As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

BACKGROUND:3D-printed bone tissue engineering scaffolds have obvious advantages in the research and clinical treatment of bone defect repair.As one of the important raw materials for 3D printed bone scaffolds,poly-L-lactic acid has a great potential for application in performing bone defect repair,but clinical patients with different bone defect causative factors have different requirements for the comprehensive performance of poly-L-lactic acid bone scaffolds.OBJECTIVE:To summarize and review the development of 3D printing technology and poly-L-lactic acid scaffolds and the design strategies chosen for scaffolds for bone repair in the setting of bone diseases such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis.METHODS:Literature from CNKI,WanFang,PubMed,Science Direct,and Web of Science databases were searched and screened from 1994 to 2024.Search terms were"3D printing,polylactic acid,bone tissue engineering scaffold,osteomyelitis,bone tumor,osteonecrosis,osteoporosis,bone defect"in Chinese and English.The screened 62 articles were systematically summarized and analyzed.RESULTS AND CONCLUSION:(1)Poly-L-lactic acid is considered to be an ideal raw material for artificial bone scaffold design due to its non-toxicity,processability,biocompatibility,and ability to self-degrade in the human environment.The application of 3D printing technology has enabled poly-L-lactic acid bone scaffolds to meet the multilayered and porous structural design requirements of biomimetic artificial bone repair materials,and to optimize the mechanical properties for better bone repair.(2)According to different bone disease microenvironments,timely adjustment of the functional design of poly-L-lactic acid scaffolds is important for the comprehensive osteogenic efficacy of the scaffolds.The article discusses the application of poly-L-lactic acid scaffolds in bone disease environments such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis,and highlights the importance of rationally grasping the timing of bone disease treatment and bone tissue regeneration for bone defects caused by different bone diseases.(3)Although poly-L-lactic acid scaffolds show potential in bone repair,there are still some problems,such as the need to further optimize the structural design of the scaffolds to fit new bone regeneration,enhance the bioactivity of the scaffolds,and take into account other functions(e.g.,antimicrobial,anti-tumor,and anti-osteoporosis)in order to adapt to the needs of bone tissue repair in different pathological environments.

BACKGROUND:3D-printed bone tissue engineering scaffolds have obvious advantages in the research and clinical treatment of bone defect repair.As one of the important raw materials for 3D printed bone scaffolds,poly-L-lactic acid has a great potential for application in performing bone defect repair,but clinical patients with different bone defect causative factors have different requirements for the comprehensive performance of poly-L-lactic acid bone scaffolds.OBJECTIVE:To summarize and review the development of 3D printing technology and poly-L-lactic acid scaffolds and the design strategies chosen for scaffolds for bone repair in the setting of bone diseases such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis.METHODS:Literature from CNKI,WanFang,PubMed,Science Direct,and Web of Science databases were searched and screened from 1994 to 2024.Search terms were"3D printing,polylactic acid,bone tissue engineering scaffold,osteomyelitis,bone tumor,osteonecrosis,osteoporosis,bone defect"in Chinese and English.The screened 62 articles were systematically summarized and analyzed.RESULTS AND CONCLUSION:(1)Poly-L-lactic acid is considered to be an ideal raw material for artificial bone scaffold design due to its non-toxicity,processability,biocompatibility,and ability to self-degrade in the human environment.The application of 3D printing technology has enabled poly-L-lactic acid bone scaffolds to meet the multilayered and porous structural design requirements of biomimetic artificial bone repair materials,and to optimize the mechanical properties for better bone repair.(2)According to different bone disease microenvironments,timely adjustment of the functional design of poly-L-lactic acid scaffolds is important for the comprehensive osteogenic efficacy of the scaffolds.The article discusses the application of poly-L-lactic acid scaffolds in bone disease environments such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis,and highlights the importance of rationally grasping the timing of bone disease treatment and bone tissue regeneration for bone defects caused by different bone diseases.(3)Although poly-L-lactic acid scaffolds show potential in bone repair,there are still some problems,such as the need to further optimize the structural design of the scaffolds to fit new bone regeneration,enhance the bioactivity of the scaffolds,and take into account other functions(e.g.,antimicrobial,anti-tumor,and anti-osteoporosis)in order to adapt to the needs of bone tissue repair in different pathological environments.

BackgroundWith the rapid development of the networking technologies， internet addiction has increasingly become a serious mental health issue. Previous studies have revealed the link between childhood trauma and internet addiction， while the mediating role of perceived stress in this link is not yet clear. ObjectiveTo investigate the role of medical students' perceived stress in the relationship between childhood trauma and internet addiction， so as to provide references for the intervention of internet addiction. MethodsFrom February to March 2023， a random sampling technique was used to select 1 232 undergraduate students from the School of Clinical Medical Sciences of Southwest Medical University as research subjects. The Childhood Trauma Questionnaire-Short Form （CTQ-SF）， Perceived Stress Scale （PSS）， Internet Gaming Disorder Scale （IGDS）， and Bergen Social Media Addiction Scale （BSMAS） were used for assessment. Pearson's correlation coefficients were calculated. The mediation effect of perceived stress in the relationship between childhood trauma and internet addiction was tested using Model 4 in the SPSS Process 4.1， and Bootstrapping procedure involving 5 000 replicates was employed to confirm the statistical significance. ResultsA total of 1 016 （82.47%） valid completed questionnaires were gathered. The CTQ-SF scores of medical students were positively correlated with PSS scores， IGD scores， and BSMAS scores （r=0.583， 0.474， 0.465， P<0.01）. PSS scores were positively correlated with IGD scores and BSMAS scores （r=0.369， 0.479， P<0.01）. Childhood trauma in medical students was found to positively predict perceived stress （β=0.191， P<0.01）， social media addiction （β=0.160， P<0.01）， and internet gaming disorder （β=0.106， P<0.01）. Perceived stress played a significant mediating role in the relationship between childhood trauma and internet gaming disorder， indirect effect value was 0.018 （95% CI： 0.009~0.027）， accounting for 16.98%. Perceived stress also exhibited a significant mediating role in the relationship between childhood trauma and social media addiction， indirect effect value was 0.063 （95% CI： 0.048~0.079）， accounting for 39.38%. ConclusionChildhood trauma in medical students may affect internet gaming disorder and social media addiction through perceived stress. ［Funded by 2022 Annual Research Project of Sichuan Applied Psychology Research Center，（number，CSXL-22102）］

Objective To explore the influencing factors of coronary artery lesion severity in patients with acute coronary syndrome (ACS). Methods Clinical data of ACS patients admitted to Zhongshan Hospital, Fudan University from December 2017 to December 2019 were consecutively collected. The modified Gensini score was used to assess the severity of coronary artery lesions. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with coronary artery lesion severity. Results A total of 1 689 ACS patients were included, with an average age of (64.04±11.45) years; 1 353 (80.11%) were male, and the mean modified Gensini score was (8.12±4.03). Multivariate linear regression analysis revealed that sex (β＝0.97, P＝0.001), age (β＝0.03, P＝0.021), estimated glomerular filtration rate (eGFR; β＝－0.03, P＜0.001), low-density lipoprotein cholesterol (LDL-C; β＝0.58, P＜0.001), apolipoprotein A1 (Apo A1; β＝－1.28, P＝0.012), lipoprotein(a) [Lp(a); β＝0.001, P＝0.033], and glycated hemoglobin A_1C (HbA_1C; β＝0.45, P＜0.001) were independent influencing factors of the modified Gensini score. Conclusions Metabolic indicators, including Apo A1, LDL-C, HbA_1C, and Lp(a), may serve as risk factors for coronary artery lesion severity in ACS patients, with Apo A1 demonstrating the strongest impact.

Organ transplantation faces the challenge of a shortage of donors. Although xenotransplantation holds great potential, it is limited by rejection. Extracellular histones, as key members of damage-associated molecular patterns, have been proven in recent years to play a crucial role in transplant rejection by activating innate immunity, regulating the coagulation-inflammation network, and modulating adaptive immune responses. However, the specific functions and key mechanisms remain to be clarified. Therefore, this article reviews the structural characteristics of histones, their release pathways, the biological functions of extracellular histones, and their potential roles in xenotransplantation. It summarizes the latest research progress of extracellular histones in xenotransplantation, analyzes the shortcomings of existing research and the direction for future research, with the expectation of providing references for the application of extracellular histones in xenogeneic kidney transplantation.

BACKGROUND: Salvianolate is a compound mainly composed of salvia magnesium acetate, which is extracted from the Chinese herb Salvia miltiorrhiza . In recent years, salvianolate injection has been widely used in the treatment of cardiovascular diseases, but the mechanism of how it can alleviate cardiotoxicity remains unclear. METHODS: The cardiac injury model was constructed by treatment with doxorubicin (Dox) or azithromycin (Azi) in zebrafish larvae. Heart phenotype, heart rate, and cardiomyocyte apoptosis were observed in the study. RNA-sequencing (RNA-seq) analysis was used to explore the underlying mechanism of salvianolate treatment. Moreover, cardiomyocyte autophagy was assessed by in situ imaging. In addition, the miR-30a/becn1 axis regulation by salvianolate was further investigated. RESULTS: Salvianolate treatment reduced the proportion of pericardial edema, recovered heart rate, and inhibited cardiomyocyte apoptosis in Dox/Azi-administered zebrafish larvae. Mechanistically, salvianolate regulated the lysosomal pathway and promoted autophagic flux in zebrafish cardiomyocytes. The expression level of becn1 was increased in Dox-induced myocardial tissue injury after salvianolate administration; overexpression of becn1 in cardiomyocytes alleviated the Dox/Azi-induced cardiac injury and promoted autophagic flux in cardiomyocytes, while becn1 knockdown blocked the effects of salvianolate. In addition, miR-30a, negatively regulated by salvianolate, partially inhibited the cardiac amelioration of salvianolate by targeting becn1  directly. CONCLUSION This study has proved that salvianolate reduces cardiomyopathy by regulating autophagic flux through the miR-30a/becn1 axis in zebrafish and is a potential drug for adjunctive Dox/Azi therapy.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Autophagy/drug effects* ; Myocytes, Cardiac/metabolism* ; Cardiomyopathies/metabolism* ; Beclin-1/genetics* ; Apoptosis/drug effects* ; Plant Extracts/therapeutic use* ; Doxorubicin

Objective:To construct a nomogram model for predicting the incidence of hepatocellular carcinoma based on serum abnormal prothrombin and alpha-fetoprotein and evaluate the predictive effect.Methods:Retrospective analysis of data from 351 patients with liver disease who received treatment at the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2023, including 285 males and 66 females, aged (52.9±11.9) years. Among the 351 patients, there were 229 cases (65.2%) of hepatocellular carcinoma, 87 cases (24.8%) of liver cirrhosis, and 35 cases (10.0%) of chronic hepatitis B. All patients were randomly divided into a training set ( n=245) and a testing set ( n=106) in a 7∶3 ratio without replacement sampling. The training set was used to construct the model, and the testing set was used to evaluate the model. At the same time, gender, age, disease type, and other indicators were compared between the two sets. The risk factors of hepatocellular carcinoma were analyzed by univariate and multivariate logistic regression based on the training set, and a nomogram was constructed to predict the incidence of hepatocellular carcinoma based on the multivariate results. Receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the predictive performance of nomogram, and decision curve analysis was used to evaluate the clinical applicability of the model. Results:There was no statistically significant difference in age, gender, disease type, etc. between the training and testing sets of patients (all P>0.05). Univariate logistic regression analysis showed that age, abnormal prothrombin logarithm (LnPIVKA-Ⅱ), alpha-fetoprotein logarithm (LnAFP), and diabetes were associated with hepatocellular carcinoma (all P<0.05). Multivariate logistic regression analysis showed that older age ( OR=1.07, 95% CI: 1.03-1.12), higher LnPIVKA-Ⅱ ( OR=2.97, 95% CI: 1.97-4.46), higher LnAFP ( OR=1.43, 95% CI: 1.11-1.84) and diabetes ( OR=5.17, 95% CI: 1.02-26.17) were risk factors for hepatocellular carcinoma (all P<0.05). Based on the above variables, a nomogram model for predicting the incidence of hepatocellular carcinoma was constructed. The area under the ROC curve analysis of the nomogram for predicting the incidence of hepatocellular carcinoma was 0.920 (95% CI: 0.886-0.953) in the training set and 0.934 (95% CI: 0.891-0.977) in the testing set. The calibration curve fit well with the standard curve, and the prediction was basically consistent with the actual situation. The decision curve analysis showed that the net benefit of the model was greater than 0 under most thresholds (0.1-1.0). Conclusion:The nomogram constructed based on age, LnPIVKA-Ⅱ, LnAFP and diabetes can effectively predict the incidence of hepatocellular carcinoma and has clinical applicability.

Objective To observe the value of nomogram of ultrasound combined with laboratory indexes for predicting axillary lymph node metastasis(ALNM)of stage cT1N0 breast invasive ductal carcinoma(IDC).Methods A total of 77 cases with pathologically diagnosed stage cT1N0 single breast IDC were retrospectively collected,including 23 cases with and 54 cases without ALNM.Univariate and multivariate binary logistic regression analysis were used to analyze clinical data,laboratory indicators and ultrasonic manifestations,then the independent predictors of ALNM of stage cT1N0 breast IDC were screened to establish laboratory indexes model,ultrasound model and combined model,respectively,and nomogram of the combined model was drawn.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive efficacy of each model.The consistency of results of combined model and actual results was analyzed using calibration curve.Decision curve analysis(DCA)was used to explore the clinical value of each model.Results Serum carbohydrate antigen 153(CA153)(OR=1.132),platelet-to-lymphocyte ratio(PLR)(OR=1.020)and echo attenuation behind the lesion on ultrasound(OR=8.789)were all independent predictors of ALNM in stage cT1N0 breast IDC(all P＜0.05),and the area under the curve(AUC)of laboratory indexes model,ultrasound model and combined model for predicting ALNM of stage cT1N0 breast IDC was 0.757,0.616 and 0.836,respectively.The consistency of the predicted results of combined model and actual results was good.When the threshold was higher than 0.15,the net benefit of combined model was higher than that of the other 2 models.Conclusion Nomogram of ultrasound combined with laboratory indexes could effectively predict ALNM of stage cT1N0 breast IDC.

Heat stroke is a life-threatening emergency characterized by a rapid elevation in core body temperature(typically>40℃)and central nervous system dysfunction(e.g.,delirium,seizures or coma),often accompanied by systemic inflammatory response,coagulation disorders,and multiple organ failure,with an extremely high mortality rate.Among the multiple organ injuries caused by heat stroke,the liver,as the core organ for metabolism and detoxification in the body,is one of the targets that are vulnerable to high temperatures.If not intervened promptly and effectively,acute liver injury(ALI)can rapidly evolve into acute liver failure(ALF),significantly increasing the complexity of clinical treatment and the risk of patient death.In recent years,with the frequent occurrence of heat wave events worldwide,the pathological mechanisms and prevention strategies of heat stroke and its related liver injuries have received increasingly widespread attention.Although basic and clinical studies have made certain progress,revealing key pathological changes such as hepatocyte necrosis,excessive inflammatory response and coagulopathy,there is still a lack of unified and standardized consensus guidelines for the clinical evaluation,diagnosis and systematic treatment of heat stroke combined with liver failure.Therefore,this article aims to systematically review and summarize the pathogenesis,clinical presentation,diagnostic approaches,and treatment strategies of current liver failure related to heat stroke,in order to provide clear diagnostic and treatment ideas and practical references for clinical workers,and thereby provide theoretical basis and clinical guidance for improving the prognosis of critically ill patients with heat stroke liver failure.