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AimThe aim of this study was to develop a validated nomogram to predict the risk of postoperative complications in colorectal cancer (CRC) patients by analyzing the factors that contribute to these complications.MethodsWe retrospectively collected clinical information on patients who underwent CRC surgery at a single clinical center from January 2021 to December 2021. Univariate and multivariate logistic regression analysis to identify independent risk factors for postoperative complications and to develop a predictive model. A receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) to assess the predicted probability. Calibration curve was drawn to compare the predicted probability of the nomogram with the actual probability, and decision curve analysis (DCA) was employed to evaluate the clinical utility of the nomogram.ResultsA total of 190 CRC patients were included in this study. We retrospectively collected baseline information, clinical information, surgical information, and nutrition-related indicators for all patients. Through multivariate logistic regression analysis, preoperative albumin (p = 0.041, OR = 0.906, 95% CI = 0.824–0.996), surgical time (p = 0.009, OR = 1.006, 95% CI = 1.001–1.010), waistline (p = 0.049, OR = 1.011, 95% CI = 1.002–1.020) and phase angle (PA) (p = 0.022, OR = 0.615, 95% CI = 0.405–0.933) were identified as independent risk factors for postoperative complications in CRC, and a nomogram prediction model was established using the above four variables. The AUC of 0.706 for the ROC plot and the high agreement between predicted and actual probabilities in the calibration curves suggested that the prediction model has good predictive power. The DCA also confirmed the good clinical performance of the nomogram.ConclusionThis study developed a nomogram to predict the risk of postoperative complications in CRC patients, providing surgeons with a reliable reference to personalized patient management in the perioperative period and preoperative nutritional interventions.

Background and ObjectiveChronic atrophic gastritis (CAG) is a complex chronic disease caused by multiple factors that frequently occurs disease in the clinic. The worldwide prevalence of CAG is high. Interestingly, clinical CAG patients often present with a variety of symptom phenotypes, which makes it more difficult for clinicians to treat. Therefore, there is an urgent need to improve our understanding of the complexity of the clinical CAG population, obtain more accurate disease subtypes, and explore the relationship between clinical symptoms and medication. Therefore, based on the integrated platform of complex networks and clinical research, we classified the collected patients with CAG according to their different clinical characteristics and conducted correlation analysis on the classification results to identify more accurate disease subtypes to aid in personalized clinical treatment.MethodTraditional Chinese medicine (TCM) offers an empirical understanding of the clinical subtypes of complicated disorders since TCM therapy is tailored to the patient’s symptom profile. We gathered 6,253 TCM clinical electronic medical records (EMRs) from CAG patients and manually annotated, extracted, and preprocessed the data. A shared symptom-patient similarity network (PSN) was created. CAG patient subgroups were established, and their clinical features were determined through enrichment analysis employing community identification methods. Different clinical features of relevant subgroups were correlated based on effectiveness to identify symptom–botanical botanical drugs correspondence. Moreover, network pharmacology was employed to identify possible biological relationships between screened symptoms and medications and to identify various clinical and molecular aspects of the key subtypes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.Results5,132 patients were included in the study: 2,699 males (52.60%) and 2,433 females (47.41%). The population was divided into 176 modules. We selected the first 3 modules (M29, M3, and M0) to illustrate the characteristic phenotypes and genotypes of CAG disease subtypes. The M29 subgroup was characterized by gastric fullness disease and internal syndrome of turbidity and poison. The M3 subgroup was characterized by epigastric pain and disharmony between the liver and stomach. The M0 subgroup was characterized by epigastric pain and dampness-heat syndrome. In symptom analysis, The top symptoms for symptom improvement in all three subgroups were stomach pain, bloating, insomnia, poor appetite, and heartburn. However, the three groups were different. The M29 subgroup was more likely to have stomach distention, anorexia, and palpitations. Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon were the most popular botanical drugs. The M3 subgroup has a higher incidence of yellow urine, a bitter tongue, and stomachaches. Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora were the botanical drugs used. Vomiting, nausea, stomach pain, and appetite loss are common in the M0 subgroup. The primary medications are Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia. Through GO and KEGG pathway analysis, We found that in the M29 subgroup, Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon may exert their therapeutic effects on the symptoms of gastric distension, anorexia, and palpitations by modulating apoptosis and NF-κB signaling pathways. In the M3 subgroup, Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora may be treated by NF-κB and JAK-STAT signaling pathway for the treatment of stomach pain, bitter mouth, and yellow urine. In the M0 subgroup, Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia may exert their therapeutic effects on poor appetite, stomach pain, vomiting, and nausea through the PI3K-Akt signaling pathway.ConclusionBased on PSN identification and community detection analysis, CAG population division can provide useful recommendations for clinical CAG treatment. This method is useful for CAG illness classification and genotyping investigations and can be used for other complicated chronic diseases.

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A–H (1–8), and two new eudesmane-type sesquiterpenes, eutypellaolides I–J (9–10), along with four known 12,8-eudesmanolide compounds 11–14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 μg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 μM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 μM, respectively.

PurposeThe aim of this study was to evaluate the effect of carbon nanoparticles staining (CNS) on colorectal cancer (CRC) surgery, lymph node tracing and postoperative complications using propensity score matching (PSM).MethodPatients who were diagnosed with CRC and underwent surgery were retrospectively collected from a single clinical center from Jan 2011 to Dec 2021. Baseline characteristics, surgical information and postoperative information were compared between the CNS group and the non-CNS group. PSM was used to eliminate bias.ResultsA total of 6,886 patients were enrolled for retrospective analysis. There were 2,078 (30.2%) patients in the CNS group and 4,808 (69.8%) patients in the non-CNS group. After using 1: 1 ratio PSM to eliminate bias, there were 2,045 patients left in each group. Meanwhile, all of their baseline characteristics were well matched and there was no statistical significance between the two groups (P > 0.05). In terms of surgical information and short-term outcomes, the CNS group had less intraoperative blood loss (P 0.05).ConclusionPreoperative CNS could help the surgeons detect more lymph nodes, thus better determining the patient's N stage. Furthermore, it could reduce intraoperative blood loss and reduce the hospital stay.

Transient receptor potential vanilloid type 4 (TRPV4) can function as an oncogene or tumor suppressor depending on the tumor types. However, little is known regarding the effect of TRPV4 in nasopharyngeal carcinoma (NPC), a highly prevalent malignancy in Southern China and Southeast Asia. We found that TRPV4 mRNA and protein levels were significantly upregulated in NPC tissues. In addition, activation of TRPV4 in NPC cell lines using GSK1016790A (100 nM) induced a Ca2+ influx, whereas pharmacological inhibition or gene knockdown of TRPV4 reduced the proliferation rates of NPC cells. TRPV4 knockdown also decreased the growth of tumor xenografts in vivo. Mechanistically, TRPV4-mediated tumorigenesis is dependent on the activation of Ca2+/calcineurin/calcineurin-nuclear factor of activated T cell 4 (NFAT4) signaling. Furthermore, NFAT4 protein level was overexpressed in NPC tissues and correlated positively with TRPV4. Taken together, TRPV4 promotes the malignant potential of NPC cells by activating NFAT4 signaling. Our findings highlight TRPV4-NFAT4 axis as a potential therapeutic target in NPC.

BackgroundThe targeted therapy for lung cancer relies on prognostic genes and requires further research. No research has been conducted to determine the effect of endothelin-converting enzyme 2 (ECE2) in lung cancer.MethodsWe analyzed the expression of ECE2 in lung adenocarcinoma (LUAD) and normal adjacent tissues and its relationship with clinicopathological characteristics from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). Immunohistochemical staining was used to further validate the findings. GO/KEGG enrichment analysis and gene set enrichment analysis (GSEA) of ECE2 co-expression were performed using R software. Data from TIMER, the GEPIA database, and TCGA were analyzed to determine the relationship between ECE2 expression and LUAD immune infiltration. To investigate the relationship between ECE2 expression levels and LUAD m6A modification, TCGA data and GEO data were analyzed.ResultsECE2 is highly expressed in various cancers including LUAD. ECE2 showed high accuracy in distinguishing tumor and normal sample results. The expression level of ECE2 in LUAD was significantly correlated with tumor stage and prognosis. GO/KEGG enrichment analysis showed that ECE2 was closely related to mitochondrial gene expression, ATPase activity and cell cycle. GSEA analysis showed that ECE2-related differential gene enrichment pathways were related to mitotic cell cycle, MYC pathway, PLK1 pathway, DNA methylation pathway, HIF1A pathway and Oxidative stress-induced cellular senescence. Analysis of the TIMER, GEPIA database, and TCGA datasets showed that ECE2 expression levels were significantly negatively correlated with B cells, CD4+ cells, M2 macrophages, neutrophils, and dendritic cells. TCGA and GEO datasets showed that ECE2 was significantly associated with m6A modification-related genes HNRNPC, IGF2BP1, IGF2BP3 and RBM1.ConclusionECE2 is associated with m6A modification and immune infiltration and is a prognostic biomarker in LUAD.

Background: NPM1 is highly expressed in a variety of solid tumors and promotes tumor development. However, there are few comprehensive studies on NPM1 analysis in gastrointestinal cancer.Methods: We used bioinformatics tools to study the expression difference of NPM1 between gastrointestinal cancer and control group, and analyzed the relationship between its expression level and the diagnosis, prognosis, functional signaling pathway, immune infiltration, m6A and cuproptosis related genes of gastrointestinal cancer. At the same time, the expression difference of NPM1 between esophageal carcinoma (ESCA) samples and control samples was verified by in vitro experiments.Results: NPM1 was overexpressed in gastrointestinal cancer. In vitro experiments confirmed that the expression of NPM1 in ESCA samples was higher than that in normal samples. The expression of NPM1 has high accuracy in predicting the outcome of gastrointestinal cancer. The expression of NPM1 is closely related to the prognosis of multiple gastrointestinal cancers. Go and KEGG enrichment analysis showed that NPM1 co-expressed genes involved in a variety of biological functions. NPM1 expression is potentially associated with a variety of immune cell infiltration, m6A and cuproptosis related genes in gastrointestinal cancers.Conclusion: NPM1 can be used as a diagnostic and prognostic marker of gastrointestinal cancer, which is related to the immune cell infiltration and the regulation of m6A and cuproptosis.

PurposeThe purpose of our study was to investigate the effect of pre-operative hypoalbuminemia on the short-term outcomes after primary colorectal cancer (CRC) surgery.Materials and methodsThe retrospective study enrolled CRC patients who underwent primary surgery from January 2011 to December 2021 in a single teaching hospital. The short-term outcomes were compared between the hypoalbuminemia group and the normal group using propensity score matching (PSM). Univariate and multivariate logistic regression analyses were used for analyzing independent predictors of overall complications and major complications.ResultsA total of 7,072 patients from a single center were enrolled in this study. There were 1,078 (15.2%) patients in the pre-operative hypoalbuminemia group and 5,994 (84.8%) patients in the normal pre-operative albumin group. After 1:1 PSM, there were 1,028 patients in the hypoalbuminemia group and 1,028 patients in the normal group. No significant differences were found in baseline information between the two groups after PSM. In terms of short-term outcomes, the hypoalbuminemia group had a longer operation time (p = 0.003), greater volume of blood loss (p = 0.036), longer hospital stays (p < 0.01), higher proportion of overall complications (p = 0.003), major complications (p = 0.016), higher incidence of pneumonia and abdominal infection (p = 0.001) than the normal group after PSM. Furthermore, hypoalbuminemia was an independent predictor for overall complications (p = 0.008) and major complications (p = 0.016).ConclusionPre-operative hypoalbuminemia increased overall complications and major complications after primary CRC surgery. Furthermore, hypoalbuminemia was an independent predictor for overall complications and major complications.

BackgroundSolute carrier family 17 member 9 (SLC17A9) encodes a member of a family of transmembrane proteins that are involved in the transport of small molecules. SLC17A9 is involved in the occurrence and development of various cancers, but its biological role in liver hepatocellular carcinoma (LIHC) is unclear.MethodsThe expression level of SLC17A9 was assessed using The Cancer Genome Atlas (TCGA) database and immunohistochemistry of tumor tissues and adjacent normal liver tissues. The receiver operating characteristic (ROC) and R software package performed diagnosis and prognosis. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes functional enrichment and co-expression of SLC17A9, gene–gene interaction (GGI), and protein–protein interaction (PPI) networks were performed using R, GeneMANIA, and STRING. Western blot, real-time quantitative PCR (RT-qPCR), immunofluorescence, colony formation, wound scratch assay, ATP production assays, and high connotation were applied to determine the effect of SLC17A9 knockdown on HEPG2 (hepatocellular liver carcinoma) cells. TIMER, GEPIA, and TCGA analyzed the relationship between SLC17A9 expression and immune cells, m6A modification, and ferroptosis.ResultsSLC17A9 expression in LIHC tissues was higher than in normal liver tissues (p < 0.001), and SLC17A9 was related to sex, DSS (disease-specific survival), and PFI (progression-free interval) (p = 0.015, 0.006, and 0.023). SLC17A9 expression has diagnostic (AUC: 0.812; CI: 0.770–0.854) and prognostic potential (p = 0.015) in LIHC. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) functional enrichment analysis showed that SLC17A9 was closely related to neuronal cell body, presynapse, axonogenesis, PI3K/Akt signaling pathway. GGI showed that SLC17A9 was closely related to MYO5A. PPI showed that SLC17A9 was closely related to SLC18A3. SLC17A9 silencing inhibited HepG2 cells proliferation, migration, colony formation, and reduced their ATP level. SLC17A9 expression level was related to immune cells: B cells (r = 0.094, P = 8.06E-02), CD4+ T cells (r = 0.184, P = 5.95E-04), and macrophages (r = 0.137, P = 1.15E-02); m6A modification: HNRNPC (r = 0.220, p < 0.001), METTL3 (r = 0.180, p < 0.001), and WTAP (r = 0.130, p = 0.009); and ferroptosis: HSPA5 (r = 0.240, p < 0.001), SLC7A11 (r = 0.180, p < 0.001), and FANCD2 (r = 0.280, p < 0.001).ConclusionOur data show that SLC17A9 may influence LIHC progression. SLC17A9 expression correlates with tumor immune infiltration, m6A modification, and ferroptosis in LIHC and may have diagnostic and prognostic value in LIHC.

Background: The incidence and mortality of sepsis are increasing year by year, and there is still a lack of specific biomarkers to predict its prognosis. Prognostic value of vascular endothelial growth factor (VEGF) in predicting the severity and mortality of sepsis has been gradually discovered.Methods: Literature was searched through Embase, PubMed, Web of Science, China National Knowledge Infrastructure(CNKI) and Cochrane Library databases in March 2022. Observational studies, evaluating the impact of VEGF in sepsis outcomes (mortality and severity) are included in this meta-analysis. Risk of bias was assessed with the Newcastle-Ottawa Scale (NOS). Sensitivity and publication bias analyses were also assessed. Meta-regression analysis were performed to identify the potential sources of heterogeneity.Result: A total of 1,574 articles were retrieved from the systematic literature search. We included 20 studies for qualitative and quantitative analysis. Deceased and critically ill patients had higher baseline VEGF levels than survivors and non-severe patients. The pooled sensitivity and specificity for VEGF predicts sepsis mortality were 0.79and 0.76, respectively. the area under the SROC curve was 0.83.Conclusion: High VEGF are associated with poor clinical outcomes for patients diagnosed with sepsis. This study was recorded on PROSPERO, under the registration ID: CRD42022323079.

PurposeThe purpose of this study is to explore the oncologic outcomes of complications on colorectal cancer (CRC) patients who underwent primary surgery using a propensity score matching (PSM) analysis.MethodsA retrospective study was conducted from Jan 2011 to Jan 2020 in a clinical center. The overall survival (OS) and disease-free survival (DFS) were compared among the no complications group, the major complications group and the minor complications group.ResultsA total of 4250 CRC patients who underwent radical primary surgery were included in the current study. Among them, 927 (21.8%) patients suffered complications. After 1:1 ratio PSM, there were 98 patients in the major complications group and in the minor complications group, and 911 patients in the overall complications group and in the no complications group. There was no significant difference in terms of baseline information after PSM (p>0.05). Complications were independent predictors of OS (p=0.000, HR=1.693, 95% CI=1.476-1.941) and DFS (p=0.000, HR=1.555, 95% CI=1.367-1.768). In terms of specific tumor stage, the no complications group had better OS on all stages (p=0.006) and stage III (p=0.003) CRC than the complications group after PSM. Furthermore, the no complications group had better DFS on all stages (p=0.005) and stage III (p=0.021) CRC than the complications group after PSM. However, there was no significant difference between the minor complications group and the major complications group in different tumor stages (p>0.05).ConclusionComplications were associated with poor prognosis of CRC and surgeons should be cautious of the adverse events.

Hydrogen sulfide (H2S) has been highlighted as an important gasotransmitter in mammals. A growing number of studies have indicated that H2S plays a key role in the pathophysiology of vascular diseases and physiological vascular homeostasis. Alteration in H2S biogenesis has been reported in a variety of vascular diseases and H2S supplementation exerts effects of vasodilation. Accumulating evidence has shown vascular potassium channels activation is involved in H2S-induced vasodilation. This review aimed to summarize and discuss the role of H2S in the regulation of vascular tone, especially by interaction with different vascular potassium channels and the underlying mechanisms.

PurposeThe purpose of the current study was to analyze the effect of intraoperative blood loss (IBL) and intraoperative blood transfusion (IBT) on the short-term outcomes and prognosis for patients who underwent primary colorectal cancer (CRC) surgery.MethodsWe retrospectively collected the patients' information from the database of a teaching hospital from January 2011 to January 2020. IBL and IBT were collected and analyzed, and the propensity score matching (PSM) analysis was performed.ResultsA total of 4,250 patients with CRC were included in this study. There were 1,911 patients in the larger IBL group and 2,339 patients in the smaller IBL group. As for IBT, there were 82 patients in the IBT group and 4,168 patients in the non-IBT group. After 1:1 ratio PSM, there were 82 patients in the IBT group and 82 patients in the non-IBT group. The larger IBL group had longer operation time (p = 0.000 < 0.01), longer post-operative hospital stay (p = 0.000 < 0.01), smaller retrieved lymph nodes (p = 0.000 < 0.01), and higher overall complication (p = 0.000 < 0.01) than the smaller IBL group. The IBT group had longer operation time (p = 0.000 < 0.01), longer hospital stay (p = 0.016 < 0.05), and higher overall complications (p = 0.013 < 0.05) compared with the non-IBT group in terms of short-term outcomes. Larger IBL (p = 0.000, HR = 1.352, 95% CI = 1.142–1.601) and IBT (p = 0.044, HR = 1.487, 95% CI = 1.011–2.188) were independent predictive factors of overall survival (OS). Larger IBL (p = 0.000, HR = 1.338, 95% CI = 1.150–1.558) was an independent predictor of disease-free survival (DFS); however, IBT (p = 0.179, HR = 1.300, 95% CI = 0.886–1.908) was not an independent predictor of DFS.ConclusionBased on the short-term outcomes and prognosis of IBL and IBT, surgeons should be cautious during the operation and more careful and proficient surgical skills are required for surgeons.

PurposeThe purpose of this meta-analysis was to analyze whether chronic kidney disease (CKD) affected the complications and prognosis after liver resection for hepatocellular carcinoma.MethodsThe PubMed, Embase, and Cochrane Library databases were searched from inception to 22 February 2022 to find eligible studies. Complications, overall survival (OS), and disease-free survival (DFS) were collected, and this meta-analysis was performed with RevMan 5.3.ResultsA total of nine studies including 6,541 patients were included in this meta-analysis. After pooling all baseline information, the CKD group had a higher rate of Child-Pugh grade B than the Non-CKD group (OR = 1.58, 95% CI = 1.3 to 1.93, P < 0.00001). As for surgery-related information, the CKD group had larger blood loss (MD = −404.79, 95% CI = −509.70 to −299.88, P < 0.00001), and higher rate of blood transfusion (OR = 2.47, 95% CI = 1.85 to 3.3, P < 0.00001). In terms of complications, the CKD group had a higher rate of overall complications (OR = 2.1, 95% CI = 1.57 to 2.81, P < 0.00001) and a higher rate of ≥ grade III complications (OR = 2.04, 95% CI = 1.57 to 2.81, P = 0.0002). The CKD group had poor OS compared with the non-CKD group (HR = 1.28, 95% CI = 1.1 to 1.49, P = 0.001). However, in terms of DFS, no significant difference was found (HR = 1.11, 95% CI = 0.96 to 1.28, P = 0.16).ConclusionPreexisting CKD was associated with higher ratio of complications and poor OS.

PurposeThe current study aims to explore the outcomes of type 2 diabetes mellitus (T2DM) on gastric cancer patients following gastrectomy through propensity score matching (PSM) analysis.MethodsA retrospective study of gastric cancer patients following gastrectomy was conducted in a single clinical center from January 2014 to December 2019. The short-term outcomes, overall survival (OS) and disease-free survival (DFS) were analyzed between T2DM group and Non-T2DM group.ResultsA total of 703 patients were enrolled in this study. After 1:1 PSM, 84 patients in T2DM group and 84 patients in Non-T2DM were matched for final analysis. No significant difference was found in terms of operation time, intra-operative blood loss, retrieved lymph nodes, postoperative stay, blood transfusion and complications between T2DM group and Non-T2DM group (p > 0.05). The Kaplan-Meier curve implied that T2DM had no impact on OS or DFS. Cox regression was conducted to identify predictive factors for prognosis. Body mass index (BMI) (p = 0.039 < 0.05, HR = 0.725, 95% CI = 0.534–0.983), pre-operative lymphocyte (p = 0.017 < 0.05, HR = 0.678, 95% CI = 0.493–0.932), pathological tumor node metastasis (pTNM) stage (p = 0.000 < 0.05, HR = 2.619, 95% CI = 2.048–3.349) and complications (p = 0.006 < 0.05, HR = 1.528, 95% CI = 1.132–2.061) were predictive factors for OS, and BMI (p = 0.013 < 0.05, HR = 0.524, 95% CI = 0.315–0.872), pTNM stage (p = 0.000 < 0.05, HR = 2.619, 95% CI = 2.048–3.349) and complications (p = 0.008 < 0.05, HR = 1.892, 95% CI = 1.179–3.036) were independent predictive factors for DFS.ConclusionT2DM did not have an impact on gastric cancer patients following gastrectomy in terms of short-term outcomes and prognosis.

Background: YTHDF1 is highly expressed in multiple tumors and affects tumor progression. However, there are only a few comprehensive studies on the analysis of YTHDF1 in esophageal cancer.Methods: We analyzed YTHDF1 expression in pan-cancer by comparing both the GEPIA and TCGA cohorts, and further verified the differences in YTHDF1 expression between the ESCA and normal groups by the GEO ESCA cohort and in vitro experiments. The correlation of YTHDF1 expression and the clinical characteristics of ESCA patients was analyzed using the TCGA ESCA clinical data. The GO and KEGG enrichment analyses of the YTHDF1 coexpressed genes were completed by bioinformatics analysis, and the GGI and PPI were constructed for the YTHDF1, respectively. The relationship between YTHDF1 expression and the infiltration of ESCA immune cells was analyzed by using the TIMER database and the TCGA ESCA cohort. The relationships between YTHDF1 expression levels and glycolysis and ferroptosis-related genes were analyzed using the TCGA and GEPIA ESCA cohorts. Finally, the ceRNA network that may be involved in YTHDF1 in ESCA was predicted and constructed through a variety of databases.Results: YTHDF1 was overexpressed in various cancers, and in vitro experiments confirmed that YTHDF1 expression was higher in ESCA samples than in normal samples. The expression of YTHDF1 has some accuracy in predicting the tumor outcome. Expression of YTHDF1 was significantly associated with multiple clinical features in ESCA patients. GO and KEGG enrichment analyses indicated that YTHDF1 coexpressed genes involved multiple biological functions. There is a potential association between YTHDF1 expression and multiple immune cell infiltration, glycolysis, and ferroptosis-related genes in ESCA. YTHDF1 may be involved in multiple ceRNA regulatory networks in ESCA, including PAXIP1-AS1/hsa-miR-376c-3p/YTHDF1 axis, THUMPD3-AS1/hsa-miR-655-3p/YTHDF1 axis, and SNHG20/hsa-miR-655-3p/YTHDF1 axis, respectively.Conclusion: YTHDF1 can serve as a biomarker of ESCA, related to the immune cell infiltration of ESCA, regulation of glycolysis and ferroptosis, and the ceRNA regulatory network.

Background: Overexpression of solute carrier family 2 member 1 (SLC2A1) promotes glycolysis and proliferation and migration of various tumors. However, there are few comprehensive studies on SLC2A1 in colorectal cancer (CRC).Methods: Oncomine, The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases were used to analyze the expression of SLC2A1 in pan-cancer and CRC and analyzed the correlation between SLC2A1 expression and clinical characteristics of TCGA CRC samples. The expression level of SLC2A1 in CRC was certified by cell experiments and immunohistochemical staining analysis. The Genome Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses of SLC2A1 relative genes were completed by bioinformatics analysis. The correlation between SLC2A1 expression level and CRC immune infiltration cell was analyzed by Tumor IMmune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and TCGA database. The correlation between SLC2A1 expression level and ferroptosis and m6A modification of CRC was analyzed by utilizing TCGA and GEO cohort. Finally, the possible competing endogenous RNA (ceRNA) networks involved in SLC2A1 in CRC are predicted and constructed through various databases.Results: SLC2A1 is highly expressed not only in CRC but also in many other tumors. ROC curve indicated that SLC2A1 had high predictive accuracy for the outcomes of tumor. The SLC2A1 expression in CRC was closely correlated with tumor stage and progression free interval (PFI). GO, KEGG, and GSEA analysis indicated that SLC2A1 relative genes were involved in multiple biological functions. The analysis of TIMER, GEPIA, and TCGA database indicated that the SLC2A1 mRNA expression was mainly positively associated with neutrophils. By the analysis of the TCGA and GEO cohort, we identified that the expression of SLC2A1 is closely associated to an m6A modification relative gene Insulin Like Growth Factor 2 MRNA Binding Protein 3 (IGF2BP3) and a ferroptosis relative gene Glutathione Peroxidase 4 (GPX4).Conclusion: SLC2A1 can be used as a biomarker of CRC, which is associated to immune infiltration, m6A modification, ferroptosis, and ceRNA regulatory network of CRC.

Background: The incidence of silent cerebral embolisms (SCEs) has been documented after pulmonary vein isolation using different ablation technologies; however, it is unreported in patients undergoing with atrial fibrillation (AF) ablation using Robotic Magnetic Navigation (RMN). The purpose of this prospective study was to investigate the incidence, risk predictors and probable mechanisms of SCEs in patients with AF ablation and the potential impact of RMN on SCE rates.Methods and Results: We performed a prospective study of 166 patients with paroxysmal or persistent AF who underwent pulmonary vein isolation. Patients were divided into RMN group (n = 104) and manual control (MC) group (n = 62), and analyzed for their demographic, medical, echocardiographic, and risk predictors of SCEs. All patients underwent cerebral magnetic resonance imaging within 48 h before and after the ablation procedure to assess cerebral embolism. The incidence and potential risk factors of SCEs were compared between the two groups. There were 26 total cases of SCEs in this study, including 6 cases in the RMN group and 20 cases in the MC group. The incidences of SCEs in the RMN group and the MC group were 5.77 and 32.26%, respectively (X2 = 20.63 P < 0.05). Univariate logistic regression analysis demonstrated that ablation technology, CHA2DS2-VASc score, history of cerebrovascular accident/transient ischemic attack, and low ejection fraction were significantly associated with SCEs, and multivariate logistic regression analysis showed that MC ablation was the only independent risk factor of SCEs after an AF ablation procedure.Conclusions: Ablation technology, CHA2DS2-VASc score, history of cerebrovascular accident/transient ischemic attack, and low ejection fraction are associated with SCEs. However, ablation technology is the only independent risk factor of SCEs and RMN can significantly reduce the incidence of SCEs resulting from AF ablation.Clinical Trial Registration: ChiCTR2100046505.

Background: The purpose of this study was to explore the effect of abdominal shape on the short-term surgical outcomes.Methods: This was a retrospective study that included 425 patients undergoing laparoscopic distal gastrectomy plus D2 lymph node dissection (LADG) from January 2013 to January 2021. The abdominal parameters, including the shortest distance of the pancreas from the anterior abdominal skin (PAAD), the lower sternum angle (LSA), the thickness of the subcutaneous fat at the navel level (SFT), the anteroposterior diameters (APD) and the left-right diameters (LRD) at the navel level, the distance from the xiphoid process to the navel (XND) and the distance from the xiphoid process to the pubis (XBD), were calculated by preoperative abdominal computed tomography (CT) imaging. The parameters and short-term surgical outcomes were analyzed.Results: In males, the number of retrieved lymph nodes was significantly higher in patients with a lower APD group (p = 0.031). The operation time was significantly shorter in the lower body mass index (BMI) (p = 0.007), lower LSA (p = 0.035), lower PAAD (p = 0.000), lower SFT (p = 0.004), lower APD (p = 0.000) and lower LRD (p = 0.014) groups. The estimated blood loss was significantly less in the lower BMI (p = 0.035), lower LSA (p = 0.001), lower PAAD (p = 0.012), lower SFT (p = 0.003), lower APD (p = 0.000) and lower LRD (p = 0.005) groups. The complications were fewer in the lower LSA (p = 0.012), lower APD (p = 0.043) and lower LRD (p = 0.023) groups. In females, the postoperative hospital stay was shorter in the lower PAAD (p = 0.027) and lower SFT (p = 0.004) groups, and the lower SFT group had fewer complications (p = 0.020). Furthermore, in multivariate analysis, higher PAAD (p = 0.037, odds ratio = 1.030, 95% CI = 1.002–1.059) was an independent factor for predicting postoperative complications in males.Conclusion: Various abdominal shapes can affect the difficulty of LADG. Higher PAAD is a simple independent index for predicting postoperative complications in males.

The sodium pump α3 subunit is associated with colorectal liver metastasis. However, the underlying mechanism involved in this effect is not yet known. In this study, we found that the expression levels of the sodium pump α3 subunit were positively associated with metastasis in colorectal cancer (CRC). Knockdown of the α3 subunit or inhibition of the sodium pump could significantly inhibit the migration of colorectal cancer cells, whereas overexpression of the α3 subunit promoted colorectal cancer cell migration. Mechanistically, the α3 subunit decreased p53 expression, which subsequently downregulated PTEN/IGFBP3 and activated mTOR, leading to the promotion of colorectal cancer cell metastasis. Reciprocally, knockdown of the α3 subunit or inhibition of the sodium pump dramatically blocked this effect in vitro and in vivo via the downregulation of mTOR activity. Furthermore, a positive correlation between α3 subunit expression and mTOR activity was observed in an aggressive CRC subtype. Conclusions: Elevated expression of the sodium pump α3 subunit promotes CRC liver metastasis via the PTEN/IGFBP3-mediated mTOR pathway, suggesting that sodium pump α3 could represent a critical prognostic marker and/or therapeutic target for this disease.

Diutina catenulata (Candida catenulata) is an ascomycete yeast species widely used in environmental and industrial research and capable of causing infections in humans and animals. At present, there are only a few studies on D. catenulata, and further research is required for its more in-depth characterization and analysis. Eleven strains of D. catenulata collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and the CHIF-NET North China Program were identified using matrix-assisted laser desorption ionization–time of flight mass spectrometry and internal transcribed spacer sequencing. The antifungal susceptibility of the Diutina catenulata strains was tested using the Clinical and Laboratory Standards Institute broth microdilution method and Sensititre YeastOne™. Furthermore, ERG11 and FKS1 were sequenced to determine any mutations related to azole and echinocandin resistance in D. catenulata. All isolates exhibited low minimum inhibitory concentration (MIC) values for itraconazole (0.06–0.12 μg/ml), posaconazole (0.06–0.12 μg/ml), amphotericin B (0.25–1 μg/ml), and 5-flucytosine (range,

PurposeThe purpose of the current meta-analysis is to analyze whether extended intraoperative peritoneal lavage (EIPL) can bring benefit on short-term outcomes or survival for patients undergoing curative gastrectomy for gastric cancer.MethodsThe PubMed, Embase, and Cochrane Library databases were searched from inception to May 3, 2021, to find eligible studies. Postoperative complications, overall survival (OS), disease-free survival (DFS), and peritoneal recurrence–free survival (PRFS) were compared between EIPL group and No EIPL group.ResultsA total of five randomized controlled trials with 1,790 patients were included in the current meta-analysis. No difference was found in baseline information (p > 0.05). After pooling up the data of overall postoperative complications, no significant difference was found between EIPL group and No EIPL group (OR = 0.88, 95% CI = 0.51 to 1.53, P = 0.65). Furthermore, there was no significant difference between EIPL group and No EIPL group in terms of OS (HR = 0.77, 95% CI = 0.36 to 1.64, P = 0.49), DFS (HR = 0.97, 95% CI = 0.71 to 1.33, P = 0.87), and PRFS (HR = 1.03, 95% CI = 0.74 to 1.43, P = 0.86). In terms of subgroup analysis of OS, no significant difference was found as well (HR = 1.05, 95% CI = 0.82 to 1.34, P = 0.69).ConclusionsEIPL did not bring benefit in terms of short-term outcomes or survival. Therefore, EIPL is not recommended for patients undergoing curative gastrectomy for gastric cancer.

PurposeThe purpose of the current study was to evaluate the impact of colorectal cancer (CRC) surgery on type 2 diabetes mellitus (T2DM) and to analyze the change in T2DM on overall survival after CRC surgery.MethodsPatients who underwent CRC surgery were retrospectively enrolled from January 2013 to December 2019. The status of T2DM pre- and 1-year after CRC surgery was recorded, and predictive factors for T2DM remission and overall survival were analyzed.ResultsA total of 296 patients were included in this study. Thirty-eight patients experienced remission of T2DM 1 year after CRC surgery, and the remission rate was 12.8%. Weight loss was significantly higher in the T2DM remission group (p = 0.038), and the T2DM duration was significantly shorter in the T2DM remission group (p = 0.015). In the multivariate logistic regression analysis, higher weight loss (p = 0.046, odds ratio = 1.060, 95% CI = 1.001–1.122) and shorter T2DM duration (p = 0.019, odds ratio = 1007, 95% CI = 1.001–1.014) were predictive factors for remission of T2DM. Furthermore, in multivariate Cox regression analysis, lower TNM stage (p = 0.000, odds ratio = 2.147, 95% CI = 1.474–3.128) and T2DM remission (p = 0.033, odds ratio = 2.999, 95% CI = 1.091–8.243) were the predictive factors for better overall survival.ConclusionPatients with concurrent CRC and T2DM had a 12.8% remission 1 year after CRC surgery. Higher weight loss and shorter T2DM duration contributed to T2DM remission, and patients with T2DM remission could improve in terms of their overall survival.

BackgroundOverexpression of NPM1 can promote the growth and proliferation of various tumor cells. However, there are few studies on the comprehensive analysis of NPM1 in lung adenocarcinoma (LUAD).MethodsTCGA and GEO data sets were used to analyze the expression of NPM1 in LUAD and clinicopathological analysis. The GO/KEGG enrichment analysis of NPM1 co-expression and gene set enrichment analysis (GSEA) were performed using R software package. The relationship between NPM1 expression and LUAD immune infiltration was analyzed using TIMER, GEPIA database and TCGA data sets, and the relationship between NPM1 expression level and LUAD m6A modification and glycolysis was analyzed using TCGA and GEO data sets.ResultsNPM1 was overexpressed in a variety of tumors including LUAD, and the ROC curve showed that NPM1 had a certain accuracy in predicting the outcome of tumors and normal samples. The expression level of NPM1 in LUAD is significantly related to tumor stage and prognosis. The GO/KEGG enrichment analysis indicated that NPM1 was closely related to translational initiation, ribosome, structural constituent of ribosome, ribosome, Parkinson disease, and RNA transport. GSEA showed that the main enrichment pathway of NPM1-related differential genes was mainly related to mTORC1 mediated signaling, p53 hypoxia pathway, signaling by EGFR in cancer, antigen activates B cell receptor BCR leading to generation of second messengers, aerobic glycolysis and methylation pathways. The analysis of TIMER, GEPIA database and TCGA data sets showed that the expression level of NPM1 was negatively correlated with B cells and NK cells. The TCGA and GEO data sets analysis indicated that the NPM1 expression was significantly correlated with one m6A modifier related gene (HNRNPC) and five glycolysis related genes (ENO1, HK2, LDHA, LDHB and SLC2A1).ConclusionNPM1 is a prognostic biomarker involved in immune infiltration of LUAD and associated with m6A modification and glycolysis. NPM1 can be used as an effective target for diagnosis and treatment of LUAD.

BackgroundGlucose transporter 1 (GLUT1) is encoded by the solute carrier family 2A1 (SLC2A1) gene and is one of the glucose transporters with the greatest affinity for glucose. Abnormal expression of GLUT1 is associated with a variety of cancers. However, the biological role of GLUT1 in esophageal carcinoma (ESCA) remains to be determined.MethodsWe analyzed the expression of GLUT1 in pan-cancer and ESCA as well as clinicopathological analysis through multiple databases. Use R and STRING to perform GO/KEGG function enrichment and PPI analysis for GLUT1 co-expression. TIMER and CIBERSORT were used to analyze the relationship between GLUT1 expression and immune infiltration in ESCA. The TCGA ESCA cohort was used to analyze the relationship between GLUT1 expression and m6A modification in ESCA, and to construct a regulatory network in line with the ceRNA hypothesis.ResultsGLUT1 is highly expressed in a variety of tumors including ESCA, and is closely related to histological types and histological grade. GO/KEGG functional enrichment analysis revealed that GLUT1 is closely related to structural constituent of cytoskeleton, intermediate filament binding, cell-cell adheres junction, epidermis development, and P53 signaling pathway. PPI shows that GLUT1 is closely related to TP53, GIPC1 and INS, and these three proteins all play an important role in tumor proliferation. CIBERSORT analysis showed that GLUT1 expression is related to the infiltration of multiple immune cells. When GLUT1 is highly expressed, the number of memory B cells decreases. ESCA cohort analysis found that GLUT1 expression was related to 7 m6A modifier genes. Six possible crRNA networks in ESCA were constructed by correlation analysis, and all these ceRNA networks contained GLUT1.ConclusionGLUT1 can be used as a biomarker for the diagnosis and treatment of ESCA, and is related to tumor immune infiltration, m6A modification and ceRNA network.

Diabetic coronary arterial disease is a leading cause of morbidity and mortality in diabetic patients. The impaired function of large-conductance calcium-activated potassium channels (BK channels) is involved in diabetic coronary arterial disease. Many studies have indicated that the reduced BK channel expression in diabetic coronary artery is attributed to ubiquitin-mediated protein degradation by the ubiquitin–proteasome system. This review focuses on the influence and the mechanisms of BK channel regulation by E3 ubiquitin ligases in diabetic coronary arterial disease. Thus, BK channels regulated by E3 ubiquitin ligase may play a pivotal role in the coronary pathogenesis of diabetic mellitus and, as such, is a potentially attractive target for therapeutic intervention.

Aim: Docosahexaenoic acid (DHA) is known to activate the vascular large-conductance calcium-activated potassium (BK) channels and has protective effects on the cardiovascular system. However, the underlying mechanisms through which DHA activates BK channels remain unclear. In this study, we determined such mechanisms by examining the effects of different concentrations of DHA on BK channels in freshly isolated rat coronary arterial smooth muscle cells (CASMCs) using patch clamp techniques.Methods and Results: We found that BK channels are the major potassium currents activated by DHA in rat CASMCs and the effects of DHA on BK channels are concentration dependent with a bimodal distribution. At concentrations of

Social functions of oxytocin (OT) have been explored extensively; however, relationship between the effect of intranasally applied OT (nasal OT) on the social preference (SP) and intracerebral actions of endogenous OT remains unclear. To resolve this question, we first observed effects of nasal OT on the SP of virgin young adult male rats toward unfamiliar virgin estrous female (EF) vs. virgin male rats. The results showed that the test male rats exhibited significantly more times and longer duration accessing the female than the male, which were acutely eliminated by nasal OT. Then, we examined the approaches mediating nasal OT effects on the activity of potential brain targets in Western blots and found that nasal OT activated the olfactory bulbs (OBs) and the supraoptic nucleus (SON), but not the piriform cortex, amygdala and hippocampus as shown by significant changes in the expression of c-Fos and/or phosphorylated extracellular signal-regulated protein kinase (pERK) 1/2. Moreover, microinjection of TTX into the OBs blocked nasal OT-evoked increases in pERK1/2 levels as well as the molecular association between ERK1/2 and OT-neurophysin in the SON. Electrolytic lesions of the lateral olfactory tract did not significantly change the basal levels of pERK 1/2 in the SON; however, upon nasal OT, pERK 1/2 levels in the SON reduced significantly. Lastly, microinjection of L-aminoadipic acid (gliotoxin) into the SON to reduce OT levels reduced the duration of the test male’s accessing the EF and blocked the nasal OT-evoked increase in the duration of test male’s accessing the male while significantly increasing pERK1/2 levels in the amygdala. These findings reveal for the first time that nasal OT acutely eliminates virgin males’ SP to EFs via the OB-SON route and that OT neurons could mediate the social effects of nasal OT by suppressing social phobia generated in the amygdala.

Background: Observational studies have suggested a possible association between hypothyroidism and increased risk of ischemic stroke. However, a causal relationship remains unclear. Methods: Data on single nucleotide polymorphisms (SNPs) associated with hypothyroidism and ischemic stroke were sourced from the FinnGens database and the UK Biobank of European descent. Both databases underwent separate two-sample Mendelian randomization (MR) analyses. A subsequent meta-analysis of MR results using a random-effects model was conducted to determine the causal relationship between hypothyroidism and ischemic stroke. Results: All five analyses indicated a positive causal relationship between hypothyroidism and ischemic stroke. MR analysis of the association between hypothyroidism and ischemic stroke yielded a result of the inverse variance weighted (IVW) method at 4.7411 (1.3598-16.5308), p = 0.0146. The analysis of ischemic stroke (without excluding controls) yielded a result of the IVW method of 4.5713 (1.3570-15.3986), p = 0.0142. MR analysis with cerebral infarction yielded a result of the IVW method at 1.0110 (1.0006-1.0215), p = 0.0373. The MR analysis with cerebrovascular disease sequelae yielded an IVW method result of 2.4556 (1.0291-5.8595), p = 0.0429. Analysis for the sequelae of cerebrovascular disease (without excluding controls) yielded an IVW method result of 2.4217 (1.0217-5.7402), p = 0.0446. No evidence of heterogeneity or horizontal pleiotropy was found. The meta-analysis of the five MR results was 2.24 (1.18-4.26), p = 0.025. Conclusion: Our two-sample Mendelian randomization study suggested a causal relationship between hypothyroidism and ischemic stroke, indicating that hypothyroidism could be a risk factor for ischemic stroke. However, further studies are required to elucidate the underlying biological mechanisms. [ABSTRACT FROM AUTHOR]

Oxytocin (OT), a hypothalamic neuropeptide, applied through nasal approach (IAO), could improve maternal health during lactation that is disrupted by mother–baby separation; however, the regulation of IAO effects on maternal behaviors and lactation as well as the underlying mechanisms remain unclear. Using lactating rats, we observed effects of intermittent pup deprivation (PD) with and without IAO on maternal behaviors and lactation as well as the activity of OT neurons in the supraoptic nucleus (SON) and the activity of hypothalamic pituitary-adrenal axis, key factors determining the milk-letdown reflex during lactation and maternal behaviors. The results showed that PD reduced maternal behaviors and lactation efficiency of rat dams as indicated by significantly longer latency to retrieve their pups and low litter’s body weight gains during the observation, respectively. In addition, PD caused early involution of the mammary glands. IAO partially improved these changes in rat dams, which was not as significant as IAO effects on control dams. In the SON, PD decreased c-Fos and increased glial fibrillary acidic protein (GFAP) filaments significantly; IAO made PD-evoked c-Fos reduction insignificant while reduced GFAP filament significantly in PD dams. IAO tended to increase the levels of phosphorylated extracellular signal-regulated kinases (pERK) 1/2 in PD dams. Moreover, PD+IAO significantly increased plasma levels of dam adrenocorticotropic hormone and corticosterone but not OT levels. Lastly, PD+IAO tended to increase the level of corticotropin-releasing hormone in the SON. These results indicate that PD disrupts maternal behaviors and lactation by suppressing the activity of hypothalamic OT-secreting system through expansion of astrocytic processes, which are partially reversed by IAO through removing astrocytic inhibition of OT neuronal activity. However, the improving effect of IAO on the maternal health could be compromised by simultaneous activation of hypothalamic pituitary-adrenocortical axis.