Wnt/ß-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target.

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and one of the leading causes of cancer-related deaths worldwide. The Wnt/ß-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/ß-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/ß-Catenin signaling pathway's function and its therapeutic implications in HCC.

Corrigendum: CCDC25 may be a potential diagnostic and prognostic marker of hepatocellular carcinoma: Results from microarray analysis.

[This corrects the article DOI: 10.3389/fsurg.2022.878648.].

Effects of levels of methionine supplementations in forms of L- or DL-methionine on the performance, intestinal development, immune response, and antioxidant system in broilers challenged with Eimeria spp.

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.

High expression of TMEM200A is associated with a poor prognosis and immune infiltration in gastric cancer.

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).

Current Status of Lymphangiogenesis: Molecular Mechanism, Immune Tolerance, and Application Prospect.

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.

CCDC25 may be a potential diagnostic and prognostic marker of hepatocellular carcinoma: Results from microarray analysis.

Background: Hepatocellular 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. Methods: The 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. Results: CCDC25 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. Conclusions: CCDC25 may be a potential diagnostic and prognostic marker for HCC and is associated with immune infiltration and ferroptosis.

Effects of Clostridium butyricum on Growth Performance, Gut Microbiota and Intestinal Barrier Function of Broilers.

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-1ß (IL-1ß) 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-1ß 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.

Selective Esophagogastric Devascularization in the Modified Sugiura Procedure for Patients with Cirrhotic Hemorrhagic Portal Hypertension: A Randomized Controlled Trial.

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.

Impact of Radiographic Bronchiectasis in COPD.

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.

Real-Time Elastography in the diagnosis of prostate cancer: a systematic review.

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.

Elective Splenectomy Combined with Modified Hassab's or Sugiura Procedure for Portal Hypertension in Decompensated Cirrhosis.

Objective: Portal hypertension is a major complication of decompensated cirrhosis. In China, modified Hassab's and Sugiura procedure are the two major methods of nonshunting surgery. This study aims to compare the efficacy and safety of the two procedures for portal hypertension. Method: Between January 1994 and December 2009, 172 elective patients diagnosed with decompensated cirrhosis with significant hypersplenism adopted elective splenectomy for hypersplenism, and also modified Hassab's (n = 91) or Sugiura (n = 81) procedure was additionally performed to reduce the risk of variceal bleeding. Postoperative mortality and morbidity data were collected, and a retrospectively comparative analysis was conducted. Results: All of the patients were treated successfully without death during operation, and no variceal bleeding occurred during hospitalization. There were 4 (4.4%) deaths in Hassab's group and 3 (3.7%) deaths in Sugiura group postoperatively (P > 0.05). During follow-up, the survival rate was 90.2%, 82.42%, and 71.43% in Hassab's group and 96.29%, 81.48%, and 75.31% in Sugiura group in 1, 3, and 5 years (P > 0.05). There were 22/71 and 12/63 patients in each groups who suffered no deadly variceal bleeding (P = 0.11). Bleeding related death and no bleeding related death occurred in 7/23 and 3/13 patients in each group (P = 0.26 and 0.14, respectively). Conclusion: Elective splenectomy combined with modified Sugiura procedure seemed to be associated with a reduced trend of no deadly variceal bleeding compared with Hassab's procedure. As statistical significance was not found, further large scale and prospective study was warranted.

PRISMA-efficacy and safety of lixisenatide for type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to systematically evaluate the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus. METHODS: PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, Google, Web of Science and the Chinese Science Citation Database were searched up to March 2018. Randomized controlled trials determining the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus were eligible for inclusion. Two authors independently extracted the data in a prespecified Microsoft Excel spreadsheet. A meta-analysis was performed using Review Manager 5.3 software. Weighted mean difference (WMD) and relative risk (RR) together with their corresponding 95% confidence intervals (CIs) were estimated, and only the random effects model was used in order to achieve a more conservative estimate of the efficacy and safety. RESULTS: Fourteen multicenter randomized controlled trials involving 11,947 patients were eligible for inclusion. Compared to placebo, lixisenatide could more significantly reduce the level of HbA1c (WMD=-0.44; 95% confidence interval [CI] [-0.55,-0.33]), and a higher proportion of lixisenatide-treated patients achieved the HbA1c level of < 7.0% (RR = 1.89, 95% CI [1.75-2.03]) and < 6.5% (RR = 3.03, 95% CI [2.54-3.63]) than the placebo-treated patients. Lixisenatide was also associated with a significant reduction in fasting plasma glucose and 2-hour postprandial plasma glucose levels. The risks for any adverse events, gastrointestinal adverse events, and symptomatic hypoglycemia significantly increased in the lixisenatide-treatedment group compared to those in the placebo group. However, lixisenatideit did not increase the risks of serious adverse events, death, or severe hypoglycemia. CONCLUSIONS: Lixisenatide was more effective than placebo in patients with type 2 diabetes mellitus, and the mild-to-moderate adverse events were found to be tolerated during the follow-up.

Efficacy and Safety of Endoscopic Intralesional Triamcinolone Injection for Benign Esophageal Strictures.

OBJECTIVES: To evaluate the efficacy and safety of endoscopic intralesional triamcinolone injection (ITI) for benign esophageal strictures combined with endoscopic dilation (ED). METHODS: Online databases including MEDLINE, EMBASE, the Cochrane Library, and Web of Science were comprehensively searched for prospective randomized control trials (RCTs) between 1966 and March 2018. A meta-analysis was conducted according to the methods recommended by the Cochrane Collaboration. RESULTS: Six RCTs consisting of 176 patients were selected. Meta-analysis results showed that additional ITI had a significant advantage in terms of stricture rate and required ED sessions. Surgery-related and non-surgery-related strictures showed similar results. Additional ITI was not associated with significantly increased risk of complications. CONCLUSIONS: Our meta-analysis showed that additional ITI therapy was supposed to be effective and safe for benign esophageal strictures as it reduced the stricture rate and required ED sessions. However, more RCTs are necessary to support these findings.

Effects of alpha-lipoic acid supplementation on growth performance, antioxidant capacity and biochemical parameters for ammonia-exposed broilers.

In order to estimate the effect of alpha-lipoic acid (LA) supplementation on relieving ammonia stress of broilers, 180 22-day-old male broilers were assigned to three groups, six replicates in each group and 10 birds per replicate. The three groups were: (1) a control group without ammonia stress; (2) exposure to 70 ppm atmospheric ammonia (AM); (3) exposure to 70 ppm atmospheric ammonia and administration of 300 mg/kg LA (AM + LA). The experimental period was 3 weeks. Results showed that average daily weight gain was increased and feed conversion ratio was decreased in the AM + LA group, compared with the AM group (P < 0.05). Total superoxide dismutase and glutathione peroxidase activities in serum, and glutathione content in liver were higher in the AM + LA group than that in the AM group (P < 0.05); however, serum malondialdehyde content was decreased by LA addition (P < 0.05). Additionally, serum glutamic-pyruvic transaminase, creatine kinase and lactate dehydrogenase activities were reduced and albumin level was increased by LA addition (P < 0.05). In conclusion, LA addition could relieve ammonia stress to restore broiler production performance to normal levels.

Hemodynamics and vasoactive substance levels during renal congestion that occurs in the anhepatic phase of liver transplantation.

AIM: To explore hemodynamics and vasoactive substance levels during renal vein congestion that occurs in the anhepatic phase of liver transplantation. METHODS: New Zealand rabbits received ligation of the hepatic pedicle, supra-hepatic vena cava and infra-hepatic vena cava [anhepatic phase group (APH); n = 8], the renal veins (RVL; n = 8), renal veins and hepatic pedicle [with the inferior vena cava left open) (RVHP; n = 8)], or a sham operation (SOP; n = 8). Hemodynamic parameters (systolic, diastolic, and mean arterial blood pressures) and the levels of serum bradykinin (BK) and angiotensin II (ANGII) were measured at baseline (0 min), and 10 min, 20 min, 30 min, and 45 min after the surgery. Correlation analyses were performed to evaluate the associations between hemodynamic parameters and levels of vasoactive substances. RESULTS: All experimental groups (APH, RVL, and RVHP) showed significant decreases in hemodynamic parameters (systolic, diastolic, and mean arterial blood pressures) compared to baseline levels, as well as compared to the SOP controls (P < 0.05 for all). In contrast, BK levels were significantly increased compared to baseline in the APH, RVL, and RVHP groups at all time points measured (P < 0.05 for all), whereas no change was observed in the SOP controls. There were no significant differences among the experimental groups for any measure at any time point. Further analyses revealed that systolic, diastolic, and mean arterial blood pressures were all negatively correlated with BK levels, and positively correlated with ANGII levels in the APH, RVL, and RVHP groups (P < 0.05 for all). CONCLUSION: In the anhepatic phase of orthotopic liver transplantation, renal vein congestion significantly impacts hemodynamic parameters, which correlate with serum BK and ANGII levels.

Effect of GP73 silencing on proliferation and apoptosis in hepatocellular cancer.

AIM: To investigate the roles of Golgi protein (GP) 73 in the regulation of cell proliferation and apoptosis. METHODS: Stealth RNAi targeting GP73 gene sequence was used to silence its expression in Hep G2 cells and Bel7402 cells. Stealth RNAi effects were assessed by reverse transcriptase polymerase chain reaction and ELISA. Cell proliferation assay and cell cycle analysis were assessed by MTT assay and flow cytometry. Apoptosis was assessed by flow cytometry and transmission electron microscopy. Apoptosis-related proteins were assessed by western immunoblot analysis. RESULTS: Stealth RNAi targeting GP73 gene sequence markedly reduced the expression of GP73 gene. The reduction of GP73 in Hep G2 cells and Bel7402 cells inhibited cell proliferation and induced apoptosis, however, terminal apoptosis occurred in Hep G2 cells, but early apoptosis occurred in Bel7402 cells. Reduced expression of GP73 gene might lead to a reduction in Bcl-2/Bax ratio, an increase in cytochrome c, but a reduction in capase-3. CONCLUSION: GP73 might play an important role in proliferation and apoptosis in hepatocellular carcinoma cells.

Chemotherapy for patients with gastric cancer after complete resection: a network meta-analysis.

AIM: To conduct a network meta-analysis to evaluate the effectiveness of different chemotherapy regimens for patients with gastric cancer. METHODS: PubMed (1966-2011.12), the Cochrane Library (2011 Issue 2) and EMBASE (1974-2011.12) were searched with the terms "gastric cancer" and "chemotherapy", as well as the medical subject headings. References from relevant articles and conferences were also included. Patients who had previous gastric surgery, radiation before or after surgery or chemotherapy before surgery were excluded. In this study, only randomized controlled trials (RCTs) were considered, and the end-point was the overall mortality. Direct comparisons were performed using traditional meta-analysis whereas indirect comparisons were performed using network meta-analysis. RESULTS: In total, 31 RCTs with 7120 patients were included. Five chemotherapy regimens, fluorouracil (FU) + BCNU, FU + methyl-CCNU (mCCNU), FU + cisplatin, FU + anthracyclines and FU + mitomycin c (MMC) + cytarabine (Ara-c), were found to be less beneficial in terms of overall mortality. In contrast, four chemotherapy regimens were effective for the patients after surgery, including FU + MMC + adriamycin (FMA), FU + MMC (FM), Tegafur and MMC, There was no significant difference in terms of overall mortality among these regimens. The evidence for the FM regimen and MMC regimen was poor. Additionally, the FMA regimen, which includes a variety of chemotherapy drugs and causes many side effects, was not better than the Tegafur regimen. CONCLUSION: Although the four chemotherapy regimens were effective in patients with gastric cancer after surgery and the overall mortality revealed no significant difference among them in the network meta-analysis, thorough analysis of the results recommends Tegafur as the first-line adjuvant chemotherapy regimen for patients after complete resection.

The effects of bariatric procedures versus medical therapy for obese patients with type 2 diabetes: meta-analysis of randomized controlled trials.

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.