1.Inhibition of subicular seizure-labeled c-fos+ neurons alleviates cognitive deficit in epilepsy
Lin YANG ; Qi ZHANG ; Xueqing WU ; Xiaoyun QIU ; Fan FEI ; Nanxi LAI ; Yuyi ZHENG ; Mengdi ZHANG ; Qingyang ZHANG ; Yu WANG ; Fei WANG ; Cenglin XU ; Yeping RUAN ; Yi WANG ; Zhong CHEN
Chinese Journal of Pharmacology and Toxicology 2023;37(7):482-483
OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.
2.The lesion characteristics and predictors of obstructive coronary artery disease with anatomy-function mismatch
Mengdi JIANG ; Xiaolei ZHANG ; Yang HOU ; Minwen ZHENG ; Jiayin ZHANG ; Bo ZHANG ; Daimin ZHANG ; Lei XU ; Xiuhua HU ; Yining WANG ; Jian YANG ; Hui LIU ; Fan ZHOU ; Guifen YANG ; Longjiang ZHANG
Chinese Journal of Radiology 2021;55(12):1287-1293
Objective:To explore the lesion characteristics and predictors of invasive coronary angiography (ICA)-verified obstructive lesions with fractional flow reserve (FFR)>0.80, that is, anatomy-function mismatch.Methods:A total of 515 obstructive vessels in 419 coronary disease patients from 11 Chinese medical centers undergoing coronary CT angiography and ICA and FFR were retrospectively analyzed. All vessels had one target lesion with diameter stenosis ≥50 % by ICA. There were 229 vessels in the match group (FFR≤0.80) and 286 vessels in the mismatch group (FFR>0.80). The lesion characteristics including lesion territory, the distance of the coronary artery ostium to the proximal end of the lesion, minimum lumen area, reference lumen area, plaque length and burden, plaque volume and component volume, remodeling index and plaque morphological complexity were measured and compared between the two groups. Optimal thresholds of quantitative plaque characteristics were defined by Yoden index. Logistic regression analysis was used to analyze the predictors of anatomy-function mismatch. Area under receiver operating characteristic curve (AUC) was used to analyze the ability of different lesion features to predict mismatched lesions.Results:The coronary stenosis, plaque burden and length, plaque volume (including each component volume) in the mismatch group were smaller than those in the match group, and FFR, minimum lumen area were larger (all P<0.05). Left anterior descending artery (LAD) lesion and severe complex plaque were more common in the match group than the mismatch group with a statistically significant difference. Univariate logistic regression analysis showed that LAD lesion, minimum lumen area>4 mm 2, plaque burden and length, plaque calcification volume<27 mm 3, plaque lipid volume<30 mm 3, plaque fiber volume<150 mm 3 and plaque morphological complexity were predictiors of anatomic function mismatched lesions; Multivariate logistic regression showed that the minimum lumen area>4 mm 2 (OR=3.371, 95%CI 1.903-5.973, P<0.001), plaque lipid volume<30 mm 3 (OR=3.014, 95%CI 1.691-5.373, P<0.001), plaque morphological complexity (mild OR=17.772, 95%CI 8.072-39.128, P<0.001, moderate OR=6.383, 95%CI 3.739-10.896, P<0.001) were independent predictors of mismatched lesions. The AUC of the model based on the minimum lumen area, plaque lipid volume and morphological complexity was 0.824, which was superior to either of the plaque feature alone ( P<0.001). Conclusions:The minimum lumen area, lipid volume and plaque morphological complexity are independent predictors of the anatomical-functional mismatch lesions, and the combination can significantly improve the prediction value.
3.Effect and mechanism of microRNA-155 on cell biological behavior of thyroid papillary carcinoma cells
Zhaoshu WU ; Wei HAN ; Yue CAO ; Mengdi CUI ; Yue YANG ; Lang ZHOU ; Min LI ; Gang WANG ; Dongchen LU ; Honglin FAN ; Kai LU
Chinese Journal of Endocrine Surgery 2020;14(2):139-143
Objective:To study the role of miR-155 in the differentiation of papillary thyroid carcinoma (PTC) cells, and to explore the possible mechanism.Methods:Human miR-155 analogues were constructed and transfected into PTC BCPAP cells in vitro. CCK8 test and Transwell test were used to observe the changes of cell proliferation and invasiveness. The miR-155 was transfected into BCPAP cells in vitro and the protein background and phosphorylation expression of MAPK pathway were detected by Western blot. ERK pathway inhibitor U0126 was given to observe whether it could reverse the abnormal proliferation and invasion of thyroid cancer cells caused by over-expression of miR-155.Results:The proliferation of BCPAP cells was detected by CCK8 test 48 hours after overexpression of miR-155, and the invasiveness of thyroid cancer cells was significantly enhanced by Transwell test 48 hours after overexpression of miR-155 ( P<0.05) ; Western blot method found that the expression of JNK, ERK and p38 in MAPK signal pathway was significantly up-regulated ( P<0.05) . At the same time, the expression of p-ERK protein in the cells was increased significantly ( P<0.05) . The expression of p-ERK in the cells treated with ERK pathway inhibitor U0126 and miR-155 was significantly lower than that in the miR-155 group ( P<0.05) . By detecting the proliferation and invasion of cells in each group, we found that the U0126 could reverse the proliferation and invasion promoting effect caused by miR-155. Conclusion:miR-155 can promote the proliferation and invasion of PTC BCPAP cells by activating the ERK pathway of MAPK pathway, which provides a potential target for the treatment of thyroid cancer.
4.Current main problems and countermeasures for prevention and control of endemic diseases in China
Dianjun SUN ; Hui LIU ; Jun YU ; Peng LIU ; Junrui PEI ; Lijun ZHAO ; Lijun FAN ; Jie HOU ; Mengdi LI
Chinese Journal of Endemiology 2023;42(1):1-3
Over the past decade, remarkable progress has been made in prevention and control of endemic diseases in China through implementation of the 12th and the 13th Five-Year National Plans for Prevention and Control of Endemic Diseases and the Three-Year Action Plan for Special Prevention and Control of Endemic Diseases. Based on the latest monitoring data of endemic diseases and the evaluation results of the control and elimination of endemic diseases of the 13th Five-Year Plan, this paper analyzed current main problems in prevention and control of endemic diseases in China, focusing on implementation of prevention and control measures for iodine deficiency disorders, endemic fluorosis, and endemic arsenicosis, as well as the treatment and management of patients. Accordingly, corresponding countermeasures and suggestions are put forward from three aspects, including prevention and control mechanism, implementation of prevention and control measures, and scientific research, so as to provide scientific basis for the country and various regions to consolidate the achievements of prevention and control of endemic diseases and accurately implement the prevention and control measures of endemic diseases.
5.Research on the correlation of brain function based on improved phase locking value.
Xin LI ; Mengdi FAN ; Xiaoqi SUN ; Quan LI ; Jie ZHANG
Journal of Biomedical Engineering 2018;35(3):350-357
The phase lock value(PLV) is an effective method to analyze the phase synchronization of the brain, which can effectively separate the phase components of the electroencephalogram (EEG) signal and reflect the influence of the signal intensity on the functional connectivity. However, the traditional locking algorithm only analyzes the phase component of the signal, and can't effectively analyze characteristics of EEG signal. In order to solve this problem, a new algorithm named amplitude locking value (ALV) is proposed. Firstly, the improved algorithm obtained intrinsic mode function using the empirical mode decomposition, which was used as input for Hilbert transformation (HT). Then the instantaneous amplitude was calculated and finally the ALV was calculated. On the basis of ALV, the instantaneous amplitude of EEG signal can be measured between electrodes. The data of 14 subjects under different cognitive tasks were collected and analyzed for the coherence of the brain regions during the arithmetic by the improved method. The results showed that there was a negative correlation between the coherence and cognitive activity, and the central and parietal areas were most sensitive. The quantitative analysis by the ALV method could reflect the real biological information. Correlation analysis based on the ALV provides a new method and idea for the research of synchronism, which offer a foundation for further exploring the brain mode of thinking.