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.

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 understand the epidemiological characteristics of a pertussis outbreak in Guangzhou, so as to provide references for outbreak response and prevention strategies. Methods: From April 5 to June 9, 2024, case screening was conducted among 246 preschool children, 35 staff members, and one full time school nurse in a kindergarten in Guangzhou based on case definition. Field epidemiological investigation methods were employed to collect relevant information, and screening samples were collected from individuals involved in the outbreak. The clinical manifestations, epidemiological characteristics, and risk factors for transmission of the outbreak were analyzed, with rate comparisons performed using the χ 2 test. Results: There were a total of 15 confirmed cases of pertussis in the kindergarten. The main clinical manifestations included intermittent cough in 14 cases ( 93.33 %), sputum production in 5 cases (33.33%), fever in 2 cases (13.33%), paroxysmal spasmodic cough in 1 case (6.67%), and vomiting in 1 case (6.67%). There was no statistically significant difference in the reporting rates of interrupted cough symptoms between pertussis cases (93.33%) and non pertussis cases (92.86%)( χ 2=3.74, P >0.05). The cases were aged 4-5 years, including 5 males and 10 females. The interval between symptom onset and diagnosis ranged from 2 to 25 days, with a median of 10 days. The outbreak involved two classes, with attack rates of 48.28% and 3.45%, respectively. Laboratory testing confirmed 14 close contacts positive for Bordetella pertussisnucleic acid. Among close contacts, only one received prophylactic medication as required. Conclusion The outbreak is a pertussis outbreak in a kindergarten caused by Bordetella pertussis infection, demonstrating distinct temporal and spatial clustering characteristics.

ObjectiveThis paper aims to explore the in vitro anti-psoriasis activity and potential mechanism of Kangfuxin liquid （KFX liquid）， providing experimental evidence for the anti-psoriasis effect of KFX liquid. MethodsFirstly， the uninduced human immortalized keratinocyte cells （HaCaT cells） were divided into seven groups， namely the control group and KFX liquid groups with different doses （5， 10， 20， 40， 80， 160 g·L^-1）. After being treated with different concentrations of KFX liquid， the effect of KFX liquid on the normal cell proliferation was detected by using the cell counting kit-8 （CCK-8） method. Secondly， the uninduced HaCaT cells were divided into six groups， namely the control group and recombinant human interleukin-7A （rh-IL-7A） groups with different doses （5， 10， 50， 100， 120 g·L^-1）. After being treated with different concentrations of recombinant human interleukin-17A （rh IL-17A） liquid， the effect of rh IL-17A on cell proliferation was detected. The optimal induction concentration was screened. Then， normal HaCaT cells were divided into a control group and KFX liquid groups with different doses （5， 10， 20， 40， 80， 160 g·L^-1）. Except for the control group， the other groups established psoriasis cell models with the optimal induction concentration of rh IL-17A. After being treated with different concentrations of KFX liquid， the effects of KFX liquid on the psoriasis-like HaCaT cell proliferation were investigated. Finally， the uninduced HaCaT cells were divided into six groups， namely the control group， rh IL-17A group， methotrexate （MTX） group， and KFX liquid groups with different doses （20， 40， 80 g·L^-1）. Except for the control group， the other groups used the optimal induction concentration of rh IL-17A to establish psoriasis cell models. After being treated with different drugs， the cell migration levels were detected through scratch assays， and real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the relative mRNA expression levels of Ki-67 antigen （Ki67）， S100 calcium-binding protein A7 （S100A7）， S100 calcium-binding protein A8 （S100A8）， and S100 calcium-binding protein A9 （S100A9）， thereby comprehensively evaluating the in vitro anti-psoriasis activity of KFX liquid. By detecting the relative mRNA expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and chemokine-20 （CXCL-20） inflammatory-related factors in psoriasis-like HaCaT cells and the protein expression levels of Janus kinase 3 （JAK3）， phosphorylated Janus kinase 3 （p-JAK3）， signal transducer and activator of transcription 3 （STAT3）， and phosphorylated signal transducer and activator of transcription 3 （p-STAT3）， the mechanism was explored. ResultsCompared with that of control group， when treated with 80 g·L^-1 KFX liquid for 72 h （P<0.05） and at different times with 160 g·L^-1 KFX liquid， the HaCaT cell proliferation activity was significantly affected （P<0.01）， while the other concentrations of KFX liquid had no significant differences in cell morphology and cell proliferation activity at different times， indicating that the KFX liquid is relatively safe for HaCaT cells and has no obvious toxic side effects. Compared with that of control group， when treated with different concentrations of rh IL-17A for 24 h， the HaCaT cell proliferation activity was significantly enhanced， and the cell activity was the strongest when the concentration was 100 μg·L^-1 （P<0.05）， with a density close to 100% and intact cell morphology， indicating that 100 μg·L^-1 is the optimal concentration for inducing HaCaT cell proliferation. The results of the KFX liquid treatment on rh IL-17A-induced psoriasis-like cells show that the KFX liquid not only effectively inhibits the rh IL-17A-induced psoriasis-like HaCaT cell proliferation activity （P<0.01）， but also significantly reduces the migration ability of rh IL-17A-induced psoriasis-like HaCaT cells （P<0.01）， and the relative mRNA expression levels of Ki67， S100A7， S100A8， and S100A9 （P<0.01）. Moreover， the KFX liquid can significantly reduce the relative mRNA expression levels of IL-1β， IL-6， and CXCL-20 in rh IL-17A-induced psoriasis-like cells （P<0.01）， and significantly inhibit the phosphorylation levels of JAK3 and STAT3 proteins （P<0.05， P<0.01）. ConclusionThe KFX liquid has no obvious toxicity to uninduced HaCaT cells. It can inhibit rh IL-17A-induced psoriasis-like HaCaT cell proliferation， reduce the cell migration ability， and has good in vitro anti-psoriasis activity. Its action mechanism may be related to downregulating the expression levels of inflammation-related cytokines in the JAK3/STAT3 signaling pathway and inhibiting the phosphorylation levels of JAK3 and STAT3 proteins.

ObjectiveThis paper aims to explore the in vitro anti-psoriasis activity and potential mechanism of Kangfuxin liquid （KFX liquid）， providing experimental evidence for the anti-psoriasis effect of KFX liquid. MethodsFirstly， the uninduced human immortalized keratinocyte cells （HaCaT cells） were divided into seven groups， namely the control group and KFX liquid groups with different doses （5， 10， 20， 40， 80， 160 g·L^-1）. After being treated with different concentrations of KFX liquid， the effect of KFX liquid on the normal cell proliferation was detected by using the cell counting kit-8 （CCK-8） method. Secondly， the uninduced HaCaT cells were divided into six groups， namely the control group and recombinant human interleukin-7A （rh-IL-7A） groups with different doses （5， 10， 50， 100， 120 g·L^-1）. After being treated with different concentrations of recombinant human interleukin-17A （rh IL-17A） liquid， the effect of rh IL-17A on cell proliferation was detected. The optimal induction concentration was screened. Then， normal HaCaT cells were divided into a control group and KFX liquid groups with different doses （5， 10， 20， 40， 80， 160 g·L^-1）. Except for the control group， the other groups established psoriasis cell models with the optimal induction concentration of rh IL-17A. After being treated with different concentrations of KFX liquid， the effects of KFX liquid on the psoriasis-like HaCaT cell proliferation were investigated. Finally， the uninduced HaCaT cells were divided into six groups， namely the control group， rh IL-17A group， methotrexate （MTX） group， and KFX liquid groups with different doses （20， 40， 80 g·L^-1）. Except for the control group， the other groups used the optimal induction concentration of rh IL-17A to establish psoriasis cell models. After being treated with different drugs， the cell migration levels were detected through scratch assays， and real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the relative mRNA expression levels of Ki-67 antigen （Ki67）， S100 calcium-binding protein A7 （S100A7）， S100 calcium-binding protein A8 （S100A8）， and S100 calcium-binding protein A9 （S100A9）， thereby comprehensively evaluating the in vitro anti-psoriasis activity of KFX liquid. By detecting the relative mRNA expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and chemokine-20 （CXCL-20） inflammatory-related factors in psoriasis-like HaCaT cells and the protein expression levels of Janus kinase 3 （JAK3）， phosphorylated Janus kinase 3 （p-JAK3）， signal transducer and activator of transcription 3 （STAT3）， and phosphorylated signal transducer and activator of transcription 3 （p-STAT3）， the mechanism was explored. ResultsCompared with that of control group， when treated with 80 g·L^-1 KFX liquid for 72 h （P<0.05） and at different times with 160 g·L^-1 KFX liquid， the HaCaT cell proliferation activity was significantly affected （P<0.01）， while the other concentrations of KFX liquid had no significant differences in cell morphology and cell proliferation activity at different times， indicating that the KFX liquid is relatively safe for HaCaT cells and has no obvious toxic side effects. Compared with that of control group， when treated with different concentrations of rh IL-17A for 24 h， the HaCaT cell proliferation activity was significantly enhanced， and the cell activity was the strongest when the concentration was 100 μg·L^-1 （P<0.05）， with a density close to 100% and intact cell morphology， indicating that 100 μg·L^-1 is the optimal concentration for inducing HaCaT cell proliferation. The results of the KFX liquid treatment on rh IL-17A-induced psoriasis-like cells show that the KFX liquid not only effectively inhibits the rh IL-17A-induced psoriasis-like HaCaT cell proliferation activity （P<0.01）， but also significantly reduces the migration ability of rh IL-17A-induced psoriasis-like HaCaT cells （P<0.01）， and the relative mRNA expression levels of Ki67， S100A7， S100A8， and S100A9 （P<0.01）. Moreover， the KFX liquid can significantly reduce the relative mRNA expression levels of IL-1β， IL-6， and CXCL-20 in rh IL-17A-induced psoriasis-like cells （P<0.01）， and significantly inhibit the phosphorylation levels of JAK3 and STAT3 proteins （P<0.05， P<0.01）. ConclusionThe KFX liquid has no obvious toxicity to uninduced HaCaT cells. It can inhibit rh IL-17A-induced psoriasis-like HaCaT cell proliferation， reduce the cell migration ability， and has good in vitro anti-psoriasis activity. Its action mechanism may be related to downregulating the expression levels of inflammation-related cytokines in the JAK3/STAT3 signaling pathway and inhibiting the phosphorylation levels of JAK3 and STAT3 proteins.

Background Benign prostatic hyperplasia (BPH) is a common chronic urinary disease in middle-aged and older men, yet the impact of long-term exposure to atmospheric particulate matter (PM) on its pathogenesis remains unclear. Objective To investigate the association between PM exposure and the risk of incident BPH in middle-aged and older men. Methods Based on four waves of follow-up data (2011–2018) from the China Health and Retirement Longitudinal Study (CHARLS), 4766 participants were enrolled. Robust Poisson regression models were employed to assess the association between exposure to PM (PM₁, PM_2.5, and PM₁₀) and the risk of incident BPH. Relative risks (RR) and their corresponding 95% confidence intervals (95%CI) were calculated. Dose-response relationships were fitted using restricted cubic splines (RCS). Subgroup analyses were performed to explore potential effect modifications, and multiple imputation was used to handle missing data. Results Over a mean follow-up of 6 years, 914 incident BPH cases were identified among the4766 participants (cumulative incidence: 19.18%). After adjusting for confounders, each 10 μg·m⁻³ increase in PM₁, PM_2.5, and PM₁₀ concentrations was associated with a 13.1% (RR=1.131, 95%CI: 1.063, 1.203), 8.5% (RR=1.085, 95%CI: 1.050, 1.122), and 5.1% (RR=1.051, 95%CI: 1.034, 1.069) increased risk of BPH, respectively. RCS analysis showed that no nonlinear relationship was found between PM₁ and PM_2.5 and the risk of BPH (P>0.05); however, a nonlinear association was observed for PM₁₀ (P=0.03), with the risk increment slowing beyond 100 μg·m⁻³. Subgroup and sensitivity analyses confirmed the robustness of these findings. Conclusion Long-term exposure to ambient particulate matter may be associated with an increased risk of incident BPH in middle-aged and older men.

Background Benign prostatic hyperplasia (BPH) is a common chronic urinary disease in middle-aged and older men, yet the impact of long-term exposure to atmospheric particulate matter (PM) on its pathogenesis remains unclear. Objective To investigate the association between PM exposure and the risk of incident BPH in middle-aged and older men. Methods Based on four waves of follow-up data (2011–2018) from the China Health and Retirement Longitudinal Study (CHARLS), 4766 participants were enrolled. Robust Poisson regression models were employed to assess the association between exposure to PM (PM₁, PM_2.5, and PM₁₀) and the risk of incident BPH. Relative risks (RR) and their corresponding 95% confidence intervals (95%CI) were calculated. Dose-response relationships were fitted using restricted cubic splines (RCS). Subgroup analyses were performed to explore potential effect modifications, and multiple imputation was used to handle missing data. Results Over a mean follow-up of 6 years, 914 incident BPH cases were identified among the4766 participants (cumulative incidence: 19.18%). After adjusting for confounders, each 10 μg·m⁻³ increase in PM₁, PM_2.5, and PM₁₀ concentrations was associated with a 13.1% (RR=1.131, 95%CI: 1.063, 1.203), 8.5% (RR=1.085, 95%CI: 1.050, 1.122), and 5.1% (RR=1.051, 95%CI: 1.034, 1.069) increased risk of BPH, respectively. RCS analysis showed that no nonlinear relationship was found between PM₁ and PM_2.5 and the risk of BPH (P>0.05); however, a nonlinear association was observed for PM₁₀ (P=0.03), with the risk increment slowing beyond 100 μg·m⁻³. Subgroup and sensitivity analyses confirmed the robustness of these findings. Conclusion Long-term exposure to ambient particulate matter may be associated with an increased risk of incident BPH in middle-aged and older men.

Objective:To develop a scientific and practical questionnaire for general practice residents, and to conduct multidimensional and comprehensive evaluation of the quality of general practice teaching clinics.Methods:A preliminary draft of the questionnaire items was formulated based on a literature review and in-depth interviews. The Delphi method was employed to conduct two rounds of consultation with 14 experts. Following revisions, a convenience sampling method was used to invite general practice residents from three standardized residency training bases to test the reliability and validity of the questionnaire.Results:The questionnaire consisted of 23 items, covering the three dimensions of preparation, implementation process, and comprehensive evaluation of the teaching clinics. The response rates for the two rounds of the expert consultation were both 100.00%, with expert authority coefficients of 0.89 and 0.90, respectively. The overall Cronbach's α coefficient of the questionnaire was 0.93, and the correlation coefficients between each item score and the total score were all >0.30. Structural validity analysis revealed that three common factors were extracted from the questionnaire, with a cumulative variance contribution rate of 77.89%. Conclusions:The General Practice Teaching Clinic Quality Evaluation Questionnaire for Residents developed in this study demonstrates high reliability and validity. The questionnaire provides a scientific basis for the standardized assessment of teaching quality in general practice clinics. By incorporating resident feedback on the teaching process, the questionnaire promotes the development of a teaching clinic quality improvement mechanism focused on residents and plays a significant role in enhancing the teaching capabilities of supervising physicians in clinics.

Objective:To review and analyze obesity-related research projects funded by the National Natural Science Foundation of China(NSFC) to understand the overall landscape and hotspots of approval in this field, and to provide reference for subsequent applicants.Methods:To assess the funding situation of obesity-related projects from 2014 to 2023, we used " obesity" as a search term to extract project information from ZCOOL, LetPub, and MedSci databases. The data were organized, frequency statistics were performed, and results were presented visually using Excel spreadsheets.Results:Over the past 10 years, the NSFC has funded a total of 778 obesity-related research projects with a funding amount of 350 million yuan, showing a constant upward trend. In terms of project types, general projects and youth projects accounted for 87.66%, with other categories, such as key projects, regional projects, major research plans, and international collaboration projects, providing diversified support for obesity research. In terms of disciplinary distribution, obesity-related projects encompass not only medical and life sciences but also fields such as chemistry, information science, earth science, mathematical sciences, management, and others, demonstrating the interdisciplinary integration of research. The primary research directions include obesity prevention and treatment and obesity-related complications. Regional analysis indicates that the issue of uneven development among provinces persists in obesity research.Conclusion:The continuous investment of NSFC in obesity-related research has contributed to the advancement of obesity research in China, enabling the country to play a leading role in the international field.

Diabetic retinopathy(DR)is a common microvascular complication of diabetes and the leading cause of blindness among working-age adults globally,posing a significant public health challenge.The 2024 Diabetic Retinopathy Preferred Practice Pattern(PPP)released by the American Academy of Ophthalmology is the authoritative guideline in this field.Building on previous editions,the latest version provides comprehensive refinements,including optimized screening protocols,strengthened multifactorial risk factor management,revised disease staging criteria,and the integration of preci-sion-based treatment strategies,aiming to enhance the quality of DR management.This article offers a detailed interpreta-tion of the PPP 2024,in an attempt to serve as a key reference for ophthalmologists in diagnostic and therapeutic decision-making.