1.Effect of miR-130a-3p targeting PPAR-γ on epithelial-mesenchymal transition in silica-induced pulmonary fibrosis
Xiaohui HAO ; Qian LI ; Yixuan JIN ; Qinxin ZHANG ; Yudi WANG ; Fang YANG
Journal of Environmental and Occupational Medicine 2025;42(2):188-195
Background At present, the treatment of silicosis is still limited, and no method is available to cure the disease. miRNAs are involved in the process of fibrosis at the transcriptional level by directly degrading target gene mRNA or inhibiting its translation. However, how miR-130a-3p regulates silicosis fibrosis has not been fully elucidated yet. Objective To investigate whether miR-130a-3p promotes epithelial-mesenchymal transition (EMT) by inhibiting peroxisome proliferators-activated receptors gamma (PPAR-γ), thereby pro-moting the process of silicotic fibrosis. To identify effective new targets for the treatment of silicotic fibrosis. Methods (1) Animal experiments: C57BL/6J mice were intratracheally injected with a one-time dose of 10 mg silica suspension (dissolved in 100 μL saline) as positive lung exposure. A silicosis model group was established 28 d after the exposure. A control group was injected with the same amount of normal saline into the trachea. Hematoxylin-eosin staining and Sirius red staining were used to observe the pathological changes and collagen deposition in lung tissues respectively. Realtime fluorescence-based quantitative polymerase chain reaction (RT-qPCR) was used to assay the expression of miR-130a-3p and PPAR-γ mRNA in lung tissues. Western blotting was used to detect the protein expression of PPAR-γ, transforming growth factor (TGF)-β1, E-cadherin, α-smooth muscle actin (α-SMA), and Collagen Ⅰ in lung tissues. (2) Cells experiments: Mouse lung epithelial cells (MLE-12) were induced with 5 µg·L−1 TGF-β1 for different time (0, 12, 24, 48 h). RT-qPCR was used to detect the expression of miR-130a-3p and PPAR-γ mRNA in cells. The binding relationship between miR-130a-3p and PPAR-γ mRNA was verified by dual luciferase reporter gene assay. MLE-12 cells were stimulated by 5 µg·L−1 TGF-β1 after transfection of miR-130a-3p inhibitor, and Western blotting was used to measure the protein expression of PPAR-γ, E-cadherin, and α-SMA in the TGF-β1-induced cells. Results In the silicosis model group, the alveolar septum was widened and the pulmonary nodules were formed. The Sirius red staining collagen deposition in pulmonary nodules indicated that a silicosis fibrosis model was successfully established. The expressions of TGF-β1, α-SMA, and Collagen Ⅰ proteins were increased, and the expressions of E-cadherin and PPAR-γ proteins were decreased in lung tissues of the silicosis group, compared with the control group (P<0.05 or P<0.01). The expression of miR-130a-3p was increased and the expression of PPAR-γ mRNA was decreased in lung tissues of the silicosis model (P<0.01). The expression of miR-130a-3p was significantly increased, while the expression of PPAR-γ mRNA was decreased in the TGF-β1 induced MLE-12 cells (P<0.05 or P<0.01). The dual luciferase reporter assay showed a direct relationship between miR-130a-3p and PPAR-γ mRNA in MLE-12 cells. The transfection of miR-130a-3p inhibitor in the TGF-β1 induced MLE-12 cells inhibited the decrease of PPAR-γ and E-cadherin proteins, and the increase of α-SMA protein in the MLE-12 cells induced by TGF-β1 (P<0.05 or P<0.01). Conclusion miR-130a-3p promotes the development of silicosis fibrosis by targeting PPAR-γ to increase pulmonary EMT.
2.Investigation on the management and nurses' cognitive level of iodinated contrast media extravasation in Henan Province
Yuanyuan SONG ; Yu WANG ; Ruonan HAO ; Fangfang DONG ; Linlin HUANG ; Qiao-fang YANG ; Xiaohui JIA ; Shan BAI
Chinese Journal of Nursing 2025;60(11):1351-1358
Objective To investigate the status of management of iodinated contrast media(ICM)extravasation in Henan Province,as well as nurses' knowledge and influencing factors,in order to provide a basis for optimizing management strategies.Methods A self-designed questionnaire was applied,employing convenience sampling,to survey nursing administrators and nurses in the radiology departments of 55 tertiary hospitals across 16 regions of Henan Province,from December 2024 to January 2025.Multiple linear regression analysis was conducted to explore the factors influencing nurses' knowledge.Results A total of 55 nursing administrators and 64 nurses participated,with a valid questionnaire response rate of 100%.The survey results reveal that only 5.45%of radiology depart-ments utilized high-pressure central venous catheters,and 32.73%employed vascular visualization techniques.When setting the high-pressure injection speed for ICM,only 54.55%of radiology departments required an assessment of the type and model of intravenous access.Additionally,only 9.09%of radiology departments mandated an observa-tion for 2 to 4 hours following ICM extravasation.Furthermore,only 50.91%of radiology departments had estab-lished an information system for ICM use.The nurses' knowledge score regarding the prevention and management of ICM extravasation was(90.00±17.59),influenced by years of experience in radiology and professional titles(P<0.05).Conclusion The prevention and management measures for ICM in radiology departments in Henan Province need further improvement.Nursing administrators should optimize management strategies,improve relevant training systems,and continuously enhance nurses' knowledge and practical abilities.
3.The time-series association between carotid intima-media thickness and bone mineral density in a Chinese population:a cross-lagged analysis based on a cohort of people undergoing physical examination
Hua HAO ; Can ZHANG ; Peiying YANG ; Hui GENG ; Xiaohui LI ; Baosen MENG ; Jun WANG ; Baibing MI ; Mao MA
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(6):1037-1044
Objective To explore the time cross-lagged effect between carotid intima-media thickness(CIMT)and bone mineral density(BMD)and to assess whether CIMT can be used as an early predictor of osteoporosis.Methods Based on the retrospective cohort study involved,people who underwent health checkups at The First Affiliated Hospital of Xi'an Jiaotong University from January 2019 to December 2023 were selected,and data related to CIMT and BMD were collected.The time-series relationship between CIMT and BMD was explored by cross-lagged modeling.Meanwhile,the effects of CIMT on BMD and its dose-response relationship were assessed using multiple linear regression and restricted cubic spline regression models.Results Analysis of 2 453 study subjects revealed a significant negative relationship between prior physical examination CIMT and subsequent BMD,and this relationship remained significant after controlling for confounders.For every 1-unit increase in CIMT,there was a mean decrease in second-stage BMD T-values of 0.113.Restricted cubic spline regression analysis showed a maximum decrease in BMD T-values of 0.121 for every 1.00 mm increase in CIMT.Conclusion The present study found that there was a significant negative cross-lag effect between CIMT and BMD,and that there was a dose-response between an increase in CIMT and a decrease in BMD.CIMT,as an easy-to-measure indicator,may be a potential marker for early prediction of osteoporosis,especially in the elderly population.
4.BRD4 regulates alveolar epithelial-mesenchymal transition through HMGB1/TGF-β1/Smad pathway
Ruru Chen ; Lu Han ; Hailan He ; Xiaohui Hao ; Heliang Liu ; Lingli Guo
Acta Universitatis Medicinalis Anhui 2025;60(2):247-254
Objective :
To investigate the mechanisms of bromodomain-containing protein 4(BRD4) in TGF-β1-induced epithelial-mesenchymal transition in alveolar type II epithelial cells.
Methods :
MLE-12 cells were stimulated with different concentrations(5 ng/ml, 10 ng/ml) of TGF-β1 for 48 h to establish an EMT cell model. The cells were pretreated with 50 nmol/L BRD4 inhibitor JQ-1, 100 μmol/L high mobility group box 1 protein(HMGB1)inhibitor glycyrrhizin acid(GA), and 3 μg/ml rHMGB1. The experimental groups were divided as follows: control group, TGF-β1 group, JQ-1 group, JQ-1+TGF-β1 group, GA group, GA+TGF-β1 group, and JQ-1+TGF-β1+rHMGB1 group. The effect of JQ-1 on cell viability was examined using cell counting kit-8(CCK-8). The protein expression levels of CDH1, ZO-1, Vimentin, α-SMA, BRD4, HMGB1, TGF-β1, Smad2/3 and p-Smad2/3 were detected by Western blot. The cell migration ability was detected by a scratch test.
Results :
Compared with the control group, the levels of Vimentin and α-SMA in the TGF-β1 group increased, and the levels of CDH1 and ZO-1 protein decreased, suggesting that the EMT model was successfully established. In this model, the expression of BRD4 and HMGB1 significantly increased. Different concentrations of JQ-1 could inhibit the cell viability of MLE-12 in a concentration-dependent manner. Both JQ-1 and GA could effectively alleviate TGF-β1-induced EMT, and reduce the increase in HMGB1 expression and the activation of TGF-β1/Smad2/3 pathway caused by TGF-β1. Moreover, rHMGB1 treatment could reduce the effects of JQ-1 on EMT and the TGF-β1/Smad2/3 pathway. Additionally, both JQ-1 and glycyrrhizin could effectively decrease TGF-β1-induced cell migration, whereas rHMGB1 could alleviate the inhibitory effect of JQ-1 on the rate of cell migration.
Conclusion
BRD4 can regulate epithelial-mesenchymal transition in alveolar type II epithelial cells via HMGB1/TGF-β1/Smad2/3 signaling cascade, and BRD4 may be a potential target for inhibition of pulmonary fibrosis.
5.Expression of β-arrestin1 in oral squamous cell carcinoma and its effect on cell proliferation,migration and invasion
Xiaohui HAO ; Min CHEN ; Nan WU ; Yunshan DING ; Lifan ZHU ; Haitao DAI
Journal of Army Medical University 2025;47(14):1632-1641
Objective To investigate the effect of β-arrestin1(ARRB1)on cell proliferation,migration and invasion in oral squamous cell carcinoma(OSCC).Methods Based on The Cancer Genome Atlas(TCGA)database,the expression profiles of ARRB1 in OSCC were analyzed,and then Gene Set Enrichment Analysis(GSEA)was used to suggest the possible signaling pathways involved,and to explore its potential impact on the prognosis of OSCC patients.Immuinohistochemistry(IHC)was performed to detect the expression of ARRB1 in OSCC tumor tissues and adjacent tissues,and the correlation between ARRB1 expression and clinicopathological features was statistically analyzed.The expression profiles of ARRB1 in SCC-15,CAL-27 and HOK cell lines were verified by qPCR and Western blotting.The ARRB1 overexpression plasmid model was constructed,and its effects on the proliferation,migration and invasion of OSCC cells were analyzed by clone formation,EdU,scratch and Transwell assays.Results TCGA showed that the expression level of ARRB1 was significantly lower in head and neck squamous cell carcinoma(HNSC)and OSCC tissues than the corresponding normal tissues(P<0.01).The expression of ARRB1 in OSCC tissues was correlated with tumor differentiation,lymph node metastasis and TNM stage(P<0.05).The OSCC patients with high expression of ARRB1 had a lower survival rate than those with low expression(P<0.01),which was consistent with the results of bioinformatics analysis.The expression level of ARRB1 in SCC-15 and CAL-27 cells was lower than that of HOK cells(P<0.01),and its overexpression significantly inhibited cell proliferation(P<0.05),migration(P<0.01)and invasion(P<0.01).Conclusion ARRB1 is lowly expressed in OSCC,its overexpression inhibits the proliferation,migration and invasion of OSCC cells,and it is related to prognosis improvement.
6.Clinical characteristics of juvenile dermatomyositis in anti-nuclear matrix protein 2 antibody-positive patients and risk factors for severity: a national multicenter retrospective study
Huiyuan YANG ; Wanzhen GUAN ; Ling2 YANG ; Haimei LIU ; Xiaoqing3 LI ; Haiguo YU ; Meiping LU ; Jun YANG ; Xiaohui LIU ; Hongxia ZHANG ; Wei ZHANG ; Jihong XIAO ; Xiaozhong LI ; Guomin LI ; Hong CHANG ; Sheng HAO ; Yue DU ; Daliang XU ; Ling WU ; Wenjie ZHENG ; Li LIU ; Xinhui JIANG ; Shaohui ZHU ; Dongmei ZHAO ; Xuemei TANG ; Li SUN
Chinese Journal of Pediatrics 2025;63(12):1299-1305
Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.
7.Meta analysis of risk factors for spontaneous bacterial peritonitis in cirrhosis patients with ascites
Xiaohui HAO ; Lufei XING ; Lihua WANG ; Wenwen LIAN
Chinese Journal of Nosocomiology 2025;35(6):867-874
OBJECTIVE To systematically evaluate the risk factors for spontaneous bacterial peritonitis(SBP)in the cirrhosis patients with ascites so as to provide bases for reducing the incidence of SBP.METHODS The literatures regarding to cirrhosis ascites complicated with SBP were retrieved from the databases such as PubMed,Embase,Cochrane Library,CBM,CNKI,Wanfang and VIP.The time frame of retrieval was limited from the establish-ment of the databases to Jan.10,2024.The quality of the literatures was evaluated by Newcastle-Ottawa Scale(NOS).The data were analyzed by using STATA 16.0.RESULTS A total of 43 pieces of literatures were included in the study,involving 9877 research subjects,3384 of whom were complicated with SBP.The result of meta a-nalysis showed that the risk factors(P<0.05)for SBP in the cirrhosis patients with ascites included the general factor(history of SBP),the disease factors(gastrointestinal hemorrhage,diarrhea,diabetes mellitus),drug fac-tors(use of proton pump inhibitors),physiological indexes[low blood sodium,low serum albumin,high serum bilirubin,rise of C-reactive protein(CRP)],liver function scoring indexes[Child-turcotte-pugh(CTP)grade C,model of end-stage liver disease(MELD)],and ascites indexes[low ascites albumin,rise of ascites white blood cells and rise of tumor necrosis factor-α(TNF-α)].CONCLUSIONS SBP is one of the most severe complications in the cirrhosis patients with ascites.Multiple risk factors may have remarkable influence on the occurrence and de-velopment of SBP.It is necessary to take targeted interventions to the controllable risk factors during the clinical practice so as to effectively reduce the risk of SBP in the cirrhosis patients with ascites.
8.Training methods and effects of individualized eyebrow shape design before eyebrow transplantation
Yunwei WANG ; Xianming QIAO ; Wei HAN ; Ao SHI ; Xiaohui LIU ; Yating QIAO ; Hao GUAN ; Yi LIU
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(5):517-522
Objective:To explore the training method for personalized eyebrow shape design before eyebrow transplantation surgery and to evaluate its effectiveness.Methods:Thirty physicians with similar foundational knowledge in facial aesthetic design and equivalent educational backgrounds were prospectively selected from the Second Hospital of Lanzhou University and Beijing Biliansheng Medical Beauty Clinic from January to December 2023. All the physicians were right-handed. Based on prior experience in eyebrow transplantation surgery, they were divided into two groups: an observation group [ n=20; 10 males, 10 females; aged (27.8±3.9) years] without experience in personalized eyebrow transplantation surgery, and a control group [ n=10; 5 males, 5 females; aged (29.6±4.0) years] with at least 2 years of experience in personalized eyebrow transplantation surgery. All the physicians received 2 hours of theoretical instruction on personalized eyebrow shape design and 8 hours of simulated operation training. Differences in personalized eyebrow design scores between the two groups were compared before and after training. After the assessment, physicians in the observation group performed eyebrow shape design on 20 eyebrow transplantation patients with randomly assigned face shapes, and patient satisfaction was evaluated. Results:Before training, personalized eyebrow design scores were 1.16±0.29 for the observation group and 3.75±0.22 for the control group, showing a statistically significant difference ( P<0.001). After operation training, the scores were 4.51±0.11 for the observation group and 4.89±0.08 for the control group, with no statistically significant difference ( P>0.05). The difference between pre- and post-training scores within the observation group was statistically significant ( P<0.05). Physicians in the observation group designed eyebrow shapes for male and female patients with various face shapes. Immediately after surgery, 80% (16/20) of patients were very satisfied, and 20% (4/20) were satisfied. Conclusion:After training of combined theoretical lectures, simulated practice, and hands-on patient design, physicians in the observation group demonstrate improved ability in personalized eyebrow shape design and achieve high patient satisfaction.
9.Efficacy of reduction robot system combined with minimally invasive, microenvironmental protection, micro-stress shielding fixator in the treatment of Sanders types II and III calcaneal fractures
Xiaohui HAO ; Yongqing WANG ; Zhanmin XU ; Xinan ZHANG ; Zhihui ZHAO ; Jingtao SUN ; Zhiqiang YANG ; Meiyue LIU ; Weiyong WU ; Baoxi HAO ; Juwen CHEN
Chinese Journal of Trauma 2025;41(5):463-470
Objective:To evaluate the efficacy of reduction robot system combined with minimally invasive, microenvironmental protection, micro-stress shielding fixator (short for "3M fixator") for Sanders types II and III calcaneal fractures.Methods:A retrospective case series study was conducted to analyze the clinical data of 26 patients (26 feet) with calcaneal fractures admitted to Fourth Affiliated Central Hospital of Tianjin Medical University from June 2022 to June 2024, including 21 males and 5 females, aged 27-69 years [(46.5±2.5)years]. Among them, 10 patients had fractures in the left foot and 16 in the right. According to the Sanders classification, the fractures were classified as type II in 16 patients and type III in 10. All the patients were treated with the close reduction with reduction robot system combined with 3M fixator in a minimally invasive procedure. The surgical waiting time, operative duration, and fracture healing time were recorded. The length, width and height of the calcaneus, B?hler′s angle and Gissane′s angle were compared before operation and at 1, 3 months after operation. The visual analogue scale (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score before operation and at 1, 3 months after operation and at the last follow-up were detected. The postoperative complications were recorded.Results:All the patients were followed up for 6-12 months [(9.7±1.1)months]. The surgical waiting time was 1-4 days [(2.0±0.8)days]. The operative duration was 36-66 minutes [(53.2±9.5)minutes]. All the fractures achieved primary union with a healing period of 3-4 months [(3.2±0.4)months]. At 1, 3 months after operation, the length of the calcaneus [(83.3±3.7)mm and (83.6±3.6)mm], width of the calcaneus [(44.3±5.8)mm and (44.3±5.7)mm], height of the calcaneus [(50.1±3.8)mm and (50.3±3.6)mm], B?hler′s angle [(29.8±2.9)° and (29.8±3.0)°], and Gissane angle [(121.1±6.7)° and (123.9±5.9)°] were significantly improved compared with those before operation [(79.3±4.5)mm, (53.6±4.1)mm, (46.2±3.7)mm, (18.9±3.8)°, (109.0±7.5)°, respectively] ( P<0.05), with no significant differences between those indicators at 1, 3 months after operation ( P>0.05). The VAS scores were (3.2±0.6)points, (1.9±0.5)points, and (1.6±0.3)points at 1, 3 months after operation and at the last follow-up, which were lower than (7.1±0.5)points preoperatively and decreased with the prolongation of follow-up time ( P<0.05). The AOFAS scores were (73.5±6.9)points, (90.1±4.3)points, and (92.0±3.6)points, which were higher than (32.0±4.6)points preoperatively and increased with the follow-up time ( P<0.05). One patient had lateral calcaneal pain after operation, and was alleviated after rehabilitation. No complications such as infection or nonunion were found after operation. Conclusion:The reduction robot system combined with 3M fixator for Sanders types II and III calcaneal fractures demonstrates significant clinical advantages, such as reduced surgical waiting time and operative duration, promoted fracture healing, early alleviated pain, enhanced ankle joint functional recovery, and decreased complication occurrence.
10.Enhanced radiotheranostic targeting of integrin α5β1 with PEGylation-enabled peptide multidisplay platform (PEGibody): A strategy for prolonged tumor retention with fast blood clearance.
Siqi ZHANG ; Xiaohui MA ; Jiang WU ; Jieting SHEN ; Yuntao SHI ; Xingkai WANG ; Lin XIE ; Xiaona SUN ; Yuxuan WU ; Hao TIAN ; Xin GAO ; Xueyao CHEN ; Hongyi HUANG ; Lu CHEN ; Xuekai SONG ; Qichen HU ; Hailong ZHANG ; Feng WANG ; Zhao-Hui JIN ; Ming-Rong ZHANG ; Rui WANG ; Kuan HU
Acta Pharmaceutica Sinica B 2025;15(2):692-706
Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [64Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [64Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [64Cu]QM-2303 from the bloodstream. Administration of a single dose of [177Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [64Cu]/[177Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [64Cu]/[177Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.


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