1.C/EBPβ-Lin28a positive feedback loop triggered by C/EBPβ hypomethylation enhances the proliferation and migration of vascular smooth muscle cells in restenosis.
Xiaojun ZHOU ; Shan JIANG ; Siyi GUO ; Shuai YAO ; Qiqi SHENG ; Qian ZHANG ; Jianjun DONG ; Lin LIAO
Chinese Medical Journal 2025;138(4):419-429
BACKGROUND:
The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis.
METHODS:
Restenosis and atherosclerosis rat models of type 2 diabetes ( n = 20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student's t -test and one-way analysis of variance were used for statistical analysis.
RESULTS:
C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitroC/EBPβ overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBPβ knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBPβ hypomethylation. Additionally, Lin28a overexpression reduced C/EBPβ methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells.
CONCLUSION
Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis.
Animals
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Cell Proliferation/genetics*
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Cell Movement/genetics*
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Muscle, Smooth, Vascular/metabolism*
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Rats
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DNA Methylation/physiology*
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CCAAT-Enhancer-Binding Protein-beta/genetics*
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Male
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Myocytes, Smooth Muscle/cytology*
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Rats, Sprague-Dawley
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RNA-Binding Proteins/genetics*
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Cells, Cultured
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Coronary Restenosis/metabolism*
2.Influence of antiviral treatment adjustment on the prognosis of chronic hepatitis B patients with low-level viremia
Mengwen HE ; Wucai YANG ; Chunyan WANG ; Yiming FU ; Chang GUO ; Jianjun WANG ; Dong JI
Journal of Clinical Hepatology 2025;41(6):1056-1061
ObjectiveTo investigate the incidence rate of primary liver cancer (PLC) and the progression of liver fibrosis in chronic hepatitis B (CHB) patients with low-level viremia (LLV) (HBV DNA<2 000 IU/mL but ≥20 IU/mL) after treatment adjustment, and to provide more robust evidence for clinical practice. MethodsA retrospective analysis was performed for the clinical data of LLV patients who initially received nucleos(t)ide analogue (NAs) for at least 48 weeks at the Fifth Medical Center of PLA General Hospital from August 2007 to April 2017 and subsequently underwent NAs adjustment due to LLV, and according to the virologic response after 48 weeks of treatment adjustment, the patients were divided into LLV group and complete virological response (CVR) group (HBV DNA<20 IU/mL). The patients were followed up once every 3 — 6 months till the primary endpoint event of PLC or October 2024. The incidence rate of PLC and the progression of liver fibrosis were observed, and the progression of liver fibrosis was defined as an increase of ≥1 grade in fibrosis-4 (FIB-4) index. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups; the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate the cumulative incidence rate of PLC, and the Log-rank test was used for comparison between groups; the Cox regression analysis was used to investigate the risk factors for PLC, and the Logistic regression analysis was used to investigate the influencing factors for the progression of liver fibrosis. ResultsA total of 307 patients were enrolled, with a mean age of 50.0 years, and the male patients accounted for 80.5%. After 48 weeks of treatment with the adjusted NAs regimen, 254 patients (82.7%) achieved CVR, and 53 patients (17.3%) still had LLV. For the LLV group, the incidence rate of PLC was 30.2% and the rate of liver fibrosis progression was 22.6%, while for the CVR group, the incidence rate of PLC was only 13.4%, and the rate of liver fibrosis progression was 7.5%. The multivariate regression analyses showed that LLV was an independent risk factor for the onset of PLC (hazard ratio=2.623, 95% confidence interval [CI]: 1.315 — 5.234, P=0.006) and the progression of liver fibrosis (odds ratio=3.213, 95%CI: 1.385 — 7.455, P=0.007). ConclusionActive adjustment of treatment is needed immediately after the diagnosis of LLV to improve CVR, and if LLV persists after treatment adjustment, it is necessary to enhance the monitoring of liver fibrosis progression and PLC, so as to facilitate early diagnosis and treatment.
3.Guidelines for the diagnosis and treatment of prurigo nodularis.
Li ZHANG ; Qingchun DIAO ; Xia DOU ; Hong FANG ; Songmei GENG ; Hao GUO ; Yaolong CHEN ; Chao JI ; Chengxin LI ; Linfeng LI ; Jie LI ; Jingyi LI ; Wei LI ; Zhiming LI ; Yunsheng LIANG ; Jianjun QIAO ; Zhiqiang SONG ; Qing SUN ; Juan TAO ; Fang WANG ; Zhiqiang XIE ; Jinhua XU ; Suling XU ; Hongwei YAN ; Xu YAO ; Jianzhong ZHANG ; Litao ZHANG ; Gang ZHU ; Fei HAO ; Xinghua GAO
Chinese Medical Journal 2025;138(22):2859-2861
4.Evidence Graph Analysis of Postoperative Pain Sensitization Induced by Perioperative Sleep Deprivation
Jianjun XUE ; Caihong WANG ; Lingling GUO ; Xiuxia LI ; Jie ZHANG ; Ziqing XU ; Huaijing HOU ; Kehu YANG
Medical Journal of Peking Union Medical College Hospital 2024;16(1):143-156
To describe and evaluate the clinical studies of postoperative pain sensitization caused by sleep deprivation through the evidence map system, understand the distribution of evidence in this field, and provide reference for subsequent evidence research. A computer-based search of PubMed, EMBASE, Cochrane library, Web of Science, CNKI, Wanfang Data, VIP and Chinese Biomedical Literature Database from inception to August 2023 was conducted to obtain intervention studies, observational studies and systematic reviews/Meta-analysis of postoperative pain sensitization caused by sleep deprivation. The research characteristics and methodological quality were analyzed and evaluated. The Cochrane Handbook for Systematic Reviews, the Newcastle-Ottawa Scale (NOS) and the AMSTAR-2 scale were used to evaluate the quality of the included studies, and the evidence was comprehensively analyzed and displayed by means of bubble chart, table and text. A total of 35 observational studies (31 cohort studies and 4 case-control studies), 15 randomized controlled trials and 4 systematic reviews/Meta-analyses were included. The number of publications increased rapidly after 2018 and peaked in 2022, and clinical studies in this field mainly focused on cohort studies, with fewer randomized controlled trials and systematic reviews/Meta-analysis studies. The results of the evidence map showed that in terms of quality, 22 studies were 'high quality', 24 studies were 'medium quality', and 8 studies were 'low quality'.Thirty studies showed that sleep deprivation could induce postoperative pain sensitization. Only 2 studies suggested that sleep disorders were not significantly associated with postoperative pain sensitization, and ten studies were uncertain whether sleep deprivation could induce postoperative pain sensitization. Overall evidence shows that sleep deprivation can induce postoperative pain sensitization, but the evaluation dimensions are limited and the methodological quality of the included literature needs to be improved. More high-quality, large-sample and standardized clinical studies should be carried out in the future to provide better scientific basis for clinical work.
5.Association of gene polymorphisms in microRNA with blood pressure responses to salt and potassium intake
Lan WANG ; Ying CUI ; Yanjie GUO ; Yanni YAO ; Beibei YANG ; Nairong LIU ; Jiaxin WANG ; Panpan LIU ; Mingfei DU ; Guilin HU ; Zejiaxin NIU ; Xi ZHANG ; Dan WANG ; Chao CHU ; Hao JIA ; Yue SUN ; Weihua GAO ; Jianjun MU ; Yang WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(3):435-442
Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure(BP)responses to the sodium and potassium diet intervention.Methods In 2004,we recruited 514 participants from 124 families in seven villages of Baoji,Shaanxi Province,China.All subjects were given a three-day normal diet,followed by a seven-day low-salt diet,a seven-day high-salt diet,and finally a seven-day high-salt and potassium supplementation.A total of 19 miRNA single nucleotide polymorphisms(SNPs)were selected for analysis.Results Throughout the sodium-potassium dietary intervention,the BP of the subjects fluctuated across all phases,showing a decrease during the low-salt period and an increase during the high-salt period,followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet.MiR-210-3p SNP rs 12364149 was significantly associated with systolic BP(SBP),diastolic BP(DBP)and mean arterial pressure(MAP)responses to low-salt diet.MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention.In addition,miR-26b-3p SNP rs115254818 was significantly correlated with SBP,DBP and MAP responses to high-salt intervention.MiR-1307-5p SNPs rs1 1191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet.MiR-4638-3p SNP rs6601178,miR-210-3p SNP rs12364149,miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet.In addition,miR-26b-3p SNP rs115254818 was significantly associated with SBP,DBP and MAP responses to potassium supplementation.MiR-1307-5p SNPs rs11191676,rs2292807,and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation.Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium,suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.
6.Effect of group exercise therapy on improving sleep quality in patients with mild to moderate depressive disorder during the acute phase
Ruinan LI ; Jianjun GUO ; Wenyang LIU ; Yu QIAO ; Lu TIAN ; Shengtao JIA ; Jingjing ZHOU
Sichuan Mental Health 2024;37(6):492-496
BackgroundPatients with depressive disorder commonly experience sleep disturbances. Previous studies have indicated that group exercise therapy is beneficial in alleviating depressive symptom among patients with depressive disorder. However, there is a lack of research on the impact of group exercise therapy on improving sleep quality in patients with depressive disorder. ObjectiveTo explore the impact of group exercise therapy on sleep quality in patients with acute mild-to-moderate depression during the acute phase, so as to provide references for clinically improving the sleep quality of patients with mild to moderate depressive disorder during the acute phase. MethodsFrom December 2018 to July 2021, patients with mild-to-moderate depressive disorder during the acute phase (n=40), who met the diagnostic criteria for depressive disorder according to International Classification of Diseases, tenth edition (ICD-10) ,were recruited from the outpatient clinic of Beijing Anding Hospital, Capital Medical University. All participants underwent an 8-week moderate-intensity group exercise therapy program comprising three sessions per week, each lasting 60 minutes. Assessments were conducted at baseline and after 2, 4, 6 and 8 weeks of intervention using Visual Analogue Scale (VAS), Hamilton Depression Scale-17 item (HAMD-17) and Pittsburgh Sleep Quality Index (PSQI). The reduction scores at each time point relative to baseline treated as the dependent variables, time as the independent variable, baseline scores as covariates, with time as a fixed effect and baseline values as random effects. Data were analyzed using a linear mixed-effects model. ResultsThe PSQI scores of patients at baseline, 2, 4 , 6 and 8 weeks after the intervention were (10.62±5.12), (9.07±3.58), (7.39±3.66), (6.54±3.84) and (5.50±3.41), respectively. The results of linear mixed effect model analysis showed that after 2, 4, 6 and 8 weeks of intervention, patients scored lower than baseline, with statistically significant differences observed in all cases (P<0.01). The HAMD-17 sleep fcctor scores at baseline, 2, 4, 6 and 8 weeks were (2.25±1.56), (2.06±1.49), (1.36±1.27), (1.22±1.46) and (0.97±1.34), respectively. The results of linear mixed effects model analysis showed that the HAMD-17 sleep factor scores of 4, 6 and 8 weeks of intervention were lower than that of baseline, and the difference was statistically significant (P<0.05 or 0.01). The VAS scores at baseline, 2, 4, 6 and 8 weeks after the intervention were (3.18±2.17), (4.74±2.22), (6.01±2.31), (6.54±2.16) and (7.90±1.64), respectively. The results of linear mixed effect model analysis showed that VAS scores of 2, 4, 6 and 8 weeks of intervention were higher than baseline,and the difference was statistically significant (P<0.01). ConclusionGroup exercise therapy may improve sleep quality and alleviate depressive symptoms in patients with mild-to-moderate depressive disorder during the acute phase. [Funded by National Key Research and Development Plan Project (number, 2016YFC1307200); Beijing Municipal Hospital Scientific Research and Cultivation Plan Project (number, PX2024070)]
7.The jujube core-shaped tissue resection technique in alar reduction
Lehao WU ; Yihao XU ; Huan WANG ; Ruobing ZHENG ; Xulong ZHANG ; Le TIAN ; Junsheng GUO ; Shan ZHU ; Fei FAN ; Jianjun YOU
Chinese Journal of Plastic Surgery 2024;40(1):88-93
Objective:To investigate the clinical effect of jujube core-shaped tissue resection technique in the treatment of alar reduction.Methods:A retrospective analysis was performed for the clinical data of patients who underwent alar reduction from February 2019 to June 2022. A spindle-shaped incision line was designed along the outer edge of the base of the nasal lobule, with a width of 4-5 mm and a length of 8-12 mm. The incision line was 1-2 mm away from the alar groove, and the inner side of the design line was extended to the inside of the nasal vestibule. After the incision was made, the subcutaneous tissue was undermining dissected with curved sharp scissors, and the shape of the extended excision tissue was similar to that of jujube core. After reduction, the incision was closed with vertical mattress suture. The surgical effect and complications were followed up after surgery, and an independent attending plastic surgeon evaluated the outcome and scarring based on photos before and at the last postoperative follow-up using the global aesthetic improvement scale (GAIS) and the Vancouver scar scale (VSS). GAIS is graded as 1, 2, 3, 4, and 5 points, and the lower the score, the better the improvement(≤3 points as effective improvement). VSS includes four parameters: color (0-3 points), thickness (0-4 points), vascular distribution (0-3 points), and softness (0-5 points). The higher the score, the more significant the scar is.Results:A total of 20 patients were enrolled, including 6 males and 14 females, aged 20 to 33 years, with an average age of 24.9 years. Before the operation, there were different degrees of alar flare and alar hypertrophy. After surgery, 13 patients had mild swelling, ecchymosis, which resolved after 3 days. There were no major complications as infection, incision dehiscence, and delayed healing. After 3 to 16 months of postoperative follow-up, 2 patients gradually developed cartilage deformation and affected the appearance of the nostrils 6 to 9 months after surgery due to the combination of rib-based rhinoplasty, and the satisfactory results were obtained after revision surgery. The symmetry of the nostrils was significantly improved. The GAIS score of 20 patients was (1.20±0.41) points, of which, 16 patients were rated as 1 point and 4 patients were rated as 2 points, all of which met the improvement criteria, and the VSS score was (1.45±0.60) points, in which the average score for color, thickness, vasculature and compliance are 0.60, 0.05, 0.55 and 0.30 points respectively.Conclusion:The application of jujube core-shaped tissue resection technique for alar reduction can increase the amount of tissue removal with the same incision width, which can not only fully narrow the alar effectively but also correct the hypertrophy of the alar tissue.
8.The jujube core-shaped tissue resection technique in alar reduction
Lehao WU ; Yihao XU ; Huan WANG ; Ruobing ZHENG ; Xulong ZHANG ; Le TIAN ; Junsheng GUO ; Shan ZHU ; Fei FAN ; Jianjun YOU
Chinese Journal of Plastic Surgery 2024;40(1):88-93
Objective:To investigate the clinical effect of jujube core-shaped tissue resection technique in the treatment of alar reduction.Methods:A retrospective analysis was performed for the clinical data of patients who underwent alar reduction from February 2019 to June 2022. A spindle-shaped incision line was designed along the outer edge of the base of the nasal lobule, with a width of 4-5 mm and a length of 8-12 mm. The incision line was 1-2 mm away from the alar groove, and the inner side of the design line was extended to the inside of the nasal vestibule. After the incision was made, the subcutaneous tissue was undermining dissected with curved sharp scissors, and the shape of the extended excision tissue was similar to that of jujube core. After reduction, the incision was closed with vertical mattress suture. The surgical effect and complications were followed up after surgery, and an independent attending plastic surgeon evaluated the outcome and scarring based on photos before and at the last postoperative follow-up using the global aesthetic improvement scale (GAIS) and the Vancouver scar scale (VSS). GAIS is graded as 1, 2, 3, 4, and 5 points, and the lower the score, the better the improvement(≤3 points as effective improvement). VSS includes four parameters: color (0-3 points), thickness (0-4 points), vascular distribution (0-3 points), and softness (0-5 points). The higher the score, the more significant the scar is.Results:A total of 20 patients were enrolled, including 6 males and 14 females, aged 20 to 33 years, with an average age of 24.9 years. Before the operation, there were different degrees of alar flare and alar hypertrophy. After surgery, 13 patients had mild swelling, ecchymosis, which resolved after 3 days. There were no major complications as infection, incision dehiscence, and delayed healing. After 3 to 16 months of postoperative follow-up, 2 patients gradually developed cartilage deformation and affected the appearance of the nostrils 6 to 9 months after surgery due to the combination of rib-based rhinoplasty, and the satisfactory results were obtained after revision surgery. The symmetry of the nostrils was significantly improved. The GAIS score of 20 patients was (1.20±0.41) points, of which, 16 patients were rated as 1 point and 4 patients were rated as 2 points, all of which met the improvement criteria, and the VSS score was (1.45±0.60) points, in which the average score for color, thickness, vasculature and compliance are 0.60, 0.05, 0.55 and 0.30 points respectively.Conclusion:The application of jujube core-shaped tissue resection technique for alar reduction can increase the amount of tissue removal with the same incision width, which can not only fully narrow the alar effectively but also correct the hypertrophy of the alar tissue.
9.A Lean Operation Management Model for Public Hospital is Constructed Based on Evidence Based Deci-sion-Making
Yaojun ZHAO ; Leichao WANG ; Jianjun LI ; Shua JIANG ; Li ZHENG ; Wenwen LIU ; Zihan MU ; Zhiping GUO
Chinese Hospital Management 2024;44(3):5-8
Comprehensively improving the new efficiency of high-quality development of public hospitals is the key top-level design for deepening the reform of public hospitals during the"14th Five-Year Plan"period.In view of the changes in the macro environment faced by public hospitals in recent years,such as the cancellation of the addi-tion of pharmaceutical consumables and the deep promotion of the reform of payment methods,as well as the out-standing problems existing at the micro level of public hospital operation,such as the separation of diagnosis and treatment business from economic operation activities,extensive decision-making methods,unreasonable alloca-tion of resources and urgent optimization of processes.By referring to relevant theories such as value management theory,a new"trinity"public hospital lean operation management model based on"integration of industry and fi-nance,lean operation and evidence-based decision-making"is explored and constructed.It breaks the relatively parallel operation barriers of clinical diagnosis and treatment business and economic operation management,innovates a new method of linear staff management with the integration of industry and finance,gives full play to the role of experts in governing hospitals,and integrates the professional committee system driven by"technology+manage-men"into the hospital decision-making staff system to provide data evidence-based basis for assisting the hospital leadership to make scientific decisions.
10.Effect of liraglutide on cardiac dysfunction and myocardial metabolism abnormality in diabetic cardiomyopathy rats
Yaxin ZHU ; Ruixia XU ; Yue ZHANG ; Huilin QU ; Wei ZHANG ; Haorui LIU ; Fang WANG ; Yuanlin GUO ; Jianjun LI
Chinese Journal of Arteriosclerosis 2024;32(6):494-502
Aim To study the effect of liraglutide on myocardial metabolites and related metabolic pathways in diabetic cardiomyopathy(DCM)rats.Methods Among 60 SPF male SD rats aged 3 weeks,10 rats were randomly selected as normal control group(n=10),and the remaining 50 rats were established by peritoneal injection of streptozoto-cin combined with high-sugar and high-fat diet for DCM rat model.A total of 36 rats were successfully modeled for DCM and randomly divided into DCM model group(DCM group,n=12),low-dose liraglutide treatment group(LL group,n=12)and high-dose liraglutide treatment group(HL group,n=12).Rats in LL group(100 μg/kg)and HL group(200μg/kg)were given intraperitoneal injection of liraglutide once a day.And after 12 weeks of intervention,the rats were killed under anesthesia after echocardiography to detect cardiac function,and the heart tissues were taken for metabolomics detection.The differential metabolites and related pathways that may be related to liraglutide improving myocardial metab-olism in DCM rats were screened and enriched.Results Compared with normal control group,left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in DCM group were significantly decreased,and the ra-tio of early to late diastolic mitralflow velocities(E/A)was significantly increased(P<0.05).Compared with DCM group,LVEF and LVFS in LL group and HL group were significantly increased,and E/A ratio was significantly decreased(P<0.05),suggesting that the impairment of left ventricular systolic and diastolic function in LL group and HL group was significantly alleviated.395 metabolites were detected by metabolomics,among which 239,116 and 187 different metab-olites and 13,6 and 20 metabolic pathways were enriched in DCM group and normal control group,LL group and DCM group,HL group and DCM group.In the above three groups,29 key differential metabolites were identified related to 3 metabolic pathways including choline metabolic pathway,caffeine metabolic pathway and valine,leucine and isoleucine bi-osynthesis pathway,among which choline metabolic pathway had the most significant differences.Conclusion These results indicated that liraglutide can ameliorate cardiac dysfunction in DCM rats through improving myocardial metabolism in which choline metabolism pathway may play a key role.

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