BACKGROUND: Optical coherence tomography (OCT) is widely used in ophthalmology for viewing the morphology of the retina, which is important for disease detection and assessing therapeutic effect. The diagnosis of retinal diseases is based primarily on the subjective analysis of OCT images by trained ophthalmologists. This paper describes an OCT images automatic analysis method for computer-aided disease diagnosis and it is a critical part of the eye fundus diagnosis. METHODS: This study analyzed 300 OCT images acquired by Optovue Avanti RTVue XR (Optovue Corp., Fremont, CA). Firstly, the normal retinal reference model based on retinal boundaries was presented. Subsequently, two kinds of quantitative methods based on geometric features and morphological features were proposed. This paper put forward a retinal abnormal grading decision-making method which was used in actual analysis and evaluation of multiple OCT images. RESULTS: This paper showed detailed analysis process by four retinal OCT images with different abnormal degrees. The final grading results verified that the analysis method can distinguish abnormal severity and lesion regions. This paper presented the simulation of the 150 test images, where the results of analysis of retinal status showed that the sensitivity was 0.94 and specificity was 0.92.The proposed method can speed up diagnostic process and objectively evaluate the retinal status. CONCLUSIONS: This paper aims on studies of retinal status automatic analysis method based on feature extraction and quantitative grading in OCT images. The proposed method can obtain the parameters and the features that are associated with retinal morphology. Quantitative analysis and evaluation of these features are combined with reference model which can realize the target image abnormal judgment and provide a reference for disease diagnosis.

• MeSH
• Diagnosis, Computer-Assisted MeSH
• Adult MeSH
• Fundus Oculi MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Tomography, Optical Coherence * MeSH
• Image Processing, Computer-Assisted * MeSH
• Signal-To-Noise Ratio MeSH
• Retina diagnostic imaging   MeSH
• Decision Making MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH

The contraction of gastrointestinal (GI) smooth muscles is regulated by both Ca(2+)-dependent and Ca(2+) sensitization mechanisms. Proline-rich tyrosine kinase 2 (Pyk2) is involved in the depolarization-induced contraction of vascular smooth muscle via a Ca(2+) sensitization pathway. However, the role of Pyk2 in GI smooth muscle contraction is unclear. The spontaneous contraction of colonic smooth muscle was measured by using isometric force transducers. Protein and phosphorylation levels were determined by using western blotting. Pyk2 protein was expressed in colonic tissue, and spontaneous colonic contractions were inhibited by PF-431396, a Pyk2 inhibitor, in the presence of tetrodotoxin (TTX). In cultured colonic smooth muscle cells (CSMCs), PF-431396 decreased the levels of myosin light chain (MLC20) phosphorylated at Ser19 and ROCK2 protein expression, but myosin light chain kinase (MLCK) expression was not altered. However, Y-27632, a Rho kinase inhibitor, increased phosphorylation of Pyk2 at Tyr402 and concomitantly decreased ROCK2 levels; the expression of MLCK in CSMCs did not change. The expression of P(Tyr402)-Pyk2 and ROCK2 was increased when CSMCs were treated with Ach. Pyk2 is involved in the process of colonic smooth muscle contraction through the RhoA/ROCK pathway. These pathways may provide very important targets for investigating GI motility disorders.

• MeSH
• Cell Culture Techniques MeSH
• Focal Adhesion Kinase 2 antagonists & inhibitors   biosynthesis   MeSH
• Muscle, Smooth drug effects   metabolism   MeSH
• Enzyme Inhibitors pharmacology   MeSH
• rho-Associated Kinases biosynthesis   MeSH
• Colon drug effects   metabolism   MeSH
• Mice, Inbred ICR MeSH
• Mice MeSH
• Organ Culture Techniques MeSH
• rho GTP-Binding Proteins biosynthesis   MeSH
• Signal Transduction drug effects   physiology   MeSH
• Muscle Contraction drug effects   physiology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The human Y-chromosome has proven to be a powerful tool for tracing the paternal history of human populations and genealogical ancestors. The human Y-chromosome haplogroup Q is the most frequent haplogroup in the Americas. Previous studies have traced the origin of haplogroup Q to the region around Central Asia and Southern Siberia. Although the diversity of haplogroup Q in the Americas has been studied in detail, investigations on the diffusion of haplogroup Q in Eurasia and Africa are still limited. In this study, we collected 39 samples from China and Russia, investigated 432 samples from previous studies of haplogroup Q, and analyzed the single nucleotide polymorphism (SNP) subclades Q1a1a1-M120, Q1a2a1-L54, Q1a1b-M25, Q1a2-M346, Q1a2a1a2-L804, Q1a2b2-F1161, Q1b1a-M378, and Q1b1a1-L245. Through NETWORK and BATWING analyses, we found that the subclades of haplogroup Q continued to disperse from Central Asia and Southern Siberia during the past 10,000 years. Apart from its migration through the Beringia to the Americas, haplogroup Q also moved from Asia to the south and to the west during the Neolithic period, and subsequently to the whole of Eurasia and part of Africa.

• MeSH
• Phylogeny MeSH
• Haplotypes genetics   MeSH
• Polymorphism, Single Nucleotide MeSH
• Humans MeSH
• Chromosomes, Human, Y genetics   MeSH
• Human Migration * MeSH
• Microsatellite Repeats genetics   MeSH
• Genetics, Population * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Asia MeSH
• China MeSH
• Siberia MeSH

In addition to Helicobacter pylori (H.pylori), gastric microbiota may be involved in carcinogenesis process. However, the longitudinal study to assess changes in the gastric microbiota associated with the development of gastric carcinogenesis is still limited. The aim of this study is to explore dynamic microbial alterations in gastric cancer (GC) development based on a 4-year endoscopic follow-up cohort in Linqu County, China. Microbial alterations were investigated by deep sequencing of the microbial 16S ribosomal RNA gene in 179 subjects with various gastric lesions, and validated in paired gastric biopsies prospectively collected before and after lesion progression and in non-progression controls. Significant differences were found in microbial diversity and community structure across various gastric lesions, with 62 candidate differential taxa between at least two lesion groups. Further validations identified Helicobacter, Bacillus, Capnocytophaga and Prevotella to be associated with lesion progression-to-dysplasia (DYS)/GC (all P < 0.05), especially for subjects progressing from intestinal metaplasia (IM) to DYS/GC. The combination of the four genera in a microbial dysbiosis index showed a significant difference after lesion progression-to-DYS/GC compared to controls (P = 0.027). The panel including the four genera identified subjects after progression-to-DYS/GC with an area under the receiver-operating curve (AUC) of 0.941. Predictive significance was found before lesion progression-to-DYS/GC with an AUC = 0.776 and an even better AUC (0.927) for subjects progressing from IM to DYS/GC. Microbiota may play different roles at different stages in gastric carcinogenesis. A panel of bacterial genera associated with gastric lesions may help to assess gastric microbial dysbiosis and show potential predictive values for lesion progression. Our findings provide new clues for the microbial mechanism of H.pylori-associated carcinogenesis.

• Publication type
• Journal Article MeSH

OBJECTIVE: Gastrointestinal microbiota may be involved in Helicobacter pylori-associated gastric cancer development. The aim of this study was to explore the possible microbial mechanisms in gastric carcinogenesis and potential dysbiosis arising from H. pylori infection. DESIGN: Deep sequencing of the microbial 16S ribosomal RNA gene was used to investigate alterations in paired gastric biopsies and stool samples in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment, relative to 49 H. pylori negative subjects. RESULTS: In H. pylori positive subjects, richness and Shannon indexes increased significantly (both p<0.001) after successful eradication and showed no difference to those of negative subjects (p=0.493 for richness and p=0.420 for Shannon index). Differential taxa analysis identified 18 significantly altered gastric genera after eradication. The combination of these genera into a Microbial Dysbiosis Index revealed that the dysbiotic microbiota in H. pylori positive mucosa was associated with advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia/dysplasia) and could be reversed by eradication. Strong coexcluding interactions between Helicobacter and Fusobacterium, Neisseria, Prevotella, Veillonella, Rothia were found only in advanced gastric lesion patients, and were absent in normal/superficial gastritis group. Changes in faecal microbiota included increased Bifidobacterium after successful H. pylori eradication and more upregulated drug-resistant functional orthologs after failed treatment. CONCLUSION: H. pylori infection contributes significantly to gastric microbial dysbiosis that may be involved in carcinogenesis. Successful H. pylori eradication potentially restores gastric microbiota to a similar status as found in uninfected individuals, and shows beneficial effects on gut microbiota.

• MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• Biopsy methods   MeSH
• Dysbiosis * diagnosis   microbiology   MeSH
• Feces microbiology   MeSH
• Gastritis, Atrophic * microbiology   pathology   MeSH
• Helicobacter pylori * isolation & purification   pathogenicity   MeSH
• Helicobacter Infections * drug therapy   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Metaplasia microbiology   pathology   MeSH
• Microbial Interactions MeSH
• Stomach Neoplasms * microbiology   pathology   MeSH
• RNA, Ribosomal, 16S isolation & purification   MeSH
• Gastrointestinal Microbiome genetics   MeSH
• Gastric Mucosa microbiology   pathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Eradication of Helicobacter pylori has been found to be effective for gastric cancer prevention, but uncertainties remain about the possible adverse consequences such as the potential microbial dysbiosis. In our study, we investigated the association between gut microbiota and H. pylori-related gastric lesions in 47 subjects by deep sequencing of microbial 16S ribosomal RNA (rRNA) gene in fecal samples. The dominant phyla in fecal samples were Bacteroidetes, Firmicutes, and Proteobacteria with average relative abundances of 54.77, 31.37 and 12.91%, respectively. Microbial diversity analysis showed that observed species and Shannon index were increased in subjects with past or current H. pylori infection compared with negative subjects. As for the differential bacteria, the average relative abundance of Bacteroidetes was found to significantly decrease from H. pylori negative (66.16%) to past infection group (33.01%, p = 0.007), as well as from normal (76.49%) to gastritis (56.04%) and metaplasia subjects (46.83%, p = 0.027). For Firmicutes and Proteobacteria, the average relative abundances showed elevated trends in the past H. pylori infection group (47.11, 20.53%) compared to negative group (23.44, 9.05%, p = 0.068 and 0.246, respectively), and similar increased trends were also found from normal (18.23, 5.05%) to gastritis (35.31, 7.23%, p = 0.016 and 0.294, respectively) or metaplasia subjects (32.33, 20.07%, both p < 0.05). These findings suggest that the alterations of fecal microbiota, especially the dominant phyla of Bacteroidetes, Firmicutes and Proteobacteria, may be involved in the process of H. pylori-related gastric lesion progression and provide hints for future evaluation of microbial changes after H. pylori eradication.

• MeSH
• DNA, Bacterial genetics   MeSH
• Adult MeSH
• Dysbiosis microbiology   pathology   MeSH
• Feces microbiology   MeSH
• Gastritis microbiology   pathology   MeSH
• Helicobacter pylori genetics   MeSH
• Helicobacter Infections diagnosis   microbiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Metaplasia microbiology   pathology   MeSH
• Stomach Neoplasms microbiology   pathology   MeSH
• Aged MeSH
• Gastrointestinal Microbiome genetics   MeSH
• Gastric Mucosa microbiology   pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVE: To clarify the full range of benefits and adverse consequences of Helicobacter pylori eradication as a strategy for gastric cancer prevention, the community-based intervention trial was launched in Linqu County, China. DESIGN: A total of 184,786 residents aged 25-54 years were enrolled in this trial and received (13)C-urea breath test. H. pylori positive participants were assigned into two groups, either receiving a 10-day quadruple anti-H. pylori treatment or lookalike placebos together with a single dosage of omeprazole and bismuth. RESULTS: The prevalence of H. pylori in trial participants was 57.6%. A total of 94,101 subjects completed the treatment. The overall H. pylori eradication rate was 72.9% in the active group. Gender, body mass index, history of stomach disease, baseline delta over baseline-value of (13)C-urea breath test, missed medication doses, smoking and drinking were independent predictors of eradication failure. The missed doses and high baseline delta over baseline-value were important contributors in men and women (all Ptrend<0.001). However, a dose-response relationship between failure rate and smoking or drinking index was found in men (all Ptrend<0.001), while high body mass index (Ptrend<0.001) and history of stomach disease were significant predictors in women. The treatment failure rate increased up to 48.8% (OR 2.87, 95% CI 2.24 to 3.68) in men and 39.4% (OR 2.67, 95% CI 1.61 to 4.42) in women with multiple factors combined. CONCLUSIONS: This large community-based intervention trial to eradicate H. pylori is feasible and acceptable. The findings of this trial lead to a distinct evaluation of factors influencing eradication that should be generally considered for future eradication therapies. TRIAL REGISTRATION NUMBER: ChiCTR-TRC-10000979 in accordance with WHO ICTRP requirements.

• MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Helicobacter pylori * MeSH
• Helicobacter Infections complications   diagnosis   drug therapy   MeSH
• Drug Therapy, Combination MeSH
• Middle Aged MeSH
• Humans MeSH
• Metronidazole therapeutic use   MeSH
• Stomach Neoplasms microbiology   prevention & control   MeSH
• Prospective Studies MeSH
• Anti-Ulcer Agents therapeutic use   MeSH
• Tetracycline therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• China MeSH

The performance of diagnostic tests in intervention trials of Helicobacter pylori (H.pylori) eradication is crucial, since even minor inaccuracies can have major impact. To determine the cut-off point for 13C-urea breath test (13C-UBT) and to assess if it can be further optimized by serologic testing, mathematic modeling, histopathology and serologic validation were applied. A finite mixture model (FMM) was developed in 21,857 subjects, and an independent validation by modified Giemsa staining was conducted in 300 selected subjects. H.pylori status was determined using recomLine H.pylori assay in 2,113 subjects with a borderline 13C-UBT results. The delta over baseline-value (DOB) of 3.8 was an optimal cut-off point by a FMM in modelling dataset, which was further validated as the most appropriate cut-off point by Giemsa staining (sensitivity = 94.53%, specificity = 92.93%). In the borderline population, 1,468 subjects were determined as H.pylori positive by recomLine (69.5%). A significant correlation between the number of positive H.pylori serum responses and DOB value was found (rs = 0.217, P < 0.001). A mathematical approach such as FMM might be an alternative measure in optimizing the cut-off point for 13C-UBT in community-based studies, and a second method to determine H.pylori status for subjects with borderline value of 13C-UBT was necessary and recommended.

• MeSH
• Algorithms * MeSH
• Breath Tests methods   MeSH
• Molecular Diagnostic Techniques standards   MeSH
• Adult MeSH
• Helicobacter Infections diagnosis   MeSH
• Carbon Isotopes MeSH
• Clinical Trials as Topic MeSH
• Middle Aged MeSH
• Humans MeSH
• Limit of Detection MeSH
• Urea MeSH
• Stomach Neoplasms diagnosis   microbiology   MeSH
• Models, Theoretical MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Validation Study MeSH

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

• MeSH
• Anti-Bacterial Agents therapeutic use   administration & dosage   MeSH
• Adult MeSH
• Helicobacter pylori * drug effects   MeSH
• Helicobacter Infections * drug therapy   epidemiology   microbiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Metronidazole therapeutic use   administration & dosage   MeSH
• Stomach Neoplasms * prevention & control   epidemiology   microbiology   MeSH
• Omeprazole * therapeutic use   administration & dosage   MeSH
• Organometallic Compounds therapeutic use   administration & dosage   MeSH
• Aged MeSH
• Tetracycline therapeutic use   administration & dosage   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• China MeSH

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

• MeSH
• Autophagy * physiology   MeSH
• Autophagosomes MeSH
• Biomarkers MeSH
• Biological Assay standards   MeSH
• Humans MeSH
• Lysosomes MeSH
• Autophagy-Related Proteins metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Guideline MeSH