1.Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection.
Xiu LIU ; Li ZHAO ; Deshen LIU ; Lingna ZHAO ; Yonghua TUO ; Qinbao PENG ; Fangze HUANG ; Zhengkun SONG ; Chuanjie NIU ; Xiaoxia HE ; Yu XU ; Jun WAN ; Peng ZHU ; Zhengyang JIAN ; Jiawei GUO ; Yingying LIU ; Jun LU ; Sijia LIANG ; Shaoyi ZHENG
Acta Pharmaceutica Sinica B 2025;15(7):3663-3684
This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.
2.Subxiphoid and subcostal arch thoracoscopic versus median sternotomy enlarged thymectomy for the treatment of myasthenia gravis complicated with thymoma: A propensity score matching study
Xunliang YIN ; Zhengwei ZHAO ; Shaoyi CHENG ; Zheng FENG ; Yize GUO ; Tianyi ZHANG ; Sha XUE ; Yong' ; an ZHOU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(06):824-829
Objective To compare clinical effects of enlarged thymectomy for the treatment of myasthenia gravis (MG) complicated with thymoma via subxiphoid and subcostal arch thoracoscopic resection versus median sternotomy resection. Methods We retrospectively analyzed the clinical data of patients with MG complicated with thymoma admitted in Tangdu Hospital of the Air Force Military Medical University between December 2011 and December 2021. Patients who underwent subxiphoid and subcostal arch thoracoscopic enlarged thymectomy were allocated to a SR group, and patients who underwent median sternotomy enlarged thymectomy were allocated to a MR group. Perioperative outcomes were compared between the two groups. Results A total of 456 patients were collected. There were 51 patients in the MR group, including 30 males and 21 females aged 23-66 (49.5±11.8) years. There were 405 patients in the SR group, among whom 51 patients were matched to the MR group by propensity score matching, including 28 males and 23 females aged 26-70 (47.2±12.2) years. The operations were accomplished successfully in all patients, and no conversion to thoracotomy occurred in the SR group. The SR group had advantages in the operation time, intraoperative blood loss, chest drainage duration, hospital stay time, patients’ satisfaction level, pain score and complications (all P<0.05). No statistical difference was found in the number of intraoperative lymph node dissection stations, number of intraoperative lymph nodes dissected or remission of MG between the two groups (P>0.05). Conclusion Subxiphoid and subcostal arch thoracoscopic enlarged thymectomy and lymphadenectomy is a safe, effective and feasible minimally invasive procedure for the treatment of MG complicated with thymoma.
3.Subxiphoid and subcostal arch thoracoscopic versus unilateral thoracoscopic thymectomy for the treatment of thymic abnormalities with myasthenia gravis: A propensity-score matching study
Xunliang YIN ; Sha XUE ; Zhengwei ZHAO ; Shaoyi CHENG ; Zheng FENG ; Yize GUO ; Tianyi ZHANG ; Jing ZHANG ; Yongan ZHOU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(04):473-478
Objective To compare clinical effects of extended thymectomy for the treatment of thymic abnormalities with myasthenia gravis (MG) between subxiphoid and subcostal arch thoracoscopic resection (SR) and the unilateral thoracoscopic resection (UR) by a propensity-score matching analysis. Methods We retrospectively analyzed the clinical data of 612 patients who presented with MG and were admitted to Tangdu Hospital of Air Force Military Medical University between December 2011 and December 2018. Of these patients, 520 patients underwent subxiphoid and subcostal arch thoracoscopic extended thymectomy (a SR group) and 92 unilateral thoracoscopic extended thymectomy (a UR group). Ninety-two patients in the SR group were matched with the UR group by propensity-score matching analysis. There were 52 males and 40 females with an average age of 26-70 (50.2±10.3) years in the SR group, and 47 males and 45 females with an average age of 20-73 (51.5±12.1) years in the UR group. The operation time, intraoperative blood loss, thoracic drainage time, postoperative hospital stay, thorough adipose tissue removal, postoperative remission of MG, patients’ satisfaction score, pain and complications were compared and analyzed between the two groups. Results All operations were accomplished successfully, without conversion to thoracotomy of the two groups. There were statistical differences between the two groups in operation time (46.2±19.5 min vs. 53.4±23.5 min), chest drainage duration (0 d vs. 3.4±1.2 d), hospital stay (2.9±1.9 d vs. 3.6±1.7 d), patients’ satisfaction score (7.9±2.1 points vs. 6.7±1.2 points) and pain scores (all P<0.05). There were no statistical differences between the two groups in intraoperative blood loss (52.2±12.7 mL vs. 51.2±10.3 mL), peripheral adipose tissue removal (8.1±0.6 vs. 7.9±0.9), remission rate of MG (89.1% vs. 85.9%) and rate of postoperative complications (10.9% vs. 6.5%) (all P>0.05). Conclusion Subxiphoid and subcostal arch thoracoscopic extended thymectomy is a safe and feasible minimally invasive procedure for the management of MG with thymic abnormalities.
4.Advances of nocoding RNA in the mechanism of epilepsy
Wujun ZHAO ; Han LI ; Bin WANG ; Shaoyi LI
Chinese Journal of Neurology 2021;54(1):48-54
In recent years, a growing number of studies have shown that non-coding RNA plays an important role in the pathogenesis and development of epilepsy, and is involved in neuroinflammation, cell apoptosis, synaptic remodeling and cell differentiation in epilepsy. This review focused on the recent research progress in the relationship between microRNA, long-nocoding RNA and circular RNA with epilepsy.
5.Molecular mechanism of zoledronic acid inhibiting angiogenesis by semi flexible binding with vascular endothelial growth factor conformation
Ruijie WANG ; Qingtong ZHAO ; Yejia YU ; Yuqiong ZHOU ; Shaoyi WANG
Chinese Journal of Stomatology 2021;56(7):679-686
Objective:To study the relationship between zoledronic acid (ZOL) and vascular endothelial growth factor (VEGF) conformation so as to reveal the mechanism of bisphosphonates inhibiting angiogenesis.Methods:The binding structures of ZOL and VEGF were preprocessed and the molecular dockings were simulated through AutoDockTools, Discovery studio4 and AutoDockVina. The best binding conformation was accurately screened. The effects of various concentrations of ZOL (group A was 0 μmol/L, groups B, C and D were 25, 50 and 100 μmol/L, respectively) on human umbilical vein endothelial cell (HUVEC) proliferation, angiogenesis and angiogenic molecules were detected by using cell counting kit-8 (CCK-8) in vivo and in vitro angiogenesis, immunofluorescence and Western blotting. Results:There was a ZOL binding site on the target protein VEGF conformation. The affinity was -5.2 kcal/mol. This binding site consisted of the hydrophobic region composed of amino acids Cys26, 51, 57, etc. and the hydrogen bond binding region of the A chain (ASP34, SER50) and B chain (CYS61, 68, LEU66, GLY59). The results of CCK-8 showed that the levels of value A in groups B, C and D were significantly lower than that in group A at each time point from 3 to 6 days ( P<0.05). In vitro vascular experiments demonstrated that the numbers of budding in groups B, C and D [(208±28), (151±21) and (62±9), respectively] were significantly lower than that in group A (276±30) ( P<0.05). In vivo vascular experiments displayed that the ratio of Matrigel gel/plasma fluorescence in group A (0.003 1±0.000 3) was significantly higher than those in group B (0.002 1±0.000 2), group C (0.001 6±0.000 2) and group D (0.000 6±0.000 1) ( P<0.05). The results of Western blotting revealed that the expression of VEGF in groups B, C and D [(0.72±0.11), (0.41±0.07) and (0.24±0.04), respectively] were significantly lower than that in group A (1.01±0.02) ( P<0.05), and the expression levels of hypoxia-inducible factor-1α (HIF-1α) in groups B, C and D [(0.68±0.09), (0.55±0.06) and (0.43±0.08), respectively] were significantly lower than that in group A (0.96±0.04) ( P<0.05). Conclusions:ZOL could inhibit cell proliferation, in vivo and in vitro vascularization and expression of VEGF/HIF-1α. The binding site of ZOL with the conformation of VEGF was located in the hydrophobic region and hydrogen-bonding region of amino acids. Designing an antagonist targeting this site might potentially alleviate the effect of ZOL in inhibiting angiogenesis.
6.Effects of hypoxia on expression of hypoxia inducible factors 1α and 2α in human lung cancer cell line A-549
Yonghai FENG ; Hongyun LI ; Shaoyi MIAO ; Xiaoshan SHI ; Wenfei ZHAO
The Journal of Practical Medicine 2019;35(3):381-383,387
Objective To investigate the changes of hypoxia-inducible factor (HIF-1α, HIF-2α) expression level in lung cancer A-549 cells under normoxic conditions, different hypoxia durations, and different oxygen concentrations. Methods A549 cells were divided into normoxic group, time control group, and oxygen concentration control group. Western blot was used to detect the expression of HIF-1α and HIF-2α in A-549 cells.Results The expression of HIF-1α and HIF-2α protein were lower under normoxia and significantly increased under hypoxic conditions. The difference was statistically significant. The lower the oxygen concentration, the more HIF-1α and HIF-2α protein expression levels were. The differences between high and high were statistically significant. The expression of HIF-1α protein increased at 2 h after hypoxia, peaked at 8 h, appeared plateau at 8 to 16 h, and decreased at 32 h, with a statistically significant difference. HIF-2α proteins gradually increased with prolonged hypoxia. Conclusions Under hypoxic conditions, the expression of HIF-1α and HIF-2α are increased, and the expression of HIF-2α has a time-dependent pattern, which may have more important biological significance.
7.Clinical comparative analysis of thymectomy between subxiphoid and subcostal arch thoracoscopic resection and open resection for the treatment of thymoma with myasthenia gravis
Xunliang YIN ; Zhengwei ZHAO ; Shaoyi CHENG ; Yan WANG ; Zheng FENG ; Yongan ZHOU
Chinese Journal of Thoracic and Cardiovascular Surgery 2019;35(4):239-242
Objective To compare and analyze clinical effects of extended thymectomy for the treatment of thymoma with myasthenia gravis(MG) between subxiphoid and subcostal arch thoracoscopic resection(SR) and the median sternotomy(MS) with a propensity-matched analysis.Methods We retrospectively analyzed 528 patients presented with MG and admitted in Tangdu Hospital of Air Force Military Medical University from December 2011 to December 2016,among whom 402 underwent subxiphoid and subcostal arch thoracoscopic extended thymectomy(SR group) and 126 median sternotomy(MS group).Another 126 patients were produced by a propensity-matched analysis in these 402 patients,to match with MS group.Perioperative outcomes were compared between SR group and MS group.Results All operations were accomplished successfully,without conversion to thoracotomy in SR group.Most postoperative outcomes were equal in remission of MG and postoperative complication between the two groups(P > 0.05).There were statistical differences between MS group and SR group in operation time [(106.3 ±32.7)min vs.(533.2 ±37.3) min],intraoperative blood loss[(138.2 ±26.7)ml vs.(38.2 ± 10.3) ml],chest drainage duration[(3.3 ± 1.6) days vs.0 day],hospital length of stay [(5.0 ± 2.5) days vs.(2.5 ± 1.8) days],patients'satisfaction level(6.1 ±2.3 vs.8.9 ± 1.2),the incidence of postoperative wound infections(4.8% vs.0.8%),the incidence of myasthenic crisis(7.1% vs.1.6%)and pain scores,all P <0.05.Conclusion Subxiphoid and subcostal arch thoracoscopic extended thymectomy is a safe and feasible minimally invasive procedure for tmanagement of MG with thymoma.
8.Detection and analysis on serum antibodies for five common pathogenic microbes in patients with Posner-Schlossmarm syndrome
Wenchieh CHEN ; Jun ZHAO ; Tianhui ZHU ; Shiming PENG ; Xiaosheng HUANG ; Shaoyi MEI ; Yan WANG
Chinese Journal of Experimental Ophthalmology 2017;35(12):1115-1119
Background Posner-Schlossman syndrome (PSS) is often recurrent and is a cause of blindness.The etiology of PSS remains to be elucidated.It is reported that there is a certain association between pathogenic microorganisms and PSS in rather small samples.Objective This study was to analyze the related serum antibody levels of cytornegalovirus (CMV),herpes simplex virus (HSV),rubella virus (RV),helicobacter pylori (HP) and anti-streptolysin O (ASO) and provide a clue for the study on pathogenesis and therapy of PSS.Methods A prospective cases-controlled study was carried out in Shenzhen Eye Hospital from December,2014 to December,2016 under the approval of Ethic Committee of this hospital and informed consent of each subject prior to initial of any medical examination.Peripheral blood samples were collected from 82 PSS patients as the PSS group and 100 age-and gender-matched healthy blood donors as the normal control group.The positive rates of serum CMV IgG,CMV IgM,HSV IgG,HSV IgM,RV IgG,RV IgM,HP IgG and HP IgM in the subjects were detected by indirect ELISA,and the positive rate of serum ASO antibody was determined by immuno-scatter turbidmetry.Results The positive rates of serum CMV-IgG,CMV-IgM,HP-IgG,HP-IgM and ASO antibody were 22.0%,17.1%,22.0%,17.1% and 17.1% in the PSS group,which were significantly higher than 5.0%,0.0%,10.0%,2.0% and 7.0% in the normal control group (x2 =11.726,18.496,4.943,12.766,4.479,all at P<0.05).The positive rates of serum HSV-IgG,HSV-IgM,RV-IgG and RV-IgM in the PSS group were not significantly different from those in the normal control group (x2 =3.305,0.986,0.898,0.503,all at P > 0.05).Conclusions CMV,HP and hemolytic streptococcal infection may participate in the occurrence and development of PSS.
9.The application of processized nutrition treatment strategy in critically ill patients
Tao HE ; Lu BAI ; Wei CHEN ; Lei LU ; Qun ZHAO ; Shaoyi XU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2017;24(6):629-632
Objective To explore the effect of processized nutrition treatment strategy on the clinical efficacy of critically ill patients.Methods A prospective study was conducted, and 195 patients admitted to Department of Intensive Care Unit of Jiaxing Second Hospital from July 2016 to February 2017 were enrolled. From July to September 2016, 94 cases were assigned in the control group, and they were given the routine nutritional treatment program. From October to November 2016, the training of processized nutrition treatment strategy was carried out and improved according to plan-do-check-act (PDCA) cycle management plan, From December 2016 to February 2017, 101 cases were assigned in the observation group and treated by the doctor and nurse processized nutrition treatment strategy. The differences of early enteral nutrition (EEN) ratio, the time reaching standard of enteral nutrition (EN) in two group were compared, the incidence of complications related to EN, mechanical ventilation time, ICU hospitalization time, ICU expense and mortality were observed between the two groups.Results Compared with the control group, the ratio of EEN was significantly increasedin the observation group [90.1% (91/101) vs. 47.9% (45/94)], the time reaching standard of EN shortened (days: 5.18±1.43 vs. 6.47±1.95), the incidences of gastrointestinal tract related complications [0.77% (9/1173) vs. 1.67% (22/1319)] and ventilator associated pneumonia [VAP: 4.90‰(4/816) vs. 15.32‰(16/1044)] were obviously decreased, ICU hospitalization time (days:11.61±5.93 vs. 14.03±8.27), mechanical ventilation time (days: 8.08±6.16 vs. 11.11±7.87), the mortality [23.76% (24/101) vs. 31.91% (30/94)] were significantly reduced in the observation group (allP < 0.05), but the ICU hospitalization expenses had no significant difference in observation group and control group (millions: 7.26±7.23 vs. 7.07±4.60,P > 0.05).Conclusions The processized nutrition treatment strategy can improve the EEN implementation rate of critically ill patients, help to establish EN as early as possible, reduce the incidence of gastrointestinal and pulmonary infections and other complications.
10.Pedigree and clinical characteristics in a Chinese family with lattice corneal dystrophy
Shiming, PENG ; Jun, ZHAO ; Tianhui, ZHU ; Xiaosheng, HUANG ; Wenjie, CHEN ; Shaoyi, MEI ; Yan, WANG
Chinese Journal of Experimental Ophthalmology 2017;35(8):704-708
Background Lattice corneal dystrophy (LCD) is a progressive disease,whose clinical features are varied in different stages.It is rarely be reported that clinical findings of different stages and factors of promoting the occurrence and development on LCD in a family.Objective The aim of this study was to identify the characteristics of the pedigree and clinical features of different stages in a LCD family,and further to discuss its influence factors.Methods A cross-sectional study was performed in this study.A Chinese family with LCD was enrolled in Shenzhen Eye Hospital from 2015 to 2016.Questionnaires for disease-related history,visual acuity measurement,ocular anterior segment examination and color photography were carried out for all the members of the family.In addition,anterior segment OCT (AS-OCT),laser scanning confocal microscope and corneal endothelium microscope were used to observe the morphology of corneal stroma and changes of corneal endothelial cells.The pedigree chart was drawn by Cyrillic2.1 software and analyzed based on Mendel law.Results This family included 5 generations of 73 members.Patients with LCD were found in each generation with similar morbidity in different gender,which followed the law of autosomal dominant inheritance.Eleven patients were found in 49 members related with Ⅲ1 of this family with the prevalence rate of 22.45% and onset age at 21-50 years old,and the course of disease was 3-34 years.All of the members had no systemic disease except for two patients (Ⅲ 1 and Ⅲ 5) with hypertension.In the early stage of LCD,some bifurcate striolae appeared in the patients' corneal stroma without symptoms for many years.In the progressive stage,there was corneal irritation symptom accompanying with vision's decrease in the eyes with LCD.The bifurcate striolae were increased,widened and interwoven into lattice lines that the boundaries gradually became fuzzy,then corneal macula was formed because of recurrent corneal infiltration,and eventually resulted in corneal leucoma.High reflection corresponding to the pathologic region was showed by laser scanning confocal microscope and AS-OCT.No significant differences were found in corneal endothelial cell density and the percentage of hexagonal cells between LCD patients and normal phenotype families (t =1.887,P=0.075;t=-0.719,P =0.481).Penetrating keratoplasty was performed in a patient with corneal opacity and serious corneal opacity occurred near the surgical incision one year after the surgery.One patient was diagnosed as LCD 2 years after laser assisted in-situ keratomileusis.One patient was a welder.Conclusions LCD is autosomal dominant inheritance in the family.The clinical manifestations of LCD in the early,progressive and late stage can be seen in the pedigree,which offers a reference for ophthahnologists.Corneal surgery and lesion may induce the onset or aggravation of LCD.

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