Development and validation of a predictive model for febrile seizures.

Febrile seizures (FS) are the most prevalent type of seizures in children. Existing predictive models for FS exhibit limited predictive ability. To build a better-performing predictive model, a retrospective analysis study was conducted on febrile children who visited the Children's Hospital of Shanghai from July 2020 to March 2021. These children were divided into training set (n = 1453), internal validation set (n = 623) and external validation set (n = 778). The variables included demographic data and complete blood counts (CBCs). The least absolute shrinkage and selection operator (LASSO) method was used to select the predictors of FS. Multivariate logistic regression analysis was used to develop a predictive model. The coefficients derived from the multivariate logistic regression were used to construct a nomogram that predicts the probability of FS. The calibration plot, area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA) were used to evaluate model performance. Results showed that the AUC of the predictive model in the training set was 0.884 (95% CI 0.861 to 0.908, p < 0.001) and C-statistic of the nomogram was 0.884. The AUC of internal validation set was 0.883 (95% CI 0.844 to 0.922, p < 0.001), and the AUC of external validation set was 0.858 (95% CI 0.820 to 0.896, p < 0.001). In conclusion, the FS predictive model constructed based on CBCs in this study exhibits good predictive ability and has clinical application value.

Cancer Therapy Empowered by Extracellular Vesicle-Mediated Targeted Delivery.

Extracellular vesicles (EVs) are a class of nanoparticles that mediate signaling molecules delivery between donor and recipient cells. Heterogeneity in the content of EVs and their membrane surface proteins determines their unique targetability. Their low immunogenicity, capability to cross various biological barriers, and superior biocompatibility enable engineering-modified EVs to be ideal drug delivery carriers. In addition, the engineered EVs that emerge in recent years have become a powerful tool for cancer treatment through the selective delivery of bioactive molecules to therapeutic targets, such as tumor cells and stroma. Our review focuses on the various types of EV modifications and their promoting therapeutic capabilities, which provide an innovative means for cancer precision therapy.

The influence of aggressive exercise on responses to self-perceived and others' pain.

Previous studies have reported relationships between exercise and pain. However, little is known about how aggressive exercise modulates individuals' responses to their own and others' pain. This present study addresses this question by conducting 2 studies employing event-related potential (ERP). Study 1 included 38 participants whose self-perceived pain was assessed after intervention with aggressive or nonaggressive exercises. Study 2 recruited 36 participants whose responses to others' pain were assessed after intervention with aggressive or nonaggressive exercise. Study 1's results showed that P2 amplitudes were smaller, reaction times were longer, and participants' judgments were less accurate in response to self-perceived pain stimuli, especially to high-pain stimuli, after intervention with aggressive exercise compared to nonaggressive exercise. Results of study 2 showed that both P3 and LPP amplitudes to others' pain were larger after intervention with aggressive exercise than with nonaggressive exercise. These results suggest that aggressive exercise decreases individuals' self-perceived pain and increases their empathic responses to others' pain.

Water-Soluble Cationic Eu3+-Metallopolymer with High Quantum Yield and Sensitivity for Intracellular Temperature Sensing.

Lanthanide-based (Ln3+) luminescent materials are ideal candidates for use in fluorescence intracellular temperature sensing. However, it remains a great challenge to obtain a Ln3+-ratiometric fluorescence thermometer with high sensitivity and quantum yield in an aqueous environment. Herein, a cationic Eu3+-metallopolymer was synthesized via the coordination of Eu(TTA)3·2H2O with an AIE active amphipathic polymer backbone that contains APTMA ((3-acrylamidopropyl) trimethylammonium) and NIPAM (N-isopropylacrylamide) units, which can self-assemble into nanoparticles in water solution with APTMA and NIPAM as the hydrophilic shell. This polymer exhibited highly efficient dual-emissive white-light emission (Φ = 34.3%). Particularly, when the temperature rises, the NIPAM units will transform from hydrophilic to hydrophobic in the spherical core of the nanoparticle, while the VTPE units are moved from inside the nanoparticle to the shell, activating its nonradiative transition channel and thereby decreasing its energy transfer to Eu3+ centers, endowing the Eu3+-metallopolymer with an extremely high temperature sensing sensitivity within the physiological temperature range. Finally, the real-time monitoring of the intracellular temperature variation is further conducted.

Effect of Butylphthalide Capsules on Smac and XIAP Expression in Rats after Ischemia Reperfusion.

INTRODUCTION: Little is known about the protective effects of butylphthalide on cerebral ischemia-reperfusion injury. This study aims to investigate the impact on the second mitochondrial-derived activator of Caspases (Smac) and X-linked inhibitor of apoptosis protein (XIAP) expression in the ischemic semidark area using a rat model of carotid artery stenosis. METHODS: Thirty Sprague-Dawley rats were randomly divided into the sham-operated group, carotid stenosis model controls, low-dose (20 mg/kg), medium-dose (40 mg/kg), and high-dose (80 mg/kg) butylphthalide groups. The neurological function was scored by the balance beam test (BBT). The morphological changes of brain tissue were detected by Hematoxylin-eosin (HE) staining, with apoptosis detected by Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling (TUNEL) staining. Smac and XIAP protein expression were detected by immunohistochemistry (IHC). The expressions of Smac and XIAP mRNA were detected by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: HE showed that neuronal loss, nuclear consolidation, and vacuolar degeneration were significantly reduced in the medium and high-dose butylphthalide groups compared with the model controls. The BBT scores and apoptotic index were significantly lower in the medium and high doses of butylphthalide compared with the model controls. RT-qPCR and IHC showed that Smac, XIAP mRNA and protein expressions in the ischemic hemispheric region were significantly reduced in low, medium, and high doses of butylphthalide compared with the model controls (P < 0.05), showing some concentration effect. CONCLUSIONS: Butylphthalide can significantly reduce Smac and XIAP mRNA and protein expression, inhibit neuronal apoptosis induced by ischemia-reperfusion injury in rats with carotid stenosis, and exert neuroprotective effects.

STIM1-regulated exosomal EBV-LMP1 empowers endothelial cells with an aggressive phenotype by activating the Akt/ERK pathway in nasopharyngeal carcinoma.

BACKGROUND: Stromal interaction molecule 1 (STIM1)-mediated Ca2+ signaling regulates tumor angiogenesis in nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-related human malignancy. However, the mechanism by which STIM1 modulates endothelial functional phenotypes contributing to tumor angiogenesis remains elusive. METHODS: NPC cell-derived exosomes were isolated via differential centrifugation and observed using transmission electron microscopy. Exosome particle sizes were assessed by nanoparticle tracking analysis (NTA). Uptake of exosomes by recipient ECs was detected by fluorescent labeling of the exosomes with PKH26. Tumor angiogenesis-associated profiles were characterized by determining cell proliferation, migration, tubulogenesis and permeability in human umbilical vein endothelial cells (HUVECs). Activation of the Akt/ERK pathway was assessed by detecting the phosphorylation levels using Western blotting. A chick embryo chorioallantoic membrane (CAM) xenograft model was employed to study tumor-associated neovascularization in vivo. RESULTS: We found that NPC cell-derived exosomes harboring EBV-encoded latent membrane protein 1 (LMP1) promoted proliferation, migration, tubulogenesis and permeability by activating the Akt/ERK pathway in ECs. STIM1 silencing reduced LMP1 enrichment in NPC cell-derived exosomes, thereby reversing its pro-oncogenic effects in an Akt/ERK pathway-dependent manner. Furthermore, STIM1 knockdown in NPC cells blunted tumor-induced vascular network formation and inhibited intra-tumor neovascularization in the chorioallantoic membrane (CAM) xenograft model. CONCLUSION: STIM1 regulates tumor angiogenesis by controlling exosomal EBV-LMP1 delivery to ECs in the NPC tumor microenvironment. Blocking exosome-mediated cell-to-cell horizontal transfer of EBV-associated oncogenic signaling molecules may be an effective therapeutic strategy for NPC.

Eyes-Open and Eyes-Closed Resting State Network Connectivity Differences.

Resting state networks comprise several brain regions that exhibit complex patterns of interaction. Switching from eyes closed (EC) to eyes open (EO) during the resting state modifies these patterns of connectivity, but precisely how these change remains unclear. Here we use functional magnetic resonance imaging to scan healthy participants in two resting conditions (viz., EC and EO). Seven resting state networks were chosen for this study: salience network (SN), default mode network (DMN), central executive network (CEN), dorsal attention network (DAN), visual network (VN), motor network (MN) and auditory network (AN). We performed functional connectivity (FC) analysis for each network, comparing the FC maps for both EC and EO. Our results show increased connectivity between most networks during EC relative to EO, thereby suggesting enhanced integration during EC and greater modularity or specialization during EO. Among these networks, SN is distinctive: during the transition from EO to EC it evinces increased connectivity with DMN and decreased connectivity with VN. This change might imply that SN functions in a manner analogous to a circuit switch, modulating resting state relations with DMN and VN, when transitioning between EO and EC.

The miRNA-185-5p/STIM1 Axis Regulates the Invasiveness of Nasopharyngeal Carcinoma Cell Lines by Modulating EGFR Activation-Stimulated Switch from E- to N-Cadherin.

Distant metastasis remains the primary cause of treatment failure and suggests a poor prognosis in nasopharyngeal carcinoma (NPC). Epithelial-mesenchymal transition (EMT) is a critical cellular process for initiating a tumor invasion and remote metastasis. Our previous study showed that the blockage of the stromal interaction molecule 1 (STIM1)-mediated Ca2+ signaling blunts the Epstein-Barr virus (EBV)-promoted cell migration and inhibits the dissemination and lymphatic metastasis of NPC cells. However, the upstream signaling pathway that regulates the STIM1 expression remains unknown. In this follow-up study, we demonstrated that the miRNA-185-5p/STIM1 axis is implicated in the regulation of the metastatic potential of 5-8F cells, a highly invasive NPC cell line. We demonstrate that the knockdown of STIM1 attenuates the migration ability of 5-8F cells by inhibiting the epidermal growth factor receptor (EGFR) phosphorylation-induced switch from E- to N-cadherin in vitro. In addition, the STIM1 knockdown inhibited the locoregional lymphatic invasion of the 5-8F cells in mice. Furthermore, we identified miRNA-185-5p as an upstream regulator that negatively regulates the expression of STIM1. Our findings suggest that the miRNA-185-5p/STIM1 axis regulates the invasiveness of NPC cell lines by affecting the EGFR activation-modulated cell adhesiveness. The miRNA-185-5p/STIM1 axis may serve as a potentially effective therapeutic target for the treatment of NPC.

Decoding subject's own name in the primary auditory cortex.

Current studies have shown that perception of subject's own name (SON) involves multiple multimodal brain regions, while activities in unimodal sensory regions (i.e., primary auditory cortex) and their interaction with multimodal regions during the self-processing remain unclear. To answer this, we combined multivariate pattern analysis and dynamic causal modelling analysis to explore the regional activation pattern and inter-region effective connection during the perception of SON. We found that SON and other names could be decoded from the activation pattern in the primary auditory cortex. In addition, we found an excitatory effect of SON on connections from the anterior insula/inferior frontal gyrus to the primary auditory cortex, and to the temporoparietal junction. Our findings extended the current knowledge of self-processing by showing that primary auditory cortex could discriminate SON from other names. Furthermore, our findings highlighted the importance of influence of the insula on the primary auditory cortex during self-processing.

Role of 18F-FDG PET/CT in patients affected by pulmonary primary lymphoma.

Background: Primary pulmonary lymphoma (PPL) is defined as clonal abnormal hyperplasia of lung parenchyma or bronchial lymphoid tissue originating from bronchial mucosal tissue. However, PPL is rare, which accounts for approximately 3-4% of extraneurotic lymphomas and 0.5-1% of all primary tumors in the lung. Owing to the lack of any typical clinical symptoms and radiological features, it is challenging to accurately diagnose PPL, which affects its clinical management and prognosis. Considering this, herein, we aim to raise awareness of this disease and help physicians understand the role of 18F-FDG PET/CT in the diagnosis of PPL. Method: A retrospective analysis was performed on the clinical and 18F-FDG PET/CT imaging data of 19 patients diagnosed with PPL by biopsy pathology at our hospital from April 2014 to December 2021. Results: Of the 19 PPL patients, 15 patients showed clinical symptoms with the most common being fever and cough. In addition, there were 4 cases that had no clinical symptoms, and all of them were MALT lymphoma. In fact, 16 patients were misdiagnosed as lobar pneumonia, lung cancer, tuberculosis, and diffuse interstitial inflammation, representing a misdiagnosis rate of 84.2%. Also, 73.7% were MALT lymphomas, representing the most common pathological pattern, along with 3 DLBCL and 2 T-cell lymphomas. With reguard to CT signs, the air-bronchial sign was found to be the most common, followed by the halo sign and the collapsed leaf sign. On the basis of the predominant radiologic features, lesions were categorized as pneumonic consolidation, nodular/mass type, diffuse interstitial type, and mixed type. The average SUVmax of lesions was 7.23 ± 4.75, the ratio of SUVmax (lesion/liver) was 3.46 ± 2.25, and the ratio of SUVmax (lesion/mediastinal blood pool) was found to be 5.25 ± 3.27. Of interest, the different pathological types of PPL showed different values of 18F-FDG uptake. The 18F-FDG uptake of DLCBL was the most prominent with a SUVmax of 15.33 ± 6.30 and was higher than that of MALT lymphoma with a SUVmax of 5.74 ± 2.65. There appeared similarity in 18F-FDG uptake between MALT lymphoma and T-cell lymphoma. For the SUVmax of lesion, we found statistical significance between MALT lymphoma and DLCBL (P value<0.001). In addition, we also found statistical significance (P value < 0.05) in SUVmax of lesions between pneumonic consolidation type and nodal/mass type, I stage, and other stages. Conclusions: On 18F-FDG PET/CT images, certain features of PPL morphology and metabolism can be identified that may contribute to a better understanding of this disease. In addition, 18F-FDG PET/CT whole-body imaging has the potential to refine the staging of PPL. Most importantly, functional 18F-FDG PET/CT imaging can readily reflect tumor cell activity, thus allowing for the selection of an optimal biopsy site.

Nasopharyngeal Carcinoma Progression: Accumulating Genomic Instability and Persistent Epstein-Barr Virus Infection.

Genomic instability facilitates the evolution of cells, tissues, organs, and species. The progression of human malignancies can be regarded as the accumulation of genomic instability, which confers a high evolutionary potential for tumor cells to adapt to continuous changes in the tumor microenvironment. Nasopharyngeal carcinoma (NPC) is a head-and-neck squamous-cell carcinoma closely associated with Epstein-Barr virus (EBV) infection. NPC progression is driven by a combination of accumulated genomic instability and persistent EBV infection. Here, we present a review of the key characteristics of genomic instability in NPC and the profound implications of EBV infection. We further discuss the significance of profiling genomic instability for the assessment of disease progression and treatment efficacy, as well as the opportunities and challenges of targeted therapies for NPC based on its unique genomic instability.

A Study on the Molecular Mechanism of High Altitude Heart Disease in Children.

Objective: High altitude heart disease (HAHD) is a common pediatric disease in high altitude areas. It usually occurs in people who have lived for a long time or have lived for more than 2500m above sea level. Its common inducement is respiratory tract infection. The clinical differential diagnosis is difficult because the symptoms of HAHD are similar to those of congenital heart disease; Due to the limitation of medical conditions, many patients are in the state of losing follow-up or not seeking medical treatment, resulting in poor prognosis of HAHD and becoming a high-altitude disease with high mortality. Clarifying the molecular mechanism of HAHD, developing early molecular screening technology and accurate treatment methods of HAHD are the key to improve the ability of prevention and treatment of HAHD. Methods: First, the literature in the PubMed and CNKI databases were screened based on keywords and abstracts. Then, the literature for the study was identified based on the fitness between the content of the literature, the research objectives, and the timeliness of the literature. Finally, a systematic molecular mechanism of HAHD was established by investigating the literature and sorting out the genetic adaptations of Tibetan populations compared with low-altitude populations that migrated to the plateau. Results: With the investigation of the 48 papers screened, it was found that genes capable of enhancing the hypoxic ventilatory response and resistance to pulmonary hypertension were all correlated with the hypoxia-inducible factor (HIF) pathway, consisting mainly of three pathways, HIF-1α, HIF-2α, and NO. Conclusion: The low prevalence of HAHD in Tibetan aboriginal children was mainly due to the genetic adaptation of the Tibetan population to the high altitude environment, which coordinated the cellular response to hypoxia by regulating the downstream hypoxia control genes in the HIF pathway.

Exosome-mediated remodeling of the tumor microenvironment: From local to distant intercellular communication.

Extracellular vesicles (EVs) are membrane-enveloped nanoscale particles that carry various bioactive signaling molecules secreted by cells. Their biological roles depend on the original cell type from which they are derived and their inclusions. Exosomes, a class of EVs, are released by almost all eukaryotic cell types, including tumor cells. Tumor cell-derived exosomes mediate signal transduction between tumor cells and surrounding non-tumor cells. This intercellular communication actively contributes to the remodeling of the tumor microenvironment (TME) to enable tumor growth, invasion, and metastasis. This review summarizes the latest progress in the exploration of exosome-mediated cell-cell communication implicated in TME remodeling and underlying mechanisms. We focus on the role of cell-cell interactions mediated by tumor cell-derived exosomes in promoting invasion and metastasis, and their potential as a therapeutic intervention target against distant metastasis. We also discuss the clinical translational significance of tumor-derived exosomes for early diagnosis, efficacy and progression evaluations.

Generating Pure Spin Current in Heterojunction Organic Solar Cells.

We propose a mechanism for generating pure spin current in heterojunction organic solar cells, with the donor and acceptor both being degenerate ground-state polymers; thus, solitons can be formed. This mechanism contains the following steps: (i) the donor is photoexcited to create the electron-hole (e-h) pairs; (ii) the excited electrons are transferred to the acceptor; (iii) the net charges in the donor and acceptor are evolved into the localized charged solitons; (iv) the intermolecule bias is applied to drive the transferred electrons back to donor, and concomitantly, charged solitons are converted to neutral solitons. Here, the on-site Coulomb interaction plays an important role in ensuring the neutral solitons' spins in the donor and acceptor are oppositely polarized. Because spins are separated between the donor and acceptor without any charge separations, pure spin current can be formed. Our mechanism opens a new avenue for exploring potential organic spintronic devices.

Why ultrafast charge separation occurs in bulk-heterojunction organic solar cells: a multichain tight binding model study.

Bulk-heterojunction (BHJ) organic solar cells (OSCs) exhibit ultrafast charge separation (UCS) which enables lower geminate charge recombination and high internal quantum efficiency. Unravelling why UCS occurs in BHJ-OSCs is important for the exploration of devices in future, however it is still far from clear. In this work, we build a multichain tight-binding model to study the conditions for realizing UCS. We propose that two conditions are important: (i) the BHJ-OSC has a morphology with donor and acceptor molecules being individually aggregated; (ii) the ratio of the donor/acceptor interfacial coupling to the internal donor/donor and acceptor/acceptor coupling should be smaller than a threshold. In addition, we suggest that increasing the donor/acceptor energetic offset will boost the UCS efficiency. As a fundamental theoretical analysis on the underlying mechanism of UCS, our work provides design rules for optimizing high-performance BHJ OSCs.

Single-cell RNA sequencing of peripheral blood mononuclear cells from acute Kawasaki disease patients.

Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. Although functional and phenotypic changes of immune cells have been reported, a global understanding of immune responses underlying acute KD is unclear. Here, using single-cell RNA sequencing, we profile peripheral blood mononuclear cells from seven patients with acute KD before and after intravenous immunoglobulin therapy and from three age-matched healthy controls. The most differentially expressed genes are identified in monocytes, with high expression of pro-inflammatory mediators, immunoglobulin receptors and low expression of MHC class II genes in acute KD. Single-cell RNA sequencing and flow cytometry analyses, of cells from an additional 16 KD patients, show that although the percentage of total B cells is substantially decreased after therapy, the percentage of plasma cells among the B cells is significantly increased. The percentage of CD8+ T cells is decreased in acute KD, notably effector memory CD8+ T cells compared with healthy controls. Oligoclonal expansions of both B cell receptors and T cell receptors are observed after therapy. We identify biological processes potentially underlying the changes of each cell type. The single-cell landscape of both innate and adaptive immune responses provides insights into pathogenesis and therapy of KD.

Effects of carbamazepine and sodium valproate on efficacy, cognitive function and uric acid in epileptic patients with first generalized seizure.

OBJECTIVE: To investigate the effects of carbamazepine and sodium valproate on efficacy, cognitive function and uric acid in epileptic patients with first generalized seizure. METHODS: 120 epilepsy patients with first generalized seizure who admitted to our hospital from March 2017 to March 2019, were selected and randomly divided into carbamazepine-group and sodium valproate-group, with 60 objects in each group. Both groups of patients received medication for one year. Subsequently, the changes in clinical efficacy, cognitive function, and blood uric acid of the two groups of patients 1 year after treatment were compared, and the correlation between blood uric acid and cognitive function was analyzed between the two groups. RESULTS: The two groups had statistically insignificant difference in the total effective rate (P>0.05). The cognitive function scores of the two groups after 6 months and 1 year of treatment were critically higher than those before treatment (P<0.05), and the comparison of cognitive function and blood uric acid degree between groups before treatment, 6 months after treatment and 1 year after treatment had statistically insignificant difference (P>0.05). There was a significant positive correlation between Mini-mental State Examination (MMSE) score of cognitive function and level of blood uric acid in patients with epilepsy (r=0.279, P=0.012). CONCLUSION: Both carbamazepine and valproate can effectively improve the cognitive function of patients with first generalized seizure, and the two medications have similar clinical efficacy. Patient's blood uric acid level increases after treatment, and there is a affirmative relationship between blood uric acid level and cognitive function of patients.

The Impact of Family Care for the Elderly on Women's Employment from the Perspective of Bargaining Power.

Due to the wishes of the elderly and the traditional family culture in China, family care is the main way of providing for the aged, and women's care is the main way. This is not conducive to the protection of women's employment rights and the realization of self-worth under the background of increasing women's autonomy. Based on the latest data of the China Health and Nutrition Survey Database (CHNS), this paper uses ordinary least squares (OLS) and the instrumental variable method of control endogeneity to analyze the influence of family care activities on the labor participation rate of married women. The innovation of this paper is to introduce family bargaining power into this kind of model for the first time, and further analyze the heterogeneity from the perspective of bargaining power differences. The empirical results show that the family elderly care activities have an obstacle effect on married women's participation in employment, and the family members with strong bargaining power will significantly hinder employment, so this paper puts forward policy recommendations in line with the actual situation, hoping to provide theoretical support for the improvement of the social security system for the elderly.

Effects of Different Degrees of Carotid Artery Stenosis on the Expression of XIAP and Smac in the Ischemic Penumbra of Rats with Cerebral Ischemia-Reperfusion.

OBJECTIVE: To investigate the effects of different degrees of carotid artery stenosis (CAS) on the expression of XIAP and Smac in ischemic penumbra of rats with cerebral ischemia-reperfusion (I/R). MATERIALS AND METHODS: Samples were collected at 12 h and 24 h after reperfusion, and then the treated groups were divided into the NC-12 group, NC-24 group, MIS-12 group, MIS-24 group, MOS-12 group, MOS-24 group, SES-12 group and SES-24 group. HE staining was used to observe the pathological changes of the brain tissue. TUNEL assay was used to detect the apoptosis in the ischemic penumbra. IHC and RT-qPCR were used to detect the expression of XIAP and Smac in the brain tissue. RESULTS: By observing the pathological sections of brain tissue, the rats in MIS, MOS and SES groups showed loose brain tissue on the infarcted side and neuronal pyknosis in the ischemic penumbra. And with the aggravation and prolongation of the degree of stenosis, the degree of brain injury deepened. It was further found that the TUNEL positive rate was significantly increased in the ischemic penumbra in the SES and MOS groups compared with that in the normal control (NC) group. The results of IHC and RT-qPCR showed that the mRNA expression of XIAP and Smac in the ischemic penumbra was significantly up-regulated in the MIS, MOS and SES groups compared with that in the NC group. CONCLUSIONS: CAS may activate XIAP/Smac signaling pathway to induce neuronal apoptosis and promote the injury in the ischemic penumbra caused by cerebral I/R.