OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

ObjectiveTo observe the changes in the levels of different subtypes of epidermal growth factor receptor （ErbB）， namely ErbB1， ErbB2， ErbB3， and ErbB4， in the spinal dorsal horn of inflammatory pain model rats， and to explore their mechanism of mediating hyperalgesia as well as the intervention mechanism of electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）". MethodsThe study was divided into five parts. In experiment 1， 14 Sprague Dawley （SD） rats were randomly divided into control and inflammatory pain group （7 rats each group） to observe the pain behavior and the protein expression of different ErbB receptor subtypes in the spinal dorsal horn. In experiment 2， 30 rats were randomly divided into control group 1， inflammatory pain group 1， and low-， medium-， and high-concentration TX1-85-1 groups， with 6 rats in each group， to observe the effect of inhibiting spinal ErbB3 on inflammatory pain. In experiment 3， 12 rats were randomly divided into control virus group and ErbB3 knockdown virus group， with 6 rats in each group， to observe the effect of knocking down ErbB3 in the spinal dorsal horn on inflammatory pain. In experiment 4， 44 rats were randomly divided into control group 2， inflammatory pain group 2， electroacupuncture group， and sham electroacupuncture group， with 11 rats in each group， to observe the effect of electroacupuncture. In experiment 5， 40 rats were randomly divided into control group 3， inflammatory pain group 3， electroacupuncture group 1， and electroacupuncture + NRG1 group， with 10 rats in each group， to observe the effect of activating ErbB3 on electroacupuncture. A rat model of inflammatory pain was established by subcutaneous injection of 100 μl of complete Freund's adjuvant into the sole of the unilateral hind foot of SD rats. Rats in the low-， medium-， and high-concentration TX1-85-1 groups were intrathecally injected with ErbB3 inhibitor TX1-85-1 on day 5 to day 7 after modeling. Rats in the ErbB3 knockdown virus group were injected with ErbB3 knockdown virus packaged with adenovirus vector-based short hairpin RNA （shRNA） into the spinal dorsal horn in situ 3 weeks before modeling. Rats in each electroacupuncture group received electroacupuncture at bilateral "Zusanli （ST 36）" and "Kunlun （BL 60）" from day 1 to day 7 after modeling， with dense-sparse waves at a frequency of 2 Hz/100 Hz and a current of 0.5-1.5 mA for 30 minutes once a day. Rats in the electroacupuncture + NRG1 group were intrathecally injected with ErbB3 ligand recombinant human neuregulin-1 （NRG1） after electroacupuncture intervention from day 5 to day 7 after modeling. The mechanical withdrawal threshold and thermal withdrawal latency of rats were measured on day 1， 3， 5， and 7 after modeling to evaluate behavior， and Western Blot was used to detect the protein and phosphorylation levels of each ErbB subtype in the spinal dorsal horn. ResultsCompared with the control group， rats in the inflammatory pain group showed decreased mechanical withdrawal threshold and thermal withdrawal latency of rats， and increased expression of phosphorylated ErbB3 （p-ErbB3） protein in the spinal dorsal horn on days 1， 3， 5， and 7 after modeling （P＜0.01）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 1， the mecha-nical withdrawal threshold and thermal withdrawal latency of rats in the medium- and high-concentration TX1-85-1 groups increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 1， 3， 5， and 7 after modeling， compared with the control virus group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the ErbB3 knockdown virus group increased （P＜0.05）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 2 and the sham electroacupuncture group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 5 and day 7 after modeling， compared with the electroacupuncture + NRG1 group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group 1 increased （P＜0.05）. ConclusionThe p-ErbB3 in the spinal dorsal horn involved in hyperalgesia in rats with inflammatory pain， and electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）" can alleviate inflammatory pain by inhibiting the expression of p-ErbB3 protein in the spinal dorsal horn of rats.

Objective: This prospective study evaluated the feasibility of chemical exchange saturation transfer (CEST) MRI for assessing disease activity in thyroid-associated ophthalmopathy (TAO). Materials and Methods: A total of 88 patients with active TAO, 76 with inactive TAO, and 30 healthy controls were enrolled. CEST MRI-derived magnetization transfer ratio (MTR) and MTR asymmetry (MTRasym) at 1 ppm, 2 ppm, and 3.5 ppm were calculated. Clinical data, MTR, and MTRasym values for the extraocular muscles (one representative muscle per eye, yielding two measurements per participant) were compared among the groups. Spearman’s correlation was used to examine associations between imaging parameters and the clinical activity score (CAS) in patients with TAO. Logistic regression analysis was used to identify independent associations between imaging parameters and disease activity in patients with TAO (active vs. inactive). Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance for discriminating active from inactive TAO. Results: Patients with active TAO showed lower MTR values (P < 0.001) and higher MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) (all P < 0.001) compared with those with inactive TAO. MTR was negatively correlated with CAS (r = -0.402; P < 0.001), while MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) were positively correlated with CAS (r = 0.369, 0.350, and 0.349, respectively;all P < 0.001). MTR and MTRasym (1 ppm) were independently associated with TAO activity. The areas under the ROC curve (AUCs) for MTR and MTRasym (1 ppm) in discriminating active from inactive TAO were 0.772 and 0.730, respectively. Combining MTR with MTRasym (1 ppm) significantly improved diagnostic performance compared with either parameter alone, achieving an AUC of 0.805 (P = 0.029 and 0.001). Conclusion MTR and MTRasym (1 ppm) were independently associated with TAO activity. Their combination further enhanced diagnostic performance in distinguishing active from inactive TAO, suggesting their potential as quantitative imaging biomarkers to guide treatment in patients with TAO.

Objective: To examine the prevalence of e-cigarette use and associated factors among primary and secondary school students in Pudong New Area, Shanghai, and to explore the pathways linking harm perception of e-cigarettes, interpersonal social influence, and attitudes toward e-cigarette use with experimentation behavior, in order to provide scientific basis for further optimizing the prevention and control strategies of e-cigarette among adolescents. Methods: From September to October 2025, a multi stage cluster random sampling method was used to select 5 144 primary and secondary school students aged 8-19 years from 47 primary and secondary schools in Pudong New Area, Shanghai, to conduct an anonymous questionnaire survey. The questionnaire collected information on e-cigarette use, harm perception of e-cigarette, interpersonal social influence, and attitudes toward e-cigarette use. The Chi-square test was applied to analyze the differences in cigarette and e-cigarette use behavior among primary and secondary school students with different demographic characteristics. Structural equation modeling (SEM) was constructed using Mplus 8.3 software, and the bootstrap method was utilized to test the mediating effects. Results: The reported rates of cigarette experimentation, e-cigarette experimentation, and current e-cigarette use among primary and secondary school students were 1.85%, 2.10%, and 0.70%, respectively. Higher reporting rates of e-cigarette experimentation were observed among boys (2.82%), secondary school students aged 16-19 (3.39%), senior high school students (3.05%), and those with weekly pocket money >100 yuan ( 6.11% ) ( χ 2=11.67, 8.61, 8.00, 54.18, all P <0.05). Structural pathway analysis results demonstrated that e-cigarette harm perception positively predicted interpersonal social influence ( β =0.61) and e-cigarette use attitude ( β = 0.53 ), and interpersonal social influence ( β =0.65) and e-cigarette use attitude ( β =0.25) further promoted e-cigarette experimentation behavior among primary and secondary school students (all P <0.01), with interpersonal social influence playing a major mediating role (indirect effect=0.40). Conclusions E-cigarette experimentation behavior among primary and secondary school students in Pudong New Area is jointly influenced by multiple psychosocial factors. Intervention strategies should strengthen interpersonal social factors such as family and peers on the basis of health education, thereby constructing a comprehensive prevention and control strategy for e-cigarette use among primary and secondary school students.

Background and Aims:Pancreatic ductal adenocarcinoma(PDAC)is a highly malignant digestive system tumor with an inferior prognosis,and its early diagnosis and treatment remain significant challenges.In recent years,RNA methylation modifications(such as m6A and m5C)have attracted considerable attention for their roles in tumor development;however,their regulatory mechanisms and clinical significance in PDAC remain unclear.This study was conducted to identify prognosis-related long noncoding RNAs(lncRNAs)associated with m6A and m5C in PDAC,construct a reliable prognostic prediction model,and explore their relationship with the tumor immune microenvironment.Methods:Based on RNA-seq data from the TCGA-PDAC cohort,differentially expressed lncRNAs(DElncRNAs)related to m6A and m5C were identified through differential expression analysis and Pearson correlation analysis.The samples were randomly divided into a training set(n=89)and a validation set(n=89).Key DElncRNAs were selected using LASSO-Cox regression to construct a prognostic model,and patients were categorized into high-and low-risk groups based on risk scores.Kaplan-Meier survival analysis,ROC curves,and multivariate Cox regression were used to evaluate the model's predictive performance.Furthermore,CIBERSORT and ESTIMATE scores were used to analyze immune cell infiltration characteristics and tumor microenvironment(TME)differences between the high-and low-risk groups.Results:To construct the prognostic model,four m6A-and m5C-related DElncRNAs(LINC00857,LINC02038,TSPOAP1-AS1,and TRPC7-AS1)were identified.Patients in the high-risk group had significantly lower overall survival than those in the low-risk group(P<0.05),and the risk score was an independent prognostic factor for PDAC(HR=1.551,95%CI=1.297-1.854,P<0.001).ROC curve analysis showed that the risk score model exhibited high predictive efficiency in both the training and validation sets(AUC values for 1,3,and 5 years:0.766,0.875,0.879;0.685,0.711,0.792,respectively).Immune analysis revealed increased infiltration of M0 macrophages with lower TME scores in the high-risk group(all P<0.05),suggesting an immunosuppressive microenvironment.Conclusion:This study successfully established a PDAC prognostic model based on m6A-and m5C-related DElncRNAs and confirmed its independent predictive value.High-risk patients exhibited M0 macrophage enrichment and immunosuppressive microenvironment characteristics,possibly contributing to poor prognosis.

The role of osteoblast(OB)autophagy in regulating bone metabolism is a research hotspot in the field of biomedicine.OB autophagy can regulate osteoporosis(OP)induced by aging,oxidative stress,estrogen deficiency,and glucocorticoids(GCs)by mediating factors such as run and cysteine rich domain containing Beclin-1 interacting protein(RUBCN),silent information regulator of transcription 1(SIRT1),and osteoprotegerin(OPG).OB autophagy can also regulate OP by activating notch receptor(Notch)and forkhead box protein O subfamily(FoxO),up-regulating the expression of osteogenic transcription factors(such as Runx2 and Osterix),and mediating the amp-activated protein kinase(AMPK),mammalian target of rapamycin complex(mTOR),Wnt,and c-Jun n terminal kinase(JNK)pathways to act on OB and osteoclast(OC)differentiation.Exercise is an important means of improving OP,and its molecular mechanism is closely related to the up-regulation of phosphatidylinositol 3 kinase(PI3K),adenosine monophosphate(AMP),tumor necrosis factor-alpha(TNF-α),and SIRT1 expression.These in turn activate key factors or pathways(including AMPK,mTOR,Wnt,PI3K/protein kinase B(Akt)/mTOR,and nuclear transcription factor-KB(NF-κB)),regulate the expression of downstream target genes(β-catenin,mTOR,FoxO3a and B cell lymphoma-2(Bcl-2))to up-regulate the expression of autophagy factors(Beclin-1,autophagy related genes(ATG),and microtubule-associated protein 1 light chain 3(LC3)),and promote OB autophagy to restore the dynamic balance in the body,thereby regulating bone formation and bone resorption and improving OP.The relationships among exercise,OB autophagy and OP,however,remain unclear and there is currently a lack of systematic reviews.Here we review and analyze the mechanism of OB autophagy in relation to exercise-induced improvements in OP,and provide a new theoretical basis and research ideas for the prevention and treatment of OP.

Immunotherapy following transplantation has long been a central focus in both anti-rejection strategies and the induction of immune tolerance. Regulatory B cells (Bregs) can directly suppress the immune system via the interaction between programmed cell death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1). Additionally, Bregs exert indirect immunosuppressive effects through the secretion of cytokines such as interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and granzyme B (GrB), among which IL-10 plays a particularly critical role. This review summarizes recent progress in the classification, functional characteristics, and activation mechanisms of Bregs, as well as their potential applications in transplantation immunotherapy, aiming to provide a theoretical foundation for Breg-targeted strategies in transplant immune modulation.

Objective:To analyze the epidemiological characteristics and influencing factors of single-cigarette use and dual cigarette-cigar use in China.Methods:This study was a cross-sectional study that selected 85 638 urban and rural residents who met the inclusion criteria from the 2018 China Health Literacy Survey as research subjects. An analysis was conducted on 21 849 users of cigarettes and cigars among them. Due to the small number of individuals who exclusively used cigars (247 cases), the research subjects were divided into two categories: exclusive cigarette users and dual users of cigarettes and cigars. The groups were categorized by age (18-34 years, 35-54 years, ≥55 years), gender (male, female), education level (primary school and below, junior high school and high school, university and above) and annual household income (<20 000 yuan, 20 000-<80 000 yuan, ≥80 000 yuan) to compare the tobacco usage rate and conduct subgroup analyses for each subgroup. Multivariate logistic regression analysis was employed, incorporating general demographic characteristic information to explore the influencing factors of exclusive cigarette use and dual use of cigarettes and cigars, respectively.Results:The rate of exclusive cigarette use in our country was 24.3%, while the dual use rate of cigarettes and cigars was 0.9%. The exclusive cigarette use rate and the dual use rate of cigarettes and cigars among males were significantly higher than those among females (48.25% vs 2.48%, and 1.84% vs 0.06%) (both P<0.001). For males, the high-risk factors for exclusive cigarette use included living in urban areas ( OR: 1.37, 95% CI: 1.23-1.54), being Han ethnicity ( OR: 1.73, 95% CI: 1.51-1.98), and having an annual household income ≥20 000 yuan ( OR: 1.54, 95% CI: 1.38-1.82) while having a junior high school education or higher was a protective factor ( OR: 0.68, 95% CI: 0.52-0.90). Age≥35 years ( OR: 3.36, 95% CI: 2.62-4.32) and having a junior high school education or higher ( OR: 1.30, 95% CI: 1.02-1.67) were risk factors for dual use of cigarettes and cigars in males. Among females, living in urban areas ( OR: 1.53, 95% CI: 1.19-1.97) and being Han ethnicity ( OR: 5.96, 95% CI: 4.47-7.96) were risk factors for exclusive cigarette use, while having a university education or higher was a protective factor ( OR: 0.28, 95% CI: 0.18-0.42). However, for female dual use of cigarettes and cigars, no significant effects were observed for any demographic characteristics. Conclusions:The use rate of cigarettes alone in China is significantly higher than that of cigarette-cigar dual use, and the rates of cigarette use alone and cigarette-cigar dual use in men are significantly higher than those in women. Tobacco use is being affected by sociodemographic factors, among which place of residence, ethnicity and education level are the main influencing factors of cigarette use alone, and gender, age and education level are the main influencing factors of cigarette-cigar dual use.

Acute kidney injury(AKI)is a syn-drome characterized by rapid decline in renal excre-tory function.Its pathogenesis is still unclear.Stud-ies have shown that macrophages are major play-ers in AKI inflammation,regulating tissue damage and regeneration repair.During AKI inflammation,macrophages can be activated into different func-tional phenotypes through molecular and signaling pathways,regulate different molecules and signal-ing pathways,and determine the progression of AKI.In this paper,the activation of macrophages and the molecular signaling pathways involved in the regulation of AKI in the past five years are re-viewed,and the mechanism of action of macro-phages in AKI is determined,which provides ideas for the study of macrophages as therapeutic tar-gets.

The aim of this study is to explore the mechanism of apigenin against transmissible gas-troenteritis virus(TGEV)infection based on network pharmacology and molecular docking.The potential targets of apigenin were obtained from Pharmmapper,Pubchem and other databases.The PubMed database was searched to obtain the relevant targets of TGEV infection.The intersection targets of apigenin and TGEV infection were identified by Draw Venn Diagram online program.A"drug-disease-target"network was constructed using STRING database and Cytoscape 3.8.2 soft-ware.Protein-protein interaction relationships were obtained from the STRING database,and core targets were analyzed.The intersection targets were subjected to GO function and KEGG pathway enrichment analysis using the DAVID database.Finally,the analysis results were validated through molecular docking and in vitro cell experiments.The study identified 431 targets for apigenin,1 177 targets for TGEV infection,and 50 intersection targets for apigenin and TGEV infection.GO enrichment analysis indicated that apigenin was mainly involved in regulating cell differentiation,cell membrane raft formation,apoptosis,and inflammatory responses.The top 15 statistically sig-nificant KEGG enrichment results mainly involve the PI3K-Akt signaling pathway and TNF signa-ling pathway.Docking analysis showed that apigenin had the strongest interaction with matrix metalloproteinase 3(MMP3)with an affinity of-9.5 kJ/mol and the binding activity of MMP3 was the best.The results of in vitro experiments demonstrated that treatment of different concen-trations of apigenin significantly reduced virus titers,virus genome copies,and the expression lev-els of MMP3 and its upstream and downstream proteins compared to the virus-infected group.Api-genin may exert its anti-TGEV effects through multiple targets and pathways,possibly by regula-ting the NF-κB-MMP3-IL-1β signaling pathway.