1.KAT7 promotes chondrocyte senescence by activating the PI3K/AKT/mTOR signaling pathway
Kang Wang ; Ying Li ; Nuo Xu ; Tingting Guo ; Yun Chen ; Xuran Zeng ; Liqi Sun ; Haochen Xu ; Wei Wei ; Shangxue Yan
Acta Universitatis Medicinalis Anhui 2025;60(8):1506-1513
Objective :
To establish an interleukin-1β (Il-1β) induced inflammatory model of rat articular chondro- cytes (ACs) , and to investigate the relationship between the expression of lysine acetyltransferase 7 (KAT7) under inflammatory stimulation and the senescence of ACs.
Methods:
Primary ACs were obtained by digestion of rat knee cartilage with collagenase type Ⅱ and identified. The inflammatory model of ACs was induced by IL-1β . KAT7 was over-expressed or knocked down in ACs by adeno-associated virus infection or small interfering RNA transfection , respectively. A negative control group was set up. Transwell assay was used to detect cell migration ability. Senes- cent cells were stained with senescence-associated β-galactosidase (SA-β-Gal) . Western blot ( WB) was used to detect the protein expression levels of KAT7 , collagen type II (Col Ⅱ ) , matrix metalloproteinase 13 (MMP13) , tumor protein p53 (p53) and cyclin-dependent kinase inhibitor 1A (p21) . The cells of negative control group and KAT7 over-expression group were performed for RNA sequencing , and WB was used to verify the related signaling pathways obtained by Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis.
Results:
Compared with the control group , the SA-β-Gal staining was enhanced , the protein expression of Col Ⅱ decreased , the pro- tein expression of MMP13 and p53 increased , the cell migration ability decreased , and the expression of KAT7 also increased in the ACs of rats after IL-1β stimulation. Compared with the negative control group , the SA-β-Gal stai- ning was enhanced , the protein expression of Col Ⅱ decreased , the protein expression of MMP13 , p53 and p21 in- creased , and the cell migration ability decreased in the KAT7 over-expression group. Compared with the negative control group , the SA-β-Gal staining was weakened , the protein expression of Col Ⅱ increased , the protein expres- sion of MMP13 , p53 and p21 decreased , and the cell migration ability was enhanced in the KAT7 knockdown inflammatory model of ACs. KEGG enrichment analysis showed that phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was activated. Compared with the negative control group , the relative protein ex⁃pression levels of phosphorylated protein kinase B (p⁃AKT)/AKT and phosphorylated mammalian target of rapamy⁃cin (p⁃mTOR)/mTOR in KAT7 over⁃expression group increased. The relative protein expression levels of p ⁃AKT/AKT and p ⁃mTOR/mTOR in KAT7 knockdown cells decreased.
Conclusion
Rat ACs with high expression of KAT7 exhibit senescence and osteoarthritis phenotype , and the mechanism may be related to the activation of PI3K/AKT/mTOR signaling pathway by KAT7.
2.Analysis of factors affecting poor incision healing after breast cancer surgery
Xuran ZHU ; Bolin ZHANG ; Yanqi YANG ; NUERBANNU·TABUSIBIEKE ; Guoan SHAO ; Shu CHEN
Journal of Clinical Surgery 2025;33(7):722-726
Objective To analyze the influencing factors of poor incision healing in postoperative patients with breast cancer.Methods The clinical data of 150 patients with breast cancer diagnosed by the Department of Nail Milk surgery of the Fifth affiliated Hospital of Xinjiang Medical University from January 2016 to December 2023 were retrospectively analyzed.According to the postoperative wound healing,the patients were divided into two groups:good healing group(n=94)and poor healing group(n=56).The general data,operation-related data and clinicopathological characteristics of the two groups were collected for univariate analysis,and the single-factor indexes with statistical significance were analyzed by multivariate Logistic analysis to screen the risk factors of poor incision healing after operation.The statistically significant indexes of regression analysis were analyzed by receiver operating characteristic(ROC)curve to further explore its predictive value in poor incision healing after breast cancer operation.Results The data of the two groups were compared and analyzed.Multivariate Logistic regression analysis showed that BMI,diabetes,age,axillary lymph node dissection and hemoglobin were independent risk factors for poor incision healing(P<0.05).ROC curve analysis of independent risk factors showed that when the age was more than 57.5,the area under the curve(AUC)was 0.635,the sensitivity was 55.4%,the specificity was 68.1%,and the critical value was 57.5.When BMI>24.9 kg/m2,the area under the curve(AUC)was 0.735,the sensitivity was 87.5%,the specificity was 61.7%,and the critical value was 24.9(P<0.001).When hemoglobin<101.5 g/L,the area under the curve(AUC)was 0.829,the sensitivity was 57.1%,the specificity was 94.7%,and the critical value was 101.5 g/L(P<0.001).Conclusion BMI,diabetes,hemoglobin,age and axillary lymph node dissection are independent risk factors for poor wound healing after breast cancer operation.When BMI>24.9 kg/m2,age>57.5 years old and hemoglobin<101.5 g/L,it can predict the occurrence of poor incision healing in patients with breast cancer.
3.Analysis of factors affecting poor incision healing after breast cancer surgery
Xuran ZHU ; Bolin ZHANG ; Yanqi YANG ; NUERBANNU·TABUSIBIEKE ; Guoan SHAO ; Shu CHEN
Journal of Clinical Surgery 2025;33(7):722-726
Objective To analyze the influencing factors of poor incision healing in postoperative patients with breast cancer.Methods The clinical data of 150 patients with breast cancer diagnosed by the Department of Nail Milk surgery of the Fifth affiliated Hospital of Xinjiang Medical University from January 2016 to December 2023 were retrospectively analyzed.According to the postoperative wound healing,the patients were divided into two groups:good healing group(n=94)and poor healing group(n=56).The general data,operation-related data and clinicopathological characteristics of the two groups were collected for univariate analysis,and the single-factor indexes with statistical significance were analyzed by multivariate Logistic analysis to screen the risk factors of poor incision healing after operation.The statistically significant indexes of regression analysis were analyzed by receiver operating characteristic(ROC)curve to further explore its predictive value in poor incision healing after breast cancer operation.Results The data of the two groups were compared and analyzed.Multivariate Logistic regression analysis showed that BMI,diabetes,age,axillary lymph node dissection and hemoglobin were independent risk factors for poor incision healing(P<0.05).ROC curve analysis of independent risk factors showed that when the age was more than 57.5,the area under the curve(AUC)was 0.635,the sensitivity was 55.4%,the specificity was 68.1%,and the critical value was 57.5.When BMI>24.9 kg/m2,the area under the curve(AUC)was 0.735,the sensitivity was 87.5%,the specificity was 61.7%,and the critical value was 24.9(P<0.001).When hemoglobin<101.5 g/L,the area under the curve(AUC)was 0.829,the sensitivity was 57.1%,the specificity was 94.7%,and the critical value was 101.5 g/L(P<0.001).Conclusion BMI,diabetes,hemoglobin,age and axillary lymph node dissection are independent risk factors for poor wound healing after breast cancer operation.When BMI>24.9 kg/m2,age>57.5 years old and hemoglobin<101.5 g/L,it can predict the occurrence of poor incision healing in patients with breast cancer.
4.Preparation and Evaluation of Poloxamer/Carbopol In-Situ Gel Loaded with Quercetin: In-Vitro Drug Release and Cell Viability Study
Pinxuan ZHENG ; Xueying LIU ; Yanqing JIAO ; Xuran MAO ; Zhaorong ZONG ; Qi JIA ; Heng Bo JIANG ; Eui-Seok LEE ; Qi CHEN
Tissue Engineering and Regenerative Medicine 2024;21(8):1153-1171
BACKGROUND:
Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system.
METHODS:
In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 lmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1 : poloxamer 407 and X2 : carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables.
RESULTS:
These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect.
CONCLUSIONS
The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.
5.Preparation and Evaluation of Poloxamer/Carbopol In-Situ Gel Loaded with Quercetin: In-Vitro Drug Release and Cell Viability Study
Pinxuan ZHENG ; Xueying LIU ; Yanqing JIAO ; Xuran MAO ; Zhaorong ZONG ; Qi JIA ; Heng Bo JIANG ; Eui-Seok LEE ; Qi CHEN
Tissue Engineering and Regenerative Medicine 2024;21(8):1153-1171
BACKGROUND:
Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system.
METHODS:
In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 lmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1 : poloxamer 407 and X2 : carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables.
RESULTS:
These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect.
CONCLUSIONS
The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.
6.Preparation and Evaluation of Poloxamer/Carbopol In-Situ Gel Loaded with Quercetin: In-Vitro Drug Release and Cell Viability Study
Pinxuan ZHENG ; Xueying LIU ; Yanqing JIAO ; Xuran MAO ; Zhaorong ZONG ; Qi JIA ; Heng Bo JIANG ; Eui-Seok LEE ; Qi CHEN
Tissue Engineering and Regenerative Medicine 2024;21(8):1153-1171
BACKGROUND:
Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system.
METHODS:
In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 lmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1 : poloxamer 407 and X2 : carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables.
RESULTS:
These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect.
CONCLUSIONS
The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.
7.Research progress of related factors affecting poor response to wet age-related macular degeneration
Haitao PAN ; Ruizhuang LI ; Qiuli ZHANG ; Xuran CHEN
International Eye Science 2024;24(4):567-571
Wet age-related macular degeneration(wARMD)emerges as a primary contributor to irreversible vision impairment in the aging demographic. In clinical practice, anti-vascular endothelial growth factor(VEGF)therapies exhibit pronounced success in managing wARMD. However, in the actual clinical application, there are significant individual differences in the prognosis of anti-VEGF drug therapy, and some patients show poor response to the treatment, which may be related to the morphological differences of retinal layers in macular area, genetics, systemic conditions and other factors. It will help develop a more rational and individualized treatment plan to judge the prognosis of patients according to their different clinical manifestations in advance, so as to reduce overtreatment and the risk of retinal damage. In recent years, most studies on treatment response mainly focus on fundus morphology, genetics and so on. In this study, the relevant factors affecting adverse response to wARMD were reviewed, aiming to provide with more accurate treatment and prognostic monitoring programs for clinicians.
8.Preparation and Evaluation of Poloxamer/Carbopol In-Situ Gel Loaded with Quercetin: In-Vitro Drug Release and Cell Viability Study
Pinxuan ZHENG ; Xueying LIU ; Yanqing JIAO ; Xuran MAO ; Zhaorong ZONG ; Qi JIA ; Heng Bo JIANG ; Eui-Seok LEE ; Qi CHEN
Tissue Engineering and Regenerative Medicine 2024;21(8):1153-1171
BACKGROUND:
Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system.
METHODS:
In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 lmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1 : poloxamer 407 and X2 : carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables.
RESULTS:
These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect.
CONCLUSIONS
The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.
9.Preparation and Evaluation of Poloxamer/Carbopol In-Situ Gel Loaded with Quercetin: In-Vitro Drug Release and Cell Viability Study
Pinxuan ZHENG ; Xueying LIU ; Yanqing JIAO ; Xuran MAO ; Zhaorong ZONG ; Qi JIA ; Heng Bo JIANG ; Eui-Seok LEE ; Qi CHEN
Tissue Engineering and Regenerative Medicine 2024;21(8):1153-1171
BACKGROUND:
Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system.
METHODS:
In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 lmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1 : poloxamer 407 and X2 : carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables.
RESULTS:
These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect.
CONCLUSIONS
The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.
10.Preliminary application of MR-Linac in breast cancer radiotherapy in a single academic center
Hao JING ; Yu TANG ; Yuan TIAN ; Ke ZHANG ; Shirui QIN ; Ying CAO ; Hui FANG ; Xuran ZHAO ; Bo CHEN ; Yongwen SONG ; Jing JIN ; Yueping LIU ; Shunan QI ; Yuan TANG ; Ningning LU ; Ning LI ; Shulian WANG ; Yexiong LI
Chinese Journal of Radiation Oncology 2022;31(1):8-14
Objective:To describe a prospective study of pre-operative tumor-bed boost performed at the 1.5 T MR-Linac in combination with adjuvant whole breast irradiation, and a first case, with an accentuation on clinical feasibility and safety.Methods:A phase II, single arm study recruiting early stage patients follows a paradigm that first boosts the tumor bed and then undergoes breast conservative surgery in 2 weeks, and last irradiates the whole breast in 6 weeks. The primary endpoint is ≥ grade 2 acute breast toxicity. A 43 years old patient affected by a breast carcinoma, not special type of the right-sided lateral quadrant, staged cT 2N 0M 0, was planned and treated. The dose, 8 Gy for one time, was calculated by Monaco on CT simulation images. Both the air electron stream effect (ESE) and the electron return effect (ERE) at the presence of 1.5 T magnetic field were evaluated. During the pre-treatment evaluation, we carried out adaptation-to-position adjustment. Results:The normal organ dosimetry is within toleration. The Dmax to the skin, the chin and the right upper arm was 8.44 Gy, 28.5 cGy and 17.8 cGy, respectively. There was no increased toxicity from ERE and ESE, and the treatment was well tolerated without > grade 1 acute toxicity. The patient received breast conservative surgery on day 7 without delayed wound healing.Conclusions:This is the first case successfully treated within a clinical trial by pre-operative tumor-bed boost under 1.5 T MR-Linac in our institution. More participants are needed to validate and optimize the paradigm.


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