AIM: To investigate the diagnostic and prognostic value of differential expression of Cyclin D1 and p53 in eyelid tumors.METHODS: This retrospective study enrolled patients who underwent surgical resection for eyelid tumors at our hospital between March 2018 and March 2023. Participants were categorized into benign and malignant groups based on tumor characteristics. Clinical data were collected. Genetic data for eyelid tumors were obtained from the GEO database, and differential gene analysis, including volcano plot visualization and KEGG pathway enrichment analysis, was performed using the Sangerbox 3.0 platform. Immunohistochemistry was used to detect the expression levels of Cyclin D1, p53, and BAX in tissue samples. Correlations with clinical features were analyzed using Spearman analysis, and prognostic factors were identified via Logistic regression analysis.RESULTS: This study included 69 patients with eyelid tumors(78 eyes), categorized into a benign group(37 patients, 41 eyes)and a malignant group(32 patients, 37 eyes)based on tumor characteristics. There were significant differences between the two groups in histological subtype, TNM staging, vascular invasion, differentiation status, and local infiltration(all P<0.05). Among benign tumors: pigmented nevi in 11 eyes(27%), hemangiomas in 9 eyes(22%), squamous cell papillomas in 5 eyes(12%), epidermoid cysts in 5 eyes(12%), seborrheic keratoses in 4 eyes(10%), neurofibromas in 3 eyes(7%), and both calcifying epithelioma and xanthelasma in 2 eyes each(5%); among malignant tumors: basal cell carcinoma in 18 eyes(49%), meibomian gland carcinoma in 8 eyes(22%), squamous cell carcinoma in 5 eyes(14%), sebaceous gland carcinoma in 4 eyes(11%), lymphoma and malignant melanoma each in 1 eye(3%). At the follow-up cutoff date of March 2025, the 2-year survival rate in the benign group(95%)was significantly higher than that in the malignant group(78%; P<0.05). Bioinformatics analysis identified 4 103 differentially expressed genes, including Cyclin D1, p53, and BAX, which were predominantly involved in pathways such as the p53 signaling pathway and calcium-related signaling. Spearman analysis revealed that local invasion(rs=0.71, P<0.05)and TNM stage(rs=0.73, P<0.05)correlated with Cyclin D1 expression; local invasion(rs=0.76, P<0.05)and histological subtype(rs=0.65, P<0.05)correlated with p53 expression. Logistic regression results indicated that Cyclin D1, p53, TNM staging, and local invasion were prognostic risk factors. ROC curve analysis demonstrated that the combined detection of these four indicators had the highest predictive value for prognosis(AUC=0.83).CONCLUSION: High expression of cyclin D1 and p53 serves as molecular markers for distinguishing benign from malignant eyelid tumors and assessing prognosis. Combined detection of these markers with TNM staging and local invasion demonstrates high predictive value for prognosis.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective To discuss the correlation between noninvasive hemodynamic parameters and major adverse cardiovascular events(MACE)in patients with acute anterior wall myocardial infarction after receiving percutaneous coronary intervention(PCI).Methods A total of 132 patients with acute anterior wall myocardial infarction,who received PCI at the Affiliated People's Hospital of Shandong First Medical University of China between October 2021 and February 2024,were collected.At 24 h and 7 d after surgery,the hemodynamic parameters,including mean arterial pressure(MAP),cardiac index(CI),cardiac output(CO),stroke volume(SV),peripheral vascular resistance index(SVRI),were recorded.Spearman correlation analysis was used to analyze the relationship between Killip grade of cardiac function and hemodynamic parameters.According to the presence or absence of MACE within 6 months after PCI,the patients were divided into MACE group and non-MACE group.The predictive value of hemodynamic parameters for MACE was analyzed by receiver operating characteristic(ROC)curves.Results The postoperative 7-day levels of CO,CI and SV were higher than their postoperative one-day levels,while the postoperative 7-day level of SVRI was lower than its postoperative one-day level(P＜0.05).Of the 132 patients,Killip classification of grade Ⅰ was seen in 39,grade Ⅱ in 62,grade Ⅲin 23 and grade Ⅳ in 8.The postoperative 7-day levels of CO,CI and SV in the patients with Killip gradeⅢ-Ⅳ were lower than those in the patients with Killip grade Ⅰ-Ⅱ,while the level of SVRI in the patients with Killip grade Ⅲ-Ⅳ was higher than that in the patients with Killip grade Ⅰ-Ⅱ(P＜0.05).The results of Spearman correlation analysis showed that Killip grade of cardiac function was negatively correlated with the postoperative 7-day levels of CO,CI and SV,while positively correlated with the postoperative 7-day level of SVRI after PCI(r=-0.518,r=-0.480,r=-0.416 and r=0.493 respectively,all P＜0.05).Six months after PCI,34 patients developed MACE.The levels of CO,CI and SV in MACE group were lower than those in the non-MACE group,while the level of SVRI in MACE group was higher than that in the non-MACE group(P＜0.05).The area under the ROC curve(AUC)of MAP,CO,CI,SV,SVRI and combination of the five indicators for predicting MACE was 0.620,0.687,0.676,0.649,0.710 and 0.860 respectively,and the AUC value of the combination of the five indicators was the greatest one.Conclusion In patients with acute anterior wall myocardial infarction after receiving PCI,the changes in the levels of MAP,CO,CI,SV and SVRI can reflect cardiac function level to a certain extent and can predict the occurrence of MACE events in the short term.

Purpose The purpose of this study was to in-vestigate programmed death ligand-1(PD-L1)expression in gastric adenocarcinoma(GAC)patients and the consistency of immunohistochemical(IHC)detection of four different clones of PD-L1 antibodies,so as to provide reference for the gradual standardization of PD-L1 IHC detection in gastric adenocarcino-ma and subsequent clinical studies.Methods This study col-lected surgically resected and pathologically confirmed specimens from 286 gastric adenocarcinoma patients,and specimens were stained with four antibodies:PD-L1 22C3,SP263,E1L3N and SP142.The consistency of the antibodies was statistically ana-lyzed under different critical values using two scoring criteria:comprehensive positive score(CPS)and tumor proportion score(TPS).Results Regardless of the TPS and CPS cut-off val-ues,the positive rate of 22C3 was the highest among the four an-tibodies.Consistency analysis showed that E1L3N had good con-sistency with SP142(κ=0.612)and SP263(κ=0.660)only when the cut-off value of CPS positive was 1.In addition,the consistency between the other antibodies was only moderate or poor.Conclusion The four PD-L1 antibodies exhibited incon-sistent concordance across various TPS and CPS positive thresh-olds,so it is not recommended to exchange reagents during clini-cal testing of GAC and the test results shall be documented in accordance with the specification.

Objective To evaluate the application value of the second generation snap shot freeze(SSF2)combined with artificial intelligence reconstruction in free heart rate coronary computed tomography angiography(CCTA).Methods The examination data of 37 patients undergoing CCTA were divided into two groups for reconstruction.Group A,reconstruction by artificial intelligence after SSF2 algorithm correction;group B,original images automatically split and multi-phase reconstruction by artificial intelligence.Image quality were compared on volume rendering(VR),curve planar reformation(CPR),maximum intensity projection(MIP)image,subjective evaluation,objective scoring,and signal-to-noise ratio(SNR).Independent samples t-test and Chi-square test were used,and P<0.05 was considered statistically significant.Results There were statistically significant differences in the image quality score and SNR of the two reconstruction methods(P=0.009).Group A scored better,with higher signal intensity,lower noise intensity,and better SNR.The difference in the number of right coronary artery(RCA)analyzable segments between the two groups was statistically significant(P<0.05).The excellent and good rate of subjective evaluation of coronary artery segments in group A RCA(98.6%)was higher than that in group B(69.6%).Conclusion Using SSF2 combined with artificial intelligence reconstruction technology can significantly improve the image quality of CCTA,improve the success rate of CCTA examination,and improve the overall work efficiency.

Objective:To compare the effectiveness of different durations of anti-seizure medications for acute symptomatic seizures in children with acute encephalitis syndrome.Methods:A total of 186 children with acute symptomatic seizures who received treatment at the Department of Neurology, Xi 'an Children's Hospital, from May 2020 to May 2022 were retrospectively included in this study. All patients were treated with anti-seizure medications. These children were divided into an observation group ( n = 93, 4-week anti-seizure medication) and a control group ( n = 93, 12-week anti-seizure medication) according to different durations of anti-seizure medication they received. The abnormal rates of electroencephalogram findings, treatment effectiveness, and recurrence rates of epileptic seizures were compared between the two groups. These children were divided into a recurrent group and a non-recurrent group based on their seizure recurrence outcomes. Clinical data from both groups were collected and compared. The factors influencing the recurrence of epileptic seizures were analyzed. Results:There were no significant differences in abnormal rates of electroencephalogram findings, treatment effectiveness, and recurrence rates of epileptic seizures between the observation and control groups (χ 2 = 1.90, 0.98, 0.36, all P > 0.05). Among the 186 children who were followed up for 1 year, epileptic seizures recurred in 12 cases, while 174 cases did not experience any recurrence. Univariate analysis revealed statistically significant differences between the recurrent and non-recurrent groups in terms of consciousness status, electroencephalogram findings, and Pediatric Cerebral Performance Category scores (χ2 = 6.16, 4.40, 5.88, all P < 0.05). Further analysis using binary logistic regression identified severe coma and Pediatric Cerebral Performance Category scores of 3-4 as independent risk factors for recurrent seizures in children with acute symptomatic seizures (both P < 0.05). Conclusion:Four-week and twelve-week anti-seizure medication for acute symptomatic seizure in children show similar effectiveness. Severe coma and Pediatric Cerebral Performance Category scores of 3-4 are significantly correlated with the recurrence of acute symptomatic seizure and therefore require clinical attention.

AIM:To investigate of the effect of Shenqifuzheng injection(SFI)combined with PD-L1 antibody on tumor immune microenvironment and its efficacy.METHODS:A subcutaneous transplanta-tion tumor model for B16F10-LUC melanoma was created.The expression of Ki67,CD31,CD8,CD16,CD163,FOXP3,LY6C,LY6G with labeling antibodies was used to detect CD8+T cells,Treg cells,NK cells,MDSCs cells,centrocytes,and granulocytes in the tumor tissues via immunohistochemistry.Flow cy-tometry was used to measure the ratios of CD11c+,IA/IE+,and CD80+cells in splenic tissue,as well as the ratios of CD8+T,CD4+T,and Treg cells in tumor tissue.Additionally,granulocyte count and NK cell expression were analyzed.RESULTS:The immuno-histochemistry results indicate that the drug admin-istration group effectively suppressed tumor angio-genesis and cell proliferation,while decreasing the expression level of immunosuppressive cytokines CD4+T cells,Treg cells,MDSCs and centroblasts.Ad-ditionally,CD8 and NK cell infiltration was promot-ed compared to the control group.The results of the flow analysis demonstrated a significant in-crease in the expression level of CD8+T cells within tumor tissues,as well as inhibition of CD4+T,Treg,and DC cell infiltration within the spleen in the drug administration group.Additionally,the tumor volume analysis indicated that the drug administra-tion group effectively inhibited tumor growth.The flow results illustrate that the group administering treatment exhibited significant increases in CD8+T cell expression levels in tumor tissue and DC cells in the spleen.Furthermore,the treatment effec-tively inhibited the infiltration of CD4+T and Treg cells.The results also indicate that the treatment significantly reduced tumor growth,with the tumor inhibition rate being better with PD-L1 antibody alone than with the SFI group.Additionally,combin-ing drugs resulted in superior results compared to the PD-L1 antibody group alone.CONCLUSION:SFI combined with a PD-L1 antibody can have synergis-tic anti-tumor effects,potentially enhancing DC cell infiltration and promoting T cell activation.Immu-nohistochemistry results indicate a positive impact on the tumor immune microenvironment.

The goal of Medical Immunology is to enable students to pay attention to integration of immunology theory with clini-cal practice,be familiar with professional English,consciously pay attention to cutting-edge knowledge,and can learn independently and lifelong.However,existing teaching models lack explanation of clinical disease related events,and arrangement of experimental content and projects is seriously disconnected from clinical practice,scientific research on solving clinical problems is clearly insuffi-cient.We established a"B to B"cycle model for immunology teaching by starting from clinical practical problems(Bedside),return to basic research(Bench),and then solve clinical problem(Bedside),which will comprehensively cultivate senior medical profession-als with clinical competence,scientific research thinking ability,innovative spirit,and international perspective.

Objective:To identify the independent factors of unplanned interruption during continuous renal replacement therapy (CRRT) and construct a risk prediction model, and to verify the clinical application effectiveness of the model.Methods:A retrospective study was conducted on critically ill adult patients who received CRRT treatment in the intensive care unit (ICU) of Zhejiang Hospital from January 2021 to August 2022 for model construction. According to whether unplanned weaning occurred, the patients were divided into two groups. The potential influencing factors of unplanned CRRT weaning in the two groups were compared. The independent influencing factors of unplanned CRRT weaning were screened by binary Logistic regression and a risk prediction model was constructed. The goodness of fit of the model was verified by a Hosmer-Lemeshow test and its predictive validity was evaluated by receiver operator characteristic curve (ROC curve). Then embed the risk prediction model into the hospital's ICU multifunctional electronic medical record system for severe illness, critically ill patients with CRRT admitted to the ICU of Zhejiang Hospital from November 2022 to October 2023 were prospectively analyzed to verify the model's clinical application effect.Results:① Model construction and internal validation: a total of 331 critically ill patients with CRRT were included to be retrospectively analyzed. Among them, there were 238 patients in planned interruption group and 93 patients in unplanned interruption group. Compared with the planned interruption group, the unplanned interruption group was shown as a lower proportion of males (80.6% vs. 91.6%) and a higher proportion of chronic diseases (60.2% vs. 41.6%), poor blood purification catheter function (31.2% vs. 6.3%), as a higher platelet count (PLT) before CRRT initiation [×10 9/L: 137 (101, 187) vs. 109 (74, 160)], lower level of blood flow rate [mL/min: 120 (120, 150) vs. 150 (140, 180)], higher proportion of using pre-dilution (37.6% vs. 23.5%), higher filtration fraction [23.0% (17.5%, 32.9%) vs. 19.1% (15.7%, 22.6%)], and frequency of blood pump stops [times: 19 (14, 21) vs. 9 (6, 13)], the differences of the above 8 factors between the two groups were statistically significant (all P < 0.05). Binary Logistic regression analysis showed that chronic diseases [odds ratio ( OR) = 3.063, 95% confidence interval (95% CI) was 1.200-7.819], blood purification catheter function ( OR = 4.429, 95% CI was 1.270-15.451), blood flow rate ( OR = 0.928, 95% CI was 0.900-0.957), and frequency of blood pump stops ( OR = 1.339, 95% CI was 1.231-1.457) were the independent factors for the unplanned interruption of CRRT (all P < 0.05). These 4 factors were used to construct a risk prediction model, and ROC curve analysis showed that the area under the curve (AUC) predicted by the model was 0.952 (95% CI was 0.930-0.973, P = 0.003 0), with a sensitivity of 88.2%, a specificity of 89.9%, and a maximum value of 1.781 for the Youden index. ② External validation: prospective inclusion of 110 patients, including 63 planned interruption group and 47 unplanned interruption group. ROC curve analysis showed that the AUC of the risk prediction model was 0.919 (95% CI was 0.870-0.969, P = 0.004 3), with a sensitivity of 91.5%, a specificity of 79.4%, and a maximum value of the Youden index of 1.709. Conclusion:The risk prediction model for unplanned interruption during CRRT has a high predictive efficiency, allowing for rapid and real-time identification of the high risk patients, thus providing references for preventative nursing.