The evolutionary arms race between life and pathogens drives diversification in immune system signaling mechanisms. Recent research has found that the TIR protein of the bacterial type II Thoeris defense system can produce a novel “hybrid” immune signaling molecule—histidine-ADP-ribose (His-ADPR). This molecule, formed by the direct linkage of an amino acid and a nucleotide, challenges the traditional view that TIR enzymes generate only pure nucleotide derivatives. This signal is specifically recognized by the Macro domain of an effector protein, triggering the transmembrane domain to disrupt the membrane for defense. The study further reveals that phages can evade immunity by expressing “signal sponge” proteins that bind and sequester His-ADPR. This offensive-defensive pressure drives TIR enzymes to continuously expand their “chemical arsenal” of signaling molecules. The discovery not only confirms the shared biochemical core of bacterial TIR signaling molecules (based on NAD⁺ modification), but also highlights their remarkable chemical plasticity and evolutionary innovative capacity. It provides a new perspective for understanding the origin and diversity of immune signaling.

OBJECTIVE To investigate the effect of plasma trough concentration of venetoclax and its influencing factors in patients with acute myeloid leukemia （AML）. METHODS After 5 days of venetoclax administration， venous blood samples were collected from AML patients before the next dose. Plasma trough concentrations of venetoclax were determined using high-performance liquid chromatography-tandem mass spectrometry. Spearman correlation was used to assess the correlations between venetoclax plasma trough concentration and various parameters （including patients’ general information， venetoclax-related indicators， liver function indicators， kidney function indicators， and blood routine indicators）. Multiple linear regression analysis was performed to identify independent factors influencing plasma trough concentration of venetoclax. Using efficacy as dependent variable [complete remission （CR）+partial remission （PR） vs. no remission （NR）]， univariate and multivariate binary Logistic regression analyses were conducted to identify factors affecting efficacy. The receiver operating characteristic （ROC） curve was used to evaluate the predictive value of venetoclax plasma trough concentration for clinical efficacy （assessed as CR）. RESULTS A total of 172 venetoclax plasma trough concentration measurements from 101 patients were included in this study. The median plasma trough concentration of venetoclax was 2.38 （1.18， 3.85） μg/mL； the median sampling time for plasma trough concentration of venetoclax was 10 （7， 15） d； the duration of venetoclax use was （34±12） d. Multiple linear regression analysis showed that alkaline phosphatase （ B ＝14.65， 95%CI： 5.35-23.95， P ＝0.002）， total bilirubin （ B ＝－101.71， 95%CI： －197.16 to －6.25， P ＝0.037）， and white blood cell count （ B ＝－106.84， 95%CI： －187.61 to －26.07， P ＝0.010） were independent factors influencing plasma trough concentration of venetoclax. Due to patient attrition during treatment， 114 venetoclax plasma trough concentration measurements from 69 patients were included for efficacy evaluation. The results showed that 46 patients （66.7%） achieved CR， 11 patients （15.9%） achieved PR， and 12 patients （17.4%） were NR. Multivariate binary Logistic regression analysis showed that age， hemoglobin， venetoclax plasma trough concentration， hematocrit， and mean corpuscular hemoglobin were independent factors affecting patient efficacy （ P ＜0.05）. ROC curve analysis showed that the cut-off value of plasma trough concentration of venetoclax for predicting patient efficacy （assessed as CR） was 1.68 μg/mL （AUC＝0.66， 95%CI： 0.54-0.78， P ＝0.014）. CONCLUSIONS There is considerable inter-individual variability in plasma trough concentration of venetoclax among AML patients. Plasma trough concentration of venetoclax is significantly correlated with alkaline phosphatase， total bilirubin， and white blood cell count. Plasma trough concentration of venetoclax is an independent factor affecting patient’s efficacy， and when the cut-off value for predicting CR is above 1.68 μg/mL， better effects may be achieved.

Objective:This study aims to analyze the trends,hotspots,and interrelations in research on retroperito-neal tumors through bibliometric methods,providing the latest scientific information support for clinicians and research-ers.Methods:Data were sourced from the SCI-expanded database of the Web of Science Core Collection,covering the period from 2004 to 2023.Statistical analysis and visualization of the number of publications,total citations,average citations per article,countries,institutions,journals,and keywords were conducted using Microsoft Excel 2019,VOS-viewer,and CiteSpace.Results:A total of 6,842 relevant articles were retrieved,with a total of 113 753 citations and an average of 16.63 citations per article.The number of publications had been increasing annually,peaking in 2022.The United States,China,and Japan are the major research countries,with the United States contributing the most.Memo-rial Sloan Kettering Cancer Center and the University of Texas MD Anderson Cancer Center are the leading research in-stitutions.The journal with the most publications was the Cureus Journal of Medical Science.Gronchi Alessandro was the most prolific author.The ain keywords were"Management","Surgery",and"Tumor",and the most cited papers focus on surgery and multicenter studies.Conclusion:Research on retroperitoneal tumors is increasing annually,with hot-spots focusing on treatment methods and prognosis analysis.The United States is the main contributor to this field,with significant international collaboration.Future research should further explore the pathogenesis of retroperitoneal tumors and more effective treatment strategies.

Objective To investigate the correlation between serum uric acid(SUA)levels and incident chronic kidney disease(CKD)in middle-aged and elderly Chinese population and gender differences.Methods Based on the longitudinal survey data of China Health and Retirement Longitudinal Study from 2011 to 2015,the CKD-Epidemiology Collaboration cystatin C formula was used to estimate the glomerular filtration rate(eGFR),and 4 119 participants with normal renal function(eGFR≥60 mL·min-1·1.72 m-2)at baseline were included.Incident CKD was defined as eGFR<60 mL·min-1·1.72 m-2 at the follow-up in 2015.Logistic regression analysis was used to analysis the association of SUA levels at baseline and incident CKD among different genders.Restricted cubic spline analysis was used to analyze the dose-response relationship.Results After 4-year follow-up,127 participants developed incident CKD,including 57 males and 70 females.Multivariate Logistic regression analysis showed that elevated SUA levels were independently associated with the risk of incident CKD(OR=1.532,P<0.001).For each 1 mg/dL increase in SUA,the risk of incident CKD increased by 33.6%in males(OR=1.336,P=0.012)and 77.5%in females(OR=1.755,P<0.001).Restricted cubic spline analysis showed a linear positive correlation between SUA levels and incident CKD in both males and females.Participants were divided into four groups according to SUA quartiles(Q1-Q4).Multivariate Logistic regression analysis indicated a significant increase in the risk of incident CKD in Q3 group(3.75 mg/dL4.43 mg/dL)compared with Q1 group in females(Q3 group:OR=2.571,P=0.045;Q4 group:OR=3.666,P=0.005).Conclusion SUA is an independent risk factor for incident CKD in the middle-aged and elderly population.In females,serum uric acid levels exceeding 3.75 mg/dL are associated with an increased risk of incident CKD.

Metabolic-bariatric surgery(MBS)has become an important treatment for pathological obesity and metabolic diseases.However,common postoperative nutritional complications—such as protein-energy malnutrition,iron deficiency anemia,and vitamin B12 deficiency—significantly affect patients' long-term prognosis.Traditional nutritional management models rely on static monitoring and standardized supplementation,which are insufficient to address individual variability and dynamic postoperative changes.Artificial intelligence(AI),through integrating multimodal data(such as biochemical indicators,imaging information,and wearable device monitoring)and intelligent modeling,offers new approaches for dynamic monitoring,risk prediction,and personalized intervention.Based on literature from 2017 to 2025,this article systematically evaluates the application of AI in perioperative nutritional management for MBS,covering key technologies including machine learning,deep learning,and natural language processing.It also analyzes current challenges in clinical translation,such as data fragmentation,lack of model interpretability,and limited long-term validation.In the future,enhanced multi-center collaboration,the development of standardized databases,and explainable models will be essential to advancing nutritional management in MBS from empirical practice to precision medicine.

Multiple myeloma(MM)is a hematologic malignancy characterized by clonal proliferation of plasma cells within the bone marrow,with pathological features including abnormal secretion of mono-clonal immunoglobulins,osteolytic bone disease,and multi-organ dysfunction.Despite significant ad-vancements in therapeutic approaches that have markedly extended patient survival,primary drug resist-ance and relapse remain major obstacles to clinical cure.The pathogenesis and progression of MM are in-tricately regulated by the bone marrow microenvironment(BMME),a dynamic network composed of di-verse cellular and non-cellular components.The BMME not only supports the survival and proliferation of MM cells but also plays a pivotal role in disease progression by modulating bone metabolic homeostasis,mediating immune escape,and promoting drug resistance.In recent years,groundbreaking therapeutic strategies targeting the BMME have emerged,including immunomodulatory drugs,bispecific antibodies,CAR T-cell therapies,and microenvironment-modulating agents.These approaches have significantly im-proved objective response rates and survival outcomes in relapsed/refractory MM by disrupting cytokine signaling,reprogramming the immunosuppressive microenvironment,or inhibiting tumor-stromal interac-tions.However,challenges such as drug resistance,treatment-related toxicity,and tumor heterogeneity persist in clinical practice.This review systematically delineates the roles of BMME components in MM pathogenesis,analyzes the molecular mechanisms underlying MM cell-BMME interactions,and explores innovative strategies to enhance therapeutic efficacy and prognosis through targeted modulation of the BMME.These insights provide a foundation for developing novel therapeutic paradigms aimed at overco-ming current limitations in MM treatment.

Objective:To summarize the best evidence for postoperative flap management in patients with oral cancer.Methods:Clinical decisions, guidelines, systematic reviews, expert consensus, and evidence summaries on postoperative flap management for patients with oral cancer were searched in databases and websites based on the 6S pyramid of evidence model. The search period was from January 1, 2014, to July 1, 2024. Two researchers trained in evidence-based nursing independently conducted a quality assessment of the literature and extracted the evidence.Results:A total of 14 articels were included, including one clinical decision, two guidelines, one evidence summary, eight systematic reviews, and two expert consensus. Twenty-eighgt pieces of evidence for postoperative flap management in patients with oral cancer were summarized from four aspects of risk factors, flap assessment, protective measures, and treatments.Conclusions:The summarized best evidence for postoperative flap management in oral cancer patients is scientific and applicable. Healthcare professionals need to select and apply the best evidence in a targeted manner, considering the clinical context.

Objective To investigate the expression of adenosine A3 receptor(ADORA3)in human glioma and its effects on prognosis and epithelial-mesenchymal transition.Methods The mRNA expression data and corresponding clinical information of ADORA3 were obtained from TCGA,CGGA,Rembrandt,Gravendeel and Gill databases,and the effects of ADORA3 expression on the prognosis of glioma patients and the process of epithelial-mesenchymal transition were analyzed.The surgically resected glioma samples of 35 cases,along with non-tumor brain tissues of 7 cases obtained from decompression surgery for severe craniocerebral injury were collected in the Department of Neurosurgery at Renmin Hospital of Wuhan University from July 2023 to April 2024,and the ADORA3 expression was detected by immunohistochemical staining.Glioblastoma multiforme(GBM)cells of U87 and U251 were transfected with NcRNA and SiRNA,respectively,as the control group and the knockdown group,and the effects of ADORA3 on cell invasion ability and epithelial-mesenchymal transition related proteins were analyzed by Transwell and Western blot.Results Bioinformatics analysis and immunohistochemical staining showed that the expression level of ADORA3 in human glioma tissues was significantly higher than that in non-tumor brain tissues(P<0.05),and the expression of ADORA3 was associated with glioma WHO grading(P<0.05).Kaplan-Meier survival curve analysis in TCGA,CGGA,Rembrandt and Gravendeel databases showed that the overall survival rate of patients with high ADORA3 expression was significantly lower than that of patients with low ADORA3 expression(P<0.001);and Cox regression analysis showed that high expression of ADORA3 was an independent risk factor for poor prognosis in patients with glioma(P<0.05);the expression level of ADORA3 in the mesenchymal type of GBM patients was significantly higher than that of the classical type and the proneural type;furthermore,ADORA3 showed significant correlations with epithelial-mesenchymal transition related markers of Vimentin,SNAI1,SNAI2,TWIST1,TWIST2,MMP2,CD44,and FN1.The knockdown of ADORA3 in vitro reduced the cell invasive ability,decreased the expression levels of MMP2,Vimentin,and SNAI1 proteins,and increased the expression of E-cadherin,with statistically significant differences(P<0.05).Conclusion ADORA3 is highly expressed in glioma,which can promote the process of epithelial-mesenchymal transition in patients,and serve as an independent risk factor for poor prognosis.

Objective To study NF1 gene variations in 10 suspected cases of neurofibromatosis type I(NF1)and their parents,thereby providing a basis for genetic counselling,clinical diagnosis,and treatment of this disease.Methods A total of 10 patients diagnosed with,or suspected of having NF1 at Northwest Women's and Children's Hospital from March to December 2023 were selected as study subjects.Whole exome sequencing(WES)was performed to analyse NF1 gene mutations in the patients and their parents,with the findings validated by Sanger sequencing.Results Pathogenic mutations were identified in 6 of the 10 families,with the remaining 4 cases showing no pathogenic gene mutations.In Family 1,a de novo mutation,c.6505A>T,was detected in the NF1 gene.In Family 2,a de novo mutation,c.6705-3C>A,was identified in the NF1 gene.In Family 3,a de novo mutation,c.6853delT,was detected in the NF1 gene.In Family 4,a de novo mutation,c.2446C>T,was found in the NF1 gene.In Family 5,a paternal mutation,c.6067T>A,was identified in the NF1 gene.In Family 6,a paternal mutation,c.2991_2993dup,was detected in the NF1 gene.Conclusion The identification of new mutation sites enriches the mutation spectrum of the NF1 gene.This study provides important guidance for genetic counselling and prenatal diagnosis,offering crucial information for families with reproductive needs.

Objective:To reveal the differences in the transcriptome maps of brain tissues in mice subjected to Flash irradiation and conventional dose rate irradiation with electron beams and to explain the biological effect and mechanisms of Flash irradiation from multiple perspectives.Methods:Following the principle of grouping based on approximate body weights, 36 female C57BL/6J mice were divided into three groups, i. e., the control, conventional dose rate irradiation (CONV), and Flash irradiation (Flash) groups, with 12 mice in each group. Both the CONV and Flash groups received a single 15 Gy whole-brain irradiation with 9 MeV electron beams. At 3 d post-irradiation, the whole-brain tissue specimens were collected for hematoxylin-eosin (HE) staining to observe pathological changes. At 1, 3, and 10 weeks post-irradiation, the motion function, cognitive ability, depression level, and spatial memory capacity of the mice were assessed using ethology. At 1 and 10 weeks after behavioral experiments, brain tissue samples were collected and snap-frozen in liquid nitrogen for reference-based transcriptome sequencing. Accordingly, the differences in the transcriptome maps of radiation-induced brain injury between CONV and Flash groups were analyzed.Results:The HE staining-based pathological result revealed that compared to the CONV group, the Flash group exhibited reduced glial cell hyperplasia and inflammatory cell infiltration in brain tissues. Ethological research result at 1 week post-irradiation showed that the CONV group manifested a significantly decreased total traveled distance compared to the control and Flash groups ( t = 5.51, 2.38, P < 0.05) and a significantly increased immobility time compared to the control group ( t = 3.60, P < 0.05). Ethological research result at 3 weeks post-irradiation indicated that compared to the CONV group, the Flash group displayed significantly alleviated cognitive impairment ( t = 3.35, P < 0.05) and reduced depression levels ( t = 2.39, P < 0.05). Ethological research result at 10 weeks post-irradiation demonstrated that the CONV group showed the worst cognitive performance, significantly differing from the control group ( t = 4.53, P < 0.05). Transcriptome sequencing result revealed that besides immune-related pathways, the Flash group also exhibited multiple upregulated metabolic pathways and fibroblast growth factor (FGF)-related pathways compared to the CONV group. Conclusions:Compared to conventional dose rate irradiation, Flash irradiation can effectively alleviate radiation-induced brain injury in mice. This effect is associated with various metabolic pathways (including amino acid metabolism) and FGF-related pathways besides immune pathways.