Objective To explore the pro-inflammation resolution and protective effects of reactive oxygen species (ROS)-responsive liposomes modified with a cardiac-targeted peptide and loaded with resolvin D1 (RvD1, C-LP-RvD1) on myocardial ischemia-reperfusion (MI/R) injury. Methods The C-LP-RvD1 nanoliposomes were constructed, characterized physically and chemically, and evaluated for in vitro release. Non-targeting peptide-modified drug-loaded liposomes (LP-RvD1) were served as controls. Apoptotic adult mouse cardiomyocytes (AMCMs) were used to verify in vitro targeted binding capacity of C-LP-RvD1. In MI/R mice models, the in vivo distribution and cardiac enrichment of C-LP-RvD1 were assessed. Levels of specialized pro-resolving mediator (SPM) and inflammatory factors in cardiac tissue homogenates and cell culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Cardiac function and fibrosis remodeling were evaluated via echocardiography and Masson staining four weeks after treatment. Biosafety was evaluated in healthy mice injected by C-LP-RvD1. Results The C-LP-RvD1 exhibited good nanoscale uniformity and stability, with ROS-triggered accelerated release characteristics. In vitro experiments showed that C-LP-RvD1 had higher binding capacity to apoptotic AMCMs than LP-RvD1, with significantly higher SPM levels (P＜0.01) and lower inflammatory factor levels (P＜0.05). In vivo experiments indicated enhanced cardiac enrichment of C-LP-RvD1 in MI/R injured hearts, with higher local myocardial SPM levels and lower inflammatory factor levels compared to LP-RvD1 (P＜0.05). Four weeks after treatment, compared with LP-RvD1, the C-LP-RvD1 mice group showed improved cardiac function indicators and reduced ventricular fibrosis remodeling ratio (P＜0.05). Safety evaluation revealed no significant systemic inflammation, immunogenicity, or coagulation abnormalities in healthy mice, with liver and kidney function and major organ histology showing no notable damage. Conclusions C-LP-RvD1 improves effective delivery of RvD1 to MI/R injured hearts through injury-targeted enrichment and ROS-responsive release, promoting inflammation resolution and suppressing excessive inflammation, thereby improving cardiac function and reducing adverse remodeling, with favorable biosafety.

Objective To summarize the clinical efficacy of modified Morrow surgery in the treatment of hypertrophic obstructive cardiomyopathy. Methods A retrospective analysis was conducted on the clinical data of patients with hypertrophic obstructive cardiomyopathy treated with modified Morrow surgery at Zhongshan Hospital Affiliated to Fudan University from 2020 to 2023. Results A total of 318 patients were enrolled, including 156 males and 162 females, with an average age of (55.6±13.1) years. Preoperative echocardiography showed a mean interventricular septal thickness of (18.1±3.8) mm, peak left ventricular outflow tract pressure difference of (86.4±24.9) mm Hg. The surgery time was (162.3±51.0) min, extracorporeal circulation time was (80.9±31.0) min, and aortic occlusion time was (44.8±20.8) min. After the surgery, transesophageal echocardiography showed that the interventricular septal thickness was (11.0±1.8) mm and left ventricular outflow tract peak pressure difference was (9.4±5.1) mm Hg. The incidence rate of postoperative complete left bundle branch block was 45.3%, Ⅲ° atrioventricular block was 3.8%, and postoperative newly developed atrial fibrillation was 3.1%. The postoperative hospital stay was (6.6±4.9) days, and one perioperative death occurred, with a mortality rate of 0.3%. The follow-up time was (10.3±9.4) months, during which the transthoracic echocardiography revealed a ventricular septal thickness of (12.9±2.9) mm and a peak left ventricular outflow tract pressure difference of (13.9±10.0) mm Hg. Conclusion The modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy is safe and effective, with good results in the short and medium term.

Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Objective:To explore the impact of adolescent mental health status on smartphone addiction, and construct a predictive model for smartphone addiction based on the eXtreme Gradient Boosting(XGBoost) algorithm and multivariate Logistic regression.Methods:In April 2023, a cross-sectional survey was conducted among 14 666 adolescents.All participants were systematically evaluated using a self-developed general information questionnaire, the middle school student mental health scale(MSSMHS), the adolescents self-harm scale(ASHS), the interaction anxiousness scale(IAS), the mobile phone addiction index(MPAI), the middle school students shame scale(MSSS), the UCLA loneliness scale(UCLA-LS), the multidimensional peer victimization scale(MPVS), and the basic psychological needs scale(BPNS).R software version 4.3.2 was used for data analysis. Participants were randomly divided into training set and validation set at the ratio of 7∶3.The XGBoost model and multivariate logistic regression model were constructed to predict the risk of smartphone addiction, and a nomogram was plotted.Model performance was evaluated using the Hosmer-Lemeshow test, area under the curve(AUC), and accuracy(ACC).Results:(1) A total of 14 036 high school students were included in the study, with 5 069(36.1%) exhibited smartphone addiction.The training set comprised 9 826 students, with 3 549(36.1%) being smartphone addicts.The validation set included 4 210 students, with 1 520(36.1%) being smartphone addicts.(2) The XGBoost model identified shame-proneness and social anxiety as the two main predictors of smartphone addiction.(3) Multivariate Logistic regression analysis revealed that anxiety( B=0.328, OR(95% CI)=1.39(1.07-1.81), P=0.015), interpersonal sensitivity( B=0.311, OR(95% CI)=1.36(1.05-1.77), P=0.018), learning pressure( B=0.606, OR(95% CI)=1.83(1.46-2.31), P<0.001), mood swings( B=0.775, OR(95% CI)=2.17(1.70-2.78), P<0.001), social anxiety( B=0.024, OR(95% CI)=1.02(1.01-1.04), P<0.001), shame-proneness( B=0.049, OR(95% CI)=1.05(1.04-1.06), P<0.001), and peer victimization( B=0.037, OR(95% CI)=1.04(1.02-1.06), P<0.001) were significant predictors of smartphone addiction.(4) The ACC and AUC values of the XGBoost model were 0.890 and 0.929 in the training set, and 0.865 and 0.864 in the validation set, respectively.The multivariate Logistic regression model achieved ACC and AUC values of 0.870 and 0.854 in the training set, and 0.867 and 0.859 in the validation set, respectively. Conclusion:Anxiety, interpersonal sensitivity, learning pressure, mood swings, social anxiety, shame-proneness, and peer victimization are identified risk predictors of smartphone addiction in high school adolescents.

Lupus nephritis(LN)is a common and serious complication of systemic lupus erythematosus(SLE).The clinical course of LN is usually characterized by alternating phases of remission and exacerbation.The onset of LN can lead to deterioration of renal function and requires prompt diagnosis and treatment.Some studies have suggested that the presence and changes of activated leukocyte cell adhesion molecule(ALCAM)may be related to the development of LN as well as LN activity.Urinary activated leukocyte cell adhesion molecule(uALCAM)is promising as a non-invasive marker for evaluating LN activity in SLE patients.Determination of uALCAM levels is helpful in early diagnosis,indication of disease activity and prediction of disease recurrence.ALCAM is expressed in a variety of cells and exerts different biological effects,including regulating cell differentiation,proliferation and migration.It is also pathologically expressed in various malignant tumors and has carcinogenic properties.This review will review the existing research on the role of ALCAM in the genesis and progression of LN,and the potential role of ALCAM as a new diagnostic marker and therapeutic target.

Objective:To clarify the current situation, needs, and effectiveness of public health emergency response training for resident physicians, further improve the training content, and enhance their ability to respond to public health emergencies.Methods:A questionnaire survey was conducted among 794 resident physicians who were undergoing standardized residency training at 5 affiliated hospitals of Shanghai Jiao Tong University School of Medicine. The questionnaire included general information, emergency training status, training needs, and emergency training effectiveness. Chi-square test, analysis of variance, and least significant difference post hoc multiple comparisons were used to analyze the awareness, training needs, and training effectiveness of residents of different training years and specialties.Results:Overall, resident physicians showed high levels of awareness about public health emergencies, but there were differences in the awareness rate among resident physicians of different training years. In terms of "clusters of unexplained diseases" and "adverse reactions to mass immunizations and drug exposures", the awareness rate of senior resident physicians was higher than that of junior resident physicians ( χ2=9.41, P<0.05; χ2=10.90, P<0.05). In terms of training status and needs, resident physicians preferred emergency capability training that combines theory, skills, and simulation exercises. They also suggested to adding training content such as risk communication skills and conflict management skills. In terms of training effectiveness, the highest self-evaluation score for training effectiveness at the behavioral level was (8.32±1.52) points, with an average score of 8 points or above for each level, indicating a "good" level of effectiveness. Moreover, the training effectiveness of emergency response capabilities varied significantly for resident physicians with different specialties ( F=4.44, P<0.001). The training effectiveness of emergency response capabilities was higher for general resident physicians than for residents in pediatrics, obstetrics and gynecology, anesthesia, internal medicine, and surgery; higher for pediatric surgery residents than for residents in pediatrics and obstetrics and gynecology; and higher for emergency medicine residents than for residents in pediatrics and obstetrics and gynecology. Conclusions:The simulation training for public health emergency response should be strengthened. In addition to the improvement of medical abilities, it is necessary to provide training on relevant legal and regulatory knowledge, risk communication skills, and conflict management skills. The effectiveness of emergency response training varies among different clinical specialties, which may be related to the nature of the clinical professional background. In future course design, targeted emergency training courses can be set up based on professional background.

AIM:To investigate the role of NLR family CARD domain containing 3(NLRC3)in endothelial cells and evaluate its diagnostic value in coronary artery disease.METHODS:Twenty male ApoE-/-C57BL/6 mice,aged eight weeks,were randomly assigned into two groups:an experimental group and a control group,with each group com-prising ten mice.The experimental group was subjected to a high-fat diet for 8 weeks to induce atherosclerosis(AS),whereas the control group was maintained on a standard diet.The expression of NLRC3 in the aorta was evaluated using RT-qPCR and immunofluorescence techniques.Additionally,human umbilical vein endothelial cells(HUVECs)were ex-posed to interleukin-1β(IL-1β)to investigate the expression levels of NLRC3.Lentiviral vectors or plasmid vectors were employed to either overexpress or knock down NLRC3 in endothelial cells,and subsequently subjected to inflammation in-duced by IL-1β.The RT-qPCR and ELISA were employed to assess the impact of NLRC3 on inflammation in endothelial cells.Western blot and immunofluorescence techniques were utilized to investigate the modulation of the NF-κB signaling pathway in endothelial cells by NLRC3.Plasma NLRC3 levels in coronary artery disease patients and healthy controls were measured using ELISA,and its diagnostic potential was assessed through ROC curve analysis.RESULTS:In AS mice,distinct plaque lesions were observed in the aorta,accompanied by a significantly reduced expression of NLRC3 in the aortic arch relative to the control group.Expression of NLRC3 exhibited a significant down-regulation in IL-1β-stimu-lated HUVECs,demonstrating both time-dependent and dose-dependent effects(P<0.01).Overexpression of NLRC3 markedly suppressed the levels of IL-6,IL-8,monocyte chemoatbactant protein-1(MCP-1),p-p65,and p-IκBα in endo-thelial cells stimulated with IL-1β(P<0.01).Conversely,knockdown of NLRC3 resulted in elevated levels of IL-6,IL-8,MCP-1,p-p65 and p-IκBα in endothelial cells(P<0.01).Coronary artery disease patients had significantly lower plasma NLRC3 levels than controls,with an AUC of 0.851(95%CI:0.785～0.918,P<0.01).A diagnostic threshold of 1.605 μg/L yielded a sensitivity of 93.8%and a specificity of 71.3%.CONCLUSION:The NLRC3 may modulate endothelial inflammation and suppress AS progression through inhibition of the NF-κB signaling pathway,and it holds potential as a diagnostic biomarker for coronary artery disease.

Objective:To investigate the expression of erythropoietin-producing hepatocyte kinase receptor A10 (EphA10) in gastric cancer and adjacent tissues, and analyze its correlation with clinical features and prognosis.Methods:The clinical data of 112 patients with gastric cancer from January 2018 to December 2023 in Eastern Theater Command Air Force Hospital were retrospectively analyzed. The expression of EphA10 in gastric cancer and adjacent tissues was detected by EnVision immunohistochemical staining. The relationship between EphA10 expression and clinicopathological features was analyzed. The Kaplan-Meier survival curve was drawn, and the comparison used the log-rank test. Multivariate Cox regression was used to analyze the independent risk factors of the overall survival time in patients with gastric cancer.Results:The positive expression rate of EphA10 in gastric cancer tissues was significantly higher than that in adjacent tissues: 44.6% (50/112) vs. 0, and there was statistical difference ( χ2 = 64.37, P<0.01). In patients with gastric cancer, the positive expression of EphA10 in gastric cancer tissues was correlated with tumor long diameter, differentiation, TNM stage and lymph node metastasis ( P<0.01 or <0.05), but without age, gender and distant metastasis ( P>0.05). Kaplan-Meier survival curve analysis result showed that the median overall survival time in patients with positive EphA10 expression was significantly lower than that in patients with negative EphA10 expression: 18 months vs. 48 months, and there was statistical difference (log-rank χ2 = 53.66, P<0.01). Multivariate Cox regression analysis result showed that tumor long diameter ≥3 cm, TNM stage Ⅲ to Ⅳ, lymph node metastasis and EphA10 positive expression were the independent risk factors of the overall survival time in patients with gastric cancer ( HR = 1.250, 1.515, 1.321 and 0.831; 95% CI 1.143 to 1.368, 1.267 to 1.813, 1.168 to 1.497 and 0.756 to 0.913; P<0.01 or <0.05). Conclusions:The expression level of EphA10 in gastric cancer tissues is up-regulated, and its expression level is correlated with the clinicopathological features. EphA10 can be used as one of the reference indicators for clinical prognosis evaluation in patients with gastric cancer.