Hepatocellular carcinoma （HCC）， as the sixth most common malignant tumor worldwide， poses a serious threat to human health due to its insidious onset and high mortality rate. This article reviews the molecular mechanisms and intervention strategies of gut microbiota （GM） homeostasis in the development and progression of HCC， in order to provide new ideas for the intervention and treatment of HCC. Studies have shown that GM dysbiosis， intestinal leakage， microbial-associated molecular pattern， bacterial translocation， and metabolic products play key roles in the progression of HCC. GM imbalance may lead to immune escape， thereby promoting tumor cell proliferation and metastasis. This article elaborates on the association between GM and HCC， deeply analyzes the mechanism of action of GM in the development and progression of HCC， investigates the role of bile acid-related metabolites， short-chain fatty acid-related metabolites， and other metabolites in HCC， and explores the strategies for targeting GM in the treatment of HCC， including probiotics， prebiotics， antibiotics， Toll-like receptor 4 antagonists， and fecal microbiota transplantation. This article emphasizes that maintaining the integrity of the intestinal barrier and GM homeostasis is of great significance in the prevention and treatment of HCC， which provides a direction for developing new diagnosis and treatment strategies.

Objective:To investigate the diagnostic performance of continuous-time random-walk (CTRW) diffusion model combined with vesical imaging-reporting and data system (VI-RADS) in the diagnosis of muscle invasion of bladder cancer.Methods:In this case-control study, 64 patients with pathologically confirmed bladder urothelial carcinoma in Peking University First Hospital were retrospectively enrolled from August 2022 to March 2023. The patients were divided into the muscle invasive bladder cancer (MIBC) group and the nonmuscle invasive bladder cancer (NMIBC) group (29 cases and 35 cases, respectively) according to the pathological results. All patients underwent bladder MRI within 4 weeks before surgery, including T 2WI, conventional diffusion weighted imaging (DWI), and multi-b-value DWI. The CTRW model was used to obtain three quantitative diffusion parameters, including D m (an anomalous diffusion coefficient), α (related to temporal diffusion heterogeneity), and β (related to spatial diffusion heterogeneity). The apparent diffusion coefficient (ADC) was calculated using a mono-exponential model. The VI-RADS scores were evaluated based on T 2WI and conventional DWI. The Mann-Whitney U test was used to compare the diffusion parameters between the MIBC group and the NMIBC group. The combination of the parameters was investigated with logistic regression analysis. The diagnostic performance for muscle invasion of bladder cancer was evaluated by receiver operating characteristic analysis and the area under the curve (AUC). The difference between AUC was compared using the DeLong test. Results:There were statistically significant differences in ADC, D m, and α between the MIBC group and the NMIBC group ( Z=-2.31, -2.91, -3.97, P=0.021, 0.004,<0.001). No significant difference was found in β between the two groups ( Z=1.69, P=0.091). The AUC (95% CI) of D m and α for diagnosing MIBC were 0.712 (0.587-0.838) and 0.790 (0.676-0.904) respectively, both of which were higher than that of ADC (AUC 0.669, 95% CI 0.537-0.801) with statistically significant differences ( Z=2.86, 2.27, P=0.004, 0.023). The AUC (95% CI) of CTRW (D m+α) was 0.782 (0.661-0.876), which was significantly higher than that of ADC ( Z=2.35, P=0.019). The AUC (95% CI) of VI-RADS score and VI-RADS combined with CTRW parameter (VI-RADS+D m+α) were 0.823 (0.716-0.930) and 0.900 (0.799-0.961) respectively, with a statistically significant difference between them ( Z=2.16, P=0.031). Conclusion:The D m and α parameters in the CTRW diffusion model show better performance than the ADC in the mono-exponential model for muscle-invasive evaluation of bladder cancer, and the CTRW diffusion model can enhance the diagnostic performance of VI-RADS.

Kupffer cells(KC),an important subset of immune cells in the liver,are essential for maintaining tissue homeostasis and responding quickly to liver damage.The complement receptor of the immuno-globulin superfamily(CRIg)is a receptor protein on the KC membrane.CRIg can not only capture pathogens in the blood flowing through the liver by complement binding but also mediate immune responses by regulating im-mune cells in the liver.Recent studies have confirmed the role of CRIg in regulating liver immunity.This article reviews the main modes of action of CRIg and the research progress of CRIg in regulating liver immunity.

Objective To observe the effects of Xiaomudan Granules on cholesterol synthesis in rats with non-alcoholic fatty liver disease(NAFLD);To explore its mechanism on the treatment of NAFLD based on mTORC1/USP20/HMGCR pathway.Methods Totally 60 SD rats were randomly divided into blank group,model group,Western medicine group(polyene phosphatidylcholine)and TCM low-,medium-and high-dosage groups(Xiaomudan Granules).The blank group was fed with ordinary diet,and the other groups were fed with high-fat diet for 12 weeks to establish NAFLD rat model.After successful modeling,each administration group was given the corresponding drug intragastric administration,and the blank group and model group were given aseptic distilled water intragastric administration for 4 weeks.Body mass and liver mass of rats were recorded,liver index was calculated,and serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)contents were detected by automatic biochemical analyzer,the morphological changes of liver tissue were observed by HE staining and oil red O staining,real-time fluorescence quantitative PCR and Western blot were used to detect ribosome S6 kinase(S6K),ubiquitin specific protease 20(USP20),3-hydroxy-3-methylglutaryl CoA reduction enzyme(HMGCR)mRNA and p-S6K,S6K,USP20,HMGCR protein expression in liver tissue.Results Compared with the blank group,the body mass,liver mass and liver index of rats in model group significantly increased(P<0.01,P<0.05),the volume of liver lobe increased,the edge was blunted;the contents of serum ALT,AST,TC,TG and LDL-C significantly increased,while HDL-C content significantly decreased(P<0.01);most hepatocytes showed steatosis,significant vacuole and inflammatory infiltration,increased lipid droplets,and significantly increased mRNA expression of USP20 and HMGCR in liver tissue(P<0.01)and protein expressions of p-S6K,USP20 and HMGCR(P<0.01).Compared with the model group,TCM high-dosage group and Western medicine group could significantly decrease body mass,liver mass and liver index of rats(P<0.01,P<0.05),and improve the appearance of liver;decrease the contents of ALT,AST,TC and LDL-C in serum,and increase the content of HDL-C(P<0.01,P<0.05);alleviate hepatocyte steatosis and balloon-like degeneration,reduce lipid droplet deposition,and decrease USP20,HMGCR mRNA and p-S6K,USP20,HMGCR protein expression in liver tissue(P<0.01,P<0.05).Conclusion Xiaomudan Granules may regulate cholesterol synthesis through mTORC1/USP20/HMGCR pathway,and thus play a role in the treatment of NAFLD in rats.

Objective To explore the mechanism of Yipi Yanggan Prescription in the treatment of precancerous lesion of liver in rats based on M1 type macrophage polarization-chronic inflammation-liver cell malignant transformation.Methods Totally 90 Wistar rats were randomly divided into blank group,model group,Hugan Tablet group and Yipi Yanggan Prescription high-,medium-and low-dosage groups,with 15 rats in each group.The blank group was injected distilled water intraperitoneally,and the other groups were injected 5 mL/kg of diethylnitrosamine intraperitoneally at 50 mg/kg per week(twice per week)for 16 weeks to induce the precancerous lesion of liver model.Starting from the second day of modeling,Yipi Yanggan Prescription high-,medium-and low-dosage groups were orally administered with 1.2,0.6 and 0.3 g/mL Yipi Yanggan Prescription,respectively.The Hugan Tablet group was orally administered with 921 mg/kg Hugan Tablet solution,the blank group and model group were orally administered with an equal amount of physiological saline for 16 consecutive weeks.The appearance of the liver was observed,ELISA was used to detect serum ALT,AST,ALP,AFU,as well as TNF-α,IL-6,iNOS and MCP-1 content,HE staining and Masson staining were used to observe the morphology of liver tissue,immunohistochemistry was used to detect the expressions of liver cell malignancy markers OV6,CK19,CD133 and EpCAM,qPCR was used to detect the mRNA expressions of CK19,CD133 and EpCAM in liver tissue,immunofluorescence co-localization was used to detect the co-expressions of M1 type macrophage markers CD68 with IL-6 and TNF-α.Results Compared with the blank group,the liver of the model group rats was hard,with a rough surface and dull edges,and a large number of nodules were visible,the contents of serum ALT,AST,ALP,AFU,TNF-α,IL-6,iNOS and MCP-1 significantly increased(P<0.01),there were large areas of dysplasia nodules,inflammatory cell infiltration,and increased collagen fibers in liver tissue,the expressions of OV6,CK19,CD133 and EpCAM in liver tissue significantly increased,and the co-expressions of CD68 with IL-6 and TNF-α significantly increased(P<0.01).Compared with the model group,the number and size of liver nodules in each treatment group of rats decreased,the contents of serum ALT,AST,ALP,AFU,TNF-α,IL-6,iNOS and MCP-1 were significantly decreased(P<0.01),hepatocellular dysplasia and inflammatory cell infiltration were significantly improved,collagen fibers decreased,and the expressions of OV6,CK19,CD133 and EpCAM in liver tissue were significantly decreased,the co-expressions of CD68 with IL-6 and TNF-α significantly decreased(P<0.05,P<0.01).Conclusion Yipi Yanggan Prescription may alleviate inflammation by inhibiting polarization of M1 type macrophages,improve liver cell malignancy,and exert therapeutic effects on rats with precancerous lesion of liver induced by diethylnitrosamine.

Liver macrophages are important immune cells in the liver,and they express proinflammatory factors and anti-inflammatory factors through polarization into M1 type and M2 type,respectively,thereby playing a role in regulating inflammatory damage response.The malignant transformation of hepatic progenitor cells is the core mechanism of the malignant progression of hepatic precancerous lesions,and its key factor is the continuous stimulation of inflammatory microenvironment,which is closely associated with M1/M2 macrophage polarization.This review mainly focuses on the association between macrophage polarization,chronic inflammation,and malignant transformation of hepatic progenitor cells,so as to provide a theoretical basis for the prevention and treatment of hepatic precancerous lesions.

Background::Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer.Methods::Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. Results::lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. Conclusion::Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.

Objective:To study the morphologic features of the fusion site of proximal tibial epiphysis in normal adults and analyze its potential clinical value based on Mimics three-dimensional (3D) reconstruction.Methods:CT images of knee joint of 68 patients without obvious abnormalities of lower limbs were retrospectively analyzed in electronic database of our hospital from June 2020 to June 2021, including 41 males and 27 females. The mean age of the patients was 38.7±8.4 years (range, 25-55 years), and the mean body mass index (BMI) was 25.3±4.0 kg/m 2 (range, 18.75-41.8 kg/m 2). Mimics 3D reconstruction technique was used to reconstruct the 3D model of the proximal tibia and epiphyseal fusion site. The relationship between the surface area of epiphyseal fusion site and age and BMI was studied, and the changes of cortical thickness and density at epiphyseal fusion site were also explored. Results:The fusion site of adult epiphyseal reconstructed by Mimics 3D reconstruction is a complex wavy surface structure in 3D space. The surface area of the epiphyseal fusion site was 2,994.7±645.3 mm 2 (range, 1,704.0-4,650.0 mm 2) obtained by 3-Matic Research 12.0. The fusing area of male epiphysis was 3 269.3±533.9 mm 2 than that of female 2,577.6±578.7 mm 2, the difference was statistically significant ( t=5.06, P<0.001). However, there was no significant correlation between the epiphyseal fusion site surface area and age ( R2=0.02, P=0.268) and BMI ( R2=0.04, P=0.125). Mimics software was used to obtain the CT values of bone cortex at the epiphysis line and the distal end of the epiphysis line at 10 mm and 20 mm levels as 451.059±74.953 Hu, 1,018.412±125.732 Hu and 1,414.162±107.848 Hu, respectively. The thickness of bone cortex was 1.814±0.090 mm, 2.511±0.089 mm and 3.189±0.185 mm at 10 mm and 20 mm layers of epiphysis line and distal epiphysis line, respectively. Conclusion:In this study, Mimics 3D reconstruction technique was used to visualize the fusion site of the proximal tibial epiphysis in normal adults. The epiphyseal fusion site of adult is a undulating plate-like structure, and the cortical bone density of epiphyseal fusion site is low and thin, theoretically, it is easy to fracture under indirect violence.

Objective:To evaluate the biomechanical stability of our slot-designed compression bolt (SCB) combined with bilateral locking compression plates (LCPs) in the treatment of intra-articular distal femur fracture.Methods:In 24 adult male knee specimens treated with formalin, the femoral bony part was preserved to establish standard models of intra-articular distal femur fracture (AO type 33-C1). According to the random number table, the fracture models were divided into 2 equal groups: an experimental group ( n=12) subjected to fixation with one SCB combined with bilateral LCPs with 10 locking screws and a control group ( n=12) subjected to fixation with bilateral LCPs with 12 locking screws. In each model, a vertical ballast test was conducted to record the maximum axial displacement of the system and a horizontal torsion test to calculate the torsional stiffness of the system. When the loading pressure was 0-1,000 N in the biomechanical machine, structural abnormalities were observed in the 2 groups of models and the system maximum axial displacement and system torsional stiffness were compared between the 2 groups. Results:When the vertical ballast pressure was 400 N, 600 N, 800 N and 1,000 N, the maximum axial displacement of the system was, respectively, (0.14±0.01) mm, (0.25±0.01) mm, (0.41±0.02) mm and (0.63 ± 0.02) mm in the experimental group, and (0.15 ± 0.01) mm, (0.26 ± 0.01) mm, (0.46 ± 0.03) mm, and (0.67 ± 0.04) mm in the control group. Compared with the control group, the average maximum axial displacement in the experimental group decreased significantly under the axial pressure of 600-1,000 N ( P<0.05). When the horizontal torsion reached 5°, the torsional stiffness was, respectively, (2.00±0.12) Nm/° and (2.02±0.07) Nm/° in the experimental group and the control group, showing no significant difference between the 2 groups ( P>0.05). Conclusions:In the treatment of intra-articular distal femur fracture, compared with simple bilateral LCPs, our SCB combined with bilateral LCPs demonstrate similar torsional stability but better axial biomechanical stability. As our SCB has advantages of bilateral compression and minimal invasion in operation, it may be a new option for the reduction and compression treatment of intra-articular fractures.