Chronic infections caused by the pathogenic biofilms on implantable medical devices pose an increasing challenge. To combat long-term biofilm-associated infections, we developed a novel dual-functional polymer coating with antibacterial and antifouling properties. The coating consists of N-vinylpyrrolidone (NVP) and 3-(acrylamido)phenylboronic acid (APBA) copolymer brushes, which bind to curcumin (Cur) as antibacterial molecules through acid-responsive boronate ester bonds. In this surface design, the hydrophilic poly (N-vinylpyrrolidone) (PVP) component improved antifouling performance and effectively prevented bacterial adhesion and aggregation during the initial phases. The poly (3-(acrylamido) phenylboronic acid) (PAPBA, abbreviated PB) component provided binding sites for Cur by forming acid-responsive boronate ester bonds. When fewer bacteria overcame the anti-adhesion barrier and colonized, the surface responded to the decreased microenvironmental pH by breaking the boronate ester bonds and releasing curcumin. This responsive mechanism enabled Cur to interfere with biofilm formation and provide a multilayer anti-biofilm protection system. The coating showed excellent antibacterial properties against Escherichia coli and Staphylococcus aureus, preventing biofilm formation for up to 7 days. The coating also inhibited protein adsorption and platelet adhesion significantly. This coating also exhibited high biocompatibility with animal erythrocytes and pre-osteoblasts. This research offers a promising approach for developing novel smart anti-biofilm coating materials.
PURPOSE: In this work, we proposed a deep-learning segmentation algorithm for cardiac magnetic resonance imaging (MRI) to aid in contouring of the left ventricle (LV), right ventricle (RV), and Myocardium (Myo). Methods: We proposed a shifted window multilayer perceptron (Swin-MLP) mixer network which is built upon a 3D U-shaped symmetric encoder-decoder structure. We evaluated our proposed network using public data from 100 individuals. The network performance was quantitatively evaluated using 3D volume similarity between the ground truth contours and the predictions using Dice score coefficient, sensitivity, and precision as well as 2D surface similarity using Hausdorff distance (HD), mean surface distance (MSD) and residual mean square distance (RMSD). We benchmarked the performance against two other current leading edge networks known as Dynamic UNet and Swin-UNetr on the same public dataset. Results: The proposed network achieved the following volume similarity metrics when averaged over three cardiac segments: Dice = 0.952±0.017, precision = 0.948±0.016, sensitivity = 0.956±0.022. The average surface similarities were HD = 1.521±0.121 mm, MSD = 0.266±0.075 mm, and RMSD = 0.668±0.288 mm. The network shows statistically significant improvement in comparison to the Dynamic UNet and Swin-UNetr algorithms for most volumetric and surface metrics with p-value less than 0.05. Overall, the proposed Swin-MLP mixer network demonstrates better or comparable performance than competing methods. Conclusions: The proposed Swin-MLP mixer network demonstrates more accurate segmentation performance compared to current leading edge methods. This robust method demonstrates the potential to streamline clinical workflows for multiple applications.
Wolfberry (Lycium, of the family Solanaceae) has special nutritional benefits due to its valuable metabolites. Here, 16 wolfberry-specific metabolites were identified by comparing the metabolome of wolfberry with those of six species, including maize, rice, wheat, soybean, tomato and grape. The copy numbers of the riboflavin and phenyllactate degradation genes riboflavin kinase (RFK) and phenyllactate UDP-glycosyltransferase (UGT1) were lower in wolfberry than in other species, while the copy number of the phenyllactate synthesis gene hydroxyphenyl-pyruvate reductase (HPPR) was higher in wolfberry, suggesting that the copy number variation of these genes among species may be the main reason for the specific accumulation of riboflavin and phenyllactate in wolfberry. Moreover, the metabolome-based neighbor-joining tree revealed distinct clustering of monocots and dicots, suggesting that metabolites could reflect the evolutionary relationship among those species. Taken together, we identified 16 specific metabolites in wolfberry and provided new insight into the accumulation mechanism of species-specific metabolites at the genomic level.
Intrahepatic Cholangiocarcinoma (iCCA) with FGFR alterations is relatively rare, and its identification is important in the era of targeted therapy. We collected a large series of FGFR-altered cases in the Chinese population and characterized their clinicopathological and genetic features. Among the 18 FGFR-altered cases out of 260 iCCAs, 10 were males and 8 were females, ranging in age from 35 to 74 years (mean, 57.3 years; median, 58 years). Pathologically, they include 9 cases of large duct (LD, 50 %) and small duct (SD, 50 %) types each. All of them (100 %, 18/18) showed microsatellite stable (MSS) and low tumor mutation burden (TMB). Genetically, FGFR alterations involved FGFR1 (20 %), FGFR2 (70 %), and FGFR3 (10 %), with FGFR2 rearrangement accounting for the most (11/18). The most frequently altered genes/biological processes were development/proliferation-related pathways (44 %), chromatin organization (20 %), and tumor suppressors (32 %). Our study further revealed the clinicopathological and genetic features of FGFR-altered iCCA and demonstrated that its occurrence may show regional or ethnic variability and is less common in the Chinese population. A significant number of LD-type iCCA cases also have FGFR alterations rather than the SD type.
Activation of the renin-angiotensin system (RAS) triggers oxidative stress and an inflammatory response in the hypothalamic paraventricular nucleus (PVN), in turn increasing the sympathetic hyperactivity that is a major cause of hypertension. Pyridostigmine has cardioprotective effects by suppressing the RAS of myocardial tissue. However, whether pyridostigmine attenuates hypertension by inhibiting the RAS of the PVN remains unclear. We thus investigated the effect and mechanism of pyridostigmine on two-kidney one-clip (2K1C)-induced hypertension. 2K1C rats received pyridostigmine, or not, for 8 weeks. Cardiovascular function, hemodynamic parameters, and autonomic activity were measured. The PVN levels of pro-/anti-inflammatory cytokines, oxidative stress, and RAS signaling molecules were evaluated. Our results showed that hypertension was accompanied by cardiovascular dysfunction and an autonomic imbalance characterized by enhanced sympathetic but diminished vagal activity. The PVN levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), NOX-2, and malondialdehyde (MDA) increased; those of IL-10 and superoxide dismutase (SOD) decreased. Moreover, the RAS signaling pathway was activated, as evidenced by increased levels of the angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the Ang II type 1 receptor (AT1R) and a decreased AT2R level. Pyridostigmine lowered blood pressure and improved cardiovascular function, associated with restoration of the autonomic balance. Meanwhile, pyridostigmine decreased PVN IL-6, TNF-α, ROS, NOX-2, and MDA levels and increased IL-10 and SOD levels. Additionally, pyridostigmine suppressed PVN ACE, Ang II, and AT1R levels and increased AT2R expression. Pyridostigmine attenuated hypertension by inhibiting PVN oxidative stress and inflammation induced by the RAS.
BACKGROUND: Persistent auditory verbal hallucinations (pAVHs) are a fundamental manifestation of schizophrenia (SCZ), yet the exact connection between pAVHs and brain structure remains contentious. This study aims to explore the potential correlation between pAVHs and alterations in grey matter volume (GMV) within specific brain regions among individuals diagnosed with SCZ. METHODS: 76 SCZ patients with pAVHs (pAVH group), 57 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) were investigated using 3 T magnetic resonance imaging. The P3 hallucination item of the Positive and Negative Syndrome Scale was used to assess the severity of pAVHs. Voxel-based morphometry was used to analyze the GMV profile between the three groups. RESULTS: Compared to the non-AVH and HC groups, the pAVH group exhibited extensive reduction in GMV within the frontotemporal cortex. Conversely, no significant difference in GMV was observed between the non-AVH and HC groups. The severity of pAVHs showed a negative correlation with GMV in several regions, including the right fusiform, right inferior temporal, right medial orbitofrontal, right superior frontal, and right temporal pole (p = 0.0036, Bonferroni correction). Stepwise linear regression analysis revealed that GMV in the right temporal pole (ß = -0.29, p = 0.001) and right fusiform (ß = -0.21, p = 0.01) were significantly associated with the severity of pAVHs. CONCLUSIONS: Widespread reduction in GMV is observed within the frontotemporal cortex, particularly involving the right temporal pole and right fusiform, which potentially contribute to the pathogenesis of pAVHs in individuals with chronic SCZ.
Cell division is a highly regulated process essential for the accurate segregation of chromosomes. Central to this process is the assembly of a bipolar mitotic spindle, a highly dynamic microtubule (MT)-based structure responsible for chromosome movement. The nucleation and dynamics of MTs are intricately regulated by MT-binding proteins. Over the recent years, various MT-binding proteins have been reported to undergo liquid-liquid phase separation, forming either single- or multi-component condensates on MTs. Herein, we provide a comprehensive summary of the phase separation characteristics of these proteins. We underscore their critical roles in MT nucleation, spindle assembly and kinetochore-MT attachment during the cell division process. Furthermore, we discuss the current challenges and various remaining unsolved problems, highlights the ongoing research efforts aimed at a deeper understanding of the role of the phase separation process during spindle assembly and orientation. Our review aims to contribute to the collective knowledge in this area and stimulate further investigations that will enhance our comprehension of the intricate mechanisms governing cell division.
Three-dimensional covalent organic frameworks (3D COFs), recognized for their tailorable structures and accessible active sites, offer a promising platform for developing advanced photocatalysts. However, the difficulty in the synthesis and functionalization of 3D COFs hinders their further development. In this study, we present a series of 3D-bcu-COFs with 8 connected porphyrin units linked by linear linkers through imine bonds as a versatile platform for photocatalyst design. The photoresponse of 3D-bcu-COFs was initially modulated by functionalizing linear linkers with benzo-thiadiazole or benzo-selenadiazole groups. Furthermore, taking advantage of the well-exposed porphyrin and imine sites in 3D-bcu-COFs, their photocatalytic activity was optimized by stepwise protonation of imine bonds and porphyrin centers. The dual protonated COF with benzo-selenadiazole groups exhibited enhanced charge separation, leading to an increased photocatalytic H2O2 production under visible light. This enhancement demonstrates the combined benefits of linker functionalization and stepwise protonation on photocatalytic efficiency.
Background: Stereotactic body radiotherapy (SBRT) is a well-established treatment modality for liver metastases in patients unsuitable for surgery. Both CT and MRI are useful during treatment planning for accurate target delineation and to reduce potential organs-at-risk (OAR) toxicity from radiation. MRI-CT deformable image registration (DIR) is required to propagate the contours defined on high-contrast MRI to CT images. An accurate DIR method could lead to more precisely defined treatment volumes and superior OAR sparing on the treatment plan. Therefore, it is beneficial to develop an accurate MRI-CT DIR for liver SBRT. Purpose: To create a new deep learning model that can estimate the deformation vector field (DVF) for directly registering abdominal MRI-CT images. Methods: The proposed method assumed a diffeomorphic deformation. By using topology-preserved deformation features extracted from the probabilistic diffeomorphic registration model, abdominal motion can be accurately obtained and utilized for DVF estimation. The model integrated Swin transformers, which have demonstrated superior performance in motion tracking, into the convolutional neural network (CNN) for deformation feature extraction. The model was optimized using a cross-modality image similarity loss and a surface matching loss. To compute the image loss, a modality-independent neighborhood descriptor (MIND) was used between the deformed MRI and CT images. The surface matching loss was determined by measuring the distance between the warped coordinates of the surfaces of contoured structures on the MRI and CT images. To evaluate the performance of the model, a retrospective study was carried out on a group of 50 liver cases that underwent rigid registration of MRI and CT scans. The deformed MRI image was assessed against the CT image using the target registration error (TRE), Dice similarity coefficient (DSC), and mean surface distance (MSD) between the deformed contours of the MRI image and manual contours of the CT image. Results: When compared to only rigid registration, DIR with the proposed method resulted in an increase of the mean DSC values of the liver and portal vein from 0.850±0.102 and 0.628±0.129 to 0.903±0.044 and 0.763±0.073, a decrease of the mean MSD of the liver from 7.216±4.513 mm to 3.232±1.483 mm, and a decrease of the TRE from 26.238±2.769 mm to 8.492±1.058 mm. Conclusion: The proposed DIR method based on a diffeomorphic transformer provides an effective and efficient way to generate an accurate DVF from an MRI-CT image pair of the abdomen. It could be utilized in the current treatment planning workflow for liver SBRT.
OBJECTIVE: To explore the clinical feasibility of different treatment methods for persistent occipitotransverse position and the influence on maternal and infant complications. METHOD: During the trial of vaginal delivery from April 2020 to March 2023 in our hospital, the cervix was fully dilated and the presentation was located at +2 station. Ninety-six pregnant women with fetal presentation at +4 station, occipitotransverse fetal position, maternal complications, abnormalities in the second stage of labor, and or fetal distress were divided into two groups: 65 patients with Kielland forceps vaginal delivery and 31 patients underwent emergency cesarean section. The delivery time, vaginal laceration rate, postpartum blood loss volume, puerperal infection rate, neonatal birth injury rate, and neonatal 1 min Apgar scores were analyzed. RESULTS: The delivery outcomes and maternal and neonatal complications of 96 pregnant women were analyzed: the application of Kielland forceps delivery time was shorter, while the vaginal laceration rate, postpartum hemorrhage, puerperal infection rate were significantly lower than that of patients undergoing emergency cesarean section and the neonatal 1 min Apgar score was higher than that of emergency cesarean section group (p < 0.05). CONCLUSION: It was clinically appropriate to use Kielland forceps in vaginal delivery when the persistent occipitotransverse position was present and delivery needed to be expediated. Use of Kielland forceps can shorten the delivery time, improve the success rate of vaginal delivery and reduce the complications of mothers and infants.
Magnetic Resonance Imaging (MRI) is increasingly being used in treatment planning due to its superior soft tissue contrast, which is useful for tumor and soft tissue delineation compared to computed tomography (CT). However, MRI cannot directly provide mass density or relative stopping power (RSP) maps, which are required for calculating proton radiotherapy doses. Therefore, the integration of artificial intelligence (AI) into MRI-based treatment planning to estimate mass density and RSP directly from MRI has generated significant interest. A deep learning (DL) based framework was developed to establish a voxel-wise correlation between MR images and mass density as well as RSP. To facilitate the study, five tissue substitute phantoms were created, representing different tissues such as skin, muscle, adipose tissue, 45% hydroxyapatite (HA), and spongiosa bone. The composition of these phantoms was based on information from ICRP reports. Additionally, two animal tissue phantoms, simulating pig brain and liver, were prepared for DL training purposes. The phantom study involved the development of two DL models. The first model utilized clinical T1 and T2 MRI scans as input, while the second model incorporated zero echo time (ZTE) MRI scans. In the patient application study, two more DL models were trained: one using T1 and T2 MRI scans as input, and another model incorporating synthetic dual-energy computed tomography (sDECT) images to provide accurate bone tissue information. The DECT empirical model was used as a reference to evaluate the proposed models in both phantom and patient application studies. The DECT empirical model was selected as the reference for evaluating the proposed models in both phantom and patient application studies. In the phantom study, the DL model based on T1, and T2 MRI scans demonstrated higher accuracy in estimating mass density and RSP for skin, muscle, adipose tissue, brain, and liver. The mean absolute percentage errors (MAPE) were 0.42%, 0.14%, 0.19%, 0.78%, and 0.26% for mass density, and 0.30%, 0.11%, 0.16%, 0.61%, and 0.23% for RSP, respectively. The DL model incorporating ZTE MRI further improved the accuracy of mass density and RSP estimation for 45% HA and spongiosa bone, with MAPE values of 0.23% and 0.09% for mass density, and 0.19% and 0.07% for RSP, respectively. These results demonstrate the feasibility of using an MRI-only approach combined with DL methods for mass density and RSP estimation in proton therapy treatment planning. By employing this approach, it is possible to obtain the necessary information for proton radiotherapy directly from MRI scans, eliminating the need for additional imaging modalities.
Deep Learning , Magnetic Resonance Imaging , Phantoms, Imaging , Proton Therapy , Magnetic Resonance Imaging/methods , Proton Therapy/methods , Humans , Animals , Swine , Radiotherapy Planning, Computer-Assisted/methods , Tomography, X-Ray Computed/methods , Radiotherapy Dosage
There is an increasingly growing demand to balance tissue repair guidance and opportunistic infection (OI) inhibition in clinical implant surgery. Herein, we developed a nanoadjuvant for all-stage tissue repair guidance and biofilm-responsive OI eradication via in situ incorporating Cobaltiprotoporphyrin (CoPP) into Prussian blue (PB) to prepare PB-CoPP nanozymes (PCZs). Released CoPP possesses a pro-efferocytosis effect for eliminating apoptotic and progressing necrotic cells in tissue trauma, thus preventing secondary inflammation. Once OIs occur, PCZs with switchable nanocatalytic capacity can achieve bidirectional pyroptosis regulation. Once reaching the acidic biofilm microenvironment, PCZs possess peroxidase (POD)-like activity that can generate reactive oxygen species (ROS) to eradicate bacterial biofilms, especially when synergized with the photothermal effect. Furthermore, generated ROS can promote macrophage pyroptosis to secrete inflammatory cytokines and antimicrobial proteins for biofilm eradication in vivo. After eradicating the biofilm, PCZs possess catalase (CAT)-like activity in a neutral environment, which can scavenge ROS and inhibit macrophage pyroptosis, thereby improving the inflammatory microenvironment. Briefly, PCZs as nanoadjuvants feature the capability of all-stage tissue repair guidance and biofilm-responsive OI inhibition that can be routinely performed in all implant surgeries, providing a wide range of application prospects and commercial translational value.
Biofilms , Pyroptosis , Biofilms/drug effects , Pyroptosis/drug effects , Animals , Mice , Reactive Oxygen Species/metabolism , Ferrocyanides/chemistry , Ferrocyanides/pharmacology , Prostheses and Implants , Macrophages/metabolism , Macrophages/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Wound Healing/drug effects , Humans , Efferocytosis
BACKGROUND: Low-temperature severely limits the growth and development of Camellia oleifera (C. oleifera). The mitogen-activated protein kinase (MAPK) cascade plays a key role in the response to cold stress. METHODS AND RESULTS: Our study aims to identify MAPK cascade genes in C. oleifera and reveal their roles in response to cold stress. In our study, we systematically identified and analyzed the MAPK cascade gene families of C. oleifera, including their physical and chemical properties, conserved motifs, and multiple sequence alignments. In addition, we characterized the interacting networks of MAPKK kinase (MAPKKK)-MAPK kinase (MAPKK)-MAPK in C. oleifera. The molecular mechanism of cold stress resistance of MAPK cascade genes in wild C. oleifera was analyzed by differential gene expression and real-time quantitative reverse transcription-PCR (qRT-PCR). CONCLUSION: In this study, 21 MAPKs, 4 MAPKKs and 55 MAPKKKs genes were identified in the leaf transcriptome of C. oleifera. According to the phylogenetic results, MAPKs were divided into 4 groups (A, B, C and D), MAPKKs were divided into 3 groups (A, B and D), and MAPKKKs were divided into 2 groups (MEKK and Raf). Motif analysis showed that the motifs in each subfamily were conserved, and most of the motifs in the same subfamily were basically the same. The protein interaction network based on Arabidopsis thaliana (A. thaliana) homologs revealed that MAPK, MAPKK, and MAPKKK genes were widely involved in C. oleifera growth and development and in responses to biotic and abiotic stresses. Gene expression analysis revealed that the CoMAPKKK5/CoMAPKKK43/CoMAPKKK49-CoMAPKK4-CoMAPK8 module may play a key role in the cold stress resistance of wild C. oleifera at a high-elevation site in Lu Mountain (LSG). This study can facilitate the mining and utilization of genetic resources of C. oleifera with low-temperature tolerance.
Camellia , Cold-Shock Response , Gene Expression Regulation, Plant , Phylogeny , Plant Proteins , Cold-Shock Response/genetics , Camellia/genetics , Gene Expression Regulation, Plant/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/metabolism , MAP Kinase Signaling System/genetics , Cold Temperature , Transcriptome/genetics , Multigene Family , Mitogen-Activated Protein Kinase Kinases/genetics , Mitogen-Activated Protein Kinase Kinases/metabolism , Gene Expression Profiling/methods , Plant Leaves/genetics
Constructing carrier materials with polysaccharides to enhance the solubility of insoluble active ingredients is a crucial strategy for improving bioavailability. This research constructed pectin-based hesperidin microcapsules (PHM) through self-assembly processes in the deep eutectic solvent, improving the solubility, storage stability, and bioavailability of hesperidin (HES). PHM exhibited high encapsulation efficiency (91.7%) and loading capacity (11.5%), with a small particle size (1.73 µm). The interaction mechanism was clarified through physical characterization and density functional theory (DFT) calculations. The vitro release demonstrated that the release ratio of PHM was only 6.4% in simulated gastric fluid (SGF), but reached 80.9% in simulated intestinal fluid (SIF). The release mechanism of PHM in SGF followed Fickian diffusion, while in SIF followed skeleton dissolution diffusion with a stable rate. Furthermore, the cell cytotoxicity experiments confirmed the remarkable biocompatibility of PHM toward human colon cells, which suggested its potential application in food and pharmaceutical fields.
Objective: We investigated the clinical characteristics, fall outcomes, and related factors of falls in patients who were hospitalized in the rehabilitation department, and explored strategies to reduce the incidence of falls and prevent falls in patients. Methods: Data from 60 patients who fell in the rehabilitation department between 2016 and 2021 were analyzed for clinical characteristics, associated factors, incidence of falls, injuries, and patient demographics. Under the random stratified sampling method, 60 patients who did not fall during the same period were selected as the control group, and relevant data was collected. Measurement data were compared using an independent sample t-test. Enumeration data were compared using chi-squared (χ2) test was employed to compare these data between the two groups. Non-parametric data were analyzed using the Mann-Whitney U-test. Factors potentially influencing falls were scrutinized through both univariate and binary logistic regression analyses. Results: The median annual incidence of falls among patients who were hospitalized in the rehabilitation department was 0.04%, while the overall fall injury rate was 60%. Falls were most prevalent within 30 days of hospitalization (71.67%). The most common fall-related condition was craniocerebral disease (83.33%). The incidents of falls location of fall were mainly reported in nearby areas of rehabilitation ward (70%). Most accidents occurred between 7:00 a.m.-12:00 p.m. and 3:01 p.m.-6:00 p.m. (63.33%), and dyskinesia was the most common cause of falls (71.67%). There were 39 patients (65.00%) with Barthel Index (BI) scores ranging between 40-60. Conclusion: Patients in the rehabilitation department had a greater incidence of falls and fall injuries. Within 30 days of admission, patients with moderately dependent craniocerebral disorders and dyskinesia frequently experienced falls during typical daytime shifts in areas characterized by endemic conditions.
BACKGROUND: Sepsis-induced myopathy (SIM) a complication of sepsis that results in prolonged mechanical ventilation, long-term functional disability, and increased patient mortality. This study was performed to identify potential key oxidative stress-related genes (OS-genes) as biomarkers for the diagnosis of SIM using bioinformatics. METHODS: The GSE13205 was obtained from the Gene Expression Omnibus (GEO) database, including 13 SIM samples and 8 healthy samples, and the differentially expressed genes (DEGs) were identified by limma package in R language. Simultaneously, we searched for the genes related to oxidative stress in the Gene Ontology (GO) database. The intersection of the genes selected from the GO database and the genes from the GSE13205 was considered as OS-genes of SIM, where the differential genes were regarded as OS-DEGs. OS-DEGs were analyzed using GO enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction (PPI) networks. Hub genes in OS-DEGs were selected based on degree, and diagnostic genes were further screened by gene expression and receiver operating characteristic (ROC) curve. Finally, a miRNA-gene network of diagnostic genes was constructed. RESULTS: A total of 1089 DEGs were screened from the GSE13205, and 453 OS-genes were identified from the GO database. The overlapping DEGs and OS-genes constituted 25 OS-DEGs, including 15 significantly upregulated and 10 significantly downregulated genes. The top 10 hub genes, including CD36, GPX3, NQO1, GSR, TP53, IDH1, BCL2, HMOX1, JAK2, and FOXO1, were screened. Furthermore, 5 diagnostic genes were identified: CD36, GPX3, NQO1, GSR, and TP53. The ROC analysis showed that the respective area under the curves (AUCs) of CD36, GPX3, NQO1, GSR, and TP53 were 0.990, 0.981, 0.971, 0.971, and 0.971, which meant these genes had very high diagnostic values of SIM. Finally, based on these 5 diagnostic genes, we found that miR-124-3p and miR-16-5p may be potential targets for the treatment of SIM. CONCLUSIONS: The results of this study suggest that OS-genes might play an important role in SIM. CD36, GPX3, NQO1, GSR, and TP53 have potential as specific biomarkers for the diagnosis of SIM.
Muscular Diseases , Oxidative Stress , Sepsis , Humans , Oxidative Stress/genetics , Sepsis/genetics , Muscular Diseases/genetics , Computational Biology , Protein Interaction Maps/genetics , MicroRNAs/genetics , ROC Curve , Biomarkers/metabolism , Gene Expression Profiling , Gene Regulatory Networks , Gene Ontology , Databases, Genetic
Purpose: To report the current practice pattern of the proton stereotactic body radiation therapy (SBRT) for prostate treatments. Materials and Methods: A survey was designed to inquire about the practice of proton SBRT treatment for prostate cancer. The survey was distributed to all 30 proton therapy centers in the United States that participate in the National Clinical Trial Network in February, 2023. The survey focused on usage, patient selection criteria, prescriptions, target contours, dose constraints, treatment plan optimization and evaluation methods, patient-specific QA, and image-guided radiation therapy (IGRT) methods. Results: We received responses from 25 centers (83% participation). Only 8 respondent proton centers (32%) reported performing SBRT of the prostate. The remaining 17 centers cited 3 primary reasons for not offering this treatment: no clinical need, lack of volumetric imaging, and/or lack of clinical evidence. Only 1 center cited the reduction in overall reimbursement as a concern for not offering prostate SBRT. Several common practices among the 8 centers offering SBRT for the prostate were noted, such as using Hydrogel spacers, fiducial markers, and magnetic resonance imaging (MRI) for target delineation. Most proton centers (87.5%) utilized pencil beam scanning (PBS) delivery and completed Imaging and Radiation Oncology Core (IROC) phantom credentialing. Treatment planning typically used parallel opposed lateral beams, and consistent parameters for setup and range uncertainties were used for plan optimization and robustness evaluation. Measurements-based patient-specific QA, beam delivery every other day, fiducial contours for IGRT, and total doses of 35 to 40 GyRBE were consistent across all centers. However, there was no consensus on the risk levels for patient selection. Conclusion: Prostate SBRT is used in about 1/3 of proton centers in the US. There was a significant consistency in practices among proton centers treating with proton SBRT. It is possible that the adoption of proton SBRT may become more common if proton SBRT is more commonly offered in clinical trials.
INTRODUCTION: Cardiopulmonary complications and cognitive impairment following craniotomy have a significantly impact on the general health of individuals with brain tumours. Observational research indicates that engaging in walking is linked to better prognosis in patient after surgery. This trial aims to explore whether walking exercise prior to craniotomy in brain tumour patients can reduce the incidence of cardiopulmonary complications and preserve patients' cognitive function. METHODS AND ANALYSIS: In this randomised controlled trial, 160 participants with supratentorial brain tumours aged 18-65 years, with a preoperative waiting time of more than 3-4 weeks and without conditions that would interfere with the trial such as cognitive impairment, will be randomly assigned in a ratio of 1:1 to either receive traditional treatment or additional combined with a period of 3-4 weeks of walking exercise of 10 000-15 000 steps per day. Wearable pedometer devices will be used to record step counts. The researchers will evaluate participants at enrolment, baseline, 14 days preoperatively, 3 days prior to surgery and 1 week after surgery or discharge (select which occurs first). The primary outcomes include the incidence of postoperative cardiopulmonary complications and changes in cognitive function (gauged by the Montreal Cognitive Assessment test). Secondary outcomes include the average length of hospital stay, postoperative pain, participant contentment, healthcare-associated costs and incidence of other postoperative surgery-related complications. We anticipate that short-term preoperative walking exercises will reduce the incidence of surgery-related complications in the short term after craniotomy, protect patients' cognitive function, aid patients' postoperative recovery and reduce the financial cost of treatment. ETHICS AND DISSEMINATION: The study protocol has been approved by Ethics Committee of Xiangya Hospital of Central South University (approval number: 202305117). The findings of the research will be shared via publications that have been reviewed by experts in the field and through presentations at conferences. TRIAL REGISTRATION NUMBER: NCT05930288.
Craniotomy , Supratentorial Neoplasms , Walking , Humans , Craniotomy/adverse effects , Adult , Middle Aged , Supratentorial Neoplasms/surgery , Female , Male , Aged , Preoperative Exercise , Prognosis , Randomized Controlled Trials as Topic , Young Adult , Postoperative Complications/prevention & control , Adolescent , Cognition
Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.
