Impact of negative emotions on upper gastrointestinal diseases: A Mendel randomization study.

Mendelian randomization method is a powerful tool in epidemiological research. The core idea is to use genetic variation as a tool to assess the causal relationship between risk factors and specific diseases. Confounding factors are important interference factors for causal inference in epidemiological studies, and genetic variation in Mendelian randomization studies follows the principle of random distribution of alleles to offspring, which is similar to randomized controlled trials. Mendel 's randomization method can effectively avoid the confounding factors, reverse causality in observational studies and the representativeness and feasibility of randomized controlled trials. Previous observational studies have reported a relationship between negative emotions and upper gastrointestinal disease. However, whether this relationship is causal remains unclear. We aimed to evaluate the causal relationship between negative emotions and upper gastrointestinal diseases using two-sample Mendelian randomization (MR). Three sets of genetic instruments from the database were obtained for analysis, including 12 anxiety-related single nucleotide polymorphisms (SNPs), 46 depression-related SNPs, and 58 nervous-related SNPs. SNPs were filtered using the Phenoscanner website, and the inverse variance weighted method, weighted median method, MR-Egger regression, MR pleiotropy residual sum, and outlier test were used for analysis. In inverse variance weighted analysis, anxiety and depression had an effect on gastroduodenal ulcer (p = 2.849×10-3, ß = 4.908, 95% CI = 1.684-8.132; and p = 6.457×10-4, ß = 1.767, 95% CI = 0.752-2.782, respectively). Additionally, depression had an effect on diseases of the esophagus, stomach, and duodenum (p = 3.498×10-5, ß = 0.926, 95% CI = 0.487-1.364). Cochran's Q-derived p-values were 0.457, 0.603, and 0.643, and MR-Egger intercept-derived p-values were 0.697, 0.294, and 0.362, respectively. Here, we show that anxiety and depression have a causal relationship with gastroduodenal ulcers, and depression has a causal relationship with diseases of the esophagus, stomach, and duodenum.

Comparative efficacy of uncut Roux-en-Y and Billroth II anastomosis in gastrointestinal reconstruction following laparoscopic radical gastrectomy for distal gastric cancer.

This study retrospectively analyzed the clinical efficacy of Uncut Roux-en-Y and Billroth II anastomoses in gastrointestinal reconstruction following laparoscopic D2 radical gastrectomy for distal gastric cancer. The primary objective was to compare the postoperative outcomes, including quality of life and complication rates, between the 2 surgical techniques. One hundred patients diagnosed with distal gastric cancer were enrolled between June 2020 and May 2023. Patients underwent laparoscopic D2 gastrectomy and were categorized into either the Uncut Roux-en-Y or Billroth II anastomosis groups based on the technique used for gastrointestinal reconstruction. The inclusion and exclusion criteria were strictly followed. Surgical parameters, quality of life assessed using the Visick grading index, and postoperative complications were also evaluated. Statistical analyses were performed using SPSS version 27.0. The groups were comparable in terms of demographic and baseline clinical parameters. The Uncut Roux-en-Y group had a significantly longer duration of surgery (P < .001). However, there were no statistically significant differences in other surgical parameters. According to the Visick grading index, patients in the Uncut Roux-en-Y group reported a significantly better quality of life than those in the Billroth II group (P < .05). Additionally, Uncut Roux-en-Y was associated with a significantly lower incidence of dumping syndrome and bile reflux (P < .05). Although Uncut Roux-en-Y anastomosis requires longer surgical time, it offers significant advantages in terms of postoperative quality of life and reduced rates of dumping syndrome and bile reflux. Our findings suggest that Uncut Roux-en-Y may be a superior option for gastrointestinal reconstruction after laparoscopic D2 gastrectomy for distal gastric cancer.

Non-coding RNAs are key players and promising therapeutic targets in atherosclerosis.

Cardiovascular disease (CVD) is the primary cause of death in humans. Atherosclerosis (AS) is the most common CVD and a major cause of many CVD-related fatalities. AS has numerous risk factors and complex pathogenesis, and while it has long been a research focus, most mechanisms underlying its progression remain unknown. Noncoding RNAs (ncRNAs) represent an important focus in epigenetics studies and are critical biological regulators that form a complex network of gene regulation. Abnormal ncRNA expression disrupts the normal function of tissues or cells, leading to disease development. A large body of evidence suggests that ncRNAs are involved in all stages of atherosclerosis, from initiation to progression, and that some are significantly differentially expressed during AS development, suggesting that they may be powerful markers for screening AS or potential treatment targets. Here, we review the role of ncRNAs in AS development and recent developments in the use of ncRNAs for AS-targeted therapy, providing evidence for ncRNAs as diagnostic markers and therapeutic targets.

Study on the blood flow characteristics of venous needle retention with different super-hydrophobic surface structures.

A venous retention needle, as an implanted device, is very likely to cause thrombosis. In view of the thrombosis phenomenon caused by retention needles, this paper compares the influence of different superhydrophobic surface retentions on blood flow. Compared with other superhydrophobic bulges, the fluid velocity of the four-prism bulge is the highest (0.08 m/s), and the vorticity and shear force of the hemispherical bulge are higher. A large number of vortices can inhibit thrombosis better. The tire vortices generated in the superhydrophobic convex grooves are important vortices to inhibit thrombosis. The enhancement and development of the tire vortex weakens the resistance near the wall of the needle and reduces the probability of platelet aggregation. The superhydrophobic surface structure studied in this paper can not only provide guidance for the design of venous retention needles with better performance but also provide corresponding technical support for the development of human implantation devices.

Functional Mechanism of Ginsenoside Compound K on Tumor Growth and Metastasis.

Ginsenosides, as the most important constituents of ginseng, have been extensively investigated in cancer chemoprevention and therapeutics. Among the ginsenosides, Compound K (CK), a rare protopanaxadiol type of ginsenoside, has been most broadly used for cancer treatment due to its high anticancer bioactivity. However, the functional mechanism of CK in cancer is not well known. This review describes the structure, transformation and pharmacological activity of CK and discusses the functional mechanisms of CK and its metabolites, which regulate signaling pathways related to tumor growth and metastasis. CK inhibits tumor growth by inducing tumor apoptosis and tumor cell differentiation, regulates the tumor microenvironment by suppressing tumor angiogenesis-related proteins, and downregulates the roles of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs). There is currently much research on the potential development of CK as a new strategy when administered alone or in combination with other compounds.

Effect of N6-methyladenosine (m6A) regulator-related immunogenes on the prognosis and immune microenvironment of breast cancer.

Background: Breast cancer is one of the most common malignant tumor and the prognosis remains unsatisfying. Various studies demonstrate that m6A modulators are new predictors of prognosis in immune microenvironment. We aimed to identify several m6A regulator-related immunogenes and explore the relationship between m6A regulator-related immunogenes and breast cancer prognosis as well as the tumor immune microenvironment (TIME). Methods: RNA sequencing data and clinical information on 21 m6A regulators in 1,047 breast cancer samples were downloaded from The Cancer Genome Atlas (TCGA), and immune gene data were downloaded from InnateDB. Kaplan-Meier survival analysis was conducted with log-rank test using the survival package. An m6A-related immunogene-prognostic signature was then constructed, followed by immune infiltration and checkpoint analyses. Results: A risk prognostic signature of m6A regulator-related immunogenes, including TOX, PSME2, MCTS1, NFKBIE, SH3BP4, RSPH1, JAK1, MLLT4, and PTGES3, was constructed. Furthermore, univariate and multivariate Cox regression analyses suggested that the tumor stage and risk score could be independent prognostic factors for patients with breast cancer. Immune infiltration analysis showed that the infiltration levels of T cells, memory B cells, activated NK cells, and macrophages between the high- and low-risk groups were significantly different. In addition, checkpoint analyses demonstrated that the levels of immune checkpoint genes, such as those of LAG3, PDCD1, CTLA4, and HAVCR2, were downregulated in the high-risk group compared to those in the low-risk group. Conclusions: Our findings suggest that the m6A regulator-related risk prognostic signature can predict the prognosis of breast cancer and that it is related to the immune microenvironment.

Bedtime administration of antihypertensive medication can reduce morning blood pressure surges in hypertensive patients: a systematic review and meta-analysis.

BACKGROUND: The risk of cardiovascular and cerebrovascular events is the highest during the first several hours post-awakening in patients with hypertension. This is largely due to surges in morning blood pressure (BP). The current meta-analysis explored whether morning BP is affected by the timing of antihypertensive drug administration. METHODS: Four medical databases were searched for clinical trials that examined the relationship between the timing of antihypertensive drug administration and morning BP levels. This meta-analysis compared morning BP surges in patients administered medication at bedtime versus patients administered medication during the day. RESULTS: The random effects model demonstrated that bedtime administration of antihypertensive drugs reduced morning systolic blood pressure (SBP) by 1.17 mmHg [with 95% confidence interval (CI): -2.47 to 0.37; P=0.08), and reduced morning diastolic blood pressure (DBP) by 0.95 mmHg (95% CI: -2.03 to 0.13; P=0.08), compared with patients who were administered medication during the daytime hours. However, the results did not demonstrate statistical significance. There was strong heterogeneity in both morning SBP (I2 =77.9% >50%, and Q test >0.1) and morning DBP results (I2 =77.9% >50%, and Q test >0.1). The funnel plots showed no publication bias in this study. DISCUSSION: Studies have shown that a 1 mmHg change was sufficient to reduce the risk of cardiovascular-related deaths by 2.1%. Therefore, changing the time of taking antihypertensive medications may significantly reduce cardiovascular-associated mortality. There were certain limitations to this meta-analysis. First, the heterogeneity of the meta-analysis was strong, with undefined reasons. Second, the sample size was relatively small, and future studies involving larger cohorts are warranted to further assess the effects of bedtime antihypertensive medication on minimizing morning BP surges.

Screening of Prognostic Factors in Early-Onset Breast Cancer.

BACKGROUND: Gene expression profiles from early-onset breast cancer and normal tissues were analyzed to explore the genes and prognostic factors associated with breast cancer. METHODS: GSE109169 and GSE89116 were obtained from the database of Gene Expression Omnibus. We firstly screened the differentially expressed genes between tumor samples and normal samples from patients with early-onset breast cancer. Based on database for annotation, visualization and intergrated discovery (DAVID) tool, functional analysis was calculated. Transcription factor-target regulation and microRNA-target gene network were constructed using the tool of transcriptional regulatory relatitionships unraveled by sentence-based text mining (TRRUST) and miRWalk2.0, respectively. The prognosis-related survival information was compiled based on The Cancer Genome Atlas breast cancer clinical data. RESULTS: A total of 708 differentially expressed genes from GSE109169 data sets and 358 differentially expressed genes from GSE89116 data sets were obtained, of which 122 common differentially expressed genes including 102 uniformly downregulated genes and 20 uniformly upregulated genes were screened. Protein-protein interaction network with a total of 83 nodes and 157 relationship pairs was obtained, and genes in protein-protein interaction, such as peroxisome proliferator-activated receptor γ, FGF2, adiponectin, and PCK1, were recognized as key nodes in protein-protein interaction. In total, 66 transcription factor-target relationship pairs were obtained, and peroxisome proliferator-activated receptor γ was the only one downregulated transcription factor. MicroRNA-target gene network contained 368 microRNA-target relationship pairs. Moreover, 16 differentially expressed genes, including 2 upregulations and 14 downregulations, were related to a significant correlation with the prognosis, including SQLE and peroxisome proliferator-activated receptor γ. CONCLUSIONS: SQLE and peroxisome proliferator-activated receptor γ might be important prognostic factors in breast cancers, and adiponectin might be important in breast cancer pathogenesis regulated by peroxisome proliferator-activated receptor γ.