Objective:To explore the effects of imperatorin(IMP)on airway remodeling in the bronchial asthma mice,and to elucidate the possible mechanisms.Methods:Forty SFP male BALB/c mice were randomly divided into control group,model group,low dose of IMP group(IMP-L group),high dose of IMP group(IMP-H group)and dexamethasone group,with 8 mice in each group.Except for contol group,the mice in the other groups were injected with an ovalbumin(OVA)suspension intraperitoneally to induce the asthma models.After one week,the daily asthma symptoms of the mice were observed and scored.After 8 weeks,the enhanced pause(Penh)values of the mice in various groups were detected to evaluate the airway reactivities.The percentages of eosinophils in the bronchoalveolar lavage fluid(BALF)of the mice in various groups were detected by flow cytometry.The levels of serum IgE,interleukin interferon-gamma(IL)-13,IL-5,IL-4 and interferon-gamma(IFN-γ)in BALF of the mice in various groups were measured by enzyme-linked immunosorbent assay(ELISA)method.HE,PAS and Masson staining were applied to observe the pathomorphology,the number of goblet cells and collagen deposition of the lung tissue of the mice in various groups.Immunohisto chemistry method was applied to detect the expressions of α-smooth muscle actin(α-SMA)and mouse mammary tumor virus(MMTV)wingless type MMTV intergration site family member 5A(Wnt5A)proteins in lung tissue of the mice in various groups.The expression levels of Wnt5A,cellular myelocytomatosis oncogene(c-Myc),β-catenin and α-SMA in lung tissue of the mice in various groups were detected by Western blotting method.The expression levels of α-SMA protein in lung tissue of the mice in various groups were detected by immunofluorescence method.Results:Compared with control group,the score of asthma symptoms of the mice in model group was increased(P<0.01);the Penh value was significantly increased(P<0.01);the serum IgE levels and the levels of IL-13,IL-5,IL-4 in BALF,as well as the percentage of eosinophils(EOS)in BALF were significantly increased(P<0.05 or P<0.01),and the level of IFN-γ was reduced(P<0.05);the expression levels of α-SMA and Wnt5A proteins in lung tissue were markedly increased(P<0.01);the expression levels of proteins associated with the Wnt/β-catenin signaling pathway in the lung tissue were significantly increased(P<0.01);the immofluorescence method results showed the expression level of α-SMA protein in lung tissue was significantly increased(P<0.01).Compared with model group,the scores of asthma symphtoms of the mice in IMP-L group,IMP-H group,and dexamethasone group were decereased(P<0.01),and the Penh values of the mice in IMP-H group were decreased(P<0.05);the serum IgE levels and the levels of IL-13,IL-5,IL-4 in BALF,as well as the percentages of EOS in BALF of the mice in IMP-L group,IMP-H group,and dexamethasone group were decreased(P<0.05 or P<0.01),and the levels of IFN-γ were increased(P<0.05);the expression levels α-SMA and Wnt5A proteins in lung tissue were decreased(P<0.05 or P<0.01);the expression levels of proteins related to the Wnt/β-catenin signaling pathway in the lung tissue were decreased(P<0.05 or P<0.01);the immunofluorescence method results showed that expression levels of the α-SMA protein in the lung tissue were reduced(P<0.05 or P<0.01).Conclusion:IMP has an improving effect on airway remodeling in the asthmatic mice and can inhibit the expression levels of Wnt/β-catenin pathway-related proteins.

Objective:To explore the mediating role of anxiety/depression emotions between sleep quality and cognitive function in adolescents with attention deficit hyperactivity disorder(ADHD).Methods:A cross-sectional study design was adopted, involving 204 ADHD adolescents aged 12-18 who were treated between January 2021 and November 2023.All participants were assessed using the Pittsburgh sleep quality index(PSQI)for sleep quality, the self-rating anxiety scale(SAS) and self-rating depression scale(SDS) for emotional states.Four cognitive information processing processes(planning, simultaneous processing, attention, and successive processing) were evaluated by the Das-Naglieri cognitive assessment system(DN: CAS). Data were statistically analyzed using SPSS 23.0 and Zstats software, including descriptive statistics, Spearman correlation analysis, and mediation effect analysis.Results:Among ADHD adolescents, girls exhibited significantly higher rates of sleep disturbance(71.59%(63/88) vs 43.97%(51/116), χ2=15.490, P<0.001)and depressive emotion(47.73%(42/88) vs 33.62%(39/116), χ2=4.159, P=0.041)compared to boys.High school students had a significantly higher rate of sleep disturbance than middle school students(64.84%(59/91) vs 48.67%(55/113), χ2=5.341, P=0.021). Spearman correlation analysis revealed that sleep quality(8.00(6.00, 11.00)) in ADHD adolescents was significantly and positively correlated with anxiety(38.00(32.00, 46.00); r=0.504, P<0.01) and depression(46.00(39.00, 54.00); r=0.427, P<0.01). And sleep quality, anxiety and depression were significantly and negatively correlated with the DN: CAS total score(109.5(91.25, 123.75); r=-0.158--0.237, P<0.05). Mediation analysis indicated that anxiety mediated the relationship between sleep quality and attention function(indirect effect β=-0.159, Bootstrap 95% CI=-0.287--0.046). Conclusion:ADHD adolescents exhibit complex interactions among sleep quality, emotion, and cognitive function, sleep quality indirectly affects attention function through anxiety.

Objective:To explore the mediating role of anxiety/depression emotions between sleep quality and cognitive function in adolescents with attention deficit hyperactivity disorder(ADHD).Methods:A cross-sectional study design was adopted, involving 204 ADHD adolescents aged 12-18 who were treated between January 2021 and November 2023.All participants were assessed using the Pittsburgh sleep quality index(PSQI)for sleep quality, the self-rating anxiety scale(SAS) and self-rating depression scale(SDS) for emotional states.Four cognitive information processing processes(planning, simultaneous processing, attention, and successive processing) were evaluated by the Das-Naglieri cognitive assessment system(DN: CAS). Data were statistically analyzed using SPSS 23.0 and Zstats software, including descriptive statistics, Spearman correlation analysis, and mediation effect analysis.Results:Among ADHD adolescents, girls exhibited significantly higher rates of sleep disturbance(71.59%(63/88) vs 43.97%(51/116), χ2=15.490, P<0.001)and depressive emotion(47.73%(42/88) vs 33.62%(39/116), χ2=4.159, P=0.041)compared to boys.High school students had a significantly higher rate of sleep disturbance than middle school students(64.84%(59/91) vs 48.67%(55/113), χ2=5.341, P=0.021). Spearman correlation analysis revealed that sleep quality(8.00(6.00, 11.00)) in ADHD adolescents was significantly and positively correlated with anxiety(38.00(32.00, 46.00); r=0.504, P<0.01) and depression(46.00(39.00, 54.00); r=0.427, P<0.01). And sleep quality, anxiety and depression were significantly and negatively correlated with the DN: CAS total score(109.5(91.25, 123.75); r=-0.158--0.237, P<0.05). Mediation analysis indicated that anxiety mediated the relationship between sleep quality and attention function(indirect effect β=-0.159, Bootstrap 95% CI=-0.287--0.046). Conclusion:ADHD adolescents exhibit complex interactions among sleep quality, emotion, and cognitive function, sleep quality indirectly affects attention function through anxiety.

Objective:To observe the clinical efficacy of exercise-based acupuncture in treating ischemic stroke and its effects in improving the patient's motor function and daily living ability. Methods:A total of 106 patients with motor dysfunction due to cerebral infarction were randomized into a trial group and a control group,each consisting of 53 cases.Both groups received conventional rehabilitation;in addition,the control group was given point-toward-point acupuncture at scalp points,and the trial group was offered exercise-based acupuncture,3 times weekly for 4 consecutive weeks.Before treatment,after 2 and 4 weeks of treatment,and at the 2-month follow-up,the Fugl-Meyer assessment(FMA)scale,Lovett scale for muscle strength,modified Ashworth scale(MAS),and activities of daily living(ADL)scale were used to assess the patient's motor function,muscle strength,muscle tension,and daily living ability. Results:After treatment,both groups gained improvements in motor function and daily living ability;after 4-week treatment and at the 2-month follow-up,the trial group had higher FMA and ADL scores than the control group(P<0.05).The MAS score decreased after treatment in both groups;after 2 and 4 weeks of treatment and at the 2-month follow-up,the MAS score was lower in the trial group than in the control group(P<0.05).After the intervention,the Lovett score increased in both groups;after 4 weeks of treatment,the Lovett score was higher in the trial group than in the control group(P<0.05). Conclusion:Based on routine rehabilitation,exercise-based acupuncture and scalp point-toward-point acupuncture both can improve the motor function and daily living ability in ischemic stroke patients;exercise-based acupuncture performs better than scalp point-toward-point acupuncture.

Ferroptosis is defined as an iron-dependent, non-apoptotic cell death pathway, with specific morphological phenotypes and biochemical changes. There is a growing realization that ferroptosis has significant implications for several neurodegenerative diseases. Even though ferroptosis is different from other forms of programmed death such as apoptosis and autophagic death, they involve a number of common protein molecules. This review focuses on current research on ferroptosis and summarizes the cross-talk among ferroptosis, apoptosis, and autophagy that are implicated in neurodegenerative diseases. We hope that this information provides new ideas for understanding the mechanisms and searching for potential therapeutic approaches and prevention of neurodegenerative diseases.
Apoptosis ; Autophagy ; Cell Death ; Ferroptosis ; Humans ; Neurodegenerative Diseases

Objective:To explore the influence of tomoxetine hydrochloride on the cognitive processing of children with attention deficit hyperactivity disorder (ADHD).Methods:From January 2018 to July 2021, 62 ADHD children who were treated with tomoxetine hydrochloride for the first time for(8±4) weeks were selected as the ADHD group.And 62 healthy children matched with age and sex were selected as the healthy control group.Pre-test and post-test by the Das-Naglieri: Cognitive Assessment System(DN: CAS) were performed to evaluate the cognitive function of all individuals.The differences of cognitive processing in pre-treatment and post-treatment of ADHD group were compared with those in healthy control group.The difference between before and after treatment of ADHD group was also compared.SPSS 26.0 statistical software was adopted for statistical analysis.The scores of ADHD group pre-treatment and post-treatment were compared by paired sample t-test, and the scores of ADHD group pre-treatment and post-treatment were compared with those of healthy control group by independent sample t-test. Results:Compared with healthy control group, there were lower of planning score((18.77±5.92) vs (28.56±5.55)), attention score((22.24±5.93) vs (29.56±6.16)), simultaneous processing ((34.21±7.75) vs (37.61±6.29)), successive processing((30.37±7.12) vs (33.74±5.43)), and the total scores((105.60±21.29) vs (134.84±22.87)) in ADHD group before treatment, and there were significant differences( t=9.49, 6.74, 2.68, 2.96, 7.36, all P<0.05). Compared with healthy control group, there were lower of planning score ((22.13±5.99)s), attention score((25.26±7.11) with significant difference( t=6.20, 3.60, both P<0.05) in ADHD group after treatment.And there was no significant difference in the simultaneous processing test and the successive processing test after treatment compared with the healthy control group(both P>0.05). In ADHD group, the scores of planning, simultaneous processing, attention, successive processing and the total score were significantly higher after treatment than those before treatment and there were significant differences( t=-6.03, -4.13, -4.77, -5.48, -8.59, all P<0.05). (2) Compared with the healthy control group, there were lower of matching number score and other 8 sub-test scales in DN: CAS test in ADHD group before treatment, and the differences were statistically significant (all P<0.05). Meanwhile, there were still lower of matching number score and other 4 sub-test scales in DN: CAS test in ADHD group after treatment, and the differences were statistically significant (all P<0.05). The matching number score and other 10 sub-test scales in DN: CAS test in ADHD group after treatment were all higher than those of before treatment(all P<0.05). Conclusion:The planning, attention, simultaneous processing, successive processing and total cognitive function of ADHD children were significantly improved after treatment with tomoxetine hydrochloride, special for simultaneous processing and successive processing.

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Overexpressing of ATP-binding cassette (ABC) transporters is the essential cause of multidrug resistance (MDR), which is a significant hurdle to the success of chemotherapy in many cancers. Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR. Olmutinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which has been approved in South Korea for advanced EGFR T790M-positive non-small cell lung cancer (NSCLC). Here, we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin (DOX) and rhodamine 123 (Rho 123) in ABC transporter subfamily G member 2 (ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [I]-iodoarylazidoprazosin (IAAP). However, olmutinib neither altered ABCG2 expression at protein and mRNA levels nor blocked EGFR, Her-2 downstream signaling of AKT and ERK. Importantly, olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients.

Objective To explore the influence of Methylphenidate Hydrochloride prolonged-release tablets on the cognitive processing of children with attention deficit hyperactivity disorder (ADHD).Methods Thirty ADHD children and 30 healthy controls were enrolled in this study,and the ADHD subjects were treated with Methylphenidate Hydrochloride prolonged-release tablets for (28 ± 3) days.Pre-test and post-test by the Das-Naglieri:Cognitive Assessment System(DN:CAS) were done to evaluate the cognitive function of all individuals.The differences of cognitive processing in pre-treatment and post-treatment of ADHD group with healthy control group were compared.The difference between before and after treatment of ADHD was also compared.Results Compared with healthy control group,there were lower of planning score [(21.86 ± 4.61) scores vs.(29.33 ± 5.06) scores],attention score [(25.00 ± 4.57) scores vs.(29.83 ± 3.79) scores],and the total scores [(111.93 ± 13.95) scores vs.(127.26 ±15.53) scores] in ADHD group,and there were significant differences (t =-5.976,-4.455,-4.023,all P ＜0.05).The matching number,planned codes,planned connections,expressive attention,number detection and receptive attention scores were also lower in ADHD group,and there were significant differences (t =-4.787,-3.703,-4.991,-2.216,-2.488,-3.219,all P ＜ 0.05).Compared with healthy control group,there were lower of planning score with significant difference [(25.53 ± 4.98) scores vs.(29.33 ± 5.06) scores,t =-2.931,P ＜ 0.05] in ADHD group after treatment,matching number and planned codes were lower with significant difference (t =-2.654,-2.044,all P ＜ 0.05) in ADHD group after treatment.In ADHD group,the scores of planning [(25.53 ± 4.98)scores vs.(21.86 ± 4.61) scores],simultaneous processing [(36.10 ± 7.10) scores vs.(34.13 ± 6.04) scores],attention [(27.90 ± 5.69) scores vs.(25.00 ± 4.57) scores] and the total score [(121.50 ± 16.55) scores vs.(111.93 ± 13.95) scores] were significantly higher after treatment than that before treatment and there were significant differences (t =-5.679,-2.949,-3.869,-5.963,all P ＜ 0.05);matching number,planned codes,planned connections,nonverbal matrices,number detection,receptive attention and word series were significantly higher after treatment than that before treatment,and there were significant differences (t =-2.528,-3.209,-3.890,-2.276,-4.489,-2.208,-2.373,all P ＜ 0.05).Conclusion The Methylphenidate Hydrochloride prolonged-release tablets can improve the function of cognitive processing in children with ADHD,especially in attention.

Objective To explore associations between mental disorders and accidental death. Methods A case-control psychological autopsy study was conducted in Fengning county in Hebei province, Kailu county in Inner Mongolia, Meixian county in Shaanxi province, Chongzhou county in Sichuan province. One hundred and fifty-seven accidental death cases were identified, based on detailed interview and cause of death listed as"accidental death"(International Classification of Diseases 10th edition codes V01-X59),"suicide"(X60-X84) or"mental disorder"(F00-F98). We used 2008 census data for three of the four counties (Fengning county in Hebei Province stopped participating in the study in 2009), to select a multistage stratified random sample of adult community residents as the living controls. Finally, 140 living controls were randomly sampled. For each cases or controls, one family member and one associate (neighbor or friend) were interviewed separately by different interviewers. For each cases, socio-demographic data, quality of life, and psychiatric diagnosis 1 month prior to accidental death (or 1 month prior to interview for the living controls), and life events and social support 12 months prior to the death or interview (for controls) were evaluated during the interview. Axis Ⅰ mental disorders, Axis Ⅱ personality disorders were diagnosed based on Structured Clinical Interviews for DSM-Ⅳ-TR Axis Ⅰ Disorders (SCID-I) and Axis Ⅱ Personality Disorders (SCID-Ⅱ). Multivariate logistic regression was used to test the association between accidental death and mental disorders. Results The accidental death group was more likely being male (χ2=37.55, P<0.001) and unmarried (χ2=8.82, P=0.003). The prevalence of Axis Ⅰ mental disorder and of axis Ⅱpersonality disorder were higher in accidental death group than that in control group (19.7%( 31/157) vs. 3.6%(5/140), χ2=18.17, P<0.01; 11.5%(18/157) vs .3.6%(5/140), χ2=6.45, P=0.011; respectively). After adjusted for demographic variables, the adjusted OR was 1.78 (95%CI: 1.26-2.51, P=0.001) for mental disorders, and 1.48(95%CI: 1.02-2.15, P=0.040) for mental disorders other than substance use disorders. Conclusion Mental disorder is an independent risk factor for accidental death, whether or not substance use disorders were excluded.