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.     

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.     

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.     

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.     

Spontaneous reduction of transvaginal small bowel evisceration after abdominal hysterectomy for cervical cancer: A case report

Rationale:Transvaginal evisceration of the small bowel is an extremely rare condition after hysterectomy, which requires urgent surgical intervention to prevent serious bowel morbidity and mortality.Patient concerns:A 65-year-old woman presented with sudden-onset severe abdominal pain and a mass protruding through the vagina. The past surgical history was significant, with an abdominal hysterectomy for cervical cancer performed 11 weeks prior to presentation.Diagnosis:Pelvic examination revealed prolapsed small-bowel loops (18-20 cm in length). Pelvic computed tomography scan confirmed the presence of transvaginal evisceration of the small bowel.Interventions:Bowel reduction and urgent laparotomy were the selected treatment approaches for a detailed inspection and thorough washing of the intrα-abdominal cavity. A Foley catheter was inserted in the emergency room, with the subject in the lithotomy position. The prolapsed bowel loops spontaneously reduced without manual reduction, and the vault defect was repaired transvaginally.Outcomes:The patient experienced no postoperative complications and remained disease-free for 9months postoperatively.Lessons:Transvaginal evisceration of the small bowel should be considered a surgical emergency. A multidisciplinary approach to prompt case management involving clinicians in gynecology, general surgery, and emergency medicine is vital for preventing serious consequences. Hysterectomy is the most frequently performed gynecological surgical procedure, and evisceration occurs most often after hysterectomy. Therefore, patients should be informed about this rare but possible hysterectomy complication.     

磁共振颅表定位网用于颅内小病灶术前定位26例临床分析

目的：观察和分析磁共振颅表定位网对颅内小病灶进行术前定位的治疗效果方法：应用磁共振颅表定位网定位技术,对26例颅内小占位病灶进行术前定位,然后进行小骨瓣开颅手术,将颅内小病灶显微镜下全切。结果：26例患者经过定位网定位后,准确而微创地切除了病灶,而且诊治过程顺利,无严重并发症发生。结论：磁共振颅表定位网具有定位准确、安全等优点,是重要的神经外科微创诊疗技术。     

158例非小细胞肺癌中3p25杂合性丢失研究

目的　探讨非小细胞肺癌组织 (NSCLC)中 3p2 5位点上等位基因的杂合性丢失 (LOH)与肺癌发生、发展的相关性。方法　采用银染聚合酶链反应结合二核苷酸 (CA)n重复程序出现多态性评价LOH ,分析 1 58例NSCLC癌组织中 3p2 5等位基因的LOH。结果　 1 58例NSCLC组织中 80例出现 3p2 5LOH ,总的杂合性丢失率为 50 .6%。腺癌组织中 3p2 5杂合性丢失率为 62 .0 % ,鳞癌为 43 .2 % ,两者间差异有显著性 (P <0 .0 5)。 3p2 5LOH与NSCLC临床分期关系不明显 ,Ⅰ、Ⅱ及Ⅲ期分别为 52 .2 %、45.0 %及 52 .8% ,4例良性肺肿瘤和 5例正常胎儿肺组织均未出现 3p2 5LOH。结论　本研究结果表明 3p2 5LOH在NSCLC中普遍存在 ,从而说明 3p2 5位点处可能存在着某些与肺癌发生、发展有关的抑癌基因     

Impact of advanced maternal age on neonatal survival of twin small-for-gestational-age subtypes

AIM: We examined the impact of advanced maternal age (>40 years old) on the survival of twin small-for-gestational-age (SGA) infants, that is, infants who were smaller in size than was expected for the baby's sex, genetic heritage, and gestational age. METHODS: The present study was a retrospective cohort study on twin live births in the USA from 1995 to 1998 inclusive. Two categories of SGA babies were defined: discordant (when only one of a twin pair was SGA) and concordant (when both were SGA). Otherwise, the twin pair was appropriate-for-gestational-age (AGA) concordant. RESULTS: 192,195 twin pairs were analyzed. The incidence of SGA discordance and concordance was 11.8% and 3.9%, respectively. The occurrence of both SGA subtypes tended to decrease with increasing maternal age. The unadjusted risk for neonatal mortality increased when both twins were affected (15.8: 22.8 and 56.6 per 1000 among AGA concordant, SGA discordant and SGA concordant twins; P-value for trend < 0.0001). Using maternal-age-specific AGA babies as reference, the adjusted risk for neonatal mortality climbed progressively with advancing maternal age in a dose-dependent pattern, being lowest among teenagers and highest in mothers aged > or =40 years. CONCLUSIONS: SGA discordance and concordance declined with advancing maternal age. In contrast, neonatal mortality of both SGA subtypes worsened with the increase in maternal age compared with that of the age-specific AGA infants. These findings are potentially useful to care providers in counseling older women, a group that is progressively increasing in size and is most susceptible to twining.