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.Advances in research on biomaterials and stem cell/exosome-based strategies in the treatment of traumatic brain injury.
Wenya CHI ; Yingying HE ; Shuisheng CHEN ; Lingyi GUO ; Yan YUAN ; Rongjie LI ; Ruiyao LIU ; Dairan ZHOU ; Jianzhong DU ; Tao XU ; Yuan YU
Acta Pharmaceutica Sinica B 2025;15(7):3511-3544
Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood-brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.
3.A Case of Concurrent Infection with Entamoeba Histolytica and Giardia Lamblia
Jing LI ; Yongzhen SI ; Feng ZHANG ; Yingying HAO ; Ye GUO
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1614-1618
4.Characteristics of asymptomatic HBV infection in HBsAg-positive blood donors from Dalian
Yingying WANG ; Xuelian DENG ; Xiaohan GUO ; Huihui GAO ; Peng SUN ; Dan LIU ; Daniel CANDOTTI ; Bing WANG
Chinese Journal of Blood Transfusion 2025;38(10):1361-1369
Objective: To analyze serological and molecular characteristics of asymptomatic HBV infection in HBV surface antigen positive (HBsAg+) blood donors from Dalian. Methods: The prevalence of HBsAg was analyzed among blood donors in Dalian between 2013 and 2022. Randomly selected HBsAg+ blood samples were subjected to HBV serological testing, HBV viral DNA quantification, and HBV genotyping. Results: Over this ten-year period, the prevalence of HBsAg decreased from 1.25% to 0.50% among blood donors in Dalian. Donors who tested positive for HBsAg prior to donation using a rapid test (RT) accounted for 92.5% of all HBsAg+ donors identified. A total of 240 confirmed HBsAg+ blood donors were randomly selected, including 125 donors with positive results and 115 with negative results in the pre-donation rapid test. HBsAg+ donors were mainly males (71.2%), with a median age of 42, and 97.5% of them being first-time donors. Based on HBV serological profiles, three stages of infection were identified: early infection (2.9%), suspected acute hepatitis (0.8%), and chronic infection (96.3%). The dominant HBV genotypes were C (68.9%) and B (28.4%). Among chronic HBV infection individuals, donors infected with HBV genotype B were older than those infected with genotype C (median age: 45y vs 38.5y, P<0.05). Additionally, they showed significantly lower HBsAg levels with a narrower distribution range than those infected with genotype C [median: 23.2 IU/mL (range: <0.05-7 910 IU/mL) vs 968 IU/mL (range: <0.05-3.4×10
), P<0.05]. However, no significant difference was observed in the HBV DNA loads between these two genotypes (P>0.05). Conclusion: Between 2013 and 2022, the prevalence of HBsAg among blood donors in Dalian showed a year-over-year decline. Chronic infection was predominant among HBsAg+ first-time blood donors. The characteristics of chronic infection in blood donors differed significantly depending on the viral genotype, manifesting as differences in age of infected individuals and HBsAg level distribution.
5.Mcart1 knockout enhances the level of macrophage inflammatory response in sepsis model mice
Yuhan LIU ; Yingying WANG ; Yucheng WANG ; Lei GUO ; Rui JU
Basic & Clinical Medicine 2025;45(5):616-621
Objective To investigate the effect of Mcart1 knockout on acute inflammation of macrophages in vitro and in vivo.Methods The Mcart1 knockout mice were used to establish a sepsis model induced by lipopolysaccharide(LPS),and the survival period was measured.Bone marrow derived macrophages(BMDM)of LPS-induced inflam-mation mice were cultured in DMEM high-glucose medium.The mRNA levels of M1 and M2 related cytokines of BM-DM after LPS stimulation were detected by RT-qPCR.The expression level of inflammation-related cytokines in serum of sepsis mice was detected by ELISA.Results Compared with wild type mice(Mcart1flox/flox),the survival time length of sepsis in Mcart1 knockout mice(Mcart1Lyz2-Cre)was significantly shortened(P<0.001).After inflammation,the mRNA level of M1-related cytokines was up-regulated in BMDM cells of Mcart1Lyz2-Cre mice(P<0.05);The mRNA level of M1-related cytokines was down-regulated(P<0.05);The expression of M1-related mediators in serum of sep-sis Mcart1Lyz2-Cre mice was up-regulated(P<0.01).Conclusions Mcart1 knockout can significantly raise the inflam-matory response of macrophages and aggravate the pathological symptoms of sepsis mice.
6.Meta-analysis of Ruiyun procedure for hemorrhoids combined with milligan-morgan hemorrhoidectomy(MMH)in the treatment of mixed hemorrhoids
Yingying GUO ; Tianyu ZHOU ; Xiaozhen CHENG ; YiZhu WANG
Journal of Shenyang Medical College 2024;26(1):30-36,42
Objective:To systematically evaluate the clinical efficacy of Ruiyun procedure for hemorrhoids(RPH)combined with milligan-morgan hemorrhoidectomy(MMH)in the treatment of mixed hemorrhoids compared with MMH alone.Methods:Relevant literature was retrieved from China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases from their establishment to Jan 2023 using computers.Clinical randomized controlled trials(RCTs)of RPH combined with MMH and MMH alone in the treatment of mixed hemorrhoids were selected and analyzed,and meta-analysis was conducted using RevMan5.3 software.Results:A total of 30 RCTs were included,involving 4 609 patients.Results of Meta-analysis showed that there were statistically significant differences in surgical efficacy(RR=1.05,95% CI:1.02-1.08,P= 0.003),postoperative margin edema(RR=0.36,95% CI:0.27-0.49,P<0.01),postoperative anal pain(RR=0.35,95% CI:0.23-0.53,P<0.01),postoperative rectal bleeding(RR=0.35,95% CI:0.17-0.72,P=0.004),postoperative anal stenosis(RR=0.26,95% CI:0.11-0.59,P=0.001)and postoperative urinary retention(RR=0.77,95% CI:0.63-0.93,P=0.007)between RPH combined with MMH group and MMH group.Conclusion:Compared with MMH alone,RPH combined with MMH in the treatment of mixed hemorrhoids can reduce the incidence of postoperative side effects,such as postoperative margin edema,anal pain,rectal bleeding,anal stenosis,and urinary retention,with a relatively higher efficiency.
7.Analysis of CEP290 gene variants and clinical phenotypes in a family with Leber congenital amaurosis type 10
Haitao ZHANG ; Ziqian ZHU ; Handong DAN ; Yingying XU ; Hanchao GUO ; Lu SHI ; Liangwei MAO
Chinese Journal of Ocular Fundus Diseases 2024;40(4):273-280
Objective:To identify and observe disease-causing gene variants and clinical phenotypes in a Han Chinese family with Leber congenital amaurosis (LCA).Methods:A retrospective study. A patient with LCA10 and his parents who had presented at Department of Ophthalmology of Henan Provincial People's Hospital on May 2022 were selected as the study subject. Detailed medical and family histories were recorded, fundus photography and flash electroretinogram (F-ERG) were performed. Peripheral venous blood samples (3 ml) of the proband and his parents were collected to extract whole genomic DNA, then whole exome sequencing (WES) and mitochondrial DNA (mtDNA) sequencing were carried out for the proband to determine the disease-causing gene and variants. All variants were annotated by bioinformatics analysis. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the pathogenicity of all detected variants were evaluated. Candidate variants were verified by Sanger sequencing, and in vitro minigene assay were performed to evaluate the impact of the missense variant with insufficient evidence on mRNA splicing.Results:The proband, male, 7-month-old, presented with an inability to follow light or objects, eye poking, photophobia, nystagmus, partial loss of retinal pigment epithelium around the fovea of the macula. At the age of 2 years old, F-ERG revealed severe reduction, elongation, or even no waveform of a-wave and b-wave in both eyes. No obvious abnormality was found in the clinical phenotype of his parents. The result of WES revealed that the proband carried two variants in exon 40 and exon 2 of CEP290, a frameshift variant c.5515_5518del (p.Glu1839Lysfs*11) (V1) and a novel missense variant c.74C>T (p.Ala25Val) (V2), respectively. The result of mitochondrial DNA sequencing was negative. Sanger sequencing confirmed that the heterozygous frameshift variant was inherited from his father and the heterozygous novel missense variant was inherited from his mother, which constituted compound heterozygous variants. In vitro minigene splicing assay confirmed that V2 created a new splicing donor at exon 2, leading to the in-frame deletion of 30bp fragment during transcription and loss of 10 amino acid residues in the protein. The two variants were pathogenic (V1) and likely pathogenic (V2) based on ACMG guidelines, respectively. Conclusions:The c.5515_5518del and novel c.74C>T compound heterozygous variants of the CEP290 gene probably are the cause of LCA10 in this family, which lead to the production of a truncated protein and aberrant splicing of pre-mRNA, respectively. LCA is characterized by early onset, severe impairment of visual function, and a wide range of disease-causing variations.
8.The mediating effect of dying anxiety between family care and quality of life in advanced lung cancer patients
Jie ZHANG ; Yingying GUO ; Xinyan YU
China Modern Doctor 2024;62(18):30-33
Objective To explore the mediating effect of dying anxiety in the relationship between famlily care and quality of life in patients with advanced lung cancer.Methods A total of 180 patients with advanced lung cancer in Zhejiang Cancer Hospital from September to December 2023 were selected by convenience sampling method to conduct a questionnaire survey using the general information questionnaire,family adaptation,partnership,growth,affection and resolve index(APGAR),death and dying anxiety scale and quality of life instrument for lung cancer patients.Results There was a negative correlation between family care and dying anxiety in advanced lung cancer patients(P<0.01),and a positive correlation between family care and quality of life in advanced lung cancer patients(P<0.01).Dying anxiety had a partial mediating effect on family care and quality of life in advanced lung cancer patients,accounting for 30.1%of the total effect.Conclusion In the daily work of treating patients with advanced lung cancer,medical staff can take a variety of intervention ways to reduce patients'dying anxiety,so as to improve the quality of life of patients with advanced lung cancer.
9.A study on correlation between triglycerides glucose index,remnant cholesterol and diabetic nephropathy
Tianyang GUO ; Hui ZHOU ; Yingying CHENG
Chinese Journal of Clinical Laboratory Science 2024;42(4):256-260
Objective To explore the relationship between the triglyceride-glucose(TyG)index,residual cholesterol(RC)and dia-betic nephropathy(T2DM).Methods A total of 410 patients with T2DM were consecutively selected from the Endocrinology Depart-ment of Jiangsu Provincial Traditional Chinese Medicine Hospital from March 2022 to March 2023.The patients were stratified into three groups based on their morning urinary albumin-to-creatinine ratio(UACR):269 patients were in simple diabetes mellitus(SDM)group,80 in early diabetic nephropathy(EDN)group and 61 in clinical diabetic nephropathy(CDN)group.Comparative an-alyses were conducted on the three groups in terms of gender,age,past medical history,body mass index(BMI),systolic blood pres-sure(SBP),diastolic blood pressure(DBP),fasting blood glucose(FBG),Urea,creatinine(Cr),urinary albumin(UA)total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C).Additionally,TyG index and RC were calculated.Spearman analysis was employed to evaluate the correlation between UACR and these various parameters.Binary Logistic regression was utilized to identify independent risk factors for diabetic nephropathy(DN).The diagnostic performances of Urea,Cr,TyG index and RC for type 2 diabetic nephropathy were assessed using receiver operating charac-teristic(ROC)curve analyses.Results Compared with SDM group,diabetes duration,SBP,Urea,UA,TG,TC,TyG index and RC showed significant increases in EDN group with statistically significant differences(P<0.05),and diabetes duration,SBP,DBP,Urea,Cr,UA,TG,TC,LDL-C,TyG index and RC in CDN group also exhibited significant increases,with statistically significant differences(P<0.05).Spearman rank correlation analysis revealed a positive correlation between RC and UACR(r=0.278,P<0.001),a positive correlation between TyG index and UACR(r=0.239,P<0.001)and a positive correlation between RC and TyG in-dex(r=0.562,P<0.001).Binary logistic regression analysis showed that diabetes duration,SBP,Urea,Cr,TyG index(OR=2.815,95%CI:1.481-5.349,P=0.002),and RC(OR=2.179,95%CI:1.038-4.574,P=0.04)were independent risk factors for DN.The area under the ROC curve(AUCROC)for RC predicting DN occurrence was 0.670(95%CI:0.616-0.725),while the AUCROC for the TyG index was 0.620(95%CI:0.564-0.676).Conclusion TyG index and RC were significantly correlated with the development of DN in the patients with T2DM,which may early facilitate clinical identification and management for the patients in the risk ofr diabetic kidney disease.
10.Design and Application of the Regional Open Sharing System for Health and Medical Data
Yi GUO ; Yingying HU ; Fei HU ; Yangyang SHEN ; Jie XU
Journal of Medical Informatics 2024;45(8):84-88,95
Purpose/Significance To achieve safe and efficient open sharing of health and medical data,and to stimulate the value of health and medical data elements.Method/Process Aiming at the current situation and problems of open sharing of health and medical data,an open sharing system of health and medical data is designed based on data integration governance,data asset management,data product supermarket,data sampling analysis and online sandbox analysis.Result/Conclusion The practice has proved that the system can effectively realize the collection,analysis,management and utilization of health and medical data.

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