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.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.
4.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.
5.Practice and thoughts of pediatric continuing education under information technology-aided medical consortium model
Qiang LI ; Sisi WANG ; Huiyi WANG ; Zhina YOU ; Fubang LI ; Wei WANG
Chinese Journal of Medical Education Research 2024;23(3):299-304
To create flexible and high-quality pediatric continuing education opportunities, the Children's Hospital of Zhejiang University School of Medicine has developed an online teaching system based on the medical consortium information system, mobile application, and website, which includes "5G+" digital classroom for case teaching, hierarchical diagnosis and treatment tracking, mobile courses, and live interactive lectures about difficult medical cases as support extensions of offline training. From 2020 to 2023, over 9 000 people participated in online activities. The results of questionnaire survey, theoretical examination, and semi-structured interview showed that the members of the medical consortium were satisfied with the training content and effect of the online medical continuing education model; medical personnel's theoretical levels were improved after training; the interviewees believed that online training was flexible and convenient with regard to time, location, and space, with positive impact for improving clinical ability and personal development. However, the online form cannot yet replace the traditional refresher training completely. In the future, we will establish a unified evaluation and assessment mechanism, form a standardized management system, and introduce advanced technologies, so as to encourage enthusiastic and effective participation, and promote the rational and efficient use of medical education resources.
6.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.
7.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.
8.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.
9.Correlation between insomnia,gastrointestinal symptoms,and glycated hemoglobin in patients with type 2 diabetes:a cross-sectional study based on the co-management platform of three disciplines of diabetes
Bo LI ; Qi YUAN ; Yongfa WANG ; Youjian FENG ; Guimiao WANG ; Weidong NIAN ; Yi ZHOU ; Tianchi HU ; Sisi MA ; Liyan JIA ; Zhihai ZHANG ; Jin LI ; Bing YAN ; Nengjiang ZHAO ; Shuyu YANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(7):989-997
Objective To investigate the relationship between insomnia,gastrointestinal symptoms,and glycosylated hemoglobin(HbA1c)levels in individuals diagnosed with type 2 diabetes mellitus(T2DM),as well as the related influencing factors.Methods A total of 910 T2DM patients treated in our multicenter from January 2022 to December 2022 were enrolled in this study.General information(gender,age,smoking and drinking history,exercise,course of disease,treatment and complications),HbA1c,Athens Insomnia Scale(AIS)scores and Gastrointestinal Symptoms Rating Scale(GSRS)scores of patients were collected.The differences of sleep and gastrointestinal symptoms between groups were analyzed,and the correlation between the differences and HbA1c was analyzed.Furthermore,the risk factors for non-standard HbA1c were analyzed.Results The AIS score and GSRS score in the HbA1c control group were less than those in the non-standard group(P<0.01).Insomnia was reported by 37.0%of T2DM patients,and the HbA1c level in the insomnia group was significantly higher than that in the non-insomnia group(10.00%±2.38%vs.8.26%±1.73%,P<0.01).Gastrointestinal symptoms were present in 57.5%of T2DM patients,and the HbA1c levels in the group with gastrointestinal symptoms were significantly higher than those in the group without gastrointestinal symptoms(9.26%±2.23%vs.8.43%±1.98%,P<0.01).Furthermore,26.3%of T2DM patients experienced both insomnia and gastrointestinal symptoms.Remarkably,the HbA1c levels in the group with both insomnia and gastrointestinal symptoms were significantly higher than those in the group without either condition(10.18%±2.44%vs.8.45%±1.86%,P<0.01).Correlation analysis demonstrated a significant association between sleep quality,gastrointestinal function,and HbA1c levels(P<0.01).The logistic regression analysis result revealed that age,GSRS score,AIS score,and the presence of insomnia combined with gastrointestinal symptoms were independent risk factors for predicting HbA1c≥6.5%(P<0.01).Having both insomnia and gastrointestinal symptoms concurrently was the strongest risk factor for substandard HbA1c control,and the risk of blood sugar control may increase about 5 times when both appear together.Conclusion Insomnia and gastrointestinal symptoms are common comorbidities in T2DM patients,showing a cross-interfering relationship,and they appear together with poor blood sugar control,interact causally,and amplify each other.
10.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.

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