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In this study, hollow mesoporous silica (HMSN) was created to facilitate drug distribution using the hard template method. The oxidized hyaluronic acid (oxiHA) was coated on the carrier surface by the Schiff base reaction, producing the pH-responsive nanoparticles HMSNs-DOX-oxiHA targeted by CD44 and preventing drug leakage from mesopores. The prepared nanoparticles had a size of 151.79 ± 13.52 nm and a surface potential of -8.42 ± 0.48 mV. The rich mesoporous structure and internal cavity of HMSNs-NH2 achieved the effective encapsulation and loading rates of doxorubicin (DOX) at 76.84 ± 0.24 % and 18.73 ± 0.05 %, respectively. Owing to the pH sensitivity of imine bonds, HMSNs-DOX-oxiHA has a good pH response and release performance. The in vitro experiments showed that the nanoparticles were not cytotoxic and could enhance HCT-116 uptake efficiency by hyaluronic acid/CD44 receptor-mediated endocytosis, effectively inhibiting tumor cell proliferation and reducing toxic side effects on normal cells. In summary, the polysaccharide-based nano-drug delivery system constructed in this experiment not only has the basic response properties of a carrier but also introduces the bioactive advantages of natural polysaccharides.
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Antineoplásicos , Nanopartículas , Ácido Hialurónico/química , Dióxido de Silicio/química , Antineoplásicos/farmacología , Doxorrubicina/farmacología , Doxorrubicina/química , Nanopartículas/química , Concentración de Iones de Hidrógeno , Porosidad , Sistemas de Liberación de Medicamentos , Liberación de FármacosRESUMEN
Tic disorder (TD) is a neurodevelopmental disorder that starts in childhood with tics as its primary clinical manifestation.It is a group of movement disorders with unknown causes.At present, the main pathogenic genes of TD have not been identified.In this paper, TD neurotransmitter-associated susceptibility genes ( DRD2, DRD4, SLC6A4, HDC, ADRA2A), related susceptibility gene variations ( ASH1L, CELSR3, PNKD, NRXN1, CNTN6), and other susceptibility genes ( FLT3, SLITRK1) were reviewed to provide references for the precision treatment based on gene variations.
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Objective To analyze the influence of intraoperative blood glucose fluctuation and postoperative insulin resistance(IR)on postoperative cognitive dyfunction(POCD)in elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia.Methods A total of 352 elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia were collected and divided into the POCD group(n=84)and the non-POCD group(n=268).The covariates between the two groups were balanced by propensity score matching method(PSM).Eighty-four cases in each group were successfully matched.The data between the two groups before and after PSM were compared.After PSM,receiver operating characteristic(ROC)curve of blood glucose fluctuation amplitude for predicting POCD was drawn,and patients were divided into the low-level blood glucose fluctuation group(n=97)and the high-level blood glucose fluctuation group(n=71)according to the cut-off value.According to the existence of postoperative IR,patients were divided into the IR group(n=53)and the non-IR group(n=115).Then,incidences of POCD between groups were compared.Logistic regression was used to analyze the influencing factors of POCD.Results Before PSM,the POCD group had older age,higher blood glucose fluctuation amplitude,IR ratio,operation time,anesthesia time,propofol dosage,remifentanil dosage and sufentanil dosage in anesthesia maintenance period than those in the non-POCD group(P<0.05).The POCD group had higher blood glucose fluctuation amplitude and IR ratio than those in the non-POCD group after PSM(P<0.05).After PSM,the incidences of POCD in the high-level blood glucose fluctuation group and the IR group were higher than those in the low-level blood glucose fluctuation group and the non-IR group(P<0.05).Logistic regression analysis showed that higher intraoperative blood glucose fluctuation(OR=9.140,95%CI:4.338-19.257)and postoperative IR(OR=4.034,95%CI:1.163-13.991)were risk factors of POCD.Conclusion The risk of POCD in elderly patients undergoing thoracoscopic radical lung cancer surgery under general anesthesia is increased in patients with higher intraoperative blood glucose fluctuation and postoperative IR.
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Objective:To investigate the association between regional white matter hyperintensity (WMH) volumes and cognitive impairment in Parkinson′s disease (PD) patients.Methods:The consecutive samples of PD cohort between October 2018 and August 2019 from the Department of Movement Disorders, Beijing Tiantan Hospital, Capital Medical University were retrospectively analyzed. Demographic and disease profiles, three-dimensional brain magnetic resonance imaging data were collected. Cognition was evaluated by Mini-Mental State Examination (MMSE), and mood was evaluated by Hamilton Anxiety Scale and Hamilton Depression Scale (HAMD). According to the MMSE score, patients were divided into PD with dementia group and PD without dementia group. WMH volume was automatically calculated using unidentified bright objects detector pipeline based on anatomical autonomic labeling atlas. Firstly, demographic and disease profiles, and WMH total volume were compared between groups with and without dementia. Then, partial correlation analysis [false discovery rate (FDR) corrected] and principal component (PC) regression analysis were used to assess the association between regional WMH volumes and the MMSE score.Results:Compared with PD without dementia group, PD with dementia group showed significantly higher WMH volume [5 125 (2 727, 13 718) mm 3vs 3 214 (1 959, 7 205) mm 3, Z=-2.256, P=0.024]. After adjusting for age, low density lipoprotein, cholesterol, and HAMD score, partial correlation analysis (FDR corrected) showed that WMH volumes in the right calcarine ( r=-0.204, PFDR-corrected=0.034), the right fusiform ( r=-0.180, PFDR-corrected=0.046), the right lingual ( r=-0.146, PFDR-corrected=0.047), the left middle temporal ( r=-0.168, PFDR-corrected=0.047), the left inferior parietal lobes ( r=-0.145, PFDR-corrected=0.047) and the right inferior parietal lobes ( r=-0.148, PFDR-corrected=0.047) were significantly associated with MMSE score. PC regression analysis demonstrated that MMSE score was significantly associated with PC2 ( B=-0.632, 95% CI -1.222--0.041, P=0.036), PC13 ( B=-1.384, 95% CI -2.155--0.613, P=0.001), and PC14 ( B=-0.913, 95% CI -1.599--0.227, P=0.009); PC2, PC13 and PC14 were mainly composed of temporo-parieto-occipital WMHs in the posterior brain, and the related WMH components accounted for 9.668% of WMH variance. Conclusions:The posterior WMH burden may be associated with cognitive impairment in PD patients. However, WMH burden may not be the main contributor to cognitive impairment in PD patients.
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BACKGROUND: Pleural effusion (PE) is a common clinical feature that presents a diagnostic challenge for clinicians. In this retrospective study, we aimed to assess the biomarkers, ratios, and multiple indicators in serum and Pleural effusion for the differential diagnosis of tuberculous pleural effusion (TPE) from non-tuberculosis effusion (non-TPE). METHODS: The participants, who were divided into two groups: TPE and non-TPE (MPE and PPE), from Ningbo First Hospital, were incorporated in this study. The clinical and laboratory features were collected and analyzed using logistic regression analysis. Twelve biomarkers and their ratios in serum and PE were investigated for TPE versus non-TPE. Additionally, the value of multiple indicators for joint diagnosis was estimated. RESULTS: Biomarkers and ratios showed good diagnostic performance. The five variables including Serum ADA, IGRA, Effusion ADA, Effusion ADA/Serum ADA and Effusion LDH/Effusion ADA were identified as valuable parameters for differential diagnosis of TPE from non-TPE. The combined diagnosis of the five indexes yielded the highest diagnostic accuracy for TPE with an AUC (0.919), sensitivity (90.30%), and specificity (94.50%). CONCLUSIONS: The biomarkers and ratios demonstrated strong diagnostic performance, and the utilization of multiple indicators for joint diagnosis can improve the diagnostic efficacy of tuberculous pleurisy.
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Derrame Pleural , Tuberculosis Pleural , Humanos , Estudios Retrospectivos , Adenosina Desaminasa/análisis , Derrame Pleural/diagnóstico , Biomarcadores , Tuberculosis Pleural/diagnóstico , Diagnóstico DiferencialRESUMEN
BACKGROUND@#Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC).@*METHODS@#We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays.@*RESULTS@#The abundance of fecal Veillonella parvula ( V . parvula ) decreased significantly after BBR administration ( P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect.@*CONCLUSION@#BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula , thereby blocking the development of colorectal tumors.@*TRIAL REGISTRAION@#ClinicalTrials.gov, No. NCT02226185.
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Animales , Humanos , Berberina/uso terapéutico , Carcinogénesis , Veillonella , Neoplasias Colorrectales/genética , Microambiente TumoralRESUMEN
Tic disorders is a neurodevelopmental disorder that occurs in childhood. Its etiology and pathogenesis are not yet fully understood, and immune factors are currently a hot and difficult research topic. This article reviews the risk factors, neuroimmune factors, peripheral immune factors, and other related immune pathogenesis and new advances in immunotherapy for Tourette′s syndrome.
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Objective:To determine the regional boundary of para-aortic lymph node (PAN) metastasis in cervical cancer, and to explore the clinical target volume (CTV) margin.Methods:Eight-six patients with cervical cancer metastasis to PAN below and above left renal vein (LRV) were retrospectively included in this study. The anatomical relationship of the metastatic PANs and surrounding structures were analyzed according tocontrast-enhanced computed tomography (CT) and three dimensional reconstruction images.Results:Eight-six patients had metastatic PANs belowLRV: metastatic nodes were located onthe medial side of ovarian vessels and ureters, behind the renal veins, duodenum, mesenteric vessels, in front of the anterior border of lumbar vertebra and psoas. The inferior mesenteric vein was close to the left anterior side of PANs. Where the duodenum appeared, no node was presenton the anterolateral side of the inferior vena cava (IVC).Above the LRV, 27 patients had retrocrural node involvement along the azygos and hemiazgos vein, and 25/27 cases were located below the junction level of cardia and oesophagus, and 5/27 patients had metastatic lymph nodes between IVC and the right crura of diaphragm, all below the level of coeliac trunk artery.Conclusions:CTV margin delineation of PAN below and above LRV is recommended:superiorly, the junction level of cardia and oesophagus; laterally, crura and the medial side of ovarian vessels and ureters and inferior mesenteric vein; anteriorly, the posterior side of the coeliac trunk artery and renal veins and duodenum, mesenteric vessels; posteriorly, the anterior border of lumbar vertebra and psoas.
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Capsule endoscopy is one of the main diagnostic methods of small bowel diseases. In small bowel capsule endoscopy, the main factors that influence the diagnostic rate of diseases include gastrointestinal examination completion rate and intestinal preparation, etc. The upper gastrointestinal transit time is one of the main influence factors of examination completion rate. This article reviewed risk factors and clinical management of prolonged upper gastrointestinal transit time in capsule endoscopy.
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Objective:To investigate the effects of iron deficiency in early life on neurobehavioral manifestations in CDH2 genetic mutation rats, in order to explore interaction between iron deficiency and CDH2 gene mutation in autism-like behavior.Methods:The 16 female SD rats with established CDH2 genetic mutations were randomly divided into 8 rats as iron deficiency group and 8 rats as normal diet control group.After mating, rats were fed low-iron diets during pregnancy and lactation or standard diets as control.The offsprings were randomly divided into 27 rats as iron deficiency group and 27 rats as control group.The voice communication ability of offspring was studied through ultrasonic vocalizations.The data and videos of open-field test, three-chamber social interaction test were recorded by animal behavioral video analysis system(Smart3.0). The characteristics of behavior changes were analyzed by statistical methods.Results:Total number of calls in rats aged 10 day in iron deficiency group[(755.67±161.86)times]were significantly lower than that in the control group[(1461.89±166.57)times]( P<0.05). Total calling duration[(41.77±16.17)s]were significantly lower than that in the control group[(86.22±10.07)s]( P<0.05). There is a certain synergistic effect of CDH2 genetic mutation and iron deficiency on the reduction of total calls in rats aged 6 and 8 day( P<0.05). The total distance, distance in zone-periphery, mean speed in zone-total and mean speed in zone-periphery of rats in iron deficiency group were all higher than that in the control group( P<0.05); the numbers of standing and rearing were reduced( P<0.05). In the second stage of the three-chamber test, the rats in the iron deficiency group had shorter communication time with the new stranger 2 and longer interaction time with the old stranger 1 compared with the control, showing a weakening trend of social ability, but the difference was not statistically significant( P>0.05). Conclusion:Autism-like behavioral changes occurred in rats with iron deficiency in early life and CDH2 genetic mutation, and there is a certain degree of synergy.Iron deficiency and CDH2 mutation may increase the risk of autism spectrum disorder.
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Objective:To analyze the mutation sites and characteristics of phospholipase CE1( PLCE1) gene in children with primary nephrotic syndrome(PNS) in Zhuang, Guangxi, China, so as to explore the expression status of PLCE1 protein in peripheral blood of PNS patients. Methods:(1)Blood samples of 154 Zhuang children with PNS and 98 healthy children of Zhuang nationality from July 2015 to September 2017 in Affiliated Hospital of Youjiang Medical College for Nationalities were collected to sequence PLCE1 gene with FastTarget target gene capture method in the combination with next generation sequencing.Based on the comparison between mutation results and information from the database, the pathogenicity, phenotype and distribution characteristics of these mutation sites were discovered and appraised.(2)The concentration of PLCE1 protein in serum samples were measured by enzyme-linked immuno sorbent assay, then the data of PNS group and healthy control group were compared and analyzed statistically with SPSS 25.0. Results:(1)A total of 18 low-frequency mutations of PLCE1 were observed, 5 of them(c.670C>T, c.578T>C, c.923G>T, c.4916C>T, and c. 5927_5929del) were found only in the PNS group, and 3 of them occurred in both PNS group and healthy control group: c.176C>T, c.389T>C, and c. 4304C>T.Five newly discovered mutations (c.923G>T, c.958T>A, c.1151C>T, c.2341A>G, and c. 3592G>C)were discovered and only c. 923 G>T is pathogenic mutation of PLCE1.(2)The concentration of PLCE1 protein in healthy control group was 414.65 (231.20, 729.81) ng/L and the level of PLCE1 in PNS group was 237.84 (116.14, 535.85) ng/L, ( Z=-3.212, P<0.001), and the value of PNS group was lower than that in the healthy control group. Conclusions:(1)As a new pathogenic mutation of PLCE1, c.923G>T was found.(2)The phenotype of PLCE1 gene mutation in Zhuang children with PNS was diverse, and they may differ by race and region.(3) PLCE1 protein of serum may act as a protective protein to guarantee various life activities of cells by participating in multiple signal transduction pathways.
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Objective:To evaluate the lung protection of pressure-controlled ventilation volume guaranteed (PCV-VG) in elderly patients undergoing laparoscopic surgery in Trendelenburg position.Methods:Sixty patients of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, aged 65-80 yr, with body mass index of 19-27 kg/m 2, scheduled for elective laparoscopic radical prostatectomy or laparoscopic radical cystectomy, were allocated into 2 groups ( n=30 each) by a random number table method: VCV group (group V) and PCV-VG group (group P). Tracheal intubation was performed after induction of anesthesia.The anesthesia machine was connected to perform mechanical ventilation with tidal volume of 7 ml/kg (corrected body weight), positive end-expiratory pressure at 5 cmH 2O, inspiratory/expiratory ratio 1∶2, fraction of inspired oxygen 50%, fresh gas flow at 2 L/min and respiratory rate 12-15 breaths/min in two groups.Recruitment maneuver was performed with a pressure of 30 cmH 2O, lasting for 30 s, starting from 5 min before the end of administration.The airway peak pressure (P peak), airway plateau pressure (P plat), driving pressure (DP), and dynamic lung compliance (Cdyn) were measured at 5 min after intubation (T 1), 5 min after changing position (T 2), 5, 30, 60, 90 and 120 min of pneumoperitoneum (T 3-7) and 5 min after restoring the supine position and after the end of pneumoperitoneum (T 8). Blood samples were collected from the radial artery for blood gas analysis at T 1, T 4 and T 6 and when modified Aldrete score reached 10 in postanesthesia care unit, and pH value, partial pressure of arterial oxygen (PaO 2), partial pressure of arterial carbon dioxide (PaCO 2), arterial oxygen saturation (SaO 2) and alveolar-arterial oxygen gradient (P A-aO 2) were recorded.Blood samples were collected from the radial artery before induction of anesthesia and at the end of surgery for determination of concentrations of Clara cell protein (CC-16), interleukin-6 (IL-6) and neutrophil elastase (NE) in serum by enzyme-linked immunosorbent assay.The development of pulmonary complications was recorded within 7 days after surgery. Results:Compared with group V, P peak was significantly decreased at T 1-8, P plat and DP were decreased at T 5-7, Cdyn was increased at T 2-7, P A-aO 2 was decreased at T 1, 4, 6, serum CC-16, IL-6 and NE concentrations were decreased at the end of surgery ( P<0.05), and no significant change was found in the incidence of pulmonary complications within 7 days after surgery in group P ( P>0.05). Conclusion:PCV-VG can produce lung protection to some extent in elderly patients undergoing laparoscopic surgery in Trendelenburg position.
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Objective@#To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease.@*Methods@#A prospective self-control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People′s Liberation Army General Hospital from January 2011 to January 2019 were collected. The long-term rapamycin treatment for all patients initiated at 1 mg/(m2·d), which was gradually adjusted to reach a blood concentration of 5-10 μg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test.@*Results@#Ninety-two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow-up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0,7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (Z=-2.404,-2.350,-2.750,P=0.016,0.019,0.006, respectively). The maximum diameter after 2-3 years, and ≥3 years were 5.0 (3.9,7.0) mm and 6.0 (1.0, 11.0) mm, without significant difference from the baseline (Z=-0.856,-0.102,P=0.393,0.919, respectively).The maximum diameters of MRC after 3 months, 6 months, 1 year,1-2 years, 2-3 years, and ≥3 years were 11.0 (5.0, 14.0) mm,3.0 (0.0,11.0) mm,5.0 (0,21.0) mm,0 (0,14.0) mm,0 (0,10.0) mm, and 0 (0,18.3) mm, respectively, but were not significantly different rom the baseline (7.0 (5.0, 15.7) mm)(Z=-0.944,-1.214,-1.035,-1.896,-1.603,-1.214,P=0.345,0.225,0.301,0.058,0.109,0.225, respectively).Twenty-nine patients (32%) had oral ulcers during the entire treatment period, and no serious adverse reactions were observed.@*Conclusions@#Rapamycin could decrease the diameter of TSC-related RAML, but could not inhibit the growth of cysts. It is well tolerated in the treatment of renal diseases associated with tuberous sclerosis complex.
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Objective To determine the median effective dose (EDs0) of etomidate inducing electroencephalogram (EEG) burst suppression (BS) in the patients with non-intracranial diseases.Methods American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 18-64 yr,with body mass index of 19-27 kg/m2,scheduled for elective non-intracranial surgery,were enrolled in this study.ED50 of etomidate was determined by Dixon's up-and-down sequential method.Etomidate was intravenously injected for 30 s at an initial dose of 0.30 mg/kg.The BS ratio was recorded within 6 min following the end of injection.Each time ED50 increased/decreased in the next patient depending on whether or not BS occurred.The difference between the two successive doses was 0.05 mg/kg.Successful induction of BS was defined as BS ratio> 10%,lasting more than 1 min.Probit analysis was used to calculate the ED50 and 95% confidence interval of etomidate inducing EEG BS in the patients with non-intracranial diseases.Results The ED50 of etomidate inducing EEG BS was 0.70 mg/kg,and the 95% confidence interval was 0.65-0.81 mg/kg in the patients with non-intracranial diseases.Conclusion The ED50 of etomidate inducing EEG BS is 0.70 mg/kg in the patients with non-intracranial diseases.
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Objective@#To evaluate the role of DNA methylation in sepsis-associated encephalopathy in mice.@*Methods@#A total of 144 clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups (n=36 each) using a random number table method: sham operation group (group Sham), sepsis group (group Sepsis), sham operation plus S-adenosyl methionine (SAM) group (group Sham+ SAM) and sepsis plus SAM group (group Sepsis+ SAM). Sepsis was produced by cecum ligation and puncture (CLP). In Sham+ SAM and Sepsis+ SAM groups, DNA methylated methyl donor SAM 100 mg/kg was intraperitoneally injected at 1 h before operation and 12 h after operation, while the equal volume of normal saline was given instead in Sham and Sepsis groups.The cognitive function was assessed using Y-maze and contextual fear conditioning test at 1, 3 and 7 days after CLP.Mice were sacrificed at 1, 3 and 7 days after CLP, and the hippocampal tissues were taken for determination of genome-wide DNA methylation (by colorimetric assay) and expression of DNA methyltransferase enzymes (DNMT1, DNMT3a, and DNMT3b), ten-eleven translocation (TET) enzymes (TET1, TET2 and TET3) and thymine-DNA glycosylase (TDG) mRNA (by fluorescent quantitative real-time).@*Results@#Compared with group Sham, the time of staying at the novel arm was significantly shortened, the percentage of time spent freezing and the total number of entries into each arm were reduced, genome-wide DNA methylation in hippocampal tissues was decreased at 1, 3 and 7 days after CLP, the expression of DNMT1, DNMT3a, TET1, TET2, TET3 and TDG was up-regulated, and the expression of DNMT3b was down-regulated in group Sepsis (P<0.05). Compared with group Sepsis, the time of staying at the novel arm was significantly prolonged, the percentage of time spent freezing and the total number of entries into each arm were increased, the expression of DNMT1, DNMT3a, TET1, TET2, TET3 and TDG mRNA was down-regulated, and the expression of DNMT3b was up-regulated in group Sepsis+ SAM(P<0.05).@*Conclusion@#DNA methylation is involved in the development of sepsis-associated encephalopathy in mice.
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Objective To evaluate the role of DNA methylation in sepsis-associated encephalopathy in mice.Methods A total of 144 clean-grade healthy male C57BL/6 mice,aged 6-8 weeks,weighing 20 -25 g,were divided into 4 groups (n=36 each) using a random number table method:sham operation group (group Sham),sepsis group (group Sepsis),sham operation plus S-adenosyl methionine (SAM) group (group Sham+SAM) and sepsis plus SAM group (group Sepsis+SAM).Sepsis was produced by cecum ligation and puncture (CLP).In Sham+SAM and Sepsis+SAM groups,DNA methylated methyl donor SAM 100 mg/kg was intraperitoneally injected at 1 h before operation and 12 h after operation,while the equal volume of normal saline was given instead in Sham and Sepsis groups.The cognitive function was assessed using Y-maze and contextual fear conditioning test at 1,3 and 7 days after CLP.Mice were sacrificed at 1,3 and 7 days after CLP,and the hippocampal tissues were taken for determination of genomewide DNA methylation (by colorimetric assay) and expression of DNA methyltransferase enzymes (DNMT1,DNMT3a,and DNMT3b),ten-eleven translocation (TET) enzymes (TET1,TET2 and TET3) and thymine-DNA glycosylase (TDG) mRNA (by fluorescent quantitative real-time).Results Compared with group Sham,the time of staying at the novel arm was significantly shortened,the percentage of time spent freezing and the total number of entries into each arm were reduced,genome-wide DNA methylation in hippocampal tissues was decreased at 1,3 and 7 days after CLP,the expression of DNMT1,DNMT3a,TET1,TET2,TET3 and TDG was up-regulated,and the expression of DNMT3b was down-regulated in group Sepsis (P<0.05).Compared with group Sepsis,the time of staying at the novel arm was significantly prolonged,the percentage of time spent freezing and the total number of entries into each arm were increased,the expression of DNMT1,DNMT3a,TET1,TET2,TET3 and TDG mRNA was down-regulated,and the expression of DNMT3b was up-regulated in group Sepsis+SAM (P<0.05).Conclusion DNA methylation is involved in the development of sepsis-associated encephalopathy in mice.
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Currently, the second-generation intact parathyroid hormone (iPTH) assay is commonly used for measuring PTH levels. The iPTH assay detects both full-length (1-84)PTH and (7-84)PTH fragments, which have antagonistic effects on (1-84)PTH in bones and kidneys. The third-generation PTH assay is specific for (1-84)PTH. This study examined the features of different PTH fragments in stage 5 chronic kidney disease (CKD) and the effects of parathyroidectomy (PTX) on the above markers in severe secondary hyperparathyroidism (SHPT) patients. The cross-sectional study included 262 stage 5 CKD patients and 90 controls. A prospective follow-up study was then conducted in 34 PTX patients. Second- and third-generation assays were used to measure plasma iPTH and (1-84)PTH levels, respectively. Circulating (7-84)PTH levels were calculated by subtracting the (1-84)PTH value from the iPTH value. Different plasma PTH fragments were higher, and (1-84)PTH/iPTH was lower in CKD patients than in controls. Plasma (1-84)PTH and (7-84)PTH concentrations increased as iPTH levels increased, and (7-84)PTH increased more evidently. Plasma iPTH, (1-84)PTH and (7-84)PTH levels were 1530.5 (885.0-2111.5) pg/ml, 683.1 (431.4-1018.0) pg/ml, and 739.3 (452.6-1261.0) pg/ml, respectively, in PTX patients. Plasma iPTH, (1-84)PTH and (7-84)PTH concentrations decreased considerably, and the (1-84)PTH/iPTH ratio increased after PTX (median follow-up interval: 10.9 months). Stage 5 CKD patients had higher plasma levels of different PTH fragments, and lower (1-84)PTH/iPTH ratio. PTX could significantly reverse these abnormalities in severe SHPT patients. The iPTH assay overestimated the function of the parathyroid glands; thus, the third-generation PTH assay is likely better for the management of CKD patients.
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Fallo Renal Crónico/sangre , Hormona Paratiroidea/sangre , Paratiroidectomía , Femenino , Humanos , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/cirugía , Masculino , Persona de Mediana Edad , Análisis de RegresiónRESUMEN
Objective@#To analyze the bone mineral density and serum osteocalcin levels in postmenopausal women with idiopathic benign paroxysmal positional vertigo.@*Methods@#A total of 64 postmenopausal women with idiopathic BPPV were selected as the study group, and 98 postmenopausal healthy women were selected as the control group. Bone mineral density and serum osteocalcin levels were analyzed and compared between the groups.χ2 test was used for numeration data and t test was used for measurement data.@*Results@#The prevalence of osteoporosis or osteopenia in BPPV group 67.2% (43/64) was significantly higher than that in the control group 51.0% (50/98) (χ2=4.139, P=0.042). Among BPPV subjects, there was a negative correlation between osteocalcin and bone density T (r=-0.469, P<0.001). Osteocalcin was found in normal bone mass subgroup (13.61±4.32)μg/L, decreased bone mass subgroup (17.49±7.61)μg/L, and osteoporosis subgroup (20.83±6.72)μg/L, respectively, and the difference was statistically significant (F=5.39, P=0.007).@*Conclusions@#Bone mineral density in BPPV group is lower than that in control group. The lower the bone mineral density of the patients, the higher the osteocalcin in BPPV group.
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Objective To investigate the effects of low GI cereals on metabolomics and pregnancy outcomes in women with gestational diabetes mellitus (GDM),in order to explore the preventive and therapeutic mechanisms and provide the basis for nutritional interventions.Metbods Pregnant women with gestational diabetes were assigned to the treatment group (n=31),using low GI grains 12 weeks for nutrition intervention and the control group (n =31) according to the random digital table method;30 healthy pregnant women were enrolled as normal control group.At 36th gestational week serum was analyzed by 1H-NMR metabolomics approach.Pregnancy outcomes were gathered for statistics after delivery.Comparison among groups and related influencing factors analysis were conducted.Results After nutritional intervention for 12 weeks,there were statistically significant differences in 15 potential biomarkers associated with gestational diabetes between the treatment group and the control group (P<0.05),and no statistically significant difference between the treatment group and the normal control group (P>0.05),that was the pregnant women in the treatment group were close to normal pregnant women.Cesarean rate,gestational weight gain,glycosylated hemoglobin during delivery,fasting insulin and newborn birth weight were significantly lower in the treatment group than in the control group.Multiple linear regression analysis showed that the GI of diet,fasting insulin and blood glucose were influencing factors for metabolomics in women with GDM.Conclusions Using low GI cereals intervention treatments,the pregnancy outcomes of GDM are improved distinctly with the possible mechanisms as adjusting the related biomarkers.Our study provides evidences for further exploring etiology and the therapeutic mechanisms of GDM,and individualized medical nutrition treatment strategy.
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Objective To explore the indications for percutaneous renal biopsy of asymptomatic hematuria in children. Methods The renal pathological types of 485 children with asymptomatic hematuria were analyzed retrospectively. According to the degree of hematuria and whether or not combined with proteinuria, the children were divided into microscopic hematuria group, gross hematuria group and hematuria with proteinuria group. The microscopic hematuria group was further divided into urine red blood cell30/HPF group according to hematuria degree. Results In 227 males and 258 females with the average age of 7.23±2.93 years, there were 318 cases in microscopic hematuria group, in which the most common pathological types were minor lesions (64.8%), followed by focal glomerular lesions (16.7%) and focal segmental glomerulosclerosis (8.2%). There were 119 cases in gross hematuria group, in which the most common pathological types were also minor lesions (26.1%), followed by IgA nephropathy (24.4%) and mesangial proliferative glomerulopathy (20.2%). There were 48 cases in hematuria with proteinuria group, in which the most common pathological types were IgA nephropathy (29.2%) and minor lesions (29.2%). The distribution of the pathological types among microscopic hematuria group, gross hematuria group and hematuria with proteinuria group were statistically different (χ2=152.03, P30/HPF. There was no difference in pathological types among three sub-groups (χ2=15.18, P=0.51), and mild lesions were the most common pathological types in each group. Conclusion Renal biopsy should be performed at earliest possible time to make pathological diagnosis in asymptomatic hematuria children with gross hematuria or proteinuria.