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.

Objective: To develop and validate a clinically actionable prediction model for postoperative pulmonary complications (PPCs) in cardiac surgery patients, focusing on modifiable preoperative risk factors amenable to targeted optimization. Methods: In this prospective observational cohort study, 492 adults undergoing open-chest cardiac surgery between August 15, 2023 and December 31, 2023 were analyzed. Prespecified predictors included gas exchange variables, pulmonary function, inspiratory muscle strength, and physical performance. Univariable and multivariable logistic regression analyses were used to develop the prediction model. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC). Results: A total of 90 patients (14.1%) developed PPCs after surgery. Five independent predictors were identified: elevated arterial PaCO2 (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.00–1.26), oxygen desaturation (SpO2<93%) (OR 12.47, 95% CI 3.51–48.13), reduced gait speed (OR 0.17, 95% CI 0.04–0.71), lower FEV1/FVC ratio (OR 0.96, 95% CI 0.92–1.00), and diminished inspiratory muscle strength (MIP % predicted) (OR 0.96, 95% CI 0.92–0.99). The model demonstrated good discriminative ability with an AUC of 0.86 (95% CI 0.80–0.93) in the training cohort and 0.87 (95% CI 0.74–0.93) in the validation cohort. Conclusion This parsimonious model achieved high predictive accuracy using five modifiable physiological variables. By targeting abnormalities in gas exchange, pulmonary mechanics, muscle strength, and functional reserve, the model offers a practical tool to guide individualized prehabilitation strategies for reducing PPC risk in cardiac surgery patients.

OBJECTIVE To investigate the distribution and drug resistance of pathogens isolated from the children with bloodstream infection in pediatric intensive care unit(PICU)so as to provide guidance for empirical clinical treatment of infections.METHODS Based on the Pediatric Intensive Care Database(PIC,http://pic.nbscn.org),the etiological data were collected from the PICU children of Children's Hospital,Zhejiang University School of Medicine by R software in 2010-2019 and were retrospectively analyzed.The species,distribution and drug resist-ance of the pathogens isolated from the children were observed.RESULTS Totally 991 strains of pathogens were isolated,727(73.36％)of which were gram-positive bacteria,213(21.49％)were gram-negative bacteria,and 51(5.15％)were fungi.Staphylococcus epidermidis(320 strains,32.29％)was the predominant species of the gram-positive bacteria,followed by Staphylococcus hominis(118 strains,11.91％),Staphylococcus capitis(55 strains,5.55％)and Enterococcus faecium(Group D,33 strains,3.33％);Klebsiella pneumoniae(59 strains,5.95％),Escherichia coli(58 strains,5.85％),Acinetobacter baumannii(25 strains,2.52％)and Pseudo-monas aeruginosa(18 strains,1.82％)were the major species of gram-negative bacteria.The analysis of drug re-sistance showed that the gram-positive bacteria were generally resistant to β lactams and maintained sensitive to vancomycin and linezolid;the gram-negative bacteria showed high drug resistance rates,especially,A.baumannii and P.aeruginosa,showed multi-drug resistance.CONCLUSIONS The gram-positive bacteria are dominant among the pathogens isolated from the PICU children with bloodstream infections.The empirical treatment should be performed based on the distribution and drug resistance data of the pathogens,and sensitive drugs should be cho-sen for optimization of the treatment regimen.

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 review the application scope of risk communication based on eHealth technology in the primary prevention of cardiovascular diseases,so as to provide references for future research and application.Methods A systematic search was conducted in PubMed,Cochrane Library,Embase,Web of Science,CINAHL,PsycINFO,CNKI,Wanfang database,and SinoMed.The search time limit was from the establishment of databases to March 1,2024.The included literature was summarized and analyzed.Results A total of 24 articles were included.The forms of eHealth technology applied in risk communication for primary prevention of cardiovascular include online websites,computerized decision support systems,electronic health records,mobile applications,email,telephone,and text messages.The functions include risk assessment,risk notification,personalized advice,risk tracking and reminders.The outcome indicators include risk perception,physiological indicators,lifestyle and behavior,psychological indicators,feasibility evaluation,decision correlation,doctor-patient communication,intention,risk score,and physician drug prescription.Conclusion The use of eHealth technology in risk communication of cardiovascular diseases has potential value in improving patients'risk perception and promoting healthy behaviors.It is necessary to continuously improve the functions of eHealth technology and enhance its precision and intelligence,so as to better meet the needs of medical staff and patients and promote the efficient implementation of primary prevention of cardiovascular diseases.

OBJECTIVE To investigate the distribution and drug resistance of pathogens isolated from the children with bloodstream infection in pediatric intensive care unit(PICU)so as to provide guidance for empirical clinical treatment of infections.METHODS Based on the Pediatric Intensive Care Database(PIC,http://pic.nbscn.org),the etiological data were collected from the PICU children of Children's Hospital,Zhejiang University School of Medicine by R software in 2010-2019 and were retrospectively analyzed.The species,distribution and drug resist-ance of the pathogens isolated from the children were observed.RESULTS Totally 991 strains of pathogens were isolated,727(73.36％)of which were gram-positive bacteria,213(21.49％)were gram-negative bacteria,and 51(5.15％)were fungi.Staphylococcus epidermidis(320 strains,32.29％)was the predominant species of the gram-positive bacteria,followed by Staphylococcus hominis(118 strains,11.91％),Staphylococcus capitis(55 strains,5.55％)and Enterococcus faecium(Group D,33 strains,3.33％);Klebsiella pneumoniae(59 strains,5.95％),Escherichia coli(58 strains,5.85％),Acinetobacter baumannii(25 strains,2.52％)and Pseudo-monas aeruginosa(18 strains,1.82％)were the major species of gram-negative bacteria.The analysis of drug re-sistance showed that the gram-positive bacteria were generally resistant to β lactams and maintained sensitive to vancomycin and linezolid;the gram-negative bacteria showed high drug resistance rates,especially,A.baumannii and P.aeruginosa,showed multi-drug resistance.CONCLUSIONS The gram-positive bacteria are dominant among the pathogens isolated from the PICU children with bloodstream infections.The empirical treatment should be performed based on the distribution and drug resistance data of the pathogens,and sensitive drugs should be cho-sen for optimization of the treatment regimen.

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 clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

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.