Objective This study investigated the regulatory effect of high mobility group protein B1 (HMGB1) in the peripheral blood of patients with primary immune thrombocytopenia (ITP) on myeloid dendritic cells (mDC) and Th17/regulatory T cells (Treg) balance. Methods The study enrolled 30 newly diagnosed ITP patients and 30 healthy controls.Flow cytometry was used to measure the proportion of mDC, Th17, and Treg cells in the peripheral blood of ITP patients and healthy controls. ELISA was conducted to quantify the serum levels of HMGB1, interleukin 6 (IL-6), IL-23, IL-17, and transforming growth factor β(TGF-β). The mRNA levels of retinoic acid-related orphan receptor γt(RORγt) and forehead box P3(FOXP3) were detected by real-time PCR. The correlation between the abovementioned cells, cytokines, and platelet count was assessed using Pearson linear correlation analysis. Results The proportion of Th17 cells and the expression levels of HMGB1, IL-6, IL-23, IL-17 and the level of RORγt mRNA in the peripheral blood of ITP patients were higher than those in healthy controls. However, the Treg cell proportion and TGF-β level were lower in ITP patients than those in healthy controls. In patients with ITP, the proportion of mDC and the level of FOXP3 mRNA did not show significant changes. The proportion of mDC cells was significantly correlated with the expression of IL-6 and IL-23. Moreover, the expression of HMGB1 showed a significant correlation with the expression of mDC, IL-6, IL-23, RORγt mRNA, and IL-17. Notably, both the proportion of mDC cells and the expression of HMGB1 were negatively correlated with platelet count. Conclusion The high expression of HMGB1 in peripheral blood of ITP patients may induce Th17/Treg imbalance by promoting the maturation of mDC and affecting the secretion of cytokines, thereby potentially playing a role in the immunological mechanism of ITP.
Humans ; Th17 Cells/cytology* ; HMGB1 Protein/genetics* ; T-Lymphocytes, Regulatory/cytology* ; Female ; Male ; Dendritic Cells/metabolism* ; Adult ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; Young Adult ; Interleukin-23/blood* ; Interleukin-17/blood* ; Interleukin-6/blood* ; Forkhead Transcription Factors/genetics* ; Myeloid Cells/cytology* ; Aged

Computational approaches for predicting drug-target interactions (DTIs) are pivotal in advancing drug discovery. Current methodologies leveraging heterogeneous networks often fall short in fully integrating both local and global network information. To comprehensively consider network information, we propose DHGT-DTI, a novel deep learning-based approach for DTI prediction. Specifically, we capture the local and global structural information of the network from both neighborhood and meta-path perspectives. In the neighborhood perspective, we employ a heterogeneous graph neural network (HGNN), which extends Graph Sample and Aggregate (GraphSAGE) to handle diverse node and edge types, effectively learning local network structures. In the meta-path perspective, we introduce a Graph Transformer with residual connections to model higher-order relationships defined by meta-paths, such as "drug-disease-drug", and use an attention mechanism to fuse information across multiple meta-paths. The learned features from these dual perspectives are synergistically integrated for DTI prediction via a matrix decomposition method. Furthermore, DHGT-DTI reconstructs not only the DTI network but also auxiliary networks to bolster prediction accuracy. Comprehensive experiments on two benchmark datasets validate the superiority of DHGT-DTI over existing baseline methods. Additionally, case studies on six drugs used to treat Parkinson's disease not only validate the practical utility of DHGT-DTI but also highlight its broader potential in accelerating drug discovery for other diseases.

Objective To develop liver cancer-targeted nanoparticles(LA-CMGL)co-loaded with miR-145/camp-tothecin(CPT)and assess their targeting specificity,combined anti-tumor effects,and magnetic resonance imaging efficacy.Methods Laser scanning confocal microscopy and flow cytometry were utilized to evaluate the targeted uptake of lactobionic acid-modified and unmodified nanoparticles by HepG2 cells and HepaRG cells;quantitative polymerase chain reaction(qPCR)was employed to assess miR-145 content in tumor cells and tissues.The cytotox-icity of CPT,LA-CPT-LNPs and LA-CMGL on HepG2 cells were assessed using the CCK-8 assay.qPCR was also used to evaluate the effect of CPT,LA-CPT-LNPs and LA-CMGL on apoptosis of HepG2 cells.MRI was performed to measure the relaxation rate of LA-CMGL and evaluate its targeting imaging effect on liver cancer cells.Results The uptake rate of LA-CMGL by HepG2 cells surpassed that of CMGL significantly.The relative miR-145 content in liver cancer cells and mouse liver cancer tissues in the LA-CMGL group was markedly higher compared to free miR-145 and CMGL groups(P＜0.001).The apoptosis rate of HepG2 cells in the LA-CMGL group exceeded that in the CMGL group and CPT group(P＜0.01).At the same Gd3+concentration,the relaxation rate of LA-CMGL significantly surpassed that of Gd-DOTA,and the MRI signal of LA-CMGL in HepG2 cells markedly increased com-pared to CMGL and Gd-DOTA.Conclusion LA-CMGL exhibits promising liver cancer-targeted delivery,com-bined anti-tumor effects,and MRI liver cancer cell-targeted imaging,offering a novel avenue for combined drug/gene therapy for liver cancer.

Objective:To explore the application of the task-driven method combined with the "7E" learning cycle mode in nurse refresher training on endoscopic retrograde cholangiopancreatography (ERCP).Methods:We assigned 54 nurses who received refresher training on ERCP in the Department of Hepatobiliary Surgery of The First Affiliated Hospital of Army Medical University from January 2019 to December 2022 into control group (28 nurses from January 2019 to December 2020) to shadow and practice ERCP in a traditional way or experimental group (26 nurses from January 2021 to December 2022) to be taught using the task-driven method combined with the "7E" learning cycle method. At the end of training, the two groups undertook a theoretical and practical examination and a questionnaire survey. SPSS 25.0 was used to perform the t test, Wilcoxon test, chi-square test, and Fisher's exact test. Results:After training, compared with the control group, the experimental group had significantly higher scores of theory [87.50 (85, 90) vs. 90.51 (89, 92), P<0.05], and practice [84.11 (82.75, 85) vs. 90.52 (89, 92), P<0.05]. The proportions of trainees rating teaching methods excellent in the experimental group and control group were 76.92% ( n=20) and 42.86% ( n=12), respectively, and the proportions of teachers rating teaching effects excellent in the experimental group and control group were 84.62% ( n=22) and 42.86% ( n=12), respectively, both showing significant between-group differences (both P<0.05). Conclusions:The combination of the task-driven method and the "7E" learning cycle mode can mobilize learning initiative and enthusiasm, improve collaboration ability, promote learning interest and comprehensive practical ability for ERCP in nurses, which is suitable for ERCP training and teaching.

With accumulating dysregulated circular RNAs(circRNAs)in pathological processes,the regulatory functions of circRNAs,especially circRNAs as microRNA(miRNA)sponges and their interactions with RNA-binding proteins(RBPs),have been widely validated.However,the collected information on experimentally validated circRNA-disease associations is only preliminary.Therefore,an updated CircR2Disease database providing a comprehensive resource and web tool to clarify the relationships between circRNAs and diseases in diverse species is necessary.Here,we present an updated CircR2Disease v2.0 with the increased number of circRNA-disease associations and novel characteristics.CircR2Disease v2.0 provides more than 5-fold experimentally validated circRNA-disease associations compared to its previous version.This version includes 4201 entries between 3077 circRNAs and 312 disease subtypes.Secondly,the information of circRNA-miRNA,circRNA-miRNA-target,and circRNA-RBP interactions has been manually collected for various diseases.Thirdly,the gene symbols of circRNAs and disease name IDs can be linked with various nomenclature databases.Detailed descriptions such as samples and journals have also been integrated into the updated version.Thus,CircR2Disease v2.0 can serve as a platform for users to systematically investigate the roles of dysregulated circRNAs in various diseases and further explore the posttranscriptional regulatory function in diseases.Finally,we propose a computational method named circDis based on the graph convolutional network(GCN)and gradient boosting decision tree(GBDT)to illustrate the applications of the CircR2Disease v2.0 database.

Guided by the development of new medical science proposed by Ministry of Education and the "Education and Training Plan for Excellent Doctors 2.0", shifted from treatment-oriented to whole life-health cycle, we have explored curriculum ideological and political education in metabolic-related curriculum chain. Firstly, we constructed a core teaching team and had the training of curriculum ideological and political education. The top-level design was made with the integration of moral education into medical education. Secondly, the syllabus was comprehensively revised, containing the connotation of "morality education". The elements relevant to curriculum ideological and political education hidden behind professional courses were excavated. Finally, the mixed teaching mode of online combining with offline was carried out. Metabolism-related curriculum chain, focused on "metabolism, diabetes, obesity and patient education", formed a progressive link from basic medical science to practice to clinical, strengthening the "prevention, treatment and health care" based "one health" philosophy and giving full play to the implicit curriculum ideological and political education hidden behind professional courses. Our practice shows that the implementation of curriculum ideological and political education in metabolism-related curriculum has been accepted by students, and curriculum ideological and political education has been become part of professional courses. The "gene chimera" mode for curriculum ideological and political education incorporation into professional courses needs to be infiltrated imperceptibly, and the effect will be visualized in the future.

Objective:To investigate the clinical effect and satisfaction of partially edentulous patients restored with posterior implant-supported single crown by digital impression technique and traditional silicon rubber impression, in order to provide clinical reference.Methods:Sixty-four partially edentulous patients who visited the Department of Prosthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University between March 2018 and January 2021 were enrolled. There were 31 male and 33 female, and the age of the group of patients was (49.3±13.3) years. The 113 implants placed in this group of patients were divided into digital impression group ( n=70) and silicone rubber impression group ( n=43) according to different impression techniques, and were restored with screw-retained full zirconia single crown, and the patients were followed up for 3-36 months after treatment. The implant survival rate, upper prosthesis, peri-implant soft tissue status, marginal bone loss and patients satisfaction were recorded to evaluate the clinical effects of two impression techniques in posterior implant-supported single crown. Results:In sixty-four patients, digital impression accounted for 62% (40/64), and silicon rubber impression accounted for 38% (24/64), the survival rate of 113 implants was 100% (113/113). The prevalence of interproximal contact loss, food impaction and mechanical complication of the upper full zirconia single crown restorations were 22.7% (41/181), 8.0% (9/113) and 2.7% (3/113) separately. All the mechanical complications were abutment screw loosening. All patients maintained good oral hygiene status, the incidences of peri-implantitis and peri-implant mucositis were 0.9% (1/113) and 4.4% (5/113) respectively. The marginal bone loss was (0.24±0.11) mm. The median of satisfaction visual analogue scale score in patients was 9-10, but no statistically significant differences of all the above results were observed between the two impression techniques ( P>0.05). Conclusions:The clinical effect of partially edentulous patients restored with posterior implant-supported single crown using two different impression techniques is good and the satisfaction of patients is high, but the long-term clinical effect remains to be further observed.

Objective To construct a human renal epithelial cell line HEK293T by CRISPR-Cas9-based site-directed knock-in of vascular endothelial growth factor 165 (VEGF165) gene, and avoid the off-target effect caused by lentivirus infection. Methods The VEGF165 expression vector with homologous arm (pUCm-T-VEGF165 plasmid) and the sgRNA expression vector [pSpCas9(BB)-2A-Puro-sgRNA plasmid] were designed and constructed based on the DNA sequence of the EZH2 gene, and then co-transfected into HEK293T cells. The expression of VEGF165 mRNA was detected by qPCR and the expressions of VEGF165 proteins were detected by Western Blot. Results The qPCR and Western Blot results showed that, comparing with the control, the pUCm-T-VEGF165 plasmid and pSpCas9(BB)-2A-Puro-sgRNA plasmid, the expression of the co-transfection plasmid were significantly increased, i.e. 3.42±0.30 vs. 1.02±0.21, 1.13±0.16 and 0.98±0.18 for the VEGF165 mRNA level (all P<0.01), and 1.13±0.16 vs. 1.02±0.06, 0.88±0.03 and 0.80±0.05 for the VEGF165 protein level (all P<0.01), respectively. Besides, the expression of EZH2 was significantly down-regulated, i.e. 0.14±0.06 vs. 1.08±0.11, 1.02±0.12 and 1.13±0.16 for the EZH2 mRNA level (all P<0.01), and 0.23±0.03 vs. 1.05±0.13, 0.91±0.04 and 0.81±0.06 for the EZH2 protein level (all P<0.01), respectively. This result showed that the VEGF165 was successfully inserted into the EZH2 genome, interfering the EZH2 expression. Conclusions VEGF165 gene can be successfully knocked into HEK293T cells by CRISPR/Cas9 system.

OBJECTIVE： To study lung tissue injury induced by long-term aerosol inhalation of 4 kinds of non-aerosol drugs in healthy SD rats， and to evaluate the safety of aerosol inhalation of non-aerosol drugs. METHODS： Totally 40 healthy SD rats （♂） were randomly divided into 8 group， i.e. blank control group， normal saline group （solvent control）， budesonide group （non-aerosol drug control， 0.1 g/L） ，silicon dioxide group （lung injury drug control， 40 g/L）and 4 kinds of non-aerosol drugs [Dingchuan decoction group （15 g/mL， calculated by crude drug）， cefatriaxone group （200 g/L）， Qingkailing group （stoste） and Tangreqing group （stoste）]， with 5 rats in each group. Except that blank control group didn’t received any treatment， other groups received aerosol inhalation， 10 mL， twice a day， for consecutive 56 days. After medication， the number of white blood cells in peripheral blood were counted and classified， and the number of white blood cells in bronchus alveolar lavage fluid were counted. The pathological changes of lung tissue were observed by HE staining and the number of dust cells was counted. The expression of leukocyte differentiation antigen 163 （CD163） in lung tissue were determined by immunohistochemical method. RESULTS： The white blood cells in peripheral blood mainly included lymphocyte and neutrophil， of which lymphocyte is the main one. Compared with blank control group， there was no statistical significance in the number of white blood cells， lymphocyte or neutrophil in peripheral blood， the number of white blood cells in alveolar lavage fluid or the number of dust cells in lung tissue of rats in normal saline group （P＞0.05）； the structures of bronchus and lung tissue were intact， and the expression of CD163 was negative. Compared with normal saline group， there was no statistical significance in the above indexed of rats in budesonide group（P＞0.05）， the structures of bronchus and lung tissue were intact， and the expression of CD163 was negative， while the number of white blood cells， lymphocyte or neutrophil in peripheral blood， the number of white blood cells in alveolar lavage fluid or the number of dust cells in lung tissue of rats in other 5 groups were all increased significantly （P＜0.05）； alveolar wall thickening and alveolar interstitial edema occurred in different degrees in lung tissue. The expression of CD163 was positive or strongly positive. CONCLUSIONS： The long-term aerosol inhalation of 4 kinds of non-aerosol drugs can induce pathological changes of lung tissue and increase the number of inflammatory cell and dust cell in alveolin in healthy SD rats.

Objective To assess the efficacy and safety of methimazole combined with selenium therapy in the treatment of hyperthyroidism .Methods 130 cases with hyperthyroidism were selected , and according to the digital table they were randomly divided into methimazole plus selenium treatment group ( ATD +Se group ) and methimazole treatment group(ATD group),65 cases in each group.The patients were followed up for 3 months.The thyroid function index and thyroid antibody index were observed before and after treatment .The adverse reactions were observed,too.Results After treatment,the serum levels of FT3,FT4,TSH in the ATD +Se group were (3.32 ± 0.53)pg/mL,(1.02 ±0.17)ng/dL,(2.72 ±0.32)mIU/L,respectively,which in the ATD group were (4.82 ± 0.75)pg/mL,(2.41 ±0.32)ng/dL,(2.72 ±0.32)mIU/L,respectively.The change ranges of the ATD +Se group were better than those of the ATD group ,the differences were statistically significant (t=4.591,3.814,3.567,all P<0.05).The TPOAb,TGAb,TRAb in the ATD+Se group were (120.3 ±23.1) IU/mL,(123.3 ±26.5) IU/mL, (1.72 ±0.89)IU/mL,respectively,which in the ATD group were (132.8 ±21.1)IU/mL,(134.8 ±21.3)IU/mL, (3.68 ±1.06)IU/mL,respectively.The changes of the ATD+Se group were more significant than those of the ATD group,the differences were statistically significant (t=4.291,3.514,3.767,all P<0.05 ).The total effective rate of the ATD+Se group was higher than that of the ATD group (90.77％vs.76.92％χ2 =13.147,P<0.05 ).The incidence rate of adverse reactions in the ATD +Se group was lower than that in the ATD group (12.31％vs.27.69％χ2 =18.685,P<0.05 ).Conclusion The results suggest that methimazole combined with selenium treatment is effective and safe for hyperthyroidism .