1.Polypeptide drugs for oral administration with nanoparticles as carriers:current situation, existing problems and developmental prospects
Chinese Journal of Tissue Engineering Research 2015;(25):4091-4095
BACKGROUND:The new formulation and preparation technology of new drugs have become a hot spot for improving the utilization of polypeptides. In particular, the development of nanotechnology in recent years has promoted the clinical application of polypeptide drugs. OBJECTIVE:To review the current research of nanoparticles as carriers of polypeptide drugs for oral administration. METHODS:A computer-based search of CNKI database and SCI database was performed for relevant articles published from 1996 to 2014 by using the keywords of“protein, peptide drugs, nanoparticles, oral administration”in Chinese and English, respectively. RESULTS AND CONCLUSION:The encapsulation efficiency, release rate of drug delivery, stability of nanoparticles in the gastrointestinal tract and penetrability of the intestinal mucosa are determined by many factors, such as the kind, size, surface charge and modification of nanoparticles. The nanoparticles can increase the stability of protein drugs and improve the bioavailability of drugs. The targeting property of the nanoparticles can decrease the adverse reactions of some drugs. The release effect of the nanoparticles can decrease the dosage of drugs and increase the drug circulating time. However, there are stil many problems to be solved in nanotechnology:the activities of some protein drugs are lost in the preparation process;theencapsulation efficiency and drug loading need to be improved;protein burst release cannot be solved completely;the mass production of nanoparticles is stil difficult.
2.Genotype-phenotype analysis in Apert syndrome
Mei LU ; Meijiao FU ; Hui XIE
Journal of Clinical Pediatrics 2016;34(8):618-622
Objectives To analyze the clinical features and gene types of Apert syndrome (AS). Methods The clinical data of one boy with AS were retrospectively revisited and FGFR 2 of the boy and his father were analyzed with PCR amplification and gene sequencing. The relevant literatures were reviewed. Results The boy was one year and one month old, with brachycephaly, exophthalmos, hypertelorism, low set ears, micrognathia, high-vaulted arch, without cleft palate, and with syndactyly of both ifngersⅠ-Ⅴ and toesⅠ-Ⅴ. A heterozygous mutation (c. 758 C?>?G,p.P 253 R) in exon 7 of FGFR 2 was detected in the boy, supporting the diagnosis of AS. The relevant gene mutation was not detected in his father. Among the 24 cases of AS retrieved from literature, 22 cases were with obvious craniofacial malformations, one with mild craniofacial malformations and one without craniofacial malformations. All cases were with syndactyly of both ifngers and toes. Thirteen cases of FGFR 2 were with S 252 W mutation, 3 cases with P 253 R , 3 cases with Alu insertion, one with 1 . 93-kb deletion, removing exon IIIc and substantial portions of the lfanking introns, one case with a heterozygous 1372 bp deletion between FGFR 2 exons IIIb and IIIc, 2 cases with (c.756_758delGCCinsCTT) in the IgIIe-IgIIIa linker region and one case with sequence variant T78.501A in intron 8. Conclusions Apert syndrome present with craniofacial malformations and syndactyly of hands and feet, S 252 W and P 253 R are main mutations of AS.
3.The application of adaptive statistical iterative reconstruction Veo in detection of pulmonary nodule by ultralow dose chest CT
Kai YE ; Qiao ZHU ; Meijiao LI ; Yuliu LU ; Huishu YUAN
Journal of Practical Radiology 2019;35(11):1840-1844,1851
Objective To explore the best percentage of adaptive statistical iterative reconstruction Veo (ASiR-V)in detection of pulmonary nodule by chest ultralow dose CT (ULDCT).Methods 81 patients with pulmonary nodule detected by chest low dose CT (LDCT)underwent a local ULDCT scan at the center of the nodule with a range of 3 cm scan length.LDCT was performed with the mode of the Assist kV (120/100 kV)/Smart mA with noise indices of 14.1 HU and reconstructed with ASiR-V 50% algorithm.ULDCT was acquired at a tube potential of 120 kV and tube current-time product of 2.8 mAs and reconstructed with ASiR-V 50%,70% and 90%algorithms.Subjective and obj ective image qualities,sensitivities of detection and diameter of nodule among all ULDCT images were compared.Results Compared with the radiation dose of LDCT [(0.9 9±0.3 6)mSv],a 90.2% decrease was seen with the ULDCT, for which the calculated mean effective radiation dose was (0.097±0.007)mSv.The noise values of fat and paravertebral muscle for ULDCT reconstructed with ASiR-V 90% were 12.33±1.86 and 14.82±2.6,which were significantly lower than those in the group of ASiR-V 50% (1 9.73±1.98, 21.19±2.46)and the group of ASiR-V 70% (15.79±1.82,17.71±2.50)(P<0.05).The subjective scores of images reconstructed with ASiR-V 70% (4.13±0.47)were the highest,which were slightly higher than those in 90%groups (4.03±0.38)(P<0.05).No significant differences for overall sensitivity of nodule detection were observed among the ULDCT reconstructed with ASiR-V 50%(86.42%),ASiR-V 70%(87.04%)and ASiR-V 90% (88.89%)(P>0.05).The mean nodule diameter measurements were (6.4±2.0)mm,(5.9±2.2)mm,(6.0±2.2)mm and (6.1 ±2.2)mm for LDCT and ULDCT (ASiR-V 50%,70% and 90%),respectively with P>0.05.Conclusion At extremely low exposure levels,ASiR-V can obviously improve the image qualities of ULDCT,and 90% is the best percentage for lung algorithm reconstruction with a high sensitivity of pulmonary nodule detection.
4.Screening and functional verification of key genes in acute myeloid leukemia
Xinge SHENG ; Meijiao HUANG ; Jiaqi WANG ; Kaiwen FAN ; Quanyi LU
Journal of Leukemia & Lymphoma 2023;32(3):153-157
Objective:To explore the key genes related to the development, progression and prognosis of acute myeloid leukemia (AML) based on bioinformatics, and to analyze their functions.Methods:The chip expression profile GSE84881 data set of AML patients including 19 AML samples and 4 normal tissue samples was downloaded from the gene expression omnibus (GEO) database. GEO online tool GEO2R was used to screen the differentially expressed genes (DEG). The DAVID online database was used to make gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEG. The STRING online database was used to analyze the protein interaction (PPI) network of DEG, and the key genes were screened by using the Cytoscape software. The weighted gene co-expression network analysis (WGCNA) was used to build co-expressed network and obtain the central genes.LC-Bio online platform was used to construct Venn diagram and the key genes and central genes in PPI were crossed to finally obtain the true key genes. RNA-seq datasets GSE2191 and GSE90062 of human tissues were downloaded from GEO database to verify the screened key genes. Kaplan-Meier method was used to analyze the effects of key genes on the overall survival (OS) of AML based on the data of GEPIA database.Results:A total of 247 DEG were identified in GSE84881 data set, including 112 up-regulated genes and 135 down-regulated genes. According to the results of GO enrichment analysis, 247 DEG were mainly enriched in the regulation of signal transduction and cell proliferation in the biological process (BP); the cell composition (CC) revealed that these genes were mainly involved in the cytoplasm and exosomes; the molecular function (MF) analysis showed that these genes were mainly enriched in protein binding and calcium binding. Further KEGG pathway enrichment analysis showed that these 247 DEG were mainly involved in NOD-like receptor signal pathway and interleukin 17 (IL-17) signal pathway. And then the 12 key genes were obtained from PPI. WGCNA software was used to screen 13 central genes from GSE84881 dataset and finally 1 real key gene EGF was obtained after taking intersection. Kaplan-Meier method showed that OS time of AML patients in EGF high expression group was decreased than that in EGF low expression group, and the difference was statistically significant( P = 0.044). Conclusions:EGF may be an important diagnosis and treatment target of AML and may become a potential biomarker for clinical treatment and prognosis prediction of AML.
5.Sensitivity factor analysis of asymmetric gait quality evaluation model based on random forest algorithm
Meijiao JIANG ; Junxia ZHANG ; Yangyang SHAO ; Fangfang LU ; Guofu YIN ; Fang YANG
Chinese Journal of Tissue Engineering Research 2024;28(36):5805-5810
BACKGROUND:The assessment of asymmetric gait quality plays a pivotal role in guiding rehabilitation training;however,the link between gait quality and kinematic-kinetic gait parameters remains ambiguous. OBJECTIVE:To formulate a machine-learning model for evaluating gait quality based on gait parameters,identify factors sensitive to gait quality from asymmetric gait parameters,investigate the relationship between gait indicators and gait quality,and provide guidance for asymmetric gait training and rehabilitation. METHODS:An asymmetric gait database was established through the creation of asymmetric conditions.Kinematic and kinetic data were collected from 8 young and 8 elderly subjects(all male,right dominant population)during gait tests.Gait quality for each test data set was assessed using symmetry indices,resulting in the creation of a gait parameter-gait quality dataset.Utilizing the Random Forest algorithm,a gait quality evaluation model was developed and key quality parameter factors were identified through differential analysis.This model was iteratively refined.The model's performance was evaluated through 10-fold cross-validation,and its effectiveness was verified using the cross-validation dataset. RESULTS AND CONCLUSION:(1)A gradient test was designed to categorize gait quality into optimal,suboptimal,intermediate,and poor groups,with 759,329,133,and 125 instances,respectively.(2)The application of the Random Forest algorithm in gait quality assessment was explored.A relationship model was established between gait indicators and gait quality,yielding a predictive model accuracy of 95.99%.(3)The 13 main parameters significantly influencing asymmetric gait quality were identified through the Random Forest model's feature importance ranking.(4)An analysis of gait quality sensitivity factors using the 13 important parameters led to the identification of five key sensitivity indexes.The Random Forest model utilizing these sensitivity factors achieved a predictive accuracy of 94.20%.
6.Evaluation of cost-effective ratio (imaging quality vs. radiation dose) of Varian cone beam CT based on figure of merit (FOM)
Junyu LI ; Hao WU ; Jingxian YANG ; Tingting LI ; Songmao YU ; Zihong LU ; Meijiao WANG ; Chenguang LI ; Weibo LI ; Yibao ZHANG
Chinese Journal of Radiological Medicine and Protection 2020;40(8):595-599
Objective:To analyze and compare the radiation dose and image quality of kilo-voltage cone beam CT systems on different Varian accelerator platforms, providing data to support clinical decisions on selecting optimal protocols for image-guided radiotherapy based on cost-effective ratio (image quality / radiation dose).Methods:The radiation dose and image quality of various CBCT systems and scanning protocols on Varian Edge, Truebeam and ix (new and old) LINACs were obtained using a CT dose index (CTDI) phantom combined with a CT ionization chamber and a Catphan604 phantom, respectively. Figure of merit (FOM) was used to evaluate the cost-effective ratio of the image guidance schemes.Results:Considerable inter-system varieties of FOMs were observed, varying from 0.65 (Image Gently-full trajectory) to 48.46 (Image Gently-half trajectory). The inter-protocol varieties were also large, where the mean±SD was 22.14±13.47.Conclusions:Considering the explicit inter-system and inter-protocol varieties, it is clinically favorable to evaluate the image guidance schemes based on machine-specific measurement. For instance, parameters and equipment with low CTDI w can be beneficial for dose-sensitive patients. High CNR regimen favors patients with high image quality requirements. For ordinary patients, cost-effective ratio in terms of FOM can be very helpful to guide the decision-making of clinical image-guided radiotherapy.
7.Workflow and error analyses of patient setup based on open-face mask immobilization combined with AlignRT for head tumor radiotherapy
Junyu LI ; Hao WU ; Jingxian YANG ; Shun ZHOU ; Zihong LU ; Songmao YU ; Jixiang CHEN ; Meijiao WANG ; Kaining YAO ; Yi DU
Chinese Journal of Radiological Medicine and Protection 2022;42(8):590-597
Objective:To propose a markless patient setup workflow based on the optical surface monitoring system (AlignRT) and open-face mask immobilization for whole-course head tumor radiotherapy, assess the setup time and repositioning frequency of the proposed workflow, and conduct a comparative analysis of the differences, correlation, and consistency of the setup errors of the AlignRT and cone beam CT (CBCT) systems.Methods:A retrospective analysis was conducted for the data on the errors of 132 fractionated setup based on open-face mask immobilization of 33 head tumor patients. AlignRT-guided markless patient setup workflow was applied throughout the radiotherapy. Meanwhile, the body structures automatically generated by the treatment planning system were used as body references. The 6-degree-of-freedom (6DoF) setup errors (lateral, vertical, longitudinal, rotation, pitch, roll, and yaw directions), setup time, and repositioning frequency of the AlignRT and CBCT systems were recorded and analyzed. The Wilcoxon and Spearman analyses were used to statistically assess the differences and correlation of the setup errors of the two systems. Moreover, the Bland-Altman analysis was employed to evaluate the consistency of the two systems.Results:The 6DoF setup errors of CBCT were within the clinical tolerance (linear motions: -0.30 to 0.30 cm; rotational motions: -2.0° to 2.0°). The setup time and repositioning frequency of CBCT were (98 ± 31) s and 1.51% (2/132), respectively. There was no significant difference in setup errors between the two systems except those in x-axis ( Z = -3.11, P= 0.002), y-axis ( Z = -7.40, P<0.001), and Pitch ( Z= -4.48, P<0.001). There was a significant positive correlation between the setup errors along lateral ( rs = 0.47, P<0.001) and vertical ( rs = 0.29, P = 0.001) directions, rotation (Rtn; rs = 0.47, P<0.001), pitch (Pitch; rs = 0.28, P = 0.001) and roll (Roll; rs = 0.45, P<0.001) of the two systems. The 95% limits of agreement (95% LoA) of 6DoF setup errors were -0.12 to 0.09 cm, -0.07 to 0.17 cm, -0.19 to 0.20 cm, -1.0° to 0.9 °, -1.0° to 1.5°, and -0.9° to 1.0°, respectively. The 95% confidence interval (95% CI) of 95% LoA was -0.14 to 0.11 cm, -0.09 to 0.19 cm, -0.23 to 0.23 cm, -1.2° to 1.1°, -1.2° to 1.7°, and-1.0° to 1.1°, respectively, all of which were within the permissible error ranges. The 6DoF setup error difference of 3.41% (27/792< 5%) was beyond the 95% LoA. The maximum absolute differences of 6DoF setup errors within the 95% LoA were 0.12, 0.16, 0.19 cm, 0.9°, 1.5°, and 1.0°, respectively. Conclusions:The proposed markless setup workflow based on AlignRT combined with open-face mask immobilization for whole-course head tumor radiotherapy exhibits reasonable agreement and consistency with the patient setup using CBCT, with acceptable clinical efficiency. It can be applied to the first radiotherapy and the real-time monitoring of therapy to improve the safety and thus is of value in clinical applications.