1.Analysis of Mechanism of Exosomes of BMSC Modified with Bushen Yisui Capsules on Promoting Differentiation and Maturation of OLN-93 Oligodendrocytes via Regulating miR-15b/Wnt Signaling Pathway
Sisi LIU ; Chunyu LI ; Chen LI ; Haixin LI ; Lei WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):115-125
ObjectiveTo investigate the effect and molecular mechanism of exosomes derived from bone marrow mesenchymal stem cells(BMSC-exos) modified with Bushen Yisui capsule(BSYS)-containing serum on promoting the differentiation and maturation of OLN-93 oligodendrocytes by regulating miR-15b/Wnt signaling pathway. MethodsOLN-93 cells were divided into 5 groups, including the normal(NC) group, BMSC-exos group, BSYS-BMSC-exos group, BSYS-BMSC+LV-miR-15b-5p inhibitor-exos group, and BSYS-BMSC+LV-miR-15b-5p NC-exos group. DiR staining was used to observe the uptake of Exos by OLN-93 cells. The effective dosage of BSYS-BMSC-exos on OLN-93 cells was assessed by cell proliferation and activity assay(CCK-8). Stable BMSCs lentiviral transfection strains were established to inhibit miR-15b-5p expression in both BMSCs and their exos, and transfection efficiency was verified by real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) detection of miR-15b-5p. The expressions of 2′,3′-cyclic nucleotide 3′-phosphodiesterase(CNPase) and myelin proteolipid protein(PLP) in OLN-93 cells were detected by immunocytochemistry(ICC) and Western blot. The mRNA expressions of miR-15b-5p and Wnt3a in OLN-93 cells were detected by Real-time PCR, and the protein expression of Wnt3a was measured by Western blot. The expression levels of key molecules in the Wnt/β-catenin signaling pathway of OLN-93 cells, including glycogen synthase kinase(GSK)-3β, β-catenin, and T-cell specific transcription factor 4/transcription factor 7-like 2(TCF4/TCF7L2), were measured by Real-time PCR and Western blot. ResultsDiR-labeled Exos were efficiently taken up by OLN-93 cells. The CCK-8 assay results indicated that 20 mg·L-1 of BSYS-BMSC-exos exhibited the most significant effect in enhancing OLN-93 cell viability(P<0.01) and this dosage was selected for subsequent experiments. Following lentiviral transfection of BMSCs, Real-time PCR results revealed that miR-15b-5p was significantly suppressed in BMSCs(P<0.01), and miR-15b-5p was also notably inhibited in BSYS-BMSC-exos(P<0.01). ICC analysis further revealed an increase in the number of differentiated, mature CNPase and PLP-positive cells following BSYS-BMSC-exos treatment(P<0.01). Western blot results demonstrated that the protein expression of CNPase and PLP was significantly enhanced with BSYS-BMSC-exos treatment(P<0.01). Additionally, BSYS-BMSC-exos also increased the expression levels of miR-15b-5p and p-β-catenin proteins in OLN-93 cells, while decreased the mRNA and protein expressions of Wnt3a, as well as the mRNA expressions of β-catenin and TCF4/TCF7L2, and the protein expression level of p-GSK-3β(Ser9) was significantly reduced(P<0.05, P<0.01). After the transfection of miR-15b-5p inhibitor into BSYS-BMSC-exos, the above effects were significantly diminished(P<0.05, P<0.01). ConclusionBSYS-BMSC-exos facilitate the differentiation and maturation of OLN-93 cells, and its mechanism is related to the upregulation of miR-15b-5p in OLN-93 cells, which inhibits the expression of Wnt3a and thereby suppresses the Wnt signaling pathway.
2.Hyperoside Alleviates LPS-induced Inflammation in Zebrafish Model via TLR4/MyD88/NF-κB Pathway
Qing LAN ; Anna WANG ; Feifei ZHOU ; Keqian LIU ; Zhao LI ; Wenjing YU ; Shuyao TANG ; Ping LI ; Shaowu CHENG ; Sisi DENG ; Zhenyan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):63-72
ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside (Hyp) on lipopolysaccharide (LPS)-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L-1 LPS or immersed in 1 g·L-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25, 50, and 100 mg·L-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate, malformation rate, body length, and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses, and macrophage migration was observed by fluorescence microscopy. Additionally, the mRNA levels of inflammation-related genes, including interleukin-1β (IL-1β), interleukin-6 (IL-6), chemokine C-C motif ligand 2 (CCL2), chemokine C-X3-C motif receptor 1 (CX3CR1), chemokine C-C motif receptor 2 (CCR2), and genes associated with the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway, were measured by Real-time quantitative polymerase chain reaction(Real-time PCR). ResultsCompared with the pure water injection group, the model group exhibited increased mortality, malformation rates and yolk sac area ratio (P0.01), reduced body length (P0.01), increased total swimming distance and high-speed swimming duration (P0.01), and up-regulated mRNA levels of TLR4, MyD88, NF-κB, IL-1β, IL-6, CCL2, CX3CR1, and CCR2 (P0.01). Hyp at low, medium and high doses, as well as aspirin, reduced the mortality and malformation rates (P0.05,P0.01), increased the body length (P0.05,P0.01), decreased the yolk sac area ratio (P0.01), reduced the high-speed swimming duration (P0.01), and down-regulated the mRNA levels of TLR4, MyD88, NF-κB, IL-1β, IL-6, CCL2, CX3CR1, and CCR2 (P0.05,P0.01) compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish, thereby exerting the anti-inflammatory effect.
3.Research progress in active substances and their mechanisms of action against porcine epidemic diarrhea virus.
Yu LIU ; Sisi SU ; Ziqian WANG ; Jiahao WU ; Hongwei CHEN ; Hongzao YANG
Chinese Journal of Biotechnology 2025;41(7):2519-2533
Porcine epidemic diarrhea virus (PEDV) is an intestinal coronavirus that can cause porcine epidemic diarrhea, leading to diarrhea, vomiting, weight loss, and even death in piglets. Due to the diversity of PEDV strains, traditional vaccines are difficult to sustainably and effectively prevent and control PEDV. This article reviews the strategies and mechanisms of active substances in regulating intracellular signaling pathways, viral proteins, and microbial metabolites to enhance the host immune function against PEDV. It emphasizes the prevention of PEDV resistance and the potential harm of PEDV breaking through interspecies barriers to the human society, aiming to provide reliable theoretical support for the development of new antiviral drugs or vaccines.
Porcine epidemic diarrhea virus/immunology*
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Animals
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Swine
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Swine Diseases/prevention & control*
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Antiviral Agents/pharmacology*
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Coronavirus Infections/virology*
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Viral Vaccines/immunology*
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Humans
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Signal Transduction
4.Risk factors of contrast medium extravasation:a systematic review and Meta-analysis
Fang WANG ; Bao LIU ; Zhijun AN ; Yingxin WANG ; Chao WANG ; Sisi HUANG
Journal of Practical Radiology 2024;40(1):127-130
Objective To systematically evaluate the risk factors of contrast medium extravasation(CME).Methods The rele-vant literature on the risk factors of CME were searched from CNKI,WanFang,VIP,CBM,Cochrane Library,ProQuest,PubMed,Ovid,Web of Science,and Embase via computer.Meta-analysis was performed via RevMan5.4.Results A total of 10 articles were included,involving 17 risk factors.The results of the Meta-analysis showed that contrast medium(CM)concentration[odds ratio(OR)=2.02],age(OR=2.22),combined tumor(OR=2.87),puncture site(OR=2.73),nursing experience(OR=2.78),osmotic pressure(OR=3.29),combined circulatory disease(OR=4.56)were the statistically significant factors.Conclusion The independ-ent risk factors of CME include CM concentration,age,combined tumor,puncture site,nursing experience,osmotic pressure,and combined circulatory disease.
5.SiO2 Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model
Wang YONGHENG ; Li NING ; Guan YI ; LI TONG ; Zhang YUXIU ; Cao HONG ; Yu ZHIHUA ; Li ZHIHENG ; Li SHUOYAN ; Hu JIAHAO ; Zhou WENXIN ; Qin SISI ; Li SHUANG ; Yao SANQIAO
Biomedical and Environmental Sciences 2024;37(6):617-627
Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.
6.Research on the framework of biosafety standards for pathogenic microbial laboratories
Jing LI ; Zhen CHEN ; Sisi LI ; Bing LU ; Siqing ZHAO ; Rong WANG ; Guoqing CAO ; Wei WANG ; Chuntao MA ; Xuexin HOU ; Yanhai WANG ; Chihong ZHAO ; Guizhen WU
Chinese Journal of Epidemiology 2024;45(2):294-299
Developing and implementing biosafety standards for pathogenic microbiology laboratories is essential to achieving scientific, efficient, and standardized management and operation. This article analyzes the current standardization construction in biosafety in pathogenic microbiology laboratories domestically and internationally. It proposes a framework for the biosafety standard system of pathogenic microbiology laboratories, which mainly includes four parts: basic standards, management standards, technical standards, and industry applications. It provides a reference for the standardization work of pathogenic microbiology laboratories and helps to standardize the biosafety industry in China.
7.Mechanism of action and potential therapeutic targets of ferroptosis suppressor protein 1 in liver diseases
Sisi WANG ; Yaru WANG ; Rui LIU ; Jie QIN
Journal of Clinical Hepatology 2024;40(7):1493-1497
Ferroptosis suppressor protein 1(FSP1)is another major ferroptosis regulator besides glutathione peroxidase 4,which can scavenge intracellular reactive oxygen species and lipid peroxides and inhibit ferroptosis.In view of the key role of the liver in iron and lipid metabolism and its susceptibility to oxidative damage,more and more evidence has shown that FSP1 plays an important role in liver diseases such as metabolic associated fatty liver disease,hepatocellular carcinoma,acute liver failure,and alcoholic liver disease,and the related targets of FSP1 are expected to become a potential treatment option.This article comprehensively reviews FSP1,with a focus on the role of FSP1 in the pathophysiology of several common liver diseases and the potential of FSP1 as a target of liver diseases,in order to provide new ideas for the treatment of liver diseases.
8.Application of transcranial ultrasound stimulation in neurorehabilitation: a bibliometric analysis
Huifang HE ; Xiang GONG ; Xihui WANG ; Sisi ZHU ; Ying SHEN
Chinese Journal of Rehabilitation Theory and Practice 2024;30(12):1420-1427
ObjectiveTo analyze the current status, research hotspots, and development trends of transcranial ultrasound stimulation (TUS) in neurorehabilitation. MethodsRelevant literature on the application of TUS in neurological rehabilitation was retrieved from CNKI, Wanfang data, and Web of Science Core Collection, covering publications from inception to December 31, 2023. VOSviewer 1.6.20 and CiteSpace 6.2.R1 were used for visualized analysis. ResultsA total of 247 articles were included, with 124 in Chinese and 123 in English, showing an increasing trend in annual publications. The major contributors to English literature were China, the United States, Canada, France and South Korea. High-frequency Chinese keywords included transcranial ultrasound, neuromodulation, Parkinson's disease, stroke and clinical efficacy. The keyword clusters were transcranial ultrasound, neuromodulation, upper limb function and Parkinson's disease. Bursting keywords included rehabilitation, neural function, ultrasound therapy, closed-loop control and low intensity. High-frequency English keywords included focused ultrasound, deep brain stimulation, transcranial magnetic stimulation, blood-brain barrier and thalamotomy. Keyword clusters covered tissue plasminogen activator, ultrasonic imaging, transcranial magnetic stimulation, thalamotomy and ultrasound. Bursting keywords featured essential tremor, neurostimulation, direct current stimulation and transcranial ultrasound stimulation. ConclusionResearch on the application of TUS in neurorehabilitation is on the rise, focusing on its efficacy and safety in Parkinson's disease, essential tremor, and ischemic stroke. Future research needs to explore the mechanisms of TUS, optimize treatment plans, and promote the development of individualized therapies.
9.The efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant recurrent ovarian cancer
Meng YANG ; Jingjing WANG ; Shaoqiong DENG ; Sisi LIANG ; Li SUN
Chinese Journal of Oncology 2024;46(7):696-702
Objectives:To investigate the efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant ovarian cancer.Methods:Thirty-five patients with pathological confirmed platinum-resistant ovarian cancer who experienced progression after receiving at least two lines of standard treatment were eligible. All of them were treated with anlotinib combined with niraparib between September 2019 and October 2021. The primary endpoint was progression-free survival (PFS). The second endpoints included overall survival, objective response rate (ORR), disease control rate (DCR) and safety. Survival analysis was performed using the Kaplan-Meier method and Log-rank test, and influence factor analysis was performed using Cox proportional risk regression models.Results:The best overall response showed that partial response was observed in 14 patients, stable disease was noted within 13 patients, and progressive disease was found in 8 patients. Therefore, the ORR and DCR of these 35 patients were 40.0% (95% CI:22.9%-57.1%) and 77.1% (95% CI:62.9%-91.4%), respectively. The median follow-up duration was 18.9 months (6.9-32.2). The median PFS was 6.5 months (95% CI:5.35-7.66). Multivariate Cox regression analysis for PFS indicated that age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, International Federation of Gynecology and Obstetrics (FIGO) stage, and BRCA mutation status were independent factors influencing PFS ( P<0.05). Additionally, the PFS in patients with BRCA mutation who have never received PARP inhibitor treatment was significantly longer than that in patients without BRCA mutation who have been exposed to prior PARPi treatment (15.0 vs 6.0 month, P=0.029). The most common treatment-related adverse reactions were fatigue (85.7%), hematologic toxic (85.7%) and hypertension (74.3%). There were no treatment-related deaths. Conclusion:Anlotinib combined with niraparib shows a promising efficacy and tolerable safety in platinum-resistant ROC patients.
10.Exploration of multi-disciplinary treatment of functional departments to improve medical quality:a case studay of Children's Hospital,Zhejiang University School of Medicine
Xiaoying CHENG ; Xuyu ZHU ; Sisi WANG ; Feibo CHEN ; Junfen FU
Modern Hospital 2024;24(1):46-49
Medical quality and safety are the foundation for the high-quality development of public hospitals.The concept of Multi-disciplinary Treatment(MDT)is of great value for functional departments of hospitals to collaborate in carrying out medi-cal quality management practices.Children's Hospital,Zhejiang University School of Medicine explored a new quality manage-ment model,constructed the MDT practice path for medical quality in administration,and formed a closed-loop management process where clinical departments actively initiate consultations,various administrative functional departments collaborate and in-teract in a two-way manner,accurately identify and solve clinical problems,and continuously track and feedback outcomes.After the inception of this path,the overall level of medical quality and safety in the hospital has been comprehensively improved,mainly manifested in the enhancement of quality control capabilities of clinical departments,optimization of core performance e-valuation indicators,and remarkable improvement in patient satisfaction,thereby holding profound significance for high-quality development of the hospital.

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