OBJECTIVES: To compare the commonly used methods for analyzing treatment switching in clinical trials to facilitate selection of optimal methods in different scenarios. METHODS: Based on the data characteristics of patient conversion in oncology clinical trials, we simulated the survival time of patients across different scenarios and compared the bias, mean square error and coverages of the treatment effects derived from different methods. RESULTS: The sample size had an almost negligible impact on the outcomes of the various methods. Compared to conventional methods, more complex methods (RPSFTM, IPCW, TSE, and IPE) resulted in lower errors across different scenarios. The IPCW method could cause a significant increase in errors in cases where the probability of conversion was high. The TSE method had the lowest error and mean squared error when the risk was low and the probability of conversion was high. The IPE method had an obvious advantage in the scenario with a low probability of conversion, but it may slightly underestimate the treatment effect when the inflation factor was small. CONCLUSIONS The choice of a specific method for analyzing cohort transition should be made based on considerations of both the probability of conversion and inflation factor in different scenarios.
Humans ; Clinical Trials as Topic/methods* ; Neoplasms/therapy*

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from spouses. Methods A total of 141 couples were included.Blood and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann-Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,respectively.Logistic models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET outcomes. Results Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization rate.However,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical pregnancy. Conclusion Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy rate.This is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive system.However,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.

Objective To explore the applicable conditions of the Cox-TEL(Cox PH-Taylor expansion adjustment for long-term survival data)method for analysis of survival data that contain cured patients.Methods The simulated survival data method based on Weibull distribution was used to simulate and generate the survival data with different cure rates,censored rates,and cure rate differences.The Cox-TEL method was used for analysis of the generated simulation data,and its performance was evaluated by calculating its type I error and power.Results Almost all the type I error of the hazard ratios(HRs)obtained by the Cox-TEL method under different conditions were slightly greater than 0.05,and this method showed a good test power for estimating the HRs for data with a large sample size and a large difference in proportions(DPs).For the data of cured patients,the type I error of the DPs obtained by the Cox-TEL method was well around 0.05,and its test power was robust in most of the scenarios.Conclusion The Cox-TEL method is effective for analyzing data of uncured patients and obtaining reliable HRs for most of the survival data with a sample size,a low censored rates,and a large difference in cure rates.The method is capable of accurately estimating the DPs regardless of the sample size,censored rates,or the cure rates.

Objective To prepare indocyanine green(ICG)-loaded platelet membrane biomimetic liposome(ICG-PLP)for tumor photothermal therapy,and to preliminarily evaluate its in vitro characteristics.Methods ICG-PLP was prepared by an ultrasound method,and its particle size and zeta potential were determined using a laser particle size analyzer.The encapsulation efficiency of ICG-PLP was detected by ultraviolet spectrophotometry.The photothermal properties of ICG-PLP were investigated under 808 nm near-infrared ray irradiation(2 W/cm2),and the retention of platelet membrane proteins was observed by sodium dodecylsulfate-polyacrylamide gel electrophoresis.The uptake of ICG-PLP by mouse macrophage RAW264.7,human non-small cell lung cancer cell A549,mouse melanoma cell B16-F10,and mouse breast cancer cell 4T1 was observed by a laser confocal microscope.Furthermore,the phototoxicity of ICG-PLP was detected by methyl thiazolyl tetrazolium assay,and the safety of ICG-PLP was preliminarily evaluated according to hemolysis rate and cytocompatibility.Besides,the in vivo retention time of ICG,ICG-loaded liposome and ICG-PLP in healthy SD rats was observed after tail vein injection.Results ICG-PLP was successfully prepared and its encapsulation efficiency,particle size,zeta potential,and the polydispersity index were(97.68±0.01)％,(109.77±0.76)nm,(-21.23±0.84)mV,and 0.22±0.01,respectively.ICG-PLP well retained the proteins on platelet membrane and showed good photothermal properties.Platelet membrane enhanced the uptake of biomimetic nanoparticles by tumor cells A549,B16-F10,and 4T1,and reduced the phagocytosis of biomimetic nanoparticles by macrophages.ICG-PLP exhibited a favorable photothermal therapy effect and could kill tumor cells.Additionally,ICG-PLP displayed a good safety.After intravenous administration,ICG-PLP prolonged the in vivo retention time of ICG in healthy SD rats.Conclusion ICG-PLP has been successfully constructed.It has a great potential in targeted drug delivery and tumor photothermal therapy.

Objective:This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD + R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods:The clinical data of 26 patients with FLT3-ITD + R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results:A total of 26 patients with FLT3-ITD + R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95% CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment ( P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion:The Gilt-based combination therapy is highly effective in treating FLT3-ITD + R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.

Objective To explore the applicable conditions of the Cox-TEL(Cox PH-Taylor expansion adjustment for long-term survival data)method for analysis of survival data that contain cured patients.Methods The simulated survival data method based on Weibull distribution was used to simulate and generate the survival data with different cure rates,censored rates,and cure rate differences.The Cox-TEL method was used for analysis of the generated simulation data,and its performance was evaluated by calculating its type I error and power.Results Almost all the type I error of the hazard ratios(HRs)obtained by the Cox-TEL method under different conditions were slightly greater than 0.05,and this method showed a good test power for estimating the HRs for data with a large sample size and a large difference in proportions(DPs).For the data of cured patients,the type I error of the DPs obtained by the Cox-TEL method was well around 0.05,and its test power was robust in most of the scenarios.Conclusion The Cox-TEL method is effective for analyzing data of uncured patients and obtaining reliable HRs for most of the survival data with a sample size,a low censored rates,and a large difference in cure rates.The method is capable of accurately estimating the DPs regardless of the sample size,censored rates,or the cure rates.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective: : The spontaneous intracerebral hemorrhage (ICH) remains a significant cause of mortality and morbidity throughout the world. The purpose of this retrospective study is to develop multiple models for predicting ICH outcomes using machine learning (ML). Methods: : Between January 2014 and October 2021, we included ICH patients identified by computed tomography or magnetic resonance imaging and treated with surgery. At the 6-month check-up, outcomes were assessed using the modified Rankin Scale. In this study, four ML models, including Support Vector Machine (SVM), Decision Tree C5.0, Artificial Neural Network, Logistic Regression were used to build ICH prediction models. In order to evaluate the reliability and the ML models, we calculated the area under the receiver operating characteristic curve (AUC), specificity, sensitivity, accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR). Results: : We identified 71 patients who had favorable outcomes and 156 who had unfavorable outcomes. The results showed that the SVM model achieved the best comprehensive prediction efficiency. For the SVM model, the AUC, accuracy, specificity, sensitivity, PLR, NLR, and DOR were 0.91, 0.92, 0.92, 0.93, 11.63, 0.076, and 153.03, respectively. For the SVM model, we found the importance value of time to operating room (TOR) was higher significantly than other variables. Conclusion : The analysis of clinical reliability showed that the SVM model achieved the best comprehensive prediction efficiency and the importance value of TOR was higher significantly than other variables.