Abstract The framework of pediatric inactivity triad (PIT) consists of three core factors:exercise deficit disorder, pediatric dynapenia, and physical illiteracy. It emphasizes that physical activity (PA) insufficiency is not a singular phenomenon but rather a vicious cycle resulting from the interaction of multiple factors. Based on the PIT framework, the paper explores its core components and their interrelationships, as well as analyzes the framework s application value and practical implications for improving PA levels among Chinese children and adolescents,to provide a systematic theoretical perspective for analyzing the complex causes of PA insufficiency in children and adolescents, and to offer a scientific basis for developing intervention strategies.

Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

Objective To detect the expression levels of tumor necrosis factor alpha induced protein 3(TN-FAIP3)and LINC00887 in clear cell renal cell carcinoma(ccRCC)tissue,and to study their relationship with clinical pathological parameters and prognosis.Methods A total of 101 ccRCC patients admitted to the hospi-tal from January 2013 to October 2018 were selected.The expression levels of TNFAIP3 and LINC00887 were detected in ccRCC cancer tissue and paired adjacent tissues,respectively.The relationship between TNFAIP3 and LINC00887 expression and clinical pathological parameters and prognosis of ccRCC patients was analyzed,and the influencing factors of poor prognosis in ccRCC patients were also analyzed.Spearman correlation coef-ficient was used to analyze the correlation between TNFAIP3 and LINC00887 expression.Results The posi-tive rate of TNFAIP3 expression in ccRCC(37.62％)was significantly lower than that in adjacent tissues(52.48％),and the difference was statistically significant(X2=4.500,P=0.034).The expression level of LINC00887 in ccRCC(1.38±0.61)was significantly higher than that in adjacent tissues(1.03±0.43),and the difference was statistically significant(t=5.396,P＜0.001).The positive rates of TNFAIP3 protein in pa-tients with maximum tumor diameter ≥4.5 cm and TNM stage Ⅲ-Ⅳ were lower than those in patients with maximum tumor diameter＜4.5 cm and TNM stage Ⅰ-Ⅱ,and the differences were statistically significant(P＜0.05).The positive rates of LINC00887 in patients with maximum tumor diameter ≥ 4.5 cm,pathologi-cal grading Ⅲ-Ⅳ,and TNM stage Ⅲ-Ⅳ were higher than those in patients with maximum tumor diameter＜4.5 cm,pathological grading Ⅰ-Ⅱ,and TNM stage Ⅰ-Ⅱ,and the differences were statistically signifi-cant(P＜0.05).Compared with the TNFAIP3 high expression group,the TNFAIP3 low expression group had a poorer prognosis,and the difference was statistically significant(x2=5.118,P=0.024).Compared with the LINC00887 low expression group of,the LINC00887 high expression group had a poorer prognosis,and the difference was statistically significant(x2=4.638,P=0.031).Low expression of TNFAIP3,high expres-sion of LINC00887,pathological grade Ⅲ-Ⅳ,and TNM stage Ⅲ-Ⅳ were risk factors for poor prognosis in ccRCC patients(P＜0.05).Spearman rank correlation analysis showed that there was a negative correlation between TNFAIP3 and LINC00887 expression in ccRCC tissue(r=-0.638,P=0.012).Conclusion TN-FAIP3 expression is down-regulated and L1NC00887 expression is up-regulated in ccRCC tissue,and there is a negative correlation.They may jointly regulate the occurrence and development of ccRCC,and have the poten-tial to become tumor markers for evaluating the prognosis of ccRCC patients.

Objective:To evaluate and screen the regimens of tigecycline intraventricular injection in extensively drug resistant Acinetobacter baumannii (XDRAB) intracranial infection based on Monte Carlo simulation and pharmacokinetic/pharmacodynamic (PK/PD) model.Methods:Nine patients with XDRAB intracranial infection confirmed as having susceptibility to tigecycline or polymyxin antimicrobials from January 1, 2018 to December 31, 2023 were screened from electronic medical record system in Second Affiliated Hospital of Shandong First Medical University. WHONET software was used to extract pathogen susceptibility data isolated from cerebrospinal fluid samples. Minimum inhibitory concentration (MIC) of tigecycline against XDRAB was analyzed by drug susceptibility test; different regimens for intraventricular tigecycline injection were designed based on MIC: 2 mg/12 h, 3 mg/12 h, 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h, with drug concentration of 0.5 mg/mL or 1.0 mg/mL once a day. Target value of PK/PD index was set as ?C max/MIC≥8; Monte Carlo was used to simulate the compliance of PK/PD index of tigecycline with different MIC against XDRAB for different dosed regimens (probability of target attainment [PTA] and cumulative fraction of response [CFR]); the best regiment was selected (screening basis: PTA≥90% or CFR≥90%). Results:(1) A total of 27 strains of pathogenic bacteria from 9 patients were extracted from drug susceptibility test, in which MIC of tigecycline against XDRAB was 55.56% for 2 mg/L, 25.93% for 4 mg/L, and 18.52% for 8 mg/L. (2) When the drug concentration was 0.5 mg/mL or 1.0 mg/mL, respectively, all 6 regimens had PTA>90% at 2 mg/L MIC; 5 regimens, except for 2 mg/12 h, had PTA>90% at 4 mg/L MIC; regimens of 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve PTA>90% at 8 mg/L MIC. (3) When the drug concentration was 0.5 mg/mL, regimens of 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve CFR>90%; when the drug concentration was 1 mg/mL, regimens of 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve CFR>92%.Conclusion:In intraventricular tigecycline injection for XDRAB intracranial infection, 2 mg/12 h regimen is available in 2 mg/L MIC, 3 mg/12 h regimen is available in 4 mg/L MIC, and 5 mg/12 h regimen is available in 8 mg/L MIC, with either 0.5 mg/mL or 1 mg/mL concentration.

Objective:To observe the effects of warming needle therapy combined with the modified Hua Tan Tong Luo Tang(decoction for dissipating phlegm and unblocking collaterals)on post-stroke cognitive impairment due to obstruction of wind-phlegm. Methods:A total of 78 patients who met the inclusion criteria were randomly assigned to an observation group and a control group,with 39 patients in each group.Both groups received conventional treatment.The control group was additionally treated with the modified Hua Tan Tong Luo Tang,while the observation group received warming needle therapy in addition to the treatment given to the control group.Scores on the mini-mental state examination(MMSE),Montreal cognitive assessment(MoCA),and activities of daily living(ADL)were assessed before and after treatment.Adverse reactions and clinical efficacy were analyzed and compared between the two groups after treatment. Results:The total effective rate was 82.1%in the observation group and 61.5%in the control group,showing statistical significance between the two groups(P<0.05).After treatment,the MMSE,MoCA,and ADL scores of both groups were significantly higher than those before treatment within each group(P<0.05).Notably,the scores in the observation group were higher than those in the control group(P<0.05).No adverse reactions occurred in either group during the treatment period. Conclusion:Based on the conventional treatment,compared to modified Hua Tan Tong Luo Tang alone,warming needle therapy combined with the modified Hua Tan Tong Luo Tang showed superior clinical efficacy in treating post-stroke cognitive impairment due to obstruction of wind-phlegm,and this combined therapy also showed high safety.

The tumor microenvironment,particularly the hypoxic property and glutathione(GSH)overexpression,substantially inhibits the efficacy of cancer therapy.In this article,we present the design of a magnetic nanoplatform(MNPT)comprised of a photosensitizer(Ce6)and an iron oxide(Fe3O4)/manganese oxide(MnO2)composite nanozyme.Reactive oxygen species(ROS),such as singlet oxygen(1O2)radicals produced by light irradiation and hydroxyl radicals(·OH)produced by catalysis,are therapeutic species.These therapeutic substances stimulate cell apoptosis by increasing oxidative stress.This apoptosis then triggers the immunological response,which combines photodynamic therapy and T-cell-mediated immunotherapy to treat cancer.Furthermore,MNPT can be utilized as a contrast agent in magnetic resonance and fluorescence dual-modality imaging to give real-time tracking and feedback on treatment.

Objective To discuss on the application of innovative quality control circle in optimizing pharmaceutical care,design pharmaceutical care model according to needs,and improve the quality of pharmaceutical care.Methods Using 10 steps of innovative quality control circle,the quality function development(QFD)was carried out by multidimensional quality tools,and the demand for pharmaceutical services was analyzed in the form of"House of Quality"Combined with PDCA cycle management tool,the situation of pharmaceutical services before and after improvement was analyzed and evaluated.Results After the implementation of the activities,many contents hd been improved,such as the dispensing time for outpatient pharmacy patients decreased from 16 min to 8 min,the finished product infusion configuration time in pharmacy intravenous admixture services decreased from 15 min to 7 min,the surgery pharmacy special management drug report automatically generated number increased from 2 copies to 6 copies,the daily order review time for each department of pharmacy decreased from 80 min to 20 min,the perfection rate of pharmaceutical care digital module increased from 65.23％to 80.34％,and the multidimensional quality tool adoption rate increased from 60.00％to 93.00％.In addition,a number of additional benefits and intangible results were obtained.Conclusion Adopting the management mode of QFD combined with PDCA cycle can effectively reconstruct the management mode of pharmaceutical care,and effectively promote the scientific and fine management of pharmaceutical care.

Objective: To examine the developmental trajectory of fine motor ability in schoolage children with attention deficit hyperactivity disorder (ADHD) for two years, so as to provide scientific evidence to promote motor development in ADHD children. Methods: From April to June 2019, 31 children aged 6-8 years old were selected from a public elementary school. They were diagnosed with ADHD by two psychiatric professionals according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Additionally, 31 typical developmental children, matched for age, sex and IQ with the ADHD group, were recruited as the control group. Fine motor ability was assessed with tasks of hand manual dexterity in Movement Assessment Battery for Children-2 (MACB-2), and a followup assessment was conducted from April to June 2021. The development changes of fine motor ability between two groups of children were compared by using t test and repeated measures analysis of variance. Results: Between baseline and followup periods after two years, the total score of hand fine motor in the ADHD group did not show significant improvement (7.4±3.0, 8.0±3.4; t=-1.05, P>0.05), while there was a small effect size improvement in typically developing control group (9.5±2.1, 10.5±2.4; t=-2.12, effect size=0.38, P<0.05). Followup after two years, coin/peg throwing scores with dominant hand improved between ADHD group and control group (7.0±3.3, 9.5±3.2; 8.4±2.8, 11.6±1.6) (t=-3.74, -6.33, P<0.01; effect size=0.67, 1.14), with a smaller improvement in the ADHD group. The score for threading beads/threads decreased in between ADHD group and control group (7.9±2.4, 5.8±3.1; 9.2±1.1, 8.2±1.9) (t=3.89, 2.78, P<0.01; effect size=0.70, 0.50), with a greater decrease in the ADHD group. Conclusions The development speed of fine motor ability in children with ADHD aged 6-8 is slow and continues to lag behind normal developmental children. Fine motor development in children with ADHD should be closely monitored, and targeted interventions should be implemented when necessary.

ObjectiveTo provide a basis for human enteroviruses prevention and control by monitoring the enterovirus （EV） and its main virus types. MethodsSamples of hand-foot-and-mouth disease， herpetic angina and fever clinic patients in Dapeng New District of Shenzhen from 2016 to 2022 were tested for EV with real-time polymerase chain reaction （PCR）. To identify the isolates of EV， VP1 genes of EV were amplified with nested reverse transcription PCR， and then sequenced.A geneticphylogenetic tree was constructed based on the VP1 gene. ResultsAmong the 1 124 suspected hand-foot-and-mouth disease cases， 740 （65.84%） tested EV positive. Coxsackievirus A6 （CVA6） and Coxsackievirus A16 （CVA16） were the main two serotypes with regular cycle trends. Of the 137 suspected herpetic angina cases， 88 （64.23%） were EV positive， with Coxsackievirus A4 （CVA4） and CVA16 as the dominant serotypes. Among 428 respiratory infection specimens， 71 （16.59%） were EV positive. Coxsackievirus A4 （CVA4） was the predominant serotype which caused herpetic angina and respiratory infection. The epidemic EV isolates CVA6 from Shenzhen had a close genetic relationship with isolates in China’s mainland. ConclusionThe main serotypes EV CVA6 and CVA16 which caused hand-foot-and-mouth disease exhibit cyclical trends . The risk of EV transmitted from abroad is low， but their genetic variation and virulence change should be monitored continuously. In addition， the monitoring of dominant isolates CVA4 which cause herpetic angina and respiratory infection should be strengthened.

Objective The occurrence of chickenpox in rapidly developing areas poses substantial seasonal risk to children.However,certain factors influencing local chickenpox outbreaks have not been studied.Here,we examined the relationship between spatial clustering,heterogeneity of chickenpox outbreaks,and socioeconomic factors in Southern China. Methods We assessed chickenpox outbreak data from Southern China between 2006 and 2021,comprising both relatively fast-growing parts and slower sub-regions,and provides a representative sample of many developing regions.We analyzed the spatial clustering attributes associated with chickenpox outbreaks using Moran's I and local indicators of spatial association and quantified their socioeconomic determinants using Geodetector q statistics. Results There were significant spatial heterogeneity in the risk of chickenpox outbreaks,with strong correlations between chickenpox risk and various factors,particularly demographics and living environment.Furthermore,interactive effects among specific are factors,such as population density and per capita residential building area,percentage of households with toilets,percentage of rental housing,exhibited q statistics of 0.28,0.25,and 0.24,respectively. Conclusion This study provides valuable insights into the spatial dynamics of chickenpox outbreaks in rapidly developing regions,revealing the socioeconomic factors affecting disease transmission.These implications extend the formulation of effective public health strategies and interventions to prevent and control chickenpox outbreaks in similar global contexts.