1.The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis.
Xiaoxuan ZHONG ; Xiang WEI ; Yan XU ; Xuehai ZHU ; Bo HUO ; Xian GUO ; Gaoke FENG ; Zihao ZHANG ; Xin FENG ; Zemin FANG ; Yuxuan LUO ; Xin YI ; Ding-Sheng JIANG
Acta Pharmaceutica Sinica B 2024;14(2):712-728
Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.
2.Discussion on the Treatment of Heart Failure from the Theory of "Sweat Pore-Collaterals-Zang and Fu Organs" Based on Mitochondrial Function
Yuxuan LI ; Wujiao WANG ; Peng LI ; Yuanyuan ZHANG ; Xingxing LI ; Junyan XIA ; Ruli FENG ; Dong LI ; Qian LIN ; Yan LI
Journal of Traditional Chinese Medicine 2024;65(13):1346-1352
Mitochondria are the main site of energy metabolism in cardiomyocytes, and at the same time mediate apoptosis and immune response, so mitochondrial dysfunction is closely related to the development of heart failure. Combined with the pathogenesis of mitochondrial dysfunction and heart failure, it is proposed that the mitochondrial function is similar to "sweat pore - collaterals - zang and fu organs", according to which the treatment of heart failure is based on the theory of "sweat pore - collaterals - zang and fu organs". It is believed that the core mechanism of heart failure is qi deficiency, and qi deficiency leads to the weakness of the sweat pore opening and closing, or even the sweat pore closure, then resulting in qi deficiency and blood stasis, collaterals stagnation fail to flourish, and qi, blood, and body fluids can not infiltrate and nourish zang-fu organs, so that the heart fail to be nourished, and the disease will develop. The treatment should be based on the method of boosting qi and opening sweat pore, using acridity to unblock the collaterals, and invigorating blood and draining water, with medicinal of boosting qi, invigorating blood, and draining water as treatment.
3.Progress in the application of decision-making aids for vaginal birth after cesarean
Jingjing JIANG ; Ke ZHANG ; Xiaoxuan BI ; Yuxuan FENG ; Dongmei LIU ; Shujie GUO ; Yanhong WANG
Chinese Journal of Modern Nursing 2024;30(3):399-405
Vaginal birth after cesarean (VBAC) can reduce the cesarean section rate and has many benefits for both mother and infant. Decision-making aids can promote communication between doctors and patients regarding childbirth methods and increase pregnant women's informed consent and decision-making participation in VBAC, thereby supporting pregnant women in making choices and improving the quality of childbirth decisions. This article summarizes the content of VBAC decision-making aids, evaluation of different VBAC decision-making aids, application of VBAC decision-making aids, and obstacles to the application of VBAC decision-making aids in China to provide reference for the development and application of domestic childbirth decision-making aids.
4.Mechanism of curcumin-regulated transcription factor FOXP3 on effects of HIV-1 infection co-receptor CCR5
Long FENG ; Qingya LI ; Hanbing LI ; Baiyan WANG ; Shan CAO ; Wenjin ZHENG ; Yuxuan GENG ; Qing LI
Chinese Journal of Immunology 2024;40(4):772-779
Objective:To investigate the mechanism of curcumin affecting HIV-1 infection co-receptor CCR5 by regulating transcription factor FOXP3.Methods:Binding sites of transcription factor FOXP3 on CCR5 promoter were predicted and analyzed by bioinformatics method.AutoDock 4.2 software was used to connect curcumin and FOXP3 flexibly.MTT assay was used to detect cyto-toxcity of curcumin on activity of Jurkat cells.qRT-PCR and Western blot were used to detect expression levels of CCR5 and FOXP3 mRNA and protein in Jurkat cells that were treated with different concentrations of curcumin.pcDNA3.1-FOXP3 expression vector was built and combined with the prediction results of transcription factors.The mutant CCR5 gene fragment was amplified by Overlap PCR,and the mutant CCR5 promoter recombinant vector pFireRluc-Mt-CCR5 was constructed.Binding site between transcription fac-tor FOXP3 and CCR5 promoter was verified by double luciferase reporter gene assay.Results:Results of JASPAR transcription factor prediction showed that there was a binding site between CCR5 promoter and transcription factor FOXP3;molecular docking results showed that curcumin could bind to the active region of FOXP3;MTT results showed that curcumin inhibited the activity of Jurkat cells after 24 hours,and the IC50 was 34.48 μmol/L.qRT-PCR and Western blot showed that expression levels of CCR5 and FOXP3 mRNA and protein were decreased in a dose-dependent manner after different concentrations of curcumin treated Jurkat cells;double luciferase reporter gene confirmed that FOXP3 could bind to CCR5 promoter,and the transcription factor FOXP3 could regulate the activity of CCR5 promoter;results of the recovery experiment of FOXP3 on curcumin showed that when the curcumin concentration was 60 μmol/L,relative value of luciferase activity in HEK293T cells with pcDNA3.1-FOXP3 and pFireRluc-Wt-CCR5 was signifi-cantly higher than that in pFireRluc-Wt-CCR5+curcumin-60 group(P<0.01).Conclusion:FOXP3 can regulate the activity of CCR5 promoter,and the mechanism may be that curcumin affects activity of CCR5 promoter by acting on binding site of FOXP3 and CCR5 promoter.
5.Systematic review of mother-infant attachment measurement tools based on Consensus-based Standards for the Selection of Health Measurement Instruments guidelines
Xiaoxuan BI ; Xueping LIANG ; Shujie GUO ; Dongmei LIU ; Ke ZHANG ; Yuxuan FENG ; Jingjing JIANG ; Yanhong WANG
Chinese Journal of Modern Nursing 2024;30(19):2586-2594
Objective:To conduct systematic review of mother-infant attachment measurement tools based on Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines.Methods:The researches on mother-infant attachment measurement tools in PubMed, Scopus, Embase, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, WanFang Data and VIP was searched by computer, and the search period was from establishment of the databases to October 30, 2023. Two reviewers trained in evidence-based methodology independently screened the literature, extracted and summarized the data, and systematically evaluated the attributes of the measurement tools using the COSMIN guideline bias risk list and good measurement attribute standards.Results:A total of 35 studies were included, including seven maternal-infant attachment measurement tools. Among them, the content validity quality of the Maternal-fetal Attachment Tool was sufficient (evidence quality was advanced), the structural validity quality was uncertain (evidence quality was intermediate), the internal consistency quality was sufficient (evidence quality was advanced) and the hypothesis testing quality was sufficient (evidence quality was advanced), which was recommended at level A.Conclusions:This study systematically evaluates seven measurement tools for maternal-infant attachment, among which the Maternal-fetal Attachment Tool is class A tool and is recommended for use.
6.A Review of Researches on Quality Evaluation and Management of Medical Big Data
Yuxuan FENG ; Tianrui HE ; Li SHEN ; Rui ZHENG ; Guangjun YU
Journal of Medical Informatics 2024;45(8):1-7
Purpose/Significance To summarize the common dimensions of data quality evaluation,and to expound the types and characteristics of medical big data quality evaluation and management methods,so as to provide references for medical big data quality e-valuation and management.Method/Process The paper reviews domestic and foreign medical big data quality related literature,and em-phatically analyzes medical big data quality evaluation dimensions,methods and management.Result/Conclusion Data quality standards are conducive to standardized management of medical big data.A scientific and reasonable medical big data quality evaluation system and a whole-process data quality management system in line with national conditions in China should be established and improved as soon as possible to promote the development and application of medical big data in our country.
7.Epigenetic drug combination induced the expression of FMR1NB in oral carcinoma
Yuxuan ZHANG ; Huan XIE ; Yanjing WANG ; Feng LI ; Guojian WANG ; Weixia NONG ; Chang LIU ; Bin LUO ; Xiaoxun XIE ; Ning SHEN ; Qingmei ZHANG
Acta Universitatis Medicinalis Anhui 2024;59(5):761-766
Objective To investigate the effects of DNA demethylation drugs combined with histone deacetylase in-hibitors on fragile X mental retardation 1 neighbor protein (FMR1NB) expression and its promoter methylation in human oral cancer cells and try to find a strategy of weakening the heterogeneity of FMR1NB expression.Methods Human oral cancer cell lines Cal27 and SCC-9 were treated with decitabine (DAC) , an inhibitor of DNA meth-yltransferase, combined with trichostatin A (TSA) and valproic acid (VPA), inhibitors of histone deacetylase.Then reverse transcription-polymerase chain reaction (RT-PCR) , quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of FMR1 NB and pyrosequencing was used to detect the methylation of FMR1NB promoter.Results Compared with the blank control group, DAC and its combination with TSA and VPA significantly induced the expression of FMR1NB mRNA and protein in Cal27 and SCC-9 cells.Compared with DAC alone group, FMR1NB mRNA expression of each DAC-combined drug groups significantly increased, but FMR1NB protein did not significantly change in Cal27 cells; for SCC-9 cells, except for DAC+TSA group, the mRNA and protein levels of FMR1NB significantly increased in all other groups.In addition, there was no signifi-cant difference in the expression of FMR1 NB mRNA and protein between the three-combined drugs group and two-combined drugs groups.Further methylation assay showed that the methylation level of the overall FMR1NB promot-er and its each CpG site measured were reduced to varying degrees in all treatment groups except for three-combina-tion drug group of SCC-9.Conclusion DAC and its combination with TSA and VPA can enhance the expression of FMR1NB by mediating the demethylation of FMR1NB promoter, wherein the enhanced expression effect of the com-bination of the two drugs is stronger, suggesting that they have the potential to weaken the heterogeneity of FMR1NB expression and improve the immunotherapy effect of oral cancer.
8.Analysis on the Current Situation,Influencing Factors and Strategies of Data Sharing in Cross-regional Specialty Medical Alliances
Jingjin SHI ; Rui YUAN ; Yuxuan FENG ; Guangjun YU
Journal of Medical Informatics 2023;44(11):30-34
Purpose/Significance To clarify the construction mode and key factors of data sharing in Chinese medical alliances,and to provide references for promoting data sharing in medical alliances.Method/Process Taking children's medical alliance of Yangtze River Delta as an example,Delphi method and qualitative interview method are used to explore the key contents and effect evaluation of specialty alliance construction,and the key factors of specialty alliance data sharing are defined based on the technology-organization-environment framework;SWOT analysis model is used to propose development strategies.Result/Conclusion Member hospitals are less satisfied with the construction effect of information interconnection.Key factors for realizing data sharing in specialty alliances include:support from government administrative departments,uniform and systematic compatibility of information standards,information security emergency response,patient privacy protection and informed consent,willingness of department directors to share,and internal communi-cation and compensation mechanism of alliances.
9.Clinical value of sodium dithionite reduction method in the diagnosis and treatment of diquat poisoning
Jinquan LI ; Zhengsheng MAO ; Jinsong ZHANG ; Zihao WANG ; Yuxuan WU ; Lili JIANG ; Feng CHEN ; Hao SUN
Chinese Journal of Emergency Medicine 2023;32(2):192-197
Objective:To explore the clinical value of urine semi-quantitative colorimetry by sodium dithionite reduction method in the diagnosis and treatment of diquat poisoning.Methods:The data of 49 patients with acute diquat poisoning treated in the First Affiliated Hospital of Nanjing Medical University from December 3, 2020 to November 23, 2022 were retrospectively analyzed, the correlation between urine colorimetric results and plasma diquat concentration was observed, and the predictive value of urine colorimetric results for target organ damage and prognosis were evaluated.Results:There was a significant correlation between urine colorimetric results and plasma diquat concentration, the correlation coefficient was r=0.89, P <0.01. The cut-off value of urine colorimetry for the predicting the damage of gastrointestinal tract, liver, kidney, and central nervous system injury were 2.5, 3.5, 3.5, 5.5, respectively; in which the urine colorimetric results showed the highest sensitivity in predicting digestive tract injury [ AUC 0.93 (95% CI:0.89-1.00)]. The cut-off value of urine colorimetry for the prognosis of death was 4.5, the positive predictive value was 64.2%, and the negative predictive value was 95.2%. Conclusions:The urine semi-quantitative method can be used for rapid prediction of the plasma diquat concentration range on admission. The urine colorimetry results can also effectively predict the occurrence of organ injury and clinical outcome related to diquat poisoning, which provides evidence for the clinical diagnosis and therapy.
10.Neoadjuvant and adjuvant therapy of intrahepatic cholangiocarcinoma
Yuxuan LIN ; Yong XIA ; Feng SHEN
Chinese Journal of Hepatobiliary Surgery 2023;29(7):552-556
Intrahepatic cholangiocarcinoma (ICC) refers to adenocarcinoma originating from the secondary bile ducts and their branches within the liver, with high malignancy and poor prognosis. Radical surgical resection is currently the only possible way to cure ICC, but only some patients meet the surgical standards, and even with surgical resection, about 60% of patients will relapse within 1~2 years. Neoadjuvant therapy and adjuvant therapy are important perioperative treatment methods for ICC, with the aim of reducing postoperative recurrence and improving postoperative survival. This article aims to elaborate on the current status and research progress of neoadjuvant therapy and adjuvant therapy for ICC.


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