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BACKGROUND: Patients with amnestic mild cognitive impairment (MCI)were considered to be going to develop into Alzheimer disease, and were the high-risk group of Alzheimer disease.OBJECTIVE: To study the implicit and explicit memory in the patient with amnestic MCI. DESIGN: Homochronous and controlled observation.SETTING: Neurological Department of the Southern Building of General Hospital of Chinese PLA.PARTICIPANTS: The research was carried out at Neurological Department of the Southern Building of General Hospital of Chinese PLA from January to June 2003. Totally 20 male patients with amnestic mild MCI,with the average age of (78.7±4.9) years and the average educational time of (8.2±1.0) years, selected from neurological out-patient clinic and ward of southern building of General Hospital of Chinese PLA, Complaint memory losing and confirmed by the relatives and close friends of the patients, Mini-mental state examination (MMSE) ≥24, activity of daily living (ADL)＜26, and clinical dementia rating equal to 0.5, Objective memory examination score reduced compared to the examiners' educational background,the memory quotient recorded by clinical memory sheet to be 63-77 (lower than the normal value with 1.5-2.5 standard deviation), were accepted, and determined as experiment group.Totally 20 healthy male veterans selected from Beijing area, with the average age of(77.9±4.7) years and the average educational time (8.1±1.1) years were selected as control group. All subjects volunteered to take part in_the examination.METHODS: Explicit memory included word free recall and re-recognition task. The Chinese characters were selected from the 1000 most commonly used ones in the books of primary and middle schools. The 30 double characters-words were chosen and randomly divided into two tasks. Recall task included 10 double character words that were target words. Re-recognition task included 20 double character words, of which one half were target words, and the other half were interfering words. Implicit memory included word free recall and character-root-complementary task. The Chinese characters were from the same source as mentioned before. Thirty Chinese characters were chosen in free recall task at beginning. These Chinese characters at least had possibility of composing over 4 commonly used double character-words in primary and middle school books. One double-Chinese character-word in four possibilities was randomly selected and the total was 30 words. Then these 30 words were divided into two groups, one was target group and the other was interfering word. All selected Chinese characters were composed either up-down structure or right-left structure. Taking a part of the Chinese character would leave a characterroot. There were 30 character-roots and they were never the same each other.There were at least four possibilities to form a Chinese character for each root as properly matching among 1000 commonly used Chinese characters.At first, the subjects were asked to read the target words loudly for 3 times in 4 tasks and tried to remember all the target words (characters) and were told to test their memorization later on. The target words (or characters)would appear in one-minute interval. The subjects were asked to repeat the words (or characters) appeared before as many as possible based on their memory in free recall task and they did not have to remember the words (or characters) in order. The correct recall rate for 10 target words was calculated. In re-recognition task, the target words and interfering words were mixed up and appeared one by one in random order and the subjects were asked to tell if the words appeared before. The correct rate of 20-word rerecognition was calculated. In free recall task, the first character in target words was mixed with the first character in interfering words and they appeared one by one in random order. The subjects were asked to form any two-character-word with appeared Chinese characters and wrote down the first word thought of in test sheet. The hitting rate of target words and interfering words were calculated. t-test for independent samples was carried 9ut respectively between the two groups.MAIN OUTCOME MEASURES: ① Semantic priming effect (the hitting rate of target words in word free recall task and the hitting rate of interfering words) and apperception priming effect (the hitting rate of target words in character-root-complementary task and the hitting rate of interfering words) in the two groups. ② Difference of explicit memory (correct rate of free recall and correct rate of re-recognition) and difference of semantic and apperception priming effect in the two groups.RESULTS: All subjects in the two groups completed the test and entered the final analysis. ① Results of inner-group analysis: In the group of MCI,the hitting rate (0.41±0.15) of target words in word free recall task was significantly higher than that of interfering words (0.31±0.12, P ＜ 0.01),suggesting that there existed semantic priming effect in the patients with amnestic MCI as completing this task. In the character-root-complementary task, the hitting rate of target words (0.17±0.10) was significantly higher than that of the hitting rate of interfering words (0.10±0.07, P ＜ 0.05), suggesting that there existed perceptional priming effect in the patients with amnestic MCI as completing this task. In the control group, the hitting rate of target words (0.45±0.11) was significantly higher than that of the interfering words (0.33±0.10, P ＜ 0.01), suggesting that there existed semantic priming effect in the elderly with normal perception as completing this task as well. In the character-root-complementary task, the hitting rate of target characters (0.18±0.08) was higher than that of interfering characters (0.13±0.07, P ＜ 0.05), suggesting that there existed perceptional priming effect in the elderly with normal perception as completing this task as well. ② Results of inter-groups analysis: Correct rates of free recall and re-recognition in the MCI group was decreased (0.10±0.09, 0.45±0.13,t=9.858, P=0.000; 0.69±0.14, 0.83±0.08, t=3.685, P=0.000). There was not significantly different in Sementic priming effect and perceptional priming effect both in the MCI group and the control group.CONCLUSION: Sementic priming effect and perceptional priming effect were existed both in the MCI experiment group and the control group, but the implicit memory was not significantly different in the two groups. However, the patients with forgetful style MCI were exhibited a decline in explicit memory. Memory function of mild MCI patients was shown double characteristics, i.e. damage of explicit memory and preservation of implicit memory. The double character in memorial function provided theoretical basis for the rehabilitative training of MCI patients.

Objective To investigate the effects of spontaneous agonal respiration on coronary perfusion pressure (CPP) during untreated cardiac arrest (ventricular fibrillation) in swine model.Methods Ten male healthy domestic swines (25.0 ± 1.5) kg were anaesthetised,intubated and mechanically ventilated.The catheterizations were separately inserted into the right atrium and thoracic aorta to monitor aortic pressure (AOP) and right atrial pressure (RAP).A pacing electrode was inserted into the right ventricle to induce ventricular fibrillation (VF).VF was induced by intra-ventricular stimulation withalternating electric current and untreated for 8 minutes.AOP and RAP were recorded until respiratory activity ceased.The CPP before and after agonal respiration was calculated and analyzed by paired-sample T test.Results All animals presented with agonal respiration from 1 to 6 minutes after VF during the first attempt.The CPP was (7.18 ±4.22) mmHg at 1 sec before agonal respiration,(11.78 ±5.16) mmHg at 0 sec after agonal respiration,(8.75 t:4.38) mmHg at 5 sec after agonal respiration and (8.23 ± 4.55)mmHg at 6 sec after agonal respiration.The CPP at 0 sec after agonal respiration was higher than that before agonal respiration (t =-3.140,P =0.012).The CPP at 5 sec after agonal respiration was higher than that at 1 sec before agonal respiration (t =-2.828,P =0.020).There was no difference in CPP between at 6 sec after agonal respiration and at 1 sec before agonal respiration (t =-1.778,P =0.109).Conclusions Agonal respiration accompanies ventricular fibrillation.After agonal respiration,the coronary perfusion pressure is increased for 5 seconds being in favor of cardiaopulmonary resuscitation.

Objective To investigate the value of platelet, serum sodium and serum creatinine levels in the prognosis of patients with liver failure. Methods The clinical data of 155 patients with liver failure were retrospectively analyzed, and the patients were divided into improvement survival group (87 cases) and deterioration died group (68 cases) according to the prognosis. The hospitalization time of every patient was divided into 4 roughly equal time period, and observed at 5 points of time:T1-T5. The levels and abnormal rates of platelet, serum sodium and serum creatinine were compared. Results The T3 - T5 serum creatinine levels in deterioration died group were significantly higher than those in improvement survival group: (102.14 ± 75.67) μmol/L vs. (78.21 ± 26.68) μmol/L, (116.45 ± 110.64)μmol/L vs. (78.77 ± 29.25) μmol/L, (161.43 ± 153.23) μmol/L vs. (76.40 ± 27.26) μmol/L, and the T1 - T5 serum sodium and platelet levels were significantly lower than those in improvement survival group:(135.05 ± 6.24) mmol/L vs. (137.52 ± 5.26) mmol/L, (137.01 ± 4.99) mmol/L vs. (139.00 ± 3.89) mmol/L, (134.80 ± 16.74) mmol/L vs. (139.15 ± 3.77) mmol/L, (134.40 ± 11.69) mmol/L vs. (138.30 ± 8.75) mmol/L, (133.30 ± 8.93) mmol/L vs. (139.01 ± 9.10) mmol/L, and (122.46 ± 72.59) × 109/L vs. (149.70 ± 71.70) ×109/L, (110.18 ± 65.10) × 109/L vs. (152.09 ± 82.79) ×109/L, (107.32 ± 70.49) ×109/L vs. (169.32 ± 100.65) ×109/L, (97.06 ± 58.15) ×109/L vs. (183.57 ± 112.68) ×109/L, (94.66 ± 57.00) × 109/L vs. (191.36 ± 118.64) ×109/L, and there were statistical differences (P<0.05). The abnormal rates of T3-T5 serum creatinine, T2 - T5 serum sodium and T1 - T5 platelet in deterioration died group were significantly higher than those in improvement survival group, the serum creatinine: 22.06%(15/68) vs. 6.90% (6/87), 27.49% (19/68) vs. 8.05% (7/87) and 42.65% (29/68) vs. 10.34% (9/87), the serum sodium: 32.35% (22/68) vs. 13.79% (12/87), 39.71% (27/68) vs. 14.94% (13/87), 48.53% (33/68) vs. 12.64%(11/87) and 60.29%(41/68) vs. 11.49%(10/87), the platelet:45.59%(31/68) vs. 21.84%(19/87), 55.88% (38/68) vs. 24.14% (21/87), 54.41% (37/68) vs. 25.29% (22/87), 55.88% (38/68) vs. 21.84%(19/87) and 61.76% (42/68) vs. 20.69% (18/87), and there were statistical differences (P<0.05). Abnormal rate of platelet was highest in each time point. Conclusions In the course of pathological changes in deterioration and dead patients, the platelet is the first and most easily affected compare with serum sodium and serum creatinine; the platelet may be a sensitive marker for predicting clinical outcome in patients with liver failure.

Objective To study the functional connectivity (FC) pattern of thalamus in patients with Alzheimer' s disease (AD).Methods In the present study,resting state functional magnetic resonance imaging (MRI) data were obtained from 30 patients with AD and 26 subjects with normal cognition (NC).The altered functional connectivity pattern in AD was evaluated by comparing to NC.Then a correlation analysis was performed between the strength of FC of the identified regions and various clinical variables for evaluating the relationships between the strength of FC and the cognitive abilities (MMSE,immediate recall and delayed recall of Auditory Verbal Learning Test) of the AD patients.Results The MMSE(19.7 ± 4.1),immediate recall (2.8 ± 1.7) and delayed recall (0.7 ± 1.3) of Auditory Verbal Learning Test in AD patients were lower than NC group (28.8 ± 1.0,5.9 ± 1.2,5.7 ± 2.2 ; t =11.09,8.09,10.51,all P ＜0.05).Compared to NC,AD patients showed decreased FC between the left thalamus and several regions of brain including right posterior/middle cingulate cortex (PCC/MCC.R),left medial prefrontal cortex (MPFC.L) and right superior frontal gyms/medial prefrontal cortex (SFG/MPFC.R).For the right thalamus,decreased FC was found in SFG/MPFC.R,PCC/MCC.R and right hippocampus.We also found increased FC between the bilateral thalamus and many regions of brain including inferior temporal gyrus,medial temporal gyrus,SFG,postcentral gyrus,paracentral lobule,inferior frontal gyms and insula.Significant correlations between the fitted FC strength and clinical variables were also detected.Conclusions FC pattern of thalamus in AD group is impaired.Increased FC in AD may indicate the presence of a compensatory mechanism.The alteration is related with cognitive function in AD.

ObjectiveTo investigate the characteristics of spontaneous activities throughout the whole brain with Alzheimer's disease (AD) by resting state functional magnetic resonance imaging ( fMRI ).Methods The subjects included 23 AD patients and 21 normal controls (NC),who underwent a neuropsychological test battery including MMSE and Auditory Verbal Learning Test (AVLT) and restingstate fMRI using GE Signa 3.0 T MR scanner.The neuropsychological scores were compared between two groups.Regional homogeneity (ReHo) method was used to explore the different regional spontaneous activities throughout the brain between normal controls and patients with AD.Results In AD group,clinical variables (MMSE scores:20 ±4,AVLT-Immediate Recall:2.6 ± 1.6,AVLT-Delay Recall:0.4 ±0.7,AVLT-Recognition:5.8 ± 3.7 ) were lower than NC group( 29 ± 1,5.9 ± 1.2,5.5 ± 2.0,9.2 ± 1.1,T =10.58,7.21,10.99,3.96,all P ＜ 0.01 ).With the threshold of P ＜ 0.01 for each voxel and a cluster size of at least 100 voxels,decreased ReHo indexes were found in default mode network (DMN) including the medial prefrontal cortex,posterior cingulate gyrus/precuneus,right superior temporal gyrus and bilateral superior parietal lobule/inferior parietal lobule in AD,while increased ReHo indexes were found in left putamen and thalamus compared with controls.ConclusionThe DMN are damaged in AD and spontaneous activities of putamen and thalamus are reinforced as compensation response of subcortical structures.

Objective To identify the characteristics of hippocampal 3-dimensional MRI in patients diagnosed as having subtypes of amnestic mild cognitive impairment(aMCI)using hippocampal surfacebased analytic technique.Methods Fifry aMCI patients and 16 healthy controls who were equivalent in age and education(NC)were recruited.Every subiect carried out a 3-dimensional MRI scan.After the imaging data were acquired.the borders of the hippocampus were manually traced in coronal vlew using the software of InsightSNAP1.4.1. Hippocampal volume was computed automatically and statistically analysed.Hippocampal 3-dimension MRI were transformed into 3-dimension parametric surface mesh models of 400×200 prids.Hippocampal radial distance measures which was the distance from the surface point to the central axis were statistically compared between two groups.The radial atrophy significance maps were acquired and adjusted for multiple comparisons.Hippocampal morphological difference maps of aMCI in contrast with NC were acquired.Results The average normalized volume of left hippocampus were(3247.5±600.2)mm3 in aMCI patients and(3467.9±451.3)mm3 in NC subjects.The average normalized volume of right hippocampus were(3416.8±699.1)mm3 in aMCI patients and(3469.1±358.9)mm3 in NC subjects.Comparison of hippocampal volume did not differ significantly between aMCI patients and NC subjects(t=1.161,P=0.255;U=0.178,P=0.859).By using hippocampal surface-based morphologic analytic technique,3-dimension hippocampal morphological difference maps between two groups were acquired,showing significant atrophy on the lateral and inferior hippocampal surface which corresponded to CA1 and subiculum hippocampal subfields bilaterally in aMCI patients compared with NC subjects. Conclusions aMCI patients do not have significant volume loss in the hippocampus. Through hippocampal surface-based morphologic analyses, partial regional atrophy of hippocampus at some degree is found, mainly localizing in the lateral and inferior hippocampal regions which correspond to CA1 and subiculum hippocampal subfields bilaterally in aMCI compared with NC. These results may reflect the early image marker in aMCI.

Objective To explore the risk factors for lower extremity amputation in patients with diabetic foot.Methods The clinical data of 1 771 patients with diabetic foot at the Air Force General Hospital of PLA from November 2001 to April 2015 were retrospectively analyzed.The patients were divided into the non-amputation and amputation groups.Within the amputation group , subjects were further divided into the minor and major amputation subgroups.Binary logistic regression analyses were used to assess the association between risk factors and lower extremity amputation.Results Among 1 771 patients with diabetic foot , 323 of them ( 18.24%) were in the amputation group ( major amputation: 41; minor amputation:282 ) and 1 448 ( 81.76%) in the non-amputation group.Compared with non-amputation patients, those in the amputation group had a longer hospital stay and higher estimated glomerular filtration rate(eGFR)levels.Fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), C-reaction protein (CRP), ESR, ferritin, fibrinogen and WBC levels of the amputation group were higher , while hemoglobin albumin, transferrin, TC, TG, HDL-C and LDL-C were lower than those of the non-amputation group (all P<0.05 ).The proportion of hypertension ( 52.48% vs 59.98%) , peripheral vascular disease ( PAD ) (68.11% vs 25.04%), and coronary heart disease (21.33% vs 28.71%) were different between the amputation and non-amputation groups (all P<0.05).Multivariable logistic regression analyses showed that Wagner′s grade , PAD and CRP were the independent risk factors associated with lower extremity amputation in hospitalized patients with diabetic foot.Conclusion Wagner′s grade, ischemia of lower limbs and infection are closely associated with amputation of diabetic foot patients.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.