Examining the evidence for mutual modulation between m6A modification and circular RNAs: current knowledge and future prospects.

The resistance of cancer cells to treatment significantly impedes the success of therapy, leading to the recurrence of various types of cancers. Understanding the specific mechanisms of therapy resistance may offer novel approaches for alleviating drug resistance in cancer. Recent research has shown a reciprocal relationship between circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification, and their interaction can affect the resistance and sensitivity of cancer therapy. This review aims to summarize the latest developments in the m6A modification of circRNAs and their importance in regulating therapy resistance in cancer. Furthermore, we explore their mutual interaction and exact mechanisms and provide insights into potential future approaches for reversing cancer resistance.

Molecular Characterization of Metastatic Oncocytoma With Exceptional Response to Treatment: A Case Report.

Comprehensive molecular characterization and effective therapy in a rare case of metastatic renal oncocytoma.

Remodeling tumor-associated macrophage for anti-cancer effects by rational design of irreversible inhibition of mitogen-activated protein kinase-activated protein kinase 2.

Mitogen-activated protein kinase-activated protein kinase 2 (MK2) emerges as a pivotal target in developing anti-cancer therapies. The limitations of ATP-competitive inhibitors, due to insufficient potency and selectivity, underscore the urgent need for a covalent irreversible MK2 inhibitor. Our initial analyses of The Cancer Genome Atlas database revealed MK2's overexpression across various cancer types, especially those characterized by inflammation, linking it to poor prognosis and highlighting its significance. Investigating MK2's kinase domain led to the identification of a unique cysteine residue, enabling the creation of targeted covalent inhibitors. Compound 11 was developed, demonstrating robust MK2 inhibition (IC50 = 2.3 nM) and high selectivity. It binds irreversibly to MK2, achieving prolonged signal suppression and reducing pathological inflammatory cytokines in macrophages. Furthermore, compound 11 or MK2 knockdown can inhibit the tumor-promoting macrophage M2 phenotype in vitro and in vivo. In macrophage-rich tumor model, compound 11 notably slowed growth in a dose-dependent manner. These findings support MK2 as a promising anticancer target, especially relevant in cancers fueled by inflammation or dominated by macrophages, and provide compound 11 serving as an invaluable chemical tool for exploring MK2's functions.

Changes in visual performance after implantation of different intraocular lenses.

AIM: To evaluate the trending visual performance of different intraocular lenses (IOLs) over time after implantation. METHODS: Ninety-one patients received cataract surgery with implantations of monofocal (Mon) IOLs, segmental refractive (SegRef) IOLs, diffractive (Dif) IOLs, and extended-depth-of-focus (EDoF) IOLs were included. The aberrations and optical quality collected with iTrace and OQAS within postoperative 6mo were followed and compared. RESULTS: Most of the visual parameters improved over the postoperative 6mo. The postoperative visual acuity (POVA) of the Mon IOL, SegRef IOL, and EDoF IOL groups achieved relative stability in earlier states compared with the Dif IOL group. Nevertheless, the overall visual performance of the 3 IOLs continued to upturn in small extents within the postoperative 6mo. The optical quality initially improved in the EDoF IOL group, then in the Mon IOL, SegRef IOL, and Dif IOL groups. POVA and objective visual performance of the Mon IOL and EDoF IOL groups, as well as POVA and visual quality of the Dif IOL group, improved in the postoperative 1mo and stabilized. Within the postoperative 6mo, gradual improvements were observed in the visual acuity and objective visual performance of the SegRef IOL group, as well as in the postoperative optical quality of the Dif IOL group. CONCLUSION: The visual performance is different among eyes implanted with different IOLs. The findings of the current study provide a potential reference for ophthalmologists to choose suitable IOLs for cataract patients in a personalized solution.

Clinical prediction of insufficient vaults after implantable collamer lens implantation.

AIM: To determine the factors related to preoperative ocular characters that are predictive of insufficient vault (<250 µm) after implantable collamer lens (ICL V4c; STAAR Surgical) implantation. METHODS: The participants underwent ICL surgery and were divided into the low (<250 µm) and normal (250-1000 µm) vault groups based on the postoperative vault at 3mo. The preoperative biometric parameters and clinical outcomes were compared between the two groups. The relationship between the 3-month vault values and preoperative ocular parameters were evaluated by Generalized estimating equations. RESULTS: Sixteen (23 eyes) and 36 patients (63 eyes) were in the low and normal vault groups, respectively. All implantation procedures were uneventful with no cataract formation in the early postoperative period. The sulcus-to-sulcus lens rise (STSL) and iris ciliary angle (ICA) were correlated with vault at 3mo after surgery. Every 0.1 mm increase in STSL was associated with 38.9 µm decrease in the postoperative 3-month vault. A rise of 1 degree in ICA is associated with a reduction of 4 µm in vault. CONCLUSION: Eyes with a narrow ciliary sulcus are associated with a higher rate of low vault after ICL implantation, suggesting a need for adjustments to the ICL size in these patients. Evaluating the characteristics of the ciliary sulcus contributes valuable information to predict low vault after surgery.

Association between indoor environmental risk factors and pneumonia among preschool children in Urumqi：A case-control study.

Background: Pediatric pneumonia presents a significant global health challenge, particularly in low- and middle-income countries. This study aimed to investigate the incidence of pneumonia in preschool children in Urumqi and its association with indoor environmental factors. Methods: This case-control study collected data from December 2018 to December 2019 on 1522 preschool children in Urumqi (779 boys and 743 girls) who were diagnosed with pneumonia by a physician. A control group of children who had never had pneumonia was matched in a 1:1 ratio based on gender, age, and ethnicity. Using questionnaires, data were collected on children's general characteristics, passive smoking, types of housing, flooring materials, and indoor dampness, analyzing potential factors associated with the incidence of pediatric pneumonia. Results: Multivariate analysis revealed that cesarean birth (odds ratio [OR] = 1.27; 95 % confidence interval [95%CI] = 1.08-1.48), being an only child (OR = 1.32; 95%CI = 1.13-1.55), antibiotic treatment during the first year of life (OR = 2.51; 95%CI = 1.98-3.19), passive smoking during the mother's pregnancy (OR = 1.62; 95%CI = 1.24-2.13), living in multi-family apartment housing (OR = 1.64; 95%CI = 1.28-2.10) and other types of housing (OR = 1.47; 95%CI = 1.09-1.99), laminate flooring (OR = 1.31; 95%CI = 1.01-1.72), and tile/stone/cement flooring flooring (OR = 1.31; 95%CI = 1.06-1.61), and dampness in dwelling (during first year of mother's pregnancy) (OR = 1.30; 95%CI = 1.04-1.63) were risk factors for pediatric pneumonia. The use of fresh air filtration systems in children's residences (OR = 0.66; 95%CI = 0.50-0.86) was identified as a protective factor. Conclusion: This study underscores the importance of indoor environmental factors in the prevention of pediatric pneumonia. Public health strategies should consider these factors to reduce the incidence of pneumonia in children. Future research needs to be conducted over a broader geographical range and consider a more comprehensive range of factors influencing pediatric pneumonia.

BiLSTM- and CNN-Based m6A Modification Prediction Model for circRNAs.

m6A methylation, a ubiquitous modification on circRNAs, exerts a profound influence on RNA function, intracellular behavior, and diverse biological processes, including disease development. While prediction algorithms exist for mRNA m6A modifications, a critical gap remains in the prediction of circRNA m6A modifications. Therefore, accurate identification and prediction of m6A sites are imperative for understanding RNA function and regulation. This study presents a novel hybrid model combining a convolutional neural network (CNN) and a bidirectional long short-term memory network (BiLSTM) for precise m6A methylation site prediction in circular RNAs (circRNAs) based on data from HEK293 cells. This model exploits the synergy between CNN's ability to extract intricate sequence features and BiLSTM's strength in capturing long-range dependencies. Furthermore, the integrated attention mechanism empowers the model to pinpoint critical biological information for studying circRNA m6A methylation. Our model, exhibiting over 78% prediction accuracy on independent datasets, offers not only a valuable tool for scientific research but also a strong foundation for future biomedical applications. This work not only furthers our understanding of gene expression regulation but also opens new avenues for the exploration of circRNA methylation in biological research.

A Pseudo Elevation of CEA Caused by Epidemic Hemorrhagic Fever.

BACKGROUND: Heterophilic antibodies (HA) are one of the main substances that interfere with immunology, especially chemiluminescence immunoassay. Non-specific binding, labeling antibodies, bridging to capture antibodies, or labeling antigens can interfere with the detection process, leading to serious discrepancies between the measured results and clinical manifestations, and even delaying clinical diagnosis and treatment. METHODS: This paper is a case of epidemic hemorrhagic fever causing pseudo CEA elevation caused by heterophagy induced antibodies in the body. RESULTS: The patient's CEA detected on the ABBOTT detection platform was 51.1 ng/mL, and on the ROCHE detection platforms it was 4.66 ng/mL, and treated by PEG precipitation it was 45.2 ng/mL, after diluting the sample the CEA was 50.2 ng/mL, meanwhile the patient's platelets were 96 x 109/L and serum creatinine was 188.4 µmol/L, epidemic hemorrhagic fever IgM antibody was positive. CONCLUSIONS: When the test results do not match clinical symptoms, further confirmation is required through additional testing. Patients who use mouse monoclonal antibody preparations for diagnosis or treatment may have human anti-mouse antibodies in their serum, and the test results may falsely increase or decrease.

The relationship between innate/adaptive immunity and gastrointestinal cancer : a multi-omics Mendelian randomization study.

BACKGROUND: Innate/adaptive immunity is the key to anti-tumor therapy. However, its causal relationship to Gastrointestinal (GI) cancer remains unclear. METHODS: Immunity genes were extracted from the MSigDB database. The Genome-wide association studies (GWAS) summary data of GI cancer were integrated with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) associated with genes. Summary-data-based Mendelian randomization (SMR) and co-localization analysis were used to reveal causal relationships between genes and GI cancer. Two-sample MR analysis was used for sensitivity analysis. Single cell analysis clarified the enrichment of genes. RESULTS: Three-step SMR analysis showed that a putative mechanism, cg17294865 CpG site regulating HLA-DRA expression was negatively associated with gastric cancer risk. HLA-DRA was significantly differentially expressed in monocyte/macrophage and myeloid cells in gastric cancer. CONCLUSION: This study provides evidence that upregulating the expression level of HLA-DRA can reduce the risk of gastric cancer.

Diagnostic role of SPP1 and collagen IV in a rat model of type 2 diabetes mellitus with MASLD.

Type 2 diabetes mellitus combined with metabolic dysfunction-associated steatotic liver disease (MASLD) leads to an increasing incidence of liver injury year by year, and patients are at a significantly higher risk of developing cirrhosis or even liver failure. No drugs have emerged to specifically treat this disease. The aim of this study is to investigate the mechanisms and causative hub genes of type 2 diabetes combined with MASLD. The data were obtained through the GEO platform for bioinformatics analysis and validated by in vitro experiments to find the causative targets of type 2 diabetes mellitus combined with MASLD, which will provide some theoretical basis for the development of future therapeutic drugs. GSE23343 and GSE49541 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) in type 2 diabetes mellitus combined with MASLD for functional enrichment analysis. And STRING database and Cytoscape software were used to construct Protein-Protein Interaction (PPI) and hub gene networks. And GO (gene ontology, GO) analysis and KEGG (Kyoto encyclopedia of genes and genomes, KEGG) enrichment analysis were performed on target genes. A total of 185 co-expressed DEGs were obtained by differential analysis, and 20 key genes involved in the development and progression of type 2 diabetes were finally screened. These 20 key genes were involved in 529 GO enrichment results and 20 KEGG enrichment results, and were mainly associated with ECM-receptor interaction, Focal adhesion, Human papillomavirus infection, PI3K-Akt signaling pathway, and the Toll-like receptor signaling pathway. A total of two target genes (SPP1, collagen IV) were found to be highly correlated with type 2 diabetes mellitus combined with MASLD. Real time PCR results showed that there was a significant difference in SPP1 and collagen IV mRNA expression among the three groups (P < 0.05). SPP1 and Collagen IV may be candidate biomarkers for type 2 diabetes mellitus combined with MASLD, as verified by bioinformatics screening and in vitro experiments. Our findings provide new targets for the treatment of type 2 diabetes combined with MASLD.

Salvianolic acid B inhibits the growth and metastasis of A549 lung cancer cells through the NDRG2/PTEN pathway by inducing oxidative stress.

Salvianolic acid B (Sal B) has demonstrated anticancer activity against various types of cancer. However, the underlying mechanism of Sal B-mediated anticancer effects remains incompletely understood. This study aims to investigate the impact of Sal B on the growth and metastasis of human A549 lung cells, as well as elucidate its potential mechanisms. In this study, different concentrations of Sal B were administered to A549 cells. The effects on migration and invasion abilities were assessed using MTT, wound healing, and transwell assays. Flow cytometry analysis was employed to evaluate Sal B-induced apoptosis in A549 cells. Western blotting and immunohistochemistry were conducted to measure the expression levels of cleaved caspase-3, cleaved PARP, and E-cadherin. Commercial kits were utilized for detecting intracellular reactive oxygen species (ROS) and NAD+. Additionally, a xenograft model with transplanted A549 tumors was employed to assess the anti-tumor effect of Sal B in vivo. The expression levels of NDRG2, p-PTEN, and p-AKT were determined through western blotting. Our findings demonstrate that Sal B effectively inhibits proliferation, migration, and invasion in A549 cells while inducing dose-dependent apoptosis. These apoptotic responses and inhibition of tumor cell metastasis are accompanied by alterations in intracellular ROS levels and NAD+/NADH ratio. Furthermore, our in vivo experiment reveals that Sal B significantly suppresses A549 tumor growth compared to an untreated control group while promoting increased cleavage of caspase-3 and PARP. Importantly, we observe that Sal B upregulates NDRG2 expression while downregulating p-PTEN and p-AKT expressions. Collectively, our results provide compelling evidence supporting the ability of Sal B to inhibit both growth and metastasis in A549 lung cancer cells through oxidative stress modulation as well as involvement of the NDRG2/PTEN/AKT pathway.

Exploring the Role of the Wnt/ß-Catenin Signaling Pathway in Hepatocellular Carcinoma Migration and Tumor Angiogenesis.

Background: Hepatocellular carcinoma (HCC) presents a challenging global health concern due to its high incidence and limited treatment efficacy. Understanding the molecular pathways driving HCC development is crucial for advancing therapeutic strategies and improving patient outcomes. Objective: This study aims to assess the impact of Salinomycin on the Wnt/ß-catenin signaling pathway in hepatocellular carcinoma, exploring its role in tumor migration and angiogenesis. Additionally, to explore the therapeutic potential of targeting this pathway for improving HCC treatment outcomes. Methods: This study employed an in vitro experimental design to investigate the role of the Wnt/ß-catenin signaling pathway in HCC progression. HepG2 cells were cultured in RPMI 1640 medium supplemented with 10% serum, penicillin (100 U/ml), and streptomycin (100 µg/ml). The cells were divided into experimental and control groups for comparative analysis. Salinomycin was administered to inhibit Wnt/ß-catenin pathway activation. The primary outcome measures included the evaluation of cell migration and tumor angiogenesis using cell migration assays and vascular endothelial growth factor (VEGF) expression analysis, respectively. Statistical analysis was performed using the two-tailed Student's t test, with significance set at P < .05. Results: Salinomycin treatment led to a dose-dependent decrease in HCC cell proliferation, with optical density values decreasing as the concentration of Salinomycin increased. Cell migration assays showed inhibited migration in cells treated with Salinomycin compared to controls. Western blot analysis revealed decreased levels of ß-catenin and increased levels of DVL in Salinomycin-treated cells, indicating inhibition of the Wnt/ß-catenin pathway. Furthermore, VEGF expression decreased after Salinomycin treatment, implicating the pathway in tumor angiogenesis. Statistical analysis, including Student's t-test, confirmed significant differences between control and experimental groups (P < .05). Conclusion: The Wnt/ß-catenin signaling pathway plays a significant role in the migration and angiogenesis of HCC when treated with Salinomycin.

A Novel Infrapatellar Fat Pad Preservation Technique in Total Knee Arthroplasty Reduced Postoperative Pain and Wound Complications.

OBJECTIVE: The management of the infrapatellar fat pad (IPFP) during total knee arthroplasty (TKA) remains controversial. This study aimed to evaluate a novel IPFP preservation technique-"the medially pedicled IPFP flap"-for reducing postoperative pain, wound complications, and improving functional recovery after TKA. METHODS: A retrospective analysis was conducted on TKA cases at our institution from 2018 to 2021, including those with IPFP preservation (medially pedicled flap) versus IPFP complete resection. Patient demographics, perioperative parameters (blood loss, operative time, length of hospital stay, visual analogue scale [VAS] score, white cell count [WBC], C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], and wound oozing), and postoperative follow-up data (VAS, Knee Society [KSS], or Knee Society functional assessment [KSFA] scores) were compared between groups. Independent sample t-tests were used to compare continuous data and chi-squared tests were used to compare categorical data between groups. RESULTS: Six hundred thirty patients were included, with 278 in the medial pedicled IPFP flap group (preservation group) and 352 in the IPFP resection group (resection group). The operative time was significantly shorter in the preservation versus resection group (125.5 ± 23.2 vs 130.3 ± 28.7 mins, p = 0.03), as was the length of hospital stay (8.4 ± 2.7 vs 9.2 ± 2.3 days, p < 0.01). Regarding pain, the preservation group had significantly lower VAS scores on postoperative day 2 (2.0 ± 0.8 vs 2.4 ± 1.2, p < 0.001) and day 3 (1.5 ± 0.5 vs 1.8 ± 1.0, p < 0.001). CRP and ESR levels on postoperative day 5 were also significantly lower in the preservation group. Wound oozing rates were significantly lower in the preservation versus resection group (0.7% vs 2.8%, p = 0.04). No significant differences existed in VAS, KSS, or KSFA scores at the last follow-up. CONCLUSION: The novel IPFP preservation technique significantly improved surgical exposure, shortened operative time and length of hospital stay. It also reduced wound pain and oozing compared to IPFP resection.

Physiological responses and transcriptome analysis of Hemerocallis citrina Baroni exposed to Thrips palmi feeding stress.

Thrips are serious pests of Hemerocallis citrina Baroni (daylily), affecting crop yield and quality. To defend against pests, daylily has evolved a set of sophisticated defense mechanisms. In the present study, induction of systemic resistance in Hemerocallis citrina 'Datong Huanghua' by Thrips palmi feeding was investigated at both biochemical and molecular levels. The soluble sugar content of daylily leaves was significantly lower than that in control check (CK) at all time points of feeding by T. palmi, whereas the amino acid and free fatty acid contents started to be significantly lower than those in CK after 7 days. Secondary metabolites such as tannins, flavonoids, and total phenols, which are harmful to the growth and reproduction of T. palmi, were increased significantly. The activities of defense enzymes such as peroxidase (POD), phenylalanine ammonia lyase (PAL), and polyphenol oxidase (PPO) were significantly increased, and the degree of damage to plants was reduced. The significant increase in protease inhibitor (PI) activity may lead to disrupted digestion and slower growth in T. palmi. Using RNA sequencing, 1,894 differentially expressed genes (DEGs) were identified between control and treatment groups at five timepoints. DEGs were mainly enriched in secondary metabolite synthesis, jasmonic acid (JA), salicylic acid (SA), and other defense hormone signal transduction pathways, defense enzyme synthesis, MAPK signaling, cell wall thickening, carbohydrate metabolism, photosynthesis, and other insect resistance pathways. Subsequently, 698 DEGs were predicted to be transcription factors, including bHLH and WRKY members related to biotic stress. WGCNA identified 18 hub genes in four key modules (Purple, Midnight blue, Blue, and Red) including MYB-like DNA-binding domain (TRINITY_DN2391_c0_g1, TRINITY_DN3285_c0_g1), zinc-finger of the FCS-type, C2-C2 (TRINITY_DN21050_c0_g2), and NPR1 (TRINITY_DN13045_c0_g1, TRINITY_DN855_c0_g2). The results indicate that biosynthesis of secondary metabolites, phenylalanine metabolism, PIs, and defense hormones pathways are involved in the induced resistance to T. palmi in daylily.

Development and Validation of a Nomogram Based on DCE-MRI Radiomics for Predicting Hypoxia-Inducible Factor 1α Expression in Locally Advanced Rectal Cancer.

RATIONALE AND OBJECTIVES: The expression levels of hypoxia-inducible factor 1 alpha (HIF-1α) have been identified as a pivotal marker, correlating with treatment response in patients with locally advanced rectal cancer (LARC). This study aimed to develop and validate a nomogram based on dynamic contrast-enhanced MRI (DCE-MRI) radiomics and clinical features for predicting the expression of HIF-1α in patients with LARC. MATERIALS AND METHODS: A total of 102 patients diagnosed with locally advanced rectal cancer were divided into training (n = 71) and validation (n = 31) cohorts. The expression statuses of HIF-1α were histopathologically classified, categorizing patients into high and low expression groups. The intraclass correlation coefficient (ICC), minimum redundancy maximum relevance (mRMR), and the least absolute shrinkage and selection operator (LASSO) were employed for feature selection to construct a radiomics signature and calculate the radiomics score (Rad-score). Univariate and multivariate analyses of clinical features and Rad-score were applied, and the clinical model and the nomogram were constructed. The predictive performance of the nomogram incorporating clinical features and Rad-score was assessed using Receiver Operating Characteristics (ROC) curves, decision curve analysis (DCA), and calibration curves. RESULTS: Seven radiomics features from DCE-MRI were used to build the radiomics signature. The nomogram incorporating CEA, Ki-67 and Rad-score had the highest AUC values in the training cohort and in the validation cohort (AUC: 0.918 and 0.920). Decision curve analysis showed that the nomogram outperformed the clinical model and radiomics signature in terms of clinical utility. In addition, the calibration curve for the nomogram demonstrated good agreement between prediction and actual observation. CONCLUSION: The nomogram based on DCE-MRI radiomics and clinical features showed favorable predictive efficacy and might be useful for preoperatively discriminating the expression of HIF-1α.

Liquid Chromatography/Tandem Mass Spectrometry Analysis of Sophora flavescens Aiton and Protective Effects against Alcohol-Induced Liver Injury and Oxidative Stress in Mice.

In this study, we investigated the hepatoprotective effects of an ethanol extract of Sophora flavescens Aiton (ESF) on an alcohol-induced liver disease mouse model. Alcoholic liver disease (ALD) was caused by the administration of ethanol to male C57/BL6 mice who were given a Lieber-DeCarli liquid diet, including ethanol. The alcoholic fatty liver disease mice were orally administered ESF (100 and 200 mg/kg bw/day) or silymarin (50 mg/kg bw/day), which served as a positive control every day for 16 days. The findings suggest that ESF enhances hepatoprotective benefits by significantly decreasing serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), markers for liver injury. Furthermore, ESF alleviated the accumulation of triglyceride (TG) and total cholesterol (TC), increased serum levels of superoxide dismutase (SOD) and glutathione (GSH), and improved serum alcohol dehydrogenase (ADH) activity in the alcoholic fatty liver disease mice model. Cells and organisms rely on the Kelch-like ECH-associated protein 1- Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) system as a critical defensive mechanism in response to oxidative stress. Therefore, Nrf2 plays an important role in ALD antioxidant responses, and its level is decreased by increased reactive oxidation stress (ROS) in the liver. ESF increased Nrf2, which was decreased in ethanol-damaged livers. Additionally, four polyphenol compounds were identified through a qualitative analysis of the ESF using LC-MS/MS. This study confirmed ESF's antioxidative and hangover-elimination effects and suggested the possibility of using Sophora flavescens Aiton (SF) to treat ALD.

Ziziphus jujuba Miller Ethanol Extract Restores Disrupted Intestinal Barrier Function via Tight Junction Recovery and Reduces Inflammation.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by the disruption of the intestinal barrier. The intestinal barrier is maintained by tight junctions (TJs), which sustain intestinal homeostasis and prevent pathogens from entering the microbiome and mucosal tissues. Ziziphus jujuba Miller (Z. jujuba) is a natural substance that has been used in traditional medicine as a therapy for a variety of diseases. However, in IBD, the efficacy of Z. jujuba is unknown. Therefore, we evaluated ZJB in Caco2 cells and a dextran sodium sulfate (DSS)-induced mouse model to demonstrate its efficacy in IBD. Z. jujuba extracts were prepared using 70% ethanol and were named ZJB. ZJB was found to be non-cytotoxic and to have excellent antioxidant effects. We confirmed its anti-inflammatory properties via the down-regulation of inflammatory factors, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). To evaluate the effects of ZJB on intestinal barrier function and TJ improvement, the trans-epithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran 4 kDa (FITC-Dextran 4) permeability were assessed. The TEER value increased by 61.389% and permeability decreased by 27.348% in the 200 µg/mL ZJB group compared with the 50 ng/mL IL-6 group after 24 h. Additionally, ZJB alleviated body weight loss, reduced the disease activity index (DAI) score, and induced colon shortening in 5% DSS-induced mice; inflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were down-regulated in the serum. TJ proteins, such as Zonula occludens (ZO)-1 and occludin, were up-regulated by ZJB in an impaired Caco2 mouse model. Additionally, according to the liquid chromatography results, in tandem with mass spectrometry (LC-MS/MS) analysis, seven active ingredients were detected in ZJB. In conclusion, ZJB down-regulated inflammatory factors, protected intestinal barrier function, and increased TJ proteins. It is thus a safe, natural substance with the potential to be used as a therapeutic agent in IBD treatment.

Estimating effects of whole grain consumption on type 2 diabetes, colorectal cancer and cardiovascular disease: a burden of proof study.

BACKGROUND: Previous studies on whole grain consumption had inconsistent findings and lacked quantitative assessments of evidence quality. Therefore, we aimed to summarize updated findings using the Burden of Proof analysis (BPRF) to investigate the relationship of whole grain consumption on type 2 diabetes (T2D), colorectal cancer (CRC), stroke, and ischemic heart disease (IHD). METHODS: We conducted a literature search in the Medline and Web of Science up to June 12, 2023, to identify related cohort studies and systematic reviews. The mean RR (relative risk) curve and uncertainty intervals (UIs), BPRF function, risk-outcome score (ROS), and the theoretical minimum risk exposure level (TMREL) were estimated to evaluate the level of four risk-outcome pairs. RESULTS: In total, 27 prospective cohorts were included in our analysis. Consuming whole grain at the range of TMREL (118.5-148.1 g per day) was associated with lower risks: T2D (declined by 37.3%, 95% UI: 5.8 to 59.5), CRC (declined by 17.3%, 6.5 to 27.7), stroke (declined by 21.8%, 7.3 to 35.1), and IHD (declined by 36.9%, 7.1 to 58.0). For all outcomes except stroke, we observed a non-linear, monotonic decrease as whole grain consumption increased; For stroke, it followed a J-shaped curve (the greatest decline in the risk of stroke at consuming 100 g whole grain for a day). The relationships between whole grain consumption and four diseases are all two-star pairs (ROS: 0.087, 0.068, 0.062, 0.095 for T2D, CRC, stroke, and IHD, respectively). CONCLUSION: Consuming 100 g of whole grains per day offers broad protective benefits. However, exceeding this threshold may diminish the protective effects against stroke. Our findings endorse replacing refined grains with whole grains as the main source of daily carbohydrates. REGISTRY AND REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYSES: We have registered our research in PROSPERO, and the identifier of our meta-analyses is CRD42023447345.

Precede-Proceed Model-dominant Nursing Combined With Nutrition Support for Patients Discharged After Hepatobiliary Surgery With T Tube.

Context: Hepatobiliary disease requires surgical treatment and T-tube installment postoperatively, and discharged patients' usually still have a T tube. Little nursing care is available in China for patients after discharge, resulting in postdischarge complications. Also, the incidence of nutritional risk in patients with hepatobiliary surgery is high. Objective: The study aimed to investigate the benefits of a precede-proceed model-dominant nursing combined with nutritional support for patients discharged after hepatobiliary surgery with a T tube, so as to improve their prognoses and promote their rehabilitation. Design: The research team conducted a prospective, single-center, randomized controlled trial. Setting: The study took place at Wuhan No. 1 Hospital, Wuhan Hospital of Traditional Chinese and Western Medicine in Wuhan, Hubei, China. Participants: Participants were 120 patients discharged after hepatobiliary surgery at the hospital between June 2020 and June 2022. Interventions: The research team randomly divided participants into two groups using the random number table method, each with 60 participants: (1) an intervention group, which received precede-proceed model-dominant nursing combined with nutrition support and (2) a control group, which received routine care. Outcome Measures: At baseline and postintervention, the research team assessed: (1) nutritional status, (2) self-care agency, (3) compliance, (4) quality of life (QoL), (5) incidence of complications. Results: At baseline, no significant differences existed between the groups in nutritional status, self-care agency, QoL, or compliance (all P > .05). Postintervention compared to the control group, the intervention group's: (1) nutritional status, including albumin (P = .015), hemoglobin (P < .001), growth hormone (P < .001), BW (P = .047), BMI (P = .046), TST (P = .001), and MAMC (P = .016) were significantly higher and transferrin (P < .001) and NRS-2002 score (P < .001) were significantly lower; (2) self-care agency, including self-concept, self-responsibility, health knowledge, and self-nursing skills were significantly higher (all P < .001); (3) compliance scores, including observing the volume and color of bile correctly, clamping and opening the T tube properly, replacing the drainage bag correctly and in a timely manner, regularly disinfecting the skin around the drainage tube, keeping a balanced diet, adhering to medical regimens, exercising adequately were significantly higher (all P < .001); (4) QoL was significantly higher (P < .001); and (5) incidence of complications was significantly lower (P = .008). Conclusions: Precede-proceed model-dominant nursing combined with nutrition support can significantly improve nutritional status, self-care agency, and QoL and can significantly decrease the incidence of complications for patients discharged after hepatobiliary surgery with a T tube and is worthy of promotion in clinics.

Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer.

BACKGROUND: The incidence and mortality of colorectal cancer (CRC) are among the highest in the world, and its occurrence and development are closely related to tumor neovascularization. When the balance between pigment epithelium-derived factors (PEDF) that inhibit angiogenesis and vascular endothelial growth factors (VEGF) that stimulate angiogenesis is broken, angiogenesis is out of control, resulting in tumor development. Therefore, it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment. AIM: To investigate the expression and significance of PEDF, VEGF, and CD31-stained microvessel density values (CD31-MVD) in normal colorectal mucosa, adenoma, and CRC. METHODS: In this case-control study, we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022. Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy (normal control group), 50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy (adenoma group), and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery (CRC group). An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens, analyze their differences, study the relationship between the two and clinicopathological factors in CRC group, record CD31-MVD in the three groups, and analyze the correlation of PEDF, VEGF, and CD31-MVD in the colorectal adenoma group and the CRC group. The F test or adjusted F test is used to analyze measurement data statistically. Kruskal-Wallis rank sum test was used between groups for ranked data. The chi-square test, adjusted chi-square test, or Fisher's exact test were used to compare the rates between groups. All differences between groups were compared using the Bonferroni method for multiple comparisons. Spearman correlation analysis was used to test the correlation of the data. The test level (α) was 0.05, and a two-sided P< 0.05 was considered statistically significant. RESULTS: The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group, adenoma group, and CRC group (100% vs 78% vs 50%, χ2 = 34.430, P < 0.001; ++~++ vs +~++ vs -~+, H = 94.059, P < 0.001), while VEGF increased gradually (0% vs 68% vs 96%, χ2 = 98.35, P < 0.001; - vs -~+ vs ++~+++, H = 107.734, P < 0.001). In the CRC group, the positive expression rate of PEDF decreased with the increase of differentiation degree, invasion depth, lymph node metastasis, distant metastasis, and TNM stage (χ2 = 20.513, 4.160, 5.128, 6.349, 5.128, P < 0.05); the high expression rate of VEGF was the opposite (χ2 = 10.317, 13.134, 17.643, 21.844, 17.643, P < 0.05). In the colorectal adenoma group, the expression intensity of PEDF correlated negatively with CD31-MVD (r = -0.601, P < 0.001), whereas VEGF was not significantly different (r = 0.258, P = 0.07). In the CRC group, the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF (r = -0.297, P < 0.05; r = -0.548, P < 0.05), while VEGF expression intensity was positively related to CD31-MVD (r = 0.421, P = 0.002). CONCLUSION: It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.