay (54%), whereas 17% of couples were not in agreement-either only husband (9%) or wife (8%) desires to move. Couples who made daily decisions together and where wives perceived higher marital satisfaction were more likely to have concordant moving desires. Couples where spouses shared each other's stress and discussed life after retirement were more likely to agree to move than to stay. Our findings suggest the importance of marital dynamics in understanding midlife couples' residential mobility after retirement.
Assuntos
Intenção , Casamento , Aposentadoria , Cônjuges , Humanos , Aposentadoria/psicologia , Masculino , Cônjuges/psicologia , Feminino , Pessoa de Meia-Idade , República da Coreia , Casamento/psicologia , Adaptação Psicológica , Satisfação Pessoal , Modelos LogísticosRESUMO
This study examined the effects of language differences between Korean and English on the performance of natural language processing in the classification task of identifying inpatient falls from unstructured nursing notes.
Assuntos
Aprendizado Profundo , Humanos , Acidentes por Quedas/prevenção & controle , Pacientes Internados , Registros Eletrônicos de Saúde , Idioma , Processamento de Linguagem NaturalRESUMO
Sarcopenia, which is characterized by an age-related decline in muscle mass and function, poses significant challenges to geriatric care. Its definition has evolved from muscle-specific criteria to include muscle mass, muscle function, and physical performance, recognizing sarcopenia as a physical frailty. Sarcopenia is associated with adverse outcomes, including mortality, falls, fractures, cognitive decline, and admission to long-term care facilities. Neuromechanical factors, protein-energy balance, and muscle protein synthesis-breakdown mechanisms contribute to its pathophysiology. The identification of sarcopenia involves screening tests and a comprehensive assessment of muscle mass, strength, and physical function. Clinical approaches aligned with the principles of comprehensive geriatric assessment prioritize patient-centered care. This assessment aids in identifying issues related to activities of daily living, cognition, mood, nutrition, and social support, alongside other aspects. The general approach to factors underlying muscle loss and functional decline in patients with sarcopenia includes managing chronic diseases and evaluating administered medications, with interventions including exercise and nutrition, as well as evolving pharmacological options. Ongoing research targeting pathways, such as myostatin-activin and exercise mimetics, holds promise for pharmacological interventions. In summary, sarcopenia requires a multifaceted approach, acknowledging its complex etiology and tailoring interventions to individual patient needs.
RESUMO
BACKGROUND: The significant rise in cardiac arrest cases within hospitals, coupled with a low survival rate, poses a critical health issue. And in most situations, nurses are the first responders. To develop nursing students' competencies in advanced cardiopulmonary resuscitation, systematic and repetitive learner-centered self-directed education that can promote the integration of knowledge and practice is necessary. OBJECTIVES: To develop an advanced cardiopulmonary resuscitation training program using a web-based serious game for nursing students and verifying its efficacy. DESIGN: The program was developed based on the stages of analysis, design, development, implementation, and evaluation, and the Input Process Outcome Model of Serious Game Design formed the theoretical basis. SETTINGS AND PARTICIPANTS: The research design employed a before-and-after non-equivalent control group, and data collection took place among 2nd and 3rd year nursing students at K University in D City, Korea, from March 2, 2023, to March 24, 2023. METHODS: The program consisted of a 120-min video lecture, 30 min of a web-based serious game, 30-min of written self-reported debriefing, and individual feedback using a video conference system. The effectiveness of the program was measured for both groups using an 89-item structured questionnaire regarding knowledge, confidence in performance, problem-solving ability, and learning transfer expectations. RESULTS: The program was effective in improving nursing students' advanced cardiopulmonary knowledge, confidence in performance, problem-solving ability, and learning transfer expectation immediately after intervention. CONCLUSIONS: This program underscores the necessity of a new direction in nursing education, emphasizing learner-centered approaches, rather than the traditional focus on the mere transmission of basic knowledge and skills, to cultivate nurses with advanced cardiopulmonary resuscitation capabilities.
RESUMO
BACKGROUND: Solid tumors promote tumor malignancy through interaction with the tumor microenvironment, resulting in difficulties in tumor treatment. Therefore, it is necessary to understand the communication between cells in the tumor and the surrounding microenvironment. Our previous study revealed the cancer malignancy mechanism of Bcl-w overexpressed in solid tumors, but no study was conducted on its relationship with immune cells in the tumor microenvironment. In this study, we sought to discover key factors in exosomes secreted from tumors overexpressing Bcl-w and analyze the interaction with the surrounding tumor microenvironment to identify the causes of tumor malignancy. METHODS: To analyze factors affecting the tumor microenvironment, a miRNA array was performed using exosomes derived from cancer cells overexpressing Bcl-w. The discovered miRNA, miR-6794-5p, was overexpressed and the tumorigenicity mechanism was confirmed using qRT-PCR, Western blot, invasion, wound healing, and sphere formation ability analysis. In addition, luciferase activity and Ago2-RNA immunoprecipitation assays were used to study the mechanism between miR-6794-5p and its target gene SOCS1. To confirm the interaction between macrophages and tumor-derived miR-6794-5p, co-culture was performed using conditioned media. Additionally, immunohistochemical (IHC) staining and flow cytometry were performed to analyze macrophages in the tumor tissues of experimental animals. RESULTS: MiR-6794-5p, which is highly expressed in exosomes secreted from Bcl-w-overexpressing cells, was selected, and it was shown that the overexpression of miR-6794-5p increased migratory ability, invasiveness, and stemness maintenance by suppressing the expression of the tumor suppressor SOCS1. Additionally, tumor-derived miR-6794-5p was delivered to THP-1-derived macrophages and induced M2 polarization by activating the JAK1/STAT3 pathway. Moreover, IL-10 secreted from M2 macrophages increased tumorigenicity by creating an immunosuppressive environment. The in vitro results were reconfirmed by confirming an increase in M2 macrophages and a decrease in M1 macrophages and CD8+ T cells when overexpressing miR-6794-5p in an animal model. CONCLUSIONS: In this study, we identified changes in the tumor microenvironment caused by miR-6794-5p. Our study indicates that tumor-derived miR-6794-5p promotes tumor aggressiveness by inducing an immunosuppressive environment through interaction with macrophage.
Assuntos
Exossomos , MicroRNAs , Neoplasias , Animais , Neoplasias/genética , Bioensaio , Transporte Biológico , Linfócitos T CD8-Positivos , MicroRNAs/genética , Microambiente TumoralRESUMO
BACKGROUND: We developed a novel drug delivery system called hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) that hybridized Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). The present study aims to assess the feasibility and safety of HPIPAC system in a large animal survival model. METHODS: Eleven pigs (eight non-survival models and three survival models) were used in the experiment. The heat module in the HPIPAC controller circulates hyperthermic CO2 in a closed-loop circuit and creates gas-based dry intraperitoneal hyperthermia. Three 12 mm trocars were placed on the abdomen. The afferent CO2 tube wound with heat generating coil was inserted into a trocar, and the efferent tube was inserted into another trocar. Heated CO2 was insufflated and circulated in a closed circuit until the intra-abdominal and peritoneal surface temperature reached 42 °C. 100 ml of 5% dextrose in water was nebulized for 5 min and the closed-loop circulation was resumed for 60 min at 42 °C. Tissue biopsies were taken from several sites from the pigs in the survival model. RESULTS: The average change in core temperature of the pigs was 2.5 ± 0.08 °C. All three pigs displayed no signs of distress, and their vital signs remained stable, with no changes in their diet. In autopsy, inflammatory and fibrotic responses at the biopsy sites were observed without serious pathologic findings. CONCLUSIONS: We successfully proved the feasibility and safety of our novel HPIPAC system in an in-vivo swine survival model.
Assuntos
Neoplasias Peritoneais , Animais , Suínos , Neoplasias Peritoneais/tratamento farmacológico , Dióxido de Carbono , Estudos de Viabilidade , Sistemas de Liberação de Medicamentos , AerossóisRESUMO
BACKGROUND: In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. METHODS: To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments. RESULTS: CD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244-/- bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. CONCLUSION: Our study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients.
Assuntos
Melanoma , Monócitos , Humanos , Animais , Camundongos , Monócitos/metabolismo , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Macrófagos/metabolismo , Linfócitos T CD8-Positivos , Carcinogênese/metabolismo , Microambiente Tumoral , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismoRESUMO
The intraoperative estimated blood loss (EBL), an essential parameter for perioperative management, has been evaluated by manually weighing blood in gauze and suction bottles, a process both time-consuming and labor-intensive. As the novel EBL prediction platform, we developed an automated deep learning EBL prediction model, utilizing the patch-wise crumpled state (P-W CS) of gauze images with texture analysis. The proposed algorithm was developed using animal data obtained from a porcine experiment and validated on human intraoperative data prospectively collected from 102 laparoscopic gastric cancer surgeries. The EBL prediction model involves gauze area detection and subsequent EBL regression based on the detected areas, with each stage optimized through comparative model performance evaluations. The selected gauze detection model demonstrated a sensitivity of 96.5% and a specificity of 98.0%. Based on this detection model, the performance of EBL regression stage models was compared. Comparative evaluations revealed that our P-W CS-based model outperforms others, including one reliant on convolutional neural networks and another analyzing the gauze's overall crumpled state. The P-W CS-based model achieved a mean absolute error (MAE) of 0.25 g and a mean absolute percentage error (MAPE) of 7.26% in EBL regression. Additionally, per-patient assessment yielded an MAE of 0.58 g, indicating errors < 1 g/patient. In conclusion, our algorithm provides an objective standard and streamlined approach for EBL estimation during surgery without the need for perioperative approximation and additional tasks by humans. The robust performance of the model across varied surgical conditions emphasizes its clinical potential for real-world application.
Assuntos
Perda Sanguínea Cirúrgica , Aprendizado Profundo , Humanos , Animais , Suínos , Redes Neurais de Computação , Algoritmos , BandagensRESUMO
PURPOSE: This study aimed to enhance tumor control and abscopal effects by applying diverse stereotactic ablative radiation therapy (SABR) schedules. METHODS AND MATERIALS: FSaII, CT-26, and 4T1 cells were used for tumor growth delay and lung metastases analysis after 1- or 5-day intervals radiation therapy (RT) with 40, 20, and 20 Gy, respectively. Immunodeficient BALB/c-nude, immunocompetent C3H, and BALB/c mouse models were used. For immune monitoring, FSaII tumors were analyzed using flow cytometry, immunofluorescence staining, and real-time quantitative reverse transcription polymerase chain reaction. The spleens were used for the ELISpot assay and flow cytometry to determine effector CD8 T cells. For abscopal effect analysis in CT-26 tumors, the volume of the nonirradiated secondary tumors was measured after primary tumors were irradiated with 1-day or 5-day intervals. RESULTS: Contrary to the high-dose 1-day interval RT, the 5-day interval RT significantly delayed tumor growth in immunocompetent mice, which was not observed in immunodeficient mice. In addition, the 5-day interval RT significantly reduced the number of lung metastases in FSaII and CT-26 tumors. Five-day spacing was more effective than 1-day interval in enhancing the antitumor immunity via increasing the secretion of tumor-specific IFN-γ, activating the CD8 T cells, and suppressing the monocytic myeloid-derived suppressor cells. The 5-day spacing inhibited nonirradiated secondary tumor growth more effectively than did the 1-day interval. CONCLUSIONS: Compared with the 1-day interval RT, the 5-day interval RT scheme demonstrated enhanced antitumor immunity of CD8 T cells associated with inhibition of myeloid-derived suppressor cells. Enhancing antitumor immunity leads to significant improvements in both primary tumor control and the abscopal effect.