Micro-RNA content of circulating extracellular vesicles in early rheumatoid arthritis as biomarkers and mediators of methotrexate efficacy.

OBJECTIVES: Extracellular vesicles (EVs) are abundant in body fluids, contributing to intercellular signalling by transferring cargo that includes microRNAs (miRs) - themselves implicated in pathobiology. For the first time we evaluated the potential of EV miRs to contribute diagnostic information in early RA, predict methotrexate (MTX) efficacy or shed light on the drug's mechanism of action. METHODS: 798 miRs isolated from serum-derived EVs of 46 patients with untreated RA, 23 with untreated polymyalgia rheumatica (PMR; inflammatory disease control group) and 12 in whom significant inflammatory disease had been excluded (non-inflammatory controls; NICs) were profiled (Nanostring); the same measurements were made for RA patients after 6 months' MTX treatment. Analyses took multiple testing into account. RESULTS: 28 EV miRs were robustly differentially expressed between early RA (but not PMR) patients and NICs after correction for age and sex, suggesting discriminatory value. Cross-validated partial least squared-discriminant analysis also indicated the predictive potential of a distinct baseline EV miR signature with respect to MTX-induced remission at 6 months. The change in expression of 13 miRs over the course of MTX treatment differed significantly between responders and non-responders, and four of those exhibiting increased relative abundance amongst responders have known roles in regulating the pathogenic potential of synovial fibroblasts, namely miR-212-3p, miR-338-5p, miR-410-3p, and miR-537. CONCLUSION: Our data highlight the potential of serum EV miRs as diagnostic and therapeutic biomarkers, highlighting a novel potential mechanism via which MTX may exert its therapeutic effect in early RA that warrants further investigation.

[Preliminary evaluation of the trueness of 5 chairside 3D facial scanning techniques].

OBJECTIVE: To quantitatively evaluate the trueness of five chairside three-dimensional facial scanning techniques, and to provide reference for the application of oral clinical diagnosis and treatment. METHODS: The three-dimensional facial data of the subjects were collected by the traditional professional three-dimensional facial scanner Face Scan, which was used as the reference data of this study. Four kinds of portable three-dimensional facial scanners (including Space Spider, LEO, EVA and DS-FScan) and iPhone Ⅹ mobile phone (Bellus3D facial scanning APP) were used to collect three-dimensional facial data from the subjects. In Geomagic Studio 2013 software, through data registration, deviation analysis and other functions, the overall three-dimensional deviation and facial partition three-dimensional deviation of the above five chairside three-dimensional facial scanning technologies were calculated, and their trueness performance evaluated. Scanning time was recorded during the scanning process, and the subject's comfort was scored by visual analogue scale(VAS). The scanning efficiency and patient acceptance of the five three-dimensional facial scanning techniques were evaluated. RESULTS: DS-FScan had the smallest mean overall and mean partition three-dimensional deviation between the test data and the reference data, which were 0.334 mm and 0.329 mm, respectively. The iPhone Ⅹ mobile phone had the largest mean overall and mean partition three-dimensional deviation between the test data and the reference data, which were 0.483 mm and 0.497 mm, respectively. The detailed features of the three-dimensional facial data obtained by Space Spider were the best. The iPhone Ⅹ mobile phone had the highest scanning efficiency and the highest acceptance by the subject. The average scanning time of the iPhone Ⅹ mobile phone was 14 s, and the VAS score of the subjects' scanning comfort was 9 points. CONCLUSION: Among the five chairside three-dimensional face scanning technologies, the trueness of the scan data of the four portable devices had no significant difference, and they were all better than the iPhone Ⅹ mobile phone scan. The subject with the iPhone Ⅹ scanning technology had the best expe-rience.

The association between sociodemographic status and COPD and asthma mortality, DALY and YLD in southern China, 2005-2015.

BACKGROUND: Little is known about the disease burden of chronic obstructive pulmonary disease (COPD) and asthma in southern China. METHOD: We calculated the mortality, disability-adjusted life-years (DALY), years lived with disability (YLD) and years of life lost (YLL) for COPD and asthma in Guangdong province between 2005 and 2015. We examined the significance of trends of mortality, DALY, YLD and YLL rates for COPD and asthma with the Cochran-Armitage trend test. We also analyzed their association with sociodemographic factors by negative binomial models. RESULT: The age-standardized mortality, DALY, YLD and YLL rates of COPD and asthma decreased significantly in Guangdong, except for an increase of 11.3% in the age-standardized YLD rate of COPD between 2005 and 2015 (all P < 0.05). Compared with females, the respective adjusted mortality rate ratio of males was 2.11 for COPD, and 0.74 for asthma. Compared with other regions, the richest region, Pearl River Delta, had the lowest mortality, DALY, YLD and YLL rate ratios (RR) of COPD and asthma (all P < 0.05). COPD and asthma mortality, DALY, YLD and YLL rates increased substantially with age. Specifically, when compared with the 25-49 years age group, the respective adjusted DALY RR of asthma was 1.91, 2.02 and 22.21 for 0-24, 50-74 and ≥75 years age group; the respective adjusted YLD RR was 2.27, 1.33 and 7.17 for 0-24, 50-74 and ≥75 years age group. CONCLUSIONS: Disease burden of COPD and asthma decreased in Guangdong province in southern China between 2005 and 2015; however, a disproportionate burden of COPD and asthma in terms of age, sex and regions was observed. The relatively high disease burden and high rate of impaired public health from the less developed regions highlight the need for focused policy making to address the problem.

[Research progress of mesenchymal stem cell in the treatment of diabetic bladder dysfunction].

Diabetic bladder dysfunction (DBD) is a common complication in the lower urinary tract of diabetes. In recent years, mesenchymal stem cell (MSC) have broad application prospects in the treatment of DBD. MSC can migrate to damaged bladder tissue and differentiate into various cell types, such as urothelial cells, myofibroblasts, smooth muscle cells and nerve cells, promote bladder tissue repair and regeneration through paracrine effects. In addition, MSC also intervene in the pathological process of DBD, reverse disease progression, and restore partial bladder function through immune regulation, improvement of oxidative stress, and regulation of blood glucose. At present, the treatment of DBD with MSC is limited to preclinical animal experiments, clinical research and application should be pursued further.

[Preliminary study on three digital analysis methods for analyzing the distribution and area of occlusal contacts].

OBJECTIVE: To analyze the distribution and area of occlusal contacts of clinical dental model using three kinds of digital analysis methods, to compare the results of these methods and traditional occlusal analysis method, and to further analyze the characteristics of each digital analysis method. METHODS: A set of plaster models of normal subjects was selected. The models were scanned by lab scanner 3shape E4 and the files were exported in a stereolithography file format. In 3D analysis software Geomagic Studio 2013 and Geomagic Qualify 2013, the corresponding results of 3D occlusal contact distribution and occlusal contact area were obtained through three digital analysis methods: "3D color difference map method", "point cloud analysis method", and "virtual articulating paper method". The occlusal contact distribution and occlusal contact area were also obtained by two traditional occlusal analysis methods: "silicone interocclusal recording material method" and "scanned articulating paper mark method". A threshold of 100 µm was used to analyze the occlusal contacts and 100 µm was also the thickness of articulating paper used in this study. The results of these five different occlusal analysis methods were evaluated qualitatively and quantitatively. RESULTS: The results of 3D occlusal contact distribution obtained by the above five methods were basically consistent. The total occlusal contact area obtained by 3D color difference map method, point cloud analysis method, virtual articulating paper method, silicone interocclusal recording material method and scanned articulating paper mark method were 133.10 mm², 142.08 mm², 128.95 mm², 163.31 mm², and 100.55 mm² respectively. There was little difference between the results of three digital analysis methods. The results of occlusal contact area obtained by the digital methods and the traditional methods were different. CONCLUSION: The three digital analysis methods can provide reliable and accurate analysis results of occlusal contact distribution and occlusal contact area of dental model. The results obtained by these methods can serve as references for the digital occlusal surface design of dental prosthesis and clinical occlusal analysis.

Intracellular expression of Vitreoscilla haemoglobin improves lipid production in Yarrowia lipolytica.

Genetic modification by overexpressing Vitreoscilla haemoglobin (VHb) is an efficient and economic method for improving O2 utilization for microbial fermentation. In this study, VHb was expressed in oleaginous yeast, Yarrowia lipolytica, and its effect on lipid accumulation was analysed. During fermentation, the dissolved oxygen (DO) concentration was controlled at 5, 10, 20 and 30 of full O2 saturation and also uncontrolled by varying the stirring speed and aeration rate. Yarrowia lipolytica harbouring the VHb gene (VHb+ strain) displayed more pseudomycelium than the control strain (VHb- strain), and VHb expression also enhanced the cell density. When DO level was controlled at 30%, the biomass of VHb+ strains reached about 19 g l-1 and increased by 27% compared to VHb- strains. Total fatty acid contents, although, were higher in VHb+ strains than in VHb- strains under all DO levels, and maximally increased by c. 40% (from 10·5 to 14·5% of the biomass) when the DO concentration was controlled at 30%. VHb overexpression, however, markedly suppressed citrate secretion. In addition, expression of VHb also induced significant changes in fatty acid composition and increased the oleic acid content. SIGNIFICANCE AND IMPACT OF THE STUDY: Genetic modification by overexpressing Vitreoscilla haemoglobin (VHb) is an efficient and economic method for improving O2 utilization for microbial fermentation. In this study, VHb was expressed in Yarrowia lipolytica, which is a most attractive model for microbial oil production because of its excellent lipid accumulation capacity and convenient genetic tools. Expression of VHb resulted in lipid accumulation increased and cell morphology shift, however, markedly suppressed citrate secretion. This study provided the new strategy for fermentation technology to improve lipid production in oleaginous micro-organisms.

[A method to evaluate the trueness of reconstructed dental models made with photo-curing 3D printing technologies].

OBJECTIVE: To establish a reference dental model used for trueness evaluation of photo-curing 3D printing technologies, and to establish a multidimensional trueness evaluation method based on the reference dental model, which can yield a comprehensive objective evaluating result. METHODS: A reference dental model was designed in 3ds Max 2018 software based on the statistical analysis results of dental crown and dental arch of Chinese population in previous studies in order to simulate a real dental model. This model was made up of several simple geometrical configurations, which could minimize the manual measurement error. Physical models were fabricated using three types of photo-curing three-dimensional printers using different techniques: Objet30 Pro (PJ), Projet 3510 HD Plus (MJP), and Perfactory DDP (DLP). The models were scanned by a laser-scanning device and the files were exported in a stereolithography file format. In Geomagic Studio 2012, 3D shape deviations (including overall 3D deviation, flatness error, parallelism error and perpendicularity error) were measured by several commands using the data obtained from the scanning. With regard to the feature size of the simulated dental crown and dental arch, linear measurements (including mesiodistal diameter, buccolingual diameter, crown height of each simulated dental crown and feature size of dental arch) were recorded for selected landmarks using a digital caliper. The measurement results of feature sizes were used to analyze the occlusal plane percentage error and the occlusogingival direction percentage error. RESULTS: For the 3D shape deviation, the results showed that the printed model made by the Objet30 Pro had the lowest overall 3D deviation, the model made by Projet 3510 HD Plus had the best perpendicularity accuracy and the model made by Perfactory DDP had the best flatness accuracy. In terms of the accuracy of the feature size, the model made by the Objet30 Pro was the most accurate in consideration of the results of the occlusal plane percentage error and the occlusogingival direction percentage error. CONCLUSION: The reference dental model and the trueness evaluation method using this model is universally applicable in evaluating the trueness of photo-curing three-dimensional printed dental model and can provide a comprehensive objective evaluating result, which can serve as a reference for the clinical use of photo-curing 3D printing technology.

Expression of Cx43 and Cx45 in Cardiomyocytes of an Overworked Rat Model.

ABSTRACT: Objective To study the effect of overwork stress response on the expression of connexin 43（Cx43） and connexin 45（Cx45） in cardiomyocytes and on cardiac function. Methods The experimental animals were divided into control group, overworked 1-month group and overworked 2-month group. A overworked rat model was established by forcing swimming of overworked group. The expressions of Cx43 and Cx45 in myocardial tissues of experimental animals were detected by Western blotting, while the corresponding myocardial tissues were stained with hematoxylin-eosin （HE） staining and Masson's staining, then histologically observed. Results Western blotting results showed that, compared with the control group, Cx43 expression in myocardial tissues of overworked rats decreased while Cx45 expression increased. HE staining and Masson's staining results showed that hypertrophy, rupture and interstitial fiber tissue hyperplasia were observed in myocardial fibers of overworked rats. Conclusion Overwork stress response may affect cardiac function as an independent factor and may even cause heart failure or arrhythmias and lead to death.

The Concept, Status Quo and Forensic Pathology of Karoshi.

ABSTRACT: "Karoshi" originates from Japan's economic take-off period in the 1960s and 1970s. It is generally believed that overwork lead to the accumulation of fatigue, which triggers the outbreak of potential diseases, and results in sudden death. Karoshi causes great harm to both the community and families because it occurs primarily in 30 to 60 year old young adults. Japan put Karoshi into the category of industrial injury for the first time in 2001 and started to undertake a series of studies in the sociological and pathological fields. However, there is a tremendous gap in the forensic pathological diagnosis domain. In China, research on Karoshi started from the 1990s and is closely related to the reform and opening up policy as well as economic development. According to the incomplete statistics, 600 thousand people die from overwork each year in China, the highest in the world. Karoshi has become one of the most serious social problems in China at the present stage, thus a systematic study in the sociology and forensic pathology fields is urgently required. This paper summarizes the past and present status of Karoshi, and puts forward the problems that need attention during the judicial expertise of Karoshi from forensic pathology perspective.

CGRP blockade by galcanezumab was not associated with reductions in signs and symptoms of knee osteoarthritis in a randomized clinical trial.

OBJECTIVE: This study tested whether galcanezumab, a humanized monoclonal antibody with efficacy against migraine, was superior to placebo for the treatment of mild or moderate osteoarthritis (OA) knee pain. METHOD: In a multicenter, double-blind, placebo- and celecoxib-controlled trial, patients with moderate to severe OA pain were randomized to placebo; celecoxib 200 mg daily for 16 weeks; or galcanezumab 5, 50, 120, and 300 mg subcutaneously every 4 weeks, twice. The primary outcome was change from baseline at Week 8 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore measured by 100 mm visual analog scale (VAS). The trial was considered positive if ≥1 dose of galcanezumab demonstrated ≥95% Bayesian posterior probability of superiority to placebo and ≥50% posterior probability of superiority to placebo by ≥9 mm. A planned interim analysis allowed termination of the study if posterior probability of superiority to placebo by ≥9 mm was ≤5%. Secondary endpoints included WOMAC function subscore and Patient Global Assessment (PGA) of OA. Safety and tolerability were also assessed. RESULTS: The study was terminated after interim analysis suggested inadequate efficacy. Celecoxib significantly reduced WOMAC pain subscore compared with placebo [-12.0 mm; 95% confidence interval (CI) -23 to -2 mm]. None of the galcanezumab arms demonstrated clinically meaningful improvement (range: 1.5 to -5.0 mm) or met the prespecified success criteria. No improvement in any secondary objective was observed. Galcanezumab was well tolerated by OA patients. CONCLUSIONS: This study failed to demonstrate sufficient statistical evidence that galcanezumab was efficacious for treating OA knee pain. STUDY IDENTIFICATION: NCT02192190.

The influence of glucocorticoid receptor single nucleotide polymorphisms on outcome after haematopoietic stem cell transplantation.

Haematopoietic stem cell transplantation (HSCT) remains the only cure for most haematological malignancies, however, the mortality rate remains high. Complications after HSCT include relapse, graft versus host disease (GvHD), graft rejection and infection. Over the last few years several groups, have demonstrated that non-HLA gene polymorphisms can be predictive of outcome after HSCT. Since the glucocorticoid cortisol is pivotal in the regulation of the immune system, we decided to examine single nucleotide polymorphisms (SNPs; rs6198, rs33388 and rs33389) within the glucocorticoid receptor (GR) and correlate with HSCT outcome. The training set consisted of patients (n = 458) who underwent HSCT for acute leukaemia between 1983 and 2005. In the recipients, the absence of the ACT haplotype and absence of the T allele of rs33388 were associated with decreased OS and the absence of the ACT haplotype, the absence of the T allele of rs33388 and the presence of the ATA haplotype were associated with increased risk of relapse. In addition, the presence of the ACT haplotype in the recipient showed a trend to be associated with increased risk of chronic graft versus host disease (cGvHD). The patients in this cohort received mainly myeloablative conditioning (n = 327). The SNPs in the glucocorticoid receptor were then investigated in a validation set (n = 251) of HSCT patients transplanted for acute leukaemia from 2006. This cohort contained significantly more patients that had received reduced intensity conditioning (RIC). Some of the results could be validated in these patients. However, contrary to the training set, the absence of the haplotype ACT in the donor in this cohort was associated with increased risk of cGvHD. Differences in the conditioning were shown to influence the results. These results are the first to associate GR SNPs with HSCT outcome and demonstrate the inherent problems of replicating SNP association studies in HSCT, due to different pre-transplant regimens.

The impact of exposure route for class-based compounds: a comparative approach of lethal toxicity data in rodent models.

Relationships of toxicities from intravenous (i.v.), intraperitoneal (i.p.), subcutaneous (s.c.) and intragastric (i.g.) exposure routes to mice were investigated. Regression analysis showed that the toxicities from i.v. route is strongly correlated with i.p. and s.c. routes, but poorly with i.g. route. Close toxicities from different routes for some compounds indicate that distribution rate is the determining step and dictates chemical concentration at the target site(s). On the other hand, the absorption rate is the determining step for many compounds, which lead to different toxicities between exposure routes. The classified compounds characterized as having either absorption or distribution rate determining step were based upon the comparison of toxicities from the different routes. We found that some aliphatic acids and benzoic acids have lower toxicity values from i.g. route compared to an i.v. route because of poor absorption. Many compounds show low toxic effects from i.g. route than those from other routes because of the first-pass metabolism in the gastrointestinal tract, resulting in the poor relationship for toxicities between i.g. and i.v. or other routes. Stepwise regression analysis showed that physicochemical properties of a compound, such as molecular volume, polarizability and hydrophobicity, significantly affect adsorption rate, which leads to different toxicities based upon exposure routes. Comparison of the toxicities between mice and rats indicate that toxic effect and the toxicokinetic processes in mice are very similar to that in rats. A universal correlation equation has been developed for the toxicities between rats and mice from different exposure routes, which can be applied to predict toxicities across species.

De Novo Computational Design for Development of a Peptide Ligand Oriented to VEGFR-3 with High Affinity and Long Circulation.

The overexpression of VEGFR-3 is correlated with a worse prognosis in lung cancer and has been regarded as a rational target for specific drug delivery. Here, VEGFR-3 homing peptide library was efficiently established by computational design. Strong fluorescent signals of selected peptides were observed in A549 cells, but much weaker in other cells. The positive immunostaining overlapped with VEGFR-3 confirmed high affinity and selectivity of one novel peptide (CP-7). In addition, cell uptake of FITC-CP-7 peptide was significantly blocked by coinjection of excess CP-7 peptide. After labeled with 131I, the profile of pharmacology and biodistribution could be traced in vivo. The 131I-radiolabeled CP-7 peptide conjugates were >85% stable in serum over 4 h and exhibited a specific uptake of 18.04 ± 2.04% ID/g at 0.5 h after injection to high VEGFR-3 expressing A549 tumor mice. More importantly, lower uptake concentration in heart (1.06 ± 0.15% ID/g) after 2 h demonstrated the safety of peptide in vivo. The high uptake in the kidneys revealed that renal clearance was the main route of 131I-CP-7 peptide elimination from the body. Lower accumulation of 131I-CP-7 peptide in VEGFR-3 negative HeLa tumor mice further indicated that CP-7 peptide exhibited a higher tumor-homing efficiency. These studies provided a straightforward analytical access to design and screen bioactive peptide based on protein structure and revealed that CP-7 peptide represented a promising homing peptide of VEGFR-3-positive cancer in vitro and in vivo which could be used as a novel target molecule to achieve efficient drug delivery.

p-Cresyl sulfate is associated with carotid arteriosclerosis in hemodialysis patients and promotes atherogenesis in apoE-/- mice.

p-Cresyl sulfate (PCS) is a risk factor of cardiovascular disease in patients with chronic kidney disease. Here we tested whether serum PCS levels were related to the rate and evolution of carotid atherosclerosis in hemodialysis patients and identified a potential mechanism. A total of 200 hemodialysis patients were categorized as with or without carotid atherosclerotic plaque and followed for 5 years. Serum PCS levels were found to be higher in patients with than without carotid atherosclerotic plaque and positively correlated with increased total plaque area during follow-up. Multiple logistic regression and mixed effects model analyses showed that serum PCS levels were independently associated with the incidence and progression of carotid atherosclerotic plaque. PCS induced inflammatory factor and adhesion molecule expression in endothelial cells and macrophages. In addition, PCS triggered monocyte-endothelial cell interaction in vitro and in vivo through increased production of reactive oxygen species. Compared with controls, increase of PCS levels produced by gavage promoted atherogenesis in 5/6-nephrectomized apoE-/- mice; a process attenuated by NADPH oxidase inhibitors. Thus, increased serum PCS levels are associated with the occurrence and progression of carotid atherosclerosis in hemodialysis patients and promote atherogenesis through increased reactive oxygen species production.

[Epidemiologic characteristics of Plasmodium ovale in China in 2011-2014].

OBJECTIVE: To investigate the epidemiological characteristics of Plasmodium ovale in 2011-2014 for malaria control policy making during the phase of malaria elimination in China. METHODS: The data of individual Plasmodium ovale case (probable and confirmed) and population during 20011-2014 were collated from China National Notifiable Infectious Disease Reporting Information System, and the data of epidemiological investigation for individual Plasmodium ovale case (imported and indigenous) during 2011-2014 were collected from China Parasite Disease Prevention and Control Information System. All of the data didn't include China's Hongkong, Macao, Taiwan and foreign cases. The epidemiological characteristics, diagnosis and reporting were compared and analyzed. RESULTS: During study period of 2011-2014, a total of 373 Plasmodium ovale imported cases were reported, with male being 98.4% and median age being 40 years old. Jiangsu (100 cases), Guangxi (76 cases), Henan (55 cases), Anhui (28 cases) and Shandong(18 cases) reported Plasmodium ovale imported cases ranked the top 5 place in the list. Totally 182 counties from 21 provinces were reported Plasmodium ovale imported cases. 94.6% of ovale malaria imported cases (353/373) got infected from African countries and comprehensive hospitals, CDCs and hospital of infectious disease reported 40.0%, 37.8%, and 16.6% of Plasmodium ovale imported cases, respectively. 4 days of median time lag of Plasmodium ovale imported cases from date of onset to diagnosis was longer than 3 days. CONCLUSION: From 2011 to 2014, the rising number of Plasmodium ovale imported cases reported from wilder scope of China. Diagnosis time lag of Plasmodium ovale was longer than that of other Plasmodium. Diagnosis and prompt treatment of Plasmodium ovale imported cases and relapse case should be highlighted.

Segmentation of epidermal tissue with histopathological damage in images of haematoxylin and eosin stained human skin.

BACKGROUND: Digital image analysis has the potential to address issues surrounding traditional histological techniques including a lack of objectivity and high variability, through the application of quantitative analysis. A key initial step in image analysis is the identification of regions of interest. A widely applied methodology is that of segmentation. This paper proposes the application of image analysis techniques to segment skin tissue with varying degrees of histopathological damage. The segmentation of human tissue is challenging as a consequence of the complexity of the tissue structures and inconsistencies in tissue preparation, hence there is a need for a new robust method with the capability to handle the additional challenges materialising from histopathological damage. METHODS: A new algorithm has been developed which combines enhanced colour information, created following a transformation to the L*a*b* colourspace, with general image intensity information. A colour normalisation step is included to enhance the algorithm's robustness to variations in the lighting and staining of the input images. The resulting optimised image is subjected to thresholding and the segmentation is fine-tuned using a combination of morphological processing and object classification rules. The segmentation algorithm was tested on 40 digital images of haematoxylin & eosin (H&E) stained skin biopsies. Accuracy, sensitivity and specificity of the algorithmic procedure were assessed through the comparison of the proposed methodology against manual methods. RESULTS: Experimental results show the proposed fully automated methodology segments the epidermis with a mean specificity of 97.7%, a mean sensitivity of 89.4% and a mean accuracy of 96.5%. When a simple user interaction step is included, the specificity increases to 98.0%, the sensitivity to 91.0% and the accuracy to 96.8%. The algorithm segments effectively for different severities of tissue damage. CONCLUSIONS: Epidermal segmentation is a crucial first step in a range of applications including melanoma detection and the assessment of histopathological damage in skin. The proposed methodology is able to segment the epidermis with different levels of histological damage. The basic method framework could be applied to segmentation of other epithelial tissues.

Associations between clinical characteristics and oncogene expression in patients with non-small cell lung cancer.

More than 40 oncogenes associated with non-small cell lung cancer (NSCLC) have been identified with varied gene expression. The correlations between specific clinical characteristics and oncogene expression in NSCLC patients were examined. From October 2011 to September 2012, a total of 60 patients with NSCLC (male:female, 34:24; mean age, 59.5 ± 10.6 years; age range, 31-81 years) were diagnosed and evaluated for treatment with radical resection at a single facility. Eligible patients exhibiting tumor node metastasis (TNM) stage I-III NSCLC confirmed by post-surgical pathology were included. mRNA expression was detected by branched DNA-liquidchip technology (bDNA-LCT) and mutations were detected at EGFR exons 18, 19, 20, and 21, KRAS exons 2 and 3, BRAF and PIK3CA exons 9 and 20. Correlations between gene expression at mutations and clinical characteristics of gender, age, histological type, degree of differentiation, smoking status, immunohistochemical (IHC) evaluation of TTF-1, TNM staging, and discrete age ("nage") were examined. Significant associations were observed between IHC staining for TTF-1 and histological type (P = 0.00001) and with BRAC1, TYMS, RRM1, and TUBB3 expression (P = 0.0187, 0.0051, 0.024, and 0.0238, respectively). Significant cross-correlations were observed between TYMS, BRAC1, TOP2A, STMN1, TUBB3, and RRM1 expression (P < 0.05), but not between EGFR exon 21, KRAS exon 2, and PIK3CA exon 9 expression and any other mutation expression (P > 0.05). Relationships between clinical characteristics and oncogene expression in NSCLC, particularly those of TTF-1 level and smoking status, may be useful indicators of prognosis and development of anti-cancer drug resistance.

Echinococcus infections in Chinese dogs: a comparison of coproantigen kits.

Coproantigen test kits for Echinococcus spp. worms in dogs, designed for commercial use, were obtained from three different Chinese producers, and were compared with a laboratory kit using reagents from New Zealand. None of the three producers would provide details of their test validation. From a known set of dog faeces obtained at necropsy from infected and uninfected dogs, and from faeces collected from dogs necropsied in the field, results differed between the kits. For field material, the Tiankang kit showed the best specificity but lacked sensitivity. The Combined kit showed best sensitivity but lacked specificity. Results for the Haitai kit were intermediate. With samples from experimentally infected dogs, both the Haitai and Combined kits lacked sensitivity. Kits will need to be validated by the user before they can be relied on to predict progress in Echinococcus spp. control in China or in other countries.

[Effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022].

OBJECTIVE: To evaluate the effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, so as to provide insights into echinococcosis control. METHODS: Administrative villages were sampled using a multi-stage cluster random sampling method from Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, and all residents at ages of 12 years and older in the sampled villages were screened for echinococcosis, and schools were sampled using a cluster sampling method, and all children at ages of 12 years and older in the sampled schools were screened for echinococcosis. Domestic dogs were sampled using a systematic random sampling method, and one domestic dog stool sample was collected from each household. Stray dog stool samples were collected outside the villages, and Echinococcus coproantigens were detected using enzyme-linked immunosorbent assay in domestic and stray dogs. In addition, echinococcosis was screened in sheep and cattle in designated slaughterhouses in Tianzhu Tibetan Autonomous County. The trends in the prevalence of echinococcosis in humans and livestock and the positive rate of Echinococcus coproantigens in dogs were examined with the Cochran-Armitage trend test. In addition, individuals screened for echinococcosis were randomly sampled from 2007 to 2022 for survey on the awareness of echinococcosis control knowledge. RESULTS: A total of 290 356 person-times were screened for echinococcosis among residents at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 094 residents detected with cystic echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ2 = 358.602, P < 0.001). A total of 32 931 person-times were screened for echinococcosis among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 296 children detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ2 = 267.673, P < 0.001). A total of 33 230 domestic dog stool samples were tested for Echinococcus coproantigens in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 777 Echinococcus coproantigens-positive samples tested, and the positive rate of Echinococcus coproantigens appeared a tendency towards a decline in domestic dogs over years (χ2 = 2 210.428, P < 0.001), while the positive rate of Echinococcus coproantigens showed a tendency towards a rise in domestic animals from 2016 to 2022 (χ2 = 37.745, P < 0.001). The positive rate of Echinococcus coproantigens remained relatively stable in stray dogs in Tianzhu Tibetan Autonomous County, Gansu Province from 2019 to 2022 (χ2 = 0.315, P = 0.575). A total of 10 973 sheep were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2007 to 2022, with 334 sheep detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a decline in sheep over years (χ2 = 53.579, P < 0.001); however, there was no significant change in the detection of echinococcosis during the period from 2015 through 2022 (χ2 = 1.520, P = 0.218). A total of 2 400 cattle were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2017 to 2022, with 231 cattle detected with echinococcosis, and the detection of echinococcosis showed a tendency towards a decline over years (χ2 = 5.579, P < 0.05). The awareness of echinococcosis control knowledge increased from 44.37% in 2007 to 94.00% in 2022 among residents at ages of 12 years and older and from 52.50% in 2007 to 92.50% in 2022 among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, respectively. CONCLUSIONS: There has been a reduction in the detection of echinococcosis in humans and domestic animals and the positive rate of Echinococcus coproantigens in dogs and a rise in the awareness of the echinococcosis control knowledge following the implementation of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province; however, integrated echinococcosis control measures are still required for further control of the prevalence of echinococcosis.