ObjectiveTo investigate the molecular mechanisms related to angiogenesis during the development and progression of diabetic retinopathy （DR）. MethodsAngiogenesis-related genes were obtained from the Gencard website and intersected with differentially expressed genes from DR datasets （GSE60436 and GSE94019）. Functional enrichment and protein-protein interaction （PPI） networks were then used to screen candidate genes and evaluate their diagnostic value. Gene set enrichment analysis （GSEA） was used to explore potential pathways underlying candidate genes， and immune infiltration analysis revealed associations between candidate genes and immune cells. Cellular experiments were conducted to validate the role of fibronectin 1 （FN1） in human retinal microvascular endothelial cells （HRMECs） under high glucose （HG） conditions. ResultsA total of 237 differentially expressed genes related to angiogenesis were identified， enriched in pathways such as phosphoinositide 3-kinase/protein kinase B signaling pathway （PI3K-Akt）， tumor suppressor protein 53 （P53）， tumor necrosis factor （TNF）， and Janus kinase （JAK）/signal transducer and activator of transcription signaling pathway （STAT）. Among them， collagen type I alpha 1 chain （COL1A1）， COL1A2， FN1， TNF， and tumor protein p53 （TP53） were key genes with high diagnostic value. GSEA indicated that these genes were involved in multiple signaling pathways， including P53. CIBERSORTx analysis revealed significant associations with the infiltration of multiple immune cells. HG treatment led to the upregulation of FN1. In HG-induced HRMECs， compared with the si-NC control group， si-FN1 significantly reduced cell proliferation， migration， and tube formation， while P53 protein expression was increased. ConclusionThis study reveals the important role of FN1 in angiogenesis in DR and suggests that it may be a potential diagnostic and therapeutic target.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Objective To investigate the tongue image characteristics of patients in postoperative colorectal cancer and significant tongue image features using a multinomial Logistic regression model.Methods Totally 213 postoperative patients with colorectal cancer were included.TFDA-1 digital tongue diagnostic instrument was used to collect the tongue images of patients,and the statistical differences of tongue image characteristics of patients with qi deficiency syndrome,yin deficiency syndrome,phlegm dampness syndrome and blood stasis syndrome were analyzed.Multiple Logistic regression was used to analyze the different tongue image indexes of different syndrome types.Results In the tongue coating index,perAll had the following distribution order:yin deficiency syndromeqi deficiency syndrome>blood stasis syndrome.In the texture indexes,CON,ENT and MEAN had the following distribution order:phlegm-dampness syndrome>yin deficiency syndrome>qi deficiency syndrome>blood stasis syndrome.ASM had the following distribution order:phlegm-dampness syndromeqi deficiency syndrome>blood stasis syndrome.TB-a had the following distribution order:phlegm-dampness syndromeqi deficiency syndrome>phlegm-dampness syndrome>blood stasis syndrome.TC-L had the following distribution order:blood stasis syndromeqi deficiency syndrome>blood stasis syndrome>phlegm-dampness syndrome.TC-b had the following distribution order:yin deficiency syndrome>qi deficiency syndrome>blood stasis syndrome.In the multinomial Logistic regression model,compared with the qi deficiency syndrome,the probability of being diagnosed with the yin deficiency syndrome increased when TB-L and TC-a decreased.Additionally,the probability of being diagnosed with the phlegm-dampness syndrome increased when TB-b and TC-a decreased and TC-b increased;TB-b and TC-L decreased,principal component 1 of texture index increased,and the probability of syndrome differentiation as blood stasis syndrome was higher.Conclusion The tongue image characteristics of different TCM syndromes in postoperative colorectal cancer patients exhibit certain patterns,which can serve as an objective reference for TCM differentiation and diagnosis.

Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

Objective:To investigate the effects of insulin-like growth factor 2 (IGF-2) on the expression of postsynaptic density protein 95 (PSD95), synaptophysin-1 (SYN1), and synaptophysin (SYP) in the mouse visual cortex and visual function after monocular deprivation (MD).Methods:Sixty-four SPF male Kunming mice aged 3 weeks were randomly divided into 4 groups: normal control group, MD group, MD+ IGF-2 recombinant protein (MD+ IGF-2) group, and MD+ fluoxetine (FLX) group, with 16 mice in each group.The MD group, MD+ IGF-2 group and MD+ FLX group were treated with right eyelid suturing at the beginning of 3 weeks old and eyelid opening at the end of 5 weeks old.The MD+ IGF-2 group was intraperitoneally injected with IGF-2 recombinant protein during MD.The MD+ FLX group was given fluoxetine via drinking water for 4 weeks after eyelid opening.The normal control group and MD group were injected intraperitoneally with bovine serum albumin every day from 3 to 5 weeks of age.At the end of 5 and 9 weeks of age, subjective visual function was evaluated by fore paw touching ground reflex experiment.At the end of 9 weeks of age, objective visual function was assessed by flash visual evoked potentials.After the mice were sacrificed, the left visual cortex of mice in each group was taken, and the expression of PSD95, SYN1, and SYP was assessed by Western blot.This study was approved by the Ethics Committee of Hunan Children's Hospital (No.HCHDWLL-2022-16). The handling of experimental animals was carried out in accordance with the Guidelines for the Management and Use of Laboratory Animals in Hunan Children's Hospital.Results:At the end of 5 and 9 weeks of age, there were overall significant differences in the success rate of fore paw touching ground among different groups of mice ( F=4.83, 3.36; both P<0.05). At the end of 5 weeks of age, the success rate was lower in MD group and MD+ FLX group than in normal control group, and significantly higher in MD+ IGF-2 group than in MD group, with statistically significant differences (all P<0.05). At the end of 9 weeks of age, the success rate was lower in MD group than in normal control group, and significantly higher in MD+ IGF-2 group and MD+ FLX group than in MD group (all P<0.05). There was a significant overall difference in P2 wave amplitude in F-VEP examination among different groups of mice ( F=13.99, P<0.01). The P2 wave amplitude was significantly lower in MD group than in normal control group and MD+ IGF-2 group (both P<0.01). There was no significant difference in the P2 wave latency of F-VEP among the four groups of mice ( F=2.83, P=0.07). The relative expression levels of PSD95, SYN1 and SYP proteins were 1.00±0.41, 1.00±0.10 and 1.00±0.27 in normal control group, 0.32±0.27, 0.68±0.20 and 0.56±0.28 in MD group, 0.78±0.32, 0.91±0.18 and 0.94±0.22 in MD+ IGF-2 group, 0.89±0.65, 0.98±0.28 and 0.94±0.47 in MD+ FLX group, respectively.There were significant differences in levels of PSD95, SYN1 and SYP in mice visual cortex among different groups ( F=4.24, 5.32, 3.40; all P<0.05). The expressions of PSD95, SYN1 and SYP proteins in the visual cortex were lower in MD group than in normal control group, and higher in MD+ IGF-2 group than in MD group (all P<0.05). Conclusions:Administration of exogenous IGF-2 to mice that underwent MD during the critical period can maintain visual cortex plasticity and protect the visual function to a certain extent.

Objective To analyze the characteristics of facial and tongue chromaticity parameters in patients with gastrointestinal tumors by setting the inspection image characteristics of patients with gastrointestinal tumors as the main research content;To establish an auxiliary diagnostic model for gastrointestinal tumors.Methods One-way ANOVA,t-test,Mann-whitney U test,canonical correlation analysis and Spearman statistical methods were used to analyze the characteristics of inspection image indexes and correlation of tumor markers of the 391 cases in the control group and 359 patients with gastrointestinal tumors.Machine learning methods such as SVM,Random Forest,KNN,Naive Bayes,XG Boost and Ada Boost were used to establish an auxiliary diagnostic model for gastrointestinal tumors.Results In terms of facial indicators,there were differences in F-R,F-G and F-B indicators among the control group,early-stage gastrointestinal cancer patients,and mid-to late-stage gastrointestinal cancer patients,in the comparison of tongue features among,TC-L,TB-L and TB-a of the control group,patients with early gastrointestinal tumors,and patients with intermediate and advanced gastrointestinal tumors showed a gradual downward trend;the AUC of the auxiliary diagnosis model of gastrointestinal tumor disease based on the chromaticity parameters of face tongue image constructed by Ada Boost algorithm was 0.930.Conclusion The auxiliary diagnostic model of gastrointestinal diseases constructed by facial and tongue images has good diagnostic effect,which can provide objective data support for in-depth exploration of the complex relationship between diagnosis and disease.

Objective:To investigate the effects of insulin-like growth factor 2 (IGF-2) on the expression of postsynaptic density protein 95 (PSD95), synaptophysin-1 (SYN1), and synaptophysin (SYP) in the mouse visual cortex and visual function after monocular deprivation (MD).Methods:Sixty-four SPF male Kunming mice aged 3 weeks were randomly divided into 4 groups: normal control group, MD group, MD+ IGF-2 recombinant protein (MD+ IGF-2) group, and MD+ fluoxetine (FLX) group, with 16 mice in each group.The MD group, MD+ IGF-2 group and MD+ FLX group were treated with right eyelid suturing at the beginning of 3 weeks old and eyelid opening at the end of 5 weeks old.The MD+ IGF-2 group was intraperitoneally injected with IGF-2 recombinant protein during MD.The MD+ FLX group was given fluoxetine via drinking water for 4 weeks after eyelid opening.The normal control group and MD group were injected intraperitoneally with bovine serum albumin every day from 3 to 5 weeks of age.At the end of 5 and 9 weeks of age, subjective visual function was evaluated by fore paw touching ground reflex experiment.At the end of 9 weeks of age, objective visual function was assessed by flash visual evoked potentials.After the mice were sacrificed, the left visual cortex of mice in each group was taken, and the expression of PSD95, SYN1, and SYP was assessed by Western blot.This study was approved by the Ethics Committee of Hunan Children's Hospital (No.HCHDWLL-2022-16). The handling of experimental animals was carried out in accordance with the Guidelines for the Management and Use of Laboratory Animals in Hunan Children's Hospital.Results:At the end of 5 and 9 weeks of age, there were overall significant differences in the success rate of fore paw touching ground among different groups of mice ( F=4.83, 3.36; both P<0.05). At the end of 5 weeks of age, the success rate was lower in MD group and MD+ FLX group than in normal control group, and significantly higher in MD+ IGF-2 group than in MD group, with statistically significant differences (all P<0.05). At the end of 9 weeks of age, the success rate was lower in MD group than in normal control group, and significantly higher in MD+ IGF-2 group and MD+ FLX group than in MD group (all P<0.05). There was a significant overall difference in P2 wave amplitude in F-VEP examination among different groups of mice ( F=13.99, P<0.01). The P2 wave amplitude was significantly lower in MD group than in normal control group and MD+ IGF-2 group (both P<0.01). There was no significant difference in the P2 wave latency of F-VEP among the four groups of mice ( F=2.83, P=0.07). The relative expression levels of PSD95, SYN1 and SYP proteins were 1.00±0.41, 1.00±0.10 and 1.00±0.27 in normal control group, 0.32±0.27, 0.68±0.20 and 0.56±0.28 in MD group, 0.78±0.32, 0.91±0.18 and 0.94±0.22 in MD+ IGF-2 group, 0.89±0.65, 0.98±0.28 and 0.94±0.47 in MD+ FLX group, respectively.There were significant differences in levels of PSD95, SYN1 and SYP in mice visual cortex among different groups ( F=4.24, 5.32, 3.40; all P<0.05). The expressions of PSD95, SYN1 and SYP proteins in the visual cortex were lower in MD group than in normal control group, and higher in MD+ IGF-2 group than in MD group (all P<0.05). Conclusions:Administration of exogenous IGF-2 to mice that underwent MD during the critical period can maintain visual cortex plasticity and protect the visual function to a certain extent.

Objective To conduct a comparative study on the biomechanical performance of using sutures for repairing inferior pole patellar fractures.Methods Compared to the normal patellar structure(Group A),four repair methods,namely,'Krackow'suture(Group B),"Kessler"fixation(Group C),'8-figure'mesh method(Group D),and modified suture bridge(Group E)were adopted.The static stiffness and dynamic stability of inferior pole patellar fractures fixed by each repair method were measured at 30°,60°,and 90° knee flexion.Results The stiffness at all flexion angles in Group E was closer to that in Group A,compared to other repair groups,followed by Group B,then Group D,and finally Group C.After the first cycle,at 30° knee flexion,Group C showed the greatest displacement,while Groups B and E had slightly larger displacements than the Group A,and the displacement of Group D was smaller than that of Group A.At 60° and 90° knee flexion,the displacement in all repair groups was smaller than that of Group A.After 200 cycles in the subsequent three cycles,displacement changes in all repair groups were smaller than those in Group A.Conclusions All repair methods were effective.In terms of biomechanical fixation performance,the modified suture bridge was superior to the'Krackow'suture and'8-figure'mesh,with Kessler fixation being the least effective.However,factors such as the injury severity,incision location,and surgical time should be comprehensively considered in actual clinical use,and it is recommended that the repair method should be selected in the following order:E,B,D,and C.

Objective To explore the mediating role of intolerance of uncertainty(IU)and moderating role of the negative emotion differentiation in the influence of perceived stress on anxiety among college students from a cognitive perspective.Methods A total of 271 participants were surveyed using the perceived stress scale,intolerance of uncertainty scale,depression anxiety and stress scale(Chinese version),and the test on negative emotional differentiation.SPSS 22.0 was used to perform descriptive statistics and correlation analyses and to test the moderated mediation model.Results Perceived stress affected anxiety and IU played a mediating role-perceived stress could affect anxiety through influencing IU.At the same time,the influence of IU on anxiety could be adjusted through the negative emotion differentiation.The higher the degree of negative emotion differentiation,the lower the degree of anxiety increase(β=0.17,t=5.70,P＜0.01).Conclusion It may be effective to develop training programs to reduce anxiety by regulating perceived stress,increasing acceptance of uncertainty,and improving the negative emotion differentiation,which can help individuals reduce anxiety by perceiving and adjusting anxiety-related emotional or cognitive factors in a timely manner.

Objective To analyze the characteristics of facial and tongue chromaticity parameters in patients with gastrointestinal tumors by setting the inspection image characteristics of patients with gastrointestinal tumors as the main research content;To establish an auxiliary diagnostic model for gastrointestinal tumors.Methods One-way ANOVA,t-test,Mann-whitney U test,canonical correlation analysis and Spearman statistical methods were used to analyze the characteristics of inspection image indexes and correlation of tumor markers of the 391 cases in the control group and 359 patients with gastrointestinal tumors.Machine learning methods such as SVM,Random Forest,KNN,Naive Bayes,XG Boost and Ada Boost were used to establish an auxiliary diagnostic model for gastrointestinal tumors.Results In terms of facial indicators,there were differences in F-R,F-G and F-B indicators among the control group,early-stage gastrointestinal cancer patients,and mid-to late-stage gastrointestinal cancer patients,in the comparison of tongue features among,TC-L,TB-L and TB-a of the control group,patients with early gastrointestinal tumors,and patients with intermediate and advanced gastrointestinal tumors showed a gradual downward trend;the AUC of the auxiliary diagnosis model of gastrointestinal tumor disease based on the chromaticity parameters of face tongue image constructed by Ada Boost algorithm was 0.930.Conclusion The auxiliary diagnostic model of gastrointestinal diseases constructed by facial and tongue images has good diagnostic effect,which can provide objective data support for in-depth exploration of the complex relationship between diagnosis and disease.