[Value of autocrine motility factors in the prediction of the disease progression of PBC- associated hepatocellular carcinoma].

Objective: To clarify the value of autocrine motility factor (ATX) in predicting the disease progression of primary biliary cholangitis (PBC)-associated hepatocellular carcinoma (HCC). Methods: A prospective cohort of 179 newly diagnosed autoimmune liver disease (PBC) patients admitted to the Department of Hepatology at the Fifth Medical Center of the People's Liberation Army General Hospital from January 2016 to January 2018 was selected. All PBC patients received ursodeoxycholic acid (UDCA) treatment and were followed up.The endpoint of the follow-up was the occurrence of primary liver cancer. The relationship between ATX and the clinical characteristics of patients and its significance in predicting disease progression and HCC were analyzed. Results: The peripheral blood ATX level was significantly higher in PBC patients than that of alcoholic cirrhosis (t = 3.278, P = 0.001) and healthy controls (t = 6.594, P < 0.001), but there was no significant difference in ATX levels compared with patients with non-PBC- associated HCC (t = -0.240, P = 0.811). The expression of ATX in liver tissue of PBC patients was significantly higher than that of healthy individuals (Z = -3.633, P < 0.001) and patients with alcoholic cirrhosis (Z = -3.283, P < 0.001), while the expression of ATX in the advanced stage was significantly higher than that in early-stage PBC patients (Z = -2.018, P = 0.034). There was a significant difference in baseline ATX levels between PBC patients without HCC and PBC patients with HCC (228.451 ± 124.093 ng/ml vs. 301.583 ± 100.512 ng/ml, t = 2.339, P = 0.021). Multivariate logistic regression analysis showed that ATX was an independent predictor of PBC progression to HCC (OR = 1.245, 95%CI 1.097-1.413). The baseline peripheral blood ATX level in predicting AUROC of PBC-associated HCC was 0.714, 95%CI 0.597-0.857 and the sensitivity and specificity were 84.6%, and 59.0%, respectively. The optimal cutoff value for predicting serum ATX levels in the occurrence of HCC was 235.254 ng/ml. Conclusion: Patients with PBC have significantly higher levels of ATX expression in their peripheral blood and liver tissue, which can be utilized to assess treatment effectiveness and predict disease progression.

[Immune pathogenesis of primary biliary cholangitis].

Primary biliary cholangitis (PBC) is an autoimmune liver disease, mainly characterized by chronic progressive cholestasis. The root cause of PBC is the loss of immune tolerance to autoantigen E2 subunit of pyruvate dehydrogenase (PDC-E2). The unique immunobiological characteristics of intrahepatic bile duct epithelial cells make it an active participant in the pathogenesis of PBC. In recent years, the detection rate of PBC has been increasing year by year, but the clinical situation of ursodeoxycholic acid monotherapy has not changed. Therefore, an in-depth understanding of the immune pathogenesis of PBC will help clinicians better prevent and treat diseases.

Pigmentation Phenotype Prediction of Chinese Populations from Different Language Families.

ABSTRACT: Objective To predict the pigmentation phenotypes of Chinese populations from different language families, analyze the differences and provide reference data for forensic anthropology and genetics. Methods The HIrisPlex-S multiplex amplification system with 41 loci related to pigmentation phenotypes was constructed in the laboratory, and 2 666 DNA samples of adult males of 17 populations from six language families, including Indo-European, Sino-Tibetan, Altaic, Hmong-Mien, Tai-Kadai and Austro-Asiatic language families distributed in different regions of China were genotyped. The pigmentation phenotype category of each individual was predicted using the online prediction system （https://HIrisPlex.erasmusmc.nl/）, and then the output data were statistically analyzed. Results About 1.92% of the individuals of Asian-European admixed populations from Indo-European and Altaic language families had blue eyes and 34.29% had brown or gold hair. The phenotypes of the color of eyes and hair of other populations had no significant difference, all individuals had brown eyes and black hair. There were differences in skin color of populations of different language families and geographical areas. The Indo-European language family had the lightest skin color, and the Austro-Asiatic language family had the darkest skin color; the southwestern minority populations had a darker skin color than populations in the plain areas. Conclusion The prediction results of pigmentation phenotype of Chinese populations are consistent with the perception of the appearance of each population, proving the reliability of the system. The color of eyes and hair are mainly related to ancestral components, while the skin color shows the differences between language families, and is closely related to geographical distribution of populations.

Arabidopsis mutants resistant to S(+)-beta-methyl-alpha, beta-diaminopropionic acid, a cycad-derived glutamate receptor agonist.

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are the predominant neuroreceptors in the mammalian brain. Genes with high sequence similarity to animal iGluRs have been identified in Arabidopsis. To understand the role of Arabidopsis glutamate receptor-like (AtGLR) genes in plants, we have taken a pharmacological approach by examining the effects of BMAA [S(+)-beta-methyl-alpha, beta-diaminopropionic acid], a cycad-derived iGluR agonist, on Arabidopsis morphogenesis. When applied to Arabidopsis seedlings, BMAA caused a 2- to 3-fold increase in hypocotyl elongation and inhibited cotyledon opening during early seedling development. The effect of BMAA on hypocotyl elongation is light specific. Furthermore, BMAA effects on early morphogenesis of Arabidopsis can be reversed by the simultaneous application of glutamate, the native iGluR agonist in animals. To determine the targets of BMAA action in Arabidopsis, a genetic screen was devised to isolate Arabidopsis mutants with a BMAA insensitive morphology (bim). When grown in the light on BMAA, bim mutants exhibited short hypocotyls compared with wild type. bim mutants were grouped into three classes based on their morphology when grown in the dark in the absence of BMAA. Class-I bim mutants have a normal, etiolated morphology, similar to wild-type plants. Class-II bim mutants have shorter hypocotyls and closed cotyledons when grown in the dark. Class-III bim mutants have short hypocotyls and open cotyledons when grown in the dark, resembling the previously characterized constitutively photomorphogenic mutants (cop, det, fus, and shy). Further analysis of the bim mutants should help define whether plant-derived iGluR agonists target glutamate receptor signaling pathways in plants.

Micronuclei in esophageal cells of Chinese youths in a high-incidence area for esophageal cancer in China.

An epidemiologic survey among 538 young persons between 15 and 26 years of age in a high-risk area for esophageal cancer in the People's Republic of China revealed a high prevalence of esophagitis. Histologically confirmed very mild, mild, and moderate esophagitis was observed in 31.6%, 10.7%, and 1.1% of 354 male and 30.4%, 4.3%, and 1.1% of 184 female subjects. The prevalence of micronuclei in esophageal smears was assayed in a subsample to investigate its possible association with esophagitis and with risk factors for esophageal lesions. Of the 186 subjects, 2.7% had mild or moderate esophagitis, 19.9% had very mild esophagitis, and 77.4% were normal. The frequency distribution of micronucleated cells in the esophageal mucosa was similar for the three diagnostic groups. Mean percentages of micronucleated cells did not differ by diagnosis of esophagitis, household status, current smoking status, presence of oral leukoplakia, or consumption of burning hot beverages or fresh fruit. Higher mean percentages were observed in the older age group of both sexes, but the difference was not statistically significant. The results suggest that if esophagitis is considered an important precursor state in the development of esophageal cancer, the scoring of micronuclei does not appear to be an efficient test for mild forms of esophagitis.

An epidemiological study of precursor lesions of esophageal cancer among young persons in a high-risk population in Huixian, China.

The occurrence of chronic esophagitis, considered a precursor condition for esophageal cancer, among persons 15 to 26 yr of age and risk factors for the disease were investigated in Huixian, Henan Province, a high-risk area for esophageal cancer in the People's Republic of China. The 538 study subjects underwent an esophagoscopy with guided biopsies and cytology, a physical examination, an interview with a questionnaire including known and suspected risk factors for esophageal lesions, and collection of a 10-ml blood sample and overnight urine. One-third of the subjects was selected from households with a case of esophageal cancer in the past 6 yr and two-thirds came from control households. Histologically confirmed very mild, mild, and moderate esophagitis was observed in 31.6%, 10.7%, and 1.1% of 354 male and 30.4%, 4.3%, and 1.1% of 184 female subjects, respectively. In the multivariate case-control analysis of mile and moderate esophagitis compared with very mild esophagitis and normal subjects, the prevalence of mild and moderate disease was found to be positively associated with the consumption of burning hot beverages [odds ratio (OR) = 4.7], the prevalence of esophagitis among siblings (OR = 4.4), and family history of esophageal cancer (OR = 1.8) and negatively associated with the frequent consumption of fresh fruits (OR = 0.3) and wheat flour products (OR = 0.4). Weaker associations were seen for cigarette smoking and the use of cottonseed oil as the main cooking oil. Univariate associations seen with a clinical diagnosis of oral leukoplakia (OR = 2.7) and seborrheic dermatitis (OR = 3.7) are probably due to common risk factors such as smoking and nutritional deficiency. The present findings suggest that exposures early in life to environmental risk factors and nutritional deficiency may be responsible for inflammation and a weakened esophageal epithelium, resulting in a condition possibly more favorable for the development of esophageal cancer.

Precursor lesions of oesophageal cancer in young people in a high-risk population in China.

Young people (15-26 years) were selected from households in a population in China at high risk of oesophageal cancer on the basis of whether a case of oesophageal cancer had (166 participants) or had not (372 participants) occurred in a first-degree relative. In an endoscopic survey 43.5% of the male subjects and 35.9% of the female subjects showed histological signs of chronic oesophagitis. The presence of these precursor lesions was significantly associated in a multivariate logistic model with consumption of burning hot beverages, a family history of oesophageal cancer (including second-degree relatives), infrequent consumption of fresh fruit, and infrequent consumption of dietary staples other than maize.