Objective:To explore the mechanism of Danxing Zhishuang Prescription in the treatment of Parkinson's disease (PD) by combining network pharmacology with animal models.Methods:TCMSP, BATMAN database, Genecards, and OMIM databases were retrieved to obtain the active components and action targets of Danxing Zhishuang Prescription. Venny 2.1.0 was used to intersect drug targets and PD related genes, and a protein interaction network of the intersection targets was constructed using the STRING 12.0 platform. Topology analysis was performed using Cytoscape 3.10.0 software to identify the key targets of Danxing Zhishuang Prescription on PD; GO functional and KEGG pathway enrichment analysis was performed on key targets using the WeChat platform, and molecular docking was validated through AutoDockTools 1.5.7. Using a random number table method, mice were divided into a blank control group, a model group, and a Danxing Zhishuang Prescription group, with 20 mice in each group; except for the blank group, all other groups of mice were orally administered fisetin to prepare PD models; Danxing Zhishuang Prescription group was orally administered with concentrated Danxing Zhishuang Prescription at a dosage of 10.5 g/kg, while the blank group and model group were orally administered with 0.2 ml of physiological saline for 21 days; Western blot was used to detect the expressions of Akt1, Bcl-2, Bax, and α-Syn proteins.Results:359 intersection targets, 69 core targets, and 185 active components were obtained the treatment of PD with Danxing Zhishuang Prescription. The main active components included quercetin, kaempferol, phenylalanine, etc., and the key targets were AKT1, TP53, TNF, ESR1, etc. KEGG analysis revealed several key signaling pathways, such as AGE-RAGE, PI3K-Akt, fluid shear stress and atherosclerosis signaling pathways. The validation experiment results showed that compared with the model group, the expression of Bcl-2 protein was up-regulated ( P<0.01), and the expressions of Bax, Akt1, and α-Syn proteins were down-regulated in the Danxing Zhishuang Prescription group ( P<0.01). Conclusions:Danxing Zhishuang Prescription has the advantages of multi target and multi pathway treatment for PD. Its mechanism may be related to down-regulating the expressions of Bax, Akt1, and α-Syn proteins, improving brain blood supply, regulating neurotransmitter balance, inhibiting oxidative stress response, and promoting nerve regeneration.

Objective:To measure the retinal structural and functional parameters of adult Macaca fascicularis, and explore the similarity of the retinal structural and functional parameters between non-human primates and normal human retinas.Methods:Six eyes of 3 5-year-old adult Macaca fascicularis were examined by in vivo detection including color fundus photography, retinal optical coherence tomography (OCT) and electroretinogram (ERG) to determine the thickness of the inner/outer retina at the fovea and 1 000/2 000 μm away from the nasal, temporal, superior and inferior regions of the fovea, the thickness of the retinal nerve fiber layer (RNFL), the area of optic disc, the area of optic cup, the area ratio of cup to disc and the biological parameters of flash ERG.Differences in the above parameters between left and right eyes were analyzed.The similarity of parameters between Macaca fascicularis and human was compared with reference to published literature.The use and care of animals complied with the Regulation on the Management of Experimental Animals.The study protocol was approved by the Institutional Animal Care and Use Committee of Hubei Topgene Biotechnology (NO.IACUC-2019-012). Results:The foveal thickness, optic disc area, cup-disc area ratio, and average RNFL thickness in normal adult Macaca fascicularis were (252.31±4.79)μm, (1.89±0.05)mm 2, 0.14±0.01, and (103.53±0.58)μm, respectively.The b-wave amplitude of dark-adapted 0.01 ERG was (66.75±7.29)μV.The a- and b-wave amplitudes of dark-adapted 3.0 ERG response were (57.15±15.01) and (122.10±25.51)μV, respectively.The a- and b-wave amplitudes, the amplitude of oscillation potentials, and the latency of dark-adapted 10.0 ERG response were (72.98±20.14)μV, (131.67±13.78)μV, (49.98±10.08)μV, and (30.02±5.76)ms, respectively.The a- and b-wave amplitudes of light-adapted 3.0 ERG were (9.16±2.75) and (40.43±5.57)μV, respectively.The latency and the amplitude of the light-adapted 30 Hz flicker was (26.61±1.19)ms and (24.72±5.10)μV, respectively.There was no significant difference in the parameters between left and right eyes (all at P>0.05). The retinal thickness in central fovea, mean RNFL thickness, waveform and amplitude of ERG of Macaca fascicularis were similar to normal human. Conclusions:The structure and function of the retina of adult Macaca fascicularis are similar to those of normal humans.As a laboratory animal for preclinical drug research, in vivo studies of Macaca fascicularis can refer to normal human retinal parameters.

Objective:To classify bladder cancer based on immune cell infiltration score and to construct a prognosis assessment model of patients with bladder cancer.Methods:The transcriptome data and clinical data of breast cancer patients were obtained from the The Cancer Genome Atlas(TCGA)database.Single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells.The classification of breast cancer patients was achieved by unsupervised clustering,and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed.The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis(WGCNA),and the key genes in the modules were identified.A risk scoring model and a nomogram for prognosis assessment of bladder cancer patients were constructed and verified.Results:B cells,mast cells,neutrophils,T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer.The patients were clustered into two groups(Cluster 1′ and Custer 2)based on immune cell infiltration scores.Compared with patients with Cluster 1′,patients with Cluster 2 were more likely to benefit from immunotherapy(P<0.05),and patients with Cluster 2 were more sensitive to Enbeaten,Docetaxel,Cyclopamine,and Akadixin(P<0.05).35 genes related to key immune cells were screened out by WGCNA and 4 genes(GPR171,HOXB3,HOXB5 and HOXB6)related to the prognosis of bladder cancer were further screened by LASSO Cox regression.The areas under the ROC curve(AUC)of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-,3-and 5-year survival of patients were 0.735,0.765 and 0.799,respectively.The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-,3-,and 5-year overall survival of bladder cancer patients.Conclusions:According to the immune cell infiltration score,bladder cancer patients can be classified.Furthermore,bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.

OBJECTIVES: To classify bladder cancer based on immune cell infiltration score and to construct a risk assessment model for prognosis of patients. METHODS: The transcriptome data and data of breast cancer patients were obtained from the TCGA database. The single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells. The classification of breast cancer patients was realized by unsupervised clustering, and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed. The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis (WGCNA), and the key genes in the modules were extracted. A risk scoring model and a nomogram for risk assessment of prognosis for bladder cancer patients were constructed and verified. RESULTS: The immune cell infiltration scores of normal tissues and tumor tissues were calculated, and B cells, mast cells, neutrophils, T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer. Breast cancer patients were clustered into two groups (Cluster 1 and Custer 2) based on immune cell infiltration scores. Compared with patients with Cluster 1, patients with Cluster 2 were more likely to benefit from immunotherapy (P<0.05), and patients with Cluster 2 were more sensitive to Enbeaten, Docetaxel, Cyclopamine, and Akadixin (P<0.05). WGCNA screened out 35 genes related to key immune cells, and 4 genes (GPR171, HOXB3, HOXB5 and HOXB6) related to the prognosis of bladder cancer were further screened by LASSO Cox regression. The areas under the ROC curve (AUC) of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-, 3- and 5-year survival of patients were 0.735, 0.765 and 0.799, respectively. The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-, 3-, and 5-year overall survival of bladder cancer patients. CONCLUSIONS According to the immune cell infiltration score, bladder cancer patients can be classified. And the bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.

BACKGROUND:N6-methyladenosine(m6A)is a hot research topic in the mechanism of pathological cardiac remodeling and plays an important role in the development of cardiovascular diseases. OBJECTIVE:To summarize the possible mechanism by which m6A modification in non-coding RNAs regulates the main processes of pathological cardiac remodeling,such as pathological cardiac hypertrophy,cardiomyocyte death,myocardial fibrosis and vascular remodeling. METHODS:"m6A,non-coding RNA,pathological cardiac hypertrophy,cardiomyocyte apoptosis,cardiomyocyte pyroptosis,cardiomyocyte ferroptosis,myocardial fibrosis,vascular remodeling"were used as search terms in Chinese and English.Relevant literature from CNKI,PubMed and Web of Science databases published from January 1974 to April 2023 was retrieved,and finally 86 eligible articles were reviewed. RESULTS AND CONCLUSION:m6A modification is a highly dynamic and reversible modification.Pathological cardiac remodeling mainly involves pathological cardiac hypertrophy,cardiomyocyte apoptosis,cardiomyocyte pyroptosis,cardiomyocyte ferroptosis,myocardial fibrosis and vascular remodeling.m6A-related enzymes can regulate pathological cardiac remodeling processes through various non-coding RNAs and different signaling pathways,which can be used as a new potential intervention for cardiovascular diseases.In pathological cardiac remodeling,research on the regulatory relationship between m6A modification and non-coding RNAs is still in its infancy.With the development of epigenetics,m6A modification in non-coding RNAs is expected to have a new development in the regulation of pathological cardiac remodeling.

Objective:To classify bladder cancer based on immune cell infiltration score and to construct a prognosis assessment model of patients with bladder cancer.Methods:The transcriptome data and clinical data of breast cancer patients were obtained from the The Cancer Genome Atlas(TCGA)database.Single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells.The classification of breast cancer patients was achieved by unsupervised clustering,and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed.The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis(WGCNA),and the key genes in the modules were identified.A risk scoring model and a nomogram for prognosis assessment of bladder cancer patients were constructed and verified.Results:B cells,mast cells,neutrophils,T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer.The patients were clustered into two groups(Cluster 1′ and Custer 2)based on immune cell infiltration scores.Compared with patients with Cluster 1′,patients with Cluster 2 were more likely to benefit from immunotherapy(P<0.05),and patients with Cluster 2 were more sensitive to Enbeaten,Docetaxel,Cyclopamine,and Akadixin(P<0.05).35 genes related to key immune cells were screened out by WGCNA and 4 genes(GPR171,HOXB3,HOXB5 and HOXB6)related to the prognosis of bladder cancer were further screened by LASSO Cox regression.The areas under the ROC curve(AUC)of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-,3-and 5-year survival of patients were 0.735,0.765 and 0.799,respectively.The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-,3-,and 5-year overall survival of bladder cancer patients.Conclusions:According to the immune cell infiltration score,bladder cancer patients can be classified.Furthermore,bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.

Objective:To classify bladder cancer based on immune cell infiltration score and to construct a prognosis assessment model of patients with bladder cancer.Methods:The transcriptome data and clinical data of breast cancer patients were obtained from the The Cancer Genome Atlas(TCGA)database.Single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells.The classification of breast cancer patients was achieved by unsupervised clustering,and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed.The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis(WGCNA),and the key genes in the modules were identified.A risk scoring model and a nomogram for prognosis assessment of bladder cancer patients were constructed and verified.Results:B cells,mast cells,neutrophils,T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer.The patients were clustered into two groups(Cluster 1′ and Custer 2)based on immune cell infiltration scores.Compared with patients with Cluster 1′,patients with Cluster 2 were more likely to benefit from immunotherapy(P<0.05),and patients with Cluster 2 were more sensitive to Enbeaten,Docetaxel,Cyclopamine,and Akadixin(P<0.05).35 genes related to key immune cells were screened out by WGCNA and 4 genes(GPR171,HOXB3,HOXB5 and HOXB6)related to the prognosis of bladder cancer were further screened by LASSO Cox regression.The areas under the ROC curve(AUC)of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-,3-and 5-year survival of patients were 0.735,0.765 and 0.799,respectively.The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-,3-,and 5-year overall survival of bladder cancer patients.Conclusions:According to the immune cell infiltration score,bladder cancer patients can be classified.Furthermore,bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.

Objective:To classify bladder cancer based on immune cell infiltration score and to construct a prognosis assessment model of patients with bladder cancer.Methods:The transcriptome data and clinical data of breast cancer patients were obtained from the The Cancer Genome Atlas(TCGA)database.Single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells.The classification of breast cancer patients was achieved by unsupervised clustering,and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed.The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis(WGCNA),and the key genes in the modules were identified.A risk scoring model and a nomogram for prognosis assessment of bladder cancer patients were constructed and verified.Results:B cells,mast cells,neutrophils,T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer.The patients were clustered into two groups(Cluster 1′ and Custer 2)based on immune cell infiltration scores.Compared with patients with Cluster 1′,patients with Cluster 2 were more likely to benefit from immunotherapy(P<0.05),and patients with Cluster 2 were more sensitive to Enbeaten,Docetaxel,Cyclopamine,and Akadixin(P<0.05).35 genes related to key immune cells were screened out by WGCNA and 4 genes(GPR171,HOXB3,HOXB5 and HOXB6)related to the prognosis of bladder cancer were further screened by LASSO Cox regression.The areas under the ROC curve(AUC)of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-,3-and 5-year survival of patients were 0.735,0.765 and 0.799,respectively.The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-,3-,and 5-year overall survival of bladder cancer patients.Conclusions:According to the immune cell infiltration score,bladder cancer patients can be classified.Furthermore,bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.

Objective:To classify bladder cancer based on immune cell infiltration score and to construct a prognosis assessment model of patients with bladder cancer.Methods:The transcriptome data and clinical data of breast cancer patients were obtained from the The Cancer Genome Atlas(TCGA)database.Single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells.The classification of breast cancer patients was achieved by unsupervised clustering,and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed.The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis(WGCNA),and the key genes in the modules were identified.A risk scoring model and a nomogram for prognosis assessment of bladder cancer patients were constructed and verified.Results:B cells,mast cells,neutrophils,T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer.The patients were clustered into two groups(Cluster 1′ and Custer 2)based on immune cell infiltration scores.Compared with patients with Cluster 1′,patients with Cluster 2 were more likely to benefit from immunotherapy(P<0.05),and patients with Cluster 2 were more sensitive to Enbeaten,Docetaxel,Cyclopamine,and Akadixin(P<0.05).35 genes related to key immune cells were screened out by WGCNA and 4 genes(GPR171,HOXB3,HOXB5 and HOXB6)related to the prognosis of bladder cancer were further screened by LASSO Cox regression.The areas under the ROC curve(AUC)of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-,3-and 5-year survival of patients were 0.735,0.765 and 0.799,respectively.The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-,3-,and 5-year overall survival of bladder cancer patients.Conclusions:According to the immune cell infiltration score,bladder cancer patients can be classified.Furthermore,bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.

Objective:To classify bladder cancer based on immune cell infiltration score and to construct a prognosis assessment model of patients with bladder cancer.Methods:The transcriptome data and clinical data of breast cancer patients were obtained from the The Cancer Genome Atlas(TCGA)database.Single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells.The classification of breast cancer patients was achieved by unsupervised clustering,and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed.The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis(WGCNA),and the key genes in the modules were identified.A risk scoring model and a nomogram for prognosis assessment of bladder cancer patients were constructed and verified.Results:B cells,mast cells,neutrophils,T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer.The patients were clustered into two groups(Cluster 1′ and Custer 2)based on immune cell infiltration scores.Compared with patients with Cluster 1′,patients with Cluster 2 were more likely to benefit from immunotherapy(P<0.05),and patients with Cluster 2 were more sensitive to Enbeaten,Docetaxel,Cyclopamine,and Akadixin(P<0.05).35 genes related to key immune cells were screened out by WGCNA and 4 genes(GPR171,HOXB3,HOXB5 and HOXB6)related to the prognosis of bladder cancer were further screened by LASSO Cox regression.The areas under the ROC curve(AUC)of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-,3-and 5-year survival of patients were 0.735,0.765 and 0.799,respectively.The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-,3-,and 5-year overall survival of bladder cancer patients.Conclusions:According to the immune cell infiltration score,bladder cancer patients can be classified.Furthermore,bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.