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Objective:To summarize initial experience of applying nanopore third-generation sequencing detection method (nanopore sequencing) for genetic diagnosis of non-classical 21 hydroxylase deficiency (NC 21-OHD), and to explore its performance and application prospects.Methods:Clinical data of the two NC 21-OHD patients, who were hospitalized at the First Affiliated Hospital of Zhengzhou University in May 2019, were collected. Peripheral venous blood was collected and genome DNA extracted. Genetic variants was detected by nanopore sequencing and underwent bioinformatic analysis. Pathogenetic mutations in CYP21A2 gene were validated with PCR-sanger sequencing in the two patients and their parents.Results:The average reads length and sequence depth in the patient one was 12, 792 bp and 27.19×. The average reads length and sequence depth in the patient two was 13, 123 bp and 21.34×. Compound variants of c.293-13C>G/c.844G>T (p.Val282Leu) and c.332_339delGAGACTAC (p.Gly111Valfs)/c.844G>T (p.Val282Leu) were detected in these two patients, which were consistent with clinical phenotype of NC 21-OHD. Further analysis showed that c.293-13C>G mutation was inherited from her father and c.844G>T (p.Val282Leu) mutation was inherited from her mother for the patient one. The c.844G>T (p.Val282Leu) mutation was inherited from her father and c.332_339delGAGACTAC (p.Gly111Valfs) mutation from her mother.Conclusions:The heterozygous mutations in CYP21A2 gene are the cause of NC 21-OHD in these two patients. Nanopore sequencing technique is a reliable new detection method for patients with NC 21-OHD.
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Objective:To investigate the regulating molecules and acting mechanism of TAB182 in HR pathway.Methods:TAB182 in human breast cancer MCF-7 cells was knocked down by shRNA strategy, the TAB182 knockdown MCF-7 as the TAB182 knockdown group, and the MCF-7 cell using the shRNA negative control as the TAB182 negative control group. RNA sequencing and qRT-PCR were performed to screen and verify the differentially expressed genes of HR pathway related to TAB182 depression. Western blot was used to detect protein expression. Immunofluorescence staining of nuclear RAD51 and BrdU was used to check the 3′ ssDNA formation by the end resection. The cell cycle arrest and apoptosis were measured by flow cytometry. Cloning formation assay was used to evaluate the sensitivity TAB182-knockdown cells to radiation.Results:Both quantitative RNA sequencing and qRT-PCR assays showed that TAB182-knockdown significantly decreased the mRNA expression of RPA2( t=17.97, P<0.05). Compared with the TAB182 negative control group, the protein level of RPA2, the number of RAD51 foci, and the 3′ ssDNA-binding nuclear protein marker BrdU in TAB182-knockdown cells were significantly reduced. At 4, 8, and 12 h after actinomycin D treatment, the attenuation of RPA2 mRNA in the TAB182-knockdown cells was accelerated ( t=5.37, 3.79, 3.69, P<0.05). Compared with the TAB182 negative control group, the radiosensitivity and radiation-induced apoptosis in the TAB182-knockdown group were increased ( t=3.48, 11.05, P<0.05), and at 24 h after irradiation, the cell cycle block time was prolonged ( t=8.40, P<0.01). Conclusions:TAB182 plays a role in maintaining RPA2 mRNA stability, thereby promoting HR repair. TAB182 knockdown cells are highly sensitive to ionizing radiation.
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OBJECTIVE@#To assess the value of re-sampling for patients who had failed non-invasive prenatal testing (NIPT) due to low cell-free fetal DNA (cffDNA) fraction.@*METHODS@#Clinical data of 20 387 patients undergoing NIPT test was reviewed. The patients were re-sampled when initial blood test did not yield a result due to cffDNA fraction. The results were analyzed, and the outcome of pregnancy was followed up.@*RESULTS@#Among all samples, 17 (0.08%) had failed to yield a result due to low cffDNA fraction, all of which accepted re-sampling. A result was attained in 16 cases, with a success rate of 94.12%. Only one sample had failed the re-test.@*CONCLUSION@#For patients who had failed the initial NIPT due to low cffDNA fraction, re-sampling should be considered with gestational week and ultrasound results taken into consideration.
Subject(s)
Female , Humans , Pregnancy , Aneuploidy , Cell-Free Nucleic Acids/genetics , DNA/genetics , Fetus , Prenatal DiagnosisABSTRACT
Objective:To evaluate the effect of epidural labor analgesia administration methods on occurrence of postpartum urinary retention in nulliparous parturients through a comparison between programmed intermittent epidural bolus (PIEB) and continuous epidural infusion.Methods:Two hundred nulliparous parturients who were at full term with a singleton fetus in vertex presentation, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, aged 22-35 yr, with body mass index of 22.4-42.6 kg/m 2, were divided into 2 groups ( n=100 each) using a random number table method: continuous epidural infusion group (group CEI) and group PIEB.Patient-controlled epidural analgesia (PCEA) was performed in active phase of labor (cervical dilatation≥1 cm) during the first stage of labor.The PCEA solution contained the mixture (10 ml) of 0.1% ropivacaine with 0.5 μg/ml sufentanil.The PCEA pump was set up to deliver a 5-ml bolus dose with a 30-min lockout interval.The analgesia solution contained the mixture (100 ml) of 0.08% ropivacaine and sufentanil 0.5 μg/ml.In group CEI, the drugs were given at 8 ml/h immediately after the initial dose.PIEB regimens were programmed as 8 ml over 80 s once an h after the initial bolus, and the administration was stopped after delivery of fetus.The labor time, consumption of analgesia solution and the incidence of postpartum urinary retention were recorded. Results:Compared with group CEI, the duration of the second stage of labor was significantly shortened, and consumption of analgesia solution and the incidence of postpartum urinary retention were decreased in group PIEB ( P<0.05). Conclusion:Compared with the continuous epidural infusion, the application of PIEB in labor analgesia can reduce the incidence of postpartum urinary retention in nulliparous parturients.
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Objective:To investigate and analyze a human brucellosis (hereinafter referred to as brucellosis) in Fushan District, Yantai City of Shandong Province, and to provide scientific basis for study the main risk factors and doing a good job in brucellosis prevention and control.Methods:Collect the epidemic data of one human brucellosis in Fushan District, Yantai City in 2017. The information comes from the infectious disease report information management system, the epidemiological case questionnaire of brucellosis in Shandong Province, and the medical records of medical institutions. The epidemic situation, cases and epidemiological investigation results were analyzed retrospectively.Results:Serological tests were carried out among 48 close contacts of the reported case and workers in the same village. Among the 3 positive cases, 2 cases had symptoms and positive bacterial culture results, which were diagnosed as confirmed cases. One patient was asymptomatic and negative bacterial culture, and was diagnosed as recessive infection. All of the three confirmed cases and one recessive infection involved in the epidemic had a history of close contact with infected animals, and without protective measures. The serological examination of 70 key people in the district was carried out and the results were all negative. A total of 166 sheep blood samples were collected, including 21 positive samples.Conclusions:The infectious source of this outbreak is the non-quarantine infected sheep. The main exposure factor is personal unprotected exposure to infected sheep. The key of prevention and control is to strengthen the monitoring and quarantine management of brucellosis among livestock, to improve the personal protection consciousness and ability of key population, and to improve the diagnosis ability of medical institutions in low epidemic areas.
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Objective:To understand the epidemiological characteristics of human brucellosis in Yantai City, Shandong Province, and to provide scientific basis for the formulation and adjustment of brucellosis prevention and control strategy.Methods:The epidemic data, demographic data and case data of human brucellosis in Yantai City in 2019 were collected from the National Health Insurance Disease Control Information System and the epidemiological case survey of brucellosis in Shandong Province. Descriptive epidemiological method was used to analyze the three distribution characteristics, clinical characteristics and infection routes of brucellosis.Results:In 2019, 158 cases of brucellosis were reported in Yantai City, with an incidence rate of 2.22/100 000 and no deaths. The incidence peak was from April to June, accounting for 43.67% (69/158). In addition to Changdao County, 12 other cities and districts had reported brucellosis cases, and Laizhou City had the largest number of reported cases, accounting for 39.87% (63/158). The ratio of men to women was 2.1 ∶ 1.0 (107 ∶ 51). The age of onset was mainly 40 - 69 years (75.95%, 120/158). Farmer was the main occupation, accounting for 83.54% (132/158). The main clinical manifestations were fever (114 cases), muscle and joint pain (107 cases), fatigue (95 cases), hyperhidrosis (85 cases). Patients had a clear history of livestock contact accounted for 58.86% (93/158). The main contact ways were breeding (68 cases) and slaughter (26 cases). Protective measures were taken in 18.28% (17/93) of the patients, and wearing gloves was the most common protective measure, accounting for 76.47% (13/17). The rate of hand washing after contact was 91.40% (85/93), of which 37.65% (32/85) were washed only with water and 62.35% (53/85) were washed with soap. The percentage of changing laundry after contact was 82.80% (77/93).Conclusions:The awareness and ability of personal protection of brucellosis key population in Yantai City are low. Improving the effectiveness of health education and behavior intervention is an important measure for prevention and control of the disease in the future.
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OBJECTIVE@#To explore the clinical effect of expanded non-invasive prenatal testing (NIPT-plus) for prenatal screening.@*METHODS@#The screening result, prenatal diagnosis and pregnancy outcome of 3700 pregnant women who volunteered NIPT-plus screening at our center from September 2018 to December 2019 were reviewed.@*RESULTS@#Among the 3700 pregnant women, 74(2.0%) were scored positive for clinically significant fetal chromosomal abnormalities and underwent NIPT-plus screening. Sixty three women with a high risk underwent invasive prenatal diagnosis, among whom 19 were diagnosed, which yielded a positive predictive value (PPVs) of 30.2% (19/63). Statistical analysis showed that NIPT-plus has higher PPVs for common aneuploidies and low-to-medium PPVs for sex chromosome aneuploidies and microdeletion/microduplication syndromes.@*CONCLUSION@#As a screening technique, NIPT-plus has broader applications compared with conventional techniques, and has reference value for clinicians and pregnant women during pregnancy.
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Female , Humans , Pregnancy , Aneuploidy , Chromosome Aberrations , Pregnancy Outcome , Prenatal Diagnosis , Sex Chromosome AberrationsABSTRACT
OBJECTIVE@#To explore whether it is necessary to choose NIPT-plus for the prenatal screening of pregnant women.@*METHODS@#The results of NIPT and NIPT-plus sequencing data, fetal DNA concentration, prenatal diagnosis and pregnancy outcome of 50 pregnant women were compared.@*RESULTS@#Compared with NIPT, NIPT-plus attained similar fetal DNA concentration and a 4.4-fold increase in sequencing data. NIPT was able to detect 4 cases of 21-trisomy, 2 cases of 18-trisomy, and 9 cases of sex chromosome aneuploidies (SCAs) signaled by NIPT-plus, but missed one 18-trisomy, and failed to detect rare chromosome aneuploidies (RCAs) and microdeletion/microduplication syndromes (MMS). The PPVs of NIPT-plus for 21-trisomy, 18-trisomy, SCAs, MMS and RCAs were 100%, 100%, 44.4%, 30.4% and 0%, respectively. And those of NIPT for 21-trisomy, 18-trisomy, and SCAs were 100%, 100%, and 44.4%, respectively.@*CONCLUSION@#It is necessary for pregnant women to select NIPT-plus to improve the detection rate of common trisomies, SCAs and disease-specific MMS, therefore reduce the occurrene of birth defect.
Subject(s)
Female , Humans , Pregnancy , Aneuploidy , Pregnant Women , Prenatal Diagnosis , Trisomy , Trisomy 13 Syndrome , Trisomy 18 SyndromeABSTRACT
OBJECTIVE@#To explore the genetic basis for a neonate with Pierre-Robin sequence.@*METHODS@#The child was subjected to chromosomal karyotyping, single nucleotide polymorphism array (SNP-array)-based comparative genomic hybridization and fluorescence in situ hybridization (FISH) analysis.@*RESULTS@#The child has featured microgthnia, glossoptosis, upper airway obstruction, mandible dehiscence and short neck. He was found to have a karyotype of 46,XY,der(4)add(4)(q34). Her mother's karyotype was determined as 46,XX,t(1;4)(q43;q34), while his father was 46,XY. SNP-array analysis suggested the child to be arr [hg19] 1q42.2q44 (232 527 958-249 202 755)× 3; 4q34.3q35.2 (168 236 901-190 880 409)× 1. The result of SNP-array for both parents was normal. FISH analysis confirmed that his mother has carried a balanced t(1;4)(q42;34) translocation. The aberrant chromosome 4 in the child has derived from his mother's translocation, which gave rise to partial 1q trisomy and 4q monosomy.@*CONCLUSION@#The 1q42.2q44 duplication and 4q34.3q35.2 deletion of the child probably underlay his abnormal phenotype of Pierre-Robin sequence.
Subject(s)
Child , Female , Humans , Infant, Newborn , Male , Comparative Genomic Hybridization , In Situ Hybridization, Fluorescence , Monosomy , Pierre Robin Syndrome/genetics , Translocation, Genetic , Trisomy/geneticsABSTRACT
OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for the detection of fetal chromosomal aneuploidies in women with twin pregnancy.@*METHODS@#A total of 2473 women with twin pregnancy underwent the NIPT test to assess the risk for fetal chromosomal aneuploidies from January 2016 to September 2019. Those with a high risk by NIPT were confirmed by amniocentesis or chorionic villus sampling. All cases were followed up to evaluate the positive prediction value of NIPT for twin pregnancies.@*RESULTS@#Among the 2473 women, the NIPT test has identified 31 cases (1.25%) with a high risk for fetal chromosomal aneuploidies, which included 5 cases of trisomy 21, 1 case of chromosome 21 deletion, 4 cases of trisomy 18, 7 cases of sex chromosome abnormality and 14 cases of microdeletion and microduplication. By invasive prenatal diagnosis or chromosomal karyotyping analysis of neonates, 5 cases of trisomy 21, 3 cases of trisomy 18, 1 case of sex chromosome abnormality, and 2 cases of microdeletion and microduplication were confirmed, which yielded a positive predictive value of 100%, 75%, 25% and 25%, respectively.@*CONCLUSION@#NIPT can be used for the screening of fetal chromosomal aneuploidies in women with twin pregnancy with high accuracy. The method is non-invasive, safe and effective for the screening of fetal chromosomal aneuploidies, in particular trisomy 21.
Subject(s)
Female , Humans , Infant, Newborn , Pregnancy , Aneuploidy , Chromosome Disorders , Pregnancy, Twin , Prenatal Diagnosis , Trisomy , Trisomy 13 Syndrome , Trisomy 18 SyndromeABSTRACT
Objective:To analyze the epidemiological characteristics of human brucellosis (referred to as brucellosis) from 2011 to 2018 in Yantai City, and to provide scientific basis for formulating and adjusting brucellosis prevention and control strategies.Methods:Descriptive epidemiological method was used to analyze the monitoring data and epidemiological survey data (time, area, population distribution and treatment behavior) of brucellosis in Yantai from 2011 to 2018.Results:From 2011 to 2018, 795 cases of brucellosis were reported in Yantai, with an annual incidence of 1.42/100 000 and no deaths. Most of the cases were sporadic, accounting for 92.20% (733/795). The incidence peak was from March to August, accounting for 67.80% (539/795). In addition to Changdao County, cases of brucellosis had been reported in 12 counties (cities, districts). The incidence rate of the top three counties (cities, districts) were 5.20/100 000 (369 cases, accounting for 46.42%) in Laizhou City, 2.13/100 000 (97 cases, accounting for 12.20%) in Zhaoyuan City, and 1.77/100 000 (62 cases, accounting for 7.80%) in Penglai City. The male and female sex ratio was 2.82 to 1.00 (587 to 208). The age of onset was mainly 40 - 69 years old, accounting for 79.62% (633/795). Occupation was mainly farmers, accounting for 83.90% (667/795). Cases were mainly found in local medical institutions, accounting for 89.56% (712/795). The average interval between onset and diagnosis was 17 days, the longest was 40 days in 2012, and the shortest was 12 days in 2018.Conclusions:From 2011 to 2018, except Changdao County, 12 counties (cities and districts) in Yantai City had reported brucellosis cases. The incidence peak was in spring and summer, mainly in middle-aged and elderly people, so we should carry out targeted prevention and control strategies for different areas and key populations.
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We report a case of non-invasive prenatal diagnosis of fetal ectodermal dysplasia caused by EDA gene mutations. The pregnant woman underwent prenatal diagnosis at 11 gestational weeks because of a childbearing history of ectodermal dysplasia. Cell-free DNA barcode-enabled single-molecule test (cfBEST) was used to detect the ectodermal dysplasia gene mutation, and chorionic villus sampling was also performed. The cfBEST results showed that the genotype of maternal EDA gene c.340C> T(p.Gln114*) was heterozygous, while the genotype of fetal EDA was normal wild-type (C/C), which were consistent with the results of villus sampling, suggesting that cfBEST can be used for non-invasive prenatal diagnosis of ectodermal dysplasia caused by EDA gene mutation.
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By removing a part of the structure, the tooth preparation provides restorative space, bonding surface, and finish line for various restorations on abutment. Preparation technique plays critical role in achieving the optimal result of tooth preparation. With successful application of microscope in endodontics for >30 years, there is a full expectation of microscopic dentistry. However, as relatively little progress has been made in the application of microscopic dentistry in prosthodontics, the following assumptions have been proposed: Is it suitable to choose the tooth preparation technique under the naked eye in the microscopic vision? Is there a more accurate preparation technology intended for the microscope? To obtain long-term stable therapeutic effects, is it much easier to achieve maximum tooth preservation and retinal protection and maintain periodontal tissue and oral function health under microscopic vision? Whether the microscopic prosthodontics is a gimmick or a breakthrough in obtaining an ideal tooth preparation should be resolved in microscopic tooth preparation. This article attempts to illustrate the concept, core elements, and indications of microscopic minimally invasive tooth preparation, physiological basis of dental pulp, periodontium and functions involved in tool preparation, position ergonomics and visual basis for dentists, comparison of tooth preparation by naked eyes and a microscope, and comparison of different designs of microscopic minimally invasive tooth preparation techniques. Furthermore, a clinical protocol for microscopic minimally invasive tooth preparation based on target restorative space guide plate has been put forward and new insights on the quantity and shape of microscopic minimally invasive tooth preparation has been provided.
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OBJECTIVE@#To explore cytogenetic characteristics and fertility of carriers of complex chromosome rearrangements (CCR) from Henan region.@*METHODS@#G-banded karyotyping analysis was carried out on peripheral blood lymphocytes derived from 160 601 patients with reproductive abnormalities. Relevant literature was retrieved from domestic and overseas databases. Cytogenetic characteristics and clinical data of CCR carriers were analyzed.@*RESULTS@#Twenty-seven CCR carriers were identified among the 160 601 patients. In addition, 6 cases were identified from the database research. Among the 33 CCR carriers, there were 17 three- and four-way exchange cases (51.5%), 10 double two-way exchange cases (30.3%), and 6 unusual CCRs (18.2%). Infertility was noted in 14 (42.4%) of the CCR carries. A total of 38 pregnancies were achieved in the remaining 19 cases (57.6%), among which spontaneous abortions or embryonic losses have occurred in 89.5% (34/38), multiple congenital abnormalities have occurred in 7.9% (3/38), while phenotypically normal offspring have occurred in 2.6% (1/38). Chromosomes 1, 11, 2, 4, 5 and 12 were more frequently involved, with their breakpoints occurred more than 3 times at 1p22, 11q23, 12p13 and 22q11.@*CONCLUSION@#CCR carriers are at a higher risk for abnormal pregnancies. Even for those with normal pregnancy, prenatal diagnosis should be provided. Chromosomes and their breakpoints involved in CCR may affect the fertility of CCR carriers. Analyzing the types of CCR and involved chromosomes and breakpoints can facilitate genetic counseling for CCR carriers.
Subject(s)
Female , Humans , Pregnancy , Chromosome Aberrations , Cytogenetic Analysis , Fertility , In Situ Hybridization, Fluorescence , Karyotyping , Translocation, GeneticABSTRACT
Objective To investigate the cytidine triphosphate synthetase 1 (CTPS1) expression in pancreatic cancer cell lines and its impaction on prognosis.Methods The GEO profiles database was searched to collect clinical data of 39 patients of pancreatic ductal adenocarcinoma.Kaplan-Meier curve was used to analyze the relationship between the patients' prognosis and the expression of CTPS1.qPCR and Western blot were applied to detect the expression of CTPS1 in 4 pancreatic cancer cell lines.Results The mRNA expression of CTPS1 in Sw1990,BxPC-3,Panc1,and MIA-Capa2 was 1.00) ± 0.20,2.92±0.95,4.29±0.14,and 2.26±0.33 (t=-16.19,-11.45,-8.09,-13.12,P＜0.05) when compared to the normal pancreatic ductal epithelial cell line HPDE of 7.70 ± 0.72.The relative protein expression of CTPS1 in pancreatic cancer cell lines Sw1990,BxPC-3,Panc1,and MIA-Capa2 was 0.40 ± 0.06,0.20±0.09,0.68±0.11,and0.48±0.06 (t=-8.97,-10.5,-4.39,-7.88,P＜0.05) when compared to HPDE of 1.09 ±0.12.The overall survival (OS) in patients with higher CTPS1 expression than adjacent tissue was 28 months (95％ CI:9.2-46.8 months),and that with lower CTPS1 expression was 13 months (95％ CI:8.2-17.8 month),(x2 =4.02,P＜0.05).Conclusions CTPS1 in the pancreatic cancer cell lines are of low expression,and the level is positively related to patients' survival time.
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This paper aims to analyze the curative effect of Jin'gangteng capsule combined with Kangfuxiaoyan suppository in the treatment of chronic pelvic inflammatory disease. 97 patients with chronic pelvic inflammatory disease admitted to our hospital from June 2015 to June 2016 were selected and randomly divided into observation group and control group. Patients in control group were treated with Kangfuxiaoyan suppository and patients in the observation group were treated with Jin'gangteng capsule combined with kangfuxiaoyan suppository treatment. The curative effect between the two groups was compared. The scores of symptoms and signs in the observation group after treatment were lower than those in the control group. The total effective rate of the observation group was higher than that of the control group, and there was significant difference between the two groups, P<0.05. Jin'gangteng capsule combined with Kangfuxiaoyan suppository in the treatment of chronic pelvic inflammatory disease can improve the treatment efficiency and promote the rapid and effective relief of clinical symptoms and signs
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OBJECTIVE:To optimize the formulation of nanostructured lipid carriers loaded with lornoxicam (LN-NLC). METHODS:Emulsification-solvent evaporation method was used to prepare the LN-NLC. Using drug-lipid ratio,dosage of soy lec-ithin,liquid-lipid ratio (proportion of liquid lipid to total lipid) and dosage of emulsifier as factors,the overall normalized value was calculated by particle size,Zeta potential and entrapment efficiency as indexes was used as comprehensive index. Central com-posite design-response surface method was used to optimize the formulation and investigate the appearance and stability of prepared LN-NLC. RESULTS:The optimal formulation were as follows as drug-lipid ratio of 1:50,dosage of soy lecithin of 162.5 mg,liq-uid-lipid ratio of 25% and emulsifier dosage of 958.2 mg. The particle size of prepared LN-NLC was(96.9±3.3)nm,Zeta poten-tial was(-16.1±0.3)mV,entrapment efficiency was(60.1±0.9)%(n=3),which showed relative error of 2.47%,-4.55%,-0.17%with predicted value,respectively. The prepared LN-NLC was spherical. It had no obvious changes in particle size and Ze-ta potential in sealed storage for 30 d in 4 ℃,and the entrapment efficiency only declined 1.2%. CONCLUSIONS:The LN-NLC formulation is successfully optimized,and the LN-NLC has good stability.
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OBJECTIVE:To optimize the formulation of nanostructured lipid carriers loaded with lornoxicam (LN-NLC). METHODS:Emulsification-solvent evaporation method was used to prepare the LN-NLC. Using drug-lipid ratio,dosage of soy lec-ithin,liquid-lipid ratio (proportion of liquid lipid to total lipid) and dosage of emulsifier as factors,the overall normalized value was calculated by particle size,Zeta potential and entrapment efficiency as indexes was used as comprehensive index. Central com-posite design-response surface method was used to optimize the formulation and investigate the appearance and stability of prepared LN-NLC. RESULTS:The optimal formulation were as follows as drug-lipid ratio of 1:50,dosage of soy lecithin of 162.5 mg,liq-uid-lipid ratio of 25% and emulsifier dosage of 958.2 mg. The particle size of prepared LN-NLC was(96.9±3.3)nm,Zeta poten-tial was(-16.1±0.3)mV,entrapment efficiency was(60.1±0.9)%(n=3),which showed relative error of 2.47%,-4.55%,-0.17%with predicted value,respectively. The prepared LN-NLC was spherical. It had no obvious changes in particle size and Ze-ta potential in sealed storage for 30 d in 4 ℃,and the entrapment efficiency only declined 1.2%. CONCLUSIONS:The LN-NLC formulation is successfully optimized,and the LN-NLC has good stability.
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Objective To study the changes in miRNAs expression in the exosomes of human umbilical vein endothelial cells(HUVECs) after 60 Co γ-rays expose using microRNA(miRNA) chips and bioinformatics techniques so as to provide new clues to the mechanism of radiation-induced vascular tissue injury and its bystander effects.Methods HUVECs exosomes were collected in the control and 4 Gy irradiated cells by ultra-high-speed centrifugation,and further confirmed using transmission electron microscopy (TEM) and Western blotting of exosomes biomarkers.miRNA microarray was used to analyze miRNA expression profiles of exosomes and cells.Also,real-time quantitative PCR(qRT-PCR) was used to verify differentially expressed miRNAs,and the miRDB and TargetScan were performed to predict the target genes of the differentially expressed miRNAs.Bioinformatics analysis was performed using DAVID,KEGG and other online tools.Results Compared with the control exosomes from non-irradiated HUVECs,miRNA microarray analysis revealed that 5 up-regulated,and 13 down-regulated miRNAs were identified in the exosomes from HUVECs at 0.5 h after 4 Gy-irradiation,and 16 up-regulated and 5 down-regulated miRNAs at 2 h after 4 Gy-irradiation.Moreover,38 and 85 miRNAs were differentially expressed respectively in the HUVECs at 0.5 h and 2 h after radiation.The difference was statistically significant(P<0.01).The results of bioinformatics showed that these miRNAs might exert the radiation-induced bystander effect (RIBE) by regulating MAPK signal pathways,RAS and PI3K-Akt signal pathways.Conclusion The ionizing radiation injury significantly alters the components and expression levels of exosomal miRNAs,which play important roles in regulating the signal pathways in response to radiation.
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Objective To investigate the safety,effectiveness and prognosis of percutaneous microwave ablation (MWA) combined with synchronous transarterial chemoembolization (TACE) to treat of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with liver metastases (LMs).Methods This retrospective study included 19 cases of GEP-NENs with LMs patients who received percutaneous MWA combined with synchronous TACE treatment from 2013 to 2016.The mRECIST standard was selected to assess the curative effect.SPSS 21.0 software was applied in the statistical analysis of overall survival (OS),progression-free survival (PFS) and factors related to prognosis.Results All patients were capable of curative effect evaluation,including 1 case of complete remission (CR),3 cases of partial remission (PR),7 cases of progressive disease (PD) and 8 cases of stable disease (SD) respectively accounting for 5 ％,16 ％,37 ％,42 ％,which exhibited 21％ of response rate (RR) and 63％ disease control rate (DCR).In the present study,the median OS and median PFS was respectively 25 months and 34 months,and the one-year survival and three-year survival was respectively 95％ and 84％.Serum CA199,the WHO classification of LMs and the tumor burden of LMs were the major risk factors of prognosis through single factor analysis of survival,which showed that G3 of the WHO classification of LMs predicted a poor OS (P＜0.05) and tumor burden of LMs was negatively related to PFS (P＜0.05).It was obviously observed that serum CgA was decreased by the therapy of percutaneous MWA with synchronous TACEfor GEP-NENs (P＜0.05).Conclusions Percutaneous MWA combined with synchronous TACE is a safe and effective method to treat GEP-NENs with LMs.