Objective To investigate the influence of surface grafting density of polyethylene glycol (PEG) molecules on the interactions of nanoparticle with the biomembrane.Methods The dynamics of polymer as well as its shielding effect on the wrap of the membrane were investigated using coarse-grained (CG) molecular dynamics simulations.A coarse grained model force field,MARTINI,was employed for its ability to reproduce experimental properties of various lipid dynamics and some kinds of polymer as well.Results As a result,structural variations and energy changes of grafted PEG molecules on the nanoparticles,adsorbing dynamics of PEGs on the membrane as well as the wrap rates of the membrane were obtained to shed light on the PEGylation-mediated shielding mechanism in the adsorption of PEGylated nanoparticles on the membrane.Conclusions The surface grafting density of PEGylated nanoparicles has been found to play a crucial role in the stealth shielding behavior of PEGylated nanocarriers.These studies are consistent with experimental observations and to some extent give a molecular level interpretation of the macroscale observations of prolonged circulation half-life of stealth nanocarriers.

OBJECTIVE:To provide reference for revising the standards of primaquine phosphate in International Pharmacopoe-ia (the fifth edition). METHODS:Based on inspection standards for primaquine phosphate and its preparations in different coun-tries,HPLC,perchloric acid potentiometric titration and sodium nitrite dead-stop titration were adopted to determine and compare the contents of primaquine phosphate. RESULTS:In HPLC,the linear range of primaquine phosphate was 128.1-384.2 μg/ml(r=0.999 9);the limit of detection was 0.18 μg/ml,the limit of quantification was 0.59 μg/ml;RSDs of precision,stability and repro-ducibility tests were lower than 1%;recovery was 99.42%-101.14%(RSD=0.6,n=9);destructive test and durability test showed good specificity;the contents of 3 batches of samples were 92.1%,92.3% and 92.0%,respectively. In perchloric acid potentiomet-ric titration,RSDs of precision and reproducibility tests were 1.6%;the titration jump was not obvious;the contents were 99.1%, 99.7% and 98.7%,respectively. In sodium nitrite dead-stop titration,RSDs of precision and reproducibility tests were lower than 1%;the titration jump was obvious;the contents were 96.9%,97.1% and 96.7%,respectively. Sodium nitrite external indicator ti-tration showed better precision than dead-stop titration;the contents were 99.6%,100.0% and 99.5%,respectively. CONCLU-SIONS:Perchloric acid potertiometric titration is simple and rapid,but with relatively poor precision and reproducibility,and it contains quinocide. Sodium nitrite dead-stop titration is simple with good precision and reproducibility but long reaction time,and it also contains quinocide,the HPLC method shows good separation and high accuracy,can effectively separate the quinocide in primaquine phosphate,and it is suitable for the quality control of primaquine phosphate.

ObjectiveTo investigate the relationship between the clinical type of attack and electroencephalogram (EEG) features of cerebral palsy (CP) children with epilepsy (EP).MethodsThe EEGs of 36 CP cases with EP were recorded under natural circumstances.Results20 cases (55.6%) had focal high amplitude spikes and wave complexes; 4 cases (11.1%) had typical hypsarrhythmia; 3 cases (8.3%) had varied hypsarrhythmia. Among them, the spikes and wave complexes of 9 cases were bilateral.ConclusionThe most of the clinical attack and EEG characters of CP children with EP are partial type.

OBJECTIVE: To evaluate and compare whole exome sequencing (WES) and targeted panel sequencing in the clinical molecular diagnosis of the Chinese families affected with inherited retinal dystrophies (IRDs). METHODS: The clinical information of 182 probands affected with IRDs was collected, including their family history and the ophthalmic examination results. Blood samples of all probands and their relatives were collected and genomic DNA was extracted by standard protocols. The first 91 cases were subjected to the WES and the other 91 cases were subjected to a specific hereditary eye disease enrichment panel (HEDEP) designed by us. All likely pathogenic and pathogenic variants in the candidate genes were determined by Sanger sequencing and co-segregation analyses were performed in available family members. Copy number variations (CNVs) detected by HEDEP were further validated by multiplex ligation-dependent probe amplification (MLPA). As PRGR ORF15 was difficult to capture by next generation sequencing (NGS), all the samples were subjected to Sanger sequencing for this region. All sequence changes identified by NGS were classified according to the American College of Medical Gene-tics and Genomics and the Association for Molecular Pathology (ACMG/AMP) variant interpretation guidelines. In this study, only variants identified as pathogenic or likely pathogenic were included, while those variants of uncertain significance, likely benign or benign were not included. RESULTS: In 91 cases with WES, pathogenic or likely pathogenic variants were determined in 30 cases, obtaining a detection rate of 33.00% (30/91); While in 91 cases with HEDEP sequencing, pathogenic or likely pathogenic variants were determined in 51 cases, achieving the diagnostic rate of 56.04% (51/91), and totally, the diagnostic rate was 44.51%. HEDEP had better sequencing coverage and read depth than WES, therefore HEDEP had higher detection rate. In addition, HEDEP could detect CNVs. In this study, we detected disease-causing variants in 29 distinct IRD-associated genes, USH2A, ABCA4 and RPGR were the three most common disease-causing genes, and the frequency of these genes in Chinese IRDs population was 11.54% (21/182), 6.59% (12/182) and 3.85% (7/182), respectively. We found 43 novel variants and 6 cases carried variants in RPGR ORF15. CONCLUSION NGS in conjunction with Sanger sequencing offers a reliable and effective approach for the genetic diagnosis of IRDs, and after evaluating the pros and cons of the two sequencing methods, we conclude that HEDEP should be used as a first-tier test for IRDs patients, WES can be used as a supplementary molecular diagnostic method due to its merit of detecting novel IRD-associated genes if HEDEP or other methods could not detect disease-causing va-riants in reported genes. In addition, our results enriched the mutational spectra of IRDs genes, and our methods paves the way of genetic counselling, family planning and up-coming gene-based therapies for these families.
DNA Copy Number Variations ; Humans ; Mutation ; Pedigree ; Retinal Dystrophies/genetics* ; Whole Exome Sequencing

Adult ; Esophageal Neoplasms ; diagnosis ; Humans ; Hypopharyngeal Neoplasms ; diagnosis ; Male ; Sarcoma, Synovial ; diagnosis

Nowadays, for gait instability phenomenon, many researches have been carried out at home and abroad. However, the relationship between plantar pressure and gait parameters in the process of balance adjustment is still unclear. This study describes the human body adaptive balance reaction during slip events on slippery level walk by plantar pressure and gait analysis. Ten healthy male subjects walked on a level path wearing shoes with two contrastive contaminants (dry, oil). The study collected and analyzed the change rule of spatiotemporal parameters, plantar pressure parameters, vertical ground reaction force (VGRF), etc. The results showed that the human body adaptive balance reaction during slip events on slippery level walk mainly included lighter touch at the heel strikes, tighter grip at the toe offs, a lower velocity, a shorter stride length and longer support time. These changes are used to maintain or recover body balance. These results would be able to explore new ideas and provide reference value for slip injury prevention, walking rehabilitation training design, research and development of walking assistive equipments, etc.
Adaptation, Physiological ; Foot ; Gait ; Humans ; Male ; Postural Balance ; physiology ; Pressure ; Reference Values ; Walking

Vitamin B1 self-assembled monolayer modified electrode (VB1-Au/SAMs/CME) was prepared and its electrochemical behavior was studied by cyclic voltammetry. The results showed that a self-assembled monolayer (SAM) was formed on the surface of gold electrode. \3-/4-redox couple was used as the electrochemical probe to study the electrochemical characteristics of SAM modified gold electrode and the results indicated that the existence of Vitamin B1 membrane on gold surface hindered the electron transfer. The electrochemical behaviors of dopamine(DA) and uric acid (UA) were investigated at VB1-Au/SAMs/CME. The results showed that the electrochemical oxidation of DA and UA could be electrocatalyzed. There were linear relationships between the anodic peak current and the concentration of DA(8.0×10-6-4.0×10-4 mol/L) and UA (6.0×10-5-2.2×10-4mol/L) respectively in differential pulse voltammograms. This modified electrode was effective to detect DA and UA in simultaneous determination of these species in a mixture.

Objective To study the effects of internal and external biliary drainage on inducible nitric oxide synthase (iNOS) mRNA expression of Kupffer cells and serum tumor necrosis factor-alpha (TNF-α) in rats with obstructive jaundice. Methods Forty-eight male Sprague-Dawley rats were randomly assigned to obstructive jaundice (OJ), sham operation (SH), internal biliary drainage (ID) and external biliary drainage (ED) groups with 12 each. Kupffer cells were isolated by in situ hepatic perfusion and digestion with collagenase type Ⅳ, and purified by cell culture attachment. The expression of iNOS mRNA of Kupffer cells was detected by reverse transcription polymerase chain reaction (RT-PCR) and the serum TNF-α concentration was measured using ELISA method. Results The serum TNF-α level was increased in OJ group[ (110.84±26.3) pg/ml ]compared with SH group [-(88.4±17.9) pg/ml, (P=0.045)]. The TNF-α level in ID group[ (89.8±28. 3) pg/ml ]was significantly lower than that in ED group[ (118.64±22.7) pg/ml, (P=0. 011) ]and OJ group (P=0. 059). Expression of iNOS mRNA of Kupffer cells was significantly higher in OJ group (0. 824± 0. 24) compared with SH group (0. 384±0.35,P=0. 005). After relieving the OJ, the iNOS mRNA expression in ED group (0. 974± 0.48) was not suppressed (P=0. 321). On the contrary, the iNOS mRNA expression in ID group was suppressed and significantly lower than that in ED group (0. 59±0. 35) (P=0. 016). Conclusions Internal biliary drainage is superior to external drainage in terms of reversing the elevated serum TNF-α and in suppressing the iNOS mRNA expression of Kupffer cells in rats with obstructive jaundice.

0.05).The level of TG,TC and LDL-C of high cholesterol group was higher than that of the other groups(P

AIM: Currently available anti-scarring regimens for glaucoma filtration surgery have potentially blinding complications and safer alternatives would be beneficial. This experiment is to investigate the effect of TGF-β2 antisense oligodeoxynucleotide on differentiation, proliferation of subconjunctival fibroblast following glaucoma filtration surgery.METHODS: Glaucoma filtration surgery were performed on both eyes of 28 rabbits. TGF-β2 antisense oligodeoxynudeotide was subconjunctivally injected in the right eyes (A group), and TGF-β2 missense oligodeoxynucleotide (B group)or PBS(C group) was used at the same method in the left eyes as controls. Rabbits were killed at 4,7,14 and 28 days after surgery. Intraocular pressure (IOP), bleb characteristics were recorded at different time point. Subconjunctival fibroblasts were examined by immunohistochemistry and electron microscopy.RESULTS: The IOP of rabbits in group A was significantly lower at 14 days (6.74± 1.18 mmHg) and 21 days (8.15± 1.97mmHg) after operation than the IOP in group B (8.53± 1.04,9.72± 1.09 mmHg)(P ＜0.01) and group C(8.79± 1.21, 9.43±1.27 mmHg) (P ＜0.05). The mean bleb survival time was longer (17.2 days) in group A than that of group B (14.5 days) and group C (13.5 days)(P＜0.05). The population of the cells expressing α -smooth muscle actin(α -SMA) and proliferating cell nuclear antigen (PCNA) was significantly reduced in group A compared with the group B and C. The ultrastructure of fibroblast was not altered by TGF-β2 anti-sense oligodeoxynucleotide.CONCLUSION:TGF-β2 antisense oligodeoxynucleotide can prevent the scar formation after glaucoma surgery by inhibit the differentiation and proliferation of subconjunctival fibroblast. It could be a potentially useful anti-scarring alternative for the prevention of late surgical failure.