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 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 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.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective:To investigate the diagnosis, treatment, clinical characteristics and potential high-risk factors of cerebral venous sinus thrombosis (CVST) during the treatment of acute lymphoblastic leukemia (ALL) with pegaspargase.Methods:The medical history, diagnosis and treatment process, laboratory examination and imaging examination results of 3 ALL patients with CVST during pegaspargase treatment in the First Affiliated Hospital of Suzhou University in March and November 2021 and September 2022 were retrospectively analyzed, and the relevant literature was reviewed.Results:Three patients were all female, with the aged between 15 and 35 years old, including 2 cases of B-ALL and 1 case of T-ALL. All patients developed nervous system symptoms after pegaspargase chemotherapy, and were diagnosed as CVST by imaging examination. During the pegaspargase treatment, 2 patients took norethisterone, and 1 patient underwent induced labor and curettage. The levels of sexual hormones in the 3 patients had non-physiological changes. The main CVST lesions were located in the superior sagittal sinus, transverse sinus and sigmoid sinus. One patient had cerebral hemorrhage at the same time. When thrombus occurred, the fibrinogen (Fib), antithrombin Ⅲ (AT Ⅲ) activity, protein C activity and protein S activity of the patients were significantly lower than those before, D-dimer was significantly higher, and lupus anticoagulant and anticardiolipin antibody were negative. The thrombosis treatment was mainly anticoagulation, and 1 patient underwent thrombolysis. Two patients had no sequelae of nervous system, and 1 patient had the sequelae of muscle weakness.Conclusions:Patients with ALL should be alert to the occurrence of CVST when they have nervous system symptoms during pegaspargase chemotherapy. The diagnosis of CVST mainly depends on cranial imaging. Anticoagulation is the main thrombosis treatment, thrombolysis and interventional thrombectomy are feasible for some patients, with few neurological sequelae. The use of second-generation progesterone drugs and the non-physiological fluctuation of sex hormones may be the potential risk factors of CVST.