BACKGROUND: Senescent human skin primary fibroblast (FB) models have been established for studying aging-related, proliferative, and inflammatory skin diseases. The aim of this study was to compare the transcriptome characteristics of human primary dermal FBs from children and the elderly with four senescence models. METHODS: Human skin primary FBs were obtained from healthy children (FB-C) and elderly donors (FB-E). Senescence models were generated by ultraviolet B irradiation (FB-UVB), D-galactose stimulation (FB-D-gal), atazanavir treatment (FB-ATV), and replication exhaustion induction (FB-P30). Flow cytometry, immunofluorescence staining, real-time quantitative polymerase chain reaction, co-culturing with immune cells, and bulk RNA sequencing were used for systematic comparisons of the models. RESULTS: In comparison with FB-C, FB-E showed elevated expression of senescence-related genes related to the skin barrier and extracellular matrix, proinflammatory factors, chemokines, oxidative stress, and complement factors. In comparison with FB-E, FB-UVB and FB-ATV showed higher levels of senescence and expression of the genes related to the senescence-associated secretory phenotype (SASP), and their shaped immune microenvironment highly facilitated the activation of downstream immune cells, including T cells, macrophages, and natural killer cells. FB-P30 was most similar to FB-E in terms of general transcriptome features, such as FB migration and proliferation, and aging-related characteristics. FB-D-gal showed the lowest expression levels of senescence-related genes. In comparisons with the single-cell RNA sequencing results, FB-E showed almost complete simulation of the transcriptional spectrum of FBs in elderly patients with atopic dermatitis, followed by FB-P30 and FB-UVB. FB-E and FB-P30 showed higher similarity with the FBs in keloids. CONCLUSIONS Each senescent FB model exhibited different characteristics. In addition to showing upregulated expression of natural senescence features, FB-UVB and FB-ATV showed high expression levels of senescence-related genes, including those involved in the SASP, and FB-P30 showed the greatest similarity with FB-E. However, D-galactose-stimulated FBs did not clearly present aging characteristics.
Humans ; Fibroblasts/drug effects* ; Cellular Senescence/physiology* ; Skin/metabolism* ; Child ; Transcriptome/genetics* ; Aged ; Ultraviolet Rays ; Cells, Cultured ; Galactose/pharmacology*

OBJECTIVE: To review the research progress of strontium (Sr) modified β-tricalcium phosphate composite biomaterials (SrTCP) promoting osteogenesis through immune regulation, and provides reference and theoretical support for the further development and research of SrTCP bone repair materials in bone tissue engineering in the future. METHODS: The literature about SrTCP promoting osteogenesis through immune regulation at home and abroad in recent years was extensively reviewed, and the preparation methods, immune mechanism and application of promoting osteogenesis were summarized and analyzed. RESULTS: The preparation methods of SrTCP include solid-state reaction sintering method, solution combustion quenching method, direct doping method, ion substitution method, etc. SrTCP has immune regulatory effects, which can play an immune regulatory role in inducing macrophage polarization, inducing angiogenesis and anti oxidative stress to promote osteogenesis. CONCLUSION At present, studies have shown that SrTCP can promote bone defect repair through immune regulation. Subsequent studies can start from the control of the optimal repair concentration and release rate of Sr, and further clarify the specific mechanism of SrTCP in promoting angiogenesis and anti oxidative stress, which is helpful to develop new materials for bone defect repair.
Calcium Phosphates/pharmacology* ; Strontium/pharmacology* ; Biocompatible Materials/pharmacology* ; Humans ; Osteogenesis/drug effects* ; Tissue Engineering/methods* ; Bone Substitutes/pharmacology* ; Bone Regeneration/drug effects* ; Animals ; Tissue Scaffolds/chemistry* ; Neovascularization, Physiologic/drug effects* ; Macrophages/immunology*

Objective:To evaluate the efficacy and tolerability of crisaborole 2% ointment in the treatment of childhood atopic dermatitis (AD) at the early stage, and to compare the efficacy of every-other-day (Qod) regimen versus twice-a-week (Biw) regimen against recurrence in the remission stage of AD.Methods:A multicenter, randomized, open-label clinical trial was conducted. Totally, 150 children with mild to moderate AD aged 2 - < 18 years were enrolled from 6 hospitals (including Beijing Children′s Hospital, Capital Medical University, etc), and randomly divided into the Qod group (76 cases) and the Biw group (74 cases). In the acute stage of AD, both groups were treated with topical crisaborole 2% ointment on skin lesions twice a day for 2 - 4 weeks, as well as with emollients throughout the whole body. The improvement of early clinical symptoms was evaluated, and the occurrence of adverse reactions was recorded in the follow up. Once the investigator′s static global assessment (ISGA) scores decreased to 1 point or less, the patient would be enrolled into the remission stage. In the remission stage of AD, patients in the Qod group and Biw group were treated with crisaborole ointment every other day and twice a week respectively; the recurrence rate of AD in the remission stage was evaluated, as well as the severity of skin lesions, itching, life quality, and the occurrence of adverse reactions at weeks 4, 8, and 12. Statistical analysis was carried out with SPSS 23.0 software by using t test for comparisons of normally distributed continuous data between two groups, Mann-Whitney U test for non-normally distributed data, chi-square test for enumeration data, and Kaplan-Meier method for analysis of survival rates. Results:A total of 142 patients were enrolled in the modified intention-to-treat population, including 71 in the Qod group and 71 in the Biw group. In the acute stage of AD, the improvement of itching and skin lesions self-reported by the children or their family members occurred on days 1.9 (1.0, 3.0) and 2.0 (1.0, 4.1) after the application of crisaborole ointment, respectively. At the end of treatment in the acute stage, 89 children (62.7%) achieved ISGA 0/1 and successfully transferred into the remission stage. The follow-up in the remission stage was completed in 83 patients (44 in the Qod group and 39 in the Biw group). In addition, recurrence occurred in 19 (43.2%) and 12 (30.8%) patients in the Qod group and Biw group respectively, and there was no significant difference in the recurrence rate between the two groups ( χ2 = 1.36, P = 0.243) ; the average time to recurrence was 64.25 (95% CI: 53.33 - 75.17) days and 75.78 (95% CI: 65.46 - 86.10) days in the Qod group and Biw group respectively. Among the patients who were in the remission stage and had not yet experienced relapse at weeks 4, 8, and 12, there were no significant differences in the eczema area and severity index (EASI) scores, ISGA scores, pruritus numerical rating scale (NRS) scores, or quality-of-life scores between the two groups (all P > 0.05) at any time points, except for the ISGA scores at week 12 (Biw group: 0 [0, 1] point vs. Qod group: 1 [0, 1] point; Z = -2.31, P = 0.021). A total of 146 patients were enrolled in the safety set. During the study period, 70 adverse events occurred in 65 patients, with an incidence rate of 44.5%, and all were mild or moderate adverse events; 55 (37.7%) patients experienced discomfort at the medication site, which mainly referred to pain (45 cases, 30.8%) and mostly occurred in the tender and skinfold areas. Conclusions:Crisaborole 2% ointment could effectively relieve clinical symptoms in children with mild to moderate AD in the early stage, and intermittent treatment could continuously relieve clinical symptoms in the remission stage. The common adverse reaction was discomfort at the application site in the early stage of AD. There was no significant difference in the impact on AD recurrence in the remission stage between the Qod regimen and Biw regimen.

Objective:To investigate the detection rate and related factors of thyroid nodules in people with abnormal lipid metabolism.Methods:From September 4, 2016 to February 1, 2017, community residents living in Lanzhou City, Longnan City, Dingxi City and Linxia City of Gansu Province for more than 5 years were selected as the respondents. General data were recorded, venous blood was collected, blood lipid related biochemical indexes were detected, and thyroid ultrasound was performed. By comparing the general data and biochemical indexes, the detection of abnormal lipid metabolism and thyroid nodules were analyzed, and the risk factors of thyroid nodules in people with abnormal lipid metabolism were analyzed by logistic regression.Results:Two thousand and fifty-nine residents were included in this study (1 049 males and 1 010 females). The total detection rate of thyroid nodules was 23.17% (477/2 059). The detection rate of thyroid nodules in people with abnormal lipid metabolism [34.16%(151/442)] was significantly higher than that in people with normal lipid metabolism [20.16% (326/1 617) , P < 0.01], and the detection rate of thyroid nodules of women [43.37% (85/196) ] was higher than that of men [26.83% (66/246) , P < 0.01]. Among the people with abnormal lipid metabolism, the highest detection rate of thyroid nodules was in mixed hyperlipidemia [57.14% (16/28)], followed by hypertriglyceridemia [34.59% (92/266)]. The detection rates of thyroid nodules in the groups with elevated total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels [35.16% (32/91), 34.85% (23/66)] were higher than those in the marginal elevated group [27.04%(86/318), 30.42% (73/240)] and the normal groups [21.76% (359/1 650), 21.73% (381/1 753), P < 0.05]. The results of logistic regression analysis showed that the risk factors of thyroid nodules in people with abnormal lipid metabolism were increased age, elevated fasting blood glucose (FPG), elevated blood glucose 2 hours (2 h PG) after oral glucose tolerance test (OGTT) load and elevated glycosylated hemoglobin [HbA1c, odds ratio ( OR)=1.065, 1.387, 1.866, 1.384, P < 0.05]. Conclusions:The prevalence of TN is higher in populations with abnormal lipid metabolism. The control of blood sugar and blood lipid levels may play a role in the prevention of thyroid nodules.

Objective To study effects of backpack gravity center position on kinetics and kinematics of lower-extremity joints in parachuting landing and evaluate the injuries. Methods Seven participants performed parachuting landing with backpack gravity center on three positions: low-back (position 1), upper-back (position 2) and abdomen (position 3). Results The peak vertical ground reaction force (GRF) with backpack on position 2 was significantly lower than that on position 1. The joint moment on sagittal plane of the hip with backpack on position 2 was significantly higher than that on position 1 and position 3. The joint energy absorption of the hip with backpack on position 2 was significantly higher than that on position 1. The angular displacement of the hip on sagittal plane with backpack on position 2 was significantly higher than that on position 1 and was significantly lower than that on position 3. The angular velocity of the hip on sagittal plane with backpack on position 2 was significantly lower than that on position 3. Conclusions Different positions of backpack gravity center could significantly influence kinetic and kinematic parameters of the hip. Backpack gravity center on upper-back position could decrease the lower-extremity injuries. The results can provide evidences for evaluating backpack gravity center and decreasing injuries in parachuting landing.

Objective To study the relationship between pulsatile tinnitus and temporal bone pneumatization grade. Methods Through the in vitro experiment, the generation and transmission pathways of the venous sound were simulated. The sound signals at the position of eardrum were recorded and analyzed. Results In case of cortical plate dehiscence, the high pressure and pulse-synchronous venous sounds were received at eardrum. The highest sound pressure occurred in the normal pneumatization case. In case of cortical plate intactness, the non-pulsatile venous sounds with pressure close to the background control sound were received at eardrum. Temporal bone air cells (TBAC) with different pneumatization grades would transmit venous sound in different frequency ranges. Conclusions Normal pneumatization TBAC exhibited the highest amplification on venous sound, while hypopneumatization TBAC exhibited the lowest amplification on venous sound. The pneumatization grade of TBAC is neither the sufficient nor essential condition of pathogenic venous sound, while the cortical plate dehiscence is the sufficient or necessary condition of pathogenic venous sound.

Objective To study the anti-depression mechanism of Dingzhixiaowan concerning on histology of hippocampal formation.Methods 40 female rats were divided into control,depression model group(model group),distilled water group(DW group) and Dingzhixiaowan group(Chinese herb group).Behavior points were measured by open field method.Serum concentrations of cortisol and estradiol(E2) were checked with ELISA.HE staining and electron microscopy were applied to observe the histology of neurons in hippocampal formation.Immunohistochemistry method was employed to detect Nestin expression.Results Compared with the control,behavior points,serum E2 level and Nestin expression decreased obviously and serum cortisol level increased markedly,CA3 neurons were seriously damaged in model and DW groups.While behavior points,serum E2 level did not change,Nestin expression increased obviously and serum cortisol level decreased markedly,CA3 neurons were basically normal in Chinese herb groups.Conclusion Dingzhixiaowan can protect hippocampal formation,which might be one of the anti-depression mechnisms.