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 observe the efficacy and safety of eye transcutaneous electrical acupoint stimulation (Eye-TEAS) on preventing the progression of pre-myopic to myopia in children aged 6-12 years. METHODS: A total of 170 pre-myopic children aged 6-12 years were randomly divided into an Eye-TEAS group (85 cases, 3 cases dropped out, 2 cases were eliminated) and a placebo Eye-TEAS group (85 cases, 3 cases dropped out, 2 cases were eliminated). The Eye-TEAS group received Eye-TEAS intervention at bilateral Cuanzhu (BL2), Yuyao (EX-HN4), Sizhukong (TE23), Taiyang (EX-HN5), Sibai (ST2), and Jingming (BL1), with continuous wave at a frequency of 4 Hz and a current of 1-2 mA for 30 min per session. The placebo Eye-TEAS group received sham intervention with the same equipment and procedure, but no electrical stimulation. Both groups received intervention once every other day, at least 3 times a week, for a duration of 20 weeks. After intervention and during the 28-week follow-up period after the intervention completion, the changes in axial length (AL), spherical equivalent refraction (SER), and the incidence of myopia were compared between the two groups. Adherence and safety during the intervention period were also evaluated. RESULTS: Compared before intervention, both groups showed an increase in AL after the intervention and during the follow-up (P<0.01). The AL during follow-up was higher than that after the intervention in the two groups (P<0.01). The Eye-TEAS group exhibited a smaller change in AL than the placebo Eye-TEAS group after the intervention and during follow-up (P<0.01, P<0.05). Compared before intervention, both groups showed a decrease in SER after the intervention and during follow-up (P<0.01). The SER during follow-up was lower than that after the intervention in the two groups (P<0.01). The Eye-TEAS group had a higher SER than the placebo Eye-TEAS group after the intervention (P<0.05). The Eye-TEAS group exhibited a smaller change in SER than the placebo Eye-TEAS group after the intervention and during follow-up (P<0.01). The incidence of myopia in the Eye-TEAS group was lower than that in the placebo group during follow-up (20.0% [14/70] vs 34.7% [25/72], P<0.05). Both groups had good adherence, with no adverse events related to the intervention. CONCLUSION Eye-TEAS can delay the progression of pre-myopic to myopia in children, and has a high safety profile.
Humans ; Child ; Male ; Female ; Acupuncture Points ; Myopia/prevention & control* ; Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Disease Progression

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.

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.

Objectives:The aim is to analyze the cost structure and coefficient of variation for hospitalized patients with malnutrition based on Diagnosis-Related Groups(DRG),providing a reference for the further application and promotion of DRG.Method:Data were collected from patients admitted to Ningxia Hui Autonomous Region People's Hospital between March 2023 and August 2023.A diagnostic system based on artificial intelligence was used to identify malnourished patients.The composition of hospitalization costs for these individuals was described and analyzed,as was the coefficient of variation for various costs within DRG groupings.A multivariate regression analysis was conducted to identify the factors that influence patient hospitalization costs.Results:The average age of hospitalized patients with malnutrition was(68.12±16.43)years,with an average length of stay of(14.55±8.47)days,with an average hospitalization cost of(32 128.89±35 345.61)yuan.Among patients within the same DRG group,the coefficient of variation for various costs was found to be lower in the malnutrition group than in the normal group.This suggests that when assessed individually,the malnutrition group exhibited a higher degree of homogeneity in their cost structures.The factors influencing total hospitalization costs were found to be:length of hospital stay(P=0.001),nutritional monitoring fees(P=0.020),number of chronic diseases(P=0.003),and Karnofsky Performance Status(KPS)score(P=0.038).Hospitalization costs were positively correlated with both length of stay and nutritional assessment fees,but negatively correlated with the number of chronic diseases and KPS scores.Conclusions:Malnutrition has a profound impact on health outcomes,medical expenses,length of hospital stay,and disease severity.The implementation of the DRG system aims to standardize and improve the nutritional diagnosis and treatment process by categorizing different stages of malnutrition.This approach can minimize variations within DRG groups,making it easier to allocate medical resources more precisely and efficiently.Furthermore,it is a valuable reference tool for promoting DRG payment reform in different regions.

OBJECTIVE To retrospectively analyze the efficacy of endoscopic prelacrimal recess approach(PLRA)surgery for sinonasal inverted papilloma(SNIP)with tumor attachment located in the maxillary sinus,and to evaluate changes in postoperative facial numbness complications.METHODS A total of 69 cases of SNIP classified as Krouse stage T2 and T3 were treated with the PLRA surgery and included in the study.The tumor attachment sites were recorded,and all patients underwent regular follow-up for at least 12 months postoperatively.Recurrence rates and treatment methods were documented.Differences in tumor attachment sites between T2 and T3 cases and the feasibility of complete tumor removal using powered instruments and high-speed drills were analyzed.Subjective scores of facial numbness were recorded using the visual analogue scale(VAS)and compared at 1,3 and 12 months postoperatively.RESULTS The PLRA surgery demonstrated good therapeutic efficacy for Krouse stage T2 and T3 SNIP cases with tumor attachment located in the maxillary sinus,with a recurrence rate of 2.9%.Tumor attachment in T2 cases was more frequently located on the medial wall of the maxillary sinus(P<0.01),while in T3 cases,attachment was more often found on the anterior wall(P=0.001)and posterior lateral wall(P=0.009).The proportion of cases where high-speed drills could be used to remove bony tumor attachment was higher in T2 cases compared to T3 cases(P=0.023).The VAS scores for facial numbness were 6.39±1.69 at 1 month postoperatively,2.83±1.52 at 3 months,and 1.25±0.93 at 12 months.Significant differences were observed between the scores at 3 months and 1 month,as well as between 12 months and 3 months(P<0.01).CONCLUSION For Krouse stage T2 and T3 SNIP with tumor attachment located in the maxillary sinus,the endoscopic PLRA surgery should be the preferred approach to ensure complete tumor resection and removal of mucosa and bone at the tumor attachment site,thereby reducing recurrence rates.Postoperative numbness in the upper lip and gingival regions may occur but gradually diminishes over time,with minimal impact on patients'quality of life.

This study aimed to address the limitations of current diagnostic methods for well leg compartment syndrome(WLCS),including invasiveness,high costs,and insufficient accuracy,by proposing a solution based on electrical impedance tomography(EIT)technology.The electrical response characteristics of the human calf muscle to changes in compartment pressure using EIT were investigated,aiming to visualize the effects of pressure variations on the electrical properties within the compartment and to provide technical support for early non-invasive detection of WLCS.EIT sensors were placed on the right calf of the experimental subjects,with pressure applied externally to the right thigh.Measurements were conducted in two phases:pre-pressure(pre)and post-pressure(post).Pre-pressure,the conductivity distribution image σpre was measured when the calf was placed horizontally.Post-pressure,the calf was raised at an angle of approximately 30°,and pressures of 0,40,80,and 120 mmHg were applied to the right thigh,and the corresponding conductivity distribution images σP=0,σP=40,σP=80,andσP=120were recorded.To quantitatively analyze the pressure effects on the compartment response,paired sample t-test was used to assess the spatial-mean conductivity((σ))from the EIT reconstructed images.Compared to the horizontal position of the right calf,raising the calf at approximately 30° resulted in a significant increase in the spatial-mean conductivity(σ)of the M1 compartment.Furthermore,when pressure was applied to the right thigh while the calf remained at a 30° angle,the spatial-mean conductivity of the M1 compartment σM1 showed an increasing trend with rising pressure.The results indicated that as compartment pressure increased,the volume of extracellular fluid and ion concentration significantly increased,leading to an increase in conductivity,which reflected ischemia and hypoxia in muscle tissue and the related pathophysiological changes.EIT,due to its high sensitivity to conductivity changes,offered a potential effective diagnostic method for non-invasively monitoring the onset and progression of muscle compartment syndrome.

Objective:To investigate the consistency of trichoscopic fields in androgenetic alopecia (AGA) patients by using scalp medical pigmentation (SMP) ink as visual marker, as well as the safety and durability.Methods:A retrospective analysis was conducted on patients with AGA who visited the Medical Cosmetology Center, Hangzhou First People’s Hospital, Westlake University School of Medicine from April to August 2024. Trichoscopic images were captured immediately and three months after using SMP ink for visual marker. Each patient’s two trichoscopic images were imported into Photoshop CC 2019 software for processing to obtain the location information of the marker, the distance between the marker center and the image center, and pigments areas. Consistency of markers during repeated trichoscopy was evaluated by comparing distances between pigment center and image center. The difference in distance between the two time points (3-month distance minus immediate-post-marking distance) was defined as "distance difference". Patients were divided into the same-operator group and different-operator group based on whether the two trichoscopy examinations were performed by the same operator. The impact of operator changes on the consistency of markers during repeated trichoscopy was assessed by comparing the "distance difference" between the two groups. Additionally, patients were categorized into single-point, double-point, and triple-point groups according to the number of markers. The influence of marker quantity on consistency of the markers was evaluated by comparing the "distance difference" among these three groups. Pigment spread was assessed by comparing pigment actural area in repeated trichoscopic images. Adverse reactions and ink fading within three months were recorded. Statistical analysis was performed using SPSS 27.0 software.The normal distribution measurement data was expressed as Mean ± SD, and the non-normal distribution measurement data was expressed as M ( Q1, Q3). The Wilcoxon signed-rank test was applied for comparison of the distance between the marker center and the image center in the preceding and subsequent trichoscopic images. Mann-Whitney U test was applied for comparison between the same-operator group and the different-operator group, and the Kruskal-Wallis rank sum test was used for comparison among the single-point, double-point, and triple-point groups. The paired sample t-test was used for comparison of the pigment actural area during repeated measurements. P<0.05 indicated statistically significant differences. Results:A total of 22 male AGA patients (aged 24-43 years) were included, with 46 pigment points marked (8 single-point, 4 double-point, 10 triple-point). Same-operator and different-operator groups comprised of 13 and 9 patients, respectively. No significant difference was found in distances between marker center and image center immediately vs. 3 months post-marking [0.91 (0.62, 1.53) mm vs. 0.83 (0.62, 1.22) mm, Z=-0.83, P=0.408]. Comparisons of the "distance difference" between the same-operator and different-operator groups, and among the single-point, double-point, and triple-point groups, showed no statistically significant differences (all P> 0.05). Pigment areas increased by (0.11±0.12) mm 2 at 3 months ( t=-6.47, P<0.001). All pigments exhibited fading within 3 months but remained identifiable without touch-up. Adverse reactions were minimal: mild puncture-site bleeding was observed, with no pigment-related allergies, foreign-body reactions, or significant scarring. Conclusion:Single-point SMP pigment enables reliable and consistent visualization of trichoscopic measurement points in AGA patients, unaffected by operator changes. The method demonstrates clinical convenience, flexibility, high safety, and long-term durability.