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

Theory and technology of Medical Immunology are widely used in scientific research.Our teaching and research group uses experimental teaching of Medical Immunology as a platform to carry out practice of scientific research project-based experi-mental system among"5+3"integration students.By completing a mini-project research including experimental design-experimental operation-research article writing,students cultivated scientific research thinking and exercised scientific research practice ability,and generally reported that the course is very difficult,but after completing it,it is very rewarding.

Objective:To explore the consistency of claudin 18.2 immunohistochemistry (IHC) using 4 different clone antibodies in gastric adenocarcinoma.Methods:A total of 226 gastric adenocarcinomas diagnosed and treated at the Drum Tower Hospital Affiliated to Nanjing University Medical College between January 2022 to March 2023 were included in this study. The cohort consisted of 165 males and 61 females, with a mean age of (61.3±12.1) years. Tumor tissues from radical resection specimens were collected for tissue microarrays. IHC detection of claudin 18.2 was performed using the EnVision method, utilizing 4 clones of antibody: OTIR157B5, 43-14A, EPR19202 and D313D22. The results were interpreted based on both the intensity of staining on tumor cell membranes and the percentage of positive tumor cells relative to the total tumor cells.Results:The positive cutoff value was set as moderately to strongly linear membrane staining in ≥75% of all viable invasive tumor cells, and clone OTIR157B5 demonstrated the highest positive expression rate at 52.2% (118/226). Additionally, the clones OTIR157B5, 43-14A, and EPR19202 were consistently and strongly positive, with all agreement rates of Cohen κ exceeding 0.8. In gastric adenocarcinoma and its three Lauren subtypes, OTIR157B5 exhibited clear membranous localization.Conclusions:Clone OTIR157B5 of claudin 18.2 antibody shows the highest rate of moderately to strongly linear membrane-positive staining, accounting for ≥75% of all viable invasive tumor cells, and clones 43-14A and EPR19202 show strong consistency and high sensitivity.

With the rapid development of artificial intelligence(AI),how to digitize the teaching of Medical Immunology is a new challenge posed by the times and education.This study is based on the advanced teaching model of Medical Immunology,which includes lectures-PAD class-flipped classrooms-expert lecture.By introducing knowledge mapping and AI teaching assistant into the entire learning process,the students not only deepen their understanding of the knowledge system of Medical Immunology,but also ex-ercise their ability to apply immunological knowledge to solve practical clinical problems,enhance their self-learning ability,expres-sion ability,communication ability,on-site performance ability,and cultivate a spirit of unity,cooperation,and exploration.The practice of empowering Medical Immunology teaching with digital intelligence achieves the integration of theory and application,the linkage between in class and out of class teaching,the connection between commonalities and individualities,and the union of abili-ties and qualities in Medical Immunology teaching.It also provides practical basis for exploring the implementation path of digital intel-ligence empowerment in Medical Immunology teaching.

OBJECTIVE To investigate the bactericidal effect of levulinic acid-sodium dodecyl sulfate(LVA-SDS)on the strains of Mycobacterium abscessus,Mycobacterium chelonae and Mycobacterium fortuitum,and to provide a new method for the prevention of common pathogenic rapidly growing non-tuberculous mycobacteria(NTM)dis-ease.METHODS The minimum inhibitory concentration(MIC)and minimal bactericidal concentration(MBC)of LVA-SDS were detected by microculture method and suspension quantitative bactericidal test,respectively.Using 1000 mg/L chlorine-containing disinfectant(sodium hypochlorite)as the control,the killing effect of LVA-SDS at different times and concentrations on M.abscessus,M.chelonae and M.fortuitum were detected.RESULTS The MIC values of LVA-SDS against M.abscessus,M.chelonae and M.fortuitum were 0.0625%LVA+0.00625%SDS,0.03125%LVA+0.003125%SDS and 0.125%LVA+0.0125%SDS,respectively.The MBC values were 0.25%LVA+0.025%SDS,0.25%LVA+0.025%SDS,and 1%LVA+0.1%SDS,repectively.Within a cer-tain range,with the increase in LVA-SDS concentration and the extension of time(1-30 min),the bactericidal effect on M.abscessus,M.chelonae and M.fortuitum gradually enhanced.The killing rates of the 18%LVA+1.8%SDS for 5 minutes and the 6%LVA+0.6%SDS for 20 minutes to M.abscessus reached 100.00%;the kill-ing rates of the 18%LVA+1.8%SDS for 10 minutes and the 10%LVA+1%SDS for 25 minutes to M.chelo-nae reached 100.00%;while the killing rates of the 18%LVA+1.8%SDS for 5 minutes and the 6%LVA+0.6%SDS for 30 minutes to M.fortuitum reached 100.00%.Compared with 1000 mg/L chlorine-containing disin-fectant(sodium hypochlorite),LVA-SDS has equivalent bactericidal effects against M.abscessus and M.chelo-nae,and a better bactericidal effect against M.fortuitum.CONCLUSION LVA-SDS has a good bactericidal effect on M.abscessus,M.chelonae and M.fortuitum,and may be used in the disinfection of NTM in the future.

Theory and technology of Medical Immunology are widely used in scientific research.Our teaching and research group uses experimental teaching of Medical Immunology as a platform to carry out practice of scientific research project-based experi-mental system among"5+3"integration students.By completing a mini-project research including experimental design-experimental operation-research article writing,students cultivated scientific research thinking and exercised scientific research practice ability,and generally reported that the course is very difficult,but after completing it,it is very rewarding.

Objective:To investigate whether the immunohistochemical results of two markers PMS2 and MSH6 (2-MMR) could replace the four markers MLH1, PMS2, MSH2 and MSH6 (4-MMR) to detect mismatch repair deficient (dMMR) cancers.Methods:A retrospective analysis was conducted with summary of immunohistochemical data from 7 867 cases of gastric cancer, colorectal cancer, endometrial cancer, and other diseases in the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, from March 2018 to March 2023. The consistency of 2-MMR and 4-MMR results was examined. Microsatellite instability (MSI) and next-generation sequencing (NGS) were performed in patients with specific phenotypes.Results:The Cohen κ values of 2-MMR and 4-MMR in gastric cancer, colorectal cancer, endometrial cancer and other diseases were 0.88, 0.99, 0.88 and 1.00, respectively. The overall consistency, sensitivity and specificity were 0.97, 99.6%, and 100.0%, respectively. Both 2-MMR and 4-MMR could detect the difference between various clinicopathological features. 24 (0.3%) of the 7 867 patients were found to have a special phenotype of MMR, and 6 of them were selected for MSI and NGS molecular testing. MSI analysis showed MSI-H in all cases, while NGS found that 5 of them had MMR-related gene mutations and 1 had POLE p.S297F mutation.Conclusions:Compared with 4-MMR, 2-MMR has high consistency, specificity and sensitivity. The cases with special phenotype only account for extremely low proportion. Therefore, 4-MMR may be replaced with 2-MMR in dMMR screening.

Objective:To explore the application value of the combination of failure mode and effects analysis (FMEA) and work breakdown structure (WBS) on management of telemetry monitoring system. Methods:Seven sets of used telemetry monitoring systems in Huzhou Third People's Hospital from March 2022 to April 2024 were selected. The routine mode was used to manage the telemetry monitoring systems from March 2022 to February 2023,and the management mode of telemetry monitoring systems based on FMEA and WBS was adopted to manage the telemetry monitoring systems from May 2023 to April 2024. FMEA method was used to analyze the quantitative risk scores of various failures in 1740 uses of the telemetry monitoring system from March 2022 to February 2023,and the fault type was represented by Fx. According to the risk quantification score,the top 5 failure types included poor radio frequency (RF) signal (F2),larger pseudo-interference (F3) of electrocardiogram (ECG),abnormal measurement of blood oxygen saturation (SpO2) (F6),excessive movement and mistake touch (F8) of patients,and identification (ID) number error (F9) of telemetry emission box. WBS quality management method combined with tree chart,countermeasure fishbone chart,task assignment matrix and other tools were performed to conduct the setting of expected objectives,countermeasure analysis,task formulation and work implementation of management of telemetry monitoring system. The above indicators were compared with the changes of the top 5 failure risk grading and incidence of failure in 1850 uses of management of telemetry monitoring system from May 2023 to April 2024. Results:After the telemetry monitoring system was used to conduct management,the risk grading of the F2,F3,F6,F8 and F9 failures with highest risk grading reduced respectively to low grade,middle grade,middle grade,low grade and middle grade. At the same time,the number of F2,F3,F6,F8,F9 failures with the highest risk grading and total failures were respectively 91,89,39,45,39 and 478 times,and the incidence rates of them were 4.92％,4.81％,2.11％,2.43％,2.11％ and 25.84％,which were significantly lower than those of adopting conventional management methods. The differences of them between two methods were statistically significant (x2=2.125,6.911,9.099,2.261,2.431,32.491,P<0.05). Conclusion:The management of combined quality management method of FMEA and WBS for telemetry monitoring system can reduce risk grading and incidence rate of equipment failure,and ensure the safety of equipment in clinical use.