Wilson disease （WD） is a hereditary disorder of copper metabolism characterized by abnormal copper accumulation in tissues， including the liver and brain， which leads to severe hepatic and neurological damage. This disease is often accompanied by lipid metabolism abnormalities， and the exploration of related mechanisms has attracted increasing attention. This article introduces the clinical features of lipid metabolism disorders in WD patients， summarizes the research advances in the serum levels of lipids and hepatic steatosis， analyzes the potential mechanisms of the interaction between copper and lipid metabolism， and highlights the significance of lipid-related molecules in disease diagnosis and clinical evaluation. In clinical practice， the monitoring and assessment of lipid metabolism parameters should be taken seriously in patients with WD， in order to promote comprehensive disease management and improve the prognosis of patients.

ObjectiveTo investigate the effect of Zishen Huoxue Formula （ZSXHF） on molecular-targeted therapy-associated proteinuria in patients with primary liver cancer （PLC）， to assess the efficacy of ZSXHF in the treatment of molecular-targeted therapy-associated proteinuria， and to provide a basis for clinical medication. MethodsA retrospective cohort study was conducted among the PLC patients with molecular-targeted therapy-associated proteinuria who were diagnosed and treated in The Department of Hepatology of Chinese PLA General Hospital， from January 1， 2022 to July 1， 2025. With ZSXHF treatment as the exposure factor， the patients with a cumulative treatment duration of ≥9 weeks were enrolled as traditional Chinese medicine （TCM） group， while those without TCM treatment were enrolled as control group. Propensity score matching was performed for the two groups at a ratio of 1∶1 based on sex， age， 24-hour urinary protein， blood urea nitrogen， and serum creatinine. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for promoting the improvement of targeted-therapy-associated proteinuria. ResultsA total of 137 PLC patients with targeted-therapy-associated proteinuria were enrolled， with 34 patients in the TCM group and 103 in the control group. After follow-up for 6 months， the TCM group had a significant improvement in urinary protein grade compared with the control group （χ²=9.261， P=0.016）. There were 25 patients in each group after propensity score matching， and after follow-up for 6 months， there were significant differences between the two groups in urinary protein grade （χ²=15.689， P<0.001） and 24-hour urinary protein （Z=-3.075， P=0.002）. After cumulative treatment with ZSXHF for ≥9 weeks， the TCM group had a significantly greater change in 24-hour urinary protein from baseline compared with the control group （t=-2.514， P=0.016）， while there were no significant differences in the changes in liver and renal function after ZSXHF intervention between the two groups （all P>0.05）. The multivariate Logistic regression analysis showed that ZSXHF treatment （odds ratio=2.901， 95% confidence interval： 1.135 — 7.417， P=0.026） was an independent influencing factor for improvement in molecular-targeted therapy-associated proteinuria. ConclusionZSHXF can effectively alleviate molecular-targeted therapy-associated proteinuria in PLC patients with a favorable safety profile， which provides a new reference for TCM prevention and treatment of molecular-targeted therapy-associated adverse reactions in PLC patients.

Enzymes are widely used in chemical and pharmaceutical industries because of their advantages of high efficiency and specificity. However， the shortcomings of the free enzymes， such as poor stability and difficulty in recycling， limit their application. Therefore， the immobilization and application of enzymes have become one of the research hotspots. The selection of the immobilization carriers is a critical step in the process of enzyme immobilization. Metal-organic frameworks（MOFs）， a kind of porous materials， are formed by the coordination of metal ions or metal clusters with organic ligands. As an emerging immobilization carrier， its advantages such as high porosity， strong stability， and surface modifiability make it ideal for immobilized enzyme carriers. By immobilizing the free enzyme on MOFs， the above mentioned deficiencies of the free enzymes can be effectively solved， which greatly broaden the applicable condition. Ligand fishing is a method to find receptor-specific ligands from complex components， which has the advantages of high efficiency， simple sample pretreatment and high specificity. The MOF-enzyme complex formed by enzyme immobilization can act as a "fishing rod" for ligand fishing， which can screen out the targets from the complex system of components. The complex chemical composition and various active ingredients of traditional Chinese medicine（TCM） make the ligand fishing technology to play a big role in the screening of enzyme inhibitors from TCM. And the screened enzyme inhibitors are expected to be further developed into the lead compounds with good efficacy and low adverse effects， so the immobilized enzymes of MOFs have a wide application in the screening of active ingredients from TCM. Based on this， this paper summarized the methods of immobilized enzymes of MOFs in recent years， analyzed the characteristics， advantages and disadvantages of each method， and summarized the laws of preparation conditions and mechanisms. Meanwhile， the application and future development of immobilized enzymes of MOFs in the field of enzyme inhibitor screening from TCM were also summarized and prospected， with a view to providing a reference for the development of natural ingredients and the modernization of TCM.

Objective To investigate the influence of different cell structures on the static and dynamic mechanical performance of porous titanium alloy scaffolds,and to provide a theoretical mechanical basis for the application of scaffolds in the repair of mandibular bone defects.Methods Porous titanium alloy scaffolds with diamond,cubic,and cross-sectional cubic cell structures were manufactured using three-dimensional printing technology.Uniaxial compression tests and ratcheting fatigue with compression load tests were conducted to analyze the static and dynamic mechanical performances of scaffolds with different cell structures.Results The elastic moduli of the diamond cell,cross-sectional cubic cell,and cubic cell scaffolds were 1.17,0.566,and 0.322 GPa,respectively,and the yield strengths were 71.8,65.1,and 31.8 MPa,respectively.After reaching the stable stage,the ratcheting strains of the cross-sectional cubic,diamond,and cubic cell scaffolds were 3.3%,4.0%,and 4.5%,respectively.The ratcheting strain increased with increasing average stress,stress amplitude,and peak holding time,and decreased with increasing loading rate.Conclusions The evaluation results of the static mechanical performance showed that the diamond cell scaffold was the best,followed by the cross-sectional cubic cell scaffold and the cubic cell scaffold.The evaluation results of the dynamic mechanical performance showed that the cross-sectional cubic cell scaffold performed the best,followed by the diamond cell scaffold,whereas the cubic cell scaffold performed the worst.The fatigue performance of the scaffold is affected by the loading conditions.These results provide new insights for scaffold construction for the repair of mandibular bone defects and provide an experimental basis for further clinical applications of this scaffold technology.

Objective To develop a portable three-dimensional foot motion analysis system based on low-cost inertial measurement units(IMU)and force sensing resistor(FSR),and to explore the feasibility of assessing three-dimensional motion of internal small joints of foot in barefoot and shod conditions. Methods The system consisted of data sampling,data transmitting and data processing parts.IMUs were employed for data acquisition of small foot joints,and FSRs were utilized to detect heel strike and toe off.All the data were transmitted via wireless local area network.Data processing was accomplished by a self-programmed Excel mac-ro.From January to July,2024,two healthy female subjects wearing the device walked in the corridor at self-se-lected pace,for ten meters.Gait analysis was used to conduct consistency test on subject 2.Dorsiflexion-plan-tarflexion,adduction-abduction and internal rotation-external rotation of the 1st metatarsal relative to the phalan-geal(Met-Ph),the midfoot relative to the 1st metatarsal(Mid-Met)were recorded and analyzed on subject 1 in consecutive barefoot walking and two types of nurse footwear walking conditions. Results The system showed good consistency between tests.Dorsiflexion-plantarflexion,adduction-abduction and inter-nal rotation-external rotation ranges of motion were reduced in both Met-Ph and Mid-Met with shoes compared with those of bare foot,they were the least in arch support. Conclusion A low-cost,portable three-dimensional foot motion analysis system has been developed,which could be used to measure barefoot motion and shod foot motion in consecutive walking.

In multiple areas such as science, technology, and economic activities, it is necessary to unify the management of repetitive tasks or concepts by standardization to obtain the best order and high efficiency. Organoids, as living tissue models, have rapidly developed in the past decade. Organoids can be used repetitively for in vitro culture, cryopreservation, and recovery for further utilization. Because organoids can recapitulate the parental tissues' morphological phenotypes, cell functions, biological behaviors, and genomic profiles, they are known as renewable "living biobanks". Organoids cover two mainstream fields: Adult stem cell-derived organoids (also known as patient-derived organoids) and induced pluripotent stem cell-derived and/or embryonic stem cell-derived organoids. Given the increasing importance of organoids in the development of new drugs, standardized operation, and management in all steps of organoid construction is an important guarantee to ensure the high quality of products. In this review, we systematically introduce the standardization of organoid construction operation procedures, the standardization of laboratory construction, and available standardization documents related to organoid culture that have been published so far. We also proposed the challenges and prospects in this field.
Organoids ; Humans ; Biological Specimen Banks/standards* ; Induced Pluripotent Stem Cells/cytology* ; Cryopreservation/methods*

Objective To study stress relaxation behaviors of cartilage scaffolds under different degradation cycles by using finite element analysis combined with theoretical models. Methods Based on the established degradation theoretical model, the elastic modulus of the scaffold was calculated under different degradation cycles. The finite element model of cartilage scaffolds was established and stress relaxation simulation was performed to analyze the variation of scaffold relaxation stress with time. The stress relaxation constitutive model was established to predict mechanical properties of the scaffold. Results The elastic modulus of cartilage scaffolds at 14 th, 28th, 42nd, 56th day after degradation was 32. 35, 31. 12, 29. 91, 28. 74 kPa, respectively. The upper layer for cartilage scaffolds was the largest. The overall relaxation stress of the scaffold decreased rapidly with time and then tended to be stable. At 8th week after degradation, the stress which the scaffold couldwithstand was still within the physiological load range of the cartilage. The predicted results of the stress relaxation constitutive model were in good agreement with the finite element simulation results. Conclusions The elastic modulus of the scaffold gradually decreases with the increase of degradation time. The longer the degradation period is, the less stress the scaffold can withstand. At the same degradation period, the larger the applied compressive strain, the larger the stress on the scaffold. Both the finite element simulation and stress relaxation constitutive model can effectively predict stress variations of cartilage scaffolds under degradation

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Gas therapy has been proven to be a promising and advantageous treatment option for cancers. Studies have shown that nitric oxide (NO) is one of the smallest structurally significant gas molecules with great potential to suppress cancer. However, there is controversy and concern about its use as it exhibits the opposite physiological effects based on its levels in the tumor. Therefore, the anti-cancer mechanism of NO is the key to cancer treatment, and rationally designed NO delivery systems are crucial to the success of NO biomedical applications. This review summarizes the endogenous production of NO, its physiological mechanisms of action, the application of NO in cancer treatment, and nano-delivery systems for delivering NO donors. Moreover, it briefly reviews challenges in delivering NO from different nanoparticles and the issues associated with its combination treatment strategies. The advantages and challenges of various NO delivery platforms are recapitulated for possible transformation into clinical applications.

Objective To study the effect of irrigation mechanical stimulation on scaffold degradation by numerical simulation, so as to predict its degradation degree. MethodsBased on perfusion experimental data, the fluid-solid coupling model was established by Comsol. The finite element model of scaffold was established by ABAQUS. Based on the models, the degradation performance of scaffold was simulated and predicted. Results The fluid-solid coupling simulation showed that the initial pressure at the speed of 15.79 mL/min was two-fold of that at 7.89 mL/min. Along the thickness of scaffold from the surface to the bottom, the pressures between the two velocities were decreased and gradually close to each other. The degradation of scaffold structure could be simulated dynamically by combining the degradation constitutive model with the finite element model. The obtained degradation data were consistent with the experimental data, and the residual molecular weight reached 0.643 on the 56th day. Compared with the experimental data, the simulation accuracy was higher than 98%. Conclusions The larger the perfusion velocity is, the greater the pressure on scaffold will be. Under the same perfusion velocity, the maximum force occurs on the surface of scaffold. The degradation pattern of scaffold can be predicted by applying the degradation constitutive model and the finite element model.