OBJECTIVE To systematically evaluate the effects of oral non-peptidic thrombopoietin receptor agonists （TPO-RAs） on hepatic enzyme in adult patients with immune thrombocytopenia. METHODS A comprehensive literature search was conducted in PubMed， Web of Science， CNKI， Wanfang database and the Chinese Medical Association Journal Full-Text Database to collect randomized controlled trials （RCTs） comparing oral non-peptidic TPO-RAs （intervention group） with placebo or conventional therapy （control group）. All databases were searched from their inception to June 2025. After literature screening， data extraction and quality assessment of the included studies， meta-analysis was conducted using RevMan 5.4.1 software. RESULTS Twelve RCTs comprising 1 388 patients were included， with 971 in the intervention group and 417 in the control group. Meta-analysis results showed that there were no significant differences between the two groups in terms of the incidence of hepatic enzyme elevation[OR＝1.24， 95%CI （0.77， 1.99）， P ＝0.37 ] ， the incidence of hepatic enzyme elevation in patients treated for ≥6 weeks[OR＝1.21， 95%CI （0.73， 1.99）， P ＝0.46 ] ， and the incidence of severe hepatic enzyme elevation[OR＝1.39， 95%CI（0.46， 4.20）， P ＝0.55 ] . Subgroup analysis showed that there were no significant differences in the incidence of hepatic enzyme elevation between the intervention group and control group among patients using eltrombopag[OR＝1.57，95%CI（0.85，2.87）， P ＝0.15 ] ， avatrombopag[OR＝0.88，95%CI （0.09，8.46）， P ＝0.91 ] ， and hetrombopag[OR＝1.04，95%CI（0.30，3.65）， P ＝0.95 ] ， respectively. CONCLUSIONS Oral non-peptidic TPO-RAs do not significantly increase the risk of hepatic enzyme elevation in adult patients with immune thrombocytopenia， and show an overall favorable hepatic safety profile.

Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective To investigate the cross-sectional associations between different fatty liver classifications and cardiac structure and function in people undergo health examination. Methods A total of 6 545 adults who underwent health examinations at the Health Management Center of Zhongshan Hospital, Fudan University between January 1 and December 31, 2017, were retrospectively included. Demographic characteristics and laboratory data were collected. The hepatic steatosis was graded by ultrasonography. And patients with fatty liver were further stratified according to alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, as well as the degree of liver fibrosis. Cardiac morphology and function were assessed by transthoracic echocardiography, and left ventricular geometric patterns were classified accordingly. Multivariate logistic regression analysis was performed to evaluate the associations between fatty liver classifications and cardiac abnormalities. Results There were 2 795 patients (42.7%) with fatty liver, of whom 832 (29.8%) had significant cardiac structural alterations and 1 500 (53.7%) had diastolic dysfunction. Severe fatty liver was risk factor for concentric remodeling and increased relative wall thickness (RWT), with odds ratios (ORs) of 1.27 (P＝0.012) and 1.27 (P＝0.009), respectively. Fatty liver accompanied by elevated ALT or AST was risk factor for concentric remodeling (OR＝1.45,1.56; P＝0.001, 0.001), increased RWT (OR＝1.48,1.57; P＜0.001, ＜0.001), and diastolic dysfunction (OR＝1.27, 1.32; P＝0.035, 0.040), respectively. Fatty liver with liver fibrosis was risk factor for concentric remodeling (OR＝1.83, P＝0.046) and diastolic dysfunction (OR＝2.64, P＝0.034). Conclusions Advanced fatty liver, including severe hepatic steatosis, accompanied by elevated liver enzymes or liver fibrosis, could increase risks of cardiac remodeling and diastolic dysfunction, while systolic function is preserved. For patients with fatty liver, it is recommended to undergo regular ultrasonography examination.

Objective Under the operation background of Diagnosis-Intervention Packet(DIP),whether there is interaction between reducing medical cost and average length of stay combined with pre-hospitalization mode,and whether there is difference between different departments and diseases in interaction.Methods Based on real-world data from 71 453 patients admitted to Guizhou Provincial People's Hospital from July to December 2021,a two-way analysis of variance was employed.When the interaction effect was statistically significant,parameter estimation was used to determine the magnitude and direction of the interaction effect,followed by subgroup analyses by department and disease.Results Without adjustment,both total medical costs and average length of stay exhibited a negative interaction effect(P＜0.05).Subgroup analyses revealed that in terms of total medical costs,the effect size for the surgical system was 0.18％,lower than that for the internal medicine system(0.70％);for core diseases,it was 6.62％,lower than that for comprehensive diseases(7.71％).Regarding average length of stay,the effect size for the surgical system was 0.55％,better than that for the internal medicine system(0.22％);for core diseases,it was 8.70％,higher than that for comprehensive diseases(2.90％).Conclusion The combination of DIP payment reform and pre-admission management model demonstrates a synergistic effect,effectively reducing patients' medical costs and length of stay.This effect is influenced by disease complexity and the standardization of diagnostic and treatment processes.

Objective To investigate the correlation of serum levels of Spexin,FoxO1 and insulin resistance(IR)with prognosis in patients with gestational diabetes mellitus(GDM).Methods A total of 198 patients with GDM were prospectively selected as the GDM group,and 195 healthy pregnant women who underwent physical examinations during the same period were selected as the control group.The age at enrollment,gestational age,triglyceride(TG),pre-pregnancy body weight,fasting insulin(FINS),parity,fasting blood glucose(FBG),total cholesterol(TC)and homeostasis model assessment of insulin resistance index(HOMA-IR)of the subjects were collected.The serum levels of Spexin and FoxO1 in subjects were detected by enzyme-linked immunosorbent assay(ELISA).According to the pregnancy outcome,the GDM patients were divided into the adverse pregnancy outcome group(96 cases)and the good pregnancy outcome group(102 cases).The correlations between serum Spexin,FoxO1,and HOMA-IR in GDM patients were analyzed by Pearson's method.Logistic regression was used to analyze risk factors affecting the pregnancy outcome of GDM patients.The predictive value of serum Spexin and FoxO1 levels for the pregnancy outcome of GDM patients was analyzed by receiver operating characteristic(ROC)curve.Results The serum levels of FINS,TG,FBG,Spexin,FoxO1 and HOMA-IR were higher in the GDM group than those in the control group(P＜0.01).Pearson correlation analysis showed that serum levels of Spexin and FoxO1 in GDM patients were positively correlated with HOMA-IR,and serum level of Spexin was positively correlated with FoxO1(P＜0.05).The incidences of gestational hypertension,cesarean section,macrosomia,neonatal malformations,low birth weight infants and neonatal asphyxia were higher in the GDM group than those in the control group(P＜0.05).Serum levels of Spexin and FoxO1 and FINS,FBG and HOMA-IR were significantly higher in the adverse pregnancy group than those in the good pregnancy group(P＜0.01).Multivariate Logistic regression analysis showed that the increased Spexin and FoxO1 were the risk factor for adverse pregnancy outcomes in GDM patients(P＜0.01).The ROC curve analysis showed that the area under the curve(AUC)of serum Spexin and FoxO1 levels for predicting pregnancy outcomes in GDM patients was 0.887 and 0.883,respectively,and the AUC of combined prediction was 0.942.Conclusion Serum levels of Spexin and FoxO1 are elevated in GDM patients,and both are related to IR.The combination of the two can assist in judging the pregnancy outcome of GDM patients.

AIM:To evaluate the safety and toler-ability of single dose oral BTK inhibitor YZJ-3058 tablets under fasting conditions in healthy adults,as well as the pharmacokinetic and pharmacologi-cal characteristics of YZJ-3058 and its metabolites.METHODS:A total of 22 healthy subjects were en-rolled in this experiment and administered a single dose orally.They were divided into three groups:50 mg,100 mg,and 200 mg.Among them,2 sub-jects were enrolled in the 50 mg dose group,and 10 subjects were enrolled in the 100 mg and 200 mg dose groups,respectively.RESULTS:In healthy subjects,YZJ-3058 tablets were administered orally on an empty stomach at doses of 50,100,and 200 mg,with a median Tmax of 1.25 to 2.00 hours and an average Cmax of 62.85,89.44,and 99.20 ng/mL,re-spectively.The average AUC0-t was 183.87,297.72,and 453.98 h·ng-1·mL,respectively.The average AUC0-∞ was 189.30,321.33,and 551.44 h·ng-1·mL,and the median t1/2 was 1.16,5.06,and 7.97 hours,respectively.After a single oral administration of 50,100,and 200 mg YZJ-3058 tablets,the highest target occupancy rate was achieved at 4 hours.The average BTK occupancy rates at 24 hours after ad-ministration were 88.95％,96.73％,and 99.24％,re-spectively.The average BTK occupancy rates at 48 hours after administration were 75.65％,89.80％,and 96.68％,respectively.No serious adverse events or adverse events leading to withdrawal oc-curred,and all subjects had good tolerability.CON-CLUSION:YZJ-3058 tablets have good safety and tolerability for single oral administration on an empty stomach in healthy subjects within the dose range of 50-200 mg.Cmax and AUC increase with dose,with fast absorption and saturation.The ter-minal elimination rate gradually slows down with dose increase,and it has a significant and sus-tained occupying effect on BTK targets.

Objective:To investigate the predictive value of platelet-to-albumin ratio (PAR) for organ failure in patients with acute pancreatitis (AP).Methods:The clinical data of 128 patients with AP from January 2021 to January 2024 in Affiliated Hospital of Jining Medical College were retrospectively analyzed. Among them, 68 patients developed organ failure (failure group), and 60 patients did not develop organ failure (non-failure group). The inflammatory indexes on admission were compared between the two groups. The severity of illness was evaluated by acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA). Pearson method was employed for correlation analysis. The receiver operating characteristic (ROC) curve was utilized to analyze the efficacy of PAR in predicting organ failure in patients with AP.Results:The APACHE Ⅱ, SOFA, white blood cell, platelet, red blood cell distribution width, C-reactive protein, fasting blood glucose, blood urea nitrogen, interleukin 6 (IL-6) and PAR in failure group were significantly higher than those in non-failure group: (25.91 ± 1.46) scores vs. (20.98 ± 1.46) scores, (7.03 ± 0.17) scores vs. (5.51 ± 0.33) scores, (11.22 ± 1.77) × 10 9/L vs. (9.32 ± 1.81) × 10 9/L, (200.12 ± 24.11) × 10 9/L vs. (173.18 ± 17.19) × 10 9/L, 0.134 ± 0.007 vs. 0.112 ± 0.007, (64.12 ± 7.38) mg/L vs. (46.93 ± 9.07) mg/L,(7.23 ± 1.09) mmol/L vs. (6.56 ± 0.87) mmol/L, (6.46 ± 1.17) mmol/L vs. (3.91 ± 0.39) mmol/L, (207.32 ± 74.29) ng/L vs. (109.27 ± 33.55) ng/L and 5.79 ± 0.98 vs. 4.30 ± 0.79, the serum calcium and albumin were significantly lower than those in non-failure group: (1.58 ± 0.09) mmol/L vs. (2.19 ± 0.32) mmol/L and (35.04 ± 4.05) g/L vs. (41.10 ± 5.79) g/L, and there were statistical differences ( P<0.01). Pearson correlation analysis result showed that PAR was positively correlated with APACHE Ⅱ, SOFA, white blood cell, platelet, red blood cell distribution width, C-reactive protein, fasting blood glucose, blood urea nitrogen and IL-6 ( r = 0.559, 0.623, 0.237, 0.782, 0.511, 0.392, 0.287, 0.555 and 0.505; P<0.01), and negatively correlated with serum calcium and albumin ( r = - 0.526 and - 0.820, P<0.01). ROC curve analysis result showed that the area under the curve of PAR for predicting organ failure in patients with AP was 0.875 (95% CI 0.818 to 0.933), with an optimal cutoff value of 4.56, sensitivity of 91.2%, and specificity of 66.7%. Conclusions:PAR can effectively predict the occurrence of organ failure in AP patients with high sensitivity, providing certain guiding significance for clinical treatment.

Objective:To explore the application value of part-cut jejunal transection in digestive tract reconstruction of totally laparoscopic total gastrectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 112 patients with gastric cancer who underwent totally laparoscopic total gastrectomy in The Second Affiliated Hospital of Anhui Medical University from June 2018 to September 2022 were collected. There were 81 males and 31 females, aged (70±8)years. Among the 112 patients, 60 patients undergoing diges-tive tract reconstruction by Roux-en-Y anastomosis with part-cut jejunum were set as the part-cut group, and 52 patients undergoing digestive tract reconstruction by traditional Roux-en-Y anasto-mosis were set as the traditional group. Observation indicators: (1) propensity score matching status and comparison of clinical data of patients between the two groups after matching; (2) intraopera-tive and postoperative conditions; (3) follow-up. Comparison of measurement data with normal dis-tribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Com-parison of ordinal data was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶1 nearest neighbor matching method, with the caliper value of 0.02. Results:(1) Propensity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 112 patients, 90 patients were successfully matched, with 45 cases in each of the part-cut group and the traditional group. After propensity score matching, the elimination of body mass index, clinical TNM staging confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After propensity score matching, the total operation time and digestive tract reconstruction time of patients in the part-cut group were (217.0±15.1)minutes and (34.7±1.8)minutes, versus (252.6±21.9)minutes and (52.6±7.4)minutes in the traditional group, respectively, showing significant differences in the above indicators between the two groups ( t=?8.97, ?15.66, P<0.05). (3) Follow-up. After propensity score matching, 90 patients were followed up postoperatively for (47±15)months. During the follow-up, no patient in either group received secondary surgery, and there was no death. There were 3 cases and 10 cases of Roux stasis syndrome in the part-cut group and the traditional group, respectively, showing a significant difference between the two groups ( χ2=4.41, P<0.05). Conclusion:Compared with traditional Roux-en-Y anastomosis, the Roux-en-Y anastomosis with part-cut jejunum in totally laparoscopic total gastrectomy can signifi-cantly shorten the time for digestive tract reconstruction and reduce the incidence of postoperative Roux stasis syndrome.

Objective:To investigate the value of coronary CTA (CCTA)-based traditional features and radiomics of plaque in the identification of culprit lesions that caused acute myocardial infarction (AMI).Methods:This was a retrospective multicenter study. From July 2016 to November 2023, a total of 344 patients from the Affiliated Hospital of Qingdao University (training cohort, n=184), Shandong Provincial Hospital Affiliated to Shandong First Medical University (validation cohort, n=88) and Qilu Hospital of Shandong University (test cohort, n=72) who received percutaneous coronary intervention (PCI) due to AMI and underwent CCTA within 48 hours of AMI were enrolled. The culprit plaques and non-culprit plaques were identified using a combination of electrocardiogram, CCTA, and angiographic findings. The vessel, plaque location, plaque type, Coronary Artery Disease-Reporting and Data System (CAD-RADS) score, high-risk plaque characteristics, plaque length, plaque volume, and burden were analyzed, and 1 904 radiomics features were extracted for each plaque. The traditional imaging model, the radiomics model, and the combined model were established by using multivariate Logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each model in identifying culprit lesions. The DeLong test was used for the comparison of AUC between every two models. The net reclassification index (NRI) was used to evaluate the incremental value of the combined model to the traditional imaging model and the radiomics model. The decision curve analysis (DCA) was used to assess the clinical net benefit of these models. A correlation heatmap was used to evaluate the correlation between the radiomics score and traditional CCTA factors. The interpretable analysis of the decision process of the combined model was performed by the Shapley Additive exPlanations (SHAP). Results:In the validation cohort and the test cohort, the AUC of the traditional imaging model developed by the vessel, plaque type, positive remodeling and CAD-RADS score was 0.898 (95% CI 0.869-0.922) and 0.881 (95% CI 0.848-0.910), respectively. The radiomics model developed by six radiomics features was 0.863 (95% CI 0.831-0.891) and 0.863 (95% CI 0.827-0.864), respectively. The AUC of the combined model was 0.930 (95% CI 0.905-0.950)and 0.919 (95% CI 0.889-0.942), respectively. In the validation cohort and the test cohort, the AUC of the combined model was higher than that of the traditional imaging model ( Z=4.013, 4.272, P<0.001) and that of the radiomics model ( Z=4.819, 3.784, P<0.001), respectively. In the validation cohort, the combined model yielded an NRI of 20.43% (95% CI 10.43%-30.44%, P<0.001) and 20.21% (95% CI 9.62%-30.80%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. In the test cohort, the combined model yielded an NRI of 28.05% (95% CI 16.72%-39.38%, P<0.001) and 23.57% (95% CI 13.58%-33.56%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. DCA showed the combined model had the highest clinical net benefit. The correlation heatmap showed the radiomics score was not correlated or only weakly correlated with traditional CCTA factors. SHAP indicated the radiomics and CAD-RADS score contributed significantly to the model. Conclusion:The CCTA-based traditional features and radiomics of plaque have favorable performance for the identification of culprit plaques in patients with AMI.

BACKGROUND:In recent years,human pluripotent stem cell derived kidney organoids and rodent models of diabetic kidney disease have also made some progress.However,because the pathogenesis of diabetic kidney disease is affected by environmental factors and genetic factors,the pathogenesis is complex,and the clinical treatment for diabetic kidney disease patients needs to vary from person to person.Therefore,more flexible and integrated approaches need to be developed,leading to the discovery of strong preclinical evidence to support more targeted interventions in patients with diabetic kidney disease.OBJECTIVE:To reviewthe research progress of diabetic kidney disease model from the aspects of diabetic kidney disease animal model,two-dimensional cell culture simulation diabetic kidney disease model,and three-dimensional organoid diabetic kidney disease model,to provide clues and ideas for further research.METHODS:China National Knowledge Network and PubMed databases were searched with"diabetes,diabetic nephropathy,diabetic kidney diseases,diabetic nephropathy models,diabetic nephropathy animal models,organoids,diabetic and organoids,diabetic and kidney organoids,kidney organoids,diabetic nephropathy cell models,diabetic nephropathy syndrome combined animal models"as Chinese and English search terms.Totally 101 articles were finally included for review and analysis.RESULTS AND CONCLUSION:Both in vivo and in vitro models of diabetic kidney disease are powerful tools to further study the pathogenesis of diabetic kidney disease.The interactions between multiple systems can be observed in animal models.Two-dimensional cell culture is easy to operate and low cost.The emerging kidney organoids fill the gap between two-dimensional and global levels,without species differences,and simulate the complexity of human kidney to a certain extent.With the continuous development of organoid technology,kidney organoids are expected to provide a new perspective for exploring the pathogenesis,pathophysiology,and drug screening of diabetic kidney disease.