Objective To establish a stable and reliable sepsis model of rat after liver transplantation (LT) for clinical translational research and analyze its characteristics. Methods The "two-sleeve method" was used to establish the in situ LT model of SD rats, and the sepsis model was constructed through cecal ligation and puncture (CLP) at 3 d after the operation. SD rats were randomly divided into 3 groups: sham operation group (Sham group), LT group, and LT + CLP group, with 6 rats in each group. The changes in body weight, rectal temperature and survival rate were compared, and the sepsis score was used for evaluation. The levels of blood biochemical indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Urea), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH)] and inflammatory factors [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α] in each group were detected, and the pathological changes and cell apoptosis in different organs were observed. Results Compared with the Sham group, the body weight of the LT group and LT + CLP group decreased (all P<0.05). The rectal temperature of the LT + CLP group showed a continuous downward trend after the operation, the sepsis score increased sharply after the operation, and the survival rate dropped to 16.7%, and the differences between the Sham group, LT group and LT + CLP group were statistically significant (all P<0.05). The levels of ALT, AST, Urea, Cr, CK, LDH, and serum IL-1β, IL-6, IL-10 and TNF-α in the LT + CLP group were higher than those in the Sham group and LT group rats within 72 hours after the operation(all P<0.05). The pathological examination of the LT + CLP group showed severe tissue structure destruction, necrosis and infiltration of inflammatory cells in multiple organs, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed an increased level of cell apoptosis in multiple organs. Conclusions Using liver transplantation combined with CLP, a stable animal model of liver transplantation infection is successfully established, which exhibits a high mortality rate, significant multi-organ damage and intense inflammatory response, providing an ideal animal model for transplantation infection research.

Objective To evaluate the predictive ability and clinical application value of artificial intelligence (AI) systems in the benign and malignant differentiation and pathological type of pulmonary nodules, and to summarize clinical application experience. Methods A retrospective analysis was conducted on the clinical data of patients with pulmonary nodules admitted to the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from February 2016 to February 2025. Firstly, pulmonary nodules were divided into benign and non-benign groups, and the discriminative abilities of AI systems and clinicians were compared. Subsequently, lung nodules reported as precursor glandular lesions (PGL), microinvasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) in postoperative pathological results were analyzed, comparing the efficacy of AI systems and clinicians in predicting the pathological type of pulmonary nodules. Results In the analysis of benign/non-benign pulmonary nodules, clinical data from a total of 638 patients with pulmonary nodules were included, of which there were 257 males (10 patients and 1 patient of double and triple primary lesions, respectively) and 381 females (18 patients and 1 patient of double and triple primary lesions, respectively), with a median age of 55.0 (47.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis of the two groups of variables showed that, except for nodule location, the differences in the remaining variables were statistically significant (P<0.05). Multivariate logistic regression analysis showed that age, nodule type (subsolid pulmonary nodule), average density, spicule sign, and vascular convergence sign were independent influencing factors for non-benign pulmonary nodules, among which age, nodule type (subsolid pulmonary nodule), spicule sign, and vascular convergence sign were positively correlated with non-benign pulmonary nodules, while average density was negatively correlated with the occurrence of non-benign pulmonary nodules. The area under the receiver operating characteristic curve (AUC) of the malignancy risk value given by the AI system in predicting non-benign pulmonary nodules was 0.811, slightly lower than the 0.898 predicted by clinicians. In the PGL/MIA/IAC analysis, clinical data from a total of 411 patients with pulmonary nodules were included, of which there were 149 males (8 patients of double primary lesions) and 262 females (17 patients of double primary lesions), with a median age of 56.0 (50.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis results showed that, except for gender, nodule location, and vascular convergence sign, the differences in the remaining variables among the three groups of PGL, MIA, and IAC patients were statistically significant (P<0.05). Multinomial multivariate logistic regression analysis showed that the differences between the parameters in the PGL group and the MIA group were not statistically significant (P>0.05), and the maximum diameter and average density of the nodules were statistically different between the PGL and IAC groups (P<0.05), and were positively correlated with the occurrence of IAC as independent risk factors. The average AUC value, accuracy, recall rate, and F1 score of the AI system in predicting lung nodule pathological type were 0.807, 74.3%, 73.2%, and 68.5%, respectively, all better than the clinical physicians’ prediction of lung nodule pathological type indicators (0.782, 70.9%, 66.2%, and 63.7% respectively). The AUC value of the AI system in predicting IAC was 0.853, and the sensitivity, specificity, and optimal cutoff value were 0.643, 0.943, and 50.0%, respectively. Conclusion This AI system has demonstrated high clinical value in predicting the benign and malignant nature and pathological type of lung nodules, especially in predicting lung nodule pathological type, its ability has surpassed that of clinical physicians. With the optimization of algorithms and the adequate integration of multimodal data, it can better assist clinical physicians in formulating individualized diagnostic and treatment plans for patients with lung nodules.

OBJECTIVE To establish a preparation method for Phellodendrine-11-O-β-D-glucuronide(M1),a metabolite of Phellodendrine(PHE),and to evaluate its regulatory effects on glycolipid metabolism disorder in insulin-resistant HepG2(IR-HepG2)cells.METHODS The preparation,extraction,separation,purification and identification of M1 were completed by in vitro incuba-tion of intestinal microsomes combined with liquid phase,mass spectrometry and NMR.With Metformin as positive control,IR-HepG2 cells were treated with low(25 μmol·L-1),medium(50 μmol·L-1)and high(100 μmol·L-1)doses of M1 for 24 h.Glucose con-sumption,glucose uptake,triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C)were quantified.The binding ability of M1 to the key targets INSR,IRS1,PI3K and AKT2 in the IRS1/PI3K/AKT pathway was explored through molecular docking technology.The effects of M1 on the mRNA and protein expression of these key targets in the IRS1/PI3K/AKT pathway were detected by qPCR and Western blot,respectively.RESULTS The purified product was confirmed by NMR as Phellodendrine-11-O-β-D-glucuronide(95%purity).Compared to the model group,all M1 do-ses significantly enhanced glucose consumption(P<0.01,P<0.001)and uptake(P<0.001)in IR-HepG2 cells,outperforming PHE(P<0.001).At medium and high doses,it could significantly reduce the content of TG and TC in cells(P<0.001),and its improve-ment effect at the TG level was better than that of PHE(P<0.01);while all concentrations decreased LDL-C(P<0.001)and in-creased HDL-C(P<0.01,P<0.001).Molecular docking revealed strong binding interactions between M1 and INSR,IRS1,PI3K,and AKT2.Compared with the model group,M1 administration group increased the expression of INSR,IRS1,PI3K,AKT2,and GLUT2 mRNA to varying degrees,downregulated the protein expression of p-IRS1/IRS1(P<0.001),and upregulated the protein ex-pression of PI3K,p-AKT/AKT,and p-GSK3β/GSK3β.CONCLUSION The established protocol enables high purity M1 prepara-tion.M1 alleviates IR by regulating IRS1/PI3K/AKT signaling pathway to improve the disorder of glycolipid metabolism.

Objective To investigate the efficacy,safety and prognosis of ultrasound-guided radiofrequency ablation(RA)for single papillary thyroid carcinoma(PTC)with calcification.Methods A retrospective analysis was performed on 163 patients with calcified single PTC who received RFA treatment from January 1,2015 to December 31,2019.The patients who underwent RFA surgery before December 31,2016 were included in the training set,the others after January 1,2017 were included in the test set.With the non-disap-pearance of ablation at the last follow-up after RFA as the end event,the independent risk factors for non-disappearance of ablation were screened out by Logistic regression analysis,and a nomogram was constructed to evaluate the predictive efficacy and clinical value.The safety and efficacy of RFA in patients with calcified PTC were also evaluated.Results Multivariate Logistic regression analysis showed that age(P=0.001),maximum lesion diameter(P=0.021)and calcification ratio(P=0.048)were independent risk factors for non-disappearance of ablation.A nomogram model was established,the area under the area(AUC)of this model was 0.780 in the training set,and 0.711 in the test set.The calibration curve showed that the nomogram model predicted the outcome of the ablation site in good agreement with the real situation.Cinical decision analysis curve indicated a good clinical potential.In 163 lesions,there were 90 le-sions(55.2％)which with less calcification content in the nodules disappeared completely,no serious complications were observed,and the volume of ablation sites was continuously reduced,8 patients(4.9％)developed metastasis and recurred.Conclusion RFA has good safety and efficacy in the treatment of calcified PTC.The predictive model of the outcome of ablation lesion after RFA in patients with calcified single PTC constructed on the basis of age,maximum lesion diameter,and calcification ratio has good differentiation and calibra-tion,which can be used to assess the postoperative efficacy of RFA after RFA in patients with calcified single PTC.

Objective:To investigate the impact of four registration methods on the accuracy of virtual occlusal records (VOR) in intraoral scanning for implant restorations with multiple missing teeth.Methods:A mandibular model simulating clinical conditions with multiple missing teeth (right first molar, left second premolar, left first molar, left second molar) and a maxillary compete dentition model were mounted on a semi-adjustable articulator. Subsequently, twelve 0.5 mm stainless steel spheres were adhered to reference positions (16, 46, 13, 43, 23, 33, 25, 35, 26, 36, 27, 37) as fiducial markers. Following this, a laboratory scanner generated reference datasets by digitizing the models in maximum intercuspation (MIP). Meanwhile, ten maxillary and mandibular scans were acquired using an intraoral scanner, with all nonarticulated scans duplicated four times to ensure data consistency. Forty VOR intraoral scans were performed in MIP using four registration protocols: left-side, right-side, anterior, and bilateral registration ( n=10 per group), randomized via a computer-generated pseudo-random sequence. For measurement, linear distances (D16-46, D13-43, D23-33, D25-35, D26-36, D27-37, D16-46 represented the single-tooth defect position, whereas D25-35, D26-36, D27-37 reflected positions in free-end edentulism areas) between opposing markers were measured in a reverse engineering software, with deviations (ΔD) from the reference scan calculated to assess accuracy. Specifically, negative ΔD values indicated vertical dimension underestimation. Given that non-normally distributed data were analyzed using medians [interquartile ranges (IQR)], trueness (median ΔD) and precision (IQR) were evaluated. The interaction effect between the registration method and the position of the measurement items was evaluated by using the generalized linear model. The accuracy was compared overall by the Kruskal-Wallis test with the two-sided significance level of α=0.05. For pairwise comparisons, post-hoc tests were conducted by Dunn′s t-test with the Bonferroni correction for the significance level. Results:The accuracy of VOR was affected by registration method ( P<0.05), with a significant position×registration method interaction observed ( P<0.05). In particular, in all four groups, only the bilateral registration group showed trueness of less than 0.1 mm for both free-end edentulism and the single tooth defect, with ΔD16-46, ΔD25-35, ΔD26-36, and ΔD27-37 being 0.059 (0.015), -0.082 (0.052), -0.065 (0.032), -0.070 (0.050) mm, respectively. Moreover, trueness in free-end edentulism showed negative values across all groups, with the largest negative deviations observed in the right-side registration group, with ΔD25-35, ΔD26-36 and ΔD27-37 being -0.410 (0.174), -0.442 (0.225), -0.439 (0.262) mm, respectively. Conclusions:In fully digital workflows of implant restorations for mandibular free-end edentulism with multiple missing teeth, registration method critically influences VOR accuracy. While four registration methods exhibited underestimation of occlusal vertical dimension, bilateral registration achieved the highest accuracy.

Primary sclerosing cholangitis(PSC)is an autoimmune disease characterized by chronic inflamma-tion and progressive fibrosis that affects both intrahepatic and extrahepatic bile ducts.Despite ongoing research,the under-lying mechanisms of PSC pathogenesis remain incompletely understood.The ductular reaction is not only a key pathologi-cal feature of PSC but also serves as a driving force in its progression.This review examines the promoting effects of the ductular reaction on PSC advancement from multiple perspectives,including the proliferation of biliary epithelial cells,in-flammation,and fibrosis.By providing theoretical insights into the pathogenesis of PSC,this review aims to facilitate the identification of novel therapeutic strategies.

Objective:To evaluate the outcomes of short-segment pedicle screw fixation after vertebroplasty augmentation using polymethylmethacrylate (PMMA) and laminectomy for stage Ⅲ Kümmell's disease with neurological symptoms.Methods:A retrospective study was conducted to analyze the clinical data of the 23 patients who had been treated at Department of Spinal Surgery, Beijing Jishuitan Hospital from January 2016 to August 2022 for single level stage Ⅲ Kümmell's disease with neurological symptoms by short-segment pedicle screw fixation after vertebroplasty augmentation using PMMA and laminectomy. There were 9 males and 14 females, with an age of (69.7±3.8) years. The visual analogue scale (VAS) for low back pain, Oswestry disability index (ODI) for low back pain, kyphotic Cobb angle of the fixed segment, and loss of the anterior vertebral body height were compared between preoperation, 2 weeks after operation, 2 years after operation, and the last follow-up. The improvements in American Spinal Injury Association (ASIA) impairment grading at the last follow-up compared to the preoperative levels, bone graft fusion rates at the last follow-up and complications were recorded.Results:All patients were followed up for (57.4±17.7) months after operation. The VAS pain scores [(2.2±0.3) points, (1.8±0.6) points and (1.6±0.5) points], ODIs (23.9%±4.5%, 21.6%±4.5% and 19.1%±3.8%), kyphotic Cobb angles of the fixed segments (12.2°±2.7°, 12.5°±2.6° and 12.8°±2.8°) and losses of the anterior vertebral body height (20.0%±3.4%, 20.2%±3.5% and 20.3%±3.5%) at 2 weeks after operation, 2 years after operation, and the last follow-up were significantly improved compared to the pre-operative values [(7.8±0.5) points, 79.7%±5.1%, 40.2°±6.2°, and 60.4%±14.2%, respectively] ( P<0.05). However, there were no significantly differences in the above values between 2 weeks after operation, 2 years after operation and the last follow-up ( P>0.05). Of the 2 patients with grade C, the ASIA grading at the last follow-up improved to grade D in one and to grade E in the other; of the 12 patients with grade D, the ASIA grading at the last follow-up improved to grade E in 11. The complications included 2 asymptomatic cases of bone cement leakage from the upper endplate of the affected vertebra, 1 asymptomatic case of bone cement leakage from the lower endplate of the affected vertebra, 1 asymptomatic case of bone cement leakage from the spinal canal, and 1 case of distant vertebral compression fracture. The last follow-up showed good bone graft fusion in all patients. Conclusion:In the treatment of stage Ⅲ Kümmell's disease with neurological symptoms, short-segment pedicle screw fixation after vertebroplasty augmentation using PMMA is a relatively minimally invasive, safe, and effective treatment, because it can alleviate back pain, improve neurological function and daily function, correct thoracolumbar kyphosis, restore vertebral height and reconstruct spinal stability without significant complications.

OBJECTIVE To establish a preparation method for Phellodendrine-11-O-β-D-glucuronide(M1),a metabolite of Phellodendrine(PHE),and to evaluate its regulatory effects on glycolipid metabolism disorder in insulin-resistant HepG2(IR-HepG2)cells.METHODS The preparation,extraction,separation,purification and identification of M1 were completed by in vitro incuba-tion of intestinal microsomes combined with liquid phase,mass spectrometry and NMR.With Metformin as positive control,IR-HepG2 cells were treated with low(25 μmol·L-1),medium(50 μmol·L-1)and high(100 μmol·L-1)doses of M1 for 24 h.Glucose con-sumption,glucose uptake,triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C)were quantified.The binding ability of M1 to the key targets INSR,IRS1,PI3K and AKT2 in the IRS1/PI3K/AKT pathway was explored through molecular docking technology.The effects of M1 on the mRNA and protein expression of these key targets in the IRS1/PI3K/AKT pathway were detected by qPCR and Western blot,respectively.RESULTS The purified product was confirmed by NMR as Phellodendrine-11-O-β-D-glucuronide(95%purity).Compared to the model group,all M1 do-ses significantly enhanced glucose consumption(P<0.01,P<0.001)and uptake(P<0.001)in IR-HepG2 cells,outperforming PHE(P<0.001).At medium and high doses,it could significantly reduce the content of TG and TC in cells(P<0.001),and its improve-ment effect at the TG level was better than that of PHE(P<0.01);while all concentrations decreased LDL-C(P<0.001)and in-creased HDL-C(P<0.01,P<0.001).Molecular docking revealed strong binding interactions between M1 and INSR,IRS1,PI3K,and AKT2.Compared with the model group,M1 administration group increased the expression of INSR,IRS1,PI3K,AKT2,and GLUT2 mRNA to varying degrees,downregulated the protein expression of p-IRS1/IRS1(P<0.001),and upregulated the protein ex-pression of PI3K,p-AKT/AKT,and p-GSK3β/GSK3β.CONCLUSION The established protocol enables high purity M1 prepara-tion.M1 alleviates IR by regulating IRS1/PI3K/AKT signaling pathway to improve the disorder of glycolipid metabolism.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To investigate the efficacy,safety and prognosis of ultrasound-guided radiofrequency ablation(RA)for single papillary thyroid carcinoma(PTC)with calcification.Methods A retrospective analysis was performed on 163 patients with calcified single PTC who received RFA treatment from January 1,2015 to December 31,2019.The patients who underwent RFA surgery before December 31,2016 were included in the training set,the others after January 1,2017 were included in the test set.With the non-disap-pearance of ablation at the last follow-up after RFA as the end event,the independent risk factors for non-disappearance of ablation were screened out by Logistic regression analysis,and a nomogram was constructed to evaluate the predictive efficacy and clinical value.The safety and efficacy of RFA in patients with calcified PTC were also evaluated.Results Multivariate Logistic regression analysis showed that age(P=0.001),maximum lesion diameter(P=0.021)and calcification ratio(P=0.048)were independent risk factors for non-disappearance of ablation.A nomogram model was established,the area under the area(AUC)of this model was 0.780 in the training set,and 0.711 in the test set.The calibration curve showed that the nomogram model predicted the outcome of the ablation site in good agreement with the real situation.Cinical decision analysis curve indicated a good clinical potential.In 163 lesions,there were 90 le-sions(55.2％)which with less calcification content in the nodules disappeared completely,no serious complications were observed,and the volume of ablation sites was continuously reduced,8 patients(4.9％)developed metastasis and recurred.Conclusion RFA has good safety and efficacy in the treatment of calcified PTC.The predictive model of the outcome of ablation lesion after RFA in patients with calcified single PTC constructed on the basis of age,maximum lesion diameter,and calcification ratio has good differentiation and calibra-tion,which can be used to assess the postoperative efficacy of RFA after RFA in patients with calcified single PTC.