BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.

Objective To explore the adverse event signals of children using macrolide drugs （azithromycin, clarithromycin, and erythromycin）, and provide reference for rational medicine use in clinical practice. Methods Data from children under 12 years old were extracted from the US FAERS database spanning from the first quarter of 2004 to the second quarter of 2023. The adverse drug reaction （ADR） signal mining for three macrolide antibiotics was conducted using the Reporting Odds Ratio （ROR） and Bayesian Confidence Propagation Neural Network （BCPNN） methods. Special emphasis was placed on analyzing and contrasting the differences in adverse events among the three drugs. Results A total of 1 615 reports for children under 12 years old were retrieved from the FAERS database, including 1 024 reports of azithromycin, 460 reports of clarithromycin, and 131 reports of erythromycin. Among azithromycin and erythromycin, there were more reports from boys than girls, while for clarithromycin, there were more reports from girls than boys. Oral administration was the most common route of administration for all three drugs. Regarding the outcome of adverse events reported, azithromycin and clarithromycin were primarily associated with other serious adverse events, whereas erythromycin was mainly associated with hospitalization and other serious adverse events. The number of adverse events reported decreased with increasing age, with a higher number of reports in the 0-3 age group. Using the ROR and BCPNN methods for signal detection, 86 signals were identified for azithromycin, 91 for clarithromycin, and 34 for erythromycin. These signals involved 22 System Organ Classes （SOCs）, with azithromycin mainly concentrated in skin and subcutaneous tissue disorders （n=21）, clarithromycin in gastrointestinal disorders （n=15）, and erythromycin in gastrointestinal disorders （n=8）. Twenty-four signals of moderate to high risk were detected, with 13 for azithromycin, 9 for clarithromycin, and 2 for erythromycin. Conclusion The adverse events induced by the three drugs with different risks in different systems. When clinically treating Mycoplasma pneumoniae pneumonia in children, the risk profiles of drugs in different systems should be considered, and personalized dosing should be implemented.

BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.

Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease mediated by T lymphocytes， and it can progress to liver cirrhosis or even liver failure without timely intervention. As a natural flavonoid compound， naringenin （NAR） shows a potential value in the prevention and treatment of AIH through multiple mechanisms such as remodeling immune homeostasis， targeted inhibition of inflammatory pathways， antioxidation， regulating hepatocyte metabolism and apoptosis， improving mitochondrial function， and regulating intestinal flora. However， the clinical translation and application of NAR is limited by issues such as low bioavailability and insufficient efficiency of liver-targeted delivery. This article systematically reviews the mechanism of action of NAR in the prevention and treatment of AIH， explores the potential signaling pathways involved in this process， and analyzes existing challenges in its translation and application and future research directions， so as to provide a reference for further research on NAR and its application in the prevention and treatment of AIH.

Obsessive-compulsive disorder （OCD） is a highly disabling mental disorder that impairs patients' social function and quality of life， and impose a substantial economic burden. Intolerance of uncertainty （IU） refers to a cognitive bias in perceiving， interpreting and responding to uncertain situations or events. IU is closely associated with the cognitive patterns of OCD patients. Based on magnetic resonance imaging （MRI）， this paper discusses the research progress of the relationship between IU and psychopathological characteristics of OCD， and put forward the research direction， aims to provide evidence-based references for the development of optimized therapeutic interventions for OCD.

Objective To develop an endothelialized microfluidic chip model that simulates the spatial architecture and bioactivity of retinal vasculature,enabling thrombosis modeling and thrombolytic efficacy validation.Methods A tri-level microvascular network chip(300/200/100 μm diameters)with bifurcated architecture was fabricated using soft lithography.Human retinal microvascular endothelial cells(HRMECs)were perfused into channels,with endothelial coverage monitored via phase-contrast microscopy and F-actin staining.Cellular bioactivity was assessed using mitochondrial membrane potential probes(5,5,6,6-Tetrachloro-1,1,3,3-tetraethylbenzimidazolylcarbocyanine iodide,JC-1)and nitric oxide(NO)quantification.Fresh blood samples from 10 healthy donors(Yongchuan Hospital Affiliated to Chongqing Medical University,March to June 2024)were perfused with digital injection pump to mimic blood flow in human body into 3 experimental groups:normal whole blood,and TNF-α-activated endothelium+normal blood,TNF-α-activated endothelium+TNF-α-treated blood.Three inlet blood flow rates of 37.8、11.1 and 3.5 μL/min were set in each group.Two experimental groups,normal saline and recombinant human tissue-type plasminogen activator(rtPA),were established using the endothelialized microfluidic thrombosis model to validate thrombolytic efficacy.Endothelial functional impacts were assessed through integrated DAPI/NO staining and thrombosis model analysis across 3 intervention phases:pre-thrombosis,post-thrombosis,and post-thrombolysis.Results A tri-level microfluidic vascular model(300/200/100 μm diameters)was successfully constructed.In 72 h after endothelial cell perfusion,complete channel coverage was achieved,with phase-contrast microscopy and F-actin staining confirming confluent cellular alignment.JC-1/NO assays validated preserved endothelial bioactivity.Compared with the whole blood group,both TNF-α-activated endothelium+normal blood and TNF-α-activated endothelium+TNF-α-treated blood groups exhibited significantly increased thrombus occupancy rates at identical flow rates(all P<0.001).Notably,TNF-α-activated endothelium+TNF-α-treated blood group demonstrated the highest thrombus ratio at 3.5 μL/min(P<0.001).The rtPA group showed superior thrombolytic efficacy versus saline(P<0.001).Endothelial monolayer integrity was maintained across intervention phases,with thrombosis triggering significant NO elevation(P<0.001).Conclusion Our retinal vasculature-mimetic microfluidic model enables precise thrombosis modeling and drug evaluation,providing new methodology for studying retinal vascular occlusive diseases.

Pancreatic cancer is a highly malignant tumor of the digestive system,with a significantly lower five-year survival rate than other malignancies.Gemcitabine(GEM)is the primary chemotherapeutic agent for pancreatic cancer,but its efficacy is often limited by chemotherapy resistance of tumor.This article elaborates on the intrinsic cellular mechanism and non-cell-autonomous mechanism of GEM resistance in pancreatic cancer and summarizes how to enhance the sensitivity of pancreatic cancer cells to GEM by inducing ferroptosis through the regulation of polyunsaturated fatty acid peroxidation,iron metabolism control,and antioxidant systems,in order to investigate the association between ferroptosis and GEM resistance mechanisms and provide new directions for the clinical treatment of pancreatic cancer.

Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.

This paper focuses on the application of health big data in cancer screening. Firstly, the sources and characteristics of health big data are introduced, then the commonly used epidemiological designs and analytical techniques in hospital-based cancer screening studies are summarized and the application scenarios of such studies are described. Finally, the challenges and future development in the application of health big data are analyzed to provide reference for the future studies.

Objective To develop a platform for reporting medication near miss events and evaluate its application effectiveness,aiming to enhance medication safety of patients.Methods Based on literature review,qualitative interviews,and expert group meetings,a medication near-miss event reporting platform was constructed,including 4 modules:event content filling,event risk grading,event handling,and statistical analysis.50 nurses were conveniently selected from the pediatric ward of a tertiary grade A hospital in Henan Province as the application subjects.The reporting situation and filling duration of medication near miss events,the score of the Medication Near Miss Reporting Disorder Scale,and the incidence of medication near miss events were compared after the application of the platform(from March to August 2023)and before the application(from September 2022 to February 2023).Results The reporting rate of medication near miss events after the application of the platform was higher than that before the application of the platform,and the comparison of the distribution of event nature and occurrence links showed statistically significant differences(P＜0.05).After the application of the platform,the reporting duration of medication near miss events was shorter than that before the application of the platform,and the score of the Medication Near Miss Reporting Disorder Scale was lower than that before the application of the platform.The differences were statistically significant(P＜0.001).There was no statistically significant difference in the incidence of medication near miss events before and after the application of the platform(P=0.241).Conclusion Using this platform can help improve the reporting rate of medication near miss events,reduce the time taken to fill out reports,and minimize reporting barriers for nurses.