[Screening of Highly Hazardous Pollutants in Groundwater of Beijing].

Groundwater contaminants pose a great threat to water safety and human health. Therefore, in this study, the traditional hazard assessment method was improved and a comprehensive system covering hazard assessment, screening, and characterization by combining the toxicological priority index (Tox Pi) framework; absorption, distribution, metabolism, and excretory (ADME) analysis; and bipartite network analysis was constructed. Then, the system was applied to hazard assessment and toxic pollutants screening from the 234 hydrophobic organic contaminants (HOCs) identified in the groundwater of Beijing. First, the top 20 pollutants with hazard potential were screened out using the Tox Pi method. Subsequently, 17 high-priority HOCs were further identified based on the ADME property analysis. Then, the molecular targets of these 17 high-priority HOCs were characterized through systematic bipartite network analysis. Finally, ten HOCs with high hazard were screened through correlation and weighted average analysis, and it was revealed that their toxic effects were mainly concentrated in the endocrine-disrupting effect, carcinogenic effect, and genetic toxicity. This study provides technical support for the prevention of regional groundwater contaminants.

Renal Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Patients with Liver Cirrhosis: A Nationwide Cohort Study.

BACKGROUND: The use of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) carries a risk of renal function deterioration in cirrhotic patients with ascites. However, whether the long-term use of ACEis/ARBs is safe in cirrhotic patients without ascites remains unknown. METHODS: In this nationwide cohort study, we identified 311,361 newly diagnosed cirrhotic patients between January 1997 and December 2013. To avoid indication and immortal time biases, patients receiving regular ACEi/ARB therapy, defined as the ACEi/ARB cohort, were matched to patients receiving regular calcium channel blockers (CCBs), defined as the CCB cohort, at a ratio of 1 : 1 by age, sex, and propensity scores for comorbidities and medications (2,188 patients in each cohort). Cumulative incidence rates and multivariate analyses of end-stage renal disease (ESRD) risk were adjusted for competing mortality. RESULTS: The 10-year cumulative incidence rates of ESRD were 2.32% (95% confidence interval [CI]: 1.45-3.20) in the ACEi/ARB cohort and 1.70% (95% CI: 1.03-2.36) in the CCB cohort (P = 0.610). In multivariate analyses, ACEi/ARB use was not associated with a higher risk of ESRD in cirrhotic patients (hazard ratio [HR] = 1.15; 95% CI: 0.69-1.94, P = 0.591). In the sensitivity test, the 10-year cumulative incidence rates of ESRD in cirrhotic patients with ascites were 6.50% (95% CI: 0.54-12.46) and 1.24% (95% CI: 0.00-2.71) in ACEi/ARB and CCB cohorts, respectively (P = 0.090). CONCLUSIONS: Long-term ACEi/ARB use was not associated with a higher risk of ESRD in cirrhotic patients. However, the risk of ESRD tended to increase in cirrhotic patients with ascites.

Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.

Importance: Antiviral therapy cannot erase hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B, and it is not indicated for most hepatitis B virus (HBV) carriers. Another effective way of reducing HCC risk needs to be developed. Aspirin may prevent cancer development, but clinical evidence in patients with HBV-related HCC remains limited. Objective: To investigate the association of daily aspirin therapy with HBV-related HCC risk. Design, Setting, and Participants: In this Taiwan nationwide cohort study, we screened 204 507 patients with chronic hepatitis B for the period January 1, 1997, to December 31, 2012. After excluding patients with confounding conditions, 2123 patients who continuously received daily aspirin for 90 or more days (treated group) were randomly matched 1:4 with 8492 patients who had never received antiplatelet therapy (untreated group) by means of propensity scores, consisting of the follow-up index date, baseline characteristics, and potentially chemopreventive drug use during follow-up. Data were analyzed from August 1 to November 30, 2018. Exposures: Daily aspirin therapy during the study period. Main Outcomes and Measures: Both cumulative incidence of and hazard ratios (HRs) for HCC development were analyzed after adjusting patient mortality as a competing risk event. Results: Of the 10 615 patients included in the analysis, 7690 (72.4%) were men; mean (SD) age was 58.8 (11.8) years. The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group in 5 years (5.20%; 95% CI, 4.11%-6.29% vs 7.87%; 95% CI, 7.15%-8.60%; P < .001). In the multivariable regression analysis, aspirin therapy was independently associated with a reduced HCC risk (HR, 0.71; 95% CI, 0.58-0.86; P < .001). Sensitivity subgroup analyses also verified this association (all HRs <1.0). In addition, older age (HR, 1.01 per year; 95% CI, 1.00-1.02), male sex (HR, 1.75; 95% CI, 1.43-2.14), and cirrhosis (HR, 2.89; 95% CI, 2.45-3.40) were independently associated with an increased HCC risk, but nucleos(t)ide analogue (HR, 0.54; 95% CI, 0.41-0.71) or statin (HR, 0.62; 95% CI, 0.42-0.90) use was correlated with a decreased HCC risk. Conclusions and Relevance: Daily aspirin therapy may be associated with a reduced risk of HBV-related HCC.

Risk of skin cancer in psoriasis patients receiving long-term narrowband ultraviolet phototherapy: Results from a Taiwanese population-based cohort study.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy is a widely used treatment for various dermatoses. The risk of skin cancer following long-term NB-UVB phototherapy has rarely been explored in skin phototypes III-V. METHODS: We conducted a nationwide-matched cohort study and identified a total of 22 891 psoriasis patients starting NB-UVB phototherapy from the Taiwan National Health Insurance Database during the period 2000-2013. Cumulative incidences of skin cancers were compared between subjects receiving less than 90 UVB treatments (S-cohort, N = 13 260) and age- as well as propensity score-matched subjects receiving more than or equal to 90 UVB treatments (L-cohort, N = 3315). RESULTS: There were no significant differences in the overall cumulative incidences of skin cancers between the two cohorts (log-rank t test, P = 0.691) during the follow-up periods. The S-cohort had a significantly lower prevalence of actinic keratosis when compared with the L-cohort (0.54% vs 1.00%, P = 0.005). CONCLUSION: Long-term NB-UVB phototherapy does not increase skin cancer risk compared with short-term NB-UVB phototherapy in psoriasis patients with skin phototypes III-V.

Effect of Nucleos(t)ide Analogue Therapy on Risk of Intrahepatic Cholangiocarcinoma in Patients With Chronic Hepatitis B.

BACKGROUND & AIMS: Chronic infection with hepatitis B virus (HBV) increases risk of intrahepatic cholangiocarcinoma (ICC), but it is not clear whether antiviral therapy reduces risk. We investigated the association between nucleos(t)ide analogue therapy and ICC risk. METHODS: We performed a nationwide long-term cohort study using Taiwan's National Health Insurance Research Database to obtain data on 185,843 patients with chronic HBV infection from October 1, 2003 through December 31, 2012. We excluded patients with confounding disorders such as infection with hepatitis C virus, HIV, or other hepatitis-associated viruses; liver flukes; biliary stone diseases; cholangitis; congenital biliary anomalies; biliary tract surgeries; or cancer. We identified 10,062 patients who received nucleos(t)ide analogue therapy (the treated group), and used propensity scores to match them (1:1) with patients who received hepatoprotectants (the untreated group). Cumulative incidences of and hazard ratios (HRs) for ICC development were analyzed. RESULTS: The cumulative incidence of ICC was significantly lower in the treated group after 3 years of therapy (1.28%; 95% CI, 0.56-2.01) than in the untreated group (3.14%; 95% CI, 2.02-4.27) and after 5 years of therapy (1.53%; 95% CI, 0.73-2.33 vs 4.32% in untreated group; 95% CI, 2.96-5.6869). In multivariable regression analysis, nucleos(t)ide analogue therapy was independently associated with a reduced risk of ICC (HR, 0.44; 95% CI, 0.25-0.78; P = .005). Older age (HR 1.05 per year; 95% CI, 1.03-1.07) and cirrhosis (HR, 2.80; 95% CI, 1.52-5.1415) were independently associated with an increased risk of ICC. Sensitivity analyses verified the association between nucleos(t)ide analogue therapy and a reduced ICC risk. CONCLUSION: A nationwide long-term cohort study in Taiwan showed that nucleos(t)ide analogue therapy for chronic HBV infection is significantly associated with a reduced ICC risk.

The occurrence of hepatocellular carcinoma in different risk stratifications of clinically noncirrhotic nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) may be a cause of hepatocellular carcinoma (HCC), but its high prevalence challenges current surveillance strategies. We aimed to evaluate HCC incidences in different risk stratifications for noncirrhotic NAFLD. Using Taiwan's National Health Insurance Research Database, we located 31,571 patients with NAFLD between the years 1998 and 2012. After excluding other causes of hepatitis, underlying cirrhosis or malignancy, 18,080 patients were recruited for final analysis. Cumulative incidences of HCC were analyzed after adjusting for competing mortality. With a median follow-up duration of 6.32 years in the study cohort, the 10-year cumulative incidence of HCC was 2.73% [95% confidence interval (CI): 1.69-3.76%]. Hepatoprotectant was used as a surrogate marker for elevated serum alanine transaminase (ALT). After adjusting for age, gender, hypertension, hypercholesterolemia, diabetes mellitus, gout, statin use, metformin use and aspirin use, elevated ALT was independently associated with an increased HCC risk [hazard ratio (HR) 6.80, 95% CI: 3.00-15.42; p < 0.001]. Multivariate stratified analysis verified this association in all subgroups (HR> 1.0). Moreover, increased age (HR 1.08 per year, 95% CI: 1.05-1.11) and statin use (HR 0.29, 95% CI: 0.12-0.68) were also identified as independent risk factors. The 10-year cumulative HCC incidence was highest in older (age >55 years) patients with ALT elevation (12.41%, 95% CI: 5.99-18.83%), but lowest in younger patients without ALT elevation (0.36%, 95% CI: 0-1.08%). The incidence of HCC was relatively low in patients with clinically noncirrhotic NAFLD, however, HCC risk was significantly increased in older patients experiencing an elevated serum ALT.

Separation and purification of skeletal muscle satellite cells for tissue engineering applications by Percoll / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate separation and purification of skeletal muscle satellite cells with improved incontinuous density Percoll gradient centrifugation technique.</p><p><b>METHODS</b>The primary skeletal muscle satellite cells of New Zealand white rabbits were cultured with different adhesion time method and incontinuous density Percoll gradient centrifugation technique. The cells were observed under invert microscope and scanning electron microscope. The degree of purification was examined by celluar immunochemical stain. The growth curve was tested by thiazolyl blue assay.</p><p><b>RESULTS</b>Over 90% satellite cells were harvested by incontinuous density Percoll gradient centrifugation technique, in contrast to which, only 30%-40% cells were harvested by different adhesion time. Morphological observation accorded with satellite cells. The growth curve indicated that the cells grew in a good status.</p><p><b>CONCLUSION</b>The high purification satellite cells can be obtained by incontinuous density Percoll gradient centrifugation technique. It is a good method to culture seed cells for tissue engineering applications.</p>