1.Evaluation of high-resolution MRI in patients with posterior circulation ischemic stroke caused by vertebral artery dissection
Qiujiao WANG ; Zhihong CAO ; Yifeng LUO
Journal of Practical Radiology 2024;40(4):535-538
Objective To evaluate the imaging features of posterior circulation ischemic stroke caused by vertebral artery dissection(VAD)by high-resolution magnetic resonance imaging(HR-MRI).Methods A total of 56 patients with highly suspected VAD were selected.According to HR-MRI characteristics,these patients were divided into ischemic stroke group(n=23)and control group(n=33).The correlation between imaging features and risk factors in the two groups was analyzed.Results The proportions of intramural hematoma,tumor-like dilatation,and degree of vessel wall enhancement in the ischemic stroke group were significantly higher than those in the control group,and the difference was statistically significant(P<0.05).However,there was no statistical significance in the double-chamber sign and intimal valve sign(P=0.075).Correlation analysis showed that the effective lumen index was significantly negatively correlated with the incidence of posterior circulation ischemic stroke in patients with VAD(r=-0.721,P<0.05),and the area under the curve(AUC)of the effective lumen index reached 0.935.Conclusion The effective features of HR-MRI in the diagnosis of posterior circulation ischemic stroke caused by VAD include intramural hematoma,tumor-like dilatation,degree of vessel wall enhancement,and reduction of effective lumen index,which are helpful for the management and prediction of patients with VAD.
2.BMSC-Exo alleviates depression-like behaviors in mice by inducing hippocampal energy metabolism and microangiogenesis
Weijia HU ; Lili CAI ; Xiaolan ZHU ; Yifeng LUO ; Zhihong CAO ; Yuefeng LI
Chinese Journal of Neuromedicine 2024;23(1):2-9
Objective:To investigate the effect of bone mesenchymal stem cells derived exosomes (BMSC-Exo) on improving hippocampal microangiogenesis, energy metabolism, and behaviors in depression mouse models.Methods:(1) Mouse bone marrow mesenchymal stem cells were isolated and cultured to extract BMSC-Exo; BMSC-Exo morphology was observed by transmission electron microscopy, BMSC-Exo particle diameter ranges were determined by Zetaview analyzer, and expressions of CD9 and CD63 in BMSC-Exo were detected by Western blotting. (2) Depression models were established in 2 mice by chronic unforeseeable mild stress (CUMS); 24 h after stereotaxic injection of phosphate buffer solution (PBS) or DiR labeled BMSC-Exo, BMSC-Exo uptake was detected by in vivo imaging system. (3) Thirty-six mice were randomly divided into control group, model group and BMSC-Exo group ( n=12); CUMS was used to establish depression models in the latter 2 groups; brain stereotaxic injection of 1 μL BMSC-Exo was given to mice in the BMSC-Exo group after modeling, and same amount of PBS was given to the control group; behaviors were observed by forced swimming test (FST), tail suspension test (TST) and open field test (OFT); hippocampal microvascular length and number were detected by alkaline phosphatase staining; energy metabolism in the hippocampus was detected by micro positron emission tomography/computed tomography (mPET/CT); glucose transporter 1 (GLUT1) expression in the hippocampus was detected by Western blotting. Results:(1) BMSC-Exo had a typical disk-like vesicle-like structure with particle size of (100.5±1.4) nm; Western blotting confirmed that CD9 and CD63 expressed in BMSC-Exo. (2) In vivo imaging showed no fluorescence in the brain and liver after PBS injection, but obvious local fluorescence after BMSC-Exo injection. (3) Compared with the control group, the model group and BMSC-Exo group had significantly longer rest time in FST and TST and shorter movement distance and time in the central region of OFT ( P<0.05); compared with the model group, BMSC-Exo group had significantly shorter rest time in FST and TST and longer movement distance and time in the central region of OFT ( P<0.05). Compared with the control group, the model group and BMSC-Exo group had significantly decreased standard uptake value (SUV) of regions of interest, microvascular length and number, and GLUT1 expression in the hippocampus ( P<0.05); compared with the model group, the BMSC-Exo group had significantly higher SUV, microvascular length and number, and GLUT1 expression in the hippocampus ( P<0.05). Positive correlations were noted between hippocampal microvascular length and SUV and between microvascular number and SUV in the 3 groups ( r=0.540, P<0.001; r=0.600, P<0.001). Conclusion:BMSC-Exo could promote microangiogenesis energy metabolism in the hippocampus to improve depression-like behaviors in depression mouse models.
3.Association between the non-rich-club connectivity synergism of brain structural network and the occurrence of post-stroke depression
Yujiao CAI ; Yang LI ; Kai XIE ; Yuhao XU ; Yan ZHU ; Yifeng LUO ; Zhihong CAO ; Yuefeng LI
Chinese Journal of Neurology 2024;57(5):481-487
Objective:To explore the association between changes in brain structural network during the early stage of stroke recovery and the onset of post-stroke depression (PSD).Methods:A total of 87 acute ischemic stroke patients scheduled for discharge, who were admitted to the Yixing Hospital Affiliated to Jiangsu University from March 2020 to May 2021, were prospectively collected. During the same period, 34 healthy control subjects matched with the stroke patients were also collected. All participants underwent systematic magnetic resonance imaging scans and scale assessments, and were followed up longitudinally for 2 years. Based on the occurrence of depression during follow-up, the stroke patients were divided into PSD group and post-stroke non-depression (PSND) group. Graph theoretical analysis was used to analyze the topological characteristics of brain structural network. Analysis of variance was used to explore the differences in brain structural network attributes among groups. Logistic regression model was used to analyze the predictive power of differential brain network attributes for PSD. Linear regression analysis was conducted to investigate the relationship between the synergism of non-rich-club regions and changes in rich-club connectivity.Results:The rich-club connectivity and synergism of the non-rich-club regions were significantly lower in the PSD group than in the PSND group (rich-club connectivity, P<0.01; synergism of feeder/local, P<0.001). The regression model demonstrated that the synergism of non-rich-club regions had a good predictive power for the occurrence of PSD ( OR=1.195, 95%CI 1.073-1.471, P<0.001). Furthermore, linear regression analysis revealed a significant correlation between the synergism of non-rich-club regions and Δrich-club connectivity ( r=-0.691, P<0.001). Conclusion:The good synergism of non-rich-club regions during the early stage of stroke recovery promotes the repair of rich-club connectivity and inhibits the onset of PSD.
4.Changes of topological attributes of brain structural network in patients with postpartum depression
Kai XIE ; Yang LI ; Xiaolan ZHU ; Yujiao CAI ; Yifeng LUO ; Zhihong CAO ; Yuefeng LI ; Jiajia SHI
Chinese Journal of Perinatal Medicine 2024;27(6):468-476
Objective:To investigate the features of the brain structural network in patients with postpartum depression (PPD).Methods:This cross-sectional study included PPD patients who visited the mental health counseling clinic after delivery at the Jiangsu University Affiliated Yixing Hospital from June 2013 to September 2022 (PPD group). Matched non-PPD postpartum women based on age, years of education, and body mass index who came for postpartum follow-up (non-PPD postpartum group), and non-pregnant women who visited the hospital or underwent physical examinations during the same period (non-pregnant group) were also included. Demographic data and diffusion tensor imaging (DTI) data were collected for all three groups. The brain was partitioned into 90 regions using an anatomical template to construct the brain structural network. Network-based statistics (NBS) were applied to further screen and construct subnetworks. The efficacy of the subnetworks in identifying PPD was evaluated through multivariable logistics regression models and receiver operating characteristic curves. A comparison of the connectivity strength of white matter tracts and topological attributes of brain structural network parameters was conducted using independent samples t-tests, and the results were corrected using the false discovery rate (FDR) method. Results:(1) A total of 116 subjects were included, with 40 in the non-pregnant group, 40 in the non-PPD postpartum group, and 36 in the PPD group. PPD group had higher Edinburgh Postnatal Depression Scale (EPDS) scores than the non-pregnant and non-PPD postpartum groups [(18.0±4.1) scores vs. (2.5±1.2) and (6.1±2.1) scores, F=340.40; t=24.65,10.60 and 16.16 in pairwise comparison; all P<0.001]. (2) Compared to the non-pregnant group, there was a decrease in the connectivity strength of nine white matter tracts within the brain structural network of the postpartum group (including left dorsolateral superior frontal gyrus-left anterior cingulate and paracingulate gyrus, left dorsolateral superior frontal gyrus-right amygdala, left dorsolateral superior frontal gyrus-left insula, left insula-left lentiform nucleus, left insula-left hippocampus, left hippocampus-right amygdala, left hippocampus-left precuneus, left anterior cingulate and paracingulate gyrus-right amygdala, and right amygdala-right hippocampus) (all P<0.05, FDR corrected). No increased connection strengths were observed. There were no significant differences in the connection strengths of these nine tracts between the non-PPD and PPD groups. (3) A characteristic subnetwork for the maternal group was successfully constructed based on the nine tracts, which exhibited typical small-world properties (σ>1). Compared to the non-PPD maternal group, the characteristic path length in the PPD group was increased [(3.904±0.328) vs. (4.130±0.433), t=-2.58], and global efficiency was decreased [(0.361±0.036) vs. (0.331±0.053), t=2.91] (both P<0.05). Local property comparisons showed that the node efficiency values for the left dorsolateral superior frontal gyrus, left insula, left anterior cingulate and paracingulate gyrus, left hippocampus, right hippocampus, right amygdala, left precuneus and left putamen in the PPD group were significantly reduced [(0.273±0.023) vs. (0.267±0.030), t=0.98; (0.299±0.035) vs. (0.276±0.041), t=2.64; (0.265±0.019) vs. (0.258±0.025), t=1.38; (0.318±0.028) vs. (0.305±0.031), t=1.92; (0.312±0.027) vs. (0.302±0.031), t=1.50; (0.322±0.030) vs. (0.298±0.026), t=3.71; (0.356±0.040) vs. (0.338±0.056), t=1.62; (0.346±0.028) vs. (0.331±0.036), t=1.74; all P<0.05]. However, only the differences in node efficiency values for the left insula and right amygdala remained significant after FDR correction (corrected P=0.041 and 0.003). (4) Global efficiency, as well as node efficiency for the left insula and right amygdala, demonstrated good value for identifying PPD [areas under the curve (AUC) and their 95% CI were 0.827 (0.732-0.922), 0.741 (0.628-0.854), and 0.761 (0.653-0.867), respectively], with even better performance when combined [0.897 (0.828-0.969)]. (5) In the PPD group, global efficiency ( r=-0.43, P=0.008), node efficiency for the left insula ( r=-0.39, P=0.019), and node efficiency for the right amygdala ( r=-0.42, P=0.011) were all negatively correlated with EPDS scores. Conclusion:Aberrations in global efficiency, node efficiency for the left insula, and node efficiency for the right amygdala may serve as characteristic neuroimaging biomarkers for PPD.
5.Research progress in the application of single-cell sequencing technology in multiple sclerosis
Zhihong MA ; Lihong ZHANG ; Yuan CAO ; Ming CHENG
Chinese Journal of Comparative Medicine 2024;34(10):161-168
Multiple sclerosis(MS)is a chronic autoimmune disease of the central nervous system characterized by neuroinflammation and neurodegeneration.The pathogenesis of the disease is complex,and involves various central nervous system and peripheral cells.Single-cell sequencing has recently been increasingly applied in the study of neurological disorders,leading to important advances in our understanding of intercellular heterogeneity,disease development mechanisms,and treatment strategies.This review summarizes research progress in single-cell sequencing and its applications in MS.
6.Application value of thyroid fine needle aspiration fluid-based thin layer cytology combined with p21 and Cyclin D1 detection in the preoperative diagnosis of papillary thyroid carcinoma
Chenchen WANG ; Jun ZHANG ; Minghong SHEN ; Dan CAO ; Rulei CHEN ; Zhihong ZHANG ; Jinghuan LÜ
Chinese Journal of Clinical and Experimental Pathology 2023;39(12):1476-1482
Purpose To explore the application value of ultrasound-guided thyroid fine needle aspiration liquid-based thin layer cytopathology combined with p21 and Cyclin D1 detection in preoperative diagnosis of papillary thyroid carcinoma.Meth-ods Immunocytochemical staining was used to detect the ex-pression differences of p21 and Cyclin D1 between benign and malignant thyroid nodules,and their correlations the clinicopath-ological features.The diagnostic efficacy of US-FNAB,p21,Cyclin D1 and the three combined detection in benign and malig-nant thyroid nodules was evaluated by constructing receiver oper-ating curve.Results The expression of p21 and Cyclin D1 was up-regulated in the papillary thyroid carcinoma group,86.36%(57/66)and 93.94%(62/66),and 1.96%(1/52)and 5.77%(3/52)in the benign nodule group,respectively;the difference between the two groups was significant(P<0.05).The positive rates of p21 and Cyclin D1 in BRAF V600E wild type PTC were 88.89%(8/9).The expression of p21 and Cyc-lin D1 was correlated with the tumor size of PTC(P<0.05),but not with gender,age,number of tumor foci,lymph node metastasis,and TNM stage(P>0.05).The sensitivity,speci-ficity,positive predictive value and negative predictive value of US-FNAB,p21 and Cyclin D1 combined detection were 95.45%,98.07%,98.43%and 94.44%,respectively,which were higher than those of US-FNAB independent detection,and the sensitivity and negative predictive value were higher than those of BRAF V600E.The area under ROC curve of US-FNAB,p21 and Cyclin D1 combined detection(AUC = 0.967 7)was larger than that of US-FNAB(AUC = 0.849 9)and the difference between the two was statistically significant(P<0.05).The area under ROC curve of the combined detection of the three was greater than that of independent detection of BRAF V600E(AUC =0.931 8),and the combined detection of US-FNAB with p21(AUC = 0.946 4)or Cyclin D1(AUC = 0.944 3).It was close to that of US-FNAB combined BRAF V600E detection(AUC = 0.971 2).Conclusion US-FNAB combined with p21 and Cyclin D1 immunohistochemical detec-tion can help improve the sensitivity of preoperative diagnosis of papillary thyroid carcinoma,and it has high diagnostic value for BRAF V600E wild-type papillary carcinoma.
7.Secular trends of dietary magnesium intakes among Chinese residents in 15 provincial-level administrative regions from 1991 to 2018
Qiuye CAO ; Zhihong WANG ; Liusen WANG ; Shaoshunzi WANG ; Weiyi LI ; Lixin HAO ; Huijun WANG ; Bing ZHANG ; Gangqiang DING ; Hongru JIANG
Journal of Environmental and Occupational Medicine 2022;39(9):968-973
Background Magnesium is an important nutrient, and participates in most metabolic processes. Many studies show an association between dietary magnesium intakes and nutrition-related diseases such as diabetes. However, the data of dietary magnesium intakes and secular trends among the whole life cycle of Chinese residents are not available. Objective To investigate the dietary magnesium intakes and associated secular trends over the past three decades in residents of all ages and China, to identify the high-risk residents of magnesium deficiency and plan nutritional interventions, and provide basic data support for the revision of dietary magnesium reference intake. Method The data came from the 10 rounds of the "China Health and Nutrition Survey" from 1991 to 2018, and the participants with complete sociodemographic and dietary data wereselected. The median intakes, insufficient rates, and secular trends of dietary magnesium intakes were analyzed in different survey years. Analysis of multiple linear regression was used to analyze the annual change characteristics of dietary magnesium intakes controlling gender, age, education, urban-rural stratum, and north-south region. Wilcoxon trend test was used to analyze the secular trends of dietary magnesium intakes in different characteristic groups. The trends of insufficient rate were analyzed by Cochran-Armitage trend test among different characteristic groups. Results A total of 127169 residents were included in the present study. The medians of dietary magnesium intakes in 1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011, 2015, and 2018 were 283.70, 283.38, 304.26, 285.50, 283.64, 275.49, 267.92, 242.93, 240.51, and 238.89 mg·d−1, respectively, showing a significant downward trend (F=2931.81, P<0.001). Dietary magnesium intakes showed significant differences in gender, age, education level, income level, urban-rural stratum, and north-south region in almost all survey years, except that there was no significant difference among different income groups in 1991. Insufficient rate of dietary magnesium intake showed a significant upward trend (Z=62.62, P<0.001), approximate 60% of Chinese residents consumed insufficient magnesium. The insufficient rate was 53.94% for male and 65.35% for female, and the insufficient rate in the 14-17 age group was as high as 71.29%. Conclusion The dietary magnesium intake shows a significant downward trend and insufficient intake of dietary magnesium is prevalent among Chinese population. It is necessary to observe the high-risk population and conduct relevant nutritional interventions, as well as to further assess the recommended intake of magnesium.
8.Effects of acute and chronic trauma on degree centrality of brain functional images in patients with post-traumatic stress disorder who lost their only child
Bo LIU ; Yifeng LUO ; Rongfeng QI ; Jiyuan GE ; Huanhuan DAI ; Qingyue LAN ; Li ZHANG ; Feng CHEN ; Zhihong CAO ; Lingjiang LI ; Guangming LU
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(6):506-512
Objective:To investigate the effects and significance of acute and chronic trauma on brain degree centrality (DC) in patients with post-traumatic stress disorder (PTSD) who lost their only child at resting state.Methods:Retrospectively, the study enrolled a total of 51 parents with PTSD, including 35 PTSD parents whose children was lost in emergencies (acute bereaved PTSD group) and 16 PTSD parents whose children was lost of chronic causes such as diseases (chronic bereaved PTSD group). Fifty local adults were also included as healthy controls (HC group). The clinical administered PTSD scale(CAPS) was used to evaluate the severity of the subjects' clinical symptoms.Resting-state functional magnetic resonance imaging(fMRI) data of all subjects were collected and DC values were calculated.SPSS 22.0 software was used for statistical analysis.Covariance analysis was performed among three groups, while post hoc was performed between any two groups.What's more, correlation analyses were utilized between abnormal brain regions and the scores of CAPS.Results:Significant group effects were found in multiple regions, including the right inferior temporal gyrus (MNI: x, y, z=66, -27, -21), right temporal pole (MNI: x, y, z=54, 15, -9), right orbital inferior frontal gyrus (MNI: x, y, z=42, 21, -15), bilateral medial superior frontal gyri (MNI: right x, y, z=6, 63, 12; left x, y, z=-3, 60, 18), left inferior parietal angular gyrus (MNI: x, y, z=-45, -36, 51) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51). Compared with HC group, the DC of two patient groups increased in the right inferior temporal gyrus (MNI: acute x, y, z=63, -27, -21; chronic x, y, z=63, -21, -27); the DC of acute bereaved PTSD group decreased in the right temporal pole (MNI: x, y, z=45, 21, -15) and the right orbital inferior frontal gyrus (MNI: x, y, z=48, 24, -12), while the DC of chronic bereaved PTSD group decreased in the left inferior parietal angular gyrus (MNI: x, y, z=-45, -36, 51) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51). Compared with chronic bereaved PTSD group, the DC of acute bereaved PTSD group increased in the left inferior parietal angular gyrus (MNI: x, y, z=-33, -39, 42) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51), while decreased in the right temporal pole (MNI: x, y, z=51, 12, -9), right orbital inferior frontal gyrus (MNI: x, y, z=42, 21, -15) and bilateral medial superior frontal gyri (MNI: left x, y, z=0, 57, 15; right x, y, z=3, 57, 15). In chronic bereaved PTSD group, the DC of the left postcentral gyrus was negatively correlated with C1 (avoid trauma-related thoughts, feelings) score in CAPS ( r=-0.606, P=0.028). In acute bereaved PTSD group, the DC of the left medial superior frontal gyrus was negatively correlated with D4 (high vigilance) score ( r=-0.416, P=0.020). Conclusion:There exist functional abnormalities of multiple brain regions in acute and chronic bereaved parents with PTSD.The high arousal symptoms of the former may be related with the abnormalities of prefrontal-amygdala neural circuit, while the latter show higher avoidance which may be associated with the dysfunction of somatosensory brain regions such as postcentral gyrus.
9.Role of coping styles in development of post-traumatic stress disorder in patients lost their only child: a brain structure study
Huanhuan DAI ; Yifeng LUO ; Rongfeng QI ; Jiyuan GE ; Bo LIU ; Qingyue LAN ; Li ZHANG ; Feng CHEN ; Zhihong CAO ; Lingjiang LI ; Guangming LU
Chinese Journal of Neuromedicine 2022;21(10):989-995
Objective:To investigate the effect of coping style on the gray matter volume in patients with post-traumatic stress disorder (PTSD) who lost their only child, and the mediating role of gray matter volume in evaluating the influence of coping style in clinical symptoms of these parents.Methods:A total of 57 parents with PTSD (PTSD group) and 162 parents without PTSD (non-PTSD group) who lost their only child from September 2016 to March 2017 were enrolled from Jiangsu Province, China. Brain MRI data at resting state were collected. Voxel-based multiple regression analysis was performed to confirm the brain areas in which coping style main effect, diagnosis main effect and their interaction had significant influences in gray matter volumes. Correlations among gray matter volume of brain areas related to coping style, coping style scale scores, and clinician-administered PTSD scale (CAPS) scores were analyzed. Structural equation modeling was used to analyze the mediating role of gray matter volume in the influence of coping style in clinical symptoms of parents lost their only child.Results:(1) The coping style main effect did not significantly influence the gray matter volume in all subjects, and the diagnosis main effect had significant influence in gray matter volume in the right lingual gyrus; their interaction had significant influence in gray matter volume in the right peritalar fissure cortex and lingual gyrus. The positive coping style in the PTSD group had significant influence in the gray matter volumes of the right peritalar fissure cortex and lingual gyrus. (2) In the PTSD group, the scores of positive coping style were positively correlated with the gray matter volumes of the right talus fissure and the lingual gyrus ( P<0.05); the scores of positive coping style, and the gray matter volumes of the right talus fissure and the lingual gyrus were negatively correlated with scores of CAPS-C 5 and CAPS-C ( P<0.05). (3) In the PTSD group, positive coping style can positively predict the gray matter volumes of the right talus fissure and the lingual gyrus; the gray matter volumes of the right talus fissure and the lingual gyrus can negatively predict the avoidance-related symptoms. Conclusion:Positive coping style has influence in the gray matter volumes of the right talar fissure and lingual gyrus of PTSD patients lost their only child; and less positive coping style may affect the brain areas related to visual information processing, thus aggravating avoidance-related symptoms of PTSD patients.
10.Determination of Pyrrotinib Concentration in Human Plasma by LC-MS/MS and Its Clinical Application
Zhenhuan ZHAO ; Weili JING ; Tao LIU ; Zhiqiang LYU ; Zhihong CAO ; Wen XU
China Pharmacy 2021;32(22):2767-2771
OBJECTIVE:To establish a method for the determination of pyrrotinib concentration in plasma ,and apply it in clinic. METHODS :After precipitated with methanol ,the plasma sample was determined by LC-MS/MS using imatinib as internal standard. The determination was performed on Ultimate AQ-C 18 column with mobile phase consisted of methanol (containing 0.1% formic acid )and water (containing 0.1% formic acid )(gradient elution )at the flow rate of 0.4 mL/min. The column temperature was 40 ℃,and the sample size was 5 µL. The ion source was electrospray ionization source ,and the positive ion scanning was carried out in multiple reaction mode. The ion pairs for quantitative analysis were m/z 583.4→138.3(pyrrotinib)and m/z 494.5→ 393.4(internal standard ),respectively. Thirty breast cancer patients taking pyrrotinib were collected from the Affiliated Hospital of Qingdao University during Jun.-Nov. 2020 to determine their steady-state trough concentrations of pyrrotinib after a week of treatment. RESULTS :The linear range of pyrrotinib were 5-300 ng/mL(r=0.999 3). The lower limit of quantification was 5 ng/mL. RSDs of intra-day and inter-day were not higher than 9.30%,and relative errors (REs)ranged -6.70%-5.04%. REs of stability tests were in the range of -1.92%-5.42%. The extraction method ,matrix effect and residual effect did not affect the quantitative analysis of the substance to be tested. The steady-state trough concentrations of pyrrotinib were 32.6-82.8 ng/mL,with an average plasma concentration of 53.8 ng/mL;there was about 2.54 fold individual difference. CONCLUSIONS :Established LC-MS/MS method is simple ,sensitive and accurate ,and can be used for the plasma concentration monitoring of pyrrotinib in breast cancer patient.

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