Objective To investigate the changes and clinical significance of pyroptosis and inflammation in children with acute lymphoblastic leukemia after chemotherapy.Methods A retrospective analysis was con-ducted on the clinical data of 98 children with acute lymphoblastic leukemia who received chemotherapy in the pediatrics and hematology and oncology departments of the hospital from May 2023 to August 2024.Accord-ing to the results of blood culture,the selected children were divided into the Gram-positive bacteria group,the Gram-negative bacteria group,the fungal group and the non-bloodstream infection group,and drug sensitivity tests were conducted.After chemotherapy,the children were divided into the granulocytosis group and the non-granulocytosis group according to the granulocyte level.The relevant indicators were detected and com-pared by methods such as blood routine,flow microsphere array technology,enzyme-linked immunosorbent assay(ELISA),and Western blot.Results After chemotherapy,the pyroptosis related indicators caspase-1,caspase-4,caspase-5,caspase-11,interleukin(IL)-1 β,IL-18,the proportion of pyroptosis cells and the relative expression level of GSDMD protein in children of each infection type were significantly increased compared with those before chemotherapy(P＜0.05).After chemotherapy,the levels of IL-4,IL-6,IL-10 and interfer-on-γ(IFN-γ)in the granulocytosis group were significantly higher than those in the non-granulocytosis group(P＜0.05),and the granulocyte level was negatively correlated with the levels of IL-4,IL-6,IL-10 and IFN-γ(P＜0.05).There were statistically significant differences in the levels of IL-4,IL-6,IL-10 and IFN-γ in dif-ferent infection states after chemotherapy(P＜0.05).Conclusion The number of granulocytes and the levels of serum cytokines can serve as potential indicators of infection in children with leukemia.The regulation of pyroptosis may provide new strategies for the treatment of childhood leukemia.

Objective:To systematically review and compare the efficacy of intranasal dexmedetomidine versus oral midazolam for premedication in the pediatric patients.Methods:PubMed, EMbase and Cochrane library were searched for all randomized controlled trials involving the efficacy of intranasal dexmedetomidine versus oral midazolam for premedication in the pediatric patients from inception to August 2019, with an English language restriction.Evaluation indexes included efficacy of preoperative sedation, acceptance of face mask for anesthesia, postoperative requirement for rescue analgesia, incidence of agitation during emergence and postoperative recovery time.The quality of the included trials was assessed according to the relevant criteria recommended in Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1.Meta-analysis was conducted using the Cochrane Collaboration′s Review Manager 5.3 software.Results:Ten randomized controlled trials involving 720 pediatric patients were included.Compared with oral midazolam group, the efficacy of preoperative sedation was better, the requirement for postoperative rescue analgesia was decreased ( P<0.01), and no significant differences were found in acceptance of face mask for anesthesia, incidence of agitation during emergence, and postoperative recovery time in intranasal dexmedetomidine group ( P>0.05). Conclusion:Intranasal dexmedetomidine provides better efficacy than oral midazolam when used for premedication in the pediatric patients.

Rapid development of biotechnology provides us with large number of omics data from different angles in biological research, including genomics, transcriptomics, proteomics, metabolomics and epigenetics. However, any single technology cannot reflect the entire picture of the biological complexity of most tumors. The integration of multiple technologies has emerged as a new approach to provide a more comprehensive view on the biological aspects of tumors. Despite the maturing of acquisition and processing approaches regarding the various omics data, integration of multi-omics data still needs to be developed. In this paper, we summarize the applications of various omics approaches in the field of cancer research, focusing on the current status of integration of omics data in the study design and strategies on cancer research.

Objective:To describe the regional and demographic differences on passive non-smokers from 10 regions involved in the China Kadoorie Biobank (CKB) study.Methods:Detailed information regarding passive smoking behaviors related to 317 486 non-smokers who were 30-79 years old from the 10 study regions were gathered and analyzed.Results:Following the standardization of the 2010 China national population, the prevalence rate of passive smoking was 56.7 %, and the prevalence rate of living with smokers was 66.5 % among the Chinese adults. Both of the aforementioned rates were higher in rural than in urban areas. Meanwhile, the regional distribution of weekly passive smoking frequency and cumulative duration of passive smoking per week and cumulative duration of passive smoking per day were significantly different. The cumulative passive smoking duration per week increased along with the weekly frequency in people living in urban areas. Among women, the weekly passive smoking frequency was the highest, and the cumulative durations per week and per day appeared the lowest in Hunan, opposite to the situation in Henan. The prevalence of passive smoking among participants living with smokers was 2.27 times (95 %CI: 2.24 -2.29) of those who were not and the association appeared stronger in women ( OR=2.61, 95 %CI: 2.58-2.64) but not in men ( OR=1.01, 95 %CI: 0.95-1.06). Almost all the indicators seemed higher in women than those in men, except for the cumulative duration per day. Furthermore, these indicators appeared higher among those who were at younger age or with less education. The prevalence rates of passive smoking and living with smokers were lower but the cumulative duration per day was higher among those with lower household income. And the two rates were higher in married women and lower in married men, as compared to their counterparts. Conclusion:Regional and demographic differences in passive smoking were noticed among study population of CKB in the 10 regions.

Objective The objective of this study was to investigate the relationship between the methylation of phosphodies-terase 4C(PDE4C)gene in peripheral blood leukocytes,and its interaction with environmental factors and the pathogenesis of breast cancer. Methods A case-control study was conducted to select 402 cases of breast cancer and 470 cancer-free controls from Octo-ber 2010 to December 2014. The specific DNA methylation-modified quantitative PCR method was used to detect the methylation of PDE4C gene. The use of crossover analysis and multivariate logistic regression was used to analyze the relationship between the level of gene methylation and its interaction with environmental factors and the pathogenesis of breast cancer. Results PDE4C methylation was not found to be significantly associated with the onset of breast cancer. High-frequency/high-intake of whole grains,vegetables, onion-based plants,poultry,milk,and regular exercise could reduce the risk of breast cancer;high-frequency/high-intake of pork, irregular menstrual cycle,and a high psychological stress index could increase the risk of breast cancer. PDE4C hypermethylation had a significant combining effect with edible onion-producing plants greater than 3 times/week,with an OR of 0. 373(95% CI:0. 208~0. 668,P=0. 001). Conclusion Hypermethylation of PDE4C is not an independent risk factor for breast cancer,and its combination with environmental factors affects the risk of breast cancer.

Objective: To investigate the efficiency and safety of domestic tyrosine kinase inhibitor (TKI) dasatinib (Yinishu) as second-line treatment for patients with chronic myeloid leukemia in chronic phase (CML-CP). Methods: A retrospective analysis of clinical data of CML-CP patients who received domestic dasatinib as second-line treatment in the CML collaborative group hospitals of Hubei province from March 2016 to July 2018 was performed. The optimal response rate, the cumulative complete cytogenetic response (CCyR), the cumulative major molecular responses (MMR), progression free survival (PFS), event free survival (EFS) and adverse effects (AEs) of the patients were assessed at 3, 6 and 12 months of treatment. Results: A total of 83 CML-CP patients were enrolled in this study. The median follow-up time was 23 months. The optimal response rates at 3, 6 and 12 months in 83 CML-CP patients treated with dasatinib were 77.5% (54/71), 72.6% (61/75) and 60.7% (51/69), respectively. By the end of follow-up, the cumulative CCyR and MMR rates were 65.5% (55/80) and 57.1% (48/73), respectively. The median time to achieving CCyR and MMR was 3 months. During follow-up time, the PFS rate was 94.0% (79/83) and the EFS rate was 77.4% (65/83). The most common non-hematological AEs of dasatinib were edema (32.5%), rash itching (18.1%) and fatigue (13.3%). The common hematological AEs of dasatinib were thrombocytopenia (31.3%), leukopenia (19.3%) and anemia (6.0%). Conclusion Domestic dasatinib was effective and safe as the second-line treatment of CML-CP patients and it can be used as an option for CML-CP patients.

Objective To investigate the effects of different clipping time of first time using permanent aneurysm clips on common carotid artery wall in rabbitsMethods Sixty healthy male Japanese white rabbits were selected.The first time permanent aneurysm clips were used to clip common carotid artery for 30 min or 60 min respectively according to the random number method (n=30 in each group).Thirty segments of common carotid artery specimens clipped by aneurysm clips were collected respectively.Mean-Whitney U test was used to conduct the comparison of histopathological damage grade of vascular wall.Results The aneurysm clips were use to clip 30 min and 60 min caused vascular wall injury could observe the middle elastic plastic plate deformation and endothelial denudation.The vascular walls in the clipping 60 min group had local necrosis with inflammatory response,and even rupture of vascular wall.There were significant differences in overall damage degree of vascular wall (U=324.00,P=0.045) and severe injury rate (0%[0/30] vs.20.0%[6/30],P=0.031) between the clipping 30 min group and the clipping 60 min group (all P<0.05).Conclusion The vascular wall injury of using disposable permanent aneurysm clips for clipping 60 min was more severe than 30 min.Attention should be paid to shortening the time of carotid artery occlusion in operation.

Objective To explore the effect of moderate hypothermia (MH) in liver ischemiareperfusion (IR) injury.Methods Male BALB/c mice (8 weeks old,n =15) were randomly divided into three groups:IR group:five mice subjected to 70％ hepatic IR (hepatic vascular triad above the bifurcation occlusion for 35 min before 24 h reperfusion) in normal temperature condition (37 ±0.5 ℃);MH + IR group:five mice were treated with MH (32 ±0.5 ℃) for 2 h before 70％ hepatic IR was performed;sham group:the other five mice were subjected to laparotomy and liver manipulations without vascular occlusion.AST and ALT in plasma were detected in all mice,and the morphological changes,cell apoptosis and the cold-inducible RNA-binding protein (CIRP) expression after MH in liver tissues were detected.Results Compared with IR group,the ALT and AST levels in MH + IR group were significantly decreased.In IR group,the liver morphology deteriorated with more severe hydropic degeneration and more cell apoptosis.In MH + IR group,the expression of CIRP began to increase after MH preconditioning.Conclusion MH preconditioning could protect against the liver ischemia-reperfusion injury.

Retinoid X receptor α (RXRα) and its N-terminally truncated version tRXRα play important roles in tumorigenesis, while some RXRα ligands possess potent anti-cancer activities by targeting and modulating the tumorigenic effects of RXRα and tRXRα. Here we describe NSC-640358 (N-6), a thiazolyl-pyrazole derived compound, acts as a selective RXRα ligand to promote TNFα-mediated apoptosis of cancer cell. N-6 binds to RXRα and inhibits the transactivation of RXRα homodimer and RXRα/TR3 heterodimer. Using mutational analysis and computational study, we determine that Arg316 in RXRα, essential for 9-cis-retinoic acid binding and activating RXRα transactivation, is not required for antagonist effects of N-6, whereas Trp305 and Phe313 are crucial for N-6 binding to RXRα by forming extra π-π stacking interactions with N-6, indicating a distinct RXRα binding mode of N-6. N-6 inhibits TR3-stimulated transactivation of Gal4-DBD-RXRα-LBD by binding to the ligand binding pocket of RXRα-LBD, suggesting a strategy to regulate TR3 activity indirectly by using small molecules to target its interacting partner RXRα. For its physiological activities, we show that N-6 strongly inhibits tumor necrosis factor α (TNFα)-induced AKT activation and stimulates TNFα-mediated apoptosis in cancer cells in an RXRα/tRXRα dependent manner. The inhibition of TNFα-induced tRXRα/p85α complex formation by N-6 implies that N-6 targets tRXRα to inhibit TNFα-induced AKT activation and to induce cancer cell apoptosis. Together, our data illustrate a new RXRα ligand with a unique RXRα binding mode and the abilities to regulate TR3 activity indirectly and to induce TNFα-mediated cancer cell apoptosis by targeting RXRα/tRXRα.
Apoptosis ; drug effects ; Cell Line, Tumor ; Enzyme Activation ; drug effects ; Humans ; Ligands ; Molecular Docking Simulation ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; genetics ; metabolism ; Oximes ; metabolism ; pharmacology ; Protein Conformation ; Proto-Oncogene Proteins c-akt ; metabolism ; Pyrazoles ; metabolism ; pharmacology ; Retinoid X Receptor alpha ; chemistry ; genetics ; metabolism ; Thiazoles ; metabolism ; pharmacology ; Transcription, Genetic ; drug effects ; Transcriptional Activation ; drug effects ; Tumor Necrosis Factor-alpha ; metabolism

ObjectiveTo improve the long term outcomes of the surgery for Stafford type A aorticdissection, we performed ascending aorta and total aortic arch replacement combined with transaorticstented graft implantation into the descending aorta for acute type A aortic dissection.MethodsFrom May 2005 to February 2011,36 consecutive patients with acute Stanford type A aorticdissection underwent this procedure.Right axillary artery cannulation was routinely used forcardiopulmonary bypass and selected cerebral perfusion.The stented elephant trunk was implanted through the aortic arch under hypothermic circulatory arrest.The stented elephant trunk was a 10 cm long selfexpandable graft.34 patients were followed up for 2 ～36 months.ResultsCardiopulmonary bypass time was (160 ± 31)min, average cross clamp time was (101 ±26)min, and average selective cerebral perfusion and lower body arrest time was (31 ± 16)min.The in-hospital mortality was 5.5％ (2/36).One patient died of multi-organ failure postoperatively and another died of cerebral infarction 9 day after surgery.No one suffered from spinal cord injury perioperatively.There was no late death during follow up.ConclusionsAscendingaorta and total aortic arch replacement combined with transaortic stented graft implantation into the descending aorta is an effective way in closing the residual false lumen of the descending aorta and might contribute to better long term outcomes of type A aortic dissection.