1.Study on blood apolipoprotein as a potential biomarker of neurodegenerative diseases
Acta Pharmaceutica Sinica 2021;56(6):1513-1520
Neurodegenerative diseases (ND) mainly include Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, ataxia, and other diseases. The number of patients with ND is increasing, but the proportion of patients who can be diagnosed and treated early is less than 30% and the cause of ND is still unclear. In order to intervene in the disease as early as possible, researchers are committed to finding biomarkers that facilitate the early diagnosis of ND. Among them, cerebrospinal fluid (CSF) closely reflects the composition of the extracellular space of the brain, and may be the most sensitive biomarker for evaluating ND. However, the method of taking cerebrospinal fluid is more complicated, and it is not a common method in primary care or elderly medical institutions for the treatment of ND patients. Imaging examinations are expensive and difficult to spread among the community. The peripheral blood collection is convenient and less traumatic, which is a potential early screening and follow-up method. There are many components in the blood for analysis and research. This article reviews the research progress of the changes of apolipoprotein in the blood of ND patients as markers.
4.Health economic evaluation of Chinese population-based screening and opportunistic testing strategies to prevent Helicobacter pylori-related diseases
Qi CHEN ; Ying FANG ; Xiao LIANG ; Hong LU ; Xizhong SHEN
Chinese Journal of Digestion 2021;41(4):234-240
Objective:To conduct health economic evaluation of Chinese population-based screening and opportunistic testing strategies for the prevention of Helicobacter pylori ( H. pylori)-related diseases. Methods:The Markov models of H.pylori infection caused non-ulcer dyspepsia, peptic ulcer (PU) and gastric cancer were established. The cost and effects of the population-based screening, opportunistic testing, and non-intervention strategies in 100 000 population of our country were simulation calculated. Wilcoxon signed rank test was used for statistic analysis. Single factor sensitivity analysis was performed to analyze the impact of single parameter uncertainty on cost-effectiveness. Probability sensitivity was used to analyze the impact of common uncertainty of all parameters on cost-effectiveness. Results:Compared with opportunistic testing strategy and non-intervention strategy, the total cost of population-based screening strategy was reduced by 0.43 million yuan(-6.63 million yuan to 7.19 million yuan) and 4.45 million yuan(-8.60 million yuan to 27.93 million yuan), quality adjusted life years (QALY), life years and asmptomatic months were prolonged by 888.00 (479.86 to 1 574.10) and 3 032.78 (1 756.04 to 5 007.84), 651.82 (294.73 to 1 211.94) and 1 868.64 (1 045.88 to 3 148.34), 28 381.91 (19 109.54 to 43 736.72)and 102 537.13 (58 649.18 to 176 868.77) respectively, gastric cancer, deaths from gastric cancer, deaths from PU and deaths from various causes were reduced by 115 cases(52 cases to 232 cases) and 464 cases(266 cases to 803 cases), 74 cases(33 cases to 148 cases) and 260 cases(149 cases to 453 cases), 46 cases(25 cases to 72 cases) and 369 cases(210 cases to 710 cases), 80 cases(42 cases to 126 cases) and 501 cases(331 cases to 772 cases) respectively, and the differences were statistically significant ( Z=1.99, 10.54, 27.39, 27.39, 27.37, 27.39, 27.39, 27.39, 27.21, 27.28, 27.22, 27.28, 27.38, 27.39, 27.39 and 27.39, all P<0.05). Compared with the non-intervention strategy, the opportunistic testing strategy reduced the total cost by 3.89 million yuan(-2.79 million yuan to 18.18 million yuan), QALY, life years and asymptomatic months were prolonged by 1 764.77 (888.70 to 3 406.62), 1 044.16 (524.46 to 1 912.75) and 62 568.69 (30 054.07 to 129 892.76) respectively, gastric cancer, deaths from gastric cancer, deaths from PU and deaths from various causes were reduced by 311 cases(164 cases to 563 cases), 164 cases (87 cases to 301 cases), 325 cases(162 cases to 644 cases) and 399 cases(234 cases to 684 cases) respectively, and the differences were statistically significant ( Z=14.20, 27.39, 27.38, 27.39, 27.25, 27.25, 27.39 and 27.39, all P<0.01). The results of singlefactor sensitivity analysis showed that the uncertainty of any parameter did not affect the cost-effectiveness of three strategies. The results of probability sensitivity analysis indicated that the probability of cost-effectiveness advantage of the population-based screening strategy was 100% and the common uncertainty of all parameters had no effect on cost-effectiveness. Conclusions:For preventing H.pylori-related diseases, the population-based screening strategy has the lowest average cost and the best average effect. However, non-intervention strategy has the highest average cost and the worst average effect. Population-based screening strategy is worthy of promotion throughout China, and opportunistic testing strategy has a higher clinical practical value.
5.Activation of Ubiquitin-Proteasome Pathway in Lung Injury Rat Induced by Hyperoxia in Early Stage
yu-ge, HUANG ; zhi-chun, FENG ; yan-liang, YU ; fang-fang, XIAO
Journal of Applied Clinical Pediatrics 1992;0(06):-
Objective To explore the extent of lung injury induced by hyperoxia,and the activity of ubiquitin-proteasome pathway(UPP) in pathophysiological progress of lung tissue in early stages.Methods Adopted completely random design,20 SD rats were divided into hyperoxia group and air control group.For the air control group,the oxygen concentration exiting the cages was analyzed with oxygen monitor and oxygen concentration remained at 210 mL/L for 72 hours;while in the hyperoxia group,the condition changed into high-density oxygen(950 mL/L) for 72 hours to estimate the hyperoxia lung injury in rats model.The contents linked morphology as pathological classification in gross finding,pathological score of lung injury and the index of pneumonedema-the ratio of moist to dry weight of lungs were mea-sured.The expressions of ubiquitin protein and the activity of proteasome 20 S and the active statement of ubiquitin-proteasome pathway were detected by immunohistochemistry and Western blot methods.Results 1.The hyperoxia lung injury rat model was successfully duplicated.2.In hyperoxia group,pulmonary edema with increased ratio of moist to dry weight of lungs could be found(P=0).3.Macroscopic observation: bright red and full-stacked lung tissue,foliated or local hemorrhage on the surface,but little pleural effusion was observed in hyperoxia group.There was statistical significance of pathological classification in gross finding between hyperoxia group and air control group(P=0.005).Light microscope observation:swelled alveolar epithelium,widened alveoli wall,capillary engorgement and telangiectasis,obvious edema in interstitial tissue of pulmonary aveolus and alveolar space,increased inflammatory cells were observed in hyperoxia group.The findings of pathological score of lung injury indicated more serious injure than control group(P=0).4.The increased expression of ubiquitin protein in lung tissue was discoved by using immunohistochemistry and Western blot findings after hyperoxia exposure 72 hours.(P=0).5.The acti-vity of proteasomes 20 S in hyperoxia group was higher than that in control group(P=0).Conclusions The mainly pathological changes of lung are generated through hyperoxic exposure for 72 hours,including alveolar epithelial cell and vascular endothelial cell injury diffusely,inflammatory cell infiltration and pulmonary edema.Active the ubiquitin-proteasome pathway is connected with the pathophysiological process of lung injury in the initial stages of hyperoxia-exposure.
6.Protective effects of MG-132 on p38 signaling pathway and cell apoptosis in lung injury induced by hyperoxia
yu-ge, HUANG ; zhi-chun, FENG ; yan-liang, YU ; fang-fang, XIAO
Journal of Shanghai Jiaotong University(Medical Science) 2006;0(08):-
Objective To investigate the protective effects of the ubiquitin proteasome inhibitor MG-132 on p38 signaling pathway and apoptosis in lung injury induced by hyperoxia. Methods Twenty-six SD rats were randomly divided into 4 groups: normal control group(n=5),MG-132 control group(n=5),hyperoxia group(n=8) and MG-132 hyperoxia group(n=8).Hyperoxia lung injury rat models were established,and proteasome inhibitor(0.5 mg/kg) was intraperitoneally injected in control group and MG-132 hyperoxia group once daily.The resected lungs were histopathologically examined,and cell apoptosis and expression of ubiquitin and p38 were detected by TUNEL and immunohistochemistry,respectively.Results After hyperoxia exposure,there were edema and inflammatory cell infiltration in the lung tissues of SD rats.The apoptosis index and expression of p38MAPK of hyperoxia group were higher than those of normal control group and MG-132 hyperoxia group(P
7.Amniotic membrane transplantation in 20 patients with disorders of ocular surface
Fang, ZHAO ; Ping, MENG ; Jing-Ming, WANG ; Xiao-Ning, BAI ; Liang, HUI ; Xiao-Fang, HUI ; Jia-Li, ZHU
International Eye Science 2009;9(7):1230-1232
·AIM: To determine the effect of amniotic membrane transplantation(AMT) on the disorders of ocular surface. ·METHODS: From May 2002 to July 2007, twenty patients (20 eyes), who had an previous experienced methods of sorts, including contact lens or tarsorrhaphy, underwent AMT. ·RESULTS: The disorders were healed after the first AMT in 10 eyes (50%) within an average of 20 days after surgery and recurred in 1 eye (10%).·CONCLUSION: AMT is helpful in the treatment of the disorders of ocular surface.
8.Liquid chromatography-tandem mass spectrometry simultaneous determination of repaglinide and metformin in human plasma and its application to bioequivalence study.
Xiao-Rong LIANG ; Xiao-Jian DAI ; Yi-Fan ZHANG ; Jue-Fang DING ; Xiao-Yan CHEN ; Da-Fang ZHONG
Acta Pharmaceutica Sinica 2013;48(4):547-553
A simple, sensitive, selective, and reproducible liquid chromatography-tandem mass spectrometric method was developed for the simultaneous determination of repaglinide and metformin in human plasma using d5-repaglinide and d6-metformin as internal standards (ISs). After a simple protein precipitation using acetonitrile as the precipitation solvent, both analytes and ISs were separated on a Venusil ASB C 18 (150 mm x 4.6 mm, 5 microm) via gradient elution using acetonitrile--10 mmol x L(-1) ammonium acetate as the mobile phase. A chromatographic total run time of 7.5 min was achieved. Mass spectrometric detection was conducted with atmospheric pressure chemical ionization under positive-ion and multiple-reaction monitoring modes. The method was linear over the 0.2 to 60.0 ng x mL(-1) concentration range for repaglinide and over the 4 to 1 000 ng x mL(-1) range for metformin. For both analytes, the intra- and inter-accuracies and precisions were within the +/- 15% acceptable limit across all concentrations. The validated method was successfully applied to a clinical bioequivalence study.
Administration, Oral
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Adolescent
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Adult
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Area Under Curve
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Carbamates
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administration & dosage
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blood
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pharmacokinetics
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Chromatography, Liquid
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Drug Stability
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Female
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Humans
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Hypoglycemic Agents
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administration & dosage
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blood
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pharmacokinetics
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Male
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Metformin
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administration & dosage
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blood
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pharmacokinetics
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Middle Aged
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Piperidines
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administration & dosage
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blood
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pharmacokinetics
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Tandem Mass Spectrometry
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Therapeutic Equivalency
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Young Adult
9.Effects of S100A4 expressed In white matter astrocytes on sensory neurite outgrowth in vitro
Zheng-Yu FANG ; Liang XIONG ; Xiao-Lin HUANG ; Kozlova ELENA ; Jian-Zhi WANG ;
Chinese Journal of Physical Medicine and Rehabilitation 2003;0(07):-
Objective To investigate the role of white matter astrocytes and their specific protein S100A4 in sensory neurite outgrowth in vitro.Methods White matter astrocyte cultures expressing S100A4 were prepared. Dissociated adult dorsal root ganglion(DRG)cells were placed on the top of the astrocytes and co-cultured for 6,12, 18,24 hours.Small interfering S100A4 RNA was used to eliminate S100A4 expression.The growth of DRG cell neu- rites on S100A4-sileneed and S100A4-expressing astrocytes was compared.Results 12,18 and 24 hours after the co-culture with S100A4-expressing or S100A4-silenced astroeytes,neurite growth from the DRG cells was observed. Neurite outgrowth was significantly greater in S100A4 siRNA treated cultures compared to control siRNA treated white matter astrocyte cultures.Conclusion These findings suggest that white matter astroeytes are able to support axonal regeneration and,furthermore,that administration of small interfering S100A4 RNA provides strong additional support for axon regeneration.