ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

Objective To determine the acetylation level of nucleophosmin(NPM)in female breast cancer and to discuss its function through mutation of modified lysine sites.To construct positive and negative NPM mutants on its acetylated lysine sites and to express them in breast cancer cells.Methods Acetylation level and acetylated lysine sites of NPM in three breast cancer tissues and para-carcinoma tissues were detected by acetylome technology;NPM mutants were constructed by site-directed mutagenesis PCR,specific PCR products were digested by DpnI and transformed into Escherichia coli(E.coli)to obtain specific plasmids for mutants;The accuracy of mutants were verified by double restriction enzyme digestion and sequencing;The mutants were expressed in BT-549 cells by transient transfection and verified by RT-PCR method.Protein expression and acetylation level of NPM were validated by Western blotting;Function of NPM acetylation was analyzed by proteomic detection and bioinformatic analysis.Results The 27th and 32nd lysine of NPM were highly acetylated in breast cancer tissues,which were 2.76 and 2.22 times higher than those in adjacent normal tissues,respectively;The NPM mutants showed the same molecular weight as that of wild type NPM and contained expected mutation sites;Corresponding NPM mRNA levels of BT-549 cells transfected with NPM mutants were significantly increased.With the increase of wild type NPM expression level,NPM acetylation level increased,while decreased after 27th lysine underwent negative mutation.NPM acetylation can significantly change the expression levels of 101 proteins in BT-549 cells,which are enriched in regulation of cellular macromolecule biosynthesis,DNA-template transcription,RNA biosynthesis and RNA metabolism process.Conclusion NPM is highly acetylated in breast cancer and can play a key role in cellular macromolecule biosynthesis,DNA-templated transcription,RNA biosynthesis and RNA metabolism process.

Objective To explore the severity of loneliness among the elderly in communities in Shanghai,and to identify factors associated with social and emotional loneliness respectively.Methods A cross-sectional study was conducted in older adults aged 65 years or above in Pudong New Area,Jing'an District and Huangpu District in Shanghai from Mar to Jun 2021.In Pudong New Area,multi-stage stratified random sampling was conducted based on the age and gender distribution of Shanghai,while in Huangpu District and Jing'an District convenience sampling was conducted.A total of 635 samples were included in the study.Loneliness was assessed using the De Jong Gierveld Loneliness Scale with social and emotional loneliness subscales.Logistic regression analyses were conducted to identify factors associated with social and emotional loneliness.Results Among the 635 participants,only 53 older adults(8.4%)were not lonely.Female(OR=0.46,95%CI:0.31-0.70),higher self-efficacy(OR=0.97,95%CI:0.94-1.00),more objective social support(OR=0.96,95%CI:0.93-0.99)were associated with less severe social loneliness.Meanwhile,higher level of education(secondary education,OR=0.56,95%CI:0.34-0.95;college or above,OR=0.30,95%CI:0.11-0.83)and higher self-efficacy(OR=0.96,95%CI:0.93-0.99)were associated with less severe emotional loneliness,while depression(OR=3.41,95%CI:1.76-6.60)and worse social capital(OR=2.02,95%CI:1.29-3.16)were associated with more severe emotional loneliness.Conclusion Up to 91.6%of the elderly in our study sample were moderately lonely or above.The factors associated with social loneliness include self-efficacy,gender and social support.The factors associated with emotional loneliness are self-efficacy,education level,depression,and social capital.

Objective To explore the role of endothelial cells in angiogenesis and myocardial remodeling in heart failure based on MAPKs pathway mediated by tumor endothelial marker 1(TEM1).Methods Sixty-four mice were equally randomized into four groups:sham operation,myocardial infarction(MI),MI+sh-NC and MI+ sh-TEM1.On the 7th day after MI,the changes of EndMT in the infarct border area were detected by immunofluo-rescence staining,and the cardiac function of mice was evaluated by echocardiography on the 28th day.Mouse aortic endothelial cells(MAECs)were divided into three groups:control,Vector and rTEM1.In addition,MAECs were pretreated with MAPK inhibitor SB203580,and the cells were treated with rTEM1 for 48 h.The changes of EndMT and MAPKs signaling pathways in endothelial cells were evaluated by Western blot.Results In the myocardium at the border of infarction,the level of TEM1-1 increased slightly on the 1st day after MI,reached the peak on the 7th day,and then decreased on the 28th day.Compared with Vector group,the expression of VE-Cadherin protein in the rTEM1 group decreased significantly(P<0.05),and the levels of α-SMA and vimentin,relative migration distance,the number of invading cells,and the number of branching formation increased signifi-cantly(P<0.05).SB203580 reversed these changes of MAECs induced by rTEM1.Compared with the MI group,the co-staining level of CD31+Vimentin+ in the MI+sh-TEM1 group decreased significantly(P<0.01).On the 28th day,the LVEF and LVFS in the MI+sh-TEM1 group were significantly higher than those in MI group(P<0.05).Compared with the MI group,the expressions of p-P38/P38 and p-JNK/JNK in the endothelial cells of the MI+sh-TEM1 group decreased.Conclusion EndMT and angiogenesis induced by TEM1 participate in the pathogenesis of cardiac fibroblasts induced by MI,which may be mechanically related to the activation of MAPKs signaling pathway.

BACKGROUND:In recent years,with the development of biological scaffold materials and bioprinting technology,tissue-engineered bone has become a research hotspot in bone defect repair. OBJECTIVE:To summarize the current treatment methods for bone defects,summarize the biomaterials and bioprinting technology for preparing tissue-engineered bone scaffolds,and explore the application of biomaterials and printing technology in tissue engineering and the current challenges. METHODS:Search terms were"bone defect,tissue engineering,biomaterials,3D printing technology,4D printing technology,bioprinting,biological scaffold,bone repair"in Chinese and English.Relevant documents published from January 1,2009 to December 1,2022 were retrieved on CNKI,PubMed and Web of Science databases.After being screened by the first author,high-quality references were added.A total of 93 articles were included for review. RESULTS AND CONCLUSION:The main treatment methods for bone defects include bone transplantation,membrane-guided regeneration,gene therapy,bone tissue engineering,etc.The best treatment method is still uncertain.Bone tissue engineering technology is a new technology for the treatment of bone defects.It has become the focus of current research by constructing three-dimensional structures that can promote the proliferation and differentiation of osteoblasts and enhance the ability of bone formation.Biological scaffold materials are diverse,with their characteristics,advantages and disadvantages.A single biological material cannot meet the demand for tissue-engineered bone for the scaffold.Usually,multiple materials are combined to complement each other,which is to meet the demand for mechanical properties while taking into account the biological properties of the scaffold.Bioprinting technology can adjust the pore of the scaffold,build a complex spatial structure,and is more conducive to cell adhesion,proliferation and differentiation.The emerging 4D printing technology introduces"time"as the fourth dimension to make the prepared scaffold dynamic.With the synchronous development of smart materials,4D printing technology provides the possibility of efficient repair of bone defects in the future.

With the evolving of information technology and push models,as an important mobile application in the Inter-net,WeChat official account is an important platform for the implementing the"Internet plus Medical"model.Effective dissemi-nation of more medical knowledge is also an important component of achieving a healthy China.This is not only a task for public hospitals,but also a responsibility.This paper takes the health communication strategy managed by the WeChat official account of Guangdong Provincial People's Hospital as the research object.From the perspective of health communication,we conducted a comprehensive analysis of its development overview,content production,and push effectiveness.On the basis of sorting and sum-marizing the existing problems,suggestions were proposed to focus on content construction,strengthen overall management,and deepen training supervision.The study aims to provide reference for public hospitals to improve the operation and construction of WeChat official account,offer practical reference for scientific,standardized,and orderly management of self media so as to a-chieve high-quality health communication.

Objective To observe the effectiveness of fluorescence labeling-based assay bundle intervention in the prevention and control of multidrug-resistant organism(MDRO)infection.Methods Patients who were detected MDRO in a hospital from January to December 2022 were selected as the research subjects.MDRO monitoring data and implementation status of prevention and control measures were collected.Fluorescence labeling assay was adopted to monitor the cleaning and disinfection effectiveness of the surrounding object surface of the bed units.Based on the bundled prevention and control measures as well as management mode of the pre-intervention group,the post-intervention group implemented enhanced rectification measures for the problems found by the pre-interven-tion group.Changes in relevant indicators between January-June 2022(before intervention)and July-December 2022(after intervention)were compared.Results There were 136 MDRO-infected patients in the pre-intervention group,208 MDRO strains were detected and 10 healthcare-associated infection(HAI)occurred.There were 128 MDRO-infected patients in the post-intervention group,198 MDRO strains were detected and 9 HAI occurred.Af-ter intervention,the total detection rates of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-re-sistant Acinetobacter baumannii(CRAB),and total MDRO from patients decreased significantly compared to before intervention(all P＜0.05).After intervention,the detection rates of MRSA,carbapenem-resistant Pseudomonas aeruginosa(CRPA),CRAB,and total MDRO from the surrounding object surface were all lower than those before intervention(all P＜0.05).The detection rate of MDRO from surrounding object surface before intervention was 34.52％,which showed a decreased trend after intervention(P＜0.05).The clearance rate of fluorescent labeled markers before intervention was 41.84％,which showed an upward trend after implementing intervention measures(from July to December),and increased to 85.00％at the end of intervention(November-December).The comp-liance rates of issuing isolation medical orders,placing isolation labels,using medical supplies exclusively,and cor-rectly handling medical waste after intervention have all increased compared to before intervention(all P＜0.05).Conclusion Adopting fluorescence labeling-based assay bundle intervention can effectively improve the effectiveness of MDRO infection prevention and control.

Objective:To investigate the expression and clinical significance of microRNA-124(miR-124)and microRNA-1976(miR-1976)in the serum of patients with Parkinson's disease(PD).Methods:A total of 58 patients with PD were selected from September 2020 to June 2022 and categorized as the PD group.The Unified Parkinson's Disease Rating Scale(UPDRS)score was used to divide the PD patients into two groups: those with a UPDRS score≤60(25 patients)and those with a UPDRS score >60(33 patients). The Hoehn-Yahr grading scale was used to grade the PD patients.Additionally, 30 healthy individuals who had undergone a physical examination during the same period were selected as the control group.After collecting the subjects' serum, we performed real-time fluorescent quantitative PCR(qRT-PCR)to detect the expressions of miR-124 and miR-1976 in the serum.Logistic regression analysis was employed to analyze the influencing factors, and the diagnostic significance of serum miR-124 and miR-1976 in PD patients was evaluated using the receiver operating characteristic(ROC)curve.To predict the target genes of miR-1976, we utilized several software including TargetScan and Mirtarbase.Results:Compared to the control group, the PD group showed a significant down-regulation of serum miR-124 expression[(1.49±0.36) vs.(1.02±0.32)]( t=8.85, P<0.001), while miR-1976 expression was sharply up-regulated[(0.98±0.30) vs.(1.33±0.37)]( t=6.92, P<0.001). The low expression of serum miR-124 and the overexpression of miR-1976 were identified as independent risk factors for PD( OR>1, P<0.05). The Hoehn-Yahr rating of PD patients with a UPDRS score above 60 was higher than that of patients with a UPDRS score below 60[(3.42 ± 0.73) vs.(2.16 ± 0.42)]( t=3.05, P<0.05). However, there was no significant difference in serum miR-124 and miR-1976 expression between groups with different UPDRS scores[miR-124: (1.09±0.26) vs.(0.98±0.38)( t=0.89, P>0.05); miR-1976: (1.42±0.43) vs.(1.23±0.68)( t=0.62, P>0.05)]. The ROC analysis results demonstrated that miR-124 and miR-1976 had area under the curve(AUC)values of 0.832 and 0.797, respectively, in diagnosing PD.The corresponding cutoff values were 1.205 and 1.196, respectively.The sensitivity for miR-124 was 74.1%, while for miR-1976 it was 51.8%.The specificity for miR-124 was 77.8%, and for miR-1976 it was 90.1%.When both miR-124 and miR-1976 were combined in the diagnosis of PD, the AUC was 0.912, with a sensitivity of 76.4% and a specificity of 93.2%.Furthermore, it was found that miR-1976 targeted the PINK1 gene, suggesting its potential as a target gene in PD. Conclusions:The expression of miR-124 was found to be decreased in PD patients, while the expression of miR-1976 was increased.Both miR-124 and miR-1976 showed some reference value in PD diagnosis, and their combined diagnostic value was higher.This suggests that further study on their significance is warranted.However, it should be noted that the expressions of miR-124 and miR-1976 were not found to be correlated with the UPDRS score of PD patients.

AIM To study the chemical constituents from the leaves of Cyanocarya paliurus(Batalin)Iljinskaja and their α-glucosidase inhibitory activities.METHODS The 95%ethanol extract from the leaves of C.paliurus was isolated and purified by macroporous resin,silica gel,Sephadex LH-20,polyamide,C18 reversed-phase silica gel and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their α-glucosidase inhibitory activities were evaluated by PNPG.RESULTS Fifteen compounds were isolated and identified as cyclopaloside C(1),cyclopaloside A(2),juglanosides E(3),vaccinin A(4),ent-murin A(5),kaempferol 3-O-α-L-rhamnopyranoside(6),kaempferol-3-O-β-D-glucopyranoside(7),kaempferol-3-O-β-D-glucuronide methyl ester(8),kaempferol-3-O-β-D-glucuronide ethyl ester(9),kaempferol-3-O-β-D-glucuronide butyl ester(10),quercetin-3-O-α-L-rhamnopyranoside(11)quercetin-3-O-β-D-glucopyranoside(12),quercetin-3-O-β-D-galactopyranoside(13),quercetin-3-O-β-D-glucuronide butyl ester(14),dihydrokaempferol(15).The IC50 value of total extracts ihibited α-glucosidase was(1.83±0.04)μg/mL,and the IC50 values of compounds 1,4-5 were(29.48±1.86),(0.50±0.07),(0.71±0.07)μmol/L,respectively.CONCLUSION Compound 1 is a new tetrahydronaphthalene glycoside.Compounds 4-5,8-10 and 14 are isolated from the leaves of C.paliurus for the first time.Compounds 4-5 are relatively rare flavonoid lignans with potential inhibitory activities against α-glucosidase.