OBJECTIVE:To study the classification of deviation in drug production. METHODS:From the perspective of dom-inant and hidden deviation,combining with the theory of risk management,risk of deviation was evaluated with different risk man-agement tools to define the severity of the deviation,and it was handled by different methods. RESULTS & CONCLUSIONS:Ac-cording to the identifiability of deviation in actual management,the deviation was divided into dominance and hidden deviation. The dominant deviation can be divided into deep and shallow level. Whether the causes of deviation could be cleared and the conse-quences could be estimates were judged after the shallow level classification,and the deviation was further divided into simple and complex deviation. As for deviation complex,it could be evaluated with the tools of risk management to define the deviation severi-ty. As for hidden deviation,it needed beforehand preventing with the tools of risk management directly to define deviation levels and provide reference for preventive measures. In the process of deviation management,key point is to relay on the scientific meth-od to identify and classify deviation,and divide the influence levels. Combining the theory of risk management to select and use risk tools is the effective way to solve the problem.

Objective:To compare the properties of three kinds of denture base materials treated and untreated by hydraulic pressure cooker. Methods: The impact strength, flexural strength, flexural elastic modulus and color difference roughness of three denture base materials, Kunshan Rijin(KR),GC UNIFAST Trad(GC), Shanghai Zhangjiang(SZ), were measured in vitro. All results were statistically analyzed with SPSS software to have ANOVA and Tamhane's T2 tests, α=0.05. Results: Comparison of the same materials between the treated materials and the untreated materials by hydraulic pressure cooker: there were significant statistical differences of impact strength for all the materials. There were significant statistical differences of color difference for KR and SZ. Comparison of the three materials: impact strength, GC>SZ>KR;flexural strength, KR>SZ>GC;flexural elastic modulus, KR>SZ>GC;roughness, GC>KR>SZ. Conclusion: The properties of denture base materials treated by hydraulic pressure cooker are good.

OBJECTIVETo study the changes of biomarkers in cerebrospinal fluid (CSF) in cerebral amyloid angiopathy (CAA) dementia and Alzheimer(')s disease.

METHODSLevels of amyloid protein β (Aβ42, Aβ40) and phosphorylated Tau-protein (P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.

RESULTSThe levels of Aβ42, Aβ40, and P-tau in CSF and ratio of Aβ42/Aβ40 were (660.4 ± 265.2) ng/L, (7111.0 ± 1033.4) ng/L, (71.8 ± 51.5) ng/L, and 0.077 ± 0.033, respectively in CAA dementia and (663.6 ± 365.6) ng/L, (5115.0 ± 2931.1) ng/L, (47.7 ± 38.8) ng/L, and 0.192 ± 0.140, respectively in Alzheimer's disease patients. There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers (all P>0.05).

CONCLUSIONMeasurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.

Aged ; Aged, 80 and over ; Amyloid beta-Peptides ; cerebrospinal fluid ; Apolipoproteins E ; genetics ; Biomarkers ; cerebrospinal fluid ; Cerebral Amyloid Angiopathy ; cerebrospinal fluid ; Dementia ; cerebrospinal fluid ; Humans ; Male ; tau Proteins ; cerebrospinal fluid

Adult ; Fever ; etiology ; Gastrointestinal Hemorrhage ; etiology ; Humans ; Male ; Polyps ; complications ; Stomach Diseases ; complications

Polymyxin E shows effective treatment of the infection induced by resistant gramnegative bacteria, but its nephrotoxicity severely limits the clinical application of this drug. In this work, methoxypolyethylene glycols 2000 (mPEG2K)-polymyxin E (PME) was synthesized via chemical grafting reaction and had been characterized. The antimicrobial activity and cytotoxicity of mPEG2K-PME in vitro were investigated on Escherichia coli and HK-2 cells, separately. Intra-abdominal infection model was further established in order to study the therapeutic effect and the toxic effect on kidney of mice. The results showed that mPEG2K-PME exhibited significant inhibitory effect on Escherichia coli and had a lower toxicity on HK-2 cells in vitro. At the same time, mPEG2K-PME had a good efficacy in the treatment of Escherichia coli infected mice in vivo. Moreover, nephrotoxicity caused by mPEG2K-PME was significantly reduced compared to free PME. mPEG2K-PME is promising in development of new preparations with high efficiency and low toxicity.
Animals ; Cell Line ; Colistin ; pharmacology ; toxicity ; Escherichia coli ; drug effects ; Escherichia coli Infections ; drug therapy ; Humans ; Kidney ; cytology ; drug effects ; Mice ; Polyethylene Glycols ; chemistry

Objective To build a foundation for determination of C reaction protein,C reaction protein was expressed and purified,and the immune reactivity of the purified protein was identified.Methods The CRP cDNA was amplified by RT-PCR from human liver cDNA library and inserted into expression vector pCRTT/NT.The recombined plasmid CRP-pCRTT/NT which expressed the fusion protein of CRP was then transferred into lysogenic host strain E coli.BL21 (DE3).The target protein was identified using SDS- polyacrylamide gel electrophoresis (SDS-PAGE).Affinity chromatography was used for protein purification.The immune reactivity of purified CRP was identified by Western blot using anti-CRP specific antibody.Results Recombiant human CRP was expressed in inclusion bodies of E.coli with a six histamine tag.The purify of recombinant protein was detected by SDS-PAGE as a single band at 30 000 and was identified by Western blot.Conclusions A plasmid expressed CRP protein is constructed and the purification system of CRP protein is established.The immune reactivity of the purified protein is identified by Western blot,which makes a good base for the preparation of CRP test kit.

Objective: To investigate the expression changes of Bcl-2-associated athanogene 1(BAG-1) and its regulatory effect on the glucocorticoid receptor(GR) activity in rat alveolar macrophages in conditions of cell inflammation and glucocorticoid therapy.Methods: The expression changes of BAG-1 were detected by Western blot after lipopolysaccharide(LPS) and Dexamethasone(Dex) treatment of rat alveolar macrophages(AMs),the interaction between BAG-1 and GR determined by immune coprecipitation experiment,and the transcriptional activation of GR measured by relative luciferase activity assay.Results:After LPS and Dex treatment,the expression of BAG-1L in total protein increased but that of BAG-1S remained changed,BAG-1L rather than BAG-1S was detected in nuclear protein and its expression increased gradually within 24 hours,the interaction between BAG-1L and GR was observed in nucleoli,and the transcriptional activation of GR decreased,with a negative correlation between BAG-1L expression and GR activity.Conclusion:LPS and Dex acting on rat alveolar macrophages,the expression of BAG-1L increases,which,coupled with GR,translocates into nucleoli and inhibits GR activity.This might be the important mechanism that underlies glucocorticoid resistance in inflammation.

BACKGROUND: Sinomenine is an alkaloid monomer extracted from a Chinese medicinal herb sinomenium acutum stem. It is used in the therapy of the rheumatoid arthritis and has clear and definite therapeutic effects, but the therapeutic mechanism is unclear.OBJECTIVE: To observe the effect of sinomenine at different doses in vitro on the activity of nuclear factor-κB(NF-κβ) and mRNA expressions of the tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) andinterleukin-10 (IL-10) in the synovial cells of the rats with adjuvant arthritis(AA) to explore the probable mechanism of sinomenine in the treatment of rheumatoid arthritis(RA).DESIGN: A controlled repeated measuring study based on the cells.SETTING: Department of traditional chinese medicine and the institute of burn research of a military medical university.MATERIALS: This study was finished at the Laboratory of the Institute of Burn Research of Chinese PLA. The experimental animals were 25 healthy male Wistar rats of clean grade. The AA model rats were made and the synovial cells were collected and grouped as follows: normal control group, AA group,AA + sinomenine 30 mg/L group, AA + sinomenine 60 mg/L group, AA + sinomenine 120 mg/L group. The activity of the NF-κB was measured by the electrophoresis mobility shift assay(EMSA) . The mRNA expressions of the TNF-α, IL-1β and IL-10 were measured by reverse transcription-PCR assay.MAIN OUTCOME MEASURES: The results of the changes of the activity of the NF-κB and the mRNA expressions of the TNF-α, IL-1β and IL-10 in the synovial cells of the rats with adjuvant arthritis after the treatment with sinomenine at different doses.RESULTS: Compared with the normal control group, the activity of the NF-κB and the mRNA expressions of the TNF-α, IL-1β and IL-10 in the synovial cells in the AA group all increased significantly and the outcomes were 17±6, 0.570±0.047, 0.730±0.093, 0. 683 ±0.081 (t= 2.71 -4.07, P < 0.05). After the administration of sinomenine, the activity of NF-κB showed a good correlation with mRNA expressions of the TNF-αandIL-13(r=0.810, P <0.001; r=0.562, P <0.05), but no statistical relevance with mRNA expression of IL-10 was established. Sinomenine showed a dose-dependent inhibition on the activity of the NF-κB and the mRNA expressions of the TNF-α and IL-1β in a certain range of concentrations(30-120 mg/L), but no dose-dependent inhibition on mRNA expression of the IL-10 was observed.CONCLUSION: Through the inhibition of the activity of the NF-κB,sinomenine decreased the mRNA expressions of the TNF-α and the IL-1β in the synovial membrane cells.

Objective To explore the association between glycated hemoglobin (HbA1c) level at admission and coronary plaque characteristics under intravenous ultrasound (IVUS) study in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). Methods 118 patients with NSTE-ACS were divided into the low(HbA1c ≤ 5.6％), medium(HbA1c 5.7％-6.4％)and high(HbA1c ≥ 6.5％)level groups based on admission HbA1c. IVUS was performed in all target lesions. Results As compared with the other two groups, patients with high level HbA1c had higher mean body weight index, higher co-morbidities of diabetes mellitus, dyslipidemia and non-ST-elevation acute myocardial infarction.The high HbA1c level group had more diffuse coronary atherosclerosis ,increased plaque burden and higher rates of positive remodeling, soft plaque and plaque rupture. Conculsions The HbAlc level of admission is associated with plaque vulnerability in NSTE-ACS patients.

ObjectiveTo investigate the effects of methylprednisolone （MP） on the proliferation and expression of glial fibrillary acidic protein (GFAP) in astrocytes after spinal cord injury in rats. MethodsThe spinal cords in T8～T10 in 48 male Wistar rats (10 weeks old) were exposed and the right site were semi-transected. 24 rats were administrated MP through tail vein as experiment group, and the other rats were injected equal volumes of normal saline as the control group. They were assessed with Basso, Beattie, and Bresnahan (BBB) score for ethological test every 4 d, and were sacrificed, perfused 3 d, 7 d, 14 d and 28 d after operation. The spinal cords were removed and postfixed, The expression of GFAP was observed with immunohistochemical staining and gray values determination. The GFAP positive cells were also counted. ResultsThere was no significant difference in BBB score between these groups until 21 d after operation; but the MP group rats showed significantly better functional recovery than the control group 25 d after operation. The number of positive astrocytes was less in the MP group than in the control group 3 and 7 d after operation, but there was no significant difference 14 d after operation. The GFAP expression in glial scar was significantly lower in the MP group than in the control in the first 21 d after operation, but no significant difference 28 d after operation. ConclusionThe large dose methylprednisolone administration can decrease the number of active AS, attenuate the formation of glial scars, and improve the functional recovery of the hind limbs after acute spinal cord injury.