Anoikis-related signature identifies tumor microenvironment landscape and predicts prognosis and drug sensitivity in colorectal cancer.

Background: Anoikis, a mechanism of programmed apoptosis, plays an important role in growth and metastasis of tumors. However, there are still few available comprehensive reports on the impact of anoikis on colorectal cancer. Method: A clustering analysis was done on 133 anoikis-related genes in GSE39582, and we compared clinical features between clusters, the tumor microenvironment was analyzed with algorithms such as "Cibersort" and "ssGSEA". We investigated risk scores of clinical feature groups and anoikis-associated gene mutations after creating a predictive model. We incorporated clinical traits to build a nomogram. Additionally, the quantitative real-time PCR was employed to investigate the mRNA expression of selected anoikis-associated genes. Result: We identified two anoikis-related clusters with distinct prognoses, clinical characteristics, and biological functions. One of the clusters was associated with anoikis resistance, which activated multiple pathways encouraging tumor metastasis. In our prognostic model, oxaliplatin may be a sensitive drug for low-risk patients. The nomogram showed good ability to predict survival time. And SIRT3, PIK3CA, ITGA3, DAPK1, and CASP3 increased in CRC group through the PCR assay. Conclusion: Our study identified two distinct modes of anoikis in colorectal cancer, with active metastasis-promoting pathways inducing an anti-anoikis subtype, which has a stronger propensity for metastasis and a worse prognosis than an anoikis-activated subtype. Massive immune cell infiltration may be an indicator of anoikis resistance. Anoikis' role in the colorectal cancer remains to be investigated.

Effect of lens surgery on health-related quality of life in preschool children with congenital ectopia lentis.

AIM: To evaluate the effect of lens surgery on health-related quality of life (HRQoL) of preschool children with congenital ectopia lentis (CEL). METHODS: A prospective self-controlled study was conducted in Zhongshan Ophthalmic Center. Children aged from 5 to 7y whom were diagnosed with CEL and underwent phacoemulsification with scleral-fixated posterior chamber intraocular lens implantation and their parents were enrolled in this study. All of them completed the child and proxy (parental) PedsQL™ 4.0 before and after the surgery. Their preoperative scores were compared to their postoperative ones. Subgroup analyses were performed based on gender and preoperative bilateral presenting visual acuity of the children. RESULTS: Thirty-two children with CEL successfully underwent surgery without any complications, among whom 8 had monocular surgery and 24 had binocular surgery. Preoperative and postoperative questionnaires were completed by 32 child-parent pairs. Surgical intervention could significantly improve the vision of affected children (P<0.001). The medians of physical, psychosocial and total health scores self-reported by the children were 68.75 (62.50, 81.25), 65.00 (60.00, 80.00) and 67.39 (60.87, 78.26) preoperatively and were 93.75 (87.50, 100.00), 90.00 (83.33, 96.67) and 89.13 (85.32, 95.65) postoperatively. The preoperative scores of the affected children were significantly lower in all scales than age-matched healthy children (P<0.001). All the postoperative scores were significantly higher than the preoperative scores in affected children and their parents (P<0.001). In the physical functioning evaluation, the preoperative score reported by parents of girls was higher than parents of boys (P=0.041), and the postoperative score of girls was higher than that of boys (P=0.036). CONCLUSION: CEL is associated with significantly worse quality of life in preschool children. Surgical intervention can significantly improve the HRQoL in affected children from both personal and family perspective.

Estimating the burden of foodborne gastroenteritis due to nontyphoidal Salmonella enterica, Shigella and Vibrio parahaemolyticus in China.

To estimate the incidence of foodborne gastroenteritis caused by nontyphoidal Salmonella enterica, Shigella, and Vibrio parahaemolyticus in China, population surveys and sentinel hospital surveillance were implemented in six provinces from July 2010 to July 2011, and a multiplier calculation model for the burden of disease was constructed. The multiplier for salmonellosis and V. parahaemolyticus gastroenteritis was estimated at 4,137 [95% confidence interval (CI) 2,320-5,663], and for shigellosis at 4,356 (95% CI 2,443-5,963). Annual incidence per 100,000 population was estimated as 245 (95% CI 138-336), 67 (95% CI 38-92), and 806 (95% CI 452-1,103) for foodborne salmonellosis, shigellosis, and V. parahaemolyticus gastroenteritis, respectively, indicating that foodborne infection caused by these three pathogens constitutes an important burden to the Chinese healthcare system. Continuous implementation of active surveillance of foodborne diseases, combined with multiplier models to estimate disease burden, makes it possible for us to better understand food safety status in China.

Complementary Transcriptomic and Proteomic Analysis in the Substantia Nigra of Parkinson's Disease.

Parkinson's disease (PD) is a disease that involves brain damage and is associated with neuroinflammation, mitochondrial damage, and cell aging. However, the pathogenic mechanism of PD is still unknown. Sequencing data and proteomic data can describe the fluctuation of molecular abundance in diseases at the mRNA level and protein level, respectively. In order to explore new targets in the pathogenesis of PD, the study analyzed molecular changes from the database by combining transcriptomic and proteomic analysis. Differentially expressed genes and differentially abundant proteins were summarized and analyzed. Enrichment and cluster analysis emphasized the importance of neurotransmitter release, mitochondrial damage, and vesicle transport. The molecular network revealed a subnetwork of 9 molecules related to SCNA and TH and revealed hub gene with differential expression at both mRNA and protein levels. It found that ACHE and CADPS could be used as new targets in PD, emphasizing that impaired nerve signal transmission and vesicle transport affect the pathogenesis of PD. Our research emphasized that the joint analysis and verification of transcriptomics and proteomics were devoted to understanding the comprehensive views and mechanism of pathogenesis in PD.

Detection of antibiotics in the urine of children and pregnant women in Jiangsu, China.

Exposure to low concentrations of antibiotics links to multiple health hazards, such as drug resistance of bacteria, and childhood obesity. In this study, seven antibiotics were measured in the urine of 107 children and 126 pregnant women in Jiangsu Province by ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). The overall urinary antibiotics detection rate was 38.6%. Most (98.3%) of the participants' antibiotics concentrations were no more than 10 ng/mL. Children had a significantly higher detection rate than pregnant women (47.7% vs. 31.0%, P = 0.009), as well as the concentration (95th percentile: 6.49 vs. 4.08 ng/mL, P = 0.002). The detection rates of individual antibiotics ranged from 0.4% to 15.0%, and the concentrations ranged from lower than the limit of detection (LOD) through up to 31.96 ng/mL individually. Two or more antibiotics were detected in 11.2% of the urines. Tetracyclines were more frequently detected than phenicols (30.9% vs.12.4%). Oxytetracycline was the most frequently detected (15.0%). Multivariate logistic regression showed that consuming puffed food every day was associated with a significantly increased likelihood of detection, and higher concentration of overall antibiotics, and of doxycycline. Children were more likely to be detected of doxycycline and florfenicol, and to have elevated concentration of doxycycline, compared with pregnant women. This study highlights the relatively heavier antibiotics exposure in children, and a possible impact of puffed food on it, which needs to be warranted in future studies.

Agreement of corneal curvature and central corneal thickness obtained from a swept-source OCT and Pentacam in ectopia lentis patients.

AIM: To assess the inter-device consistency of corneal curvature and central corneal thickness between Pentacam and a swept-source Fourier-domain anterior segment optical coherence tomography (AS-OCT) in ectopia lentis patients. METHODS: Totally 72 eyes of ectopia lentis patients were recruited. Central corneal thickness (CCT), corneal curvature values and corneal astigmatism were obtained from both the Pentacam and AS-OCT (CASIA2). Repeatability was evaluated for both devices. The coefficient of repeatability (COR) and the relative COR was calculated. Bland-Altman plots were conducted to evaluate the inter-device agreement of measurement. Orthogonal linear regression was used to examine any proportional bias. RESULTS: The mean difference of CCT, steep anterior corneal curvature (anterior KS), flat anterior corneal curvature (anterior Kf), anterior corneal astigmatism (ACA), steep posterior corneal curvature (posterior KS), flat posterior corneal curvature (posterior Kf), posterior corneal astigmatism (PCA), steep true net power (TNP KS), flat true net power (TNP Kf) and total corneal astigmatism (TCA) between Pentacam and CASIA2 were 7.03±9.70 µm, -0.19±0.41 D, -0.27±0.35 D, 0.04±0.47 D, -0.17±0.23 D, -0.11±0.11 D, -0.02±1.02 D -0.41±0.43 D, -0.52±0.46 D, and -0.15±0.96 D, respectively. For measurement of TNP Kf with the Pentacam and CASIA2, a mean difference of 0.52 D and COR of 0.90 with P=0.02 was detected. There was no significant difference in CCT (P=0.393), anterior Kf (P=0.107), anterior Ks (P=0.414), ACA (P=0.131), posterior Kf (P=0.286), posterior Ks (P=0.418), PCA (P=0.105), TNP Ks (P=0.054), and TCA (P=0.977) between Pentacam and CASIA2. CONCLUSION: Our study reveals good agreement of CCT, corneal curvature and corneal astigmatism measured by CASIA2 and Pentacam in ectopia lentis patients. However, there was significant difference for CCT and corneal curvature values obtained by the two devices.

Frontline Science: Two flavonoid compounds attenuate allergic asthma by regulating epithelial barrier via G protein-coupled estrogen receptor: Probing a possible target for allergic inflammation.

Allergic asthma is a common chronic lung inflammatory disease and seriously influences public health. We aim to investigate the effects of formononetin (FMN) and calycosin (CAL), 2 flavonoids in Radix Astragali, on allergic asthma and elucidate possible therapeutic targets. A house dust mite (HDM)-induced allergic asthma mouse model and TNF-α and Poly(I:C) co-stimulated human bronchial epithelial cell line (16HBE) were performed respectively in vivo and in vitro. The role of G protein-coupled estrogen receptor (GPER) was explored by its agonist, antagonist, or GPER small interfering RNA (siGPER). E-cadherin, occludin, and GPER were detected by western blotting, immunohistochemistry, or immunofluorescence. The epithelial barrier integrity was assessed by trans-epithelial electric resistance (TEER). Cytokines were examined by enzyme-linked immunosorbent assay (ELISA). The results showed that flavonoids attenuated pulmonary inflammation and hyperresponsiveness in asthmatic mice. These flavonoids significantly inhibited thymic stromal lymphopoietin (TSLP), increased occludin and restored E-cadherin in vivo and in vitro. The effects of flavonoids on occludin and TSLP were not interfered by ICI182780 (estrogen receptor antagonist), while blocked by G15 (GPER antagonist). Furthermore, compared with PPT (ERα agonist) and DPN (ERß agonist), G1 (GPER agonist) significantly inhibited TSLP, up-regulated occludin, and restored E-cadherin. siGPER and TEER assays suggested that GPER was pivotal for the flavonoids on the epithelial barrier integrity. Finally, G1 attenuated allergic lung inflammation, which could be abolished by G15. Our data demonstrated that 2 flavonoids in Radix Astragali could alleviate allergic asthma by protecting epithelial integrity via regulating GPER, and activating GPER might be a possible therapeutic strategy against allergic inflammation.

Surveillance for foodborne disease outbreaks in China, 2003 to 2008.

Knowledge of implicated food vehicles and contributing factors derived from foodborne disease outbreak (FBDO) investigations allows consumers to be educated on decreasing high-risk behavior to reduce the risk of being affected by foodborne diseases. Food safety regulatory authorities also need summary of outbreak data, as these data indicate where the existing food supply system should be improved. To obtain information on epidemiology of FBDOs in China, FBDOs reported to the China National Foodborne Diseases Surveillance Network by 12 surveillance provinces that include 43% of the Chinese population was summarized. Between 2003 and 2008, 2795 FBDOs were reported, resulting in 62559 illnesses, 31261 hospitalizations, and 330 deaths. Outbreak size ranged from 2 to 464 cases, with a median of 14 cases. The outbreak rate had decreased from 1.37 per 1 million population in 2003 to 0.46 per 1 million population in 2008. Of the 2176 outbreaks with a single known etiology, bacteria (1051 outbreaks, 48%), man-made chemical hazards (550 outbreaks, 25%), and animal and plant toxins (536 outbreaks, 25%) were the main courses. Only one outbreak was caused by virus. Of the 1930 outbreaks with a single commodity, plant-based foods were the most common reported (930 outbreaks, 48%), followed by animal-based foods (590 outbreaks, 31%). Outbreaks most frequently occurred in private residences (32%), workplace cafeterias (21%), and restaurants (17%). The most common factor reported in the 2190 outbreaks with known contributing factors were improper cooking (510 outbreaks, 23%), contaminated ingredient (503 outbreaks, 23%), cross contamination (475 outbreaks, 22%) and improper storage (295 outbreaks, 13%). It is considered that FBDOs continue to be an important public health problem in China.

Burden of self-reported acute gastrointestinal illness in China: a population-based survey.

BACKGROUND: Acute gastrointestinal illness (AGI) is an important public-health problem worldwide. Previous national studies of the incidence of AGI in China were performed decades ago, and detailed information was not available. This study therefore sought to determine the magnitude, distribution, and burden of self-reported AGI in China. METHODS: Twelve-month, retrospective face-to-face surveys were conducted in 20 sentinel sites from six provinces between July 2010 and July 2011. RESULTS: In total, 39686 interviews were completed. The overall adjusted monthly prevalence of AGI was 4.2% (95% confidence interval, 4.0-4.4), corresponding to 0.56 episodes of AGI per person-year. Rates of AGI were highest in children aged < 5 years. Healthcare was sought by 56.1% of those reporting illness. Of the cases who visited a doctor, 32.7% submitted a stool sample. The use of antibiotics was reported by 49.7% of the cases who sought medical care and 54.0% took antidiarrhoeals. In the multivariable model, gender, age, education, household type, residence, season, province and travel were significant risk factors of being a case of AGI. CONCLUSIONS: This first population-based study in China indicated that AGI represents a substantial burden of health. Further research into the specific pathogens is needed to better estimate the burden of AGI and foodborne disease in China.

The protection of selenium on ROS mediated-apoptosis by mitochondria dysfunction in cadmium-induced LLC-PK(1) cells.

Selenium, an essential trace element, showed the significant protective effects against liver and kidney damage induced by some heavy metals. However, the mechanism how selenium suppresses cadmium (Cd)-induced cytotoxicity remains unclear. In this study, we investigated the protective mechanism of selenium on Cd-induced apoptosis in LLC-PK(1) cells via reactive oxygen species (ROS) and mitochondria linked signal pathway. Studies of PI and Annexin V dual staining analysis demonstrated that 20 microM Cd-induced apoptosis as early as 18 h. A concomitant by the generation of ROS, the loss of mitochondrial membrane potential, cytochrome c (cyt c) release, activation of caspase-9, -3 and regulation of Bcl-2 and Bax were observed. N-acetylcysteine (NAC, 500 microM), a free radical scavenger, was used to determine the involvement of ROS in Cd-induced apoptosis. During the process, selenium played the same role as NAC. The anti-apoptosis exerted by selenium involved the blocking of Cd-induced ROS generation, the inhibition of Cd-induced mitochondrial membrane potential collapse, the prevention of cyt c release, subsequent inhibition of caspase activation and the changed level of Bcl-2 and Bax. Taken together, we concluded that Cd-induced apoptosis was mediated by oxidative stress and selenium produced a significant protection against Cd-induced apoptosis in LLC-PK(1) via ameliorating the mitochondrial dysfunction.

Effect of liquiritigenin, a flavanone existed from Radix glycyrrhizae on pro-apoptotic in SMMC-7721 cells.

Liquiritigenin is a flavanone existed in Radix glycyrrhizae. The objective of this study is to explore the effects of liquiritigenin on SMMC-7721 cells and its possible mechanism. The viability of liquiritigenin treat cells was decreased in a dose-dependent manner assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazolium bromide (MTT), and apoptotic morphological changes also be observed, such as chromatin condensation and nuclear fragmentation. Assessment of apoptotic cells by flow cytometry indicated that cells fell into apoptosis after 0.4mM liquiritigenin treatment. In addition, a concomitant time-dependent increase in caspase-3 activity was also observed. The level of p53 protein increased and Bcl-2 protein decreased time-dependently. Further studies found the induction of apoptosis by liquiritigenin was accompanied with the production of reactive oxygen species (ROS), disruption of mitochondrial membrane potential and depletion of antioxidant enzymes. The significant ROS generation was firstly found at 3h and being time-dependent until 9h. A time-dependent decrease in membrane potential occurred, and significant loss appeared at 9h and 12h. Furthermore, pretreatment of N-acetyl-cysteine (NAC), ROS production and apoptosis induced by liquiritigenin were both suppressed. In sum, this paper indicated the cytotoxicity of liquiritigenin on SMMC-7721 cells may via effect on generation of ROS, later lead to cell apoptosis.