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.Mechanism of action and clinical research progress of iguratimod in connective tissue diseases
Xiaorong YANG ; Shuhong ZHOU ; Lijiang GUO ; Ying CHEN ; Yingying JI ; Lijie XU
China Pharmacy 2024;35(5):629-634
As a new type of immunosuppressant,iguratimod can mediate the anti-inflammatory signaling pathway by inhibiting the proliferation of inflammatory cells and reducing the release of inflammatory cytokines, and play the role of anti-inflammatory. It can affect the proliferation of immune cells and the expression of immune factors,reduce the production and deposition of immune complexes in the body,and play the role of immune regulation. It can regulate bone metabolism by mediating signaling pathways such as Wnt/β-catenin,Toll-like receptor 4/nuclear factor-κB and osteoprotegerin/nuclear factor-κB receptor activating factor ligand, and play a role in bone protection. It can inhibit pulmonary fibrosis by inhibiting the expression of transforming growth factor β1/ Smad2/3 signaling pathway,tumor necrosis factor-α,interleukin-1,interleukin-6,matrix metalloproteinase-9 and other inflammatory cytokines in lung tissue,and inhibiting the expression of collagen and fibronectin. Its efficacy and safety have been confirmed in the clinical application of rheumatoid arthritis and primary Sjogren syndrome and included in the diagnosis and treatment of the disease. It has also shown good efficacy in the clinical application of other connective tissue diseases such as systemic lupus erythematosus and ankylosing spondylitis,and no obvious safety risks have been found.
6.Exploration of Pathogenesis and Treatment Methods of Qi-Ying Fen Transformation in Warm Diseases
Yingying SONG ; Hai GUO ; Jin YANG ; Kaifeng WEI
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(6):550-554
Pathogenesis and treatment methods of qi-ying fen transformation in warm diseases are explored.It is believed that warm diseases are caused by yang pathogenic factors and are most likely to damage the organs and body fluids.Body fluids,as important components of human body's healthy qi,are usually present in the lungs as lung fluids,in the stomach as stomach fluids,in the intes-tines as intestinal fluids,and in blood vessels as nutrient yin.During the transformation from qi fen syndrome to ying fen syndrome,vis-ceral parenchymal damage acts as its important pathological mechanism and fluid depletion in blood vessels is an important reason for exacerbating qi-ying fen transformation.Excessive fire-toxicity,as an initial factor,promotes qi-ying fen transformation.Fluid deple-tion is the pathological basis for exacerbating qi-ying fen transformation.Clearing heat and protecting fluids,with sweet-flavored and cold-natured drugs to generate fluids,salty-flavored and cold-natured drugs to clear heat,and combination of sweet-flavored and bit-ter-flavored drugs,is an inevitable treatment method for preventing and treating qi-ying fen transformation in warm diseases,and it al-so has important clinical guidance value for internal miscellaneous diseases and acute severe cases.
7.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.
8.Prognostic value of frailty assessment in elderly patients with heart failure
Yuhui ZENG ; Yuhao WAN ; Chen MENG ; Yingying LI ; Yao LUO ; Ning SUN ; Di GUO ; Lingling CUI ; Jiefu YANG ; Hua WANG
Chinese Journal of Geriatrics 2024;43(8):1013-1018
Objective:To assess the prognostic impact of frailty on elderly inpatients with heart failure.Methods:This prospective cohort study enrolled 121 in elderly patients with heart failure from Beijing Hospital, the General Hospital of the People's Liberation Army, and Beijing Tsinghua Changgung Hospital between September 2018 and April 2019.Patients were assessed for frailty using the Fried frailty phenotype and categorized into frail and non-frail groups.Follow-ups were conducted at 3-, 6-, and 12-months post-enrollment through clinic visits or phone calls to record adverse events.Composite endpoints include all-cause mortality and rehospitalization duo to deterioration of heart failure.Results:The study included 121 patients with an average age of 78.0±7.4 years, of whom 71(58.7%)were male and 57(47.1%)were classified as frail.Compared to the non-frail group, the frail group had lower estimated glomerular filtration rates[49.5±20.7 ml/(min·1.73m 2) vs.(64.0±27.1)ml/(min·1.73m 2)], lower scores in Basic Activities of Daily Living[5.0(4.0, 6.0) vs.6.0(5.0, 6.0)], Instrumental Activities of Daily Living[2.0(1.3, 7.8) vs.7.0(5.0, 8.0)], and Mini-Mental State Examination[26.0(16.0, 28.0) vs.27.0(22.3, 29.0)], all P<0.05.They also experienced longer hospital stays[10.5(6.0, 18.8)days vs.8.0(6.0, 11.8)days, P=0.008].During the follow-up period, the incidence of composite endpoint events was significantly higher in the frail group(43.9% vs.25.0%, P=0.029).Kaplan-Meier survival analysis demonstrated that the one-year incidence of composite endpoint events was significantly higher in the frail group( P=0.013).Multivariable Cox regression analysisindicated that frailty was an independent risk factor for composite endpoint events( HR=2.201, 95% CI: 1.089-4.447, P=0.028). Conclusions:Frailty is an independent risk factor for poor outcomes in elderly hospitalized patients with heart failure and should be considered a crucial factor in clinical assessment and treatment strategies.
9.Exploration of Decision-Making Methods Based on Syndrome Differentiation by “Data-Knowledge” Dual-Driven Models: A Case Study of Gastric Precancerous State
Weichao XU ; Yanru DU ; Xiaomeng LANG ; Yingying LOU ; Wenwen JIA ; Xin KANG ; Shuo GUO ; Kun ZHANG ; Chunzhi SU ; Junbiao TIAN ; Xiaona WEI ; Qian YANG
Journal of Traditional Chinese Medicine 2024;65(2):154-158
Data analysis models may assist the transmission of traditional Chinese medicine (TCM) experience and clinical diagnosis and treatment, and the possibility of constructing a “data-knowledge” dual-drive model was explored by taking gastric precancerous state as an example. Data-driven is to make clinical decisions around data analysis, and its syndrome-differentiation decision-making research relies on hidden structural models and partially observable Markov decision-making processes to identify the etiology of diseases, syndrome elements, evolution of pathogenesis, and syndrome differentiation protocols; knowledge-driven is to make use of data and information to promote decision-making and action processes, and its syndrome-differentiation decision-making research relies on convolutional neural networks to improve the accuracy of local disease identification and syndrome differentiation. The “data-knowledge” dual-driven model can make up for the shortcomings of single-drive numerical simulation accuracy, and achieve a balance between local disease identification and macroscopic syndrome differentiation. On the basis of previous research, we explored the construction method of diagnostic assisted decision-making platform for gastric precancerous state, and believed that the diagnostic and decision-making ability of doctors can be extended through the assistance of machines and algorithms. Meanwhile, the related research methods were integrated and the core features of gastric precancerous state based on TCM syndrome differentiation and endoscopic pathology diagnosis and prediction were obtained, and the elements of endoscopic pathology recognition based on TCM syndrome differentiation were explored, so as to provide ideas for the in-depth research and innovative application of cutting-edge data analysis technology in the field of intelligent TCM syndrome differentiation.
10.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.

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