Role of NLRP3 inflammasome in central nervous system diseases.

The central nervous system (CNS) is the most delicate system in human body, with the most complex structure and function. It is vulnerable to trauma, infection, neurodegeneration and autoimmune diseases, and activates the immune system. An appropriate inflammatory response contributes to defence against invading microbes, whereas an excessive inflammatory response can aggravate tissue damage. The NLRP3 inflammasome was the first one studied in the brain. Once primed and activated, it completes the assembly of inflammasome (sensor NLRP3, adaptor ASC, and effector caspase-1), leading to caspase-1 activation and increased release of downstream inflammatory cytokines, as well as to pyroptosis. Cumulative studies have confirmed that NLRP3 plays an important role in regulating innate immunity and autoimmune diseases, and its inhibitors have shown good efficacy in animal models of various inflammatory diseases. In this review, we will briefly discuss the biological characteristics of NLRP3 inflammasome, summarize the recent advances and clinical impact of the NLRP3 inflammasome in infectious, inflammatory, immune, degenerative, genetic, and vascular diseases of CNS, and discuss the potential and challenges of NLRP3 as a therapeutic target for CNS diseases.

Season, household registry and isolated birth defects: a population-based case-control study in Danyang, China.

BACKGROUND: A birth population-based study was conducted in Danyang, Jiangsu Province, to evaluate major birth defects in emerging regions in China with similar maternal and neonatal care conditions. METHODS: We conducted a population-based study in a cohort of infants born in Danyang from 2014 to 2021, including 55 709 perinatal infants. Four categories of isolated birth defects were defined as cases: congenital heart defects (CHDs; n=2138), polydactyly (n=145), cleft lip with or without palate (CL/P; n=76) and accessory auricles (n=93). Infants with congenital malformations were identified by the Chinese Birth Defects Monitoring Network. RESULTS: Compared with autumn, conception in spring (OR=1.31 [1.16-1.48]) and winter (OR=1.39 [1.23-1.58]) was associated with an increased risk of CHD. Increased risk of CHD, CL/P and accessory auricles was significantly associated with non-local registered residence (OR=1.17 [1.07-1.28], OR=2.73 [1.52-4.88] and OR=2.11 [1.20-3.71], respectively). Individuals of Han nationality were less likely to have polydactyly (OR=0.23 [0.05-0.98]). CONCLUSIONS: The season of pregnancy was significantly associated with CHDs. Offspring of mothers with non-local registered hometown had greater risks of CHDs, CL/P and accessory auricles.

Polyimide Films Based on ß-Cyclodextrin Polyrotaxane with Low Dielectric and Excellent Comprehensive Performance.

In order to prepare polyimide (PI) films with a low dielectric constant and excellent comprehensive performance, a two-step method was employed in this study to integrate ß-cyclodextrin into a semi-aromatic fluorine-containing polyimide ternary system. By introducing trifluoromethyl groups to reduce the dielectric constant, the dielectric constant was further reduced to 2.55 at 10 MHz. Simultaneously, the film exhibited noteworthy thermal stability (a glass transition temperature exceeding 300 °C) and a high coefficient of thermal expansion. The material also demonstrated outstanding mechanical properties, boasting a strength of 122 MPa and a modulus of 2.2 GPa, along with high optical transparency (transmittance reaching up to 89% at 450 nm). Moreover, the inherent high transparency of colorless polyimide (CPI) combined with good stretchability contributed to the attainment of a low dielectric constant. This strategic approach not only opens up new opportunities for novel electroactive polymers but also holds potential applications in flexible displays, circuit printing, and chip packaging.

Alterations of DNA methylation profile in peripheral blood of children with simple obesity.

Purpose: To investigate the association between DNA methylation and childhood simple obesity. Methods: Genome-wide analysis of DNA methylation was conducted on peripheral blood samples from 41 children with simple obesity and 31 normal controls to identify differentially methylated sites (DMS). Subsequently, gene functional analysis of differentially methylated genes (DMGs) was carried out. After screening the characteristic DMGs based on specific conditions, the methylated levels of these DMS were evaluated and verified by pyrosequencing. Receiver operating characteristic (ROC) curve analysis assessed the predictive efficacy of corresponding DMGs. Finally, Pearson correlation analysis revealed the correlation between specific DMS and clinical data. Results: The overall DNA methylation level in the obesity group was significantly lower than in normal. A total of 241 DMS were identified. Functional pathway analysis revealed that DMGs were primarily involved in lipid metabolism, carbohydrate metabolism, amino acid metabolism, human diseases, among other pathways. The characteristic DMS within the genes Transcription factor A mitochondrial (TFAM) and Piezo type mechanosensitive ion channel component 1(PIEZO1) were recognized as CpG-cg05831083 and CpG-cg14926485, respectively. Furthermore, the methylation level of CpG-cg05831083 significantly correlated with body mass index (BMI) and vitamin D. Conclusions: Abnormal DNA methylation is closely related to childhood simple obesity. The altered methylation of CpG-cg05831083 and CpG-cg14926485 could potentially serve as biomarkers for childhood simple obesity. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-024-00275-w.

A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Immune checkpoint inhibitors (ICIs) have been widely used to treat various tumors and have changed the landscape of tumor management, but the data from real-world studies of ICIs for TNBC treatment remain limited. The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real-world setting and to explore possible correlates. Methods: The clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army (PLA) General Hospital were collected. Treatment responses, outcomes and adverse events (AEs) were assessed. Results: Eighty-one patients were included in the study. The confirmed objective response rate (ORR) was 32.1%, and the disease control rate (DCR) was 64.2%. The median progression-free survival (PFS) was 4.2 months, and the median overall survival (OS) was 11.0 months. PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later-line ICIs and higher levels of inflammation; specifically, patients with higher TILs had longer PFS. Overall AEs were tolerable. Conclusions: ICIs are effective in the treatment of advanced TNBC, and the adverse reactions are tolerable. A panel of biomarkers including LDH, ALP, and bNLR were identified to predict the efficacies of ICIs in TNBC treatment.

Evaluation of the in vitro performance of generic and original adapalene gel.

OBJECTIVE: The aim was to evaluate the difference of the in vitro behavior between the commercially available generic adapalene gel and original product with Topical Classification System (TCS), and to analyze the effect of changes of excipients on the release behavior. SIGNIFICANCE: Establishing in vitro performance assays to understand the impact of formulation variables on the critical quality attributes (CQA) is critical for the quality assessment of semi-solid generic drug. METHODS: In vitro release (IVR), in vitro permeation (IVP), viscosity, and pH measurement methods for adapalene gels were established and validated. The differences between generic adapalene gel from 7 companies and original products were evaluated by correlation analysis (CA) and principal component analysis (PCA), and the relationship among 4 parameters was elucidated. The effect of excipients on the above variables was examined by univariate tests. RESULTS: There were some differences between the gels of 5 of the 7 imitation enterprises and reference listed drug (RLD). There were varying degrees of correlation between viscosity, pH, the adapalene amount retained in skin and release rate. The result validated the key role of IVR, and identified that pH value, type of suspending agent, the amount of carbomer, etc. had certain effects on the release rate. CONCLUSIONS: The factors mentioned above should be considered when developing and manufacturing generic adapalene gels, and the application of TCS in the evaluation of generic topical drugs was advanced. Additionally, our research revealed some discrepancies from USP<1724>, which could be valuable information for the revision.

Quercetin Attenuates Atherosclerosis via Modulating Apelin Signaling Pathway Based on Plasma Metabolomics.

OBJECTIVE: To interpret the pharmacology of quercetin in treatment of atherosclerosis (AS). METHODS: Fourteen apolipoprotein E-deficient (ApoE-/-) mice were divided into 2 groups by a random number table: an AS model (ApoE-/-) group and a quercetin treatment group (7 in each). Seven age-matched C57 mice were used as controls (n=7). Quercetin [20 mg/(kg·d)] was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic evaluation. Besides morphological observation, the distribution of CD11b, F4/80, sirtuin 1 (Sirt1) and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue senescence. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MSC/MS) was performed to study the pharmacology of quercetin against AS. Then, simultaneous administration of an apelin receptor antagonist (ML221) with quercetin was conducted to verify the possible targets of quercetin. Key proteins in apelin signaling pathway, such as angiotensin domain type 1 receptor-associated proteins (APJ), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), tissue plasminogen activator (TPA), uncoupling protein 1 (UCP1) and angiotensin II receptor 1 (AT1R), were assayed by Western blot. RESULTS: Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE-/- aortas in vivo. Quercetin decreased the densities of CD11b, F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE-/- mice (all P<0.05). Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty acyls. Bioinformatics analysis suggested that the apelin signaling pathway was one of the main pathways. Quercetin treatment increased the protein expressions of APJ, AMPK, PGC-1α, TPA and UCP1, while decreased the AT1R level (all P<0.05). After the apelin pathway was blocked by ML221, the effect of quercetin was abated significantly, confirming that quercetin attenuated AS by modulating the apelin signaling pathway (all P<0.05). CONCLUSION: Quercetin alleviated AS lesions by up-regulation the apelin signaling pathway.

Effect of a two-phase tobacco control regulation on incidence from ischemic stroke and hemorrhagic stroke, Shenzhen, China, 2007-2016.

INTRODUCTION: The Shenzhen government is widely considered to be most efficiently implementing smoke-free legislation in China. We evaluated and compared the impact of Shenzhen's two-phase smoke-free regulation on the incidence rates for ischemic and hemorrhagic stroke. METHODS: An interrupted time series design was used to capture immediate and annual incidence changes from 2007 to 2016 for both ischemic and hemorrhagic stroke due to two-phase smoke-free regulation in Shenzhen, China, by using a generalized additive model. The first phase, implemented on 9 March 2010, required five main public places to be smoke-free. In the second phase, the comprehensive law was expanded to the whole city on 1 March 2014. RESULTS: The regulation implementation during phase I was associated with a strong immediate decline in the incidence rate of ischemic stroke (-14.2%, 95% CI: -19.6 - -8.4) and hemorrhagic stroke (-10.1%, 95% CI: -18.2 - -1.2), but without showing the annual changes (p>0.05). Following the implementation of the comprehensive law, the gradual annual effect showed a significant change in ischemic stroke, with a 6.3% (95% CI: 8.9 - -3.6) reduction. Neither the immediate nor gradual decreases in hemorrhagic stroke incidences associated with the comprehensive regulation were statistically significant during phase II (p>0.05). Subgroup analyses indicate that a much larger health effect of the regulation during phase I was greater among those aged ≥65 years than among those aged 35-64 years. CONCLUSIONS: Shenzhen's two-phase smoke-free regulation was well implemented. Even though the regulation did not extend to the whole city, the immediate health benefits on the incidence rates of ischemic stroke and hemorrhagic stroke could be seen. However, the health benefits brought by the implementation of comprehensive smoke-free legislation were attenuated by previous smoke-free regulations in five main public places, which were more evident in hemorrhagic stroke.

A Generic Interactive Membership Function for Categorization of Quantities.

The membership function is to categorize quantities along with a confidence degree. This article investigates a generic user interaction based on this function for categorizing various types of quantities without modification, which empowers users to articulate uncertainty categorization and enhance their visual data analysis significantly. We present the technique design and an online prototype, supplementing with insights from three case studies that highlight the technique's efficacy among different types of quantities. Furthermore, we conduct a formal user study to scrutinize the process and reasoning users employ while utilizing our technique. The findings indicate that our technique can help users create customized categories. Both our code and the interactive prototype are made available as open-source resources, intended for application across varied domains as a generic tool.

Could tumour volume and major and minor axis based on CTA statistical anatomy improve the pre-operative T-stage in oesophageal cancer?

OBJECTIVES: To statistically study the 3D shape of oesophageal cancer (EC) and its spatial relationships based on computed tomography angiography (CTA) 3D reconstruction, to determine its relationship with T-stages, and to create an optimal T-stage diagnosis protocol based on CTA calculation. METHODS: Pre-operative CTA images of 155 patients with EC were retrospectively collected and divided into four groups: T1-T4. We used Amira software to segment and 3D reconstruct the EC, oesophagus, aorta, pericardium and peripheral lymph nodes and measured their surface area, volume, major axis, minor axis, longitudinal length, roughness and relationship to the aorta of the EC. One-way ANOVA, independent sample t-test, ROC, etc., were performed and critical values between different T-stages were calculated. We also invited two radiologists to evaluate the measurements. RESULTS: There were no significant differences in EC longitudinal length, roughness score and relationship with the aorta between the different T-stages of EC. There were significant differences in EC surface area, EC volume and mean major and minor axis among the different T-stages. The volumes of the T1-T4 tumours were 12,934.36 ± 7739.25, 23,095.27 ± 14,975.67, 37,577.98 ± 36,085.64 and 58,579.25 ± 41,073.96 mm3 separately (p < 0.05), and the T1-T4 volume cut-off values were 11,712.00, 19,809.00 and 44,103.50 mm3 separately. For comparison with radiologists, the AUC value of our measurements was 0.704, which was higher than the radiologists of AUC = 0.630. CONCLUSIONS: EC volume, major and minor axis can be used as important factors for surgeons in the T-stage diagnosis of EC, which helps to improve prognosis and treatment decisions after CTA.

Iodine status and its association with prevalence of thyroid diseases in adults from Jiangxi Province, China.

BACKGROUND: Iodine is an essential element for the biosynthesis of thyroid-stimulating hormone (TSH). Both excessive and deficient iodine are major risk factors for thyroid diseases, including thyroid dysfunction, thyroid nodules, and thyroid autoimmunity (TAI). This study aimed to elucidate the relationship between iodine status and the prevalence of thyroid diseases through a national cross-sectional epidemiological survey in Jiangxi province (China). METHODS: This population-based, cross-sectional study enrolled 2636 Chinese local inhabitants who aged over 18 years old from April to August in 2015. Physical examination was performed and biochemical indices, urinary iodine concentration (UIC), and TSH level were measured. The Chi-square test, nonparametric test, and 4 multivariate logistic regression models adjusted for risk factors were applied to analysis. Spearman correlation coefficients were calculated to investigate the relationship between iodine intake level and the prevalence of thyroid diseases. RESULTS: The median UIC was 176.4 µg/L, and a significant difference was found in median UIC between men (182.45 µg/L) and women (169.25 µg/L) (P = 0.03). Among these study subjects, 14.4%, 44.5%, 26.1%, and 15.0% had deficient, adequate, more than adequate, and excessive iodine concentrations, respectively. The prevalence rates of hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, subclinical hypothyroidism, thyroid nodules, and TAI were 0.91%, 0.57%, 0.34% and 7.89%, 9.45%, and 12.7%, respectively. Significant differences were found in iodine status, waist circumstance, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), TSH, thyroid nodules, and TAI between men and women (P < 0.05). Compared with those with adequate UIC, subjects with excessive UIC had higher prevalence rates of thyroid dysfunction (odds ratio (OR) = 1.74, 95% confidence interval (CI): 1.40-2.54) and thyroid nodules (OR = 3.33, 95%CI 1.32-8.42). In addition, subjects with deficient and excessive UIC were at the higher risk of TAI compared with those with adequate UIC (OR = 1.68, 95%CI: 1.19-2.60; OR = 1.52, 95%CI: 1.04-2.96, respectively). UIC was positively correlated with the prevalence rates of thyroid nodules (r = -0.44, P < 0.01) and TAI (r = -0.055, P < 0.01). On the contrary, UIC was negatively correlated with the risk of thyroid dysfunction (r = -0.24, P > 0.05). CONCLUSION: Adult inhabitants from Jiangxi province in the TIDE study were in the adequate iodine status. Excessive iodine status was noted as a risk factor for thyroid dysfunction and thyroid nodules. In addition, both iodine deficiency and excessive iodine were risk factors for TAI.

Dynamic Crosslinked Injectable Mussel-Inspired Hydrogels with Adhesive, Self-Healing, and Biodegradation Properties.

The non-invasive tissue adhesives with strong tissue adhesion and good biocompatibility are ideal for replacing traditional wound treatment methods such as sutures and needles. The self-healing hydrogels based on dynamic reversible crosslinking can recover their structure and function after damage, which is suitable for the application scenario of tissue adhesives. Herein, inspired by mussel adhesive proteins, we propose a facile strategy to achieve an injectable hydrogel (DACS hydrogel) by grafting dopamine (DOPA) onto hyaluronic acid (HA) and mixing it with carboxymethyl chitosan (CMCS) solution. The gelation time and rheological and swelling properties of the hydrogel can be controlled conveniently by adjusting the substitution degree of the catechol group and the concentration of raw materials. More importantly, the hydrogel exhibited rapid and highly efficient self-healing ability and excellent biodegradation and biocompatibility in vitro. Meanwhile, the hydrogel exhibited ~4-fold enhanced wet tissue adhesion strength (21.41 kPa) over the commercial fibrin glue. This kind of HA-based mussel biomimetic self-healing hydrogel is expected to be used as a multifunctional tissue adhesive material.

PCNN Model Guided by Saliency Mechanism for Image Fusion in Transform Domain.

In heterogeneous image fusion problems, different imaging mechanisms have always existed between time-of-flight and visible light heterogeneous images which are collected by binocular acquisition systems in orchard environments. Determining how to enhance the fusion quality is key to the solution. A shortcoming of the pulse coupled neural network model is that parameters are limited by manual experience settings and cannot be terminated adaptively. The limitations are obvious during the ignition process, and include ignoring the impact of image changes and fluctuations on the results, pixel artifacts, area blurring, and the occurrence of unclear edges. Aiming at these problems, an image fusion method in a pulse coupled neural network transform domain guided by a saliency mechanism is proposed. A non-subsampled shearlet transform is used to decompose the accurately registered image; the time-of-flight low-frequency component, after multiple lighting segmentation using a pulse coupled neural network, is simplified to a first-order Markov situation. The significance function is defined as first-order Markov mutual information to measure the termination condition. A new momentum-driven multi-objective artificial bee colony algorithm is used to optimize the parameters of the link channel feedback term, link strength, and dynamic threshold attenuation factor. The low-frequency components of time-of-flight and color images, after multiple lighting segmentation using a pulse coupled neural network, are fused using the weighted average rule. The high-frequency components are fused using improved bilateral filters. The results show that the proposed algorithm has the best fusion effect on the time-of-flight confidence image and the corresponding visible light image collected in the natural scene, according to nine objective image evaluation indicators. It is suitable for the heterogeneous image fusion of complex orchard environments in natural landscapes.

Risk assessment of severe postpartum hemorrhage after invasive placenta accreta based on three-dimensional reconstruction of magnetic resonance imaging.

Background: The aim of this study was to investigate the significance and feasibility of risk assessments based on the three-dimensional (3D) reconstruction of magnetic resonance imaging (MRI) of invasive placenta accreta (IPA) to create individualized surgical protocols and perioperative management plans in late pregnancy. Methods: MRI and clinical data of 36 pregnant women with IPA admitted to Southwest Hospital from January 2017 to June 2021 were retrospectively analyzed. The patients were divided into the following 4 groups: peripartum hysterectomy (PH), abdominal aortic balloon block (AABB), PH with AABB, and nonsurgical treatment. Each group was then divided into severe and nonsevere postpartum hemorrhage subgroups based on postpartum hemorrhage volumes of not more than 2,000 mL and more than 2,000 mL, respectively. The uteri, placentas, IPA, and urinary bladders in each group were segmented and 3-dimensionally reconstructed using Amira 5.2.2 (Visage Imaging, Richmond, Australia) software, and their surface areas and volumes were calculated. A multifactorial unconditional logistic regression analysis was performed to evaluate the 3D morphological parameters of postpartum hemorrhage and calculate the optimal threshold. Results: The bleeding volume, IPA area, placental area:uterine area ratio, IPA area:placental area ratio, maximum depth of IPA, placental position score, IPA position score, and implantation volume were greater in the severe postpartum hemorrhage subgroup than in the nonsevere postpartum hemorrhage subgroup of all groups. In the multifactorial regression analysis, the areas under the receiver operating characteristic curve of the implantation area, implantation volume, maximum depth of implantation, and implantation area:placental area ratio exceeded 0.9 and correlated strongly with severe postpartum hemorrhage, while those of the uterine area, uterine volume, placental area, placental volume, and placental area:uterine area ratio were between 0.5 and 0.7 and correlated with severe postpartum hemorrhage. The threshold (cutoff values) determining severe postpartum hemorrhage were 20,286.25 mm2 of the implantation area, 0.01271 of the implantation area:placental area ratio, 15.03 mm of the maximum depth of implantation, and 46,846 mm3 of the implantation volume. Conclusions: The MRI 3D reconstruction of IPA and its adjacent structures can accurately display the location, anatomical morphology, and spatial relationship of IPA, which can be used to improve the accuracy of IPA diagnosis, predict postpartum hemorrhage, and provide optimized treatment decisions for obstetricians.

Enhanced liquidity of p62 droplets mediated by Smurf1 links Nrf2 activation and autophagy.

BACKGROUND: Macro-autophagy/Autophagy is an evolutionarily well-conserved recycling process to maintain the balance through precise spatiotemporal regulation. However, the regulatory mechanisms of biomolecular condensates by the key adaptor protein p62 via liquid-liquid phase separation (LLPS) remain obscure. RESULTS: In this study, we showed that E3 ligase Smurf1 enhanced Nrf2 activation and promoted autophagy by increasing p62 phase separation capability. Specifically, the Smurf1/p62 interaction improved the formation and material exchange of liquid droplets compared with p62 single puncta. Additionally, Smurf1 promoted the competitive binding of p62 with Keap1 to increase Nrf2 nuclear translocation in p62 Ser349 phosphorylation-dependent manner. Mechanistically, overexpressed Smurf1 increased the activation of mTORC1 (mechanistic target of rapamycin complex 1), in turn leading to p62 Ser349 phosphorylation. Nrf2 activation increased the mRNA levels of Smurf1, p62, and NBR1, further promoting the droplet liquidity to enhance oxidative stress response. Importantly, we showed that Smurf1 maintained cellular homeostasis by promoting cargo degradation through the p62/LC3 autophagic pathway. CONCLUSIONS: These findings revealed the complex interconnected role among Smurf1, p62/Nrf2/NBR1, and p62/LC3 axis in determining Nrf2 activation and subsequent clearance of condensates through LLPS mechanism.

Understanding the multi-modal affective expression of net language in computer-mediated communication.

The fast development of technology and the popularity and prevalence of social media are constantly changing people's way of living especially their communication patterns. Computer-mediated communication facilitates human contact. Meanwhile, net language becomes widely accepted by computer-mediated communicators. Originating from the text-based form, net language evolves into a multi-modal physical form with a combination of texts, symbols, emojis, pictures and other forms of messages. The multi-modality of net language gives rise to difficulties for hearers or readers of the computer-mediated communication to understand the hidden message due to the ambiguous and polysemic nature of symbols. To clarify hearer's understanding and ensure the smooth conduct of computer-mediated communication, the conceptual blending theory will be useful in processing the multi-modal net language. With a four-space network and three operation mechanism, the emergent meaning will be constructed.

The value of QT interval in differentiating vasovagal syncope from epilepsy in children.

BACKGROUND: Both vasovagal syncope (VVS) and epilepsy present with transient loss of consciousness and are often difficult to identify. Hence this study aimed to explore the value of QT interval in the differentiation of VVS and epilepsy in children. METHODS: One hundred thirteen children with unexplained transient loss of consciousness were selected. 56 children with VVS (VVS group), including 37 males and 19 females, the average age is 9.88 ± 2.55 years old. 57 children with epilepsy (epilepsy group), including 36 males and 21 females, the average age is 8.96 ± 2.67 years old. At the same time, the 60 healthy individuals (control group) were examined according to age and sex. The QT interval of 12-lead electrocardiogram in a basal state of three groups was measured and statistically analyzed by SPSS 24.0 software. RESULTS: Compared with the control group, (1) QTcmax, QTcmin and QTcd were significantly longer in VVS group (P < 0.05), QTmax and QTmin were significantly shorter in VVS group (P < 0.05), and there were no significant differences in QTd between the two groups (P > 0.05). (2) The QTmax and QTmin were significantly shorter in epilepsy group (P < 0.05), and there were no significant differences in QTd, QTcmax, QTcmin, QTcd between the two groups (P > 0.05). Compared with the epilepsy group, The QTcmax, QTcmin, QTcd were significantly longer in VVS group (P < 0.05), and there were no significant differences in QTd, QTmax, QTmin between the two groups (P > 0.05). When QTcmax > 479.84 ms, QTcmin > 398.90 ms and QTcd > 53.56 ms, the sensitivity and specificity of diagnosing VVS were 62.5% and 77.19%, 82.14% and 50.88%, 82.14% and 38.60% respectively. CONCLUSION: QTcmax, QTcmin and QTcd have certain value in differentiating VVS from epilepsy in children.

Neuroprotection of cannabidiol in epileptic rats: Gut microbiome and metabolome sequencing.

Aims: Epilepsy is a neurological disease occurring worldwide. Alterations in the gut microbial composition may be involved in the development of Epilepsy. The study aimed to investigate the effects of cannabidiol (CBD) on gut microbiota and the metabolic profile of epileptic rats. Materials and methods and results: A temporal lobe epilepsy rat model was established using Li-pilocarpine. CBD increased the incubation period and reduced the epileptic state in rats. Compared to epileptic rats, the M1/M2 ratio of microglia in the CBD group was significantly decreased. The expression of IL-1ß, IL-6, and TNF-α in the CBD group decreased, while IL-10, IL-4, and TGF-ß1 increased. 16S rDNA sequencing revealed that the ANOSIM index differed significantly between the groups. At the genus level, Helicobacter, Prevotellaceae_UCG-001, and Ruminococcaceae_UCG-005 were significantly reduced in the model group. CBD intervention attenuated the intervention effects of Li-pilocarpine. Roseburia, Eubacterium_xylanophilum_group, and Ruminococcus_2 were strongly positively correlated with proinflammatory cytokine levels. CBD reversed dysregulated metabolites, including glycerophosphocholine and 4-ethylbenzoic acid. Conclusion: CBD could alleviate the dysbiosis of gut microbiota and metabolic disorders of epileptic rats. CBD attenuated Epilepsy in rats might be related to gut microbial abundance and metabolite levels. Significance and impact of study: The study may provide a reliable scientific clue to explore the regulatory pathway of CBD in alleviating Epilepsy.

Smurf1 Suppression Enhances Temozolomide Chemosensitivity in Glioblastoma by Facilitating PTEN Nuclear Translocation.

The tumor suppressor PTEN mainly inhibits the PI3K/Akt pathway in the cytoplasm and maintains DNA stability in the nucleus. The status of PTEN remains therapeutic effectiveness for chemoresistance of the DNA alkylating agent temozolomide (TMZ) in glioblastoma (GB). However, the underlying mechanisms of PTEN's interconnected role in the cytoplasm and nucleus in TMZ resistance are still unclear. In this study, we report that TMZ-induced PTEN nuclear import depends on PTEN ubiquitylation modification by Smurf1. The Smurf1 suppression decreases the TMZ-induced PTEN nuclear translocation and enhances the DNA damage. In addition, Smurf1 degrades cytoplasmic PTEN K289E (the nuclear-import-deficient PTEN mutant) to activate the PI3K/Akt pathway under TMZ treatment. Altogether, Smurf1 interconnectedly promotes PTEN nuclear function (DNA repair) and cytoplasmic function (activation of PI3K/Akt pathway) to resist TMZ. These results provide a proof-of-concept demonstration for a potential strategy to overcome the TMZ resistance in PTEN wild-type GB patients by targeting Smurf1.

Construction and Verification of a Fibroblast-Related Prognostic Signature Model for Colon Cancer.

Traditionally, cancer-associated fibroblasts (CAFs), an essential component of tumor microenvironment, were exert a crucial part in colon cancer progression. In this study, single-cell RNA-sequencing (scRNA-seq) data from 23 and bulk RNA-seq data from 452 colon cancer patients were extracted from the GEO database and TCGA-COAD and GEO databases, respectively. From single-cell analysis, 825 differentially expressed genes (DEGs) in CAFs were identified between each pair of six newly defined CAFs, named enCAF, adCAF, vaCAF, meCAF, erCAF, and cyCAF. Cell communication analysis with the iTALK package showed communication relationship between CAFs, including cell autocrine, cytokine, and growth factor subtypes, such as receptor-ligand pairs of TNFSF14-LTBR, IL6-F3, and IL6-IL6ST. Herein, we demonstrated the presence and prognostic value of adCAF and erCAF in colon cancer based on CIBERSORTx, combining single-cell marker genes and transcriptomics data. The prognostic significance of the enCAF and erCAF has been indirectly proved by both the correlation analysis with macrophages and CAFs, and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) experiment based on 20 paired tumor samples. A prognostic model was constructed with 10 DEGs using the LASSO Cox regression method. The model was validated using two testing datasets, indicate a significant survival accuracy (p < 0.0025). Correlation analyses between clinical information, such as age, gender, tumor stage and tumor features (tumor purity and immune score), and risk scores revealed our CAF-related model's robustness and excellent performance. Cell infiltration analysis by xCell revealed that the interaction between CAFs and multiple non-specific immune cells such as macrophages and the dendritic cell was a vital factor affecting immune score and prognosis. Finally, we analyzed how common anti-cancer drugs, including camptothecin, docetaxel and bortezomib, and immunotherapy, such as anti-PD-1 treatment, could be different in low-risk and high-risk patients inferred from our CAF-related model. In conclusion, the study utilized refined colon cancer fibroblast subsets and established the prognostic effects from the interaction with nonspecific immune cell.