Frequent occurrence of disaster rescue and public health emergencies has increased demand for rapidly and efficiently emergent medical rescue.This study modified a closed van which equipped a rapid testing module for physiological indicators,clinical blood transfusion module,detection and sampling module of etiology,and module for health and epidemic prevention.This research designed one kind of emergent vehicle for rapidly comprehensive detection,which integrated test vehicle,blood transfusion vehicle,biosafety testing vehicle,and vehicle for health and epidemic prevention in one vehicle.This vehicle can meet various demands of emergently medical rescue and other tasks in clinical test,which can improve the response capability and emergency handling capability for disasters and public health emergencies,at the same time,it also can save manpower.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

BACKGROUND:Developmental dysplasia of hip causes groin pain in patients with prolonged activity or standing due to the presence of deformities of the acetabulum and femoral head in terms of structure,size and orientation,and if not effectively treated,patients' normal activities will be severely limited.OBJECTIVE:Finite element model of the hip joint of solid-liquid biphase fiber reinforced cartilage based on FEBio was established to explore the biomechanical properties of the cartilage for patients with developmental dysplasia of hip and the normal hip joint.METHODS:A patient with developmental dysplasia of hip and a normal volunteer were chosen to build their left hip models including left pelvis,left femur,and cartilage attached thereto. The solid-liquid biphase fiber reinforced cartilage of normal hip was verified to be effective. The cartilage equal contact stress,fluid pressure,solid effective stress,and fluid support rate differences between the developmental dysplasia of hip patients hip and the normal one in the case of one leg of static load (2130 N) were compared after establishing finite element models of developmental dysplasia of hip patients.RESULTS AND CONCLUSION:(1) Compared with the finite element results of the normal hip model,the cartilage contact position of developmental hip dysplasia patient hip showed obvious edge contact,the peak contact stress (3.86 Mpa) and peak fluid pressure (3.76 Mpa) were both higher than normal hip model. (2) After 1500 s (stable load-bearing capacity),peak contact stress and peak fluid pressure in both models decreased,but the cartilage contact position of developmental hip dysplasia patient hip moved from the edge of cartilage to the center,and fluid support rate decreased from 97.41％ to 91.08％. The fluid support rate in normal hip was decreased by 0.58％ from 95.24％ to 94.66％. (3) It is indicated that under the physiological load of standing on one leg,the cartilage of developmental dysplasia of hip patients showed obvious edge load,and the decrease of peak contact stress,fluid pressure,and fluid formation rate was greater than that of normal cartilage. Considering the solid-liquid biphasic fiber reinforcement characteristics of cartilage,it is of great clinical significance to evaluate the biomechanical properties of hip cartilage in developmental dysplasia of hip patients,to understand the pathophysiological mechanism of developmental dysplasia of hip,and make preoperative plan.

BACKGROUND:Developmental dysplasia of hip causes groin pain in patients with prolonged activity or standing due to the presence of deformities of the acetabulum and femoral head in terms of structure,size and orientation,and if not effectively treated,patients' normal activities will be severely limited.OBJECTIVE:Finite element model of the hip joint of solid-liquid biphase fiber reinforced cartilage based on FEBio was established to explore the biomechanical properties of the cartilage for patients with developmental dysplasia of hip and the normal hip joint.METHODS:A patient with developmental dysplasia of hip and a normal volunteer were chosen to build their left hip models including left pelvis,left femur,and cartilage attached thereto. The solid-liquid biphase fiber reinforced cartilage of normal hip was verified to be effective. The cartilage equal contact stress,fluid pressure,solid effective stress,and fluid support rate differences between the developmental dysplasia of hip patients hip and the normal one in the case of one leg of static load (2130 N) were compared after establishing finite element models of developmental dysplasia of hip patients.RESULTS AND CONCLUSION:(1) Compared with the finite element results of the normal hip model,the cartilage contact position of developmental hip dysplasia patient hip showed obvious edge contact,the peak contact stress (3.86 Mpa) and peak fluid pressure (3.76 Mpa) were both higher than normal hip model. (2) After 1500 s (stable load-bearing capacity),peak contact stress and peak fluid pressure in both models decreased,but the cartilage contact position of developmental hip dysplasia patient hip moved from the edge of cartilage to the center,and fluid support rate decreased from 97.41％ to 91.08％. The fluid support rate in normal hip was decreased by 0.58％ from 95.24％ to 94.66％. (3) It is indicated that under the physiological load of standing on one leg,the cartilage of developmental dysplasia of hip patients showed obvious edge load,and the decrease of peak contact stress,fluid pressure,and fluid formation rate was greater than that of normal cartilage. Considering the solid-liquid biphasic fiber reinforcement characteristics of cartilage,it is of great clinical significance to evaluate the biomechanical properties of hip cartilage in developmental dysplasia of hip patients,to understand the pathophysiological mechanism of developmental dysplasia of hip,and make preoperative plan.

Frequent occurrence of disaster rescue and public health emergencies has increased demand for rapidly and efficiently emergent medical rescue.This study modified a closed van which equipped a rapid testing module for physiological indicators,clinical blood transfusion module,detection and sampling module of etiology,and module for health and epidemic prevention.This research designed one kind of emergent vehicle for rapidly comprehensive detection,which integrated test vehicle,blood transfusion vehicle,biosafety testing vehicle,and vehicle for health and epidemic prevention in one vehicle.This vehicle can meet various demands of emergently medical rescue and other tasks in clinical test,which can improve the response capability and emergency handling capability for disasters and public health emergencies,at the same time,it also can save manpower.

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.

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/)

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.