Objective:To investigate the value of tumor volume to uterine volume ratio (N/U) combined with the expression of alpha-fetoprotein (AFP), sugar antigen 199 (CA199) and human epididymal secretory protein 4 (HE4) in evaluating the pathologic grade and prognosis of endometrial carcinoma (EC) .Methods:A total of 160 EC patients admitted to Linyi Central Hospital from Jan. 2021 to Dec. 2023 were divided into low-grade group and high-grade group according to FIGO grading method, and were divided into poor prognosis group and good prognosis group according to cancer death, recrudescence. The levels of N/U, AFP, CA199 and HE4 in patients with different pathologic grades and prognosis were compared. COX regression was used to analyze the influencing factors of EC adverse prognosis, ROC curve was used to analyze the value of N/U combined with serum AFP, CA199 and HE4 in predicting EC adverse prognosis, and a nomogram model was constructed.Results:Pathological examination of 160 EC patients showed that 12 cases were non-endometrioid adenocarcinoma, 148 cases were endometrioid adenocarcinoma, 41 cases were high-grade and 119 cases were low-grade.According to the follow-up, 94 of the 160 EC patients had good prognosis and 66 had poor prognosis. The levels of N/U, AFP, CA199 and HE4 in the poor prognosis group were higher than those in the good prognosis group ( P<0.05). COX regression analysis showed that high levels of N/U, AFP, CA199 and HE4 were all factors affecting the poor prognosis of EC patients ( P<0.05). The AUC value of combined detection of N/U, AFP, CA199 and HE4 in predicting adverse prognosis of EC patients was higher than that of single detection ( Z=3.140, 3.658, 4.277, 4.378, P<0.05) .The ROC curve AUC (95% CI) of the training set and the validation set were 0.84 (0.77-0.92) and 0.90 (0.81-0.98) respectively for the training set and the validation set to predict the adverse prognosis of EC patients. Calibration curve results showed that the calibration curve for EC patients predicted by the nomogram model was close to the ideal curve ( P=0.521, 0.743). The DCA curve shows that the probability threshold of the nomogram model has a higher positive net return at 20%~100%. Conclusion:The levels of N/U, AFP, CA199 and HE4 in EC patients are related to the pathologic grade, and the combined detection of these indicators can predict the poor prognosis of EC patients, and the nomogram model constructed based on these indicators has high predictive value.

Objective:To investigate the value of tumor volume to uterine volume ratio (N/U) combined with the expression of alpha-fetoprotein (AFP), sugar antigen 199 (CA199) and human epididymal secretory protein 4 (HE4) in evaluating the pathologic grade and prognosis of endometrial carcinoma (EC) .Methods:A total of 160 EC patients admitted to Linyi Central Hospital from Jan. 2021 to Dec. 2023 were divided into low-grade group and high-grade group according to FIGO grading method, and were divided into poor prognosis group and good prognosis group according to cancer death, recrudescence. The levels of N/U, AFP, CA199 and HE4 in patients with different pathologic grades and prognosis were compared. COX regression was used to analyze the influencing factors of EC adverse prognosis, ROC curve was used to analyze the value of N/U combined with serum AFP, CA199 and HE4 in predicting EC adverse prognosis, and a nomogram model was constructed.Results:Pathological examination of 160 EC patients showed that 12 cases were non-endometrioid adenocarcinoma, 148 cases were endometrioid adenocarcinoma, 41 cases were high-grade and 119 cases were low-grade.According to the follow-up, 94 of the 160 EC patients had good prognosis and 66 had poor prognosis. The levels of N/U, AFP, CA199 and HE4 in the poor prognosis group were higher than those in the good prognosis group ( P<0.05). COX regression analysis showed that high levels of N/U, AFP, CA199 and HE4 were all factors affecting the poor prognosis of EC patients ( P<0.05). The AUC value of combined detection of N/U, AFP, CA199 and HE4 in predicting adverse prognosis of EC patients was higher than that of single detection ( Z=3.140, 3.658, 4.277, 4.378, P<0.05) .The ROC curve AUC (95% CI) of the training set and the validation set were 0.84 (0.77-0.92) and 0.90 (0.81-0.98) respectively for the training set and the validation set to predict the adverse prognosis of EC patients. Calibration curve results showed that the calibration curve for EC patients predicted by the nomogram model was close to the ideal curve ( P=0.521, 0.743). The DCA curve shows that the probability threshold of the nomogram model has a higher positive net return at 20%~100%. Conclusion:The levels of N/U, AFP, CA199 and HE4 in EC patients are related to the pathologic grade, and the combined detection of these indicators can predict the poor prognosis of EC patients, and the nomogram model constructed based on these indicators has high predictive value.

Objective:To investigate the causal impact of maternal smoking around birth(MSAB)on off-spring's risk of attention deficit hyperactivity disorder(ADHD),autism spectrum disorder(ASD),bipolar disorder(BD),and major depressive disorder(MDD).Methods:The datasets for MSAB and 4 psychiatric disorders were extracted from genome-wide association studies(GWAS).Mendelian randomization(MR)was employed,using in-verse variance weighting(IVW)as the primary analysis method.Sensitivity analyses and outlier correction were conducted using weighted median(WM),MR-Egger regression,and MR-PRESSO.The results were expressed as odds ratios(OR)and corrected for false discovery rate(FDR).Results:MR analysis showed significant causal re-lationships between MSAB and increased risk of ADHD(OR=5.36,95％CI=2.58-7.63,PFDR=0.003),MDD(OR=1.92,95％CI=1.29-2.88,PFDR=0.003),and BD(OR=6.33,95％CI=1.56-8.73,PFDR=0.013).However,no statistically significant association was found between MSAB and ASD(OR=1.66,95％CI=0.23-5.87,PFDR=0.616).Conclusion:This study suggests a potential causal link between maternal smoking around the time of birth and an increased risk of attention deficit hyperactivity disorder,bipolar disorder,and major depressive disorder in offspring.

Objective:To investigate the causal impact of maternal smoking around birth(MSAB)on off-spring's risk of attention deficit hyperactivity disorder(ADHD),autism spectrum disorder(ASD),bipolar disorder(BD),and major depressive disorder(MDD).Methods:The datasets for MSAB and 4 psychiatric disorders were extracted from genome-wide association studies(GWAS).Mendelian randomization(MR)was employed,using in-verse variance weighting(IVW)as the primary analysis method.Sensitivity analyses and outlier correction were conducted using weighted median(WM),MR-Egger regression,and MR-PRESSO.The results were expressed as odds ratios(OR)and corrected for false discovery rate(FDR).Results:MR analysis showed significant causal re-lationships between MSAB and increased risk of ADHD(OR=5.36,95％CI=2.58-7.63,PFDR=0.003),MDD(OR=1.92,95％CI=1.29-2.88,PFDR=0.003),and BD(OR=6.33,95％CI=1.56-8.73,PFDR=0.013).However,no statistically significant association was found between MSAB and ASD(OR=1.66,95％CI=0.23-5.87,PFDR=0.616).Conclusion:This study suggests a potential causal link between maternal smoking around the time of birth and an increased risk of attention deficit hyperactivity disorder,bipolar disorder,and major depressive disorder in offspring.

OBJECTIVE To understand the safety of Ilaprazole sodium for injection in clinical practice. METHODS From Jan. 1st 2019 to Feb. 29th 2020， the data of 3 926 valid hospitalized patients receiving Ilaprazole sodium for injection were collected prospectively from 5 third-level hospitals through CHPS， and the post-marketing safety analysis was performed by using retrospective multicenter single cohort study. At the same time， a nested case-control study （the ratio of trial group and control group was 1∶4） was used to confirm the baseline stability of this study cohort and the correlation between adverse reactions and Ilaprazole sodium for injection. RESULTS Among 3 926 patients， 3 patients experienced 5 adverse drug events after using Ilaprazole sodium for injection， with the incidence of 0.076%. There was no serious adverse event， and the occurrence time was 2 days after medication； adverse drug events mainly include elevated liver function indicators （alanine transaminase， aspartate transaminase， total bilirubin）， which were mild and untreated， and all adverse drug events were improved. The results of the nested case-control study showed that the trial group and the control group belonged to the same background baseline， and the occurrence of adverse drug events was more closely related to Ilaprazole sodium for injection. CONCLUSIONS The overall safety of Ilaprazole sodium for injection is relatively high， and the occurrence of adverse events is more related to it.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

AIM: To evaluate the bioequivalence of the test and reference formulations of mycophenolate mofetil capsule in Chinese healthy male subjects under fasting and fed conditions. METHODS: This was a 2-treatment, 2-sequence, 4-period, fully replicated crossover study that included 80 Chinese healthy male subjects (40 subjects in the fasting group and 40 subjects in the fed group, respectively). Subjects were assigned to receive a single oral administration of the test or reference formulation at a dose of 0.25 g in each period. The plasma concentration of mycophenolate mofetil (MMF) and metabolite mycophenolic acid (MPA) were analyhed by LC-MS/MS. The major pharmacokinetic parameters of MMF and MPA were calculated using non-compartmental analysis by WinNonlin 8.0. The statistical analysis was performed by SAS 9.4. Average bioequivalence (ABE) analysis was applied where it has been demonstrated that the within-subject standard deviation of the reference formulation (S

Development of thoracolumbar vertebra (TLV) and rib primordium (RP) is a common evolutionary feature across vertebrates, although whole-organism analysis of the expression dynamics of TLV- and RP-related genes has been lacking. Here, we investigated the single-cell transcriptome landscape of thoracic vertebra (TV), lumbar vertebra (LV), and RP cells from a pig embryo at 27 days post-fertilization (dpf) and identified six cell types with distinct gene expression signatures. In-depth dissection of the gene expression dynamics and RNA velocity revealed a coupled process of osteogenesis and angiogenesis during TLV and RP development. Further analysis of cell type-specific and strand-specific expression uncovered the extremely high level of HOXA10 3'-UTR sequence specific to osteoblasts of LV cells, which may function as anti-HOXA10-antisense by counteracting the HOXA10-antisense effect to determine TLV transition. Thus, this work provides a valuable resource for understanding embryonic osteogenesis and angiogenesis underlying vertebrate TLV and RP development at the cell type-specific resolution, which serves as a comprehensive view on the transcriptional profile of animal embryo development.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

AIM: To study chronopharmacokinetics of helicid and its metabolites. METHODS: An HPLC-MS method for simultaneous determination of helicid and its three phase I metabolites were established and validated. At 8:00, 14:00 and 0:00, the rats were given helicid 50 mg/kg by gavage, respectively. Blood samples were collected from ophthalmic venous plexus. Then plasma concentration was measured. Pharmacokinetic behaviors of the original drug and its metabolites after administration at different time points were calculated and compared. RESULTS: This established HPLC-MS/MS method was successfully applied to simultaneous determination of helicid and its three metabolites in rat plasma after intragastric administration. Using AUC