Appraising associations between signature lipidomic biomarkers and digestive system cancer risk: novel evidences from a prospective cohort study of UK Biobank and Mendelian randomization analyses.

BACKGROUND: The roles of serum lipids on digestive system cancer (DSC) risk were still inconclusive. In this study, we systematically assessed indicative effects of signature lipidomic biomarkers (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)) on DSC (oesophagus, stomach, colorectal, liver, gallbladder, and pancreas cancers) risk. METHODS: HDL-C, LDL-C, and TG concentration measurements were respectively analyzed with enzyme immunoinhibition, enzymatic selective protection, and GPO-POD methods in AU5800 supplied from Beckman Coulter. The diagnoses of DSCs were coded using International Classification of Diseases, Tenth Revision (ICD-10) codes updated until October 2022 in the UK Biobank (UKB). In this study, we assessed phenotypic association patterns between signature lipidomic biomarkers and DSC risk using restricted cubic splines (RCSs) in multivariable-adjusted Cox proportional hazards regression models. Moreover, linear and nonlinear causal association patterns of signature lipidomic biomarkers with DSC risk were determined by linear and nonlinear Mendelian randomization (MR) analyses. RESULTS: A median follow-up time of 11.8 years was recorded for 319,568 participants including 6916 DSC cases. A suggestive independent nonlinear phenotypic association was observed between LDL-C concentration and stomach cancer risk (Pnonlinearity < 0.05, Poverall < 0.05). Meanwhile, a remarkable independent linear negative phenotypic association was demonstrated between HDL-C concentration and stomach cancer risk (Pnonlinearity > 0.05, Poverall < 0.008 (0.05/6 outcomes, Bonferroni-adjusted P)), and suggestive independent linear positive associations were observed between HDL-C concentration and colorectal cancer risk, and between TG concentration and gallbladder cancer risk (Pnonlinearity > 0.05, Poverall < 0.05). Furthermore, based on nonlinear and linear MR-based evidences, we observed an suggestive independent negative causal association (hazard ratio (HR) per 1 mmol/L increase: 0.340 (0.137-0.843), P = 0.020) between LDL-C and stomach cancer risk without a nonlinear pattern (Quadratic P = 0.901, Cochran Q P = 0.434). Meanwhile, subgroup and stratified MR analyses both supported the category of LDL-C ≥ 4.1 mmol/L was suggestively protective against stomach cancer risk, especially among female participants (HR: 0.789 (0.637-0.977), P = 0.030) and participants aged 60 years or older (HR: 0.786 (0.638-0.969), P = 0.024), and the category of TG ≥ 2.2 mmol/L concluded to be a suggestive risk factor for gallbladder cancer risk in male participants (HR: 1.447 (1.020-2.052), P = 0.038) and participants aged 60 years or older (HR: 1.264 (1.003-1.593), P = 0.047). CONCLUSIONS: Our findings confirmed indicative roles of signature lipidomic biomarkers on DSC risk, notably detecting suggestive evidences for a protective effect of high LDL-C concentration on stomach cancer risk, and a detrimental effect of high TG concentration on gallbladder cancer risk among given participants.

Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial.

Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 µg/kg bolus over 3-5 minutes followed by an infusion of 1.0 µg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Conclusions and Relevance: Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03740958.

An internal hernia caused by Meckel's diverticulum: a case report.

BACKGROUND: Meckel's diverticulum is a remnant of the omphalomesenteric duct. It can lead to intestinal perforation, obstruction and gastrointestinal bleeding. While the internal hernia caused by Meckel's diverticulum is rarely reported. CASE PRESENTATION: We report a case of a 45-year old female patient who presented with intestinal obstruction and on laparotomy was found to have Meckel's diverticulum with internal hernia causing intestinal gangrene. Segmental bowel resection was performed and the patient had uneventful recovery. CONCLUSIONS: In patients with acute intestinal obstruction without previous abdominal surgery, Meckel's diverticulum and its complications should be suspected.

A Prognostic Model Based on the Immune-related Genes in Colon Adenocarcinoma.

Background: Immune-related genes (IRGs) are critically involved in the tumor microenvironment (TME) of colon adenocarcinoma (COAD). Here, the study was mainly designed to establish a prognostic model of IRGs to predict the survival of COAD patients. Methods: The Cancer Genome Atlas (TCGA), Immunology Database and Analysis Portal (ImmPort) database, and Cistrome database were utilized for extracting data regarding the expression of immune gene- and tumor-related transcription factors (TFs), aimed at the identification of differentially expressed genes (DEGs), differentially expressed IRGs (DEIRGs), and differentially expressed TFs (DETFs). Univariate Cox regression analysis was subsequently performed for the acquisition of prognosis-related IRGs, followed by establishment of TF regulatory network for uncovering the possible molecular regulatory association in COAD. Subsequently, multivariate Cox regression analysis was conducted to further determine the role of prognosis-related IRGs for prognostic prediction in COAD. Finally, the feasibility of a prognostic model with immunocytes was explored by immunocyte infiltration analysis. Results: A total of 2450 DEGs, 8 DETFs, and 79 DEIRGs were extracted from the corresponding databases. Univariate Cox regression analysis revealed 11 prognosis-related IRGs, followed by establishment of a regulatory network on prognosis-related IRGs at transcriptional levels. Functionally, IRG GLP2R was negatively modulated by TF MYH11, whereas IRG TDGF1 was positively modulated by TF TFAP2A. Multivariate Cox regression analysis was subsequently performed to establish a prognostic model on the basis of seven prognosis-related IRGs (GLP2R, ESM1, TDGF1, SLC10A2, INHBA, STC2, and CXCL1). Moreover, correlation analysis of immunocyte infiltration also revealed that the seven-IRG prognostic model was positively associated with five types of immunocytes (dendritic cell, macrophage, CD4 T cell, CD8 T cell, and neutrophil), which may directly reflect tumor immune state in COAD. Conclusions: Our present findings indicate that the prognostic model based on prognosis-related IRGs plays a crucial role in the clinical supervision and prognostic prediction of COAD patients at both molecular and cellular levels.

Comparison of Structural and Functional Characterizations of Arabinoxylans from Different Wheat Processing Varieties.

Water-extracted arabinoxylans (WEAXs) of different varieties and structures have important effects on wheat end products. However, the functional performances of WEAXs, particularly relating to prebiotic potential, are not yet clear. The present study compared the structural features, physicochemical properties, and prebiotic potential of WEAXs from three wheat varieties, which were used as special wheat varieties to make steamed buns, bread flour, and noodles. The results showed that WEAX-1, WEAX-2, and WEAX-3, derived from Jinqiang wheat, American red hard spring wheat, and Australian white wheat, respectively, had different structural properties, gelation properties, and prebiotic potential. WEAX-3 had a low arabinose to xylose (A/X) ratio (0.49), high ferulic acid content (2300 µg/g), and excellent gelation capacity. WEAX-2 had a high A/X ratio (0.62), low ferulic acid content (1300 µg/g), and poor gelation capacity. When fermented with human feces, WEAX-3 significantly increased the numbers of bifidobacteria and lactobacilli and increased the production of short-chain fatty acids (SCFAs), while WEAX-2 had weaker effects on the number of beneficial bacteria and SCFAs production (P < 0.05). The physicochemical properties and prebiotic potential of WEAXs depended strongly on their structural properties. WEAX with a low A/X ratio and a high ferulic acid content showed excellent gelation property and a strong prebiotic potential.

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy.

Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence and mortality, deprives countless patients of health and even life. According to global cancer statistics, there were an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths in 2020, with the age-standardized incidence and mortality rates of 201.0 and 100.7 per 100,000, respectively. Although remarkable advancements have been made in therapeutic strategies recently, the overall prognosis of cancer patients remains not optimistic. Consequently, there are still many severe challenges to be faced and difficult problems to be solved in cancer therapy today. Epigallocatechin gallate (EGCG), a natural polyphenol extracted from tea leaves, has received much attention for its antitumor effects. Accumulating investigations have confirmed that EGCG can inhibit tumorigenesis and progression by triggering apoptosis, suppressing proliferation, invasion, and migration, altering tumor epigenetic modification, and overcoming chemotherapy resistance. Nevertheless, its regulatory roles and biomolecular mechanisms in the immune microenvironment, metabolic microenvironment, and immunotherapy remain obscure. In this article, we summarized the most recent updates about the effects of EGCG on tumor microenvironment (TME), metabolic reprogramming, and anti-cancer immunotherapy. The results demonstrated EGCG can promote the anti-cancer immune response of cytotoxic lymphocytes and dendritic cells (DCs), attenuate the immunosuppression of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), and inhibit the tumor-promoting functions of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), and various stromal cells including cancer-associated fibroblasts (CAFs), endothelial cells (ECs), stellate cells, and mesenchymal stem/stromal cells (MSCs). Additionally, EGCG can suppress multiple metabolic reprogramming pathways, including glucose uptake, aerobic glycolysis, glutamine metabolism, fatty acid anabolism, and nucleotide synthesis. Finally, EGCG, as an immunomodulator and immune checkpoint blockade, can enhance immunotherapeutic efficacy and may be a promising candidate for antitumor immunotherapy. In conclusion, EGCG plays versatile regulatory roles in TME and metabolic reprogramming, which provides novel insights and combined therapeutic strategies for cancer immunotherapy.

Effects of Co-Modification by Extrusion and Enzymatic Hydrolysis on Physicochemical Properties of Black Wheat Bran and Its Prebiotic Potential.

Black wheat bran (BWB) is an important source of dietary fiber (DF) and phenolic compounds and has stronger nutritional advantages than ordinary WB. However, the low content of soluble dietary fiber (SDF) negatively influences its physicochemical properties and nutritive functions. To obtain a higher content of SDF in BWB, we evaluated the impact of co-modification by extrusion and enzymes (cellulase, xylanase, high-temperature α-amylase, and acid protease) on water extractable arabinoxylan (WEAX) in BWB. An optimized co-modification method was obtained through single-factor and orthogonal experiments. The prebiotic potential of co-modified BWB was also evaluated using pooled fecal microbiota from young, healthy volunteers. The commonly investigated inulin served as a positive control. After co-modification, WEAX content was dramatically increased from 0.31 g/100 g to 3.03 g/100 g (p < 0.05). The water holding capacity, oil holding capacity, and cholesterol adsorption capacity (pH = 2.0 and pH = 7.0) of BWB were increased by 100%, 71%, 131%, and 133%, respectively (p < 0.05). Scanning electron microscopy demonstrated a looser and more porous microstructure for co-modified BWB granules. Through in vitro anerobic fermentation, co-modified BWB achieved a higher content of Bifidobacterium and Lactobacillus than inulin fermentation. In addition, co-modified BWB induced the highest butyric acid production, indicating high potential as prebiotics. The results may contribute to improving technologies for developing high-fiber-content cereal products.

The potential of epigallocatechin gallate in the chemoprevention and therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), one of the most notorious malignancies globally, has a high fatality and poor prognosis. Though remarkable breakthroughs have been made in the therapeutic strategies recently, the overall survival of HCC remains unsatisfactory. Consequently, the therapy of HCC remains a great challenge. Epigallocatechin gallate (EGCG), a natural polyphenol extracted from the leaves of the tea bush, has been extensively investigated for its antitumor effects. In this review, we summarize the previous literature to elucidate the roles of EGCG in the chemoprophylaxis and therapy of HCC. Accumulating evidence has confirmed EGCG prevents and inhibits the hepatic tumorigenesis and progression through multiple biological mechanisms, mainly involving hepatitis virus infection, oxidative stress, proliferation, invasion, migration, angiogenesis, apoptosis, autophagy, and tumor metabolism. Furthermore, EGCG enhances the efficacy and sensitivity of chemotherapy, radiotherapy, and targeted therapy in HCC. In conclusion, preclinical studies have confirmed the potential of EGCG for chemoprevention and therapy of HCC under multifarious experimental models and conditions. Nevertheless, there is an urgent need to explore the safety and efficacy of EGCG in the clinical practice of HCC.

A cuproptosis-related lncRNA signature to predict prognosis and immune microenvironment of colon adenocarcinoma.

Cuproptosis is a novel cell death modality but its regulatory role in the colon cancer remains obscure. This study is committed to establishing a cuproptosis-related lncRNA (CRL) signature to forecast the prognosis for colon adenocarcinoma (COAD). The Cancer Genome Atlas (TCGA) samples were randomly divided into training and validation cohorts. LASSO-COX analysis was performed to construct a prognostic signature consisting of five CRLs (AC015712.2, ZEB1-AS1, SNHG26, AP001619.1, and ZKSCAN2-DT). We found the patients with high-risk scores suffered from poor prognosis in training cohort (p < 0.001) and validation cohort (p = 0.004). Nomogram was created based on the 5-CRL signature. Calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) demonstrated the nomogram performed well in 1­, 3­, and 5­year overall survival (OS). Subsequently, we observed increased infiltration of multiple immune cells and upregulated expression of immune checkpoints and RNA methylation modification genes in high-risk patients. Additionally, gene set enrichment analysis (GSEA) revealed two tumor-related pathways, including MAPK and Wnt signaling pathways. Finally, we found AKT inhibitors, all-trans retinoic acid (ATRA), camptothecin, and thapsigargin had more sensitivity to antitumor therapy in high-risk patients. Collectively, this CRL signature is promising for the prognostic prediction and precise therapy of COAD.

The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.

The occurrence and progression of tumors are inseparable from glucose metabolism. With the development of tumors, the volume increases gradually and the nutritional supply of tumors cannot be fully guaranteed. The tumor microenvironment changes and glucose deficiency becomes the common stress environment of tumors. Here, we discuss the mutual influences between glucose deprivation and other features of the tumor microenvironment, such as hypoxia, immune escape, low pH, and oxidative stress. In the face of a series of stress responses brought by glucose deficiency, different types of tumors have different coping mechanisms. We summarize the tumor studies on glucose deficiency in the last decade and review the genes and pathways that determine the fate of tumors under harsh conditions. It turns out that most of these genes help tumor cells survive in glucose-deprivation conditions. The development of related inhibitors may bring new opportunities for the treatment of tumors.

A network causal relationship between type-1 diabetes mellitus, 25-hydroxyvitamin D level and systemic lupus erythematosus: Mendelian randomization study.

BACKGROUND: Observational studies have suggested a relationship between type-1 diabetes mellitus (T1DM) and systemic lupus erythematosus (SLE). In both autoimmunities, 25-hydroxyvitamin D (25-OHD) deficiency is common. However, the causality between T1DM, 25-OHD level and SLE remains largely unknown. METHODS: Independent genetic variants associated with T1DM, 25-OHD level, and SLE from the largest genome-wide association studies were used to conduct two-sample bidirectional Mendelian randomization (BIMR) and two-step Mendelian randomization (MR) analysis to estimate causal relationship between T1DM, 25-OHD level and SLE, and further multivariable Mendelian randomization (MVMR) was used to verify direct causality of T1DM and 25-OHD level on SLE. A series of sensitivity analysis as validation of primary MR results were performed. RESULTS: Consistent with the results of BIMR, there was strong evidence for a direct causal effect of T1DM on the risk of SLE (ORMVMR-IVW = 1.249, 95% CI = 1.148-1.360, PMVMR-IVW = 1.25×10-5), and 25-OHD level was negatively associated with the risk of SLE (ORMVMR-IVW = 0.305, 95% CI = 0.109-0.857, PMVMR-IVW = 0.031). We also observed a negative causal effect of T1DM on 25-OHD level (ORBIMR-IVW = 0.995, 95% CI = 0.991-0.999, PBIMR-IVW = 0.030) while the causal effect of 25-OHD level on the risk of T1DM did not exist (PBIMR-IVW = 0.106). In BIMR analysis, there was no evidence for causal effects of SLE on the risk of T1DM and 25-OHD level (PBIMR-IVW > 0.05, respectively). CONCLUSION: Our MR analysis suggested that there was a network causal relationship between T1DM, 25-OHD level and SLE. T1DM and 25-OHD level both have causal associations with the risk of SLE, and 25-OHD level could be a mediator in the causality of T1DM and SLE.

470-Million-year-old black corals from China.

Phosphatic (possibly secondarily phosphatised) remains of antipatharian coralla, previously unknown in the fossil record, occur abundantly in the early Ordovician Fenxiang Formation in the Hubei Province, southern China. Probably two species (and genera) are represented, which differ in spinosity of branches. The more spinose one, Sinopathes reptans, has its lateral spines bearing regular, longitudinally arranged costellae. The early Floian geological age of this finding, about 470 Ma, supports predictions on the timing of anthozoan phylogeny derived from the molecular phylogenetic evidence. Black corals (Antipatharia) are basal to the scleractinians in the Hexacorallia clade, being more derived than sea anemones and the Zoantharia. Based on calibration of the molecular clock with Mesozoic data, the first split of lineages within the scleractinian hexacorals was proposed to take place approximately 425 million years ago. This implies that the origin of Antipatharia should precede this date. They have not been known in the fossil record because of unmineralised skeleton composed primarily of laminar chitin complexed with a protein. Unlike all recent species, the encrusting basal part of the colony dominated in the Ordovician ones and only occasionally erect branches developed, rather chaotically ramified. This presumably plesiomorphic trait seems consistent with ancient geological age and suggests that some problematic fossils from the Late Cambrian may be their, even less-derived, relatives.

DEK modulates both expression and alternative splicing of cancer­related genes.

DEK is known to be a potential proto­oncogene and is highly expressed in gastric cancer (GC); thus, DEK is considered to contribute to the malignant progression of GC. DEK is an RNA­binding protein involved in transcription, DNA repair, and selection of splicing sites during mRNA processing; however, its precise function remains elusive due to the lack of clarification of the overall profiles of gene transcription and post­transcriptional splicing that are regulated by DEK. We performed our original whole­genomic RNA­Seq data to analyze the global transcription and alternative splicing profiles in a human GC cell line by comparing DEK siRNA­treated and control conditions, dissecting both differential gene expression and potential alternative splicing events regulated by DEK. The siRNA­mediated knockdown of DEK in a GC cell line led to significant changes in gene expression of multiple cancer­related genes including both oncogenes and tumor suppressors. Moreover, it was revealed that DEK regulated a number of alternative splicing in genes which were significantly enriched in various cancer­related pathways including apoptosis and cell cycle processes. This study clarified for the first time that DEK has a regulatory effect on the alternative splicing, as well as on the expression, of numerous cancer­related genes, which is consistent with the role of DEK as a possible oncogene. Our results further expand the importance and feasibility of DEK as a clinical therapeutic target for human malignancies including GC.

The Prognostic and Molecular Landscape of Autophagy-Related Long Noncoding RNA in Colorectal Cancer.

Current evidence suggests that autophagy is closely correlated with the pathogenesis and development of malignant tumors. This study is aimed at assessing the potential prognostic significance of autophagy-related long noncoding RNA (ARlncRNA) in colorectal cancer (CRC). 3145 ARlncRNAs were obtained from autophagy-related genes (ARGs) by Pearson correlation analysis, and we established a competing endogenous RNA (ceRNA) network mediated by ARlncRNAs. A novel six-ARlncRNA prognostic signature was constructed based on TCGA samples used as the training group. Kaplan-Meier survival analysis and independent prognosis analysis were performed on the internal (training and test groups) and external validations (GEO datasets) to assess the accuracy and clinical practicability. Moreover, the nomogram combining the two independent prognostic factors (age and ARlncRNA-risk score (ARlncRNA-RS)) intuitively displayed overall survival. Gene set enrichment analysis (GSEA) conducted on the prognostic signature revealed that the gene set of the high-risk group was significantly enriched in the hallmark gene set "hypoxia" and the gene set of the low-risk group was enriched in KEGG pathways, including "peroxisome," "the citrate cycle (TCA cycle)," and "other glycan degradation." Assessment of antineoplastic therapy susceptibility and microsatellite instability (MSI) analysis were performed on CRC samples based on the prognostic signature. Moreover, Spearman correlation analysis was conducted on the expression of six ARlncRNAs of the prognostic signature and cancer stem cell (CSC) index as well as the tumor microenvironment (TME). In conclusion, this study established a six-ARlncRNA prognostic signature, which yielded favorable prognostic significance and demonstrated the correlation between ARlncRNAs and CRC progression.

Genetic estimation of correlations and causalities between multifaceted modifiable factors and gastro-oesophageal reflux disease.

Background: Gastro-oesophageal reflux disease (GORD) is a common gastrointestinal dysfunction that significantly affects the quality of daily life, and health interventions are challenging to prevent the risk of GORD. In this study, we used Mendelian randomization framework to genetically determine the causal associations between multifaceted modifiable factors and the risk of GORD. Materials and methods: Sixty-six exposures with available instrumental variables (IVs) across 6 modifiable pathways were included in the univariable MR analysis (UVMR). Summary-level genome-wide association studies (GWAS) datasets for GORD were retrieved from the Neale Lab (GORD Neale , Ncases = 29975, Ncontrols = 390556) and FinnGen (GORD Finn , Ncases = 13141, Ncontrols = 89695). Using the METAL software, meta-analysis for single nucleotide polymorphisms (SNPs) from GORD Neale and GORD Finn was conducted with an inverse variance weighted (IVW) fixed-effect model. Moreover, we leveraged partition around medoids (PAM) clustering algorithm to cluster genetic correlation subtypes, whose hub exposures were conditioned for multivariable MR (MVMR) analyses. P-values were adjusted with Bonferroni multiple comparisons. Results: Significant causal associations were identified between 26 exposures (15 risk exposures and 11 protective exposures) and the risk of GORD. Among them, 13 risk exposures [lifetime smoking, cigarette consumption, insomnia, short sleep, leisure sedentary behavior (TV watching), body mass index (BMI), body fat percentage, whole body fat mass, visceral adipose tissue, waist circumference, hip circumference, major depressive disorder, and anxious feeling], and 10 protective exposures (leisure sedentary behavior (computer use), sitting height, hand grip strength (left and right), birth weight, life satisfaction, positive affect, income, educational attainment, and intelligence) showed novel significant causal associations with the risk of GORD. Moreover, 13 exposures still demonstrated independent associations with the risk of GORD following MVMR analyses conditioned for hub exposures (educational attainment, smoking initiation and BMI). In addition, 12 exposures showed suggestive causal associations with the risk of GORD. Conclusion: This study systematically elucidated the modifiable factors causally associated with the risk of GORD from multifaceted perspectives, which provided implications for prevention and treatment of GORD.

PTEN Expression Was Significantly Associated with PD-L1 Score but Not with EBV Infection in Gastric Cancer.

Purpose: Gastric cancer (GC) remains a prevalent aggressive tumor with high morbidity and mortality globally. The identification of GC subtypes based on molecular features improved the prediction of prognosis and the selection of targeted therapies. PTEN is a characteristic tumor suppressor, while its association with different GC subtypes was unknown. Patients and Methods: The cohort consisted of 248 patients diagnosed with gastric cancer who were hospitalized and received radical gastrectomy. In addition, PTEN gene expression matrix of STAD was retrieved from TCGA. The mRNA and protein levels of PTEN and PD-L1 were detected using qRT-PCR and IHC staining. Multivariate logistic regression and Kaplan-Meier analysis were used to examine the relationship between PTEN expression and clinical characteristics. Results: In our study, PTEN was downregulated in gastric tumors both in mRNA and protein levels. Its inactivation was closely linked to higher histological grade (P = 0.005), neural invasion (P = 0.012), depth of invasion (P = 0.021), lymph metastasis (P = 0.026), and TNM stage (P = 0.001) of GC in the present study. Moreover, according to the molecular subtypes, high PTEN expression was related to high TPS score of PD-L1 positively (P = 0.010) but was not associated with MSI and EBV infection. Further, TCGA data validated that PTEN was indeed correlated with histological grade and invasion depth and positively related to PD-L1 expression (R = 0.29, adjusted P < 0.001). Conclusion: The above results suggested that PTEN expression was a useful marker in gastric carcinogenesis and progression and in the selection of immunotherapy-based treatments for GC patients.

Multi-Omics Prognostic Signatures Based on Lipid Metabolism for Colorectal Cancer.

Background: The potential biological processes and laws of the biological components in malignant tumors can be understood more systematically and comprehensively through multi-omics analysis. This study elaborately explored the role of lipid metabolism in the prognosis of colorectal cancer (CRC) from the metabonomics and transcriptomics. Methods: We performed K-means unsupervised clustering algorithm and t test to identify the differential lipid metabolites determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) in the serum of 236 CRC patients of the First Hospital of Jilin University (JLUFH). Cox regression analysis was used to identify prognosis-associated lipid metabolites and to construct multi-lipid-metabolite prognostic signature. The composite nomogram composed of independent prognostic factors was utilized to individually predict the outcome of CRC patients. Glycerophospholipid metabolism was the most significant enrichment pathway for lipid metabolites in CRC, whose related hub genes (GMRHGs) were distinguished by gene set variation analysis (GSVA) and weighted gene co-expression network analysis (WGCNA). Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis were utilized to develop the prognostic signature. Results: Six-lipid-metabolite and five-GMRHG prognostic signatures were developed, indicating favorable survival stratification effects on CRC patients. Using the independent prognostic factors as variables, we established a composite nomogram to individually evaluate the prognosis of CRC patients. The AUCs of one-, three-, and five-year ROC curves were 0.815, 0.815, and 0.805, respectively, showing auspicious prognostic accuracy. Furthermore, we explored the potential relationship between tumor microenvironment (TME) and immune infiltration. Moreover, the mutational frequency of TP53 in the high-risk group was significantly higher than that in the low-risk group (p < 0.001), while in the coordinate mutational status of TP53, the overall survival of CRC patients in the high-risk group was significantly lower than that in low-risk group with statistical differences. Conclusion: We identified the significance of lipid metabolism for the prognosis of CRC from the aspects of metabonomics and transcriptomics, which can provide a novel perspective for promoting individualized treatment and revealing the potential molecular biological characteristics of CRC. The composite nomogram including a six-lipid-metabolite prognostic signature is a promising predictor of the prognosis of CRC patients.

Quality improvement effects of electrolyzed water on rice noodles prepared with semidry-milled rice flours.

To investigate the effects of electrolyzed water treatment on the qualities of rice noodles prepared with semidry- milled rice flour, pasting properties and thermal properties of rice flour, and the cooking and textural properties of rice noodles were determined. Higher peak viscosity and lower melting enthalpy were observed in electrolyzed water (EW) treated rice flour. The hardness, gumminess and chewiness of rice noodle in slightly acidic electrolyzed water treated rice noodles with available chlorine concentration (ACC) 20.32 mg/L were increased significantly (p < 0.05). The cooking loss decreased significantly in strong acidic electrolyzed water treated noodles with ACC 10.09 mg/L treatment (p < 0.05). The results indicated that EW could promote the gelatinization of rice flour, and improve the textural qualities of rice noodles. Therefore EW was appropriate to be used in rice noodle production.

Painful Diabetic Peripheral Neuropathy Study of Chinese Outpatients (PDNSCOPE): A Multicentre Cross-Sectional Registry Study of Clinical Characteristics and Treatment in Mainland China.

INTRODUCTION: This aim of this study was to delineate current clinical scenarios of painful diabetic peripheral neuropathy (PDN) and associated anxiety and depression among patients in Mainland China, and to report current therapy and clinical practices. METHODS: A total of 1547 participants were enrolled in the study between 14 June 2018 and 11 November 2019. Recruitment was conducted using a multilevel sampling method. Participants' demographics, medical histories, glucose parameters, Douleur Neuropathique 4 Questionnaire (DN4) scores, visual analogue scale (VAS) pain scores, Patient Health Questionnaire 9 (PHQ-9) scores, Generalised Anxiety Disorder 7 (GAD-7) scores and therapies were recorded. RESULTS: The male-to-female ratio was 1.09:1 (807:740), and the mean age at onset was 61.28 ± 11.23 years. The mean DN4 score (± standard deviation) was 4.91 ± 1.88. The frequencies of DN4 sub-item phenotypes were: numbness, 81%; tingling, 68.71%; pins and needles, 62.90%; burning, 53.59%; hypoaesthesia to touch, 50.16%; electronic shocks, 43.31%; hypoaesthesia to pinprick, 37.94%; brushing, 37.82%; painful cold, 29.61%; and itching, 25.86%. Age, diabetic duration, depression history, PHQ-9 score and GAD-7 score were identified as risk factors for VAS pain score. Peripheral artery disease (PAD) was a protective factor for VAS pain score. For all participants currently diagnosed with PDN and for those previously diagnosed PDN, fasting blood glucose (FBG) was a risk factor for VAS; there was no association between FBG and VAS pain score for PDN diagnosed within 3 months prior to recruitment. Utilisation rate of opium therapies among enrolled participants was 0.71% , contradiction of first-line guideline recommendation for pain relief accounted for 9.43% (33/350) and contradiction of second-line guideline recommendation for opium dosage form was 0.57% (2/350). CONCLUSION: Moderate to severe neuropathic pain in PDN was identified in 73.11% of participants. Age, diabetic duration, depression history, PHQ-9 score, GAD-7 score and FBG were risk factors for VAS pain scores. PAD was protective factor. The majority of pain relief therapies prescribed were in accordance with guidelines. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03520608, retrospectively registered, 2018-05-11.

A Prognostic Model Based on Six Metabolism-Related Genes in Colorectal Cancer.

An increasing number of studies have shown that abnormal metabolism processes are closely correlated with the genesis and progression of colorectal cancer (CRC). In this study, we systematically explored the prognostic value of metabolism-related genes (MRGs) for CRC patients. A total of 289 differentially expressed MRGs were screened based on The Cancer Genome Atlas (TCGA) and the Molecular Signatures Database (MSigDB), and 72 differentially expressed transcription factors (TFs) were obtained from TCGA and the Cistrome Project database. The clinical samples obtained from TCGA were randomly divided at a ratio of 7 : 3 to obtain the training group (n = 306) and the test group (n = 128). After univariate and multivariate Cox regression analyses, we constructed a prognostic model based on 6 MRGs (AOC2, ENPP2, ADA, GPD1L, ACADL, and CPT2). Kaplan-Meier survival analysis of the training group, validation group, and overall samples proved that the model had statistical significance in predicting the outcomes of patients. Independent prognosis analysis suggested that this risk score might serve as an independent prognosis factor for CRC patients. Moreover, we combined the prognostic model and the clinical characteristics in a nomogram to predict the overall survival of CRC patients. Furthermore, gene set enrichment analysis (GSEA) was conducted to identify the enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the high- and low-risk groups, which might provide novel therapeutic targets for CRC patients. We discovered through the protein-protein interaction (PPI) network and TF-MRG regulatory network that 7 hub genes were retrieved from the PPI network and 4 kinds of differentially expressed TFs (NR3C1, MYH11, MAF, and CBX7) positively regulated 4 prognosis-associated MRGs (GSTM5, PTGIS, ENPP2, and P4HA3).