Serum transfer RNA‐derived fragment tRF‐31‐79MP9P9NH57SD acts as a novel diagnostic biomarker for non‐small cell lung cancer

BackgroundtRNA‐derived fragments (tRFs) have been found to have a crucial function in the pathophysiology of cancers. However, the function of tRFs in non‐small cell lung cancer (NSCLC) is yet unknown. The goal of this study was to assess the tRF‐31‐79MP9P9NH57SD serum expression from NSCLC patients and to determine its diagnostic usefulness.MethodsBy using stem‐loop quantitative real‐time PCR, we were able to detect various tRF‐31‐79MP9P9NH57SD expressions in 96 NSCLC serum samples, 96 healthy controls, and 20 pairs of NSCLC serum samples pre‐ and post‐surgery (qRT‐PCR). After that, we analyzed its diagnostic effectiveness using the receiver operating characteristic (ROC) curve.ResultsSerum tRF‐31‐79MP9P9NH57SD expression was higher in NSCLC patients, and levels of tRF‐31‐79MP9P9NH57SD were linked to the clinical stage (p = 0.002) and the malignancy of lymph node (p = 0.012). In addition, after the procedure, the serum tRF‐31‐79MP9P9NH57SD expression in NSCLC patients dropped. With 48.96 percent sensitivity and 90.62 percent specificity, the area under ROC curve (AUC) was 0.733.Conclusionserum tRF‐31‐79MP9P9NH57SD possibly is a new and groundbreaking biomarker for the NSCLC.     

Effects of Apnea,Obesity, and Statin Therapy on Proprotein Convertase Subtilisin/Kexin 9 Levels in Patients with Obstructive Sleep Apnea

ObjectivesObstructive sleep apnea (OSA) is a common condition closely related to obesity, insulin resistance, dyslipidemia, and cardiovascular disease. The aim of this study was to explore the possible relationship between OSA and proprotein convertase subtilisin/kexin type 9 (PCSK9).MethodsFull-night polysomnography was performed on 150 participants who were divided into three groups: controls, OSA patients on statin therapy, and OSA patients not on statin therapy. Biochemical markers, plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, and PCSK9 were determined.ResultsPCSK9 was highest in OSA patients on statins compared to the control group and to OSA patients not on statins (p = 0.036 and p = 0.039, respectively), after adjustment for body mass index (BMI). LDL diameter was greater in OSA patients not on statins compared to OSA patients on statins (p = 0.032). PCSK9 was highest in the group of patients with all three risk factors (diagnosed OSA, statins, BMI ≥25 kg/m²) compared to groups with no, one, and two risk factors (p = 0.031, p = 0.001, and p = 0.029, respectively). Presence of OSA, statin therapy, and BMI ≥25 kg/m² when combined were independently associated with higher levels of PCSK9 when adjusted for antihypertensive therapy, small dense LDL, and HDL 3c subclass (odds ratio = 2.849; interquartile range [1.026–7.912], p = 0.044).ConclusionStatin therapy was closely related to PCSK9. OSA along with obesity and statin use induces elevation of PCSK9.     

Translation,validation and exploration of the factor structure in the French version of the Posttraumatic Cognitions Inventory (PTCI)

Le Posttraumatic Cognitions Inventory (PTCI) is one of the most used instruments to assess posttraumatic cognitions. Since its release, many studies have tried to validate and translate this questionnaire, but they had difficulty to confirm its structure and then suggested alternatives. Faced with no consensus, a short version in nine statements was developed and showed good psychometric properties. To date, no French version of the PTCI has been validated, thereby preventing studies from investigating the role of posttraumatic cognitions in French speaking populations.ObjectivesIn order to validate a French version of the PTCI, this study investigates two objectives using two French speaking samples: (1) test 10 factor structures identified in prior studies, and (2) assess the other psychometric properties of the best fitting factor structure.MethodThe PTCI was translated in French using a reverse translation method and administered to 202 university students and 114 aid workers. Suitability indexes of the appropriate factor structures previously identified in prior studies were examined. Internal consistency, correlations between subscales and convergent, divergent and discriminant validities in the most appropriate structure were evaluated.ResultsResults support that only Wells et al.''s short 9-item version of the PTCI and three factors shows excellent suitability indexes. This version also outlines an excellent internal consistency and solid convergent, divergent, and discriminant validities.ConclusionsThis study confirms the empirical validity, fidelity, and utility of Wells et al.''s short version of the PTCI. This is the first PTCI French validation, which is a major advantage when it comes to assess posttraumatic cognitions in French trauma victims.     

Pregnancy management for a woman with extensive vulvar and pelvic malformations caused by Klippel–Trénaunay syndrome

Klippel–Trénaunay syndrome (KTS) is a rare congenital disorder defined by a triad of capillary malformation, venous malformation, and soft tissue or bone hypertrophy most commonly affecting unilateral lower limbs. Due to the rarity of KTS, evidence‐based guidelines for the management of pregnancy in people with KTS are still lacking. A 34‐year‐old woman (gravidity 1; parity 0) presented at 25 weeks of gestation with malformations of the right side of her body. The extent of the KTS affecting the vulva, pelvis, and right leg was remarkable. As the prenatal MRI showed massive vascular malformations of the pelvis and vulva, we performed an elective cesarean section to avoid severe perinatal hemorrhage during a vaginal delivery. Intraoperatively, we observed varices on the parietal peritoneum within the vesico‐uterine pouch and the isthmocervical transition of the uterus, which were not identifiable in the preoperative MRI. Although KTS patients have been discouraged from pregnancy in the past because of a high risk for complications, successful and uncomplicated pregnancies are possible. For this purpose, we believe a multidisciplinary strategy that is crucial.     

Chronic Δ9-Tetrahydrocannabinol in rats: Effect on social interactions,mouse killing,motor activity,consummatory behavior,and body temperature

Behavioral and physiologic effects of daily administration of ⁹-tetrahydrocannabinol (THC) were assessed over a 60-day period, investigating different dose levels (10, 20, 50 mg/kg), routes of administration (i.p., p.o.), drug vehicles [5%–18% propylene glycol(PG)/1% Tween 80-saline; sesame oil], and rat strains (Sprague-Dawley, Wistar, Long-Evans, Fischer). All THC-treated rats showed compulsive motor routines (i.e., forepaw treading, rhythmic jaw movements, prolonged head grooming, and biting of cage wires) after 3–4 weeks. Whether maintained on a restricted feeding regimen or not, three was no evidence for increased aggressive behavior between cagemates in any of the treatment groups. Mouse killing was induced in 70%–75% of all Sprague-Dawley (i.p., PG/Tween 80-saline vehicle) and Fischer rats (p.o., sesame oil vehicle), but not in the other THC-treated groups. Rearing activity was greatly decreased in all THC-treated groups throughout the treatment period. Food and water intake decreased by approximately 40% during the first 2–6 days of THC administration. Growth rate was reduced for the entire treatment period in THC-treated rats. THC decreased rectal temperature on the 1st day, and also on the 2nd day in Fischer rats receiving the drug in sesame oil, but not thereafter. This pattern of effects shows that tolerance develops rapidly to THC's effects on body temperature and consummatory behavior, but not to changes of certain motor activities.     

Acute systemic exposure to silver-based nanoparticles induces hepatotoxicity and NLRP3-dependent inflammation

Nanoparticles (NPs) are increasingly being commercialized for use in biomedicine. NP toxicity following acute or chronic exposure has been described, but mechanistic insight into this process remains incomplete. Recent evidence from in vitro studies suggested a role for NLRP3 in NP cytotoxicity. In this study, we investigated the effect of systemic administration of composite inorganic NP, consisting of Ag:Cu:B (dose range 1–20?mg/kg), on the early acute (4–24?h post-exposure) and late phase response (96?h post-exposure) in normal and NLRP3-deficient mice. Our findings indicate that systemic exposure (≥2?mg/kg) was associated with acute liver injury due to preferential accumulation of NP in this organ and resulted in elevated AST, ALT and LDH levels. Moreover, within 24?h of NP administration, there was a dose-dependent increase in intraperitoneal neutrophil recruitment and upregulation in gene expression of several proinflammatory mediators, including TNF-α, IL-1β and S100A9. Histological analysis of liver tissue revealed evidence of dose-dependent hepatocyte necrosis, increase in sinusoidal Kupffer cells, lobular granulomas and foci of abscess formation which were most pronounced at 24?h following NP administration. NP deposition in the liver led to a significant upregulation in gene expression of S100A9, an endogenous danger signal recognition molecule of phagocytes, IL-1β and IL-6. The extent of proinflammatory cytokine activation and hepatotoxicity was significantly attenuated in mice deficient in the NLRP3 inflammasome, demonstrating the critical role of this innate immune system recognition receptor in the response to NP.     

Isoproterenol disperses distribution of NADPH oxidase,MMP-9, and pPKCε in the heart,which are mitigated by endothelin receptor antagonist CPU0213

Aim： Spatial dispersion of bioactive substances in the myocardium could serve as pathological basis for arrhythmogenesis and cardiac impairment by β-adrenoceptor stimulation. We hypothesized that dispersed NADPH oxidase, protein kinase Cε （PKCε）, early response gene （ERG）, and matrix metalloproteinase 9 （MMP-9） across the heart by isoproterenol （ISO） medication might be mediated by the endothelin （ET） - ROS pathway. We aimed to verify if ISO induced spatially heterogeneous distribution of pPKCε, NAPDH oxidase, MMP-9 and ERG could be mitigated by either an ET receptor antagonist CPU0213 or iNOS inhibitor aminoguanidine. Methods：Rats were treated with ISO （1 mg/kg sc） for 10 days, and drug interventions （mg/kg） either CPU0213 （30 sc） or aminoguanidine （100 ip） were administered on days 8-10. Expression of NADPH oxidase, MMP-9, ERG, and PKCε in the left and right ventricle （LV, RV） and septum （S） were measured separately. Results： Ventricular hypertrophy was found in the LV, S, and RV, in association with dispersed QTc and oxidative stress in ISO-treated rats. mRNA and protein expression of MMP-9, PKCε, NADPH oxidase and ERG in the LV, S, and RV were obviously dispersed, with augmented expression mainly in the LV and S. Dispersed parameters were re-harmonized by either CPU0213, or aminoguanidine. Conclusion： We found at the first time that ISO-induced dispersed distribution of pPKCε, NADPH oxidase, MMP-9, and ERG in the LV, S, and RV of the heart, which were suppressed by either CPU0213 or aminoguanidine. It indicates that the ET-ROS pathway plays a role in the dispersed distribution of bioactive substances following sustained β-receptor stimulation.     

VEGF与MMP-9蛋白在食管鳞癌中的表达及其意义

目的检测VEGF和MMP-9蛋白在食管鳞癌中的表达,探讨其病理临床意义及其相关性。方法应用免疫组化SP法检测51例食管鳞癌组织、27例癌旁非典型增生和15例正常食管黏膜组织中VEGF和MMP-9蛋白的表达,分析其与食管癌的临床分期、分化程度、浸润深度、淋巴结转移的关系及二者的相关性。结果VEGF和MMP-9蛋白在食管鳞癌组织中的表达明显高于癌旁非典型增生组织和正常食管黏膜(P<0.05),在中晚期食管癌组织中的表达高于早期,在侵及纤维膜组中的表达明显高于未侵及纤维膜组,在有淋巴结转移组中的表达高于无淋巴结转移组,差异均有统计学意义(均P<0.05),但VEGF在高分化组和低分化组的表达差异无统计学意义(P>0.05),而MMP-9在高分化组和低分化组的表达差异有统计学意义(P<0.05);两者的表达呈正相关关系(rs=0.419)。结论VEGF和MMP-9在食管癌组织中的表达和临床分期、浸润深度、淋巴结转移有关,两者的表达呈正相关性。     

SKP2及MRP-1/CD9在声门癌及癌旁组织中的表达及其临床意义

目的:观察声门癌及癌旁组织中SKP2及MRP-1/CD9蛋白的变化意义及其对声门癌手术安全切除范围的指导意义。方法:用免疫组织化学SP法检测38例声门鳞状细胞癌组织及距癌组织边缘2、5、10mm的组织中SKP2及MRP-1/CD9蛋白的表达,并取10例声带息肉组织作对照。结果:SKP2蛋白产物异常表达按息肉黏膜组织、癌旁组织(2、5、10mm)及癌组织的顺序依次递减,差异有统计学意义(均P<0.05);MRP-1/CD9蛋白产物异常表达按息肉黏膜组织、癌旁组织(2、5、10mm)及癌组织的顺序依次递增,差异有统计学意义(均P<0.05)。结论:SKP2及MRP-1/CD9均可作为判断喉癌生物学特性的参考指标,声门癌手术安全切缘以距肿瘤≥5mm的标准较为适宜。     

Café-au-lait macules and pediatric malignancy caused by biallelic mutations in the DNA mismatch repair (MMR) gene PMS2

A 14-year-old male presented with a T4 sigmoid adenocarcinoma, <10 colonic adenomas and multiple café-au-lait macules. Family history was not suggestive of a dominant hereditary form of colorectal cancer. Evaluation of the tumor revealed abnormal immunohistochemical staining of the PMS2 protein and high frequency microsatellite instability. Germline analysis identified biallelic PMS2 missense mutations. A new cancer syndrome caused by biallelic mutations in the mismatch repair genes, including PMS2, is now emerging and is characterized by café-au-lait macules, colonic polyps and a distinctive tumor spectrum.