[摘 要] 目的：探讨间充质基质细胞来源细胞外囊泡（MSC-EV）对小鼠免疫检查点抑制剂相关肺炎（CIP）模型的改善作用及分子机制。方法：选取Foxp3DTR小鼠，皮下接种MC38小鼠结肠癌细胞，待肿瘤生长至可触及后，随机分为3组（每组n = 6）：①对照组；②CIP模型组[接种MC38细胞后腹腔注射白喉毒素（DT）及anti-PD-1抗体，构建Treg细胞耗竭联合anti-PD-1抗体诱导的小鼠CIP模型]；③MSC-EV干预组（CIP模型基础上，经鼻滴注MSC-EV干预，剂量109个/只，每3天1次，共2次）。体内实验采用H-E染色观察肺组织病理损伤，测定肺干湿比评估肺水肿程度，ELISA检测支气管肺泡灌洗液（BALF）中IL-1β、IL-6及TNF-α水平，流式细胞术检测BALF中Ly6G⁺粒细胞浸润比例，监测肿瘤体积评价抗肿瘤疗效。体外实验采用DiO荧光标记观察细胞外囊泡（EV）被骨髓来源巨噬细胞摄取的情况，WB法检测NOD样受体家族含Pyrin域蛋白3（NLRP3）炎症小体关键蛋白（剪切型GSDMD、成熟型IL-1β）的表达水平。结合GEO数据库miRNA测序数据（GSE69909）、Dicer敲低及miR-21/miR-125抑制剂干预揭示潜在机制。结果：MSC-EV经鼻滴注可减轻CIP模型小鼠肺部炎症损伤，降低BALF中IL-1β、IL-6、TNF-α水平及Ly6G⁺粒细胞浸润比例（P < 0.05），且不削弱anti-PD-1抗体的抗肿瘤疗效。体外DiO标记示踪显示MSC-EV可被巨噬细胞摄取，WB法检测结果显示，MSC-EV可降低NLRP3炎症小体关键活化蛋白（剪切型GSDMD、成熟型IL-1β）水平（P < 0.05）。体外实验中，Dicer敲低后制备的MSC-EV 对巨噬细胞IL-1β的下调作用减弱（P < 0.05）。miRNA测序显示miR-21、miR-125在MSC-EV中高表达，抑制miR-21或miR-125后，相应MSC-EV对巨噬细胞IL-1β剪切的抑制作用降低（P < 0.05）。结论：MSC-EV通过其携带的miR-21和miR-125等miRNA发挥抗炎效应，其机制可能与抑制巨噬细胞NLRP3炎症小体活化有关，可有效改善CIP且不影响免疫检查点抑制剂的抗肿瘤疗效。

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To evaluate the ability of longitudinal changes in urinary extracellular domain of neurotrophin receptor p75(p75ECD)to serve as a prognostic biomarker of severity,progression and survival time in patients with amyotrophic lateral sclerosis(ALS).Methods Forty patients with ALS attended follow-up appointments at 3-to 6-month interval,and 51 healthy control(HC)volunteers were recruited.The concentrations of urinary p75ECD were tested by a sandwich ELISA.The ALSFRS-r was used to quantify the severity of ALS.The change rate of urinary p75ECD(Δp75ECD)was calculated as the average monthly change during the period between the first and the last sampling.Results The concentration of urinary p75ECD was higher at the last follow-up than at baseline(P=0.002 3).Spearman analysis showed that there was a negative correlation between urinary p75ECD and ALSFRS-r score(r=-0.35,P=0.001 3);the course of ALS in the fast-changing Δp75ECD group was shorter than that in the slow-changing group(P=0.015 8);the Δp75ECD and course of ALS showed a negative correlation(r=-0.39,P=0.014),and the Δp75ECD in the fast-progression ALS group was significantly higher than in the slow-progression group(P=0.001 6).There was a positive correlation between Δp75ECD and progression in ALS patients(r=0.34,P=0.005).Kaplan-Meier survival analysis showed a longer median survival time in those with slow-changing Δp75ECD(P=0.03).Conclusion The change rate of urinary p75ECD has shown great potential as a biomarker for the prognosis of the severity,progression and survival time of ALS.

Objective To develop dynamic prediction models based on multiple postnatal time points to support early diagnosis and individualized intervention for bronchopulmonary dysplasia(BPD)in preterm infants with gestational age<32 weeks.Methods Clinical data of 472 preterm infants with gestational age<32 weeks admitted to the Second Xiangya Hospital of Central South University between January 2016 and November 2020 were retrospectively analyzed.Multivariable logistic regression was applied to develop five independent prediction models at postnatal days 1,7,14,21,and 28.The performance of the models was assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Results Baseline characteristics such as gestational age and birth weight differed significantly between the BPD group(n=147)and the non-BPD group(n=325)(P<0.05).Predictors of BPD evolved across time points:on day 1,key predictors included gestational age,birth weight,Score for Neonatal Acute Physiology II(SNAP-II),invasive mechanical ventilation,and fraction of inspired oxygen>30%;by day 7,additional variables emerged,including fasting duration>2 days,mean feeding advancement rate<8.5 mL/(kg·d),neonatal respiratory distress syndrome,apnea of prematurity,and positive sputum culture;from day 14 onward,nutrition-and treatment-related indicators were incorporated additionally.The models demonstrated good discrimination at postnatal days 1,7,14,21,and 28,with AUCs of 0.917,0.927,0.939,0.944,and 0.968,respectively,and good calibration(Hosmer-Lemeshow P>0.05).Internal validation showed AUCs ranging from 0.899 to 0.958,indicating robust performance.Conclusions Dynamic postnatal prediction models incorporating indicators spanning perinatal factors,respiratory support,nutritional management,and therapeutic interventions demonstrate high predictive performance and facilitate dynamic risk assessment for BPD in preterm infants with gestational age<32 weeks.

Mesenchymal stem cells(MSCs)play a crucial role in tissue repair and regeneration,and the extracellular vesicle(EV)released by them holds great promise for applications in clinical biomarkers,vaccines,and drug delivery.However,MSCs-derived EV(MSCs-EV)face challenges such as low pro-duction yield,poor retention,and targeted delivery issues.There-fore,engineering MSCs-EV to enhance their performance and en-able visual research has become a hot topic.Curcumin(CUR),an active component in traditional chinese medicine,exhibits pharmacological effects but has limited bioavailability.Using MSCs-EV as a carrier for CUR delivery can address its solubility and bioavailability challenges.This article reviews the drug loading methods,engineering strategies of MSCs-EV,and their important applications in the delivery and treatment of CUR for cartilage injury diseases.It provides a basis for the clinical ap-plication of engineered MSCs-EV in CUR delivery for cartilage repair,offering potential solutions to the challenges in cartilage tissue repair.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

Objective To explore the protective effect of resveratrol on myocardial damage caused by sepsis in rats.Methods Forty SD rats were randomly divided into control group,model group,experimental group and combined group,with 10 rats in each group.Except the control group,the other rats were intraperitoneally injected with 20 mg·kg-1 lipopolysaccharide,while the control group was injected with the same amount of normal saline.Two hours before modeling,the experimental group and combinated group were given 50 mg·kg-1 resveratrol by gavage,and the control group and model group were given the same amount of normal saline by gavage.The combined group was injected with 10 nmol of micro RNA-155(miR-155)agomir through the tail vein,and the other group was injected with equal volume of normal saline through the tail vein.Left ventricular function parameters of rats were measured by echocardiography.The level of myocardial injury markers was detected by colorimetry.Quantitative reverse transcription polymerase chain reaction was used to detect the expression of miR-155.The expression of sirtuin 1(SIRT1)and related proteins of nuclear factor κB signaling pathway were detected by Western blot.Results The left ventricular ejection fraction of control group,model group and experimental group were(80.78±12.85)％,(55.92±7.86)％and(71.55±10.71)％,respectively;left ventricular fractional shortening were(34.08±5.75)％,(22.92±2.96)％,(28.72±4.25)％,respectively;left ventricular end disatolic diameter were(3.12±0.46),(6.34±0.69),(4.95±0.57)mm,respectively;the left ventricular end systolic diameter were(5.98±0.65),(7.24±0.80),(6.16±0.78)mm,respectively;the fractional shortening were(38.91±5.38)％,(22.67±3.53)％,(30.74±3.97)％,and the expression levels of creatine kinase-MB were(661.56±85.44),(1181.41±142.14),(915.02±105.19)U·L-1,respectively;the expressions levels of cardiac troponin Ⅰ were(148.17±28.48),(448.17±60.34)and(375.44±49.01)ng·mL-1,respectively.The expression of miR-155 in control group,model group,experimental group and combined group were 1.00±0.12,3.79±0.45,1.87±0.23 and 4.03±0.49,respectively;the protein relative expression levels of nuclear factor κB(NF-κB)were 1.00±0.08,5.04±0.59,2.73±0.35,5.58±0.63,respectively;the protein relative expression levels of inhibitor of NF-κB-β were 1.00±0.11,3.03±0.37,1.35±0.15 and 2.89±0.34,respectively;the protein relative expressions of inhibitor of NF-κB-α were 1.00±0.13,0.86±0.08,1.21±0.18,0.77±0.09,respectively;the protein relative expression levels of SIRT1 were 1.00±0.16,0.66±0.07,0.93±0.14,0.54±0.06,respectively.The above indicators of the model group were compared with the control group,the experimental group were compared with the model group,and the above indicators of the combined group were compared with the experimental group,and the differences were statistically significant(all P＜0.05).Conclusion Resveratrol can alleviate myocardial injury and improve cardiac function in sepsis rats,which may be achieved by down-regulating the expression of miR-155,up-regulating the level of SIRT1,and inhibiting the nuclear factor κB signaling pathway.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To observe the association between afterschool physical exercise and sleep quality among preschool children,and to explore the proper afterschool physical exercise model for better sleep quality.Methods A cross-sectional study was conducted.From Apr to Jun 2024,a total of 1 430 children from three public kindergartens in Minhang district were enrolled to participate in the survey.Parents were invited to complete the basic sociodemographic information,afterschool physical exercise information and the Children's Sleep Habits Questionnaire.One-way ANOVA and linear mixed effects models were used to explore the relationship between afterschool exercise and sleep quality.Results A total of 1 430 questionnaires were sent out and 1 384 were recovered with a recovery rate of 96.78%.Among them 1 366 were valid,with an effective rate of 95.52%.The average age of the children was(5.19±0.87)years old with gender ration of 1.07∶1(male:female).The prevalence of poor sleep quality was 80.60%(regarding a CSHQ total score>41 as cutoff).A one-way ANOVA indicated that time on afterschool physical exercise was significantly associated with sleep duration,Night waking,and sleep onset delay(P<0.05).After adjusting for age,gender,the only child or not,main caregiver,and parental education and occupation,linear mixed effects models showed that engaging in afterschool physical activity for at least 180 mins per week has a statistically significant predictive effect on sleep duration scores(β=-0.50,z=-4.52,95%CI:-0.72,-0.28,P<0.001),night waking scores(β=-0.16,z=-2.34,95%CI:-0.29,-0.02,P=0.020),and sleep onset delay scores(β=-0.14,z=-2.35,95%CI:-0.26,-0.02,P=0.019).Conclusion Afterschool exercise was significantly associated with sleep quality among preschool children in Minhang district of Shanghai.The time≥180 min on afterschool exercise per week in preschool children was significantly positively associated with maintaining sleep duration,reducing night wakings and shortening the latency to fall asleep.The habit of afterschool exercise and the time on afterschool exercise should be emphasized by parents and the society to improve sleep quality among preschool children.