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 investigate the association between plasma atherogenic index of plasma(AIP)and metabolism-associated steatotic liver disease(MASLD),and to evaluate the potential value of AIP as a predictive marker for MASLD risk.Methods We enrolled a total of 4 850 health check-up participants from The Second Affiliated Hospital of Xi'an Jiaotong University between June 2021 and May 2023.The participants were divided into quartiles(Q1-Q4)according to their AIP level.Biochemical indicators and MASLD prevalence were compared across groups.Logistic regression,subgroup analysis,and restricted cubic splines(RCS)were used to explore the relationship between AIP and MASLD.Results Among the 4 850 participants,the prevalence of MASLD was 26.08％(1 265/4 850).MASLD prevalence increased across AIP quartiles:4.0％,13.8％,30.8％,and 55.6％in Q1-Q4,respectively(P＜0.001).Compared with Q1,Q2-Q4 groups showed higher proportions of males,BMI,smokers,overweight/obesity,central obesity,prediabetes,hypertension,serum uric acid,and fatty liver index(FLI)(all P＜0.001).Lipid profiles worsened with increased AIP:total cholesterol,triglycerides,and LDL-C increased,while HDL-C decreased(P＜0.001).RCS analysis demonstrated a significant linear relationship between AIP and MASLD risk.After adjusting for confounders,the participants in Q4 had an 8.71-fold higher risk of MASLD than those in Q1(OR:8.71,95％CI:6.20-12.23,P＜0.001).A composite model incorporating AIP,BMI,and FLI showed superior discriminative performance(AUC:0.883,95％CI:0.873-0.892).Interaction analysis suggested that AIP had significant interactions with BMI,hypertension,and prediabetes(P＜0.05).In individuals without these metabolic abnormalities,the association between AIP and MASLD was more pronounced.Conclusion Elevated AIP was significantly associated with an increased risk of MASLD,with a stronger association observed in individuals with normal BMI,blood pressure,and blood glucose levels,suggesting that AIP may serve as a potential indicator for early screening of MASLD.

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.

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 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 explore the feasibility and preliminary efficacy of domestic single-port robotic surgical system in the surgical treatment of thyroid cancer. Methods:Thyroid cancer patients who underwent domestic single-port robotic surgery in the Department of Head and Neck Surgery of Sichuan Cancer Hospital from June 2024 to January 2025 were prospectively included. Clinical data, oncological characteristics, and perioperative indicators were systematically collected. Results:A total of 7 patients were included, including 3 males and 4 females, with an age of （34.57±10.26） years. All procedures were successfully completed without conversion to open surgery. Operative time was（180.00±30.41） minutes. Blood loss was（5.00[15.00 ]）mL. Postoperative drainage volume was （167.86±130.95） mL. The postoperative pathological results were all thyroid papillary carcinoma. There were no system failures, no device-related complications and adverse events were observed during the operation and perioperative period. No tumor recurrence or metastasis was observed during the follow-up period. Conclusion:Preliminary data indicate that the domestic single-port robotic surgical system is safe and feasible for the surgical treatment of thyroid cancer, providing a practical basis for subsequent multi-disease, multi-center, and large-sample studies.
Humans ; Thyroid Neoplasms/surgery* ; Robotic Surgical Procedures/instrumentation* ; Male ; Female ; Adult ; Thyroidectomy/methods* ; Operative Time ; Middle Aged ; Prospective Studies

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

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.