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 application efficacy of the continuous oral care program led by dental nurses in adolescent patients with fixed orthodontics and to provide a reference for continuous care to enhance the oral health level of patients.Methods:A randomized controlled trial was carried out in the Orthodontic Department of Shanghai Stomatological Hospital from June to December 2022. A total of 132 adolescent patients with fixed orthodontics were selected through the convenience sampling method and divided into the experimental group and the control group by the random number table method, with 66 patients in each group. The experimental group was provided with the continuous oral care program led by dental specialist nurses, while the control group received routine care. The intervention lasted for 12 months. The Oral Health Impact Scale, the Oral Health Self-Management Ability Questionnaire, and the plaque index were utilized to assess the intervention effect before and after the intervention.Results:A total of 65 participants in the experimental group completed the study, with an age of (14.41 ± 1.60) years, comprising 32 males and 33 females. In the control group, 64 participants completed the study, with an age of (14.15 ± 1.69) years, including 28 males and 36 females. Prior to intervention, there were no statistically significant differences in scores for oral health self-management ability, Oral Health Impact Profile-14, or total plaque index between the experimental and control groups (all P>0.05). Following intervention, the score for oral health self-management ability in the experimental group was (77.42 ± 11.70) points, significantly higher than (70.47 ± 17.49) points of the control group ( t = 2.65, P<0.05). Additionally, the score on the Oral Health Impact Profile-14 for the experimental group was (16.40 ± 3.45) points and their total plaque index was measured at 1.68 ± 0.55 both significantly lower than those recorded in the control group at (18.16 ± 3.79) points and a total plaque index of 1.92 ± 0.47 respectively ( t = - 2.75, - 2.55, both P<0.05). Conclusions:The implementation of the continuous oral care program led by dental specialist nurses is conducive to improving the oral health self-management ability of adolescent patients with fixed orthodontics, reducing dental plaque, improving oral cleanliness, and improving the oral health-related quality of life of patients.

Objective:To investigate the characteristics of elastic program of excited shear wave of plantar soft tissue of diabetic patients and its correlation with levels of glucose metabolism.Methods:A total of 92 patients with type 2 diabetes who admitted to Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine during January 2022 and January 2023 were selected as diabetes group,and another 92 patients in the prediabetes stage were included in the prediabetes group.Both groups of patients used excited shear wave with different frequencies(400,450,500,550,and 600 Hz)under elastic technique of shear wave.The velocities of shear waves at the 1st metatarsal head,the 3rd metatarsal head and calcaneus of plantar soft tissue,and the thickness of soft tissue of these patients were assessed.The fasting plasma glucose(FPG),2-hour postprandial glucose(2hPG),and glycosylated hemoglobin(HbA1c)levels of sugar metabolism level of two groups were measured,and the correlations between velocity of shear wave,thickness of soft tissue,and level of glucose metabolism were further analyzed.The occurrence of diabetic foot ulcer in the diabetes group was investigated by using follow-up.The receiver operating characteristic(ROC)curve was adopted to assess the predictive value of the velocity of shear wave,and the thickness of soft tissue for diabetic foot ulcer.Results:The FPG,2hPG and HbA1c of glucose metabolism level in the diabetes group were(6.48±0.48)mmol/L,(9.64±1.31)mmol/L and(6.21±0.15)%,respectively,all of which were higher than those[(8.03±0.62)mmol/L,(12.26±1.25)mmol/L and(7.66±0.42)%]in the prediabetes group,and the differences were statistically significant(t=18.961,18.961,31.185,P<0.05).The thickness level of soft tissue at the first metatarsal head was(10.42±3.11)mm in the diabetes group,which was less than(11.76±3.24)mm in the prediabetes group,with a statistically significant difference(t=2.862,P<0.05).Spearman correlation analysis showed that the velocity of shear wave at 500 Hz frequency had a strongest correlation with FPG and HbA1c(r=0.320,0.256,P<0.05),respectively.In the follow-up for patients of diabetes group,14 cases occurred ulcers and 78 cases did not occur ulcers.The velocities of shear wave of the first metatarsal head of 14 patients with ulcers were higher than those of patients without ulcers at all tested frequencies(400,450,500,550,and 600 Hz).The area under curve(AUC)value of ROC curve,specificity and sensitivity of 500 Hz were respectively 0.775,88.46%,and 78.57%in predicting plantar ulcer of patients with diabetes.Conclusion:The velocity of shear wave of soft tissue at the first metatarsal head is significantly correlated with abnormal glucose metabolism in patients with type 2 diabetes.The velocity of shear wave appeared strongest correlation with FPG and HbA1c at500 Hz frequency,which has higher predictive value for diabetic foot ulcer.

Objective:To investigate the relationship between lean lipid accumulation product (LAP) and metabolic associated fatty liver disease (MAFLD).Methods:This cross-sectional study consecutively enrolled 1 990 adult subjects who underwent health examinations at the Second Affiliated Hospital of Xi′an Jiaotong University between June 2021 and May 2023. All recruited participants had a body mass index (BMI)<23 kg/m2. Data collection included general information, physical examination, serum biochemical parameter measurements, and liver ultrasonography. Participants were divided into four groups (Q1-Q4) according to quartiles value of LAP from low to high. The differences of biochemical parameters and the prevalence of lean MAFLD were compared among the groups. Logistic regression, restricted cubic spline (RCS) and receiver operating characteristic (ROC) curve analysis were used to explore the relationship between LAP and lean MAFLD and assess the diagnostic predictive value of LAP for lean MAFLD.Results:A total of 1990 participants were selected, and the detection rate of lean MAFLD was 4.97% (99 cases). The detection rate of lean MAFLD showed a significant increasing trend from Q1 to Q4 groups ( P<0.001) and respectively was 0.40%, 0.81%, 4.01% and 14.70%. The average age, male proportion, BMI and waist circumference significantly increased in a dose-response manner from Q1 to Q4 (all P<0.001). Indirect bilirubin, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltranspeptidase, alkaline phosphatase, total cholesterol, triglycerides, low-density lipoprotein, serum uric acid, fasting blood glucose, fatty liver index, fibrosis-4 index and every metabolic syndrome component in groups Q2 to Q4 were significantly higher than in the Q1 group, while high-density lipoprotein levels gradually decreased (all P<0.05). RCS showed that the risk of lean MAFLD rose significantly with the increase of LAP ( P<0.005), presenting a nonlinear relationship between them ( P for nonlinear<0.001). Logistic regression analysis revealed that after adjusting other confounding factors, the risk of lean MAFLD in the Q4 group remained 4.75 times higher than that in the Q1 group (95% CI: 11.22-31.69, P<0.05). ROC curve demonstrated that LAP had a better predictive value for lean MAFLD than BMI and waist circumference, with area under the curve of 0.839, critical value of 19.59, diagnostic sensitivity of 82.8% and specificity of 75.1%. Conclusions:Elevated LAP is independently and positively correlated with the risk of lean MAFLD, and its predictive efficacy is significant superior to traditional obesity indicators.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Objective:This study starts from the main problems existing in the current stage of the development of pediatric clinical research in China and focuses on the construction of a clinical research management system. By innovating the platform management model and enhancing personnel skills, we can provide support and assurance for improving the clinical research platform and its sustainable development in the future.Methods:This study established an integrated management platform for Industry-Sponsored Initiated Clinical Research Trial (IST) and Investigator Initiated Clinical Research (IIT) and implement integrated management of IST and IIT projects. At the same time, in response to the weak links in quality management, synchronous training of management and research talents should be implemented to achieve dual improvement in project management quality and platform service efficiency throughout the process.Results:We had optimized the clinical research organization structure, improved the management system, and strengthened the quality supervision of IIT projects by establishing rules and systems to improve the quality and efficiency of project management.Conclusions:Based on analyzing the current situation in China and referring to international experience, we have built a clinical research management platform in line with the development of the hospital, and implemented centralized management of the entire process of IST and IIT projects, strengthened project process quality control, which is expected to provide a reference for peers.

Objective:In response to the current situation where Investigator-Initiated Trial (IIT) management system of pediatric medical institutions in our country is inadequate and the management of high-risk projects needs to be strengthened, a pediatric hospital in Beijing has been selected as a pilot to develop a system and process suitable for IIT management. We aim to explore personalized management models for different types of research projects, especially high-risk ones, to improve the quality of pediatric IIT, reduce research risks, and enhance management efficiency.Methods:By analyzing the current management situation of high-risk pediatric IIT, optimization strategies were proposed to improve the internal IIT project management system and processes of the pilot unit, and effective management measures are promoted.Results:By revising the IIT project management system, improving the project application and approval processes, strengthening process quality control and personnel training, the risk control and quality supervision of such projects had been enhanced, thereby improving project quality and ensuring the rights and interests of research participants.Conclusions:After the pilot unit trialed a series of management measures for high-risk IIT projects, researchers' risk awareness has significantly increased, and project quality has been effectively improved. The Results provide a reference and model for peers in establishing management rules and also offer theoretical and practical foundations for improving the management system of high-risk clinical research.

Objective:To systematically analyze the incidence and influencing factors of frailty in elderly patients with hematologic malignancies.Methods:Research on frailty in elderly patients with hematologic malignancies was retrieved from Chinese and English databases such as China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science. The search period was from database establishment to August 23, 2024. Two researchers screened the included studies, conducted quality assessment, and extracted data. Meta-analysis was conducted using Stata 18 and RevMan 5.4.Results:A total of seven studies were included, encompassing 19 076 elderly hematologic malignancy patients, with a frailty incidence of 59% [95% CI (0.48, 0.69) ]. Meta-analysis revealed that age [ MD=4.31, 95% CI (3.67, 4.96) ], gender [ OR=0.88, 95% CI (0.83, 0.93) ], alcohol consumption [ OR=1.67, 95% CI (1.15, 2.44) ], self-care ability [ MD=-1.79, 95% CI (-3.17, -0.41) ], anemia [ OR=6.67, 95% CI (2.94, 15.14) ], infection [ OR=1.81, 95% CI (1.16, 2.84) ], and neuropathy [ OR=2.52, 95% CI (1.38, 4.61) ] were the influencing factors of frailty in elderly patients with hematologic malignancies. Conclusions:The incidence of frailty is high in elderly patients with hematologic malignancies. Elderly patients with hematologic malignancies who are older, female, consume alcohol, have low self-care ability, anemia, infections, and neuropathy are prone to frailty. Healthcare providers can conduct early screening and intervention for high-risk populations of frailty based on risk factors to improve the quality of life for elderly hematologic malignancy patients.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To investigate the clinical characteristics and prognosis of T-lymphoblastic lymphoma (T-LBL).Methods:A retrospective case series study was conducted. Clinical data of patients diagnosed with T-LBL at the Affiliated Hospital of Jining Medical University from January 2013 to March 2023 were retrospectively analyzed, and their clinical characteristics and prognosis were statistically analyzed.Results:A total of 22 T-LBL patients were included. Among them, there were 19 males (86.4%) and 3 females (13.6%), and the median age at onset was 19.5 (15, 28) years old. Based on Ann Arbor staging, 3 cases (13.6%) were classified as stage Ⅰ-Ⅱ, while 19 cases (86.4%) were stage Ⅲ-Ⅳ; 10 cases (45.5%) presented with B symptoms, 12 cases (54.5%) without B symptoms; 16 cases (72.7%) showed elevated lactic dehydrogenase (LDH) level. At onset, 7 patients (31.8%) had mediastinal masses, 3 patients (13.6%) had central nervous system involvement, and 17 patients (77.3%) had bone marrow involvement. The overall response rate (ORR) and complete remission rate among the 22 patients were 81.82% (18/22) and 31.82% (7/22), respectively. The ORR was 84.21% (16/19) in 19 patients treated with ALL-like regimens. Among 3 patients treated with NHL-like regimens, 1 case achieved complete remission and 1 case achieved partial remission. Seven patients received allogeneic hematopoietic stem cell transplantation, with a median overall survival (OS) time of 22 months; the median OS time of patients without allogeneic hematopoietic stem cell transplantation was 14 months. The 3-year OS rates in the allogeneic hematopoietic stem cell transplantation group and group without allogeneic hematopoietic stem cell transplantation were 64.30% and 16.00%, and the difference in OS between the two groups was statistically significant ( P = 0.043). Two patients with disease progression prior to transplantation died of multidrug-resistant bacterial infections after transplantation. Conclusions:T-LBL is rare, and it is a highly aggressive tumor that predominantly occurs in adolescent males. Allogeneic hematopoietic stem cell transplantation can prolong OS, reduce relapse and improve the prognosis of patients.