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Abstract Background Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. Methods Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. Results We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1high neutrophils. In the chronic stage, the “FOXO1-transferrin receptor (TFRC)” mechanism contributes to FOXO1high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. Conclusions FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.

Abstract To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non‐sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non‐sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non‐sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4–6), p = 0.008]. The serum levels of d‐lactate (p = 0.033), intestinal fatty acid‐binding protein (p = 0.005), interleukin‐6 (p = 0.001), white blood cells (p = 0.007), C‐reactive protein (p = 0.001), and procalcitonin (p

Abstract Background Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Intestinal mucosal barrier injury is one of the important manifestations of sepsis. Interleukin-9 (IL-9) and IL-9-producing CD4(+) T cells were emerging pro-inflammatory mediators with development of intestinal injury. However, it is unclear whether IL-9 is related to the intestinal barrier injury of sepsis. Methods To investigate the roles of IL-9-producing CD4(+) T cells and IL-9 in the process of barrier injury in sepsis, serum IL-9-producing CD4(+) T cell percentages, IL-9, and D-lactate levels were measured in septic patients and controls. The markers of barrier function in serum and intestinal tissue were also collected in septic rats. Moreover, the barrier injury degree and survival rate of septic rats were also investigated after increasing or interfering with IL-9 expression. Results The serum IL-9-producing CD4(+) T cell percentages, IL-9, and D-lactate levels were significantly higher in septic patients or rats than those in controls. IL-9-producing CD4(+) T cells and IL-9 levels were positively correlated with D-lactate levels and had a high predictive value of 28-day mortality in septic patients. The non-survivors had significantly higher serum T cell percentages, IL-9, and D-lactate levels compared with survivors. In septic rats, IL-9 increased the expression levels of D-lactate, whereas that decreased the expression levels of zonula occludens 1. Moreover, the barrier injury was aggravated or alleviated by increasing or interfering with IL-9 expression, respectively. Survival rate analysis also showed that IL-9 decreased the 14-day survival rate of septic rats. Conclusion IL-9 is closely related to intestinal mucosal barrier injury and mortality in sepsis. IL-9 blockade has the potential to improve the barrier injury in sepsis. Trial registration The study was registered at ClinicalTrials.gov (ID: NCT03791866, Date: December 2018).

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non‐sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non‐sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non‐sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4–6), p = 0.008]. The serum levels of d‐lactate (p = 0.033), intestinal fatty acid‐binding protein (p = 0.005), interleukin‐6 (p = 0.001), white blood cells (p = 0.007), C‐reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non‐sivelestat group. The sivelestat group also demonstrated longer ICU‐free days [18 (0–22) vs. 13 (0–17), p = 0.004] and ventilator‐free days [22 (1–24) vs. 16 (1–19), p = 0.002] compared with the non‐sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients. [ABSTRACT FROM AUTHOR]

Aim: To investigate the current status of experience and support of nurses as second victims and explore its related factors in nurses. Design: A sequential, explanatory, mixed-method study was applied. Methods: A total of 406 nurses from seven tertiary hospitals in China were chosen as participants between September to October 2023. The Chinese version of the Second Victim Experience and Support Questionnaire (SVEST), Somatic Complaints of Sub-health Status Questionnaire (SCSSQ) and Generalized Anxiety Disorder (GAD-7) were applied to collect quantitative data. Eight nurses were selected for a qualitative study through in-depth interviews. Through interpretive phenomenological analysis, the interview data were analysed to explore the experience and support of nurses as second victims. Results: Practice distress (15.74 ±  4.97) and psychological distress (15.48 ±  3.74) were the highest dimensions, indicating Chinese nurses experienced second victim-related practice and psychological distress. Nurses with different gender, age, education, marital status, income, working hours, professional titles, and unit types have different levels of second victim-related experience and support (p <  0.05). In addition, the score of SVEST was positively associated with SCSSQ (r =  0.444) and GAD-7 (r =  0.490) (p <  0.05). This qualitative study found that the experience and support of nurses as second victims included nurses' perceptions and needs for patient safety events; psychological, physical and practice distress of nurses; and nurses and hospitals coping style after patient safety events. Discussion: Our findings suggest that nurses who are second victims of patient safety events experience severe practice and psychological distress, indicating that nursing managers should pay attention to psychological and practice distress of nurses after patient safety events and provide effective preventive measures. [ABSTRACT FROM AUTHOR]

Background and aim: Previous studies reported inconsistent results on the prevalence and prognostic implications of frailty among older adults with gastric cancer. This systematic review synthesized available literature pertaining on this topic to establish the prevalence and unfavorable outcomes of frailty in older adults with gastric cancer. Methods: A comprehensive search was conducted across multiple English databases including PubMed, Cochrane Library, CINAHL, Embase, and Web of Science as well as Chinese databases, namely, CNKI, Wan Fang, and CBM, from inception to July 4, 2023, to identify potential studies. Data related to the incidence of frailty and its unfavorable outcomes in older adults with gastric cancer were extracted. RevMan5.3 and R 4.2.2 were used to evaluate pooled prevalence, hazard ratios (HR), and 95% confidence interval (CI). Results: This review comprehensively selected 13 studies, comprising 9 cohort studies and 4 cross-sectional studies, on 44,117 older adults diagnosed with gastric cancer. The incidence of frailty among older adults with gastric cancer ranged from 10 to 71%. The pooled prevalence of frailty was 29% (95% CI 0.21–0.39). Frailty was found to be associated with an elevated risk of postoperative complications (HR = 1.99, 95% CI 1.45–2.73), prolonged postoperative hospital stay (HR = 2.68, 95% CI 2.38–3.02), likelihood of readmission (HR = 3.28, 95% CI 1.77–6.08), and an increased mortality risk (HR = 1.60, 95% CI 1.36–1.90). Conclusions: Frailty was associated with a poor prognosis in older adults with gastric cancer. Clinical medical staff should focus on the frailty of older adults with gastric cancer, conduct large-scale, multicenter, and prospective studies and early screening of patients, and provide guidance for the implementation of prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Abstract Tibial dyschondroplasia (TD) is the most-prevalent leg disorder in fast-growing chickens; it is intractable and characterized by abnormal endochondral bone formation of proximal tibial growth-plates (TGPs). Previous studies have shown that bone is a highly vascularized tissue dependent on the coordinated coupling between angiogenesis and osteogenesis, but the underlying mechanisms of bone formation and bone remodeling are poorly defined in TD chickens. Here, we observed that inhibition of vasculogenesis and angiogenesis remarkably impaired vascular invasion in the hypertrophic chondrocyte zone of the TGPs, resulting in the massive death of chondrocytes due to a shortage of blood vessels and nutrients. Moreover, the balance of the OPG (osteoprotegerin)/RANKL (receptor activator of nuclear factor-kB ligand) system is also severely disrupted during the osteogenesis process while coupling with angiogenesis, both of which eventually lead to abnormal endochondral bone formation in TD chickens. Thus, the process of vascular formation in endochondral bone appears to initiate the pathological changes in TD, and improvement of this process during coupling with osteogenesis may be a potential therapeutic approach to treat this intractable disease.

Background: The tumor area may be a potential prognostic indicator. The present study aimed to determine and validate the prognostic value of tumor area in curable colon cancer. Methods: This retrospective study included a training and validation cohorts of patients who underwent radical surgery for colon cancer. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were identified using Cox proportional hazards regression models. The prognostic discrimination was evaluated using the integrated area under the receiver operating characteristic curves (iAUCs) for prognostic factors and models. The prognostic discrimination between tumor area and other individual factors was compared, along with the prognostic discrimination between the tumor-node-metastasis (TNM) staging system and other prognostic models. Two-sample Wilcoxon tests were carried out to identify significant differences between the two iAUCs. A two-sided P < 0.05 was considered statistically significant. Results: A total of 3051 colon cancer patients were included in the training cohort and 872 patients in the validation cohort. Tumor area, age, differentiation, T stage, and N stage were independent prognostic factors for both OS and DFS in the training cohort. Tumor area had a better OS and DFS prognostic discrimination characteristics than T stage, maximal tumor diameter, differentiation, tumor location, and number of retrieved lymph nodes. The novel prognostic model of T stage + N stage + tumor area (iAUC for OS, 0.714, P < 0.001; iAUC for DFS, 0.694, P < 0.001) showed a better prognostic discrimination than the TNM staging system (T stage + N stage; iAUC for OS, 0.664; iAUC for DFS, 0.658). Similar results were observed in an independent validation cohort. Conclusions: Tumor area was identified as an independent prognostic factor for both OS and DFS in curable colon cancer patients, and in cases with an adequate number of retrieved lymph nodes. The novel prognostic model of combining T stage, N stage, and tumor area may be an alternative to the current TNM staging system. [ABSTRACT FROM AUTHOR]

Abstract Tibial dyschondroplasia (TD) is an intractable poultry problem that is characterized by the appearance of non-vascularized and non-mineralized cartilage masses in tibial growth plates (TGPs). However, the role of angiogenesis inhibition in the occurrence of TD remains unknown. In this study, we found that, compared to low-altitude Arbor Acres chickens (AACs), high-altitude Tibetan chickens showed higher tibial vascular distributions that were accompanied by up-regulation of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA) and VEGF receptors. These observations provide insights into hypoxia-induced angiogenesis, which may be related to the absence of TD in high-altitude native Tibetan chickens. Importantly, hypoxia experiments also showed that during hypoxia, tibial angiogenesis was enhanced, which was due to pro-angiogenic factor up-regulation (including VEGFA, VEGFR1, VEGFR2, and IL-8), in AACs. Moreover, we observed that thiram-induced TD could strongly inhibit tibial angiogenesis in the hypertrophic zone through coordinated down-regulation of HIF-1α and pro-angiogenic factors, leading to a disruption in the blood supply to the TGP. Taken together, these findings reveal that the occurrence of TD is highly associated with inhibition of tibial angiogenesis through down-regulated expression of HIF-1α, VEGFA and VEGF receptors, which results in suppression of TGP development.

Cold-inducible RNA-binding protein (CIRP), a key regulatory protein, could be facilitated by mild hypothermia in the brain, heart and liver. This study observed the effects of mild hypothermia at 31 ± 0.5°C on traumatic brain injury in rats. Results demonstrated that mild hypothermia suppressed apoptosis in the cortex, hippocampus and hypothalamus, facilitated CIRP mRNA and protein expression in these regions, especially in the hypothalamus. The anti-apoptotic effect of mild hypothermia disappeared after CIRP silencing. There was no correlation between mitogen-activated extracellular signal-regulated kinase activation and CIRP silencing. CIRP silencing inhibited extracellular signal-regulated kinase-1/2 activation. These indicate that CIRP inhibits apoptosis by affecting extracellular signal-regulated kinase-1/2 activation, and exerts a neuroprotective effect during mild hypothermia for traumatic brain injury.

Learning invariant (causal) features for out-of-distribution (OOD) generalization have attracted extensive attention recently, and among the proposals, invariant risk minimization (IRM) is a notable solution. In spite of its theoretical promise for linear regression, the challenges of using IRM in linear classification problems remain. By introducing the information bottleneck (IB) principle into the learning of IRM, the IB-IRM approach has demonstrated its power to solve these challenges. In this paper, we further improve IB-IRM from two aspects. First, we show that the key assumption of support overlap of invariant features used in IB-IRM guarantees OOD generalization, and it is still possible to achieve the optimal solution without this assumption. Second, we illustrate two failure modes where IB-IRM (and IRM) could fail in learning the invariant features, and to address such failures, we propose a Counterfactual Supervision-based Information Bottleneck (CSIB) learning algorithm that recovers the invariant features. By requiring counterfactual inference, CSIB works even when accessing data from a single environment. Empirical experiments on several datasets verify our theoretical results. [ABSTRACT FROM AUTHOR]

We investigated Japanese encephalitis virus (JEV) prevalence in high-altitude regions of Tibet, China, by using standard assays to test mosquitoes, pigs, and humans. Results confirmed that JEV has spread to these areas. Disease prevention and control strategies should be used along with surveillance to limit spread of JEV in high-altitude regions of Tibet.

Abstract Zinc hydroxide fluoride (Zn(OH)F) with novel flower-like morphology has been prepared via a microwave-assisted ionic liquid route. The flower-like Zn(OH)F particle has six petals and every petal is composed of lots of acicular nano-structure. Nanoporous ZnO is obtained by thermal decomposition of as-prepared Zn(OH)F in air, and the flower-like morphology is well retained. In the process of synthesis, ionic liquid 1-Butyl-3-methylimidazolium tetrafluoroborate is used as both the reactant and the template.

The aim of this study was to investigate the risk factors of hypoalbuminemia and effects of different albumin levels on the prognosis of surgical septic patients. We preformed a retrospective clinical study including 135 adult patients from September 2011 to June 2014. The albumin levels and severity markers were recorded during the first 48 h after enrollment, and logistic regression analyses were used to determine the risk factors. The outcomes of patients with different albumin levels were also compared. The acute physiology and chronic health evaluation II (APACHE II) score (OR 1.786, 95% CI [1.379–2.314], P < 0.001), C-reactive protein (CRP) (OR 1.016, 95% CI [1.005–1.027], P = 0.005), and blood lactate (OR 1.764, 95% CI [1.141–2.726], P = 0.011) were established as the independent risk factors of hypoalbuminemia in patients with surgical sepsis. The severity markers and outcomes of patients with albumin levels ≤20 g/L were significantly worse than that of 21–25 g/L and ≥26 g/L, whereas the latter two groups had similar prognosis. Every 1 g/L decrease of albumin level below the optimal cut-off (23 g/L) was associated with a 19.4% increase in hospital mortality and a 28.7% increase in the incidence of multiple organ dysfunction syndrome. In conclusion, APACHE II score (≥14.5), CRP (≥34.25 mg/L), and blood lactate (≥.35 mmol/L) were established as the independent risk factors of hypoalbuminemia in the early stage of surgical sepsis. Patients with baseline albumin level ≤20 g/L had worse prognosis than that of albumin level ≥21 g/L. Albumin levels were negatively correlated the prognosis of surgical sepsis when below about 23 g/L.

Objective : This study was conducted to examine the factors associated with stigma in breast cancer women. Methods: PubMed, Embase, the Cochrane Library, Web of Science, and two Chinese electronic databases were electronically searched to identify eligible studies that reported the correlates of stigma for patients with breast cancer from inception to July 2022. Two researchers independently performed literature screening, data extraction, and risk of bias assessment. R4.1.1 software was used for statistical analysis. Results: Twenty articles including 4161 patients were included in the systematic review and meta-analysis. Results showed that breast cancer stigma was positively correlated with working status, type of surgery, resignation coping, depression, ambivalence over emotional expression, and delayed help-seeking behavior and negatively correlated with age, education, income, quality of life, social support, confrontation coping, psychological adaptation, self-efficacy, and self-esteem. Descriptive analysis showed that breast cancer stigma was positively correlated with intrusive thoughts, body image, anxiety, and self-perceived burden but negatively correlated with a sense of coherence, personal acceptance of the disease, sleep quality, cancer screening attendance and doctor’s empathy. Conclusion: Many demographic, disease-related, and psychosocial variables are related to breast cancer stigma. Our view can serve as a basis for health care professionals to develop health promotion and prevention strategies for patients with breast cancer. [ABSTRACT FROM AUTHOR]

Reconstruction of object or scene surfaces has tremendous applications in computer vision, computer graphics, and robotics. The topic attracts increased attention with the emerging pipeline of deep learning surface reconstruction, where implicit field functions constructed from deep networks (e.g., multi-layer perceptrons or MLPs) are proposed for generative shape modeling. In this paper, we study a fundamental problem in this context about recovering a surface mesh from an implicit field function whose zero-level set captures the underlying surface. To achieve the goal, existing methods rely on traditional meshing algorithms (e.g., the de-facto standard marching cubes); while promising, they suffer from loss of precision learned in the implicit surface networks, due to the use of discrete space sampling in marching cubes. Given that an MLP with activations of Rectified Linear Unit (ReLU) partitions its input space into a number of linear regions, we are motivated to connect this local linearity with a same property owned by the desired result of polygon mesh. More specifically, we identify from the linear regions, partitioned by an MLP based implicit function, the analytic cells and analytic facesthat are associated with the function's zero-level isosurface. We prove that under mild conditions, the identified analytic faces are guaranteed to connect and form a closed, piecewise planar surface. Based on the theorem, we propose an algorithm of analytic marching, which marches among analytic cells to exactly recover the mesh captured by an implicit surface network. We also show that our theory and algorithm are equally applicable to advanced MLPs with shortcut connections and max pooling. Given the parallel nature of analytic marching, we contribute AnalyticMesh, a software package that supports efficient meshing of implicit surface networks via CUDA parallel computing, and mesh simplification for efficient downstream processing. We apply our method to different settings of generative shape modeling using implicit surface networks. Extensive experiments demonstrate our advantages over existing methods in terms of both meshing accuracy and efficiency. Codes are at https://github.com/Karbo123/AnalyticMesh. [ABSTRACT FROM AUTHOR]

Unsupervised domain adaptation (UDA) is to learn classification models that make predictions for unlabeled data on a target domain, given labeled data on a source domain whose distribution diverges from the target one. Mainstream UDA methods strive to learn domain-aligned features such that classifiers trained on the source features can be readily applied to the target ones. Although impressive results have been achieved, these methods have a potential risk of damaging the intrinsic data structures of target discrimination, raising an issue of generalization particularly for UDA tasks in an inductive setting. To address this issue, we are motivated by a UDA assumption of structural similarity across domains, and propose to directly uncover the intrinsic target discrimination via constrained clustering, where we constrain the clustering solutions using structural source regularization that hinges on the very same assumption. Technically, we propose a hybrid model of Structurally Regularized Deep Clustering, which integrates the regularized discriminative clustering of target data with a generative one, and we thus term our method as H-SRDC. Our hybrid model is based on a deep clustering framework that minimizes the Kullback-Leibler divergence between the distribution of network prediction and an auxiliary one, where we impose structural regularization by learning domain-shared classifier and cluster centroids. By enriching the structural similarity assumption, we are able to extend H-SRDC for a pixel-level UDA task of semantic segmentation. We conduct extensive experiments on seven UDA benchmarks of image classification and semantic segmentation. With no explicit feature alignment, our proposed H-SRDC outperforms all the existing methods under both the inductive and transductive settings. We make our implementation codes publicly available at https://github.com/huitangtang/H-SRDC. [ABSTRACT FROM AUTHOR]

This paper focuses on the challenging task of learning 3D object surface reconstructions from RGB images. Existing methods achieve varying degrees of success by using different surface representations. However, they all have their own drawbacks, and cannot properly reconstruct the surface shapes of complex topologies, arguably due to a lack of constraints on the topological structures in their learning frameworks. To this end, we propose to learn and use the topology-preserved, skeletal shape representation to assist the downstream task of object surface reconstruction from RGB images. Technically, we propose the novel SkeletonNet design that learns a volumetric representation of a skeleton via a bridged learning of a skeletal point set, where we use parallel decoders each responsible for the learning of points on 1D skeletal curves and 2D skeletal sheets, as well as an efficient module of globally guided subvolume synthesis for a refined, high-resolution skeletal volume; we present a differentiable Point2Voxel layer to make SkeletonNet end-to-end and trainable. With the learned skeletal volumes, we propose two models, the Skeleton-Based Graph Convolutional Neural Network (SkeGCNN) and the Skeleton-Regularized Deep Implicit Surface Network (SkeDISN), which respectively build upon and improve over the existing frameworks of explicit mesh deformation and implicit field learning for the downstream surface reconstruction task. We conduct thorough experiments that verify the efficacy of our proposed SkeletonNet. SkeGCNN and SkeDISN outperform existing methods as well, and they have their own merits when measured by different metrics. Additional results in generalized task settings further demonstrate the usefulness of our proposed methods. We have made our implementation code publicly available at https://github.com/tangjiapeng/SkeletonNet. [ABSTRACT FROM AUTHOR]