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BACKGROUND: The major concern in patients who have suffered from cardiac arrest (CA) and undergone successful extracorporeal cardiopulmonary resuscitation (E-CPR) is poor neurological outcomes. In this study, we aimed to introduce a rat model of selective brain perfusion (SBP) during E-CPR to improve the neurological outcome after CA. METHODS: The rats underwent 7 min of untreated asphyxial CA and then were resuscitated with E-CPR for 30 min. The right external jugular vein and right femoral artery were separately cannulated to the E-CPR outflow and inflow. The right common carotid artery was cannulated from the proximal to the distal side for SBP. Subsequently, rats were removed from E-CPR, wounds were closed, and 90 min of intensive care were provided. Neurological deficit scores were tested after 4 h of recovery when the rats were mechanical ventilation-free. S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein (GFAP) were detected through immunohistochemistry (IHC) of brain tissue. RESULTS: The rats that received SBP while resuscitated by E-CPR showed markedly better neurological performances after 4-h recovery than those resuscitated by E-CPR only. The IHC staining of GFAP and S100B in the hippocampus was low in the rats receiving SBP during E-CPR, but only GFAP showed significant differences. CONCLUSIONS: We successfully developed a novel and reproducible rat model of SBP while resuscitated by E-CPR to ameliorate the neurological performances after CA. This achievement might have opportunities for studying how to improve the neurological outcome in the clinical condition.
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Encéfalo , Reanimação Cardiopulmonar , Modelos Animais de Doenças , Oxigenação por Membrana Extracorpórea , Parada Cardíaca , Ratos Sprague-Dawley , Animais , Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Parada Cardíaca/fisiopatologia , Ratos , Masculino , Encéfalo/patologia , Encéfalo/irrigação sanguínea , Oxigenação por Membrana Extracorpórea/métodos , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Perfusão/métodos , Proteína Glial Fibrilar Ácida/metabolismo , Circulação CerebrovascularRESUMO
Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A, are widely used to treat hypercholesterolemia. In addition, statins have been suggested to reduce the risk of cardiovascular events owing to their pleiotropic effects on the vascular system, including vasodilation, anti-inflammation, anti-coagulation, anti-oxidation, and inhibition of vascular smooth muscle cell proliferation. The major beneficial effect of statins in maintaining vascular homeostasis is the induction of nitric oxide (NO) bioavailability by activating endothelial NO synthase (eNOS) in endothelial cells. The mechanisms underlying the increased NO bioavailability and eNOS activation by statins have been well-established in various fields, including transcriptional and post-transcriptional regulation, kinase-dependent phosphorylation and protein-protein interactions. However, the mechanism by which statins affect the metabolism of L-arginine, a precursor of NO biosynthesis, has rarely been discussed. Autophagy, which is crucial for energy homeostasis, regulates endothelial functions, including NO production and angiogenesis, and is a potential therapeutic target for cardiovascular diseases. In this review, in addition to summarizing the molecular mechanisms underlying increased NO bioavailability and eNOS activation by statins, we also discuss the effects of statins on the metabolism of L-arginine.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Óxido Nítrico/metabolismo , Células Endoteliais/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Endotélio Vascular , Arginina/metabolismo , BiologiaRESUMO
Fetuin-A, a hepatokine secreted by hepatocytes, binds to insulin receptors and consequently impairs the activation of the insulin signaling pathway, leading to insulin resistance. Apigenin, a flavonoid isolated from plants, has beneficial effects on insulin resistance; however, its regulatory mechanisms are not fully understood. In the present study, we investigated the molecular mechanisms underlying the protective effects of apigenin on insulin resistance. In Huh7 cells, treatment with apigenin decreased the mRNA expression of fetuin-A by decreasing reactive oxygen species-mediated casein kinase 2α (CK2α)-nuclear factor kappa-light-chain-enhancer of activated B activation; besides, apigenin decreased the levels of CK2α-dependent fetuin-A phosphorylation and thus promoted fetuin-A degradation through the autophagic pathway, resulting in a decrease in the protein levels of fetuin-A. Moreover, apigenin prevented the formation of the fetuin-A-insulin receptor (IR) complex and thereby rescued the PA-induced impairment of the insulin signaling pathway, as evidenced by increased phosphorylation of IR substrate-1 and Akt, and translocation of glucose transporter 2 from the cytosol to the plasma membrane. Similar results were observed in the liver of HFD-fed mice treated with apigenin. Collectively, our findings revealed that apigenin ameliorates obesity-induced insulin resistance in the liver by targeting fetuin-A.
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Resistência à Insulina , Camundongos , Animais , alfa-2-Glicoproteína-HS/metabolismo , Apigenina/farmacologia , Apigenina/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Insulina/metabolismo , alfa-Fetoproteínas/metabolismoRESUMO
The identification of tissue origin of body fluid can provide clues and evidence for criminal case investigations. To establish an efficient method for identifying body fluid in forensic cases, eight novel body fluid-specific DNA methylation markers were selected in this study, and a multiplex singlebase extension reaction (SNaPshot) system for these markers was constructed for the identification of five common body fluids (venous blood, saliva, menstrual blood, vaginal fluid, and semen). The results indicated that the in-house system showed good species specificity, sensitivity, and ability to identify mixed biological samples. At the same time, an artificial body fluid prediction model and two machine learning prediction models based on the support vector machine (SVM) and random forest (RF) algorithms were constructed using previous research data, and these models were validated using the detection data obtained in this study (n=95). The accuracy of the prediction model based on experience was 95.79%; the prediction accuracy of the SVM prediction model was 100.00% for four kinds of body fluids except saliva (96.84%); and the prediction accuracy of the RF prediction model was 100.00% for all five kinds of body fluids. In conclusion, the in-house SNaPshot system and RF prediction model could achieve accurate tissue origin identification of body fluids.
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OBJECTIVE@#To explore the risk factors for poor prognosis in sepsis-associated acute kidney injury (SA-AKI) and establish a nomogram predictive model.@*METHODS@#The clinical data of patients with SA-AKI admitted to the department of critical care medicine of Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2019 to September 2022 were retrospectively analyzed, including demographic information, worst values of blood cell counts and biochemical indicators within 24 hours of SA-AKI diagnosis, whether the patient received renal replacement therapy (RRT), mechanical ventilation, vasopressor therapy during hospitalization, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), fibrinogen-to-albumin ratio (FAR) within 24 hours of diagnosis, acute kidney injury (AKI) staging, total length of hospital stay, length of intensive care unit (ICU) stay, and others. According to the 28-day outcome, the patients were divided into survival group and death group, and the indicators between the two groups were compared. Univariate and multivariate Logistic regression analyses were used to screen for risk factors associated with mortality in SA-AKI patients. A nomogram predictive model for SA-AKI prognosis was constructed based on the identified risk factors. Receiver operator characteristic curve (ROC curve) and calibration plots were generated to evaluate the predictive value of the nomogram model for SA-AKI prognosis.@*RESULTS@#A total of 113 SA-AKI patients were included, with 67 in the survival group and 46 in the death group. The 28-day mortality among SA-AKI patients was 40.7%. The comparison between the two groups showed that there were statistically significant differences in age ≥ 65 years, AKI stage, mechanical ventilation, vasopressors, RRT, length of ICU stay, and laboratory indicators cystatin C (Cys C), fibrinogen (Fib), and FAR. Multivariate Logistic regression analysis showed that age ≥ 65 years [odds ratio (OR) = 7.967, 95% confidence interval (95%CI) was 1.803-35.203, P = 0.006], cystatin C (OR = 7.202, 95%CI was 1.756-29.534, P = 0.006), FAR (OR = 2.444, 95%CI was 1.506-3.968, P < 0.001), and RRT (OR = 7.639, 95%CI was 1.391-41.951, P = 0.019) were independent risk factors for mortality in SA-AKI patients. ROC curve analysis showed that the area under the ROC curve (AUC) for age ≥ 65 years, cystatin C, FAR, and RRT in predicting SA-AKI patient mortality were 0.713, 0.856, 0.911, and 0.701, respectively. A nomogram predictive model for SA-AKI patient prognosis was constructed based on age ≥ 65 years, cystatin C, FAR, and RRT, with an AUC of 0.967 (95%CI was 0.932-1.000) according to ROC curve analysis. The calibration plot indicated good consistency between predicted and actual probabilities.@*CONCLUSIONS@#Age ≥ 65 years, cystatin C, FAR, and RRT are independent risk factors for mortality in SA-AKI patients. The nomogram predictive model based on these four factors can accurately predict SA-AKI patient prognosis, helping physicians adjust treatment strategies in a timely manner and improve patient outcomes.
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Humanos , Idoso , Cistatina C , Estudos Retrospectivos , Unidades de Terapia Intensiva , Sepse/diagnóstico , Injúria Renal Aguda/terapia , Prognóstico , Curva ROC , FibrinogênioRESUMO
Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.
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OBJECTIVE@#To establish and modify quantitative real-time polymerase chain reaction (qPCR)-based serotyping assays to distinguish 97 pneumococcal serotypes.@*METHODS@#A database of capsular polysaccharide ( cps) loci sequences was generated, covering 97 pneumococcal serotypes. Bioinformatics analyses were performed to identify the cps loci structure and target genes related to different pneumococcal serotypes with specific SNPs. A total of 27 novel qPCR serotyping assay primers and probes were established based on qPCR, while 27 recombinant plasmids containing serotype-specific DNA sequence fragments were constructed as reference target sequences to examine the specificity and sensitivity of the qPCR assay. A panel of pneumococcal reference strains was employed to evaluate the capability of pneumococcal serotyping.@*RESULTS@#A total of 97 pneumococcal serotyping assays based on qPCR were established and modified, which included 64 serotypes previously reported as well as an additional 33 serotypes. Twenty-seven novel qPCR serotyping target sequences were implemented in the pneumococcal qPCR serotyping system. A total of 97 pneumococcal serotypes, which included 52 individual serotypes and 45 serotypes belonging to 20 serogroups, could not be identified as individual serotypes. The sensitivity of qPCR assays based on 27 target sequences was 1-100 copies/µL. The specificity of the qPCR assays was 100%, which were tested by a panel of 90 serotypes of the pneumococcal reference strains.@*CONCLUSION@#A total of 27 novel qPCR assays were established and modified to analyze 97 pneumococcal serotypes.
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Reação em Cadeia da Polimerase em Tempo Real , Sorotipagem , Streptococcus pneumoniae/genética , SorogrupoRESUMO
Objective: To analyze and predict the epidemic trend of overweight and obesity among children and adolescents aged 7-18 years in China from 1985 to 2019. Methods: Data were collected from the Chinese National Survey on Students Constitution and Health in 1985, 1995, 2000, 2005, 2010, 2014, and 2019 with the sample size of 409 945, 204 931, 209 209, 234 420, 215 317, 214 353, and 212 711, respectively. Overweight and obesity were evaluated according to the "classification standard of the weight index value of overweight and obesity screening for Chinese school-age children and adolescents" of the Working Group on Obesity in China (WGOC). The detection rate and average annual growth rate of overweight and obesity, and single obesity among children and adolescents aged 7-18 years were calculated, and ArcGis10.6 software was used to analyze the difference in the prevalence of overweight and obesity among children and adolescents in different regions in 2019. Polynomial regression function was used to fit the prevalence and average annual growth rate of overweight and obesity, and single obesity among children and adolescents from 1985 to 2019, and to predict the prevalence of overweight and obesity and single obesity among children and adolescents in China. Results: In 2019, the total prevalence of overweight and obesity among children and adolescents aged 7-18 years in China was 23.4%, and the prevalence of single obesity was 9.6%. The prevalence of overweight and obesity among urban children and adolescents was higher than that in rural areas (25.4% vs. 21.5%), and the prevalence in boys was higher than that in girls (28.4% vs. 18.4%) (both P values<0.001). In 2019, there was a large regional disparity in the prevalence of overweight and obesity in different provinces, with the lowest in Guangdong (12.2%) and the highest in Shandong (38.9%), and the high epidemic areas were mainly concentrated in North China and Northeast China. From 1985 to 2019, the prevalence of overweight and obesity among children and adolescents aged 7-18 years in China increased from 1.2% to 23.4%, with an increase of 18.1 times, while the prevalence of obesity alone increased from 0.1% to 9.6%, with an increase of 75.6 times. The prevalence of overweight and obesity in urban boys, urban girls, rural boys and rural girls increased from 1.3%, 1.5%, 0.5%, and 1.6% in 1985 to 31.2%, 19.4%, 25.6%, and 17.4% in 2019, with an increase of 22.3, 11.7, 54.2, and 10.1 times, respectively. According to the prediction model, the prevalence of overweight and obesity among children and adolescents aged 7-18 years in China will increase from 23.4% in 2019 to 32.7% in 2030, and the prevalence of obesity alone will increase from 9.6% in 2019 to 15.1% in 2030. The growth of rural children and adolescents is obvious. By 2025, the prevalence of overweight and obesity among rural children and adolescents in China will comprehensively exceed that of urban, and there will be an "urban-rural reversal" phenomenon. At the same time, the prevalence of children's obesity in China's low, medium and high epidemic areas will also continue to increase. By 2035, the prevalence of overweight and obesity among children and adolescents in medium epidemic areas will exceed that in high epidemic areas, and there will be a "provincial reversal" phenomenon. Conclusion: From 1985 to 2019, the overweight and obesity of children and adolescents in China will continue to grow rapidly with large regional differences.
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OBJECTIVE@#To analyze the association between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years, and to provide suggestions for the prevention and control of metabolic syndrome in Chinese children and adolescents.@*METHODS@#Data were collected from the research project "Development and Application of Technology and Related Standards for Prevention and Control of Major Diseases among Students" of public health industry in 2012. This project is a cross-sectional study design. A total of 65 347 students from 93 primary and secondary schools in 7 provinces including Guangdong were selected by stratified cluster random sampling method. Given the budget, 25% of the students were randomly selected to collect blood samples. In this study, 10 176 primary and middle school students aged 7 to 17 years with complete physical measurements and blood biochemical indicators were selected as research objects. Chi-square test was used to compare the distribution differences of growth patterns under different demographic characteristics. Birth weight, waist circumference and blood biochemical indexes were expressed in the form of mean ± standard deviation, and the differences among different groups were compared by variance analysis. Binary Logistic regression model was used to analyze the relationship between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years.@*RESULTS@#The prevalence of metabolic syndrome in children and adolescents was 6.56%, 7.18% in boys and 5.97% in girls. The risk of metabolic syndrome was higher in the catch-down growth group than in the normal growth group (OR=1.417, 95%CI: 1.19-1.69), and lower in the catch-up growth group(OR=0.66, 95%CI: 0.53-0.82). After adjusting for gender, age and so on, the risk of developing metabolic syndrome in the catch-down growth group was higher than that in the normal growth group (OR=1.25, 95%CI: 1.02-1.52), but there was no significant difference between the catch-up growth group and the normal growth group (OR=0.79, 95%CI: 0.62-1.01). Stratified analysis showed that the association between different growth patterns and metabolic syndrome was statistically significant in the 7-12 years group, urban population, and Han Chinese student population.@*CONCLUSION@#There is a correlation between different growth patterns and metabolic syndrome in children and adolescents. The risk of developing metabolic syndrome in children and adolescents with catch-down growth is higher than that in the normal growth group, which suggests that attention should be paid to the growth and development of children and adolescents, timely correction of delayed growth and prevention of adverse health outcomes.
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Masculino , Feminino , Humanos , Criança , Adolescente , Síndrome Metabólica/epidemiologia , Estudos Transversais , Estudantes , População Urbana , Povo Asiático , China/epidemiologia , PrevalênciaRESUMO
OBJECTIVE@#To investigate the status of depression and social anxiety in children and adolescents, and to analyze the association between body fat distribution and depression, social anxiety in children and adolescents.@*METHODS@#A total of 1 412 children aged 7 to 18 years in Beijing were included by stratified cluster random sampling method. Body fat distribution, including total body fat percentage (total BF%), Android BF%, Gynoid BF% and Android-to-Gynoid fat ratio (AOI), were obtained by dual-energy X-ray absorption method. Depression and social anxiety were evaluated by Children Depression Inventory and Social Anxiety Scale for Children. Multivariate linear regression and restricted cubic spline analysis were used to estimate the linear and non-linear correlation between body fat distribution and depression and social anxiety.@*RESULTS@#13.1% and 31.1% of the children and adolescents had depressive symptoms and social anxiety symptoms respectively, and the detection rate of depression and social anxiety in the boys and young groups was significantly lower than those in the girls and old groups. There was no significant linear correlation between total BF%, Android BF%, Gynoid BF%, AOI and depression and social anxiety in the children and adolescents. However, total BF% and Gynoid BF% had significant nonlinear correlation with depression, showing an inverted U-shaped curve relationship with the tangent points of 26.8% and 30.9%, respectively. In terms of the nonlinear association of total BF%, Android BF%, Gynoid BF% and AOI with depression and social anxiety, the change trends of the boys and girls, low age group and high age group were consistent. The overall anxiety risk HR of body fat distribution in the boys was significantly higher than that in the girls, and the risk HR of depression and social anxiety were significantly higher in the high age group than those in the low age group.@*CONCLUSION@#There was no significant linear correlation between body fat distribution and depression and social anxiety in children and adolescents. Total BF% and depression showed an inverted U-shaped curve, mainly manifested in Gynoid BF%, and this trend was consistent in different genders and different age groups. Maintaining children and adolescents' body fat distribution at an appropriate level is the future direction of the prevention and control of depression and social anxiety in children and adolescents.
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Humanos , Feminino , Criança , Masculino , Adolescente , Estudos Transversais , Raios X , Depressão/epidemiologia , Absorciometria de Fóton/métodos , Índice de Massa Corporal , Distribuição da Gordura Corporal , Ansiedade/epidemiologia , Tecido Adiposo , Composição CorporalRESUMO
Objective:To investigate the risk factors of postoperative hypoxemia in patients admitted to intensive care unit (ICU) for resuscitation.Methods:Clinical data of 220 postoperative patients admitted to the ICU for resuscitation in Shandong Provincial Hospital Affiliated to Shandong University from June to August 2020 were collected and retrospectively analyzed. According to their oxygenation index within 30 minutes after admission to ICU, they were divided into hypoxemia group (oxygenation index≤ 300 mmHg, 1 mmHg≈0.133 kPa) and non-hypoxemia group (oxygenation index > 300 mmHg). Baseline data and perioperative indicators were compared between the two groups, and risk factors for early postoperative hypoxemia were analyzed. The improvement of oxygenation index of patients with hypoxemia in next morning after admission to ICU was observed, and the factors related to the improvement of hypoxemia were analyzed.Results:The incidence of hypoxemia was 36.8% (81/220) in the cohort. The majority cases of hypoxemia were from general surgery department, accounting for 42.0% (34/81). The incidence rate of hypoxemia from orthopaedic was the highest at 53.3% (16/30). Univariate analysis showed that body mass index (BMI), intraoperative hypoxemia, minimally invasive surgery were all risk factors of postoperative hypoxemia (test values were -2.566, 12.352 and 0.033; P values were 0.010, 0.000 and 0.019, respectively). Multivariate analysis showed that intraoperative hypoxemia and BMI were independent risk factors for postoperative hypoxemia [intraoperative hypoxemia: odds ratio ( OR) = 3.602, 95% confidence interval (95% CI) was 1.143-3.817, P = 0.001; BMI: OR = 1.119, 95% CI was 1.026-1.208, P = 0.036]. The improvement rate of hypoxemia next morning after admission to ICU was 63.0% (51/81). Pulmonary dysfunction was the independent risk factor for the improvement of hypoxemia ( OR = 0.200, 95% CI was 0.052-0.763, P = 0.019). Conclusions:Hypoxemia might occur early after surgery. Intraoperative hypoxemia and BMI were independent risk factors for postoperative hypoxemia.
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ObjectiveTo investigate the potential pharmacological mechanism of Xinmaikang tablets in the treatment of atherosclerosis cardiovascular disease by using network pharmacology and cell experimental validation. MethodThe components of Xinmaikang tablets were searched by BATMAN-TCM database and the active ingredients and potential targets were screened. The atherosclerosis related disease targets were searched in GeneCards and online mendelian inheritance in man(OMIM) disease databases. The therapeutic targets were obtained by mapping the intersection of the tablets and disease targets. Therapeutic targets were uploaded to STRING database to construct protein-protein interaction(PPI) network. Cytoscape software was used to create a "drug-active component-therapeutic target" network map, and a network topology algorithm was used to screen key action targets. David software was used for gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) function enrichment analysis. The key targets of drug therapy were validated by in vitro cell assay. ResultA total of 19 active ingredients, 132 potential targets and 4703 atherosclerotic disease-related target genes of Xinmaikang tablets were retrieved and screened, and 84 intersection targets were obtained. 3 key therapeutic targets of Xinmaikang tablets in the treatment of atherosclerotic diseases were screened, including Calmodulin 1(CALM1), voltage-dependent L-type calcium channel subunit alpha-1C(CACNA1C) and Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform(PIK3CA). A total of 313 biological processes, 89 molecular functions and 53 cell components were obtained by GO enrichment. A total of 40 pathways were obtained from KEGG functional enrichment, including purine metabolism, renin secretion, CGMP/PKG signaling pathway and so on. In vitro cell experiment results verified that Xinmaikang tablets can up-regulate the expression of CALM1 and CACNA1C, down-regulate the expression of PIK3CA, so as to inhibit the activity of inflammatory response, and play a therapeutic role in atherosclerotic diseases. ConclusionXinmaikang tablets may treat atherosclerosis cardiovascular disease through betulin, methyleugenol and other compounds, through purine metabolism, renin secretion, cGMP/PKG signaling pathway and other pathways, which acts on CALM1, CACNA1C, PIK3CA and other targets.
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The succession of microbiota is closely associated with several essential factors, including race, sex, health condition, lifestyle, postmortem interval, etc., and it has great potential application value in forensic medicine. This paper summarizes recent studies on the forensic applications of the microbiome, including individual identification, geographical feature identification, origin identification of the tissue or body fluid, and postmortem interval estimation, and introduces the current machine learning algorithms for microbiology research based on next-generation sequencing data. In addition, the current problems facing forensic microbiomics such as the extraction and preservation of samples, construction of standardization and database, ethical review and practical applicability are discussed. Future multi-omics studies are expected to explore micro ecosystems from a comprehensive and dynamic perspective, to promote the development of forensic microbiomics application.
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Humanos , Medicina Legal , Autopsia , Microbiota/genética , Algoritmos , Sequenciamento de Nucleotídeos em Larga Escala , Mudanças Depois da MorteRESUMO
Objective:To study the performance of immune reconstitution in patients with chimeric antigen receptor (CAR)-T cell immunotherapy bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 61 patients with acute B lymphocytic leukemia (B-ALL) who received CAR-T cell bridging allo-HSCT in Beijing Lu Daopei Hospital from August 2018 to December 2021 were enrolled, and the clinical medical records of the above patients were retrospectively analyzed. The average age was 14 (7, 30) years old, including 39 males and 22 females. 32 patients were treated with CAR-T cell immunotherapy(CAR-T Group) and 29 didn't with CAR-T cell immunotherapy(non-CAR-T group). The follow-up period was 561 (235,784) days. Multicolor flow cytometry was used to detect the peripheral blood lymphocyte subsets, i.e. total lymphocytes, T lymphocytes, helper T cells, cytotoxic T cells, B lymphocytes, NK cells, and Treg cell counts before transplantation and 1, 2, 3, 6, 8, 10, and 12 months after transplantation, to evaluate the immune reconstitution performance post allo-HSCT.Results:Serum globulin before transplantation: The IgA level in the CAR-T group was 0.18 (0.06, 0.49) g/L, which was lower than that of 1.03 (0.63, 1.56) g/L in the non-CAR-T group ( U=103.5, P<0.001). The IgG level in the CAR-T group was 5.54 (4.04, 7.09) g/L, lower than that of 6.78 (5.27, 9.26) g/L in the non-CAR-T group, ( U=1 298.5, P=0.017), and the IgM level in the CAR-T group was 0.18 (0.05, 0.30) g/L, lower than that of 0.40 (0.26, 0.71) g/L in the non-CAR-T group ( U=166.0, P<0.001). In the CAR-T group before transplantation, the absolute count of total lymphocyte in peripheral blood was 833.00 (335.00, 1 727.50) /μl, lower than that of 1 052.00 (545.75, 1 812.50) /μl in the non-CAR-T group ( U=404.0, P<0.001). The absolute count of T lymphocyte in the CAR-T group before transplantation was 686.00 (233.00, 1 307.00)/μl, lower than that of 860.00 (391.00, 1 419.75) /μl in the non-CAR-T group ( U=406.0, P<0.001). The absolute count of helper T lymphocytes in the CAR-T group was 146.00 (40.50, 327.50) /μl, lower than that of 162.50 (66.00, 384.75) /μl in the non-CAR-T group ( U=494.0, P=0.002). The absolute count of cytotoxic T lymphocytes in the CAR-T group was 343.00 (56.50, 924.00) /μl, lower than that of 478.00 (143.50, 992.25) /μl in the non-CAR-T group ( U=483.5, P=0.001). The absolute count of B lymphocytes in CAR-T group was 22.00 (6.00, 186.00) /μl, lower than that of 33.00 (8.00, 220.00) /μl in the non-CAR-T group ( U=498.0, P=0.002). And when two groups of patients were monitored after transplantation, there was no statistical difference in absolute cell counts of each immune cell subpopulation( P>0.05). Comparing the clinical features of the two groups, the pre-transplant history of the CAR-T group was 981.00 (368.50, 1 514.75) d, longer than that of 323.00 (167.50, 450.50) d in the non-CAR-T group ( U=263.0, P=0.004). The dose of rabbit anti-human thymic immunoglobulin (ATG) in the pretreatment protocol of patients in the CAR-T group was 5.00 (5.00, 7.50) mg/Kg, lower than that of 7.00 (5.00, 7.50) mg/kg in the non-CAR-T group ( U=288.5, P=0.018). The infusion dose of CD34 +cells in the CAR-T group was 5.91 (4.23, 6.02) ×10 6/kg, higher than that of 4.51 (4.00, 5.93)×10 6/kg in the non-CAR-T group ( U=291.0, P=0.012). The duration of the application of cyclosporine after transplantation in the CAR-T group was 167.00 (119.25, 299.50) d, which was shorter than that of 197.00 (102.50, 450.50) d in the non-CAR-T group ( U=421.0, P=0.001). Conclusions:For patients in CAR-T group with low immune function before transplantation, it may be possible to make them comparable to non-CAR-T group in immune reconstitution state by reducing the dose of pretreatment ATG, increasing the counts of CD34 + cells infusion in the graft, and discontinuing cyclosporine as soon as possible after transplantation.
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Objective: To explore the epidemiological characteristics and geographical distribution of unhealthy lifestyle among children and adolescents of Han nationality in China and obtain evidence for proposing the related strategies to improve the well-being of this population. Methods: Students aged 6-22 years old were selected from the Chinese National Survey on Students Constitution and Health in 2019. The prevalence of unhealthy lifestyles (physical inactivity, lack of outdoor activity, sedentary behavior, excessive screen time, sleep insufficiency, unhealthy eating behavior) between sex, residence, and age groups was calculated and compared. Multilevel logistic regression was used to explore the influencing factors of unhealthy lifestyle. Results: The prevalence of moderate-to-vigorous physical activity less than 1 h/d or 30 min/d were 82.06% and 54.69%, respectively. The prevalence of less than 2 h/d or 3 h/d of outdoor activities were 95.20% and 83.26%, respectively. The prevalence of more than 2 h/d or 3 h/d of sitting time were 50.64% and 31.92%, respectively. The prevalence of more than 2 h/d or 3 h/d of screen time were 42.02% and 27.79%, respectively. The prevalence of sleep insufficiency, excessive sugary beverages consumption (≥ 1 time/d), and insufficient consumption of eggs, milk, and breakfast (<7 d/week) were 66.49%, 20.97%, 83.36%, 70.71%, and 34.34%, respectively. The prevalence of severe sleep insufficiency, excessive sugary beverages consumption (≥ 3 times/d), and insufficient consumption of eggs, milk, and breakfast (≤2 d/week) were 27.77%, 8.21%, 47.21%, 32.36% and 9.73%, respectively. Conclusion: In 2019, unhealthy lifestyle is common among Han students aged 6-22 years in China. It is of importance to propose policies to strengthen the health education and initiatives to support healthy behaviors in Han children and adolescents. Jointly promotion on the creation of a healthy environment for Han children and adolescents, and formulation of targeted improvement measures in accordance with the epidemic characteristics in various regions are essential to improve the healthy lifestyle of this population.
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Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Prevalência , Privação do Sono , Etnicidade , Estilo de Vida , China/epidemiologiaRESUMO
Objective:To investigate the significance of multicolor flow cytometry (MFC) monitoring of minimal residual disease (MRD) in the course of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CD19-chimeric antigen receptor(CAR)-T cell immunotherapy for patients with refractory, relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL).Methods:37 patients with r/r B-ALL admitted to Hebei Yanda Lu Daopei Hospital from January to July 2019, aged 15 (6, 19) years old, including 24 males and 13 females, were treated with CD19-CAR-T cell immunotherapy bridging allo-HSCT. MFC with cytoplasmic CD79a antibody to set up B-cell gates was used to monitor patients′ bone marrow (BM), cerebrospinal fluid (CSF), and tissue samples on day 0 (prior to the CAR-T cell immunotherapy), day 15, day 28 post CAR-T cell immunotherapy, and post transplantation.The MRD values of these samples were analyzed to evaluate the residual tumor cells and metastasis. The killing effect of the CAR-T cells was evaluated by the recovery of CD19+B cells before transplantation and the period between the timepoint when CD19+B cells was recovered and the timepoint when CAR-T cells were infused. Peripheral blood CAR-T cells were counted at different time points. Statistic analysis was performed by Kaplan-Meie assay and Log-rank test to analyze the difference of univariate cumulative survival.Results:(1)Among the 37 patients, 8 died and 29 survived. 5 patients relapsed after transplantation, of which 4 relapsed patients died and 1 survived. (2)MFC MRD negative remission rate of the death group was lower than that of the survival group at the following time points: post-CAR-T therapy and prior to transplantation (5/8 vs. 28/29, χ 2=7.540, P=0.006); day 15 of the CAR-T cell reinfusion (3/8 vs. 24/29, χ 2=6.512, P=0.011); day 28 of the reinfusion (3/8 vs. 276/29, χ 2=10.065, P=0.002). The probability of extramedullary MFC MRD positive tumor infiltration in the death group was higher than that in the survival group(7/8 vs. 14/29, χ 2=3.931, P=0.047). After CAR-T cell immunotherapy, the recovery period of CD19-positive cells in the death group, or the time for CAR-T cells to kill CD19-positive cells, was shorter than that in the survival group [42.00 days(30.00,49.00) vs. 55.00 days(41.50,73.50), Z=0.022, P=0.020]. Conclusion:The positive results of MRD by MFC at the following timepoints may predict unfavorable outcomes, such as post-CAR-T therapy and prior to transplantation, day 15 and 28 of the CAR-T cell immunotherapy, which may provide some guidance for clinical management.
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Objective:To investigate the effectiveness of detecting MC B/P in PB by FCM for EBV+PTLD screening.Methods:481 patients with fever and large lymph nodes after allogenic hematopoietic stem cell transplantation (ALLO-SCT) in Ludaopi Hospital from 2018 to 2019 were retrospectively analyzed. The results of post-transplantation days, viral load (EBV, CMV) and MCB/P were detected. To evaluate the value of MC B/P in the diagnosis of PTLD by the sensitivity, specificity, positive predictive value and negative predictive. Logistic regression was used to analyze the clinical influencing factors of EBV-associated PTLD. The median fellow-up time was 449 days (range: 184 days to 700 days).Results:The diagnosis of PTLD was established in 51 patients. 55 patients who detecting MC B/P by FCM were positive. There were significant differences between the PTLD negative and positive groups in lymph node enlargement, age, EBV, CMV, monoclonal B cells, and monoclonal plasma cells ( P<0.05). Monoclonal plasma, monoclonal B and days after transplantation are important relationship with the diagnosis of PTLD, which have good diagnostic value for EBV-associated PTLD. Conclusion:FCM screening peripheral blood MC B/P has good diagnostic performance for EBV-associated PTLD. Monoclonal B, monoclonal plasma and the number of days of PTLD after transplantation were correlated with EBV-associated PTLD.
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Objective:This study aims to analyze the counts (per kilogram of body weight) or percentages of transplanted lymphocyte subgroups in children with non-infectious pulmonary complications (NIPC) and air-leak syndrome (ALS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explore its significance in the progression of lung complications after transplantation.Methods:The patients with NIPC and ALS after allo-HSCT from January 2013 to December 2019 in Hebei Yanda Ludaopei Hospital were retrospectively studied and the influencing factors in the progress of NIPC after HSCT were statistically analyzed.Results:Of the 2026 children who received HSCT treatment, 59 patients (34 males and 25 females) developed NIPC, the probability was 2.9% (59/2 026), and the probability of combined ALS was 1.4% (28/206). The differences in the comparison between NIPC progressed to ALS group (ALS group) and failed to progress to ALS group (non-ALS group) in the patient′s age( P=0.028), disease condition before transplantation( P=0.022), NIPC onset time( P=0.004) were significant. The P values of the percentage of NKT-like cells in the bone marrow ( P=0.008) or peripheral stem cells ( P=0.003) accounted for the lymphocytes. CD4+CD25+dim cells in bone marrow ( P=0.029) or peripheral stem cells ( P=0.036) accounted for the CD4+lymphocytes and the ratio of CD4/CD8 in bone marrow( P=0.004) or peripheral stem cells ( P=0.020) were less than 0.05, which meant the differences in patients′ refusion cells were significant. In the binary logistic regression model, the percentage of bone marrow NKT-like cells to lymphocytes, the ratio of bone marrow CD4+/CD8+and the percentage of peripheral stem NK cells to lymphocytes were important risk factors for the progression of NIPC to ALS. The rest factors were excluded from the model (AUC=0.918, P<0.05). Conclusion:During allo-HSCT transplantation, a high proportion of NKT-like cell and NK cell levels, and a high CD4+/CD8+ratio in the infusion of donors with high immune tolerance have an important correlation with the progression of the NIPC.
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OBJECTIVE@#To analyze the secular trend, ranking change, age- and regional- characteristics of leading infectious diseases among Chinese students population aged 6 to 22 years from 2008 to 2017.@*METHODS@#Data were drawn from the national surveillance from 2008 to 2017, and the participants were students aged from 6 to 22 years who were diagnosed with notifiable infectious diseases. A total of 40 infectious diseases were classified into three groups based on national notifiable infectious diseases classification of A, B and C. The morbidity and mortality rates from infectious diseases were calculated using the numbers of students published by the ministry of education as the denominator. The age- and province-specific infectious diseases with the highest incidence were selected as the leading infectious diseases for analysis.@*RESULTS@#From 2008 to 2017, the incidence rate, the number of cases and the number of deaths of infectious diseases among the boys aged 6-22 years in China were higher than that of the girls, and the overall trend was downward during the study period. The incidence rates in the boys and girls decreased from 2008 to 2015 with decrease of 43.4% and 40.1%, respectively. However, by 2017, the increase rate rebounded with the increases of 47.1% and 53.8%. The rebound trend was mainly caused by the increase of group C of infectious diseases. During the past decade, the top leading three diseases of groups A and B of infectious diseases were viral hepatitis, tuberculosis and dysentery in 2018, respectively, which changed to tuberculosis, scarlet fever and viral hepatitis in 2017. The top leading three infectious diseases in terms of mortality were rabies, tuberculosis, and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) in 2008, which were transformed into HIV/AIDS, rabies, and tuberculosis in 2017. There was no significantly obvious change in the incidence and mortality order of group C of infectious diseases during the decade. In the analysis of age groups and regions, the leading infectious diseases in groups A and B transferred from viral hepatitis to scarlet fever and tuberculosis, while in group C, mumps and infectious diarrhoea almost always dominated the leading infectious diseases. But in recent years, influenza and hand-foot-and-mouth disease increased significantly in the eastern region.@*CONCLUSION@#During the past decade, China has got remarkable achievements in the prevention and control of children infectious disease. However, the change patterns and characteristics of notifiable infectious diseases among children and adolescents show the urgent need for prevention and control of respiratory tract infectious diseases, HIV/AIDS and other sexually transmitted diseases as well as new emerging infectious diseases in China in the future. This study provides important basis for policy making of Chinese national school-based infectious disease prevention and control mechanism.
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Adolescente , Animais , Criança , Feminino , Humanos , Masculino , China/epidemiologia , Doenças Transmissíveis/epidemiologia , Incidência , Estudantes , TuberculoseRESUMO
OBJECTIVE@#To analyze the characteristics of the age at peak height velocity and peak height velocity of primary and middle school students in Zhongshan City, Guangdong Province, and to explore the law of the sudden increase in adolescent height in this area, and to understand the law of height growth spurt in adolescence by longitudinal tracking of the height of children and adolescents in Zhong-shan City.@*METHODS@#Based on the physical examination database of primary and middle school students in Zhongshan City, Guangdong Province from 2005 to 2016, individuals who had been continuously tracked for more than 6 times were selected as research samples. SITAR model was used to fit the height data of the sample population, and the age at peak height velocity and peak height velocity were calcula-ted.@*RESULTS@#A total of 49 579 subjects were included in this study, including 26 524 boys and 26 008 urban students. The median follow-up ages of boys and girls were 7.74 and 7.72 years, respectively. The boy's height spurt peak age was (12.72±0.89) years, and later than the girls at the age of (10.98±0.95) years (t=207.639, P < 0.001), the boy's height spurt peak velocity of (10.12±1.49) cm/year, higher than the girls of (8.35±1.12) cm/year (t=150.826, P < 0.001). The gender differences of height spurt peak age and height spurt peak speed in urban and rural students were consistent with the whole sample. The height surge peak age of urban male students was earlier than that of rural male students, and the height surge peak speed of urban female students was lower than that of rural female students.@*CONCLUSION@#The peak age of the surge of girls was earlier than that of boys, but the peak rate of the surge of girls was lower than that of boys, the peak age of urban students was earlier than that of rural students, but the peak rate of urban boys was lower than that of rural boys in Guangdong Province.