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BACKGROUND: Lymph node ratio (LNR) was demonstrated to play a crucial role in the prognosis of many tumors. However, research concerning the prognostic value of LNR in postoperative gastric neuroendocrine neoplasm (NEN) patients was limited. AIM: To explore the prognostic value of LNR in postoperative gastric NEN patients and to combine LNR to develop prognostic models. METHODS: A total of 286 patients from the Surveillance, Epidemiology, and End Results database were divided into the training set and validation set at a ratio of 8:2. 92 patients from the First Affiliated Hospital of Soochow University in China were designated as a test set. Cox regression analysis was used to explore the relationship between LNR and disease-specific survival (DSS) of gastric NEN patients. Random survival forest (RSF) algorithm and Cox proportional hazards (CoxPH) analysis were applied to develop models to predict DSS respectively, and compared with the 8th edition American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging. RESULTS: Multivariate analyses indicated that LNR was an independent prognostic factor for postoperative gastric NEN patients and a higher LNR was accompanied by a higher risk of death. The RSF model exhibited the best performance in predicting DSS, with the C-index in the test set being 0.769 [95% confidence interval (CI): 0.691-0.846] outperforming the CoxPH model (0.744, 95%CI: 0.665-0.822) and the 8th edition AJCC TNM staging (0.723, 95%CI: 0.613-0.833). The calibration curves and decision curve analysis (DCA) demonstrated the RSF model had good calibration and clinical benefits. Furthermore, the RSF model could perform risk stratification and individual prognosis prediction effectively. CONCLUSION: A higher LNR indicated a lower DSS in postoperative gastric NEN patients. The RSF model outperformed the CoxPH model and the 8th edition AJCC TNM staging in the test set, showing potential in clinical practice.

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BACKGROUND: Understanding of the early immune response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infections is limited. METHODS: Ninety-eight patients with coronavirus disease 2019 (COVID-19) breakthrough infections were divided into two groups, with intervals from receiving the second dose of inactivated vaccine to the onset of illness <60 or ≥60 days. RESULTS: The median lymphocyte count and the median anti-SARS-CoV-2 spike immunoglobulin G (IgG) and immunoglobulin M (IgM) titers were higher in the <60-day interval group compared with the corresponding medians in the ≥60-day interval group (p = 0.005, p = 0.001, and p = 0.001, respectively). The median interleukin-6 (IL-6) level in the <60-day interval group was significantly lower than the median IL-6 level in the ≥60-day interval group (p < 0.001). CONCLUSIONS: Our results highlight the different anti-SARS-CoV-2 spike IgG and IgM antibody titers among patients with different intervals from receiving the second dose of inactivated vaccine to the onset of illness.

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BACKGROUND: Due to dietary patterns, the aging population, and other high-risk factors, the occurrence of pancreatic cancer (PC) has been rapidly increasing in China. AIM: To present the epidemiological trends of PC in China over the past decade and the estimated trend in 2025 and to compare the international differences in PC morbidity and mortality. METHODS: This study used a series of nationally representative data from the National Central Cancer Registry of China (NCCR), the International Agency for Research on Cancer and the Institute for Health Metrics and Evaluation databases. Age-standardized data of the PC incidence and mortality from 2006 to 2015 in China were extracted from the NCCR database. Linear regression models were used to estimate the incidence and mortality rates of PC in 2025. RESULTS: The age-standardized rates of PC in China increased from 3.65 per 100000 in 2006 to 4.31 per 100000 in 2015 and were estimated to reach up to 5.52 per 100000 in 2025. The mortality went from 3.35 per 100000 in 2006 to 3.78 per 100000 in 2015, estimated to reach up to 4.6 per 100000 in 2025. The number of new cases and deaths was low before 45 years and the peak age of onset was 85-89 years. The incidence and mortality rates in men were higher than those in women regardless of the region in China. In addition, the incidence and mortality rates in China were higher than the average level around the world. Likewise, disability-adjusted life years attributed to PC in China were 197.22 years per 100000, above the average level around the world. CONCLUSION: This study presented an increasing trend of PC in China and differences in morbidity, mortality and disability-adjusted life years between Chinese and global populations. Efforts need to be made to decrease the PC incidence and improve patient outcomes.

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BACKGROUND: Sulfation of tyrosine, yielding O-sulfotyrosine, is a common but fixed post-translational modification in eukaryotes. Patients with increased circulating O-sulfotyrosine levels experience a faster decline in renal function with progression to end-stage renal disease (ESRD). In the present study, we measured serum O-sulfotyrosine levels in individuals with chronic kidney disease (CKD) and acute kidney injury (AKI) to explore its ability to differentiate AKI from CKD. METHODS: A total of 135 patients (20 with AKI and 115 with CKD) were recruited prospectively for liquid chromatography-mass spectrometry assessment of circulating O-sulfotyrosine. We also studied C57BL/6 mice with CKD after 5/6 nephrectomy (Nx). Blood samples were drawn from the tail vein on Day 1, 3, 5, 7, 14, 30, 60, and 90 after CKD. Serum separation and characterization of creatinine, blood urea nitrogen (BUN), and O-sulfotyrosine was performed. Thus, the time-concentration curves of the O-sulfotyrosine level demonstrate the variation of kidney dysfunction. RESULTS: The serum levels of O-sulfotyrosine were markedly increased in patients with CKD compared with AKI. Median O-sulfotyrosine levels in CKD patients versus AKI, respectively, were as follows:243.61 ng/mL(interquartile range [IQR] = 171.90-553.86) versus 126.55 ng/mL (IQR = 48.19-185.03, P = 0.004). In patients with CKD, O-sulfotyrosine levels were positively correlated with creatinine, BUN, and Cystatin C (r = 0.63, P < 0.001; r = 0.49, P < 0.001; r = 0.61, P < 0.001, respectively) by the multivariate linear regression analysis (ß = 0.71, P < 0.001; ß = 0.40, P = 0.002; ß = 0.73, P < 0.001, respectively). However, this association was not statistically significant in patients with AKI (r = - 0.17, P = 0.472; r = 0.11, P = 0.655; r = 0.09, P = 0.716, respectively). The receiver operating characteristic (ROC) analysis illustrated that the area under the curve was 0.80 (95% confidence interval [CI] 0.71-0.89; P < 0.001) and the optimal cut-off value of serum O-sulfotyrosine suggesting AKI was < 147.40 ng/mL with a sensitivity and specificity of 80.90 and 70.00% respectively. In animal experiments, serum levels of O-sulfotyrosine in mice were elevated on Day 7 after 5/6 nephrectomy (14.89 ± 1.05 vs. 8.88 ± 2.62 ng/mL, P < 0.001) until Day 90 (32.65 ± 5.59 vs. 8.88 ± 2.62 ng/mL, P < 0.001). CONCLUSION: Serum O-sulfotyrosine levels were observed correlated with degrading renal function and in CKD patients substantially higher than those in AKI patients. Thus serum O-sulfotyrosine facilitated the differential diagnosis of AKI from CKD.

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BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of any detectable organic illnesses. Interest in the effect of dietary opponents to the IBS pathogenesis has been increased in recent years. This study aims to review previous studies to determine the relationship between IBS prevalence in community and dietary energy and macronutrients intakes according to the national nutrition surveys. METHODS: A literature search was conducted in PubMed and EMBASE to September, 2018, to identify population-based studies that reported the prevalence of IBS. Daily energy intake, daily carbohydrates, and protein and fat percent contribution to energy intake (%) were obtained from study population-based national nutrition survey. The correlations of prevalence of IBS and dietary intakes were obtained by Spearman coefficient or Pearson coefficient. RESULTS: Global prevalence of IBS was 11.7%. There was no correlation between overall prevalence of IBS of individual countries and national energy intake (P = 0.785), protein proportion (P = 0.063), carbohydrates proportion (P = 0.505), or fat proportion (P = 0.384) according to the years when the studies were conducted. No correlations were detected between dietary intake and male or female IBS prevalence. Interestingly, protein proportion was positively correlated with the prevalence of IBS in Rome III criteria (r = 0.569). CONCLUSION: Our findings demonstrate that dietary energy and macronutrients intake do not play a direct role in prevalence of IBS. However, IBS diagnostic criteria seem to have a bias on the correlation between prevalence of IBS and dietary intake. Further studies are needed to confirm the correlation between prevalence of IBS and specific dietary intake.

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AIM: To perform a systematic review to grade guidelines and present recommendations for clinical management of non-alcoholic fatty liver disease (NAFLD). METHODS: A database search was conducted on PubMed for guidelines published before May 2016, supplemented by reviewing relevant websites. The Appraisal of Guidelines for Research and Evaluation (ARGEE) Instrument II was a tool designed to appraise the methodological rigor and transparency in which a clinical guideline is developed and it is used internationally. It was used to appraise the quality of guidelines in this study. The inclusion criteria include: clinical NAFLD guidelines for adults, published in English, and released by governmental agencies or key organizations. RESULTS: Eleven guidelines were included in this study. Since 2007, guidelines have been released in Asia (3 in China, 1 in South Korea, and 1 in Japan), Europe (1 in Italy), America (1 in United States and 1 in Chile) and three international agencies [European associations joint, Asia-Pacific Working Party and World Gastroenterology Organization (WGO)]. Using the ARGEE II instrument, we found US 2012 and Europe 2016 had the highest scores, especially in the areas of rigor of development and applicability. Additionally, Italy 2010 and Korea 2013 also presented comprehensive content, rigorous procedures and good applicability. And WGO 2014 offered various algorithms for clinical practice. Lastly, a practical algorithm for the clinical management was developed, based on the recommended guidelines. CONCLUSION: This is the first systematic review of NAFLD guidelines. It may yield insights for physicians and policy-makers in the development and application of guidelines.

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Introducción: la betatrofina es una novedosa adipoquina que provoca la proliferación de células ß pancreáticas e interviene en el metabolismo de los lípidos. Objetivos: el propósito de este estudio es evaluar el papel de la betatrofina en el síndrome metabólico. Método: se llevó a cabo un estudio hospitalario de casos y controles según sexo y edad. El nivel de betatrofina en suero fue evaluado mediante ensayo por inmunoabsorción ligado a enzimas. Se midieron las concentraciones en suero de 12 adipoquinas para evaluar las asociaciones con la betatrofina usando los kits comerciales Adipokine Magnetic Bead Panel. Los análisis estadísticos incluyeron correlación bivariada, análisis de curva ROC y análisis de regresión lineal multivariable. Resultados: el nivel de betatrofina en suero fue más elevado en pacientes con síndrome metabólico (997,36 ± 475,92 pg/ml, p = 0,001) que en los controles (735,35 ± 526,51 pg/ml). Frente al tercil más bajo, el tercil más alto del nivel de betatrofina mostró una asociación con mayor riesgo de síndrome metabólico (odds ratio ajustado = 3,521, intervalo de confianza [IC] 95% [1,191-10,413], p = 0,023). Se desarrolló la curva ROC de betatrofina para pronosticar la presencia de síndrome metabólico (área bajo la curva ROC = 0,682 [95% IC, 0,597-0,767], p < 0,001). Además, la betatrofina mostró correlación con distintos parámetros, como edad (r = 0,286, p < 0,001), índice de masa corporal (r = 0,160, p = 0,046), índice cintura-cadera (r = 0,241, p = 0,002), lipoproteína de alta densidad (r = -0,167, p = 0,037), lipoproteína de baja densidad (r = -0,195, p = 0,015), glucosa plasmática en ayunas (r = 0,266, p = 0,001), hemoglobina A1C (r = 0,314, p < 0,001), índice de resistencia a la insulina mediante HOMA (r = 0,272, p = 0,001) y diversas adipoquinas, entre ellas resistina (r = 0,571, p < 0,001), interleucina-8 (r = 0,435, p < 0,001), factor de necrosis tumoral alfa (r = 0,295, p = 0,011) y lipocalina-2 (r = 0,346, p = 0,003). Conclusiones: este estudio demuestra que la betatrofina en suero desempeña una importante labor en el síndrome metabólico, implicando la regulación del metabolismo de la glucosa y los lípidos y la inflamación.

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Background: Betatrophin is a novel adipokine that provokes pancreatic β-cell proliferation and is involved in lipid metabolism. Aims: This study aims to evaluate the role of serum betatrophin in metabolic syndrome (MetS). Methods: A hospital-based, age-/gender-matched case control study was conducted. The serum betatrophin level was evaluated by enzymelinked immunosorbent assay. Serum concentrations of 12 adipokines were measured to assess their associations with serum betatrophin, using commercial Adipokine Magnetic Bead Panel kits. Statistical analyses included bivariate correlation, receiver operating characteristic (ROC) curve, and multivariate stepwise linear regression. Results: Serum betatrophin showed a higher level in MetS patients (997.36 ± 475.92 pg/ml, p = 0.001) compared with controls (735.35 ± 526.51 pg/ml). Compared with the lowest tertile, the highest tertile of serum betatrophin level indicated an association with higher risk of MetS (adjusted odds ratio = 3.521, 95% confidence interval [CI] [1.191-10.413], p = 0.023). ROC curve of betatrophin was developed to predict the presence of MetS (area under ROC = 0.682 [95% CI, 0.597-0.767], p < 0.001). Furthermore, betatrophin correlated with several parameters, e.g. age (r = 0.286, p < 0.001), body mass index (r = 0.160, p = 0.046), waist-to-hip ratio (r = 0.241, p = 0.002), high-density lipoprotein cholesterol (r = -0.167, p = 0.037), low-density lipoprotein cholesterol (r = -0.195, p = 0.015), fasting plasma glucose (r = 0.266, p = 0.001), hemoglobin A1C (r = 0.314, p < 0.001), homeostasis model assessment of insulin resistance (r = 0.272, p = 0.001), and various adipokines, e.g. resistin (r = 0.571, p < 0.001), interleukin-8 (r = 0.435, p < 0.001), tumor necrosis factor-α (r = 0.295, p = 0.011) and lipocalin-2 (r = 0.346, p = 0.003). Conclusions: This study supports that serum betatrophin plays an important role in MetS, involving the regulations of glucose and lipid metabolism and inflammation (AU)

Introducción: la betatrofina es una novedosa adipoquina que provoca la proliferación de células β pancreáticas e interviene en el metabolismo de los lípidos. Objetivos: el propósito de este estudio es evaluar el papel de la betatrofina en el síndrome metabólico. Método: se llevó a cabo un estudio hospitalario de casos y controles según sexo y edad. El nivel de betatrofina en suero fue evaluado mediante ensayo por inmunoabsorción ligado a enzimas. Se midieron las concentraciones en suero de 12 adipoquinas para evaluar las asociaciones con la betatrofina usando los kits comerciales Adipokine Magnetic Bead Panel. Los análisis estadísticos incluyeron correlación bivariada, análisis de curva ROC y análisis de regresión lineal multivariable. Resultados: el nivel de betatrofina en suero fue más elevado en pacientes con síndrome metabólico (997,36 ± 475,92 pg/ml, p = 0,001) que en los controles (735,35 ± 526,51 pg/ml). Frente al tercil más bajo, el tercil más alto del nivel de betatrofina mostró una asociación con mayor riesgo de síndrome metabólico (odds ratio ajustado = 3,521, intervalo de confianza [IC] 95% [1,191-10,413], p = 0,023). Se desarrolló la curva ROC de betatrofina para pronosticar la presencia de síndrome metabólico (área bajo la curva ROC = 0,682 [95% IC, 0,597-0,767], p < 0,001). Además, la betatrofina mostró correlación con distintos parámetros, como edad (r = 0,286, p < 0,001), índice de masa corporal (r = 0,160, p = 0,046), índice cintura-cadera (r = 0,241, p = 0,002), lipoproteína de alta densidad (r = -0,167, p = 0,037), lipoproteína de baja densidad (r = -0,195, p = 0,015), glucosa plasmática en ayunas (r = 0,266, p = 0,001), hemoglobina A1C (r = 0,314, p < 0,001), índice de resistencia a la insulina mediante HOMA (r = 0,272, p = 0,001) y diversas adipoquinas, entre ellas resistina (r = 0,571, p < 0,001), interleucina-8 (r = 0,435, p < 0,001), factor de necrosis tumoral alfa (r = 0,295, p = 0,011) y lipocalina-2 (r = 0,346, p = 0,003). Conclusiones: este estudio demuestra que la betatrofina en suero desempeña una importante labor en el síndrome metabólico, implicando la regulación del metabolismo de la glucosa y los lípidos y la inflamación (AU)

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It is thought that carbamylated modification plays a crucial role in the development and progression of cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). However, information on the biological effects of carbamylated high-density lipoprotein (C-HDL) in ESRD is poor. The present study investigated the carbamylation level of HDL in ESRD and the effects of C-HDL on endothelial repair properties. HDL was isolated from healthy control subjects (n = 22) and patients with ESRD (n = 30). The carbamylation level of HDL was detected using ELISA. Isolated C-HDL for use in tissue culture experiments was carbamylated in vitro to a similar extent to that observed in ESRD. Human arterial endothelial cells were treated with C-HDL or native HDL to assess their migration, proliferation, and angiogenesis properties. HDL-associated paraoxonase 1 activity was also determined by spectrophotometry assay. Compared with healthy control subjects, the carbamylation level of HDL in ESRD patients was increased and positively correlated with blood urea concentration. In vitro, C-HDL significantly inhibited migration, angiogenesis, and proliferation in endothelial cells. Mechanistic studies revealed that HDL-associated paraoxonase 1 activity was decreased and negatively correlated with the carbamylation level of HDL in ESRD patients. In addition, C-HDL suppressed the expression of VEGF receptor 2 and scavenger receptor class B type I signaling pathways in endothelial cells. In conclusion, the present study identified a significantly increased carbamylation level of HDL in ESRD. Furthermore, C-HDL inhibited endothelial cell repair functions.

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BACKGROUND: Coronary heart disease has become a major health concern over the past several decades. Several reviews have assessed the effects of socioeconomic status on the coronary heart disease epidemic in communities and countries, but only a few reviews have been performed at a global level. This study was to explore the relationship between the prevalence of coronary heart disease and socioeconomic development worldwide using the Human Development Index. DESIGN: Systematic review. METHODS: The data in this study were collected from the MEDLINE database. Cross-sectional studies reporting the prevalence of coronary heart disease until November 2014 were collected. The Human Development Index was sourced from the United Nations Development Programme Database and was used to measure the socioeconomic achievements of countries. Each country was classified as a developing or developed country based on its level of development according to the Human Development Index value. RESULTS: Based on the data analysis on the global level, coronary heart disease prevalence had no association with the national Human Development Index (rho = 0.07). However, there was a positive association between coronary heart disease prevalence and the national Human Development Index in developing countries, although a negative association existed in developed countries (rho = 0.47 and -0.34, respectively). In addition, the past decades have witnessed a growing coronary heart disease epidemic in developing countries, with reverse trends observed in developed countries (P = 0.021 and 0.002, respectively). CONCLUSIONS: With the development of socioeconomic status, as measured by the Human Development Index, the prevalence of coronary heart disease is growing in developing countries, while declining in developed countries. Future research needs to pay more attention to the reasonable allocation of medical resources and control of coronary heart disease risk factors.

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BACKGROUND: Endoscopic resection methods, including endoscopic mucosal resection and endoscopic submucosal dissection, have become standard treatment modalities for patients with early gastric cancer (EGC) and absolute indications, with en bloc resection being more frequent with the latter. Endoscopic resection, however, has been associated with higher recurrence and metachronous cancer rates than gastrectomy. This meta-analysis compared the efficacy and safety of endoscopic resection and gastrectomy for EGC. METHODS: PubMed, EMBASE and Web of Science were electronically searched for relevant studies comparing endoscopic resection and gastrectomy for EGC from 1976 through March 2015. The primary endpoints were en bloc resection and histologically complete resection rates. The secondary endpoints were duration of hospital stay and rates of complications, recurrence, metachronous cancer and overall survival. RESULTS: This meta-analysis enrolled 10 studies with 2070 patients: 993 patients who underwent endoscopic resection and 1077 who underwent gastrectomy. Endoscopic resection was associated with shorter hospital stay (standardized mean difference -2.02; 95 % confidence interval [CI] -2.64 to -1.39) and lower complication rate (relative risk [RR] 0.41; 95 % CI 0.22-0.76) than gastrectomy. However, endoscopic resection was associated with lower rates of en bloc resection (odds ratio [OR] 0.05; 95 % CI 0.02-0.16) and histologically complete resection (OR 0.04; 95 % CI 0.01-0.11) and higher rates of recurrence (RR 5.23; 95 % CI 2.43-11.27) and metachronous cancer (RR 5.22; 95 % CI 2.40-11.34) than gastrectomy. Overall survival rate (OR 1.18; 95 % CI 0.76-1.82) was similar. CONCLUSIONS: Endoscopic resection is minimally invasive and as effective as surgery, suggesting that the former be considered standard treatment for EGC. It should be recommended as standard treatment for EGC with indications. Additional randomized controlled trials from more countries are required.

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Recent animal studies support close associations of Periostin with hepatosteatosis and steatohepatitis. This study is to evaluate the role of serum periostin in non-alcoholic fatty liver disease (NAFLD). A hospital-based age-/sex-matched case-control study was conducted. Binary logistic regression and receiver operating characteristic (ROC) curve were performed. Serum adipokines were measured by Adipokine Magnetic Bead Panel kits. The serum concentration of Periostin in NAFLD (1914.16 [1323.59-2654.88] ng/ml, P < 0.001) was higher than it in control (1244.94 [837.87-2028.55] ng/ml). The frequency of NAFLD grew (29.8, 52.6, and 67.2%, P < 0.001), as Periostin concentration increased among its tertiles. Compared with the 1st tertile, the 2nd and the 3rd tertiles of Periostin indicated significant associations with higher odds of NAFLD [adjusted odds ratio = 2.602 (95% confidence interval (CI) 1.030-6.575), P = 0.043 and 2.819 (95% CI 1.629-4.878), P < 0.001]. ROC curve of Periostin was developed to predict the presence of NAFLD (area under ROC = 0.693 [95% CI 0.614-0.771], P < 0.001). Lastly, Periostin correlated with several adipokines, including Resistin (r = 0.269, P = 0.018), Adiponectin (r = -0.352, P = 0.002), Interleukin (IL)-6 (r = 0.359, P = 0.001), IL-8 (r = 0.364, P = 0.001), Lipocalin-2 (r = 0.623, P < 0.001), Hepatocyte growth factor (r = 0.522, P < 0.001), and Nerve growth factor (r = 0.239, P = 0.036). It suggests Periostin as a potential biomarker in the management of NAFLD.

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In the study, we investigated the effect of histamine microinjected into cerebellar fastigial nucleus (FN) on stress gastric mucosal damage (SGMD), and its mechanisms in rats. The model of SGMD was established by restraining and water (21±1°C)-immersion for 3h. The gastric mucosal damage index (GMDI) indicated the severity of gastric mucosal damage. Histamine or receptor antagonist was microinjected into the FN. The decussation of superior cerebellar peduncle (DSCP) and the lateral hypothalamic area (LHA) were destroyed, respectively. The pathological changes of gastric mucosa were evaluated using biological signal acquisition system, Laser-Doppler flowmeter, and western blotting. We found that the microinjection of histamine (0.05, 0.5, and 5µg) into FN significantly attenuated the SGMD, in a dose-dependent manner, whereas, the microinjection of histamine H2 receptor antagonist, ranitidine, and glutamic acid decarboxylase antagonist, 3-mercaptopropionic acid (3-MPA) exacerbated the SGMD. The protective effect of histamine on SGMD was abolished by electrical lesion of DSCP or chemical ablation of LHA. The microinjection of histamine decreased the discharge frequency of the greater splanchnic nerve, and the gastric mucosal blood flow was increased. In addition, the cellular proliferation was enhanced, but the cellular apoptosis was reduced in the gastric mucosa. Also the pro-apoptosis protein, Bax, and caspase-3 were down-regulated, and the anti-apoptosis protein, Bcl-2 was up-regulated following microinjection of histamine. In conclusion, the FN participated in the regulation of SGMD after histamine microinjected into FN, and cerebellar-hypothalamic circuits (include: DSCP, LHA) contribute to the process, which may provide a new therapeutic strategy for SGMD.

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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a great health burden. Neuregulin 4 (Nrg4) is a recently identified secret factor that may be associated with NAFLD. AIM: To investigate the association between serum Nrg4 level and NAFLD by conducting a case-control study. METHOD: A total of 174 subjects were included. 87 NAFLD subjects and 87 age- and sex-matched non-NAFLD controls were identified by hepatic ultrasound examination. Anthropometric and biochemical data were measured and recorded. Serum Nrg4 level was evaluated by using enzyme-linked immunosorbent assay. SPSS software was used for statistical analyses. RESULTS: Compared to the controls, subjects with NAFLD presented with reduced level of serum Nrg4 (0.40 (0.27, 0.55) vs. 0.50 (0.30, 0.81)ng/mL (median (interquartile range)), P=0.029). By multivariate logistic regression analysis, reduced serum levels of Nrg4 were associated with higher NAFLD odds (OR=0.251, 95% confidence interval=0.081-0.779, P=0.017). By dividing the distribution of serum Nrg4 level into quartiles, there was borderline statistical difference of NAFLD prevalence among the four groups (P=0.058). There was no significant difference of serum Nrg4 levels in subjects according to the grades of fatty liver by ultrasound (P=0.080). No statistical difference of serum Nrg4 level was observed between obese and non-obese subjects (P=0.932). CONCLUSION: Decreased serum Nrg4 level is prevalent in NAFLD subjects compared to non-NAFLD controls, and is an independent risk factor associated with NAFLD, indicating that Nrg4 might have a protective role in the development of NAFLD.

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PURPOSE: We aim to investigate the association between angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) therapy and colorectal cancer (CRC) by conducting a systematic review with meta-analysis. METHODS: Literature was searched on PubMed, Scopus, and the Cochrane library to identify relevant studies evaluating ACEIs/ARBs therapy and risk of CRC incidence or survival of CRC patients. Pooled risk ratio (RR) with 95% confidence intervals was calculated for the association between ACEIs/ARBs and CRC risk and mortality. RESULTS: Eleven observational studies were included in the systematic review. A meta-analysis of six studies totaling 113,048 individuals indicated a 6% decreased risk of CRC in ACEIs/ARBs users compared to non-users (95% CI 0.89-0.98). In the four case-control studies, individuals using ACEIs/ARBs were associated with a 6% decreased risk of CRC (95% CI 0.90-0.99). The meta-analysis of three studies investigating the relationship between ACEIs/ARBs and survival of CRC did not show a significantly decreased mortality in ACEIs/ARBs users (RR 0.81, 95% CI 0.60-1.09). Seven studies evaluated the dose-response relationship between ACEIs/ARBs therapy and CRC, and two of them showed that the association was related to longer duration and higher dose. CONCLUSIONS: CEIs/ARBs therapy might be associated with a reduce risk of CRC development, but whether use of these medications improves the outcomes of CRC remains unknown. Large-scale and more robust studies are needed to further explore this association.

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AIM: To investigate the relationship between the economy and the adult prevalence of fatty liver disease (FLD) in mainland China. METHODS: Literature searches on the PubMed and Chinese National Knowledge Infrastructure databases were performed to identify eligible studies published before July 2014. Records were limited to cross-sectional surveys or baseline surveys of longitudinal studies that reported the adult prevalence of FLD and recruited subjects from the general population or community. The gross domestic product (GDP) per capita was chosen to assess the economic status. Multiple linear regression and Loess regression were chosen to fit the data and calculate the 95%CIs. Fitting and overfitting of the models were considered in choosing the appropriate models. RESULTS: There were 27 population-based surveys from 26 articles included in this study. The pooled mean prevalence of FLD in China was 16.73% (95%CI: 13.92%-19.53%). The prevalence of FLD was correlated with the GDP per capita and survey years in the country (adjusted R (2) = 0.8736, P GDP per capita = 0.00426, P years = 0.0000394), as well as in coastal areas (R (2) = 0.9196, P GDP per capita = 0.00241, P years = 0.00281). Furthermore, males [19.28% (95%CI: 15.68%-22.88%)] presented a higher prevalence than females [14.1% (95%CI: 11.42%-16.61%), P = 0.0071], especially in coastal areas [21.82 (95%CI: 17.94%-25.71%) vs 17.01% (95%CI: 14.30%-19.89%), P = 0.0157]. Finally, the prevalence was predicted to reach 20.21% in 2020, increasing at a rate of 0.594% per year. CONCLUSION: This study reveals a correlation between the economy and the prevalence of FLD in mainland China.

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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a growing health issue around the world. AIM: This study is to investigate whether adult prevalence of NAFLD correlates with national economic status. METHODS: Literature search on PubMed database was conducted to identify eligible records fully published before September 2014. Gross national income (GNI) per capita was chosen to evaluate national economic status. Pearson coefficient, linear regression, and unpaired t test were performed in the statistical analyses. RESULTS: Twenty-one population-based surveys (seven in East Asia, five in South Asia, three in Middle East, and six in Europe) were included. The pooled prevalence of NAFLD was 24.24%, and the global prevalence was positively correlated with GNI per capita (r = 0.4782, P = 0.0283). Europe witnessed a higher prevalence (28.04%) than Middle East (12.95%, P = 0.0092) and East Asia (19.24%, P = 0.0083). Male presented a higher prevalence than female (P = 0.019), especially in Europe (P = 0.0132) and in Caucasians (P = 0.0383). Furthermore, male prevalence and rural prevalence individually were correlated with economic status (r = 0.5725, P = 0.0257 and r = 0.7389, P = 0.0060). Lastly, the urban (23.93%) witnessed a higher prevalence than the rural or the urban + rural (12.65%, P = 0.0141) in the countries of GNI per capita <$10,000. CONCLUSIONS: This study suggested that countries with higher economic status tend to present a higher prevalence of NAFLD. It is believed to provide a distinctive epidemiologic perspective to global situation of NAFLD.

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BACKGROUND: Alcohol intake is closely related to colorectal cancer, which remains inconsistent with studies on the relation between alcohol consumption and risk of colorectal serrated polyp (SP) which was proven to have potential of developing into malignant serrated neoplasm. AIM: A meta-analysis investigating the association between alcohol intake and colorectal SP with the dose-response of alcohol intake was conducted. METHODS: The literature search was performed on PubMed to identify pertinent articles presenting results for at least three categories of alcohol consumption dated up to October 2014. Summarized relative risks (RRs) with 95 % confidence intervals (CIs) were estimated using random or fixed effects models based on statistical heterogeneity. RESULTS: A total of ten observational studies were identified in this meta-analysis. All drinkers were associated with 24 % increased risk of colorectal SP compared with non-/occasional drinkers. In particular, the light alcohol intake was not related to an increased risk of colorectal SP (RR 1.05, 95 % CI 0.93-1.18), whereas the RRs were 1.19 (95 % CI 1.02-1.40) for moderate alcohol intake and 1.60 (95 % CI 1.35-1.91) for heavy alcohol intake. The risks were consistent in further dose-response analysis. Meanwhile, subgroup analyses demonstrated that patients in America had more increased risk of SP with respect to those in Europe and Asia. In terms of subtype of colorectal SP, alcohol consumption had a greater influence on SSA than HP. CONCLUSIONS: This is the first meta-analysis that demonstrated the relationship between moderate and heavy alcohol consumption and increasing risks of colorectal SP.

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Replenishing the insulin-producing ß-cell mass is considered to be a potential cure for diabetes. A recent study identified a secreted protein, known as betatrophin, which potently induces pancreatic ß-cell proliferation. Notably, a number of studies reportedly identified betatrophin, which is also known as lipasin, atypical angiopoietin-like 8 and refeeding-induced fat and liver protein, and considered to be a novel regulator in lipid metabolism according to the studies. The identification of betatrophin was considered to create novel opportunities for potential diabetes therapy. In the present study, the current knowledge of betatrophin is reviewed, with regards to its character and function in lipid homeostasis and pancreatic ß-cell proliferation.

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BACKGROUND AND AIM: There are a multitude of cross-sectional surveys that provide the prevalence of irritable bowel syndrome (IBS) in the community. However, the data regarding the influence of socioeconomic status on prevalence of IBS were sparse. This study is to investigate the possible relation between human development and prevalence of IBS, at national level. METHODS: EMBASE Classic, EMBASE, and MEDLINE were searched (until October 2013) to identify population-based studies that reported prevalence of IBS. Human Development Index (HDI) was chosen to assess socioeconomic status at national level. RESULTS: Firstly, no correlation was observed between prevalence of IBS and national HDI (P = 0.848). Specifically, there was no statistical significance in prevalence between developing and developed countries (P = 0.319). Moreover, prevalence of IBS failed to witness a downtrend in worldwide over the past two decades. Interestingly, the ratio of female/male prevalence was correlated with national HDI according to linear regression analysis (r = 0.395), and the ratio in the developing was significant lower than that in the developed (P = 0.0394). Lastly, except methods of data collection (P < 0.000), it shows no difference between developing and developed countries in diagnostic criteria, IBS subtypes, and age distribution (P = 0.119, 0.327, and 0.845 respectively). CONCLUSIONS: This study is the first time to investigate the relation between IBS prevalence and national socioeconomic status, with consideration of years, gender, and other factors. It demonstrates that national development is not a direct indicator for prevalence of IBS.

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