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Objective:To analyzed the characteristics of the cognitive domains of the montreal cognitive assessment(MOCA)scale in cognitively impaired or normal elderly people from the perspective of structural equation modeling(SEM).Methods:There were 335 old individuals in this study, including 166 cognitively normal individuals, 130 patients with mild cognitive impairment(MCI)and 39 individuals with dementia.The average age of the individuals was 81.5±9.0.Data on the Montreal cognitive assessment(MoCA, Beijing version)were gathered.Following exploratory factor analysis and selection of latent and manifest variables, a structural equation model was established.After assessment of data from the domains of the scale in the elderly, participants were divided into a normal group and a patient group, which formed the basis of the model.Results:The KMO value of the data calculated by exploratory factor analysis was 0.762.The dimensions measured by the scale were divided into four main latent variables: memory, visuospatial execution, language ability and attention.The CMIN value of the overall model was 44.039 and the P value was 0.168.The parameters of the overall model and individual dimensions all indicated a good fit.The model showed that visuospatial execution had the largest impact on cognitive function, with a path coefficient of 0.742, and language ability had the least impact, with a path coefficient of only 0.091.As a latent variable, attention had path coefficients of 0.372 and 0.236 for memory, 1.663 and 1.102 for visuospatial execution, and 1.090 and 0.798 for language ability, respectively, for the two groups, with clear statistically significant differences between the groups(all P<0.05). Conclusions:SEM can improve researchers' overall understanding of the impacts of the individual components of the scale and their use and interpretation of the scale.
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Objective@#To determine human tear proteins using nanoliter liquid chromatography coupled to quadrupole orbitrap mass spectrometry (NanoLC-Q-Orbitrap-MS), and perform a bioinformatics analysis of main proteins.@*Methods@#Human tear samples were collected with capillary, transferred to 3 kDa ultrafiltration tubes containing 400 μL of superpure water and centrifuged at 12 000×g for 15 min. Repeated extraction of tear proteins were performed four times, and following digestion with trypsin, the proteins were separated using the Waters NanoAcquity peptide BEH C18 column (1.7 μm, 100 μm×100 mm) and determined using NanoLC-Q-Orbitrap-MS with the mobile phase of 0.1% formic acid aqueous solution and acetonitrile (0.1% formic acid) in the full MS/dd-MS2 mode. The types of proteins were characterized in the Uniprot database using the software Proteome Discoverer version 2.1 and verified using bovine serum albumin. The tear proteins were subjected to gene annotation analysis using the String database.@*Results@#A total of (387±160) human tear proteins were yielded, with a relative standard deviation (RSD) of 4.13%, and there were 25 types of proteins with a relative high abundance, including lipocalin 1, lysozyme and lactoferrin. The peptide sequence coverage of bovine serum albumin was (86.08±2.61)%, with a RSD of 3.03%. The 25 major tear proteins were involved in substance transduction among cells, homeostasis process, negative regulation of the endopeptidase activity, detection of chemical stimulants and humoral immune responses, and the 16 proteins had close interactions. Lacritin, lipocalin 1, lactoferrin, lysozyme and zinc-α 2-glycoprotein, which had a relative high abundance, had close biological connections.@*Conclusion@#NanoLC-Q-Orbitrap-MS is stable, reliable and feasible for detection of multiple proteins in tears.
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Objective:To investigate the clinical manifestations of familial amyloid multiple neuropathy (FAP) caused by Ala117Ser mutation, and to improve the clinical recognition of FAP.Methods:The clinical manifestations, electrophysiological examination, pathology and gene mutation characteristics of a case of FAP, who admitted to Fujian Medical University Union Hospital on November 25, 2014, were analyzed, and the literatures on the FAP cases caused by Ala117Ser mutation were reviewed and summarized.Results:The patient was a 59-year-old male from Fujian province. The first symptom was numbness in the extremities, followed by obvious autonomic nerve symptoms and motor disorder, and fatal cardiac dysfunction occurred in the later stage of the disease. The skin biopsy showed amyloidosis, and transthyretin gene analysis indicated the mutation of c.349G>T p.Ala117Ser. The clinical manifestations of FAP caused by Ala117Ser mutation reported in literatures are consistent with this case. And the reported FAP cases in China are concentrated in southern regions such as Fujian Province and Guangdong Province.Conclusions:Ala117Ser mutation in FAP patients is usually late onset and clinically manifested as multiple sensorimotor peripheral neuropathy, accompanied by prominent autonomic symptoms. The distribution of the patients has significant regional characteristics. Histopathological and genetic tests for the clinical diagnosis are of great significance.
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Objective To design and build a set of experimental equipment for neutron radiation irradiation by using the 241Am-Be neutron source. Methods In the preliminary work, the spatial distribution data of the neutron energy spectrum and the gamma energy spectrum inside and outside the device were simulated by Monte Carlo method, and the changes of radiation fluence rate with spatial distribution was studied. The model of the 241Am-Be neutron device was established, and the neutron transport process in the irradiation field was studied using the method of shadow cone, inverse square law and other data analysis methods. Results Based on the simulation results, the normalized effective does of fast neutron fluence at the measurement point is about 72.9 pSv/n, and the one of photon fluence is about 3.04 pSv/γ. The ratio of effective dose of photon fluence to neuteon is about 4.17%. Conclusion Using Monte Carlo method, a standard model of 241Am-Be neutron source was constructed, the shadow cone design was optimized, and the feasibility of using the shadow cone conversion method to establish a standard neutron source radiation device was discussed.
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Objective:To investigate the effect of serum cystatin C level on the occurrence and its long-term prognosis of contrast agent-induced acute kidney injury(CI-AKI)after percutaneous coronary intervention(PCI)in elderly patients.Methods:A total of 848 elderly patients(≥60 years)undergoing PCI in our department between Mar 2015 and Dec 2017 were enrolled in a prospective cohort.The CI-AKI was defined as the increase of serum creatinine ≥44.2 μmol/L within 48-72 h after using iodine contrast agent or more than 25 % higher than base level within 48-72 h after PCI.A receiver operating characteristic curve was used to analyze the optimal cut-off value of Cystatin C for predicting CI-AKI after PCI.Patients were divided into 2 groups based on the optimal cut-off value of Cystatin C: the high Cystatin C group(Cystatin C ≥1.3 mg/L, n=178)and the control group(Cystatin C<1.3 mg/L, n=670). The differences in the incidence of CI-AKI after PCI and major adverse cardiac events(MACE)at 1 year follow-up were compared between the two groups.The Cox regression model was further used to analyze the predictors of the long-term prognosis after PCI.Results:Of 848 patients receiving PCI, the incidence of CI-AKI was 9.4%.The incidence of MACE at 1 year after PCI was higher in the high Cystatin C group than in the control group(15.7% vs.9.3%, χ2=6.524, P=0.011). Cox regression analysis confirmed that the high baseline level of Cystatin C was the most independent predictive factor for MACE at 1 year of follow-up( HR=16.244, P<0.001). Conclusions:The high baseline level of Cystatin C(≥1.3 mg/L)is an independent risk factor for CI-AKI and is also the most important predictor for the occurrence of long-term MACE in elderly patients undergoing PCI.
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BACKGROUND@#Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS's response to SD.@*METHODS@#Middle-aged wild-type (WT) C57BL/6 and CX3CR1-/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes.@*RESULTS@#CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1-/- S group, the CX3CR1-/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted.@*CONCLUSIONS@#These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.
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Animals , Mice , Cognitive Dysfunction , Mice, Inbred C57BL , Microglia , Neuroinflammatory Diseases , Sleep DeprivationABSTRACT
Objective:To observe the intrinsic association between cognitive function in patients with Parkinson′s disease (PD) and retinal structural changes in retina nerve fiber layer thickness, macular volume and macular thickness.Methods:A total of 36 patients with PD and 12 normal controls matched with age and sex were selected randomly. Examinations of Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Unified Parkinson′s Disease Rating Scale Ⅲ (UPDRS-Ⅲ), Hoehn-Yahr stage were performed in all subjects. The PD patients were divided into three groups according to the score of MoCA: PD without cognitive impairment (PD-NCI; n=12), PD with mild cognitive dysfunction (PD-MCI; n=13) and PD dementia (PDD; n=11). The retinal nerve fiber layer thickness, macular volume and thickness which were corrected with body mass index (BMI) were determined and analyzed by optical coherence tomography imaging. Results:The total RNFL thickness (μm/BMI) of the PD with cognitive impairment group (PD-MCI group: 3.55±0.12 ( t=2.552, P=0.014), PDD group: 3.07±0.18 ( t=4.122, P=0.000)) was thinner than that of the normal control group (4.05±0.16). The RNFL thickness in each quadrant of the PD with cognitive impairment group (PD-MCI group and PDD group) was thinner than those of the normal control group. The RNFL thickness gradually became thinner with the cognitive impairment increasing ( r=0.558 3, P<0.001). The macular volume (mm 3/BMI) of PD group (PD-NCI group: 0.274±0.010 ( t=2.523, P=0.015), PD-MCI group: 0.268±0.010 ( t=2.848, P=0.007), PDD group: 0.266±0.010 ( t=2.604, P=0.013)) was smaller than that in the normal control group (0.316±0.010), and the macular volume gradually decreased with the severity of cognitive impairment ( r=0.234 1, P=0.024). The macula thickness in each subgroup of PD was thinner than that of the normal control group. The macula thickness gradually became thinner with the cognitive impairment increasing ( r=0.283 9, P<0.001). The macular thickness (normal controls: (10.67±0.12) μm/BMI, PD group: (9.51±0.07) μm/BMI, t=8.312, P<0.001) and volume (normal controls: (0.316±0.010) mm 3/BMI, PD group: (0.270±0.010) mm 3/BMI, t=3.570, P<0.001) became thinner and smaller in patients with PD. Conclusions:In patients with PD, the thickness of the retina nerve fiber layer, the volume and thickness of the macula become thinner/smaller with the severity of cognitive impairments increasing. Macular thickness and volume in patients with PD appear thinner/smaller, which can be used as a valuable biological marker in the early stage of PD. The retina nerve fiber layer thickness in patients with PD becomes thinner, which may be accompanied by cognitive impairment.
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Objective@#To screen and quantify 16 kinds of β-lactam antibiotics in pork by high performance liquid chromatography-quadrupole/electrostatic field orbit trap mass spectrometry（UPLC-Q-Orbitrap）.@*Methods@#The pork samples were extracted by ultrasound with acetonitrile，then the supernatant was centrifuged and purified by HLB solid phase extraction column. The analytes were separated by Waters HSS T3 column（100 mm×2.1 mm，1.8 μm）with gradient elution. Mass spectrometry adopted positive ion scanning and targeted SIM/dd-MS2 monitoring mode to complete the separation of analytes in samples and mass spectrometry analysis within 10 minutes. The chromatographic retention time and fragments in mass spectrometry were compared with prepared standards to determine whether the samples contained the antibiotics tested，then the positive samples were quantified.@*Results@#The 16 kinds of β-lactam antibiotics had good linear relationship in the range of 5-400 ng/mL（all the correlation coefficients >0.99）. The detection limits ranged from 0.08 μg/kg to 0.41 μg/kg，recovery rate ranged from 85.5% to 116.7%，and relative standard deviation（RSD）ranged from 3.6% to 12.8%. One of twenty pork samples detected was found penicillin G（28 μg/kg）and ampicillin（18.5 μg/kg）.@*Conclusion@#UPLC-Q-Orbitrap has high resolution and can reduce matrix interference to improve the accuracy. This method is simple，fast and efficient，thus can be used to screen and quantify β-lactam antibiotics in pork.
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Objective To investigate the correlations of plasma homocysteine(Hcy)levels with cerebral white matter lesion(WML)severity and cognitive impairment in elderly hypertension patients.Methods A retrospective case-control study was conducted.Ninty-eight elderly patients with hypertension were enrolled.Based on the presence or absence of hyperhomocysteinemia(hypertension with plasma Hcy levels ≥10μmol/L was defined as H-type hypertension),patients were divided into two groups:a control group(n =48) and an H-type hypertension group(n =50).The degree of WML was rated by the Fazekas scale using magnetic resonance imaging(MRI)analysis.Neuropsychological examinations including mini-mental state examination(MMSE)and Montreal cognitive assessment (MoCA)were taken to assess cognitive function.The degree of WML and cognitive impairment were compared between the two groups.Correlations of plasma Hcy levels with the degree of WML and cognitive impairment were analyzed.Results Compared with the control group,scores of the Fazekas scale(3.2 ± 1.0 vs.2.5 ± 1.0,P ＜0.05) and deep white matter hyperintensity on MRI(1.7 ± 0.8 vs.1.3±0.7,P＜0.05)increased,and scores of MMSE(24.9±3.3 vs.27.7±1.8,P＜0.05)and MoCA(18.6±3.9 vs.25.0±3.0,P＜0.05)decreased in the H-type hypertension group.Plasma Hcy levels were positively correlated with the degree of WML (r =0.430,P ＜ 0.01) and negatively correlated with cognitive function(r=-0.406 in MMSE and-0.663 in MoCA,P＜0.01).Multivariate logistic regression showed that Hcy,fasting blood-glucose,deep WML,low-density lipoprotein cholesterolin,age and systolic pressure were influencing factors for cognitive impairment (P ＜ 0.01).Conclusions WML and cognitive function are worse in elderly H-type hypertension patients than in hypertension patients with normal Hcy levels.WML and cognitive impairment are aggravated with increased plasma Hcy levels.The plasma Hcy level may be an effective clinical indicator of cognitive function in elderly people with hypertension.
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Objective To investigate the constitution and drug resistance status of the major pathogens in mechanically ventilated patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD),so as to provide evidences for clinical treatment.Methods From patients with AECOPD undergoing mechanical ventilation in EICU or ICU of the Second Affiliated Hospital of Wenzhou Medical University from January 2016 to December 2017,various specimens were collected for identification and drug susceptibility testing of pathogens;the clinical data and test results were analyzed.Results A total of 104 patients were included in the study.Total of 163 strains of pathogens were isolated from the specimens,of which gram-negative pathogens were the most common,accounting for 74.8％ of any pathogens.Drug resistance analysis showed that gram-negative pathogens were severely resistant to third generation cephalosporins,and were more sensitive to Sulperazon and carbapenems;gram-positive cocci were more sensitive to vancomycin and linezolid.Fungi were more sensitive to amphotericin B and 5-fluorocytosine.Most of the pathogens were multi-resistant.Conclusions In selecting antibiotics for the treatment of critical patients with AECOPD,emphasis should be placed on bacterial culture and drug susceptibility testing,so as to reduce irrational drug use and the emergence of drug-resistant strains or superinfection.
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Objective To investigate the diagnostic value of dynamic-extended focused assessment with sonography for trauma (D-EFAST) in patients with multiple trauma in intensive care unit (ICU). Methods A prospective clinical study was conducted. Eighty patients with multiple trauma admitted to ICU of Anhui Provincial Hospital from September 1st, 2014 to December 31st, 2016 were enrolled. Extended focused assessment with sonography for trauma (E-FAST) check was conducted at first, for those who had positive findings diagnosis was confirmed by immediately CT examination or surgical exploration. If it was negative, the patients received E-FAST every morning for 7 days (defined as D-EFAST), for those with positive findings, immediately CT or surgery was performed to clarify the diagnosis. The final clinical diagnosis was used as the "gold standard" to calculate the diagnostic accordance rate of EFAST and D-EFAST examination technique for pneumothorax, pleural effusion, spleen injury, kidney damage, liver damage, gastrointestinal injury, pericardial effusion, bladder rupture, and pancreatic injury, as well as their sensitivity, specificity, positive predictive value, negative predictive value, accuracy rate, and missed diagnosis rate, and the difference between EFAST and D-EFAST was compared. Results There were 4 patients excluded because of death and abandoning treatment, and finally 76 patients were included in the study. The total sensitivity of E-FAST examination technique for pneumothorax, pleural effusion, spleen injury, liver damage, gastrointestinal injury, pericardial effusion, and bladder rupture was 75.9% (66/87), and the specificity was 98.3% (587/597), the positive predictive value was 86.8% (66/76), and the negative predictive value was 96.5% (587/608), the accuracy rate was 95.5% (653/684), and the rate of missed diagnosis was 24.1% (21/87). The most of the delayed injury in patients with multiple trauma occurred at 2-7 days after injury with incidence of 4.8% (33/684). The diagnostic sensitivity of D-EFAST for delayed injury was 98.3% (118/120), the specificity was 99.8% (563/564), the positive predictive value was 99.2% (118/119), the negative predictive value was 99.6% (563/565), the diagnostic accuracy rate was 99.6% (681/684), and rate of missed diagnosis was 1.7% (2/120). When the final clinical diagnosis was set as the "gold standard", D-EFAST technology for the detection rate was 98.3% (118/120) for patients with multiple trauma on organ injury while the detection rate of E-FAST was 75.9% (66/87), with statistical significant difference (P < 0.01), indicating that D-EFAST was better than E-FAST in check of multiple trauma patients with organ injury. Conclusion Although the E-FAST technology can quickly diagnose the multiple trauma patients and win the rescue time for critical patients, multiple trauma patients injured after 2-7 days prone to delayed damage and are difficult to detect, and D-EFAST can be used to find delayed damage earlier, and reduce the misdiagnosis rate of multiple trauma patients.
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Objective To explore the impact of Enalapril-folic acid tablet on development of contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) in elderly patients with coronary heart diseases(CHD) complicated with mild renal insufficiency. Methods A total of 935 old patients (≥60 years) undergoing selective PCI at our hospital from January 2013 to June 2016 were enrolled in this retrospective study.Based on treatments during the perioperative phase ,the 935 patients were divided into Enalapril-folic acid tablet intervention group (n= 296 ,31.7％ ) ,and other RAS blocker control group with Angiotensin eonverting-enzyme inhibitor (ACEI) or Angiotensin Ⅱreceptor blocker (ARB) (n=639 ,68.3％ ). The levels of serum creatinine for 72 hours after operation were monitored and evaluated.Baseline data and CIN incidence were compared between two groups.The clinical events within 1 month after contrast media application were recorded.Multivariate Logistic regression analysis was used to analyze independent risk factors for CIN after PCI. Results The incidence of CIN after PCI was lower in the intervention group than in the control group with no statistical significance[7.1％ (21/296) vs.11.1％ (71/639) ,χ2 = 3.679 ,P= 0.059].Multivariate regression analysis showed that age (OR=1.103 ,P=0.001) ,hypertension (OR=3.362 ,P=0.017) , and hyper-homocysteinemia (OR=3.528 ,P=0.003) were independent risk factors ,but the treatment with Enalapril-folic acid tablet might be a protective factor for development of CIN after PCI (OR=0.443 ,P=0.042).During the 1-month follow-up ,the rate of recurrent angina pectoris was lower in the intervention group than in the control group ( P < 0.05 ) ,while there were no statistically significant differences between two groups in the rates of rehospitalization due to worsening renal dysfunction ,dialysis/hemofiltration ,acute heart failure ,and new myocardial infarction (all P>0.05). Conclusions The treatment with enalapril-folic acid tablet may prevent the occurrence of CIN after PCI in elderly patients with coronary heart disease and mild renal insufficiency.
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Objective To explore the probability to unify the scores of different neuropsychological scales under the guideline of item response theory (IRT).Methods Two hundred and three old individuals with a mean age of (80.86±9.52) years were enrolled in this study,including 101 normal individuals and 102 patients with mild cognitive impairment (MCI).The data of cognitive ability assessed using MoCA and MMSE scales were collected and analyzed according to IRT with Stata 14.0 software.The population,qualitative data,and scaled data were analyzed by Hybrid model,2PL model,and GRM model,respectively.Finally,model fitting was conducted in these data.We used test characteristic curves(TCC)to calculate corresponding theta values of the scores of MMSE and MoCA,and draw cartograms after fitting the model.Results The data of MoCA and MMSE conformed to the characteristics of unidimension.The scores of MoCA and MMSE were 26.37 ±2.63 and 29.06±1.32,respectively,in the normal group,and those were 21.57±3.47 and 26.62± 2.89,respectively,in the MCI group.The Log likelihood for the fitting model of MoCA and MMSE was-1 670.9012 and-773.9797,respectively.The TCC indicated that the score of MoCA was lower than that of MMSE at the same level of theta value.The TCC of the two scales were both steep at first,and then became flat.In evaluating the cognition ability,the MoCA score was more precise than MMSE score,and MMSE score was easier to show ceiling effect than MoCA score.Conclusions Under the guideline of item response theory,we can unify the scores of two scales in order to make the scores of two scales fit with each other and be in common use during study and research.
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Objective To investigate the findings and prognosis of head MRI and brain parenchymal lesions in patients with intracranial venous sinus thrombosis. Methods The clinical manifestations and imaging data of 41 patients with intracranial venous sinus thrombosis were analyzed retrospectively. According to the head MRI,the patients were divided into a brain parenchymal lesion positive group (n = 21)and a negative group (n =20). The clinical manifestations and the difference of the affected venous sinus in patients of both groups were analyzed. Results The proportion of dehydration,epilepsy,motor disorders,and psychiatric symptoms in the positive group were 28.6% (n =6)vs. 0% (n =0),57. 1% (n =12)vs. 15. 0%(n = 3),47. 6% (n = 10)vs. 5. 0% (n = 1),and 33. 3% (n = 7)vs. 5. 0% (n = 1),respectively. There were significant differences (all P < 0. 05). The proportion of the occurrence of superior sagittal sinus thrombosis in the positive group was lower than that in the negative group (47. 6% [n = 10]vs. 80. 0%[n = 16];P = 0. 031). At discharge,the proportion of complete recovery (modified Rankin score 0 -1)in the positive group was lower than that in the negative group (71. 4% [n = 15]vs. 100% [n = 20];P =0. 032). Conclusion Compare with the clinical symptoms of the positive patients,the patients with intracranial venous sinus thrombosis and those with negative brain parenchymal lesions are relatively minor,their prognoses are better,and the thrombi are more involved in superior sagittal sinus.
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Objective To assess the value of noninvasive MR imaging biomarkers in evaluating the early efficacy of anti?angiogenesis drugs. Methods Subcutaneous colon cancer xenograft models in thirty nude mice were established. The mice were randomly divided into three groups (n=10 for each): avastin injection group (dose 10 mg/kg), fluorouracil group (dose 150 mg/kg), physiological saline group (dose 20 mg/kg). Dynamic contrast?enhanced (DCE?MRI) and multiple b value diffusion weighted imaging (muti?b?value DWI) were acquired before or 1 h, 24 h and 48 h after the treatment. The parameters of contrast transfer coefficient (Ktrans), reflux constant (Kep), plasma volume fraction (Vp), extravascular extracellular volume fraction (Ve) and various apparent diffusion coefficients (ADCs) (ADC10b, ADChigh and ADCperf) were measured. Forty eight hours after the treatment, the mice were sacrificed following MRI. Aimmunohistochemical examination determined microvessel density (MVD) and proliferating cell nuclear antigen (PCNA) score. A repeated measures analysis of variance was used to compare the difference between the quantitative parameters among the three groups. A multivariate variance analysis was performed to compare the difference between the parameters at the same time point among the three groups. The correlation between MRI quantitative parameters with MVD and PCNA score were analyzed by Pearson and Spearman correlation analysis respectively. Factor analysis method summarized MRI quantitative parameters. Results One hour after the treatment, the parameters of Ktrans, Kep, ADC10b, ADChigh and ADCperf value immediately changed, they were(0.009 ± 0.005)/s,(0.042 ± 0.031)/s,(0.043 ± 0.002)× 10?3 mm2/s,(0.031 ± 0.005)× 10?3 mm2/s,(0.089 ± 0.006)× 10?3 mm2/s, Ktrans, Kep, ADC10b and ADChigh values all had significant differences in the three groups (F=42.058, 25.979, 9.870 and 8.511, respectively, all P<0.05). There were also statistical difference in the change trend of the above parameters among the three groups (F=22.108, 7.280, 65.698 and 19.900, respectively, all P<0.05). The change trend of ADCperf showed significant difference among the three groups (F=38.780, P<0.01). Ktrans, Kep and ADCperf positively correlated with the MVD count and PCNA score (r values were 0.421 to 0.811, both P<0.01), while ADC10b showed a negative correlation (r=-0.656 and-0.560, both P<0.01), ADChigh had negative correlation with the PCNA score (r=-0.568, P<0.05). Ktrans, Vp, Kep and ADCperf were classified as tumor microcirculation factor, whereas ADC10b and ADChigh were normalized for cell metabolism factor through the factor analysis. Conclusions Combination of DCE?MRI and muti?b?value DWI can reflect the early changes of drug therapy from the aspects of tumor microcirculation and cell metabolism. Ktrans, Kep, ADCperf, ADC10b and ADChigh can be taken as noninvasive imaging biomarkers to quantify the early efficacy of anti?angiogenesis drugs.
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Objective To systematically assess the efficacy of memantine on moderate to severe Alzheimer's disease (AD).Methods With the evaluation method of the Cochrane system,searches were made in the Cochrane Library,MEDLINE,Embase,Forest Laboratories,CNKI,Wanfang Data,and VIP Data up to February 2013 for double blind,randomized,and placebo-controlled trials (RCTs) evaluating the efficacy of memantine for moderate to severe AD.A meta-analysis of included clinical trials was conducted using the Revman 5.2 software to evaluate the efficacy of memantine on overall clinical status,cognitive function activities of daily living,and behavioral and psychological disturbances.Results A total of 8 RCTs were included (2 527 patients with moderate to severe AD).Results of the meta-analysis showed that,for patients with moderate to severe AD,memantine had better efficacy than placebo on overall clinical status,cognitive function,and activities of daily living (MD=-0.24,95％CI:0.340.15;SMD=-0.26,95％CI:-0.340.18;SMD=-0.13,95％CI:-0.21-0.05),but there was no significant difference in efficacy on behavioral and psychological function between memantine and placebo (P =0.08).Analysis of subgroups showed that memantine had better efficacy than placebo on cognitive function in moderate AD patients (SMD =-0.22,95％CI:-0.37 0.06) and on overall clinical status,cognitive function,and activities of daily living in severe AD patients (MD-0.29,95％CI:-0.40 0.18;SMD=-0.31,95％CI:0.46-0.15;SMD=-0.16,95％ CI:-0.25 0.06;MD=-3.13,95％ CI:-4.88-1.39;respectively).Conclusions Memantine has efficacy on overall clinical status,cognitive function and activities of daily living in patients with moderate to severe AD,especially in patients with severe AD.
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Objective To explore the feasibility and value of dynamic contrast-enhanced (DCE-MRI) parameters in assessing early effects of anti-angiogenesis medicine in targeted therapy for tumors.Methods Twenty BALB/C-nu nude mice were injected subcutaneously with human colon cancer cells HT-29 to the right hind leg.The nude mice were evenly divided into the experimental group and control group with 10 mice in each group.The mice of experimental group were intraperitoneally injected with bevacizumab,and the control group were injected with the same volume of saline.DCE-MRI was performed before medication and one hour,24 h and 48 h after medication.The Ktrans,Kep,Ve and initial area under enhancement curve (iAUC) of DCE-MRI were analyzed.The animals were sacrificed 48 hours after medication.Microvessel density (MVD) of the tumors was detected by immunohistochemistry.One way analysis of variance was performed to analyze parameters of DCE-MRI.The Pearson correlation coefficient was used to analyze the correlation between parameters of DCE-MRI and MVD.Results Under DCE-MRI,the edge of subcutaneous colon cancer xenografts was obviously gradually enhanced,pseudo color indicated high perfusion,the strength degree of the central region was low and which meant low perfusion.The differences in Kep of different time point of experimental group were statistically significant (F=3.752,P=0.016) ; there as no significant difference in other parameters of DCE MRI (all P＞0.05).There was no significant difference in Ktrans and Kep before medication and one hour after medication (all P＞0.05).There were significant difference in Ktrans and Kep 24 hour and 48 hour after medication between experimental group (24 hour∶ (0.095 ± 0.039) min-1 and (0.297 ± 0.141) min-1,48 hour∶ (0.090±0.033) min 1 and (0.314±0.148) min-1) and control group (24 hour∶ (0.150±0.074) nin-1 and (0.494±0.126) min-1,48 hour∶ (0.171±0.045) min-1 and (0.441± 0.092) min-1) (F24h =4.824 and 11.386,F48h =22.605 and 5.455,all P＜0.05).There was no significant difference in Ve and iAUC between two groups at different time points (all P＜0.05).MVD of experimental group was lower than that of control group.Ktrans and Kep were positively correlated with MVD (r=0.745 and 0.400,both P＜0.05).Conclusion Ktrans and Kep parameters of DCE-MRI may be used in monitoring the earlier effects of anti-angiogenesis medicine in targeted therapy for colon cancer.
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OBJECTlVE To investigate the association between CYP3A5 genotypes and the early efficacy of tacrolimus ( Tac) and cyclosporin A ( CsA) in renal transplantation recipients, and provide a basis for individualized treatment. METHODS Seventy-four kidney transplantation recipients were en-rolled in this study between August 2012 and April 2013. Thirty-one patients were treated with the combi-nation of CsA, MMF and methylprednisolone while the rest were treated with Tac, MMF and methylpred-nisolone. The genotype CYP3A5 was detected by sequence specific primer-polymerase chain reaction ( SSP-PCR) before transplantation. The levels of Tac and CsA were detected by ELlSA and chemilumi-nescence, respectively, to monitor the blood concentration/dose of drugs ( c/D) at 2 weeks, 1 month, 2 months, 3 months and 6 months after transplantation. Simultaneously, the concentrations of blood glu-cose, creatinine, urea nitrogen and uric acid were determined with hexokinase method, creatininase method, urease method and uricolase method, respectively. RESULTS Among the 74 recipients, 9.5%carried CYP3A5?1/?1, 48.6%carried CYP3A5?1/?3 and 41.9%carried CYP3A5?3/?3. According to the phenotype of CYP3A5, the patients were divided into CYP3A5 expression group ( including CYP3A5?1/?1 and CYP3A5?1/?3) and non-expression group ( including CYP3A5?3/?3) , which accounted for 58.1%and 41.9%of the cases, respectively. Among the patients taking Tac, the median value of c/D at 2 weeks, 1 month, 2 months, 3 months and 6 months was 25.49, 49.64, 53.72, 51.9 and 44.5 in CYP3A5 expression group, and 65.48,100.84,99.54,123.01 and 133.21 in non-expression group. The c/D ratio of CYP3A5 non-expressers was higher than among CYP3A5 expressers at each time point ( P<0.05) . The initial dose of Tac 0.1 mg·kg-1 was high for CYP3A5 non-expressers, and the kidney function recovered more slowly than among CYP3A5 expressers and kidney damage occurred. However, there was no association between CYP3A5 genotype and the early efficacy of CsA. The levels of blood glucose, creatinine, urea nitrogen and uric acid were not significantly different between CYP3A5 expression and non-expression groups. CONCLUSlON CYP3A5 non-expression recipients whose starting amount of Tac was 0.1 mg·kg-1 have drug overdoses. CYP3A5 genotype is one of the factors affecting the efficacy of Tac. CYP3A5 genotype has no association with the efficacy of CsA in renal transplantation recipients.
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A sequential clean-up method was developed for the quantification of 10 plant growth regulators in bean sprout by the gas chromatography / mass spectrometry (GC / MS). The analytes were firstly extracted by the acided acetonitrile. Extraction was concentrated and re-dissovled by methanol. Then, it was divided to two aliquots. One of that was analyzed for 2,4-D-butyl ester and 2,4-D-ethyl ester after the purification by QuECHERS cartridge. Another one was treated by MCS solid phase extraction column including diverse eluting steps. After eluting by 5 mL methanol, composition 1 was obtain, concentrated, and methyl esterified by 10% boron trifluoride methanol solution. The treated extract was used for the determination of 4-chlorophenoxy acetic acid, β-naphthyl acetic acid, 2,4-dichlorophenoxy acetic acid, indole acetic acid and indole butyric acid. Composition 2 collected by eluting with 5 mL 5% amonium methanol was used for the determination of paclobutrazol, Kinetin, 6-Benzylaminopurine. The clean-up procedures are designed according to different chemistry properties of these plant growth regulators. The results showed that after spiking of 0. 01-0. 1 mg / kg selected plant growth regulators, average recovery ranged from 70. 0% to 93. 2%and relative standard deviation were 5. 2% -12. 3% . Limit of quantification (LOQ S / N≥10) and limit of detection (LOD S / N≥3) were 0. 01-0. 025 mg / kg and 0. 003-0. 008 mg / kg respectively. The developed purification method is easy, fast and accurate, and can be applied to routine test of plant growth regulators in bean sprout.
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Objective To study the effect of Tacrolimus on blood lipid after renal transplantation,and the relationship between C825T polymorphism in G protein beta 3 subunit (GNB3) gene and serum lipid levels.Method Eighty-one cases of recipients patients after renal transplantation were divided into two groups in terms of Tacrolimus concentration:normal blood concentration group (group A) and low blood concentration group (group B).The serum lipid levels at 1st,3rd,6th,and 12th month after renal transplantation were measured.Genotype was determined by the simple sequence-specific primer polymerase chain reaction (SSP-PCR).Result The percentage of patients with hypertriglyceride in group A was significantly higher than in group B during the one-year follow-up period.There was significant difference between the two groups in the serum triglyceride levels but no difference in the serum cholesterol levels.The 825C/T polymorphism in the GNB3 gene was not associated with hypertriglyceride in renal transplantations in Wenzhou.Conclusion The serum triglyceride levels in renal transplantations in Wenzhou was associated with the Tacrolimus concentration,and the incidence of hypertriglyceride is not associated with the 825C/T polymorphism in the GNB3 gene.