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Objective To analyze the burden and changing trend of testicular cancer in China from 1990 to 2019.Methods Based on the 2019 Global Burden of Disease Database(GBD 2019),analyze the incidence,mortality,disability-adjusted life years(DALYs),years of life lost(YLLs),years lived with disability(YLDs)and their variation trend of testicular cancer in Chinese population from 1990 to 2019.Evaluating changes in age standardized rate(ASR)by calculating annual estimated percentage change(EAPC).According to the age grouping,analyze the age distribution characteristics of testicular cancer disease burden by age group.Results In 2019,the incident cases,deaths,age-standardized incidence rate,and age-standardized mortality rate of testicular cancer in China were 17.17×103,1.21×103,2.39/105,and 0.16/105,respectively.Compared to 1990,incident cases,deaths,and age-standardized incidence rate increased obviously in China,which was consistent with the global change trend,while the increase was higher than the global level.However,both Chinese and global age-standardized mortality rate showed a downward trend.From 1990 to 2019,DALYs,YLLs and YLDs of testicular cancer increased by 29.66%,9.83%and 720.91%respectively in China.The two age groups,0-15 years group and 30-35 years group,were with highest incidence of testicular cancer,while the highest disease burden of testicular cancer was 30-35 years.Conclusion From 1990 to 2019,the disease burden of testicular cancer in China showed an upward trend.Adolescents and young adults should be the priority population for screening and prevention due to their higher incidence and disease burden.
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Fatigue-related traffic accidents and fatalities have been extensively studied by scholars globally.Specialized vehicles,due to their unique mission profiles,are more likely to cause driving-related fatigue and serious consequences.This paper reviews the current research of fatigue driving by using an inductive analysis method to summarize the mechanisms,risk factors,and monitoring methods.This paper also offers a vision of priorities and methodologies for research in the future.It is recommended that the mechanisms of driving fatigue be explored at the molecular biological level and that fatigue monitoring systems be made more feasible via the combined application of non-intrusive monitoring in order to reduce the toll on life and property taken by driving fatigue.
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BACKGROUND:The patella-patellar tendon junction is a high-incidence area of injury in patellar tendinopathy.The rabbit patella-patellar tendon injury model is a commonly used animal experimental research object.At present,the stress analysis of the injury mechanism and modeling method is not comprehensive. OBJECTIVE:Based on the previous histological and mechanical measurements,this study used micro CT to scan and model the whole patella,the patella-patellar tendon junction and the tendon quadriceps junction,to analyze the characteristics of changes in stress,and explore the potential impact of different forms of exercise on patellar tendon degeneration so as to provide a theoretical basis for injury prevention and animal model establishment. METHODS:Female healthy adult New Zealand rabbits were selected to study the patella and tendons at both ends of the left knee joint.After the material was taken,the samples were scanned and saved with micro CT.Mimics,Geomagic Studio and SolidWorks were used to establish a three-dimensional model.Finite element analysis was carried out with Ansys Workbench.The equivalent displacement,stress and strain of the target region were analyzed under different loading conditions(load size and direction changes,different action modes). RESULTS AND CONCLUSION:(1)Load direction change affected trend and value change;load size change affected value change.(2)Compared with other areas,the stress concentration was more obvious at the insertion point of the patellar tendon,and the strain value was the lowest.(3)At the insertion point of the patellar tendon,the stress concentration was greater in valgus than in varus and pronation than in extorsion.(4)The stress concentration effect and stress shielding during knee flexion and extension are the main causes of patellar tendon insertion injury.The stress in pronation and valgus states is also a potential factor leading to damage,which needs further study.The animal model established by jumping and running is more in line with the characteristics of sports injury.
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BACKGROUND:Rheumatoid arthritis is a chronic autoimmune disease characterized by joint pain,swelling,and dysfunction.Acupuncture,as a traditional medical treatment,has proved its effectiveness and safety in many diseases.However,the efficacy of acupuncture in the treatment of rheumatoid arthritis remains controversial.Therefore,the purpose of this study is to evaluate and explore the effect of Tiaodu Tongmai acupuncture in the treatment of preclinical rheumatoid arthritis of different ages through the generalized estimating equation,and to provide a basis for the application of acupuncture in rheumatoid arthritis. OBJECTIVE:To investigate the effect of Tiaodu Tongmai acupuncture therapy on preclinical rheumatoid arthritis(pre-RA)patients at different ages based on generalized estimating equation. METHODS:A total of 123 patients with preclinical rheumatoid arthritis treated from January to September 2023 were selected as the study objects and divided into study group(n=64)and control group(n=59)according to different treatment methods.The study group was given Tiaodu Tongmai acupuncture treatment,and the control group was given acetaminophen tablets.The baseline balance was adjusted by propensity score matching method.The clinical efficacy and cytokine levels before and after treatment between the two groups were compared.The generalized estimating equation model was established to evaluate the efficacy of Tiaodu Tongmai acupuncture therapy on preclinical rheumatoid arthritis patients at different ages. RESULTS AND CONCLUSION:(1)After 0 days of treatment,there were significant differences in joint pain and C-reactive protein expression between study and control groups(P<0.05).After 4 weeks of treatment,there were significant differences in visual analogue scale scores,joint pain,C-reactive protein and erythrocyte sedimentation rate between the two groups(P<0.05).After 8 weeks of treatment,there were significant differences in visual analogue scale scores,C-reactive protein and erythrocyte sedimentation rate between the two groups(P<0.05).After 12 weeks of treatment,there were significant differences in visual analogue scale scores,C-reactive protein and erythrocyte sedimentation rate between the two groups(P<0.05).(2)The total effective rate of the study group was 93.75%,while that of the control group was 79.17%.The clinical efficacy of the study group was significantly better than that of the control group(P<0.05).(3)There were significant differences in interleukin-6,interferon-γ,macrophage migration inhibitory factor,rheumatoid factor IgA,rheumatoid factor IgM,metallomatrix proteinase 3,metallomatrix proteinase 9,and anti-cyclic citrulline antibody in the study group before and after treatment(P<0.05).The levels of interleukin-6,interferon-γ,rheumatoid factor IgA,rheumatoid factor IgM,metallomatrix proteinase 3,metallomatrix proteinase 9,and anti-cyclic citrulline antibody in the control group after treatment were significantly different from those before treatment(P<0.05).There were significant differences in interleukin-6,interferon-γ,macrophage migration inhibitory factor,rheumatoid factor IgA,rheumatoid factor IgM,metallomatrix proteinase 3,and anti-cyclic citrulline antibody between the two groups after treatment(P<0.05).(4)After 12 weeks of treatment,the comprehensive efficacy of patients of all ages in the study group was better than that of the control group(P<0.05).After 8 weeks of treatment,the comprehensive efficacy of patients aged 23-35,36-50,and 51-60 years old in the study group was better than that of the control group(P<0.05),and the comprehensive efficacy of patients aged 18-22 years old was comparable between the two groups.After 4 weeks of treatment,the comprehensive efficacy of patients aged 36-50 and 51-60 years old in the study group was better than that of the control group(P<0.05),and the comprehensive efficacy was comparable between the two groups of patients aged 18-22 and 23-35 years.Overall,Tiaodu Tongmai acupuncture therapy has advantages in treating preclinical rheumatoid arthritis patients aged 36-50 and 51-60 years.
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Purpose To explore the correlation between phosphatidylinositol 3 kinase/serine-threonine kinase(PI3K/AKT)signaling pathway and elastic characteristics of breast lesions.Materials and Methods A total of 115 breast lesions were prospectively analyzed in 114 patients who underwent surgery from May 2021 to May 2022 at Chinese PLA General Hospital.Ultrasound and shear wave elastography were performed preoperatively.Immunohistochemical staining was used to detect the expression of PI3K/AKT protein levels in the tissue specimens,and the correlation between the staining results and the elastic parameters of shear wave elastography was analyzed.Results Surgical pathology revealed benign breast lesions in 50 cases and malignant lesions in 65 cases(25 cases with axillary lymph node metastasis).The maximum modulus of elasticity(F=40.47),the average modulus of elasticity(F=45.11),the ratio of elasticity of the lesion to that of the surrounding tissue(F=48.98),the detection rate of"hard ring sign"(χ2=62.25),the expression level of PI3K/p-PI3K(F=15.19,58.95)and AKT/p-AKT(F=46.94,74.21)were found in benign and malignant lesions without axillary lymph node metastasis,malignant lesions with axillary lymph node metastasis(all P<0.05).The expression levels of PI3K/p-PI3K and AKT/p-AKT were positively correlated with the maximum elastic modulus value,the mean elastic modulus value,and the ratio of elasticity of the lesion to the surrounding tissues(r=0.475,0.475,0.451;r=0.533,0.540,0.542;r=0.371,0.402,0.445;r=0.482,0.455,0.545,all P<0.05).Conclusion The expression level of PI3K/AKT in breast lesions is correlated with elastic characteristics,suggesting that it plays an important role in the regulation of elastic characteristics of breast lesions.
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Objective:To investigate the clinical efficacy of three-connections and four-screwings technique in the treatment of high double column acetabular fractures through a single ilioinguinal approach.Methods:A retrospective study was conducted to analyze the data of 42 patients who had been treated for high double column acetabular fractures from June 2017 to June 2020 at Trauma Ward 2, Department of Orthopedics and Traumatology, The First Hospital of Traditional Chinese Medicine of Changde. There were 19 males and 23 females with an age of (42.7±25.6) years. 29 injuries were due to a traffic accident, 12 ones to fall from a height, and one to fall. The time from injury to operation was (4.5±2.1) days. All the patients were treated by the three-connections and four-screwings technique through a single ilioinguinal approach. Briefly, the anterior column was connected and secured to the main bone using 3 routes, and the posterior column was attached and fixated to the anterior column reset using 2 or 3 of the 4 screwings. The operation time, intraoperative blood loss, fracture reduction quality, fracture healing time, hip function at the last follow-up and complications during the follow-up were recorded.Results:For this cohort, the operation time was (150.0±30.5) min, and intraoperative blood loss (300.0±50.0) mL. According to the Matta scale for postoperative acetabular fracture reduction, 34 cases were excellent, 6 cases good, and 2 cases acceptable, with an excellent and good rate of 95.2% (40/42). After operation one patient had fat liquefaction and wound exudation which responded to drainage and dressing change. The 42 patients were followed up for (15.0±3.4) months. All fractures healed after (11.0±2.0) months. By the modified Merle d'Aubigné & Postel scoring system, the hip function was evaluated at the last follow-up as excellent in 33 cases, as good in 6 cases, and as fair in 3 cases, yielding an excellent and good rate of 92.9% (39/42).Conclusions:In the treatment of high double column acetabular fractures, the three-connections and four-screwings technique through a single ilioinguinal approach can lead to fine reduction and rigid fixation by lag screw compression and neutralization plate protection. Consequently, early functional exercises can be performed to secure good therapeutic outcomes for the patients.
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Objective:To confirm the transportation and evaporation efficiency of micro droplets sprayed by high-pressure nozzles from purified tritium-containing wastewater with carrier gas in the horizontal evaporation chamber.Methods:A scale test bench with a single high-pressure nozzle had been built based on design conditions and similarity criteria to explore the designed evaporation characteristics of generated micro droplets in the horizontal evaporation chamber. At the same time, combined with experimental data, a suitable evaporation model was constructed using the Discrete Phase Model (DPM) in Ansys Fluent. On this basis, further simulation and analysis were conducted on the evaporation process and efficiency under the condition of multiple nozzles in the desighed horizontal evaporation chamber.Results:For single nozzle tests, the particle size of micro droplets along the nozzle centerline was between 12-50 μm and the particle size distribution was similar to the Rosin-Rammler distribution. Besides, the relative light intensity decreased exponentially with distance, indicating that the particle size and concentration of micro droplets both decreased rapidly, which means the evaporation rate of micro droplets was rapid. For the simulation of multiple nozzles injection in the desighed horizontal evaporation chamber, even for the hardest design condition, the evaporation percentage reached up to 99%, and small amount of the escaping micro droplets continued to evaporate during the process of mixing with other process exhaust until complete evaporation in the vertical chimney section.Conclusions:Under the conditions of desighed sprayed particle size distribution, typical operating conditions and the incoming flow similar to the supposed area, the complete evaporation of the micro droplets can be basically achieved in the horizontal evaporation chamber, so as to ensure the complete evaporation of purified tritium-containing wastewater from the outlet of the chimney.
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Objective:To construct 68Ga-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD44 as a novel atherosclerosis tracer targeting hyaluronic acid (HA), and evaluate its biological property and molecular imaging features. Methods:Low molecular weight (LMW) recombinant human CD44 protein was selected, and the C-terminal of the protein was modified by sulfonation and coupled to the bifunctional ligand NOTA to synthesize a novel molecular probe 68Ga-NOTA-CD44 targeting HA. The biological properties of the probe, such as labeling rate and in vitro stability, were studied. Three atherosclerotic plaque model mice and three normal C57BL/6 mice were studied by 68Ga-NOTA-CD44 microPET/CT imaging and pathological examination. Results:68Ga-NOTA-CD44 tracer was synthesized and purified with the radiochemical purity above 99%, and the specific activity was up to 62.22 MBq/nmol. lts stability was good in PBS, and the radiochemical purity was over 90% after incubation for 3 h. After intravenous injection, the probe was metabolized mainly by the kidneys, and its metabolic level decreased successively in the liver, lungs and blood. MicroPET/CT imaging results of atherosclerotic model mice suggested that the uptake in the plaque of abdominal aorta was higher at 60 min after injection, with SUV max and target/background ratio (TBR) max of 1.14±0.02 and 4.95±0.93, and the probe had certain atherosclerotic plaque eroded targeting, which was consistent with the pathological result. Conclusions:As a novel probe, 68Ga-NOTA-CD44 is simple to prepare and has a high labeling rate. It has good physicochemical properties and in vivo biological properties, and can display atherosclerotic eroded plaques sensitively. 68Ga-NOTA-CD44 has a promising prospect to be a new molecular probe for early noninvasive recognition of atherosclerotic eroded plaques.
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ObjectiveThis study aimed to identify a potential miRNA-mRNA axis in neurofibromatosis type 2 (NF2)-negative meningiomas, investigate their target relationships, and determine their biological functions. MethodsThe GSE17792 dataset, which contains data related to NF2-negative meningiomas, was downloaded from the Gene Expression Omnibus (GEO) database. The limma package of R software was used to determine the differentially expressed miRNAs (DeMiRNAs). The miRWalk 2.0 database was applied to obtain the target genes of DeMiRNAs. The Search Tool for the Retrieval of Interacting Genes (STRING) database was utilized to build protein-protein interaction (PPI) networks, and hub genes were identified via Cytoscape software. The expression and biological roles of the screened miRNAs were further validated. ResultsAltogether, 86 DeMiRNAs, consisting of 52 upregulated and 34 downregulated miRNAs, were found in NF2-negative meningioma tumor samples compared with arachnoid tissue controls. Fourteen miRNAs associated with 274 target genes were identified among these DeMiRNAs, and miRNA-target gene networks were constructed based on these data. Analysis with cytoHubba showed that two miRNAs (hsa-miR-650 and hsa-miR-623) were among the top 20 key hub genes in the PPI network. Further qRT-PCR experimental verification suggested that the expression of hsa-miR-650 was significantly higher in NF2-negative meningiomas than in normal brain tissues. Downregulation of hsa-miR-650 inhibited the proliferation and induced the apoptosis of NF2-negative meningioma cells. Finally, RAC1 was identified as a target of hsa-miR-650. ConclusionHsa-miR-650 acts as a tumor promoter and might function as a therapeutic target for patients with NF2-negative meningiomas.
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Intestinal organoids are constructed by crypts or stem cells from the intestine under the 3D support of the culture matrix. They contain all mature cells of the intestine, and have become a new and efficient platform for studying the mechanism of intestinal diseases. Compared with 2D cell culture, organoids can not only more effectively simulate the physiological structure and function of the intestine, but also better restore the true ecology of the intestine in different external environments. Therefore, it is more widely used in the study of pathogenesis of different intestinal diseases. This article reviewed the new progress of intestinal organoids culture, and the application and progress of intestinal organoids in the pathogenesis of inflammatory bowel diseases, colorectal cancer and celiac disease in recent years, and also discussed the application of intestinal organoids in drug research and development and screening.
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【Objective】 To analyze the characteristics of blood transfusion consultation cases and establish the consultation route, so as to provide reference for blood transfusion doctors to participate in blood transfusion consultation practice. 【Methods】 The cases involved in clinical transfusion consultation in the blood transfusion department of our hospital from 2020 to 2023 were collected from the hospital information system (HIS), and then classified by department and consultation type to summarize the main points of transfusion consultation, formulate transfusion consultation routes, and conduct typical cases analysis. 【Results】 There were 315 clinical transfusion consultations from 2020 to 2023, with an increasing trend year by year (26 in 2020, 67 in 2021, 81 in 2022, 141 in 2023). The consultations involved 24 departments, including cardiovascular medicine 14.0%(44/315), orthopedics 12.7%(40/315), intensive care medicine 8.9%(28/315), general medicine 8.3%(28/315), cardiopulmonary disease 6.0%(19/315), etc. There were 8 categories of consultations, including 35.6%(112/315) autologous ozonized blood transfusion, 23.8%(75/315) plasma exchange, 14.9%(47/315) perioperative mass blood preparation (transfusion), 11.4%(36/315) platelet- rich plasma therapy and 6.3%(20/315) autologous blood collection, etc. The clinical blood transfusion consultation route was formulated according to the consultation points. Six patients with various diseases were treated by blood transfusion department. With effective treatment measures taken, all of them improved and were discharged. 【Conclusion】 The summary of key points of clinical blood transfusion consultation and formulation of the blood transfusion consultation route by department of blood transfusion are conducive to the implementation of blood transfusion consultation and guarantee the safety of patients.
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Objective@#Progressive supranuclear palsy (PSP) involves a variety of visual symptoms that are thought to be partially caused by structural abnormalities of the retina. However, the relationship between retinal structural changes, disease severity, and intracranial alterations remains unknown. We investigated distinct retinal thinning patterns and their relationship with clinical severity and intracranial alterations in a PSP cohort. @*Methods@#We enrolled 19 patients with PSP (38 eyes) and 20 age-matched healthy controls (40 eyes). All of the participants underwent peripapillary and macular optical coherence tomography. Brain 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography imaging were also performed in patients with PSP. We investigated the association between retinal thickness changes and clinical features, striatal dopamine transporter availability, and cerebral glucose metabolism. @*Results@#The peripapillary retinal nerve fiber layer (pRNFL) and macula were significantly thinner in patients with PSP than in controls. The thickness of the superior sector of the pRNFL demonstrated a significant negative relationship with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III and Hoehn and Yahr staging scale scores. A significant negative correlation was found between outer inferior macular thickness and disease duration. Outer temporal macular thickness was positively correlated with Montreal Cognitive Assessment scores. In PSP, lower outer temporal macular thickness was also positively correlated with decreased dopamine transporter binding in the caudate. @*Conclusion@#The pRNFL and macular thinning may be candidate markers for monitoring disease severity. Additionally, macular thinning may be an in vivo indicator of nigrostriatal dopaminergic cell degeneration in PSP patients.
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There are various etiologies for extrahepatic bile duct stenosis, and pharmacotherapy and endoscopic intervention can achieve a good clinical effect in benign stenosis. Early diagnosis and timely surgical treatment of malignant stenosis may prolong the survival time of patients. However, there are still difficulties in the differential diagnosis of malignant bile duct stenosis. This article reviews the application of serology, radiology, endoscopic techniques, and artificial intelligence in the differential diagnosis of malignant bile duct stenosis, so as to provide strategies and references for formulating clinical diagnosis and treatment regimens.
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OBJECTIVE@#To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN).@*METHODS@#A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014.@*RESULTS@#A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer.@*CONCLUSIONS@#No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
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Humains , Études rétrospectives , Incidence , Carcinome hépatocellulaire , Tumeurs du foie/épidémiologie , Maladies du rein/induit chimiquement , Acides aristolochiques/effets indésirablesRÉSUMÉ
OBJECTIVE@#To explore effect of nerve growth factor (NGF) antibody on knee osteoarthritis (KOA) pain model was evaluated by in vitro model.@*METHODS@#Thirty male SPF rats aged 28-week-old were divided into blank group (10 rats with anesthesia only). The other 20 rats were with monoiodoacetate (MIA) on the right knee joint to establish pain model of OA, and were randomly divided into control group (injected intraperitoneal injection of normal saline) and treatment group (injected anti-NGF) intraperitoneal after successful modeling, and 10 rats in each group. All rats were received retrograde injection of fluorogold (FG) into the right knee joint. Gait was assessed using catwalk gait analysis system before treatment, 1 and 2 weeks after treatment. Three weeks after treatment, right dorsal root ganglia (DRG) were excised on L4-L6 level, immunostained for calcitonin gene-related peptide (CGRP), and the number of DRGS was counted.@*RESULTS@#In terms of gait analysis using cat track system, duty cycle, swing speed and print area ratio in control and treatment group were significantly reduced compared with blank group (P<0.05). Compared with control group, duty cycle and swing speed of treatment group were significantly improved (P<0.05), and there was no significant difference in print area ratio between treatment group and blank group (P>0.05). The number of FG-labeled DRG neurons in control group was significantly higher than that in treatment group and blank group (P<0.05). The expression of CGRP in control group was up-regulated, and differences were statistically significant compared with treatment group (P<0.05).@*CONCLUSION@#Intraperitoneal injection of anti-NGF antibody inhibited gait injury and upregulation of CGRP in DRG neurons. The results suggest that anti-nerve growth factor therapy may be of value in treating knee pain. NGF may be an important target for the treatment of knee OA pain.
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Sujet âgé , Animaux , Mâle , Rats , Peptide relié au gène de la calcitonine/métabolisme , Modèles animaux de maladie humaine , Ganglions sensitifs des nerfs spinaux/métabolisme , Articulation du genou , Facteur de croissance nerveuse/usage thérapeutique , Gonarthrose/traitement médicamenteux , Douleur/métabolisme , Rat Sprague-Dawley , Anticorps/usage thérapeutiqueRÉSUMÉ
Objective To explore the dynamic process of fluid-structure interaction(FSI)between venous blood and valves and the physiological mechanism that guarantees unidirectional blood reflux back to the heart.Methods A three-dimensional(3D)numerical model of the venous system was established using the immersed boundary/finite element method.In the simulation,information from medical images of human lower-extremity veins and the anatomical structure and size of the bovine great saphenous vein were applied.Moreover,a hyperelastic constitutive model was used to describe the incompressible,nonlinear,and hyperelastic mechanical responses of the venous valve under physiological conditions.Results The simulations visualized the process of venous blood transport and the function of venous valves in preventing reflux.The periodic characteristics of venous valve motion and blood flow were reproduced,and important physiological data during the entire cardiac cycle were discussed and quantified,including the pressure,velocity,and flow rate of venous blood;opening area of the venous valve;and stress and strain distributions on the valve surface.Conclusions The 3D FSI model numerically reproduces the physiological dynamic process within veins and potentially provides important references and guidance for revealing the pathological mechanism of venous diseases.
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The unclear connotation and fragmented governance of the multi-tiered medical security system pose challenges to its high-quality development.This article redefines the concept and connotation of the multi-tiered medical security system using holistic governance theory.It distinguishes the bottom layer,basic layer,and supplementary layer from the perspective of the essential attributes and direct functions of each system.Furthermore,from the perspective of holistic governance,the article analyzes the current reform practice and finds that fragmented management thinking,unclear positioning of sub-system functions,insufficient policy coordination,single participation subject,and lack of equal negotiation mechanisms are constraints on the overall effectiveness of the multi-tiered medical security system.Therefore,it is necessary to adopt systematic and targeted reform measures from the perspective of holistic governance to improve the system.
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OBJECTIVE To investigate the effect of eukaryotic translation elongation factor 1A1(eEF1A1)on the replication of vesicular stomatitis virus(VSV)and Herpes simplex virus 1(HSV-1)to identify a potential target for broad-spectrum regulation of viruses.METHODS Small interfering RNA(si-eEF1A)was transfected into human skin fibroblasts(BJ-5ta)to inhibit the expression of eEF1A1,and the negative control group was set up.The transfection efficiency was detected by real-time fluo-rescence quantitative PCR(RT-qPCR)and Western blotting,the cell model of eEF1A1 gene silencing was constructed.The cell model was infected with VSV,the gene copy number and protein expression of VSV in the cells were detected.The cell model was infected with HSV-1,the mRNA and protein expres-sion of HSV-1 in the cells were detected.The cell models were transfected with polyinosinic acid[Poly(I:C)]or sodium deoxyribonucleic acid(HT-DNA),respectively.The mRNA expression of interferon-β(IFN-β),C-X-C Motif Chemokine 10(CXCL10)and interferon-stimulated gene 56(ISG56)were detected by RT-qPCR.The phosphorylation expression of interferon regulatory factor 3(IRF3)and TANK binding kinase 1(TBK1)were detected by Western blotting.RESULT Compared with the negative control group,the mRNA and protein expression of eEF1A1 in the eEF1A1 gene silencing group were signifi-cantly decreased(P<0.01),the cell model of eEF1A1 gene silencing was successfully constructed.Compared with the negative control group,the VSV gene copy number of the eEF1A1 gene silencing group decreased by 70%-80%.The VSV protein expression decreased significantly(P<0.01).The mRNA expression of HSV-1 was decreased by 50%-60%,and the protein expression of HSV-1 was significantly decreased(P<0.01).After stimulation with Poly(I:C)or HT-DNA,compared with the negative control group.there was no significant difference in the mRNA expressions of IFN-β,ISG56 and CXCL10 and the protein phosphorylation expression of IRF3 and TBK1 in the eEF1A1 gene silencing group.CONCLUSION eEF1A1 silencing can inhibit VSV and HSV-1 virus replication,suggesting that eEF1A1 has a potential broad-spectrum regulatory effect on RNA viruses and DNA viruses,and may not recog-nize activated immune pathways through intracellular nucleic acid recognition.
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Objective @#To develop a CD30-targeted CAR-T cell drug based on the multi-chain chimeric antigen re- ceptor T cells (CAR-T) of the bridging protein DAP12 , and to study the in vitro and in vivo preclinical efficacy of CD30 CAR-T on Hodgkin lymphoma tumor cells .@*Methods @#Through gene synthesis and molecular cloning tech- niques , a CAR plasmid targeting CD30 was designed and constructed , and the obtained lentivirus was packaged . The T cells were transfected with the lentivirus , where the multi-chain CAR-T targeting CD30 was the CD30 - KIRS2/Dap12-BB group , the single-chain second-generation CAR-T was the CD30-41BBζgroup , and the T cells without virus infection were the NTD group . The positive rate of CAR was detected by flow cytometry , the cytotoxic- ity of the cells was detected by lactate dehydrogenase (LDH) release assay , the secretion level of the cytokine in- terferon γ(IFN-γ) was detected by enzyme-linked immunosorbent assay ( ELISA) , and the antitumor activity of CD30 CAR-T in mice was further detected by a mouse xenograft tumor model . @*Results @#A comparison was made between the multi-chain CAR-T targeting CD30 and the single-chain second-generation CAR-T. It was found that the antitumor effect of the multi-chain CAR-T was similar to that of the single-chain CAR-T. However , it was worth noting that the IFN-γsecretion level of the multi-chain CAR-T was higher (P < 0 . 001) . More importantly , in the mouse tumor model experiment , the multi-chain CAR-T achieved complete tumor regression . @*Conclusion @#The multi-chain CAR-T targeting CD30 is superior to the traditional single-chain CAR-T in terms of antitumor activity .
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@#Objective To explore the the correlation between cystatin C(Cys C),beta-2 microglobulin(β2-MG)and ischemic cerebral small vessel disease(CSVD)and its subgroups.Methods Totally 234 patients with CSVD were assigned to the study group,and 92 elderly people with no abnormal findings in head MRI were selected as controls.The CSVD patients were further divided into the subgroups of lacunar infarction(LI),white matter lesion(WML)and LI+WML.Each group was compared risk factors include the blood level of Cys C and β2-MG.Results There were statistically significant differences between CSVD group and control group in cystatin C(Cys C)and β2-MG(P<0.05).Cystatin C(Cys C)and β2-MG there were statistically significant differences between WML group and control group(P<0.05),and also between WML+LI group and control group(P<0.05).Logistic regression analysis and comparison across subgroups showed Cys C and β2-MG to be the common risk factors for WML group and WML+LI group inpatients with ischemic cerebral small vessel disease.Conclusion Cys C and β2-MG are the common risk factors for WML group and WML+LI group inpatients with ischemic cerebral small vessel disease.The risk factors vary across different CSVD subgroups.