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.Association between short-term ambient air pollution exposure and arterial stiffness and effect modification of obesity
Yinxi TAN ; Hexiang PENG ; Yi ZHENG ; Siyue WANG ; Yiqun WU ; Xueying QIN ; Jin LI ; Tao WU ; Dafang CHEN ; Mengying WANG ; Yonghua HU
Chinese Journal of Epidemiology 2024;45(12):1639-1648
Objective:To assess the association between short-term ambient air pollution exposure and arterial stiffness and whether obesity modifies these associations.Methods:A cross-sectional study was conducted based on Fangshan family cohort in Beijing. The 24 hours average air pollutant levels on the day cohort participants took baseline survey were calculated as short-term air pollution. A generalized additive model (GAM) with Gaussian links was used to estimate changes in typical carotid artery intima-media thickness (CIMT), brachial-ankle pulse wave velocity (BAPWV), pulse pressure (PP) and ankle-branchial index (ABI) after short-term exposure to each air pollution (PM 2.5, PM 10, SO 2, NO 2, CO). The cross-product terms of each air pollution, body mass index (BMI), and waist-to-hip ratio were included in the GAM model to test the interaction. Further, they conducted a stratified analysis to test their effects on the relationship between short-term exposure to each air pollution and the arterial stiffness indicators. Results:A total of 4 211 individuals were included in the analysis. Individuals' age was (58.9±8.7) years, of which 2 268 (53.9%) were female. Several covariates, including sociodemographic factors, lifestyle behaviors, and history of drugs, were included in the analysis. The results of the GAM analysis showed that an increase in PM 2.5 ( β=2.912×10 -4, 95% CI: 1.424×10 -4-4.400×10 -4, P<0.001), CO ( β=0.027, 95% CI: 0.011-0.043, P<0.001), SO 2 ( β=2.070×10 -3, 95% CI: 7.060×10 -4-3.430×10 -3, P=0.003), and NO 2 ( β=3.650×10 -4, 95% CI: 2.340×10 -5-7.060×10 -4, P=0.036) were associated with an increase in CIMT, while an increase in PM 10 ( β=0.018, 95% CI: 0.002-0.033, P=0.028) was associated with an increase in PP in the study population. Besides, the waist-to-hip ratio had an effect-modification on the correlation of short-term exposure of PM 2.5 (interaction P=0.015), NO 2 (interaction P=0.008), and CO (interaction P=0.044) with CIMT, and the correlation between short-term exposure of PM 2.5 (interaction P=0.002), NO 2 (interaction P=0.010), CO (interaction P=0.029), PM 10 (interaction P<0.001) with PP. The significant association between CIMT, PP, and air pollution concentrations was more visible in people with lower waist-to-hip ratios. Conclusions:Short-term ambient air pollution exposure was associated with arterial stiffness indicators, and there was an effect modification of waist-to-hip ratio on these associations, and lower waist-to-hip ratios may enhance the association between air pollution exposure and indicators.
3.Effect of transcutaneous electrical acupoint stimulation bracelet at Neiguan acupoint on post-operative nausea and vomiting after thyroidectomy under general anesthesia
Ming GONG ; Hongwei ZHU ; Dongyu ZHENG ; Na WANG ; Yonghua LI ; Hongbin YUAN
The Journal of Clinical Anesthesiology 2024;40(2):124-127
Objective To explore the effect of transcutaneous electrical acupoint stimulation bracelet at Neiguan acupoint on the postoperative nausea and vomiting after thyroidectomy under general an-esthesia.Methods Seventy-two female patients underwent thyroidectomy,aged 18-50 years,ASA physical status Ⅰ or Ⅱ,were enrolled.The patients were assigned 1 ∶ 1 to two groups by permuted block randomization:the electrical stimulation group and the control group,36 patients in each group.Before an-esthesia induction,patients in both groups wore domestic transcutaneous electrical acupoint stimulation bracelets,and the electrodes were aimed at Neiguan acupoint.The electrical stimulation group started to stimulate Neiguan acupoint,and adjusted the proper intensity to make the patient feel tingling in the related area of the hand.When the bracelet was fixed firmly,turned it off.At the end of the operation,the bracelet was turned on with the stimulation intensity set before induction for 24 hours.Patients in the control group also wore the bracelet for 24 hours,but it was never turned on.The number of cases of postoperative nausea and vomiting(PONV)and the number of remedial cases of antiemetic drugs were recorded.Results Compared with the control group,the incidence of PONV and postoperative vomiting in the electrical stimula-tion group were significantly reduced within 24 hours after surgery(P<0.05),and the differences were mainly in 1-6 hours after surgery(P<0.05).There was no significant difference in the rate of remedial ca-ses of antiemetic drugs between the two groups at different time periods.Conclusion Transcutaneous electri-cal stimulation bracelet at Neiguan acupoint can effectively reduce the incidence of PONV within 24 hours after thyroidectomy.
4.Berberine regulates polarization of macrophages:a mechanistic study based on PI3K/Akt1 signaling pathway
Yushan CHEN ; Tingting WANG ; Zhonghua MENG ; Shasha SHANG ; Junmeng ZHENG ; Yonghua ZONG ; Chunying SI ; Yazhou LIANG ; Huaimin GUAN
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(6):694-698
Objective To explore the effect and possible mechanism of berberine on the macro-phage polarization of human myeloid leukemia monocytic cell line THP-1 induced by oxidized low-density lipoprotein(ox-LDL).Methods THP-1 cells were induced into macrophages by PMA,and then according to different concentrations of berberine,the cells were divided into con-trol group,and 5,10,20,40 and 50 μmol/L berberine groups.After intervention for 24 or 48 h,CCK8 assay was used to detect cell viability for optimal concentration and time of berberine treat-ment.PMA-induced THP-1 macrophages were assigned into blank group,model group(ox-LDL),berberine group,inhibitor group(phosphatidyl inositol 3-kinase(PI3K)inhibitor LY294002)and berberine+inhibitor group(berberine+LY294002).The contents of inducible nitric oxide syn-thase(iNOS)and TGF-β1 were detected by ELISA.qPCR was employed to measure the mRNA expression of TNF-α,arginase 1(Arg1),PI3K and protein kinase B Akt1,and Western blotting was applied to detect the protein levels of Akt1 and phosphorylated protein kinase B antibody(p-Akt1).Results In 24 h after intervention,the macrophage activity was significantly lower in the 40 and 50 μmol/L berberine groups than the control group(P<0.05),and after 48 h,the ac-tivity in all the 5 doses of berberine groups was obviously lower than that in the control group[(0.89±0.02)%,(0.82±0.03)%,(0.71±0.02)%,(0.62±0.03)%and(0.53±0.02)%vs(1.01±0.01)%,P<0.05].Berberine treatment of 20 μmol/L for 24 h had little effect on cell viability,and the dose and the time were regarded as the best concentration and time.Compared with the blank group,iNOS content and TNF-α mRNA level were increased in the model group,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1,and p-Akt1/Akt1 protein levels were de-creased(P<0.05).iNOS content and TNF-α mRNA level were decreased,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1s were increased in the berberine group than the model group(P<0.05).Compared with the berberine group,iNOS con-tent and TNF-α mRNA level were increased,while mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1 were decreased in the berberine+inhibitor group(P<0.05).Con-clusion Berberine can inhibit the inflammatory response of THP-1 macrophages induced by ox-LDL by activating PI3K/Akt1 pathway,and inhibit the M1 polarization and promote the M2 polarization of macrophages.
5.Droplet freeze-thawing system based on solid surface vitrification and laser rewarming.
Wenxin ZHU ; Ping'an PAN ; Yonghua HUANG ; Wei CHEN ; Sha HAN ; Zheng LI ; Jinsheng CHENG
Journal of Biomedical Engineering 2023;40(5):973-981
Ultra-rapid cooling and rewarming rate is a critical technical approach to achieve ice-free cells during the freezing and melting process. A set of ultra-rapid solid surface freeze-thaw visualization system was developed based on a sapphire flim, and experiments on droplet freeze-thaw were carried out under different cryoprotectant components, volumes and laser energies. The results showed that the cooling rate of 1 μL mixed cryoprotectant [1.5 mol/L propylene glycol (PG) + 1.5 mol/L ethylene glycol (EG) + 0.5 mol/L trehalose (TRE)] could be 9.2×10 3 °C/min. The volume range of 1-8 μL droplets could be vitrified. After comparing the proportions of multiple cryoprotectants, the combination of equal proportion mixed permeability protectant and trehalose had the best vitrification freezing effect and more uniform crystallization characteristics. During the rewarming operation, the heating curve of glassy droplets containing gold nanoparticles was measured for the first time under the action of 400-1 200 W laser power, and the rewarming rate was up to the order of 10 6 °C/min. According to the droplet images of different power rewarming processes, the laser power range for ice-free rewarming with micron-level resolution was clarified to be 1 400-1 600 W. The work of this paper simultaneously realizes the ultra-high-speed temperature ramp-up, transient visual observation and temperature measurement of droplets, providing technical means for judging the ice free droplets during the freeze-thaw process. It is conducive to promoting the development of ultra-rapid freeze-thaw technology for biological cells and tissues.
Freezing
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Vitrification
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Cryopreservation/methods*
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Trehalose
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Gold
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Rewarming
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Metal Nanoparticles
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Cryoprotective Agents
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Lasers
6.Application Status and Prospect of Rehabilitation Assessment Technology.
Tianhai HUANG ; Quchao ZOU ; Yonghua CHU ; Kun ZHENG ; Zhikang WANG
Chinese Journal of Medical Instrumentation 2023;47(3):298-303
Rehabilitation assessment is the basis and important part of rehabilitation diagnosis and treatment. At present, clinical evaluation is usually carried out by observation method and scale method. At the same time, researchers monitor patients' physical condition data through sensor system and other equipment as a supplement. The purpose of this study is to review the application and development of objective rehabilitation assessment technology in clinical practice, and to discuss its limitations and strategies to provide reference for related research.
Humans
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Technology
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Rehabilitation
7.Clinical value of a new direct visualization system of China-made peroral cholangiopancreatography (with video)
Yonghua SHEN ; Jun CAO ; Wei CAI ; Ruhua ZHENG ; Yi WANG ; Yuling YAO ; Xiaoping ZOU ; Lei WANG
Chinese Journal of Digestive Endoscopy 2022;39(3):187-191
Objective:To investigate the efficacy and safety of a new China-made direct visualization system of peroral cholangiopancreatography in the diagnosis and treatment of biliopancreatic diseases.Methods:Clinical data of 37 patients who underwent endoscopic examination through the direct visualization system of peroral cholangiopancreatography at Digestive Endoscopy Center of Nanjing Drum Tower Hospital from April 2020 to June 2021 were retrospectively analyzed. Technical success rate and complications were analyzed.Results:The examination was completed in 37 patients through the system. The technical success rate was 100.0%. The nature of biliary stricture was confirmed in 24 cases, presenece or absence of bleeding or residual stones in the bile duct was confirmed in 6 cases, neoplasm or residual stones in the pancreatic duct was determined in 2 cases, biliary stricture was passed assisted with visualized guidewire in 2 cases, and lithotripsy was performed assisted with biliary laser in 3 cases. Nine patients were pathologically diagnosed as having malignant biliary stricture, and 8 of them were confirmed malignant by the system. Drainage was performed in 34 cases after the examination. There were 3 cases of cholangitis, 4 cases of bacteremia and 2 cases of postoperative pancreatitis after the operation, which were relieved in a short time after conservative treatment. Bleeding occurred in 1 case which was improved after two times of endoscopic hemostasis.Conclusion:The new direct visualization system of peroral cholangiopancreatography is safe and effective in the diagnosis and treatment of biliopancreatic diseases.
8.The prevalence of depressive disorders in school students aged 6-16 years in Beijing
Huili XU ; Jiahui CHU ; Yonghua CUI ; Ying LI ; Yi ZHENG
Chinese Journal of Applied Clinical Pediatrics 2022;37(12):924-928
Objective:To investigate the prevalence of depressive disorders among school students aged 6-16 years in Beijing, the effect of age and gender on the prevalence, and the behavioral and emotional profiles of identified students with depressive disorders.Methods:The prevalence of depressive disorders in primary and secondary school students aged 6-16 years in Beijing from January 2012 to December 2014 was examined by a multistage stratified random sampling method.In the first stage, the Achenbach′s Child Behavior Checklist (CBCL) was used to identify high-risk children and adolescents.In the second stage, the high-risk group was further screened by Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), and then two psychiatrists made the final diagnosis according to the diagnostic criteria of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-Ⅳ). This study was a prospective epidemiological investigation.The effect of age and gender on the disease prevalence was analyzed by Chi- square test. Results:About 2.29% (234/10 215 cases) of the school students aged 6-16 years in Beijing had depressive disorders.The incidence of depressive disorders was 1.80% (106/5 866 cases) in boys and 2.94% (128/4 349 cases) in girls.There is an age effect on the prevalence of depression.As the age increases, the morbidity of depressive disorders increases.The age of 12 years was a critical turning point, and the peak incidence was reached at around the age of 15 years.The emotional and behavioral problems of patients with depressive disorders mainly include social problems, withdrawal depressed, anxiety and depressed, somatic complaints, and aggressive behavior.Conclusions:The prevalence of depressive disorders among school students aged 6-16 years in Beijing is 2.29%.Depressive disorders occur in primary and middle school students of all ages.More attention should be paid to the mood of students before and after the entrance exams for junior high school and senior middle school, especially the girls′ mood.In the process of screening, diagnosis and treatment of depressive disorders, the atypical symptoms of depression need to be paid more attention.
9.Long-term outcomes of fully covered self-expanding metal stent for benign refractory pancreatic stenosis (with video)
Jun CAO ; Yonghua SHEN ; Ruhua ZHENG ; Xiaoliang ZHOU ; Zhengyan QIN ; Lei WANG ; Xiaoping ZOU
Chinese Journal of Digestive Endoscopy 2022;39(6):447-452
Objective:To investigate the safety and long-term outcomes of fully covered self-expanding metal stent (FCSEMS) placement in patients with benign refractory pancreatic stenosis.Methods:Data of 18 patients with benign refractory pancreatic stenosis who underwent endoscopic treatment with FCSEMS in Nanjing Drum Tower Hospital between March 2013 and July 2020 were collected. The technical success, clinical success, adverse events and long-term outcomes were analyzed.Results:FCSEMS placement was successful in all 18 patients, with technical success rate of 100.0% (18/18). After stenting, the visual analogue scale (VAS) significantly decreased [2.00 (1.75, 3.00) VS 6.00 (5.00, 7.00), Z=-3.572, P<0.001]. The VAS decreased by more than 50% in 15 cases, and the clinical success rate was 83.3% (15/18). Stent-related adverse events included intolerable pain in 3 patients, stented-induced de novo stricture in 2 patients, and distal migration of stent in 2 patients. The stents were successfully removed in all patients after 137.5 (59.0, 417.0) days. There was significant reduction in terms of decreased upstream ductal dilatation after stent removal [9.1 (6.7, 14.1) mm VS 11.0 (7.6, 16.2) mm, Z=10.508, P<0.001]. After stent removal, 10 of the 14 patients maintained the response to pancreatic stenting and 4 recurred during the follow-up of 37-1 246 days. Conclusion:FCSEMS placement appears to be safe and effective in the treatment of benign refractory pancreatic stenosis and can provide persistent improvement in the stricture.
10.Comparative effectiveness research on small IT knife pre-cut and conventional guidewire cannulation on selective biliary intubation (with video)
Yonghua SHEN ; Qibin HE ; Yi WANG ; Ruhua ZHENG ; Wen LI ; Yuling YAO ; Jun CAO ; Yiyang ZHANG ; Lei WANG ; Xiaoping ZOU
Chinese Journal of Digestive Endoscopy 2021;38(1):48-51
Objective:To evaluate the application value of small IT knife pre-cut in assistance to duodenal papillary cannulation compared with conventional guidewire cannulation.Methods:A retrospective analysis was performed on the data of 90 patients with choledocholithiasis including 52 patients with small IT knife pre-cut assisted intubation (small IT knife group) and 38 patients with conventional guidewire intubation (conventional group) in endoscopic retrograde cholangiopancreatography (ERCP) from May 2016 to July 2019 in the digestive endoscopy center of Nanjing Drum Tower Hospital. The basic data, curative effect and complications of the two groups were collected and compared.Results:There was statistically significant difference in gender composition between the small IT knife group and the conventional group ( χ2=5.679, P=0.017), but no significant difference in other baseline data between the two groups (all P>0.05). The median intubation time of the small IT knife group was significantly shorter than that of the conventional group (141.5 s VS 270.0 s, Z=1 268.0, P=0.022). There were no significant differences in the success rate of intubation [98.1% (51/52) VS 94.7% (36/38), χ2=0.760, P=0.571], the incidence of intraoperative bleeding [15.4% (8/52) VS 7.9% (3/38), χ2=1.148, P=0.345], postoperative pancreatitis [5.8% (3/52) VS 7.9% (3/38), χ2=0.159, P=0.694], and postoperative cholangitis [1.9% (1/52) VS 5.3% (2/38), χ2=0.760, P=0.571] between the two groups. No perforation occurred in the two groups. After stratifying according to the operator′s proficiency, the median intubation time was significantly different between the small IT knife expert group and the conventional expert group (116.0 s VS 258.0 s, Z=276.0, P=0.038), while there was no significant difference in the intubation time among other groups (all P>0.05). Conclusion:The small IT knife is safe and effective to pre-cut and assist intubation in ERCP, and it may shorten the intubation time.

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