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 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 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 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.

Chronic kidney disease (CKD) commonly used dietary assessments including 24-hour dietary recall (24 h DR)/3-day dietary recall (3DDR), food frequency questionnaire (FFQ), dietary records, and estimation of dietary protein intake based on nitrogen balance. Given the high prevalence of CKD patients in Asian population and the scarcity of research using FFQ method, it is crucial to develop an FFQ suitable for Chinese CKD patients. This review summarizes the advantages and disadvantages of dietary assessment methods for CKD, the current research status, and the content and steps involved in establishing an FFQ, with the aim of providing reference for the modification of FFQ for Chinese CKD patients.

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 investigate how flavokawain B (FKB) affects the proliferation and migration of triple-negative breast cancer (TNBC) cells by downregulating the androgen receptor (AR). Methods The expression of AR in breast cancer and normal tissues was analyzed using the GEPIA2 database. Expression of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and AR was detected in six breast cancer cell lines (SUM159PT, MCF-7, T47D, BT474, Hs-578T, and MDB-MA-231) by Western blotting. The effect of FKB (0, 10, 20, 30, 40, 50, 60 μmoL/L) treatment of 24, 48, and 72 h on the proliferative activity of SUM159PT breast cancer cells was assessed using the CCK-8 assay under normal or androgen deprivation conditions. The mRNA and protein of AR expression was measured by qRT-PCR and Western blotting after 30 μmoL/L FKB treatment of SUM159PT cells for 0, 4 and 8 h. SUM159PT cells were set as control group (treatment with 0.1% DMSO), dihydrotestosterone (DHT) group (treatment with 10 nmol/L DHT), FKB group (treatment with 15 μmol/L FKB), DHT+FKB group (treatment with 10 nmol/L DHT and 15 μmol/L FKB), AR antagonist enzalutamide (ENZA) group (treatment with 40 μmol/L ENZA), and DHT+ENZA group (treatment with 10 nmol/L DHT and 40 μmol/L ENZA) under androgen deprivation conditions. Cell proliferation, migration, and colony formation abilities in the above groups were determined using the CCK-8 method, Transwell assay, and clone formation test. Western blotting was also used to detect the expression levels of EMT-related proteins (N-cadherin, Occludin, Vimentin) and AR protein. Results AR mRNA expression level was significantly higher in breast cancer tissue than in normal breast tissue (P<0.05). AR was expressed at comparable levels in five different breast cancer cell lines (SUM159PT, MCF-7, T47D, BT474, and Hs-578T) in addition to MDB-MA-231. FKB can downregulate AR mRNA and protein levels (P<0.05). Western blotting results showed that DHT could upregulate AR protein levels in SUM159PT cells, but FKB could prevent the DHT-induced upregulation of AR protein levels (P<0.05). FKB and ENZA decreased SUM159PT cell proliferation and migration and DHT-mediated cell proliferation and migration (P<0.05). FKB and ENZA can reduce N-cadherin and Vimentin protein levels and counteract DHT-induced increases in N-cadherin and Vimentin protein levels (P<0.05). In addition, FKB may increase Occludin expression and counteract the DHT-induced decrease in Occludin protein expression (P<0.05). Conclusion Flavokawain B could inhibit the proliferation, migration, and clonogenic ability of TNBC cells by regulating AR expression.

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 whether dexmedetomidine (DEX) can alleviate exertional heatstroke (EHS)-induced rhabdomyolysis (RM) in rats by activating adrenergic α2 receptors, and to explore its potential mechanism based on the reactive oxygen species (ROS)/NOD-like receptor protein 3 (NLRP3)/interleukin-1β (IL-1β) pathway. Methods Thirty-six male Sprague-Dawley (SD) rats, after a 7-day acclimatization training, were randomly divided into six groups: control group (CN group), EHS group, low-dose DEX group (EHS+low DEX group), high-dose DEX group (EHS+high DEX group), DEX combined with yohimbine (YOH) group (EHS+high DEX+YOH group), and YOH group (EHS+YOH), with six rats in each group. Before modeling, EHS+high DEX+YOH group and EHS+YOH group were intraperitoneally injected with YOH at 1 mg/kg, while the other four groups were injected intraperitoneally with an equal dose of physiological saline (0.9% NS). During modeling, except for CN group, the other 5 groups of rats were subjected to heat exercise in a high-temperature and high-humidity chamber to construct an EHS rat model. After successful modeling, EHS+low DEX group was intraperitoneally injected with DEX at 10 μg/kg, EHS+high DEX group and EHS+high DEX+YOH group were intraperitoneally injected with DEX at 30 μg/kg, and CN group, EHS group and DEX+YOH group were intraperitoneally injected with equal doses of saline. After 6 h of observation, all rats were anesthetized, and their blood from the abdominal aorta and gastrocnemius muscle tissue were taken. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and myoglobin (MB) in rats; biochemical assay kit was used to measure the level of creatine kinase (CK) in rat serum; HE staining was used to observe pathological changes in rat gastrocnemius muscle tissues; transmission electron microscopy was used to observe ultrastructural changes in gastrocnemius muscle; 2′,7′-dichlorofluorescent yellow diacetate (DCFH-DA) fluorescent probe was used to detect the level of reactive oxygen species (ROS); and Western blotting was performed to detect the expression levels of NOD-like receptors 3 (NLRP3), aspartic protease-1 (caspase-1) and adrenergic α2A receptor (ADRA2A). Results Compared with CN group, the levels of serum IL-6, IL-1β, TNF-α, CK and MB in EHS group rats were significantly elevated (P<0.01). HE staining results revealed that the gastrocnemius muscle tissues of rats in EHS group had these pathological manifestations such as disarray of muscle fibrous structure, hemorrhage, edema, and infiltration of inflammatory cells. Transmission electron microscopy results showed that the ultrastructure of the gastrocnemius muscle in EHS group exhibited myofibroblasts with swelling and enlarging in size, cytoplasmic vacuolization, and mitochondria with obvious swelling, degranulation, and disappearance of double cristae. Compared with CN group, the expression levels of ROS, NLRP3, and caspase-1 in gastrocnemius of rats in EHS group significantly increased (P<0.01); Compared with EHS group, the levels of TNF-α, IL-6, IL-1β, CK, MB and the expression levels of ROS, NLRP3, caspase-1 in gastrocnemius tissue of rats in EHS+low DEX group and EHS+high DEX group decreased in a dose-dependent manner (P<0.05), and the pathological damage observed with HE staining and transmission electron microscopy was alleviated by DEX. After YOH pretreatment, compared with the EHS+high DEX group, the serum levels of TNF-α, IL-6, IL-1β, CK, MB and ROS, NLRP3 and caspase-1 in the gastrocnemius muscle tissue of rats in EHS+high DEX+YOH group relatively increased (P<0.05), and the pathological damage observed with HE staining and transmission electron microscopy was exacerbated. The expression of ADRA2A in gastrocnemius muscle of EHS group significantly decreased compared with CN group (P<0.01), and the expression of ADRA2A in muscle of rats in DES+low DEX group and EHS+high DEX group was higher than that in EHS group (P<0.05). Conclusions DEX can alleviate EHS-induced RM by activating ADRA2A, potentially through inhibiting the ROS-dependent NLRP3/IL-1β inflammatory pathway.

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.