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.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Objective To investigate the effects of patient bone mass differences on the stability of unicondylar knee arthroplasty(UKA)prostheses.Methods A UKA finite element model was established to quantify the effects of five different bone quality conditions on the proximal tibial von Mises stress,bone-prosthesis fixation interface contact stress,and bone-prosthesis fixation interface micromotion,using the medial knee force and joint motion predicted by the individualized UKA musculoskeletal multibody dynamics model as boundary conditions.Results The influences of bone strength on the proximal tibia von Mises stress and bone-prosthesis fixation interface contact stress were not obvious,and the difference in peak values of the proximal tibia von Mises stress between two groups of models with the largest difference in bone strength was not more than 5％,and the difference in peak values of the bone-prosthesis fixation interface contact stress was only 2.37 MPa.However,the influence of bone strength on the bone-prosthesis fixation interface micromotion was significant,and the weaker bones were more prone to cause the bone-prosthesis fixation interface micromotion.However,bone strength had a significant effect on the bone-prosthesis fixation interface micromotion,and weak bone was more likely to cause changes in the bone-prosthesis fixation interface micromotion.Compared to patients with the neutral bone quality,the prosthesis fixation interface micromotion increased by 84.67％at 20％gait cycles for patients with the weakest bone quality.Conclusions UKA patients with a weaker bone quality have a higher risk of prosthesis loosening.It is recommended that surgeons should carefully choose their surgical strategy in order to reduce the rate of postoperative revision in UKA.

Purpose To construct a nomogram model based on conventional ultrasound(US)and contrast-enhanced ultrasound(CEUS)features for predicting extrathyroidal extension(ETE)of papillary thyroid carcinoma,and to evaluate its diagnostic performance.Materials and Methods A retrospective analysis of clinical and ultrasound data from 715 papillary thyroid carcinoma patients in the First Medical Center of Chinese PLA General Hospital from January 2017 to December 2022 was conducted.The patients were divided into two groups based on the presence or absence of ETE.Univariate and Multivariate analyses was performed to identify independent risk factors associated with ETE.Three models were established:clinical,clinical+US and clinical+US+CEUS.The nomogram of the best model was constructed and validated.Results The model based on clinical+US+CEUS features performed the best,the area under the curve was 0.885.Multivariate analysis indicated that older age(OR=1.029,95%CI 1.011-1.047),higher body mass index(OR=1.108,95%CI 1.049-1.171),capsular contact<25%(OR=4.716,95%CI 2.079-10.701),capsular contact 25%-50%(OR=21.320,95%CI 8.240-55.160),capsular contact>50%(OR=24.045,95%CI 6.792-85.126),nodules adjacent to the lateral side(OR=4.265,95%CI 1.366-13.318),nodules adjacent to the medial side(OR=6.416,95%CI 2.067-19.920)and interrupted capsular enhancement(OR=6.044,95%CI 3.588-10.180)were independent risk factors for ETE(all P<0.05).Decision curve analysis and clinical impact curve indicated high net benefit and strong clinical utility of the model.Ten-fold cross-validation showed good model stability.Conclusion The nomogram model constructed based on US and CEUS features demonstrates good predictive performance and holds significant clinical utility.

In patients with heart failure with reduced ejection fraction(HFrEF),some individuals demonstrate significant improvement in left ventricular ejection fraction(LVEF)during subsequent evaluations after treatment.The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America(AHA/ACC/HFSA)heart failure management guidelines introduced the term"heart failure with improved ejection fraction(HFimpEF)"to describe patients with prior LVEF≤40%that subsequently increased above 40%during follow-up.Studies indicate that HFimpEF patients exhibit lower all-cause mortalities and heart failure rehospitalization rates,with a significantly better prognosis compared to HFrEF patients,establishing HFimpEF as a staged therapeutic target for HFrEF.Current discussion on HFimpEF primarily focuses on two aspects:characteristics of the target population and effective methods for LVEF improvement,and maintenance strategies for cardiac function preservation in HFimpEF patients;particularly the latter lacks clear clinical-guideline recommendations.Therefore,reviewing existing research to systematically summarize therapeutic strategies that promote the HFrEF-to-HFimpEF transition and effective maintenance approaches for HFimpEF becomes crucial.This article comprehensively reviews the LVEF-improving effects of current pharmacological,device-based,and surgical interventions,along with monitoring and management strategies for HFimpEF patients.In HFrEF patients,clinical evidence suggests that β-blockers and cardiac resynchronization therapy can significantly improve LVEF beyond 40%.Regarding HFimpEF management,sodium-glucose cotransporter-2 inhibitors(SGLT2i)and renin-angiotensin system inhibitors(RASi)demonstrate efficacy in maintaining LVEF and cardiac function.Additionally,this review identifies current research limitations in HFimpEF and proposes potential future research directions.

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 evaluate the short-term efficacy of surgical treatment for severe pulmonary stenosis(PS) in infants and young children, and to clarify the impact of different surgical timings on the efficacy of PS treatment.Methods:A retrospective analysis was conducted on 24 infants and young children who underwent surgical treatment for severe PS at the General Hospital of Northern Theater Command, PLA, from January 1, 2020, to October 1, 2024. Among them, 13 were males and 11 were females. The average weight of the patients was(9.2±3.6) kg, the average gestational age was(39.3±1.7) weeks, and the average age was(15.0±13.5) months. Preoperative clinical symptoms and signs(e.g., cyanosis, shortness of breath), transpulmonary valve pressure gradient(TPVPG), right ventricular systolic pressure(RVSP), and Em/Am were recorded. The patients were divided into two groups based on surgical timing: the infant group(under 1 year old, n=12) and the toddler group(1-3 years old, n=12).Results:There were no deaths among all patients. The postoperative ICU stay was significantly longer in the infant group compared to the toddler group( P<0.05). Compared to preoperative values, surgical treatment significantly improved TPVPG, reduced RVSP, and enhanced right ventricular diastolic function, which stabilized by 3 months postoperatively( P<0.05). Intergroup comparisons revealed that the infant group had significantly lower TPVPG at 6 months postoperatively compared to the toddler group. Additionally, right ventricular diastolic function improved significantly in the infant group postoperatively, while no significant improvement was observed in the toddler group. Younger age and reduced right ventricular diastolic function were identified as major risk factors for prolonged mechanical ventilation(>24 hours). Conclusion:Surgical treatment for PS during infancy and early childhood is safe and effective. Comprehensive preoperative evaluation is crucial, and early surgical intervention is recommended for patients with impaired right ventricular function to improve prognosis.

Objective To investigate the effects of patient bone mass differences on the stability of unicondylar knee arthroplasty(UKA)prostheses.Methods A UKA finite element model was established to quantify the effects of five different bone quality conditions on the proximal tibial von Mises stress,bone-prosthesis fixation interface contact stress,and bone-prosthesis fixation interface micromotion,using the medial knee force and joint motion predicted by the individualized UKA musculoskeletal multibody dynamics model as boundary conditions.Results The influences of bone strength on the proximal tibia von Mises stress and bone-prosthesis fixation interface contact stress were not obvious,and the difference in peak values of the proximal tibia von Mises stress between two groups of models with the largest difference in bone strength was not more than 5％,and the difference in peak values of the bone-prosthesis fixation interface contact stress was only 2.37 MPa.However,the influence of bone strength on the bone-prosthesis fixation interface micromotion was significant,and the weaker bones were more prone to cause the bone-prosthesis fixation interface micromotion.However,bone strength had a significant effect on the bone-prosthesis fixation interface micromotion,and weak bone was more likely to cause changes in the bone-prosthesis fixation interface micromotion.Compared to patients with the neutral bone quality,the prosthesis fixation interface micromotion increased by 84.67％at 20％gait cycles for patients with the weakest bone quality.Conclusions UKA patients with a weaker bone quality have a higher risk of prosthesis loosening.It is recommended that surgeons should carefully choose their surgical strategy in order to reduce the rate of postoperative revision in UKA.

Objective:To evaluate the short-term efficacy of surgical treatment for severe pulmonary stenosis(PS) in infants and young children, and to clarify the impact of different surgical timings on the efficacy of PS treatment.Methods:A retrospective analysis was conducted on 24 infants and young children who underwent surgical treatment for severe PS at the General Hospital of Northern Theater Command, PLA, from January 1, 2020, to October 1, 2024. Among them, 13 were males and 11 were females. The average weight of the patients was(9.2±3.6) kg, the average gestational age was(39.3±1.7) weeks, and the average age was(15.0±13.5) months. Preoperative clinical symptoms and signs(e.g., cyanosis, shortness of breath), transpulmonary valve pressure gradient(TPVPG), right ventricular systolic pressure(RVSP), and Em/Am were recorded. The patients were divided into two groups based on surgical timing: the infant group(under 1 year old, n=12) and the toddler group(1-3 years old, n=12).Results:There were no deaths among all patients. The postoperative ICU stay was significantly longer in the infant group compared to the toddler group( P<0.05). Compared to preoperative values, surgical treatment significantly improved TPVPG, reduced RVSP, and enhanced right ventricular diastolic function, which stabilized by 3 months postoperatively( P<0.05). Intergroup comparisons revealed that the infant group had significantly lower TPVPG at 6 months postoperatively compared to the toddler group. Additionally, right ventricular diastolic function improved significantly in the infant group postoperatively, while no significant improvement was observed in the toddler group. Younger age and reduced right ventricular diastolic function were identified as major risk factors for prolonged mechanical ventilation(>24 hours). Conclusion:Surgical treatment for PS during infancy and early childhood is safe and effective. Comprehensive preoperative evaluation is crucial, and early surgical intervention is recommended for patients with impaired right ventricular function to improve prognosis.

In patients with heart failure with reduced ejection fraction(HFrEF),some individuals demonstrate significant improvement in left ventricular ejection fraction(LVEF)during subsequent evaluations after treatment.The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America(AHA/ACC/HFSA)heart failure management guidelines introduced the term"heart failure with improved ejection fraction(HFimpEF)"to describe patients with prior LVEF≤40%that subsequently increased above 40%during follow-up.Studies indicate that HFimpEF patients exhibit lower all-cause mortalities and heart failure rehospitalization rates,with a significantly better prognosis compared to HFrEF patients,establishing HFimpEF as a staged therapeutic target for HFrEF.Current discussion on HFimpEF primarily focuses on two aspects:characteristics of the target population and effective methods for LVEF improvement,and maintenance strategies for cardiac function preservation in HFimpEF patients;particularly the latter lacks clear clinical-guideline recommendations.Therefore,reviewing existing research to systematically summarize therapeutic strategies that promote the HFrEF-to-HFimpEF transition and effective maintenance approaches for HFimpEF becomes crucial.This article comprehensively reviews the LVEF-improving effects of current pharmacological,device-based,and surgical interventions,along with monitoring and management strategies for HFimpEF patients.In HFrEF patients,clinical evidence suggests that β-blockers and cardiac resynchronization therapy can significantly improve LVEF beyond 40%.Regarding HFimpEF management,sodium-glucose cotransporter-2 inhibitors(SGLT2i)and renin-angiotensin system inhibitors(RASi)demonstrate efficacy in maintaining LVEF and cardiac function.Additionally,this review identifies current research limitations in HFimpEF and proposes potential future research directions.