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Spontaneous cerebellar hemorrhage (SCH) patients have a low success rate in extubation, but there are currently no guidelines establishing specifically for SCH patients extubation. The study included 68 SCH patients who received mechanical ventilation for more than 24 h, with 39 cases (57.3%) resulting in successful extubation. The multivariate analysis identified four factors significantly associated with extubation success: patient age under 66 years, an Intracerebral Hemorrhage (ICH) score less than 4 points, the presence of tissue shift, and a Glasgow Coma Scale (GCS) score (excluding language) above 6 points at extubation. By simplifying the prediction model, we obtained the Spontaneous Cerebellar Hemorrhage Extubation Success scoring system (SCHES-SCORE). Within the scoring system, 2 points were allocated for a GCS score (excluding language) above 6 at extubation, 1 point each for age under 66 years and an ICH score below 4, while tissue shift was assigned a negative point. A score of Grade A (SCHES-SCORE = 3-4) was found to correlate with a 92.9% success rate for extubation. The area under the receiver operating characteristic curve was 0.923 (95% CI, 0.863 to 0.983). Notably, successful extubation was significantly linked to reduced durations of mechanical ventilation, intensive care unit (ICU) stay, and total hospital stay. In conclusion, the scoring system developed for assessing extubation outcomes in SCH patients has the potential to enhance the rate of successful extubation and overall patient outcomes.

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OBJECTIVE: The objective of this study is to assess and compare the efficacy of oXiris with conventional continuous renal replacement therapy (CRRT) in managing severe abdominal infections. METHODS: A retrospective analysis encompassing cases from 2017 to 2023 was conducted at the Department of Critical Care Medicine within the First Affiliated Hospital of Fujian Medical University. Parameters including heart rate (HR), mean arterial pressure (MAP), oxygenation index (OI), lactate (Lac), platelet count (PLT), neutrophil ratio (N%), procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), norepinephrine (NE) dosage, acute physiology and chronic health evaluation II (APACHE II), and sequential organ failure assessment (SOFA) were recorded prior to treatment initiation, at 24 hours, and 72 hours post-treatment for both the oXiris and conventional CRRT groups. Additionally, the duration of respiratory support, CRRT treatment, length of stay in the intensive care unit (ICU), total hospitalization period, as well as mortality rates at 14 and 28 days for both groups were recorded. RESULTS: 1) Within the conventional CRRT group, notable enhancement was observed solely in Lac levels at 24 hours post-treatment compared to pre-treatment levels. Also, at 72 hours post-treatment, improvements were evident in HR, Lac, CRP, and IL-6 levels. 2) Conversely, the oXiris group exhibited improvements in HR, MAP, Lac, OI, N%, and IL-6 at 24 hours post-treatment when compared to baseline values. Additionally, reductions were observed in APACHE II and SOFA scores. At 72 hours post-treatment, all parameters demonstrated enhancement except for PLT. 3) Analysis of the changes in the indexes (Δ) between the two groups at 24 hours post-treatment revealed variances in HR, MAP, Lac, NE dosage, CRP levels, IL-6 levels, APACHE II scores, and SOFA scores. 4) The Δ indexes at 72 hours post-treatment indicated more significant improvements following oXiris treatment for both groups, except for PCT. 5) The 14-day mortality rate (24.4%) exhibited a significant reduction in the oXiris group when compared to the conventional group (43.6%). However, no significant difference was observed in the 28-day mortality rate between the two groups. 6) Subsequent to multifactorial logistic regression analysis, the results indicated that oXiris treatment correlated with a noteworthy decrease in the 14-day and 28-day mortality rates associated with severe abdominal infections, by 71.3% and 67.6%, respectively. CONCLUSION: oXiris demonstrates clear advantages over conventional CRRT in the management of severe abdominal infections. Notably, it reduces the fatality rates, thereby establishing itself as a promising and potent therapeutic option.

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PURPOSE: To establish and validate a delta-radiomics-based model for predicting progression-free survival (PFS) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) following induction chemotherapy (IC). METHODS AND MATERIALS: A total of 250 LA-NPC patients (training cohort: n = 145; validation cohort: n = 105) were enrolled. Radiomic features were extracted from MRI scans taken before and after IC, and changes in these features were calculated. Following feature selection, a delta-radiomics signature was constructed using LASSO-Cox regression analysis. A prognostic nomogram incorporating independent clinical indicators and the delta-radiomics signature was developed and assessed for calibration and discrimination. Risk stratification by the nomogram was evaluated using Kaplan-Meier methods. RESULTS: The delta-radiomics signature, consisting of 12 features, was independently associated with prognosis. The nomogram, integrating the delta-radiomics signature and clinical factors demonstrated excellent calibration and discrimination. The model achieved a Harrell's concordance index (C-index) of 0.848 in the training cohort and 0.820 in the validation cohort. Risk stratification identified two groups with significantly different PFS rates. The three-year PFS for high-risk patients who received concurrent chemoradiotherapy (CCRT) or radiotherapy plus adjuvant chemotherapy (RT+AC) after IC was significantly higher than for those who received RT alone, reaching statistical significance. In contrast, for low-risk patients, the three-year PFS after IC was slightly higher for those who received CCRT or RT+AC compared to those who received RT alone; however, this difference did not reach statistical significance. CONCLUSIONS: Our delta MRI-based radiomics model could be useful for predicting PFS and may guide subsequent treatment decisions after IC in LA-NPC.

Asunto(s)

Quimioterapia de Inducción , Imagen por Resonancia Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Radiómica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quimioterapia de Inducción/métodos , Imagen por Resonancia Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/radioterapia , Pronóstico , Resultado del Tratamiento

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Objective: Intracranial hemorrhage (ICH), the second most common subtype of stroke, exacerbates the disruption of the blood-brain barrier (BBB), leading to vasogenic edema, plasma protein extravasation, and infiltration of neurotoxic substances. The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage. This study aimed to investigate the effect of circadian rhythms on BBB function, neuronal damage, and clearance capabilities. Methods: The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH. After intervention with different light groups, neuronal apoptosis was determined, glial phagocytosis was analyzed, the expression of endogenous clearing-related proteins aquaporin 4 (AQP4) and low-density lipoprotein receptor-related protein 1 (LRP1) was detected by western blotting and immunofluorescence dual standard method, and the expression of the tight junction protein occludin and melatonin receptor 1A (MTNR1A) was quantitatively analyzed. Results: Circadian rhythms play a key role in maintaining the integrity of the BBB, reducing oxidative stress-induced neuronal damage, and improving microglial phagocytosis. Meanwhile, the expression of occludin and MTNR1A in neurovascular unit (NVU) co-cultured with hemoglobin improved the expression of AQP4 and LRP1, the key proteins in the NVU's endogenous brain clearance system. Conclusion: Circadian rhythm (alternating black and white light) protects the NVU BBB function after ICH, promotes the expression of proteins related to the clearance of the hematoma, provides new evidence for the clinical treatment of patients recovering from ICH, and improves the circadian rhythm to promote brain metabolism and hematoma clearance.

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Barrera Hematoencefálica , Ritmo Circadiano , Técnicas de Cocultivo , Hemoglobinas , Ritmo Circadiano/fisiología , Barrera Hematoencefálica/metabolismo , Hemoglobinas/metabolismo , Animales , Fagocitosis , Neuronas/metabolismo , Neuronas/fisiología , Masculino

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Hen egg low-density lipoprotein (heLDL), as alternative of serum-derived LDL, was used as drug delivery system of ceftiofur (CEF). The CEF-loaded hen egg low-density lipoprotein (CEF-heLDL) with complete apolipoprotein structure and high drug loading rate was synthesized, possesses suitable particle size. CEF-heLDL undergoes cellular uptake and colocalizes with lysosomes in vitro. An intracellular infection model of the bovine endometrial epithelial cells and a coeliac-induced inflammation model of mice by Staphylococcus aureus (S. aureus) were established, and significantly lower intracellular S. aureus levels of CEF-heLDL group than CEF-free group (P < 0.001) was observed. The antibacterial efficacy was sustained for 24 h. Up to 400 mg/kg of CEF-heLDL, 20 times the clinical practice, were intraperitoneally administrated, and no significant toxicity signs on mice were observed. HeLDLs is an effective, safe, and cheap drug carrier, and could also be used for transmembrane delivering other antibiotics.

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Antibacterianos , Cefalosporinas , Pollos , Lipoproteínas LDL , Staphylococcus aureus , Animales , Staphylococcus aureus/efectos de los fármacos , Lipoproteínas LDL/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Ratones , Cefalosporinas/farmacología , Cefalosporinas/farmacocinética , Cefalosporinas/química , Bovinos , Femenino , Portadores de Fármacos/química , Infecciones Estafilocócicas/tratamiento farmacológico , Huevos

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Xeroderma pigmentosum is a rare autosomal recessive genodermatoses characterized by a deficiency in nucleotide excision repair. Erythropoietic protoporphyria is a rare inherited metabolic disease caused by the perturbation of heme. Xeroderma pigmentosum-erythropoietic protoporphyria is exceedingly rare. Hereby, we firstly report a young Chinese patient of xeroderma pigmentosum Group A with erythropoietic protoporphyria carrying an XPA Met214AsnfsTer7 frameshift mutation and a homozygous splicing mutation, c.315-48T>C, in the proband's intron3 of FECH.

Asunto(s)

Ferroquelatasa , Protoporfiria Eritropoyética , Xerodermia Pigmentosa , Humanos , Protoporfiria Eritropoyética/genética , Protoporfiria Eritropoyética/complicaciones , Xerodermia Pigmentosa/genética , Xerodermia Pigmentosa/complicaciones , Ferroquelatasa/genética , Masculino , Proteína de la Xerodermia Pigmentosa del Grupo A/genética , Mutación , Pueblo Asiatico/genética , Femenino , China , Mutación del Sistema de Lectura , Pueblos del Este de Asia

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Cancer poses a significant global public health challenge, with commonly used adjuvant or neoadjuvant chemotherapy often leading to adverse side effects and drug resistance. Therefore, advancing cancer treatment necessitates the ongoing development of novel anticancer agents with diverse structures and mechanisms of action. Natural products remain crucial in the process of drug discovery, serving as a primary source for pharmaceutical leads and therapeutic advancements. Triterpenoids are particularly compelling due to their complex structures and wide array of biological activities. Recent research has demonstrated that naturally occurring triterpenes and their derivatives have the potential to serve as promising candidates for new drug development. This review aims to comprehensively explore the anticancer properties of triterpenoids and their synthetic analogs, with a focus on recent advancements. Various aspects, such as synthesis, phytochemistry, and molecular simulation for structure-activity relationship analyses, are summarized. It is anticipated that triterpenoid derivatives will emerge as notable anticancer agents following further investigation into their mechanisms of action and in vivo studies.

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Imbalanced Sirtuin 1 (SIRT1) levels may lead to liver diseases through abnormal regulation of autophagy, but the roles of SIRT1-regulated autophagy in hepatocellular carcinoma are still controversial. In this study, we found that SIRT1 mRNA and protein levels were upregulated in hepatocellular carcinoma, and high SIRT1 expression hinted an advanced stage and a poor prognosis. The differentially expressed proteins were significantly elevated in autophagy, cellular response to stress, and immune signaling pathways. In a thioacetamide-induced hepatocellular carcinoma mouse model, we found that SIRT1 expression was highly increased with increased autophagy and excessive macrophage inflammatory response. Next, we established a Hepa 1-6 cells and macrophage co-culture system in vitro to model the alteration of tumor microenvironment, and found that the medium from CCl4-treated or SIRT1-overexpressing Hepa 1-6 cells triggered the polarization of macrophage M1, and the culture medium derived from M1 macrophage promoted Hepa 1-6 cells growth and intracellular oxidative stress. The progression of liver fibrosis in the CCl4-induced liver fibrosis mouse model showed that inhibition of SIRT1 alleviated inflammatory response and ameliorated liver fibrosis. These findings suggest that SIRT1-regulated autophagy and inflammation are oncogenic in hepatocarcinogenesis.

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Autofagia , Carcinoma Hepatocelular , Inflamación , Neoplasias Hepáticas , Sirtuina 1 , Sirtuina 1/metabolismo , Sirtuina 1/genética , Animales , Autofagia/efectos de los fármacos , Ratones , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inducido químicamente , Inflamación/patología , Inflamación/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inducido químicamente , Humanos , Macrófagos/metabolismo , Línea Celular Tumoral , Masculino , Carcinogénesis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Cirrosis Hepática/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos

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Background: Diabetes is a prevalent chronic disease. Although self-care is the crucial element in managing diabetes, older Korean immigrants with diabetes face challenges in performing effective self-care related to vulnerability as minority immigrants. Purpose: This study measures sociodemographics, self-efficacy, social support, diabetes knowledge, and diabetes self-care activities among older Korean immigrants in the United States. This study also aims to demonstrate the direct and indirect effects of the related factors on diabetes self-care activities using a path analysis. Methods: This study uses a cross-sectional design. Convenience sampling targeted Korean immigrants aged 55 or older using paper and online surveys. Four instruments were used to measure variables: self-efficacy was measured by the General Self-Efficacy scale, diabetes knowledge by the Simplified Diabetes Knowledge Test, social support by the Lubben Social Network Scale-6, and diabetes self-care by the Summary of Diabetes Self-Care Activities questionnaire. Using path analysis, the effects of related factors on self-care activities were analyzed. Results: 190 older Korean immigrants participated, 53.2% female, and 46.8% male. The mean age was 67.2 (SD = 9.9; range, 58-93). A path model shows that sociodemographics (sex, age, education, and years in the United States), diabetes knowledge, self-efficacy, and family support predict diabetes self-care. Conclusions: The path model demonstrates the effects of sociodemographics, self-efficacy, diabetes knowledge, and social support on diabetes self-care among older Korean immigrants. The findings can help to understand diabetes self-care among the minority ethnic older group and can be used to develop culturally tailored education, counseling, and healthcare services. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01363-6.

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Background: Pyroptosis plays a crucial role in immune responses. However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC. PRSlow is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRSlow marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC.

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Inmunoterapia , Terapia Neoadyuvante , Piroptosis , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patología , Terapia Neoadyuvante/métodos , Microambiente Tumoral/inmunología , Inmunoterapia/métodos , Masculino , Pronóstico , Femenino , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Multiómica

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Melon (Cucumis melo L.) is a global commercial crop that is sensitive to seed-borne wilt infections caused by Fusarium oxysporum f. sp. melonis (Fom). To address the challenge of detecting Fom contamination, we designed a probe-based real-time PCR method, TDCP2, in combination with rapid or column-based DNA extraction protocols to develop reliable molecular detection methods. Utilizing TDCP2, the detection rate reached 100% for both artificially Fom-inoculated (0.25-25%) and pod-inoculated melon seeds in conjunction with DNA samples from either the rapid or column-based extraction protocol. We performed analyses of precision, recall, and F1 scores, achieving a maximum F1 score of 1 with TDCP2, which highlights the robustness of the method. Additionally, intraday and interday assays were performed, which revealed the high reproducibility and stability of column-based DNA extraction protocols combined with TDCP2. These metrics confirm the reliability of our developed protocols, setting a foundation for future enhancements in seed pathology diagnostics and potentially broadening their applicability across various Fom infection levels. In the future, we hope that these methods will reduce food loss by improving the control and management of melon diseases.

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Fusarium , Enfermedades de las Plantas , Reacción en Cadena en Tiempo Real de la Polimerasa , Semillas , Fusarium/genética , Fusarium/aislamiento & purificación , Semillas/microbiología , Enfermedades de las Plantas/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Cucurbitaceae/microbiología , ADN de Hongos/genética , ADN de Hongos/aislamiento & purificación , Cucumis melo/microbiología , Reproducibilidad de los Resultados

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OBJECTIVES: The purpose of this study was to provide a comprehensive overview of the prevalence, measurement tools, influencing factors, and interventions for fear of falling (FOF) in stroke survivors. METHODS: A PRISMA-guided systematic literature review was conducted. PubMed, EMBASE, Cochrane, and Web of Science were systematically searched. The search time was up to February 2023. All observational and experimental studies investigating FOF in stroke patients were included. The assessment tool of the Joanna Briggs Institute was used to assess the quality of the included studies and the risk of bias assessment. (PROSPERO: CRD42023412522). RESULT: A total of 25 observational studies and 10 experimental studies were included. The overall quality of the included studies was "low" to "good." The most common tool used to measure the FOF was the Falls Efficacy Scale-International (FES-I). The prevalence of FOF was 42%- 93.8%. Stroke survivors with physical impairments have the highest prevalence of FOF. The main risk factors for the development of FOF in stroke survivors were female gender, use of assistive devices, balance, limb dysfunction, and functional mobility. The combination of cognitive behavioral and exercise interventions is the most effective strategy. CONCLUSIONS: This review suggests that the prevalence of FOF in stroke survivors is high and that understanding the factors associated with FOF in stroke patients can help develop multifactorial prevention strategies to reduce FOF and improve quality of life. In addition, a uniform FOF measurement tool should be used to better assess the effectiveness of interventions for stroke survivors. ETHICS APPROVAL: PROSPERO registration (CRD42023412522).

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PURPOSE: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown. METHODS: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry. RESULTS: The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8. CONCLUSION: The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.

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Carcinoma Hepatocelular , Movimiento Celular , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , Células Madre Neoplásicas , Transducción de Señal , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Movimiento Celular/genética , Regulación hacia Abajo/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Línea Celular Tumoral , Transducción de Señal/genética , Factor 4 Similar a Kruppel , Masculino , Femenino , Animales , Glutatión Peroxidasa/metabolismo , Glutatión Peroxidasa/genética , Persona de Mediana Edad , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Ratones Endogámicos BALB C

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Background: Induction chemotherapy (IC) combined with concurrent chemoradiotherapy has become the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Data on the prognostic value of the lymph node-to-primary tumor ratio (NTR) of positron emission tomography (PET) standardized uptake value (SUV) for patients treated with IC were limited. Objectives: To evaluate the prognostic value of the SUV NTR for patients with LA-NPC treated with IC. Design: In all, 467 patients with pretreatment 18F-fluorodeoxyglucose PET/computed tomography (CT) scans between September 2017 and November 2020 were retrospectively reviewed. Methods: The receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value of SUV NTR. Kaplan-Meier method was used to evaluate survival rates. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. Results: The optimal cutoff value of SUV NTR was 0.74. Multivariate analyses showed that SUV NTR and overall stage were independent predictors for distant metastasis-free survival (DMFS) and regional recurrent-free survival (RRFS). Therefore, an RPA model based on the endpoint of DMFS was generated and categorized the patients into three distinct risk groups: RPA I (low risk: SUV NTR < 0.74 and stage III), RPA II (medium risk: SUV NTR < 0.74 and stage IVa, or SUV NTR ⩾ 0.74 and stage III), and RPA III (high risk: SUV NTR ⩾ 0.74 and stage IVa), with a 3-year DMFS of 98.9%, 93.4%, and 84.2%, respectively. ROC analysis showed that the RPA model had superior predictive efficacy than the SUV NTR or overall stage alone. Conclusion: SUV NTR was an independent prognosticator for distant metastasis and regional recurrence in locoregionally advanced NPC. The RPA risk stratification model based on SUV NTR provides improved DMFS and RRFS prediction over the eighth edition of the TNM (Tumor Node Metastasis) staging system.

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Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+-CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.

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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Compuestos de Fenilurea , Quinolinas , Humanos , Oxaliplatino/uso terapéutico , Gemcitabina , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Linfocitos T CD8-positivos , Conductos Biliares Intrahepáticos , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Proteínas Reguladoras de la Apoptosis , Receptores Depuradores

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Background and Purpose: Patients undergoing surgery are at risk of pressure injury development and should be assessed to ensure measures are taken for prevention. The study's purpose was to examine the causal relationships and reliability of the Munro Pressure Injury Risk Assessment Scale for Perioperative Patients (Munro Scale). The Munro Scale is the first dynamic risk scale available for this patient population in the acute clinical setting. Methods: This study was a retrospective review to explore the relationships of the variables in the Munro Scale, identify the strongest predictors, and measure the reliability of previously collected data from two northeastern community hospitals. A total of 630 risk assessments were analyzed to obtain regression, correlation, and reliability evidence for the Munro Scale. Results: The correlation analysis among the 15 risk variables and combined comorbidities revealed commonalities among the variables and significant relationships to the final postoperative injury score. The model as a whole is significant to predict the final level of risk. Coefficient alpha revealed a lower than anticipated reliability when compared to the Chinese, Turkish, and Brazilian versions of the Munro Scale. Conclusions: There are significant relationships among the variables, and the scale is acceptable for use in the acute perioperative practice setting. This study has both clinical and statistical significance.

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Úlcera por Presión , Humanos , Encuestas y Cuestionarios , Úlcera por Presión/prevención & control , Reproducibilidad de los Resultados , Medición de Riesgo , Hospitales Comunitarios

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OBJECTIVE: To analyze the interrelation between radiation dose and radiation-induced nasopharyngeal ulcer (RINU) in locoregional recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS: Clinical data were collected from 363 patients with locoregional recurrent NPC who received re-irradiated with definitive IMRT from 2009 to 2017. Twenty-nine patients were diagnosed with RINU. Univariate and multivariate analyses were used to re-evaluate the first and second radiotherapy plans and to identify predictive dosimetric factors. RESULTS: All dosimetric parameters were notably associated with the progression to RINU (p < 0.01) using paired samples Wilcoxon signed rank tests. Multivariate analysis showed that EQD2_ [Formula: see text]D80 (dose for 80 percent volume of the unilateral nasopharynx lesion) was an independent prognostic factor for RINU (p = 0.001). The area under the ROC curve for EQD2_ [Formula: see text]D80 was 0.846 (p < 0.001), and the cutoff point of 137.035 Gy could potentially be the dose tolerance of the nasopharyngeal mucosa. CONCLUSIONS: The sum of equivalent dose in 2 Gy fractions (EQD2) in the overlapping volumes between initial and re-irradiated nasopharyngeal mucosal tissue can be effective in predicting the hazard of developing RINU in NPC patients undergoing radical re­irradiation with IMRT and we propose a EQD2_ [Formula: see text]D80 threshold of 137.035 Gy for the nasopharynx.

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Neoplasias Nasofaríngeas , Traumatismos por Radiación , Radiodermatitis , Radioterapia de Intensidad Modulada , Reirradiación , Humanos , Carcinoma Nasofaríngeo/radioterapia , Radioterapia de Intensidad Modulada/efectos adversos , Neoplasias Nasofaríngeas/patología , Úlcera/etiología , Dosificación Radioterapéutica , Traumatismos por Radiación/etiología , Estudios Retrospectivos , Nasofaringe/patología , Radiodermatitis/etiología

RESUMEN

BACKGROUND: Minimal residual disease (MRD) is proposed to be responsible for tumor recurrence. The role of circulating tumor DNA (ctDNA) to detect MRD, monitor recurrence, and predict prognosis in liver cancer patients undergoing liver transplantation (LT) remains unrevealed. METHODS: Serial blood samples were collected to profile ctDNA mutational changes. Baseline ctDNA mutational profiles were compared with those of matched tumor tissues. Correlations between ctDNA status and recurrence rate (RR) and recurrence-free survival (RFS) were analyzed, respectively. Dynamic change of ctDNA was monitored to predict tumor recurrence. RESULTS: Baseline mutational profiles of ctDNA were highly concordant with those of tumor tissues (median, 89.85%; range 46.2-100%) in the 74 patients. Before LT, positive ctDNA status was associated with higher RR (31.7% vs 11.5%; p = 0.001) and shorter RFS than negative ctDNA status (17.8 vs 19.4 months; p = 0.019). After LT, the percentage of ctDNA positivity decreased (17.6% vs 47.0%; p < 0.001) and patients with positive ctDNA status had higher RR (46.2% vs 21.3%; p < 0.001) and shorter RFS (17.2 vs 19.2 months; p = 0.010). Serial ctDNA profiling demonstrated patients with decreased or constant negative ctDNA status had lower RR (33.3% vs 50.0%; p = 0.015) and favorable RFS (18.2 vs 15.0 months, p = 0.003) than those with increased or constant positive ctDNA status. Serial ctDNA profiling predicted recurrence months ahead of imaging evidence and serum tumor biomarkers. CONCLUSIONS: ctDNA could effectively detect MRD and predict tumor recurrence in liver cancer patients undergone LT.

Asunto(s)

ADN Tumoral Circulante , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , ADN Tumoral Circulante/genética , Recurrencia Local de Neoplasia/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Biomarcadores de Tumor/genética

RESUMEN

Objective To study the acupoint selection and medication rules of acupoint application as an advantageous therapy in treating stroke.Methods The clinical literature from CNKI,Wanfang,CBMdisc,and other databases were searched,and Excel 2013 was used to count the frequency of disease,acupoint selection,and medication,and to analyze the acupoint selection rules using SPSS 25.0 and SPSS Modeler.Results Finally,523 articles were included in the literature,among which,the literature on the treatment of post-stroke constipation with acupoint patch was the most,and the related literature was further screened to analyze the acupoint selection and medication rules,and it was concluded that the most frequently applied acupoints of acupoint application for the treatment of post-stroke constipation were Shenque(RN8),Tianshu(ST25),Zhongwan(RN12),Zusanli(ST36),and the acupoints were mainly taken from conception vessel,stomach meridian and gallbladder meridian,and the core prescriptions were Shenque,Tianshu,Zhongwan,Qihai(RN6),Guanyuan(RN4),Zusanli.For the treatment of post-stroke constipation,acupoint application is often used with Rhei Radix et Rhizoma,Aurantii Fructus Immaturus,Cortex Magnoliae Officinalis,Natrii Sulfas Exsiccatus and Borneolum Syntheticum,among which,warm and cold nature drugs are mainly used,and bitter drugs are most frequently used among five flavors,and most frequently enter to the spleen meridian;and the core prescription is Rhei Radix et Rhizoma,Aurantii Fructus Immaturus,Cortex Magnoliae Officinalis,Natrii Sulfas Exsiccatus and Borneolum Syntheticum.Conclusion Acupoint application is an advantageous treatment for treating post-stroke constipation.The selection of acupoints was based on the conception vessel and stomach meridian,and the medication used were mainly focusing on those with functions of unblocking the bowels and directing qi downward,supplemented by strengthening the spleen and benefiting qi,warming the meridians and nourishing the blood.

RESUMEN

Objective@#To explore the impact of the sense of security on interpersonal relationships among impoverished college students, so as to provide empirical evidence for effective interpersonal communication cirsis prevention among impoverished college students.@*Methods@#In March 2023, a stratified random sampling method was used to select one university from Shanghai, Jiangsu, Henan, Anhui, Inner Mongolia, Gansu, Guangxi respatively. A total of 1 687 impoverished college students from 7 universities were surveyed using the Sense of Security Scale, Interpersonal Relationship Comprehensive Diagnosis Scale, Stress Perception Scale (SPS), and Mindfulness Attention Awareness Scale (MAAS). Moderated mediation effect analysis was performed using Model 7 in the SPSS macro program PROCESS.@*Results@#There was significant gender differences in the sense of security among impoverished college students (t=-2.31，P<0.05), and significant difference in interpersonal relationships by grade was observed (F=3.60，P<0.05). A sense of security was negatively associated with difficulties in interpersonal relationships among impoverished college students (β=-0.17, t=-9.27, P<0.01). Psychological stress partially mediates the relationship between the two, accounting for 19.54% of the total effect. Mindfulness regulates the first half of the path (β=0.10, t=5.32, P<0.01).@*Conclusions@#The sense of security shows impacts on interpersonal relationships among impoverished college students through psychological pressure. And it strengthens with the improvement of mindfulness level. Attention should be paid to cultivating a sense of security among impoverished college students, improving their level of mindfulness, and preventing interpersonal crisis due to excessive psychological pressure.