Interleukin-1 receptor associated kinase 4 (IRAK4) plays a crucial role in signal transduction and regulation in the TLRs/IL-1R signaling pathway, coordinating multiple inflammatory pathways involving immune system activation, cytokine production, and cell proliferation and differentiation. IRAK4 is associated with the pathogenesis and progression of hematological malignancies, including myelodysplastic syndrome, acute myeloid leukemia, chronic lymphocytic leukemia, and lymphoma. Therefore, IRAK4 may serve as an effective therapeutic target for hematologic malignancies. This review summarizes the research advances in the structure and function of IRAK4, as well as its mechanism of action and therapeutic implications in hematological malignancies, aiming to provide insights into pathogenesis of related diseases and targeted therapy research.

Objective To analyze the factors affecting pathological complete response (pCR) of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy, and construct a nomogram to forecast the pCR rate. Methods The clinical and pathological data of 348 TNBC patients who received neoadjuvant chemotherapy in the Air Force Medical University-Affiliated Xijing Hospital from May 2018 to May 2021 were collected and set as modeling set. The clinical and pathological data of 69 TNBC patients who received neoadjuvant chemotherapy in the Xi'an No.3 Hospital from May 2018 to May 2021 were collected and set as validation set. The clinical and pathological characteristics were compared between the modeling set and the validation set. In the modeling set, the independent risk factors of pCR in TNBC patients after neoadjuvant chemotherapy were screened by LASSO regression model analysis, and the nomogram model was constructed. Internal validation of the model was conducted using Bootstrap method, and the discrimination of the model was assessed by receiver operating characteristic (ROC) curve. The accuracy of the model was evaluated by the calibration curve and the clinical benefits and application value of the model were evaluated by clinical decision curve analysis (DCA). Results There were significant differences in surgical method and T stage between the patients in modeling set and validation set (P<0.05). The results of analysis of LASSO regression model showed that T stage, N stage, the use of platinum drugs and clinical efficacy evaluation were independent risk factors of pCR in TNBC patients after neoadjuvant chemotherapy (P<0.05). Based on the above variables, the nomogram models were constructed. In modeling set, area under curve (AUC) was 0.811 (95%CI 0.763-0.859); in validation set, AUC was 0.801 (95%CI 0.727-0.928). The Bootstrap method showed the C-index for internal validation was 0.79, indicating the model has good discrimination in both the modeling and validation sets. The calibration curve analysis showed that model predicted pCR rates had a good consistency with the actual observed values, and the DCA showed that model can bring clinical benefit. Conclusion The nomogram can accurately predict the pCR rates of TNBC patients after neoadjuvant chemotherapy and provide scientific basis for clinical diagnosis and treatment.

Objective To investigate the potential risk factors for immune checkpoint-related pneumonia (CIP) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), to identify high-risk patients with CIP at an early stage. Methods A total of 728 NSCLC patients treated with ICIs at the First Affiliated Hospital of Zhengzhou University from January 2020 to June 2023 were retrospectively selected, including 47 cases with CIP (CIP group), and 141 matched NSCLC patients without CIP (control group). Clinical data, laboratory tests, and CT images before the first immunotherapy were collected for all patients in two groups. The FACT medical imaging software was utilized for quantitative emphysema assessment in patients' CT scans. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with CIP. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of these factors for CIP occurrence in NSCLC patients. Results Among the 47 CIP patients, 40(85.1%) were male, with 25(53.0%) aged between 41 and 65 years. Grade 3 pneumonia according to the Common Terminology Criteria for Adverse Events (CTCAE) was found in 28(59.6%) cases, characterized by a predominant reticular radiographic pattern. Multivariate logistic regression analysis showed that a low albumin level (OR=0.889, 95%CI 0.808-0.979, P=0.017), targeted therapy (OR=9.204, 95%CI 1.678-50.486, P=0.011), anti-angiogenic therapy (OR=0.056, 95%CI 0.020-0.161, P<0.001), and a high percentage of low attenuation area (LAA%) (OR=1.227, 95%CI 1.053-1.430, P=0.009) were significant factors influencing CIP occurrence. The combined predictive model using these four factors showed an area under the ROC curve of 0.888 (95%CI 0.838-0.939), with a sensitivity of 0.894 and a specificity of 0.801 for predicting CIP in NSCLC patients. Conclusions Low serum albumin, first-line targeted therapy, and high LAA% are identified as risk factors for CIP occurrence, while anti-angiogenic therapy is a protective factor. The predictive model based on these four variables effectively predicts the risk of CIP in NSCLC patients.

Objective To explore the influence factors and predictors of treatment response after adrenocorticotropic hormone (ACTH) in infantile epileptic spasms syndrome(IESS). Methods A retrospective analysis was conducted on 80 cases of IESS infants(50 males and 30 females) who were diagnosed and treated with ACTH in Chengdu Women's and Children's Central Hospital from January 2016 to December 2020. Patients were divided into effective group (n=39) and ineffective group (n=41) based on their response of ACTH treatment after 28 days, and their clinical data including the patients' basic information, etiology, treatment programmer, per- and post-treatment Kramer scores of electroencephalogram (EEG) hypsarrhythmia severity and so on, were collected to compare and analyze between the two groups. A modified Poisson regression model was constructed to discover predictors of outcome, and the receiver operating characteristic (ROC) curves were used to assess the prognosis evaluation of the positive predictive value. Results The ages at seizure onset ranged from one month and seven days to one year and nine months. Seizure types included simple epileptic spasms in 66 cases and combined with other types(focal and secondarily generalized seizures) in 14 cases. Thirty-two cases had been given anti-seizure medications (ASMs) before ACTH treatment. The median Kramer scores per-treatment and at 14 days post-treatment were 10.0 (8.3, 12.0) and 6.0 (4.0, 7.0), respectively. After ACTH treatment, 39(48.8%) cases were effective. Compared with the effective group, the ineffective group had significantly higher proportion of abnormal perinatal conditions, unknown aetiology with normal development, ASMs given before ACTH treatment, the dosages of ACTH greater than 2 U/(kg·d), combinations of two or more ASMs, poor control, and still seizure attack after ACTH treatment of 14 days (P<0.05). Additionally, the Kramer scores after ACTH treatment of 14 days in the ineffective group were also significantly higher (P<0.05). The modified Poisson regression model showed that there were significant statistic differences between the two groups on ASMs given before ACTH treatment (RR=0.546, 95%CI 0.357-0.833, P=0.005) and Kramer scores of hypsarrhythmia severity (RR=0.701, 95%CI 0.620-0.792, P<0.001),while there were no significant differences between the two groups in term of ages, gender, perinatal conditions, etiologies, seizure types, Kramer scores before treatment, time lag between onset and treatment, duration of ACTH treatment, kinds of ASMs combination. ROC curve analysis showed that only Kramer scores at 14 days after ACTH treatment could predict the treatment response with sensitivity and specificity of 92.7% and 84.6%, respectively, with Youden index of 0.773. The area under the ROC curve was 0.930 (95%CI 0.873-0.987, P<0.001) and the cut-point of the score was 6, indicating that the higher the Kramer scores at 14 days after ACTH treatment, the worse the treatment response. The treatment response rate would reduce by about 30.0% if the Kramer score increased by one point. Conclusion ASMs given before ACTH treatment may influence the treatment response. Kramer scores greater than 6 at day 14 after ACTH treatment may be used as a predictor of treatment response after ACTH in IESS patients.

Objective To determine the effective dose of dexmedetomidine administered intranasally combined with oral midazolam sedation before pediatric magnetic resonance image (MRI). Methods This is a prospective modified sequential study. Children scheduled for MRI at the Children's Hospital of Zhejiang University School of Medicine from February to March 2023, aged 1 month to 6 years old, with a weight of 6.0-23.5 kg, were enrolled in this study. All children received 0.5 mg/kg oral midazolam, followed by intranasal dexmedetomidine. The initial dose of dexmedetomidine was 0.5 μg/kg, and the intranasal dose of dexmedetomidine was determined using the modified Dixon's up-and-down method with increments or decrements of 0.1 μg/kg. Probit analysis was used for calculating the half effective dose (ED₅₀), 95% effective dose (ED₉₅) and the corresponding 95% confidence interval (CI) of intranasal dexmedetomidine combined with oral midazolam for pediatric sedation during MRI. The sedation onset time, wake-up time, vital signs and adverse reactions were recorded. Results Among all the children,the sedation onset time of successful sedation children was (31.21±7.47) min, and the wake-up time was (81.21±26.04) min. The ED₅₀ for effective sedation with intranasal dexmedetomidine combined with oral medication at a dose of 0.5 mg/kg was calculated to be 0.392 μg/kg, with a 95%CI of 0.302-0.461 μg/kg; the ED₉₅ was 0.549 μg/kg, with a 95%CI of 0.473-0.996 μg/kg.There was a statistically significant difference (P<0.05) in heart rate and diastolic blood pressure after sedation compared to the baseline before medication. Two cases of restlessness during the awakening period were observed, but no other adverse reactions occurred. Conclusions The sedation regimen of intranasal dexmedetomidine combined with oral midazolam is non-invasive, easy to implement, safe, and effective. It can be widely used in pediatric MRI.

Objective To investigate the predictive value of central venous oxygen saturation (ScvO₂) in elderly patients with acute kidney injury (AKI) after robot-assisted partial nephrectomy (RAPN). Methods Seventy-eight elderly patients who underwent RAPN in the Department of Urology, the Third Medical Center of Chinese PLA General Hospital from February to September 2022 were selected. AKI was diagnosed according to the International Nephropathy Improving Global Prognosis Criteria, and the patients were divided into AKI group (n=22) and non-AKI group (n=56) according to whether AKI occurred after surgery. Blood gas analysis of venous blood was taken after central venous puncture (T₀), 5 min after renal artery occlusion (T₁), 5 min after renal artery opening (T₂), and after surgery (T₃). Hemoglobin (Hb), arterial blood lactic acid (Lac), arterial oxygen partial pressure (PaO₂), ScvO₂ were recorded respectively. Oxygen uptake rate (O₂ER) were calculated. Multivariate logistic regression analysis was used to analyze the risk factors for postoperative AKI. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of ScvO₂ for AKI in elderly patients after RAPN. Results Compared with non-AKI group, fasting plasma glucose (FPG) level in AKI group significantly increased at T₁-T₂ (P<0.05). Compared with T₀, FPG level in two groups obviously increased at T₁-T₃ (P<0.01). Compared with T₁, the FPG level in T₃ significantly increased in non-AKI group (P<0.01). Compared with non-AKI group, ScvO₂ in AKI group significantly increased at T₁-T₂ (P<0.01), Lac level at T₂ significantly increased (P<0.05). There was no significant difference in O₂ER between the two groups at each time point (P>0.05). Compared with T₀, O₂ER in T₁-T₃ significantly decreased (P<0.01), and ScvO₂ in both groups significantly increased (P<0.01). Compared with T₁, ScvO₂ in non-AKI group significantly increased at T₂-T₃ (P<0.05 or P<0.01). Compared with T₂, ScvO₂ in non-AKI group significantly increased in T₃ (P<0.05). Multiple-factor analysis showed that T₁ ScvO₂ (OR=1.127, 95%CI 1.006-1.263, P=0.039) was an independent risk factor for AKI after RAPN. ROC curve analysis showed that T₁ ScvO₂ had a sensitivity of 77.3%, specificity of 71.4%, truncation value of 81%, and area under the curve (AUC) of 0.761 in predicting AKI after RAPN. Conclusion ScvO₂ has certain predictive value for the occurrence of short-term AKI after RAPN.

Objective Based on data from the US SEER database, this study investigates the incidence, epidemiological characteristics, treatment modalities, prognosis assessment, and risk stratification of advanced-stage lung adenocarcinoma in young patients. Methods SEER*Stat software was used to collect the incidence rates of lung adenocarcinoma among people under 50 in the US from 2000 to 2020, with annual percentage changes (APCs) calculated using Joinpoint software. Clinical data of 4490 advanced-stage lung adenocarcinoma patients under 50 years old from the SEER database (2010-2018) were retrospectively collected and analyzed. Kaplan-Meier method was used to calculate overall survival, log-rank test to estimate survival rates, and Cox proportional hazards regression model to conduct univariate and multivariate prognostic analyses, and a nomogram model was established to predict the survival of young advanced lung adenocarcinoma patients. The predictive performance of the nomogram was evaluated using ROC curves and calibration curves. X-Tile software was used for risk stratification of the prognosis of young advanced lung adenocarcinoma patients. Results From 2000 to 2020, the incidence rates of young lung adenocarcinoma in men and women in the US decreased from 2.1/100 000 and 2.2/100 000 to 1.1/100 000 and 1.5/100 000 respectively, with APCs of -2.16 and -1.39 (P<0.05). Compared to patients aged 40 to <50 years, patients under 40 were more likely to develop bone metastasis, liver metastasis, and lung metastasis, had a higher probability of receiving chemotherapy, tumors were more likely to occur in the lower or middle lobes of the lung, but had a lower probability of receiving radiotherapy, with statistically significant differences (P<0.05). Cox regression analysis showed that gender, age, race, N stage, M stage, subsite, liver metastasis, and bone metastasis were prognostic factors for young advanced lung adenocarcinoma patients (P<0.05); male patients had worse prognosis than female patients (HR=1.17, 95%CI 1.09-1.25); African American patients had worse prognosis than Caucasian patients (HR=1.12, 95%CI 1.02-1.23), other races had better prognosis than Caucasian patients (HR=0.83, 95%CI 0.77-0.97); patients aged 40 to <50 had worse prognosis than those under 40 (HR=1.34, 95%CI 1.21-1.48); patients with bone metastasis (HR=1.29, 95%CI 1.19-1.40) and liver metastasis (HR=1.40, 95%CI 1.28-1.54) had worse prognosis, with statistically significant differences (P<0.05). Based on the above prognostic factors, a nomogram model was established to predict 1-year, 3-year, and 5-year survival with areas under the curve (AUC) of 0.717, 0.692, and 0.699 respectively, and the calibration curve was close to the 45° diagonal. According to the risk scores, patients were divided into low-risk group [1017 cases (22.7%)], medium-risk group [2871 cases (63.9%)], and high-risk group [602 cases (13.4%)]. The difference is statistically significant comparing the survival rates among three groups (P<0.0001). Conclusion Gender, age, race, N stage, M stage, subsite, liver metastasis, and bone metastasis are prognostic factors for young advanced lung adenocarcinoma patients, and the nomogram model established based on these factors has high predictive performance.

Objective To explore the effects of different side tension pneumothorax on hemodynamics in pigs, providing data support for the optimization of on-site first-aid procedures for pneumothorax. Methods Twelve Bama pigs were randomly divided into left-sided tension pneumothorax group and right-sided tension pneumothorax group (6 in each group). During the occurrence of pneumothorax and as the pleural pressure gradually increases by 1 mmHg increments, the key indicators were collected using pulse indicator continuous cardiac output (PICCO) technology: hemodynamic indicators [global ejection fraction (GEF), cardiac output (CO), global end-diastolic volume (GEDV), intrathoracic blood volume (ITBV), stroke volume (SV), mean arterial pressure (MAP)], basic vital signs [heart rate (HR), diastolic blood pressure (DBP), systolic blood pressure (SBP)], and arterial blood gas parameters [partial pressure of oxygen (PO₂), partial pressure of carbon dioxide (PCO₂)]. Mediastinal localization was subsequently performed using radiographs. Differences were investigated through comparison between the two groups and within each group before and after the procedure. Results By comparing the hemodynamic changes and X-ray examination results, twelve Bama pigs tension pneumothorax models were successfully constructed. Hemodynamic analysis showed that in left-sided tension pneumothorax model when the pleural pressure reached 8 mmHg, SBP, DBP, MAP, CO, GEF, SV, GEDV and ITBV were significantly lower than those during the occurrence of ipsilateral pneumothorax (P<0.05). In right-sided tension pneumothorax model, when the pleural pressure reached about 3 mmHg, SBP, DBP, MAP, SV, GEDV, and ITBV were significantly lower than those during the occurrence of ipsilateral pneumothorax (P<0.05). Blood gas analysis showed that at 8 mmHg for left-sided and 3 mmHg for right-sided tension pneumothorax, compared with the occurrence of their respective ipsilateral pneumothorax, PO₂ was significantly lower (P<0.05) and PCO₂ was significantly higher (P<0.05). Conclusions There are different effects on hemodynamics in different side tension pneumothorax. Compared with left tension pneumothorax, right tension pneumothorax can lead to serious consequences under a smaller pleural pressure. Different side tension pneumothorax models can be constructed according to the actual situation when performing pneumothorax related experiments.

Objective To investigate the role of necroptosis key genes in spinal cord injury using bioinformatics methods to provide new targets for the diagnosis and treatment of spinal cord injury. Methods The peripheral blood transcriptome data of spinal cord injury samples (n=38) and healthy control samples (n=10) were obtained from GSE151371 data set in Gene Expression Omnibus (GEO) database. R software was used to identify differentially expressed genes and perform functional enrichment analysis. Machine learning algorithms (random forest and LASSO) and protein-protein interaction (PPI) networks are used to screen for necroptosis key genes and construct a diagnostic nomogram for spinal cord injury. Establish a rat spinal cord injury model to further verify the expression of necroptosis key genes by Western blotting and immunofluorescence staining. Results A total of 2050 differentially expressed genes were identified in the two groups. KEGG pathway enrichment analysis showed that the differentially expressed genes were involved in the nucleotide-binding oligomerization domain (NOD)‑like receptor signaling pathway, hematopoietic cell lineage, and necroptosis; GO enrichment analysis showed that the differentially expressed genes were involved in the activation of leukocytes, tertiary granulation, and regulation of the defense response, and so on. Intersection analysis screened 15 necroptosis differentially expressed genes. KEGG pathway enrichment analysis showed that necroptosis differentially expressed genes were involved in necroptosis, influenza, and NOD-like receptor signaling pathways; GO enrichment analysis showed that necroptosis differentially expressed genes were significantly enriched in the cellular response to cytokine stimulation, cytokine-mediated signaling pathways, and response to cytokines. Integration of two machine learning algorithms and PPI analysis further screened two necroptosis key genes (IL1B and PLA2G4A). The nomogram established using IL1B and PLA2G4A can be used for early prediction of the occurrence of spinal cord injury. The validation results of the rat spinal cord injury model showed that the protein expression of IL-1β and PLA2G4A in the spinal cord injury group were significantly higher than those in the sham group (P<0.05). Conclusions IL1B and PLA2G4A as key genes of necroptosis involved in the development of spinal cord injury, can be used to predict the development of spinal cord injury with the promise of being new targets for the prevention and treatment of spinal cord injury

Objective To investigate the effects of astragaloside Ⅳ (AS-Ⅳ) on axon growth inhibitory factor A (Nogo-A) and its downstream pathway protein RHO-associated coiled spiral kinase 2 (ROCK2) in experimental autoimmune encephalomyelitis (EAE) mice, and to explore the mechanism by which it promotes axon repair and regeneration. Methods EAE model was induced in C57BL/6 female mice by subcutaneous injection of myelin oligodendrocyte glycoprotein 35-55 (MOG35-55). Mice were randomly divided into EAE group and AS-Ⅳ group (n=8 per group). EAE group received intraperitoneal injection of PBS on the 3rd day post-immunization, while AS-Ⅳ group was administered AS-Ⅳ at a dosage of 30mg/(kg.d) once daily, 0.2 ml per injection, for 25 consecutive days. On the 28th day post-immunization, the expression levels of growth-associated protein 43 (GAP-43), neuronal core antigen (NeuN), microtubule associated protein 2 (MAP-2), glial fibroacidic protein (GFAP), and Iba1 in the spinal cord were detected using immunofluorescence assay. Real-time fluorescence quantitative PCR (qRT-PCR) was conducted to detect mRNA expression levels of GAP-43, Nogo-A, and Nogo receptor (NgR) genes. Western blotting was utilized to determine the expression levels of GAP-43, Nogo-A, ROCK2, phosphorylated myosin phosphatase (p-MYPT1), B-lymphoblastoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax). Results Compared with EAE group, AS-Ⅳ treatment significantly reduced the positive cell expression rates of Iba1 microglia and GFAP astrocyte in spinal cord (P<0.01 and P<0.001,respectively), while it also increased the positive expression rates of NeuN and MAP-2 (P<0.001 and P<0.05, respectively). The treatment also upregulated the expression level of anti-apoptotic factor Bcl-2 (P<0.001) and downregulated the expression level of pro-apoptotic factor Bax (P<0.05), leading to an increase in Bcl-2/Bax ratio (P<0.05). Furthermore, AS-Ⅳ enhanced the expression of GAP-43 protein (P<0.05) and decreased the mRNA expression levels of neuroregeneration inhibitor Nogo receptor (NgR) and ROCK2 gene (P<0.001, P<0.05, respectively); as well as decreased the expression levels of Nogo-A, ROCK2 and p-MYPT1 proteins (P<0.05, P<0.001). Conclusion AS-IV may inhibit the activation of microglia and astrocytes and neuronal apoptosis in EAE mice by inhibiting Nogo-A and downstream pathway ROCK2, thereby promoting the expression of GAP-43, NeuN and MAP-2, alleviating neuronal damage, and facilitating axon repair and regeneration.