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Tonsillectomy is among the most frequently performed surgical procedures in pediatric patients. The incidence of postoperative pain in children after tonsillectomy is high. Patient age and postoperative pain are significant factors that increase the incidence of emergence agitation in children. The study aims to evaluate the impact of spraying dexmedetomidine and lidocaine on the bilateral tonsillar fossa before tonsillectomy on postoperative pain and agitation in children. A total of 140 children aged 4-12 years, who underwent elective tonsillectomy were randomly assigned to four groups: Group N received 5 ml of normal saline, Group L received 5 ml of 2%lidocaine(2 mg/kg) plus saline, Group D received 5 ml of 2 µg/kg dexmedetomidine plus saline, and Group LD received 5 ml of 2 µg/kg dexmedetomidine plus 2 mg/kg 2%lidocaine plus saline. These solutions were applied to the bilateral tonsillar fossa 3 min before surgical incision, following intubation and under general anesthesia. Heart rate and mean arterial pressure were monitored at six time points: upon entering the room(T0),start of operation(T1),end of operation(T2),5 min after extubation (T3),10 min after extubation (T4),and 20 min after extubation (T5).Restlessness was assessed using the Pediatric Anesthesia Emergence Delirium scale at T3, T4, and T5.Postoperative pain was evaluated with the FLACC(Face, Legs, Activity, Cry, Consolability) scale at T3, T4, T5, one hour (T6), and six hours (T7) post-extubation. Anesthetic drug dosage, extubation time, sinus bradycardia, respiratory adverse events, nausea, vomiting, and reoperation for hemostasis within 24 h were documented. Dexmedetomidine groups (D and LD) exhibited reduced agitation and pain compared to non-dexmedetomidine groups (N and L) (P < 0.05), and required less anesthesia during surgery (P < 0.05). Lidocaine did not alleviate postoperative pain or agitation (P > 0.05). Dexmedetomidine slightly decreased heart rate and mean arterial pressure (P < 0.05), but without clinical significance. No differences were observed in operation duration, PACU stay, postoperative nausea/vomiting, or respiratory events among all groups (P > 0.05). In summary, preoperative tonsillar spraying of dexmedetomidine contributes to reduced emergence agitation and postoperative pain in pediatric patients undergoing tonsillectomy.But spraying lidocaine doesn't help with that.
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Detection of microRNAs (miRNAs) reveals tumor information at the transcriptional level, which is crucial for early diagnosis and prognosis of tumors. However, the rapid detection of miRNAs in biological samples without relying on large equipment remains a significant challenge. In this work, a double-layer NiCo heterostructure (DL-H) for enhancing the reaction efficiency of DNA labels, and dual-target cycling reaction system were developed to improve detection sensitivity and shorten the detection time within 30 min. The DL-H and catechol provide favorable condition for methylene blue (MB) oxidation and single-electron transfer of ferrocene (Fc). The target cycling reaction allows one target to release multiple Fc/MB labels from the electrode surface, enhancing the signal differentiation triggered by the target. The obtained sensor possesses a linear detection range of 10 fM-900 pM for miRNA-574-5p and miRNA-1254. The detection limit is 302 aM for miRNA-574-5p, while 85 aM for miRNA-1254. And the detection results of clinical samples present a strong correlation with the PCR. More importantly, a sensing automatic preparation-detection system was developed based on microfluidic chip, to resolve the reliance on highly trained technicians for the electrochemical sensing preparation. This development provides a valuable foundation for the advancement of portable detection tool of tumor biomarker.
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OBJECTIVES: This study evaluated the effectiveness of a social media-based life review intervention on happiness in advanced cancer patient-caregiver dyads and explored participants' subjective experiences. METHODS: A mixed-methods design was employed in oncology wards of a medical center in northern Taiwan between September 2024 and January 2025. Sixty patient-caregiver dyads were recruited through convenience sampling and randomly assigned to an experimental (social media-based life review) or control group (standard care). Final analysis included 28 dyads in the experimental group and 29 in the control group. Quantitative data were collected at baseline and post-intervention using the Subjective Happiness Scale and analyzed with descriptive statistics, t-tests, chi-square tests, and generalized estimating equations (GEE). Qualitative data were collected through two consecutive semi-structured interviews and were analyzed thematically to explore participants' experiences of happiness. RESULTS: Patients in the experimental group maintained stable happiness, whereas those in the control group decline significantly (p = 0.023). Between-group differences were non-significant. Caregivers in the experimental group demonstrated a significant improvement in happiness (p = 0.025), with no change in control group. Patient happiness was positively associated with family support and self-acceptance, whereas caregiver happiness was influenced by age, family support, and patient educational. Qualitative themes were "Always being there is happiness" and "Rediscovering us through memories." CONCLUSION: Social media-based life review intervention enhanced caregiver happiness and prevented decline in patient happiness, highlighting the potential of digitally mediated, family-centered interventions in advanced cancer care. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06559917.
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Cuidadores , Felicidad , Neoplasias , Medios de Comunicación Sociales , Humanos , Cuidadores/psicología , Femenino , Masculino , Neoplasias/psicología , Persona de Mediana Edad , Anciano , Taiwán , Adulto , Apoyo Social , Calidad de Vida/psicologíaRESUMEN
Cancer stem cells (CSCs)/tumor-initiating cells (TICs) withstand metabolic stress and maintain cell survival by means of metabolic reprogramming. However, the underlying mechanisms remain largely unclear. Additionally, it is unknown how to orchestrate metabolic vulnerability of CSCs. LGR5 has been implicated as a CSC marker in colorectal cancer, but in liver cancer, LGR5 has been less studied and its function is not yet explicit. Here, we showed that LGR5 can be used as a marker for liver cancer stem cells (LCSCs), and hepatocellular carcinoma (HCC) cells with high LGR5 expression are more metabolically plastic. In addition, we discovered that LGR5 promotes cancer cell survival by enhancing glycolytic capacity to resist glucose starvation. Mechanistically, LGR5 activates mTORC2 via the RAC1/AKT/FOXO3a axis to induce aerobic glycolysis during metabolic stress. Furthermore, given that p-AMPK was significantly reduced in HCC cells with high expression of LGR5, we found that metformin, an agonist of p-AMPK, inhibits the abnormal phenotypes of HCC cells both in vivo and in vitro by targeting metabolic vulnerabilities. Taken together, these findings establish LGR5 as an important regulator of glycolysis and suggest LGR5 as a potential therapeutic target for LCSCs.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Diana Mecanicista del Complejo 2 de la Rapamicina , Receptores Acoplados a Proteínas G , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamiento farmacológico , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 2 de la Rapamicina/genética , Animales , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/efectos de los fármacos , Ratones , Línea Celular Tumoral , Glucólisis , Transducción de Señal , Carcinogénesis/metabolismo , Metformina/farmacología , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica , Plasticidad de la CélulaRESUMEN
The mortality of hepatocellular carcinoma (HCC) is high. Plant-derived bioactive compounds have emerged as potential therapies for HCC. Procyanidin (PAC) has been shown to possess immune-modulating and anti-tumor properties. However, the role and mechanism of total PAC in treating HCC remain unclear. We established subcutaneous and orthotopic HCC mouse models to assess the effect of PAC on tumor growth. Multi-omics analyses and in vitro experiments were conducted to investigate the changes in the gut microbiota, related-metabolites, and the tumor microenvironment (TME). 16S rDNA sequencing revealed that PAC could reshape the gut microbiota, notably increasing Lactobacillus murinus abundance. Furthermore, transplantation of Lactobacillus murinus reduced tumor volumes in mice. Single-cell RNA sequencing showed upregulation of the MAPK pathway in B cells within the TME. Metabolomic analysis suggests that 5-Hydroxytryptophan (5-HTP) derived from Lactobacillus murinus was significantly increased in B cells from mesenteric lymph nodes (MLNs) in the PAC-treated group. In vitro experiments revealed that 5-HTP could significantly upregulate the MAPK pathway in B cells. Additionally, 5-HTP-educated B cells could activate IFN-γ+CD8+T cells through B cell-T cell interactions, indicating that 5-HTP is a key metabolite in the therapeutic effect of PAC. Finally, feeding 5-HTP to HCC mice reduced tumor volume, upregulated the MAPK pathway in B cells from MLNs, and activated IFN-γ+CD8+T cells in the TME. PAC reshapes the gut microbiota and metabolites, upregulates the MAPK pathway in B cells from MLNs, and activates CD8+T cells in the TME through the gut-liver axis, thereby inhibiting HCC progression.
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Linfocitos B , Biflavonoides , Carcinoma Hepatocelular , Catequina , Microbioma Gastrointestinal , Neoplasias Hepáticas , Sistema de Señalización de MAP Quinasas , Proantocianidinas , Proantocianidinas/farmacología , Proantocianidinas/uso terapéutico , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/microbiología , Catequina/farmacología , Catequina/uso terapéutico , Ratones , Biflavonoides/farmacología , Biflavonoides/uso terapéutico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Linfocitos B/metabolismo , Linfocitos B/efectos de los fármacos , Humanos , Masculino , Microambiente Tumoral/efectos de los fármacos , Línea Celular Tumoral , Ratones Endogámicos BALB CRESUMEN
This study aimed to evaluate the representativeness of HER2-low and ultralow status in core needle biopsies (CNB) with AI assistance and investigate the clinicopathological and molecular characteristics of HER2-ultralow, HER2-null, and HER2-low breast cancer patients in the Chinese population. CNB-surgical excision biopsy (SEB) concordance was high between HER2-null and ultralow/low groups but limited in the ultralow subgroup. Univariate analyses showed that TNBC subtype, HR negative expression, high Ki-67 index, and AR negative expression were potential indicative factors for the discordance of HER2 status between CNB and SEB. Clinicopathological features showed no significant differences between low and ultralow groups. Genomic analysis revealed subtle mutation pattern differences. The HER2 copy number level did not show additional value in distinguishing subgroups. Conclusions highlight the need to address CNB-SEB diagnostic discordance, particularly in ultralow cases, emphasizing the necessity of HER2 retesting in surgical specimens.
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The intersection of cannabis use disorder (CUD) and critical illness outcomes in cancer patients represents a burgeoning area of research, particularly as cannabis legalization and therapeutic applications expand globally. Adjusted analyses of a retrospective cohort study by Sager et al revealed significantly lower odds of all-cause mortality (adjusted odds ratio (aOR) = 0.83) and respiratory failure (aOR = 0.8) in CUD-positive patients, alongside elevated hospitalization costs. These findings suggest the potential immunomodulatory and organ-protective effects of cannabinoids on sepsis. Future research must prioritize mechanistic studies, prospective clinical trials, and socioeconomic interventions to translate these findings into actionable clinical strategies, to align policy recommendations with guidelines, including those presented by the National Comprehensive Cancer Network.
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We report the results of LINUX (NCT05594095), a multicenter, randomized, controlled phase II platform trial aiming to identify effective precision treatments for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer after resistance to cyclin-dependent kinase 4/6 inhibitor. A total of 105 patients were categorized into four similarity network fusion (SNF) subtypes by artificial intelligence-assisted classification and randomly assigned to receive subtyping-based precision therapy (N = 70) or treatment of physician's choice (N = 35). Results demonstrate superior primary endpoint of objective response rates in the subtyping-based groups compared to controls: 10% versus 0% for SNF1, 65% versus 30% for SNF2, 40% versus 30% for SNF3, and 70% versus 20% for SNF4. Grade 3-4 treatment-related adverse events occurred in 37% of both groups. These findings highlight the clinical benefits of subtyping-based precision therapies, particularly for SNF2 and SNF4 subtypes, warranting further validation in phase III trials.
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BACKGROUND: Prior studies have provided conflicting evidence about association between dairy intake and childhood obesity. This study aimed to investigate the associations between different types of dairy intakes and general and abdominal obesity in children. METHODS: Continuous variables were presented as mean ± standard deviation, whereas categorical variables were shown as numbers and percentages. The differences in participant characteristics among dairy intake groups were compared using independent groups t-test or one-way ANOVA for continuous variables. Logistic regression models were fitted to assess the association between total dairy intake, full-fat dairy intake, low-fat dairy intake, milk and yogurt and the risk of general and abdominal obesity. RESULTS: A total of 7,765 children (53.72% boys) aged 9.08 ± 1.73 years participated in this analysis. Of these children, 87.60% (6,802/7,765) did not reach the recommended daily intake of 300 ml of dairy. Overweight and obese children had higher intakes of low-fat dairy (19.62 ± 2.10 vs. 26.02 ± 0.82 vs. 36.75 ± 1.98 vs. 38.86 ± 4.86, p < 0.001) and yogurt (41.80 ± 2.48 vs. 49.54 ± 0.92 vs. 55.27 ± 1.96 vs. 59.47 ± 4.93, p < 0.001) than other peers. Similarly, these trends were observed among children with abdominal and non-abdominal obesity. After adjusting for confounders, higher intakes of low-fat dairy (body mass index z- scores (BMIz): OR = 1.060, 95% CI: 1.038-1.082, p < 0.001; waist circumference (WC): OR = 1.057, 95% CI: 1.034-1.081, p < 0.001; waist-to-height ratio (WHtR): OR = 1.049, 95% CI: 1.027-1.070, p < 0.001) and yogurt (BMIz: OR = 1.026, 95% CI: 1.006-1.047, p = 0.006; WC: OR = 1.024, 95% CI: 1.002-1.047, p = 0.031; WHtR: OR = 1.028, 95% CI: 1.008-1.048, p = 0.006) were associated with higher odds ratio of general and abdominal obesity. CONCLUSION: The association between dairy intake and general as well as abdominal obesity in children varies depending on the type of dairy. Low-fat dairy intake and yogurt intake are positively associated with childhood general and abdominal obesity.
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Productos Lácteos , Obesidad Abdominal , Obesidad Infantil , Yogur , Humanos , Masculino , Femenino , Yogur/estadística & datos numéricos , Estudios Transversales , Niño , China/epidemiología , Productos Lácteos/estadística & datos numéricos , Obesidad Abdominal/epidemiología , Obesidad Abdominal/etiología , Obesidad Infantil/epidemiología , Obesidad Infantil/etiología , Pueblos del Este de AsiaRESUMEN
The silent progression and lack of reliable biomarkers for early-stage hepatocellular carcinoma (HCC) often lead to late-stage diagnoses, where conventional chemotherapies are highly toxic and offer limited efficacy. To bridge this diagnostic-therapeutic gap, we designed a DNA nanocomputer that functions as a biological logic gate, converting a pathological marker into a therapeutic command. This "dual-lock" system uses sialic acid 'caps' to mask galactose ligands on a DNA scaffold. Tumor-overexpressed neuraminidase 3 (NEU3) first cleaves the caps, exposing galactose to trigger asialoglycoprotein receptor (ASGPR)-mediated internalization, thus completing an HCC-exclusive activation cascade. In orthotopic HCC models, the system suppressed tumor growth by 82 % and abrogated the off-target hepatotoxicity of free doxorubicin. Its specificity was confirmed by differential cytotoxicity between HCC and normal hepatocytes and by spatially confined tumor apoptosis. By programming a therapeutic response to a tumor-specific enzymatic circuit, this work establishes a new paradigm for metabolically guided nanomedicine, transforming a pathological hallmark into a therapeutic trigger to resolve the precision-toxicity dichotomy of conventional chemotherapy.
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Background: The empowerment capacity of caregivers exerts a significant impact on children's prognosis. This study aims to analyze the empowerment ability of primary caregivers of children who have undergone craniotomy, thereby providing evidence-based support for pediatric nursing practice. Methods: Participants in this study included main caregivers of children with intracranial tumors who underwent surgical treatment in our hospital between February 2022 and April 2025. The empowerment ability of these main caregivers was assessed using the Main Caregivers' Empowerment Measurement (MCEM) scale. Correlation analysis and multiple linear stepwise regression analysis were performed to identify potential influencing factors. Results: A total of 242 main caregivers were enrolled in this study. The average empowerment score among these caregivers was 160.64 ± 15.07. The "Personal Resources" and "Care Knowledge and Skills" dimensions yield the lowest scores across all dimensions. Correlation analysis demonstrated that the child's age (r = 0.581), place of residence (r = 0.546), caregiver's gender (r = 0.604), caregiver's age (r = 0.626), educational level (r = 0.615), and monthly per capita income (r = 0.586) were all significantly associated with the empowerment ability (all p < 0.05). Furthermore, multivariate linear regression analysis identified those factors as significant influencing factors of caregiver empowerment. These selected variables accounted for 58.8% of the variance in caregivers'empowerment ability. Conclusion: Given the substantial room for improvement in the empowerment levels of main caregivers, targeted strategies are urgently needed to address this gap. Healthcare professionals should therefore design interventions that are tailored to the identified influencing factors to enhance caregivers' empowerment capacities.
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Background: Personalized nutritional management during cancer remains challenging in clinical practice. The development of an electronic patient-reported outcome platform (ePROM) provides novel opportunities. Objective: This study aimed to evaluate the effectiveness and adherence of nutritional management using ePROM in patients with cancer. Methods: This multicenter prospective longitudinal cohort study included 6124 patients diagnosed with cancer. Exposure was defined as adherence to the ePROM journal, measured by the longest consecutive month of weekly entries. Dietary intake was reported via food selection, voice input, or meal photos. The primary outcomes were adequate energy intake (EI, ≥25 kcal/kg/day) and protein intake (PI, ≥1 g/kg/day), defined according to European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines. Logistic regression analysis was conducted to identify the factors associated with EI and PI, reporting odds ratios (ORs) and 95% CIs. A restricted cubic spline plot was used to illustrate the association between the adjusted ORs and adherence duration. The semMediation approach was applied to assess the impact of multiple mediators on the outcomes. Results: The study cohort comprised 3741/6124 (61.1%) men and 2383 (38.9%) women, with a median age of 60.85 (IQR 53.3-68.3) years. Overall, 1024/6124 (16.7%) and 2591/6124 (42.3%) patients achieved adequate EI and PI scores, respectively. At one month, 499/1024 patients (48.7%) in the adequate EI group and 1287/2591 (49.7%) in the adequate PI group continued journaling, compared with 1879/5100 (36.8%) and 1091/3533 (30.9%) in the corresponding inadequate groups (P<.001). This trend remained significant in the second, third, and sixth months. Logistic regression analysis demonstrated that longer adherence to ePROM journaling was independently associated with adequate EI (OR 1.05, 95% CI 1.01-1.08; P=.01) and PI (OR 1.22, 95% CI 1.16-1.28; P<.001) after adjusting for confounders. Mediation analysis revealed that most symptoms did not significantly mediate these effects, except for constipation, reflux, and delirium, which showed statistical significance but minimal indirect effects. Conclusions: Nutritional management via ePROM is a feasible approach, with improved effectiveness as adherence duration increases. The observed benefits resulted primarily from direct effects rather than from symptom improvement.
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Neoplasias , Cooperación del Paciente , Medición de Resultados Informados por el Paciente , Humanos , Masculino , Femenino , Neoplasias/dietoterapia , Neoplasias/terapia , Persona de Mediana Edad , Estudios Longitudinales , Estudios Prospectivos , Anciano , Cooperación del Paciente/estadística & datos numéricos , Ingestión de Energía , Estado NutricionalRESUMEN
Patients with hyperthyroidism frequently present with hematological abnormalities; however, the underlying mechanisms remain incompletely understood. This study enrolled 166 treatment-naïve hyperthyroidism patients and 56 age- and sex-matched healthy controls, comparing their complete blood count parameters. Additionally, a murine model of hyperthyroidism was established, and flow cytometry was employed to assess the quantity, proportion, cell cycle status, and apoptosis of hematopoietic stem/progenitor cells (HSPCs) in the bone marrow. Clinical data analysis revealed that, compared to the healthy control group, hyperthyroidism patients exhibited significant reductions in peripheral white blood cell counts-particularly neutrophils, eosinophils, and basophils-as well as in red blood cell parameters, including hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (HCH), and mean corpuscular hemoglobin concentration (MCHC). These alterations were more pronounced in female patients. Animal experiments confirmed that hyperthyroid mice also developed leukopenia and neutropenia. Further investigation demonstrated a decreased number of HSPCs in the bone marrow of hyperthyroid mice. The primary cause was identified as cell cycle arrest rather than increased apoptosis. This study reveals that elevated thyroid hormone levels may lead to alterations in peripheral blood cell counts by inducing cell cycle arrest in bone marrow HSPCs, thereby impairing their proliferation and differentiation capabilities. These findings provide a novel cellular perspective for understanding the mechanisms underlying hematological abnormalities in hyperthyroidism and offer a theoretical foundation for potential clinical intervention strategies.
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Células Madre Hematopoyéticas , Hipertiroidismo , Hipertiroidismo/sangre , Hipertiroidismo/patología , Hipertiroidismo/complicaciones , Animales , Femenino , Masculino , Humanos , Ratones , Adulto , Persona de Mediana Edad , Células Madre Hematopoyéticas/patología , Modelos Animales de Enfermedad , Apoptosis , Estudios de Casos y Controles , Índices de EritrocitosRESUMEN
Background: Intussuscepted anastomoses in esophagectomy reduce the risks of anastomotic leakage and gastroesophageal reflux, but anastomotic stricture remains a significant concern. This study presents a novel hand-sewn technique, "H anastomosis," designed to minimize stricture formation while preserving antileakage and antireflux functionality. Methods: H anastomosis was simulated by using the esophagus and stomach of a Bama pig. The patency and antireflux function were assessed by injecting water into the ex vivo organs to stimulate the flow of food through the anastomotic stoma. Clinical data from 32 patients with esophageal squamous cell carcinoma who underwent minimally invasive esophagectomy with H anastomosis were retrospectively reviewed. Postoperative follow-up included reflux and dysphagia evaluations, as well as 24-hour pH monitoring. Results: In the animal model, H anastomosis allowed smooth water flow with a maximum antireflux capacity of 90 mm H2O. Clinically, 30 of 32 patients (93.8%) reported no gastroesophageal reflux in the supine position postprandially, as confirmed by normal DeMeester scores. The most common postoperative complication was pneumonia (34.4%), and only 1 patient experienced anastomotic leakage, which healed with conservative management. No significant anastomotic stricture was observed. Conclusions: H anastomosis effectively prevents anastomotic leakage and gastroesophageal reflux without causing stricture. Further validation through larger studies is necessary to confirm its long-term efficacy.
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Background: Neoadjuvant chemotherapy (NACT) is an important part of comprehensive breast cancer treatment. However, considering that not all patients respond well, how to identify responders as soon as possible is a significant issue. Magnetic resonance imaging (MRI) shows excellent diagnostic accuracy in breast cancer, while whether it is able to identify NACT responders is not clear. In this study, we aim to evaluate the role of early percentage apparent diffusion coefficient change (ΔADC%) in predicting response to NACT in patients with breast cancer. Methods: We searched studies in PubMed, Web of Science, and Cochrane Library up to April 28, 2025. The inclusion criteria were: predicting response to NACT in breast cancer; using ΔADC% as prediction parameter; diffusion-weighted imaging (DWI)-MRI images were acquired before NACT beginning and early during NACT (after 1 or 2 cycles); providing exact criteria for responders. The exclusion criteria were: not in English or Chinese; animal studies; review/meta-analysis/abstract/case report; the number of true-positive (TP), false-negative (FN), false-positive (FP), and true-negative (TN) findings cannot be extracted directly or indirectly. The methodological quality of the included studies was assessed by Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2. Sensitivity, specificity, and summary receiver operating characteristic (SROC) curve were used to evaluate the prediction accuracy. Sub-group analyses were used to find the source of heterogeneity. For the retrospective study, 47 patients with breast cancer from our hospital were included. We used the Mann-Whitney U test to compare the ΔADC% between the pathological complete response (pCR) and non-pCR group. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the prediction ability. Results: In the meta-analysis, 11 studies and 681 patients were included. Pooled sensitivity and specificity were 0.71 [95% confidence interval (CI): 0.60-0.79] and 0.78 (95% CI: 0.68-0.85), respectively. AUC was 0.81 (95% CI: 0.77-0.84). There was no obvious difference between the sub-groups. In the validation study, ΔADC% was significantly higher in the pCR group than in the non-pCR group. When 20.3% was chosen as the cut-off value, ΔADC% had a sensitivity of 64.7% and a specificity of 73.3% in predicting pCR. Conclusions: ΔADC% may be valuable in early prediction of response to NACT in breast cancer. The results need further validation in a larger population.
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Previous studies have demonstrated that PRMT1 was involved in the progression of multiple lung diseases. However, its specific function within the bronchial epithelium was still limited and needed further exploration. In the present study, human bronchial epithelial cell line 16HBE was chosen to elucidate the biological role of PRMT1 in lung epithelium. Cell proliferation, cell-cycle distribution, cell apoptosis, and cell motility capacity were systematically evaluated following CRISPR/Cas9-mediated knockout of PRMT1. We showed that knockout of PRMT1 in 16HBE inhibited cell proliferation, redistributed cell cycle, promoted cell apoptosis, and accelerated cell migration via a series of regulated cyclins, cyclin-dependent kinase regulators, and EMT markers. Taken together, these findings identify PRMT1 as a potential modulator of epithelial cell proliferation, survival, and motility in the human bronchial epithelium, offering new insights into its possible role in epithelial remodeling during pulmonary disorders.
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Bronquios , Movimiento Celular , Proliferación Celular , Células Epiteliales , Proteína-Arginina N-Metiltransferasas , Proteínas Represoras , Humanos , Movimiento Celular/genética , Proliferación Celular/genética , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/citología , Bronquios/citología , Bronquios/metabolismo , Línea Celular , Apoptosis/genética , Técnicas de Inactivación de Genes , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Ciclo Celular/genética , Sistemas CRISPR-CasRESUMEN
Dysregulation of intracellular pH (pHi) is a hallmark biological feature of cancer cells, which hijack pHi homeostasis to sustain malignant phenotypes including uncontrolled proliferation, invasion, and metabolic reprogramming. Meanwhile, alkaliptosis, a newly defined pH-dependent form of regulated cell death specifically triggered by the small-molecule compound JTC-801, has emerged as a promising therapeutic target for cancer intervention. However, reliable tools for monitoring dynamic pHi changes during alkaliptosis remain insufficient. RpHluorin2 is an optimized ratiometric pH-sensitive green fluorescent protein variant with enhanced fluorescence intensity and stability. Herein, we established a stable RpHluorin2-expressing cell line and further developed a multi-dimensional fluorescence detection workflow, which encompasses a microplate reader, fluorescence microscopy, flow cytometry, a small animal imaging system (IVIS Spectrum), and a protein dot blot assay coupled with IVIS. Our results demonstrated a strong linear correlation between RpHluorin2 fluorescence intensity and cell number, with a coefficient of determination (R 2) of 0.9998. Furthermore, across all employed detection methods, JTC-801 treatment induced dose-dependent and time-dependent reductions in RpHluorin2 fluorescence, an observation that is consistent with the elevation of pHi during alkaliptosis. This platform enables high-throughput screening, single-cell analysis, and biochemical validation, providing a robust tool for mechanistic research on alkaliptosis and the development of pH-targeted anticancer therapies.
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This report examines the development and implementation of Taiwan's direct-acting antiviral (DAA) reimbursement policy and evaluates outcomes using a return-on-investment (ROI) framework. Aggregating model-based estimates across 173,747 reimbursed patients, we project 614,980 discounted quality-adjusted life years (QALYs) and 1,085,742 undiscounted QALYs. Valuing discounted QALYs at a threshold equal to Gross Domestic Product (GDP) per capita yields an economic value of about NTD672 billion. Against National Health Insurance (NHI) DAA spending of NTD28.74 billion (2017-2024), the ROI is 22.4; using undiscounted QALYs, the value is about NTD1.187 trillion and the ROI is about 40.3. These findings indicate a high-return public investment, with gains from extended life expectancy and improved quality of life rather than short-term budget savings. Achievements reflect concerted efforts by clinicians, policymakers, administrators, and other stakeholders. Key lessons include the importance of early treatment access, dedicated funds with proactive financial risk management, use of a national patient registry for outcome tracking, and periodic professional monitoring to guide adaptive policy adjustments within a comprehensive elimination strategy.