Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.

This study aims to investigate the effect of Lactiplantibacillus plantarum LP12 on obe-sity prevention.In our study,Lactiplantibacillus plantarum LP12 was added to the diet for feed-ing,and the blood biochemistry status of rabbit,as well as the antioxidant effect of serum and liver samples were analyzed by determining the body weight change and feed intake of Japanese White rabbits.The changes in colony structure and abundance were also analyzed by 16S rDNA sequen-cing.The results showed that supplementation of Lactiplantibacillus plantarum LP12 inhibits weight gain,decreases serum glucose and ALT levels,and increases SOD activity in the liver.16S RNA gene sequencing analysis showed that the addition of Lactiplantibacillus plantarum LP12 increases the abundance of Bacteroidetes and Desulfovibrioides at the phylum level,and the supple-mentation of Lactiplantibacillus plantarum LP12 increases the abundance of Muribaculaceae at the genus level.Predictive analysis of microbiota function revealed that the supplementation of Lactiplantibacillus plantarum LP12 positively regulated iron-sulfur clusters and Zn-dependent proteases.In conclusion,the addition of Lactiplantibacillus plantarum effectively inhibits weight gain in Japanese White rabbits,enhances the antioxidative activity of the liver,and induces altera-tions in the gut microbiota composition of these rabbits.These findings lay an experimental foun-dation for further exploring the mechanisms by which Lactobacillus plantarum LP12 exerts its preventive effects against obesity and promotes metabolic health.

Objective To explore the value of MRI subtraction technique(ST)for evaluating the efficacy of systemic therapy for advanced hepatocellular carcinoma(HCC)and predicting prognosis after combining with surgery.Methods Totally 35 patients with 39 HCC lesions who received systemic therapy+radical resection were retrospectively collected.Based on preoperative MRI,tumor activity ratio(recorded as tumor activityST)was obtained with ST,while tumor activity value(recorded as tumor activitypathology)was obtained through postoperative pathology,and their correlation was analyzed.The patients were regularly followed up after surgery,and the survival data were recorded.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of tumor activityST for predicting patients'survival status.Then the patients were divided into survival benefit group and no survival benefit group according to the cut-off value,and survival analysis was conducted.Results Tumor activityST was positively correlated with tumor activitypathology(r=0.900,P＜0.001).The median follow-up time was 32.93 months,during which 8 patients died,and the median survival time was 29.9 months.The area under the curve(AUC)of tumor activityST for predicting patients'survival status was 0.67,and the cut-off value was 0.36.Thirty patients with tumor activityST＜0.36 were enrolled in survival benefit group,while 5 patients≥0.36 were collected in no survival benefit group.The overall survival in survival benefit group was longer than that in no survival benefit group(P＜0.001).Conclusion MRI ST could be used to non-invasively evaluate the efficacy of systemic therapy for advanced HCC and predict prognosis after combining with surgery.

This study aims to investigate the effect of Lactiplantibacillus plantarum LP12 on obe-sity prevention.In our study,Lactiplantibacillus plantarum LP12 was added to the diet for feed-ing,and the blood biochemistry status of rabbit,as well as the antioxidant effect of serum and liver samples were analyzed by determining the body weight change and feed intake of Japanese White rabbits.The changes in colony structure and abundance were also analyzed by 16S rDNA sequen-cing.The results showed that supplementation of Lactiplantibacillus plantarum LP12 inhibits weight gain,decreases serum glucose and ALT levels,and increases SOD activity in the liver.16S RNA gene sequencing analysis showed that the addition of Lactiplantibacillus plantarum LP12 increases the abundance of Bacteroidetes and Desulfovibrioides at the phylum level,and the supple-mentation of Lactiplantibacillus plantarum LP12 increases the abundance of Muribaculaceae at the genus level.Predictive analysis of microbiota function revealed that the supplementation of Lactiplantibacillus plantarum LP12 positively regulated iron-sulfur clusters and Zn-dependent proteases.In conclusion,the addition of Lactiplantibacillus plantarum effectively inhibits weight gain in Japanese White rabbits,enhances the antioxidative activity of the liver,and induces altera-tions in the gut microbiota composition of these rabbits.These findings lay an experimental foun-dation for further exploring the mechanisms by which Lactobacillus plantarum LP12 exerts its preventive effects against obesity and promotes metabolic health.

Objective To explore the value of MRI subtraction technique(ST)for evaluating the efficacy of systemic therapy for advanced hepatocellular carcinoma(HCC)and predicting prognosis after combining with surgery.Methods Totally 35 patients with 39 HCC lesions who received systemic therapy+radical resection were retrospectively collected.Based on preoperative MRI,tumor activity ratio(recorded as tumor activityST)was obtained with ST,while tumor activity value(recorded as tumor activitypathology)was obtained through postoperative pathology,and their correlation was analyzed.The patients were regularly followed up after surgery,and the survival data were recorded.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of tumor activityST for predicting patients'survival status.Then the patients were divided into survival benefit group and no survival benefit group according to the cut-off value,and survival analysis was conducted.Results Tumor activityST was positively correlated with tumor activitypathology(r=0.900,P＜0.001).The median follow-up time was 32.93 months,during which 8 patients died,and the median survival time was 29.9 months.The area under the curve(AUC)of tumor activityST for predicting patients'survival status was 0.67,and the cut-off value was 0.36.Thirty patients with tumor activityST＜0.36 were enrolled in survival benefit group,while 5 patients≥0.36 were collected in no survival benefit group.The overall survival in survival benefit group was longer than that in no survival benefit group(P＜0.001).Conclusion MRI ST could be used to non-invasively evaluate the efficacy of systemic therapy for advanced HCC and predict prognosis after combining with surgery.

The volume of research funding in public hospitals is increasing year by year,with the majority of research funding being used to purchase research materials and services.Traditional offline procurement methods have problems such as inadequate management systems,difficulty in ensuring product quality,blind spots in procurement processes,and high risks in invoice receipt and storage.Public hospitals urgently need to adopt digital methods,introduce research procurement platforms,and implant key control points into the platform based on reshaping the procurement business process,achieve full process supervision and traceability control of research procurement business,and strengthen internal control and risk management of research

Objective The aim of this study was to evaluate the effects of collagen modification on the osteogenic performance of different surface-modified titanium,including alkaline etching,alkaline etching followed by silaniza-tion,and alkaline etching followed by dopamine modifi-cation.The proliferation,adhesion,and osteogenic differ-entiation abilities of MC3T3-E1 cells on the surfaces with collagen modification were analyzed and compared.Methods Collagen was immobilized on the surfaces of pure titanium(Ti-C),alkaline-etched titanium(Ti-Na-C),alkaline-etched and silanized titanium(Ti-A-C),and alkaline-etched and dopamine-modified titanium(Ti-D-C),with pure titanium(Ti)as the control group.The surface morphology was observed by scanning electron microscopy(SEM),and the surface elemental composition was analyzed by X-ray photoelectron spectroscopy(XPS).Contact angle measurements were conducted to evaluate the hydrophilicity of the surfaces.MC3T3-E1 cells were cultured on the surfaces,and their proliferation,adhesion,and osteogenic differentiation abilities were assessed using CCK-8 assay,laser scanning confocal microscope,alkaline phosphatase(ALP)staining,Alizarin red staining and quantitative analysis,as well as real-time quan-titative polymerase chain reaction(RT-qPCR)to evaluate the mRNA expression levels of osteogenic-related genes,includ-ing ALP,typeⅠcollagen(COL-1),osteocalcin(OCN),osteopontin(OPN).Results SEM and XPS results confirmed the successful immobilization of collagen on the titanium surfaces,with the Ti-Na-C group exhibiting a higher amount of col-lagen modification.Contact angle measurements showed improved hydrophilicity of the surfaces after collagen modifica-tion.CCK-8 results indicated good compatibility of the materials with MC3T3-E1,with enhanced cell proliferation on the collagen-modified surfaces.Cell fluorescence staining revealed better cell spreading on the collagen-modified surfaces,and ALP and Alizarin red staining results suggested that the Ti-Na-C group exhibited the best osteogenic performance,with significantly higher absorbance values in the Alizarin red quantification analysis.RT-qPCR analysis showed that the Ti-Na-C group had the highest expression of the osteogenic-related gene OPN.Conclusion Among the different colla-gen modification approaches employed in this study,collagen modification on alkaline-etched titanium surfaces showed the most conducive effects on MC3T3-E1 cell adhesion,spreading,proliferation,and osteogenic differentiation.This ap-proach can be considered as the optimal collagen modification strategy for enhancing osteogenesis on titanium surfaces.

Objective To investigate the value of CT radiomics models based on intranodal and perinodal in distinguishing pulmonary cryptococcosis(PC)from lung adenocarcinoma.Methods A total of 194 patients,including PC(n=94)and lung adenocarcinoma(n=100),confirmed by surgical or puncture pathology were analyzed retrospectively and randomly divided into training set and test set in a ratio of 7∶3.3D Slicer was used to delineate and extract the intranodal and perinodal volume of interest(VOI)radiomics features within a 5 mm range.The minimum redundancy maximum relevance(mRMR)and least absolute shrinkage and selection operator(LASSO)methods were used to dimensionality reduction.Statistically significant indicators were screened by one-way logistic regression and further incorporated into the multifactor logistic regression model.Support vector machine(SVM)was used to construct the intranodal image-based radiomics model,the perinodal image-based radiomics model,the intranodal-and-perinodal image-based radiomics model,and the combined model.The diagnostic efficacy of each model was evaluated by receiver operating characteristic(ROC)curve.Results In the test set,the area under the curve(AUC)of the clinical imaging model,the intranodal image-based radiomics model,the perinodal image-based radiomics model,the intranodal-and-perinodal image-based radiomics model,and the combined model were 0.84,0.88,0.85,0.90,and 0.94,respectively.Conclusion The combined model based on clinical imaging features,intranodal and perinodal radiomics features can improve the ability of differentiating PC from lung adenocarcinoma.

Objective:To investigate the clinical manifestations, pathological, and gene mutation characteristics of ABCB4 gene variant-associated cholestatic liver disease in adults. Methods:Eight adult cases of ABCB4 gene variant-associated cholestatic liver disease who were hospitalized in the Department of Hepatology, Fifth Medical Center of the People's Liberation Army General Hospital from May 2010 to December 2022 were enrolled in this study. The clinical manifestations, pathological features, gene variant features, and prognostic conditions were analyzed. Patient gene testing and biological information analysis were performed using whole-exome next-generation sequencing. SPSS 19.0 software was used to conduct descriptive analysis. Results:Among the eight adult cases of the ABCB4 gene variant, there were three males and five females, with a median age of onset of 24 (20, 37) years. There were three cases with a compound heterozygous variant in ABCB4, and the clinical phenotypes included two cases of progressive familial intrahepatic cholestasis type 3 and one case of intrahepatic cholestasis of pregnancy overlapping with low-phospholipid-associated cholelithiasis syndrome. There were five cases with a single heterozygous variant in ABCB4, and the clinical phenotypes included two cases of intrahepatic cholestasis of pregnancy overlapping with drug-induced liver injury and three cases of low-phospholipid-associated cholelithiasis syndrome. Imaging of all eight cases showed liver fibrosis, and six cases already had cirrhosis. All patients underwent liver histopathological examination, which mainly showed cholestasis and portal fibrosis in eight cases, small bile duct hyperplasia in seven cases, copper deposition in three cases, and cirrhosis in five cases. ABCB4 screening revealed 11 different mutations, including eight new mutations. The pathogenicity assessment showed that c.2394+82C>T (intron) was a benign mutation, and the rest were deleterious mutations. Ursodeoxycholic acid was the treatment for all patients, with a follow-up time of 7.5 (0.5, 12.7) years. One case died of end-stage liver disease, two cases developed cholestatic cirrhosis, and five cases were in stable condition. Conclusion:The adult ABCB4 gene variant-associated cholestatic liver disease are mostly single heterozygous mutations, the clinical phenotypes are diverse and overlapping, the disease is more severe in those who carried non-functional mutations.

Objective:To analyze the clinical manifestations, pathology, and gene variant characteristics in children with progressive familial intrahepatic cholestasis type 3 (PFIC3).Methods:This retrospective study assessed the clinical manifestations, pathological features, gene variants, and prognosis data of 11 children with PFIC3 hospitalized in the Department of Hepatology, Fifth Medical Center, PLA General Hospital, from January 2015 to December 2022. Panel or whole exome sequencing was performed on the probands, followed by Sanger sequencing for verification within the family. Detected pathogenic variants were compared with known disease databases. Additionally, the new variants were predicted the deleteriousness and protein structure using relevant software to evaluate their pathogenicity.Results:Among the 11 PFIC3 children, 8 were boys and 3 were girls. The age of onset was 3.1 (0.2, 15.6) years. The main complaint of onset was different in the 11 patients;5 of them were abnormal liver function, 3 of them were liver and spleen enlargement, 2 of them were abdominal distension, and 1 of them was jaundice. Alanine aminotransferase, asparate aminotransferase and γ-glutamyltransferase increased in all the patients, which were(113±40), (150±44) and (270±156) U/L respectively. Moreover, direct bilirubin increased in 9 patients, and cholestasis was showed in 8 patients. All patients showed liver fibrosis on imaging, and 8 patients had cirrhosis. The pathological features of 8 cases by liver biopsy were as follows: 8 cases of fibrosis in the portal area, 7 cases of small bile duct hyperplasia, 4 cases of positive copper staining, and 5 cases of cirrhosis. A total of 17 ABCB4 gene variants were detected, including 9 new variants: c.589C>T(p.Q197X), c.1230+1G>A(Splicing), c.2914G>A(P.D972N), c.1058G>A(p.C353Y), c.956G>T(p.G319V), c.473T>A(p.L158Q), c.164T>C(p.L55S), c.2493G>C(p.R831S), and c.1150G>C(p.G384R). All 11 patients were treated with ursodeoxycholic acid and followed up for 5.1(0.6, 7.4) years. Among them, 4 cases of cirrhosis progressed continuously, 3 cases had liver transplantations, and the remaining 4 cases were stable after medical treatment.Conclusions:Children with PFIC3 have early onset, diverse clinical manifestations, rapid progression of fibrotic and cholestasis, as well as poor prognosis. Genetic testing helps to confirm the diagnosis.