[Random survival forest: applying machine learning algorithm in survival analysis of biomedical data].

Traditional survival methods have a wide application in the field of biomedical research. However, applying traditional survival methods requires data to meet a set of special assumptions while the Random Survival Forest model can overcome this inconvenience. Herein, we used the clinical data of Primary Biliary Cholangitis (PBC) from Mayo Clinic to introduce and demonstrate Random Survival Forest model from mathematical principles, model building, practical example and attentions, aiming to provide a novel method for doing survival analysis.

[Urine proteomics signatures associated with alcohol drinking among residents attending the National Upper Gastrointestinal Cancer Early Detection Program in Linqu, Shandong province].

The liquid chromatography tandem mass spectrometry was used to detect the urinary proteomics of 223 residents aged 40-69 years old who participated in the National Upper Gastrointestinal Cancer Early Detection Program in Linqu County, Shandong Province from November 22 to December 7, 2018, and analyze the alcohol consumption related proteomic profiles and individual urinary protein. There were significant differences in urinary protein profiles between alcohol consumption group and non-alcohol consumption group. The expression of 26 urinary proteins was up-regulated and 20 urinary proteins were down-regulated in alcohol consumption group (P<0.05). The differentially expressed proteins had enzyme inhibitor activity and phospholipid binding function, and mainly enriched in pathways involving proximal tubule bicarbonate regeneration, complement and coagulation cascade, and cholesterol metabolism. The protein expressions of complement factor I (CFI), angiotensin converting enzyme 2 (ACE2) and protein C inhibitor (SERPINA5) were positively correlated with daily alcohol consumption.

Spectral broadening in femtosecond pulse written filamentary waveguides in periodically poled lithium niobate.

The authors report the filamentary waveguide formation and the significant spectral broadening based on periodically poled lithium niobate substrate. The modified morphology contributes to the combined effects of optical diffraction and self-focusing with the dependence on pulse intensity. Up to 4 times broadening of the FF wave and about 47 nm spanning of the SH wave with the pump power of 19.5 mW are achievable under 1550 nm excitation. Spectral evolution by cubic nonlinearity inside the waveguide has been obtained numerically, and provides a reasonable agreement with the experimental results.

[The risk of incident gastric cancer for populations with different precancerous gastric lesions: a prospective follow-up study].

Objective: To provide evidence for optimizing the screening strategy for gastric cancer (GC), we evaluated the risk of incident GC for individuals with different precancerous gastric lesions in a prospective cohort study. Methods: Based on the National Upper Gastrointestinal Cancer Early Detection Program launched in Linqu, Shandong, a high-risk area of gastric cancer in China, we included a total of 14 087 subjects diagnosed with different gastric lesions stages by endoscopic screening from 2012 to 2018. Study subjects were prospectively followed up until December 31, 2019. The incidence of GC during the follow-up was ascertained by repeated endoscopic examinations, cancer, death registry reports, and active follow-up of study subjects and was confirmed by reviewing medical records extracted from the hospital information management system. The Poisson regression model was applied to calculate the relative risk (RR) and 95%CI for GC occurrence among subjects with different gastric lesions. Results: Among 14 087 subjects with different gastric lesions as determined by their first endoscopic examination in 2012-2018, 7 608 (54.00%) had a global diagnosis of superficial gastritis (SG), 2 848 (20.22%) had chronic atrophic gastritis (CAG), 3 103 (22.03%) had intestinal metaplasia (IM), and 520 (3.69%) had low-grade intestinal neoplasia (LGIN). During the follow-up, 109 subjects were diagnosed with GC, including 63 with high-grade intestinal neoplasia (HGIN) and 46 with invasive GC. Compared to subjects having normal gastric mucosa or SG, those with CAG (RR=3.85, 95%CI: 2.04-7.28), IM (RR=5.18, 95%CI: 2.79-9.60), and LGIN (RR=19.08, 95%CI: 9.97-36.53) had significantly increased risk of progression to GC. Individuals with these gastric lesions had an elevated risk of developing HGIN and invasive GC. For subjects with LGIN, the RR was 22.96 (95%CI: 9.71-54.27) for developing HGIN and 14.64 (95%CI: 5.37-39.93) for developing invasive GC. Subgroup analyses found that all age group subjects with LGIN diagnosed during the initial endoscopic examination had a significantly increased risk of developing the GC. Conclusions: Our large-scale prospective study on a high-risk area of GC showed that most residents aged 40-69 years had gastric lesions of different stages. Subjects with more advanced gastric lesions had a significantly increased risk of progression to GC.

Allium vegetables and reduced risk of stomach cancer.

Interviews with 564 patients with stomach cancer and 1,131 controls in an area of China where gastric cancer rates are high revealed a significant reduction in gastric cancer risk with increasing consumption of allium vegetables. Persons in the highest quartile of intake experienced only 40% of the risk of those in the lowest. Protective effects were seen for garlic, onions, and other allium foods. Although additional research is needed before etiologic inferences can be made, the findings are consistent with recent reports of tumor inhibition following administration of allium compounds in experimental animals.

Cigarette smoking and other risk factors for progression of precancerous stomach lesions.

BACKGROUND: Stomach cancer is generally thought to evolve through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. PURPOSE: Our purpose was to assess risk factors for intestinal metaplasia and gastric dysplasia arising from chronic atrophic gastritis in a general population at high risk for stomach cancer. METHODS: A population-based gastroscopic screening of more than 3000 residents was conducted in a county in China with one of the world's highest rates of stomach cancer. Information on the lifestyle and other characteristics of the participants was obtained by interview, and responses were compared between those in whom the most advanced gastric lesion was dysplasia or intestinal metaplasia versus those with chronic atrophic gastritis. RESULTS: Cigarette smoking was found to nearly double the risk of transition to dysplasia and to be a mild risk factor for intestinal metaplasia. Smoking accounted almost entirely for the 55% higher prevalence of dysplasia among men than among women. Risk of transition to dysplasia had a weak association with several dietary factors and was increased among those participants with a family history of stomach cancer and with blood type A. CONCLUSIONS: The findings provide strong evidence for a role of tobacco consumption and offer clues to other environmental and genetic factors involved in the process of gastric carcinogenesis.

Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors.

BACKGROUND: Gastric cancer is generally thought to arise through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. To identify such determinants, we launched a follow-up study in 1989-1990 among 3433 adults in Linqu County, China, a region with very high rates of gastric cancer. METHODS: Data on cigarette smoking, alcohol consumption, and other characteristics of the participants were obtained by interview in 1989-1990, when an initial endoscopy was taken. At study entry, antibodies to Helicobacter pylori were assayed in 2646 adults (77% of people screened), and levels of serum micronutrients were measured in approximately 450 adults. Follow-up endoscopic and histopathologic examinations were conducted in 1994. Antibodies to H. pylori, levels of serum micronutrients, and other baseline characteristics were compared between subjects whose condition showed progression to dysplasia or gastric cancer from study entry to 1994 and subjects with no change or with regression of their lesions over the same time frame. All P: values are two-sided. RESULTS: The presence of H. pylori at baseline was associated with an increased risk of progression to dysplasia or gastric cancer (odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.2-2.6). The risk of progression to dysplasia or gastric cancer also was moderately increased with the number of years of cigarette smoking. In contrast, the risk of progression was decreased by 80% (OR = 0.2; 95% CI = 0.1-0.7) among subjects with baseline ascorbic acid levels in the highest tertile compared with those in the lowest tertile, and there was a slightly elevated risk in those individuals with higher levels of alpha-tocopherol. CONCLUSIONS: H. pylori infection, cigarette smoking, and low levels of dietary vitamin C may contribute to the progression of precancerous lesions to gastric cancer in this high-risk population.

Diet and high risk of stomach cancer in Shandong, China.

A case-control investigation involving interviews with 564 stomach cancer patients and 1131 population-based controls was conducted to evaluate reasons for the exceptionally high rates of stomach cancer in Linqu, a rural county in Shandong Province in northeast China. Daily consumption of sour pancakes, a fermented indigenous staple, was associated with a 30% increase in risk. Risks of stomach cancer were also increased by 2- to 3-fold among persons with prior chronic gastritis or gastric ulcer, by 80% among those with stomach cancer in a family member, by 50% among men who smoked one or more packs of cigarettes/day, by 40% among those who preferred salty foods, and by 50% among families with moldy grain supplies. In contrast, risks tended to decrease in proportion to increasing consumption of fresh vegetables and fruits. This protective effect was more pronounced for vegetables, with those in the highest quartile of intake at less than one-half the risk of those in the lowest. Stomach cancer risks also declined with increasing dietary intake of carotene, vitamin C, and calcium, but not retinol. These findings provide leads to dietary factors that contribute to the high rates in Linqu, where stomach cancer is the leading cause of cancer and has not yet begun to decline as in other parts of the world.

Precancerous gastric lesions in a population at high risk of stomach cancer.

A population-based screening for detection of early cancers evaluated the prevalence of precancerous gastric lesions in an area in Shandong province, China, with one of the world's highest rates of stomach cancer. A total of 3433 residents aged 35 to 64 yr received gastroscopical examinations with biopsies taken from standard locations. Chronic atrophic gastritis was nearly universal; less than 2% of the population had biopsies showing entirely normal mucosa or only superficial gastritis. Intestinal metaplasia was the most advanced lesion for 33% and gastric dysplasia for 20%, although the prevalence of each increased significantly with age. Intestinal metaplasia and gastric dysplasia were detected throughout the stomach, but the lesions were more pronounced along the lesser curvature, especially in the angulus and antrum. There was no sex difference in rates of chronic atrophic gastritis, but males had a slightly higher prevalence of intestinal metaplasia, a 1.6-fold increase in dysplasia, and a 3-fold excess of gastric cancer. The data quantify the extensiveness of gastric lesions likely to be involved in the natural history of stomach cancer in this high-risk population.

Comparison of two enzyme-linked immunosorbent assay tests for diagnosis of Helicobacter pylori infection in China.

An ELISA based on a pool of United States strains of Helicobacter pylori was compared with a newly developed ELISA based on a pool of Chinese strains. Both assays were tested using sera from 132 Chinese study subjects with biopsy-proven H. pylori infection. Using cutpoints designed to yield equal specificities of 94.9% in an uninfected control population, the sensitivity of the Chinese assay was 100.0%, compared to 97.7% for the United States assay (P = 0.25 by McNemar test). These results suggest that a H. pylori assay based on pooled antigens from United States strains will perform as well in the rural Chinese population as one based on antigens from Chinese strains.

Familial predisposition to precancerous gastric lesions in a high-risk area of China.

Aggregation of intestinal metaplasia and dysplasia was investigated among families participating in a population-based gastroscopic screening survey in an area of China with one of the world's highest rates of stomach cancer. The prevalence of gastric dysplasia was significantly increased among those with dysplasia among siblings or spouses, but not parents. The odds of dysplasia were nearly doubled if an eldest brother or a spouse was affected. Sibling and spousal associations for intestinal metaplasia were much less pronounced and not statistically significant. The specificity of the findings suggests that familial risk of advanced precancerous lesions (dysplasia) is influenced not only by genetic factors, but also by environmental factors operating in childhood and early adult life.

Serum pepsinogens in relation to precancerous gastric lesions in a population at high risk for gastric cancer.

Concentrations of serum pepsinogens (PG) I and II were determined for 3252 randomly selected adults who participated in a population-based gastroscopic screening in an area of China with one of the world's highest rates of gastric cancer. PG I and II concentrations in both sexes tended to be higher than reported in other countries, with levels generally higher among males than females. PG I tended to decrease and PG II to increase with age, but the most pronounced associations were between PG I:II ratios and gastric histology. Median PG I:II ratios monotonically declined from 9.1 to 7.2 to 5.7 to 5.4 to 3.8 among those with superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia, and stomach cancer, respectively. The prevalence of dysplasia was nearly 3 times greater among those with PG I:II ratios less than 3 compared with those whose PG I:II ratios were greater than 10. While average levels differed significantly among the histologic groups, the PG I:II ratios were neither sensitive nor specific markers of an individual's likelihood of advanced gastric lesions in this population.

Helicobacter pylori antibodies in relation to precancerous gastric lesions in a high-risk Chinese population.

Helicobacter pylori infection is a major cause of gastritis and may be a key risk factor for stomach cancer, but its role in the process of gastric carcinogenesis is not well understood. Herein, we examine H. pylori prevalence in relation to demographic and lifestyle factors and to severity of precancerous lesions in an area of China with one of the highest rates of stomach cancer in the world. H. pylori serum IgG antibody positivity was assayed among 2646 adults, ages 35-64, participating in a population-based gastroscopic screening survey in the high-risk area. The prevalence of positivity was evaluated according to gastric histology, environmental and lifestyle variables determined by interviews during the screening, and level of serum pepsinogens. The odds of advanced precancerous lesions (intestinal metaplasia and dysplasia) of the stomach among those with antibody positivity were estimated by logistic regression. Seventy-two % of the population was H. pylori antibody-positive, with nonsignificant variation by sex, age, income, education, family size, and cigarette smoking habits. H. pylori positivity was higher among those who ate sour pancakes, a fermented indigenous staple that is a risk factor for gastric dysplasia and stomach cancer in this population. The prevalence of H. pylori varied most notably, however, with gastric pathology. The percent of H. pylori positivity increased from 55 to 60 to 87% among those with superficial (nonatrophic) gastritis, mild chronic atrophic gastritis, and severe chronic atrophic gastritis, respectively, before falling to 78% among those with intestinal metaplasia or dysplasia. H. pylori antibody positivity also was strongly correlated with serum pepsinogen concentrations, particularly pepsinogen II, but knowledge of H. pylori status did not markedly improve serological identification of advanced precancerous lesions above that provided by pepsinogen ratios alone. The findings suggest that H. pylori infection contributes to the process of gastric carcinogenesis, particularly during the early stages, in this high-risk area.

Nitrite, N-nitroso compounds, and other analytes in physiological fluids in relation to precancerous gastric lesions.

Levels of gastric juice nitrite, several urinary N-nitroso compounds, and other analytes were examined among nearly 600 residents in an area of Shandong, China, where precancerous gastric lesions are common and rates of stomach cancer are among the world's highest. Gastric juice nitrite levels were considerably higher among those with gastric juice pH values above 2.4 versus below 2.4. Nitrite was detected more often and at higher levels among persons with later stage gastric lesions, especially when gastric pH was high. Of those with intestinal metaplasia, 17.5% had detectable levels of gastric nitrite, while this analyte was detected in only 7.2% of those with less advanced lesions. Relative to those with undetectable nitrite, the odds of intestinal metaplasia increased from 1.5 (95% confidence interval = 0.6-4.1) to 4.1 (95% confidence interval = 1.8-9.3) among those with low and high nitrite concentrations, respectively. Urinary acetaldehyde and formaldehyde levels also tended to be higher among those with more advanced pathology, particularly dysplasia. However, urinary excretion levels of total N-nitroso compounds and several nitrosamino acids differed little among those with chronic atrophic gastritis and intestinal metaplasia and dysplasia, consistent with findings from recent studies in the United Kingdom, France, and Colombia. The data from this high-risk population suggest that elevated levels of gastric nitrite, especially in a high pH environment, are associated with advanced precancerous gastric lesions, although specific N-nitroso compounds were not implicated.

Helicobacter pylori prevalence and CagA status among children in two counties of China with high and low risks of gastric cancer.

BACKGROUND: Studies in adult populations in selected countries with widely varying rates of gastric cancer have shown a weak correlation between gastric cancer mortality rates and the prevalence of CagA+ strains of H. pylori. However, only limited data are available in ethnically homogenous populations with varying rates in the same region. METHODS; We compared the prevalence of H. pylori in general and of CagA+ strains in particular among children in Shandong Province, China in areas at high (Linqu County) and low risk (Cangshan County) of gastric cancer. H. pylori status among children aged 3 to 12 years was determined by 13C-UBT, and CagA status was determined by enzyme-linked immunosorbent assay (ELISA). Because of the difficulty in obtaining blood from young children aged 3 to 4 years and from some children aged 5 years, CagA status was determined among part of children 5 years old and children 6 to 12 years old. RESULTS; Among 98 children aged 3 to 12 years in Linqu, 68 (69.4%) was H. pylori-positive, as compared with 29 (28.7%) among 101 children in Cangshan. Among children positive for 13C-UBT, the proportion of the CagA+ strains were identified was 46 (88.5%) of 52 in Linqu and 13 (81.3%) of 16 in Cangshan, respectively. CONCLUSIONS: The prevalence of H. pylori was nearly three times higher among children in Linqu than in Cangshan, which may contribute to the large differential in gastric cancer rates for two neighboring populations in Shandong Province.

Possible contribution from epidemiological studies.

The problem of chemically contaminated water supplies are in general terms followed by a description of three examples of water supply problems in China. A large-scale prospective epidemiological study, now in the early planning stages, to be carried out in China is also described.

Blood type and family cancer history in relation to precancerous gastric lesions.

BACKGROUND: The increased odds of stomach cancer among subjects with blood type A have been reported in epidemiological studies. AIM: To study the relation of family history of gastric cancer and ABO blood type with precancerous gastric lesions in a high-risk area for stomach cancer. Subjects and setting We examined 3400 adults aged 35-64 in a population-based gastric endoscopic screening in a county in China with one of the highest rates of stomach cancer in the world. METHODS: In this cross-sectional study, data on family cancer history, ABO blood type and other characteristics of the participants were obtained by interview and blood test. Responses were compared between those with the most advanced gastric lesions, dysplasia (DYS) or intestinal metaplasia (IM), versus those with chronic atrophic gastritis (CAG) or superficial gastritis (SG). RESULTS: The prevalence odds ratio (OR) for blood type A relative to other types was 1.39 (95% CI : 1.12-1.73) for DYS and 1.28 (95% CI : 1.06-1.53) for IM. The OR associated with parental history of stomach cancer was 1.88 (95% CI : 1.20-2.95) for DYS, but the numbers were too small to evaluate aggregation among siblings. The combined OR associated with blood type A and a parental of history of gastric cancer was 2.61 (95% CI : 1.59-4.30) for DYS and 1.46 (95% CI : 0.93-2.31) for IM. CONCLUSIONS: The findings suggest that genetic factors play a role in developing precancerous gastric lesions.

Helicobacter pylori infection and mode of transmission in a population at high risk of stomach cancer.

BACKGROUND: Helicobacter pylori (H. pylori) is a recognized cause of chronic gastritis and peptic ulcer disease, and is strongly suspected to play a role in the aetiology of stomach cancer but little is known about the mode of transmission. AIM: To determine the prevalence of H. pylori infection in children and investigate potential modes of transmission in rural China. SUBJECTS AND SETTING: We examined 98 children aged 3-12 years and 289 adults aged 35-64 years in a village in Linqu County, China, which has one of the highest rates of stomach cancer in the world. METHOD: H. pylori infection was determined by 13C-urea breath test in children and by an enzyme-linked immunosorbent assay in adults. RESULTS: Among 98 tested children, 68 (69%) were H. pylori positive, but the prevalence rates varied as a function of age, rising from about 50% at ages 3-4 to 85% at ages 9-10 before falling to 67% at ages 11-12. Boys had a higher infection rate than girls (77.8% versus 59.1%, P < 0.05). Among 289 adults, 195 (68%) were H. pylori positive, with a somewhat higher rate of positivity in younger compared to older age groups. The prevalence of H. pylori infection clustered within families. In families with at least one infected parent, 85% of children were H. pylori positive, while in families with both parents uninfected, only 22% of children were H. pylori positive (odds ratio [OR] = 30.4, 95% CI : 4.0-232). CONCLUSIONS: These findings demonstrate the acquisition of H. pylori infection during early childhood in a population at high risk of stomach cancer, in a manner consistent with a person-to-person mode of transmission between parents and children.

Helicobacter pylori infection, garlic intake and precancerous lesions in a Chinese population at low risk of gastric cancer.

BACKGROUND: Cangshan County of Shandong Province has one of the lowest rates of gastric cancer (GC) in China. While intestinal metaplasia (IM) and dysplasia (DYS) are less common in Cangshan than in areas of Shandong at high risk of GC, these precursor lesions nevertheless affect about 20% of adults age > or = 55. SUBJECTS AND SETTING: In order to evaluate determinants of IM and DYS in Cangshan County, a low risk area of GC a survey was conducted among 214 adults who participated in a gastroscopic screening survey in Cangshan County in 1994. METHOD: A dietary interview and measurement of serum Helicobacter pylori antibodies were performed. RESULTS: The prevalence of H. pylori was lowest (19%) among those with normal gastric mucosa, rising steadily to 35% for superficial gastritis (SG), 56% for chronic atrophic gastritis (CAG), 80% for IM, and 100% for DYS. The prevalence odds of precancerous lesions were compared with the odds of normal histology or SG. The odds ratio (OR) or CAG associated with H. pylori positivity was 4.2 (95% confidence interval [CI] : 1.7-10.0), while the OR of IM/DYS associated with H. pylori positivity was 31.5 (95% CI: 5.2-187). After adjusting for H. pylori infection, drinking alcohol was a risk factor for CAG (OR = 3.2, 95% CI: 1.1-9.2) and IM/DYS (OR = 7.8, 95% CI: 1.3-47.7). On the other hand, consumption of garlic showed non-significant protective effects and an inverse association with H. pylori infection. CONCLUSIONS: The findings of this study suggest that infection with H. pylori is a risk factor and garlic may be protective, in the development and progression of advanced precancerous gastric lesions in an area of China at relatively low risk of GC.

Precancerous lesions in two counties of China with contrasting gastric cancer risk.

BACKGROUND: Gastric cancer (GC) is one of the most common cancers worldwide and shows remarkable geographical variation even within countries such as China. Linqu County in Shandong Province of northeast China has a GC rate that is 15 times higher than that of Cangshan County in Shandong, even though these counties are within 200 miles of each other. METHOD: In order to evaluate the frequency of precancerous gastric lesions in Linqu and Cangshan Counties we examined 3400 adults in Linqu County and 224 adults in Cangshan County. An endoscopic examination with four biopsies was performed in each individual of the two populations. RESULTS: The prevalence of intestinal metaplasia (IM) and dysplasia (DYS) was 30% and 15.1%, respectively, in Linqu compared to 7.9% and 5.6% in Cangshan (P < 0.01). Within these histological categories, advanced grades were found more often in Linqu than in Cangshan. The prevalences of IM and DYS were more common at each biopsy site in Linqu, where the lesions also tended to affect multiple sites. CONCLUSIONS: The findings of this study support the concept that IM and DYS are closely correlated with risks of GC and represent late stages in the multistep process of gastric carcinogenesis.