A causal analysis of the relationship between exposure to sunlight and colorectal cancer risk: A Mendelian randomization study.

Several observational studies have found that exposure to sunlight reduces the risk of colorectal cancer (CRC). However, sun exposure remains ambiguous in its relationship to CRC. We carried out a Mendelian randomization (MR) study to explore the potential associations between them. We examined the exposure to sunlight summary statistics of the UK Biobank Consortium using a 2-sample MR analysis. Using data from the FinnGen consortium, we derived summary statistics for CRC. We conducted our analysis with various methods, incorporating inverse variance weighted (IVW) along with 4 other approaches. A Cochran Q statistic was used to measure the heterogeneity of instrumental variables (IVs). We screened 133 single nucleotide polymorphisms (SNPs) (time spent outdoors in summer), 41 SNPs (time spent outdoors in winter), and 35 SNPs (frequency of solarium/sunlamp use) representing sunlight exposure for MR analysis. All selected SNPs had an F-statistic >20, indicating that IVs did not weakly bias the results. The summer outdoor activity trait exhibited significant heterogeneity (Cochran Q statistic = 183.795, P = .002 < 0.05), but we found no horizontal polymorphisms or significant heterogeneity for the other exposure traits. According to IVW estimates, no causal association exists between time spent outdoors in summer and CRC (Odds Ratio, OR = 0.735, 95% confidence interval, CI = 0.494-1.017, P = .128 > 0.017). No causal relationship existed between time spent outdoors in winter and CRC, as indicated by Bonferroni-corrected adjusted p-values. The OR was 0.877 with a 95% CI of 0.334-2.299, and the P value was .789, more significant than the significance threshold of 0.017. The solarium/sunlamp use frequency was not associated with CRC (OR = 1.567, 95%CI = 0.243-10.119, P = .637 > .017). Also, an IVW with random effects was applied to determine the causal relationship between summer outdoor time and CRC. No causal association between summer outdoor time and CRC was found (OR = 0.735, 95% CI = 0.494-1.017, P = .128 > .017). Additionally, 4 additional analyses yielded similar results. The findings of our study suggest that exposure to sunlight may reduce CRC risk, but the causal relationship remains unsolved. There is no evidence to suggest that exposure to sunlight prevents CRC. Randomized, controlled trials are needed to determine whether sunlight exposure protects against CRC.

Comparison between models for detecting hepatocellular carcinoma in patients with chronic liver diseases of various etiologies: ASAP score versus GALAD score.

BACKGROUND: Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma (HCC). Based on age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II) with/without AFP-L3, ASAP and GALAD models are potential diagnostic panels. The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases (CLDs). METHODS: A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chinese hospitals. The etiologies of CLDs included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). Using area under the receiver operating characteristic curve (AUC) values, the diagnostic performances of ASAP and GALAD models were compared to detect HCC among patients with various etiologies of CLDs. RESULTS: Among 248 HCC patients and 722 CLD controls, the ASAP model demonstrated the highest AUC (0.886) to detect HCC at any stage, outperforming the GALAD model (0.853, P = 0.001), as well as any individual biomarker (0.687-0.799, all P < 0.001). In the subgroup analysis of various CLDs etiologies, the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology. In addition, the ASAP model performed better in detecting early-stage (BCLC stage 0/A) HCC versus the GALAD model. CONCLUSIONS: Despite using one less laboratory variable (AFP-L3), the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various etiologies of CLDs-related HCC.

Metabolically healthy obesity is associated with longitudinal changes in high-density lipoprotein cholesterol in Chinese adults.

PURPOSE: Whether metabolically healthy obesity (MHO) is associated with longitudinal changes in high-density lipoprotein cholesterol (HDL-C) remains unclear. METHODS: MHO was defined as participants with overweight and obesity (BMI ≥ 24.0 kg/m2, n = 2921), free of history of metabolic diseases, and without abnormalities of blood pressure, fasting blood glucose, hemoglobin A1c, lipid profile, carotid artery and liver ultrasonographic findings at baseline. Metabolically healthy normal weight (MHN) was defined as participants with normal weight (BMI < 24.0 kg/m2, n = 9578) and without above-mentioned abnormalities. HDL-C, fasting blood glucose, hemoglobin A1c, and blood pressure were assessed annually. Glucose abnormality was considered if either FBG ≥ 5.6 mmol/L or HbA1c ≥ 5.7%; while, high blood pressure (HBP) was considered if either systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 80 mmHg during 5 years of follow-up. RESULTS: Compared with the MHN group, the adjusted mean difference in HDL-C change rate was - 0.005 mmol/L per year [95% confidence interval (CI) - 0.007, - 0.003] for MHO after adjustment for a series of potential confounders. Furthermore, transiting to abnormality of blood glucose, but not high blood pressure, was associated with lower cumulative average of HDL-C in MHN group, compared with those remained in metabolically healthy status. CONCLUSIONS: MHO and transiting from metabolically healthy to abnormality of blood glucose were associated with HDL-C in Chinese adults. LEVEL OF EVIDENCE: III, cohort study.

GastroPanel® Biomarker Assay: The Most Comprehensive Test for Helicobacter pylori Infection and Its Clinical Sequelae. A Critical Review.

BACKGROUND/AIM: Several clinical conditions seriously hamper the diagnostic accuracy of the commonly used tests for Helicobacter pylori (Hp), 13C-urea breath test (UBT) and stool antigen test (SAT). The present communication is a critical review of the potential limitations of UBT and SAT, and describes the approach on how these can be avoided. Drawbacks of the Hp tests: False-negative results are most often due to low bacterial load in the stomach due to: i) use of proton pump inhibitor medication; ii) use of antibiotics; iii) presence of atrophic gastritis and hypoacid stomach; iv); bleeding peptic ulcer; v) gastric cancer (GC) and vi) mucosal-associated lymphatic tissue lymphoma. The UBT also gives false-positive results when urease-producing bacterial species, other than Hp colonize an acid-free stomach. Importantly, neither UBT nor SAT are capable of diagnosing atrophic gastritis, thus missing the patients at highest risk for GC. GastroPanel® (Biohit Oyj, Finland) circumvents these shortcomings with a serological test consisting of a panel of stomach-specific biomarkers: pepsinogen I, pepsinogen II, gastrin-17 and Hp antibodies. GastroPanel® is a tool for non-invasive examination of i) dyspeptic patients for exclusion or diagnosis of Hp or atrophic gastritis, also disclosing the status of gastric acid output; ii) for screening of asymptomatic individuals at risk of GC; and iii) for comprehensive diagnosis of Hp infection. GastroSoft® application integrates the biomarker profile with the patient's medical information, accurately classifying the biomarker profiles into eight diagnostic categories. CONCLUSION: Given that Hp is the single most important risk factor of GC, the non-invasive diagnosis and screening of Hp should be based on more accurate and more comprehensive testing than UBT or SAT alone. The GastroPanel® is such test, being completely devoid of the known serious shortcomings of UBT and SAT.

Handgrip Strength Index Predicts Nutritional Status as a Complement to Body Mass Index in Crohn's Disease.

BACKGROUND: Body mass index [BMI] is widely used to measure nutritional status in Crohn's disease [CD] patients, but limitations remain. Measuring handgrip strength index, in addition to BMI, may aid in overcoming limitations. METHODS: A total of 150 patients with CD and 254 controls were included in this study. All patients and controls underwent BMI, handgrip strength and bioelectrical impedance analysis. Bioelectrical impedance analysis included body cell mass, bone mineral content, skeletal muscle mass and body fat mass. A total of 88 CD patients were age-, sex- and BMI-matched with healthy controls for further analysis. RESULTS: BMI, body cell mass, body cell mass index, handgrip strength and handgrip strength index were all significantly decreased in the group of CD patients compared with controls [p < 0.0001]. When paired by BMI, healthy controls had significantly increased body cell mass index[p = 0.0344] and handgrip strength index [p = 0.0010] compared to patients. In addition, handgrip strength was well correlated with body cell mass [r = 0.8365, p < 0.0001]. CONCLUSIONS: BMI is widely used for detecting malnutrition, but it is less sensitive in predicting loss of body cell mass and skeletal muscle mass. Our study shows that handgrip strength index is an effective and convenient parameter to predict the functional nutritional status and muscular health in CD patients.

Cholesterol metabolism and expression of its relevant genes in cultured steatotic hepatocytes.

OBJECTIVE: To investigate the cholesterol metabolism and mRNA expression of the relevant genes in cholesterol synthesis of the cultured steatotic hepatocytes model. METHODS: A steatotic model of hepatocytes was constructed by adding palmitic acid to the growing L-02 cells. These cells were collected at day 3 and 6, respectively. Cells with the culture solution without palmitic acid added served as the control. The contents of intracellular triglyceride (TG) and total cholesterol (TC) were detected by the analysis kit. The expression of sterol-regulatory element binding protein-2 (SREBP-2) and its target gene hydroxymethylglutaryl CoA reductase (HMGCR) and low-density lipoprotein receptor (LDLR) were measured by RT-PCR. RESULTS: Hepatocyte steatosis was observed at day 3 and became more intense at day 6. The contents of intracellular TG and TC were increased and the expression of the SREBP-2, HMGCR and LDLR mRNA were upregulated in a time-dependent manner in the model group. Compared with the control group, the content of intracellular TG was higher at both day 3 and 6 (P < 0.05), while the content of intracellular TC was significantly increased only at day 6; The expression of HMGCR and LDLR mRNA was upregulated in steatotic hepatocytes at both day 3 and 6 (P < 0.05), whereas the SREBP-2 mRNA was increased only at day 6 (P < 0.05). CONCLUSION: Cholesterol accumulation is probably due to the upregulated expression of the relevant genes in the cholesterol synthesis of the steatotic hepatocytes.

Assessment of health-related quality of life in Chinese patients with minimal hepatic encephalopathy.

AIM: To evaluate the health-related quality of life (HRQOL) based on the Chinese version of SF-36 and Chronic Liver Disease Questionnaire (CLDQ) in subjects with chronic hepatitis B, liver cirrhosis, including patients with minimal hepatic encephalopathy (MHE). METHODS: The SF-36 and CLDQ were administered to 160 healthy volunteers, 20 subjects with chronic hepatitis B and 106 patients with cirrhosis (33 cases exhibited MHE). HRQOL scores were compared among the different study groups. The SF-36 includes eight health concepts: physical functioning, role-physical, body pain, general health, vitality, social functioning, role-emotion, and mental health. Six domains of CLDQ were assessed: abdominal symptoms, fatigue, systemic symptoms, activity, emotional function and worry. RESULTS: Compared with healthy controls (96.9 +/- 4.5, 86.6 +/- 18.4, 90.1 +/- 12.5, 89.0 +/- 5.7, 87.5 +/- 4.3, 95.8 +/- 7.1, 88.5 +/- 15.9, 88.7 +/- 5.2 in SF-36 and 6.7 +/- 0.5, 6.1 +/- 0.6, 6.3 +/- 0.6, 6.5 +/- 0.5, 6.3 +/- 0.5, 6.8 +/- 0.4 in CLDQ), patients with chronic hepatitis B (86.3 +/- 11.0, 68.8 +/- 21.3, 78.9 +/- 14.4, 60.8 +/- 10.5, 70.8 +/- 8.6, 76.1 +/- 12.6, 50.0 +/- 22.9, 72.2 +/- 10.6 and 5.5 +/- 1.0, 4.5 +/- 1.0, 5.2 +/- 1.1, 5.3 +/- 0.9, 4.8 +/- 0.9, 4.9 +/- 1.0) and cirrhosis (52.8 +/- 17.4, 32.8 +/- 27.9, 61.6 +/- 18.9, 30.2 +/- 18.3, 47.9 +/- 20.1, 54.0 +/- 19.2, 28.9 +/- 26.1, 51.1 +/- 17.8 and 4.7 +/- 1.2, 3.9 +/- 1.2, 4.7 +/- 1.2, 4.7 +/- 1.3, 4.7 +/- 1.0, 4.4 +/- 1.1) had lower HRQOL on all scales of the SF-36 and CLDQ (P < 0.01 for all). Increasing severity of liver cirrhosis (based on the Child-Pugh score/presence or absence of MHE) was associated with a decrease in most components of SF-36 and CLDQ, especially SF-36. CONCLUSION: The Chinese version of SF-36 along with CLDQ is a valid and reliable method for testing MHE in patients with liver cirrhosis. Cirrhosis and MHE are associated with decreased HRQOL.

[Assessment of the health-related quality of life of patients with minimal hepatic encephalopathy].

OBJECTIVE: The Medical Outcome Study of 36-item Short-Form Health Survey (SF-36) is a well-validated generic questionnaire widely used to assess health-related quality of life (HRQOL), and the Chronic Liver Disease Questionnaire (CLDQ) is a specific HRQOL assessment designed for patients with liver diseases. The aim of our study is to evaluate the HRQOL based on SF-36 and CLDQ (Chinese version) in patients with chronic hepatitis B and liver cirrhosis, especially in the status of minimal hepatic encephalopathy (MHE). METHODS: The SF-36 and CLDQ were answered by 160 healthy volunteers, 20 patients with chronic hepatitis B and 106 patients with cirrhosis. HRQOL scores of the groups with different liver disease severities and with or without MHE were compared. The SF-36 includes one multi-item scale that assesses eight health categories: physical functioning, role-physical, body pain, general health, vitality, social functioning, role-emotion, and mental health. CLDQ assesses 6 categories: abdominal symptoms, fatigue, systemic symptoms, activity, emotional function and worry. RESULTS: Compared with the healthy controls, patients with chronic hepatitis B and liver cirrhosis at baseline had a lower HRQOL on all scales of the SF-36 and CLDQ (P < 0.01 for all). Increased severity of liver cirrhosis (based on the Child-Pugh score but with MHE or without) was associated with a decrease in most components, both in SF-36 and in CLDQ. However, patients with Child-Pugh B and C disease had similar HRQOL scores on both the SF-36 and CLDQ (P > 0.05), except role-physical and vitality on SF-36. There was a significant difference between patients with and without MHE on the SF-36 score (P < 0.01), and no significant difference (P > 0.05) on CLDQ scores except in abdominal symptoms. CONCLUSION: The Chinese version of SF-36 along with CLDQ are valid and reliable methods for testing MHE in patients with liver cirrhosis.

[The effect of ligand of peroxisome proliferators-activated receptor gamma 15d-PGJ2 on the proliferation and activation of hepatic stellate cells].

OBJECTIVE: To observe the effect of ligand of peroxisome proliferators-activated receptor gamma (PPAR gamma) 15d-PGJ2 on the proliferation and activation of hepatic stellate cells (HSC) and to study the role played by PPAR gamma during the process of HSC activation. METHODS: By using RT-PCR and cell culture, we investigated the effects of 5 micro mol/L and 10 micro mol/L 15d-PGJ2 on culture-activated HSC and on PDGF-induced HSC proliferation, production of extracellular matrix and expression of chemokines. RESULTS: The expression of alpha-SMA was significantly suppressed by 5mumol/L 15d-PGJ2, and the expression of PPAR gamma was significantly higher in the 15d-PGJ2 treated group than in the untreated group (0.64+/-0.03 vs 0.09+/-0.01, t=36.0517, P<0.01); PDGF-induced HSC proliferation was dose-dependently suppressed by 15d-PGJ2; the expressions of PPAR gamma in 5 micro mol/L and also in 10 micro mol/L 15d-PGJ2 plus PDGF pre-treated group increased much more than those in the PDGF-treated group (0.03+/-0.02 vs 0.60+/-0.03, t=42.6616, P<0.01 and 0.03+/-0.02 vs 0.69+/-0.04, t=33.83, P<0.01); the expressions of alpha-SMA, alpha 1 (I)-collagen and MCP-1 were suppressed. CONCLUSION: Activation of PPAR gamma can modulate pro-fibrotic and pro-inflammatory roles of HSC and the increased expression of PPAR gamma may become a new target for antifibrosis.

[The role of peroxisome proliferators-activated receptor gamma (PPARgamma) during activation of hepatic stellate cells].

OBJECTIVES: To observe the role of PPARgamma during the activation process of hepatic stellate cells (HSC). METHODS: By morphology and RT-PCR, we study the changes of expression of PPARgamma in culture-activated HSC or in vivo activated HSC induced by dimethylnitrosamine (DMN). RESULTS: In vitro, the expression level of PPARgamma in freshly isolated HSC (0.72+/-0.01) significantly reduced to 0.48+/-0.03 on the third day of culture (t = 19.8372, P<0.01), and reduced 70% on the seventh culture-day and could not be detected after the second passage. In vivo, HSC freshly isolated from normal control rats expressed PPARgamma (0.76+/-0.01). During the development of rat liver fibrosis induced by DMN, the expression level significantly reduced to 0.46+/-0.02 after the third injection of DMN (t = 29.5318, P<0.01), and reduced 66% on the end of first week and could not be detected on the end of second and third week. CONCLUSION: The expression of PPARgamma might play an important role on the maintenance of resting-form of HSC, and the reduction of expression of PPARgamma might be an early event during the activation process of HSC.

Effect of lipid on proliferation and activation of rat hepatic stellate cells (I).

AIM:To study the effect of lipid (triglyceride and very low-density lipopro tein, VLDL) on proliferation and activation of rat hepatic stellate cells (HSC).METHODS:HSC were isolated and cultured from liver of Wistar rats by in situ perfusion with pronase and collagenase and density gradient centrifugation with Nycodenz.HSC proliferation was examined with MTT colorimetric assay.RESULT: Triglyceride of had a promoting effect on proliferation of HSC (P< 0.05), 25, 50, 100 and 200mg/L had no effects (P >0.05),but 400mg/L had an inhibiting effect (P <0.01). VLDL of 6.25 and 12.5mg/L had no effect on proliferation of HSC (P > 0.05), but increased concentration of VLDL could promote the HSC proliferation (P < 0.05).CONCLUSION:Lipid had an effect on proliferation of HSC. Triglyceride and VLDL may promote HSC proliferation and may be associated with fatty liver and hepatic fibrogenesis.