1.Research progress of non-insulin hypoglycemic drugs in the treatment of type 1 diabetes mellitus
Zejie XU ; Jiaoni ZHENG ; Jing LUO ; Liangyu WANG ; Wei YAN ; Qiang HE ; Xuefeng SHAN
China Pharmacy 2026;37(2):263-267
Traditional treatment for type 1 diabetes mellitus (T1DM) primarily involves insulin replacement, yet some patients encounter issues such as significant blood glucose fluctuations, high risk of hypoglycemia, and weight gain. In recent years, the adjuvant therapeutic role of non-insulin hypoglycemic drugs in T1DM has gradually gained attention. This article reviews the mechanisms of action and clinical research progress of five types of non-insulin hypoglycemic drugs in the treatment of T1DM: amylin analogues (pramlintide), biguanides (metformin), sodium-glucose co-transporter 2 inhibitor, dipeptidyl peptidase-4 inhibitor, and glucagon-like peptide-1 receptor agonist. It is found that these drugs can enhance clinical benefits for T1DM patients by improving insulin sensitivity, delaying gastric emptying, promoting urinary glucose excretion, and regulating incretin levels, thereby reducing glycated hemoglobin levels, decreasing insulin dosage, and managing body weight. Simultaneously, these drugs also present limitations such as low patient compliance due to complex dosing regimens, increased risk of diabetic ketoacidosis, and heterogeneity in glycemic control. Future research could focus on developing individualized treatment strategies, combining pharmacogenomics with novel biomarkers to precisely identify subpopulations of patients who may benefit, and delving into the potential value of these drugs in delaying diabetic vascular complications and improving patients’ quality of life.
2.Analysis of risk factors, pathogenic bacteria characteristics, and drug resistance of postoperative surgical site infection in adults with limb fractures.
Yan-Jun WANG ; Zi-Hou ZHAO ; Shuai-Kun LU ; Guo-Liang WANG ; Shan-Jin MA ; Lin-Hu WANG ; Hao GAO ; Jun REN ; Zhong-Wei AN ; Cong-Xiao FU ; Yong ZHANG ; Wen LUO ; Yun-Fei ZHANG
Chinese Journal of Traumatology 2025;28(4):241-251
PURPOSE:
We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery.
METHODS:
A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics.
RESULTS:
Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%.
CONCLUSION
Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.
Humans
;
Surgical Wound Infection/epidemiology*
;
Male
;
Female
;
Risk Factors
;
Retrospective Studies
;
Middle Aged
;
Adult
;
Case-Control Studies
;
Fractures, Bone/surgery*
;
Aged
;
Drug Resistance, Bacterial
;
Logistic Models
;
Anti-Bacterial Agents/therapeutic use*
;
Incidence
;
Bacteria/drug effects*
3.Survival predictor in emergency resuscitative thoracotomy for blunt trauma patients: Insights from a Chinese trauma center.
Shan LIU ; Lin LING ; Yong FU ; Wen-Chao ZHANG ; Yong-Hu ZHANG ; Qing LI ; Liang ZENG ; Jun HU ; Yong LUO ; Wen-Jie LIU
Chinese Journal of Traumatology 2025;28(4):288-293
PURPOSE:
Emergency resuscitative thoracotomy (ERT) is a final salvage procedure for critically injured trauma patients. Given its low success rate and ambiguous indications, its use in blunt trauma scenarios remains highly debated. Consequently, our study seeks to ascertain the overall survival rate of ERT in blunt trauma patients and determine which patients would benefit most from this procedure.
METHODS:
A retrospective case-control study was conducted for this research. Blunt trauma patients who underwent ERT between January 2020 and December 2023 in our trauma center were selected for analysis, with the endpoint outcome being in-hospital survival, divided into survival and non-survival groups. Inter-group comparisons were conducted using Chi-square and Fisher's exact tests, the Kruskal-Wallis test, Student's t-test, or the Mann-Whitney U test. Univariate and multivariate logistic regression analyses were conducted to assess potential predictors of survival. Then, the efficacy of the predictors was assessed through sensitivity and specificity analysis.
RESULTS:
A total of 33 patients were included in the study, with 4 survivors (12.12%). Multivariate logistic regression analysis indicated a significant association between cardiac tamponade and survival, with an adjusted odds ratio of 33.4 (95% CI: 1.31 - 850.00, p = 0.034). Additionally, an analysis of sensitivity and specificity, targeting cardiac tamponade as an indicator for survivor identification, showed a sensitivity rate of 75.0% and a specificity rate of 96.6%.
CONCLUSION
The survival rate among blunt trauma patients undergoing ERT exceeds traditional expectations, suggesting that select individuals with blunt trauma can significantly benefit from the procedure. Notably, those presenting with cardiac tamponade are identified as the subgroup most likely to derive substantial benefits from ERT.
Adult
;
Female
;
Humans
;
Male
;
Middle Aged
;
Case-Control Studies
;
China
;
Logistic Models
;
Resuscitation/mortality*
;
Retrospective Studies
;
Survival Rate
;
Thoracotomy/methods*
;
Trauma Centers/statistics & numerical data*
;
Wounds, Nonpenetrating/surgery*
4.Evaluating the effectiveness of immediate vs. elective thoracic endovascular aortic repair for blunt thoracic aortic injury.
Zhaohui HUA ; Baoning ZHOU ; Wenhao XUE ; Zhibin ZHOU ; Jintao SHAN ; Lei XIA ; Yunpeng LUO ; Yiming CHAI ; Zhen LI
Chinese Journal of Traumatology 2025;28(1):22-28
PURPOSE:
To evaluate the relationship between the timing of thoracic endovascular aortic repair (TEVAR) for blunt thoracic aortic injury (BTAI) and prognosis.
METHODS:
This is a single-center retrospective cohort study. Patients who received TEVAR for BTAI at our institution from October 2016 to September 2023 were divided into 2 categories depending on the injury severity score (ISS) (≤ 25 vs. > 25) and when the TEVAR was performed for BTAI (within 24 h vs. after 24 h), respectively. The analysis included all patients who received TEVAR treatment after being diagnosed with BTAI through whole-body CT angiography. Patients treated with open repair and non-operative management were excluded. After propensity-score matching for various factors, outcomes during hospitalization and follow-up were compared. These factors included demographics, comorbidities, concomitant injuries, cause and location of aortic injury, Glasgow coma scale score, society for vascular surgery grading, hemoglobin concentration, creatinine concentration, shock, systolic blood pressure, and heart rate at admission. The comparison was conducted using SPSS 26 software. Continuous variables were presented as either the mean ± standard deviation or median (Q1, Q3), and were compared using either the t-test or the Mann-Whitney U test. Categorical variables were expressed as n (%), and comparisons were made between the 2 groups using the χ2 test or Fisher's exact test. Statistical significance was defined as a 2-sided p < 0.05.
RESULTS:
In total, 110 patients were involved in the study, with 65 (59.1%) patients having ISS scores > 25 and 32 (29.1%) receiving immediate TEVAR. The perioperative overall mortality rate in the group with ISS > 25 was significantly higher than that in the group with ISS ≤ 25 (11 (16.9%) vs. 2 (4.4%), p < 0.001). Upon admission, the elective group exhibited a notably higher Glasgow coma scale score (median (Q1, Q3)) compared to the immediate group (15 (12, 15) vs. 13.5 (9, 15), p = 0.039), while the creatinine concentration (median (Q1, Q3)) at admission was significantly higher in the immediate group (90.5 (63.8, 144.0) vs. 71.5 (58.3, 80.8), p = 0.012). The final sample included 52 matched patients. Complications occurred significantly less frequently in the elective group compared to the immediate group (16 (50.0%) vs. 3 (10.0%), p < 0.001). Single-factor analysis of variance showed that complications in hospitalized patients were significantly associated with immediate TEVAR as the sole independent risk factor (odds ratio: 9.000, 95% confidence interval: 2.266-35.752, p = 0.002).
CONCLUSION
In this propensity-score matched analysis of patients undergoing TEVAR for BTAI, elective TEVAR was significantly associated with a lower risk of complication rates. In this study using propensity-score matching, patients who underwent elective TEVAR for BTAI had lower complication rates than immediate TEVAR.
Humans
;
Retrospective Studies
;
Male
;
Aorta, Thoracic/surgery*
;
Female
;
Endovascular Procedures/methods*
;
Wounds, Nonpenetrating/mortality*
;
Middle Aged
;
Adult
;
Aged
;
Injury Severity Score
;
Elective Surgical Procedures
;
Time Factors
;
Treatment Outcome
;
Endovascular Aneurysm Repair
5.Analysis of burden and equality of lower extremity peripheral artery disease in people aged 40 and above in the Belt and Road partner countries from 1990 to 2021.
Guangdian SHEN ; Longzhu ZHU ; Jiayao YING ; Shiyi SHAN ; Zeyu LUO ; Denan JIANG ; Jing WU ; Yuefeng ZHU
Journal of Zhejiang University. Medical sciences 2025;54(1):10-20
OBJECTIVES:
To analyze the disease burden and inequalities of lower extremity peripheral artery disease (LEPAD) among people aged 40 and above in the Belt and Road partner countries from 1990 to 2021.
METHODS:
Data were retrieved from the Global Burden of Disease 2021 database. The age-standardized prevalence rates, mortality rates, and the annual rate of years lived with disability (YLDs) of LEPAD were analyzed. Trends were measured using the estimated annual percentage change (EAPC), and the slope index of inequality (SII) and concentration index were used to quantify the absolute and relative inequalities.
RESULTS:
In 2021, the age-standardized prevalence and mortality rates of LEPAD were 3168.26/105 and 3.09/105, increasing by 4.30% and 19.31% compared to 1990, while YLDs rates decreased by 4.00%. Females had higher age-standardized prevalence and YLDs rates, while males had higher mortality rates. The EAPC for prevalence rates was slightly higher in males (0.22%) than in females (0.17%); while the EAPC of age-standardized mortality rate was 2.02% for females, compared to 1.45% for males. From 1990 to 2021, the age-standardized YLDs rates decreased from 16.23/105 to 15.58/105, with a faster decline in females (-0.12%) than in males (-0.06%). LEPAD prevalence varied across countries, with higher burden in Europe and faster growth in Gulf states. Higher socio-demographic index countries had higher prevalence. Inequity improved, with the SII at 52.90/105 and concentration index at 0.038 in 2021. Gender disparities persisted, with concentration index increased to 0.058 in females and reduced to -0.026 in males.
CONCLUSIONS
LEPAD prevalence and mortality among people aged 40 and above in the Belt and Road partner countries increased, while YLDs rates decreased from 1990 to 2021. Significant differences among people exist depending on gender and country, highlighting the need for enhanced screening, health education, and shared public health strategies across the Belt and Road partner countries.
Humans
;
Peripheral Arterial Disease/mortality*
;
Male
;
Female
;
Middle Aged
;
Adult
;
Aged
;
Prevalence
;
Lower Extremity/blood supply*
;
Global Burden of Disease
;
Cost of Illness
6.Relationships between Molecular Genetics and Clinical Features of Children with Acute Myeloid Leukemia.
Fei LONG ; Hao XIONG ; Li YANG ; Ming SUN ; Zhi CHEN ; Wen-Jie LU ; Shan-Shan QI ; Fang TAO ; Lin-Lin LUO ; Jing-Pei CHEN
Journal of Experimental Hematology 2025;33(1):69-74
OBJECTIVE:
To analyze the molecular genetic spectrum of children with acute myeloid leukemia (AML), and explore its correlation with clinical characteristics and prognosis.
METHODS:
The clinical and molecular genetic data of 116 children with newly diagnosed AML in Wuhan Children's Hospital from September 2015 to August 2022 were retrospectively analyzed. The Fisher's exact test was used to analyze the correlation of gene mutations with clinical features, and Kaplan-Meier curve was used to analyze the influences of gene mutations on the prognosis.
RESULTS:
NRAS (22%), KRAS (14.9%), and KIT (14.7%) mutations were the most common genetic abnormalities in 116 children with AML. Children with KIT, CEBPA and GATA2 mutations showed a higher median onset-age than those without mutations (all P < 0.05). Children with FLT3-ITD mutation exhibited a higher white blood cell count at initial diagnosis compared to those without mutations (P < 0.05). Children with ASXL2 mutation had lower platelet count and hemoglobin at initial diagnosis than those without mutations (both P < 0.05). KIT mutations were often co-occurred with t(8;21)(q22;q22). There was no significant relationship between gene mutation and minimal residual disease (MRD) remission rate after the first and second induction therapy (P >0.05). KIT and NRAS mutations were not associated with prognosis significantly (P >0.05). The overall survival (OS) rates of children with CEBPA and FLT3-ITD mutations were superior to those without mutations, but the differences were not statistically significant (P >0.05). The 3-year OS rate of 61 children treated by allogeneic hematopoietic stem cell transplantation was 89.8%, which was significantly higher than 55.2% of those only treated by chemotherapy (P < 0.001).
CONCLUSIONS
Gene mutations are common in children with AML, and next-generation sequencing can significantly improve the detection rate of gene mutations, which can guide the risk stratification therapy. In addition, FLT3-ITD and KIT mutations may no longer be poor prognostic factors.
Humans
;
Leukemia, Myeloid, Acute/genetics*
;
Mutation
;
Prognosis
;
Retrospective Studies
;
fms-Like Tyrosine Kinase 3/genetics*
;
Child
;
Proto-Oncogene Proteins c-kit/genetics*
;
Male
;
Female
;
CCAAT-Enhancer-Binding Proteins/genetics*
;
Membrane Proteins/genetics*
;
Child, Preschool
;
Adolescent
;
GATA2 Transcription Factor/genetics*
;
GTP Phosphohydrolases/genetics*
;
Proto-Oncogene Proteins p21(ras)/genetics*
7.Comparative analysis of the predictive value of fried frailty phenotype, liver fraily index and short physical performance battery in the prognosis of patients with liver cirrhosis
Jia LUO ; Dai ZHANG ; Shan SHAN ; Xiaoming WANG ; Xiaojuan OU ; Yu WANG ; Jidong JIA
Journal of Clinical Hepatology 2025;41(9):1818-1828
ObjectiveTo investigate the value of Fried Frailty Phenotype (FFP), liver frailty index (LFI), and Short Physical Performance Battery (SPPB) in predicting 2-year all-cause mortality and decompensation events in patients with liver cirrhosis. MethodsA total of 277 patients with liver cirrhosis who were hospitalized in Beijing Friendship Hospital, Capital Medical University, from December 2020 to December 2021 were enrolled, and FFP, LFI, and SPPB were used to assess the state of frailty. Based on the scores of each tool, these patients were divided into frail and non-frail groups. These three tools were compared in terms of consistency and independent predictive performance. The primary endpoints were 2-year all-cause mortality rate and composite endpoints (death+decompensation events), and the Cox regression analysis, the receiver operating characteristic (ROC) curve, net reclassification index (NRI), and integrated discrimination improvement (IDI) index were used to analyze the predictive value of the three tools. Normally distributed continuous data were compared between two groups using the independent samples t-test, while non-normally distributed continuous data were compared using the Mann-Whitney U test. Categorical data were compared between groups using the chi-square test or Fisher’s exact test. The agreement among different frailty tools was evaluated using Cohen’s Kappa statistic. The Kaplan-Meier survival curve was plotted, and a survival analysis was performed using the log-rank test. ResultsThe prevalence rate of frailty assessed by FFP, LFI, and SPPB was 37.2%, 22.4%, and 20.2%, respectively, with a moderate consistency between FFP and LFI/SPPB (κ=0.57, 95% confidence interval [CI]: 0.47 — 0.67; κ=0.51, 95%CI: 0.41 — 0.62) and a relatively high consistency between LFI and SPPB (κ=0.87, 95%CI: 0.80 — 0.94). Compared with the non-frailty group, the frailty group had significantly higher all-cause mortality rate and incidence rate of composite endpoints (P0.001). After multivariate adjustment, FFP, LFI, and SPPB had a hazard ratio of 2.42(95%CI: 1.51 — 5.11), 2.21(95%CI: 1.11 — 4.42), and 2.21(95%CI: 1.14 — 4.30), respectively, in predicting all-cause mortality, as well as a hazard ratio of 2.51(95%CI: 1.61 — 3.91), 2.40(95%CI: 1.51 — 3.80), and 2.20(95%CI: 1.39 — 3.47), respectively, in predicting composite endpoints. Compared with Child-Pugh score, FFP had a significantly greater area under the ROC curve (AUC) in predicting all-cause mortality (0.79 vs 0.69, P=0.032) and composite endpoints (0.75 vs 0.68, P=0.044). Frailty assessment tools combined with Child-Pugh score significantly improved the performance in predicting all-cause mortality and composite endpoints, with an AUC of 0.81 — 0.82 and 0.77 — 0.78, respectively (P0.05). NRI and IDI analyses further confirmed the improvement of the combined model in classification (all P0.001). ConclusionFFP, LFI, and SPPB can independently predict adverse outcomes in patients with liver cirrhosis, among which FFP has the best predictive performance, and the combination of frailty assessment tools with Child-Pugh score can significantly enhance the accuracy of prognostic evaluation.
8.Research on the value of narrative medicine in bridging differences in shared decision-making
Shan LUO ; Dabin WANG ; Jiawen ZHANG ; Fang XIE ; Hong LIU
Chinese Medical Ethics 2025;38(6):679-686
Shared Decision-Making (SDM) is a crucial concept in modern medicine, emphasizing the joint participation of doctors and patients in the medical decision-making process. However, the authoritative position of doctors and the passive role of patients in traditional medical models often overlook the personal wishes and needs of patients, leading to tense doctor-patient relationships and medical disputes. By listening to and understanding their stories, narrative medicine helps doctors gain a more comprehensive understanding of patients’ situations and balances medical advice with patient needs in the decision-making process. Through systematic literature analysis and theoretical exploration, this paper investigated the application effects and mechanisms of narrative medicine in different medical contexts, as well as analyzed its specific role in the process of SDM. The aim is to explore the value of narrative medicine in bridging differences in SDM, revealing its role in promoting doctor-patient communication, enhancing decision-making participation, and improving medical outcomes. Researches had found that narrative medicine enhanced doctors’ “narrative ability”, promoted emotional communication and trust between doctors and patients, reduced conflicts and misunderstandings in decision-making, and improved patients’ sense of participation and trust, thus playing an important role in SDM. Therefore, by enhancing doctor-patient communication and understanding, promoting SDM and treatment selection between doctors and patients, personalized care and treatment optimization, advocating for doctor-patient co-construction, improving consultation efficiency, restoring the patient’s subject position, and other methods, it can bridge doctor-patient differences, promote communication and enhance decision-making participation, and improve medical outcomes and patient satisfaction.
9.DUSP26 inhibits proliferation, migration, and invasion of lung adenocarcinoma A549 cells by suppressing the TGF-β1/SMAD2/3 signaling pathway
LUO Fengheng ; WU Min ; ZHOU Shan ; XIAO Yanan ; ZHAN Zhiqiang
Chinese Journal of Cancer Biotherapy 2025;32(7):738-745
[摘 要] 目的:探究双特异性磷酸酶26(DUSP26)在肺腺癌(LUAD)A549细胞增殖、迁移和侵袭中的作用及其分子机制。方法:检索肿瘤数据库GEPIA2网站DUSP26表达数据,分析DUSP26在LUAD患者和正常人肺组织中的表达差异。收集2022年10月至2023年10月期间萍乡市人民医院手术切除的12例LUAD组织和癌旁组织标本,通过免疫组织化学(IHC)和WB法检测DUSP26在LUAD组织和癌旁组织之间的表达差异;通过WB法检测DUSP26在4种LUAD细胞(A549、SK-LU-1、Calu-3、H1299)和2种正常支气管上皮细胞(BEAS-2B、HBEC)中的表达差异。利用慢病毒转染细胞的方法构建稳定过表达DUSP26(DUSP26-OE)及阴性对照(DUSP26-OENC)的A549细胞,通过克隆形成、划痕愈合实验、Transwell实验分别检测DUSP26过表达对细胞增殖、迁移及侵袭能力的影响,WB法检测各组细胞中TGF-β1/SMAD2/3通路、EMT相关蛋白的表达水平,细胞免疫荧光法检测细胞中Ki-67、cyclin D1表达水平。加入TGF-β1重组蛋白进行回复实验。构建A549细胞裸鼠荷瘤模型,观察DUSP26过表达对移植瘤体内生长的影响,WB法检测移植瘤组织中TGF-β1/SMAD2/3通路、EMT相关蛋白表达水平,免疫荧光染色法检测移植瘤组织中Ki-67、cyclin D1表达水平。结果:DUSP26在LUAD组织和细胞中均呈低表达(P < 0.05或P < 0.01或P < 0.001或P < 0.000 1)。与DUSP26-OENC组相比,DUSP26-OE组A549细胞的增殖、迁移和侵袭能力均显著降低(P < 0.01或P < 0.001),TGF-β1、p-SMAD2/3、vimentin、N-cadherin、snail、Ki-67、cyclin D1表达均降低(P < 0.01或P < 0.001或P < 0.000 1),E-cadherin表达升高(P < 0.000 1)。加入5 ng/mL TGF-β1重组蛋白后,可部分逆转在体外实验中由DUSP26过表达导致的结果。成功构建裸鼠A549细胞荷瘤模型,DUSP26-OE组裸鼠移植瘤生长速度缓慢,体积和质量均减小(均P < 0.001),移植瘤组织中TGF-β1、p-SMAD2/3、vimentin、N-cadherin、snail、Ki-67、cyclin D1表达均降低(P < 0.01或P < 0.001),E-cadherin表达升高(P < 0.000 1)。结论:DUSP26在LUAD组织和细胞中均呈低表达状态,上调DUSP26的表达水平能够通过抑制TGF-β1/SMAD2/3信号通路抑制A549细胞的增殖、迁移和侵袭。
10.Systemic comparison of molecular characteristics in different skin fibroblast senescent models.
Xiaokai FANG ; Shan ZHANG ; Mingyang WU ; Yang LUO ; Xingyu CHEN ; Yuan ZHOU ; Yu ZHANG ; Xiaochun LIU ; Xu YAO
Chinese Medical Journal 2025;138(17):2180-2191
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*

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