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 analyze the experiences and practice in the reform of public hospital salary system in Sichuan province, summarize the typical modes of such reform in the province, and provide references for further reform.Methods:As of October 29, 2021, the research group received 77 sets of typical experience materials submitted by the health commissions and public hospitals in Sichuan province on enforcing the reform of the public hospital salary system. The analysis framework was based on the five main elements proposed in the Guidance to Deepening the Reform of the Salary System of Public Hospitals for the purpose of furthering the reform. These five elements refer to " reasonably determining the level of salary in public hospitals" " fully implementing the autonomy of internal distribution in public hospitals " " establishing and improving the incentive and restraint mechanism for the remuneration of public hospital leaders" " improving the assessment and evaluation mechanism oriented to public welfare" and " funding sources ". A quantitative analysis was made on the typical experience materials using the social network analysis method, while a qualitative analysis was made on the typical experience materials using the content analysis method. Results:The results of social network analysis showed that the network density was 0.272; the highest point centrality was " fully implement the autonomy of internal distribution in public hospitals" (0.935), and the highest intermediary centrality was " improving the assessment and evaluation mechanism oriented to public welfare" (0.870), while the closeness to centrality of " establishing and improving the incentive and constraint mechanism for the salary of public hospital leaders" (0.434) and " funding sources" (0.421) were relatively low. The results of content analysis showed that the ones with higher frequency among all the typical experience materials were " fully implementing the autonomy of internal distribution of hospitals" (72 times) and " improving the assessment and evaluation mechanism oriented to public welfare" (67 times), while the ones with lower frequency were " establishing and improving the salary incentive and constraint mechanism for public hospital leaders" (17 times) and " funding sources" (14 times). In terms of unity and synergy, the typical models of public hospital salary system reform in the province could be categorized as the fine standard mode, the fair value mode, the autonomous synergy mode and the circular symbiosis mode.Conclusions:Deepening the reform of the salary system of public hospitals should unify the standards and improve the fair and refined assessment and evaluation mechanism; explore various forms of distribution and build an internal autonomous and synergistic incentive mechanism; pay attention to the weak remuneration incentive mechanism for hospital leaders and the problem of a relatively single source of funding.

Objective:To analyze the salary characteristics of medical institutions and the influencing factors of personnel expenditure as found in the salary system reform of public hospitals in Sichuan province, for reference in furthering such reform in public hospitals.Methods:The data of personnel expenditure, business operation and medical services came from 96 medical institutions in 21 cities(prefectures)of Sichuan province from 2017 to 2020 by means of institutional survey. The average salary level and salary structure of medical staff were used to describe the salary characteristics, and the total salary was presented by the level of personnel expenditure. The measurement data was represented by M(IQR), the counting data was described by frequency and constituent ratio, and the influencing factors of personnel expenditure were analyzed by generalized linear mixed model. Results:From 2017 to 2020, the personnel expenditure of medical institutions increased by 13.04% annually. In 2020, the per capita salary level of medical staff was 151 900 yuan, while the basic salary and performance salary accounted for 16.20% and 54.60% of personnel expenditure respectively. The analysis results of the generalized linear mixed model showed that the average cost of patients per visit( β=0.596), the level of drugs and sanitary materials consumed per 100 yuan medical income( β=0.286), the number of medical visits( β=0.328), and the years [(2018, 2019, 2020) β=0.025, 0.052, 0.066] were positively correlated to personnel expenditure, while the average length of stay( β=-0.693), the proportion of medical service income( β=-0.392), and the balance rate of income and expenditure( β=-0.062)were negatively correlated to personnel expenditure( P<0.05). The proportion of fiscal subsidy revenue, regional GDP and asset-liability ratio were not the influencing factors of personnel expenditure( P> 0.05). Conclusions:In the reform of the salary system of the province, its salary level of medical institutions has surpassed the current wage ceiling of these institutions. As the salary distribution was mainly made based on the workload, the " baton" role of the salary system reform has begun to pay off. However, the basic guarantee role of compensation has not yet been fully leveraged.Further reform is needed in upgrading refined management, and timely dynamic adjustment of personnel expenditure in combination with the hospital's financial performance and cost analysis, and reasonably optimizing the level of medical staff compensation.

Objective:To investigate the efficacy and safety of hemodiafiltration (HDF) in treating CAR-T related grade 3-4 cytokine release syndrome after ineffective treatment with IL-6 receptor inhibitors.Methods:Between July 2015 and July 2021, retrospective analysis of hemodiafiltration for the treatment of 3 patients, including 2 cases of acute B-lymphoblastic leukemia and 1 case of diffuse large B-cell lymphoma, with grade 3-4 CRS after CAR-T cell therapy and ineffective treatment with IL-6 receptor inhibitor was carried out.Results:The patient's clinical symptoms, including body temperature, blood pressure, and blood oxygen, were relieved within 12 hours of all treatments, and the cytokines (IL-6, IL-10, TNF-α, INF-γ) and C-reactive protein (CRP) levels decreased significantly. No adverse side effects were observed during the follow-up period of 3 months.Conclusion:HDF can be a safe and feasible method to treat CAR-T related grade 3- 4 CRS after ineffective treatment with IL-6 receptor inhibitors.

Recent studies have shown that metabolic syndrome (MetS), e.g., obesity, diabetes mellitus, insulin resistance, and nonalcoholic fatty liver disease (NAFLD), and drinking coexist in a considerable number of individuals, suggesting the overlap of alcoholic liver disease (ALD) and NAFLD promotes the development and progression of fatty liver disease and aggravates the adverse outcome of fatty liver disease in a synergistic and interactive way. The evolution of the disease spectrum of fatty liver disease challenges the exclusive diagnosis system which divides fatty liver disease into ALD and NAFLD. This article summarizes the research advances in recent years and introduce the latest international consensus on the renaming of NAFLD, aiming to pay attention to the influence of drinking and MetS on NAFLD, put forward our insights into the diagnosis of fatty liver disease, and thus provide a new basis for reexamination the diagnosis and individualized treatment of fatty liver disease.

Objective:To estimate the burden of hip fractures and related factors among the Chinese middle-aged and elderly population.Methods:Based on the data of China Health and Retirement Longitudinal Study (CHARLS) in 2015, the burden of hip fractures among Chinese middle-aged and elderly population was evaluated as the years lived with disability (YLD) rate. The relationship between gender, age (45-49, 50-59, 60-69 and ≥70 years old), educational level (no education, elementary school, junior high school, high school and above), region (urban, rural), gross domestic production (GDP) per capita (low, medium and high) and geographic area (northern, eastern, south-central, northwest and southwest regions) and the YLD rate of hip fractures were analyzed, respectively.Results:Excluding items with missing basic information and hip fracture data, a total of 17,830 subjects (8,405 males and 9,425 females) were included in the study with average age 61.6±9.8 years (range 45 to 105 years). The average age in male was 61.9±9.6 years, and that in female was 61.2±10.1 years. The prevalence of hip fractures was 2.3% (410/17,830). The total YLD rate was [694/100,000 (95% Uncertainty Interval ( UI): 462/100,000, 989/100,000)]. The YLD rates were similar between male [693/100,000 (95% UI: 461/100,000, 988/100,000)] and female [696/100,000 (95% UI: 463/100,000, 992/100,000)] subgroups. The YLD rate of hip fractures was increasing with age, which reached at maximum of 1,155/100,000 (95% UI: 769/100,000, 1,646/100,000) for participants aged 70 years or above. The rate was gradually decreased with the upgrade of the educational level. The participants with high school education and above reached the lowest of 434/100,000 (95% UI: 289/100,000, 619/100,000). In addition, the YLD rate of hip fractures in rural areas [721/100,000 (95% UI: 480/100,000, 1,027/100,000)] was higher than that in urban areas [650/100,000 (95% UI: 433/100,000, 926/100,000)]. The YLD rate in areas with higher GDP per capita [545/100,000 (95% UI: 363/100,000, 777/100,000)] was lower than that in areas with lower GDP per capita [761/100,000 (95% UI: 506/100,000, 1,084/100,000)]. Moreover, the participants living in the Northwest region were with the highest YLD rate of hip fractures [1,056/100,000 (95% UI: 703/100,000, 1,506/100,000)], followed by the Southwest region [887/100,000 (95% UI: 590/ 100,000, 1,264/100,000)] and the Northeast region [317/100,000 (95% UI: 211/100,000, 452/100,000)]. Conclusion:Hip fractures exerted heavy burdens on the Chinese middle-aged and elderly population. The YLD rate of hip fractures varied according to geographical regions, greater age, rural areas, low educational levels and low GDP per capita. These related factors could affect the disease burden of hip fractures in China.

Objective: In view of the difficulty of the shortage of new coronavirus nucleal acid test in the early COVID-19 outbreak, to explore the application value of chest CT in screening COVID-19 patients. Methods: Retrospective analysis was performed on the data of patients with fever who received chest CT and new coronavirus nucleal acid test during January 25, 2020 to February 2, 2020 in Zhongnan Hospital of Wuhan University. A total of 587 patients were enrolled, including 290 males and 297 females, aged from 11.0 to 96.0 (51.3±17.1) years old. Take the nucleic acid test results as the gold standard, the sensitivity, specificity and rate of missed diagnosis of CT screening COVID-19 were calculated. Results: Among the 587 patients, there were 433 positive cases (73.8%, 433/587) and 154 negative cases (26.2%, 154/587) of novel coronavirus nucleic acid test. Using CT screening, 494 cases (84.2%, 494/587) were positive and 93 cases (15.8%, 93/587) were negative. The sensitivity of CT screening COVID-19 was 97.7% (423/433), specificity was 53.9% (83/154) and rate of missed diagnosis was 2.3% (10/433). Conclusions In the early COVID-19 outbreak, CT screening has the advantages of high sensitivity and low rate of missed diagnosis of COVID-19, which can compensate for the shortage of new coronavirus nucleal acid test and can be used as the basis for rapid screening for early prevention and control of COVID-19 outbreak.

Objective To explore a method for rapidly establishing a mouse model of atopic dermatitis (AD).Methods C57BL/6 mice served as model animals,and were randomly divided into 3 groups:calcipotriol + ovalbumin (OVA) group (n =6) topically treated with calcipotriol and OVA on the mouse ears,calcipotriol group (n =6) topically treated with calcipotriol on the ears,and control group (n =3) topically treated with 75％ alcohol on the ears.The treatment lasted 12 days.Before the model establishment and on day 14,the photos of the mouse ears were taken,and ear thickness was measured;moreover,blood samples were obtained from the mouse caudal vein,and serum levels of total IgE and OVAspecific IgE were detected.On day 14,the skin tissues of mouse auricles were resected and subjected to histopathological examination.Results On day 14,erythematous swelling,dryness and desquamation occurred on the mouse ear skin in the calcipotriol + OVA group and calcipotriol group,and both the two groups showed significantly increased ear thickness compared with those before the model establishment (both P ＜ 0.001).However,there was no significant difference in the ear thickness between the calcipotriol + OVA group (0.355 ± 0.03 mm) and calcipotriol group (0.370 ± 0.05 mm,q =0.674,P =0.231).Histopathological examination of the ear skin showed more obvious epidermal hyperplasia and infiltration of dermal inflammatory cells including eosinophils and mastocytes in the calcipotriol + OVA group compared with the calcipotriol group and control group.Immunohistochemical study revealed that there was no significant difference in the expression of thymic stromal lymphopoietin (TSLP) and interferon (IFN)-γ among the 3 groups (both P ＞ 0.05),while the expression of interleukin (IL)-13 significantly differed among the 3 groups (F =5.159,P =0.032),and was significantly higher in the calcipotriol + OVA group (77.12 ± 5.46) than in the control group (55.49 ± 9.92,q =3.170,P =0.021).On day 14,the calcipotriol + OVA group and calcipotriol group both showed markedly increased total serum IgE levels compared with those before the treatment,and the calcipotriol + OVA group showed a more significant increase (8 278.56 ± 3 297.68 vs.892.64 ± 82.83 μ g/L,t =4.132,P =0.026).Meanwhile,the serum level of OVA-specific IgE was significandy higher in the calcipotriol + OVA group (192.846 ± 15.391 μg/L) than in the calcipotriol group (8.492 ±:3.879 μg/L,q =22.476,P ＜ 0.001) on day 14.Conclusion The mouse model of allergeninduced AD can be rapidly established by topical application of calcipotriol and OVA for 12 consecutive days,which lays a foundation for further study on allergen-related pathogenesis of AD.

Objective To investigate the correlation between aryl hydrocarbon receptor (A hR) gene polymorphisms and haplotypes and susceptibility of ulcerative colitis (UC) .Methods From January 2010 to October 2017 ,at the Second Affiliated Hospital of Wenzhou Medical University ,the First Affiliated Hospital of Wenzhou Medical University , Central Hospital of Wenzhou City and Wenzhou People Hospital ,a total of 396 UC patients were recruited as the UC group .In the same period ,573 age-and gender-matched healthy individuals were taken as the healthy control group . Three single nucleotide polymorphisms (SNP) of A hR (rs10249788 ,rs2066853 ,rs2158041) were examined by modified multiple ligase detection reaction technique .The correlation between the differences in the frequency of each SNP mutant alleles ,genotypes and clinical pathological features of UC was analyzed by unconditional logistic regression analysis .Haploview 4 .2 software was applied to analyze the linkage disequilibrium (LD) . Results The frequency of mutant allele C and genotype TC+CC of AhR (rs10249788) of UC group were higher than those of the healthy control group (75 .00％ ,594/792 vs .69 .98％ ,802/1146 ;95 .45％ , 378/396 vs .91 .10％ ,522/573) ,the differences were statistically significant (odds ratio (OR)=1 .287 , 95％ confidence interval (CI) 1 .049 to 1 .579 , P=0 .016 ;OR=2 .052 ,95％ CI 1 .180 to 3 .568 , P=0 .011) .Compared with the patients with distal colitis ,the frequencies of mutant allele C and genotype TC +CC of AhR (rs10249788) were higher in the patients with extensive colitis (71 .34％ ,341/478 vs . 80 .57％ ,253/314;93 .31％ ,223/239 vs .98 .73％ ,155/157) ,and the differences were statistically significant (OR=1 .666 ,95％ CI 1 .183 to 2 .347 ,P=0 .003 ;OR=5 .561 ,95％ CI 1 .260 to 24 .530 ,P=0 .023) .The results of LD analysis indicated that rs10249788 and rs2066853 ,rs10249788 and rs2158041 , rs2066853 and rs2158041 were linked to each other (D′=0 .636 ,0 .430 and 0 .980 ;r2 =0 .270 ,0 .023 and 0 .177 ) . Compared with the healthy control group , the frequency of haplotype TAC of UC group decreased (20 .20％ ,231 .5/1146 .0 vs .16 .24％ ,128 .6/792 .0) ,however the frequency of haplotype CAC increased (14 .43％ , 165 .4/1146 .0 vs . 20 .47％ , 162 .1/792 .0 ) , and the differences were statistically significant (OR=0 .767 ,95％ CI 0 .605 to 0 .973 , P=0 .029 ;OR=1 .529 ,95％ CI 1 .204 to 1 .941 ,P<0 .01) .The results of further analysis demonstrated that the frequency of haplotype CGC was higher in patients with extensive colitis than that of patients with distal colitis (38 .69％ ,121 .5/314 .0 vs . 29 .48％ ,140 .9/478 .0) ,and the difference was statistically significant (OR=1 .511 ,95％ CI 1 .119 to 2 .040 ,P= 0 .007) ,while the frequency of haplotype TAC in patients with extensive colitis was lower than that of patients with distal colitis (12 .10％ , 38/314 .0 vs . 17 .55％ , 83 .9/478 .0 ) , and the difference was statistically significant (OR= 0 .646 ,95％ CI 0 .483 to 0 .983 , P= 0 .037) .Conclusion A hR (rs10249788) may be a potential locus affecting susceptibility to UC ,and synergistically influence the risk and the location of UC .

Objective To observe the effects of carotid artery stenting (CAS) on ophthalmic artery blood flow in patients with ischemic ophthalmopathy (IOP).Methods A prospective case-control study.Sixty IOP patients (60 eyes) who met inclusive criteria for CAS were enrolled in this study.There was 50％ stenosis of internal carotid artery on one side at least confirmed by color doppler flow imaging (CDFI).Among 60 eyes,there were 3 eyes with central retinal artery occlusion,15 eyes with retinal vein occlusion,37 eyes with ischemic optic neuropathy,5 eyes with ocular ischemia syndrome.The patients were randomly divided into CAS group (32 eyes of 32 patients) and medicine therapy group (28 eyes of 28 patients).The difference of age (t=1.804) and sex (x2=1.975) between two groups was not significant (P＞0.05).The examinations of fundus fluorescein angiography (FFA),CDFI and digital substraction angiography (DSA) were performed before,1 week and 6 months after treatment.The following parameters were recorded:arm-retinal circulation time (A-Rct),peak systolic velocity (PSV),end-diastolic velocity (EDV),and resistance index (RI) in the ophthalmic artery (OA) and central retinal artery (CRA),and the best corrected visual acuity (BCVA).Results There was no significant differences in A-Rct (t=1.354) and BCVA (t=0.376) between the two groups before treatment (P＞0.05).Also,there was no significant differences in PSV (t=-0.294,-2.446),EDV (t=0.141,-0.305),and RI (t=-0.222,-0.694) of OA and CRA between the two groups before treatment before treatment (P＞0.05).Compared with the medicine therapy group,the lower A-Rct was found in the CAS group at different time points after the treatment.The difference was significant on 1 week after treatment (t=-3.205,P＜0.05),but not on 6 months after treatment (t=1.345,P＞0.05).The BCVA of eyes in the two groups were increasing with the extending of time of therapy.Compared with the medicine therapy group,the better BCVA was found in the CAS group at different time points after the treatment (t=0.800,1.527;P＜0.05).Compared with the medicine therapy group,the higher PSV,EDV and lower RI of OA and CRA were found in the CAS group at different time points after the treatment.(P＜0.05).Conclusion Compared with conventional medicine therapy,CAS shows earlier effects in improving ocular hemodynamics for IOP patients with carotid artery stenosis,which benefits visual function improvement of the patients.