Intelligent algorithm based on deep learning to predict the dosage for anesthesia: A study on prediction of drug efficacy based on deep learning.

Background and Aims: Anesthetic drugs play a vital role during surgery, however, due to individual differences and complex physiological mechanisms, the prediction of anesthetic drug dosage has always been a challenging problem. In this study, we propose a model for predicting the dosage of anesthetic drugs based on deep learning to help anesthesiologists better control their dosage during surgical procedures. Methods: We design a model based on the artificial neural network to predict the dosage of preoperative anesthetic, and use the SELU activation function and the loss function for weighted regularization to solve the problem of unbalanced sample. Moreover, we design a CNN-based model for the prior extraction of intraoperative features by using a 7 × 1 convolution kernel to enhance the receptive field, and combine maximum pooling and average pooling to extract key features while eliminating noise. A predictive model based on the LSTM network is designed to predict the intraoperative dosage of the anesthetic, and the bidirectional propagation-based LSTM network is used to improve the ability to learn the trend of changes in the physiological states of the patient during surgery. An attention module is added before the connection layer to appropriately attend to areas containing prominent features. Results: The results of experiments showed that the proposed method reduced values of the MAPE to 15.83% and 12.25% compared with the traditional method in predictions of the preoperative and intraoperative doses of the anesthetic, respectively, and increased the values of R2 to 0.887 and 0.915, respectively. Conclusion: The intelligent anesthesia prediction algorithm designed in this study can effectively predict the dosage of anesthetic drugs needed by patients, assist clinical judgment of anesthetic drug dose, and assist the anesthesiologists to ensure the smooth progress of the operation.

Predictive value of the domain specific PLA2R antibodies for clinical remission in patients with primary membranous nephropathy: A retrospective study.

BACKGROUND: M-type phospholipase A2 receptor (PLA2R) is a major auto-antigen of primary membranous nephropathy(PMN). Anti-PLA2R antibody levels are closely associated with disease severity and therapeutic effectiveness. Analysis of PLA2R antigen epitope reactivity may have a greater predictive value for remission compared with total PLA2R-antibody level. This study aims to elucidate the relationship between domain-specific antibody levels and clinical outcomes of PMN. METHODS: This retrospective analysis included 87 patients with PLA2R-associated PMN. Among them, 40 and 47 were treated with rituximab (RTX) and cyclophosphamide (CTX) regimen, respectively. The quantitative detection of -immunoglobulin G (IgG)/-IgG4 targeting PLA2R and its epitope levels in the serum of patients with PMN were obtained through time-resolved fluorescence immunoassays and served as biomarkers in evaluating the treatment effectiveness. A predictive PMN remission possibility nomogram was developed using multivariate logistic regression analysis. Discrimination in the prediction model was assessed using the area under the receiver operating characteristic curve (AUC-ROC).Bootstrap ROC was used to evaluate the performance of the prediction model. RESULTS: After a 6-month treatment period, the remission rates of proteinuria, including complete remission and partial remission in the RTX and CTX groups, were 70% and 70.21% (P = 0.983), respectively. However, there was a significant difference in immunological remission in the PLA2R-IgG4 between the RTX and CTX groups (21.43% vs. 61.90%, P = 0.019). Furthermore, we found differences in PLA2R-CysR-IgG4(P = 0.030), PLA2R-CTLD1-IgG4(P = 0.005), PLA2R-CTLD678-IgG4(P = 0.003), and epitope spreading (P = 0.023) between responders and non-responders in the CTX group. Multivariate logistic analysis showed that higher levels of urinary protein (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.26-0.95; P = 0.035) and higher levels of PLA2R-CTLD1-IgG4 (OR, 0.79; 95%CI,0.62-0.99; P = 0.041) were independent risk factors for early remission. A multivariate model for estimating the possibility of early remission in patients with PMN is presented as a nomogram. The AUC-ROC of our model was 0.721 (95%CI, 0.601-0.840), in consistency with the results obtained with internal validation, for which the AUC-ROC was 0.711 (95%CI, 0.587-0.824), thus, demonstrating robustness. CONCLUSIONS: Cyclophosphamide can induce immunological remission earlier than rituximab at the span of 6 months. The PLA2R-CTLD1-IgG4 has a better predict value than total PLA2R-IgG for remission of proteinuria at the 6th month.

Study on Gesture Recognition Method with Two-Stream Residual Network Fusing sEMG Signals and Acceleration Signals.

Currently, surface EMG signals have a wide range of applications in human-computer interaction systems. However, selecting features for gesture recognition models based on traditional machine learning can be challenging and may not yield satisfactory results. Considering the strong nonlinear generalization ability of neural networks, this paper proposes a two-stream residual network model with an attention mechanism for gesture recognition. One branch processes surface EMG signals, while the other processes hand acceleration signals. Segmented networks are utilized to fully extract the physiological and kinematic features of the hand. To enhance the model's capacity to learn crucial information, we introduce an attention mechanism after global average pooling. This mechanism strengthens relevant features and weakens irrelevant ones. Finally, the deep features obtained from the two branches of learning are fused to further improve the accuracy of multi-gesture recognition. The experiments conducted on the NinaPro DB2 public dataset resulted in a recognition accuracy of 88.25% for 49 gestures. This demonstrates that our network model can effectively capture gesture features, enhancing accuracy and robustness across various gestures. This approach to multi-source information fusion is expected to provide more accurate and real-time commands for exoskeleton robots and myoelectric prosthetic control systems, thereby enhancing the user experience and the naturalness of robot operation.

Longitudinal association between the dynamic nature of depression with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH).

BACKGROUND: Depression is associated with an increased risk of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). Whether the dynamic nature of depression affects the incidence of LUTS/BPH remains unknown. A four-year cohort study based on the China Health and Retirement Longitudinal Study (CHARLS) was conducted to assess their association. METHODS: This study included 3433 Chinese men from the CHARLS 2011, representative of > 95 million individuals. All eligible individuals underwent three assessments of LUTS/BPH and depression in 2011, 2013 and 2015. The dynamic nature of depression was classified as acute depression with remission, acute depression with recurrence, or chronic major depression. Weighted, generalized additive analyses with three binomial models were used to investigate the relationship between LUTS/BPH and the dynamic nature of depression. RESULTS: During the four-year follow-up, 11.5% (95% confidence interval [95% CI] = 9.5-13.3%) of Chinese men were diagnosed with newly incident LUTS/BPH. Meanwhile, there were 60.6% (95% CI = 58.5-62.7%) of the individuals without depression and 8.9% (95% CI = 7.9-10%) of the individuals with chronic major depression. A total of 25.1% (95% CI = 23.4-26.9%) and 5.4% (95% CI = 4.6-6.3%) of the individuals were categorized as acute depression with remission and recurrence. After weighted, adjusted all included confounding risk factors, chronic major depression (RR = 1.63, 95% CI = 1.14-2.33, P < 0.01) but not acute depression with remission (RR = 1.2, 95% CI = 0.92-1.56, P = 0.18) and recurrence (RR = 1.32, 95% CI = 0.82-2.10, P = 0.26) significantly increased the incidence of LUTS/BPH compared with no depression. The subgroup analysis showed that the above relationships appeared to be evident among Chinese men < 60 years. CONCLUSIONS: Our results suggest that the dynamic nature of depression has a different effect on the incidence of LUTS/BPH. The monitoring and treatment of depression are important in preventing LUTS/BPH.

Flow field analysis of cigarette filter through micro-CT-based geometries and CFD simulation.

The cigarette filter is an essential component of modern cigarettes and studying the flow distribution within the cigarette filter is of great significance in reducing the harm of cigarettes and optimizing smoking sensations. As the object of numerical simulation research, a three-dimensional model of the cigarette was accurately constructed through micro-CT reverse engineering, achieving a scanning accuracy of 4.05 µm. An overall porous media model of the cigarette filter was established to characterize the pressure distribution inside the filter. Based on the three-dimensional reconstruction, a local simulation model of the cavity-filtered filter was created by extracting a 1/36 geometric model. The simulation results of the overall porous media model of the cigarette filter were used as the pressure boundary conditions for the local simulation model of the cavity-filtered filter, and the effects of the wrapped paper and cavity on the flow field were analyzed. The results show that the simulated pressure drop in the overall porous media model of the cigarette filter had a deviation of less than 3.5% compared to the experimental results. This suggests that the porous media model can effectively predict the changes in pressure drop within the filter. When both wrapped paper and cavity were present, the velocity at the interface between acetate fiber and wrapped paper increased by 141.54%, while the pressure approached 0 Pa. Similarly, at the interface between acetate fiber and cavity, the velocity increased by 130.77%. It indicates that both wrapped paper and cavity significantly influenced the flow field characteristics within the cigarette filter. Additionally, as the porosity of the wrapped paper gradually increased from 0.69 to 0.99 in the radial direction, the fluid velocity increased by 14.46%, while the fluid pressure decreased by 29.09%. These changes were particularly evident when the porosity was below 0.87.

Fully endoscopic approach for resection of brainstem cavernous malformations: a systematic review of the literature.

BACKGROUND: Brainstem cavernous malformations (BCMs) are benign lesions that typically have an acute onset and are associated with a high rate of morbidity. The selection of the optimal surgical approach is crucial for obtaining favorable outcomes, considering the different anatomical locations of various brainstem lesions. Endoscopic surgery is increasingly utilized in treating of BCMs, owing to its depth illumination and panoramic view capabilities. For intra-axial ventral BCMs, the best surgical options are endoscopic endonasal approaches, following the "two-point method. For cavernous hemangiomas on the dorsal side of the brainstem, endoscopy proves valuable by providing enhanced visualization of the operative field and minimizing the need for brain retraction. METHODS: In this review, we gathered data on the fully endoscopic approach for the resection of BCMs, and outlined technical notes and tips. Total of 15 articles were included in this review. The endoscopic endonasal approach was utilized in 19 patients, and the endoscopic transcranial approach was performed in 3 patients. RESULTS: The overall resection rate was 81.8% (18/22). Among the 19 cases of endoscopic endonasal surgery, postoperative cerebrospinal fluid (CSF) leakage occurred in 5 cases, with lesions exceeding 2 cm in diameter in 3 patients with postoperative CSF rhinorrhea. Among the 20 patients with follow-up data, 2 showed no significant improvement after surgery, whereas the remaining 18 patients showed significant improvement compared to their admission symptoms. CONCLUSIONS: This systematic literature review demonstrates that a fully endoscopic approach is a safe and effective option for the resection of BCMs. Further, it can be considered an alternative to conventional craniotomy, particularly when managed by a neurosurgical team with extensive experience in endoscopic surgery, addressing these challenging lesions.

Research progress of flexible pressure sensor based on MXene materials.

Flexible pressure sensors overcome the limitations of traditional rigid sensors on the surface of the measured object, demonstrating broad application prospects in fields such as sports health and vital sign monitoring due to their excellent flexibility and comfort in contact with the body. MXene, as a two-dimensional material, possesses excellent conductivity and abundant surface functional groups. Simultaneously, MXene's unique layered structure and large specific surface area offer a wealth of possibilities for preparing sensing elements in combination with other materials. This article reviews the preparation methods of MXene materials and their performance indicators as sensing elements, discusses the controllable preparation methods of MXene materials and the impact of their physical and chemical properties on their functions, elaborates on the pressure sensing mechanism and evaluation mechanism of MXene materials. Starting from the four specific application directions: aerogel/hydrogel, ink printing, thin film/electronic skin, and fiber fabric, we introduce the research progress of MXene flexible pressure sensors from an overall perspective. Finally, a summary and outlook for developing MXene flexible pressure sensors are provided.

Nondestructive Determination of Epicarp Hardness of Passion Fruit Using Near-Infrared Spectroscopy during Storage.

The hardness of passion fruit is a critical feature to consider when determining maturity during post-harvest storage. The capacity of near-infrared diffuse reflectance spectroscopy (NIRS) for non-destructive detection of outer and inner hardness of passion fruit epicarp was investigated in this work. The passion fruits' spectra were obtained using a near-infrared spectrometer with a wavelength range of 10,000-4000 cm-1. The hardness of passion fruit's outer epicarp (F1) and inner epicarp (F2) was then measured using a texture analyzer. Moving average (MA) and mean-centering (MC) techniques were used to preprocess the collected spectral data. Competitive adaptive reweighted sampling (CARS), successive projection algorithm (SPA), and uninformative variable elimination (UVE) were used to pick feature wavelengths. Grid-search-optimized random forest (Grids-RF) models and genetic-algorithm-optimized support vector regression (GA-SVR) models were created as part of the modeling process. After MC preprocessing and CARS selection, MC-CARS-Grids-RF model with 7 feature wavelengths had the greatest prediction ability for F1. The mean square error of prediction set (RMSEP) was 0.166 gN. Similarly, following MA preprocessing, the MA-Grids-RF model displayed the greatest predictive performance for F2, with an RMSEP of 0.101 gN. When compared to models produced using the original spectra, the R2P for models formed after preprocessing and wavelength selection improved. The findings showed that near-infrared spectroscopy may predict the hardness of passion fruit epicarp, which can be used to identify quality during post-harvest storage.

BmNPV Bm60 is a key target gene used by a resistant strain of Bombyx mori to inhibit BmNPV proliferation.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a pathogen that causes significant losses to the silkworm industry. Numerous antiviral genes and proteins have been identified by studying silkworm resistance to BmNPV. However, the molecular mechanism of silkworm resistance to BmNPV is unclear. We analyzed the differences between the susceptible strain 871 and a near-isogenic resistant strain 871C. The survival of strain 871C was significantly greater than that of 871 after oral and subcutaneous exposure to BmNPV. Strain 871C exhibited a nearly 10,000-fold higher LD50 for BmNPV compared to 871. BmNPV proliferation was significantly inhibited in all tested tissues of strain 871C using HE strain and fluorescence analysis. Strain 871C exhibited cellular resistance to BmNPV rather than peritrophic membrane or serum resistance. Strain 871C suppressed the expression of the viral early gene Bm60. This led to the inhibition of BmNPV DNA replication and late structural gene transcription based on the cascade regulation of baculovirus gene expression. Bm60 could also interact with the viral DNA binding protein and alkaline nuclease, as well as host proteins Methylcrotonoyl-CoA carboxylase subunit alpha, mucin-2-like protein, and 30 K-8. Overexpression of 30 K-8 significantly inhibited BmNPV proliferation. These results increase understanding of the molecular mechanism behind silkworm resistance to BmNPV and suggest targets for the breeding of resistant silkworm strains and the controlling pest of Lepidoptera.

APE1 inhibition enhances ferroptotic cell death and contributes to hepatocellular carcinoma therapy.

Ferroptosis, a regulated form of cell death triggered by iron-dependent lipid peroxidation, has emerged as a promising therapeutic strategy for cancer treatment, particularly in hepatocellular carcinoma (HCC). However, the mechanisms underlying the regulation of ferroptosis in HCC remain to be unclear. In this study, we have identified a novel regulatory pathway of ferroptosis involving the inhibition of Apurinic/apyrimidinic endonuclease 1 (APE1), a key enzyme with dual functions in DNA repair and redox regulation. Our findings demonstrate that inhibition of APE1 leads to the accumulation of lipid peroxidation and enhances ferroptosis in HCC. At the molecular level, the inhibition of APE1 enhances ferroptosis which relies on the redox activity of APE1 through the regulation of the NRF2/SLC7A11/GPX4 axis. We have identified that both genetic and chemical inhibition of APE1 increases AKT oxidation, resulting in an impairment of AKT phosphorylation and activation, which leads to the dephosphorylation and activation of GSK3ß, facilitating the subsequent ubiquitin-proteasome-dependent degradation of NRF2. Consequently, the downregulation of NRF2 suppresses SLC7A11 and GPX4 expression, triggering ferroptosis in HCC cells and providing a potential therapeutic approach for ferroptosis-based therapy in HCC. Overall, our study uncovers a novel role and mechanism of APE1 in the regulation of ferroptosis and highlights the potential of targeting APE1 as a promising therapeutic strategy for HCC and other cancers.

Quantitative detection and prognostic value of antibodies against M-type phospholipase A2 receptor and its cysteine-rich ricin domain and C-type lectin domains 1 and 6-7-8 in patients with idiopathic membranous nephropathy.

BACKGROUND: M-type phospholipase A2 receptor (PLA2R) is the major autoantigen in adult idiopathic membranous nephropathy (IMN). Although reactive epitopes in the PLA2R domains have been identified, the clinical value of these domains recognized by anti-PLA2R antibodies remains controversial. Accordingly, this study aimed to quantitatively detect changes in the concentrations of different antibodies against epitopes of PLA2R in patients with IMN before and after treatment to evaluate the clinical value of epitope spreading. METHODS: Highly sensitive time-resolved fluorescence immunoassay was used to quantitatively analyze the concentrations of specific IgG and IgG4 antibodies against PLA2R and its epitopes (CysR, CTLD1, CTLD6-7-8) in a cohort of 25 patients with PLA2R-associated membranous nephropathy (13 and 12 in the remission and non-remission groups, respectively) before and after treatment, and the results were analyzed in conjunction with clinical biochemical indicators. RESULTS: The concentration of specific IgG (IgG4) antibodies against PLA2R and its epitopes (CysR, CTLD1 and CTLD6-7-8) in non-remission group was higher than that in remission group. The multipliers of elevation of IgG (IgG4) antibody were 5.6(6.2) fold, 3.0(24.3) fold, 1.6(9.0) fold, and 4.2(2.6) fold in the non-remission/remission group, respectively. However, the difference in antibody concentrations between the two groups at the end of follow-up was 5.6 (85.2), 1.7 (13.1), 1.0 (5.1), and 1.5 (22.3) times higher, respectively. When detecting concentrations of specific IgG antibodies against PLA2R and its different epitopes, the remission rate was 66.67% for only one epitope at M0 and 36.36% for three epitopes at M0. When detecting concentrations of specific IgG4 antibodies against PLA2R and its different epitopes, the remission rate was 100.00% for only one epitope at M0 and 50.00% for three epitopes at M0. A trivariate logistic regression model for the combined detection of eGFR, anti-CTLD678 IgG4, and urinary protein had an AUC of 100.00%. CONCLUSION: Low concentrations of anti-CysR-IgG4, anti-CTLD1-IgG4, and anti-CTLD6-7-8-IgG4 at initial diagnosis predict rapid remission after treatment. The use of specific IgG4 against PLA2R and its different epitopes combined with eGFR and urinary protein provides a better assessment of the prognostic outcome of IMN.

MicroRNA regulation of adrenal glucocorticoid and androgen biosynthesis.

Steroid hormones are derived from a common precursor molecule, cholesterol, and regulate a wide range of physiologic function including reproduction, salt balance, maintenance of secondary sexual characteristics, response to stress, neuronal function, and various metabolic processes. Among the steroids synthesized by the adrenal and gonadal tissues, adrenal mineralocorticoids, and glucocorticoids are essential for life. The process of steroidogenesis is regulated at multiple levels largely by transcriptional, posttranscriptional, translational, and posttranslational regulation of the steroidogenic enzymes (i.e., cytochrome P450s and hydroxysteroid dehydrogenases), cellular compartmentalization of the steroidogenic enzymes, and cholesterol processing and transport proteins. In recent years, small noncoding RNAs, termed microRNAs (miRNAs) have been recognized as major post-transcriptional regulators of gene expression with essential roles in numerous biological processes and disease pathologies. Although their role in the regulation of steroidogenesis is still emerging, several recent studies have contributed significantly to our understanding of the role miRNAs play in the regulation of the steroidogenic process. This chapter focuses on the recent developments in miRNA regulation of adrenal glucocorticoid and androgen production in humans and rodents.

PLAU and GREM1 are prognostic biomarkers for predicting immune response in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a common malignant tumor. Identification of biomarkers and understanding their potential functions will facilitate the treatment and diagnosis in LUAD patients. The yellow module (cor = 0.31, P = 2e-6) was selected as the core module based on weighted gene co-expression network analysis (WGCNA) by integrating RNA-seq data and tumor stage. Two upregulated genes (PLAU and GREM1) in yellow module were identified to be biomarkers. Kaplan-Meier curve analysis displayed that high expression levels of them had a poor overall survival (OS). And, their high expression levels revealed higher tumor stage and relapse possibility in LUAD patients, and could be a prognostic parameter. Both biomarkers showed similar immune cell expression profiles in low- and high-expression groups. Strongly positive correlation between both biomarkers and biomarkers of tumor-infiltrating lymphocytes were also clarified in TCGA-LUAD cohort. Importantly, single gene GSEA showed that transcriptional mis-regulation in cancer and microRNAs in cancer were enriched in LUAD patients. Therefore, a miRNA-mRNA-transcription factors (TFs) co-expression regulatory networks was constructed for each biomarker, various miRNAs and TFs were related to PLAU and GREM1. Among which, 6 downstream TFs were overlapped genes for both biomarkers. Notably, 2 of these TFs (FOXF1 and TFAP2A) exhibited significantly abnormal expression levels. Among which, FOXF1 was downregulated and TFAP2A was upregulated in TCGA-LUAD cohort. Both TFs showed a significantly positive correlation with the expression level of PLAU. In conclusion, we identified 2 biomarkers related to immune response and achieved a good accuracy in predicting OS in patients with LUAD.

Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery.

Cepharanthine is a secondary metabolite isolated from Stephania. It has been reported that it has anti-conronaviruses activities including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we assemble three Stephania genomes (S. japonica, S. yunnanensis, and S. cepharantha), propose the cepharanthine biosynthetic pathway, and assess the antiviral potential of compounds involved in the pathway. Among the three genomes, S. japonica has a near telomere-to-telomere assembly with one remaining gap, and S. cepharantha and S. yunnanensis have chromosome-level assemblies. Following by biosynthetic gene mining and metabolomics analysis, we identify seven cepharanthine analogs that have broad-spectrum anti-coronavirus activities, including SARS-CoV-2, Guangxi pangolin-CoV (GX_P2V), swine acute diarrhoea syndrome coronavirus (SADS-CoV), and porcine epidemic diarrhea virus (PEDV). We also show that two other genera, Nelumbo and Thalictrum, can produce cepharanthine analogs, and thus have the potential for antiviral compound discovery. Results generated from this study could accelerate broad-spectrum anti-coronavirus drug discovery.

Establishment and external validation of prognosis prediction nomogram for patients with distant metastatic intrahepatic cholangiocarcinoma: based on a large population.

BACKGROUND: Most patients with intrahepatic cholangiocarcinoma (ICC) have developed distant metastasis at the time of diagnosis, while there is rear related nomogram to predict the prognosis. METHODS: Clinical data of patients pathologically diagnosed of ICC with distant metastasis were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database during 2005 to 2019. Finally, patients diagnosed as ICC in the Second Affiliated Hospital of Nanchang University from 2014 to 2019 were collected for external verification. All data were divided into training cohort and validation cohort in a ratio of 7:3. The nomogram was established based on independent prognostic factors using Cox univariate and multivariate analyses. The area under the receiver operating characteristic (ROC) curves (AUC), the calibration curve and the decision curve analysis (DCA) were used to determine the prediction accuracy of the nomogram. RESULTS: This study finally included 572 ICC with distant metastasis patients, another 32 patients collected by the author's hospital were used as external verification. Results showed that age, surgery, radiotherapy and chemotherapy were independent prognostic factors, and nomogram was established. The AUC of predicting 3, 6, 9-month overall survival were 0.866, 0.841 and 0.786. The ROC curves and calibration curves showed that the nomogram had good predictive accuracy, and DCA showed that the nomogram had good clinical applicability. CONCLUSIONS: The nomogram has good accuracy in predicting prognosis of DM-ICC patients, which would be of good significance to improve the prognosis of these patients.

Construction of an Immune-Related Prognostic Signature and lncRNA‒miRNA-mRNA ceRNA Network in Acute Myeloid Leukaemia.

The progression of acute myeloid leukaemia (AML) is influenced by the immune microenvironment in the bone marrow and dysregulated intracellular competing endogenous RNA (ceRNA) networks. Our study utilized data from UCSC Xena, Cancer Genome Atlas Program, Gene Expression Omnibus, Immunology Database and Analysis Portal. Using Cox regression analysis, we identified an immune-related prognostic signature. Genomic analysis of prognostic mRNA was conducted through Gene Set Cancer Analysis (GSCA), and a prognostic ceRNA network was constructed using the Encyclopedia of RNA Interactomes. Correlations between signature mRNAs and immune cell infiltration, checkpoints, and drug sensitivity were assessed using R software, GEPIA, and CellMiner, respectively. Adhering to the ceRNA hypothesis, we established a potential lncRNA/miRNA/mRNA regulatory axis. Our findings pinpointed nine immune-related prognostic mRNAs (KIR2DL1, CSRP1, APOBEC3G, CKLF, PLXNC1, PNOC, ANGPT1, IL1R2, and IL3RA). GSCA analysis revealed the impact of copy number variations and methylation on AML. The ceRNA network comprised 14 differentially expressed prognostic lncRNAs (DE-lncRNAs), six prognostic DE-miRNAs, and three prognostic immune-related IR-DEmRNAs. Correlation analyses linked these mRNA's expression to 22 immune cell types, six immune checkpoints, and potential sensitivity to 27 antitumor drugs. Finally, we identified a potential LINC00963/hsa-miR-431-5p/CSRP1 axis. This study offers innovative insights for AML diagnosis and treatment through a novel immune-related signature and ceRNA axis. Identified novel biomarkers, including two mRNAs (CKLF, PNOC), one miRNA (hsa-miR-323a-3p), and ten lncRNAs (SNHG25, LINC01857, AL390728.6, AC127024.5, Z83843.1, AP002884.1, AC007038.1, AC112512, AC020659.1, AC005921.3) present promising candidates as potential targets for precision medicine, contributing to the ongoing advancements in the field.

Adjuvant medial versus entire supraclavicular lymph node irradiation in high-risk early breast cancer (SUCLANODE): a protocol for a multicenter, randomized, open-label, phase 3 trial.

BACKGROUND: Supraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes. Consequently, many radiation oncologists advocate for enlarging the SCL irradiation target volume to include both the medial and posterolateral SCL regions. Nevertheless, it remains uncertain whether adding the posterolateral SCL irradiation improves survival outcomes for high-risk breast cancer patients. METHODS: The SUCLANODE trial is an open-label, multicenter, randomized, phase 3 trial comparing the efficacy and adverse events of medial SCL irradiation (M-SCLI group) and medial plus posterolateral SCL irradiation (entire SCL irradiation, E-SCLI group) in high-risk breast cancer patients who underwent breast conserving-surgery or mastectomy. Patients with pathological N2-3b disease following initial surgery, or clinical stage III or pathological N1-3b if receiving neoadjuvant systemic therapy, are eligible and randomly assigned (1:1) to M-SCLI group and E-SCLI group. Stratification is by chemotherapy sequence (neoadjuvant vs. adjuvant), T stage (T3-4 vs. T1-2), N stage (N1-2 vs. N3), and ER status (positive vs. negative). Other radiation volumes are identical in the two arms, including breast/chest wall, undissected axillary lymph node, and internal mammary node. Advanced intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), or tomotherapy techniques are recommended. Both hypofractionated and conventional fractionation schedules are permitted. The primary end point is invasive disease-free survival, and secondary end points included overall survival, SCL recurrence, local-regional recurrence, distance recurrence, safety outcome, and patient-reported outcomes. The target sample size is 1650 participants. DISCUSSION: The results of the SUCLANODE trial will provide high-level evidence regarding whether adding posterolateral SCL irradiation to medial SCL target volume provides survival benefit in patients with high-risk breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05059379. Registered 28 September 2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT05059379 .

Preparation of PEG/P(U-AM-ChCl) composite hydrogels using ternary DES light polymerization and their properties.

Deep eutectic solvents (DES) were prepared using urea (U) and acrylamide (AM) as hydrogen bond donors (HBD) and choline chloride (ChCl) as hydrogen bond acceptor (HBA), and polyethylene glycol (PEG) was selected as a filler and uniformly dispersed in DES to prepare PEG/P(U-AM-ChCl) composite hydrogels by light polymerization. The composite hydrogels were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The effects of the content of PEG on the swelling properties, mechanical properties and fatigue resistance of the composite hydrogels were investigated. The results showed that the compressive strength and fatigue strength of the composite hydrogels were gradually enhanced with the increase of the PEG content in the composite hydrogels, in which the maximum compressive strength of the hydrogels with 1 wt% PEG added was increased by 1.86 times. The composite hydrogel had excellent swelling properties, and the equilibrium swelling degree of the hydrogel with 1 wt% PEG added reached 10.15. Meanwhile, the PEG/P(U-AM-ChCl) composite hydrogel had excellent self-healing properties, and the self-healing rate of the composite hydrogel with a PFG content of 1 wt% could reach 91.93% after 48 hours of healing. This study provides a convenient and efficient method to prepare composite hydrogels with superior swelling properties and self-healing properties.

Crosstalk among mitophagy, pyroptosis, ferroptosis, and necroptosis in central nervous system injuries.

Central nervous system injuries have a high rate of resulting in disability and mortality; however, at present, effective treatments are lacking. Programmed cell death, which is a genetically determined form of active and ordered cell death with many types, has recently attracted increasing attention due to its functions in determining the fate of cell survival. A growing number of studies have suggested that programmed cell death is involved in central nervous system injuries and plays an important role in the progression of brain damage. In this review, we provide an overview of the role of programmed cell death in central nervous system injuries, including the pathways involved in mitophagy, pyroptosis, ferroptosis, and necroptosis, and the underlying mechanisms by which mitophagy regulates pyroptosis, ferroptosis, and necroptosis. We also discuss the new direction of therapeutic strategies targeting mitophagy for the treatment of central nervous system injuries, with the aim to determine the connection between programmed cell death and central nervous system injuries and to identify new therapies to modulate programmed cell death following central nervous system injury. In conclusion, based on these properties and effects, interventions targeting programmed cell death could be developed as potential therapeutic agents for central nervous system injury patients.