1.Relationship of lncRNA UCA1 and miR-665 with coronary restenosis in patients with ACS after interventional therapy
Yichao ZHANG ; Siliang HAN ; Shaoqing SHEN ; Junmin XIE
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(2):140-144
Objective To investigate the correlation between the peripheral blood levels of long non-coding RNA urothelial carcinoma associated 1(lncRNA UCA1)and miR-665 with the occur-rence of coronary restenosis in patients with ACS after interventional treatment.Methods A total of 315 ACS patients admitted to the Affiliated Hospital of Hebei University from July 2022 to Ju-ly 2023 were recruited and then divided into occurrence group(62 cases)and non-occurrence group(253 cases)according to the occurrence of coronary restenosis.The expression of lncRNA UCA1 and miR-665 in peripheral blood samples was detected by real-time fluorescence quantita-tive PCR.Pearson analysis was applied to analyze the correlation between peripheral blood ln-cRNA UCA1 and miR-665 in ACS patients.Logistic regression analysis was used to identify the influencing factors for coronary restenosis in ACS patients.ROC curve was plotted to analyze the predictive value of peripheral blood lncRNA UCA1 and miR-665 for the restenosis,and their AUC values were calculated.Results The peripheral blood expression of lncRNA UCA1 was signifi-cantly higher,and that of miR-665 was obviously lower in the occurrence group than the non-occurrence group(1.28±0.22 vs 1.01±0.21,P=0.001;0.76±0.24 vs 1.01±0.22,P=0.001).Pearson analysis showed there was a negative correlation between miR-665 and lncRNA UCA1 expression levels in the ACS patients(r=-0.585,P<0.05).Multivariate logistic regression anal-ysis indicated that LncRNA UCA1 was a risk factor(OR=2.124,95%CI:1.324-3.406,P=0.002),and miR-665 was a protective factor(OR=0.765,95%CI:0.653-0.897,P=0.001)for the occurrence of coronary restenosis in ACS patients after interventional treatment.ROC curve analysis revealed that the combination of peripheral blood lncRNA UCA1 and miR-665 had the highest AUC value in predicting the occurrence of coronary restenosis,which was better than the value of single molecule(Z=2.256,P=0.024;Z=2.904,P=0.004).Conclusion Combination of peripheral blood levels of lncRNA UCA1 and miR-665 has good performance for predicting coro-nary restenosis in ACS patients after interventional therapy.
2.Effect of miR-137 on atherosclerotic vulnerable plaques in mice through targeting sex determining region Y box protein 4
Siliang HAN ; Yichao ZHANG ; Junmin XIE ; Zhe WANG ; Shaoqing SHEN ; Fanchang KONG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(5):642-649
Objective To investigate the effect and underlying mechanism of miR-137 on athero-sclerosis(AS)plaques in apolipoprotein E(ApoE)gene knockout(ApoE)mice.Methods Sixty ApoE-/-mice were fed with high-fat diet for 12 weeks to establish an AS model.Then they were assigned into AS group,negative control group,miR-137 group,Ad negative control group,and combination group,with 12 mice in each group;Another 12 wild-type C57BL/6 mice fed with chow diet were subjected as the Control group.Fully automated biochemical analyzer was applied to detect serum lipid levels,including total cholesterol(TC),triglycerides(TG),low-density lipo-protein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C).ELISA was con-ducted to detect the levels of serum inflammatory factors,including TNF-α,IL-4,IL-6,and IL-10.HE staining was used to observe the morphological changes of mouse aortic tissue.Oil red O stai-ning was employed to observe the overall formation of aortic plaques.Immunofluorescence stai-ning was utilized to detect the expression of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1)in the aortic tissue.Real-time qPCR was applied to detect the mRNA expression of miR-137 and sex determining region Y box protein 4(SOX4)in the aorta.Results The miR-137 group has significantly lower serum levels of TG,TC,LDL-C,TNF-α and IL-6,and higher levels of HDL-C,IL-10 and IL-4 when compared with the AS group and negative control group(P<0.05).The combination treatment resulted in increased serum levels of TG,TC,LDL-C,TNF-αand IL-6,while decreased levels of HDL-C,IL-10 and IL-4 in comparison with the Ad negative control group(P<0.05).Larger aortic plaque area,more severe overall aortic plaque injury and stronger iNOS fluorescence intensity were observed in the AS group than the control group(P<0.05).Treatment of miR-137 reversed above histological changes,resulting in smaller aortic plaque area,attenuated overall aortic plaque injury,decreased iNOS fluorescence intensity,and elevated Arg-1 fluorescence intensity when compared with the AS group and negative control group(P<0.05).Compared with the Ad negative control group,the aortic plaque area,overall aortic plaque injury and iNOS fluorescence intensity were increased,while the Arg-1 fluorescence intensity was significantly decreased in the combined group(P<0.05).Double luciferase assay showed that the luciferase activity of SOX4-containing wild-type cells was significantly decreased after transfection of miR-137 mimics when compared with transfection of mimics negative control(0.37±0.05 vs 1.00±0.08,P<0.05).Conclusion Overexpression of miR-137 inhibits the activa-tion of rat sarcoma/mitogen-activated protein kinase pathway probably by down-regulating SOX4 expression,and then suppress M1 macrophage polarization and promote M2 macrophage polariza-tion,reduces inflammatory response and the formation of AS plaques.
3.Relationship of lncRNA UCA1 and miR-665 with coronary restenosis in patients with ACS after interventional therapy
Yichao ZHANG ; Siliang HAN ; Shaoqing SHEN ; Junmin XIE
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(2):140-144
Objective To investigate the correlation between the peripheral blood levels of long non-coding RNA urothelial carcinoma associated 1(lncRNA UCA1)and miR-665 with the occur-rence of coronary restenosis in patients with ACS after interventional treatment.Methods A total of 315 ACS patients admitted to the Affiliated Hospital of Hebei University from July 2022 to Ju-ly 2023 were recruited and then divided into occurrence group(62 cases)and non-occurrence group(253 cases)according to the occurrence of coronary restenosis.The expression of lncRNA UCA1 and miR-665 in peripheral blood samples was detected by real-time fluorescence quantita-tive PCR.Pearson analysis was applied to analyze the correlation between peripheral blood ln-cRNA UCA1 and miR-665 in ACS patients.Logistic regression analysis was used to identify the influencing factors for coronary restenosis in ACS patients.ROC curve was plotted to analyze the predictive value of peripheral blood lncRNA UCA1 and miR-665 for the restenosis,and their AUC values were calculated.Results The peripheral blood expression of lncRNA UCA1 was signifi-cantly higher,and that of miR-665 was obviously lower in the occurrence group than the non-occurrence group(1.28±0.22 vs 1.01±0.21,P=0.001;0.76±0.24 vs 1.01±0.22,P=0.001).Pearson analysis showed there was a negative correlation between miR-665 and lncRNA UCA1 expression levels in the ACS patients(r=-0.585,P<0.05).Multivariate logistic regression anal-ysis indicated that LncRNA UCA1 was a risk factor(OR=2.124,95%CI:1.324-3.406,P=0.002),and miR-665 was a protective factor(OR=0.765,95%CI:0.653-0.897,P=0.001)for the occurrence of coronary restenosis in ACS patients after interventional treatment.ROC curve analysis revealed that the combination of peripheral blood lncRNA UCA1 and miR-665 had the highest AUC value in predicting the occurrence of coronary restenosis,which was better than the value of single molecule(Z=2.256,P=0.024;Z=2.904,P=0.004).Conclusion Combination of peripheral blood levels of lncRNA UCA1 and miR-665 has good performance for predicting coro-nary restenosis in ACS patients after interventional therapy.
4.Effect of miR-137 on atherosclerotic vulnerable plaques in mice through targeting sex determining region Y box protein 4
Siliang HAN ; Yichao ZHANG ; Junmin XIE ; Zhe WANG ; Shaoqing SHEN ; Fanchang KONG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(5):642-649
Objective To investigate the effect and underlying mechanism of miR-137 on athero-sclerosis(AS)plaques in apolipoprotein E(ApoE)gene knockout(ApoE)mice.Methods Sixty ApoE-/-mice were fed with high-fat diet for 12 weeks to establish an AS model.Then they were assigned into AS group,negative control group,miR-137 group,Ad negative control group,and combination group,with 12 mice in each group;Another 12 wild-type C57BL/6 mice fed with chow diet were subjected as the Control group.Fully automated biochemical analyzer was applied to detect serum lipid levels,including total cholesterol(TC),triglycerides(TG),low-density lipo-protein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C).ELISA was con-ducted to detect the levels of serum inflammatory factors,including TNF-α,IL-4,IL-6,and IL-10.HE staining was used to observe the morphological changes of mouse aortic tissue.Oil red O stai-ning was employed to observe the overall formation of aortic plaques.Immunofluorescence stai-ning was utilized to detect the expression of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1)in the aortic tissue.Real-time qPCR was applied to detect the mRNA expression of miR-137 and sex determining region Y box protein 4(SOX4)in the aorta.Results The miR-137 group has significantly lower serum levels of TG,TC,LDL-C,TNF-α and IL-6,and higher levels of HDL-C,IL-10 and IL-4 when compared with the AS group and negative control group(P<0.05).The combination treatment resulted in increased serum levels of TG,TC,LDL-C,TNF-αand IL-6,while decreased levels of HDL-C,IL-10 and IL-4 in comparison with the Ad negative control group(P<0.05).Larger aortic plaque area,more severe overall aortic plaque injury and stronger iNOS fluorescence intensity were observed in the AS group than the control group(P<0.05).Treatment of miR-137 reversed above histological changes,resulting in smaller aortic plaque area,attenuated overall aortic plaque injury,decreased iNOS fluorescence intensity,and elevated Arg-1 fluorescence intensity when compared with the AS group and negative control group(P<0.05).Compared with the Ad negative control group,the aortic plaque area,overall aortic plaque injury and iNOS fluorescence intensity were increased,while the Arg-1 fluorescence intensity was significantly decreased in the combined group(P<0.05).Double luciferase assay showed that the luciferase activity of SOX4-containing wild-type cells was significantly decreased after transfection of miR-137 mimics when compared with transfection of mimics negative control(0.37±0.05 vs 1.00±0.08,P<0.05).Conclusion Overexpression of miR-137 inhibits the activa-tion of rat sarcoma/mitogen-activated protein kinase pathway probably by down-regulating SOX4 expression,and then suppress M1 macrophage polarization and promote M2 macrophage polariza-tion,reduces inflammatory response and the formation of AS plaques.
5.Modelling the difference of circulating lymphocytes between conventional fractionation radiotherapy and stereotactic body radiation therapy for lung cancer based on convolution operation
Shuling LI ; Yichao SHEN ; Kuifei CHEN ; Meng CHEN ; Haihua YANG
Chinese Journal of Radiation Oncology 2022;31(11):998-1003
Objective:To evaluate the difference between conventional fractionation radiotherapy (CRT) and stereotactic body radiation therapy (SBRT) in lung cancer.Methods:A model was constructed based on convolution operation and finite element method, simulating the dose delivered to circulating lymphocytes (CL) in radiotherapy. The model was trained on a training group ( n=3) and validated in an independent validation group between SBRT ( n=10) and CRT ( n=10). The peak cumulative dose of circulating lymphocyte (PCDC) was compared between the two schemes, and the effect of different PTV volumes and treatment time on the cumulative dose was also analyzed. The correlation between PCDC and CL change value was discussed. Results:In the training group, PCDC with CRT to CL were 1.26 Gy,1.79 Gy, 2.54 Gy in PTV of 38 cm 3, 63 cm 3 and 114 cm 3, and PCDC with SBRT to CL were 0.84 Gy, 1.22 Gy, 1.55 Gy in PTV of 38 cm 3, 63 cm 3, 114 cm 3, respectively. PCDC gap of SBRT to CL was decreased by 0.42 Gy, 0.57 Gy, 0.99 Gy, respectively. In the validation group, the lymphocyte change value in SBRT and CRT were (1.10±0.64)×10 9/L and (0.42±0.48)×10 9/L, and there was significant difference ( P=0.015). PCDC in SBRT and CRT were 3.56 (2.79, 3.82) Gy and 1.24 (0.697, 1.73) Gy, and there was significant difference ( P<0.001). There was a positive correlation between lymphocyte change value and PCDC ( r=0.455, P<0.05). Conclusions:SBRT, compared to CRT, will lead to lower PCDC and CL lymphocyte change value, which may cause a greater impact on the difference of PCDC along with the enlargement of PTV. CRT and large PTV volume may cause more significant effect upon the body immune function.
6.Predictive value of neutrophil-lymphocyte ratio for Trousseau’s syndrome in patients with acute multiple cerebral infarctions
Lelin YU ; Hailong SHANG ; Hongdi DU ; Ying WANG ; Yichao WANG ; Changhe XU ; Zhenkai LI ; Shiwei ZHAO ; Fanghui ZHENG ; Hailin SHEN
International Journal of Cerebrovascular Diseases 2022;30(3):174-178
Objective:To investigate the predictive value of neutrophil-lymphocyte ratio (NLR) for Trousseau’s syndrome (TS) in patients with acute multiple cerebral infarctions (AMCI).Methods:The patients with AMCI in Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine from July 2013 to March 2022 were retrospectively enrolled. The demographic and baseline clinical data of patients with TS and those without TS were compared. Multivariate logistic regression analysis was used to determine the independent influencing factors of TS-AMCI, and receiver operating characteristic (ROC) curve was used to evaluate the predictive value of NLR for TS-AMCI. Results:A total of 59 patients with AMCI were enrolled, including 43 males and 16 females, aged 64.9±14.0 years. There were 16 patients in the TS-AMCI group and 43 in the non-TS-AMCI group. The proportions of patients with diabetes mellitus, hypertension and previous stroke or transient ischemic attack in the TS-AMCI group were significantly lower than those in the non-TS-AMCI group (all P<0.05), while the proportion of patients with ischemic heart disease were significantly higher than that in the non-TS-AMCI group ( P<0.05). The proportion of patients with bilateral infarction in the TS-AMCI group was significantly higher than that in the non-TS-AMCI group ( P<0.001). The D-dimer, NLR, white blood cell count, neutrophil count, monocyte count, percentage of neutrophils, total cholesterol and low-density lipoprotein cholesterol in the TS-AMCI group were significantly higher than those in the non-TS-AMCI group (all P<0.001), while the lymphocyte count, lymphocyte percentage, red blood cell count, hemoglobin and hematocrit were significantly lower than those in the non-TS-AMCI group (all P<0.001). Multivariate logistic regression analysis showed that high NLR was an independent predictor of TS-AMCI (odds ratio [ OR] 2.897, 95% confidence interval [ CI] 1.270-6.527; P=0.011), while high hemoglobin was independently negatively correlated with TS-AMCI ( OR 0.839, 95% CI 0.723-0.975; P=0.022). ROC curve analysis showed that the area under the curve of NLR for predicting TS-AMCI was 0.929 (95% CI 0.831-0.979; P<0.001). When the NLR cutoff value was 4.01, the corresponding Youden index was 0.744. At this time, the sensitivity and specificity were 100% and 74.42% respectively. Conclusion:NLR has high predictive value for TS-AMCI.
7.Expression of vasohibin-1 and VEGF-A and its clinical significance in gastric cancer
Yichao YAN ; Chao SHEN ; Ning NING ; Yankai ZHANG ; Wenyue WANG ; Yingjiang YE ; Shan WANG
Chinese Journal of General Surgery 2021;36(8):612-615
Objective:To explore the expression of vasohibin-1 (VASH1) and vascular endothelial growth factor A (VEGF-A) and clinical significance of VASH1 in gastric carcinoma.Methods:The expression of VASH1 and VEGF-A were detected by immunohistochemistry in formalin-fixed and paraffin-embedded sections in 56 pairs of gastric cancer and corresponding paraneoplastic tissue specimens. The correlation between the expression of VASH1, VEGF-A, clinicopathological parameters and prognosis were analyzed.Results:VASH1 and VEGF-A expression was significantly higher in gastric cancer tissues than normal paraneoplastic tissues. VASH1 and VEGF-A protein were expressed in 79% and 82% of gastric cancer tissues, respectively. A positive correlation was found between Vasohibin-1 and VEGF-A expression in gastric cancer tissues. VASH1 expression has significant positive correlation with TNM stage, tumor stromal invasion, tumor gross types and distant metastasis. Patients with high VASH1 expression had significantly worse overall survival (OS) and progression-free survival (PFS) than those with low VASH1 expression.Conclusion:VASH1 might be a clinically relevant predictor of patients in gastric cancer.
8.Expert Concensus on Triune Personalized Treatment of Pelvic Tumor Based on Three-Dimensional Printing
Songtao AI ; Zhengdong CAI ; Feiyan CHEN ; Kerong DAI ; Yang DONG ; Lingjie FU ; Yongqiang HAO ; Yingqi HUA ; Wenbo JIANG ; Jiong MEI ; Yuhui SHEN ; Wei SUN ; Rong WAN ; Yichao WANG ; Zhiwei WANG ; Haifeng WEI ; Wen WU ; Jianru XIAO ; Wangjun YAN ; Xinghai YANG ; Chunlin ZHANG ; Weibin ZHANG
Journal of Medical Biomechanics 2021;36(1):E001-E005
The adjacent anatomy of the pelvis is complicated, with digestive, urinary, reproductive and other organs as well as important blood vessels and nerves. Therefore, accurate resection of pelvic tumors and precise reconstruction of defects after resection are extremely difficult. The development of medical 3D printing technology provides new ideas for precise resection and personalized reconstruction of pelvic tumors. The “triune” application of 3D printing personalized lesion model, osteotomy guide plate and reconstruction prosthesis in pelvic tumor limb salvage reconstruction treatment has achieved good clinical results. However, the current lack of normative guidance standards such as preparation and application of 3D printing personalized lesion model, osteotomy guide plate and reconstruction prosthesis restricts its promotion and application. The formulation of this consensus provides normative guidance for 3D printing personalized pelvic tumor limb salvage reconstruction treatment.
9.Expression of CD157 in colorectal cancer tissues and its clinical significances
Chao SHEN ; Yichao YAN ; Bin LIANG ; Yingjiang YE ; Wenyue WANG
Chinese Journal of General Surgery 2020;35(7):554-557
Objective:To investigate the expression of CD157 and its significance in colorectal cancer.Methods:The expression of CD157 was detected in 50 cases of colorectal cancer tissues and corresponding adjacent normal colorectal tissues by immunohistochemistry. The correlation between the expression of CD157 and clinicopathological parameters and prognosis was analyzed statistically.Results:Higher expression of CD157 protein was observed in colorectal cancer than that in normal colorectal tissues (72% vs. 20%, χ 2=25.09, P<0.01). Moreover, High expression of CD157 was correlated with the tumor size (χ 2=7.368, P=0.007), TNM stage (χ 2=9.223, P=0.002), the depth of tumor infiltration (χ 2=4.158, P=0.041), distant metastasis (χ 2=5.521, P=0.019), vascular invasion (χ 2=6.307, P=0.012) and microsatellite instability (χ 2=4.778, P=0.029), but not with gender, age, histology type, location, differentiation grade, lymph node metastasis, nerve infiltration or Kras mutation (all P>0.05 respectively). Patients with low expression of CD157 had longer survival (45±4 )months than those with high expression (30±3)months (χ 2=5.234, P=0.022). Conclusions:High expression of CD157 in colorectal cancer tissue is related to poor survival of postoperative patients.
10.Development of the triazole-fused pyrimidine derivatives as highly potent and reversible inhibitors of histone lysine specific demethylase 1 (LSD1/KDM1A).
Zhonghua LI ; Lina DING ; Zhongrui LI ; Zhizheng WANG ; Fengzhi SUO ; Dandan SHEN ; Taoqian ZHAO ; Xudong SUN ; Junwei WANG ; Ying LIU ; Liying MA ; Bing ZHAO ; Pengfei GENG ; Bin YU ; Yichao ZHENG ; Hongmin LIU
Acta Pharmaceutica Sinica B 2019;9(4):794-808
Histone lysine specific demethylase 1 (LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound (IC = 3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound (IC = 49 nmol/L, and = 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3K4me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency of compound . Compound also showed strong antiproliferative activity against four leukemia cell lines (OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, significantly inhibited colony formation and caused remarkable morphological changes. Compound induced expression of CD86 and CD11b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation. The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazole-fused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1A inhibitors.

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