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Abstract. Background:. Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients. Methods:. We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177+ neutrophils, and CD40L+ T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs. persistent histological inflammation using Kaplan–Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. Results:. We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X1 + 0.758X2 + 1.347X3 − 7.745 (X1, X2, and X3 represent the proportions of CD177+ neutrophils, eosinophils, and CD40L+ T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y

ObjectivePatients with rheumatoid arthritis (RA) have an increased risk of developing pulp and periapical disease (PAP), but the causal relationship and shared genetic factors between these conditions have not been explored. This study aimed to investigate the bidirectional causal relationship between RA and PAP and to analyze shared genes and pathogenic pathways.MethodsWe utilized GWAS data from the IEU Open GWAS Project and employed five Mendelian randomization methods (MR Egger, weighted median, inverse variance weighted, simple mode, and weighted mode) to investigate the bidirectional causal relationship between RA and PAP. Transcriptome data for RA and irreversible pulpitis (IRP) were obtained from the GEO database. Hub genes were identified through differential analysis, CytoHubba, machine learning (ML), and other methods. The immune infiltration of both diseases was analyzed using the ssGSEA method. Finally, we constructed a regulatory network for miRNAs, transcription factors, chemicals, diseases, and RNA-binding proteins based on the identified hub genes.ResultsRA was significantly associated with an increased risk of PAP (OR = 1.1284, 95% CI 1.0674-1.1929, p < 0.001). However, there was insufficient evidence to support the hypothesis that PAP increased the risk of RA. Integrating datasets and differential analysis identified 84 shared genes primarily involved in immune and inflammatory pathways, including the IL-17 signaling pathway, Th17 cell differentiation, and TNF signaling pathway. Using CytoHubba and three ML methods, we identified three hub genes (HLA-DRA, ITGAX, and PTPRC) that are significantly correlated and valuable for diagnosing RA and IRP. We then constructed a comprehensive regulatory network using the miRDB, miRWalk, ChipBase, hTFtarget, CTD, MalaCards, DisGeNET, and ENCORI databases.ConclusionRA may increase the risk of PAP. The three key genes, HLA-DRA, ITGAX, and PTPRC, have significant diagnostic value for both RA and IRP.

BackgroundTraditional anthropometric measures, including body mass index (BMI), are insufficient for evaluating gallstone risk. This study investigated the association between novel anthropometric indices and gallstone risk among 6,848 participants from the National Health and Nutrition Examination Survey in the United States.MethodsMeasures calculated included weight (WT), BMI, waist circumference (WC), waist-to-height ratio (WtHR), conicity index (CI), A Body Shape Index (ABSI), Body Roundness Index (BRI), Abdominal Volume Index (AVI), and Weight-adjusted Waist Index (WWI). Logistic regression and smooth curve fitting assessed the relationships between these indices and gallstones, complemented by receiver operating characteristic (ROC) curve analysis to evaluate their discriminative power.ResultsThe results indicated significant differences between study groups, with a positive and independent correlation identified between gallstones and all measures except ABSI. Specifically, per 1 SD increase in WC, WT, BMI, WtHR, and AVI was associated with a 57%, 59%, 52%, 53%, and 53% increased risk of gallstones, respectively. Dose-response analysis confirmed a positive correlation between these indices and gallstone risk. ROC analysis highlighted WtHR and BRI as having superior discriminative abilities (AUC = 0.6703). Further, among participants with a BMI < 30 kg/m2, elevated levels of WT, WtHR, CI, BRI, and WWI significantly increased the risk of gallstones (P < 0.001). Likewise, elevated BMI heightened the risk at low levels of WT, WC, WtHR, BRI, AVI, and CI (P < 0.001).ConclusionThis study supports the positive association between various anthropometric indicators and gallstones, recommending that newer anthropometric indices be considered more extensively to enhance gallstone prevention and treatment strategies.

Introduction Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%–6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy.Methods and analysis This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable.Ethics and dissemination The study protocol has been approved by the ethics committees of the Sixth People’s Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences.Trial registration number ChiCTR2300073864.

BackgroundLife’s essential’ 8 (LE8) is a newly updated cardiovascular health (CVH) metrics from the American Heart Association, with close relevance to metabolism. Our objective is to explore the association between LE8 scores and incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) and advanced liver fibrosis in American adults.MethodsThis population-based cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018, encompassing adults aged 20 years or older. Validated non-invasive scoring systems were employed to define liver steatosis and advanced liver fibrosis. Multivariable logistic regression and smooth curve fitting techniques were applied to evaluate the associations. All analyses were adjusted for the survey’ complex design parameters and accounted for sample weights.ResultsA total of 11,820 participants were included. A higher LE8 score was found to be inversely associated with the incidence of MAFLD and advanced liver fibrosis, with odds ratios (OR) of 0.64 (95% CI: 0.57–0.71) for MAFLD and 0.75 (95% CI: 0.61–0.92) for advanced liver fibrosis per 1 standard deviation (SD) increase in LE8 score. Similar patterns were found in the relationship between health behaviors/factors score and incidence of MAFLD and advanced liver fibrosis. In subgroup analyses, the interaction test showed that age, education level, marital status, CVD, hypertension and diabetes had a significant impact on the association between LE8 score and MAFLD (all P for interaction < 0.05). Among male, elderly, wealthy, other race, CVD, diabetes and depression participants, the correlation between LE8 score and advanced liver fibrosis was not statistically significant (P > 0.05). Younger participants exhibited a more pronounced negative association between the CVH metric and both MAFLD and advanced life fibrosis.ConclusionLE8 and its subscales score were inversely associated with the presence of MAFLD and advanced liver fibrosis in non-linear patterns. Optimal LE8 score may significantly reduce the risk of liver steatosis and fibrosis.

Background: Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn’s disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial. Objectives: To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram. Design: Cross-sectional study. Methods: The simplified endoscopic activity score for CD (SES-CD), Crohn’s disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed. Results: The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort ( p

Objective: To analyze the current research status, hotspots, and frontiers in the field of Gastrointestinal (GI) cancer and quality of life (QoL) through the bibliometrics method, and to provide references and guidance for future research. Methods: Literature related to GI cancer and QoL from April 1, 2003 to March 31, 2023 was retrieved from the Web of Science Core Collection database. CiteSpace 6.2.R1 was performed for collaboration analysis, keyword co-occurrence analysis, and document co-citation analysis. Results: A total of 1224 publications were included in this study. There has been a significant increase in the number of publications in this field over the past two decades. The United States, the Karolinska Institute and the University of Amsterdam, and Pernilla Lagergren are the most prolific country, institution, and author, respectively. The links between most of the research constituents were relatively thin (centrality

ABSTRACTIntestinal epithelial cell (IEC) regulation of barrier function and mucosal homeostasis enables the establishment of a harmonious gut microenvironment. However, host-derived regulatory networks that modulate intestinal antimicrobial defenses have not been fully defined. Herein we generated mice with IEC-specific deletion of Gpr65 (Gpr65ΔIEC) and investigated the role of epithelial GPR65 using DSS- and C. rodentium-induced murine colitis models. RNA sequencing analysis was conducted on colonic IECs from Gpr65fl/fl and Gpr65ΔIEC mice, and colonoids and colonic epithelial cell lines were used to evaluate the pH-sensing effect of GPR65. The expression of GPR65 was determined in IECs from patients with inflammatory bowel disease (IBD) and DSS colitis mice by qRT-PCR, Western blot, and immunohistochemistry, respectively. We observed that the absence of GPR65 in IECs abrogated homeostatic antimicrobial programs, including the production of antimicrobial peptides (AMPs) and defense response-associated proteins. Gpr65ΔIEC mice displayed dysbiosis of the gut microbiota and were prone to DSS- and C. rodentium-induced colitis, as characterized by significantly disrupted epithelial antimicrobial responses, pathogen invasion, and increased inflammatory infiltrates in the inflamed colon. RNA sequencing analysis revealed that deletion of GPR65 in IECs provoked dramatic transcriptome changes with respect to the downregulation of immune and defense responses to bacteria. Forced AMP induction assays conducted in vivo or in ex vivo colonoids revealed that IEC-intrinsic GPR65 signaling drove antimicrobial defense. Mechanistically, GPR65 signaling promoted STAT3 phosphorylation to optimize mucosal defense responses. Epithelial cell line and colonoid assays further confirmed that epithelial GPR65 sensing pH synergized with IL-22 to facilitate antimicrobial responses. Finally, the expression of GPR65 was markedly decreased in the inflamed epithelia of IBD patients and DSS colitis mice. Our findings define an important role of epithelial GPR65 in regulating intestinal homeostasis and mucosal inflammation and point toward a potential therapeutic approach by targeting GPR65 in the treatment of IBD.

Background/Aims: Chemoresistance is a common event after cancer chemotherapy, which is associated with the deregulation of circular RNAs (circRNAs). The objective of this study was to clarify the role of circ-LDLRAD3 in cisplatin (DDP)-resistant gastric cancer (GC). Methods: The expression of circ-LDLRAD3, miR-588, and SRY-box transcription factor 5 (SOX5) mRNA was detected by quantitative real-time polymerase chain reaction. Cell viability and the half maximal inhibitory concentration (IC50) value were measured by CCK8 assay. Cell proliferation was assessed by colony formation and EdU assays. Cell apoptosis and cell invasion were assessed by flow cytometry assay and transwell assay, respectively. The expression of SOX5 protein was detected by Western blotting. A xenograft model was established to verify the role of circ-LDLRAD3 in vivo. Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy and the expression of exosome-related proteins. Results: circ-LDLRAD3 was overexpressed in DDP-resistant GC tissues and cells. circ-LDLRAD3 knockdown decreased the IC50 of DDP-resistant cells and suppressed cell proliferation, survival and invasion. miR-588 was a target of circ-LDLRAD3, and miR-588 inhibition attenuated the inhibition of DDP resistance, proliferation, survival and invasion in DDP-resistant GC cells caused by circ-LDLRAD3 knockdown. SOX5 was a target of miR-588, and the inhibition of the DDP resistance, proliferation, survival and invasion of DDP-resistant GC cells by miR-588 restoration was largely rescued SOX5 overexpression. circ-LDLRAD3 knockdown inhibited DDP resistance and tumor growth in vivo. circ-LDLRAD3 was overexpressed in exosomes isolated from DDP-resistant GC cells. Conclusions: circ-LDLRAD3 knockdown reduced DDP resistance and blocked the malignant development of DDP-resistant GC by modulating the miR-588/SOX5 pathway.

Abstract Objectives To investigate the incidence and influencing factors of thyroid dysfunction (TD) in patients with primary liver cancer (PLC) induced by PD-1 monoclonal antibodies. Methods Clinical data were collected from 195 PLC patients treated with PD-1. They were divided into TD group and normal thyroid function (NTF) group, and further divided into TD subgroups, the differences between groups and subgroups were analyzed. Results A total of 113 of 195 (57.9%) PLC patients developed TD. The positive rate of thyroid antibody (20.6% vs. 0%, P = 0.041) and the median value of TSH (6.20 vs. 2.16 mU/L, P = 0.000) in TD group were higher than those in NTF group. Ten patients (8.8%) had the CTCAE grade of TD above grade 3, of which 2 patients died of liver failure. There were 20 patients (17.7%) in hyperthyroidism group and 93 patients (82.3%) in hypothyroidism group. The decompensated cirrhosis in hyperthyroidism group was lower than that in hypothyroidism group (33.3% vs. 65.6%, P = 0.010), and the proportion of patients who had previously received surgical treatment was higher than that in hypothyroidism group (35.0% vs. 9.7%, P = 0.003); The proportion of clinical hyperthyroidism was higher than that of clinical hypothyroidism (70.0% vs. 31.2%, P = 0.001), the proportion of decompensated liver cirrhosis in clinical hyperthyroidism group was lower than that in clinical hypothyroidism group (23.1% vs. 68.0%, P = 0.022), and the proportion of previous or combined surgical resection was much higher than that in clinical hypothyroidism group (42.9% vs. 7.1%, P = 0.018); The proportion of decompensated cirrhosis in primary TD group was lower than that in secondary TD group (36.5% vs. 83.3%, P = 0.002), and the proportion of patients using antitumor targeted drugs was higher than that in secondary TD group (73.1% vs. 45.0%, P = 0.014). Conclusion Patients with PLC had high incidence of TD after receiving PD-1 treatment, primary or subclinical hypothyroidism was the main manifestation type, which was related to the degree of disease and treatment.

Abstract Background The best intervention approach for residual choledocholithiasis after choledocholithotomy T-tube drainage remains controversial, especially during the period of indwelling T tube and the formation of a sinus. The purpose of the study was to estimate the effects of two therapeutic modalities, namely endoscopic retrograde cholangiopancreatography (ERCP) and choledochfiberscope via the T-tube sinus tract (CDS) on residual choledocholithiasis after choledocholithotomy T-tube drainage. Methods A total of 112 patients with residual choledocholithiasis after choledochotomy were included in the study, 50 of which underwent ERCP and 62 patients experienced choledochoscopy via the T-tube sinus tract. The primary outcome measures included the success rate of remove biliary stones, T-tube drainage time, and the average length of hospital stay. The secondary objective was to consider incidence of adverse events including cholangitis, bile leakage, T-tube migration, pancreatitis, bleeding and perforation. After hospital discharge, patients were followed up for two years and the recurrence of choledocholithiasis was recorded. Results There was no significant difference in the success rate of stone removal between the two groups. Compared to CDS group, T-tube drainage time and the average length of hospital stay was significantly shorter in the ERCP group. The incidence of complications (cholangitis and bile leakage) in the ERCP group was lower than that in the CDS group, but there was no statistically significant difference. When the T-tube sinus tract is not maturation, ERCP was the more appropriate endoscopic intervention to remove residual choledocholithiasis, particularly complicated with cholangitis at this time period. Conclusions ERCP is a safe and effective endoscopic intervention to remove residual choledocholithiasis after choledocholithotomy T-tube Drainage without the condition of T-tube sinus tract restriction.

Abstract The aim of this study was to investigate the prevalence, correlation, and differences of C-shaped root canals (CSRCs) morphology in permanent mandibular premolars and molars in Eastern Chinese individuals using cone-beam computed tomography (CBCT). A total of 8000 mandibular first premolars (MFPs), mandibular second premolars (MSPs), mandibular first molars (MFMs), and mandibular second molars (MSMs) CBCT images from 1000 patients (692 females and 308 males) were collected. The prevalence, correlation, bilateral/unilateral presence, the morphology of CSRCs, level of canal bifurcation, gender differences, and location of radicular grooves (RGs) were evaluated. The prevalence of CSRCs in MFPs, MSPs, MFMs and MSMs were 10.25%, 0.25%, 0.55% and 47.05%, respectively. The prevalence of CSRCs in MFPs of males was higher than that in females, while the prevalence of CSRCs in MSMs of females was higher than that in males (P

Monocyte chemotactic protein-1-induced protein-1 (MCPIP-1) is highly expressed in activated immune cells and negatively regulates immune responses, while the mechanisms underlying the immunoregulation of neutrophils in acute bacterial infection and liver injury remain elusive. Here, we examined the role of MCPIP-1 in regulating neutrophil functions during acute bacterial peritonitis and liver injury. Mice with myeloid cell-specific overexpression (McpipMye-tg) or knockout (McpipΔMye) of MCPIP-1 were generated. We found that reactive oxygen species and myeloperoxidase production, formation of neutrophil extracellular traps, and migratory capacity were deficient in McpipMye-tg neutrophils but enhanced in McpipΔMye neutrophils. The recruitment of neutrophils and pathogen clearance were markedly suppressed in McpipMye-tg mice following intraperitoneal infection with Salmonella typhimurium while intensified in McpipΔMye mice. Severe acute S. typhimurium-infected peritonitis and liver injury occurred in McpipMye-tg mice but were alleviated in McpipΔMye mice. RNA sequencing, RNA-binding protein immunoprecipitation and qPCR analysis revealed that MCPIP-1 downregulated the protective functions of neutrophils via degrading the mRNA of cold inducible RNA-binding protein. Consistently, MCPIP-1 was highly expressed in neutrophils of patients with acute infectious diseases, especially in those with liver injury. Collectively, we uncover that MCPIP-1 negatively regulates the antibacterial capacities of neutrophils, leading to exacerbating severe acute bacterial peritonitis and liver injury. It may serve as a candidate target for maintaining neutrophil homeostasis to control acute infectious diseases.

The RNA methylation of N6 adenosine (m6A) plays a crucial role in various biological processes. Strong evidence reveals that the dysregulation of long non-coding RNAs (lncRNA) brings about the abnormality of downstream signaling in multiple ways, thus influencing tumor initiation and progression. Currently, it is essential to discover effective and succinct molecular biomarkers for predicting colorectal cancer (CRC) prognosis. However, the prognostic value of m6A-related lncRNAs for CRC remains unclear, especially for progression-free survival (PFS). Here, we screened 24 m6A-related lncRNAs in 622 CRC patients and identified five lncRNAs (SLCO4A1-AS1, MELTF-AS1, SH3PXD2A-AS1, H19 and PCAT6) associated with patient PFS. Compared to normal samples, their expression was up-regulated in CRC tumors from TCGA dataset, which was validated in 55 CRC patients from our in-house cohort. We established an m6A-Lnc signature for predicting patient PFS, which was an independent prognostic factor by classification analysis of clinicopathologic features. Moreover, the signature was validated in 1,077 patients from six independent datasets (GSE17538, GSE39582, GSE33113, GSE31595, GSE29621, and GSE17536), and it showed better performance than three known lncRNA signatures for predicting PFS. In summary, our study demonstrates that the m6A-Lnc signature is a promising biomarker for forecasting patient PFS in CRC.

Background: Here, we establish a prognostic signature based on glycosyltransferase-related genes (GTRGs) for head and neck squamous cell carcinoma (HNSCC) patients.Methods: The prognostic signature of GTRGs was constructed via univariate and multivariate Cox analyses after obtaining the expression patterns of GTRGs from the TCGA. A nomogram based on the signature and clinical parameters was established to predict the survival of each HNSCC patient. Potential mechanisms were explored through gene set enrichment analysis (GSEA) and immune cell infiltration, immune checkpoints, immunotherapy, and tumor mutational burden (TMB) analyses. The expression differences and prognostic efficacy of the signature were verified through the gene expression omnibus (GEO) and several online databases.Results: The prognostic signature was constructed based on five glycosyltransferases (PYGL, ALG3, EXT2, FUT2, and KDELC1) and validated in the GSE65858 dataset. The pathways enriched in the high- and low-risk groups were significantly different. The high-risk group had higher tumor purity; lower infiltration of immune cells, such as CD8+ T cells and Tregs; higher cancer-associated fibroblast (CAF) infiltration; lower immune function; and lower checkpoint expression. The signature can also be applied to distinguish whether patients benefit from immunotherapy. In addition, the high-risk group had a higher TMB and more gene mutations, including those in TP53, CSMD1, CDKN2A, and MUC17.Conclusion: We propose a prognostic signature based on glycosyltransferases for HNSCC patients that may provide potential targets and biomarkers for the precise treatment of HNSCC.

Abstract Background Circular RNA (circRNA) is increasingly attracting attention in gastric cancer (GC). Hsa_circ_0032821 (circ_0032821) has been declared to be upregulated in human GC tissues. However, the biological role of circ_0032821 remains undisclosed in GC cells. Methods Expression of circ_0032821 was measured by real-time quantitative PCR. Cell proliferation, autophagy, Epithelial-mesenchymal transition (EMT), migration, and invasion were evaluated by Cell counting kit-8 assay, western blotting or transwell assays. Expression of proliferating cell nuclear antigen (PCNA), Matrix metalloproteinase 2 (MMP2), MMP9, Light chain 3 (LC3), p62, total and phosphorylated Extracellular signal-regulated kinase 1/2 (ERK1/2) and Mitogen-activated protein kinase’s kinase 1 (MEK1) was evaluated by western blotting. Xenograft tumor model was established to measure tumor growth in vivo. Results Circ_0032821 was significantly upregulated in human GC tumors and cells. Moreover, circ_0032821 might be a biomarker for the advanced Tumor node metastasis (TNM) stage, lymphoid node metastasis and poor prognosis in gastric cancer. Knockdown of circ_0032821 by transfection induced decrease of cell proliferation, EMT, migration and invasion, but increase of autophagy of AGS and HGC-27 cells in vitro, as well as induced tumor growth inhibition in vivo. Besides, overexpression of circ_0032821 by transfection functioned the opposite effects in human GC cells. Mechanically, the MEK1/ERK1/2 signaling pathway was activated when circ_0032821 upregulation, whereas inhibited when circ_0032821 silencing. Conclusion Circ_0032821 expression induced cell proliferation, EMT, migration, invasion, and autophagy inhibition in human GC cells in vitro and in vivo through activating MEK1/ERK1/2 signaling pathway, suggesting circ_0032821 as an oncogenic role in GC.

In order to analyze the primary sources of air pollutants in Chang-Zhu-Tan region, this article selected the environmental monitoring data and meteorological data in the winter of 2019 to calculate the backward airflow trajectories with the Chang-Zhu-Tan region as the starting point by using the backward trajectory model. Combined with the ground concentration monitoring data, cluster analysis, potential source contribution factor (PSCF) analysis, and concentration weighted trajectory (CWT) analysis were carried out to determine the pollutant transportation paths and sources of the potential source area. The results show that air mass transportation mainly comes from three directions: northwest, northeast, and southwest China. The airflow in northwest China moves faster and cleaner, while the airflow from the northeast and southwest moves slowly and carries a high concentration of pollutants. PSCF and CWT analyses show that the critical potential sources are mainly located in this area and some cities next to the study area. This study has important practical significance for the environmental research of Chang-Zhu-Tan region and can provide theoretical reference for regional joint prevention and control of air pollution.

Both tumour-infiltrating immune cells and inflammation-related genes that can mediate immune infiltration contribute to the initiation and prognosis of patients with colon cancer. In this study, we developed a method to predict the survival outcomes among colon cancer patients and direct immunotherapy and chemotherapy. We obtained patient data from The Cancer Genome Atlas (TCGA) and captured inflammation-related genes from the GeneCards database. The package “ConsensusClusterPlus” was used to generate molecular subtypes based on inflammation-related genes obtained by differential expression analysis and univariate Cox analysis. A prognostic signature including four genes (PLCG2, TIMP1, BDNF and IL13) was also constructed and was an independent prognostic factor. Cluster 2 and higher risk scores meant worse overall survival and higher expression of human leukocyte antigen and immune checkpoints. Immune cell infiltration calculated by the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumour immune dysfunction and exclusion (TIDE), and tumour stemness indices (TSIs) were also compared on the basis of inflammation-related molecular subtypes and the risk signature. In addition, analyses of stratification, somatic mutation, nomogram construction, chemotherapeutic response prediction and small-molecule drug prediction were performed based on the risk signature. We finally used qRT–PCR to detect the expression levels of four genes in colon cancer cell lines and obtained results consistent with the prediction. Our findings demonstrated a four-gene prognostic signature that could be useful for prognostication in colon cancer patients and designing personalized treatments, which could provide new versions of personalized management for these patients.

In forming of AA7075 tee valve by multi-direction loading, continuous dynamic recrystallization (CDRX) will occur and significantly affect the final microstructure and performance of formed parts. In this paper, the developed physically-based internal state variable model for CDRX and finite element (FE) simulation were used to investigate the influence law of forming parameters (deformation temperature, punch fillet radius, friction factor, and the loading speed of punch) on CDRX in the intersecting region (complex deformation and possible weak zone) of the formed tee valve. By considering the grain size and its distributing uniformity in the intersecting region, the reasonable forming parameters were obtained, under which, the evolution behavior and law of the dislocation density, subgrain size, average misorientation of subgrain boundary and average grain size were revealed. The results can provide a guide for the quick prediction of CDRX and selection of the reasonable forming parameters for multi-direction loading forming of tee valves. Keywords: Tee valve, Continuous dynamic recrystallization, Internal state variable method, Finite element analysis

The cooling processes of hot working for TA15 titanium alloy are highly nonlinear, during which non-isothermal and non-isokinetic phase transformations often occur leading to the changes in the microstructures and mechanical properties. The existing phase transformation models, that are established based on isothermal transformations, are either difficult to reflect the real transformation process or complicated for use. Therefore, in this paper a succinct model suitable for the transformations at any cooling path was developed by separating the transformation process into a series of linear cooling steps. First, the transformation behaviors during linear cooling processes were studied by thermal expansion experiments, and then a kinetic model of the transformations at constant cooling rates was developed based on the JMAK law. Second, the additivity of the transformations during linear cooling processes was proved, and therefore the additivity rule was extended to calculate the incubation period of the transformation during non-linear cooling process. Finally, based on the crystallization model built by T. Ozawa, the new transformation model was established, and its reliability was proved by experiments.

Abstract The use of peripherally inserted central catheters (PICCs) is increasing rapidly worldwide. A number of patient-related, clinical-related and device-related characteristics might be risk factors for PICC-related thrombosis. We retrospectively reviewed a database of 320 consecutive patients who underwent PICC insertion between December 2014 and December 2015 at the First Affiliated Hospital of Xi’an Jiaotong University to explore the potential associations between risk factors and PICC-associated thrombosis. A novel nomogram for predicting risk was developed based on the data. The nomogram prediction model included ten risk factors that were derived from different relevant estimates. The nomogram prediction model showed good discriminatory power (Harrell’s C-index, 0.709) and a high degree of similarity to actual thrombosis occurring after calibration. Furthermore, principal component analysis was performed to identify the factors that most influence PICC-related thrombosis. Our novel nomogram thrombosis risk prediction model was accurate in predicting PICC-related thrombosis. Karnofsky performance scores, D-dimer and blood platelet levels and previous chemotherapy were principal components. Our findings might help clinicians predict thrombosis risk in individual patients, select proper therapeutic strategies and optimize the timing of anticoagulation therapy.

Abstract Forests contain one of the world’s largest carbon (C) pools and represent opportunities for cost-effective climate change mitigation through programmes such as the United Nations-led “Reducing Emissions from Deforestation and Forest Degradation” Programme (REDD). Generic estimates for the conversion of forest biomass into C stock are not sufficiently accurate for assessing the utility of harvesting forest to offset carbon dioxide emissions, currently under consideration by the REDD Programme. We examined the variation in C concentration among tree species and tree functional types (classified based on leaf morphological and phenological traits) in a subtropical forest and evaluated the effects of these variations on stand-level estimations of C stock. This study was conducted in the Paiyashan Forest State Farm and the Dashanchong Forest Park, Hunan Province, China. C concentrations differed significantly among tree species (P

Neutrophils have been found to play an important role in the pathogenesis of inflammatory bowel disease (IBD), and anti-TNF-α mAb (i.e., infliximab) therapy is demonstrated to be effective in the induction of clinical remission and mucosal healing in these patients. However, how anti-TNF-α mAb regulates the functions of neutrophils is still unknown. Herein, we found that anti-TNF-α therapy significantly downregulated infiltration of neutrophils in inflamed mucosa of IBD patients. Importantly, anti-TNF-α mAb could inhibit neutrophils to produce proinflammatory mediators, such as ROS, calprotectin, IL-8, IL-6, and TNF-α. These data indicate that TNF-α plays a critical role in the induction of mucosal inflammatory response, and that blockade of TNF-α modulates intestinal homeostasis through balancing immune responses of neutrophils.

The AP2/ERF transcription factor family, one of the largest families unique to plants, performs a significant role in terms of regulation of growth and development, and responses to biotic and abiotic stresses. Moso bamboo (Phyllostachys edulis) is a fast-growing non-timber forest species with the highest ecological, economic and social values of all bamboos in Asia. The draft genome of moso bamboo and the available genomes of other plants provide great opportunities to research global information on the AP2/ERF family in moso bamboo. In total, 116 AP2/ERF transcription factors were identified in moso bamboo. The phylogeny analyses indicated that the 116 AP2/ERF genes could be divided into three subfamilies: AP2, RAV and ERF; and the ERF subfamily genes were divided into 11 groups. The gene structures, exons/introns and conserved motifs of the PeAP2/ERF genes were analyzed. Analysis of the evolutionary patterns and divergence showed the PeAP2/ERF genes underwent a large-scale event around 15 million years ago (MYA) and the division time of AP2/ERF family genes between rice and moso bamboo was 15-23 MYA. We surveyed the putative promoter regions of the PeDREBs and showed that largely stress-related cis-elements existed in these genes. Further analysis of expression patterns of PeDREBs revealed that the most were strongly induced by drought, low-temperature and/or high salinity stresses in roots and, in contrast, most PeDREB genes had negative functions in leaves under the same respective stresses. In this study there were two main interesting points: there were fewer members of the PeDREB subfamily in moso bamboo than in other plants and there were differences in DREB gene expression profiles between leaves and roots triggered in response to abiotic stress. The information produced from this study may be valuable in overcoming challenges in cultivating moso bamboo.

Background. T393C polymorphism in the gene GNAS1, which encodes the G-protein alpha s subunit (Gαs) of heterotrimeric G protein, is significantly associated with the clinical outcome of patients suffering from several cancers. However, studies on the role and protein expression of Gαs subunit in prostate cancer were still unavailable. Methods. The immunohistochemical staining was used to assess Gαs expression through tissue microarray procedure of 56 metastatic PCas, 291 localized PCas, and 67 benign hyperplasia (BPH). Gαs expression was semiquantitatively scored and evaluated the correlation with pathologic parameters and biochemical recurrence of prostate-specific antigen (PSA). Results. Gαs expression was localized in nuclear and cytoplasm in prostate cancer cells and downregulated in metastatic PCa compared to localized PCa and BPH (P

A rapid and sensitive method for determining aesculin of Cortex fraxini in rat was developed using high-performance liquid chromatography (HPLC) quadrupole time-of-flight (QTOF) tandem mass (MS/MS). Rat plasma was pretreated by fourfold methanol to remove plasma proteins. Chromatographic separation was performed on a reverse phase column. A tandem mass spectrometric detection with an electrospray ionization (ESI) interface was achieved using collision-induced dissociation (CID) under positive ionization mode. The MS/MS patterns monitored were m/z 341.2716 → m/z 179.1043 for aesculin and m/z 248.3025 → m/z 120.9130 for tinidazole (internal standard). The linear range was calculated to be 10.0–1500.0 ng/mL with a detection limit of 2.0 ng/mL. The inter- and intraday accuracy and precision were within ±7.0%. Pharmacokinetic study showed that aesculin was confirmed to be a one-compartment open model. The method is believed to have good linear range, high sensitivity and recoveries, and superior analytical efficiency. It will probably be an alternative for pharmacokinetic study of aesculin.

TA15 Ti-alloy is widely used to form key load-bearing components in the aerospace field, where excellent service performance is needed. Near-β forging technology provides an attractive way to form these complicated Ti-alloy components but subsequent heat treatment has a great impact on the final microstructure and mechanical properties. Therefore evaluation and determination of the heat treatment route is of particular significance. In this paper, for the near-β forged TA15 alloy, the formation and evolution of microstructures under different subsequent heat treatment routes (annealing, solution and aging, toughening and strengthening) were studied and the cooling mode after forging was also considered. Then, the type and characteristics of the obtained microstructures were discussed through quantitative metallographic analysis. The corresponding mechanical properties (tensile, impact toughness, and fracture toughness) and effects of microstructural characteristics were investigated. Finally, for a required microstructure and performance a reasonable heat treatment route was recommended. The work is of importance for the application and development of near-β forging technology.