Paramyxoviruses are important respiratory pathogens with substantial clinical relevance in pediatric infectious diseases. During infection, multiple forms of programmed cell death (PCD) may be induced, and this plays pivotal roles in viral replication, dissemination, and host immune responses, thereby profoundly influencing the viral life cycle and disease progression. On one hand, PCD facilitates the clearance of infected cells, restricts viral spread, and activates host immune defenses, thereby enhancing antiviral immunity. On the other hand, excessive or dysregulated cell death may lead to tissue damage and immune imbalance, creating a microenvironment conducive to viral replication and exacerbating disease severity. For instance, apoptosis-mediated by both extrinsic and intrinsic pathways-contributes to infection control but may also be hijacked by viruses to promote dissemination. Pyroptosis, driven by inflammasome activation, triggers lytic cell death and the release of pro-inflammatory cytokines. Necroptosis, mediated by the RIPK1-RIPK3-MLKL signaling axis, and pyroptosis both amplify innate immune responses but may concurrently induce inflammatory dysregulation. Immunogenic cell death (ICD), characterized by the release of damage-associated molecular patterns and neoantigens, activates antigen-specific immune responses and holds therapeutic potential for antiviral and antitumor interventions. Emerging evidence suggests that ferroptosis, through the modulation of iron metabolism and associated transporters, may also participate in viral replication and infected cell clearance. This review comprehensively summarizes the roles of apoptosis, pyroptosis, necroptosis, ICD, and ferroptosis in paramyxovirus infection, aiming to deepen the understanding of paramyxovirus pathogenesis and to provide insights for developing novel antiviral strategies.
Humans ; Paramyxoviridae Infections/pathology* ; Pyroptosis ; Apoptosis ; Virus Replication ; Necroptosis ; Inflammasomes ; Immunity, Innate ; Immunogenic Cell Death ; Paramyxoviridae/physiology* ; Signal Transduction

BACKGROUND:Mesenchymal stem cell-derived exosomes inherit the advantages of low immunogenicity and strong tumor homing ability,garnering significant attention in targeted drug delivery.However,exosomes are prone to rapid clearance from the circulation before reaching target cells.Additionally,due to the complex surface properties and uptake mechanisms of exosomes,their targeting specificity is not distinctly apparent,necessitating engineered strategies to enhance delivery efficiency.OBJECTIVE:To elucidate mechanisms for enhancing the delivery efficiency of exosomes,preclinical applications,and challenges encountered by reviewing various approaches to engineering modifications of exosomes derived from mesenchymal stem cells so as to provide a theoretical basis for further clinical applications.METHODS:Relevant literature from the establishment of databases to 2024 was retrieved from databases including CNKI,VIP,WanFang,and PubMed.The search terms used were"mesenchymal stem cells,exosomes,engineered exosomes,targeted delivery,antineoplastic agents"in both English and Chinese.Literature focusing on engineered mesenchymal stem cell-derived exosomes for targeted delivery of antitumor drugs was screened,resulting in the inclusion of 85 articles for review and analysis.RESULTS AND CONCLUSION:(1)The engineering modification of mesenchymal stem cell-derived exosomes is complex and diverse.The delivery efficiency of exosomes can be improved by significantly enhancing their targeting ability to organs or tissues,increasing their residence time in the blood circulation,and reducing the expression of tumor-promoting molecules in exosomes.(2)Current examples of mesenchymal stem cell-derived exosome delivery of traditional and novel drugs demonstrate their tremendous potential.(3)There are still some safety issues that preclude their clinical translation.Future research will further improve and delve into the delivery mechanisms,with the hope of developing more efficient and safe therapeutic strategies.

Objective:To investigate the effects of maternal consumption of A1-type β-casein protein free (A1PF) bovine milk during lactation on breast milk composition and gastrointestinal health in term breastfeeding mother-infant dyads.Methods:This two-arm, double-blind, randomized controlled pilot study was conducted at Jinhua Wenrong Hospital and Qiubin community health center (Wucheng district, Jinhua) from June 13 to August 17, 2023. Participants were randomly assigned to the A1PF group (A1PF milk, 25 dyads of term) or control group (regular milk, 25 dyads of term). Mothers consumed 200 ml of assigned milk twice daily for 14 days. Breast milk composition, maternal gastrointestinal health, and their effects on gastrointestinal health and crying-sleep patterns of infants were analyzed at baseline, day 1, and day 14. Statistical analyses included independent t-test, paired t-test, Mann-Whitney U, Wilcoxon signed-rank, and Fisher's exact tests. Results:Calcium [A1PF group: (1.68±0.26), (1.78±0.24), and (2.17±0.21) mmol/L, F=8.62; control: (1.75±0.26), (1.79±0.31), and (2.05±0.31) mmol/L, F=4.69] and iron concentrations [A1PF group: (1.19±0.31), (1.26±0.28), and (1.79±0.27) μg/ml, F=7.85; control: (1.09±0.41), (1.16±0.31), and (1.38±0.31) μg/ml, F=3.87] increased significantly over time in both groups (all P<0.001). At day 14, A1PF group showed higher breast milk iron and zinc levels [(24.72±5.15) vs. (21.56±3.82) μmol/L] versus control ( t=4.23 and 2.31; both P<0.05). Maternal biomarkers in A1PF group exhibited reduced salivary levels of interleukin-4 [480.89 (457.20-509.50) vs. 526.34 (475.03-561.97) ng/L; Z=－2.25], interleukin-6 [19.27 (18.83-21.47) vs. 21.75 (20.15-23.29) ng/L; Z=－3.50], immunoglobulin A [15.18 (14.62-16.59) vs. 16.72 (15.02-17.64) μg/ml; Z=－2.27], immunoglobulin E [3.95 (3.81-4.33) vs. 4.43 (4.16-4.57) μg/ml; Z=－2.91], elevated salivary glutathione [(97.07±5.84) vs. (93.30±6.94) ng/L; t=2.02], and increased fecal short-chain fatty acids [568.50 (452.74-795.26) vs. 371.22 (288.32-556.07) μg/ml; Z=2.18] on day 14 (all P<0.05). Corresponding improvements occurred in breastfed infant salivary/fecal biomarkers. No significant differences in crying or sleep patterns were observed (all P>0.05). Conclusions:Compared to regular milk, A1PF milk consumption reduces maternal gastrointestinal/systemic inflammation and improves gastrointestinal symptoms among term mothers, with benefits extending to breastfed infants. However, a large multi-centered clinical trial is required to confirm this conclusion.

In the tumor microenvironment(TME),the metabolic reprogramming of macrophages and T cells plays a critical role in the formation of an immunosuppressive state and tumor immune escape.Polyamines are key signaling molecules and precursors for biosyn-thesis,and the metabolic state of polyamines profoundly regulate the functions of tumor cells and immune cells.Cytokines and other substances within the TME induce the expression of enzymes related to polyamine metabolism,drive the metabolic reprogramming of polyamines,and thus influence macrophage polarization and T cell differentiation;meanwhile,the metabolic reprogramming of poly-amines leads to the competitive depletion of polyamine resources within the TME,promote tumor cells to optimize their metabolic strat-egies for survival advantages,and inhibit the function of immune cells.Therefore,inhibitors of polyamine metabolism may be used as antitumor drugs by regulating metabolic reprogramming.

Craniofacial fibrous dysplasia (CFD) is a rare skeletal disorder characterized by the abnormal replacement of normal bone tissue with fibrous tissue. This article provides a systematic review of the latest advancements in the genetic basis, molecular mechanisms, clinical manifestations, and diagnostic and therapeutic strategies of CFD. Elucidate, which leads to bone homeostasis imbalance and fibrotic abnormalities. It focuses on the molecular mechanisms underlying multi-pathway network dysregulation induced by GNAS gene mutations and explores the roles of key molecules like cAMP-response element binding protein, interleukin-6 and Fibroblast growth factor 23 in disease progression. Additionally, it evaluates the limitations of traditional treatments and the translational potential of novel strategies, including targeted therapies, offering a theoretical foundation for clinical practice and future research directions.

Objective:To investigate the current status and challenges of pediatric life support training in China and provide references for improving training quality.Methods:A cross-sectional study was conducted to collect data from pediatric life support training centers across the country，covering basic institutional information，training capacity and training faculty，training program funding，as well as existing challenges and issues.The domestic registry of training centers in 2023 was obtained through the American Heart Association's online platform.After contacting and verifying each center，an online questionnaire was distributed，and the aggregated data were statistically analyzed.Results:A total of 42 institutions participated in the survey，including 19 children's hospitals，14 general hospitals，6 maternal and child health hospitals，2 women and children’s hospitals，and 1 training institution.The distribution of training centers showed a concentration in coastal areas，with the top three provinces/municipalities being Guangdong（7/42，16.7%），Zhejiang（6/42，14.3%），and Shanghai（4/42，9.5%）.As of December 31 2023，the 42 institutions had an annual basic life support（BLS）training volume of 8 587 individuals，the median was 120 (100,200)，and an annual pediatric advanced life support（PALS）training volume of 2 448 individuals，the median was 30 (20,50).Among the 42 institutions，there were 598 BLS instructors and 306 PALS instructors.Among the surveyed institutions，24（24/42，57.1%）reported BLS instructor teams comprising fewer than 10 members，and 33（33/42，78.6%）reported PALS instructor teams comprising fewer than 10.Only 7 centers(7/42,16.7%）reported having dedicated funding support.The top three challenges were：training sessions occupying instructors’personal time（27/42，64.3%），low instructor compensation（16/42，38.1%），and issues with the data submission system（16/42，38.1%）.Conclusion:Pediatric life support training centers in China are primarily children’s hospitals，with a geographical concentration in coastal areas，which is also reflected in the distribution of training scale and instructor resources.Most centers have relatively small training scales and limited instructor capacity，with many instructors conducting training during their personal time.These issues may hinder the implementation and effectiveness of training programs.

Craniofacial fibrous dysplasia (CFD) is a rare skeletal disorder characterized by the abnormal replacement of normal bone tissue with fibrous tissue. This article provides a systematic review of the latest advancements in the genetic basis, molecular mechanisms, clinical manifestations, and diagnostic and therapeutic strategies of CFD. Elucidate, which leads to bone homeostasis imbalance and fibrotic abnormalities. It focuses on the molecular mechanisms underlying multi-pathway network dysregulation induced by GNAS gene mutations and explores the roles of key molecules like cAMP-response element binding protein, interleukin-6 and Fibroblast growth factor 23 in disease progression. Additionally, it evaluates the limitations of traditional treatments and the translational potential of novel strategies, including targeted therapies, offering a theoretical foundation for clinical practice and future research directions.

Objective:To investigate the current status and challenges of pediatric life support training in China and provide references for improving training quality.Methods:A cross-sectional study was conducted to collect data from pediatric life support training centers across the country，covering basic institutional information，training capacity and training faculty，training program funding，as well as existing challenges and issues.The domestic registry of training centers in 2023 was obtained through the American Heart Association's online platform.After contacting and verifying each center，an online questionnaire was distributed，and the aggregated data were statistically analyzed.Results:A total of 42 institutions participated in the survey，including 19 children's hospitals，14 general hospitals，6 maternal and child health hospitals，2 women and children’s hospitals，and 1 training institution.The distribution of training centers showed a concentration in coastal areas，with the top three provinces/municipalities being Guangdong（7/42，16.7%），Zhejiang（6/42，14.3%），and Shanghai（4/42，9.5%）.As of December 31 2023，the 42 institutions had an annual basic life support（BLS）training volume of 8 587 individuals，the median was 120 (100,200)，and an annual pediatric advanced life support（PALS）training volume of 2 448 individuals，the median was 30 (20,50).Among the 42 institutions，there were 598 BLS instructors and 306 PALS instructors.Among the surveyed institutions，24（24/42，57.1%）reported BLS instructor teams comprising fewer than 10 members，and 33（33/42，78.6%）reported PALS instructor teams comprising fewer than 10.Only 7 centers(7/42,16.7%）reported having dedicated funding support.The top three challenges were：training sessions occupying instructors’personal time（27/42，64.3%），low instructor compensation（16/42，38.1%），and issues with the data submission system（16/42，38.1%）.Conclusion:Pediatric life support training centers in China are primarily children’s hospitals，with a geographical concentration in coastal areas，which is also reflected in the distribution of training scale and instructor resources.Most centers have relatively small training scales and limited instructor capacity，with many instructors conducting training during their personal time.These issues may hinder the implementation and effectiveness of training programs.

BACKGROUND:Mesenchymal stem cell-derived exosomes inherit the advantages of low immunogenicity and strong tumor homing ability,garnering significant attention in targeted drug delivery.However,exosomes are prone to rapid clearance from the circulation before reaching target cells.Additionally,due to the complex surface properties and uptake mechanisms of exosomes,their targeting specificity is not distinctly apparent,necessitating engineered strategies to enhance delivery efficiency.OBJECTIVE:To elucidate mechanisms for enhancing the delivery efficiency of exosomes,preclinical applications,and challenges encountered by reviewing various approaches to engineering modifications of exosomes derived from mesenchymal stem cells so as to provide a theoretical basis for further clinical applications.METHODS:Relevant literature from the establishment of databases to 2024 was retrieved from databases including CNKI,VIP,WanFang,and PubMed.The search terms used were"mesenchymal stem cells,exosomes,engineered exosomes,targeted delivery,antineoplastic agents"in both English and Chinese.Literature focusing on engineered mesenchymal stem cell-derived exosomes for targeted delivery of antitumor drugs was screened,resulting in the inclusion of 85 articles for review and analysis.RESULTS AND CONCLUSION:(1)The engineering modification of mesenchymal stem cell-derived exosomes is complex and diverse.The delivery efficiency of exosomes can be improved by significantly enhancing their targeting ability to organs or tissues,increasing their residence time in the blood circulation,and reducing the expression of tumor-promoting molecules in exosomes.(2)Current examples of mesenchymal stem cell-derived exosome delivery of traditional and novel drugs demonstrate their tremendous potential.(3)There are still some safety issues that preclude their clinical translation.Future research will further improve and delve into the delivery mechanisms,with the hope of developing more efficient and safe therapeutic strategies.

Objective:To investigate the effects of maternal consumption of A1-type β-casein protein free (A1PF) bovine milk during lactation on breast milk composition and gastrointestinal health in term breastfeeding mother-infant dyads.Methods:This two-arm, double-blind, randomized controlled pilot study was conducted at Jinhua Wenrong Hospital and Qiubin community health center (Wucheng district, Jinhua) from June 13 to August 17, 2023. Participants were randomly assigned to the A1PF group (A1PF milk, 25 dyads of term) or control group (regular milk, 25 dyads of term). Mothers consumed 200 ml of assigned milk twice daily for 14 days. Breast milk composition, maternal gastrointestinal health, and their effects on gastrointestinal health and crying-sleep patterns of infants were analyzed at baseline, day 1, and day 14. Statistical analyses included independent t-test, paired t-test, Mann-Whitney U, Wilcoxon signed-rank, and Fisher's exact tests. Results:Calcium [A1PF group: (1.68±0.26), (1.78±0.24), and (2.17±0.21) mmol/L, F=8.62; control: (1.75±0.26), (1.79±0.31), and (2.05±0.31) mmol/L, F=4.69] and iron concentrations [A1PF group: (1.19±0.31), (1.26±0.28), and (1.79±0.27) μg/ml, F=7.85; control: (1.09±0.41), (1.16±0.31), and (1.38±0.31) μg/ml, F=3.87] increased significantly over time in both groups (all P<0.001). At day 14, A1PF group showed higher breast milk iron and zinc levels [(24.72±5.15) vs. (21.56±3.82) μmol/L] versus control ( t=4.23 and 2.31; both P<0.05). Maternal biomarkers in A1PF group exhibited reduced salivary levels of interleukin-4 [480.89 (457.20-509.50) vs. 526.34 (475.03-561.97) ng/L; Z=－2.25], interleukin-6 [19.27 (18.83-21.47) vs. 21.75 (20.15-23.29) ng/L; Z=－3.50], immunoglobulin A [15.18 (14.62-16.59) vs. 16.72 (15.02-17.64) μg/ml; Z=－2.27], immunoglobulin E [3.95 (3.81-4.33) vs. 4.43 (4.16-4.57) μg/ml; Z=－2.91], elevated salivary glutathione [(97.07±5.84) vs. (93.30±6.94) ng/L; t=2.02], and increased fecal short-chain fatty acids [568.50 (452.74-795.26) vs. 371.22 (288.32-556.07) μg/ml; Z=2.18] on day 14 (all P<0.05). Corresponding improvements occurred in breastfed infant salivary/fecal biomarkers. No significant differences in crying or sleep patterns were observed (all P>0.05). Conclusions:Compared to regular milk, A1PF milk consumption reduces maternal gastrointestinal/systemic inflammation and improves gastrointestinal symptoms among term mothers, with benefits extending to breastfed infants. However, a large multi-centered clinical trial is required to confirm this conclusion.