Objective To investigate the effects of indirubatin derivative E804 on proliferation and migration of non-small cell lung cancer(NSCLC)A549 cells,and to elucidate the possible mechanism of Nrf2-HO-1/GPX4 pathway.Methods Lung cancer A549 cells were used as the cell model.The proliferation and migration of differ-ent specific inhibitors(Nec-1,CQ,Z-VAD,DFO,Fer-1 and Lip-1)in 0,10 μmol/L E804 and 10 μmol/L E804+groups were observed by MTT and cell scratch assay.The contents of reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescence probe method,the contents of Fe2+were detected by colorimetric method,the contents of reduced glutathione(GSH)were detected by spectrophotometry,and the contents of malondialdehyde(MDA)were detected by micromethod.The expression levels of SLC7A11,Transferrin,GPX4,SLC40A1,Nrf2 and HO-1 were detected by Western blot in cells of 0,2.5,5 and 10 μmol/L E804 groups.Results Compared with the control group(0 μmol/L E804),2.5,5 and 10 μmol/L E804 significantly increased intracellular ROS,Fe2+and MDA levels,and decreased intracellular GSH content(P＜0.01).Meanwhile,the expression levels of SLC7A11,GPX4,SLC40A1,Nrf2 and HO-1 significantly decreased(P＜0.01),and the expression level of Transferrin increased(P＜0.05).Compared with the 10 μmol/L E804 group alone,the apoptosis inhibitor(Z-VAD)group and the ferroptosis inhibitor(DFO,Fer-1 and Lip-1)group could significantly reverse the inhibition of proliferation and migration of A549 cells by 10 μmol/L E804(P＜0.01).Conclution E804 can induce ferrop-tosis and inhibit the proliferation and migration of A549 cells,which may be related to the inhibition of Nrf2-HO-1/GPX4 pathway.

Objective To investigate the effects of modified Yupingfeng Powder medicated serum on the inflammatory response of rat lung epithelial type Ⅱ cells RLE-6TN;To explore the mechanism based on nuclear factor(NF)-κB signaling pathway.Methods The inflammatory reaction of RLE-6TN cells was induced by lipopolysaccharide,and the cells were divided into control group,model group,dexamethasone medicated serum group,and 5%,10%and 20%TCM serum group,and the cell model was intervened with different serum.After 24 hours,the content of lactate dehydrogenase(LDH)in cell supernatant was detected by kit,and the content of reactive oxygen species(ROS)in cells were detected by fluorescence staining,Hoechst/PI double staining was used to observe cell apoptosis,and ELISA was used to detect tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β contents in cell supernatant,RT-qPCR was used to detect Toll like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and NF-κB inhibitory protein α(IκBα)mRNA expression,Western blot was used to detect protein expressions of TLR4,MyD88,NF-κBp65 and IκBα.Results Compared with the control group,the contents of LDH,TNF-α,IL-6,IL-1β in RLE-6TN cell supernatant and ROS content in cells of model group significantly increased(P<0.01),the cell apoptosis rate significantly increased(P<0.01),the expressions of TLR4 and MyD88 mRNA and protein significantly increased(P<0.01),the expression of IκBα mRNA significantly decreased(P<0.01),and the ratio of p-NF-κBp65/NF-κBp65 and p-IκBα/IκBα significantly increased(P<0.01).Compared with the model group,the content of LDH,TNF-α,IL-6,IL-1 in RLE-6TN cell supernatant and ROS content in cells significant decreased in the 20%TCM serum group and dexamethasone medicated serum group(P<0.01),the cell apoptosis rate significantly decreased(P<0.01),the expressions of TLR4 and MyD88 mRNA and protein significantly decreased(P<0.05,P<0.01),the expression of IκBα mRNA significantly increased(P<0.01),and the ratio of p-NF-κBp65/NF-κBp65 and p-IκBα/IκBα significantly decreased(P<0.05,P<0.01).Conclusion Modified Yupingfeng Powder medicated serum can reduce RLE-6TN cells inflammatory reaction,and its mechanism may be related to the regulation of NF-κB signaling pathway.

Rett syndrome(RTT) is a severe and rare progressive developmental disorder, as a complex multisystem disease with a variety of clinical manifestations ranging from neurological to non-neurological symptoms.This article reviews the evidence-based update of RTT-related peripheral system comorbidities, so as to improve the understanding of RTT multisystem comorbidities and provide guidance for the multidisciplinary management of RTT patients.

Objective:To investigate the effect of Fu-Fang-Yu-Jie(FFYJ)granules on LPS-induced inflammation model in bone marrow-derived macrophages(BMDM)and its intervention of FFYJ on nucleotide-bound oligomeric domain-like receptor protein 3(NLRP3)inflammatory signaling pathway in macrophages.Methods:Primary cells were extracted and isolated from the leg bone mar-row of C57BL/6 mice and BMDM macrophages were obtained after 7 days of induction with 50 ng/ml M-CSF.Groups included control group(Control),model group(LPS+ATP),FFYJ low dose group(FFYJ 50 μg/ml),FFYJ medium dose group(FFYJ 100 μg/ml),FFYJ high dose group(FFYJ 200 μg/ml)and positive drug dexamethasone group(DEX).BMDM in FFYJ treatment group and posi-tive drug group were pretreated for 1 hour before modeling.Lactate dehydrogenase(LDH)release assay was used to detect the level of LDH in the supernatant of each group of cells;ELISA was used to detect the level of inflammatory factors TNF-α,IL-6 and IL-1β in the supernatant of each group of cells;qRT-PCR was used to detect the levels of TNF-α,IL-6 and IL-1β in each group of cells;protein levels of NF-κB,p-NF-κB,NLRP3,Caspase-1 p45,Caspase-1 p20 and GSDMD-N in each group of cells were detected by Western blot;inverted fluorescence microscope was used to observe the cell pyroptosis of each group after Hoechst-PI staining.Results:Compared with control group,the levels of LDH,TNF-α,IL-6 and IL-1β in the supernatant of the model group were signifi-cantly higher(P<0.000 1);the mRNA levels of TNF-α,IL-6 and IL-1β in the model group were significantly higher(P<0.000 1);the protein levels of p-NF-κB,NLRP3,Caspase-1 p20 and GSDMD-N were significantly higher(P<0.05);and the number of PI-posi-tive cells was significantly higher(P<0.05).Compared with the model group,FFYJ and DEX significantly reduced the levels of LDH,TNF-α,IL-6 and IL-1β in the supernatant of BMDMs(P<0.05);down-regulated the mRNA levels of TNF-α,IL-6 and IL-1β in the cells(P<0.05);and inhibited the expressions of p-NF-κB,NLRP3,Caspase-1 p20 and GSDMD-N protein expressions(P<0.05);and significantly reduced the number of PI-positive cells(P<0.05).Conclusion:FFYJ exerts anti-inflammatory effects by inhibiting NLRP3 inflammasome activation in BMDM macrophages.

Aim To explore the effect of succinate/G protein coupled receptor 91(GPR91)on mitochondria in vascular endothelial cells and its regulatory mechanisms.Methods Transmission electron microscopy,Western blot and fluorescence microscopy were used to observe the effects of succinate analogues diethyl succinate(DS),GPR91 agonist and inhibitor on the mitochondrial morphology,cristae,cristate homeostasis related proteins reactive oxygen species(ROS)content,Ca2+concentration,mitochondrial membrane potential,the expression of dihydroorotate dehydrogenase(DHODH)and oxidized coenzyme Q10(CoQlO).Fluorescence probes were used to observe the effect of DHODH inhib-itor and CoQ10 on ROS level and Ca2+concentration of endothelial cells.Results After DS treatment,the mitochon-dria showed pyknosis and mitochondrial volume significantly decreased,electron density of the mitochondrial membrane in-creased,and the number of cristae decreased in endothelial cells;the expression of cristae homeostasis related proteins MIC60 decreased by 23％,while cellular ROS level and Ca2+concentration increased;mitochondrial membrane potential decreased(P＜0.05 or P＜0.01).After GPR91 agonist treatment,the expression of cristae homeostasis related proteins MIC60 decreased by 31％,meanwhile,cellular ROS level increased by 27％and Ca2+concentration increased by 36％;mitochondrial membrane potential decreased(P＜0.05 or P＜0.01).After GPR91 inhibitor treatment,the expression of cristae homeostasis related proteins MIC60 increased by 22％and ATP5I increased by 40％;the levels of ROS decreased by 41％and Ca2+concentration decreased by 67％;and the mitochondrial membrane potential was restored to normal(P＜0.05 or P＜0.01).After DS treatment,the expression of DHODH decreased by 43％and the level of oxidized CoQ10 in-creased by 120％(P＜0.05 or P＜0.01).After GPR91 agonist treatment,the expression of DHODH decreased by 22％and the level of oxidized CoQ10 increased by 36％(P＜0.05 or P＜0.01).After GPR91 inhibitor treatment,the expres-sion of DHODH increased by 40％and the level of oxidized CoQ10 decreased by 39％(P＜0.01).After DHODH inhibi-tor treatment,the ROS level increased by 20％and Ca2+concentration increased by 28％,and mitochondrial membrane po-tential reduced at same time(P＜0.05 or P＜0.01).Exogenous oxidized CoQ10 inhibited ROS production by 30％and decreased Ca2+concentration by 20％(P＜0.05 or P＜0.01).Conclusion Succinate/GPR91 promotes mitochondrial damage in endothelial cells,and its mechanism may relate to down-regulating the expression of DHODH and inhibiting the reduction of CoQ10 by affecting the mitochondrial cristae homeostasis.

Background::Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods::We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).Results::Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence. Conclusions::Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Objective:To construct a Nurses′ Growth Mindset Assessment Scale, and to test the reliability and validity of the scale, so as to provide an assessment tool for accurately assessing nurses′growth mindset ability.Methods:From June to October 2021, taking the growth mindset theory as the research framework, at the same time, the related researches on the growth mindset were reviewed and analyzed, the item pool of the scale was comprehensively constructed, and the formal version of the scale was formed through factor analysis, Delphi method and other research methods. A total of 578 nurses from Qilu Hospital of Shandong University and Shandong Provincial Hospital were investigated to test the reliability and validity of the scale by simple sampling method.Results:The constructed formal scale consisted of 31 items and 3 dimensions. The 3 dimensions were self-awareness, attitude towards challenges and resilience to setbacks. The cumulative variance contribution rate was 65.954%. The Cronbach′s alpha coefficient was 0.926, and the Spearman-Brown split-half reliability coefficient was 0.750.Conclusions:Nurses′ Growth Mindset Assessment Scale has good reliability and validity, and can be used to evaluate the nurses′ growth mindset ability.

Objective:To explore the differences on clinical characteristics, concomitant diseases and treatment status between psoriasis and psoriatic arthritis (PsA), and provide clues for the early diagnosis and treatment of PsA.Methods:Data were collected by in-person interview of 225 patients with psoriasis and 299 patients with PSA who visited the department of rheumatology and Immunology and Department of Dermatology in People′s Hospital of Peking University from November 2020 to May 2021. After informed consent, the questionnaire was completed on site. The differences of clinical characteristics, concomitant diseases, mental health evaluation and treatment status between patients with arthritis (PsA) and patients with psoriasiswere analyzed and compared. Enumeration data were described by frequency. Chi square test was used to compare categorical variables. Multivariate Logistic regression analysis was used to determine the independent risk factors. P value of less than 0.05 was considered statistically significant. Results:Dactylitis [ OR(95% CI)=8.439(4.677,15.226), P<0.001], hip pain [ OR(95% CI)=3.442(1.829,6.480), P<0.001], heel pain [ OR(95% CI)=2.621(1.652,4.157), P<0.001] and low back pain [ OR(95% CI)=1.924(1.156,3.203), P=0.012] may be closely related to the progression of PsA ( P<0.05). The three most common concomitant diseases of patients with PsA and psoriasis both were overweight [43.1%(129/299)、29.3%(66/225)], fatty liver [(28.4%(85/299)、23.1%(52/225)]and hypertension[24.1%(72/299、13.3%(30/225)]. The proportion of osteoporosis in PsA group at the age of 30-39 and 40-49 years old was significantly higher than those in psoriasis group (30-39 years old:12.5%(10/80) vs 1.5%(1/65), χ2=6.14, P=0.013; 40~49 years old: 19.2%(15/78) vs 2.0%(1/51), χ2=8.46, P=0.004]. The proportion of hypertension in PsA group was also higher than that in psoriasis group at the age of 40~49 years old[7.0% (21/78) vs 2.7%(6/51), χ2=4.99, P=0.026)]. And the proportion of fatty liver in PsA group was also higher than that in psoriasis group at the age ≥60 years old [(46.0%(23/50) vs 29.1(7/24), χ2=4.99, P=0.025)]. Among 299 PsA patients, 47.1%(141/299) had anxiety tendency, 45.2%(135/299) had sleep disorder and 41.8%(125/299) had depression tendency. Among 225 psoriasis patients, 44.4%(100/225) had anxiety tendency, 40%(90/225) had sleep disorder and 36.9%(83/225) had depression tendency, there was no significant difference in above-mentioned situations between the PsA and psoriasis patients ( P>0.05). Conclusion:More attention should be paid to the management of concomitant diseases and psychological intervention in patients with PsA. When psoriasis patients occur with heel pain, dactylitis, low back pain and hip pain, the risk of development into PsA should be considered.

Perception ; Pupil ; Social Interaction