Nomogram based on liver stiffness and spleen area with ultrasound for posthepatectomy liver failure: A multicenter study.

BACKGROUND: Liver stiffness (LS) measurement with two-dimensional shear wave elastography (2D-SWE) correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve. The size of the spleen increases due to tissue proliferation, fibrosis, and portal vein congestion, which can indirectly reflect the situation of liver fibrosis/cirrhosis. It was reported that the size of the spleen was related to posthepatectomy liver failure (PHLF). So far, there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF. This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area (SPA) for the prediction of PHLF in hepatocellular carcinoma (HCC) patients and to develop a risk prediction model. AIM: To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model. METHODS: This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022. Within 1 wk before partial hepatectomy, ultrasound examination was performed to measure LS and SPA, and blood was drawn to evaluate the patient's liver function and other conditions. Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram. Nomogram performance was validated further. The diagnostic performance of the nomogram was evaluated with receiver operating characteristic curve compared with the conventional models, including the model for end-stage liver disease (MELD) score and the albumin-bilirubin (ALBI) score. RESULTS: A total of 562 HCC patients undergoing hepatectomy (500 in the training cohort and 62 in the validation cohort) were enrolled in this study. The independent predictors of PHLF were LS, SPA, range of resection, blood loss, international normalized ratio, and total bilirubin. Better diagnostic performance of the nomogram was obtained in the training [area under receiver operating characteristic curve (AUC): 0.833; 95% confidence interval (95%CI): 0.792-0.873; sensitivity: 83.1%; specificity: 73.5%] and validation (AUC: 0.802; 95%CI: 0.684-0.920; sensitivity: 95.5%; specificity: 52.5%) cohorts compared with the MELD score and the ALBI score. CONCLUSION: This PHLF nomogram, mainly based on LS by 2D-SWE and SPA, was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.

ExpOmics: a comprehensive web platform empowering biologists with robust multi-omics data analysis capabilities.

MOTIVATION: High-throughput technologies yield a broad spectrum of multi-omics datasets, which offer unparalleled insights into complex biological systems. However, effectively analyzing this diverse array of data presents challenges, considering factors such as species diversity, data types, costs, and limitations of the available tools. RESULTS: Herein, we present ExpOmics, a comprehensive web platform featuring seven applications and four toolkits, with 28 customizable analysis functions spanning various analyses of differential expression, co-expression, Weighted Gene Co-expression Network Analysis (WGCNA), feature selection, and functional enrichment. ExpOmics allows users to upload and explore multi-omics data without organism restrictions, supporting various expression data, including genes, mRNAs, lncRNAs, miRNAs, circRNAs, piRNAs, and proteins and is compatible with diverse gene nomenclatures and expression values. Moreover, ExpOmics enables users to analyze 22,427 transcriptomic datasets of 196 cancer subtypes sourced from 63 projects of The Cancer Genome Atlas Program (TCGA) to identify cancer biomarkers. The analysis results from ExpOmics are presented in high-quality graphical formats suitable for publication and are available for free download. A case study using ExpOmics identified two potential oncogenes, SERPINE1 and SLC43A1, that may regulate colorectal cancer through distinct biological processes. In summary, ExpOmics can serves as a robust platform for global researchers to explore multi-omics data, gain biological insights, and formulate testable hypotheses. AVAILABILITY AND IMPLEMENTATION: ExpOmics is available at http://www.biomedical-web.com/expomics. CONTACT: zhangwl25@mail3.sysu.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Predicting bone metastasis-free survival in non-small cell lung cancer from preoperative CT via deep learning.

Accurate prediction of bone metastasis-free survival (BMFS) after complete surgical resection in patients with non-small cell lung cancer (NSCLC) may facilitate appropriate follow-up planning. The aim of this study was to establish and validate a preoperative CT-based deep learning (DL) signature to predict BMFS in NSCLC patients. We performed a retrospective analysis of 1547 NSCLC patients who underwent complete surgical resection, followed by at least 36 months of monitoring at two hospitals. We constructed a DL signature from multiparametric CT images using 3D convolutional neural networks, and we integrated this signature with clinical-imaging factors to establish a deep learning clinical-imaging signature (DLCS). We evaluated performance using Harrell's concordance index (C-index) and the time-dependent receiver operating characteristic. We also assessed the risk of bone metastasis (BM) in NSCLC patients at different clinical stages using DLCS. The DL signature successfully predicted BM, with C-indexes of 0.799 and 0.818 for the validation cohorts. DLCS outperformed the DL signature with corresponding C-indexes of 0.806 and 0.834. Ranges for area under the curve at 1, 2, and 3 years were 0.820-0.865 for internal and 0.860-0.884 for external validation cohorts. Furthermore, DLCS successfully stratified patients with different clinical stages of NSCLC as high- and low-risk groups for BM (p < 0.05). CT-based DL can predict BMFS in NSCLC patients undergoing complete surgical resection, and may assist in the assessment of BM risk for patients at different clinical stages.

Chromone-deferiprone hybrids as novel MAO-B inhibitors and iron chelators for the treatment of Alzheimer's disease.

A series of chromone-deferiprone hybrids were designed, synthesized, and evaluated as inhibitors of human monoamine oxidase B (hMAO-B) with iron-chelating activity for the treatment of Alzheimer's disease (AD). The majority exhibited moderate inhibitory activity towards hMAO-B and potent iron-chelating properties. Particularly, compound 25c demonstrated remarkable selectivity against hMAO-B with an IC50 value of 1.58 µM and potent iron-chelating ability (pFe3+ = 18.79) comparable to that of deferiprone (pFe3+ = 17.90). Molecular modeling and kinetic studies showed that 25c functions as a non-competitive hMAO-B inhibitor. According to the predicted results, compound 25c can penetrate the blood-brain barrier (BBB). Additionally, it has been proved to display significant antioxidant activity and the ability to inhibit neuronal ferroptosis. More importantly, compound 25c reduced the cognitive impairment induced by scopolamine and showed significant non-toxicity in short-term toxicity assays. In summary, compound 25c was identified as a potential anti-AD agent with hMAO-B inhibitory, iron-chelating and anti-ferroptosis activities.

Iron Nanostructure Primes Arbuscular Mycorrhizal Fungi Symbiosis Tightly Connecting Maize Leaf Photosynthesis via a Nanofilm Effect.

It is crucial to clarify how the iron nanostructure activates plant growth, particularly in combination with arbuscular mycorrhizal fungi (AMF). We first identified 1.0 g·kg-1 of nanoscale zerovalent iron (nZVI) as appropriate dosage to maximize maize growth by 12.7-19.7% in non-AMF and 18.9-26.4% in AMF, respectively. Yet, excessive nZVI at 2.0 g·kg-1 exerted inhibitory effects while FeSO4 showed slight effects (p > 0.05). Under an appropriate dose, a nano core-shell structure was formed and the transfer and diffusion of electrons between PS II and PS I were facilitated, significantly promoting the reduction of ferricyanide and NADP (p < 0.05). SEM images showed that excessive nZVI particles can form stacked layers on the surface of roots and hyphae, inhibiting water and nutrient uptake. TEM observations showed that excessive nanoparticles can penetrate into root cortical cells, disrupt cellular homeostasis, and substantially elevate Fe content in roots (p < 0.05). This exacerbated membrane lipid peroxidation and osmotic regulation, accordingly restricting photosynthetic capacity and AMF colonization. Yet, appropriate nZVI can be adhered to a mycelium surface, forming a uniform nanofilm structure. The strength of the mycelium network was evidently enhanced, under an increased root colonization rate and an extramatrical hyphal length (p < 0.05). Enhanced mycorrhizal infection was tightly associated with higher gas exchange and Rubisco and Rubisco enzyme activities. This enabled more photosynthetic carbon to input into AMF symbiont. There existed a positive feedback loop connecting downward transfer of photosynthate and upward transport of water/nutrients. FeSO4 only slightly affected mycorrhizal development. Thus, it was the Fe nanostructure but not its inorganic salt state that primed AMF symbionts for better growth.

Diving technique of cochlear implant electrode insertion for hearing preservation: how I do it.

BACKGROUND: Preservation of intracochlear structures and residual hearing has become a major concern in modern cochlear implant. Consequently, many efforts have been made to minimize intraoperative trauma, especially while cochlear fenestration and electrode insertion. METHODS: Building on the core concept of "soft surgery", a modified approach, described as diving technique for cochlear implant electrode array insertion is proposed. Steps and technical points are presented with figures, video and review of relevant anatomy. CONCLUSIONS: This novel diving technique is operationally feasible and safe, promising to minimize intraoperative invasion and thus preserve residual hearing in cochlear implant.

[Huaier triggering mitochondria apoptosis in colorectal cancer cells through oxidative stress].

This study investigates the specific mechanisms of Huaier-induced mitochondrial apoptosis in colorectal cancer. HCT116 and SW480 cells were subjected to Huaier treatment. Cell proliferation and migration capabilities were examined through CCK-8 and scratch experiments, respectively. Apoptotic cells were clarified with Annexin-PE staining. DCFH-DA staining, malondialdehyde(MDA), and glutathione(GSH) were used to evaluate the oxidative stress damage level of cells. MitoSOX and JC-1 probes were used to selectively target mitochondria reactive oxygen species(mtROS) and mitochondria membrane potential(MMP) for the evaluation of mitochondria damage. Western blot(WB) experiment was performed to determine apoptosis proteins and PINK1/Parkin pathway. Experiments reveal that in different concentrations of Huaier treatment, the proliferation and migration capabilities of HCT116 and SW480 cells were both restrained. Additionally, mitochondrial apoptosis was activated. Compared with the control group, excessive ROS in colorectal cancer cells was generated in the Huaier group, while MDA increased, and GSH decreased, indicating oxidative stress damage. mtROS increased, and MMP decreased in colorectal cancer cells treated with Huaier, indicating mitochondrial damage. WB result revealed that Huaier suppressed the PINK1/Parkin pathway, hindered the clearance of impaired mitochondria, and subsequently facilitated apoptosis. In conclusion, Huaier impairs colorectal cancer cells through oxidative stress and mitochondria damage. Furthermore, it suppressed the PINK1/Parkin pathway, promoting mitochondria apoptosis in colorectal cancer cells.

[Effect of CD8+ CD28- T Cells on Acute Graft-Versus-Host Disease after Haploidentical Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the effect of CD8+ CD28- T cells on acute graft-versus-host disease(aGVHD) after haploidentical hematopoietic stem cell transplantation(haplo-HSCT). METHODS: The relationship between absolute count of CD8+ CD28- T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT, and the differences in the incidence rate of chronic graft-versus host disease(cGVHD), infection and prognosis between different CD8+ CD28- T absolute cells count groups were compared. RESULTS: aGVHD occurred in 40 of 60 patients after haplo-HSCT, with an incidence rate of 66.67%. The median occurrence time of aGVHD was 32.5(20-100) days. At 30 days after the transplantation, the absolute count of CD8+ CD28- T cells of aGVHD group was significantly lower than that of non-aGVHD group (P =0.03). Thus the absolute count of CD8+ CD28- T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent. At 30 days after transplantation, the incidence rate of aGVHD in the low cell count group (CD8+ CD28- T cells absolute count < 0.06/µl) was significantly higher than that in the high cell count group (CD8+ CD28- T cells absolute count ≥0.06/µl,P =0.011). Multivariate Cox regression analysis further confirmed that the absolute count of CD8+ CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD, and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group (P =0.015). The incidence of cGVHD, fungal infection, EBV infection and CMV infection were not significantly different between the two groups with different CD8+ CD28- T cells absolute count. The overall survival, non-recurrent mortality and relapse rates were not significantly different between different CD8+ CD28- T cells absolute count groups. CONCLUSION: Patients with delayed CD8+ CD28- T cells reconstitution after haplo-HSCT are more likely to develop aGVHD, and the absolute count of CD8+ CD28- T cells can be used to predict the incidence of aGVHD to some extent. The absolute count of CD8+ CD28- T cells after haplo-HSCT was not associated with cGVHD, fungal infection, EBV infection, and CMV infection, and was also not significantly associated with the prognosis after transplantation.

Gasdermin D Inhibitor Necrosulfonamide Alleviates Angiotensin II-Induced Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice.

Abdominal aortic aneurysm (AAA) is a chronic aortic disease that lacks effective pharmacological therapies. This study was performed to determine the influence of treatment with the gasdermin D inhibitor necrosulfonamide on experimental AAAs. AAAs were induced in male apolipoprotein E-deficient mice by subcutaneous angiotensin II infusion (1000 ng/kg body weight/min), with daily administration of necrosulfonamide (5 mg/kg body weight) or vehicle starting 3 days prior to angiotensin II infusion for 30 days. Necrosulfonamide treatment remarkably suppressed AAA enlargement, as indicated by reduced suprarenal maximal external diameter and surface area, and lowered the incidence and reduced the severity of experimental AAAs. Histologically, necrosulfonamide treatment attenuated medial elastin breaks, smooth muscle cell depletion, and aortic wall collagen deposition. Macrophages, CD4+ T cells, CD8+ T cells, and neovessels were reduced in the aneurysmal aortas of necrosulfonamide- as compared to vehicle-treated angiotensin II-infused mice. Atherosclerosis and intimal macrophages were also substantially reduced in suprarenal aortas from angiotensin II-infused mice following necrosulfonamide treatment. Additionally, the levels of serum interleukin-1ß and interleukin-18 were significantly lower in necrosulfonamide- than in vehicle-treated mice without affecting body weight gain, lipid levels, or blood pressure. Our findings indicate that necrosulfonamide reduced experimental AAAs by preserving aortic structural integrity as well as reducing mural leukocyte accumulation, neovessel formation, and systemic levels of interleukin-1ß and interleukin-18. Thus, pharmacologically inhibiting gasdermin D activity may lead to the establishment of nonsurgical therapies for clinical AAA disease.

Fangchinoline inhibits mouse oocyte meiosis by disturbing MPF activity.

Fangchinoline (FA) is an alkaloid derived from the traditional Chinese medicine Fangji. Numerous studies have shown that FA has a toxic effect on various cancer cells, but little is known about its toxic effects on germ cells, especially oocytes. In this study, we investigated the effects of FA on mouse oocyte maturation and its potential mechanisms. Our results showed that FA did not affect meiosis resumption but inhibited the first polar body extrusion. This inhibition is not due to abnormalities at the organelle level, such as chromosomes and mitochondrial, which was proved by detection of DNA damage and reactive oxygen species. Further studies revealed that FA arrested the oocyte at the metaphase I stage, and this arrest was not caused by abnormal kinetochore-microtubule attachment or spindle assembly checkpoint activation. Instead, FA inhibits the activity of anaphase-promoting complexes (APC/C), as evidenced by the inhibition of CCNB1 degeneration. The decreased activity of APC/C may be due to a reduction in CDC25B activity as indicated by the high phosphorylation level of CDC25B (Ser323). This may further enhance Maturation-Promoting Factor (MPF) activity, which plays a critical role in meiosis. In conclusion, our study suggests that the metaphase I arrest caused by FA may be due to abnormalities in MPF and APC/C activity.

The Effect of One Year Aneurysm Sac Dynamics on Five Year Mortality and Continued Aneurysm Sac Evolution.

OBJECTIVE: One year aneurysm sac dynamics after endovascular abdominal aortic aneurysm repair (EVAR) were independently associated with a greater all cause mortality risk in prior registry studies but were limited in completeness and granularity. This retrospective analysis aimed to study the impact of sac dynamics on survival within the Endurant Stent Graft Global Registry (ENGAGE) with five year follow up. METHODS: A total of 1 263 subjects were enrolled in the ENGAGE Registry between March 2009 and April 2011. One year aneurysm sac changes were calculated between the one month post-operative imaging scans and the scan closest to the time of one year follow up. Sac regression was defined as a sac decrease of ≥ 5 mm and sac expansion as aneurysm sac growth ≥ 5 mm. The primary outcome was the five year all cause mortality rate. Kaplan-Meier estimates for freedom from all cause death were calculated. Multivariable Cox regression was used to determine the association between sac dynamics and all cause death. RESULTS: At one year, 441 of the 949 study participants with appropriate imaging (46%) had abdominal aortic aneurysm sac regression, 462 (49%) remained stable, and 46 (4.8%) had sac expansion. For patients with sac regression, the five year all cause mortality rate was 20%, compared with 28% for stable sac (p = .007) and 37% for the sac expansion (p = .010) cohorts. After adjustment, the sac expansion and stable sac cohorts were associated with a greater all cause mortality rate (expansion: hazard ratio [HR] 1.8; 95% CI 1.1 - 3.2; p = .032; stable: HR 1.4; 95% CI 1.1 - 1.9; p = .019). CONCLUSION: In the ENGAGE Global Registry, the one year rate of sac regression was 46%, and one year sac regression was observed to be associated with greater five year survival, corroborating prior findings using data from vascular registries. Sac regression could become the new standard for success after EVAR.

Parallel CNN-Deep Learning Clinical-Imaging Signature for Assessing Pathologic Grade and Prognosis of Soft Tissue Sarcoma Patients.

BACKGROUND: Traditional biopsies pose risks and may not accurately reflect soft tissue sarcoma (STS) heterogeneity. MRI provides a noninvasive, comprehensive alternative. PURPOSE: To assess the diagnostic accuracy of histological grading and prognosis in STS patients when integrating clinical-imaging parameters with deep learning (DL) features from preoperative MR images. STUDY TYPE: Retrospective/prospective. POPULATION: 354 pathologically confirmed STS patients (226 low-grade, 128 high-grade) from three hospitals and the Cancer Imaging Archive (TCIA), divided into training (n = 185), external test (n = 125), and TCIA cohorts (n = 44). 12 patients (6 low-grade, 6 high-grade) were enrolled into prospective validation cohort. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/Unenhanced T1-weighted and fat-suppressed-T2-weighted. ASSESSMENT: DL features were extracted from MR images using a parallel ResNet-18 model to construct DL signature. Clinical-imaging characteristics included age, gender, tumor-node-metastasis stage and MRI semantic features (depth, number, heterogeneity at T1WI/FS-T2WI, necrosis, and peritumoral edema). Logistic regression analysis identified significant risk factors for the clinical model. A DL clinical-imaging signature (DLCS) was constructed by incorporating DL signature with risk factors, evaluated for risk stratification, and assessed for progression-free survival (PFS) in retrospective cohorts, with an average follow-up of 23 ± 22 months. STATISTICAL TESTS: Logistic regression, Cox regression, Kaplan-Meier curves, log-rank test, area under the receiver operating characteristic curve (AUC)，and decision curve analysis. A P-value <0.05 was considered significant. RESULTS: The AUC values for DLCS in the external test, TCIA, and prospective test cohorts (0.834, 0.838, 0.819) were superior to clinical model (0.662, 0.685, 0.694). Decision curve analysis showed that the DLCS model provided greater clinical net benefit over the DL and clinical models. Also, the DLCS model was able to risk-stratify patients and assess PFS. DATA CONCLUSION: The DLCS exhibited strong capabilities in histological grading and prognosis assessment for STS patients, and may have potential to aid in the formulation of personalized treatment plans. TECHNICAL EFFICACY: Stage 2.

Analysis of tumor microenvironment alterations in partially responsive rectal cancer patients treated with neoadjuvant chemoradiotherapy.

PURPOSE: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. METHODS: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. RESULTS: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and ß-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). CONCLUSIONS: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.

Effective treatment of corticosteroid-induced facial erythema using fractional radiofrequency microneedling.

OBJECTIVES: To investigate the efficacy of Fractional Radiofrequency Microneedling (FRM) in treating corticosteroid-induced facial erythema. METHODS: A retrospective study was conducted involving eight patients diagnosed as corticosteroid-induced facial erythema. Each patient underwent a single session of FRM. Evaluative measures included Clinician's Erythema Assessment (CEA), Patient's Self-Assessment (PSA), assessment of telangiectasia severity, procedure-associated pain (10-point scale), patient satisfaction (3-point scale) and secondary outcomes. RESULTS: The study found a 75% success rate and 100% effectiveness rate in alleviating erythema symptoms. CEA and PSA scores decreased by 67.7% and 78.1%, respectively. No cases of erythema rebound were recorded during the 3-month follow-up period. CONCLUSIONS: FRM demonstrated effectiveness and safety in treating facial erythema, offering promising advancement in dermatologic therapeutics.

CT-based radiomics and clinical characteristics for predicting bone metastasis in lung adenocarcinoma patients.

Background: The occurrence of bone metastasis (BM) will seriously shorten the survival time of lung adenocarcinoma patients and aggravate the suffering of patients. Computed tomography (CT)-based clinical radiomics nomogram may help clinicians stratify the risk of BM in lung adenocarcinoma patients, thereby enabling personalized individualized clinical decision making. Methods: A total of 501 patients with lung adenocarcinoma from March 2017 to March 2019 were enrolled in the study. Based on plain chest CT images, 1130 radiomics features were extracted from each lesion. One-way analysis of variance (ANOVA) and least absolute shrinkage selection operator (LASSO) algorithm were used for radiomics features selection. Univariate and multivariate analyses were used to screen for clinical characteristics and identify independent predictors of BM. Three models (radiomics model, clinical model and combined model) were constructed to predict BM in lung adenocarcinoma patients. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the performance of the three models. The DeLong test was used to compare the performance of the models. Results: Finally, the clinical model for predicting BM in lung adenocarcinoma patients was constructed based on 5 independent predictors: cytokeratin 19-fragments (CYFRA21-1), stage, Ki-67, edge, and lobulation. The radiomics model was constructed based on 5 radiomics features. The combined model incorporating clinical independent predictors and radiomics was constructed. In the validation cohort, the area under the curve (AUC) of the clinical model, radiomics model and combined model was 0.824, 0.842 and 0.866, respectively. Delong test showed that in the training cohort, the AUC values of the radiomics model and the combined model were statistically different (P=0.03), and the AUC values of the other models were not statistically different. DCA showed that the nomogram had a highest net clinical benefit. Conclusions: The CT-based clinical radiomics nomogram can be used as a non-invasive and quantitative method to help clinicians stratify the risk of BM in patients with lung adenocarcinoma, thereby enabling personalized clinical decision making.

Impact of homocysteine on acute ischemic stroke severity: possible role of aminothiols redox status.

BACKGROUND: Acute ischemic stroke (AIS) is one of the most common cerebrovascular diseases which accompanied by a disruption of aminothiols homeostasis. To explore the relationship of aminothiols with neurologic impairment severity, we investigated four aminothiols, homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CG) and glutathione (GSH) in plasma and its influence on ischemic stroke severity in AIS patients. METHODS: A total of 150 clinical samples from AIS patients were selected for our study. The concentrations of free reduced Hcy (Hcy), own oxidized Hcy (HHcy), free reduced Cys (Cys), own oxidized Cys (cysteine, Cyss), free reduced CG (CG) and free reduced GSH (GSH) were measured by our previously developed hollow fiber centrifugal ultrafiltration (HFCF-UF) method coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The concentration ratio of Hcy to HHcy (Hcy/HHcy), Cys to Cyss (Cys/Cyss) were also calculated. The neurologic impairment severity of AIS was evaluated using National Institutes of Health Stroke Scale (NIHSS). The Spearman correlation coefficient and logistic regression analysis was used to estimate and perform the correlation between Hcy, HHcy, Cys, Cyss, CG, GSH, Hcy/HHcy, Cys/Cyss and total Hcy with NIHSS score. RESULTS: The reduced Hcy and Hcy/HHcy was both negatively correlated with NIHSS score in AIS patients with P = 0.008, r=-0.215 and P = 0.002, r=-0.249, respectively. There was no significant correlation of Cys, CG, GSH, HHcy, Cyss, Cys/Cyss and total Hcy with NIHSS score in AIS patients with P value > 0.05. CONCLUSIONS: The reduced Hcy and Hcy/HHcy, not total Hcy concentration should be used to evaluate neurologic impairment severity of AIS patient.

Elevated Na is a dynamic and reversible modulator of mitochondrial metabolism in the heart.

Elevated intracellular sodium Nai adversely affects mitochondrial metabolism and is a common feature of heart failure. The reversibility of acute Na induced metabolic changes is evaluated in Langendorff perfused rat hearts using the Na/K ATPase inhibitor ouabain and the myosin-uncoupler para-aminoblebbistatin to maintain constant energetic demand. Elevated Nai decreases Gibb's free energy of ATP hydrolysis, increases the TCA cycle intermediates succinate and fumarate, decreases ETC activity at Complexes I, II and III, and causes a redox shift of CoQ to CoQH2, which are all reversed on lowering Nai to baseline levels. Pseudo hypoxia and stabilization of HIF-1α is observed despite normal tissue oxygenation. Inhibition of mitochondrial Na/Ca-exchange with CGP-37517 or treatment with the mitochondrial ROS scavenger MitoQ prevents the metabolic alterations during Nai elevation. Elevated Nai plays a reversible role in the metabolic and functional changes and is a novel therapeutic target to correct metabolic dysfunction in heart failure.

The effect of autophagy on hemoporfin-mediated photodynamic therapy in human umbilical vein endothelial cells.

SIGNIFICANCE: Hemoporfin-mediated photodynamic therapy (HMME-PDT) has been recognized as a safe and effective treatment for port wine stain (PWS). However, some patients show limited improvement even after multiple treatments. Herein, we aim to explore the effect of autophagy on HMME-PDT in human umbilical vein endothelial cells (HUVECs), so as to provide theoretical basis and treatment strategies to enhance clinical effectiveness. METHODS: Establish the in vitro HMME-PDT system by HUVECs. Apoptosis and necrosis were identified by Annexin Ⅴ-FITC/PI flow cytometry, and autophagy flux was detected by monitoring RFP-GFP-LC3 under the fluorescence microscope. Hydroxychloroquine and rapamycin were employed in the mechanism study. Specifically, the certain genes and proteins were qualified by qPCR and Western Blot, respectively. The cytotoxicity was measured by CCK-8, VEGF-A secretion was determined by ELISA, and the tube formation of HUVECs was observed by angiogenesis assay. RESULTS: In vitro experiments revealed that autophagy and apoptosis coexisted in HUVECs treated by HMME-PDT. Apoptosis was dominant in early stage, while autophagy gradually increased in the middle and late stage. AMPK, AKT and mTOR participated in the regulation of autophagy induced by HMME-PDT, in which AMPK was positive regulation, while AKT and mTOR were negative regulation. Hydroxychloroquine could not inhibit HMME-PDT-induced autophagy, but capable of blocking the fusion of autophagosomes with lysosome. Rapamycin might cooperate with HMME-PDT to enhance autophagy in HUVECs, leading to increased cytotoxicity, reduced VEGF-A secretion, and weakened angiogenesis ability. CONCLUSIONS: Both autophagy and apoptosis contribute to HMME-PDT-induced HUVECs death. Pretreatment of HUVECs with rapamycin to induce autophagy might enhance the photodynamic killing effect of HMME-PDT on HUVECs. The combination of Rapamycin and HMME-PDT is expected to further improve the clinical efficacy.

Family resilience and vulnerability of patients at diagnosis of lung cancer: A qualitative study.

AIM: To explore and analyse the adaptation process of patients and their families at the point of lung cancer diagnosis. METHODS: Totally 23 operable lung cancer patients were included in this study. Colaizzi's method of phenomenology was employed for data analysis. RESULTS: This study found two different aspects of family adaptation at the diagnosis of lung cancer. For family resilience, three themes emerged: (1) Positive family belief systems (giving meaning to a cancer diagnosis and maintaining a positive/optimistic attitude), (2) Flexible family organizational patterns (maintaining the stability of family structure and function, adjusting the relationship between patients and family members and receiving external support and help) and (3) Good communication and problem-solving strategies (open communication on an equal basis, positive and open expression of emotions and collaborative problem-solving). For family vulnerability, three themes were as follows: (1) Negative family belief systems (negative attitudes and concealment and self-isolation due to stigma), (2) Rigid family organizational patterns (adaptation lost, conflicts between family support and patients' willingness and pressure upon social support) and (3) Unhealthy communication and problem-solving (poor communication, emotional asymmetry of family members and tendency to solve problems alone). CONCLUSION: The study highlights the existence of the family resilience and family vulnerability at the point of lung cancer diagnosis and provides patient's perspective for understanding family resilience in specific cultural contexts. PATIENT CONTRIBUTION: The data were collected through face-to-face interviews. TRAIL REGISTRATION NUMBER: ChiCTR2300074801.

Rehabilitation exercises for kidney transplant recipients in an organ transplant ward: a best practice implementation project.

INTRODUCTION AND OBJECTIVES: Kidney transplantation is an effective treatment for end-stage kidney disease. Kidney transplant recipients (KTRs) are prone to experiencing reduced physical function, depression, fatigue, and lack of exercise motivation due to their sedentary lifestyle before surgery. Exercise is an effective intervention for KTRs, but it has not been properly implemented in many practice settings. This project aimed to promote evidence-based exercises as part of KTRs' rehabilitation to improve their health outcomes. METHODS: This project was informed by the JBI Evidence Implementation Framework. The project was conducted in the organ transplant ward of a tertiary comprehensive hospital in Changsha, China. Based on a summary of best evidence, 12 audit criteria were developed for the baseline and follow-up audits involving 30 patients and 20 nursing staff. The JBI Practical Application of Clinical Evidence System (PACES) and Getting Research into Practice (GRiP) tool were used to identify barriers and facilitators and develop targeted strategies to improve issues. RESULTS: Compared with the baseline audit, significant improvements were achieved in most of the criteria in the follow-up audit, with 9 of the 12 criteria reaching 100% compliance. Notably, the 6-minute walk distance test results were significantly higher, while the Self-Rating Depression Scale and Self-Rating Anxiety Scale scores were significantly lower ( p < 0.05). CONCLUSIONS: This project demonstrates that evidence-based practice can improve the clinical practice of rehabilitation exercises for KTRs. The GRiP strategies proved to be extremely useful, notably, the formulation of a standardized rehabilitation exercise protocol, training, and enhancement of the exercising environment. Head nurses' leadership and decision-making also played an important role in the success of this project. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A180.