Heat sensitive protein medicines are increasingly exhibiting their critical importance on treatment of various diseases at present. But their popularization and application meet a great challenge because of their heat instability. In the present study, insulin was taken as a heat sensitive protein medicine and amino acid as bio-protective agent in order to investigate if these amino acids can protect the insulin from losing its bioactivity due to desiccation. The experiment was performed by using replica exchange molecular simulation (REMD) method and Gromacs software with Gromos96 (53a6) force field. The REMD results indicated that these amino acids could protect the bioactive structure of insulin during desiccation. The configurations of the protected insulin were preserved very well. Those results proved that amino acid is a kind of good bioactive protective agent for the heat sensitive protein medicines.
Amino Acids ; chemistry ; Desiccation ; Drug Stability ; Insulin ; chemistry ; Molecular Dynamics Simulation ; Software

Objective To explore the incidence and risk factors of bacterial infection after othtotopic liver transplantation (OLT). Methods Altogether 56 OLT recipients from January 2005 to October 2007 were included in the study. The incidents and the related variables of the infection were analyzed retrospectively. The related variables were evaluated using multivariate logistic regression model to identify the significant risk factors. Results Bacterial infection was confirmed in 29 recipients (51.8%). Among them, the lung infection was the most common site (53.7%). The Gram-positive cocci were 46.3%, while the Gram-negative bacilli were 53.7%. The risk factors for bacterial infection included duration of the operation and detained respirator using. Conclusion Bacterial infection is a major complication following OLT. Surveillance for the risk factors, enhancement the skill of operation, and improving the recovery of respiratory function is the key to decreasing the incidence of bacterial infection after transplantation.

Objective:To establish the detection method of double-antibody sandwich ELISA about CYFRA 21-1 in human ser-um.Methods:The paired antibody were screened among four strains mAbs of CYFRA 21-1, which was marked by sodium periodate method.The detecting method of double antibody sandwich ELISA was optimizted , and evaluated by specificity , stability and sensitivi-ty.Results:The results showed that a paired of antibody , which was 2F9 as the coated antibody and 6F11 as the labeled antibody, was selected from four mAbs .It was the optimum condition of double antibody sandwich ELISA that the coating antigen concentration of 2F9 was 0.50 μg/ml, while the labeled antibody of 6F11 was diluted 6 000 times.The linear range of standard curve was 0.7-25 ng/ml with r2 =0.990 8, while the limit of detection was 0.666 8 ng/ml, the recovery rate was 98.14%.The cross-reactions with the oth-er analogues in serum were less than 0.1%.The coefficient of variation in group (n=10) was 6.8%, whereas coefficient of variation among group(n=5) was 11.4%.The correlation compared with other foreign ELISA kit was 91.42%.Conclusion:In brief, we suc-cessfully established the method of double antibody sandwich ELISA detecting CYFRA 21-1 level in human serum , laying the foundation for the production of CYFRA21-1 ELISA kit.

Objective:The response surface methodology (RSM) and Box-Behnken design were adopted to optimize the preparation for citrus oils β-cyclodextrin microspheres inclusion compound. And the physical characterization and heat stability were evaluated.Methods:The best preparation technology included inverse emulsion polymerization and saturated water solution method, with volatile oil weight ratio and microspheres, microspheres and water feeding ratio, inclusion temperature as impact factors, inclusion rate as the response value, establish regression model,. We explored the orange peel naphtha beta ring paste by microscopy, infrared spectroscopy (IR), differential scanning calorimetry (DSC) and heat stability test.Results:The best preparation technology included the essential oil with beta ring paste microspheres ( V: m), the ratio of 1:10, beta ring paste small ball and the ratio of water (m: V) for 1:15, and inclusion temperature for 41 ℃. The average encapsulation efficiency and the average rate of yield under optimized conditions were 62.21% and 85.24%, respectively. The physical characterization and thermal stability tests demonstrated that the β-cyclodextrin microsphere inclusion complex of volatile oil from Citrus was successfully prepared and the physical properties were stable. Conclusion:The preparation method of citrus oils β-cyclodextrin microspheres inclusion compound by using the response surface methodology.

OBJECTIVETo investigate the effect of unaggregated Abeta(25.35) on delayed rectifier potassium current (I(K)) in neonatal rat hippocampal CA3 pyramidal neurons.

METHODSThe rat hippocampal neurons were enzymatically isolated from 10-11-day-old Wistar rat. The I(K) was recorded using whole-cell patch clamp technique.

RESULTSThe inhibitory effect of unaggregated Abeta(25-35) on I(K) was time-dependent, because I(K) significantly decreased from (6.987 +/- 1.152) nA to (2.540 +/- 0.349) nA after adding unaggregated Abeta(25-35) and reached a stabilized level after 5-7 min (n = 8, P <0.01). However, the inhibitory effect was not concentration-dependent, because the decrease of the I(K) amplitude in different concentration groups were all around 60%. Unaggregated Abeta(25-35) also remarkably affected the half-activation potential, which was (4.114 +/- 0.730) mV and (-5.463 +/- 0.950) mV before and after its application (n = 15, P <0.05); however, the slope factor of activation curve was not significantly changed.

CONCLUSIONThe inhibitory effect of unaggregated Abeta(25-35) on I(K) may be a possible mechanism involved in the pathogenesis of Alzheimer's disease.

Alzheimer Disease ; metabolism ; Amyloid beta-Peptides ; chemistry ; pharmacology ; Animals ; Animals, Newborn ; Cells, Cultured ; Female ; Hippocampus ; cytology ; Male ; Mice ; Neurons ; drug effects ; metabolism ; Patch-Clamp Techniques ; Potassium ; metabolism ; Rats ; Rats, Wistar

Objective:To assess the configuration and systolic function of the left ventricle in patients with chronic thromboembolic pulmonary hypertension (CTEPH) by routine ultrasound, two-dimensional speckle tracking imaging and three-dimensional echocardiography, and to observe the recovery after pulmonary endarterectomy (PEA).Methods:The patients who were diagnosed with CTEPH, underwent PEA and had no left heart disease were enrolled as the CTEPH group ( n=30) in the China-Japan Friendship Hospital from November 2016 and June 2021. The right heart catheterization data before and after surgery were recorded. In the meantime, gender- and age-matched healthy individuals who sought for physical examination during the same period were included as the control group ( n=23). Echocardiography findings before and after PEA were comparatively analyzed and compared between the two groups, including left ventricular end-diastolic diameter (LVEDd), right and left ventricular cross-section ratio (RVd/LVd), left ventricular global longitudinal strain (LVGLS), left ventricular end-diastolic/systolic volume index (LVEDVi/LVESVi), left ventricular ejection fraction (LVEF) and left ventricular stroke volume (LVSV). Associations between the mean pulmonary arterial pressure (mPAP)/pulmonary vascular resistance (PVR) and left ventricular function were discussed. Results:When compared with the control group, the LVEDd, LVEDVi, LVESVi, LVSV, LVGLS and the mitral early to late diastolic flow velocity ratio (E/A) in the CTEPH group were lower (all P<0.05). There were no significant differences between the two groups regarding LVEF, cardiac output (CO), and cardiac index (CI) (all P>0.05). There were no statistical differences of the left ventricular volume and LVSV between PEA group and the control group (both P>0.05), while the LVGLS and E/A remained lower (both P<0.05). Correlation analysis showed negative associations between mPAP and LVSV as well as E/A ( r=-0.490, -0.455; both P<0.05). Conclusions:There are changes in left ventricular configuration with abnormal filling pattern and potential systolic dysfunction in CTEPH patients. The PEA surgery could lead to recovery of the left ventricular configuration and volume, but the filling pattern and LVGLS at follow-up can not recover completely.

Nowadays various protein medicines are increasingly playing significant roles in the treatment of many diseases, but the bioactive structures of such kinds of protein medicines are unstable because they are heat sensitive. Therefore, it is very important to explore a protective method and to explain the protective mechanism of protein medicines. In the present research, insulin was chosen as a heat-sensitive protein medicine, and a Group 3 late embryogenesis abundant (LEA) protein was chosen as its bioactive protectant during desiccation. The results of replica exchange molecular dynamics simulation suggest that comparing with insulin without any protection, the bioactive 3D structure and secondary structure of the insulin protected by LEA protein were preserved very well. All analyzing results proved that the LEA protein was a good bioactive protectant for heat sensitive protein medicines.
Animals ; Cold Temperature ; Drug Stability ; Freeze Drying ; Helminth Proteins ; chemistry ; Insulin ; chemistry ; Nematoda ; Plant Proteins ; pharmacology ; Protein Interaction Domains and Motifs ; Protein Structure, Secondary

OBJECTIVETo evaluate clinical feasibility and efficacy of endoscopic metal stenting combined with radiotherapy for treatment of medium and late stages of esophageal carcinoma.

METHODSThirty-four patients of late stage esophageal carcinoma were treated with endoscopic stent implantation in combination with radiotherapy. Evaluations of CES stainless steel metal stent on the effect of radiation, clinical symptom alleviation and complication and survival rates in both groups were made.

RESULTS(1) CES stainless steel metal stent had no effect on radiation dosage distribution. (2) Dysphagia was markedly alleviated in both groups and different complication rates were observed between the two groups. (3) Six, nine and twelve month survival rates of inpatients treated with combined therapies were significantly higher than in simple stent implantation patients.

CONCLUSIONEndoscopic metal stenting in combination with radiotherapy was a feasible and practical management in treating medium and late stages esophageal carcinoma and was superior to simple metal stent implantation.

Aged ; Combined Modality Therapy ; Deglutition Disorders ; etiology ; Esophageal Neoplasms ; mortality ; therapy ; Female ; Humans ; Male ; Middle Aged ; Palliative Care ; Radiotherapy Dosage ; Stents ; adverse effects ; Survival Rate

Objective To assess the association between rs7597593 polymorphism of ZNF804A gene and schizophrenia,and to assess the relationship between rs7597593 polymorphism and working memory.Methods Schizophrenia patients and healthy controls were diagnosed in accordance with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-Ⅳ) ; 767 schizophrenia patients and 690 healthy controls were involved.Restriction fragment length polymorphism (RFLP) was carried out to genotype rs7597593 polymorphism.The cognitive function of working memory was assessed by the N-back task.Statistical analyses were carried out with SPSS19.0 software.Results The study found no significantly different genotype frequencies (x2=1.519,P=0.468) and allele frequencies(x2=1.263,P=0.261) of rs7597593 polymorphism between schizophrenia patients and healthy controls,however in the subgroup of higher IQ (IQ ≥ 110),there were significant different distributions of both genotype and allele (x2 =9.411 and 6.529; P=0.009 and 0.011 respectively).It was also found in this subgroup that risk T allele was associated with more error at 1-back task (F=6.854,P=0.009).Conclusion These results indicated that rs7597593 polymorphism was associated with individuals having spared cognitive function; carriers of T allele had worse cognitive function,which maybe a pathway that it contributes to schizophrenia.