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.

Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

Objective:To evaluate the accuracy and feasibility of an automated scanning and uptake system to assist pathologists with hu-man epidermal growth factor receptor 2(HER2)FISH interpretation.Methods:HER2 gene amplification is detected using FISH,and"result interpretation by independent pathologists"is regarded as the"gold standard."The consistency of"human-machine dialogue results"(use of a CytoVision* system combined with manual interpretation)and"CytoVision*-based automated interpretation"with the"gold standard"was assessed.Results:Consistency between"human-machine dialogue results"and the"gold standard"can surpass 91%,with the former method saving up to 50%of the manual operation time.The tendency of each cell nucleus's HER2 copy number to be"underestimated"is the main reason for the low sensitivity observed in cases with low copy number amplification and HER2 heterogeneous expression cases in"human-machine dialogue interpretation."Conclusions:Automatic FISH image analysis and uptake systems simulate the process of manu-ally interpreted cell selection,ensure random cell selection,and improve work efficiency.With its accurate selection of the hybridization re-gion and"human-computer dialogue,"the system is expected to"replace"interpretation by independent pathologists.

Objective To assess the prognostic value of serum lysine hydroxylase 3(PLOD3)and cytokeratin 19 fragment(CYFRA21-1)in predicting the efficacy of three-dimensional brachytherapy in patients with pulmonary metastases.Methods A total of 102 patients with lung metastases who underwent three-dimensional brachytherapy at our hospital were selected as the lung metastasis group from August 2021 to August 2023.During the same period,a control group consisting of 60 healthy individuals who underwent physical examinations was selected.The lung metastasis group was further divided into an effective group(n=66)and an ineffective group(n=36)based on therapeutic outcomes.Enzyme-linked immunosorbent assay was employed to measure the levels of serum PLOD3 and CYFRA21-1.Multiple logistic regression analysis was conducted to identify factors influencing the efficacy of three-dimensional brachytherapy in the lung metastasis group.Receiver operating characteristic(ROC)curves were used to assess the predictive value of serum PLOD3 and CYFRA21-1 for treatment efficacy.Results The levels of serum PLOD3 and CYFRA21-1 in the case group were(34.47±6.17)μg/L,(27.85±5.14)μg/L,respectively,which exhibited significantly higher values compared to those observed in the control group(7.26±2.21)μg/L,(9.31±2.46)μg/L(P<0.05).A positive correlation was found between serum PLOD3 and CYFRA21-1 in the Lung metastasis group(r=0.667,P=0.000).Logistic regression analysis revealed that multiple metastatic lesions along with elevated serum levels of PLOD3 and CYFRA21-1 were identified as risk factors for the efficacy of three-dimensional brachytherapy in patients with lung metastases(P<0.05).Furthermore,when combined with three-dimensional brachytherapy,the area under the curve(AUC)for serum PLOD3 and CYFRA21-1 was calcu-lated as 0.868,demonstrating a superior performance compared to individual measurements of either serum PLOD3 alone(AUC=0.815)or CYFRA21-1 alone(P<0.05).Conclusions The levels of serum PLOD3 and CYFRA21-1 are elevated in patients with lung metastases,exhibiting a significant correlation with the efficacy of three-dimensional brachytherapy.The combined utilization of these two biomarkers demonstrates a robust predictive value for treatment efficacy in patients suffering from lung metastases.

Objective To investigate the prevalence of comorbidity of oral frailty and sarcopenia in elderly inpatients,and to explore their influencing factors,so as to provide a basis for formulating targeted interventions for patients with oral frailty and sarcopenia.Methods A total of 515 elderly patients hospitalized in 3 tertiary hospitals in Zhengzhou City and 1 second-class hospital in Shangqiu City from January 2024 to April 2024 were selected as the research subjects by convenience sampling,and the general information questionnaire,Oral Frailty Index-8,Sarcopenia Screen Questionnaire,Mini Nutritional Assessment Short Form,Social Support Rating Scale and Hospital Anxiety and Depression Scale(HADS)were used for investigation.Logistic regression was used to analyze the influencing factors of oral frailty and sarcopenia comorbidities in elderly inpatients.Results 508 valid questionnaires were collected.The prevalence of sarcopenia and oral frailty in elderly inpatients was 22.8％,and age,dysphagia,number of chronic diseases,and history of hypertension or stroke,multiple drug use,depression,bad nutrition and low level of social support were the risk factors(P＜0.05).Conclusion The incidence of oral frailty combined with sarcopenia was higher in elderly hospitalized patients.Nurses should take nursing measures according to its influencing factors to prevent and control the development of oral frailty combined with sarcopenia.

Objective To analyze the factors affecting the prevalence of hyperuricemia(HUA)in an island troop.Methods A total of 1 113 soldiers stationed on an island from December 2021 to December 2022 were selected as research objects by cluster sampling.Their lifestyle and health information were collected.Physical examination and laboratory detection were conducted.Multivariate logistic regression was used to analyze the influencing factors of HUA.Results The prevalence rate of HUA was 21.02%(234/1 113).There were significant differences in the body mass index(BMI),waist-to-hip ratio,triglyceride,alanine aminotransferase,and creatinine between the soldiers with hyperuricemia and the soldiers with normal blood uric acid(P<0.05).Multivariate logistic regression analysis showed that BMI≥24(OR=1.49,95%CI:1.09-2.05),abnormal liver function(OR=2.26,95%CI:1.31-3.92),and dyslipidemia(OR=1.46,95%CI:1.01-2.12)were positively correlated with hyperuricemia;age>30 years old(OR=0.59,95%CI:0.37-0.93)and exercise time>1 h per week(OR=0.46,95%CI:0.22-0.97)were negatively correlated with HUA.Conclusion The prevalence rate of hyperuricemia is at a high level in an island troop.BMI≥24,age≤30 years old,exercise time≤1 h per week,abnormal liver function,and dyslipidemia are the risk factors for HUA.Prevention and control measures should be taken as early as possible for the soldiers with these risk factors.

Objective:In the context of China's cardiovascular disease(CVD)high-risk population screening and intervention project,this study systematically evaluates the applicability of the EQ-5D-5L and SF-6Dv2 instruments among individuals at high risk of CVD.Methods:Convergent validity was assessed using Spearman's correlation coefficient.Measurement agreement was evaluated through intraclass correlation coefficients(ICC)and Bland-Altman plots.Factors influencing utility differences were explored using multiple linear regression analysis.Kruskal-Wallis test and t-test were used to examine discriminant validity.Sensitivity was compared by effect size(ES),relative efficiency(RE),and the area under the receiver operating characteristic curve(ROC-AUC).Floor and ceiling effects were also compared.Results:Among 5,415 individuals at high risk of CVD,the two instruments showed moderate overall correlation and acceptable convergent validity,but dimension-specific correlations were weak,and measurement consistency was low(ICC=0.367).Both instruments effectively distinguished different health states,yet the SF-6Dv2 demonstrated superior sensitivity and a milder ceiling effect.Conclusion:When measuring the health utility value of CVD patients,scale selection should be cautious,especially for high-risk groups,and SF-6Dv2 is more appropriate.

Objective:To investigate the value of sequential ultrasound in assessing skeletal muscle and diaphragm thickness in elderly septic patients.Methods:A retrospective study was conducted.Fifty-one elderly patients with sepsis who underwent ultrasound examinations at Beijing Chaoyang Hospital from August 2021 to August 2023 were selected, including 30 males and 21 females.Ultrasound technology was used to measure the thickness of limb skeletal muscles(biceps brachii, flexor carpi radialis, quadriceps femoris, and tibialis anterior)and diaphragm, and sequential monitoring was performed at different time points(admission, the 3rd day after admission, and the 7th day after admission)to analyze the variation rules of their thickness.The correlations between the changes in muscle thickness and the severity of the disease[such as the Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)scores and the Sepsis Organ Failure Assessment(SOFA)scores], mechanical ventilation time, and length of hospital stay were analyzed.Results:Compared with those at admission, the thickness of limb skeletal muscles and diaphragm in elderly septic patients with mechanical ventilation significantly decreased with the prolongation of hospital stay( P<0.05).The degree of thickness reduction in the flexor carpi radialis and rectus femoris was positively correlated with the APACHE II score.The degree of thickness reduction in the biceps brachii was positively correlated with the SOFA score.The degree of thickness reduction in the flexor carpi radialis, rectus femoris, and diaphragm was positively correlated with both mechanical ventilation time and hospital stay( P<0.05).Correlation heatmap analysis showed that the thickness of the flexor carpi radialis was significantly correlated with hospital stay days and APACHE II score(correlation coefficients were 100.20 and 67.47, respectively), indicating that the longer the hospital stay and the more severe the condition, the more serious the atrophy of the flexor carpi radialis. Conclusions:Measuring the thickness of skeletal muscles and the diaphragm in elderly sepsis patients using ultrasound serves as an efficient and non-invasive method for assessing the disease state, predicting prognosis, and guiding clinical treatment decisions.This approach provides vital imaging-based evidence for refining diagnostic and therapeutic strategies for elderly sepsis patients, thereby promising to enhance clinical outcomes and the quality of rehabilitation for these individuals.