Hepatolenticular degeneration， also known as Wilson disease （WD）， is a hereditary disease caused by mutations in the ATP7B gene， leading to copper metabolism disorders. Gene mutations result in impaired synthesis of copper-binding protein， and abnormal excretion of copper through bile leads to pathological deposition of copper in various organs， ultimately causing multi-organ damage. The insidious onset and low specificity of symptoms make it difficult to diagnose this disease. On the basis of existing studies and the theory of latent toxin， this paper proposes that latent toxin in kidney collaterals is the main pathogenesis of renal injury in WD. It is pointed out that health Qi deficiency and latent pathogen are the premises for the occurrence of this disease， and the transformation of latent pathogen into toxin is the ley pathological process. Toxin damaging kidney collaterals is the ultimate result. According to the pathogenesis， this paper proposes the treatment principle of reinforcing healthy Qi and resolving toxin and treatment based on syndrome differentiation. This review provides new ideas for the diagnosis and treatment of renal injury in WD with traditional Chinese medicine.

ObjectiveTo observe the clinical efficacy of Gandouling decoction combined with neuromuscular electrical stimulation （NMES） in the treatment of dysphagia in Wilson disease （WD） with combined phlegm and stasis. MethodsA total of 80 WD patients with dysphagia due to combined phlegm and stasis treated in the Department of Encephalopathy， the First Affiliated Hospital of Anhui University of Chinese Medicine were randomized into a control group and an observation group， with 40 patients in each group. In addition， 40 healthy volunteers were recruited as the normal group. The control group was treated with basic copper drainage combined with NMES. The observation group was treated with Gandouling Decoction on the basis of the therapy in the control group. Each course of treatment lasted for 8 days， and the patients were treated for a total of 4 courses. All subjects underwent video fluoroscopic swallowing study （VFSS） before and after treatment. During the examination， contrast agents with 4 different characters were used for the swallowing action， and the passing time was recorded. The TCM syndrome score， water swallow test score， standard swallowing assessment （SSA） score， and 24-h urinary copper level before and after treatment were analyzed. ResultsWhen performing VFSS， the passing time of contrast agents of different characters in the oral stage was longer in the WD group than in the normal group （P<0.01）， while it had no significant difference in the pharyngeal stage. After treatment， the passing time in the oral stage shortened in the control and observation groups （P<0.01）， and the observation group outperformed the control group （P<0.01）. After treatment， both the control and observation groups showed declines in TCM syndrome score and SSA score （P<0.01） and an increase in water swallow test score （P<0.01）， and the changes were more obvious in the observation group than in the control group （P<0.01）. In addition， the treatment in the control and observation groups elevated the 24-h urinary copper level （P<0.01）， and the elevation in the observation group was more obvious than that in the control group （P<0.01）. Neither group showed obvious adverse reaction. ConclusionGandouling decoction combined with NMES can significantly ameliorate dysphagia in WD patients with the syndrome of combined phlegm and stasis regarding the TCM syndrome score， water swallow test score， and SSA score， demonstrating definite clinical efficacy and high safety.

Objective To propose an innovative self-supervised learning method for vascular segmentation in computed tomography angiography (CTA) images by integrating feature reconstruction with masked autoencoding. Methods A 3D masked autoencoder-based framework was developed, where in 3D histogram of oriented gradients (HOG) was utilized for multi-scale vascular feature extraction. During pre-training, random masking was applied to local patches of CTA images, and the model was trained to jointly reconstruct original voxels and HOG features of masked regions. The pre-trained model was further fine-tuned on two annotated datasets for clinical-level vessel segmentation. Results Evaluated on two independent datasets (30 labeled CTA images each), our method achieved superior segmentation accuracy to the supervised neural network U-Net (nnU-Net) baseline, with Dice similarity coefficients of 91.2% vs. 89.7% (aorta) and 84.8% vs. 83.2% (coronary arteries). Conclusion The proposed self-supervised model significantly reduces manual annotation costs without compromising segmentation precision, showing substantial potential for enhancing clinical workflows in vascular disease management.

OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject， the lenvatinib-resist cell model （Huh7-LR） was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1， autophagic adapter protein sequestosome 1 （p62）， microtubule-associated protein 1 light chain 3 （LC3） and autophagic level. Furthermore， an autophagy activation model was constructed by cell starvation， the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection， and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells， the drug resistance index of Huh7-LR cells was 6.2； protein expression of p62 was increased significantly， while apoptotic rate， protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly （P＜0.05 or P＜0.01）； the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells （P＜0.05） and autophagy level， and significantly increase its apoptotic rate （P＜0.05）. CONCLUSIONS Autophagy is involved in lenvatinib resistance， and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.

Objective:To investigate the effects of gene silencing inducible cyclooxygenase-2 (COX-2) combined with hyperbaric oxygen (HBO) on neuronal cell edema, apoptosis, autophagy and neural functional recovery in rats with intracerebral hemorrhage.Methods:SPF-grade adult male SD rats ( n=96) were used to establish a cerebral hemorrhage model through stereotactic injection of thrombin VII into the caudate nucleus. They were randomized (random number) into 4 groups ( n=24/group): control group, hyperbaric oxygen (HBO) group, COX-2 RNAi group and combined group (COX-2 RNAi+HBO). The siRNA plasmid targeting silencing COX-2 gene expression was constructed. After group treatment, the four rats were randomly selected from each group for testing in each category. Postoperative day 1, 7, and 14 were assessed using the modified neurological severity score (mNSS) for evaluating neurofunctional deficits. On the 7th day, the water content of the brain tissue was measured using the dry/wet weight method. The blood-brain barrier permeability was assessed using the Evans method. Annexin V and TUNEL assays were employed to assess the apoptotic rate of neural cells. The mRNA expression level of COX-2 in brain tissue was determined using the RT-PCR method. The protein expression levels of Beclin-1, COX-2, aquaporin 4 (AQP-4), B cell lymphoma/lewkmia-2 (Bcl-2), caspase-3, hypoxia-inducible factor-1α (HIF-1α) and matrix metalloprotein-2/9 (MMP-2/9) were detected by Western blot (WB). SPSS software was used for data analysis. One-way ANOVA was used for inter group comparisons and LSD- t test was used for further pairwise comparison. Results:The SD rat intracerebral hemorrhage model and plasmid construction were successfully achieved. The mNSS scores were significantly decreased in COX-2 RNAi, HBO and combined groups compared with control group on the 7th day and 14th day (all P<0.01), especially in combined group ( P<0.01). The contents of Evans blue and the water content of brain tissue of all treatment groups were significantly lower than those in control group (all P<0.05), especially in combined group ( P<0.01). The apoptotic rate of neural cells decreased in all treatment groups compared with the control group (all P<0.05), and the combined group decreased the most ( P<0.01). The mRNA expression levels of COX-2 were significantly decreased in all treatment groups compared with the control group (all P<0.01), and combined group silenced COX-2 expression most obviously ( P<0.05). The results of WB showed that the protein expression levels of Beclin-1, COX-2, AQP-4, Caspase-3, HIF-1α, MMP-2/9 were significantly lower than control group (all P<0.05), while the expression of Bcl-2 was increased in all treatment groups (all P<0.01). Among them, the combined group exhibited the most pronounced trend ( P<0.01). Conclusions:Gene silencing of COX-2 in combination with hyperbaric oxygen therapy can effectively restore neurological function in rats with cerebral hemorrhage. The mechanism may be associated with reduced blood-brain barrier permeability, alleviated brain edema, and inhibition of neuronal apoptosis and autophagy.

The prevalence of diabetes mellitus in China has recently been increasing year by year,and spontaneous skin ulcers in diabetic patients,as one of the most serious complications,often develop on the patient's extremities represented by foot ulcers.Due to the complexity and variety of its pathogenesis,it leads to poor clinical outcomes and difficulty in healing.Thus,pa-tients often face the risk of amputation and death.Therefore,the exploration of mechanisms of the vascular pathogenesis of diabetic delayed-healing wounds and targeted screening of therapeutic agents has become a current research hotspot.Herein,in this paper,we briefly review the role of impaired angiogenesis and vascular dysfunction in diabetic skin ulcers,and the research progress of classical hypoglycemic and natural compounds against vascular lesions is preliminarily summarized to provide a theoretical basis for effective clinical treatment.

Objective It aims to construct an evaluation index system for the development level of intelligent health insurance,which can serve as a reference for health insurance management departments in assessing the develop-ment level of intelligent health insurance and the implementation of health insurance informatization.Methods Key events in intelligent health insurance were identified based on event system theory and text analysis.The evaluation index system was determined through a combination of expert interviews and Delphi expert consultations.The entro-py method was used to calculate the weights of each index,followed by the assessment of the current and ideal de-velopment levels.Results A total of 16 experts were consulted.After two rounds of Delphi expert consultation,two first-level indicators and 18 second-level indicators were finally included in the system.The current development level of intelligent health insurance in China is at the intelligent development stage(2.524 points),while the ideal de-velopment level is at the intelligent improvement stage(4.073 points).The positivity coefficient of both rounds of Del-phi expert consultation was 100%,with an authority coefficient of 0.842,and the degree of expert coordination im-proved with each round.Conclusion The constructed evaluation index system exhibits high scientificity,stability,and generalizability.It can provide an effective evaluation tool for the development of intelligent health insurance in various pooled areas.