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

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 investigate the diagnostic value of quantitative energy spectrum CT and multi-parameter magnetic resonance imaging(MRI)on epidermal growth factor receptor(EGFR)mutation in lung adenocarcinoma.Methods Clinical data of 93 patients diagnosed with lung adenocarcinoma and EGFR mutation status by pathology in Jingdezhen Hospital of Traditional Chinese Medicine from June 2020 to June 2022 were retrospectively analyzed.They were divided into mutation group(52 cases)and wild-type group(41 cases)according to EGFR mutation status,and all patients were given quantitative spectral CT and MRI examinations.Changes in parameters between two groups were compared.Results CT40kev,CT70kev,spectral curve slope(λHU),effective atomic number and iodine concentration in arterial and venous phases in mutation group were significantly higher than those in wild-type group(P<0.05).Apparent diffusion coefficient(ADC)and true diffusion coefficient(D)of mutant group were significantly higher than those of wild-type group,while volume transport constant(Ktrans)and reflux rate constant(Kep)of mutant group were significantly lower than those of wild-type group(P<0.05).Analysis of receiver operating characteristics curve showed that area under the curve(AUC)value for CT40kev,CT70kev,λHU,effective atomic number,iodine concentration,CT comprehensive parameters,ADC,D,Ktrans,Kep and MRI comprehensive parameters for diagnosing EGFR mutation status in lung adenocarcinoma were 0.615,0.622,0.680,0.715,0.655,0.855,0.899,0.795,0.740,0.751 and 0.968 respectively.There was statistically significant difference in AUC between CT comprehensive parameters and MRI comprehensive parameters(P<0.05).Conclusion Both quantitative energy spectrum CT and multi-parameter MRI have high diagnostic value in the diagnosis of EGFR mutation status of lung adenocarcinoma,but MRI has higher diagnostic value,which is helpful to provide objective basis for accurate assessment of EGFR mutation status.

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.

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 evaluate the effect of esketamine for cesarean section under epidural an-esthesia and maternal and fetal outcome.Methods The parturients all were singleton pregnancies at term and scheduled for elective cesarean delivery.Ninety parturients undergoing elective cesarean delivery under epidural anesthesia,aged 20-40 years,BMI 18-35 kg/m2,ASA physical status Ⅱ,were randomly alloca-ted into two groups:esketamine group(group K)and control group(group C),45 cases in each group.When the targeted upper sensory block level was achieved,esketamine 0.15 mg/kg was administered intra-venously for 1 minute before skin incision in group K,the same volume of normal saline was intravenously injected in group C.Visceral traction reaction during the operation was recorded.Apgar score was assessed 1 minute and 5 minutes after birth.The pH value,partial pressure of carbon dioxide,oxygen partial pressure,and lactic acid value of the neonatal umbilical vein blood were recorded.Adverse events such as nausea,vomiting,hallucination,dizziness and nightmare were monitored in the two groups.Results Compared with group C,visceral traction reaction was significantly lower in group K(P＜0.05).The neonatal Apgar score,pH value,carbon dioxide partial pressure,oxygen partial pressure,and lactic acid value of the neo-natal umbilical vein blood did not differ between the two groups.There were no differences in the incidence of nausea,vomiting and dizziness between the two groups.Hallucinations and nightmares were not encoun-tered in either group.Conclusion Esketamine 0.15 mg/kg can effectively reduce visceral traction reaction during cesarean delivery under epidural anesthesia.There was no significant effect on neonatal Apgar score and blood gas analysis,with no noticeable maternal and neonatal adverse effect.