Evaluation of antibody kinetics and durability in health subjects vaccinated with inactivated COVID-19 vaccine (CoronaVac): A cross-sectional and cohort study in Zhejiang, China

BackgroundAlthough inactivated COVID-19 vaccines are proven to be safe and effective in the general population, the dynamic response and duration of antibodies after vaccination in the real world should be further assessed. MethodsWe enrolled 1067 volunteers who had been vaccinated with one or two doses of CoronaVac in Zhejiang Province, China. Another 90 healthy adults without previous vaccinations were recruited and vaccinated with three doses of CoronaVac, 28 days and 6 months apart. Serum samples were collected from multiple timepoints and analyzed for specific IgM/IgG and neutralizing antibodies (NAbs) for immunogenicity evaluation. Antibody responses to the Delta and Omicron variants were measured by pseudovirus-based neutralization tests. ResultsOur results revealed that binding antibody IgM peaked 14-28 days after one dose of CoronaVac, while IgG and NAbs peaked approximately 1 month after the second dose then declined slightly over time. Antibody responses had waned by month 6 after vaccination and became undetectable in the majority of individuals at 12 months. Levels of NAbs to live SARS-CoV-2 were correlated with anti-SARS-CoV-2 IgG and NAbs to pseudovirus, but not IgM. Homologous booster around 6 months after primary vaccination activated anamnestic immunity and raised NAbs 25.5-fold. The NAb inhibition rate subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron (p=0.004), and the response rate for Omicron rose from 7.9% (7/89) to 17.8% (16/90). ConclusionsTwo doses of CoronaVac vaccine resulted in limited protection over a short duration. The homologous booster slightly increased antibody responses to the Delta and Omicron variants; therefore, the optimization of booster procedures is vital. FundingKey Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation.

Topical Transplantation of Bone Marrow Mesenchymal Stem Cells Made Deeper Skin Wounds Regeneration.

Current wound healing models generally employ full-thickness or irregular split wounds. Consequently, assessing the type of healing at varying wound depths and determining the deepest level at which wounds can regenerate has been a challenge. We describe a wound model that allows assessment of the healing process over a continuous gradient of wound depth, from epidermal to full-thickness dermal loss. Further, we investigate whether green fluorescent protein-labeled bone marrow mesenchymal stem cells (BM-MSCs/GFP) transplantation could regenerate deeper wounds that might otherwise lead to scar formation. A wound gradient was created on the back of 120 Sprague Dawley rats, which were randomized into the BM-MSCs/GFP and control group. These were further subdivided into 6 groups where terminal biopsies of the healing wounds were taken at days 1, 3, 5, 7, 14, and 21 post-operatively. At each observed time point, the experimental animals were anesthetized and photographed, and depending on the group, the animals euthanized and skin taken for rapid freezing, haemotoxylin and eosin staining, and vascular endothelial growth factor (VEGF) immunohistochemistry. We found the deepest layer to regenerate in the control group was at the level of the infundibulum apex, while in the BM-MSCs/GFP group this was deeper, at the opening site of sebaceous duct at hair follicle in which had the appearance of normal skin and less wound contraction than the control group (P value less than .05). The expression of VEGF in BM-MSCs/GFP group was higher than that in control group (P value less than .05). The number of vessels increased from 2.5 ± 0.2/phf of control group to 5.0 ± 0.3/phf of BM-MSCs/GFP (P value less than .05). The progressively deepening wound model we described can identify the type of wound repair at increasing depths. Further, topical transplantation of BM-MSCs/GFP significantly improved regeneration of deeper wounds from infundibulum apex (maximum depth of control group regeneration) to the opening site of sebaceous duct at hair follicle level.

Les modèles actuels de cicatrisation des plaies font généralement appel à des plaies pleine épaisseur ou de forme irrégulière. Il est donc difficile d'évaluer le type de cicatrisation à diverses profondeurs et de déterminer la profondeur maximale à laquelle les plaies se régénèrent. Les auteurs décrivent un modèle de plaie qui permet d'évaluer le processus de cicatrisation d'après un gradient continu de la profondeur de plaie, entre la perte épidermique et la perte dermique pleine épaisseur. Ils ont également examiné si la transplantation de cellules souches mésenchymateuses marquées de protéines fluorescentes vertes (BM-MSCs/GFP) peut régénérer des plaies plus profondes qui formeraient autrement des cicatrices. Les chercheurs ont créé un gradient de plaie sur le dos de 120 rats Sprague-Dawley divisés de manière aléatoire entre le groupe BM-MSCs/GFP et le groupe témoin. Ils ont ensuite subdivisé ces deux groupes en six groupes, dans lesquels ils ont prélevé des biopsies terminales des plaies en voie de cicatrisation les 1er, 3e, 5e, 7e, 14e et 21e journées après l'opération. À chaque journée d'observation, ils ont anesthésié et photographié les animaux expérimentaux et, selon le groupe, les ont euthanasiés et en ont prélevé la peau en vue de leur congélation rapide, de leur coloration HE et de l'immunohistochimie VEGF. Les chercheurs ont découvert que l'apex infundibulum était la couche la plus profonde à se régénérer dans le groupe témoin, mais que dans le groupe BM-MSCs/GFP, la régénération était plus profonde, à l'entrée du follicule pileux dans la glande sébacée, a repris l'apparence de la peau normale et se contractait moins que dans le groupe témoin (p<0,05). L'expression du VEGF dans le groupe BM-MSCs/GFP était plus élevée que dans le groupe témoin (valeur p inférieure à 0,05). Le nombre de vaisseaux observé était de 2,5±0,2/phf dans le groupe témoin et de 5,0±0,3/phf dans le groupe BM-MSCs/GFP (p<0,05). Le modèle de plaie de plus en plus profonde peut déterminer le type de réparation selon la profondeur. De plus, la transplantation topique de BM-MSCs/GFP améliore considérablement la régénération des plaies plus profondes, qui passe de l'apex de l'infundibulum (profondeur de régénération maximale dans le groupe témoin) à l'entrée du follicule pileux dans la glande sébacée.

Distinguishing COVID-19 from influenza pneumonia in the early stage through CT imaging and clinical features

PurposeTo identify differences in CT imaging and clinical features between COVID-19 and influenza pneumonia in the early stage, and to identify the most valuable features in the differential diagnosis. Materials and MethodA consecutive cohort of 73 COVID-19 and 48 influenza pneumonia patients were retrospectively recruited from five independent institutions. The courses of both diseases were confirmed to be in the early stages (2.66 {+/-} 2.62 days for COVID-19 and 2.19 {+/-} 2.10 days for influenza pneumonia after onset). The chi-square test, students t-test, and Kruskal-Wallis H-test were performed to compare CT imaging and clinical features between the two groups. Spearman or Kendall correlation tests between feature metrics and diagnosis outcomes were also assessed. The diagnostic performance of each feature in differentiating COVID-19 from influenza pneumonia was evaluated with univariate analysis. The corresponding area under the curve (AUC), accuracy, specificity, sensitivity and threshold were reported. ResultsThe ground-glass opacification (GGO) was the most common imaging feature in COVID-19, including pure-GGO (75.3%) and mixed-GGO (78.1%), mainly in peripheral distribution. For clinical features, most COVID-19 patients presented normal white blood cell (WBC) count (89.04%) and neutrophil count (84.93%). Twenty imaging features and 6 clinical features were identified to be significantly different between the two diseases. The diagnosis outcomes correlated significantly with the WBC count (r=-0.526, P<0.001) and neutrophil count (r=-0.500, P<0.001). Four CT imaging features had absolute correlations coefficients higher than 0.300 (P<0.001), including crazy-paving pattern, mixed-GGO in peripheral area, pleural effusions, and consolidation. ConclusionsAmong a total of 1537 lesions and 62 imaging and clinical features, 26 features were demonstrated to be significantly different between COVID-19 and influenza pneumonia. The crazy-paving pattern was recognized as the most powerful imaging feature for the differential diagnosis in the early stage, while WBC count yielded the highest diagnostic efficacy in clinical manifestations.

Altered expression profile and function of microRNA-301a in gastric stromal tumor / 实用医学杂志

Objective The aim was to screen the expression profiles of microRNAs (miRNAs) in gastrointestinal stromal tumors (GIST) and explore the function of microRNA-301 a (miR-301 a). Methods Collected the tumor and adjacent normal tissues of 45 patients, who were diagnosed primary GIST. The expression profiles of tumor miRNAs in 5 of the 45 patients were obtained by microarray technology, and the abnormal expression levels of miRNAs in the remaining 40 patients were detected by Real Time-PCR as a validation experiment. Correlation analysis was analyzed between the significantly up-regulated expression of miR-301 a and the clinicopathological features of the patients. The MTT experiment was used to explore the effect of miR-301 a on the growth of GIST cell lines. Results Five kinds of miRNAs with high expression and five kinds of miRNAs with low expression were screened out from GIST, of which the expression of miR-301 a was up-regulated most obviously. The expression of miR-301 a was closely related to tumor risk grade, tumor size, mitosis and necrosis (P < 0.05). The overexpression of miR-301 a in GIST cell lines could significantly enhance the proliferation of cells. Conclusions MiR-301 a was up-regulated in GIST, which was closely related to malignant clinicopathological features and could affect the growth and proliferation of tumor cells in vitro. MiR-301 a might be a potential target for future treatment of GIST.