1.Jieduan Niwan Formula regulates AMPK to alleviate mitochondrial damage in HepG2 cells
Ruimin MA ; Hanjing WANG ; Wenxin ZHANG ; Chongyang MA ; Qiuyun ZHANG ; Yuqiong DU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):193-204
Objective:
To investigate the regulatory effect of Jieduan Niwan Formula (JDNWF) drug-containing serum on AMPK-mediated mitochondrial quality control in D-GalN-induced HepG2 cells.
Methods:
Twenty male Wistar rats were randomly divided into blank control and JDNWF-containing serum groups, 10 rats per group. The JDNWF-containing serum group was gavaged with JDNWF (21.7 g/kg), whereas the blank control group was gavaged with saline. Blood was collected to prepare JDNWF-containing and blank control serum. Cell viability, mitochondrial damage indicators, and MQC pathway protein expression levels were evaluated to determine the optimal volume fraction of JDNWF. HepG2 cells were divided into control, D-GalN, DMSO, AMPK inhibitor, JDNWF drug-containing serum, and JDNWF drug-containing serum plus AMPK inhibitor groups, and corresponding drug interventions were administered to each group. Cells were collected after the interventions, and the CCK-8 assay was used to measure cell viability, the 2′-7′-dichlorodihydrofluorescein diacetate fluorescent probe was used to detect reactive oxygen species (ROS) levels, JC-1 was used to detect mitochondrial membrane potential, thiobarbituric acid was used to measure malondialdehyde (MDA) levels, WST-8 was used to measure superoxide dismutase (SOD) activity, and western blotting was used to detect the expression levels of mitochondrial quality control-related proteins, including p-AMPK, AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1.
Results:
5% JDNWF drug-containing serum most significantly restored cell viability, mitochondrial damage markers, and MQC pathway protein expression in the model group. Therefore, it was chosen for intervention in subsequent experiments. Compared to the control group, the cell viability of the D-GalN, DMSO, and AMPK inhibitor groups was significantly reduced (P<0.01). In contrast, the heterogeneity of mitochondrial membrane potential, ROS, and MDA levels was significantly increased (P<0.01), and SOD activity was significantly decreased (P<0.01). The p-AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1 protein expression levels were significantly decreased (P<0.01). After JDNWF drug-containing serum intervention, compared to the DMSO group, cell viability significantly increased (P<0.01), mitochondrial membrane potential heterogeneity, ROS, and MDA levels significantly decreased (P<0.01), SOD activity significantly increased (P<0.01), and p-AMPK, PGC-1α, NRF1, TFAM, and MFN2 protein expression levels significantly increased (P<0.01), whereas DRP1 protein expression significantly decreased (P<0.01). Compared to the JDNWF drug-containing serum group, the cell viability in the JDNWF plus AMPK inhibitor group significantly decreased (P<0.01), mitochondrial membrane potential heterogeneity and ROS levels significantly increased (P<0.01), MDA levels significantly increased (P<0.05), SOD activity significantly decreased (P<0.05), p-AMPK, PGC-1α, NRF1, and TFAM protein expression levels significantly decreased (P<0.01), MFN2 protein expression significantly decreased (P<0.05), and DRP1 protein expression significantly increased (P<0.01).
Conclusion
JDNWF drug-containing serum may restore mitochondrial function and improve D-GalN-induced HepG2 cell injury by regulating AMPK-mediated mitochondrial quality control.
2.An innovative method of uretero-ileal anastomosis:magnetic anastomosis based on rabbit models
Miaomiao ZHANG ; Jiahui WAN ; Ruimin GONG ; Qiuye ZHONG ; Yi LYU ; Xiaopeng YAN
Journal of Modern Urology 2025;30(4):339-342
Objective: To investigate the feasibility of magnetic anastomosis for uretero-ileal anastomosis using experimental rabbit models. Methods: Six experimental rabbits were used as the models.The lower part of the left ureter was cut with scissors,the daughter magnet (DM) was placed in the middle of the ureter,and the distal end of the ureter was ligated.After that,the ileum wall was opened,the parent magnet (PM) was inserted through it,the positions of the PM and DM were adjusted so that their ends were attracted to each other,and then ileum wall incision was sutured.The operation time,intraoperative blood loss,postoperative complications and magnet discharge time were recorded.Two weeks after operation,left ureterography was performed to obtain the specimens of the uretero-ileal anastomosis,and to observe the patency of the anastomosis.The formation of the anastomosis was observed with naked eyes and light microscope. Results: Uretero-ileal magnetic anastomosis was performed successfully in 6 experimental rabbits.The operation time was 28-39(32.50±3.94) min,and the intraoperative blood loss was less than 5 mL.The rabbits recovered well after operation,and no complications were observed.All animals survived to the end point of observation.The disconnection time of magnet after operation was 9-13(10.83±1.72) days.The gross specimen showed that the anastomosis was patent.The histological observation showed that the mucosa of the anastomosis was continuous and smooth,and the anastomosis was well formed. Conclusion: Magnetic anastomosis is feasible for uretero-ileal anastomosis with simple operation and good anastomosis formation.After further experimental verification,this technique is expected to be used in clinical practice.
3.Epidemiological features of visceral leishmaniasis cases in Henan Province from 2021 to 2023
Chengyun YANG ; Dan WANG ; Deling LU ; Zhiquan HE ; Penghui JI ; Dan QIAN ; Ying LIU ; Yuanjing KOU ; Suhua LI ; Ruimin ZHOU ; Yan DENG ; Hongwei ZHANG
Chinese Journal of Schistosomiasis Control 2024;36(4):393-398
Objective To analyze the characteristics of visceral leishmaniasis cases in Henan Province, so as to provide insights into formulation of the visceral leishmaniasis control srtrategy. Methods All epidemiological data of reported visceral leishmaniasis cases in Henan Province from 2021 to 2023 were retrieved from the National Notifiable Disease Report Information Management System of Chinese Center for Disease Control and Prevention, and the epidemiological features and diagnosis of visceral leishmaniasis cases were descriptively analyzed. Results A total of 93 visceral leishmaniasis cases were reported in Henan Province from 2021 to 2023, with a male to female ratio of 2.58∶1, and including 2 imported cases from other provinces and 91 local cases. The number of visceral leishmaniasis cases peaked during the period between March and May, and between July and October. The reported visceral leishmaniasis cases had ages of 7 months to 74 years, with the largest number of cases found at ages of 0 to 9 years (26 cases, 27.96%), followed by at ages of 60 to 70 years (24 cases, 25.81%). Farmer (47 cases, 50.54%) and diaspora children (19 cases, 20.43%) were predominant occupations, and 91 local visceral leishmaniasis cases were found in 6 cities of Zhengzhou, Luoyang, Anyang, Hebi, Sanmenxia and Xuchang. The median duration from onset of visceral leishmaniasis to diagnosis was 20 days, and there were 25.81% (24/93) cases with 10 days and less duration from onset to diagnosis, 38.71% (36/93) cases receiving diagnosis at 11 to 30 days following onset, and 35.48% (33/93) cases receiving diagnosis for more than 30 days following onset. All cases were predominantly diagnosed in province- (60.00%) and city-level (28.89%) medical institutions. Conclusions The number of visceral leishmaniasis is on the rise in Henan Province, with a gradually expanding coverage. Intensified monitoring of visceral leishmaniasis cases, dogs, and vectors, dog management, sandflies control and improved individual protection are recommended to prevent the spread of visceral leishmaniasis.
4.Comparative analysis of cerebrospinal fluid laboratory test results between multiple sclerosis and Guillain-Barré syndrome
Ruimin MA ; Xinyi RAO ; Yuxin CHEN ; Hong LYU ; Guojun ZHANG
Chinese Journal of Laboratory Medicine 2024;47(2):136-141
Objective:To compare the characteristics of cerebrospinal fluid (CSF) oligoclonal band electrophoresis examination results between patients with multiple sclerosis (MS) and Guillain-Barré syndrome (GBS), and to provide a basis for the differential diagnosis of the two types of neurological demyelinating diseases.Methods:Case analysis.The retrospective study method was used, and the patients who visited Beijing Tiantan Hospital, Capital Medical University from January 2020 to August 2023 were selected as the research subjects, including 70 MS patients[19 males and 51 females, aged 34 (28, 44) years] and 70 GBS patients [44 males and 26 females, aged 50 (36, 61) years]. The oligoclonal band electrophoresis and immunoglobulin G(IgG) index (IgG I) were performed on the clinical specimens from MS and GBS patients, and CSF routine, CSF biochemistry (glucose, chloride, protein), lactate, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α), antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), rubella virus (RV), toxoplasma gondii (TOX), Epstein-Barr virus (EBV), and coxsackievirus were detected simultaneously. The enumeration data were treated with the chi-square test. The measurement data didn′t accord with normal distribution, and were treated with the Mann-Whitney U test. Results:The positive rate of oligoclonal band (OCB) electrophoresis in MS and GBS patients were 80.00% (56/70) and 4.29% (3/70), respectively. The positive rate in MS patients was significantly higher than that in GBS patients (χ 2=82.289, P<0.001). The white blood cells count [5.50 (3.00, 11.00)/μl] and the level of chlorine [127 (125, 128) mmol/L] in CSF of MS patients was higher than that of GBS patients [3.50(2.00, 7.00)/μl, 126(124, 128) mmol/L] ( U=-2.245, P<0.05; U=-2.028, P<0.05), while the levels of CSF protein [33.40(27.61, 39.17)mg/L], glucose [3.59(3.36, 3.88) mmol/L], and lactate [1.55(1.40, 1.73) mmol/L] of MS patients were lower than those of GBS patients [6.71(43.78, 138.30) mg/L, 3.97(3.55, 4.54) mmol/L, 1.80(1.60, 2.00) mmol/L]( U=-6.747, P<0.001; U=-3.651, P<0.001; U=-4.531, P<0.001). The levels of IL-6 [3.36(2.34, 5.02) pg/ml], IL-8 [55.40(46.75, 66.40) pg/ml], and TNF-α [5.63(4.25, 6.63) pg/ml] in CSF of MS patients were lower than those of GBS patients [6.12(3.61, 11.73) pg/ml, 120.00(74.90, 187.80) pg/ml, 6.57(5.25, 8.03) pg/ml]( U=-3.463, P<0.05; U=-5.225, P<0.001; U=-2.785, P<0.05). The positive rates of CMV IgG, TOX IgG, and EBVCA IgG in CSF of MS patients were 36.36% (24/66), 0 and 0, respectively,and the positive rates of those of GBS patients were 85.71% (54/63), 30.16% (19/63), and 19.05% (12/63), respectively. The positive rates of CMV IgG, TOX IgG, and EBVCA IgG in CSF of MS patients were significantly lower than those of GBS patients (χ 2=32.839, P<0.001; χ 2=23.343, P<0.001; χ 2=13.861, P<0.001). Conclusions:The MS patients mainly showed the higher positive rates of OCB. The GBS patients showed elevated CSF protein levels but no significant increase in white blood cell count, namely albuminocytologic dissociation in CSF. Meanwhile, the GBS patients showed elevated levels of intrathecal immunity and inflammation indicators, and a higher positive rate of pathogen antibodies.
5.Construction of A Macro-evaluation Tool for Dampness Syndrome Animal Model in Traditional Chinese Medicine
Chuang LI ; Peng XU ; Ruimin TIAN ; Zhaorui CAO ; Mingjia LIU ; Lei ZHANG ; Zhaoyu LU ; Taohua LAN ; Xiaowan WANG ; Wei MAO
Journal of Traditional Chinese Medicine 2024;65(14):1449-1457
ObjectiveTo construct a macro-evaluation tool for dampness syndrome (DS) animal model, which will provide a basis for experimental research on dampness syndrome in traditional Chinese medicine (TCM). MethodsConceptual framework of this study was clarified through discussions within the core working group, and dimensions of the evaluation of the animal model of DS were identified according to TCM principles. We searched CNKI, Wanfang, VIP and SinoMed databases from the inception to June 30th, 2023, on experiments involving dampness syndrome animals to create a pool of items about DS animal models. The core items were selected and extracted for factor analysis and cluster analysis. An expert importance rating questionnaire was developed based on the results of the literature review, analyzing the distribution of item scores, importance averages, and coefficient of variation. Through a comprehensive analysis of literature, expert importance scoring, and specific expert opinions, items that did not meet anyone of the criteria of average importance rating ≥2.04, coefficient of variation ≤30%, or literature eva-luation frequency ≥2% were removed, thereafter, the macro-evaluation tool for DS animal model was preliminarily constructed. ResultsSpirit and body state, autonomic activity state, body surface characteristics, diet, urination and defecation, tongue manifestation, and motor behavior assessment were constructed as the seven dimensions in the evaluation of DS animal model. A total of 348 papers about animal experiments were included and analyzed, resulting in a saturated pool of 72 items, which was refined to 38 core items of DS animal models. Factor analysis obtained 16 common factors, which were further clustered into two categories, named dampness transforming from heat syndrome and dampness transforming from cold syndrome. The expert importance scoring showed that the Kendall harmony coefficient was 0.359 (P<0.05) indicating a high level of agreement, coordination and reliability among the experts. Notably, 50% or more of the experts considered the items thick and greasy tongue coating, unclean perianal area, loose stools, lethargy, unformed stools, and listless expression as very important. The median scores for all items were 2.04(1.73, 2.37), with a coefficient of variation ranging from 19.73% to 53.38%. After expert evaluation, the macro-evaluation tool for DS animal model in TCM with 33 items and corresponding criteria for assessing the formation of DS models was finally contructed. ConclusionThe Macro-evaluation tool for DS animal model in TCM is highly scientific, credible, and operable, and can be utilized in DS animal experiments after its characteristics are actually evaluated.
6.Short-term efficacy evaluation of single-session microwave ablation for benign thyroid nodules
Junsong LIU ; Chongwen XU ; Xiaobao YAO ; Ruimin ZHAO ; Shiyang WANG ; Qian ZHAO ; Honghui LI ; Yanxia BAI ; Shaoqiang ZHANG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(7):414-420
OBJECTIVE To evaluate the short-term efficacy of single-session microwave ablation for benign thyroid nodule.METHODS Patients with benign thyroid nodules treated by microwave ablation between June 2019 and December 2022 at the Department of Otolaryngology Head and Neck Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,were included for analysis.Thyroid function was tested 1 month after treatment,and ultrasound and thyroid function were performed 3 months,6 months and 1 year after treatment.Volume reduction rates(VRR)of nodules were calculated.Data of the last follow-up within 1 year were included for analysis.Variables including gender,age,whether Hashimoto's thyroiditis was present,longitudinal diameter of nodules,solid volume of nodules were included for univariate and multivariate analysis.RESULTS A total of 151 patients with 163 nodules were included.The perioperative complication rate was 1.99%(3/151).The VRR at half year after treatment was(79.58±17.70)%,and the success rate at half year after treatment was 93.43%(128/137).The VRR of at 1year after treatment was(81.24±24.29)%.The 1-year treatment success rate was 92.77%(77/83).Univariate and multivariate analysis showed that nodular solid volume and age were independent factors affecting VRR after ablation.Regression coefficient of age and solid volume was 0.34(P<0.05)and-0.47(P<0.05),respectively.For every 1 cm3 increase in solid volume,1-year VRR(%)decreased by 0.47.Regression equation:1-year VRR=68.92+0.34×age-0.47×solid volume.Serum FT4 gradually decreased and the thyroid stimulating hormone(TSH)gradually increased within 6 months after ablation,and the differences were statistically significant(P<0.05).After 6 months,serum FT4 gradually recovered to the normal level and TSH gradually recovered.However,TSH still did not reach the preoperative level one year after ablation.FT3 decreased gradually after treatment,but there was no significant difference between the values at each time point(P=0.40).After the ablation of thyroid nodule,the mean value of thyroid function index fluctuated,but all of them were within the normal reference range.CONCLUSION Microwave ablation is a safe and effective treatment method for benign thyroid nodules,with an overall success rate of over 90%.Solid nodule volume and age are independent factors affecting the microwave ablation effect of benign thyroid nodules.
7.Clinical characteristics and management status of Turner syndrome in 1 089 children
Yan LIANG ; Haiyan WEI ; Ruimin CHEN ; Zhixin ZHANG ; Xinran CHENG ; Na TAO ; Chunlin WANG ; Yu YANG ; Ying XIN ; Xin FAN ; Xingxing ZHANG ; Geli LIU ; Shengquan CHENG ; Min ZHU ; Hongwei DU ; Yan SUN ; Linqi CHEN ; Lanwei CUI ; Xiaoping LUO
Chinese Journal of Pediatrics 2024;62(10):962-968
Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.
8.11C-methionine PET/CT radiomics model for evaluating isocitrate dehydrogenase1 status of glioblastoma
Yue PAN ; Haodan DANG ; Xiaolin MENG ; Cong ZHANG ; Yu LIN ; Ruimin WANG ; Baixuan XU
Chinese Journal of Medical Imaging Technology 2024;40(6):832-837
Objective To explore the value of 11C-methionine(MET)PET/CT radiomics model for evaluating isocitrate dehydrogenase1(IDH1)status of glioblastoma.Methods Data of 157 patients with glioblastoma who underwent 11C-MET PET/CT examination,including 68 cases of IDH1 mutation and 89 cases of IDH1 wild-type were retrospectively analyzed.The patients were divided into training set(n=125)and validation set(n=32)at the ratio of 8:2.Based on PET/CT images,lesions ROI were delineated and radiomics features were extracted and screened to establish radiomics models with logistic regression(LR),support vector machine(SVM)and decision trees(DT),respectively.Meanwhile,the nomogram based on patients'age and radiomics features was drawn.The efficacy of radiomics models and clinical-radiomics nomogram for evaluating IDH1 status were comparatively observed.Results The area under the curve(AUC)of DT radiomics model for evaluating IDH1 status of glioblastoma in training set was 0.910,higher than that of LR(0.697)and SVM(0.698)models(both P<0.05).In validation set,the AUC of DT model for evaluating IDH1 status of glioblastoma was 0.805,which was higher than that of LR model(0.740)and clinical-radiomics nomogram(0.704)(both P<0.05).Conclusion 11C-MET PET/CT radiomics model based on DT was helpful for evaluating IDH1 status of glioblastoma.
9.Correlation and consistency evaluation between electrochemiluminescence and direct chemiluminescence in detecting 12 tumor markers
Miao MA ; Jie LIU ; Ruimin MA ; Pingyan LI ; Jing LU ; Huiwen XU ; Danwei YU ; Guojun ZHANG
China Medical Equipment 2024;21(5):20-25
Objective:To assess the correlation and consistency of electrochemiluminescence and direct chemiluminescence in detecting 12 tumor markers.Methods:A total of 2426 serum specimens were selected from the physical examination in Beijing Tiantan Hospital,Capital Medical University from March to August 2023.These specimens included 446 cases for alpha fetoprotein(AFP),284 cases for carcinoembryonic antigen(CEA),289 cases for carbohydrate antigen 72-4(CA72-4),87 cases for carbohydrate antigen 19-9(CA19-9),205 cases for carbohydrate antigen 125(CA-125),216 cases for carbohydrate antigen 15-3(CA 15-3),292 cases for total prostate specific antigen(TPSA),292 cases for free prostate specific antigen(FPSA),84 cases for serum cytokeratin 19 fragment(Cyfra21-1),84 cases for neuron specific enolase(NSE),84 cases for squamous cell carcinoma associated antigen(SCC)and 63 cases for pro-gastrin-releasing peptide(PROGrp).The electrochemiluminescence and direct chemiluminescence methods were respectively used to detect the above 12 indexes,and then,the correlation and consistency between the two detection methods were analyzed.Results:The results of Pearson and Spearman correlation analysis showed that there were significantly positive correlations between electrochemiluminescence and direct chemiluminescence methods in detecting 12 tumor indexes(AFP,CEA,CA72-4,CA19-9,CA125,CA15-3,TPSA,FPSA,Cyfra21-1,NSE,SCC and PROGrp)(r=0.971,0.934,0.945,0.975,0.900,0.948,0.994,0.984,0.982,0.828,0.879,0.922,P<0.05),respectively.The total coincidence rates between the two methods were respectively 98.21%,98.24%,98.27%,98.85%,97.07%,99.54%,99.66%,99.32%,92.86%,92.86%,95.24%and 96.83%.There were consistencies between electrochemiluminescence and direct chemiluminescence methods for 10 indexes excepted CA15-3 and NSE that could not calculate Kappa values due to data reasons(Kappa=0.848,0.728,0.930,0.794,0.485,0.887,0.664,0.540,0.477,0.652,P<0.05),respectively.Conclusion:In the detections of electrochemiluminescence and direct chemiluminescence methods for tumor indexes,there are favorable correlations and consistencies between them in detecting AFP,CA72-4,CA19-9 and TPSA,and there are favorable correlations between them in detecting CEA,CA125,FPSA,Cyfra21-1,SCC and PROGrp but the consistencies between them are average in detecting these indexes,and there are favorable correlations between them in detecting CA15-3 and NSE.Clinical detection should pay attention to there may be differences in the results between different detection methods when the detection is conducted in reference laboratory.
10.Effects of APOE on subcortical Aβ deposition and functional connectivity changes in patients with Alzheimer′s disease based on 11C-PIB PET/MR
Yan CHANG ; Xiwan ZHANG ; Shina WU ; Jiajin LIU ; Huaping FU ; Jinming ZHANG ; Ruozhuo LIU ; Baoci SHAN ; Ruimin WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(5):285-290
Objective:To investigate the effects of apolipoprotein E (APOE) ε4 allele on β-amyloid (Aβ) deposition in subcortical structures and functional connectivity (FC) between brain regions in patients with Alzheimer′s disease (AD). Methods:Forty-three patients with probable mild/moderate AD were prospectively enrolled from the First Medical Centre, Chinese PLA General Hospital between January 2023 and October 2023, including 23 APOE ε4+ patients (12 males and 11 females, age (74.8±8.4) years), 20 APOE ε4- patients (14 males and 6 females, age (77.6±8.9) years) and 20 normal cognitive volunteers (NC) (15 males and 5 females, age (75.3±6.2) years). All subjects underwent 11C-Pittsburgh compound B (PIB) PET/MR brain imaging. The differences of gray matter volume (GMV) in subcortical structures (hippocampus, amygdala) among the three groups were analyzed by one-way analysis of variance and least significant difference (LSD) t test. Independent-sample t test and Pearson correlation analysis were used to analyze difference in Aβ deposition between APOE ε4+ patients and APOE ε4- patients, and the correlation between subcortical structure and brain FC. Results:The GMV of bilateral amygdala between NC group and APOE ε4+ gene carrier group, and between APOE ε4+ and APOE ε4- gene carrier groups were significantly different ( F=6.43, P=0.002; P values: 0.002, 0.003). Significant difference of GMV was observed in the bilateral hippocampus among three groups ( F=5.34, P=0.030). Abnormal PIB uptake was detected in both the hippocampus and amygdala of both APOE ε4+ and APOE ε4- gene carrier groups, with a more pronounced effect observed in the APOE ε4+ group ( t values: 3.14, 2.19, P values: 0.032, 0.009). Taking the hippocampus as the seed point, there was no obvious abnormality in the whole brain connectivity map among APOE ε4+, APOE ε4- carriers and NC groups. With the amygdala as the seed point, the whole brain connectivity in the APOE ε4+ gene carrier group was significantly reduced, and the connectivity between the amygdala and the cingulate gyrus, parietal lobe and temporal lobe was significantly reduced in the APOE ε4+ gene carrier group compared with NC group, while the connectivity between the amygdala and the whole brain was not significantly reduced in the APOE ε4- gene carrier group. Aβ deposition in amygdala was positively correlated with FC coefficients of frontal brain regions, gyrus rectus, right middle occipital gyrus and left temporal lobe ( r values: 0.56-0.70, all P<0.05). Conclusion:APOE influences GMV and Aβ deposition of hippocampus and amygdala, and FC of amygdala, and may be involved in the pathological mechanism of cognitive impairment.


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