Explore the vast range of titles available.

Background Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19. Methods The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 10 8 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging. Results Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 10 9 /L vs. 1.78 × 10 9 /L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients. Conclusions Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 10 9 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population. Trial Registration : MEXCOVID, NCT04276987.

Background Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. Methods haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC–MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. Results The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at − 80°C, 3 months at − 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 10 8 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. Conclusion haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.

Purpose To study the influence of sex, age and thyroid function indices on dual-energy computed tomography (DECT)-derived quantitative parameters of thyroid in patients with or without Hashimoto’s thyroiditis (HT). Material and methods A total of 198 consecutive patients who underwent DECT scan of neck due to unilateral thyroid lesions were retrospectively enrolled. Iodine concentration (IC), total iodine content (TIC) and volume of normal thyroid lobe were calculated. Influences of sex, age and thyroid function indices on DECT-derived parameters in overall study population, subgroup patients with, and those without HT were assessed using Mann–Whitney U test, Student’s T-test, and Spearman correlation analyses, respectively, as appropriate. Results HT group showed significantly lower IC and TIC, while higher volume than No-HT group (all p  < 0.001). The volume was larger in male than that in female in overall study population and No-HT group ( p  = 0.047 and 0.010, respectively). There was no significant difference in any DECT-derived parameters between low (≤ 35 years) and high (> 35 years) age group in all three groups (all p  > 0.05). TPOAb and TgAb correlated positively with IC and TIC, and negatively with volume in overall study population (all p  < 0.05). TPOAb and TgAb also correlated positively with IC in HT group ( p  = 0.002 and 0.007, respectively). Conclusion DECT-derived parameters of thyroid differed significantly between patients with and without HT. Sex and thyroid function indices could affect the DECT-derived parameters. Aforementioned physiological factors should be considered when analyzing the DECT-derived parameters of thyroid.

Objectives To explore the added value of arterial enhancement fraction (AEF) derived from dual-energy computed tomography CT (DECT) to conventional image features for diagnosing cervical lymph node (LN) metastasis in papillary thyroid cancer (PTC). Methods A total of 273 cervical LNs (153 non-metastatic and 120 metastatic) were recruited from 92 patients with PTC. Qualitative image features of LNs were assessed. Both single-energy CT (SECT)–derived AEF (AEF S ) and DECT-derived AEF (AEF D ) were calculated. Correlation between AEF D and AEF S was determined using Pearson’s correlation coefficient. Multivariate logistic regression analysis with the forward variable selection method was used to build three models (conventional features, conventional features + AEF S , and conventional features + AEF D ). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. Results Abnormal enhancement, calcification, and cystic change were chosen to build model 1 and the model provided moderate diagnostic performance with an area under the ROC curve (AUC) of 0.675. Metastatic LNs demonstrated both significantly higher AEF D (1.14 vs 0.48; p  < 0.001) and AEF S (1.08 vs 0.38; p  < 0.001) than non-metastatic LNs. AEF D correlated well with AEF S ( r  = 0.802; p  < 0.001), and exhibited comparable performance with AEF S (AUC, 0.867 vs 0.852; p  = 0.628). Combining CT image features with AEF S (model 2) and AEF D (model 3) could significantly improve diagnostic performances (AUC, 0.865 vs 0.675; AUC, 0.883 vs 0.675; both p  < 0.001). Conclusions AEF D correlated well with AEF S , and exhibited comparable performance with AEF S . Integrating qualitative CT image features with both AEF S and AEF D could further improve the ability in diagnosing cervical LN metastasis in PTC. Clinical relevance statement Arterial enhancement fraction (AEF) values, especially AEF derived from dual-energy computed tomography, can help to diagnose cervical lymph node metastasis in patients with papillary thyroid cancer, and complement conventional CT image features for improved clinical decision making. Key Points • Metastatic cervical lymph nodes (LNs) demonstrated significantly higher arterial enhancement fraction (AEF) derived from dual-energy computed tomography (DECT) and single-energy CT (SECT)–derived AEF (AEF S ) than non-metastatic LNs in patients with papillary thyroid cancer. • DECT-derived AEF (AEF D ) correlated significantly with AEF S , and exhibited comparable performance with AEF S . • Integrating qualitative CT images features with both AEF S and AEF D could further improve the differential ability.

The thyroid imaging reporting and data system (TIRADS) and Bethesda system for reporting thyroid cytopathology (BSRTC) have been used for interpretation of ultrasound and fine-needle aspiration cytology (FNAC) results of thyroid nodules. BRAF(V600E) mutation analysis is a molecular tool in diagnosing thyroid carcinoma. Our objective was to compare the diagnostic value of these methods in differentiating high-risk thyroid nodules. Total 220 patients with high-risk thyroid nodules were recruited in this prospective study. They all underwent ultrasound, FNAC and BRAF(V600E) mutation analysis. The sensitivity and specificity of TIRADS were 73.1% and 88.4%. BSRTC had higher specificity (97.7%) and similar sensitivity (77.6%) compared with TIRADS. The sensitivity and specificity of BRAF(V600E) mutation (85.1%, 100%) were the highest. The combination of BSRTC and BRAF(V600E) mutation analysis significantly increased the efficiency, with 97.8% sensitivity, 97.7% specificity. In patients with BSRTC I-III, the mutation rate of BRAF(V600E) was 64.5% in nodules with TIRADS 4B compared with 8.4% in nodules with TIRADS 3 or 4A (P < 0.001). Our study indicated that combination of BSRTC and BRAF(V600E) mutation analysis bears a great value in differentiating high-risk thyroid nodules. The TIRADS is useful in selecting high-risk patients for FNAB and patients with BSRTC I-III for BRAF(V600E) mutation analysis.

Objective： Study blood vessel injury and gene expression indicating vascular endothelial cell apoptosis induced by mannitol with and without administration of anti-oxidative vitamins. Methods： Healthy rabbits were randomly divided into four groups. Mannitol was injected into the vein of the rabbit ear in each animal. Pre-treatment prior to mannitol injection was per- formed with normal saline （group B）, vitamin C （group C） and vitamin E （group D）. Blood vessel injury was assessed under electron and light microscopy. In a second experiment, cell culture specimen of human umbilical vein endothelial cells were treated with mannitol. Pre-treatment was done with normal saline （sample B）, vitamin C （sample C） and vitamin E （sample D）. Total RNA was extracted with the original single step procedure, followed by hybridisation and analysis of gene expression. Results： In the animal experiment, serious blood vessel injury was seen in group A and group B. Group D showed light injury only, and normal tissue without pathological changes was seen in group C. Of all 330 apoptosis-related genes analysed in human cell culture specimen, no significant difference was seen after pre-treatment with normal saline, compared with the gene chip without pre-treatment. On the gene chip pre-treated with vitamin C, 45 apoptosis genes were down-regulated and 34 anti-apoptosis genes were up-regulated. Pre-treatment with vitamin E resulted in the down-regulation of 3 apoptosis genes. Conclusion： Vitamin C can protect vascular endothelial cells from mannitol-induced injury.

The thyroid imaging reporting and data system (TIRADS) and Bethesda system for reporting thyroid cytopathology (BSRTC) have been used for interpretation of ultrasound and fine-needle aspiration cytology (FNAC) results of thyroid nodules. BRAF V600E mutation analysis is a molecular tool in diagnosing thyroid carcinoma. Our objective was to compare the diagnostic value of these methods in differentiating high-risk thyroid nodules. Total 220 patients with high-risk thyroid nodules were recruited in this prospective study. They all underwent ultrasound, FNAC and BRAF V600E mutation analysis. The sensitivity and specificity of TIRADS were 73.1% and 88.4%. BSRTC had higher specificity (97.7%) and similar sensitivity (77.6%) compared with TIRADS. The sensitivity and specificity of BRAF V600E mutation (85.1%, 100%) were the highest. The combination of BSRTC and BRAF V600E mutation analysis significantly increased the efficiency, with 97.8% sensitivity, 97.7% specificity. In patients with BSRTC I-III, the mutation rate of BRAF V600E was 64.5% in nodules with TIRADS 4B compared with 8.4% in nodules with TIRADS 3 or 4A ( P  < 0.001). Our study indicated that combination of BSRTC and BRAF V600E mutation analysis bears a great value in differentiating high-risk thyroid nodules. The TIRADS is useful in selecting high-risk patients for FNAB and patients with BSRTC I-III for BRAF V600E mutation analysis.

Purpose. To determine the relationship between Hashimoto’s thyroiditis (HT) and all stages of papillary thyroid carcinoma (PTC) with or without local lymph node metastasis (LNM). Methods. We conducted a retrospective study of thyroidectomies from 2008–2013 in First Affiliated Hospital of Nanjing Medical University. We categorized patients according to the presence of histopathologically proven HT. The prevalence of mPTC (maximum diameter ≤ 10 mm) and crPTC (clinical relevant PTC) and local LNM rates were compared. Results. We evaluated 6,432 consecutive thyroidectomies. In total, 1,328 specimens were confirmed as HT. The prevalence of PTC in this HT cohort was 43.8%, significantly higher than non-HT group. After adjustment of gender and age, the prevalence of PTC was still higher in HT group. HT was a risk factor for PTC in multivariate analysis with odds ratio 2.725 (95% CI, 2.390–3.109) ( P < 0.001 ). However, no correlation was found between HT and LNM of PTC. Conclusion. HT was associated with an increased prevalence of all stages of PTC, independent of tumor size, gender, and age. In contrast, locally advanced disease defined by LNM was unrelated to HT. These data suggest an association of HT with low risk PTC and a potential protective immunologic effect from further disease progression.

Objective: To detect the expression of long non-coding RNAs (lncRNAs) DOCK9-AS2 in papillary thyroid carcinoma (PTC) and its effects on the proliferation and migration of PTC cells. Methods: PTC samples and the corresponding adjacent tissues were collected from The First Affiliated Hospital of Nanjing Medical University during June 2016 and June 2017. The qRT-PCR was performed to detected the expression of DOCK9-AS2 in the tissues, and the relationship between DOCK9-AS2 expression and the patients clinicopathological data was analyzed. The cell transfection technology was used to establish the PTC BCPAP cell downregulating DOCK9-AS2 stably. CCK8 was carried out to investigate the effect of DOCK9-AS2 on the proliferation of the BCPAP cells. The wound-healing assay was used to dectect the effect of DOCK9-AS2 on the migration of the BCPAP cells. Results: : The expression of DOCK9-AS2 in PTC tissues (0.0097±0.0044) was significantly higher than that of adjacent tissues (0.0026±0.0010) (P<0.05). The expression of

R736; 目的 检测长链非编码RNA DOCK9-AS2在甲状腺乳头状癌(PTC)中的表达水平及对PTC细胞增殖、迁移能力的影响.方法 收集2016年6月至2017年6月间在南京医科大学第一附属医院手术切除的PTC标本及对应的癌旁组织,采用qRT-PCR检测62对组织中DOCK9-AS2的表达,并分析其与患者临床病理资料的关系.通过细胞转染技术构建沉默DOCK9-AS2的甲状腺癌BCPAP细胞株,用CCK8方法检测DOCK9-AS2对PTC细胞增殖能力的影响;划痕实验观察沉默下调DOCK9-AS2的表达对细胞侵袭转移能力的影响.结果 DOCK9-AS2在PTC的mRNA表达水平(0.0097±0.0044)高于癌旁组织(0.0026±0.0010),差异具有统计学意义(P<0.05).DOCK9-AS2在PTC组织中的表达与淋巴结转移、腺外侵犯有关(P<0.05).在BCPAP细胞中下调DOCK9-AS2的表达时,PTC细胞的增殖和侵袭转移能力减弱(P<0.05).结论 DOCK9-AS2在PTC中表达显著增高,沉默DOCK9-AS2的表达可抑制PTC细胞的增殖、侵袭和转移.