4.Treatment of Renal Injury in Wilson Disease Based on Pathogenesis of Latent Toxin in Kidney Collaterals
Ke DIAO ; Wenming YANG ; Xiang LI ; Yue YANG ; Yulong YANG ; Zhihong RAO ; Shuzhen FANG ; Yufeng DING
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):132-139
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.
5.Clinical Efficacy of Gandouling Decoction Combined with Neuromuscular Electrical Stimulation on Dysphagia in Wilson Disease with Combined Phlegm and Stasis
Zhihong RAO ; Wenming YANG ; Yue YANG ; Xiang LI ; Peng HUANG ; Yulong YANG ; Ke DIAO ; Shuzhen FANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):155-162
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.
6.Feature reconstruction-based self-supervised learning model for vessel segmentation
Bowen ZHOU ; Hui SUN ; Kaiyue DIAO ; Qing XIA ; Kang LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(06):779-784
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.
7.TCM-HIN2Vec: A strategy for uncovering biological basis of heart qi deficiency pattern based on network embedding and transcriptomic experiment
Lihong Diao ; Xinyi Fan ; JIang Yu ; Kai Huang ; Edouard C Nice ; Chao Liu ; Dong Li ; Shuzhen Guo
Journal of Traditional Chinese Medical Sciences 2024;11(3):264-274
Objective:
To elucidate the biological basis of the heart qi deficiency (HQD) pattern, an in-depth understanding of which is essential for improving clinical herbal therapy.
Methods:
We predicted and characterized HQD pattern genes using the new strategy, TCM-HIN2Vec, which involves heterogeneous network embedding and transcriptomic experiments. First, a heterogeneous network of traditional Chinese medicine (TCM) patterns was constructed using public databases. Next, we predicted HQD pattern genes using a heterogeneous network-embedding algorithm. We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq. Finally, we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.
Results:
Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism, signal transduction pathways, and immune processes. Moreover, we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern. Furthermore, herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.
Conclusion
Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes, but also deciphering the basis of HQD pattern. Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns, leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.
8.Research progress on optical coherence tomography-based morphological changes in the fundus of patients with chronic obstructive pulmonary disease
Yingying DIAO ; Weihua YANG ; Dong FANG ; Wangting LI ; Shaochong ZHANG
International Eye Science 2024;24(10):1563-1568
Chronic obstructive pulmonary disease(COPD)is a group of lung diseases characterized by persistent airflow limitation, often accompanied by chronic hypoxia. This chronic hypoxia can lead to structural and functional changes in the walls of blood vessels throughout the body, causing vascular injury and altered vascular reactivity. The retina and choroid are key ocular structures with rich blood supply and are particularly prone to microstructural changes due to ischemia and hypoxia. Optical coherence tomography(OCT), an ideal tool for observing these microstructural changes, serves as a non-invasive method for assessing retinal microstructures and microvascular pathology. Currently, there is a lack of comprehensive reviews summarizing OCT-based morphological changes in the eyes of COPD patients. This paper provides an in-depth review of existing studies on ocular OCT in COPD patients, focusing on structural and blood flow changes in the retina and choroid. The primary goal of this review is to summarize the impact of COPD on ocular microstructures, explore the underlying mechanisms of these morphological changes, and offer new perspectives for assessing eye diseases in COPD patients.
9.Regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib
Dahong CHEN ; Yafei WU ; Wenjing DIAO ; Huihua YANG ; Pengjuan MAO ; Qin LI
China Pharmacy 2024;35(8):961-966
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.
10.Effects of gene silencing Cyclooxygenase-2 cooperated with hyperbaric oxygen on neurological repair and apoptosis, autophagy in cerebral hemorrhage rats
Qiang PAN ; Lin ZHU ; Yong GAO ; Jun ZHU ; Shuai ZHANG ; Qiang LI ; Xingtao DIAO ; Chunyu SONG
Chinese Journal of Emergency Medicine 2024;33(1):39-46
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.


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