ObjectiveTo characterize the changes of metabolites of Blumea balsamifera in the process of sweating by non-targeted metabolomics， and to investigate the influence of sweating processing on the constituents of B. balsamifera. MethodsUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS） metabolomics was used to identify the metabolites in no sweating group（F1）， sweating 2 d group（F2） and sweating 4 d group（F3）， the differences of metabolites between the groups were compared by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， and differential metabolites were screened according to the variable importance in the projection（VIP） value>1 and P<0.05， and the pathway enrichment of the differential metabolites was analyzed by Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultsThe results of PCA and OPLS-DA showed a clear distinction between the three groups of samples， indicating significant differences in the compositions of the three groups of samples. A total of 433 differential metabolites were screened between the F1 and F2， with 154 up-regulated and 279 down-regulated， the significant up-regulated metabolites were tangeritin， 5-O-demethylnobiletin and so on， while the metabolites with significant down-regulation included alternariol， fortunellin， etc. A total of 379 differential metabolites were screened between the F2 and F3， with 150 up-regulated and 229 down-regulated， the significant up-regulated metabolites were isoimperatorin， helianyl octanoate and so on， and the significant down-regulated metabolites were hovenoside I， goyasaponin Ⅲ， etc. KEGG pathway enrichment analysis showed that tyrosine metabolism， isoquinoline alkaloid biosynthesis， phenylalanine， tyrosine and tryptophan biosynthesis， tryptophan metabolism， valine， leucine and isoleucine biosynthesis， pantothenate and coenzyme A biosynthesis may be the key pathways affecting metabolite differences of B. balsamifera after sweating treatment. ConclusionSweating can reduce the content of endophytic mycotoxins in B. balsamifera and has a great impact on the synthesis and metabolic pathways of total flavonoids and auxin. This study can provide a reference for the process research on the sweating conditions of B. balsamifera.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.

Aim To verify the therapeutic effect of the Qushi Huoxue decoction(QSHXF)on a mouse model of non-alcoholic fatty liver disease(NAFLD)using network pharmacology and experimental approaches,to examine the changes in the PI3K-AKT-lipid metabo-lism signaling pathway,and to elucidate its molecular mechanisms.Methods The potential active ingredi-ents and targets of the QSHXF were identified using the TCMSP platform.NAFLD-related genes were sourced from the GeneCards,PharmGkb,TTD,and OMIM data-bases.The intersection of drug targets and NAFLD treatment targets was analyzed to identify the key tar-gets of the QSHXF in treating NAFLD.The STRING database and Cytoscape 3.9.1 software were utilized to construct networks linking traditional Chinese medicine active ingredients to disease targets and PPI networks,allowing for the screening of key active ingredients and core targets.GO and KEGG enrichment analyses of the intersecting targets were conducted using R version 4.2.2.The NAFLD model was established by feeding mice a methionine-choline deficient diet for a duration of five weeks.Following successful modeling,low,me-dium,and high doses of the QSHXF were administered for intervention over a period of six weeks.The efficacy was verified and the underlying mechanisms were ex-plored using methods such as HE staining,Oil Red O staining,and Western blot analysis.Results The net-work pharmacology prediction indicated that QSHXF might effectively treat NAFLD through key components such as quercetin and kaempferol,as well as core tar-gets including STAT3,AKT1,and HIF1A.KEGG en-richment analysis further suggested that QSHXF might exert its therapeutic effects on NAFLD via signaling pathways such as AGE-RAGE and PI3K-AKT.Verifi-cation through animal experiments demonstrated that QSHXF could significantly reduce hepatic steatosis and lipid droplet accumulation in NAFLD mice.Specifical-ly,it markedly decreased serum levels of TC,TG,ALT,AST,and LDL,while increasing HDL levels.Addition-ally,the treatment significantly reduced the protein ex-pression levels of p-PI3K,p-AKT,SREBP-1c,FASN,and ACC1 in the liver.Conclusions QSHXF can sig-nificantly enhance liver function,improve blood lipid levels,and alleviate hepatic steatosis in NAFLD mice,with its mechanism potentially linked to the inhibition of the PI3K-AKT-lipid metabolism signaling pathway.

Objective To explore the correlation between psoas major index(PMI)in patients with diffuse large B-cell lymphoma(DLBCL)and prognosis after rituximab,cyclophosphamide,doxorubicin,vincristine,prednisone(R-CHOP)chemotherapy.Methods Totally 148 DLBCL patients who received R-CHOP chemotherapy were retrospectively enrolled.Based on axis CT image at L3 vertebral transverse process,bilateral psoas muscles were delineated,and PMI was calculated.Then the patients were divided into muscle reduction group(≤lower quartile,n=37)and control group(＞lower quartile,n=111)according to the lower quartile of PMI.Clinical and imaging data were compared between groups,and the correlations of PMI with the above indexes were analyzed.The impact factors of prognosis of DLBCL were observed.Results Significant differences of body mass index(BMI),Eastern Cooperative Oncology Group(ECOG)score,international prognostic index(IPI),the proportion of B symptoms,mortality rate,3-year survival rate,β2-microglobulin,hemoglobin,albumin and PMI were found between groups(all P＜0.05).PMI of DLBCL patient was negatively correlated with age,ECOG score,IPI,β2-microglobulin and lactate dehydrogenase(LDH)(r=—0.126,-0.225,—0.262,—0.232,—0.229,all P＜0.05),but positively correlated with BMI and hemoglobin(r=0.282,0.376,both P＜0.05).The age,ECOG score,IPI and PMI were all independent impact factors of overall survival in DLBCL patients(all P＜0.05).Conclusion PMI was an independent impact factor of prognosis of DLBCL after R-CHOP chemotherapy.

Objective:To investigate the inpact of thyroid cancer-derived cancer-associated fibroblasts(CAF) autophagy on papillary thyroid cancer(PTC).Methods:CAF and normal fibroblasts were isolated from cancerous and adjacent normal thyroid tissues from four PTC patients. Expressions of fibroblast activation protein(FAP) and α-smooth muscle actin in cells were assessed. Conditioned medium of CAF and normal fibroblasts were prepared and used to culture PTC cells. The effects of CAF and normal fibroblasts on survival, proliferation, migration, invasion and iodine uptake of PTC cells were evaluated through cell proliferation assay, cell scratch assay, cell invasion assay, and cell iodine uptake assay. The autophagy level of CAF was also evaluated. Autophagy inhibition and activation were used to regulate the autophagy of CAF, and then their effects on PTC cell proliferation, migration and invasion were further evaluated. The in vivo effect of CAF autophagy on PTC xenograft tumor growth was evaluated.Results:CAF exhibited higher FAP expression and basal autophagy levels. PTC cells co-cultured with CAF-conditioned media showed enhanced proliferation, migration, invasion, and reduced iodine uptake. Autophagy inhibition reduced these effects, while autophagy activation further promoted them. In vivo, inhibiting CAF autophagy suppressed tumor growth.Conclusions:CAF promotes PTC cell malignancy through autophagy activation, enhancing proliferation, migration, and invasion while reducing iodine uptake.

Objective To investigate the influencing factors associated with early neurological deterioration(END)in patients with minor acute ischemic stroke(mAIS),develop a clinical prediction model for END,and identify independent risk factors for 90-day neurological functional outcomes after stroke.Methods mAIS patients admitted consecutively to the Department of Neurology,Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College),from July 2023 to July 2024 were retrospectively collected.A minor ischemic stroke was defined as acute ischemic stroke with a National Institutes of Health stroke scale(NIHSS)score≤5 on admission.Baseline,clinical,and imaging data of all mAIS patients were collected and recorded,including demographic information(age,sex),past medical history(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,alcohol consumption,baseline blood pressure,pre-onset modified Rankin scale(mRS),NIHSS scores at admission and during hospitalization(24 hours,48 hours,72 hours after admission),motor component subscore of the NIHSS scores,NIHSS scores at discharge,trial of Org 10172 in acute stroke treatment(TOAST)classification,laboratory indicators(fasting blood glucose,hemoglobin A1c[HbA1c],total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein),clinical treatment information(intravenous thrombolysis,mono antiplatelet therapy,dual antiplatelet therapy,anticoagulation therapy)and length of stay.The status of stenosis and occlusion in the culprit vessel were assessed based on imaging results.Mild-to-moderate stenosis was defined as a stenosis rate of 0％to 69％,severe stenosis as a stenosis rate of 70％to 99％,and occlusion as complete interruption of the supplying artery.END was defined as an increase in NIHSS score of ≥2 points from baseline within 72 hours after admission,combined with an increase of at least 1 point in the motor score compared to the score at admission.Prognosis was assessed via telephone follow-ups at 90-day after onset using mRS score,with an mRS score ≤ 2 indicating a favorable outcome and an mRS score＞2 indicating a poor outcome.Variables with P＜0.05 in the univariate analysis were incorporated into multivariate Logistic regression analysis to identify the independent risk factors for END in mAIS patients.A nomogram model was constructed,and calibration curves along with decision curve analysis were plotted to evaluate the model's goodness-of-fit and clinical utility.Univariate and multivariate Logistic regression analyses were performed to identify factors associated with poor 90-day functional outcome after mAIS.Results(1)A total of 826 patients were included,aged 33-94 years,with a median age of 67(57,76)years.There were 571 males and 255 females.The NIHSS score at admission ranged from 0 to 5,with a median NIHSS score at admission of 3(2,4).The NIHSS motor subscore at admission ranged from 0 to 5,with a median baseline NIHSS motor score of 2(0,2).Among them,119 patients(14.4％)were in the END group and 707 patients(85.6％)were included in the non-END group.At 90days after stroke,744 patients(90.1％)had a favorable outcome,while 82 patients(9.9％)had a poor outcome.(2)Univariate analysis showed that there were statistically significant differences between the END group and the non-END group in terms of HbA1c,fasting blood glucose,baseline NIHSS score,baseline NIHSS motor subscore,history of alcohol consumption,diabetes mellitus,culprit vessel stenosis and occlusion,and TOAST classification(all P＜0.05).Statistically significant differences were observed between the favorable outcome group and the poor outcome group in HbA1c,fasting blood glucose,incidence of END,baseline NIHSS score,discharge NIHSS score,culprit vessel stenosis and occlusion,TOAST classification,and history of alcohol consumption(all P＜0.05).(3)Multivariate Logistic regression analysis indicated that mAIS patients with severe stenosis of the culprit vessel(OR,5.88,95％CI2.32-14.91,P＜0.01),occlusion of the culprit vessel(OR,5.74,95％CI 2.25-14.62,P＜0.01),history of alcohol consumption(OR,5.59,95％CI3.41-9.17,P＜0.01),elevated HbA1c(OR,1.67,95％CI 1.35-2.08,P＜0.01),and higher baseline NIHSS motor score(OR,1.43,95％CI 1.08-1.89,P=0.012)had an increased risk of END.A higher discharge NIHSS score(OR,2.59,95％CI 1.89-3.57,P＜0.01)and the occurrence of END(OR,18.42,95％CI 5.13-66.18,P＜0.01)were associated with poor 90-day functional outcome after mAIS.(4)The nomogram model constructed based on independent risk factors of END in mAIS patients demonstrated an AUC of 0.78(95％CI 0.73-0.83)for predicting END,with a sensitivity of 0.8 and a specificity of 0.7.The model showed good calibration,and the Hosmer-Lemeshow test indicated good agreement between predicted and observed values(P=0.333).Decision curve analysis revealed that the model provided a high net benefit across a range of high-risk thresholds(0.1-0.7),suggesting its potential clinical utility.Conclusions Severe stenosis of the culprit vessel,occlusion of the culprit vessel,glycated hemoglobin levels,baseline NIHSS motor subscale scores,and history of alcohol consumption are independent risk factors for END in patients with mAIS.The nomogram model constructed based on these factors demonstrated good predictive performance.END and NIHSS scores at discharge are independent predictors of poor 90-day outcomes in patients with mAIS.

Objective:To explore the current status of perceived vulnerability and its influencing factors among parents of children with type 1 diabetes mellitus (T1DM) .Methods:A convenience sampling method was used to select 220 parents of children with T1DM from the diabetes care and consultation outpatient clinic at Beijing Children's Hospital, Capital Medical University, from June to November 2023. The parents were surveyed using a general information questionnaire, the Parental Perceived Vulnerability Scale, the Family Care Index, and the Parental Illness Uncertainty Scale.Results:A total of 220 questionnaires were distributed, with 192 valid responses. The total score on the Parental Perceived Vulnerability Scale was (13.91±5.39), the total score on the Family Care Index was (5.39±2.73), and the total score on the Parental Illness Uncertainty Scale was (75.36±17.34). Multiple linear regression analysis showed that whether the child was an only child, family monthly income per capita, parents' religious beliefs, family care level, and illness uncertainty were significant influencing factors for perceived vulnerability ( P<0.05), explaining 36.5% of the variance. Conclusions:Healthcare professionals should pay more attention to parents who have only children, have lower family income, and do not have religious beliefs. Interventions aimed at improving family care levels and reducing illness uncertainty may help decrease the perceived vulnerability among parents of children with T1DM.