Non-invasive imaging of pathological scars using a portable handheld two-photon microscope / 中华医学杂志(英文版)

BACKGROUND@#Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo . This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients.@*METHODS@#Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment.@*RESULTS@#Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth ( t = 9.917, P <0.001), thickness ( t = 4.037, P <0.001), occupation ( t = 2.169, P <0.050), orientation of collagen ( t = 3.669, P <0.001), and the DEJ contour ratio ( t = 5.105, P <0.001).@*CONCLUSIONS@#Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

Causal Inference of CNS-regulated Hormones in COVID-19: A Bidirectional Two-sample Mendelian Randomization Study

ObjectivesWe assessed the causal association of three COVID-19 phenotypes with insulin-like growth factor 1 (IGF-1), estrogen, testosterone, dehydroepiandrosterone (DHEA), thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). MethodsWe used a bidirectional two-sample univariate and multivariable Mendelian randomization (MR) analysis to evaluate the direction, specificity, and causality of the association between CNS-regulated hormones and COVID-19 phenotypes. Genetic instruments for CNS-regulated hormones were selected from the largest publicly available genome-wide association studies in the European population. Summary-level data on COVID-19 severity, hospitalization, and susceptibility were obtained from the COVID-19 host genetic initiative. ResultsDHEA was associated with increased risks of very severe respiratory syndrome (OR=4.21, 95% CI: 1.41-12.59), consistent with the results in multivariate MR (OR=3.72, 95% CI: 1.20-11.51), and hospitalization (OR = 2.31, 95% CI: 1.13-4.72) in univariate MR. LH was associated with very severe respiratory syndrome (OR=0.83; 95% CI: 0.71-0.96) in univariate MR. Estrogen was negatively associated with very severe respiratory syndrome (OR=0.09, 95% CI: 0.02-0.51), hospitalization (OR=0.25, 95% CI: 0.08-0.78), and susceptibility (OR=0.50, 95% CI: 0.28-0.89) in multivariate MR. ConclusionsWe found strong evidence for the causal relationship of DHEA, LH, and estrogen with COVID-19 phenotypes.

A Generalized Multinomial Probabilistic Model for SARS-CoV-2 Infection Prediction and Public Health Intervention Assessment in an Indoor Environment

SARS-CoV-2 Omicron has become the predominant variant globally. Current infection models are limited by the need for large datasets or calibration to specific contexts, making them difficult to cater for different settings. To ensure public health decision-makers can easily consider different public health interventions (PHIs) over a wide range of scenarios, we propose a generalized multinomial probabilistic model of airborne infection to systematically capture group characteristics, epidemiology, viral loads, social activities, environmental conditions, and PHIs, with assumptions made on social distancing and contact duration, and estimate infectivity over short time-span group gatherings. This study is related to our 2021 work published in Nature Scientific Reports that modelled airborne SARS-CoV-2 infection (Han, Lam, Li, et al., 2021).1 It is differentiated from former works on probabilistic infection modelling in terms of the following: (1) predicting new cases arising from more than one infectious in a gathering, (2) incorporating additional key infection factors, and (3) evaluating the effectiveness of multiple PHIs on SARS-CoV-2 infection simultaneously. Although our results reveal that limiting group size has an impact on infection, improving ventilation has a much greater positive health impact. Our model is versatile and can flexibly accommodate other scenarios by allowing new factors to be added, to support public health decision-making.

Effects of acute ammonia exposure on antioxidant and detoxification metabolism in clam Cyclina sinensis.

To investigate the defensive strategies of clam Cyclina sinensis in response to environmental ammonia exposure, we investigate the 96 h median lethal concentration (LC50-96 h) and the 96 h safe concentration (SC) of total ammonia nitrogen (TAN) for C. sinensis, and on the basis we examined glutamine synthetase (GS) activity, glutamine content, urea content and the antioxidant enzyme activities of super oxide dismutase (SOD) and catalase (CAT) in 96 h at three different levels of TAN as 0 (control), 73.94 (T1) and 227.04 mg/L (T2). Results showed that LC50-96 h and SC for C. sinensis were 65.79 and 6.58 mg/L, respectively. The LC50-96 h and SC of NH3 were 1.70 and 0.17 mg/L, respectively. Ammonia exposure had significantly effects on SOD and CAT activities in the hepatopancreas tissue. Both the level of SOD activity and CAT activity increased with increasing concentration of TAN. No significant differences between T1 and T2 were found in GS activity from 3 h to 96 h after exposed to ammonia, whereas they were significantly higher than those in the control. Both the level of glutamine content in T1 and T2 increased significantly from 6 h to 24 h after exposed to ammonia and they were significantly higher than those in the control. There were no significantly differences were found in the level of urea concentration between T1 and T2 from 6 h to 96 h, while they were significantly higher those in the control. In conclusion, enhancing hepatopancreas antioxidant responses as well as converting ammonia into glutamine and urea worked in combination to allow C. sinensi to defend against acute ammonia exposure.

Targeted-knockdown of Yes-associated protein inhibits the Warburg effect and the invasion of laryngeal cancer cells / 中华耳鼻咽喉头颈外科杂志

Objective@#To investigate the migration and invasion behaviors of Hep-2 after the targeted knockdown of yes-associated protein (YAP).@*Methods@#Hep-2 cells were knock-downed for YAP by shRNA as YAP-shRNA group, Hep-2 treated with non-specific shRNA as YAP-NC group, and Hep-2 with no treatment as control. Glucose uptake and lactate production in the cells were examined to assess Warburg effect. The migration and invasion behaviors of cells in three groups were observed. The expressions of vimentin and E-cadherin were detected by RT-PCR and Western Blot. The statistical software GraphPad Prism 7.0 was used to analyze significance of data. Two tailed Student′ s t-tests was used to determine significance when only two groups were compared. P values of less than 0.05 was considered statistically significant.@*Results@#Downregulation of YAP led to a obvious decrease in glucose uptake [(18.51±1.72)%] and lactate production [103.40±8.32] in Hep-2 cells compared with control [(41.20±1.11)% and 743.69±19.49, t=19.20 and 52.33, respectively, both P<0.01] and YAP-NC group [(39.60±0.78)% and 705.22±17.20, t=19.34 and 54.56, respectively, both P<0.01]. Compared with the control group (78.32±4.04) and YAP-NC group (77.28±3.11), the scratch healing ability of Hep-2 cells was significantly decreased in YAP-shRNA group (44.71±4.68). The P value was less than 0.01 (t=9.42 and 10.04). The number of cells with YAP-shRNA (33.30±4.19) passing through compartments was remarkable fewer than the control group (133.71±6.72) and YAP-NC group (126.32±4.21). The P value was less than 0.01 (t=21.96 and 27.13). The expression of E-cadherin protein in cells of YAP-shRNA group (6.16±0.11) was up-regulated compared with control (0.97±0.10, t=35.70, P<0.01) and YAP-NC group (1.13±0.09, t=36.28, P<0.01), while the expression of vimentin protein in cells of YAP-shRNA group (1.08±0.09) was down-regulated compared with control (5.67±0.12, t=29.91, P<0.01) and YAP-NC group (5.51±0.12, t=29.04, P<0.01).@*Conclusions@#The down-regulation of YAP in Hep-2 inhibits the migration and invasion of cells via suppressing Warburg and EMT program.