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AIM:To explore the key points of per-sonalized treatment and medication monitoring by clinical pharmacists in the perioperative period of moyamoya disease patients with endometriosis.METHODS:This study showed a moyamoya disease patient with endometriosis who accepting dual an-tiplatelet therapy and how to adjust medication during the perioperative period.Besides,monitor-ing the use proton pump inhibitors in the perioper-ative period and the formulating a plan of DIE post-operative recurrence prevention are also our objec-tives.RESULTS:Through individualized assessment of the patient,a personalized medication adjust-ments for dual antiplatelet therapy was deter-mined.Individualized perioperative proton pump inhibitor regimen and postoperative prevention plan for endometriosis recurrence were developed.CONCLUSION:The development of individualized medication regimens and medication monitoring is the breakthrough point for clinical pharmacists to carry out pharmaceutical services.
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Breast cancer brain metastasis (BCBM) is the second most common brain metastasis cancer, which is usually characterized by multiple lesions. Radiotherapy is an important local treatment for BCBM, which includes stereotactic radiotherapy, whole brain radiotherapy (WBRT) combined with simultaneous integrated boost and WBRT (such as conformal WBRT and hippocampal avoidance - WBRT) . Meanwhile, systemic treatment of BCBM has progressed rapidly, showing a positive effect in delaying the incidence of brain metastases, maintaining asymptomatic or unprogressive brain metastases, and delaying initial or salvage local treatments. In recent years, some studies have shown that radiotherapy combined with systemic treatment for BCBM has better application prospect compared with radiotherapy alone. In this article, the radiotherapy progress of brain metastases, the role of systemic therapy in BCBM, and the clinical research of radiotherapy combined with systemic therapy were reviewed, aiming to provide some reference for clinical research in this field.
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Zuoguiwan, one of the classic formulas of traditional Chinese medicine (TCM), has the effects of nourishing genuine Yin, supplementing essence, and replenishing marrow, and it is widely used in the clinical treatment of diseases caused by congenital essence deficiency. This article systematically reviewed the ancient books involving congenital deficiency and the modern research reports on the treatment of congenital deficiency with Zuoguiwan. From the formulation principle of Zuoguiwan and the TCM concept of congenital deficiency, this article discussed the theoretical basis of treating congenital deficiency with Zuoguiwan based on the modern research results. Ancient physicians have discovered that the deficiency of parents can lead to abnormal physical development and weakness of the offspring. ZHANG Jingyue divided congenital essence Qi into genuine Yin and primordial Yang and formulated Zuoguiwan based on the principle of Yin-Yang mutual assistance for supplementing congenital genuine Yin. Experimental studies have shown that Zuoguiwan can up-regulate the expression of connexin 43 (Cx43) protein and improve gap junction intercellular communication (GJIC) function to promote osteogenic differentiation and maturation of bone marrow mesenchymal stem cells and ameliorate abnormal bone development caused by congenital essence deficiency. Zuoguiwan can enhance the expression and activity of Reelin to ameliorate abnormal brain development. It can upregulate the expression of Cx43 protein to intervene in the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway, thus repairing the reproductive functions. Zuiguiwan can promote the development and maturation of T cells and activate the Wnt/β-catenin signaling pathway in the thymus to improve immune functions. In addition, it can promote the expression of β-catenin and inhibit the expression of microtubule-associated proteins 1 light chain 3 (LC3) to attenuate skin dysfunctions. Moreover, Zuoguiwan can guide the differentiation of stem cells via the correlation between essence and vitality in TCM. Zuoguiwan has demonstrated significant therapeutic effects on some diseases in the pediatric, andrological, gynecological, geriatric, internal medicine, orthopedic and skin disease departments. On the basis of the results of experiments and clinical applications, this paper analyzes the specific connotation of congenital deficiency proposes that congenital deficiency should be subdivided into the four aspects of essence, Qi, Yin, and Yang. Congenital essence deficiency as the deficiency of genuine Yin can lead to deficiency of kidney essence in the offspring and dysfunction of kidney storing essence. Pharmacological studies have discovered that Cuscutae Semen, Lycii Fructus, and Achyranthis Bidentatae Radix in Zuoguiwan contain active components such as quercetin and kaempferol, which act on the targets such as recombinant prostaglandin endoperoxide synthase 2 (PTGS2), interleukin-6 (IL-6), mitogen-activated protein kinases (MAPK14), tumor necrosis factor (TNF), TP53, Vascular permeability factor A (VEGFA), and albumin (ALB) to play a role in reproductive system development and hormone responses. Zuoguiwan has unique advantages over Liuwei Dihuangwan in nourishing congenital genuine Yin in the kidney and can achieve better therapeutic effects on the syndromes and diseases caused by congenital essence deficiency. This review is expected to enrich the knowledge about the efficacy and clinical application of Zuoguiwan, provide new perspectives and methods for the prevention and treatment of congenital deficiency and congenital essence deficiency, and give insights into the application of Zuoguiwan in modern healthcare, especially in the nurturing of offspring.
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Biological evidence is relatively common evidence in criminal cases,and it has strong pro-bative power because it carries DNA information for individual identification.At the scene of fire-related cases,the complex thermal environment,the escape of trapped people,the firefighting and res-cue operations,and the deliberate destruction of criminal suspects will all affect the biological evi-dence in the fire scene.Scholars at home and abroad have explored and studied the effectiveness of biological evidence identification in fire scenes,and found that the blood stains,semen stains,bones,etc.are the main biological evidence which can be easily recovered with DNA in fire scenes.In order to analyze the research status and development trend of biological evidence in fire scenes,this paper systematically sorts out the relevant research,mainly including the soot removal technology,appearance method of typical biological evidence,and possibility of identifying other biological evidence.This pa-per also prospects the next step of research direction,in order to provide reference for the identifica-tion of biological evidence and improve the value of biological evidence in fire scenes.
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Objective:In the context of China′s increasing standardized management requirements of clinical research, this article aims to explore the management methods of investigator-initiated trials in the new period, to provide possible reference for other medical institutions dedicated to clinical research.Methods:According to the requirements set forth by the"Administrative Measures for Investigator-Initiated Trials in Medical and Health Institutions (Trial)", combined with the hospital management practice, experiences regarding the research management system construction and implementation, management system construction and its implementation effects are summarized and analyzed.Results:By exploring and summarizing the connotation of high-quality clinical research under the New Policy, tailored clinical research management system in our hospital was developed and implemented. And the hospital′s clinical research capability and level have been greatly improved, which enhancing the hospital academic influence, as well as its competence for serving the development of national and regional clinical research.Conclusions:Along with the rapid progress of clinical research, hospitals need to assure the compliance of national laws and regulations, and develop appropriate and applicable institutional management measures to empower the conduct of high quality clinical research.
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Background@#Dysfunction of vascular endothelial cells (ECs) plays a central role in the pathogenesis of cardiovascular complications in diabetes. SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5) is a key regulator of chromatin structure and DNA repair, but its role in ECs remains surprisingly unexplored. The current study was designed to elucidate the regulated expression and function of SMARCA5 in diabetic ECs. @*Methods@#SMARCA5 expression was evaluated in ECs from diabetic mouse and human circulating CD34+ cells using quantitative reverse transcription polymerase chain reaction and Western blot. Effects of SMARCA5 manipulation on ECs function were evaluated using cell migration, in vitro tube formation and in vivo wound healing assays. Interaction among oxidative stress, SMARCA5 and transcriptional reprogramming was elucidated using luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation. @*Results@#Endothelial SMARCA5 expression was significantly decreased in diabetic rodents and humans. Hyperglycemia-suppressed SMARCA5 impaired EC migration and tube formation in vitro, and blunted vasculogenesis in vivo. Contrarily, overexpression of SMARCA5 in situ by a SMARCA5 adenovirus-incorporated hydrogel effectively promoted the rate of wound healing in a dorsal skin punch injury model of diabetic mice. Mechanistically, hyperglycemia-elicited oxidative stress suppressed SMARCA5 transactivation in a signal transducer and activator of transcription 3 (STAT3)-dependent manner. Moreover, SMARCA5 maintained transcriptional homeostasis of several pro-angiogenic factors through both direct and indirect chromatin-remodeling mechanisms. In contrast, depletion of SMARCA5 disrupted transcriptional homeostasis to render ECs unresponsive to established angiogenic factors, which ultimately resulted in endothelial dysfunction in diabetes. @*Conclusion@#Suppression of endothelial SMARCA5 contributes to, at least in part, multiple aspects of endothelial dysfunction, which may thereby exacerbate cardiovascular complications in diabetes.
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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.
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Objective The risk prediction factors of patients with chronic kidney disease (CKD) complicated with pulmonary tuberculosis were analyzed, and the risk prediction model was constructed to provide theoretical basis for the prevention and treatment of pulmonary tuberculosis in patients with CKD. Methods Stratified sampling was used to randomly select 289 patients with CKD admitted to our hospital as the investigation objects. According to whether patients complicated with tuberculosis, they were divided into experimental group (n=65, CKD complicated with tuberculosis) and control group (n=224, CKD). Univariate analysis and logistic regression were used to analyze the influencing factors of pulmonary tuberculosis in PATIENTS with CKD. According to the regression results, the risk prediction model of pulmonary tuberculosis in CKD patients was established, and the ROC curve was used to predict the efficacy of the model. Results Among 289 patients with CKD, 65 cases (22.49%) had pulmonary tuberculosis. Chest X-ray showed 54 cases of infiltrating pulmonary tuberculosis, 5 cases of voiding pulmonary tuberculosis, 4 cases of caseous pneumonia and 2 cases of tuberculous pleurisy. The main clinical manifestations of CKD complicated with pulmonary tuberculosis were low fever, poor appetite and fatigue in 36 cases, cough and expectoration in 18 cases, high fever in 9 cases and pleural effusion in 2 cases. Mycobacterium tuberculosis culture was positive in 23 cases (35.38%). There were no significant differences in age, CKD stage, past tuberculosis history, low immunity, malnutrition, dialysis treatment, anemia and hypoproteinemia between 2 groups (P-(0.496+0.839×(low immunity)+ 0.892×(malnutrition)+ 1.247×(dialysis)]; ROC curve was used to analyze the predictive efficacy of the regression model. The results showed that the AUC of pulmonary tuberculosis predicted by the risk prediction model was 0.779, 95%Cl(0.668-0.889) for CKD patients. Conclusion The risk of tuberculosis in CKD is higher,low immunity, malnutrition, dialysis treatment of CKD patients is high risk for tuberculosis, according to the specific situation of the patients, take targeted measures to prevention, can reduce the risk of tuberculosis in patients with CKD.
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Abstract@#In recent years, the incidence of mental disorders among children and adolescents has been increasing worldwide. To decrease the incidence of mental health problems, many relevant policies and regulations have been successively issued and mental health services have been implemented in China. The article focused on the development and progression of mental health problems during the transition from childhood to adolescence, emphasized possible determinants on the association between physical and mental health, and presented causality in psychiatry and related models. Especially, the article highlighted some viewpoints from the clinical perspective and put forward relevant considerations and suggestions.
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Objective@#To study the relationship between motor coordination, social communication impairment, and restricted/repetitive behaviors (RRBs) in children with autism spectrum disorder (ASD).@*Methods@#A total of 123 ASD children aged 2-12 were recruited from rehabilitation service institutions for autistic children in Guangzhou, including 105 boys and 18 girls. The Developmental Coordination Disorder Questionnaire, Social Communication Questionnaire, and Restrictive Behavior Scale Revised were collected to measure motor coordination, social communication skills and RRBs, respectively. Multiple linear regression was used to explore the association between motor coordination and core symptoms.@*Results@#In children aged 2-5 years old, those without motor coordination deficits scored lower in social interaction (7.73±4.00) than others (9.76±2.90)( Z=-2.29, P <0.05). In children aged 6-12 years old, those without motor coordination deficits scored lower in restricted, repetitive, and stereotyped patterns of behavior (4.22±1.93), repetitive sensory-motor behaviors (3.91±2.63), and insistence on sameness (13.52±10.59) than those with motor coordination deficits (6.11±1.54, 14.00±8.49, 31.33±15.05)( Z=-2.48, -3.83, -3.28, P <0.01)。Multiple linear regression analysis showed that fine motor/handwriting and control during movement were negatively correlated with the severity of social communication impairment and RRBs respectively among children aged 2-5 and 6-12( β=-0.85--0.03, -2.98--0.17, P <0.05).@*Conclusion@#Among autistic children, those with motor deficits suffered from more severe core symptoms. Motor assessment should be included in the ASD screening, diagnosis and management. Motor intervention should also be promoted in the rehabilitation in order to improve the prognosis and life quality.
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Objective@#To explore changes in the social interactions of school aged children with autism spectrum disorder (ASD) enrolled in ordinary schools and special education institutions during a one year observation period.@*Methods@#A total of 44 children with ASD were recruited from the Research Center of Children and Adolescent Psychological and Behavioral Development in the Department of Public Health, Sun Yat sen University, during 2017 and 2018. At the baseline and follow up periods, a self report questionnaire (completed by parents) was administered in order to collect demographic information related to the children, the survey included the Social Responsiveness Scale (SRS), Strengths and Difficulties Questionnaire (SDQ), Social Communication Questionnaire (SCQ), Screen for Child Anxiety Related Emotional Disorder (SCARED) and the Swan son Nolan and Pelham, Version IV Scale(SNAP-IV).@*Results@#At baseline, compared with children in ordinary schools, the total score of SRS (114.56±6.02, 93.63 ±3.82) and its subscale scores (social awareness:13.54±0.71, 11.02±0.45; social cognition:22.73±1.16, 18.19±0.73; social interaction:37.47±2.12, 30.40±1.35; autistic mannerisms: 23.11±1.70, 19.02±1.08) were higher in children attending special education institutions, as well as the SCQ total score (20.37±1.60, 12.92±1.02) and its subscale scores(social interaction domain:8.77±0.92, 4.23±0.58; social communication domain:6.07±0.55, 4.19±0.35)( P <0.05). Further comparison of baseline and follow up results showed no significant difference in time effect or in the interaction between time and the educational environment( P >0.05).@*Conclusion@#Compared with special education institutions, school aged children with ASD in ordinary schools had lower levels of social impairment. During the one year observation period, there was no correlation between the educational environment and changes in symptoms of children and their parents. Parents should choose an appropriate educational environment according to the children s abilities, and ordinary schools and teachers should be prepared for inclusive education.
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Objective@#To investigate the association between parenting style and sleep problems among school aged children with autism spectrum disorder (ASD).@*Methods@#A total of 98 children with ASD aged 6-10 years old and 98 age and gender matched typically developing (TD) children from mainstream schools were recruited. Parenting style and sleep problems were measured via Parent Behavior Inventory (PBI) and Children s Sleep Habits Questionnaire(CSHQ), respectively. The symptom severity and intelligence level were also evaluated. Generalized linear model was used to analyze the relationship between parenting style and sleep problems.@*Results@#There was no statistically significant difference in the parenting style of the two groups of children( P > 0.05 ); weekend sleep time of children with ASD was significantly shorter than that of the TD group [(9.1±0.7)(9.5±0.8)h, P < 0.01 ], and the score of sleep onset delay was significantly higher than that of the TD group[(1.8±0.7)(1.5±0.7), P <0.01]. However, there was no statistically significant difference in the incidence of total sleep problems and various problems between the two groups of children( P >0.05). The parental support/engagement of children with ASD was negatively associated with the total score of sleep problems( β=-2.68, 95%CI =-4.88--0.47), bedtime resistance ( β=-1.65, 95%CI =-2.54--0.77) and sleep anxiety( β=-1.01, 95%CI =-1.70--0.32). The parental hostility/coercion was positively correlated with score of daytime sleepiness( β=1.41, 95%CI =0.53-2.29)( P <0.05).@*Conclusion@#Parenting style of support/engagement is associated with lower sleep problems in children with ASD, while hostile/coercion is associated with higher sleep problems. It should be improve parental style to reduce the sleep problems in children with ASD.
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Objective@#To investigate the associations between early life exposure to particulate matter with an aerodynamic diameter less than 2.5 μm (PM 2.5 ) and the risk of autism spectrum disorder (ASD) among school aged children.@*Methods@#A total of 165 children with ASD and 165 age and gender matched typical development (TD) children were recruited. Children s basic information were obtained via questionnaires, and the severity of ASD symptoms was assessed with Social Responsiveness Scale (SRS). Early life PM 2.5 exposure (preconception, entire pregnancy, and the first two years after birth) were extracted from the Tracking Air Pollution in China (TAP) datasets. Conditional Logistic regression and generalized linear model were used to evaluate the associations of early life exposure to PM 2.5 with the risk and the ASD severity symptoms, respectively.@*Results@#The PM 2.5 exposure of ASD group during preconception[(55.08±9.34)μg/m 3], entire pregnancy[(50.44±8.71)μg/m 3], the first year after birth [(45.04± 8.25 )μg/m 3] and the second year after birth [(40.19±7.12)μg/m 3] were significant higher than those in TD children [(47.66± 7.63 , 44.19±7.16, 38.95±6.07, 35.76±5.65)μg/m 3]( t =7.94, 7.13, 7.70, 6.32, P <0.05). After adjusting for potential confounding, each increase of 1 μg/m 3 in PM 2.5 was associated with higher risk of ASD during preconception ( OR=1.21, 95%CI =1.13-1.29), entire pregnancy( OR=1.18, 95%CI =1.11-1.26), the first year after birth ( OR=1.30, 95%CI =1.18-1.43) and the second year after birth ( OR=1.29, 95%CI =1.17-1.42). No similar results were observed regarding the analyses of SRS total and sub scale scores( P >0.05).@*Conclusion@#Early life exposure to PM 2.5 is relate to the risk of ASD, these findings indicated that more attention should be paid to ambient PM pollution in the early life prevention and control of ASD.
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Objective: To establish and optimize a TaqMan-probe quantitative real-time PCR (qPCR) assay for the detection of 7 important Rickettsiales pathogens and simultaneous identification of the infection types. Methods: Based on the ompB gene of Rickettsia prowazekii, Rickettsia mooseri and spotted fever group rickettsiae, the groEL gene of Orientia tsutsugamushi, the 16S rRNA of Ehrlichia chaffeensis, the gltA gene of Anaplasma phagocytophilum and the com1 gene of Coxiella burnetii, we synthesized primers and TaqMan-probes and optimized the reaction system and reaction process to same solution. The sensitivity, specificity and reproducibility of this assay were evaluated and the assay was used for the detection of simulated and actual samples. Results: The Ct value of the standard curves of the 7 pathogens showed a good linear relationship with the number of DNA copies (all R2 >0.990 0), the minimum detection limit was 10 copies/μl, showing good specificity. In the 96 tick nucleic acid extracts, Coxiella burnetii was detected in 1 sampleand spotted fever group Rickettsiae was detected in 3 samples. In the 80 blood samples from patients with undefined febrile illness, Orientia tsutsugamushi was detected in 1 sample and spotted fever group rickettsiae was detected in 2 samples. Conclusions: In this study, based on the established TaqMan-probe qPCR assay, the reaction system and reaction condition of the 7 important pathogens of Rickettsiales were optimized to the same solution. This method overcomes the shortcomings of using different reaction systems and reaction conditions for different pathogens, which can precisely identify the species of 7 important pathogens of Rickettsiales in clinical sample detections and is important for the infection type identification and laboratory detection time reduction to facilitate precise treatment of the patients.
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Humans , Alphaproteobacteria , Real-Time Polymerase Chain Reaction , RNA, Ribosomal, 16S , Reproducibility of Results , Orientia tsutsugamushi , Spotted Fever Group RickettsiosisABSTRACT
Cardiovascular disease is a class of diseases involving the heart or blood vessels, which accounts for about one-third of all deaths worldwide each year. Unhealthy diet, lack of physical activity, smoking and excessive alcohol consumption are all risk factors for cardiovascular disease. With the increasing number of night shift workers, the number of patients with cardiovascular disease has increased, and night shift work has gradually become a risk factor of cardiovascular disease. At present, the mechanism of cardiovascular disease caused by night shift work is still unclear. This review summarizes the relationship between night shift work and cardiovascular disease and its related biochemical indicators, and discusses the research on related mechanisms.
Subject(s)
Humans , Shift Work Schedule/adverse effects , Work Schedule Tolerance , Cardiovascular Diseases , Risk Factors , SmokingABSTRACT
Objective:To investigate the predictive value of multimodal magnetic resonance imaging (MRI) based radiomics model for microsatellite instability (MSI) of rectal cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 117 patients with rectal cancer who were admitted to 2 medical centers, including 74 in Ningbo Urology & Nephrology Hospital and 43 in the First Affiliated Hospital of Zhejiang University School of Medicine, from January 2020 to December 2022 were collected. There were 73 males and 44 females, aged (63±5)years. Based on random number table, all 117 patients were divided into the training dataset of 70 cases and the test dataset of 47 cases with a ratio of 7:3. All patients underwent pelvic MRI exami-nation. Observation indicators: (1) construction of radiomics prediction model and analysis of charac-teristics; (2) analysis of factors influencing MSI of rectal cancer in the training dataset; (3) construc-tion and evaluation of the prediction model for MSI of rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and compari-son between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Univariate analysis was conducted using the one way ANOVA and multivariate analysis was conducted using the Logistic regression model with forward method. The receiver operating characteristic curve was drawn, and the area under the curve (AUC), decision curve, calibration curve and Delong test were used to evaluate the predictive ability of prediction model. Results:(1) Construction of radiomics prediction model and analysis of characteristics. Five thousand five hundred and eighty radiomics features were finally extracted from the 117 patients. Based on the feature selection using the maximum correlation minimum redundancy method, and the least absolute shrinkage and selection operator fitting algorithm, 9 radiomics features were finally selected. The radiomics prediction model was constructed based on calculation of the radiomics score. (2) Analysis of factors influencing MSI of rectal cancer in the training dataset. Results of multivariate analysis showed that platelet count was an independent influencing factor for MSI of rectal cancer [ odds ratio=1.13, 95% confidence interval ( CI) as 1.06-1.21, P<0.05]. (3) Construction and evaluation of the prediction model for MSI of rectal cancer. The clinical prediction model and clinical-radiomics combined prediction model were constructed based on the results of multivariate analysis. The AUC of clinical prediction model, radiomics prediction model, clinical-radiomics combined prediction model in the training dataset was 0.94 (95% CI as 0.86-0.98), 0.96 (95% CI as 0.88-0.99), 0.99 (95% CI as 0.93-1.00), respectively, with the sensitivity and specificity as 90.7%, 91.2%, 96.9% and 85.0%, 88.9%, 94.3%. Results of Delong test showed that there was a significant difference in the predictive performance between the clinical-radiomics combined prediction model and the clinical prediction model ( Z=2.20, P<0.05), and there was no significant difference between the radiomics prediction model and the clinical-radiomics combined prediction model or the clinical prediction model ( Z=1.94, 0.60, P>0.05). The AUC of clinical prediction model, radiomics prediction model, clinical-radiomics combined prediction model in the test dataset was 0.97 (95% CI as 0.88-1.00), 0.86 (95% CI as 0.73-0.95), 0.97(95% CI as 0.87-1.00), respectively, with the sensitivity and specificity as 99.3%, 95.8%, 99.3% and 85.7%, 73.9%, 90.5%. Results of Delong test showed that there was a significant difference in the predictive performance between the clinical-radiomics combined prediction model and the radiomics prediction model ( Z=2.21, P<0.05), and there was no significant difference between the clinical prediction model and the clinical-radiomics combined prediction model or the radiomics prediction model ( Z=0.17, 1.82, P>0.05). Results of calibration curve showed that clinical prediction model, radiomics prediction model, clinical-radiomics combined prediction model had good ability in predicting the MSI status of rectal cancer. Results of decision curve showed that compared to clinical prediction model and radiomics prediction model, clinical-radiomics combined prediction model had greatest net gain in predicting the MSI of rectal cancer. Conclusion:The prediction model based on 9 radiomics features after selecting can effectively predict the MSI status of rectal cancer, and the clinical-radiomics combined prediction model has a better prediction efficiency.
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This study assessed and explored the pharmacological effects and mechanisms of action of IMMH002 {2-amino-2-(2-(4ʹ-(2-ethyloxazol-4-yl)-[1,1ʹ-biphenyl]-4-yl)ethyl)propane-1,3-dio}, a selective sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator, in a concanavalin A (ConA)-induced autoimmune hepatitis (AIH) mouse model. The experimental protocol strictly adhered to the guidelines of the Ethics Committee for Animal Research of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No.: 00004046). Male ICR mice were pre-treated with the drug for four days, followed by induction of AIH through tail vein injection of ConA protein. Liver function, hepatic tissue pathology, peripheral blood parameters, as well as immunoglobulin G (IgG), inflammatory cytokines, T cell distribution, and inflammatory pathways were evaluated in mice. Results demonstrated that IMMH002 significantly reduced liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated hepatic tissue inflammation and necrotic damage, decreased serum IgG levels, and lowered the expression of inflammatory mediators including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). Additionally, it facilitated T lymphocyte homing, downregulated the phosphorylation of nuclear factor kappa-B (NF-κB), IκB kinase β (IKKβ) and nuclear factor inhibitor protein-α (IκBα) proteins in hepatic tissue and cellular inflammation models. Collectively, IMMH002 effectively ameliorated ConA-induced autoimmune hepatitis in mice, exhibiting extensive anti-inflammatory and anti-necrotic effects, thereby laying a theoretical foundation for AIH clinical treatment.
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【Objective】 To discuss the regulating effect of stored red blood cells (RBCs) transfusion on BMDMs in inflammatory conditions, and the relationship between stored RBCs transfusion and inflammatory response induced by bacterial infection. 【Methods】 Forty C57BL/6 male mice of 6-8 weeks (18-22 g/mouse) were randomly divided into experimental group and control group. Each mouse was infected with 200 µL Pseudomonas aeruginosa injecting into the tail vein, and 400 µL fresh (storage >14 d) and stored RBCs (storage 0.05). F4/80 of experimental group and control group 2, 4 and 8 hours after RBCs infused were 1.83±0.11 vs 0.75±0.06, 0.46±0.06 vs 0.33±0.06 (P0.05), respectively. iNOS, TNF-α, MCP1 of M1 in liver of experimental group and control group 2, 4 and 8 hours after RBCs infused were respectively: iNOS 3.44±0.20 vs 2.46±0.08, 9.25±0.55 vs 2.67±0.12, 2.80±0.08 vs 2.39 ±0.01; TNF-α 1.69±0.22 vs 1.13±0.03, 1.44±0.24 vs 0.96±0.09, 1.31±0.05 vs 0.96±0.06; MCP1 4.96±0.08 vs 4.28±0.27, 4.63±0.04 vs 2.07±0.09, 2.28±0.19 vs 1.33±0.03 (P0.05). 【Conclusion】 Stored RBCs infusion can greatly promote the M1 polarization of BMDMs in liver.
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Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment (TME). In this environment, myeloid cells, such as myeloid-derived suppressor cells (MDSCs), play a pivotal role in suppressing antitumor immunity. Lipometabolism is closely related to the function of myeloid cells. Here, our study reports that acetyl-CoA acetyltransferase 1 (ACAT1), the key enzyme of fatty acid oxidation (FAO) and ketogenesis, is significantly downregulated in the MDSCs infiltrated in GBM patients. To investigate the effects of ACAT1 on myeloid cells, we generated mice with myeloid-specific (LyzM-cre) depletion of ACAT1. The results show that these mice exhibited a remarkable accumulation of MDSCs and increased tumor progression both ectopically and orthotopically. The mechanism behind this effect is elevated secretion of C-X-C motif ligand 1 (CXCL1) of macrophages (Mφ). Overall, our findings demonstrate that ACAT1 could serve as a promising drug target for GBM by regulating the function of MDSCs in the TME.
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OBJECTIVES@#To observe the clinical efficacy of acupoint thread-embedding for children with tic disorders of spleen deficiency and liver hyperactivity and its effect on serum level of neuron-specific enolase (NSE).@*METHODS@#A total of 68 children with tic disorders of spleen deficiency and liver hyperactivity were randomized into an observation group (34 cases, 1 case dropped out) and a control group (34 cases, 3 cases dropped out, 1 case was eliminated). In the observation group, acupoint thread-embedding was applied at Baihui (GV 20) and bilateral Hegu (LI 4), Taichong (LR 3), Pishu (BL 20), Ganshu (BL 18), Quchi (LI 11), Zusanli (ST 36),etc., once every 4 weeks. In the control group, tiapride hydrochloride tablet was given orally, twice a day. Both groups were treated for 12 weeks. Before and after treatment, the Yale global tic severity scale (YGTSS) score and serum level of NSE were observed in the two groups, and the clinical efficacy was evaluated.@*RESULTS@#After treatment, except for vocal tic score of YGTSS in the control group, the each-item scores and total scores of YGTSS and serum levels of NSE in the two groups were decreased compared with those before treatment (P<0.05); the each-item scores and total score of YGTSS and serum level of NSE in the observation group were lower than those in the control group (P<0.05). The total effective rate in the observation group was 87.9% (29/33), which was higher than 76.7% (23/30) in the control group (P<0.05).@*CONCLUSIONS@#Acupoint thread-embedding has a good effect in the treatment of children with tic disorders of spleen deficiency and liver hyperactivity, could reduce the YGTSS score and serum level of NSE.