Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.

BackgroundThe middle school stage represents a crucial period for the development of borderline personality features. Negative parenting styles and emotional regulation strategies are associated with the formation of borderline personality features. However， the moderating role of emotional regulation strategies between negative parenting styles and borderline personality features among middle school students remains unclear. ObjectiveTo explore the moderating influence of emotional regulation strategies in the relationship between negative parenting styles and borderline personality features among middle school students， and to provide references for the intervention of borderline personality features. MethodsIn October 2023， a total of 5 965 middle school students from three middle schools in Nanning， Guangxi Zhuang Autonomous Region were selected by cluster sampling， and assessed by the Borderline Personality Features Scale for Children （BPFS-C）， the Egna Minnen Barndoms Uppfostran （EMBU）， and the Emotion Regulation Questionnaire-Chinese Revised Version （ERQ-CRV）. Pearson correlation analysis was used to test the correlation between the scores of each scale， and the model 1 of the Process macro program was used to conduct the moderating effect test. ResultsA total of 5 572 middle school students （93.41%） completed this study， and 1 388 of them （24.91%） were identified as having high borderline personality features. The BPFS-C score of middle school students was positively correlated with the score of the negative parenting style dimension of EMBU （r=0.367， P<0.01）， negatively correlated with the score of the cognitive reappraisal dimension of ERQ-CRV （r=-0.168， P<0.01）， and positively correlated with the score of the expression inhibition dimension of ERQ-CRV （r=0.344， P<0.01）. Cognitive reappraisal played a negative moderating effect between negative parenting styles and borderline personality features （β=-0.072， 95% CI： -0.104–-0.041， P<0.01）， while expressive suppression played a positive moderating effect （β=0.076， 95% CI： 0.055–0.097， P<0.01）. ConclusionCognitive reappraisal strategy may help mitigate the negative influence of negative parenting styles on middle school students' borderline personality features， while expressive suppression may exacerbate the harm of negative parenting styles to the borderline personality features of middle school students.

Objective: To evaluate the effects of green tea extract (GTE) and its main catechin monomers on erythrocyte lesion (such as hemolysis, decreased energy metabolism and oxidative stress) during in vitro storage, and to explore its potential as a novel additive for erythrocyte preservation solutions. Methods: The composition of GTE was analyzed by high-performance liquid chromatography (HPLC). Using an in vitro simulated storage model, erythrocytes were stored in CPDA-1 preservation solution supplemented with GTE and the three most abundant catechin monomers (EGCG, ECG, EGC) for 60 days. Hemolysis rate and ATP content were dynamically monitored during storage. Flow cytometry was used to analyze phosphatidylserine (PS) exposure. Meanwhile, the protective effects of each component were verified in an acute oxidative stress model, and erythrocyte membrane stability was assessed by osmotic fragility test. Results: After 60 days of storage at 4℃, the hemolysis rate at the end of storage in the GTE group was <0.8%, which was superior to that in the control group and the single catechin-supplemented groups. Erythrocyte osmotic fragility assay showed that GTE could enhance the stability of erythrocyte membranes. In the acute oxidative stress experiment, the protective rate of GTE against erythrocyte injury exceeded 99%, which was better than that of the single catechin groups. At the initial stage of storage, ATP content decreased in all catechin-treated groups, but PS exposure was not significantly increased. Conclusion: The addition of GTE can effectively alleviate storage lesions of erythrocytes, with efficacy superior to that of single catechins. GTE enhances the antioxidant capacity and membrane stability of stored erythrocytes. Our results provide new experimental evidence for the development of GTE-based erythrocyte preservation additives.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

BACKGROUND:Macrophages are an important part of innate immunity.When the internal environment of the body changes,macrophages can produce different polarization phenotypes and play the corresponding inflammatory immune function.Mesenchymal stem cells can secrete a large number of extracellular vesicles into the internal environment of the body,which have the functions of intercellular signaling and immune regulation.Studies have shown that mesenchymal stem cells and mesenchymal stem cells-extracellular vesicles can affect the M1/M2 polarization balance of macrophages so as to treat immune inflammatory diseases.OBJECTIVE:To explore the signaling mechanism of how mesenchymal stem cells and their extracellular vesicles interfere with autoimmune diseases by regulating the polarization of macrophages,as well as the related research progress of engineered extracellular vesicles in this field.METHODS:The first author searched the relevant literature published in PubMed,CNKI and other databases until June 2024.Chinese search terms were"mesenchymal stem cells,extracellular vesicles,exosomes,apoptotic bodies,apoptotic vesicles,macrophage polarization,M1 polarization,M2 polarization,autoimmune diseases,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,type 1 diabetes mellitus,inflammatory bowel disease,autoimmune dacryadenitis,engineered extracellular vesicles,engineering exosomes,drug delivery."English search terms were"macrophage polarization,M1 macrophage,M2 macrophage,autoimmune disease,type 1 diabetes,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,autoimmune dacryadenitis,inflammatory bowel disease,mesenchymal stem cells,extracellular vesicles,engineered extracellular vesicles,engineering exosomes,drug delivery."The title and abstract of each paper were read and initially screened.Finally,70 articles were selected for induction and analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cells can regulate M1/M2 polarization by releasing or indirectly acting on functional proteins.(2)Mesenchymal stem cells can regulate macrophage M2 polarization through inflammasome.(3)Mesenchymal stem cells can be combined with commonly used drugs to enhance drug efficacy.(4)Mesenchymal stem cells can regulate the release of mesenchymal stem cells-extracellular vesicles after inflammatory stimulation and affect the polarization of macrophages.(5)Mesenchymal stem cells-extracellular vesicles can regulate autoimmune diseases by targeting macrophage polarization through PTEN,NOTCH,nuclear factor κB,Toll-like receptors,PI3K/AKT and other pathways.(6)Engineered extracellular vesicles can achieve non-invasive targeted drug delivery,prolong the half-life of drugs,promote the oral administration of exosomes,reduce allograft reaction,improve the bioavailability of Chinese herbs and overcome the blood-brain barrier,opening up a new path for drug delivery.

Objective To develop an effective intervention strategy to improve medication adherence among chronic disease patients.Methods Based on the behavior change wheel theory and integrating literature analysis,questionnaire surveys,clinical practice experience,the initial draft of the intervention strategies was developed.The intervention strategies were revised and refined through two rounds of Delphi expert consultation.Results The effective response rates for the two rounds of expert consultation questionnaires were 95%and 100%,respectively.The expert authority coefficient was 0.91.The Kendall's coefficient of concordance for the importance of the first and second rounds of expert consultation was 0.224 and 0.202,while the Kendall's coefficient of concordance for feasibility was 0.172 in the second round of expert consultation.The differences were statistically significant(P﹤0.05).The coefficient of variation of entries was 0.00-0.23.Based on the experts'feedback,adjustments were made to several items,resulting in a final intervention strategy that includes 3 primary indicators,9 secondary indicators and 41 intervention measures.Conclusion This strategy demonstrates a high level of scientific rigor and practicality,making it applicable in clinical settings to enhance medication adherence among chronic disease patients effectively,thus providing robust support for patient management.

Objective To investigate the association between UGT1A1 inhibitors-induced liver injury(DILI)and UGT1A1 gene polymorphisms through a pharmacogenomics approach.Methods Information on relevant drugs that may induce liver injury,blood routine tests,and liver function tests was collected from hospitalized patients diagnosed with DILI between June 2022 and June 2024.Relevant databases were searched to categorize DILI-associated drugs into UGT1A1 enzyme inhibitors and those without interaction with UGT1A1.Sanger sequenc-ing or MassARRAY SNP typing technology was utilized to detect and genotype the UGT1A1 gene.Results A total of 219 patients with drug-induced liver injury(DILI)were enrolled,including 98 males,with a mean age of 46.32±14.95 years.A literature search of relevant databases revealed that 20 drugs(16.26%,20/123)associated with DILI had inhibitory effects on the UGT1A1 enzyme.The proportion of DILI cases related to UGT1A1 inhibitors was 60.73%(133/219).Compared to non-UGT1A1 inhibitor-related DILI group,the UGT1A1 inhibitor-related DILI group exhibited significantly higher levels of ALT,AST,ALP,and GGT(P<0.05),while no significant differences were observed in age,gender,TBIL,IBIL,WBC,Hb,PLT,injury type,or injury grade(P>0.05).The prevalence of UGT1A1 polymorphisms was significantly higher in the UGT1A1 inhibitor-related DILI group(68.42%)com-pared to the non-UGT1A1 inhibitor-related DILI group(51.16%),with an odds ratio(OR)of 2.068(95%CI:1.183 to 3.617;χ2=6.58,P=0.010).There was also a significant difference in the distribution of genotypes between the UGT1A1 inhibitor-related and non-UGT1A1 inhibitor-related DILI groups(χ2=9.60,P=0.022).Univariate logistic regression analysis indicated that ALT and UGT1A1*6 were associated with UGT1A1 inhibitor-related DILI,while multivariate analysis confirmed that UGT1A1*6 was independently associated with UGT1A1 inhibitor-related DILI[OR(95%CI)=3.143(1.398 to 7.067),P=0.006].Conclusion The UGT1A1*6 allele increases the susceptibility to drug-induced liver injury(DILI)associated with UGT1A1 inhibitory drugs.

Objective To develop and validate an automated organoid image segmentation approach based on deep learning for addressing the issues of high misidentification rate,blurred boundary and poor generalization in current organoid segmentation,thereby facilitating researchers to monitor and analyze organoid growth more efficiently.Methods The wavelet scattering coefficient matrix and capsule convolution module were integrated into the U-Net architecture to construct the organoid image segmentation model OrgCapsU-Net which was trained and evaluated on 3 organoid image datasets from different tissue sources.Results Compared with current mainstream segmentation algorithms,OrgCapsU-Net could better distinguish organoid and impurity,and lead to smoother segmentation boundaries,achieving superior performance across 4 evaluation metrics on 3 datasets.Conclusion OrgCapsU-Net delivers excellent segmentation performance and can be applied to organoids from various tissue sources,showing strong potential for applications in the in vitro model establishment,high-throughput drug screening,and personalized medicine.

Objective:To investigate the risk factors of colorectal adenomatous polyps.Methods:The clinical data of 395 patients who underwent colonoscopy in the Tongzhou branch, Tongzhou District, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine from August 2017 to August 2021 were analyzed. According to the examination results, adenomatous polyps were divided into adenomatous polyps group (193 cases) and non-polyp group (202 cases). The risk factors of colorectal adenomatous polyps were screened by univariate analysis and multivariate logistic regression analysis.Results:The results of single factor analysis suggested that: body mass index (BMI), sex, age, proportion of blood type A, history of large intestine polyps, history of Helicobacter pylori (Hp) infection, history of alcohol consumption, history of smoking, proportion of heavy oil diet, history of oral calcium, history of oral statins, history of oral non-steroidal anti-inflammatory drugs, history of oral antibiotics, and high fat diet (pork, beef, and animal organs), high salt diet, love of pickled food, love of sweet food, love of greasy, good mood, anxiety, depression, impatience and irritability, history of hypertension, diabetes and hyperlipidemia were statistically significant in the adenomatous polyp group and the non-polyp group (all P<0.05). Factors with P<0.05 in the above single factor analysis were taken as independent variables, and the incidence of disease was taken as dependent variable for multi-factor logistic regression analysis. The results showed that BMI, age, blood type A, Hp infection history, drinking history, smoking history, oral non-steroidal anti-inflammatory drugs history, oral antibiotics history, high salt diet, good mood, hypertension were the influencing factors for the incidence of adenomatous polyps (all P<0.05). Conclusions:High BMI, old age, blood type A, history of Hp infection, smoking history, oral non-steroidal anti-inflammatory drug history, oral antibiotics history, high salt diet and hypertension are risk factors for the development of adenomatous polyps. Drinking alcohol and good mood can reduce the risk of colorectal adenomatous polyps. Therefore, targeted intervention measures can be formulated for high-risk patients to reduce the risk of colorectal adenomatous polyps.

Objective:To investigate the risk factors of colorectal adenomatous polyps.Methods:The clinical data of 395 patients who underwent colonoscopy in the Tongzhou branch, Tongzhou District, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine from August 2017 to August 2021 were analyzed. According to the examination results, adenomatous polyps were divided into adenomatous polyps group (193 cases) and non-polyp group (202 cases). The risk factors of colorectal adenomatous polyps were screened by univariate analysis and multivariate logistic regression analysis.Results:The results of single factor analysis suggested that: body mass index (BMI), sex, age, proportion of blood type A, history of large intestine polyps, history of Helicobacter pylori (Hp) infection, history of alcohol consumption, history of smoking, proportion of heavy oil diet, history of oral calcium, history of oral statins, history of oral non-steroidal anti-inflammatory drugs, history of oral antibiotics, and high fat diet (pork, beef, and animal organs), high salt diet, love of pickled food, love of sweet food, love of greasy, good mood, anxiety, depression, impatience and irritability, history of hypertension, diabetes and hyperlipidemia were statistically significant in the adenomatous polyp group and the non-polyp group (all P<0.05). Factors with P<0.05 in the above single factor analysis were taken as independent variables, and the incidence of disease was taken as dependent variable for multi-factor logistic regression analysis. The results showed that BMI, age, blood type A, Hp infection history, drinking history, smoking history, oral non-steroidal anti-inflammatory drugs history, oral antibiotics history, high salt diet, good mood, hypertension were the influencing factors for the incidence of adenomatous polyps (all P<0.05). Conclusions:High BMI, old age, blood type A, history of Hp infection, smoking history, oral non-steroidal anti-inflammatory drug history, oral antibiotics history, high salt diet and hypertension are risk factors for the development of adenomatous polyps. Drinking alcohol and good mood can reduce the risk of colorectal adenomatous polyps. Therefore, targeted intervention measures can be formulated for high-risk patients to reduce the risk of colorectal adenomatous polyps.