Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and beta-cyclodextrin (beta-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of beta-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s(-1). Then, the synergetic drug delivery systems were prepared with the ratio of 6.74 : 1 (w/w) for beta-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in beta-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, beta-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems approximately lipid microspheres < beta-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and beta-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by beta-CD through hydrogen bonds.
Acetaminophen ; administration & dosage ; chemistry ; Administration, Oral ; Drug Delivery Systems ; Electrical Equipment and Supplies ; Electrochemical Techniques ; instrumentation ; methods ; Hydrogen Bonding ; Kinetics ; Lipids ; chemistry ; Microspheres ; Solubility ; Taste ; drug effects ; beta-Cyclodextrins ; chemistry

OBJECTIVETo develop a more reliable and stable method for determining monoclonal antibody (mAb) affinity constant based on competitive antibody/antigen binding.

METHODSThe Kd value was calculated based on the relationship between the binding proportion of the antigen and the original concentration of the mAb that competed for the binding site of the antigen.

RESULTSThe Kd values measured with this improved method under two different conditions were 2.61x10(-12) mol/L and 2.39x10(-12) mol/L, and those with Friguent method in these two conditions were 5.57x10(-10) mol/L and 1.41x10(-10) mol/L, respectively.

CONCLUSIONCompared with Friguent method, the Kd values measured with this improved method are closer to the actual value, and the measurement results under different experiment conditions are more stable.

Antibodies, Monoclonal ; immunology ; Antibody Affinity ; immunology ; Antigen-Antibody Complex ; immunology ; Binding, Competitive ; Enzyme-Linked Immunosorbent Assay ; Humans

In the context of internationalization of education,the military graduate education concepts and models also come to change,and opportunities and challenges coexist.In this article,the challenges and problems of army medical college graduate education were mentioned and analyzed,and the exploration and attempt of graduate education in the process of international were summarized.

Objective To investigate the clinical outcome of patients receiving stereotacticcannula placement for hypertensive intracerebral hematoma drainage and the relationship between thedrainage cannula and the cerebral angioarchitecture. Methods Sixty-three patients with hypertensiveintracerebral hematoma underwent operations for stereotactic placement of a soft tube for hematomadrainage. CT angiography and CT venography were performed prior to cannula withdrawal after thepatients' condition was stabilized or complete hematoma drainage. The relationship between the drainagecarmula, cerebral angioarchitecture and the entry route of the cannula were observed. ResultsPostoperative CT angiography and CT venography showed that the entry route of the cannula allowedsafe passage of the cannula along the cerebral arteries and veins, and the position of the cannula wasaccurate in all the patients. Satisfactory hematoma drainage and good postoperative recovery wasachieved in all the patients, and no significant injuries to the adjacent cerebral arteries or veins occurredin these cases. Conclusion Stereotactic cannula placement with the minimally invasive technique forhemotoma drainage causes minimal injury and is safe, effective, cost-effective and convenient fortreatment of hypertensive intracerebral hematoma.

Objective To analysis the spatial autocorrelation on the small-scale distribution of the genetic variation in the population of Oncomelania hupensis in Puge county, Sichuan province, using simple sequence repeat (SSR) marker. Methods 5 pairs of SSR primer were used to amplify the genomic DNA of Oncomelania hupensis, and the alleles with frequency ranging from 15% to 85% were used to calculate Moran' s I spatial autocorrelation coefficients in 14 distance band based on equal numbers of paired samples. Results A total of 274 alleles were scored by 5 pairs of SSR primer, the average polymorphic information content of the 274 alleles were 0.965 which indicated a high level of genetic diversity. 39 alleles showed different patterns of positive spatial autocorrelation of genetic variation, which was non-random spatial structure. When the distance band increased, the spatial auto-correlativity decreased based on the average Moran' s I value at 14 distance band. The alleles which showed a negative spatial autocorrelation were not found in any distance band. Conclusion The spatial distribution of the genetic variation of SSR showed positive spatial autocorrelation in the population of Oncomelania hupensis, and the spatial auto-correlativity decreased with the increase of distance band.

Objective To investigate the reference interval of neonatal nutrition assessment biochemical factor,including total protein (TP),serum albumin (ALB),serum prealbumin (PA) and serum retinol binding protein (RBP).Methods From December 2016 to August 2017,403 serum specimens were collected from health neonates in Hunan Children's Hospital and the serum concentration of TP,ALB,RBP and PA was detected.The results of each item were grouped according to sex and age,and then the reference interval of each item was established.Results When data was separated by gender of each item,there was no statistical significance between each group of each item (P ＞ 0.05).For the TP,ALB and RBP,separating the data of each item by weeks,there were also no statistical significance between each group (P ＞ 0.05).But there was statistical difference between one week old group and the rest groups in the data of PA (P ＜ 0.05).The normal reference interval of neonatal serum total protein,albumin,retinol binding protein and pre-albumin are as follow:(40.69-65.72) g/L,(28.77-42.3) g/L,(12.13-33.19) mg/L,(42.26-161.52) mg/L (no more than 7 days old) and (59.05-170.23) mg/L (range from 8 to 28 days old).Conclusions We can establish the reference interval of TP,ALB and RBP without differentiating gender and weeks.But for the PA,the reference interval of one-week-old neonate needs to differentiate from other neonates.

OBJECTIVETo investigate enhancement of the bystander effect by tanshinone IIA (Tan) in HSV-tK/GCV system and the correlation with expression of connexin 43 mRNA.

METHODSThe cytotoxic effect in HSV-tK/GCV in cervical carcinoma cell line ME180 (ME) and ME/TK was examined by MTT assays. Cx43 mRNA expression was detected by fluor-quantitative RT-PCR.

RESULTSTan markedly increased sensitivity of ME/TK cells for GCV in HSV-tK/GCV system. In the presence of 2 micro g/ml GCV, compared with the absence of Tan (0 mol/L), an obvious decrease in survival rate was seen at any given mixture of ME and ME/TK cells exposed to 1.3 x 10(-9) mol/L Tan. Statistics showed significant difference (P < 0.05). However, enhancement of bystander mediated cell killing occurred only in the range of Tan concentrations used (1.3 x 10(-8), 1.3 x 10(-9) mol/L). RT-PCR showed that the ratio of relative copy number of Cx43 mRNA increased by 8.83 and 8.47-fold in ME cells exposed to 1.3 x 10(-8) and 1.3 x 10(-9) mol/L Tan, respectively.

CONCLUSIONFor the first time we report that in cervical carcinoma ME180 cell line, Tan possesses a remarkable enhancing role on the bystander effect in the HSV-tK/GCV system. It is associated with up-regulation of Cx43 mRNA expression.

Antineoplastic Agents, Phytogenic ; pharmacology ; Bystander Effect ; Cell Line, Tumor ; Cell Survival ; drug effects ; Connexin 43 ; genetics ; Diterpenes, Abietane ; Female ; Ganciclovir ; pharmacology ; Genetic Therapy ; Humans ; Phenanthrenes ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Simplexvirus ; enzymology ; Thymidine Kinase ; genetics ; Uterine Cervical Neoplasms ; therapy

Objective To detect and analyze the clusters of schistosomiasis on marshland and lake areas based on geographic information system (GIS) in 2008 and to provide suggestions for the development of integrated methodology on the detection of clusters on related diseases. Methods Moran' s I of global spatial autocorrelation, Getis-Ord Gi of local spatial autocorrelation and SaTScan were used to detect the schistosomiasis clusters based on GIS and comparison of the results for different methods were performed. Results Results from the global Moran' s I tests for all the marshland and lake areas related to the schistosomiasis were statistically significant (P＜0.05)and indicated spatial heterogeneity; the z-score outcomes as calculated by Getis-Ord Gi indicated high cluster that 50 clusters were categorized at the 0.05 significance level and the z-score of these 45 clusters were more than 0. Results of SaTScan statistics appeared the same as local spatial autocorrelation and almost showing the existence of 5 cluster areas. Conclusion The geographical distribution of clusters where schistosomiasis was prevalent showed that it was closely corresponded to the middle and lower Yangtse river and in particular, many clusters were located near the boundary of Hubei and Hunan province.

The patient was a female infant aged 1 month and 29 days. She was admitted to the hospital due to convulsions for 6 days and increased blood glucose level for 5 days. She had unstable blood glucose levels. The level of glycosylated hemoglobin was too high to measure. Urine glucose was positive (+ - ++++). The levels of fasting C-peptide and insulin were 0.19 ng/mL and 11.68 μIU/mL respectively. High-throughput sequencing of the genetic endocrine disease gene Panel (412 detected genes, including 49 known diabetes-related genes) showed that the EIF2AK3 gene in the infant had two novel compound heterozygous mutations, c.2731_2732delAG and c.2980G>A, both of which were located in the kinase domain. The infant was diagnosed with Wolcott-Rallison syndrome (WRS). As a rare autosomal recessive disease, WRS is characterized by neonatal diabetes, multiple epiphyseal dysphasia and liver disease. Neonatal diabetes is a prerequisite for the diagnosis of WRS. The EIF2AK3 gene is the pathogenic gene of WRS.
Diabetes Mellitus, Type 1 ; Epiphyses ; abnormalities ; Female ; Humans ; Infant ; Mutation ; Osteochondrodysplasias ; eIF-2 Kinase

Objective:To compare the efficacy of robot-assisted and conventional fluoroscopy-guided percutaneous vertebroplasty (PVP) combined with pediculoplasty in treating symptomatic chronic thoracolumbar osteoporotic vertebral fracture (SCOVF) without neurological symptoms.Methods:A retrospective cohort study was used to analyze the clinical data of 120 patients with thoracolumbar SCOVF without neurological symptoms, who were admitted to Honghui Hospital Affiliated to Xi′an Jiaotong University from January 2015 to January 2020. The patients included 34 males and 86 females, aged 63-85 years [(72.9±5.7)years]. All patients were treated with PVP combined with pediculoplasty. A total of 87 patients were treated with robot-assisted and C-arm X-ray machine guided puncture (robot group) and 33 patients with C-arm X-ray machine fluoroscopic-guided puncture (conventional group). The operation time, amount of bone cement injection and puncture accuracy were compared between the two groups. The results of vertebral body index, Cobb angle, visual analogue scale (VAS), and Oswestry disability index (ODI) were also compared before operation, at 1 day and 1 year after operation and at the final follow-up. Complications such as bone cement leakage and displacement were observed.Results:All patients were followed up for 24-36 months [(29.4±3.4)months]. The operation time was (85.2±10.5)minutes in the robot group, significantly longer than (37.2±3.7)minutes in the conventional group ( P<0.01). The amount of bone cement injection was (5.0±0.7)ml in the robot group, significantly less than (5.3±0.8)ml in the conventional group ( P<0.05). The puncture accuracy in the robot group was 95.4% (83/87), significantly higher than 81.8% (27/33) in the conventional group ( P<0.01). There were no significant differences in vertebral body index, Cobb angle, VAS or ODI between the two groups before operation (all P>0.05). The values of vertebral body index were 87.1±4.5, 86.9±4.3, 86.8±4.3 in the robot group at 1 day after operation, 1 year after operation and the final follow up, respectively, which were significantly higher than 83.6±4.4, 84.1±3.8, 84.4±3.9 in the conventional group (all P<0.01). There were no significant differences in Cobb angle or ODI between the two groups at 1 day after operation, 1 year after operation or the final follow-up (all P>0.05). The values of VAS were (2.9±1.0)points, (1.8±0.7)points, (1.8±0.7)points in the robot group at 1 day after operation, 1 year after operation and the final follow-up, respectively, which were significantly lower than (4.4±1.1)points, (3.1±0.8)points, (3.0±0.9)points in the conventional group (all P<0.01). The bone cement leakage occurred in 7 patients in the robot group [8.0%(7/87)] and in 10 in the conventional group [30.3%(10/33)] ( P<0.01). No delayed bone cement displacement [0.0%(0/87)] occurred in the robot group from 1 day after operation to the final follow-up, but 3 patients [9.1%(3/33)] were noted in the conventional group ( P<0.05). Conclusion:Both robot-assisted and conventional fluoroscopy-guided PVP combined with pediculoplasty have satisfactory effect for SCOVF patients without neurological impairment, but the robot-assisted one has the advantages of higher puncture accuracy, more satisfactory vertebral height recovery, more rapid pain relief, lower incidence of bone cement leakage and effective avoidance of cement displacement.