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.Drug resistance mutation analysis of HIV-1 among blood donors in Dalian:2011-2020
Xiaohan GUO ; Xuelian DENG ; Xiaochun LIU ; Yingying WANG ; Liang ZANG ; Jun ZHOU
Chinese Journal of Blood Transfusion 2024;37(8):902-907
Objective To study the distribution and trend of HIV-1 drug resistance mutation in Dalian blood donors be-tween 2011 and 2020.Methods The protease-reverse transcriptase(PR-RT)region was sequenced in Dalian blood donors tested HIV-1 positive between 2011 and 2020.Drug resistance mutation(DRM)rate and level of resistance to selected drugs were analyzed by the Stanford HIV Drug Resistance Database.Results DRM were detected in 17.2%(30/174)of samples,while transmitted drug resistance(TDR)was5.7%(10/174).Between2011 and2020,DRM and TDR rates in-creased significantly in 2019 and reached their highest levels in 2020(44.4%and 22.2%,respectively).DRM carriage was associated with people with college degree or above and with local residents(P<0.05).NNRTI DRMs were the most fre-quently detected(12.6%,22/174),followed by PIs(5.7%,10/174),with V179D/E/T and M46I being the main DRMs detected.Only one HIV-1strain(0.57%,1/174)carried a NRTI DRM(L74I).The overall rate of predicted high level re-sistance to antiretroviral drugs was 6.9%(12/174),with the highest proportion of NNRTI resistance(83.3%,10/12).Two samples were classified as highly resistant to EFV and NVP,accounting for 1.1%(2/174).CRF55_01B strains showed a significantly higher DRM rate than strains of other HIV-1 genotypes(P<0.05).Conclusion Between 2011 and 2020,the rate of HIV-1 DRMs in blood donors in Dalian showed a significant upward trend,particularly in 2019-2020,with NNRTI resistance being the most common.The combination of DRMs detection before and after implementation of ART un-der the latest national ART treatment plan would improve the effectiveness of HIV-1 prevention and control locally.
7.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.
8.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.
9.Influencing factors of telangiectasia secondary to diabetic retinopathy
Yingying LI ; Dengshan GUO ; Pengwei YANG
International Eye Science 2024;24(1):140-143
AIM:To investigate the influencing factors of abnormal telangiectasia secondary to diabetic retinopathy(DR).METHODS: Prospective studies. A total of 153 cases(240 eyes)with DR treated in our hospital from January 2021 to January 2023 were selected to analyze the risk factors of abnormal telangiectasia secondary to DR and its predictive efficacy.RESULTS: The patients were divided into dilated group(77 eyes of 40 cases)and non-dilated group(163 eyes of 113 cases)according to whether they had secondary abnormal telangiectasia. There were significant differences in diabetic macular edema, hard exudates grade and fasting blood glucose level between the two groups(P<0.05). Logistic regression analysis showed that diabetic macular edema, high hard exudates grade and high blood glucose level were the risk factors for abnormal telangiectasia secondary to DR(P<0.05).CONCLUSION: The occurrence of telangiectasia secondary to DR may be related to diabetic macular edema, grade 3 hard exudates and high blood glucose level.
10.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.

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