The pathogenesis of attention deficit and hyperactive disorder(ADHD)remains unclear.Evidence from epidemiological,biomarker,and genetic studies indicates that inflammation may play a crucial role in ADHD development.Inflammation can influence the onset and progression of ADHD through various mechanisms,such as activation of the hypothalamic-pituitary-adrenal(HPA)axis,alterations in neurotransmitter metabolism,maternal immune activation,disruption of the blood-brain barrier integrity,and impacts on neurodevelopment.A deeper understanding of the relationship between inflammation and ADHD could provide valuable insights into the pathophysiological mechanisms of ADHD and open new perspectives for clinical diagnosis and treatment.

BACKGROUND:Avascular necrosis of the femoral head is a refractory orthopedic disease that seriously affects the normal life of patients.Hip preservation is recommended for young patients due to the limited prosthesis longevity and revision.Accurate prediction of the mechanical properties of the necrotic area in the early stage and then intervention is the key to hip preservation. OBJECTIVE:To establish a dynamic contact mechanics finite element model of necrotic femoral head based on human hip CT data and predict effects of both necrotic volume magnitude and its position on biomechanics of the necrotic region under walking movement. METHODS:CT data of a volunteer were collected and then geometry model of the hip was rebuilt.Finite element model of the necrotic femoral head was established using the Abaqus software.Nine different necrotic femoral models were constructed by combined both three different necrotic volume magnitudes(small,medium and big volume)and three different necrotic positions(coincided with,medium deviated with and kept away from the line of the force).The Von Mises of the necrotic region for all models were predicted under both 3 000 N static load and dynamical loads of one whole ISO walking gait cycle.The collapse risk for all models was evaluated based on collapse criterion. RESULTS AND CONCLUSION:(1)More approaching of the necrotic region to the line of force and bigger collapse volume made the maximum Von Mises increasing.This also enlarged the collapse risk of the necrotic region.(2)For different load types,walking movement increased the maximum Von Mises of the necrotic region than that of the value under static load under the same necrotic volume and location.(3)In conclusion,dynamic load would result in increasing of the maximum Von Mises of the necrotic region comparing to static load during exercise.Therefore,the risk of local collapse will increase due to greater Von Mises.However,the overall collapse risk is lower than that of static load due to the dynamic change of bearing area.This factor should be carefully considered by surgeons when they evaluate the mechanical performance of the necrotic femoral head.

Objective To explore the risk factors of apathy and correlations with cognitive function in patients with hypertension combined with cerebral small vessel disease(CSVD).Methods Totally 141 patients with hypertension combined with CSVD were prospectively enrolled and were divided into apathy group(n=43)and non-apathy group(n= 98)according to neuropsychiatric inventory-apathy scale(NPI-Apathy)scores.The general data,imaging marker scores and total imaging burden scores were compared between groups.In hypertension combined with CSVD patients,multivariate logistic regression analysis was performed to screen the independent risk factors of apathy,and Spearman correlation analysis was also performed to observe the correlation of apathy and cognitive function.Results The patients'age,high density lipoprotein cholesterol(HDL-C),Fazekas scores of lateral periventricular white matter hyper-intensity(WMH),cerebral microbleed of depth/infratentorial and total imaging burden scores of apathy group were all higher,while mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)scores were both lower than those of non-apathy group(all P＜0.05).HDL-C and Fazekas scores of lateral periventricular WMH were both independent risk factors for apathy(both P＜0.05),while NPI-Apathy scores were moderately negatively correlated with cognitive function in patients with hypertension combined with CSVD(r=-0.543,-0.484,both P＜0.001).Conclusion HDL-C and Fazekas scores of lateral periventricular WMH were both independent risk factors for apathy in patients with hypertension combined with CSVD.The more severe the apathy,the lower the cognitive function.

Objective:To explore genes related to costimulatory molecule related to the prognosis of bladder cancer,and to construct and evaluate prognosis model based on costimulatory molecule-based signature(CMS).Methods:Gene expression matrix and clinical information of bladder cancer patients were downloaded from TCGA database and GEO database(GSE31684),and costimulatory molecule-related genes were retrieved from the literature.The univariate and multivariate Cox analysis were used to screened prognostic-related genes and constructed prognostic model.Forecast accuracy of model was verified in TCGA training group,TCGA validation data group and GEO group by Kaplan-Meier survival analysis and receiver operating characteristic curve(ROC).Considering risk score and clinical characteristics,we constructed a nomogram and evaluated its performance by consistency analysis and ROC.CIBERSORT algorithm was used to analyze immune cell composition of tumor microenvironment infiltration,and gene set enrichment analysis(GSEA)was performed to explore the potential mechanism.Results:Four prognostic-related CMSs were found:TNFRSF14,CD276,ICOS and TMIGD2,of which three were included in the risk score construction.Multivariate Cox regression results showed that the risk score based on CMS was an independent prognostic factor for bladder cancer patients.Consistency analysis and ROC results showed that the nomogram had ideal prognosis prediction accuracy.Immune infiltration analysis showed that the high risk group was likely to be in immunosuppressive state.GSEA results suggested that genes in high risk group were enriched in extracel-lular matrix(ECM)receptors interaction,cell cycle and other pathways.Conclusion:TNFRSF14,CD276 and ICOS may be potential prognostic biomarkers for bladder cancer patients.CMS-based risk score and nomogram could contribute to early prognosis and choice of personalized treatment.

Objective To observe the effects of Xixin Decoction on the blood-brain barrier permeability and the expressions of P-glycoprotein(P-gp),cannabinoid receptor 1(CB1)and cannabinoid receptor 2(CB2)in hippocampal tissue of rapidly aging mice(SAMP8);To explore the possible mechanism of Xixin Decoction in the treatment of Alzheimer disease(AD).Methods Totally 60 SAMP8 mice were randomly divided into model group,probiotics group,and Xixin Decoction high-,medium-and low-dosage groups,with 12 mice in each group,another 12 SAMR1 mice were set as control group.The medicated groups received corresponding drugs by gavage for 10 weeks respectively,while the control group and model group were gavaged with equal volume of distilled water.Morris water maze test was used to detect the learning and memory ability of mice,the blood-brain barrier permeability was detected by Evans blue method,the contents of matrix metalloproteinase 9(MMP9),nuclear factor(NF)-κB and tumor necrosis factor-α(TNF-α)in serum were determined by ELISA,the expressions of P-gp,CB1 and CB2 in hippocampal tissue were detected by Western blot,P-gp expression in hippocampal tissue was detected by immunofluorescence staining.Results Compared with the control group,the learning and memory ability of mice in model group significantly decreased,Evans blue exudation in brain tissue significantly increased,the contents of MMP9,TNF-α and NF-κB in serum significantly increased,the expressions of P-gp and CB2 protein significantly decreased,the expression of CB1 protein significantly increased,with statistical significance(P<0.01,P<0.05).Compared with the model group,the learning and memory ability of mice in Xixin Decoction high-dosage group significantly increased,the Evans blue exudation in brain tissue significantly decreased,the contents of MMP9,TNF-α and NF-κB in serum significantly decreased,the protein expressions of P-gp and CB2 significantly increased,and the protein expression of CB1 significantly decreased,with statistical significance(P<0.01,P<0.05).Conclusion Xixin Decoction can improve the spatial learning and memory ability of AD model mice,and its mechanism is related to regulating the permeability of the blood-brain barrier and related protein expression,and inhibiting neuroinflammation.

Objective:To evaluate the mechanical performance of customized metal prosthesis with tibia stems of varying lengths for tibial bone defects reconstruction.Methods:Morphologically matched postoperative finite element models of bone defect revision were developed, with three gradients (15 mm, 30 mm, and 45 mm) according to the degree of bone defect and were reconstructed with 3D printed tantalum metal prosthesis using three tibial stem lengths (80 mm, 120 mm, and 150 mm), respectively. Conventional static and dynamic (walking gait) loading was performed to analyze the peak tibial stress distribution and accumulated sliding distance at the prosthetic interface, and to assess the effects of the three tibial stems of different lengths on the stability of the customized tibial defect restorations and the internal tibial stress state.Results:The peak accumulated sliding distance of the dynamically loaded morphologically matched restorations ranged from 17.94 to 21.31 mm with static loading, which were 68% to 84.3% higher than those of 10.26 to 11.69 mm with static loading. The peak tibial stresses in the dynamically loaded model were greater than those in the statically loaded model, with an increase of 28%-49.2%, including 132.94-143.88 MPa in the statically loaded model and 170.41-200.14 MPa in the dynamically loaded model. The overall accumulated sliding distance of the tibia prosthetic model gradually decreased from the tibial osteotomy surface, and the accumulated peak sliding distances ranged from 10.26 to 11.69 mm for static loading, and from 17.94 to 21.31 mm for dynamic loading. The bone tissue stresses in the anterolateral and medial-posterior tibia increased gradually from top to bottom, and the maximum stress value in each section was in the posterior medial tibia (the maximum value was 200.14 MPa). The highest bone tissue stress in the lateral tibia was affected by the tibial stem length, which resulted in a different location, and it was the area most affected by stress shielding (maximum value of 170.65 MPa).Conclusion:For stability assessment of morphologically matched tantalum customized prosthesis, physiological gait dynamic loading studies are more reliable than static loading; the choice of tibial stem length depends on a combination of accumulated peak sliding distances and tibial bone stress distribution factors.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Objective For patient-specific open-wedge high tibial osteotomy(OWHTO),a novel anatomical fixation plate was designed,and the effects of geometric parameters and material selection on biomechanical fixation were studied.Methods A patient-specific OWHTO anatomical fixation plate was designed and constructed,and the effects of design parameters(thickness,width,and length of the fixation plate)and four different materials(stainless steel,titanium alloy,magnesium alloy,and PEEK)on the biomechanics of the OWHTO fixation system were studied using finite element analysis.The biomechanical differences between the anatomical fixation plate and TomoFix fixation plate were also compared.Results The thickness had a greater effect on the micromotion of the osteotomy space than the length and width of the fixation plate did.Titanium alloy or magnesium alloy fixation plates were more conducive than stainless steel and PEEK materials in obtaining reasonable stability and mechanical transfer simultaneously.Compared with that of the TomoFix plate,the maximum von Mises stress of the anatomical fixation plate was reduced by 13.5%;the maximum von Mises stress of the screws and tibia was increased by 9.8%and 18.4%,respectively;and the micromotion at the maximum osteotomy space cc was increased by 49.3%.Conclusions Anatomical fixation plates have a positive effect on reducing the stress-shielding effect and improving biomechanical properties under the premise of ensuring stability.This study provides a reference for the development of OWHTO anatomical fixation plates.

Objective To investigate the efficacy and safety of retroperitoneal single-port laparoscopic (LESS) adrenal tumor resection.Methods The clinical data of 130 patients receiving multi-port and single-port laparoscopic adrenal tumor resection in this hospital from January 2015 to March 2023 were retrospec-tively analyzed.There were 50 cases in the LESS group and 80 cases in the traditional laparoscopic adrenal tumor resection (LA) group.The age,gender,tumor location,complicating underlying diseases and tumor size were collected in the two groups.The related perioperative indicators were compared between the two groups. Results The operation time[(95±52)min vs. (101±58)min],drainage tube indwelling time[(4.9±1.5)d vs. (6.7±1.0)d],postoperative incision satisfaction degree and pain situation had statistically significant differences between the LESS group and LA group (P<0.05).The intraoperative bleeding volume[(20.2±13.2)mL vs. (25.6±11.3)mL]and hospitalization duration[(5.9±1.3)d vs. (7.8±1.0)d]had no statisti-cal differences between the two groups (P>0.05).No intraoperative and postoperative complications oc-curred in the two groups.There was 1 case of conversion to open operation in the LA group.Conclusion The LESS adrenal tumor resection is safe and effective,and the incision is more beautiful compared with multi-port laparoscopic operation.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis. METHODS: Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups. RESULTS: Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed. CONCLUSION: Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis. CLINICAL TRIAL REGISTRATION https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies ; Brain Neoplasms/genetics*