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Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and patho-logical conditions.Herein,airflow-assisted desorption electrospray ionization-MSI(AFADESI-MSI)was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone(AMI).High-coverage imaging of＞1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI.Following AMI treatment at different times,15 metabolites of AMI involved in N-desethylation,hydroxylation,deiodination,and desaturation metabolic reactions were identified,and according to their spatiotemporal dynamics features,the metabolic pathways of AMI were proposed.Subsequently,the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis.The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism,providing considerable evidence for the mechanism of AMI hepatotoxicity.In addition,a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI.The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal infor-mation for drugs,drug metabolites,and endogenous metabolites after AMI treatment,providing an effective tool for in vitro drug hepatotoxicity evaluation.
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Deconvolution of potential drug targets of the central nervous system (CNS) is particularly challenging because of the complicated structure and function of the brain. Here, a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging. This strategy can map various substances including exogenous drugs, isotopically labeled metabolites, and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways. The strategy revealed that the sedative-hypnotic drug candidate YZG-331 was prominently distributed in the pineal gland and entered the thalamus and hypothalamus in relatively small amounts, and can increase glutamate decarboxylase activity to elevate γ-aminobutyric acid (GABA) levels in the hypothalamus, agonize organic cation transporter 3 to release extracellular histamine into peripheral circulation. These findings emphasize the promising capability of spatiotemporally resolved metabolomics and isotope tracing to help elucidate the multiple targets and the mechanisms of action of CNS drugs.
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Objective:To investigate the effectiveness of postoperative radiotherapy using shrinking field for patients with extremity soft tissue sarcoma (STS), mainly focusing on the local control rate and adverse events.Methods:Clinical data of 49 extremity STS patients who received postoperative intensity-modulated radiotherapy in the First Hospital of Tsinghua University from October 2017 to March 2021 were retrospectively analyzed. Target volumes were contoured on CT and MRI fusion images. The tumor bed was defined as GTV tb, with 3 cm expansion in the longitudinal direction and 1.5 cm expansion in the radial direction to construct CTV (the target volume should be properly repaired according to the anatomical barrier, and the edema area around the tumor should be included). GTV tb and CTV were expanded in all directions by 0.5 cm to construct PTV1 and PTV2 respectively, at a dose of 95%PTV1 63-66 Gy, 95%PTV2 50-56 Gy,1.8-2.0 Gy/f. The dose of surgical volume should be given at 70 Gy for patients who had a microscopic positive margin. Results:The median follow-up time was 32.1 months (7.9-45.6 months). The 3-year local failure-free survival (LFFS), overall survival (OS)and distant metastasis-free survival (DMFS) were 91.7%,77.6% and 71.5%, respectively. Univariate analysis showed that patients with a microscopic positive margin were more likely to develop local recurrence ( P<0.05). The incidence of grade 2 or above wound complications, joint stiffness, fracture, edema and skin fibrosis were 2%, 4.1%, 2%, 8.2% and 26.5%, respectively. Conclusion:Postoperative radiotherapy with shrinking field provides excellent local control rate and low incidence of late adverse events in patients with extremity STS.
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Objective:To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) therapy in the primary prevention of concurrent chemoradiotherapy-induced neutropenia.Methods:In this single-center, open-label, single-arm clinical observation, the efficacy of PEG-rhG-CSF in the primary prevention of neutropenia after concurrent chemoradiotherapy in 58 patients admitted to Tianjin Medical University Cancer Institute and Hospital from June 2018 to June 2019 was evaluated.Results:During the whole concurrent chemoradiotherapy, chemotherapy delay occurred in 6 patients (10%). Three patients (5%) had delayed concurrent chemotherapy due to leukopenia or neutropenia. The completion rate of chemotherapy cycle was 94.6%(106/112). Radiotherapy delay occurred in 10 patients (17%) including 2 patients (3%) of delayed radiotherapy due to leukopenia or neutropenia. No patient developed febrile neutropenia (FN). Subgroup analysis found that after completing 1 cycle of concurrent chemoradiotherapy, the incidence rates of grade 4 leukopenia and neutropenia were both 0. After completing 2 cycles of concurrent chemoradiotherapy, the incidence rates of grade 4 leukopenia and neutropenia were 0 and 2%.Conclusion:During the chemoradiotherapy, application of PEG-rhG-CSF in the primary preventation can significantly reduce the incidence of FN, grade 4 leukopenia and neutropenia, which is beneficial to ensure the smooth progress of concurrent chemoradiotherapy.
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Objective:To investigate the clinical value of monitoring serum complement C1q/tumor necrosis factors-associated protein 3 (CTRP3) and lipoprotein-associated phospholipase A2(Lp-PLA2) levels in patients with coronary heart disease, especially patients with acute myocardial infarction (AMI).Methods:This case-control study included 99 patients with angina pectoris aged (60.4±10.4) years, 105 patients with AMI aged (61.7±14.3) years, and 60 healthy individuals aged (43.6±9.5) years. Serum CTRP3 was detected by ELISA, and Lp-PLA2 was detected by automatic biochemical analyzer. Logistic regression analysis was performed to determine the correlation between CTRP3, Lp-PLA2 in angina pectoris and AMI patients. The diagnostic efficiency of each index was analyzed by receiver operating characteristic (ROC) curve.Results:Serum Lp-PLA2 was significantly higher in AMI group than in angina pectoris group ([313.1±68.1] U/L vs [205.8±71.4] U/L, P<0.001), while CTRP3 was significantly lower in AMI group than in angina pectoris group ([64.2±18.5] μg/L vs [84.8±25.0] μg/L, P<0.001). Logistic regression showed that serum CTRP3 was negatively correlated with AMI ( OR=0.964, 95% CI 0.935-0.993, P=0.019), and Lp-PLA2 was positively correlated with AMI ( OR=1.020, 95% CI 1.008-1.032, P=0.001). ROC analysis showed that the AUC (95% CI) of AMI diagnosed by CTRP3 was 0.753 (0.685-0.821), P<0.001; the AUC (95% CI) of AMI diagnosed by Lp-PLA2 was 0.884 (0.833-0.935), P<0.001; the AUC (95% CI) of diagnosis efficacy by combined indices was 0.910 (0.870-0.950), P<0.001. Conclusions:Lower serum CTRP3 and higher serum Lp-PLA2 levels are associated with increased risk for AMI. Combined detection of both indices can improve the diagnostic efficacy of AMI.
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Objective:Analysis of the oxidative products of DNA and RNA in patients with hypertension by determination of 8-oxo Gsn and 8-oxo dGsn, respectively.Methods:This is an observational study. During August and December, 2018, 139 hypertension patients without other chronic diseases with an average age of (49.6±12.4) years old, and 139 apparently healthy volunteers without hypertension with an average age of (48.5±11.7) years old were recruited. Fasting morning urine were collected. The oxidative products of DNA: 8-oxo Gsn and the products of RNA: 8-oxo dGsn were analyzed using liquid chromatography tandem mass spectrometry. Urine Cr(U-Cr), and other serum biomarkers such as ALT, Cr, UA, Glu, TG, TC were analyzed using automatic biochemical analyzers.Results:of 8-oxo Gsn and 8-oxo dGsn were presented as median(quartile). Statistical analysis was performed using SPSS 22.0 and GraphPad Prism 5. Nonparametric test was used to compare the difference of 8-oxo Gsn and 8-oxo dGsn between the hypertension patients and the healthy controls. Results The DNA and RNA oxidative products of 8-oxo Gsn and 8-oxo dGsn in patients with hypertension and their U-Cr-corrected 8-oxo Gsn/U-Cr and 8-oxo dGsn/U-Cr were 14.38(10.39-19.91)ng/ml, 12.97(7.92-18.96)ng/ml, 1.10(0.88-1.38)μg/μmol and 0.96(0.75-1.30) μg/μmol, respectively, which were significantly higher than those in the healthy controls: 11.95(7.52-18.01) ng/ml, 10.12(6.42-15.04) ng/ml, 0.86(0.59-1.21) μg/μmol and 0.72(0.50-1.02) μg/μmol, respectively. After grouped by sex, 8-oxo Gsn in males, 8-oxo Gsn and 8-oxo dGsn in females showed no significant difference between patients with hypertension and healthy controls, however, after U-Cr correction, both males′ and females′ 8-oxo Gsn/U-Cr and 8-oxo dGsn/U-Cr in patients with hypertension were higher than that in the healthy controls.Conclusion:The oxidative products of DNA and RNA in patients with hypertension were significantly higher than that in healthy controls.
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OBJECTIVE@#To explore the characteristics of differentially methylated genes and gene ontology associated with neural tube defects (NTDs).@*METHODS@#Twelve subjects from 3 NTDs pedigrees were enrolled. Patients with NTDs have served as the case group, while their family members with normal phenotypes have served as the control group. Genomic DNA was extracted from peripheral venous blood samples of the families and used for DNA methylation analysis. Pairwise comparison was carried out primarily for patient-offspring pairs, and co-segregation of methylation pattern with NTDs was analyzed. Pathway related to differentially methylated genes was predicted with DAVID software.@*RESULTS@#Pairwise comparison indicated that VTRNA2-1 was the only gene in which all CpG sites were methylated. Co-segregation of VTRNA2-1 gene methylation with NTDs was found in all pedigrees. Pathways of hypermethylated genes included plasma membrane component, regulation of cellular protein metabolic process, and regulation of actin cytoskeleton organization, while the pathways of hypomethylated genes have included transcription regulator activity, cell adhesion, and neuronal differentiation.@*CONCLUSION@#Methylation of the VTRNA2-1 gene has co-segregated with NTDs in the studied pedigrees. The pathways of differentially methylated genes has involved with mechanism of neural tube development.
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Humanos , Islas de CpG , Metilación de ADN , Ontología de Genes , MicroARNs , Genética , Defectos del Tubo Neural , Genética , LinajeRESUMEN
Objective To explore the value of ultra-high b-value diffusion-weighted imaging(DWI) in diagnosis of prostate cancer. Methods According to inclusion and exclusion criteria, 73 consecutive examinees in Chinese PLA General Hospital from June 2014 to May 2015 were screened. Written informed consent was obtained from all patients. T2WI, conventional DWI with b-value of 1 000 s/mm2and ultra-high b-value DWI with 2 000 s/mm2and 3 000 s/mm2were performed in each examinee. Images were interpreted and were corresponding to histological results conducted by ultrasound guided prostate systematic biopsy. Reference biopsy as the gold standard,the sensitivity,specificity, positive predictive value(PPV) and negative predictive value (NPV) were calculated for each image. Sensitivity and specificity differences between ultra-high b-value DWI and conventional DWI were analyzed. The areas under the curves (AUCs) between ultra-high b-value DWI and other modalities were compared. Results The sensitivity and specificity for ultra-high b-value DWI were 92.5 % and 68.8 % with b-value of 3 000 s/mm2, and they were 88.1 % and 53.1 % for 2 000 s/mm2in peripheral zone. The sensitivity and specificity for ultra-high b-value DWI were 88.0 % and 88.2 % with a b-value of 3 000 s/mm2, and they were 80.0 % and 52.9 % for 2 000 s/mm2in transition zone. The values of sensitivity for ultra-high b-value DWI were significantly higher than those for conventional DWI both in peripheral zone and transition zone (all P <0.000 1). The detection of lesions was comparable with ultra-high b-value DWI at 2 000 s/mm2and 3 000 s/mm2in peripheral zone (P >0.05), whereas the value of specificity for 3 000 s/mm2were significantly higher than that for 2 000 s/mm2in transition zone (P<0.000 1). PPV and NPV for 3 000 s/mm2were significantly higher than those for the other three modalities both in peripheral zone(86.1 % and 81.5 %) and transition zone (91.7 % and 83.3 %). In peripheral zone, the AUCs were 0.591, 0.553, 0.698 and 0.806 in T2WI, conventional DWI and ultra-high b-value DWI at 2 000 s/mm2 and 3 000 s/mm2respectively, for the diagnosis of transition zone cancer were 0.693, 0.506, 0.665 and 0.881 respectively, and the AUCs for the ultra-high b-value with 3 000 s/mm2were the largest. Conclusion Ultra-high b-value DWI is an accurate and reliable method in the diagnosis of prostate cancer.
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Objective To strengthen the understanding of granulocytic sarcomas(GS)by investigating the clinical characteristics of GS of spine. Methods The clinical data of 2 GS patients were retrospectively analyzed, and the related literature was reviewed. Results Because of the double lower limbs numbness, the 2 GS patients came to orthopedics department of the 306th Hospital of PLA. Magnetic resonance imaging (MRI) of the 2 patients showed an epidural mass located at the 9th-11th and 2nd-4th thoracic levels. Their histopathological examination and immunohistochemistry revealed GS.For example 1,she was diagnosed with acute promyelocytic leukemia(APL)and has been morphologic complete commission(CR) from 1995 to 2015. Chemotherapy and all-trans retinoic acid (ATRA) were performed after extramedullary relapse in thoracic spine,breast,ovary,sternum bone and lymph nodes.So far,the patient is still in follow-up.For example 2,he was diagnosed as isolated GS by morphology, immune phenotype, chromosome and gene examinations. Because he refused chemotherapy, radiotherapy was performed after surgical intervention. So far, he is loss of follow-up. Conclusions Spinal epidural of GS is rare. Surgery can reduce or remove nerve compression symptoms, and help clear diagnosis. The current recommended treatment regimen in patients presenting with isolated GS or GS presenting concomitantly with AML is conventional AML-type chemotherapeutic protocols. The differences in prognosis of GS patients may be partially attributed to different characteristics of patient.
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Upconversion nanomaterials (UCNPs) have attracted much attention in recent years due to their unique advantages.Compared to the traditional luminescence materials,UCNPs could convert low energy near-infrared excitation light into ultraviolet and visible light,which have some advantages,such as strong tissue penetration,low cytotoxicity,and weak background fluorescence.Combined with high resolution CT and MRI,UCNPs make multimodality imaging and accurate treatment possible.This review summarizes the research progress of UCNPs in biological imaging and cancer therapy.
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With the rapid development and wide application of traditional Chinese medicine injection (TCMI), a number of adverse events of some TCMIs have incessantly been reported and have drawn broad attention in recent years. Establishing effective and practical analytical methods for safety evaluation and quality control of TCMI can help to improve the safety of TCMIs in clinical applications. In this study, a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the quantitative determination of potentially harmful substance 5,5'-oxydimethylenebis (2-furfural, OMBF) in TCMI samples. Chromatographic separation was performed on a C18 reversed-phase column (150 mm × 2.1 mm, 5 µm) by gradient elution, using methanol-water containing 0.1% formic acid as mobile phase at the flow rate of 0.3 mL/min. MS/MS detection was performed on a triple quadrupole mass spectrometer with positive electrospray ionization in the multiple reaction-monitoring mode. The method was sensitive with a limit of quantification of 0.3 ng/mL and linear over the range of 0.3-30 ng/mL (=0.9998). Intra- and inter-day precision for analyte was <9.52% RSD with recoveries in the range 88.0-109.67% at three concentration levels. The validated method was successfully applied to quantitatively determine the compound OMBF in TCMIs and glucose injections. Our study indicates that this method is simple, sensitive, practicable and reliable, and could be applied for safety evaluation and quality control of TCMIs and glucose injections.
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Recently clinical MR contrast media consists mainly of gadolinium based small molecule complexes,such as Gd-dTPA,Gd dOTA,etc,but small molecule complexes are defective in the relaxation and early diagnosis.With the development of nanotechnology,molecular nanoprobes not only have the advantages of small particle size,good biocompatibility,enhanced penetration and retention (EPR) effect and long half-life,but also their relaxation rates are higher than that of common gadolinium contrast media.The application of current MR molecular probe,such as liposomes,dendrimers,mesoporous silica,polymer micelles,carbon nanotubes,nano-gold and paramagnetic nanoparticles were mainly introduced in this paper.
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Objective To investigate the methylation alteration of genomic DNA (gDNA) and its significance in pedigree neural tube defects (NTDs).Methods Twelve subjects from 3 NTDs pedigrees were enrolled in this study.NTDs patients were served as the case group,and their family members with normal phenotype were served as the control group.Peripheral vein blood was extracted,then gDNA was extracted.The extracted gDNA was treated with sodium bisulfite propagated as DNA segments in the way of whole genome amplification,which was put in I11umina Infinium human methylation 450k bead chip to perform hybridization,elution,extension,and imaging.The chip was scanned by iScan.Genome Studio was used to read the outcome.Illumina methylation analyzer software was used to analyze the methylation data.Results Gene differential methylation analysis showed that differential methylation sites only accounted for 0.2％ of the detected CpG sites and there were 617 differential hypermethylation sites (P ＜ 0.05),and 63 of them represented significant difference(P ＜ 1 × 10-4),including zinc finger E-box binding homebox 2,5,10-methylenetetrahydrofolate dehydrogenase 1 etc;there were 104 differential hypomethylation sites (P ＜ 0.05),and 65 of them represented significant difference (P ＜ 0.01),including Homeobox B7 and runt-related transcription factor 3 etc.Clustering analysis indicated that the tendency of DNA hypermethylation was consistent with NTDs patients,but the tendency of DNA hypomethylation was consistent with the controls.Conclusion In NTDs pedigree,the abnormal DNA methylation alterations may be the risk factor for NTDs occurrence.
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OBJECTIVE:To compare the differences between artificially cultivated and wild Xinjiang Artemisia rupestris,and screen the different components. METHODS:HPLC-MS was adopted to establish the fingerprints of artificially cultivated and wild Xinjiang A. rupestris from different origin and harvest time. Principal component analysis was conducted by Marker ViewTM soft-ware and SIMCA-P 11.5 software,the characteristics of principal components were analyzed,difference variable was screened, and different components of artificially cultivated and wild varieties were obtained. RESULTS:Fingerprints of 22 batches of A. rup-estris(12 batches of wild varieties,10 batches of artificially cultivated varieties)were established. According to the principal com-ponent analysis,artificially cultivated and wild varieties were well grouped,with obvious differences;the principal components of artificially cultivated varieties with different harvest time showed certain difference,mainly before and after flowering,concentrat-ing in to-be flowering and full flowering periods. Wild varieties from different origins had obvious regional difference,showing cer-tain differences in composition and content. 268 variables were found in matrix of positive ion mode and 155 in negative ion mode. 28 groups of variables were extracted by difference variable,and 19 variables were determined. CONCLUSIONS:Artificially culti-vated and wild varieties have obvious difference in principal component,mainly in flowering period and picking places. It can pro-vide theoretical basis for the standardized cultivation and origin protection of Xinjiang A. rupestris.
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Objective:To explore the adjustment factors to the migration and functional activity on macrophages in the uterine of inflammatory mice induced by LPS.Methods:150 Kunming female mouse were divided into control group (group A),LPS model group (group B),MCP-1 blocking-up group (group C),the mice uterines were extracted separately at hour 1,3,6,12,24.The number of CD14+ macrophages and the expression of CD14 macrophages were detected by Immunohistochemistry,ELISA detects the expression of TNF-α and MCP-1.Results:①Compared with group A,the number of CD14+ macrophages and the expression of CD14 in endometrium,myometrium,perimrtrium of group B were highly significantly increased (P<0.01) at every time points,the endometrium,myometrium of group C were closely to normal level at 1,3,6 h;compared with group B,the number of CD14+ macrophages and the expression of CD14 were highly significantly decreased(P<0.01)at 1,3,6 h of perimrtrium of group C and every time points of endometrium,myometrium of group C.②Compared with group A,the content of TNF-α and MCP-1 were highly significantly increased (P<0.01) at every time points of group B and 12,24 h of group C;compared with group B,the content of TNF-α and MCP-1 of group C were highly significantly decreased(P<0.01) at every time points.Conclusion:The migration of macrophages and the expression of CD14 and TNF-α in the uterine of inflammatory mice induced by LPS were regulated by MCP-1.
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Objective To investigate the correlation between neural tube defects (NTDs) and DACT1 gene, and provide the basic data for disease diagnosis and genetic counseling. Methods Blood samples were obtained from 163 NTDs patients and 480 unrelated healthy individuals. Mutation detection of DACT1 gene and DNA direct sequencing was carried out by PCR amplification. Bioinformatics analysis of these mutated loci was performed. Results Six mutations were found in NTDs patients, including 4 missense mutations (p.R45W, p.D142G, p.N356K and p.V702G). But these mutations were not found in 480 healthy individuals. Three mutated amino acid residues (p.45R, p.142D and p.356N) were highly conservative in evolution, and the mutated carriers were female patients, and suffered from anencephaly. Conclusion DACT1 gene mutation may be a risk factor of NTDs in Han population of northern China.
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In this paper,we analyzed one case of primary multifocal extranodal non-Hodgkin's lymphoma and reviewed the related literatures.We investigated the clinical data of this case with primary multifocal extranodal lymphoma and retrospected the related references.The key words,primary extranodal lymphoma and multifocal,were used to search Pubmed and Wanfang Database,and finally only three cases were found.The 68-yea-old woman was confirmatively diagnosed as primary multifocal extranodal B cell non-Hodgkin's lymphoma.The positron emission tomography/computed tomography (PET/CT) scan showed multiple hypermetabolic lesions in the left humerus,both kidneys and ileum.The confirmative diagnosis was based on clinical manifestations and serological tests,imaging features of CT and PET/CT,and especially on the histopathological and immunohistochemical studies.After one cycle chemotherapy (rituximab,Vincristine and prednisone) and another cycle (rituximab,Vincristine,cyclophosphamide and prednisone),a repeat PET/CT scan showed a complete metabolic resolution of the lesions in the kidneys and ileum,and a partial metabolic resolution of the left humerus.After four cycles of chemotherapy,there were new extensive involvements of the right supraclavicular and intrapulmonary lymph nodes,bilateral pleural and pericardium,and the patient gave up chemotherapy.This case demonstrated the imaging findings of an uncommon primary multifocal extranodal lymphoma in left humerus,both kidneys and ileum,and highlighted the usefulness of CT and PET/CT scan in identifying the extent of disease involvement,in guiding a biopsy,and in assessing the treatment response of lymphoma.It is essential to differentiate between primary multifocal extranodal lymphoma and lymphoma extensive metastases.
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Objective To analyze the vitamin D status among apparently healthy younger and elder adults in Beijing based on liquid chromatography tandem mass spectrometry.Methods This is an observational study.Participants included 287 apparently healthy young adults(143 males and 144 females) with an average of (32.2 ± 6.9) years old (19-44 years).At the same time 198 middle-and elder-aged adults were recruited [90 males,108 females,(55.6 ± 7.6) years],and fasting blood samples were collected and serum were isolated.They measured 25-hydroxyvitamin D (25OHD:25OHD2 and 25OHD3)using liquid chromatography tandem mass spectrometry method.Vitamin D with deficiency,insufficiency,sufficiency and intoxication was categorized as 25OHD ＜ 20 ng/ml,20-30 ng/ml,30-150 ng/ml,and ≥ 150 ng/ml,respectively.ALT,Ca,P,Cr,Glu,TG,TC and iPTH wereanalyzed using automatic analyzers.Statistical analysis was performed using SPSS17.0.Results The median 25OHD level in the total studied younger adults was 16.0 [2.5％-97.5％:(6.1-29.0) ng/ml] which didn't show significant difference with that of middle-and elder-aged adults.Younger males had significant higher level of 25OHD than females [17.9 (8.3-32.3) ng/ml vs.14.4 (5.4-26.4) ng/ml,Z =-4.238,P ＜ 0.01].Of the total younger subjects,the rate of vitamin D with deficiency (＜ 20 ng/ml),insufficiency (20-30 ng/ml)and sufficiency (≥30 ng/ml) was 72.8％,25.1％,2.1％,respectively,while that of middle-and elderaged adults was 76.3％,21.2％,2.5％ respectively,and that of younger males was 65.0％,30.8％,4.2％,respectively while that of younger females was 80.6％,19.4％,0％,respectively.Younger females had significantly higher rate of 25OHD deficiency (x2 =31.766,P ＜ 0.01).With adjusting sex,age and BMI,serum iPTH (r =-0.264,P ＜ 0.01) was significantly negatively correlated with 25OHD while Cr (r =0.221,P ＜ 0.01) showed significantly positively correlation with 25OHD.Conclusion Vitamin D deficiency is prevalent in both younger and elder adults in Beijing,especially in younger females.
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Recently clinical MR contrast media consists mainly of gadolinium based small molecule complexes,such as Gd-dTPA,Gd dOTA,etc,but small molecule complexes are defective in the relaxation and early diagnosis.With the development of nanotechnology,molecular nanoprobes not only have the advantages of small particle size,good biocompatibility,enhanced penetration and retention (EPR) effect and long half-life,but also their relaxation rates are higher than that of common gadolinium contrast media.The application of current MR molecular probe,such as liposomes,dendrimers,mesoporous silica,polymer micelles,carbon nanotubes,nano-gold and paramagnetic nanoparticles were mainly introduced in this paper.
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Objective To investigate the methylation alteration of genomic DNA (gDNA) and its significance in pedigree neural tube defects (NTDs).Methods Twelve subjects from 3 NTDs pedigrees were enrolled in this study.NTDs patients were served as the case group,and their family members with normal phenotype were served as the control group.Peripheral vein blood was extracted,then gDNA was extracted.The extracted gDNA was treated with sodium bisulfite propagated as DNA segments in the way of whole genome amplification,which was put in I11umina Infinium human methylation 450k bead chip to perform hybridization,elution,extension,and imaging.The chip was scanned by iScan.Genome Studio was used to read the outcome.Illumina methylation analyzer software was used to analyze the methylation data.Results Gene differential methylation analysis showed that differential methylation sites only accounted for 0.2％ of the detected CpG sites and there were 617 differential hypermethylation sites (P ＜ 0.05),and 63 of them represented significant difference(P ＜ 1 × 10-4),including zinc finger E-box binding homebox 2,5,10-methylenetetrahydrofolate dehydrogenase 1 etc;there were 104 differential hypomethylation sites (P ＜ 0.05),and 65 of them represented significant difference (P ＜ 0.01),including Homeobox B7 and runt-related transcription factor 3 etc.Clustering analysis indicated that the tendency of DNA hypermethylation was consistent with NTDs patients,but the tendency of DNA hypomethylation was consistent with the controls.Conclusion In NTDs pedigree,the abnormal DNA methylation alterations may be the risk factor for NTDs occurrence.