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Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and one of the leading causes of cancer-related deaths worldwide. The Wnt/β-Catenin signaling pathway is a highly conserved pathway involved in several biological processes, including the improper regulation that leads to the tumorigenesis and progression of cancer. New studies have found that abnormal activation of the Wnt/β-Catenin signaling pathway is a major cause of HCC tumorigenesis, progression, and resistance to therapy. New perspectives and approaches to treating HCC will arise from understanding this pathway. This article offers a thorough analysis of the Wnt/β-Catenin signaling pathway’s function and its therapeutic implications in HCC.

ABSTRACT: The study was conducted to investigate the effects of 2 isoforms of methionine on growth performance and intestinal health induced by methionine (Met) deficiency and Eimeria infection in broilers. A total of 720 one-day old male chicks (Cobb500) were randomly allocated to 10 groups in a 2 × 5 factorial arrangement (6 reps/group, 12 birds/cage) with diets and Eimeria challenge as the main factors. Hundred percent DL-Met, 100% L-Met, 80% DL-Met, and 80% L-Met diets were formulated to meet approximately 100 or 80% of the total sulfur amino acid (TSAA) requirement with DL-Met or L-Met as Met supplementation sources. The 60% TSAA basal diet (60% Met) was formulated without Met supplementation. At d14, the challenge groups were gavaged with mixed Eimeria spp. Growth performance was recorded on d7, 14, 20 (6-day postinfection [DPI]), and 26 (12 DPI). The gut permeability was measured on 5 and 11 DPI. Antioxidant status and gene expression of immune cytokines and tight junction proteins were measured on 6 and 12 DPI. Data were analyzed by 1-way and 2-way ANOVA before and after the challenge, respectively. Orthogonal polynomial contrasts were used for post hoc comparison. Overall, the Eimeria challenge and 60% Met diet significantly reduced growth performance, antioxidant status, and mRNA expression of tight junction genes and immune cytokines. For other Met treatments, the L-Met groups had significantly higher BWG and lower FCR than the DL-Met group from d 1 to 20. The L-Met groups had less gut permeability than the DL-Met groups on 5 DPI. Compared to the 80% Met groups, the 100% Met groups reduced gut permeability. At 6 DPI, the 80% Met groups showed higher ZO1 expression than the 100% Met groups. The challenge groups had higher Muc2 expression and GSH/GSSG compared to the nonchallenge groups, and SOD activity was lower in the L-Met groups compared to the DL-Met groups at 6 DPI. The 100% Met groups had higher GPx activity than the 80% Met groups at 12 DPI. In conclusion, during coccidiosis, the 100% Met groups had better gut integrity and antioxidant status. Met supplementation in the form of L-Met improved growth performance in the starter phase and gut permeability in the challenge phase.

Background: Gastric cancer (GC) is one of the global malignant tumors with high incidence and poor prognosis. Exploring new GC molecular markers is important to improve GC prognosis. Transmembrane protein 200A (TMEM200A) is a member of the family of transmembrane proteins (TMEM). This study is the first to investigate the potential function of TMEM200A and its relationship with immune infiltration in GC.Methods: The differential expression of TMEM200A was determined through the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The receiver operating characteristic (ROC) curve was drawn to assess the diagnostic value of TMEM200A for GC. The relationship between TMEM200A and the clinical characteristics of patients with GC was investigated using the Wilcoxon test and the Kruskal-Wallis test. The effect of TMEM200A on overall survival (OS) was identified using the Kaplan-Meier method, the Log-rank test, the univariate/multivariate Cox regression analysis, and the nomogram prediction model. The co-expressed genes and gene set enrichment analysis (GSEA) were used to explore the potential biological functions of TMEM200A. We used the Tumor Immune Estimation Resource (TIMER) database and the ssGSEA algorithm to estimate the relationship between TMEM200A and immune cell infiltration. Furthermore, we investigated the correlation of TMEM200A with immune checkpoint/immune cell surface markers using the TCGA-STAD data set. Finally, we identified prognosis-related methylation sites in TMEM200A using MethSurv.Results: TMEM200A was highly expressed in GC tissues. TMEM200A had a good diagnostic value for GC. High expression of TMEM200A may shorten the OS of GC patients and may be an independent risk factor for OS in GC patients. TMEM200A participates in the construction of a predictive model with a good predictive effect on the survival rate of GC patients at 1, 3, and 5 years. Co-expressed genes and GSEA indicated that TMEM200A may be an adhesion molecule closely associated with tumor invasion and metastasis. In addition, TMEM200A may be significantly associated with immune cell infiltration and immune checkpoint expression. We also found that TMEM200A contains three methylation sites associated with a poor prognosis.Conclusion: Upregulated TMEM200A may be a promising prognostic marker for GC and is closely associated with the tumor microenvironment (TME).

BackgroundHepatocellular carcinoma (HCC) is a tumor with a high recurrence rate, poor prognosis, and rapid progression. Therefore, it is necessary to find a novel biomarker for HCC. Coiled-coil domain containing 25 (CCDC25) has been identified as a target molecule that mediates liver metastasis in colon cancer. However, the molecular mechanisms of CCDC25 in HCC are unknown. This study aimed to explore the role of CCDC25 in HCC.MethodsThe expression of CCDC25 in HCC was identified through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Receiver operating characteristic curve (ROC) curves were drawn to evaluate the diagnostic value of CCDC25 for HCC. The effect of CCDC25 on the prognosis of HCC was analyzed by using the Kaplan–Meier plotter. Co-expressed genes and Gene Set Enrichment Analysis (GSEA) were used to explore the related functions and regulatory signaling pathways of CCDC25. Moreover, we employed the Tumor Immune Estimation Resource (TIMER) database and CIBERSORT algorithm to investigate the relationship between CCDC25 and the tumor immune microenvironment (TME) in HCC. Meanwhile, the effect of CCDC25 on the sensitivity of HCC patients to chemotherapy drugs was evaluated. Finally, we explored the prognostic methylation sites of CCDC25 using the MethSurv database.ResultsCCDC25 expression was low in HCC. Low CCDC25 expression was significantly associated with poor overall survival of HCC and may be comparable to the ability of AFP to diagnose HCC. Dysregulation of glucose metabolism, fatty acid metabolism, amino acid metabolism, ubiquitination modification, and apoptosis inhibition caused by CCDC25 downregulation may be the causes and results of HCC. In addition, CCDC25 was positively correlated with the infiltration level of various adaptive antitumor immune cells. The levels of immune cell infiltration and immune checkpoint expression were lower in the samples with high CCDC25 expression. What is more, we found that downregulated CCDC25 may increase the sensitivity or resistance of HCC patients to multiple drugs, including sorafenib. We also identified a methylation site for CCDC25, which may be responsible for poor prognosis and low CCDC25 expression in HCC patients. Finally, CCDC25 may be associated with HCC ferroptosis.ConclusionsCCDC25 may be a potential diagnostic and prognostic marker for HCC and is associated with immune infiltration and ferroptosis.

The lymphatic system is a channel for fluid transport and cell migration, but it has always been controversial in promoting and suppressing cancer. VEGFC/VEGFR3 signaling has long been recognized as a major molecular driver of lymphangiogenesis. However, many studies have shown that the neural network of lymphatic signaling is complex. Lymphatic vessels have been found to play an essential role in the immune regulation of tumor metastasis and cardiac repair. This review describes the effects of lipid metabolism, extracellular vesicles, and flow shear forces on lymphangiogenesis. Moreover, the pro-tumor immune tolerance function of lymphatic vessels is discussed, and the tasks of meningeal lymphatic vessels and cardiac lymphatic vessels in diseases are further discussed. Finally, the value of conversion therapy targeting the lymphatic system is introduced from the perspective of immunotherapy and pro-lymphatic biomaterials for lymphangiogenesis.

The objective of present study was to investigate the effects of alpha-lipoic acid (ALA) dietary supplementation on the behavior, physiological and oxidant stress indicators, and bone quality in broilers under high stocking density (HSD) stress. A total of one thousand eight hundred 22-day-old Arbor Acres male broiler chicks were randomly allocated to 18 pens (2.97 × 2.03 m) in 3 groups: 14 birds/m2 (NSD, normal stocking density) or 18 birds/m2 (HSD) or 18 birds/m2 plus 300 mg/kg ALA dietary supplement (HSD + ALA, high stocking density + alpha-lipoic acid). Each treatment had 6 replicates, and the experiment lasted 3 wk. The HSD group was significantly lower than the NSD group (P 0.05) in the standing and preening behavior, alkaline phosphatase activity, PTH concentration, H/L ratio, CAT, T-AOC, MDA, SOD, and GSH-Px. These results indicate that the increase of stocking density lowered the bone quality, increased the physiological and oxidative stress indicators, and modified the behavior of broilers, whereas ALA dietary supplementation could counteract the reduction in the performance and physiological responses of broilers under high-density environmental stress.

This study was conducted to evaluate the effects of Clostridium butyricum dietary supplementation on the growth, antioxidant, immune response, gut microbiota, and intestinal barrier function of broilers under high stocking density (HSD) stress. A total of 324 1-day-old Arbor Acres male broilers were randomly assigned to three treatments with six replicates, each replicate including 18 chickens (18 birds/m2). The experiment lasted 6 weeks. The three treatments were basal diet (control, CON), basal diet supplemented with 1 × 109 colony forming units (cfu)/kg C. butyricum (CB), and basal diet supplemented with 10 mg/kg virginiamycin (antibiotic, ANT). The results showed that the body weight (BW) and average daily gain (ADG) of broilers in the CB group were significantly higher than those in the CON group in three periods (p < 0.05). The total antioxidant capacity (T-AOC) and the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in serum of the CB group were significantly increased compared with those in the CON and ANT groups at 42 days (p < 0.05). At 42 days, the serum immunoglobulin M (IgM) and immunoglobulin G (IgG) levels of the CB group were significantly higher than those of the CON group. Compared with the CON group, interleukin-1β (IL-1β) in the CB group was significantly decreased in the starter and grower stages (p < 0.05), but there was no significant difference between the two treatment groups (p > 0.05). C. butyricum significantly decreased the high stocking density-induced expression levels of IL-1β and tumor necrosis factor-α (TNF-α) in the ileum of broilers at different stages. Additionally, C. butyricum could increase the expressions of claudin-1 and zonula occludens-1 (ZO-1) in intestinal tissue. Moreover, C. butyricum significantly increased the Sobs and Shannon indices in the CB group compared with the ANT group (p < 0.05), while the Ace index in the CB group was significantly higher than that of the CON group (p < 0.05). Furthermore, by using 16S rRNA gene sequencing, the proportion of Bacteroides in the CB group was increased compared to those in the CON and ANT groups at the genus level. In conclusion, C. butyricum supplemented into feed could improve the growth performance and feed utilization of broilers by promoting immune and intestinal barrier function and benefiting the cecal microflora.

Objective The study was conducted to evaluate the effect of stocking density and alpha-lipoic acid (ALA) on the growth performance, feed utilization, carcass traits, antioxidative ability and immune response of broilers. Methods A total of 1,530 22-day-old male broilers (Arbor Acres) with comparable body weights (731.92±5.26) were placed into 18 cages (2.46×2.02 m) in groups of 75 birds (15 birds/m2, 37.5 kg/m2; low stocking density [LD]), 90 birds (18 birds/m2, 45.0 kg/m2; high stocking density [HD]) and 90 birds with 300 mg/kg ALA added to the basal diet (18 birds/m2, 45.0 kg/m2; HD+ALA, high stocking density+α-lipoic acid); each treatment was represented by 6 replicates. The experimental period was 3 weeks. Results The results showed that the high stocking density regimen resulted in a decreased growth, feed conversion ratio, carcass weight, thigh yield and bursa weight relative to body weight (p

Aim. Portal hypertension is a series of syndrome commonly seen with advanced cirrhosis, which seriously affects patient’s quality of life and survival. This study was designed to access the efficacy and safety of selective esophagogastric devascularization in the modified Sugiura procedure for patients with cirrhotic hemorrhagic portal hypertension. Methods. Sixty patients with hepatitis B cirrhotic hemorrhagic portal hypertension and meeting the inclusion criteria were selected and randomly divided by using computer into the selective modified Sugiura group (sMSP group, n = 30) and the modified Sugiura group (MSP group, n = 30). The primary endpoint measurement is the postoperative rebleeding rate. Secondary endpoint measurements included free portal venous pressure, liver Child–Pugh score, liver volume, portal vein width and blood flow velocity, survival rate, quality of life, and dysphagia as well as other complications one year postoperatively. This trial is registered with ChiCTR, number ChiCTR2000033468. Results. There was no statistically significant difference in rebleeding rates within one year after surgery between patients in the sMSP and MSP groups (χ = 0.11, p=0.73). In comparison with the MSP group, the Child–Pugh score of liver function in the sMSP group significantly increased (χ = 6.4, p=0.04) and the incidence of dysphagia was significantly reduced (χ = 6.23, p=0.01) one year after surgery. There was a statistically significant difference in the quality of life between the two groups. However, there were no statistically significant differences in free portal venous pressure (MD = −3.44, 95% CI: −7.87 to 0.98, p=0.12), postoperative liver volume (3 months: MD = -258.81, 95% CI: −723.21 to 205.57, p=0.24; 1 year: MD = −320.12, 95% CI: −438.43 to 102.78, p=0.16), postoperative portal vein width (3 months: MD = −0.06, p=0.50; 1 year: MD = 0.17, p=0.21), portal vein flow velocity (3 months: MD = 1.64, p=0.21; 1 year: MD = −1.19, p=0.57), 1-year survival rate (χ = 1.01, p=0.31), and other complications between the two groups. Conclusions. Selective esophagogastric devascularization in the modified Sugiura procedure may not lower the incidence of rebleeding in the short term based on our findings. However, it may significantly improve quality of life of patients with cirrhotic hemorrhagic portal hypertension, improve liver function, and reduce postoperative dysphagia.

BACKGROUND: COPD and bronchiectasis frequently coexist, which creates an emerging phenotype with a worse prognosis. However, the impact of bronchiectasis on the natural history of COPD has not been fully evaluated and is still controversial. This meta-analysis was performed to clarify the associations of the presence of bronchiectasis with the prognosis and quality of life of patients with COPD. METHODS: A systematic review and meta-analysis was performed following a search of medical databases, and included articles published up to April 2019. The following outcome measures were analyzed: age, sex, smoking history, body mass index, exacerbation rate, lung function, inflammatory biomarkers, albumin, colonization by potentially pathogenic microorganisms, Pseudomonas aeruginosa isolates, Haemophilus influenzae isolates, hospital admissions, and mortality. RESULTS: A total of 415,257 subjects with COPD from 18 observational studies were eligible; bronchiectasis was present in 25,929 subjects (6.24%). The coexistence of COPD and bronchiectasis occurred more often in older subjects with lower body mass index. The presence of bronchiectasis in the subjects with COPD increased the risk of daily sputum production (odds ratio [OR] 1.80, 95% CI 1.24-2.61), exacerbation (weighted mean difference [WMD] 0.72 times, 95% CI 0.59-0.85), frequent hospital admissions (WMD 0.35 times, 95% CI 0.21-0.49), and follow-up (>3 years) mortality (OR 2.26, 95% CI 0.95-5.36). The subjects with COPD and bronchiectasis showed poorer pulmonary function (FEV1/FVC: WMD -3.37%, 95% CI -5.63 to -1.11), lower albumin (Standardized mean difference [SMD] -0.17, 95% CI -0.26 to -0.08), elevated C-reactive protein (SMD 0.40, 95% CI 0.06-0.74), a greater proportion of chronic colonization by potentially pathogenic microorganisms (OR 6.65, 95% CI 4.44-9.95), and a higher isolation rate of P. aeruginosa (OR 5.13, 95% CI 4.89-5.38) or H. influenzae (OR 1.90, 95% CI 1.29-2.79) than the subjects with COPD without bronchiectasis. CONCLUSIONS: This meta-analysis confirmed the significant associations of the presence of bronchiectasis with the natural history, disease course, and outcomes in COPD. The COPD-bronchiectasis phenotype had adverse effects on subjects' health condition and prognosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: COPD and bronchiectasis frequently coexist, which creates an emerging phenotype with a worse prognosis. However, the impact of bronchiectasis on the natural history of COPD has not been fully evaluated and is still controversial. This meta-analysis was performed to clarify the associations of the presence of bronchiectasis with the prognosis and quality of life of patients with COPD. METHODS: A systematic review and meta-analysis was performed following a search of medical databases, and included articles published up to April 2019. The following outcome measures were analyzed: age, sex, smoking history, body mass index, exacerbation rate, lung function, inflammatory biomarkers, albumin, colonization by potentially pathogenic microorganisms, Pseudomonas aeruginosa isolates, Haemophilus influenzae isolates, hospital admissions, and mortality. RESULTS: A total of 415,257 subjects with COPD from 18 observational studies were eligible; bronchiectasis was present in 25,929 subjects (6.24%). The coexistence of COPD and bronchiectasis occurred more often in older subjects with lower body mass index. The presence of bronchiectasis in the subjects with COPD increased the risk of daily sputum production (odds ratio [OR] 1.80, 95% CI 1.24-2.61), exacerbation (weighted mean difference [WMD] 0.72 times, 95% CI 0.59-0.85), frequent hospital admissions (WMD 0.35 times, 95% CI 0.21-0.49), and follow-up (>3 years) mortality (OR 2.26, 95% CI 0.95-5.36). The subjects with COPD and bronchiectasis showed poorer pulmonary function (FEV1/FVC: WMD -3.37%, 95% CI -5.63 to -1.11), lower albumin (Standardized mean difference [SMD] -0.17, 95% CI -0.26 to -0.08), elevated C-reactive protein (SMD 0.40, 95% CI 0.06-0.74), a greater proportion of chronic colonization by potentially pathogenic microorganisms (OR 6.65, 95% CI 4.44- 9.95), and a higher isolation rate of P. aeruginosa (OR 5.13, 95% CI 4.89-5.38) or H. influenzae (OR 1.90, 95% CI 1.29-2.79) than the subjects with COPD without bronchiectasis. CONCLUSIONS: This meta-analysis confirmed the significant associations of the presence of bronchiectasis with the natural history, disease course, and outcomes in COPD. The COPDbronchiectasis phenotype had adverse effects on subjects' health condition and prognosis. [ABSTRACT FROM AUTHOR]

Objective. To assess the effects of bariatric surgery versus medical therapy for type 2 diabetes mellitus. Methods. The Cochrane library, PubMed, Embase, Chinese biomedical literature database, and Wanfang database up to February 2012 were searched. The literature searches strategies contained terms ("diabetes*", "surg*", and "medic*" were used), combined with the medical subject headings. Randomized controlled trails (RCTs) of frequently used bariatric surgery for obese patients with type 2 diabetes were included. Study selection, data extraction, quality assessment, and data analyses were performed according to the Cochrane standards. Results. Three randomized controlled trials (RCTs) involving 170 patients in the bariatric surgery groups and 100 patients in the medical therapy group were selected. Compared with medical therapy, bariatric surgery for type 2 diabetes can significantly decrease the levels of HbA1c, FBG, weight, triglycerides, and the dose of hypoglycemic, antihypertensive, and lipid-lowering medicine, while increasing the rate of diabetes remission (RR = 9.74,95%CI, (1.36,69.66)) and the levels of high-density lipoprotein. However, there are no statistical differences in serious adverse events between the surgical and medical groups (RR = 1.23, 95%CI, (0.80,1.87)). Conclusions. Surgical procedures were more likely to help patients achieve benefits than medical therapy alone. Further intensive RCTs of high-quality, multiple centers and long-term followup should be carried out to provide more reliable evidence. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the diagnostic accuracy of real-time elastography as a method for detecting prostate cancer.Material and Methods: Relevant studies applying real-time elastography as the diagnostic modality and biopsy as the reference standard, published by March 1, 2018 were retrieved from PubMed, EMBASE, Web of Science and Cochrane Library databases. Two independent reviewers inspected all these articles to confirm the matching of the inclusion criteria. One reviewer with methodological expertise extracted the data from the included studies. Sensitivity, specificity and diagnostic odds ratio (DOR) were used to obtain overall estimates. Randomized effect method, meta-regression and subgroup analysis were performed.Results: Twenty-four studies out of 1156 identified articles met the inclusion criteria. Three groups were set: analysisby patient (Group 1), by core (Group 2), and by image (Group 3) and subgroups set in Group 1. The pooled estimate ofreal-time elastography sensitivity/ specificity/ DOR calculated with the identical P-value 0.00. Within subgroups "Asia" and"PSA>=10 ng/ml", the pooled sensitivity, specificity and DOR were 0.83, 0.65 (p=0.01, I2=73.40%; p=0.02, I2=69.5%), 0.80, 0.82 (p=0.66, I2=0.00%; p=0.58, I2=0.00%) and 20.2, 8.67 (p=0.09, I2=54.2%; p=0.20, I2=35.5%), respectively. In these three groups, the areas under the SROC curve were 0.7417, 0.9246, and 0.6213 independently.Conclusions: Real-time elastography is a promising, reliable modality for the non-invasive diagnosis of patients with prostate cancer. The diagnostic accuracy of real-time elastography correlates tightly to the presence of higher PSA level and may help avoid unnecessary biopsy. It seems to be a useful tool in systemic biopsy. [ABSTRACT FROM AUTHOR]