ObjectiveTo observe the clinical efficacy and safety of Bushen Ruyan Formulation （补肾乳岩方， BRF） in treating premenopausal breast cancer patients of disharmony of the chong （冲） and ren （任） meridian type under endocrine intensive therapy. MethodsA total of 88 premenopausal breast cancer patients who received endocrine intensive therapy and were diagnosed with disharmony of the chong and ren meridian by traditional Chinese medicine （TCM） were included and randomly divided into a control group and a treatment group， with 44 cases in each group. The control group received ovarian function suppression （OFS） combined with endocrine therapy， while the treatment group was given oral BRF additionally. Both groups were treated for three months. The clinical efficacy was evaluated by comparing the pre- and post-treatment results of the Functional Assessment of Cancer Therapy-Breast （FACT-B）， modified Kupperman score， T cell subsets （CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺）， sex hormone levels， including estradiol （E₂）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， progesterone （P）， testosterone （T）， and prolactin （PRL）， tumor markers， such as carcinoembryonic antigen （CEA）， carbohydrate antigen 125 （CA125）， and carbohydrate antigen 153 （CA153）， TCM syndrome score， and TCM syndrome efficacy. Blood routine tests， liver function and kidney function were monitored to assess safety. ResultsThe FACT-B scores of each domains and the total scores of the treatment group increased， while the social/family status score of the control group decreased. The treatment group had significantly higher scores in all domains and total score compared to the control group （P＜0.05 or P＜0.01）. The modified Kupperman score and TCM syndrome score of the treatment group decreased， and were lower than those of the control group （P＜0.01）. The levels of CD3⁺ and CD4⁺ in the treatment group increased， and were higher than those of the control group （P＜0.05）. Serum testosterone levels in the treatment group were lower than those in the control group （P＜0.05）. The total effective rate of TCM syndrome efficacy in the treatment group was 67.44%， significantly higher than the 23.26% in the control group （P＜0.05）. No significant abnormalities were observed in the blood routine tests or liver/kidney function indicators in either group before or after treatment. ConclusionBRF can effectively improve quality of life， alleviate symptoms， increase serum CD3⁺ and CD4⁺ levels， and enhance clinical efficacy in premenopausal breast cancer patients undergoing endocrine intensive endocrine therapy. It is also safe with no significant adverse effects.

Objective To verify the genetic characteristics associated with gastric cancer,and to propose a hybrid feature selection method for identifying target genes,further analyzing their significance and establishing a new diagnostic prediction model.Methods Analysis of variance in bioinformatics was performed on the original gastric cancer data,and then machine learning methods such as random forest,recursive feature elimination of support vector machine,and LASSO algorithm were used to screen gastric cancer associated genes,and the intersection of results was taken as the key gene set.The key genes were identified and verified through enrichment analysis.The diagnosis and prediction models based on 8 kinds of machine learning classification algorithms such as multi-layer perceptron,logistic regression and decision tree,were constructed using the key genes.Results The key genes selected by the hybrid feature selection method were closely related to the tumorigenesis and development.Eight key genes(TXNDC5,BMP8A,ONECUT2,COL10A1,JCHAIN,INHBA,LCTL and TRIM59)were identified as potential markers of good diagnostic efficacy in gastric cancer.The ROC curve and accuracy results demonstrated that among the 8 classification models,MLP is the best gastric cancer prediction model,with an accuracy of 97.77%,which was 3.83%higher than that of Xgboost gastric cancer prediction model.Conclusion The study identifies 8 key genes for the diagnosis and prevention of gastric cancer,and establishes the optimal prognosis model.

Tumors are serious diseases threatening human health,and the early diagnosis is essential to improve treatment success and patient survival.The study of tumor gene expression data has become a major tool for revealing tumor disease mechanisms,in which artificial intelligence plays an important role.The potential advantages of supervised learning,unsupervised learning and deep learning in tumor prediction and classification are explored from the perspective of machine learning methods.Special attention is paid to the impact of feature selection algorithms on gene screening and their importance in high-dimensional gene expression data.By providing a comprehensive overview of the application and development of artificial intelligence in the analysis of tumor gene expression data,the study aims to provide an outlook for future research directions and promote further development.

Objective:To analyze the types and functions of CD34 + cells in full-thickness skin defect wounds of normal mice and diabetic mice by single-cell RNA sequencing. Methods:This study was an experimental study. The CD34 + cell lineage tracing mouse was produced, and the visualization of CD34 + cells under the fluorescent condition was realized. Six male CD34 + cell lineage tracing mice aged 7-8 weeks (designated as diabetic group) were intraperitoneally injected with streptozotocin to establish a diabetic model, and full-thickness skin defect wounds were prepared on their backs when they reached 13 weeks old. Another 6 male CD34 + cell lineage tracing mice aged 13 weeks (designated as control group) were also subjected to full-thickness skin defect wounds on their backs. On post-injury day (PID) 4, wound tissue was collected from 3 mice in control group and 2 mice in diabetic group, and digested to prepare single-cell suspensions. CD34 + cells were screened using fluorescence-activated cell sorting, followed by single-cell RNA sequencing. The Seurat 4.0.2 program in the R programming language was utilized for dimensionality reduction, visualization, and cell clustering analysis of CD34 + cell types, and to screen and annotate the marker genes for each CD34 + cell subpopulation. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis was performed to analyze the differentially expressed genes (DEGs) of CD34 + fibroblasts (Fbs), smooth muscle cells (SMCs), keratinocytes (KCs), and chondrocyte-like cells (CLCs) in the wound tissue of two groups of mice for exploring cellular functions. Results:On PID 4, CD34 + cells in the wound tissue of both groups of mice were consisted of 7 cell types, specifically endothelial cells, Fbs, KCs, macrophages, T cells, SMCs, and CLCs. Among these, Fbs were further classified into 5 subpopulations. Compared with those in control group, the proportions of CD34 + endothelial cells, Fbs subpopulation 1, Fbs subpopulation 4, KCs, and CLCs in the wound tissue of mice were increased in diabetic group, while the proportions of CD34 + Fbs subpopulation 2, Fbs subpopulation 3, and SMCs were decreased. The marker genes for annotating CD34 + CLCs, endothelial cells, Fbs subpopulation 1, Fbs subpopulation 2, Fbs subpopulation 3, Fbs subpopulation 4, Fbs subpopulation 5, KCs, macrophages, SMCs, and T cells were respectively metastasis-associated lung adenocarcinoma transcript 1, fatty acid binding protein 4, Gremlin 1, complement component 4B, H19 imprinted maternally expressed transcript, Dickkopf Wnt signaling pathway inhibitor 2, fibromodulin, keratin 5, CD74 molecule, regulator of G protein signaling 5, and inducible T-cell co-stimulator molecule. KEGG and GO enrichment analysis revealed that, compared with those in control group, DEGs with significant differential expression (SDE) in CD34 + Fbs from the wound tissue of mice in diabetic group on PID 4 were significantly enriched in terms related to inflammatory response, extracellular matrix (ECM) organization, regulation of cell proliferation, and aging (with Pvalues all <0.05), DEGs with SDE in CD34 + SMCs were significantly enriched in terms related to cell migration, apoptotic process, positive regulation of transcription, and phagosome (with P values all <0.05), DEGs with SDE in CD34 + KCs were significantly enriched in terms related to mitochondrial function, transcription, and neurodegenerative diseases (with P values all <0.05), and DEGs with SDE in CD34 + CLCs were significantly enriched in terms related to rhythm regulation, ECM, and viral infection (with P values all <0.05). Conclusions:CD34 + cells display high heterogeneity in the healing process of full-thickness skin defect wounds in both normal mice and diabetic mice. The significantly enriched functions of DEGs with SDE in CD34 + cell subpopulations in the wound tissue of the two mouse groups are closely related to the wound healing process.

Autism spectrum disorder（ASD）is a neurodevelopmental disorder characterized by social disorders and restricted，repetitive stereotyped behaviors.The pathogenesis of ASD is not clear.There are no recognized drugs that could be used to improve the core symptoms of ASD.Drug treatment is mainly aimed at their emotional problems and inappropriate behavior.Atypical second-generation antipsychotic drugs such as risperidone and aripiprazole are commonly used to deal with the emotional and behavioral problems of children with ASD.Comorbidities such as attention deficit hyperactivity disorder，epilepsy，gastrointestinal symptoms and sleep disorder are common in children with ASD.Methylphenidate and atomoxetine are the first choice for the treatment of ASD with attention deficit hyperactivity disorder.At present，there are still some drugs that have not been widely used in clinical practice，and need further support from evidence-based medicine.

Objective:To investigate the mechanism of Wenjing Decoction in the treatment of hepatic fibrosis through network pharmacological methods, and conducting animal experiments to verify the core targets.Methods:The TCMSP database platform was used to screen the active components and related targets of Wenjing Decoction, and the Uniprot database was used to obtain the target genes corresponding to the active components of Wenjing Decoction. The network diagram of "Chinese materia medica-compound-target" was constructed in Cytoscape 3.7.2, and the GeneCards database was used to search liver fibrosis related targets. String database was used to construct a protein interaction network (PPI) to screen the core components and key targets of liver fibrosis, and GO analysis and KEGG pathway enrichment were performed. Animal experiments were conducted to verify the results of the analysis. 10 mice were selected as the blank group, and the remaining 45 rats were induced with carbon tetrachloride induced liver fibrosis model. After modeling, 40 successfully modeled rats were divided into model group and Wenjing Decoction high, medium-, and low-dosage groups using a random number table method, with 10 rats in each group. Wenjing Decoction high, medium-, and low-dosage groups were orally administered with 1.5×3.18, 3.18, and 0.5×3.18 g/kg Wenjing Decoction, respectively. The blank group was orally administered with equal volume distilled water once a day for 8 consecutive weeks. HE staining was used to observe the histopathological and morphological changes in the liver of rats. The serum GPT and GOT levels of rats were detected using a fully automated biochemical analyzer, and the expressions of TNF, AKT, and IL-6 proteins in rat liver tissue was detected using Western Blot.Results:A total of 188 active components of Wenjing Decoction were obtained, and the active components with higher degree values were β-sitosterol, quercetin, naringenin, etc. 799 liver fibrosis gene targets were collected, and the core target genes of the PPI network were TNF, AKT, IL6, etc. The key anti-hepatic fibrosis related pathways were obtained by GO function and KEGG analysis, including pathway in cancer, TNF, PI3K-Akt and other signalling pathways. Results of animal experiments showed that there were obvious inflammatory infiltration, collagen fibre and pseudo lobe generation in the liver tissue of rats in the model group, and the levels of inflammation and fibrosis in the liver tissue of rats in the Wenjing Decoction high, medium-, and low-dosage groups were improved to different degrees compared with that of the model group; compared with the model group, the levels of serum GPT and GOT decreased ( P<0.05); the protein expressions of TNF, AKT and IL6 in the Wenjing Decoction high, medium-, and low-dosage groups decreased ( P<0.05). Conclusion:Wenjing Decoction may exert anti-liver fibrosis effects by intervening in TNF, AKT, IL6 targets, regulating cancer pathways, TNF, PI3K Akt and other signaling pathways.

AIM:To investigate the effects of epal-restat(Epa)on the mitochondrial oxidative stress damage of radiation pneumonitis(RP)mice and to explore its possible mechanism.METHODS:C57BL/6 mice were randomly divided into control(CON),Irradiation(IR),IR combined with Epa(10 mg/kg)and IR combined with Epa(20 mg/kg)group,16 mice in each group.Mouse models of RP were es-tablished by whole thorax irradiation at a dose of 15Gy using a 6-MV linear accelerator.Continuous intragastric administration after IR for 6 or 8 weeks.Lung histopathology was analyzed by HE staining.The expression of aldose reductase(AR)was deter-mined by immunohistochemistry.Mitochondrial morphology of lung tissues was observed by trans-mission electron microscopy.The levels of inflam-matory cytokines(IL-6,TNF-α and TGF-β1)in plas-ma were detected by ELISA.The contents of Malo-ndialdehyde(MDA)and 4-hydroxynonenal(4-HNE)in lung tissues were determined by colorimetry.Sin-gle cell suspension of lung tissues was prepared and reactive oxygen species(ROS)levels in the cells was examined using a DCFH-DA fluorescent probe.Real-time quantitative PCR was used to determine the expression of AR,IL-6,TNF-α and TGF-β1.The protein levels of AR,IL-6,TNF-α,TGF-β1,BAX,Bcl2,Cleaved Caspase-3,8-oxoguanine DNA glycosylase 1(OGG1)and silent information regulator 3(SIRT3)were detected by Western blot analysis.RESULTS:Compared with the CON group,the alveolar hyper-plasia,alveolar septum thickening and inflammato-ry cell infiltration were observed in the IR group.Moreover,the content of inflammatory factors such as IL-6,TNF-α and TGF-β1 and the expression of BAX and Cleaved Caspase-3 were significantly in-creased,and the expression of Bcl2 was obviously decreased after irradiation.Compared with the IR group,Epa robustly alleviated RP.Meanwhile,Epa down-regulated inflammatory cells infiltration and the expression of inflammatory cytokines,such as IL-6,TNF-α and TGF-β1.In addition,Epa could down-regulate the expression of BAX and Cleaved Caspase-3,and up-regulate Bcl2 in lung tissues.Compared with the CON group,the expression of AR,the levels of ROS,MDA and 4-HNE were signifi-cantly increased,the expression of OGG1 and SIRT3 were significantly decreased,and mitochon-drial damage was aggravated in the IR group.Com-pared with IR group,the expression of AR was sig-nificantly down-regulated,the levels of ROS,MDA and 4-HNE were significantly decreased,the expres-sions of OGG1 and SIRT3 were significantly in-creased,and the mitochondrial damage was signifi-cantly alleviated in IR group after 6 to 8 weeks of Epa administration.CONCLUSION:Epa has a pro-tective effect on RP,which may be related to the in-hibition of AR expression,the reduction of mito-chondrial oxidative stress injury,and the inhibition of inflammatory response and cell apoptosis.

Objective    To evaluate the short-term therapeutic effect of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of acute type A aortic dissection (ATAAD). Methods    From November 2019 to July 2020, 28 patients with ATAAD were treated by extended adventitial inversion with graft eversion anastomosis technique in the Department of Cardiovascular Surgery, Dalian Municipal Central Hospital, including 19 males and 9 females, aged 60.11±11.11 years. The intima of the ascending aorta was trimed to 5 mm above the sinotubular junction. The adventitia of the ascending aorta was longitudinally cut to the reserved intima margin along the junction of the three aortic valves. The extended adventitial inversion was sutured continuously, no coronary sinus was sutured over the aortic annulus, and the left and right coronary sinus was sutured above the coronary ostium. The anastomotic graft was everted and inserted into the aortic lumen, and the everted graft was continuously sutured at the level of sinotubular junction which was 5 mm away from the edge of graft. Results    There was no intraoperative death, intractable root hemorrhage, residual root false lumen, root dilatation, anastomotic hematoma or other complications. There was no recurrence of the pain in the back of all patients, and the results of the CT angiography were not significantly changed. In 22 patients with no regurgitation, only 1 (4.55%) patient had a mild regurgitation. In 6 patients with mild aortic regurgitation, the disappearance rate of regurgitation was 50.0% (3/6). Conclusion    The treatment of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of aortic dissection eliminates the residual dissection at the root. The anastomotic hemorrhage is prevented, the root structure of aortic dissection is reconstructed and strengthened, the root function is restored, and the possible expansion of the root is prevented. The short-term results are satisfactory.

Objective:To evaluate the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in striatum in paclitaxel-induced neuropathic pain and the relationship with GABA B receptors in rats. Methods:Healthy clean-grade male Sprague-Dawley rats, aged 6-9 weeks, weighing 180-220 g, were used in this study.The neuropathic pain model was established by intraperitoneal injection of paclitaxel 2 mg/kg once every 2 days for 7 consecutive days in anesthetized rats, and then intrathecal catheterization was performed.Fifty rats in which intrathecal catheters were successfully implanted were divided into 5 groups ( n=10 each) using a random number table method: paclitaxel group (P group), paclitaxel plus normal saline group(N group), paclitaxel plus lentivirus empty vector group (BV group), paclitaxel plus HCN4 channel lentivirus group (H group), and paclitaxel plus HCN channel inhibitor ZD7288 group (I group). Ten rats of the same age were selected as the blank control group (C group). At 15 days after intraperitoneal injection of paclitaxel, normal saline 20 μl was intrathecally injected in group N, group BV received intrathecal injection of HCN4 channel lentivirus empty vector 1×10 8 TU/ml, 20 μl, group H received intrathecal injection of HCN4 channel lentivirus 1×10 8 TU/ml, 20 μl, and group I received intrathecal injection of ZD728830 μg, 20 μl.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before paclitaxel injection and 14 and 21 days after injection.The cerebral striatum tissues were obtained at T 2, and the expression of HCN4 channel and GABA B receptors was determined by immunohistochemistry and Western blot. Results:Compared with group C, the MWT was significantly decreased, HCN4 channel expression was up-regulated, and GABA B receptor expression was down-regulated in group P ( P<0.05). Compared with group P, the MWT was significantly increased, HCN4 channel expression was down-regulated, and GABA B receptor expression was up-regulated in group H and group I ( P<0.05), and no significant change was found in the parameters mentioned above in group N and group BV ( P>0.05). Conclusion:Up-regulation of expression of HCN4 channels in striatum can induce down-regulation of GABA B receptor expression, which is involved in the pathophysiological mechanism of paclitaxel-induced neuropathic pain in rats.