Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder influenced by both genetic and environmental factors, remains poorly understood regarding how its polygenic risk score (PRS) impacts functional networks and symptomology. This study capitalized on data from 11,430 children in the Adolescent Brain Cognitive Development study to explore the interplay between PRS_ADHD, brain function, and behavioral problems, along with their interactive effects. The results showed that children with a higher PRS_ADHD exhibited more severe attention deficits and rule-breaking problems, and experienced sleep disturbances, particularly in initiating and maintaining sleep. We also identified the central executive network, default mode network, and sensory-motor network as the functional networks most associated with PRS and symptoms in ADHD cases, with potential mediating roles. Particularly, the impact of PRS_ADHD was enhanced in children experiencing heightened sleep disturbances, emphasizing the need for early intervention in sleep issues to potentially mitigate subsequent ADHD symptoms.
Humans ; Attention Deficit Disorder with Hyperactivity/physiopathology* ; Male ; Female ; Sleep Wake Disorders/physiopathology* ; Adolescent ; Child ; Brain/diagnostic imaging* ; Multifactorial Inheritance ; Genetic Predisposition to Disease

Objective To explore the effect and mechanism of microRNA-133a-3p(miR-133a-3p)on invasion and apoptosis of breast cancer cells through targeted regulation of cullin-associated NEDD8-dissociated 1(CAND1).Methods MCF-7 cells were divided into overexpression group(mimics miR-133 a-3p transfection),NC group(mimics control transfection),co-transfection group(mimics miR-133a-3p transfection with pcDNA-CAND1 co-transfection)and control group(only adding the same amount of transfection reagents).Flow cytometry was used to detect cell apoptosis,Transwell assay was used to detect cell invasion,and real-time fluorescence quantitative polymerase chain reaction was used to detect miR-133a-3p and CAND1 expression.Results After transfection,the expression levels of miR-133a-3p in control group,NC group,overexpression group and co-transfection group were 0.50±0.08,0.51±0.09,1.06±0.10 and 1.05±0.15,respectively;the expression of CAND1 mRNA were 0.91±0.09,0.91±0.07,0.80±0.10 and 1.21±0.10,respectively.There were statistically significant differences in the above indexes between the co-transfection group and the control group,the NC group(all P＜0.05),and there were statistically significant differences between the overexpression group and the control group,the NC group(all P＜0.05).The apoptosis rates in control group,NC group,overexpression group and co-transfection group were(7.88±1.62)％,(8.87±2.01)％,(53.41±5.46)％,(29.54±3.78)％,respectively.The number of invasive cells in control group,NC group,overexpression group and co-transfection group were 161.02±10.31,155.87±12.30,85.21±9.11 and 118.37±10.84,respectively.There were statistically significant differences in the above indexes between transfection group and overexpression group,control group and NC group(all P＜0.05),and there were statistically significant differences between overexpression group and control group and NC group(all P＜0.05).Conclusion Overexpression of miR-133a-3p in human breast cancer cells MCF-7 can inhibit CAND1 and promote apoptosis and invasion of MCF-7 cells.

Objective:To analyze the clinical phenotype and genetic etiology of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1).Methods:Clinical data of a 2-year-old boy who had presented at the Affiliated Hospital of Qingdao University in March 2023 for "intermittent limb twitching for 2 years" was collected. Peripheral blood samples were collected from the child and his parents for whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).Results:The child had manifested with distinctive facial features, limb deformities, hypotonia, motor and intellectual delays, and epileptic seizures. WES revealed that he has harbored compound heterozygous variants of the PIGN gene, namely c. 963G>A (p.Q321=) and c. 994A>T (p.I332F), which were inherited from his phenotypically normal mother and father, respectively. Based on the ACMG guidelines, the c. 963G>A was classified as a pathogenic variant (PVS1+ PM2_Supporting+ PM3), whilst the c. 994A>T was classified as a variant of uncertain significance (PM2_Supporting+ PP3). Conclusion:Above discovery has expanded the mutational spectrum of the PIGN gene variants associated with MCAHS1, which may facilitate delineation of its genotype-phenotype correlation.

Objective To construct curcumin pyrazole derivative by the reaction of diketone of curcumin and benzylhydrazine based on the above structure-activity relationship,and to explore its antioxidant activity to provide experimental basis for the development of curcumin antioxidant derivative.Methods Curcumin-N-substituted pyrazole derivative was synthesized from curcumin and benzylhydrazine.The structures of the derivative were confirmed by infrared spectroscopy(IR),nuclear magnetic resonance spectroscopy(1H-NMR,13C-NMR)and LC-MS.The antioxidant activity in vitro of the derivative was evaluated by determination of curcumin and its pyrazole derivative scavenging ability for 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid(ABTS)free radical.Results Curcumin pyrazole derivative was successfully synthesized.Curcumin and its pyrazole derivative showed good free radical scavenging effects in the range of 4.6-73.6,6.25-100 μg·mL-1,respectively,with a significant dose-effect relationship.The half-maximal inhibition(IC50)values of curcumin and its pyrazole derivatives determined by DPPH method were 14.24,40.37 μg·mL-1,respectively,while the IC50 values of curcumin and its pyrazole derivatives determined by ABTS method were 36.65,19.26 μg·mL-1,respectively.Conclusion The antioxidant activity of β-dione of curcumin was retained through the substitution of the pyrazole ring,and the curcumin pyrazole derivative deserves further investigation as a potential antioxidant.

Objective:To investigate the association between high-density lipoprotein cholesterol (HDL-C) and the risk of diabetes mellitus (DM) in Chinese adults.Methods:This study was a secondary analysis of a multicenter, retrospective cohort study using data from the Chinese health screening program in the DATADRYAD database. Between 2010 and 2016, 211833 Chinese adults aged 20 years or older were screened for diabetes at baseline in 32 sites and 11 cities across the country. Baseline HDL-C level was the target independent variable and the risk of DM at follow-up was the dependent variable. Cox proportional hazards regression analysis assessed the independent association between HDL-C levels and the risk of developing DM. In this paper, the generalized Additive Model (GAM) and the smoothing curve fitting method were used to study the nonlinear relationships. In addition, subgroup analyses were conducted to assess the consistency of the correlations among different subgroup and to further validate the reliability of the results.Results:After adjusting for potential confounding factors such as age, sex and body mass index, HDL-C level was positively correlated with the development of diabetes ( HR=1.43, 95% CI: 1.08-1.90, P=0.012). The level of HDL-C showed a non-linear relationship with the risk of DM, and the inflection point was 1.81 mmol/L. The HR (95% CI) of the left and right sides of the inflection point were 0.94 (0.56-1.55) and 2.54 (1.93-3.30), respectively. When HDL-C>1.81 mmol/L, HDL-C was positively correlated with the occurrence of DM. Each 1.00 mmol/L increase in HDL-C increased the risk of diabetes mellitus by 1.54 times ( P<0.001); when HDL-C<1.81 mmol/L, the risk of diabetes decreased by 6% for every 1.00 mmol/L increase in HDL-C ( P=0.798). Subgroup analysis showed that, in the age, male, BMI 24.5-52.7 kg/m 2 subgroups, all the systolic blood pressure subgroups, diastolic blood pressure 69-77 and 78-164 mmHg (1 mmHg=0.133 kPa) subgroups, total cholesterol 0.02-4.26 and 5.00-17.84 mmol/L subgroups, all the triglyceride subgroups, low-density lipoprotein 0-2.42 and 2.99-12.60 mmol/L subgroups, alanine aminotransferase 23.4-1 508.4 U/L subgroups, aspartate transaminase 0-19.7 and 24.8-1 026.2 U/L subgroups, all the urea nitrogen subgroups, creatinine 61.5-76.9, 77.0-1 116.6 μmol/L subgroups, never smoking subgroup, subgroup with frequent alcohol consumption or family history of diabetes mellitus, the effect values of HDL-C and the risk of diabetes mellitus in Chinese adults showed good stability (all HR>1.00). Conclusions:High levels of HDL-C are associated with an increased risk of DM in Chinese adults. When HDL-C is greater than 1.81 mmol/L, HDL-C is positively correlated with DM.

Objective: The objective of this study was to analyze the different brain oxygen metabolism statuses in preeclampsia using magnetic resonance imaging and investigate the factors that affect cerebral oxygen metabolism in preeclampsia. Materials and Methods: Forty-nine women with preeclampsia (mean age 32.4 years; range, 18–44 years), 22 pregnant healthy controls (PHCs) (mean age 30.7 years; range, 23–40 years), and 40 non-pregnant healthy controls (NPHCs) (mean age 32.5 years; range, 20–42 years) were included in this study. Brain oxygen extraction fraction (OEF) values were computed using quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude-based OEF mapping (QSM + quantitative blood oxygen level-dependent imaging or QQ) obtained with a 1.5-T scanner. Voxel-based morphometry (VBM) was used to investigate the differences in OEF values in the brain regions among the groups. Results: Among the three groups, the average OEF values were significantly different in multiple brain areas, including the parahippocampus, multiple gyri of the frontal lobe, calcarine, cuneus, and precuneus (all P-values were less than 0.05, after correcting for multiple comparisons). The average OEF values of the preeclampsia group were higher than those of the PHC and NPHC groups. The bilateral superior frontal gyrus/bilateral medial superior frontal gyrus had the largest size of the aforementioned brain regions, and the OEF values in this area were 24.2 ± 4.6, 21.3 ± 2.4, and 20.6 ± 2.8 in the preeclampsia, PHC, and NPHC groups, respectively. In addition, the OEF values showed no significant differences between NPHC and PHC. Correlation analysis revealed that the OEF values of some brain regions (mainly involving the frontal, occipital, and temporal gyrus) were positively correlated with age, gestational week, body mass index, and mean blood pressure in the preeclampsia group (r = 0.361–0.812). Conclusion Using whole-brain VBM analysis, we found that patients with preeclampsia had higher OEF values than controls.

Humans ; Melphalan/therapeutic use* ; Multiple Myeloma/therapy* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Transplantation Conditioning

Objective: To investigate the clinical efficacy and safety of anti-IgE monoclonal antibody (omazumab) in the treatment of allergic united airway disease (UAD) in the real-wold. Methods: Retrospective cohort study summarizes the case data of patients with allergic united airway disease who were treated with anti IgE monoclonal antibody (omalizumab) for more than 16 weeks from March 1, 2018 to June 30, 2022 in the Peking University First Hospital.The allergic UAD is defined as allergic asthma combined with allergic rhinitis (AA+AR) or allergic asthma combined with chronic sinusitis with nasal polyps (AA+CRSwNP) or allergic asthma combined with allergic rhinitis and nasal polyps (AA+AR+CRSwNP). The control of asthma was evaluated by asthma control test (ACT), lung function test and fractional exhaled nitric oxide (FeNO). The AR was assessed by total nasal symptom score (TNSS). The CRSwNP was evaluated by nasal visual analogue scale (n-VAS), sino-nasal outcome test-22 (SNOT-22), nasal polyps score (TPS) and Lund-Mackay sinus CT grading system. The global evaluation of omalizumab for the treatment of allergic UADwas performed by Global Evaluation of Treatment Effectiveness(GETE).The drug-related side effects were also recorded. Matched t test and Wilcoxon signed-rank test were used to compare the score changes of IgE monoclonal antibody (omazumab) before and after treatment, and multivariate logistic regression analysis was used to determine the influencing factors of IgE monoclonal antibody (omazumab) response. Results: A total of 117 patients with UAD were enrolled, ranging in age from 19 to 77 years; The median age of patients was 48.7 years; Among them, 60 were male, ranging from 19 to 77 years old, with a median age of 49.9 years; There were 57 females, ranging from 19 to 68 years old, with a median age of 47.2 years. There were 32 cases in AA+AR subgroup, 59 cases in AA+CRSwNP subgroup, and 26 cases in AA+AR+CRSwNP subgroup. The total serum IgE level was 190.5 (103.8,391.3) IU/ml. The treatment course of anti IgE monoclonal antibody was 24 (16, 32) weeks. Compared with pre-treatment, omalizumab increased ACT from 20.0 (19.5,22.0) to 24.0 (23.0,25.0) (Z=-8.537, P<0.001), increased pre-bronchodilator FEV1 from 90.2 (74.8,103.0)% predicted value to 95.4 (83.2,106.0)% predicted value (Z=-5.315,P<0.001), increased FEV1/FVC from 80.20 (66.83,88.38)% to 82.72 (71.26,92.25)% (Z=-4.483,P<0.001), decreased FeNO from(49.1±24.8) ppb to (32.8±24.4) ppb (t=5.235, P<0.001), decreased TNSS from (6.5±2.6)to (2.4±1.9) (t=14.171, P<0.001), decreased n-VAS from (6.8±1.2) to (3.4±2.0)(t=14.448, P<0.001), decreased SNOT-22 from (40.0±7.9) to (21.3±10.2)(t=15.360, P<0.001), decreased TPS from (4.1±0.8) to (2.4±1.0)(t=14.718, P<0.001) and decreased Lund-Mackay CT score from (6.0±1.3) to (3.1±1.6)(t=17.012, P<0.001). The global response rate to omalizumab was 67.5%(79/117). The response rate in AA+AR (90.6%,29/32) was significantly higher than that in AA+CRSwNP (61.0%,36/59) and AA+AR+CRSwNP (53.8%,14/26) subgroups (χ²=11.144,P=0.004). Only 4 patients (3.4%,4/117) had mild side effects. Conclusion: The real-world study showed favorable effectiveness and safety of anti-IgE monoclonal antibody for treatment of allergic UAD. To provide basis for preventing the progress and precise treatment of allergic UAD.
Female ; Humans ; Male ; Middle Aged ; Young Adult ; Adult ; Aged ; Nasal Polyps/drug therapy* ; Omalizumab/therapeutic use* ; Rhinitis/drug therapy* ; Retrospective Studies ; Asthma/diagnosis* ; Rhinitis, Allergic/drug therapy* ; Sinusitis/drug therapy* ; Antibodies, Monoclonal/therapeutic use* ; Chronic Disease

Objective:To explore the risk factors of acute kidney injury(stage 3)developed within 48 hours in elderly patients with sepsis, and to use them to develop a risk prediction model and then evaluate and externally validate the model.Methods:Clinical data of all elderly patients(age≥ 60 years)with sepsis in the intensive care medicine information database(MIMIC-Ⅳ v1.0)were extracted.Independent risk factors were determined by multivariate logistic regression analysis.A risk prediction model was constructed, a nomogram was drawn, and the receiver operating characteristic curve(ROC)and the Hosmer-Lemeshow(H-L)test were used to evaluate the model's prediction accuracy and R-squared.Clinical data of elderly patients(age≥ 60 years)with sepsis admitted to the Department of Critical Care Medicine of the Second People's Hospital of Hefei from May 2019 to October 2021 were retrospectively collected and fed into the prediction model to conduct external validation.Results:A total of 1 977 elderly patients with sepsis were screened out from the MIMIC-IV database and included in the training set, of whom, 544 developed AKI-stage 3 within 48 hours.Univariate analysis was performed for factors that might be associated with acute kidney injury in elderly patients with sepsis.Compared with the normal group that did not progress to AKI stage 3, there were statistically significant differences in 28 indicators, such as the duration of ICU stay, intravenous fluid intake in 24 hours, and use of vasoactive drugs[5(3, 9)d vs.7(4, 12)d; 2.05(1.17, 3.27)ml·kg -1·h -1vs.2.37(1.47, 4.10)ml·kg -1·h -1; 761(53.11%) vs.375(68.93%), P<0.001]. Based on the results of multivariate logistic regression analysis, a prediction model was finally constructed with 9 variables: albumin( OR=0.983, 95% CI: 0.966-0.999, P=0.040), aspartate transaminase( OR=1.000, 95% CI: 1.000-1.000, P<0.001), APTT( OR=1.005, 95% CI: 1.001-1.009, P=0.028), total bilirubin( OR=1.003, 95% CI: 1.001-1.004, P=0.001), serum creatinine( OR=1.005, 95% CI: 1.004~1.007, P<0.001), Charlson score( OR=1.117, 95% CI: 1.061-1.177, P<0.001), intravenous fluid intake in 24 hours( OR=1.101, 95% CI: 1.034-1.173, P=0.003), weight( OR=1.023, 95% CI: 1.018-1.029, P<0.001), and mechanical ventilation( OR=2.412, 95% CI: 1.843-3.157, P<0.001). Then a nomogram was generated.The area under the ROC curve(AUC)of the prediction model was 0.755(95% CI: 0.731-0.780), and the H-L test was conducted( χ2=10.89, P=0.208>0.05), indicating a good fit.Data from 102 elderly patients were included in the validation set, with 27 cases that had developed AKI-stage3 within 48 hours, and were fed into the prediction model, with an AUC of 0.778(95% CI: 0.676-0.880)and χ2=3.72 and P=0.882>0.05 from the H-L test, consistent with the results of the training set. Conclusions:The model has some predictive value for acute kidney injury in elderly patients with sepsis.