Objective:The association between air pollutants and the risk of sudden cardiac death (SCD) remains controversial. This study aimed to investigate the relationship between five air pollutants—PM 2.5, PM 2.5–10, PM 10, NO 2, and NO?—and the risk of SCD. Methods:We analyzed data from 460 862 participants in the UK Biobank cohort, all enrolled between 2006 and 2010, with no baseline SCD. Follow-up continued until the study endpoint. Annual average concentrations of the five pollutants were assessed. Associations between pollutants and SCD were evaluated using Cox proportional hazards models, followed by Mendelian randomization (MR) to assess causality.Results:Over a mean follow-up of 12.4 years, 2 662 SCD cases were recorded. After adjusting for confounders, no significant associations were found between air pollutants and SCD risk: PM 2.5 ( HR 1.03, 95% CI 0.99–1.07, P = 0.14), PM 2.5–10 ( HR 1.04, 95% CI 1.00–1.08, P = 0.08), PM 10 ( HR 1.01, 95% CI 0.99–1.03, P = 0.26), NO? ( HR 1.00, 95% CI 0.99–1.00, P = 0.26), and NO x ( HR 1.00, 95% CI 1.00–1.01, P = 0.19). MR analysis further supported the absence of causal relationships: PM 2.5 ( β = -0.149, P = 0.90), PM 2.5–10 ( β = 0.387, P = 0.62), PM 10 ( β = -0.994, P = 0.62), NO? ( β = –0.005, P = 0.99), and NO 2 ( β = –0.827, P = 0.25). Conclusions:This study found no evidence linking PM 2.5, PM 2.5–10, PM 10, NO?, or NO 2 to an increased risk of SCD. Mendelian randomization confirmed the lack of causal associations between these pollutants and SCD.

OBJECTIVE: Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms. METHODS: In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods (GNRs) and tetrahedral framework nucleic acids (tFNA) loaded with the anti-tumor drug doxorubicin (DOX). RESULTS: Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation. CONCLUSION This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
Doxorubicin/chemistry* ; Gold/chemistry* ; Nanotubes/chemistry* ; Humans ; Nanocomposites/chemistry* ; Cell Line, Tumor ; Nucleic Acids/chemistry* ; Antibiotics, Antineoplastic/pharmacology* ; Antineoplastic Agents/administration & dosage*

OBJECTIVES: To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children. METHODS: In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance. RESULTS: Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype. CONCLUSIONS Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.
Humans ; Medulloblastoma/diagnosis* ; Lipidomics ; Child ; Male ; Female ; Child, Preschool ; Cerebellar Neoplasms/blood* ; Biomarkers, Tumor/blood* ; Neoplasm Metastasis ; Prospective Studies ; Adolescent ; Lipids/blood*

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.

BACKGROUND:Remyelination in the central nervous system is a basic repair process triggered by demyelinating events,mainly through the proliferation,migration,and differentiation of oligodendrocyte precursor cells into oligodendrocytes.The process of remyelination is affected by many factors such as astrocytes,myelin debris,microglia,macrophages,endothelial cells,pericytes,T cells,and age.OBJECTIVE:Astrocytes play an important role in regulating synaptic activity,nutritional support,and tissue repair in the central nervous system.This review aims to provide potential therapeutic targets for demyelinating diseases of central nervous system by reviewing the role of astrocytes in remyelination.METHODS:A search was conducted on relevant literature collected from CNKI,PubMed,and Web of Science from 2014 tO 2024.The search terms were"astrocytes,oligodendrocyte precursor cells,remyelination"in both Chinese and English.Finally,66 articles were included after screening and summarized.RESULTS AND CONCLUSION:(1)The treatment of demyelinating diseases,such as multiple sclerosis,is limited to disease-modifying therapies,and there is no available method to overcome the failure of remyelination.Therefore,it is necessary to explore targets related to remyelination to promote myelin repair.(2)Remyelination is a process in which oligodendrocyte precursor cells proliferate,migrate,differentiate,and mature into oligodendrocytes,and the latter produce myelin to wrap axons to form myelin sheath.(3)Astrocytes regulate remyelination by phagocytosis of myelin debris,participating in inflammatory response,transforming into oligodendrocyte lineage cells,providing energy supply for oligodendrocyte lineage cells,releasing neurotrophic factors,and secreting extracellular matrix components.(4)The drugs screened in this paper use astrocytes and their derived factors as intervention targets to regulate the remyelination.Some drugs have satisfactory effects,but their effectiveness and safety still need more basic research and clinical trials to verify.(5)The mechanism of action of astrocytes in remyelination has not been fully elucidated,and the related molecular targets and signaling pathways can be further studied.

Aim To investigate the effect of ACSL4 on the malignant biological behavior of esophageal cancer cells and gefitinib resistance by regulating FASN,and to explore the related mechanism.Methods Thirty-five fresh esophageal cancer tissues and adjacent nor-mal tissues,and 30 esophageal cancer tissues with ge-fitinib resistance were collected.The expressions of ACSL4 and FASN were detected by qRT-PCR and im-munohistochemistry.The expression levels of ACSL4 and FASN in human normal esophageal cells HET-1 A,esophageal cancer cell lines ECA109,EC9706,TE-1 and TE-1/GR were detected by qRT-PCR.Cells in each group were constructed by liposome transfection technique,and the drug resistance and proliferation a-bility of cells were detected by cloning and CCK-8 as-say,cell apoptosis was detected by flow cytometry,cell invasion ability was detected by Transwell,and EMT pathway protein expression was detected by Western blot.Results Compared with adjacent normal tis-sues,the expression of ACSL4 and FASN genes in cancer tissues increased,and there was a positive corre-lation.The expression of ACSL4 significantly increased in ECA109,EC9706 and TE-1 cells compared with HET-1 A cells.With the increase of gefitinib concen-tration,the expression of ACSL4 in TE-1 cells gradually increased,and the expression of ACSL4 in TE-1/GR cells was higher than that of TE-1.Compared with the control group and the si-NC group,the cell proliferation and invasion ability of si-ACSL4 group decreased,the number of apoptosis increased,the expression of E-Cadherin increased,and the expression of N-Cadherin,Vimentin and β-catenin decreased.The response ex-periment showed that compared with the si-ACSL4 group and the si-ACSL4+oe-NC group,the cells in the si-ACSL4+oe-FASN group increased drug resistance,increased proliferation and invasion ability,decreased apoptosis number and decreased expression of E-Cad-herin.The expressions of N-Cadherin,Vimentin and β-catenin increased.Conclusions By down-regulating the expression of FASN,ACSL4 reverses the resistance of esophageal cancer TE-1/GR cells to gefitinib and in-hibits the proliferation,invasion and accelerates apopto-sis of TE-1/GR cells,which may be related to the regu-lation of EMT signaling pathway.

BACKGROUND:Remyelination in the central nervous system is a basic repair process triggered by demyelinating events,mainly through the proliferation,migration,and differentiation of oligodendrocyte precursor cells into oligodendrocytes.The process of remyelination is affected by many factors such as astrocytes,myelin debris,microglia,macrophages,endothelial cells,pericytes,T cells,and age.OBJECTIVE:Astrocytes play an important role in regulating synaptic activity,nutritional support,and tissue repair in the central nervous system.This review aims to provide potential therapeutic targets for demyelinating diseases of central nervous system by reviewing the role of astrocytes in remyelination.METHODS:A search was conducted on relevant literature collected from CNKI,PubMed,and Web of Science from 2014 tO 2024.The search terms were"astrocytes,oligodendrocyte precursor cells,remyelination"in both Chinese and English.Finally,66 articles were included after screening and summarized.RESULTS AND CONCLUSION:(1)The treatment of demyelinating diseases,such as multiple sclerosis,is limited to disease-modifying therapies,and there is no available method to overcome the failure of remyelination.Therefore,it is necessary to explore targets related to remyelination to promote myelin repair.(2)Remyelination is a process in which oligodendrocyte precursor cells proliferate,migrate,differentiate,and mature into oligodendrocytes,and the latter produce myelin to wrap axons to form myelin sheath.(3)Astrocytes regulate remyelination by phagocytosis of myelin debris,participating in inflammatory response,transforming into oligodendrocyte lineage cells,providing energy supply for oligodendrocyte lineage cells,releasing neurotrophic factors,and secreting extracellular matrix components.(4)The drugs screened in this paper use astrocytes and their derived factors as intervention targets to regulate the remyelination.Some drugs have satisfactory effects,but their effectiveness and safety still need more basic research and clinical trials to verify.(5)The mechanism of action of astrocytes in remyelination has not been fully elucidated,and the related molecular targets and signaling pathways can be further studied.

Aim To investigate the effect of ACSL4 on the malignant biological behavior of esophageal cancer cells and gefitinib resistance by regulating FASN,and to explore the related mechanism.Methods Thirty-five fresh esophageal cancer tissues and adjacent nor-mal tissues,and 30 esophageal cancer tissues with ge-fitinib resistance were collected.The expressions of ACSL4 and FASN were detected by qRT-PCR and im-munohistochemistry.The expression levels of ACSL4 and FASN in human normal esophageal cells HET-1 A,esophageal cancer cell lines ECA109,EC9706,TE-1 and TE-1/GR were detected by qRT-PCR.Cells in each group were constructed by liposome transfection technique,and the drug resistance and proliferation a-bility of cells were detected by cloning and CCK-8 as-say,cell apoptosis was detected by flow cytometry,cell invasion ability was detected by Transwell,and EMT pathway protein expression was detected by Western blot.Results Compared with adjacent normal tis-sues,the expression of ACSL4 and FASN genes in cancer tissues increased,and there was a positive corre-lation.The expression of ACSL4 significantly increased in ECA109,EC9706 and TE-1 cells compared with HET-1 A cells.With the increase of gefitinib concen-tration,the expression of ACSL4 in TE-1 cells gradually increased,and the expression of ACSL4 in TE-1/GR cells was higher than that of TE-1.Compared with the control group and the si-NC group,the cell proliferation and invasion ability of si-ACSL4 group decreased,the number of apoptosis increased,the expression of E-Cadherin increased,and the expression of N-Cadherin,Vimentin and β-catenin decreased.The response ex-periment showed that compared with the si-ACSL4 group and the si-ACSL4+oe-NC group,the cells in the si-ACSL4+oe-FASN group increased drug resistance,increased proliferation and invasion ability,decreased apoptosis number and decreased expression of E-Cad-herin.The expressions of N-Cadherin,Vimentin and β-catenin increased.Conclusions By down-regulating the expression of FASN,ACSL4 reverses the resistance of esophageal cancer TE-1/GR cells to gefitinib and in-hibits the proliferation,invasion and accelerates apopto-sis of TE-1/GR cells,which may be related to the regu-lation of EMT signaling pathway.

BACKGROUND:Recently,regenerative endodontic therapy is a promising alternative to the maturation of tissue engineering.Inflammatory microenvironment plays a key role in regulating pulp regeneration. OBJECTIVE:To focus on the change in the inflammatory pulp microenvironment,the balance between inflammation and regeneration,and the research advances in tissue-engineered regenerative endodontic therapy within the context of the inflammatory microenvironment to provide a reference for future investigations into regenerative endodontic therapy. METHODS:We conducted a literature search on PubMed and CNKI using search terms"pulp regeneration,inflammation,regenerative endodontic therapy,tissue engineering"in Chinese and English for articles published between 2013 and 2023.The review finally included 61 relevant articles. RESULTS AND CONCLUSION:(1)The changes in the microenvironment of pulpitis involve a complex interplay of cellular and molecular reactions,which,as inflammation progresses,ultimately the microenvironment hinders tissue repair more than facilitates it.(2)Inflammation can promote dental pulp regeneration through stem cell recruitment and activate the complement system,but it can also hinder the regenerative process through immunosuppression and fibrosis.(3)Tissue engineering's three components(stem cells,growth factors,scaffold materials)collaborate to balance inflammation and regeneration,for example,by using interleukin-6 to regulate dental pulp stem cells and foster a regenerative environment.(4)Current research has been largely silent on infection and inflammation issues.The mechanisms underlying changes in the microenvironment of pulpitis are still not fully understood.One promising avenue for improving the clinical applicability of regenerative dental pulp therapy is to achieve precise regulation of the inflammatory-regeneration balance and create a regenerative microenvironment by synergistically leveraging the three elements of tissue engineering.However,this field of investigation still exhibits significant gaps in understanding,necessitating further exploration into innovative strategies for facilitating dental pulp regeneration under inflammation.As such,additional animal experimentation and randomized clinical trials are required to establish a robust foundation for the clinical practice of tissue engineering-based regenerative dental pulp therapy.

Child safety seats have been proven to be one of the most effective tools for protecting child passengers. However, the widespread phenomenon of safety seats being "unavailable," "owned but not used," or "used incorrectly" is prevalent globally. This paper aims to summarize the obstacles to the use of child safety seats from four aspects: Individual, society, environment and policy, in order to provide a basis for follow-up comprehensive intervention to ensure the safety of children.