1.Application of PET-based neuroimaging ATN framework in the diagnosis of Alzheimer′s disease
Min XIONG ; Hongji YOU ; Xiaoming LUO ; Yipei LIU ; Shengnan JIANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(12):705-711
Objective:To explore the value of the amyloid-tau-neurodegeneration (ATN) framework in neuroimaging based on PET for diagnosing mild cognitive impairment (MCI) and Alzheimer′s disease (AD), and analyze its relationship with clinical cognition.Methods:From May 2022 to March 2024, a total of 98 cases (23 males and 75 females, age (67.8±8.6) years) with a diagnosis of AD, MCI, or non-AD (control patients, CP) who underwent 18F-FDG, 18F-AV45, and 18F-AV1451 PET/CT imaging in the Second Affiliated Hospital of Guangzhou Medical University were included retrospectively. The clinical data, Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA) scores were recorded. Cases were divided into MCI group, mild AD group, moderate AD group, moderate-severe AD group, and CP group. PET images were visually and semi-quantitatively evaluated. SUV mean and SUV ratio (SUVR) were obtained from independent brain regions of 18F-FDG ( n=8), 18F-AV45 ( n=14) and 18F-AV1451 ( n=14). ROC curve analysis was performed with clinical diagnosis as a criterion. The consistency between visual assessment and the clinical diagnosis was analyzed by Cohen′s Kappa coefficient. Semi-quantitative comparisons between groups were performed using the independent-sample t test, one-way analysis of variance, Mann-Whitney U test, or Kruskal-Wallis rank sum test. Age was used as a covariate to calculate the partial correlation coefficient between SUVR and cognitive scores. Results:The sensitivity and specificity of comprehensive visual assessment in diagnosing AD+ MCI were 87.65%(71/81) and 14/17 respectively, showing a moderate consistency with clinical diagnosis ( Kappa=0.60, P<0.001). Semi-quantitative analysis showed that 18F-FDG uptakes in all independent brain regions of MCI patients were higher than those of AD patients, whereas the uptakes of 18F-AV45 and 18F-AV1451 were lower ( t values: 2.66-3.95, z values: 4.98-15.04, all P<0.05). The difference in 18F-AV45 uptake among the three subgroups of AD was relatively small ( H values: 0.46-4.06, F values: 0.03-0.08, all P>0.05). Except for the medial temporal and occipital lobes, the 18F-AV1451 uptake in the moderate-severe AD group tended to be higher than that in the moderate and mild AD groups, though not statistically significant ( H values: 0.20-5.17, all P>0.05). 18F-FDG PET semi-quantitatively distinguished MCI from CP with a high sensitivity (13/14), 18F-AV45 demonstrated a high sensitivity for diagnosing AD+ MCI (92.59%, 75/81), and 18F-AV1451 had a high specificity for distinguishing AD from MCI (14/14) (AUCs: 0.87, 0.90 and 0.92). The uptakes of 18F-FDG in gray matter of AD and MCI patients were positively correlated with MMSE and MoCA scores ( r values: 0.30-0.43, 0.29-0.45, all P<0.05), while the uptakes of 18F-AV45 and 18F-AV1451 were negatively correlated with MMSE and MoCA scores ( 18F-AV45, r values: from -0.39 to -0.30, from -0.38 to -0.30, all P<0.05; 18F-AV1451, r values: from -0.50 to -0.28, from -0.53 to -0.28, except for medial temporal lobe P>0.05, all others P<0.05). Conclusion:The PET-based neuroimaging ATN framework is helpful for early diagnosis of MCI and AD, as well as for AD staging, and may reflect the disease progression and clinical cognitive status of AD to a certain extent.
2.Analysis of the Evidence Map of Clinical Research on Treatment of Hyperlipidemia with Traditional Chinese Medicine
Wenjie HAN ; Chidao ZHANG ; Lanxin LI ; Yanze LIU ; Ruipeng WU ; Yipei AN ; Mingjun ZHU ; Xinlu WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(10):1611-1620
Objective To comprehensively review the clinical research on the treatment of hyperlipidemia with traditional Chinese Medicine(TCM)through the evidence mapping,and to understand the distribution of evidence in this field. Methods Databases including CNKI,Wangfang,VIP,SinoMed,PubMed,Cochrane Library,and Embase were searched from January 2004 to December 2023 to collect clinical studies,systematic reviews/meta-analyses,guidelines and clinical pathways related to the treatment of hyperlipidemia with TCM. The results were analyzed and displayed in charts and graphs according to the screening criteria,and the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool and the Preferred Reporting Item for Systematic Review and Meta-analysis of Chinese herbal medicine (PRISMA-CHM) were used to evaluate the quality of the systematic review/meta-analysis. Results A total of 1223 studies were included in the analysis according to Population,Intervention,Comparison,Outcome and Study design(PICOS) principles,involving 920 RCTs,249 non-RCTs,49 systematic reviews/meta-analyses,and 5 guidelines/expert consensus. In recent years,the overall number of clinical research publications has shown a downward trend. Hyperlipidemia frequently occurs in middle-aged and elderly people,and age of onset tends to be younger. The sample size of randomized controlled studies is mostly concentrated in 60-300 cases. There are many types of clinical treatment regimens for the treatment of hyperlipidemia with TCM,among which TCM decoction (50.13%) and Chinese patent medicine (38.41%) account for a relatively high proportion,and TCM exercise therapy (0.51%) is the lowest treatment. Jiangzhi Decoction has attracted more attention in trial group of TCM decoction,while Xuezhikang Capsule has attracted more attention in trial group of Chinese patent medicine. In terms of methodological design,199 papers(21.63%) explicitly mentioned the method of generating random sequence,17 papers(1.85%) mentioned allocation concealment,37 papers (4.02%) mentioned blinding. The control group was dominated by the statins,including simvastatin and atorvastatin. The outcome indicators mainly include the total effective rate,TCM syndrome score,blood lipid level,coagulation index,and adverse reactions,while the attention of TCM characteristic efficacy,inflammation,oxidative stress,and vascular endothelial index were low. The methodological and reporting quality of the systematic review/Meta-analysis were generally not high. AMSTAR-2 evaluation was extremely low,and the average PRISMA-CHM score was 15. Conclusion TCM has certain advantages in the treatment of hyperlipidemia,but there is a lack of high-quality evidence-based proof,and more high-quality clinical studies are still needed to further provide evidence supports in the future. It has been suggested that more large-sample and multi-center clinical studies should be carried out in the future. We should formulate systematic reviews/Meta analysis and guidelines/expert consensus according to the guidelines of clinical practice issues,also consult international standards and regulations,enhance normativity and reliability to improve the quality of their evidence.
3.Expression, purification and characterization of a novel bis (hydroxyethyl) terephthalate hydrolase from Hydrogenobacter thermophilus.
Yangyang CHEN ; Jian GAO ; Yipei ZHAO ; Hao WANG ; Xu HAN ; Jie ZHANG ; Qun GU ; Ying HOU ; Weidong LIU
Chinese Journal of Biotechnology 2023;39(5):2015-2026
PET (polyethylene terephthalate) is one of the most important petrochemicals that is widely used in mineral water bottles, food and beverage packaging and textile industry. Because of its stability under environmental conditions, the massive amount of PET wastes caused serious environmental pollution. The use of enzymes to depolymerize PET wastes and upcycling is one of the important directions for plastics pollution control, among which the key is the depolymerization efficiency of PET by PET hydrolase. BHET (bis(hydroxyethyl) terephthalate) is the main intermediate of PET hydrolysis, its accumulation can hinder the degradation efficiency of PET hydrolase significantly, and the synergistic use of PET hydrolase and BHET hydrolase can improve the PET hydrolysis efficiency. In this study, a dienolactone hydrolase from Hydrogenobacter thermophilus which can degrade BHET (HtBHETase) was identified. After heterologous expression in Escherichia coli and purification, the enzymatic properties of HtBHETase were studied. HtBHETase shows higher catalytic activity towards esters with short carbon chains such as p-nitrophenol acetate. The optimal pH and temperature of the reaction with BHET were 5.0 and 55 ℃, respectively. HtBHETase exhibited excellent thermostability, and retained over 80% residual activity after treatment at 80 ℃ for 1 hour. These results indicate that HtBHETase has potential in biological PET depolymerization, which may facilitate the enzymatic degradation of PET.
Hydrolases/metabolism*
;
Bacteria/metabolism*
;
Hydrolysis
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Polyethylene Terephthalates/metabolism*
4.Engineering the plastic degradation enzyme Ple629 from marine consortium to improve its thermal stability.
Yipei ZHAO ; Hao WANG ; Pan WU ; Zhishuai LI ; Fufeng LIU ; Qun GU ; Weidong LIU ; Jian GAO ; Xu HAN
Chinese Journal of Biotechnology 2023;39(5):2040-2052
Petrochemical-derived polyester plastics such as polyethylene terephthalate (PET) and polybutylene adipate terephthalate (PBAT) have been widely used. However, the difficulty to be degraded in nature (PET) or the long biodegradation cycle (PBAT) resulted in serious environmental pollution. In this connection, treating these plastic wastes properly becomes one of the challenges of environment protection. From the perspective of circular economy, biologically depolymerizing the waste of polyester plastics and reusing the depolymerized products is one of the most promising directions. Recent years have seen many reports on polyester plastics degrading organisms and enzymes. Highly efficient degrading enzymes, especially those with better thermal stability, will be conducive to their application. The mesophilic plastic-degrading enzyme Ple629 from the marine microbial metagenome is capable of degrading PET and PBAT at room temperature, but it cannot tolerate high temperature, which hampers its potential application. On the basis of the three-dimensional structure of Ple629 obtained from our previous study, we identified some sites which might be important for its thermal stability by structural comparison and mutation energy analysis. We carried out transformation design, and performed expression, purification and thermal stability determination of the mutants. The melting temperature (Tm) values of mutants V80C and D226C/S281C were increased by 5.2 ℃ and 6.9 ℃, respectively, and the activity of mutant D226C/S281C was also increased by 1.5 times compared with that of the wild-type enzyme. These results provide useful information for future engineering and application of Ple629 in polyester plastic degradation.
Plastics/metabolism*
;
Polyethylene Terephthalates/metabolism*
;
Biodegradation, Environmental
;
Metagenome
5.Current situation of trademark registration and brand protection of grade-A tertiary hospitals in China
Huihui ZHAI ; Yuqing DUAN ; Bin LIU ; Yipei WANG ; Rui ZHOU ; Changxiao JIN
Chinese Journal of Hospital Administration 2023;39(10):787-790
Objective:To investigate the trademark registration situation of grade-A tertiary hospitals in China, so as to analyze the current situation of hospital brand protection and explore suggestions for hospital brand protection.Methods:The top 50 hospitals ranked in the 2021 National Hospital Comprehensive Ranking by the Hospital Management Research Institute of Fudan University, excluding military hospitals, were selected as the sample hospitals. The trademark registration information of the 50 sample hospitals was queried through the China Trademark Website of the Trademark Office of China National Intellectual Property Administration on March 15, 2023, and the registration of the full name, abbreviation, hospital emblem and other trademarks of the hospitals was counted. Results:Among the 50 sample hospitals, 26 hospitals already held hospital brand trademarks, which meant that at least one of the hospital′s full name, abbreviation, and emblem was registered as a trademark, accounting for 52%; 7 hospitals did not hold any trademarks, accounting for 14%; 17 hospitals held other trademarks but did not hold hospital brand trademarks, accounting for 34%. Among the 26 hospitals that already held brand trademarks, 11 hospitals only registered in one category. There were 3 hospitals with expired registered trademarks.Conclusions:Nearly half of the sample hospitals did not hold hospital brand trademarks, indicating that the trademark registration and brand protection of tertiary hospitals in China need to be strengthened. It is suggested to establish a hospital brand protection system, clarify the trademark management department, standardize the responsibilities of trademark management, and improve the use of trademarks, so as to do a good job in hospital trademark registration and brand protection.
6.Etiology and characteristics of accidental injury in 350 children in PICU
Yipei LI ; Chunfeng LIU ; Liang PEI
Chinese Pediatric Emergency Medicine 2022;29(10):803-807
Objective:To analyze the causes and characteristics of children′s accidental injuries, and provide reference for preventing accidental injury in children.Methods:The case data of 350 children who were hospitalized due to accidental injury in the PICU at Shengjing Hospital of China Medical University from June 2017 to May 2020 were collected, and their age characteristics, family factors, accident time, location, cause of injury and prognosis were analyzed.Results:A total of 350 children with accidental injury were treated during three years, accounting for 12.2% of the total number of children admitted to the PICU during the same period, and the fatality rate was 10.6%.There were 200 males and 150 females; infants and young children were still the high-risk group of accidental injuries, accounting for 42.9%, while adolescent children accounted for 27.4%.The top three causes of accidental injury were poisoning in 149 cases (42.6%), traffic injury in 75 cases (21.4%), and fall injury in 65 cases (18.6%). The accident occurred most frequently in summer, mainly from 12∶00 to 18∶00, the average hospitalization days were 8.04 days, and the average hospitalization cost was 28 686.74 yuan.Conclusion:At present, accidental injuries of children are still an important factor endangering children′s health.The fatality rate is high and the characteristics of the disease are closely related to age, season, location, etc.Targeted prevention and intervention measures should be carried out according to different characteristics.
7.The significance of advanced glycation end-product receptors in sepsis organ damage
Chinese Pediatric Emergency Medicine 2020;27(10):762-766
It is one of the ten leading causes of death worldwide and has become one of the leading causes in children.The receptor for advanced glycation end products (RAGE) is a membrane protein that belongs to the immunoglobulin superfamily.Recently, studies have shown that RAGE can be involved in sepsis induced myocardial injury, kidney injury, lung injury, abnormal coagulation function, liver injury and neuropathy, which is closely related with the development and prognosis of sepsis.
8.Animal cell screening system based on GS efficient expression vector and its application
Zhaogang GAO ; Yong SHAO ; Lihua GAO ; Yun PAN ; Yu LIU ; Yipei LI ; Xianwen HU ; Huipeng CHEN
Military Medical Sciences 2014;(10):807-810
Objective To obtain highly expressing cell lines by inserting the glutamine synthetase (GS) screening system and replacing the promoter of the vector.Methods The mutation of the point BamHⅠwas induced to build a new vector pIRES2-EGFP.The marker gene GS was inserted by AseⅠ and NheⅠ, and the promoter hCMV was replaced by PacⅠand NheⅠ.The new vector pHGS1.0 and the vector pIRES2-enhanced screen fluorescein protein( EGFP)-B were inserted by the recombinant protein TEM8 ( 1-227 )-VEGFR1 domain2-IgG2 ( TV-IgG2 ) gene to analyze the advantages of the expression.Results The glutamine synsthetase is successfully inserted, the human cytomegalovirus replaced, and recombinant protein is increased 5-fold by human immunoglobulin quantification kit.Conclusion The GS system is a highly protein expressing system.
9.Effect of Xiaoyao Powder on Alzheimer's disease in hippocampal CA3 region of rats PP-2A, GSK-3βexpression
Weixian ZHAO ; Gaoshen LI ; Baowei WANG ; Yipei LI ; Jiantao LIU ; Meizhen GUO ; Junling LIU
Chinese Journal of Immunology 2014;(5):623-626
Objective:To study the effect of Xiaoyao Powder on Alzheimer's disease in hippocampal CA 3βregion of rats PP-2A,GSK-3βexpression.Methods:Rats were randomly divided into four groups , including model group, western medicine group,Chi-nese medicine group were treated with intraperitoneal injection of D-gal and A-β1-42 peptide bilateral hippocampal injection mold-ing, physiological group only with equal volume of sterile saline intraperitoneal and hippocampal injection molding .The model was completed, normal group, model group were perfused with saline , western medicine group and Chinese medicine group were treated with oxiracetam solution and Xiaoyao decoction , four groups of intragastric volume was 0.5 ml/100 g, 1 time a day, continuous 28 d. After intragastric administration of isolated rat brain immediately , packet marking in 4℃4%glutaraldehyde solution of glass container , stored at 4℃.Repair piece, cut from the hippocampus, embedded in paraffin, sliced.Dilution of PP-2A for 1∶200, GSK-3βdilution of 1∶150.Images were analyzed by using Image-pro Plus 5 image analysis system, data were conducted by SPSS11.5 statistical analysis software, the comparison between 4 groups by single factor analysis of variance , between the two two groups was compared by LSD-t test, the test level of α=0.05.Results:The expression of PP-2A positive cell number and the positive area , average optical density, integral optical density index , in Xiaoyao Powder orally intervention compared with the model group increased significantly (P<0.01);GSK-3βabove indices were significantly decreased than that in model group after Xiaoyao Powder after intragastric ad -ministration (P<0.01).Conclusion:Xiaoyao Powder can up regulate the expression of PP-2A and down regulate expression of GSK-3β, may be condensed A-β1-42 peptide induced hyperphosphorylation of Tau has certain inhibition .
10.Increased Expression of EMMPRIN and VEGF in the Rat Brain after Gamma Irradiation.
Ming WEI ; Hong LI ; Huiling HUANG ; Desheng XU ; Dashi ZHI ; Dong LIU ; Yipei ZHANG
Journal of Korean Medical Science 2012;27(3):291-299
The extracellular matrix metalloproteinase inducer (EMMPRIN) has been known to play a key regulatory role in pathological angiogenesis. A elevated activation of vascular endothelial growth factor (VEGF) following radiation injury has been shown to mediate blood-brain barrier (BBB) breakdown. However, the roles of EMMPRIN and VEGF in radiation-induced brain injury after gamma knife surgery (GKS) are not clearly understood. In this study, we investigated EMMPRIN changes in a rat model of radiation injury following GKS and examined potential associations between EMMPRIN and VEGF expression. Adult male rats were subjected to cerebral radiation injury by GKS under anesthesia. We found that EMMPRIN and VEGF expression were markedly upregulated in the target area at 8-12 weeks after GKS compared with the control group by western blot, immunohistochemistry, and RT-PCR analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals colocalized with caspase-3 and VEGF-positive cells. Our data also demonstrated that increased EMMPRIN expression was correlated with increased VEGF levels in a temporal manner. This is the first study to show that EMMPRIN and VEGF may play a role in radiation injuries of the central nervous system after GKS.
Animals
;
Antigens, CD147/*metabolism
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Brain/blood supply/metabolism/pathology/*radiation effects
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Brain Injuries/metabolism/pathology
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Caspase 3/metabolism
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Gamma Rays/*adverse effects
;
Immunohistochemistry
;
Male
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Microscopy, Electron, Transmission
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Parietal Lobe/metabolism/pathology/radiation effects
;
Radiation Injuries, Experimental/metabolism
;
Radiosurgery/adverse effects
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Rats
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Rats, Wistar
;
Time Factors
;
Vascular Endothelial Growth Factor A/*metabolism

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