To compare the therapeutic effects of short-term spinal cord stimulation (stSCS) and long-term spinal cord stimulation (ltSCS) on patients with prolonged disorders of consciousness(pDoC).

ObjectiveTo investigate the diagnostic accuracy and grading capability of ultrasound-derived fat fraction （UDFF）， controlled attenuation parameter （CAP）， and hepatic/renal ratio （HRR） in assessing hepatic steatosis in metabolic associated fatty liver disease （MAFLD） with magnetic resonance imaging-proton density fat fraction （MRI-PDFF） as the gold standard. MethodsA total of 150 patients with MAFLD who attended The First Hospital of Hebei Medical University from January 2023 to December 2024 were enrolled， and 148 healthy volunteers were recruited. All subjects underwent MRI-PDFF， UDFF， CAP， and HRR examinations. Hepatic steatosis was graded based on MRI-PDFF （S0：148 cases； S1：92 cases； S2：21 cases； S3：37 cases）， and the MAFLD patients with different grades of hepatic steatosis were compared in terms of UDFF， CAP， HRR， and clinical features. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups and the Tukey HSD test was used for further comparision between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Mann-Whitney U test was used for further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The Spearman correlation analysis was used to investigate the correlation between UDFF， CAP， HRR， and MRI-PDFF in different grades of MAFLD； the receiver operating characteristic （ROC） curve was used to investigate the efficacy of UDFF， CAP， and HRR in the diagnosis of different degrees of hepatic steatosis in MAFLD； the Bland-Altman difference plot was used to analyze the consistency between UDFF and MRI-PDFF in different degrees of hepatic steatosis in MAFLD. ResultsUDFF measurement gradually increased with the increase in the grade of fatty liver （H=201.52，P0.001）. The Spearman correlation analysis showed that there was a strong correlation between any two indicators of UDFF， CAP， HRR， and MRI-PDFF in S1， S2， and S3 MAFLD （all P0.001）， with the strongest correlation between UDFF and MRI-PDFF （r_s1=0.884，r_s2=0.962，r_s3=0.929， all P0.001）. The ROC curve analysis showed that UDFF had a larger area under the ROC curve （AUC） than CAP and HRR in the graded diagnosis of S1 and S3 （all P0.05）， while in the diagnosis of S2 MAFLD， UDFF had a significantly larger AUC than HRR （P0.05） and a similar AUC to CAP （P0.05）. The Bland-Altman difference plot showed good consistency between UDFF and MRI-PDFF in different degrees of hepatic steatosis in MAFLD. ConclusionCompared with CAP and HRR， UDFF can accurately measure liver fat content and has good efficacy in identifying varying degrees of hepatic steatosis in MAFLD.

Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

Objective To investigate the effect and mechanism of bromodomain-containing protein 2(BRD2)on regulation of antitumor immunity,and to explore a novel target for immunotherapy.Methods The REMBRANDT glioma database and GlioVis and TIMER websites were used to compare the expression levels of BRD2 in tumor tissues and normal ones.The correlations between BRD2 expression levels and the prognosis of patients with glioblastoma multiforme(GBM)and those between BRD2 expression levels and immune cell infiltration in GBM were studied.The interference plasmid targeting the BRD2 gene was constructed.The lentivirus was packaged and used to infect murine glioma cells GL261.The positive cells were screened with blasticidin for 6 days,and the expression level of BRD2 protein was detected by Western blot.The CellTiter-Glo kit was used to detect the cell viability of GL261 cells after BRD2 knockdown,which were transplanted into the subcutaneous tissue of C57BL/6J mice to form subcutaneous tumors.The tumor volume was measured periodically.Twenty-eight days after tumor inoculation,the tumors were removed and tumor cells isolated.The infiltration of CD8+T cells within the subcutaneous tumor tissue was analyzed using flow cytometry and immunohistochemistry.Results BRD2 was highly expressed in a variety of tumor tissues.The prognosis of glioma patients with high BRD2 expressions was poor,and the BRD2 expression level was negatively correlated with CD8+T cell infiltration in the tumor.The growth rate of subcutaneously transplanted GL261 tumor cells after BRD2 knockdown was decelerated,and the infiltration level of CD8+T cells in subcutaneous tumor tissue was increased.Conclusion BRD2 over-expression inhibits the infiltration of CD8+T cells in GBM tumors and promotes the growth of tumors.

Objective To analyze the clinical significance and predictive indicators of N-terminal pro-brain natriuretic peptide(NT-proBNP)levels exceeding the upper limit of detection range in acute myocardial infarction(AMI).Methods A total of 669 pa-tients with AMI were enrolled and divided into two groups based on their peak NT-proBNP levels:exceeding the upper limit of detection range group(n=50)and detectable group(n=619).The two groups were matched using propensity score matching(1∶2).The clinical and laboratory indicators,coronary artery features,and in-hospital prognosis were compared,and multivariate Logistic regression analysis was used to explore early predictive indicators of NT-proBNP exceeding the upper limit of detection range.Results The neutrophil-to-lymphocyte ratio(NLR),high-sensitivity C-reactive protein levels,and fibrinogen levels were higher in the group with NT-proBNP levels exceeding the upper limit of detection range.These findings were consistent after propensity score matching.In terms of in-hospital prognosis,patients in the group with NT-proBNP levels exceeding the upper limit of detection range had a higher propor-tion of Killip class 2 or higher,longer hospital stays,lower left ventricular ejection fraction,and higher incidence of major adverse cardio-vascular and cerebrovascular events.These findings remained consistent after propensity score matching,but there was no statistically sig-nificant difference in peak myocardial enzyme levels between the two groups before and after propensity score matching.Multivariate Logis-tic regression analysis showed that early predictive indicators of NT-proBNP exceeding the upper limit of detection range included higher NLR,lower use of antiplatelet drugs,high fibrinogen levels,left anterior descending branch occlusion,and older age.After propensity score matching,the predictive indicators of NT-proBNP exceeding the upper limit of detection range were right coronary artery occlusion,high NLR,high fibrinogen levels,and left anterior descending branch occlusion.Conclusion AMI patients with NT-proBNP levels ex-ceeding the upper limit of detection range have poorer in-hospital prognosis.NLR and fibrinogen levels on admission can serve as early predictive indicators of NT-proBNP levels exceeding the upper limit of detection range.

This paper,based on Marx's theory of productivity and in line with the practical needs for high-quality devel-opment in China's healthcare sector,identifies key points in the development of new quality productive forces in healthcare,in-cluding"focusing on fairness and extensiveness","highlighting the composite and diverse nature of talent cultivation","focusing on the objectives and effectiveness of technology transfer",and"focus on the guidance and assurance provided by systems and mechanisms".The study suggests that from a strategic perspective of coordinating the overall situation,it is necessary to grasp the key points and bottlenecks in systemic transformation and to promote coordinated efforts in terms of spiritual guidance,education and research,industrial ecology cultivation,and institutional synergy.

It is difficult to accurately distinguish pharyngitis caused by Group A Streptococcus(GAS) from other pathogens according to the clinical presentation alone, which cannot effectively guide the rational use of antimicrobials.The pharyngeal swab culture, rapid antigen detection test, nucleic acid test, and blood test can help definitively diagnose GAS pharyngitis.However, there are differences in different guidelines on who the laboratory test methods are intended for, interpretation of laboratory test results and so on.This article summarizes and analyses the laboratory diagnostic modalities and their characteristics, as well as recommendations for GAS pharyngitis in different guidelines to provide references for the clinical diagnosis, antimicrobial treatment, and further study of GAS pharyngitis.

Objective:To analyze the clinical characteristics of children with systemic lupus erythematosus (SLE) combined with thrombotic microangiopathy (TMA), and clarify the clinical outcomes and related risk factors of pediatric patients through their treatment and follow-up.Methods:This was a single-center retrospective case-control study. Children diagnosed with SLE combined with TMA between January 2017 and January 2023 at Beijing Children′s Hospital, Capital Medical University, were selected as the TMA group, and SLE children without TMA were selected as the control group.According to the prognosis, children in the TMA group were further divided into the good prognosis group and the poor prognosis group.The data of the children were collected, including age, gender, SLE disease activity, clinical presentations at the time of diagnosis and at the time of thrombosis, laboratory examinations, treatment strategies, prognosis, and follow-up results.The chi-square test and Z-test were used for comparison of count data.The t-test was used for comparison of metrological pairing data.The Fisher′s exact test was used to compare the differences between the 2 groups in categorical variables.The univariate Logistic regression was used to analyze the risk factors of poor prognosis. Results:There were 29 cases in the TMA group, and the incidence of TMA accounted for 2.53% of SLE patients; 33 cases were in the control group.The age at diagnosis of TMA was 13 years and 5 months (ranging from 9 years, 1 month and 5 days to 17 years and 4 months).The common clinical manifestations in order of prevalence were renal involvement (28 cases, 96.55%), hematologic involvement (26 cases, 89.66%), serous effusion (17 cases, 58.62%), rash (13 cases, 44.82%), and neurologic involvement (12 cases, 41.38%).Pleurisy or pericarditis, renal involvement and neurological involvement occurred more often in the TMA group than in the control group (17 cases vs.3 cases, 28 cases vs.10 cases, 12 cases vs.3 cases), and the TMA group showed less facial rash and arthritis than the control group (13 cases vs.25 cases, 4 cases vs.17 cases), and the differences were statistically significant (all P<0.05).The Systemic Lupus Erythematosus Disease Activity Index score in the TMA group [(24.14±9.42) scores] was significantly higher than that in the control group [(10.18±9.42) scores], and the difference was statistically significant ( t=3.233, P<0.05).The hemoglobin level, platelet count, and complement C3 level of the children in the TMA group were significantly lower than those in the control group, whereas the double stranded DNA antibody, lactate dehydrogenase, D-dimer, urea, creatinine, ferritin level, and urine protein quantitation were significantly higher than those in the control group, and the differences were statistically significant (all P<0.05).In the TMA group, 5 cases had decreased ADAMTS13 activity, and 5 cases had significantly increased complement C5b9.A total of 15 cases (51.72%) in the TMA group underwent renal biopsy, and 13 of them had combined renal TMA.In the TMA group, 28 patients (96.6%) received hormone therapy, 17 patients received plasma exchange, and 12 patients were treated with immunosuppressants and biologics; 19 patients (65.5%) improved, and 10 patients (34.5%) gave up the treatment due to deterioration of the disease.The urea level and peripheral blood fragmented erythrocyte rate in the good prognosis group were significantly lower than those in the poor prognosis group [(13.18±4.39) mmol/L vs.(21.16±10.14) mmol/L, t=2.975, P=0.006; 8/17 (47.06%) vs.7/7 (100%), χ2=5.929, P=0.015].The univariate Logistic regression analysis showed that the fragmented erythrocyte, ADAMTS13 activity and urea were the independent risk factors for poor prognosis (all P<0.05). Conclusions:SLE patients with moderate-to-severe disease activity, especially children with hemolytic anemia, thrombocytopenia, and renal dysfunction as prominent manifestations, should be alert to the risk of TMA.Early diagnosis and treatment are crucial.