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This study reported a case of MELAS syndrome presenting as the initial imaging characteristics of Fahr’s syndrome with “near” sudden unexpected death in epilepsy (SUDEP) and lateralized periodic discharges (LPD). The patient, a young boy, experienced loss of consciousness 2 days prior, which was followed by two limb and facial convulsions. He was later found in cardiac arrest during hospitalization, but regained consciousness gradually after receiving cardiopulmonary resuscitation and tracheal intubation. The patient exhibited short stature, intellectual disability, poor sports abilities, and academic performance since childhood, but had no family history. Emergency head computed tomography (CT) revealed high density calcification in bilateral caudate nucleus, lentiform nucleus, thalamus, and dentate nucleus with evidence of an acute process. The patient was transferred to the neurology department where he continued to recover consciousness, though he experienced dysarthria, left limb hemiplegia, and hemiparesthesia. Changes in head magnetic resonance imaging (MRI) findings were noted at admission, 1 month later, and 6 months later. LPD were observed in his video electroencephalogram. The CT urography indicated a narrow left ureteropelvic junction with left hydronephrosis, which was suggestive of ureteropelvic junction obstruction. Ultimately, a diagnosis of near-SUDEP was suspected in this patient, indicating a rare case of MELAS syndrome with near-SUDEP and LPD. The gene tests results revealed the presence of the mitochondrial DNA A3243G mutation, leading to the final diagnosis of MELAS syndrome. This case expands the clinical disease spectrum of the MELAS syndrome.

Introduction: IL4I1, also known as Interleukin-4-induced gene 1, is an enzyme that can modulate the immune system by acting as a L-amino acid oxidase. Nevertheless, a precise understanding of the correlation of IL4I1 with immunological features and immunotherapy efficacy in bladder cancer (BLCA) remains incomplete.Methods: We analyzed RNA sequencing data from the Cancer Genome Atlas (TCGA) to investigate the immune function and prognostic importance of IL4I1 across different cancer types. We further examined the TCGA-BLCA cohort for correlations between IL4I1 and various immunological characteristics of tumor microenvironment (TME), such as cancer immune cycle, immune cell infiltration, immune checkpoint expression and T cell inflamed score. Validation was conducted using two independent cohort, GSE48075 and E-MTAB-4321. Finally, RNA sequencing data from the IMvigor210 cohort and immunohistochemistry assays were employed to validate the predictive value of IL4I1 for the TME and immunotherapy efficacy.Results: In our findings, a positive correlation was observed between IL4I1 expression and immunomodulators expression, immune cell infiltration, the cancer immune cycle, and T cell inflamed score in BLCA, suggesting a significant link to the inflamed TME. In addition, studies have shown that IL4I1 elevated levels of individuals tend to be more performance for basal subtype and exhibit enhanced response rates to diverse treatment modalities, specifically immunotherapy. Clinical data from the IMvigor 210 cohort confirmed a higher rate of response to immunotherapy and better survival benefits in patients with high IL4I1 expression.Discussion: To summarize, our research showed that elevated IL4I1 levels are indicative of an inflamed TME, the basal subtype, and a more favorable response to various treatment methods, especially immune checkpoint blockade therapy in BLCA.

ObjectiveUlcerative colitis (UC) and metabolic dysfunction-associated steatotic liver disease (MASLD) are closely intertwined; however, the precise molecular mechanisms governing their coexistence remain unclear.MethodsWe obtained UC (GSE75214) and MASLD (GSE151158) datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were acquired by the ‘edgeR’ and ‘limma’ packages of R. We then performed functional enrichment analysis of common DEGs. Hub genes were selected using the cytoHubba plugin and validated using GSE87466 for UC and GSE33814 for MASLD. Immunohistochemistry was employed to validate the hub genes’ expression in clinical samples. Immune infiltration and gene set enrichment analyses of the hub genes were performed. Finally, we estimated the Spearman’s correlation coefficients for the clinical correlation of the core genes.ResultsWithin a cohort of 26 differentially regulated genes in both UC and MASLD, pathways involving cytokine-mediated signaling, cell chemotaxis, and leukocyte migration were enriched. After further validation, CXCR4, THY1, CCL20, and CD2 were identified as the hub genes. Analysis of immune infiltration patterns highlighted an association between elevated pivotal gene expression and M1 macrophage activation. Immunohistochemical staining revealed widespread expression of pivotal genes in UC- and MASLD-affected tissues. Furthermore, significant correlations were observed between the increased expression of hub genes and biochemical markers, such as albumin and prothrombin time.ConclusionThis bioinformatics analysis highlights CXCR4, THY1, CCL20, and CD2 as crucial genes involved in the co-occurrence of UC and MASLD, providing insights into the underlying mechanisms of these two conditions.

Generalized pustular psoriasis (GPP) is a rare chronic inflammatory pustular dermatosis that presents as painful erythema with sterile pustules on nonacral skin. No unified standard and guideline for the treatment of GPP has been established. Several biologics have been tried for GPP, with varying success. Acrodermatitis continua of Hallopeau (ACH) is a very rare disabling variant of pustular psoriasis characterized by sterile pustules on the fingers and toes, including the nail bed. Comparatively, treating ACH is highly challenging due to its commonly therapy-resistant disease course. The pathogenic role of IL-36 signaling axis has been currently identified in GPP development. Spesolimab, the first anti-interleukin-36 receptor biologic, has been approved for treating GPP flares and shown promising results. In view of a shared pathogenesis between GPP and ACH, specolimab may be an effective treatment for ACH. Currently, there is no case and clinical trial data exist on this condition. Therefore, this case was aim to describe real-world experience of spesolimab use in ACH coexisting with GPP. We report an Asian patient with a 16-year-history of GPP and ACH with marked pustulosis on the nail bed and onychodystrophy. He received conventional systemic regimen acitretin, cyclosporine and biologics adalimumab and secukinumab, but experienced relapse for skin lesions and refractory for nail lesions. He was then treated with a single dose of spesolimab in combination with secukinumab, which resulted in skin clearance and nearly complete resolution of nail lesions over a 32-week period. Our observation suggests that spesolimab should be considered for the treatment of ACH, especially in the patients with intractable nail lesions and concomitant GPP.

IntroductionVisual hallucination is a prevalent psychiatric disorder characterized by the occurrence of false visual perceptions due to misinterpretation in the brain. Individuals with Parkinson’s disease often experience both minor and complex visual hallucinations. The underlying mechanism of complex visual hallucinations in Parkinson’s patients is commonly attributed to dysfunction in the visual pathway and attention network. However, there is limited research on the mechanism of minor hallucinations.MethodsTo address this gap, we conducted an experiment involving 13 Parkinson’s patients with minor hallucinations, 13 Parkinson’s patients without hallucinations, and 13 healthy elderly individuals. We collected and analyzed EEG and MRI data. Furthermore, we utilized EEG data from abnormal brain regions to train a machine learning model to determine whether the abnormal EEG data were associated with minor hallucinations.ResultsOur findings revealed that Parkinson’s patients with minor hallucinations exhibited excessive activation of cortical excitability, an imbalanced interaction between the attention network and the default network, and disruption in the connection between these networks. These findings is similar to the mechanism observed in complex visual hallucinations. The visual reconstruction of one patient experiencing hallucinations yields results that differ from those observed in subjects without such symptoms.DiscussionThe visual reconstruction results demonstrated significant differences between Parkinson’s patients with hallucinations and healthy subjects. This suggests that visual reconstruction techniques may offer a means of evaluating hallucinations.

With the increasing demand for reliable power supply and the widespread integration of distributed energy sources, the topology of distribution networks is subject to frequent changes. Consequently, the dynamic alterations in the connection relationships between distribution transformers and feeders occur frequently, and these changes are not accurately monitored by grid companies in real-time. In this paper, we present a data-driven machine learning approach for identifying the feeder-transformer relationship in distribution networks. Initially, we preprocess the collected three-phase voltage magnitude data of distribution transformers, addressing data quality and enhancing usability through three-phase voltage normalization. Subsequently, we derive the correlation coefficient calculations between distribution transformers, as well as between distribution transformers and feeders. To tackle the challenging task of determining the correlation coefficient threshold, we propose a multi-feature fusion approach. We extracted additional features from the feeders and combined them with the correlation coefficients to create a feature matrix. Machine learning algorithms were then applied to calculate the results. Through experimentation on a real distribution network in Jiangxi province, we demonstrated the effectiveness of the proposed method. When compared to other approaches, our method achieved outstanding results with an F1 score of 0.977, indicating high precision and recall. The precision value was 0.973 and the recall value was 0.981. Importantly, our method eliminates the need for additional measurement installations, as the required data can be obtained using existing collection devices. This significantly reduces the application cost associated with implementing our approach.

PurposePatients with non-muscle invasive bladder cancer (NMIBC) have a high possibility of recurrence after surgery. We aimed to assess the factors associated with tumor recurrence and to construct a nomogram model that can contribute to personalized treatment plans of each patient.Methods496 patients with primary bladder cancer (BC) from 2 centers were retrospectively analyzed. Preoperative neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and traditional clinical parameters were collected, then using univariate and multivariate Cox regression analysis to find out the independent risk factors associated with tumor recurrence among them, and then these independent factors were incorporated into the nomogram model. The internal calibration curves and the external calibration curves were used to verify their usefulness.ResultsIn the training cohort, 150 patients (43.1%) experienced recurrence. After Cox regression analysis, the independent risk factors affecting recurrence-free survival (RFS) were tumor grade, immediate postoperative instillation therapy (IPPIT), NLR, and SII. These factors were used to construct a model to predict RFS 1, 2, 3, and 5 years of NMIBC patients after surgery. And then, we found that the constructed model outperforms the conventional model in terms of accuracy and predictability, the results were verified by statistical tests.ConclusionPreoperative inflammatory response markers have a predictive value for postoperative recurrence in patients with NMIBC. The constructed nomogram model can be helpful in guiding personalized clinical evaluation and subsequent treatment.

BackgroundNon-obstructive azoospermia (NOA) is the most severe type that leads to 1% of male infertility. Wnt signaling governs normal sperm maturation. However, the role of Wnt signaling in spermatogonia in NOA has incompletely been uncovered, and upstream molecules regulating Wnt signaling remain unclear.MethodsBulk RNA sequencing (RNA-seq) of NOA was used to identify the hub gene module in NOA utilizing weighted gene co-expression network analyses (WGCNAs). Single-cell RNA sequencing (scRNA-seq) of NOA was employed to explore dysfunctional signaling pathways in the specific cell type with gene sets of signaling pathways. Single-cell regulatory network inference and clustering (pySCENIC) for Python analysis was applied to speculate putative transcription factors in spermatogonia. Moreover, single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) determined the regulated genes of these transcription factors. Finally, spatial transcriptomic data were used to analyze cell type and Wnt signaling spatial distribution.ResultsThe Wnt signaling pathway was demonstrated to be enriched in the hub gene module of NOA by bulk RNA-seq. Then, scRNA-seq data revealed the downregulated activity and dysfunction of Wnt signaling of spermatogonia in NOA samples. Conjoint analyses of the pySCENIC algorithm and scATAC-seq data indicated that three transcription factors (CTCF, AR, and ARNTL) were related to the activities of Wnt signaling in NOA. Eventually, spatial expression localization of Wnt signaling was identified to be in accordance with the distribution patterns of spermatogonia, Sertoli cells, and Leydig cells.ConclusionIn conclusion, we identified that downregulated Wnt signaling of spermatogonia in NOA and three transcription factors (CTCF, AR, and ARNTL) may be involved in this dysfunctional Wnt signaling. These findings provide new mechanisms for NOA and new therapeutic targets for NOA patients.

BackgroundEndoplasmic reticulum stress (ERS) is a critical factor in the development of ulcerative colitis (UC); however, the underlying molecular mechanisms remain unclear. This study aims to identify pivotal molecular mechanisms related to ERS in UC pathogenesis and provide novel therapeutic targets for UC.MethodsColon tissue gene expression profiles and clinical information of UC patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database, and the ERS-related gene set was downloaded from GeneCards for analysis. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were utilized to identify pivotal modules and genes associated with UC. A consensus clustering algorithm was used to classify UC patients. The CIBERSORT algorithm was employed to evaluate the immune cell infiltration. Gene Set Variation Analysis (GSVA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore potential biological mechanisms. The external sets were used to validate and identify the relationship of ERS-related genes with biologics. Small molecule compounds were predicted using the Connectivity Map (CMap) database. Molecular docking was performed to simulate the binding conformation of small molecule compounds and key targets.ResultsThe study identified 915 differentially expressed genes (DEGs) and 11 ERS-related genes (ERSRGs) from the colonic mucosa of UC patients and healthy controls, and these genes had good diagnostic value and were highly correlated. Five potential small-molecule drugs sharing tubulin inhibitors were identified, including albendazole, fenbendazole, flubendazole, griseofulvin, and noscapine, among which noscapine exhibited the highest correlation with a high binding affinity to the targets. Active UC and 10 ERSRGs were associated with a large number of immune cells, and ERS was also associated with colon mucosal invasion of active UC. Significant differences in gene expression patterns and immune cell infiltration abundance were observed among ERS-related subtypes.ConclusionThe results suggest that ERS plays a vital role in UC pathogenesis, and noscapine may be a promising therapeutic agent for UC by affecting ERS.

BackgroundAlzheimer's disease (AD) is difficult to diagnose on the basis of language because of the implicit emotion of transcripts, which is defined as a supervised fuzzy implicit emotion classification at the document level. Recent neural network-based approaches have not paid attention to the implicit sentiments entailed in AD transcripts.MethodA two-level attention mechanism is proposed to detect deep semantic information toward words and sentences, which enables it to attend to more words and fewer sentences differentially when constructing document representation. Specifically, a document vector was built by progressively aggregating important words into sentence vectors and important sentences into document vectors.ResultsExperimental results showed that our method achieved the best accuracy of 91.6% on annotated public Pitt corpora, which validates its effectiveness in learning implicit sentiment representation for our model.ConclusionThe proposed model can qualitatively select informative words and sentences using attention layers, and this method also provides good inspiration for AD diagnosis based on implicit sentiment transcripts.

AimsWe conducted bibliometric and visualization analyses to evaluate the current research status, hotspots, and trends related to the human microbiota markers in colorectal cancer screening.MethodsThe related studies were acquired from the Web of Science Core Collection (WoSCC) database on 5 January 2023. Analyses of the co-occurrence and cooperation relationships between the cited authors, institutions, countries/regions, cited journals, cited articles, and keywords in the studies were carried out using CiteSpace 5.8.R3 software and the Online Analysis platform of Literature Metrology. Additionally, relevant knowledge graphs were drawn to perform visualization analyses; a keywords cluster analysis and a burst analysis were also conducted.ResultsAfter analyzing 700 relevant articles, this bibliometric analysis found that the annual publications showed an increasing trend from 1992 to 2022. Yu Jun from the Chinese University of Hong Kong had the highest cumulative number of publications, whereas Shanghai Jiao Tong University was the most productive institution. China and the USA have contributed the largest number of studies. The keywords frequency analysis demonstrated that “colorectal cancer,” “gut microbiota,” “Fusobacterium nucleatum,” “risk,” and “microbiota” were the most frequent keywords, and the keywords cluster analysis found that the current hotspots were as follows: (a) the precancerous lesions of colorectal cancer (CRC) that need to be screened, such as inflammatory bowel disease (IBD) and advanced adenoma, (b) the gut-derived microbiome for CRC screening, and (c) the early detection of CRC. The burst analysis further showed that the combination of microbiomics with metabolomics might be the future research trend in the field of CRC screening.ConclusionThe findings of the current bibliometric analysis firstly provide an insight into the current research status, hotspots, and future trends in the field of CRC screening based on the microbiome; the research in this field is becoming more in-depth and diversified. Some human microbiota markers, especially “Fusobacterium nucleatum,” are promising biomarkers in CRC screening, and a future hotspot might be the combined analysis of microbiomics and metabolomics for CRC risk screening.

Growing evidence suggests that micronutrient status may have some impact on the course of inflammatory bowel disease (IBD). However, micronutrient deficiencies are easily overlooked during the treatment of IBD patients. There have been many studies on micronutrient supplementation, in which several clinical trials have been conducted targeting vitamin D and iron, but the current research is still preliminary for other vitamins and minerals. This review provides an overview of the adjunctive therapeutic effects of micronutrient supplementation in IBD, to summarize the available evidence, draw the attention of clinicians to micronutrient monitoring and supplementation in patients with IBD, and also provide some perspectives for future research directions.

Background: Immunogenic cell death (ICD) plays an important role in the development of cancers. This study attempted to explore the role of ICD in the prognosis of hepatocellular carcinoma (HCC).Methods: Gene expression and clinical data were downloaded from The Cancer Genome Alas and Gene Expression Omnibus dataset. The immune/stromal/Estimate scores of the tumor microenvironment (TME) were calculated by ESTIMATE and CIBERSORT algorithms. Kaplan-Meier analysis, functional enrichment analysis, least absolute shrinkage and selection operator (LASSO) analysis, and univariate and multivariate Cox regression analysis were used for prognostic gene screening and prognostic model construction. The correlation of immune cell infiltration and risk scores was analyzed as well. Molecular docking was used to explore the relevance of related genes to anti-cancer drugs.Results: Ten ICD associated differentially expressed genes in HCC were found, and all of them had good predictive ability for HCC. ICD gene high amount of expression group was associated with poor prognosis (p = 0.015). The TME, immune cell infiltration and gene expression were different between ICD high and low groups (all p < 0.05). Six ICD associated genes (BAX, CASP8, IFNB1, LY96, NT5E and PIK3CA) which could predict the survival status were identified and used to construct the prognostic model for HCC. A risk score was calculated and it could be used as an independent prognostic factor in HCC patients (p < 0.001). In addition, the risk score had a positive correlation with macrophage M0 (r = 0.33, p = 0.0086). Molecular docking indicated that sorafenib could bind strongly to the target protein, representing that sorafenib may exert anticancer effects through these six ICD associated genes.Conclusion: This study established a prognostic model including six ICD associated genes for HCC, which may deepen our understanding of ICD and guide therapy for HCC patients.

ObjectivesThis study aimed to determine the prevalence and risk factors for poor sleep quality in inflammatory bowel disease (IBD) patients.Methods2,478 IBD patients were enrolled to investigate their sleep quality using the Pittsburgh sleep quality index (PSQI). Clinical and psychological characteristics were collected to explore the risk factors for poor sleep quality. A hurdle model was conducted to predict poor sleep quality based on the risk factors. Among this hurdle model, the logistic regression model was used to determine risk factors of the presence of poor sleep quality, and the zero-inflated negative binomial model was employed to identify risk factors of the severity of poor sleep quality.ResultsIn this study, 1,491 (60.17%) IBD patients had poor sleep quality, and the proportion in the older group was higher than younger group (64.89% vs. 58.27%, p = 0.003). According to multivariable logistic regression, age (OR, 1.011; 95% CI [1.002,1.020]; p = 0.014), Patient Health Questionnaire-9 (PHQ-9) score (OR, 1.263; 95% CI [1.228,1.300]; p

Objective: Curcumin is a plant polyphenol extracted from the Chinese herb turmeric. It was found that curcumin has good anti-cancer properties in a variety of cancers, but the exact mechanism is not clear. Based on the network pharmacology and molecular docking to deeply investigate the molecular mechanism of curcumin for the treatment of colon cancer, it provides a new research direction for the treatment of colon cancer.Methods: Curcumin-related targets were collected using PharmMapper, SwissTargetPrediction, Targetnet and SuperPred. Colon cancer related targets were obtained using OMIM, DisGeNET, GeneCards and GEO databases. Drug-disease intersection targets were obtained via Venny 2.1.0. GO and KEGG enrichment analysis of drug-disease common targets were performed using DAVID. Construct PPI network graphs of intersecting targets using STRING database as well as Cytoscape 3.9.0 and filter core targets. Molecular docking via AutoDockTools 1.5.7. The core targets were further analyzed by GEPIA, HPA, cBioPortal and TIMER databases.Results: A total of 73 potential targets of curcumin for the treatment of colon cancer were obtained. GO function enrichment analysis yielded 256 entries, including BP(Biological Progress):166, CC(celluar component):36 and MF(Molecular Function):54. The KEGG pathway enrichment analysis yielded 34 signaling pathways, mainly involved in Metabolic pathways, Nucleotide metabolism, Nitrogen metabolism, Drug metabolism - other enzymes, Pathways in cancer,PI3K-Akt signaling pathway, etc. CDK2, HSP90AA1, AURKB, CCNA2, TYMS, CHEK1, AURKA, DNMT1, TOP2A, and TK1 were identified as core targets by Cytoscape 3.9.0. Molecular docking results showed that the binding energies of curcumin to the core targets were all less than 0 kJ-mol-1, suggesting that curcumin binds spontaneously to the core targets. These results were further validated in terms of mRNA expression levels, protein expression levels and immune infiltration.Conclusion: Based on network pharmacology and molecular docking initially revealed that curcumin exerts its therapeutic effects on colon cancer with multi-target, multi-pathway. Curcumin may exert anticancer effects by binding to core targets. Curcumin may interfere with colon cancer cell proliferation and apoptosis by regulating signal transduction pathways such as PI3K-Akt signaling pathway,IL-17 signaling pathway, Cell cycle. This will deepen and enrich our understanding of the potential mechanism of curcumin against colon cancer and provide a theoretical basis for subsequent studies.

AimsThis study aimed to conduct a bibliometric analysis of the relevant literature on the interaction between microbiota and immune in intestinal inflammatory diseases, and show its current status, hotspots, and development trends.MethodsThe related literature was acquired from the Web of Science Core Collection on October 12, 2022. Co-occurrence and cooperation relationship analysis of authors, institutions, countries, references, and keywords in the literature were carried out through CiteSpace 6.1.R3 software and the Online Analysis platform of Literature Metrology. At the same time, the relevant knowledge maps were drawn, and the keywords cluster analysis and emergence analysis were performed.Results3,608 related publications were included, showing that the number of articles in this field is increasing year by year. The results showed that Gasbarrini A and Sokol H were the authors with the highest cumulative number of articles with 25, and the institution with the most articles was Harvard University with 142 articles. The USA was far ahead in the article output, with 1,131 articles, and had a dominant role, followed by China with 707 articles. The journal Frontiers in Immunology contributed the most to this research field with 213 articles. In the cooperation network analysis, the USA, Harvard University, and Xavier RJ were the most widely collaborated country, institution, and author, respectively, which implied a high level of influence. Keywords analysis showed that there were 770 keywords, which were mainly classified as internal related diseases, such as “inflammatory bowel disease”, “irritable bowel syndrome”, “colorectal cancer”, and the mechanism of interaction of microbiota and immune, such as “intestinal microbiota”, “commensal microbiota”, “regulatory T cell”, “dendritic cell”, “barrier function”, “activation”, “anti-inflammatory properties”, “intestinal epithelium”, and “diversity”. Emerging analysis showed that future research hotspots and trends might be the short-chain fatty acid, gut dysbiosis, gut-liver axis, and fusobacterium nucleatum.ConclusionThis research was the first bibliometric analysis of publications in the field of interaction between microbiota and immune in intestinal inflammatory diseases using visualization software and data information mining, and obtained the current status, hotspots, and development of this field, which provides a theoretical basis for its scientific research.

IntroductionPost-hepatectomy liver failure (PHLF) is one of the most serious complications and causes of death in patients with hepatocellular carcinoma (HCC) after hepatectomy. This study aimed to develop a novel machine learning (ML) model based on the light gradient boosting machines (LightGBM) algorithm for predicting PHLF.MethodsA total of 875 patients with HCC who underwent hepatectomy were randomized into a training cohort (n=612), a validation cohort (n=88), and a testing cohort (n=175). Shapley additive explanation (SHAP) was performed to determine the importance of individual variables. By combining these independent risk factors, an ML model for predicting PHLF was established. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value, and decision curve analyses (DCA) were used to evaluate the accuracy of the ML model and compare it to that of other noninvasive models.ResultsThe AUCs of the ML model for predicting PHLF in the training cohort, validation cohort, and testing cohort were 0.944, 0.870, and 0.822, respectively. The ML model had a higher AUC for predicting PHLF than did other non-invasive models. The ML model for predicting PHLF was found to be more valuable than other noninvasive models.ConclusionA novel ML model for the prediction of PHLF using common clinical parameters was constructed and validated. The novel ML model performed better than did existing noninvasive models for the prediction of PHLF.

AimsThis study aimed to conduct a bibliometric analysis of the relevant literature on the diagnosis of inflammatory bowel disease (IBD), and show its current status, hot spots, and development trends.MethodsThe literature on IBD diagnosis was acquired from the Science Citation Index Expanded of the Web of Science Core Collection. Co-occurrence and cooperation relationship analysis of authors, institutions, countries, journals, references, and keywords in the literature were carried out through CiteSpace software and the Online Analysis platform of Literature Metrology. At the same time, the relevant knowledge maps were drawn, and the keywords cluster analysis and emergence analysis were performed.Results14,742 related articles were included, showing that the number of articles in this field has increased in recent years. The results showed that PEYRIN-BIROULET L from the University Hospital of Nancy-Brabois was the author with the most cumulative number of articles. The institution with the most articles was Mayo Clin, and the United States was far ahead in the article output and had a dominant role. Keywords analysis showed that there was a total of 818 keywords, which were mainly focused on the research of related diseases caused or coexisted by IBD, such as colorectal cancer and autoimmune diseases, and the diagnosis and treatment methods of IBD. Emerging analysis showed that future research hotspots and trends might be the treatment of IBD and precision medicine.ConclusionThis research was the first bibliometric analysis of publications in the field of IBD diagnosis using visualization software and data information mining, and obtained the current status, hotspots, and development of this field. The future research hotspot might be the precision medicine of IBD, and the mechanism needed to be explored in depth to provide a theoretical basis for its clinical application.

ObjectivesThere is an urgent need for biomarkers that predict the survival outcome of patients diagnosed with metastatic pancreatic cancer, undergoing systemic chemotherapy. This study aimed to identify biomarkers associated with the survival of mPC patients treated with modified FOLFIRINOX (mFOLFIRINOX) as first-line chemotherapy.MethodsThis was a retrospective study of 30 patients with mPC who received mFOLFIRINOX between October 2018 and March 2021. Data on carcinoembryonic antigen (CEA), cancer antigen (CA)199, interleukin (IL)-6, C-reactive protein (CRP), neutrophils, platelets, lymphocytes, and albumin were collected and dichotomized using the upper or lower limit, as appropriate. These markers were examined for their association with progression-free survival (PFS). A receiver operating characteristic (ROC) curve analysis was used to explore a suitable model to predict mFOLFIRINOX effectiveness.ResultsIL-6 and CRP levels were associated with poor progression (P = 0.004 and P =

This study analyzed the differences in subtypes and characteristics of advanced lung adenocarcinoma (LUAD) patients based on the pentose phosphate metabolic pathway-related long non-coding RNAs (lncRNAs), along with their potential regulatory mechanisms. Using the expression profiling and corresponding clinical information of LUAD patients from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). Differential pathway scores between normal and tumor samples from TCGA were identified by rank-sum tests. Pearson correlation coefficients between pentose phosphate scores of the pentose phosphate samples and lncRNAs of the corresponding datasets were calculated. Next, the clusterProfiler software package was used for functional annotation. Clustering of pentose phosphate-related lncRNAs from LUAD samples categorized two molecular subtypes (C1, and C2). C1 was associated with a lower pentose phosphate score and a good prognosis; the C2 showed a higher pentose phosphate score and was related to poorer prognoses. The C2 was markedly associated with energy metabolic pathways. The expression of most immune cells were markedly higher in C1 subtype. Some crucial immune checkpoints, including CTLA4, CD274, and CD47, were also significantly upregulated in C1 subtype, leading to a higher score of clinical effect on the C1 subtype. Finally, one TF, BACH1, was found to be significantly upregulated in C1 subtypes; the pathways activated by this TF may be associated with tumor progression and poor prognoses. LUAD typing based on pentose phosphate metabolic pathway-related lncRNAs was confirmed. Differences in characteristics between C1 and C2 subtypes improved the current LUAD detection and treatment.

Aggressive natural killer cell leukemia (ANKL) is a rare malignant tumor, especially uncommon in children. ANKL has very aggressive clinical course and bad prognosis and is usually caused by Epstein-Barr virus infection. ANKL often has clinical manifestations of hemophagocytic lymphohistiocytosis (HLH) and can be easily treated as HLH, which might complicate this aggressive disease. Here we report an ANKL in adolescent whose clinical presentation was highly aggressive and response to L-asparaginase containing chemotherapy was very bad. Early-onset Flow cytometry of peripheral blood and bone marrow help make the diagnosis.

AimsThis study aimed to investigate the distant metastasis pattern from newly diagnosed colorectal cancer (CRC) and also construct and validate a prognostic nomogram to predict both overall survival (OS) and cancer-specific survival (CSS) of CRC patients with distant metastases.MethodsPrimary CRC patients who were initially diagnosed from 2010 to 2016 in the SEER database were included in the analysis. The independent risk factors affecting the OS, CSS, all-cause mortality, and CRC-specific mortality of the patients were screened by the Cox regression and Fine–Gray competitive risk model. The nomogram models were constructed to predict the OS and CSS of the patients. The reliability and accuracy of the prediction model were evaluated by consistency index (C-index) and calibration curve. The gene chip GSE41258 was downloaded from the GEO database, and differentially expressed genes (DEGs) were screened by the GEO2R online tool (p < 0.05, |logFC|>1.5). The Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway and Gene Ontology (GO) annotation and String website were used for enrichment analysis and protein–protein interaction (PPI) analysis of DEGs, respectively, and Cytoscape software was used to construct PPI network and screen function modules and hub genes.ResultsA total of 57,835 CRC patients, including 47,823 without distant metastases and 10,012 (17.31%) with metastases, were identified. Older age, unmarried status, poorly differentiated or undifferentiated grade, right colon site, larger tumor size, N2 stage, more metastatic sites, and elevated carcinoembryonic antigen (CEA) might lead to poorer prognosis (all p < 0.01). The independent risk factors of OS and CSS were included to construct a prognosis prediction model for predicting OS and CSS in CRC patients with distant metastasis. C-index and calibration curve of the training group and validation group showed that the models had acceptable predictive performance and high calibration degree. Furthermore, by comparing CRC tissues with and without liver metastasis, 158 DEGs and top 10 hub genes were screened. Hub genes were mainly concentrated in liver function and coagulation function.ConclusionThe big data in the public database were counted and transformed into a prognostic evaluation tool that could be applied to the clinic, which has certain clinical significance for the formulation of the treatment plan and prognostic evaluation of CRC patients with distant metastasis.

Background and AimsEmergency endoscopy is recommended for patients with acute esophageal variceal bleeding (EVB) and their prognosis has improved markedly over past decades due to the increased specialization of endoscopic practice. The study aimed to compare outcomes following emergency endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) in cirrhotic patients with acute EVB.MethodsCirrhotic patients with acute EVB who underwent emergency endoscopy were retrospectively enrolled from 2013 to 2020 across 34 university hospitals from 30 cities. The primary outcome was the incidence of 5-day rebleeding after emergency endoscopy. Subgroup analysis was stratified by Child-Pugh class and bleeding history. A 1:1 propensity score matching (PSM) analysis was performed.ResultsA total of 1,017 and 382 patients were included in EIS group and EVL group, respectively. The 5-day rebleeding incidence was similar between EIS group and EVL group (4% vs. 5%, P = 0.45). The result remained the same after PSM (P = 1.00). Among Child-Pugh class A, B and C patients, there were no differences in the 5-day rebleeding incidence between the two groups after PSM (P = 0.25, 0.82, and 0.21, respectively). As for the patients with or without bleeding history, the differences between EIS group and EVL group were not significant after PSM (P = 1.00 and 0.26, respectively).ConclusionThe nationwide cohort study indicates that EIS and EVL are both efficient emergency endoscopic treatment strategies for acute EVB. EIS should not be dismissed as an economical and effective emergency endoscopic treatment strategy of acute EVB. ClincialTrials.gov number NCT04307264.

Ultraviolet (UV) irradiation has been well documented to be linked with almost all skin problems we know, and both dermis and epidermis may be affected to varying degrees by UV irradiation. Every time when exposed to sunlight without protection, our skin will step closer to photoaging, leading to irreversible consequences ultimately. Heat shock protein 27 (HSP27) is a vital protein involved in cell growth, autophagy, apoptosis, drug resistance, tumor genesis and metastasis. Evidence suggests that the organism is subjected to various internal and external environmental stresses (heat, oxidative stress, organic toxicants, etc.), and HSP27 with high expression has protective function. However, the expression of HSP27 in coping with UV irradiation have not been examined thoroughly. In this study, photodamage models were developed through different doses of UVB irradiation in human epidermal keratinocytes (HEKs) (30 mJ/cm2), human dermal fibroblasts (HDFs) (150 mJ/cm2) and mouse skin (2,700 mJ/cm2). HSP27 knockdown decreased cell viability and increased the incidence of UVB-induced reactive oxygen species (ROS) production. We got consistent results in vivo and vitro. Compared with that in the UVB group, the expression of LC3B was significantly lower, while the expression of p62 was significantly higher in the UVB + si-HSP27 group. It was also revealed that HSP27 knockdown reduced the expressions of some antioxidants, such as superoxide dismutase (SOD) and catalase (CAT), which accelerated UVB-induced ROS release. Moreover, histological results showed that epidermis was thickened and collagen fibers were disorganized in the UVB + si-HSP27 group. These findings have demonstrated that HSP27 might play a photoprotective role in the UVB-induced skin damage process by maintaining the normal autophagy and antioxidant level. It is implied that HSP27 could be a potential therapeutic target of photodamage. However, determination of the definitive mechanism requires further exploration.

ObjectiveBoys with Duchenne muscular dystrophy (DMD) are at risk of bone damage and low bone mineral density (BMD). The aim of the study is to examine lumbar BMD values measured by QCT and identify the factors associated with BMD loss using a multilevel mixed-effects model.MethodsLumbar BMD was evaluated by quantitative computed tomography (QCT) at diagnosis, 1 and 2 years follow up in patients with DMD who were treated with GC. Demographic data, functional activity scores (FMSs), laboratory parameters and steroid use were recorded. A multilevel mixed-effects model was used to analyze BMD loss.ResultsNineteen patients with DMD who had a total of sixty complete records between January 2018 and October 2021 were retrospectively analyzed. At baseline, 15.8% of patients (3/19) had low lumbar BMD (Z score ≤ −2), and the mean BMD Z score on QCT was -0.85 (SD 1.32). The mean BMD Z score at 1 and 2 years postbaseline decreased to -1.56 (SD 1.62) and -2.02 (SD 1.36), respectively. In our model, BMD Z score loss was associated with age (β=-0.358, p=0.0003) and FMS (β=-0.454, p=0.031). Cumulative GC exposure and serum levels of calcium, phosphorus, 25(OH)-vitamin D and creatinine kinase did not independently predict BMD loss.ConclusionsThis study demonstrates that in DMD patients, lumbar BMD decreased gradually and progressively. Age and FMS are the main contributors to BMD loss in boys with DMD. Early recognition of risk factors associated with BMD loss may facilitate the development of strategies to optimize bone health.

Plant circadian clock coordinates endogenous transcriptional rhythms with diurnal changes of environmental cues. OsPRR37, a negative component in the rice circadian clock, reportedly regulates transcriptome rhythms, and agronomically important traits. However, the underlying regulatory mechanisms of OsPRR37-output genes remain largely unknown. In this study, whole genome bisulfite sequencing and high-throughput RNA sequencing were applied to verify the role of DNA methylation in the transcriptional control of OsPRR37-output genes. We found that the overexpression of OsPRR37 suppressed rice growth and altered cytosine methylations in CG and CHG sequence contexts in but not the CHH context (H represents A, T, or C). In total, 35 overlapping genes were identified, and 25 of them showed negative correlation between the methylation level and gene expression. The promoter of the hexokinase gene OsHXK1 was hypomethylated at both CG and CHG sites, and the expression of OsHXK1 was significantly increased. Meanwhile, the leaf starch content was consistently lower in OsPRR37 overexpression lines than in the recipient parent Guangluai 4. Further analysis with published data of time-course transcriptomes revealed that most overlapping genes showed peak expression phases from dusk to dawn. The genes involved in DNA methylation, methylation maintenance, and DNA demethylation were found to be actively expressed around dusk. A DNA glycosylase, namely ROS1A/DNG702, was probably the upstream candidate that demethylated the promoter of OsHXK1. Taken together, our results revealed that CG and CHG methylation contribute to the transcriptional regulation of OsPRR37-output genes, and hypomethylation of OsHXK1 leads to decreased starch content and reduced plant growth in rice.

Background: Acute high altitude (HA) exposure results in blood pressure (BP) variations in most subjects. Previous studies have demonstrated that higher BP is potentially correlated with acute mountain sickness (AMS). The BP load may be of clinical significance regarding systemic circulation status.Objectives: This study aimed to examine HA-induced BP changes in patients with AMS compared to those in healthy subjects. Further, we provided clinical information about the relationship between variations in 24-h ambulatory parameters (BP level, BP variability, and BP load) and AMS.Methods: Sixty-nine subjects were enrolled and all participants ascended Litang (4,100 m above sea level). They were monitored using a 24-h ambulatory blood pressure device and underwent echocardiography within 24 h of altitude exposure. The 2018 Lake Louise questionnaire was used to evaluate AMS.Results: The AMS group comprised more women than men [15 (65.2%) vs. 13 (28.3%), P < 0.001] and fewer smokers [4 (17.4%) vs. 23 (50.0%), P = 0.009]. The AMS group exhibited significant increases in 24-h BP compared to the non-AMS group (24-h SBP variation: 10.52 ± 6.48 vs. 6.03 ± 9.27 mmHg, P = 0.041; 24-h DBP variation: 8.70 ± 4.57 vs. 5.03 ± 4.98 mmHg, P = 0.004). The variation of mean 24-h cBPL (cumulative BP load) (mean 24-h cSBPL: 10.58 ± 10.99 vs. 4.02 ± 10.58, P = 0.016; 24-h mean cDBPL: 6.03 ± 5.87 vs. 2.89 ± 4.99, P = 0.034) was also obviously higher in AMS subjects than in non-AMS subjects after HA exposure. 24-h mean cSBPL variation (OR = 1.07, P = 0.024) and 24-h mean cDBPL variation (OR = 1.14, P = 0.034) were independent risk factors of AMS. Moreover, variation of 24-h mean cSBPL showed a good correlation with AMS score (R = 0.504, P < 0.001).Conclusions: Our study demonstrated that patients with AMS had higher BP and BP load changes after altitude exposure than healthy subjects. Excessive BP load variations were associated with AMS. Thus, BP load could be an effective indicator regarding systemic circulation status of AMS.

Insufficient cardiorespiratory compensation is closely associated with acute hypoxic symptoms and high-altitude (HA) cardiovascular events. To avoid such adverse events, predicting HA cardiorespiratory fitness impairment (HA-CRFi) is clinically important. However, to date, there is insufficient information regarding the prediction of HA-CRFi. In this study, we aimed to formulate a protocol to predict individuals at risk of HA-CRFi. We recruited 246 volunteers who were transported to Lhasa (HA, 3,700 m) from Chengdu (the sea level [SL],

Higenamine, a natural product with multiple targets in heart diseases, is originally derived from Aconitum, which has been traditionally used in China for the treatment of heart disease, including heart failure, arrhythmia, bradycardia, cardiac ischemia/reperfusion injury, cardiac fibrosis, etc. This study is aimed to clarify the role of higenamine in heart diseases. Higenamine has effects on improving energy metabolism of cardiomyocytes, anti-cardiac fibroblast activation, anti-oxidative stress and anti-apoptosis. Accumulating evidence from various studies has shown that higenamine exerts a wide range of cardiovascular pharmacological effects in vivo and in vitro, including alleviating heart failure, reducing cardiac ischemia/reperfusion injury, attenuating pathological cardiac fibrosis and dysfunction. In addition, several clinical studies have reported that higenamine could continuously increase the heart rate levels of healthy volunteers as well as patients with heart disease, but there are variable effects on systolic blood pressure and diastolic blood pressure. Moreover, the heart protection and therapeutic effects of higenamine on heart disease are related to regulating LKB1/AMPKα/Sirt1, mediating the β2-AR/PI3K/AKT cascade, induction of heme oxygenase-1, suppressing TGF-β1/Smad signaling, and targeting ASK1/MAPK (ERK, P38)/NF-kB signaling pathway. However, the interventional effects of higenamine on heart disease and its underlying mechanisms based on experimental studies have not yet been systematically reviewed. This paper reviewed the potential pharmacological mechanisms of higenamine on the prevention, treatment, and diagnosis of heart disease and clarified its clinical applications. The literature shows that higenamine may have a potent effect on complex heart diseases, and proves the profound medicinal value of higenamine in heart disease.

Nausea and vomiting of pregnancy (NVP) is a common condition that affects up to 70% of pregnant women. Hyperemesis gravidarum (HG) is considered the serious form of NVP, which is reported in 0.3–10.8% of pregnant women. NVP has a relatively benign course, but HG can be linked with some poor maternal, fetal, and offspring outcomes. The exact causes of NVP and HG are unknown, but various factors have been hypothesized to be associated with pathogenesis. With the advance of precision medicine and molecular biology, some genetic factors such as growth/differentiation factor 15 (GDF15) have become therapeutic targets. In our review, we summarize the historical hypotheses of the pathogenesis of NVP and HG including hormonal factors, Helicobacter pylori, gastrointestinal dysmotility, placenta-related factors, psychosocial factors, and new factors identified by genetics. We also highlight some approaches to the management of NVP and HG, including pharmacological treatment, complementary treatment, and some supporting treatments. Looking to the future, progress in understanding NVP and HG may reduce the adverse outcomes and improve the maternal quality of life during pregnancy.

Background: Acute high-altitude (HA) exposure results in blood pressure (BP) and cardiac function variations in most subjects, some of whom suffer from acute mountain sickness (AMS). Several previous studies have found that cardiovascular function indicators are potentially correlated with AMS.Objectives: This study aims to examine HA-induced cardiovascular adaptations in AMS patients and compare them with healthy subjects. It also aims to investigate the relationship between cardiovascular function indicators and AMS, as well as to provide some insightful information about the prevention and treatment of AMS.Methods: Seventy-two subjects were enrolled in this cohort study. All the subjects ascended Litang (4,100 m above sea level). They were monitored by a 24-h ambulatory blood pressure (ABP) device and underwent echocardiography examination within 24 h of altitude exposure. The 2018 Lake Louise questionnaire was used to evaluate AMS.Results: Acute mountain sickness group consisted of more women (17 [60.7%] vs. 10 [22.7%], p = 0.001) and fewer smokers (5 [17.9%] vs. 23 [52.3%], p = 0.003). Compared with subjects without AMS, subjects with AMS had lower pulse pressure (PP) (daytime PP, 45.23 ± 7.88 vs. 52.14 ± 4.75, p < 0.001; nighttime PP, 42.81 ± 5.92 vs. 49.39 ± 7.67, p < 0.001) and lower effective arterial elastance (Ea) (1.53 ± 0.24 vs. 1.73 ± 0.39, p = 0.023). Multivariate regression indicated that female sex (OR = 0.23, p = 0.024), lower daytime PP (OR = 0.86, p = 0.004), and lower Ea (OR = 0.03, p = 0.015) at low altitude (LA) were independent risk factors for AMS. Combined daytime PP and Ea at LA had a high predictive value for AMS (AUC = 0.873; 95% CI: 0.789–0.956). Correlation analysis showed that AMS-induced headache correlated with daytime PP (R = −0.401, p < 0.001) and nighttime PP at LA (R = −0.401, p < 0.001).Conclusion: Our study demonstrated that AMS patients had a lower PP and Ea at LA. These baseline indicators of vasodilation at LA were closely associated with AMS, which may explain the higher headache severity in subjects with higher PP at LA.

Ribulose 5-phosphate (Ru5P) and guanosine 5′-triphosphate (GTP) are two key precursors of riboflavin, whereby Ru5P is also a precursor of GTP. Ribulose 5-phosphate 3-epimerase (Rpe) catalyzes the conversion of ribulose 5-phosphate into xylulose 5-phosphate. Inactivation of Rpe can reduce the consumption of Ru5P, enhancing the carbon flux toward riboflavin biosynthesis. Here we investigated the effect of mutation of rpe and other related genes on riboflavin production, physiological and metabolic phenotypes in Bacillus subtilis LY (BSLY). Introducing single nucleotide deletion (generated BSR) or nonsense mutation (generated BSRN) on the genomic copy of rpe, resulting in more than fivefold increase of riboflavin production over the parental strain. BSR process 62% Rpe activity, while BSRN lost the entire Rpe activity and had a growth defect compared with the parent strain. BSR and BSRN exhibited increases of the inosine and guanine titers, in addition, BSRN exhibited an increase of inosine 5′-monophosphate titer in fermentation. The transcription levels of most oxidative pentose phosphate pathway and purine synthesis genes were unchanged in BSR, except for the levels of zwf and ndk, which were higher than in BSLY. The production of riboflavin was increased to 479.90 ± 33.21 mg/L when ribA was overexpressed in BSR. The overexpression of zwf, gntZ, prs, and purF also enhanced the riboflavin production. Finally, overexpression of the rib operon by the pMX45 plasmid and mutant gnd by pHP03 plasmid in BSR led to a 3.05-fold increase of the riboflavin production (977.29 ± 63.44 mg/L), showing the potential for further engineering of this strain.

BackgroundIncreasing evidence indicates that alternative polyadenylation (APA) is associated with the prognosis of cancers.MethodsWe obtained gene expression and APA profiles of 259 sarcoma patients from the TCGA dataportal and TC3A database, respectively. The prognostic signatures, clinical nomograms, and regulatory networks were studied by integrated bioinformatics analyses. Then, the immune cell infiltration profile was obtained from the ImmuCellAI. The association between APA-based signature and immune cells was studied.ResultsA total of 61 and 38 APA events were identified as overall survival (OS)- and progress free-survival (PFS)-related biomarkers, respectively. Two signatures were generated. The area under the curves (AUC) values of OS signature were 0.900, 0.928, and 0.963 over 2-, 4-, and 6-years, respectively. And the AUC values of PFS signature at 2-, 4-, and 6-years were 0.826, 0.840, and 0.847, respectively. Overall and subgroup analyses indicated that high-risk patients had a worse prognosis than low-risk patients (all p-values < 0.05). In addition, immunomics analyses indicated that there are different patterns of immune cell infiltration between low- and high-risk patients. Furthermore, two clinical-APA nomograms were established and the C-indexes were 0.813 and 0.809 for OS nomogram and PFS nomogram, respectively. Finally, two APA regulatory networks were constructed. FIP1L1-VPS26B was identified as a key regulating relationship and validated in the pan-cancer analyses.ConclusionIn this study, we identified prognostic predictors based on APA events with high accuracy for risk stratification in sarcoma patients and uncovered interesting regulatory networks in sarcoma that could be underlying mechanisms. This study not only provides novel potential prognostic biomarkers but promote precision medicine and provide potential novel research interests for immunotherapy.

Background and Aims: The dietary inflammatory index (DII) is associated with non-communicable disease. We conducted an umbrella review to systematically evaluate meta-analyses of observational studies on DII and diverse health outcomes.Methods: We comprehensively searched the PubMed, Web of Science, and Embase databases to identify related systematic reviews and meta-analyses of observational studies. Those investigating the association between DII and a wide range of health outcomes in humans were eligible for inclusion. For each meta-analysis, we estimated the summary effect size by using fixed and random effects models, the 95% confidence interval, and the 95% prediction interval. We assessed heterogeneity, evidence of small-study effects, and excess significance bias.Results: The umbrella review identified 35 meta-analyses assessing associations between DII and various health outcomes: cancer (n = 24), mortality (n = 4), metabolic (n = 4), and other (n = 3). The methodological quality was high or moderate. Of the 35 meta-analyses, we observed highly suggestive evidence for harmful associations between digestive tract cancer, colorectal cancer, overall cancer, pharyngeal cancer, UADT cancer, and CVD mortality. Moreover, 11 harmful associations showed suggestive evidence: hormone-dependent cancer, rectal cancer, colon cancer, breast and prostate cancer, gynecological cancer, breast cancer, ovarian cancer, colorectal cancer, prostate cancer, all-cause mortality, and depression.Conclusion: DII is likely to be associated with harmful effects in multiple health outcomes. Robust randomized controlled trials are warranted to understand whether the observed results are causal.Systematic Review Registration: CRD42021218361

IntroductionPulmonary artery pressure (PAP) is increased and right ventricular (RV) function is well preserved in healthy subjects upon exposure to high altitude (HA). An increase in PAP may trigger notching of the right ventricular outflow tract Doppler flow velocity envelope (RVOT notch), which is associated with impaired RV function in patients with pulmonary hypertension. However, whether HA exposure can induce RVOT notch formation and the subsequent impact on cardiac function in healthy subjects remains unclear.MethodsA total of 99 subjects (69 males and 30 females) with a median age of 25 years were enrolled in this study; they traveled from 500 to 4100 m by bus over a 2-day period. All subjects underwent a comprehensive physiological and echocardiographic examination 1 day before ascension at low altitude and 15 ± 3 h after arrival at HA. The RVOT notch was determined by the presence of a notched shape in the RVOT Doppler flow velocity envelope. The systolic PAP (SPAP) was calculated as Bernoulli equation SPAP = 4 × (maximum tricuspid regurgitation velocity)2+5 and mean PAP (mPAP) = 0.61 × SPAP+2. Cardiac output was calculated as stroke volume × heart rate. Pulmonary capillary wedge pressure (PCWP) was calculated as 1.9+1.24 × mitral E/e’. Pulmonary vascular resistance (PVR) was calculated as (mPAP-PCWP)/CO.ResultsAfter HA exposure, 20 (20.2%) subjects had an RVOT notch [notch (+)], and 79 (79.8%) subjects did not have an RVOT notch [notch (−)]. In the multivariate logistic regression analysis, the SPAP, right ventricular global longitude strain (RV GLS), and tricuspid E/A were independently associated with the RVOT notch. The SPAP, mPAP, PVR, standard deviations of the times to peak systolic strain in the four mid-basal RV segments (RVSD4), peak velocity of the isovolumic contraction period (ICV), and the peak systolic velocity (s’) at the mitral/tricuspid annulus were increased in all subjects. Conversely, the pulse oxygen saturation (SpO2), RV GLS, and tricuspid annulus plane systolic excursion (TAPSE)/SPAP were decreased. However, the increases of SPAP, mPAP, PVR, and RVSD4 and the decreases of SpO2, RV GLS, and TAPSE/SPAP were more pronounced in the notch (+) group than in the notch (−) group. Additionally, increased tricuspid ICV and mitral/tricuspid s’ were found only in the notch (−) group.ConclusionHA exposure-induced RVOT notch formation is associated with impaired RV function, including no increase in the tricuspid ICV or s’, reduction of RV deformation, deterioration in RV-pulmonary artery coupling, and RV intraventricular synchrony.

Background: The expression of long non-coding RNA (lncRNA) is associated with the epithelial-mesenchymal transition (EMT) in tumorigenicity, but the role of EMT-related lncRNA in colorectal cancer (CRC) remains unclear.Methods: The clinical data and gene expression profile of CRC patients were obtained from The Cancer Genome Atlas database. Differential expression analysis, Cox regression model, and Kaplan-Meier analysis were used to study the relationship between EMT-related lncRNAs and the prognosis of CRC. Functional analysis and unsupervised clustering analysis were performed to explore the influence of certain lncRNAs on CRC. Finally, Cytoscape was used to construct mRNA-lncRNA networks.Results: Two signatures incorporating six and ten EMT-related lncRNAs were constructed for predicting the overall survival (OS) and disease-free survival (DFS), respectively. Kaplan-Meier survival curves indicated that patients in the high-risk group had a poorer prognosis than those in the low-risk group. The results of the functional analysis suggested that the P53 and ECM-receptor pathways affect the prognosis of CRC, and AL591178.1 is a key prognostic EMT-related lncRNA, which is negatively related to immune cells, P53 pathway, and ECM-receptor pathway.Conclusion: Six OS-related and ten DFS-related EMT-related lncRNAs were correlated with the prognosis of CRC by potentially affecting the immune microenvironment, and AL591178.1 plays a key role as a prognostic factor.

BackgroundEndometrial cancer (EC) is one of the most common female malignant tumors. The immunity is believed to be associated with EC patients’ survival, and growing studies have shown that aberrant alternative splicing (AS) might contribute to the progression of cancers.MethodsWe downloaded the clinical information and mRNA expression profiles of 542 tumor tissues and 23 normal tissues from The Cancer Genome Atlas (TCGA) database. ESTIMATE algorithm was carried out on each EC sample, and the OS-related different expressed AS (DEAS) events were identified by comparing the high and low stromal/immune scores groups. Next, we constructed a risk score model to predict the prognosis of EC patients. Finally, we used unsupervised cluster analysis to compare the relationship between prognosis and tumor immune microenvironment.ResultsThe prognostic risk score model was constructed based on 16 OS-related DEAS events finally identified, and then we found that compared with high-risk group the OS in the low-risk group was notably better. Furthermore, according to the results of unsupervised cluster analysis, we found that the better the prognosis, the higher the patient’s ESTIMATE score and the higher the infiltration of immune cells.ConclusionsWe used bioinformatics to construct a gene signature to predict the prognosis of patients with EC. The gene signature was combined with tumor microenvironment (TME) and AS events, which allowed a deeper understanding of the immune status of EC patients, and also provided new insights for clinical patients with EC.

Over the past two decades, scholars developed various unmanned sailboat platforms, but most of them have specialized designs and controllers. Whereas these robotic sailboats have good performance with open-source designs, it is actually hard for interested researchers or fans to follow and make their own sailboats with these open-source designs. Thus, in this paper, a generic and flexible unmanned sailboat platform with easy access to the hardware and software architectures is designed and tested. The commonly used 1-m class RC racing sailboat was employed to install Pixhawk V2.4.8, Arduino Mega 2,560, GPS module M8N, custom-designed wind direction sensor, and wireless 433 Mhz telegram. The widely used open-source hardware modules were selected to keep reliable and low-cost hardware setup to emphasize the generality and feasibility of the unmanned sailboat platform. In software architecture, the Pixhawk V2.4.8 provided reliable states’ feedback. The Arduino Mega 2,560 received estimated states from Pixhawk V2.4.8 and the wind vane sensor, and then controlled servo actuators of rudder and sail using simplified algorithms. Due to the complexity of introducing robot operating system and its packages, we designed a generic but real-time software architecture just using Arduino Mega 2,560. A suitable line-of-sight guidance strategy and PID-based controllers were used to let the autonomous sailboat sail at user-defined waypoints. Field tests validated the sailing performance in facing WRSC challenges. Results of fleet race, station keeping, and area scanning proved that our design and algorithms could control the 1-m class RC sailboat with acceptable accuracy. The proposed design and algorithms contributed to developing educational, low-cost, micro class autonomous sailboats with accessible, generic, and flexible hardware and software. Besides, our sailboat platform also facilitates readers to develop similar sailboats with more focus on their missions.

BackgroundAcute high altitude (HA) exposure elicits blood pressure (BP) responses in most subjects, and some of them suffer from acute mountain sickness (AMS). However, a 24-h ambulatory BP (ABP) change and the correlation with the occurrence of AMS in different sexes are still unclear.ObjectivesThis prospective study aimed to investigate HA induced BP responses in males and females and the relationship between AMS and 24-h ABP.MethodsForty-six subjects were matched according to demographic parameters by propensity score matching with a ratio of 1:1. All the subjects were monitored by a 24-h ABP device; the measurement was one period of 24 h BP. 2018 Lake Louise questionnaire was used to evaluate AMS.ResultsBoth the incidence of AMS (14 [60.9%] vs. 5 [21.7%], P = 0.007) and headache (18 [78.3%] vs. 8 [34.8%], P = 0.003) were higher in females than in males. All subjects showed an elevated BP in the early morning [morning systolic BP (SBP), 114.72 ± 13.57 vs. 120.67 ± 11.10, P = 0.013]. The elevation of morning SBP variation was more significant in females than in males (11.95 ± 13.19 vs. −0.05 ± 14.49, P = 0.005), and a higher morning BP surge increase (4.69 ± 18.09 vs. −9.66 ± 16.96, P = 0.005) was observed after acute HA exposure in the female group. The increase of morning SBP was associated with AMS occurrence (R = 0.662, P < 0.001) and AMS score (R = 0.664, P = 0.001). Among the AMS symptoms, we further revealed that the incidence (R = 0.786, P < 0.001) and the severity of headache (R = 0.864, P < 0.001) are closely correlated to morning SBP.ConclusionsOur study demonstrates that females are more likely to suffer from AMS than males. AMS is closely associated with elevated BP in the early morning period, which may be correlated to higher headache incidence in subjects with higher morning SBP.

Skin aging caused by UV radiation is called photoaging is characterized by skin roughness and dryness accompanied by a significant reduction of dermal collagen. Rapamycin is a macrolide immunosuppressant which has been shown to exhibit “anti-aging” effects in cells and organisms, however, its roles in the skin photoaging remains unclear. Here, we investigate the role of rapamycin and HSP27, which we have previously identified as an inhibitor of UV-induced apoptosis and senescence in HaCat cells, in a UVA-induced photoaging model of primary human dermal fibroblasts (HDFs). Results from senescence-associated beta-galactosidase (SA-β-gal) staining revealed that rapamycin significantly reduced senescence in UVA-treated HDFs. In addition, treatment with rapamycin significantly increased cell autophagy levels, decreased the expression of p53 and phosphorylated HSP27, and reduced genotoxic and oxidative cellular stress levels in UVA-induced HDFs. Knockdown of HSP27 resulted in a significant increase of MMP-1 and MMP-3 as well as a decrease in type I collagen expression. Rapamycin mitigated these effects by activation of the classical TGF-β/Smad signaling pathway and increasing the transcriptional activity of MAPK/AP-1. Taken together, these results suggest that rapamycin may potentially serve as a preventive and therapeutic agent for UVA-induced photoaging of the skin.

Male novel coronavirus disease (COVID-19) patients tend to have poorer clinical outcomes than female patients, while the myocardial injury is strongly associated with COVID-19-related adverse events. Owing to a lack of corresponding data, we aimed to investigate the sex differences in the incidence of myocardial injury in COVID-19 patients and to identify the potential underlying mechanisms, which may partly account for the sex bias in the incidence of adverse events. This retrospective study included 1,157 COVID-19 patients who were hospitalized in Huoshenshan Hospital from 12 March 2020 to 11 April 2020. Data on the patients’ demographic characteristics, initial symptoms, comorbidities and laboratory tests were collected. Totally, 571 (49.4%) female and 586 (50.6%) male COVID-19 patients were enrolled. The incidence of myocardial injury was higher among men than women (9.2 vs. 4.9%, p = 0.004). In the logistic regression analysis, age, and chronic kidney disease were associated with myocardial injury in both sexes. However, hypertension [odds ratio (OR) = 2.25, 95% confidence interval (CI) 1.20–4.22], coronary artery disease (OR = 2.46, 95% CI 1.14–5.34), leucocyte counts (OR = 3.13, 95% CI 1.24–7.86), hs-CRP (OR = 4.45, 95% CI 1.33–14.83), and D-dimer [OR = 3.93 (1.27–12.19), 95% CI 1.27–12.19] were independent risk factors only in the men. The correlations of hs-CRP and D-dimer with hs-cTnI and BNP were stronger in the men. The incidence of myocardial injury in COVID-19 patients is sex-dependent, predominantly in association with a greater degree of inflammation and coagulation disorders in men. Our findings can be used to improve the quality of clinical management in such settings.

BackgroundAmong colon cancer patients, liver metastasis is a commonly deadly phenomenon, but there are few prognostic models for these patients.MethodsThe clinicopathologic data of colon cancer with liver metastasis (CCLM) patients were downloaded from the Surveillance, Epidemiology and End Results (SEER) database. All patients were randomly divided into training and internal validation sets based on the ratio of 7:3. A prognostic nomogram was established with Cox analysis in the training set, which was validated by two independent validation sets.ResultsA total of 5,700 CCLM patients were included. Age, race, tumor size, tumor site, histological type, grade, AJCC N status, carcinoembryonic antigen (CEA), lung metastasis, bone metastasis, surgery, and chemotherapy were independently associated with the overall survival (OS) of CCLM in the training set, which were used to establish a nomogram. The AUCs of 1-, 2- and 3-year were higher than or equal to 0.700 in the training, internal validation, and external validation sets, indicating the favorable effects of our nomogram. Besides, whether in overall or subgroup analysis, the risk score calculated by this nomogram can divide CCLM patients into high-, middle- and low-risk groups, which suggested that the nomogram can significantly determine patients with different prognosis and is suitable for different patients.ConclusionHigher age, the race of black, larger tumor size, higher grade, histological type of mucinous adenocarcinoma and signet ring cell carcinoma, higher N stage, RCC, lung metastasis, bone metastasis, without surgery, without chemotherapy, and elevated CEA were independently associated with poor prognosis of CCLM patients. A nomogram incorporating the above variables could accurately predict the prognosis of CCLM.

Among all fatal gynecological malignant tumors, ovarian cancer has the highest mortality rate. The purpose of this study was to develop a stable and personalized glycometabolism-related prognostic signature to predict the overall survival of ovarian cancer patients. The gene expression profiles and clinical information of ovarian cancer patients were derived from four public GEO datasets, which were divided into training and testing cohorts. Glycometabolism-related genes significantly associated with prognosis were selected. A risk score model was established and validated to evaluate its predictive value. We found 5 genes significantly related to prognosis and established a five-mRNA signature. The five-mRNA signature significantly divided patients into a low-risk group and a high-risk group in the training set and validation set. Survival analysis showed that high risk scores obtained by the model were significantly correlated with adverse survival outcomes and could be regarded as an independent predictor for patients with ovarian cancer. In addition, the five-mRNA signature can predict the overall survival of ovarian cancer patients in different subgroups. In summary, we successfully constructed a model that can predict the prognosis of patients with ovarian cancer, which provides new insights into postoperative treatment strategies, promotes individualized therapy, and provides potential new targets for immunotherapy.

The aims of this study were to explore the effect of high-altitude (HA) exposure on the incidence, determinants, and impacts of right ventricular dyssynchrony (RVD). In our study, 108 healthy young men were enrolled, and physiological and echocardiographic variables were recorded at both sea level and 4,100 m. By using two-dimensional speckle-tracking echocardiography, RVD was evaluated by calculating the R–R interval-corrected standard deviation of the time-to-peak systolic strain for the four mid-basal RV segments (RVSD4) and defined by RVSD4 > 18.7 ms. After HA exposure, RVSD4 was significantly increased, and the incidence of RVD was approximately 32.4%. Subjects with RVD showed lower oxygen saturation (SaO2) and RV global longitudinal strain and higher systolic pulmonary artery pressure than those without RVD. Moreover, myocardial acceleration during isovolumic contraction was increased in all subjects and those without RVD, but not in those with RVD. Multivariate logistic regression revealed that SaO2 is an independent determinant of RVD at HA (odds ratio: 0.72, 95% CI: 0.56–0.92; P = 0.009). However, the mean pulmonary artery pressure was linearly correlated with the magnitude of RVD in the presence of Notch. No changes were found in RV fractional area change, tricuspid annular motion, or tricuspid s’ velocity between subjects with and without RVD. Collectively, we demonstrated for the first time that HA exposure could induce RVD in healthy subjects, which may be mainly attributed to the decline in SaO2 as well as RV overload; the incidence of RVD was associated with reduced RV regional function and blunted myocardial acceleration.

Purpose: To investigate whether a combination of radiomics and automatic machine learning applied to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of primary breast cancer can non-invasively predict axillary sentinel lymph node (SLN) metastasis.Methods: 62 patients who received a DCE-MRI breast scan were enrolled. Tumor resection and sentinel lymph node (SLN) biopsy were performed within 1 week after the DCE-MRI examination. According to the time signal intensity curve, the volumes of interest (VOIs) were delineated on the whole tumor in the images with the strongest enhanced phase. Datasets were randomly divided into two sets including a training set (~80%) and a validation set (~20%). A total of 1,409 quantitative imaging features were extracted from each VOI. The select K best and least absolute shrinkage and selection operator (Lasso) were used to obtain the optimal features. Three classification models based on the logistic regression (LR), XGboost, and support vector machine (SVM) classifiers were constructed. Receiver Operating Curve (ROC) analysis was used to analyze the prediction performance of the models. Both feature selection and models construction were firstly performed in the training set, then were further tested in the validation set by the same thresholds.Results: There is no significant difference between all clinical and pathological variables in breast cancer patients with and without SLN metastasis (P > 0.05), except histological grade (P = 0.03). Six features were obtained as optimal features for models construction. In the validation set, with respect to the accuracy and MSE, the SVM demonstrated the highest performance, with an accuracy, AUC, sensitivity (for positive SLN), specificity (for positive SLN) and Mean Squared Error (MSE) of 0.85, 0.83, 0.71, 1, 0.26, respectively.Conclusions: We demonstrated the feasibility of combining artificial intelligence and radiomics from DCE-MRI of primary tumors to predict axillary SLN metastasis in breast cancer. This non-invasive approach could be very promising in application.

Appetite loss is a common symptom that occurs in high altitude (HA) for lowlanders. Previous studies indicated that hypoxia is the initiating vital factor of HA appetite loss. PPARA, EPAS1, EGLN1, HIF1A, HIF1AN, and NFE2L2 play important roles in hypoxic responses. We aimed to explore the association of these hypoxia-related gene polymorphisms with HA appetite loss. In this study, we enrolled 416 young men who rapidly ascended to Lhasa (3700 m) from Chengdu (

The deep scattering layer (DSL), a stratum of the marine diel vertical migration (DVM) organisms inhabiting the mesopelagic ocean, plays a crucial role in transporting carbon and nutrients from the surface to depth through the migration of its organisms. Using 18 months of in-situ observations and altimeter sea level data, we reveal for the first time the intraseasonal variations and underlying mechanisms of the DSL and the DVM to the east of the Taiwan Island. Substantial vertical speeds acquired from the Acoustic Doppler Current Profiler were used to examine the distribution and variation of the DVM. Innovatively, the results for the power spectrum analysis of the scattering intensity demonstrated a significant intraseasonal variability (ISV) with an 80- day period in the DSL. Furthermore, the variation in the DVM was closely linked to the DSL and showed an 80-day ISV during the observation. A dynamic relationship between the ISV of the DSL east of Taiwan Island and the westward-propagating mesoscale eddies was established. Anticyclonic (cyclonic) eddy movement toward Taiwan Island triggers downward (upward) bending of the local isotherms, resulting in a layer of DSL warming (cooling) and subsequent upper boundary layer deepening (rising). These findings underscore the substantial influence of mesoscale eddies on biological activity in the mesopelagic ocean, establishing a novel understanding of ISV dynamics in the DSL and their links to eddy-induced processes. [ABSTRACT FROM AUTHOR]

Edge detection is one of the fundamental components of advanced computer vision tasks, and it is essential to preserve computational resources while ensuring a certain level of performance. In this paper, we propose a lightweight edge detection network called the Parallel and Hierarchical Network (PHNet), which draws inspiration from the parallel processing and hierarchical processing mechanisms of visual information in the visual cortex neurons and is implemented via a convolutional neural network (CNN). Specifically, we designed an encoding network with parallel and hierarchical processing based on the visual information transmission pathway of the "retina-LGN-V1" and meticulously modeled the receptive fields of the cells involved in the pathway. Empirical evaluation demonstrates that, despite a minimal parameter count of only 0.2 M, the proposed model achieves a remarkable ODS score of 0.781 on the BSDS500 dataset and ODS score of 0.863 on the MBDD dataset. These results underscore the efficacy of the proposed network in attaining superior edge detection performance at a low computational cost. Moreover, we believe that this study, which combines computational vision and biological vision, can provide new insights into edge detection model research. [ABSTRACT FROM AUTHOR]

Background: Endoplasmic reticulum stress (ERS) is a critical factor in the development of ulcerative colitis (UC); however, the underlying molecular mechanisms remain unclear. This study aims to identify pivotal molecular mechanisms related to ERS in UC pathogenesis and provide novel therapeutic targets for UC. Methods: Colon tissue gene expression profiles and clinical information of UC patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database, and the ERS-related gene set was downloaded from GeneCards for analysis. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were utilized to identify pivotal modules and genes associated with UC. A consensus clustering algorithm was used to classify UC patients. The CIBERSORT algorithm was employed to evaluate the immune cell infiltration. Gene Set Variation Analysis (GSVA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore potential biological mechanisms. The external sets were used to validate and identify the relationship of ERS-related genes with biologics. Small molecule compounds were predicted using the Connectivity Map (CMap) database. Molecular docking was performed to simulate the binding conformation of small molecule compounds and key targets. Results: The study identified 915 differentially expressed genes (DEGs) and 11 ERS-related genes (ERSRGs) from the colonic mucosa of UC patients and healthy controls, and these genes had good diagnostic value and were highly correlated. Five potential small-molecule drugs sharing tubulin inhibitors were identified, including albendazole, fenbendazole, flubendazole, griseofulvin, and noscapine, among which noscapine exhibited the highest correlation with a high binding affinity to the targets. Active UC and 10 ERSRGs were associated with a large number of immune cells, and ERS was also associated with colon mucosal invasion of active UC. Significant differences in gene expression patterns and immune cell infiltration abundance were observed among ERS-related subtypes. Conclusion: The results suggest that ERS plays a vital role in UC pathogenesis, and noscapine may be a promising therapeutic agent for UC by affecting ERS. [ABSTRACT FROM AUTHOR]