Remodelling of the translatome controls diet and its impact on tumorigenesis.

Fasting is associated with a range of health benefits1-6. How fasting signals elicit changes in the proteome to establish metabolic programmes remains poorly understood. Here we show that hepatocytes selectively remodel the translatome while global translation is paradoxically downregulated during fasting7,8. We discover that phosphorylation of eukaryotic translation initiation factor 4E (P-eIF4E) is induced during fasting. We show that P-eIF4E is responsible for controlling the translation of genes involved in lipid catabolism and the production of ketone bodies. Inhibiting P-eIF4E impairs ketogenesis in response to fasting and a ketogenic diet. P-eIF4E regulates those messenger RNAs through a specific translation regulatory element within their 5' untranslated regions (5' UTRs). Our findings reveal a new signalling property of fatty acids, which are elevated during fasting. We found that fatty acids bind and induce AMP-activated protein kinase (AMPK) kinase activity that in turn enhances the phosphorylation of MAP kinase-interacting protein kinase (MNK), the kinase that phosphorylates eIF4E. The AMPK-MNK-eIF4E axis controls ketogenesis, revealing a new lipid-mediated kinase signalling pathway that links ketogenesis to translation control. Certain types of cancer use ketone bodies as an energy source9,10 that may rely on P-eIF4E. Our findings reveal that on a ketogenic diet, treatment with eFT508 (also known as tomivosertib; a P-eIF4E inhibitor) restrains pancreatic tumour growth. Thus, our findings unveil a new fatty acid-induced signalling pathway that activates selective translation, which underlies ketogenesis and provides a tailored diet intervention therapy for cancer.

α-lipoic acid ameliorates consequences of copper overload by up-regulating selenoproteins and decreasing redox misbalance.

α-lipoic acid (LA) is an essential cofactor for mitochondrial dehydrogenases and is required for cell growth, metabolic fuel production, and antioxidant defense. In vitro, LA binds copper (Cu) with high affinity and as an endogenous membrane permeable metabolite could be advantageous in mitigating the consequences of Cu overload in human diseases. We tested this hypothesis in 3T3-L1 preadipocytes with inactivated Cu transporter Atp7a; these cells accumulate Cu and show morphologic changes and mitochondria impairment. Treatment with LA corrected the morphology of Atp7a-/- cells similar to the Cu chelator bathocuproinedisulfonate (BCS) and improved mitochondria function; however, the mechanisms of LA and BCS action were different. Unlike BCS, LA did not decrease intracellular Cu but instead increased selenium levels that were low in Atp7a-/- cells. Proteome analysis confirmed distinct cell responses to these compounds and identified upregulation of selenoproteins as the major effect of LA on preadipocytes. Upregulation of selenoproteins was associated with an improved GSH:GSSG ratio in cellular compartments, which was lowered by elevated Cu, and reversal of protein oxidation. Thus, LA diminishes toxic effects of elevated Cu by improving cellular redox environment. We also show that selenium levels are decreased in tissues of a Wilson disease animal model, especially in the liver, making LA an attractive candidate for supplemental treatment of this disease.

Features of attention network impairment in patients with temporal lobe epilepsy: Evidence from eye-tracking and electroencephalogram.

AIM: To explore multiple features of attention impairments in patients with temporal lobe epilepsy (TLE). METHODS: A total of 93 patients diagnosed with TLE at Xiangya Hospital during May 2022 and December 2022 and 85 healthy controls were included in this study. Participants were asked to complete neuropsychological scales and attention network test (ANT) with recording of eye-tracking and electroencephalogram. RESULTS: All means of evaluation showed impaired attention functions in TLE patients. ANT results showed impaired orienting (p < 0.001) and executive control (p = 0.041) networks. Longer mean first saccade time (p = 0.046) and more total saccadic counts (p = 0.035) were found in eye-tracking results, indicating abnormal alerting and orienting networks. Both alerting, orienting and executive control networks were abnormal, manifesting as decreased amplitudes (N1 & P3, p < 0.001) and extended latency (P3, p = 0.002). The energy of theta, alpha and beta were all sensitive to the changes of alerting and executive control network with time, but only beta power was sensitive to the changes of orienting network. CONCLUSION: Our findings are helpful for early identification of patients with TLE combined with attention impairments, which have strong clinical guiding significance for long-term monitoring and intervention.

Efficacy and safety of pocket-creation method for early gastric cancers.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard endoscopic treatment for early gastric cancers (EGCs). However, obscured view and difficulty in submucosal lifting during ESD have been demonstrated. Additionally, ESD is time-consuming and poses a high risk of perforation and bleeding when performed in challenging locations. The pocket-creation method (PCM) is a newly developed strategy for colorectal tumors, while the outcomes of application in the treatment of EGCs are rarely reported. In the present study, we aimed to compare the technical efficacy and safety of PCM-ESD and the conventional ESD (c-ESD) technique for the treatment of EGCs. METHODS: This was a single-center retrospective study consisting of 162 patients with EGCs who underwent ESD between February 2019 and February 2021. One-to-one propensity score matching (PSM) was performed. In addition, clinicopathological characteristics and treatment outcomes were also compared. RESULTS: PCM-ESD was more likely to be used in patients with larger lesions than c-ESD with/without traction. In addition, the resection speed for lesions of the PCM-ESD was faster compared with c-ESD without traction (median dissection speed: 19.6 mm2/min vs. 15 mm2/min; p < 0.001) and c-ESD with traction (median dissection speed after PSM: 19.9 mm2/min vs. 15 mm2/min; p = 0.001). In multiple linear regression analysis, significant factors related to a higher dissection speed were the treatment method of PCM-ESD (p = 0.034), the long diameter of the resected lesion (p = 0.001), and lesion location (p = 0.046). CONCLUSIONS: Collectively, PCM-ESD appeared to be a safer and more effective treatment for EGCs than c-ESD. In addition, PCM-ESD could significantly improve the speed of tumor resection.

A novel variant of the POLR3A gene in a Chinese patient with POLR3-related leukodystrophy.

BACKGROUND: POLR3-related leukodystrophy is a group of rare neurodegenerative disorders characterized by degeneration of the white matter with different combinations of major clinical features. CASE: An 18-year-old lady was admitted for no menstruation since childhood. She gradually developed slight symptoms, such as choking after drinking water and unsteady walking in the last 2 years. Furthermore, her test scores and response capability were far lower than that of her peers. Physical examination revealed her to be of a slightly short stature, with stiff expressions and bilateral breast enlargement. She revealed clumsy movements when examined for ataxia, with an SARA score of 9. FINDINGS: The laboratory data revealed a decreased level of estradiol, FSH, and LH, with a MoCA score of 7. Conventional karyotype analysis revealed a 46 XX 9qh + karyotype. Ultrasound indicated primordial uterus (19 × 11 × 10 mm). Brain MRI showed bilateral cerebral hemisphere myelin dysplasia, brain atrophy, thin corpus callosum, and small pituitary gland with uneven reinforcement and enlarged ventricles. Exome sequencing exhibited two missense mutations in the POLR3A gene (c.3013C > T and c.1757C > T), which were inherited from her mother and father, respectively. CONCLUSION: Collectively, we identified novel compound heterozygous mutations of the POLR3A gene that caused POLR3A-related hypomyelinating leukodystrophy with hypogonadism in the patient combined with the clinical presentation, MRI brain pattern, and medical exome sequencing. TEACHING POINTS: The complexity of clinical phenotypes and heterogeneity of genotypes raise new challenges in genetic diagnoses. This study will further aid our understanding of POLR3A-related leukodystrophy and promote further analysis of phenotype-genotype correlations of related diseases.

Systematic molecular analysis of the human secretome and membrane proteome in gastrointestinal adenocarcinomas.

The human secretome and membrane proteome are a large source of cancer biomarkers. Membrane-bound and secreted proteins are promising targets for many clinically approved drugs, including for the treatment of tumours. Here, we report a deep systematic analysis of 957 adenocarcinomas of the oesophagus, stomach, colon and rectum to examine the cancer-associated human secretome and membrane proteome of gastrointestinal tract adenocarcinomas (GIACs). Transcriptomic data from these GIACs were applied to an innovative majority decision-based algorithm. We quantified significantly expressed protein-coding genes. Interestingly, we found a consistent pattern in a small group of genes found to be overexpressed in GIACs, which were associated with a cytokine-cytokine interaction pathway (CCRI) in all four cancer subtypes. These CCRI associated genes, which spanned both one secretory and one membrane isoform were further analysed, revealing a putative biomarker, interleukin-1 receptor accessory protein (IL1RAP), which indicated a poor overall survival, a positive correlation with cancer stemness and a negative correlation with several kinds of T cells. These results were further validated in vitro through the knockdown of IL1RAP in two human gastric carcinoma cell lines, which resulted in a reduced indication of cellular proliferation, migration and markers of invasiveness. Following IL1RAP silencing, RNA seq results showed a consistent pattern of inhibition related to CCRI, proliferation pathways and low infiltration of regulatory T cells (Tregs) and CD8 naive cells. The significance of the human secretome and membrane proteome is elucidated by these findings, which indicate IL1RAP as a potential candidate biomarker for cytokine-mediated cancer immunotherapy in gastric carcinoma.

27-Hydroxycholesterol is a specific factor in the neoplastic microenvironment of HCC that causes MDR via GRP75 regulation of the redox balance and metabolic reprogramming.

OBJECTIVE: Due to the tissue specificity of the liver, long-term exposure to a high concentration of 27-hydroxycholesterol (27HC) is a special characteristic of the tumour microenvironment in hepatocellular carcinoma (HCC). However, what occurs after HCC cells are long-term exposure to 27HC and the molecular mechanisms involved remain largely unexamined. METHODS: A long-term 27HC-treated HepG2 cell line and the xenografts in nude mice were used as experimental models. Molecular mechanisms were investigated using bioinformatics analysis and molecular biological experiments. RESULTS: Here, we found that by inducing an increase in oxidative stress signalling, 27HC activated glucose-regulated protein 75 (GRP75). On the one hand, GRP75 resulted in a change in the redox balance by regulating ROS generation and antioxidant system activity via affecting MMP, NRF2, HO-1, and NQO1 levels. On the other hand, GRP75 modified the metabolic reprogramming process by regulating key factors (HIF-1α, p-Akt, and c-myc) and glucose uptake, facilitating HCC cell growth in the inhospitable microenvironment. These two factors caused HCC cells to resist 27HC-induced cytotoxicity and attain multidrug resistance (MDR). CONCLUSIONS: Our present study not only identified 27HC, a characteristic component of the neoplastic microenvironment of HCC that causes MDR via GRP75 to regulate the redox balance and metabolic reprogramming, but also revealed that targeted intervention by the "switch"-like molecule GRP75 could reverse the effect of 27HC from cancer promotion to cytotoxicity in HCC, suggesting a new strategy for specific intervention of HCC.

Validity and reliability of the Chinese version of the epilepsy stigma scale.

OBJECTIVE: This study was conducted to test the validity and reliability of the Chinese version of the epilepsy stigma scale (ESS), which aims to better understand the stigma of patients with epilepsy (PWEs), lays the foundation for future investigation and explores appropriate strategies to mitigate PWEs' stigma in Chinese culture. METHODS: The scale was translated following standard procedures. For psychometric validation, the Chinese version of the ESS was administered to 214 PWEs above the age of 16 who were diagnosed with epilepsy by two trained epileptologists and were taking anti-seizure drugs for at least a month. All of the patients were recruited from Xiangya Hospital of Central South University of China from August 2021 to September 2021. RESULTS: The Cronbach's alpha coefficient was 0.893 for the entire scale, 0.903 for felt stigma, and 0.688 for enacted stigma. Exploratory and confirmatory factor analyses were conducted and showed that the scale was grouped under two dimensions, and the results of confirmatory factor analysis support the structure. CONCLUSION: The Chinese version of the ESS is a valid and reliable tool to assess epilepsy-related stigma in Chinese culture.

A retrospective study on risk factors and disease burden for hospital-acquired pneumonia caused by multi-drug-resistant bacteria in patients with intracranial cerebral hemorrhage.

PURPOSE: Hospital-acquired pneumonia (HAP) is becoming a serious problem in China, especially caused by multi-drug resistant (MDR), which is a risk factor for poor prognosis of intracranial cerebral hemorrhage (ICH). We investigate the risk factors for HAP among patients with ICH and study the antibiotic use and medical costs of MDR infection. METHODS: We performed a retrospective, case-control, parallel study in Xiangya Hospital. Patients included in this study and diagnosed with basal ganglia hemorrhage were admitted between January 2017 and December 2019. RESULTS: Univariate analysis discovered some personal risk factors including gender (p = .002), age (p = .023), and underlying conditions such as diabetes (p = .036), coronary heart disease (p = .009), and renal insufficiency (p = .001). Invasive medical operations including endotracheal intubation, tracheotomy, ventilator use, lumbar puncture, urinary catheter insertion, and peripherally inserted central catheter (PICC) (p < .001 all) were also risk factors for HAP. Binary logistics regression indicated hospital duration, antibiotic exposure, and urinary catheter insertion explained 91.4% of the variance on HAP (p < 0.01). As for the antibiotic treatment, there were no difference in the duration of use days and total dose per patient between MDR and non-MDR group, except for Tigecycline. Antibiotic costs for the MDR group were significantly higher than those for the non-MDR group and no infection group (p < 0.001). CONCLUSION: To better prevent HAP particularly caused by MDR bacteria, we emphasize the aseptic technique especially in the management of equipment in patient care.

Correlation between gastritis cystica profunda and the risk of lymph node metastasis in early gastric cancer.

In early gastric cancer (EGC) patients, lymph node metastasis (LNM) risk assessment is particularly important for the selection of surgical methods. In this study, we investigated the correlation between gastritis cystica profunda (GCP) and the risk of LNM in EGC. From January 2014 to December 2019, EGC patients who underwent curative radical gastrectomy were enrolled in this study. The clinicopathological features were analyzed, and the correlation between GCP and the risk of lymph node metastasis was assessed. Data for 180 EGC patients were analyzed, and 17.8% (32/180) had LNM. The incidence of LNM was 2.6% in the GCP-positive group and 21.8% in the GCP-negative group. Univariate analysis revealed that GCP, depth of tumor invasion, and lymphovascular invasion were the risk factors of LNM in EGC patients. Multiple regression analysis showed that GCP was associated with the risk of LNM in EGC patients (OR=0.097, 0.121, 0.100, p<0.05). The curve fitting results showed that there was a negative correlation between the GCP and LNM in EGC, which was consistent between different tumor sites, size, ulceration, differentiation types, depth of tumor invasion, lymphovascular invasion, and no significant interaction was found among these factors (p for interaction range 0.224-0.717). GCP is closely related to LNM in EGC. Preoperative assessment of whether EGC is combined with GCP is beneficial for the assessment of the risk of LNM.

Construction of a circRNA-miRNA-mRNA network based on differentially co-expressed circular RNA in gastric cancer tissue and plasma by bioinformatics analysis.

BACKGROUND: Increasing evidence implicates circular RNAs (circRNAs) have been involved in human cancer progression. However, the mechanism remains unclear. In this study, we identified novel circRNAs related to gastric cancer and constructed a circRNA-miRNA-mRNA network. METHODS: Microarray datasets GSE83521 and GSE93541 were obtained from the Gene Expression Omnibus (GEO). Then, we used computational biology to identify circRNAs that were differentially expressed in both GC tissue and plasma compared to normal controls; then, we detected the expression of the selected circRNAs in gastric cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). We also identified circRNA-related candidate miRNAs and their target genes with online tools. Combining the predicted miRNAs and target mRNAs, a competing endogenous RNA regulatory network was established. Functional and pathway enrichment analyses were performed, and interactions between proteins were predicted by using String and Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the possible functions of these differentially expressed circRNAs. The regulatory network constructed using the microarray datasets (GSE83521 and GSE93541) contained three differentially co-expressed circRNAs (DECs). A circRNA-miRNA-mRNA network was constructed based on 3 circRNAs, 43 miRNAs and 119 mRNAs. RESULTS: GO and KEGG analysis showed that the regulation of apoptotic signaling pathway and PI3K-Akt signaling pathway were highest degrees of enrichment respectively. We established a protein-protein interaction (PPI) network consisting of 165 nodes and 170 edges and identified hub genes by using MCODE plugin in Cytoscape. Furthermore, a core circRNA-miRNA-mRNA network was constructed based on hub genes. Hsa_circ_0001013 was finally determined to play an important role in the pathogenesis of GC according to the core circRNA-miRNA-mRNA network. CONCLUSIONS: We propose a new circRNA-miRNA-mRNA network that is associated with the pathogenesis of GC. The network may become a new molecular biomarker and could be used to develop potential therapeutic strategies for gastric cancer.

Copper-dependent amino oxidase 3 governs selection of metabolic fuels in adipocytes.

Copper (Cu) has emerged as an important modifier of body lipid metabolism. However, how Cu contributes to the physiology of fat cells remains largely unknown. We found that adipocytes require Cu to establish a balance between main metabolic fuels. Differentiating adipocytes increase their Cu uptake along with the ATP7A-dependent transport of Cu into the secretory pathway to activate a highly up-regulated amino-oxidase copper-containing 3 (AOC3)/semicarbazide-sensitive amine oxidase (SSAO); in vivo, the activity of SSAO depends on the organism's Cu status. Activated SSAO oppositely regulates uptake of glucose and long-chain fatty acids and remodels the cellular proteome to coordinate changes in fuel availability and related downstream processes, such as glycolysis, de novo lipogenesis, and sphingomyelin/ceramide synthesis. The loss of SSAO-dependent regulation due to Cu deficiency, limited Cu transport to the secretory pathway, or SSAO inactivation shifts metabolism towards lipid-dependent pathways and results in adipocyte hypertrophy and fat accumulation. The results establish a role for Cu homeostasis in adipocyte metabolism and identify SSAO as a regulator of energy utilization processes in adipocytes.

Lynch syndrome-associated repeated stroke with MLH1 frame-shift mutation.

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2, which predisposes patients to various malignant neoplasms. Previous studies showed that MLH1, MSH2, MSH6, and PMS2 mutation in LS were associated with an elevated risk of colorectal, gastric, endometria, ovarian, and other cancers among family members. Patients of these kinds of cancers had high incidence of synchronous and metasynchronus. We describe the case of a 34-year-old female patient with 50 days of sudden dizziness and left limb weakness, whose head CT scan showed large infarction in the right frontal temporal parietal lobe and basal ganglia area. Imaging examinations and pathological biopsy indicated high-grade serous carcinoma (HGSC) IIIA1 of the right ovary. In addition, a novel frame-shift mutation in the MLH1 gene (c.1621dupG, p.A541Gfs*16) was found in the genetic panel sequence. It may render declining of MLH1 protein and also associate with the patient's progressive clinical manifestations of multiple systems. Therefore, the timely use of prenatal diagnosis to prevent unnecessary new cases of this severe genetic disease is available.

Knowledge, attitudes and anxiety toward COVID-19 among domestic and overseas Chinese college students.

BACKGROUND: To investigate the knowledge, attitudes and anxiety toward COVID-19 among Chinese college students studying in China and abroad. METHOD: A structured questionnaire, comprised of demographic characteristics, knowledge and attitudes toward COVID-19 and the State-Trait Anxiety Inventory (STAI), was used to collect data for 566 domestic students and 126 students studying abroad. RESULTS: Domestic students were better than students abroad in knowledge of epidemiology and manifestations. Domestic students showed a significant higher enthusiasm for voluntary services than students abroad, including medical science popularization, community services, traffic dispersion, logistics transportation and being volunteers for vaccine trials. The scores (Mean ± SD) of S-AI and T-AI among students abroad were 59.48 ± 8.63 and 54.10 ± 7.20, respectively, which were significantly higher than those of domestic students (39.46 ± 8.16 and 39.25 ± 7.72). CONCLUSIONS: Our study showed a better understanding of knowledge, more positive attitudes and less anxiety toward COVID-19 among domestic students, compared with students studying abroad. In light of this information, more attention and appropriate psychological and social intervention should be paid to college students with anxiety, especially those studying abroad.

The Efficacy and Safety of Botulinum Toxin Injections in Preventing Postoperative Scars and Improving Scar Quality: A Systematic Review and Meta-Analysis.

BACKGROUND: Scars exposed on the body surface lead to a large psychological burden on patients. However, no satisfactory scar treatments exist. Botulinum toxin type A is a neurotoxin that has been widely applied in the plastic and cosmetic surgery field. The purpose of this meta-analysis was to assess the efficacy and safety of botulinum toxin in scar management. METHODS: PubMed, the Cochrane Library, EMBASE, MEDLINE, and Web of Science were searched for randomized controlled trials that evaluated the efficacy of botulinum toxin injections in preventing postoperative scars and improving scars quality and were published prior to Dec. 29, 2020. The outcome indicators were the visual analog scale score, Vancouver scar scale score, Stony Brook scar evaluation scales score, scar width, patient self-assessment results, and complications. RESULTS: Seventeen randomized controlled trials with a total of 633 cases were identified in this meta-analysis. The quantitative synthesis results showed that compared with the control group, the botulinum toxin group had a significantly lower VSS score (MD = -0.97, 95%CI = -1.56 to -0.39, p = 0.001), higher VAS score (MD = 1.26, 95%CI = 1.04 to 1.47, p < 0.00001), thinner scar width (MD = -0.25, 95%CI = -0.37 to -0.12, p < 0.0001) and higher patient satisfaction (RR = 3.38 95%CI = 1.45 to 7.89, p = 0.005). There were no significant differences between the two groups in the number of adverse events. CONCLUSIONS: This meta-analysis demonstrated that botulinum toxin injections can significantly improve cosmetic appearance and postoperative scar quality. At the therapeutic dose, no significant complications were observed, indicating that botulinum toxin injections are safe. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Copper Transport and Disease: What Can We Learn from Organoids?

Many metals have biological functions and play important roles in human health. Copper (Cu) is an essential metal that supports normal cellular physiology. Significant research efforts have focused on identifying the molecules and pathways involved in dietary Cu uptake in the digestive tract. The lack of an adequate in vitro model for assessing Cu transport processes in the gut has led to contradictory data and gaps in our understanding of the mechanisms involved in dietary Cu acquisition. The recent development of organoid technology has provided a tractable model system for assessing the detailed mechanistic processes involved in Cu utilization and transport in the context of nutrition. Enteroid (intestinal epithelial organoid)-based studies have identified new links between intestinal Cu metabolism and dietary fat processing. Evidence for a metabolic coupling between the dietary uptake of Cu and uptake of fat (which were previously thought to be independent) is a new and exciting finding that highlights the utility of these three-dimensional primary culture systems. This review has three goals: (a) to critically discuss the roles of key Cu transport enzymes in dietary Cu uptake; (b) to assess the use, utility, and limitations of organoid technology in research into nutritional Cu transport and Cu-based diseases; and (c) to highlight emerging connections between nutritional Cu homeostasis and fat metabolism.

MicroRNAs and target genes in epileptogenesis.

Epilepsy is a chronic brain dysfunction. Current antiepileptic medicines cannot prevent epileptogenesis. Increasing data have shown that microRNAs (miRNAs) are selectively altered within the epileptic hippocampi of experimental models and human tissues, and these alterations affect the genes that control epileptogenesis. Furthermore, manipulation of miRNAs in animal models can modify epileptogenesis. As a result, miRNAs have been proposed as promising targets for treating epilepsy. We searched PubMed using the terms "microRNAs/miRNAs AND epilepsy", "microRNAs/miRNAs AND epileptogenesis", and "microRNAs/miRNAs AND seizure". We selected the articles in which the relationship between miRNAs and target gene(s) was validated and manipulation of miRNAs in in vivo epilepsy models modified epileptogenesis during the chronic phase via gene regulation. A total of 13 miRNAs were found in the present review. Based on the current analysis of miRNAs and their target gene(s), each miRNA has limitations as a potential epilepsy target. Importantly, miR-211 or miR-128 transgenic mice displayed seizures. These findings highlight new developments for epileptogenesis prevention. Developing novel strategies to modify epileptogenesis will be effective in curing epilepsy patients. This article provides an overview of the clinical application of miRNAs as novel targets for epilepsy.

Evaluation of anxiety, depression, and sleep quality among parents of children with epilepsy in Southern China.

PURPOSE: The purpose of the study was to evaluate sleep quality in the parents of children with epilepsy (CWE) as well as their symptoms of anxiety and depression in Southern China. METHOD: A structured questionnaire, comprised of The State-Trait Anxiety Inventory (STAI), Center for Epidemiologic Studies Depression Scale (CES-D), and the Pittsburgh Sleep Quality Index (PSQI), was administered to parents of CWE (n = 234) in Xiangya Hospital and parents of healthy children (n = 230) during 2019-2020. RESULTS: The scores (Mean ±â€¯SD) of State Anxiety Inventory (S-AI) and Trait Anxiety Inventory (T-AI) among parents of CWE were 51.850 ±â€¯11.380 and 48.201 ±â€¯9.526, respectively, which were significantly higher than those of control group (37.172 ±â€¯8.047 and 37.478 ±â€¯7.314, respectively) (p < 0.001). Compared with 10.84% in parents of healthy children, 23.51% of parents of CWE had symptoms of depression (p < 0.001). The mean score of total PSQI among parents of CWE (6.944 ±â€¯3.814) was statistically higher than that of parents of healthy children (5.039 ±â€¯3.390) (p < 0.001). Moreover, anxiety and depression subscores among parents of infants with epilepsy were significantly higher than in other groups. The T-AI and CES-D could explain 43.9% of the variance (R2 = 0.444, F = 92.215, p < 0.001) on the PSQI. CONCLUSIONS: Our study showed more severe symptoms of anxiety and depression as well as poorer sleep quality among parents of CWE, especially in the infants group. In light of this information, more attention should be paid to early identification and intervention of symptoms of anxiety and depression in susceptible parents who are the main caregivers of their CWE.

A Blockchain-Assisted Intelligent Transportation System Promoting Data Services with Privacy Protection.

Being able to obtain various environmental and driving data from vehicles is becoming more and more important for current and future intelligent transportation systems (ITSs) to operate efficiently and economically. However, the limitations of privacy protection and security of the current ITSs are hindering users and vehicles from providing data. In this paper, we propose a new ITS architecture by using blockchain technology solving the privacy protection and security problems, and promoting users and vehicles to provide data to ITSs. The proposed architecture uses blockchain as a trust infrastructure to protect users' privacy and provide trustworthy services to users. It is also compatible with the legacy ITS infrastructure and services. In addition, the hierarchical organization of chains enables the scalability of the system, and the use of smart contracts provides a flexible way for introducing new services in the ITS. The proposed architecture is demonstrated by a proof of concept implementation based on Ethereum. The test results show that the proposed architecture is feasible.

Methylxanthine derivatives promote autophagy in gastric cancer cells targeting PTEN.

Methylxanthine derivatives, such as caffeine and theophylline, enhance cell apoptosis and autophagy and reportedly induce the activity of phosphatase and tensin homologue (PTEN) and inhibit the mammalian target of rapamycin (mTOR). This study investigated the impacts of caffeine and theophylline on gastric cancer cell apoptosis and autophagy using a gastric cancer cell line (MGC-803) and a nude mouse model. Peritumoural and tumour tissues were collected from five patients diagnosed with gastric carcinoma who underwent laparoscopic radical gastrectomy at our hospital. Autophagy was suppressed in gastric cancer tumour tissue compared with peritumoural tissue. In vitro, both caffeine and theophylline effectively suppressed MGC-803 cell proliferation and migration and induced autophagy. To assess the involvement of PTEN in caffeine-mediated and theophylline-mediated gastric cancer cell death, we transiently transfected MGC-803 cells with an siRNA targeting PTEN. PTEN knockdown impaired the methylxanthine derivative-mediated inhibition of PI3K/Akt/mTOR signalling. In nude mice treated with caffeine or theophylline, MGC-803 cell tumours injected with siPTEN were larger than those injected with negative control siRNA. These results show that the methylxanthine derivatives (caffeine and theophylline) effectively induce gastric cancer cell apoptosis and autophagy by PTEN activation and PI3K/Akt/mTOR pathway suppression and strongly support the use of methylxanthine derivatives as potential anticancer therapeutics.