Wait Times and Survival in Lung Cancer Patients across the Province of Quebec,Canada

Lung cancer is the leading cause of cancer death worldwide, with a five-year survival of 22% in Canada. Guidelines recommend rapid evaluation of patients with suspected lung cancer, but the impact on survival remains unclear. We reviewed medical records of all patients with newly diagnosed lung cancer in four hospital networks across the province of Quebec, Canada, between 1 February and 30 April 2017. Patients were followed for 3 years. Wait times for diagnosis and treatment were collected, and survival analysis using a Cox regression model was conducted. We included 1309 patients, of whom 39% had stage IV non-small cell lung cancer (NSCLC). Median wait times were, in general, significantly shorter in patients with stage III–IV NSCLC or SCLC. Surgery was associated with delays compared to other types of treatments. Median survival was 12.9 (11.1–15.7) months. The multivariate survival model included age, female sex, performance status, histology and stage, treatment, and the time interval between diagnosis and treatment. Longer wait times had a slightly protective to neutral effect on survival, but this was not significant in the stage I–II NSCLC subgroup. Wait times for the diagnosis and treatment of lung cancer were generally within targets. The shorter wait times observed for advanced NSCLC and SCLC might indicate a tendency for clinicians to act quicker on sicker patients. This study did not demonstrate the detrimental effect of longer wait times on survival.     

Identification of Potential mRNA Biomarkers in Milk Small Extracellular Vesicles of Enzootic Bovine Leukosis Cattle

Enzootic bovine leukosis (EBL) is a disease caused by bovine leukemia virus (BLV); only a small percentage of BLV-infected cattle develop EBL and present with B-cell lymphosarcoma. There is no vaccine against BLV, treatment for EBL, or method for predicting the possibility of EBL onset, thus making EBL control difficult. Herein, to explore biomarkers for EBL in milk, we examined the mRNA profiles of small extracellular vesicles (sEVs) in milk from four BLV-uninfected and four EBL cattle by microarray analysis. It was revealed that 14 mRNAs were encapsulated in significantly higher quantities, and these mRNAs were therefore selected as biomarker candidates. Primers for these mRNAs were designed, and nine primer sets were available for quantitative real-time PCR. Nine mRNAs were evaluated for their availability as biomarkers for EBL using sEVs from newly-collected milk of 7 uninfected and 10 EBL cattle. The quantities of eight mRNAs (TMEM156, SRGN, CXCL8, DEFB4A, FABP5, LAPTM5, LGALS1, and VIM) were significantly higher in milk sEVs of EBL cattle than in those of uninfected cattle. Therefore, our findings indicate that these eight mRNAs in milk sEVs can be used as potential EBL biomarkers with combination use, although single mRNA use is not enough. Consequently, cattle at risk of EBL onset can be identified by monitoring the fluctuation in quantities of these mRNAs in milk before they develop EBL.     

Protective effect of valerian extract capsule (VEC) on ethanol- and indomethacin-induced gastric mucosa injury and ameliorative effect of VEC on gastrointestinal motility disorder

ContextValerian extract capsule (VEC) is an effective Chinese patent medicine used for gastrointestinal (GI) diseases.ObjectiveTo investigate the detailed pharmacological activity for VEC clinical effects in GI diseases.Materials and methodsSprague-Dawley rats were divided into six groups: control, model, and drug-treated (VEC-L, VEC-M, VEC-H, and teprenone). Rats were orally administered VEC (124, 248, 496 mg/kg) and teprenone (21.43 mg/kg) for 3 consecutive days. After 1 h, the five groups (except the control group) were orally given ethanol (10 mL/kg) for 1 h or indomethacin (80 mg/kg) for 7 h. The spasmolytic activity of VEC (0.01–1 mg/mL) on ACh/BaCl₂-induced New Zealand rabbit smooth muscle contraction was performed. The C57BL/6 mice carbon propelling test evaluated the effects of VEC (248–992 mg/kg) on intestinal motility in normal and neostigmine/adrenaline-induced mice.ResultsCompared with the model group, VEC treatment reduced the gastric lesion index and mucosal damage. Further experiments showed that the pathological ameliorative effect of VEC was accompanied by augmentation of the enzymatic antioxidant system and cytoprotective marker (COX-1, p < 0.01; PGI2 p < 0.05;), along with the alleviation of the levels of MPO (ethanol: 15.56 ± 0.82 vs. 12.15 ± 2.60, p < 0.01; indomethacin: 9.65 ± 3.06 vs. 6.36 ± 2.43, p < 0.05), MDA (ethanol: 1.66 ± 0.44 vs. 0.81 ± 0.58, p < 0.01; indomethacin: 1.71 ± 0.87 vs. 1.09 ± 0.43, p < 0.05), and inflammatory mediators. VEC decreased the high tone induced by ACh/BaCl₂ and promoted intestinal transit in normal and neostigmine/adrenaline-induced mice.Discussion and conclusionsVEC showed a potential gastroprotective effect, suggesting that VEC is a promising phytomedicine for the treatment of GI diseases.     

干细胞技术在血管组织工程中的应用

随着冠状动脉粥样硬化性心脏病发病率和冠状动脉旁路移植手术数量的逐年增加,自体桥血管和人造血管已不能满足临床治疗的需求,组织工程为此带来了希望。干细胞的定向分化能力和超强的扩增能力,有望成为组织工程中理想的种子细胞。文章概述了目前干细胞技术在血管组织工程中的应用情况。     

Prenatal Bisphenol a Exposure and Postnatal Trans Fat Diet Alter Small Intestinal Morphology and Its Global DNA Methylation in Male Sprague-Dawley Rats,Leading to Obesity Development

In this study, we aimed to determine whether a postnatal trans fat diet (TFD) could aggravate prenatal bisphenol A (BPA) exposure effects on offspring’s small intestine and adulthood obesity, due to the relatively sparse findings on how the interaction between these two variables interrupt the small intestinal cells. Twelve pregnant rats were administered with either unspiked drinking water (control; CTL) or BPA-spiked drinking water throughout pregnancy. Twelve weaned pups from each pregnancy group were then given either a normal diet (ND) or TFD from postnatal week (PNW) 3 until PNW14, divided into control offspring on normal diet (CTL-ND), BPA-exposed offspring on normal diet (BPA-ND), control offspring on trans fat diet (CTL-TFD), and BPA offspring on trans fat diet (BPA-TFD) groups. Body weight (BW), waist circumference, and food and water intake were measured weekly in offspring. At PNW14, small intestines were collected for global DNA methylation and histological analyses. Marked differences in BW were observed starting at PNW9 in BPA-TFD (389.5 ± 10.0 g; p < 0.05) relative to CTL-ND (339.0 ± 7.2 g), which persisted until PNW13 (505.0 ± 15.6 g). In contrast, water and food intake between offspring were significantly different (p < 0.01–0.05) at earlier ages only (PNW4–6 and PNW7–9, respectively). Furthermore, substantial differences in the general parameters of the intestinal structures were exclusive to ileum crypt length alone, whereby both BPA-ND (150.5 ± 5.1 μm; p < 0.001), and BPA-TFD (130.3 ± 9.9 μm; p < 0.05) were significantly longer than CTL-ND (96.8 ± 8.9 μm). Moreover, BPA-ND (2.898 ± 0.147%; p < 0.05) demonstrated global small intestinal hypermethylation when compared to CTL-ND and CTL-TFD (1.973 ± 0.232% and 1.913 ± 0.256%, respectively). Prenatal BPA exposure may significantly affect offspring’s physiological parameters and intestinal function. Additionally, our data suggest that there might be compensatory responses to postnatal TFD in the combined BPA prenatal group (BPA-TFD).     

Research Progress on Emerging Viral Pathogens of Small Ruminants in China during the Last Decade

China is the country with the largest number of domestic small ruminants in the world. Recently, the intensive and large-scale sheep/goat raising industry has developed rapidly, especially in nonpastoral regions. Frequent trading, allocation, and transportation result in the introduction and prevalence of new pathogens. Several new viral pathogens (peste des petits ruminants virus, caprine parainfluenza virus type 3, border disease virus, enzootic nasal tumor virus, caprine herpesvirus 1, enterovirus) have been circulating and identified in China, which has attracted extensive attention from both farmers and researchers. During the last decade, studies examining the etiology, epidemiology, pathogenesis, diagnostic methods, and vaccines for these emerging viruses have been conducted. In this review, we focus on the latest findings and research progress related to these newly identified viral pathogens in China, discuss the current situation and problems, and propose research directions and prevention strategies for different diseases in the future. Our aim is to provide comprehensive and valuable information for the prevention and control of these emerging viruses and highlight the importance of surveillance of emerging or re-emerging viruses.     

Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Long considered merely a trophic and mechanical support to neurons, astrocytes have progressively taken the center stage as their ability to react to acute and chronic neurodegenerative situations became increasingly clear. Reactive astrogliosis starts when trigger molecules produced at the injury site drive astrocytes to leave their quiescent state and become activated. Distinctive morphological and biochemical features characterize this process (cell hypertrophy, upregulation of intermediate filaments, and increased cell proliferation). Moreover, reactive astrocytes migrate towards the injured area to constitute the glial scar, and release factors mediating the tissue inflammatory response and remodeling after lesion. A novel view of astrogliosis derives from the finding that subsets of reactive astrocytes can recapitulate stem cell/progenitor features after damage, fostering the concept of astroglia as a promising target for reparative therapies. But which biochemical/signaling pathways modulate astrogliosis with respect to both the time after injury and the type of damage? Are reactive astrocytes overall beneficial or detrimental for neuroprotection and tissue regeneration? This debate has been animating this research field for several years now, and an integrated view on the results obtained and the possible future perspectives is needed. With this Commentary article we have attempted to answer the above-mentioned questions by reviewing the current knowledge on the molecular mechanisms controlling and sustaining the reaction of astroglia to injury and its stem cell-like properties. Moreover, the cellular/molecular mechanisms supporting the detrimental or beneficial features of astrogliosis have been scrutinized to gain insights on possible pharmacological approaches to enhance astrocyte neuroprotective activities.     

Impact of Ocular Residual Astigmatism on Visual Outcomes of Myopic Astigmatism Correction after Small Incision Lenticule Extraction

Objective: To calculate ocular residual astigmatism (ORA) by vector analysis and to evaluate the impact of ocular residual astigmatism on refractive and visual outcomes after correction of myopic astigmatism by small incision lenticule extraction (SMILE). Methods: In this prospective case-series study, 115 eyes with myopic astigmatism were treated with SMILE from Jauary 2019 to August 2019 atRefractive Center of Ophthalmology Department, Shengjing Hospital, China Medical University. ORA was calculated by vector analysis and patients were divided into two groups according to the magnitude of ORA: high ORA group (ORA≥1.00 D) with 42 eyes and low ORA group (ORA<1.00 D) with 73 eyes. The follow-up period was 3 months after the operation. Uncorrected visual acuity (UCVA) and pythagorean length were measured and compared after the operation. The following measurements were compared: refractive outcomes, total higher order aberrations (tHOAs), vertical trefoil, vertical coma, horizontal coma, oblique trefoil, oblique quadrafoil, oblique secondary astigmatism, spherical aberration, vertical secondary astigmatism, and vertical quadrafoil. Contrast sensitivity was compared between the high and low ORA groups under either 85 cd/m2 or 3 cd/m2 illumination from 1.5 c/d to 18 c/d. The data were analyzed by an independent-samples t test and Mann-Whitney U test to compare the differences between the two groups. Results: Three months postoperatively, refractive outcomes showed that postoperative residual astigmatism in the high ORA group was significantly higher than in the low ORA group (t=3.293, P=0.001). Vector analysis showed that the error vector (EV), absolute error of angle (absolute EA) and index of success (SI) were higher in the high ORA group (t=-3.235, P=0.001; t=-2.326, P=0.020; t=-2.587, P=0.010). After SMILE，all cases had achieved a desirable visual acuity: high ORA group: -0.15±0.05, low ORA group: -0.15±0.05. There were no statistically significant differences in visual acuity, pythagorean length, tHOAs, vertical trefoil, vertical coma, horizontal coma, oblique trefoil, oblique quadrafoil, oblique secondary astigmatism, spherical aberration, vertical secondary astigmatism, or vertical quadrafoil between the two groups. An obvious difference was found in contrast sensitivity, which showed a higher contrast sensitivity at a spatial frequency of 18 c/d with 85 cd/m2 in the low ORA group than in the high ORA group (t=-2.877, P=0.005), but this tendency was not present at 3 cd/m2 . Conclusions: Ocular residual astigmatism impacts the precision of SMILE in correcting myopic astigmatism. This leads to a tendency of more residual astigmatism in refractive outcomes, and reduces contrast sensitivity at high spatial frequencies. However, it does not affect the outcome of obtaining good visual quality in both visual acuity and higher order aberrations.