OBJECTIVES: To investigate the effect of avitinib for suppressing NLRP3 inflammasome activation and alleviating septic shock and explore the underlying mechanism. METHODS: Mouse bone marrow-derived macrophages (BMDM), human monocytic leukemia cell line THP-1, and peripheral blood mononuclear cells (PBMC) isolated from healthy volunteers were pre-treated with avitinib, followed by activation of the canonical NLRP3 inflammasome using agonists including nigericin, monosodium urate (MSU) crystals, or adenosine triphosphate (ATP). Non-canonical NLRP3 inflammasome activation was induced via intracellular transfection of lipopolysaccharide (LPS). Western blotting was used to detect the secretory protein markers of NLRP3 inflammasome activation and assess pyroptosis, and the levels of inflammatory cytokines in cell culture supernatant were determined with ELISA. In a mouse model of LPS-induced septic shock, the effect of avitinib treatment on the levels of inflammatory cytokines in serum and peritoneal lavage fluid were examined with ELISA, and survival curves of the mice were plotted using the Kaplan-Meier method. RESULTS: Avitinib significantly inhibited NLRP3 inflammasome activation in multiple cell types, and dose-dependently reduced IL-1β secretion and caspase-1 cleavage while suppressing GSDMD-mediated pyroptosis without obviously affecting IL-6 or TNF-α levels. In the mouse models of LPS-induced septic shock, avitinib significantly lowered IL-1β levels in serum and peritoneal fluid and extended survival time of the mice. CONCLUSIONS Avitinib suppresses NLRP3 inflammasome activation and alleviates septic shock in mice.
Animals ; Shock, Septic/metabolism* ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Inflammasomes/drug effects* ; Humans ; Macrophages/metabolism* ; Interleukin-1beta/metabolism* ; Lipopolysaccharides

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

Objective:To explore the mediating role of self-perceptions of aging between frailty and cognitive function in community-dwelling older adults.Methods:From February to July 2021, a total of 528 elderly people in Xinxiang community were investigated with the frailty phenotype, the brief self-perceptions ageing questionnaire and the Mini-mental state examination(MMSE) scale.According to the MMSE total score and education level, the subjects were divided into cognitive impairment group (illiteracy≤17, primary school≤20, junior high school and above≤24, n=74) and cognitive normal group( n=454). SPSS 25.0 software was used for common method deviation test, descriptive statistics and correlation analysis, while AMOS 24.0 software was used to build structural equation model and Bootstrap method was used for intermediary effect test. Results:(1)The prevalence of cognitive impairment among the elderly in the community was 14.1%. The differences between the cognitively normal group and cognitively impaired group were statistically significant in terms of age, education, number of chronic diseases suffered and depression ( χ2=59.21, 6.53, 9.84, 25.47, all P<0.05). The differences were statistically significant in terms of frailty( χ2=75.65, P<0.001) and self-perceptions of aging ( t=77.67, P<0.001). (2)Self-perceptions of aging in the cognitively impaired group (47.39±8.66) was higher than that in the cognitively normal group (38.22±8.24) ( t=77.67, P<0.001) .Frailty score in cognitively impaired group (2.00 (1.00, 3.00)) was higher than that in the cognitively normal group (0.00 (0.00, 1.00))( Z=-8.63, P<0.001) . (3)Frailty was negatively correlated with cognitive function ( r=-0.492, P<0.01), and positively correlated with self-perceptions of aging ( r=0.540, P<0.01). Self-perceptions of aging was negatively correlated with cognitive function ( r=-0.541, P<0.01) . After controlling the influencing factors such as age, education level, chronic diseases and depression, the correlation was still significant (all P<0.01) . (4) Self-perceptions of aging played a partially mediating role in the relationship between frailty and cognitive function, the mediating effect accounted for 58.5% of the total effect. Conclusion:Frailty and self-perceptions of aging have a significant impact on the cognitive function of the elderly in the community, and self-perceptions of aging plays a partial intermediary role between the frailty and cognitive function of the elderly in the community.

The dynamic changes of cognitive function has been paid more and more attention by foreign scholars.Dynamic assessment based on ecological momentary assessment(EMA)can capture subtle changes in cognitive function and provide more comprehensive information for early identification and timely intervention of people with cognitive impairment, which is an effective supplement to traditional cognitive assessment.This paper reviewed the concept of ecological momentary assessment, its advantages in cognitive assessment, its feasibility and effectiveness, and its application status in the evaluation of cognitive function in the elderly, so as to provide a reference for making ecological assessment of the cognitive function for older adults that is in line with China's national conditions.

Objective:To analyze and summarize the application and significance of the computer-assisted surgery system in precision surgery of mediastinal tumors in children.Methods:The clinical data of 54 children that underwent mediastinal tumor resection surgery in the Affiliated Hospital of Qingdao University from August 2008 to November 2021 were collected.According to whether the Hisense CAS computer-assisted surgery system was used before the operation, the patients were divided into three-dimensional (3D) reconstruction group (29 cases, 53.70%) and two-dimensional (2D) CT group (25 cases, 46.30%). The surgical indicators, postoperative hospital stay, and the incidence of surgical complications were compared between the two groups.The t-test, Mann- Whitney U test, χ2 test or Fisher′ s exact test were carried out for statistical analysis.Simulated surgery and actual surgery were compared for both 3D reconstruction and 2D CT groups. Results:There were no significant differences in gender, age, height, weight, maximum tumor diameter and tumor location between the 3D reconstruction group and 2D CT group (all P>0.05). The operation time of the 3D reconstruction group was [(125.14±41.37) min] was shorter than that of the 2D CT group [(149.24±44.53) min] ( P=0.044). The intraoperative blood loss in the 3D reconstruction group [15.00(13.50, 25.00) mL] was less than that in the 2D CT group [36.00(30.00, 75.00) mL] ( P<0.001). In addition, the indwelling time the closed thoracic drainage tube [4.00 (3.00, 5.50) d] and postoperative hospitalization days [(8.83±3.39) d] in the 3D reconstruction group were shorter than those in the 2D CT group [7.00(5.00, 11.50) d, (11.00±4.10) d] ( P=0.001, 0.038). No significant difference in postoperative complication rates was found between the 3D reconstruction group and 2D CT group ( P>0.05). The simulated operation was consistent with the actual operation in the 3D reconstruction group. Conclusions:3D reconstruction by the computer-assisted surgery system can truly reveal the anatomical relationship between tumors and surrounding organs and blood vessels, and improve the accuracy and safety of surgical resection of mediastinal tumors in children.

Objective:To look into the security of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) using rabbit anti-human thymocyte immunoglobulin (rATG) .Methods:Twenty-seven patients who used rATG in the first and second allo-HSCT at the Institute of Hematology, Peking University were enrolled in the study. Experienced toxicities associated with the conditioning protocol within 10 days (-5 d to +3 d) following the beginning of the rATG application, including fever, diarrhea, arrhythmia, reduced blood pressure, liver damage, seizures, and other problems.Results:The overall incidence of conditioning regimen early adverse reactions during the first transplantation and the second allo-HSCT conditioning regimen was 96.3% and 77.8% ( P=0.043) . Fever rates were 81.5% and 63.0% ( P=0.129) , diarrhea rates were 59.3% and 25.9% ( P=0.013) , liver damage rates were 22.2% and 25.9% ( P=0.75) , and the rates of other events (cardiac arrhythmia, low blood pressure, and epilepsy) were 3.7% and 18.5% ( P=0.083) . Adverse reactions that occurred during both the first and second course of rATG applications have been improved with symptomatic treatment, and no treatment interruptions occurred. Conclusion:Reusing rATG in a second transplant was risk-free and did not result in higher early toxicities.

The ways of treating diabetes mellitus with depression by using Traditional Chinese Medicine (TCM) include internal treatment, external treatment and combining internal and externalmethod, mostly based on the viscera syndrome differentiation and Qi blood phlegm stasis syndrome differentiation, focusing on soothing the liver qi and regulating, liver and spleen. The internal treatments mainly include self-made prescriptions or classic prescriptions, such as Jiawei-Xiaoyao Powder, Danggui-Shaoyao Decoction, Wendan Decoction, etc; External treatments mainly include common acupuncture, ear acupuncture, scalp acupuncture, abdominal acupuncture, acupoint application, etc. The above treatments can improve the symptoms of depression, and control the blood glucose level.

Objective To detect the expression levels of miR-7-5p and POLE4 in non-small cell lung cancer cells and their effect on cells proliferation, migration and invasion. Methods qRT-PCR was used to detect the relative expression levels of miR-7-5p and POLE4 mRNA in NSCLC tissues, adjacent tissues, tumor cells and human normal bronchial epithelial cells. Luciferase reporter gene was used for analyzing of the targeting relation between POLE4 and miR-7-5p in NSCLC cells. si-NC and si-POLE4 were transfected into SPC-A-1 cells as the si-NC group and si-POLE4 group, and the control group was set at the same time. MTT method, scratch test and Transwell test were used to detect cell proliferation, migration and invasion. Results The expression levels of miR-7-5p in NSCLC tissues and cells were reduced, and the expression levels of POLE4 were increased. miR-7-5p could target to combine with POLE4. After 72 hours of culture, the OD value in si-POLE4 group was significantly lower than those in the control group and si-NC group (P < 0.05). The migration rate and the number of transmembrane cells in the si-POLE4 group cultured for 48 hours were lower than those in the control group and the si-NC group (P < 0.05). Conclusion miR-7-5p may inhibit the proliferation, migration and invasion of non-small cell lung cancer cells by targeting POLE4.

Objective:To explore the current status and influencing factors of knowledge, attitude and practice of drug clinical trials among ovarian cancer patients.Methods:We selected 268 ovarian cancer patients from a ClassⅢ Grade A cancer hospital in Zhejiang Province from January to December 2018 by convenience sampling. The mature Knowledge, Attitude and Practice Questionnaire was used to investigate the current status of knowledge, attitude and practice in drug clinical trials. According to the survey results, patients were divided into the high cognition group and the low cognition group. Univariate and multivariate Logistic regression were used to analyze the influencing factors.Results:Among 268 patients, the scores of knowledge, attitude and practice were (31.67±3.59) , (16.35±2.71) and (10.56±1.43) respectively. Univariate analysis showed that there were statistical differences in knowledge, attitude and practice among patients with different education levels, residence places, medical insurance, occupation, fertility, medical attention, medical relatives and friends, and annual income ( P<0.05) . Multivariate analysis indicated that the influencing factors of knowledge, attitude and practice in drug clinical trials of ovarian patients included education levels, medical insurance, medication attention and annual income. Conclusions:Patients with ovarian cancer are not optimistic about the level of knowledge, attitude and practice in drug clinical trials, which clinical nurses should pay great attention to. We should carry out individualized health education for patients with different backgrounds and characteristics.