1.The evaluating value of hippocampal subfield's T2 signal intensity before and after the treatment for mild cognitive impairment
Xiaojie ZHANG ; Zhihong CAO ; Yu LIU ; Yifeng LUO ; Liwei WU ; Hairong SHAN ; Yiwen LIU ; Wenchao XIE
Journal of Practical Radiology 2017;33(5):658-661
Objective To investigate the value of the hippocampal subfield's MRI T2 signal intensity in evaluating the effect of the hydrochloric donepezil for mild cognitive impairment(MCI).Methods 20 MCI patients with hydrochloric donepezil (treatment group) and 20 patients with placebo (control group) were scanned by MRI using FSE-T2 sequence.The margin of hippocampal subfields was outlined manually for each side to measure the MRI T2 signal intensity.The relationship between hippocampal MRI T2 signal intensity and MMSE scores was analyzed in the treatment group.Results Before the treatment, there was no significant difference of the MRI T2 signal intensity between groups.After the treatment, the MRI T2 signal intensity in the bilateral head of the treatment group was significantly decreased compared with the control group(P<0.05).There was an inverse relationship between the MRI T2 signal intensity of the bilateral hippocampal head and MMSE scores in the treatment group(P<0.05).Conclusion The MRI T2 signal intensity in the bilateral hippocampal head could be regarded as a valuable marker in making clinical diagnosis and evaluating the effect of the treatment for MCI in its early stage.
2.Application of Hippocampal Subfield Magnetic Resonance Imaging T2 Signal Intensity for Amnestic Mild Cognitive Impairment
Xiaojie ZHANG ; Zhihong CAO ; Yifeng LUO ; Yu LIU ; Liwei WU ; Hairong SHAN ; Yiwen LIU ; Yuefeng LI ; Dongqing WANG
Chinese Journal of Rehabilitation Theory and Practice 2017;23(5):575-579
Objective To apply the MRI T2 signal intensity of hippocampal subfield in patients with amnestic mild cognitive impairment (aMCI) as early imageology. Methods From October, 2014 to August, 2015, 20 aMCI patients accepted cognitive training (training group), 20 aMCI patients accepted speech communication (speech group), and 20 age-and gender-matched healthy old people (control group) were scanned with MRI using FSE-T2 sequence. The margin of hippocampal subfields were outlined manually for each side to measure the T2 sig-nal intensity. The correlation between hippocampal T2 signal intensity and the scores of Mini-Mental State Examinatlon (MMSE) was ana-lyzed in the training group. Results Before treatment, T2 signal intensity in the bilateral hippocampal head was significantly high in the aM-CI patients compared with that in the control group (P<0.05). After treatment, T2 signal intensity in left hippocampal head decreased in the training group compared with that in the speech group (P<0.05), similar to the control group (P>0.05). There was negative correlation be-tween left hippocampal head's T2 signal intensity and the scores of MMSE in the training group before and after treatment (r=-0.61, r=-0.54, P<0.05). Conclusion The T2 signal intensity in left hippocampal head may respond to the cognitive function in patients with aMCI in the early stage, that could be used for diagnosis and evaluation in clinic.
3.Evaluation of an aided diagnosis system for vitreous and retinal diseases by analyzing B-scan ultrasound images based on deep convolutional neural network
Yi YU ; Yiwen ZHOU ; Di CHEN ; Shan HU ; Yanning YANG
Chinese Journal of Experimental Ophthalmology 2021;39(9):792-797
Objective:To explore the clinical value of a diagnostic system of ophthalmic B-scan ultrasound images based on deep convolutional neural network.Methods:A total of 3 600 ophthalmic B-scan ultrasound images of 1 278 patients with an average age of (49.32±7.69) years at the Eye Center of Renmin Hospital of Wuhan University from January 2018 to October 2020 were collected to build an image database.These B-scan images were labeled by three ophthalmologists.The database was divided into the training dataset of 2 812 images and the testing dataset of 788 images.The deep learning algorithm was used to build a diagnostic model, which can identify retinal detachment (RD), vitreous hemorrhage (VH) and posterior vitreous detachment (PVD), and the accuracy of the model was evaluated.Another 120 B-scan ultrasound images were collected for the human-computer comparison between the model and 3 senior ophthalmologists.Eight junior clinicians were selected to evaluate another 150 B-scan images with and without the assistance of the model, and the accuracy was analyzed to evaluate the effect of the model.This study adhered to the Declaration of Helsinki and the study protocol was approved by Renmin Hospital of Wuhan University (No.WDRY2020K-192).Results:The accuracy of the model for identifying normal fundus, RD, VH, PVD and other diseases were 0.954, 0.909, 0.881, 0.990 and 0.920, respectively.The accuracy of the model was similar to that of senior doctors, and the time the model used was almost half that of doctors.With the assistance of the model, the diagnostic accuracy of the 8 junior clinicians who participated in the training was significantly improved ( P<0.01). Conclusions:The accuracy of RD, VH and PVD identification of the intelligent evaluation system is good, and the system can improve the accuracy and efficiency of clinical examinations, and can better assist clinicians in clinical evaluation.
4.Pathogenesis of Respiratory Syncytial Virus Infection-Induced Asthma and Progress in Its Prevention and Treatment with Traditional Chinese Medicine
Ziyu ZHU ; Xia ZHAO ; Jianjian JI ; Jiabao WU ; Yiwen SHAN ; Hua YAN
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(8):855-863
Respiratory syncytial virus(RSV)infection is a potential susceptibility factor for recurrent wheezing,which can affect the occurrence and development of asthma through immune damage,airway epithelial barrier damage,airway inflammatory infiltration,airway hyperresponsiveness,and high expression of induced susceptibility genes.Traditional Chinese medicine believes that asthma caused by RSV infection is mostly caused by the imbalance of the body's qi after infection and the retention of evil qi.By combing the mechanism of RSV infection in the occurrence and development of asthma and the research on traditional Chinese medicine intervention in recent years,it is hoped to provide ideas for the future application of combined Chinese and Western medicine to prevent and treat asthma.
5.Effects of Guben Fangxiao Beverage (固本防哮饮) on Lung Tissue Oxidative Stress and AMPK/Nrf2/HO-1 Pathway in Mice with Bronchial Asthma in Remission
Xiaohan DAI ; Xia ZHAO ; Hua YAN ; Yiwen SHAN
Journal of Traditional Chinese Medicine 2024;65(2):205-212
ObjectiveTo investigate the possible mechanism of Guben Fangxiao Beverage (固本防哮饮) for the prevention and treatment of chronic airway inflammation during asthma remission. MethodsThirty-six female Balb/c mice were randomly divided into normal group, model group, low-, medium-, and high-dose of Guben Fangxiao Beverage group and montelukast sodium group, with 6 mice in each group. Except for the normal group, ovalbumin and respiratory syncytial virus were used in other groups to establish a mouse model of bronchial asthma in remission stage. After molding, the low-, medium-, and high-dose groups of Guben Fangxiao Beverage were respectively given 12, 24, and 36 g/(kg·d), the montelukast sodium group was given montelukast sodium granule 2.6 mg/(kg·d), and the mice in the normal group and model group were given 20 ml of double-distilled water, all by gavage, once a day for 28 days. The levels of interleukin 4 (IL-4) and interleukin 5 (IL-5) in the lung tissue of mice were detected; HE staining was used to observe the pathology of the lung tissue and to score the inflammation; DHE staining was used to observe the level of reactive oxygen species (ROS) in the lung tissue, and the activities of mitochondrial respiratory chain complexes Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅴ in the lung tissue were detected; the levels of serum superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and adenosine triphosphate (ATP) were detected; the protein expression levels of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase 1 (HO-1) and cAMP responsive element binding protein (CREB) in the lung tissues of the model group were detected by Western blot. ResultsCompared with the normal group, the histopathological results of the lungs of mice in the model group showed an increase in inflammatory cells around the airways and an increase in inflammatory score; DHE staining showed an increase in the level of ROS, and an increase in the levels of IL-4 and IL-5 in the lung tissues; the levels of serum SOD, CAT, and ATP were reduced, and the level of MDA was elevated; the activities of the mitochondrial respiratory chain complexes Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅴ of the lung tissues were reduced, and the activities of p-AMPK, Nrf2, CREB protein expression decreased (P<0.05). Compared with the model group, the lung tissue inflammatory cells and inflammation scores of mice in each Guben Fangxiao Beverage dose group and montelukast sodium group were reduced; the levels of ROS, IL-4 and IL-5 in the lung tissue were reduced; the levels of CAT and ATP in the serum increased, and the content of MDA was reduced; and the activities of mitochondrial respiratory chain complexes Ⅰ and Ⅱ, as well as the expression of CREB protein, were elevated in the lung tissue (P<0.05). Compared with the high-dose group, the MDA level of the medium-dose Guben Fangxiao Beverage group decreased (P<0.05). The activity of mitochondrial respiratory chain complex V in the medium-dose group was higher than that in the montelukast sodium group, and the activity of mitochondrial respiratory chain complex Ⅳ in the medium- and high-dose groups was higher than that in the low-dose group (P<0.05). ConclusionGuben Fangxiao Beverage can inhibit oxidative stress and improve mitochondrial function to relieve chronic airway inflammation in bronchial asthma model mice during asthma remission, and its mechanism may be related to the activation of AMPK/Nrf2/HO-1 signaling pathway.
6.Effect of estrogen-related receptor α-mediated lipophagy on proliferation and migration abilities of nasopharyngeal cancer cells
Xiuzhi KONG ; Ying SHAN ; Yiwen YOU ; Miao GU ; Haijuan XIAO ; Mengdie YOU ; Bo YOU
Cancer Research and Clinic 2024;36(2):105-111
Objective:To investigate the effect of estrogen-related receptor α (ESRRA)-mediated lipophagy on the proliferation and migration abilities of nasopharyngeal carcinoma cells.Methods:A total of 16 clinical samples diagnosed by pathology in the Affiliated Hospital of Nantong University from 2021 to 2023 were selected, including 8 normal nasopharyngeal mucosa tissues and 8 nasopharyngeal carcinoma tissues. Immortalized normal nasopharyngeal epithelial cell line NP69 and nasopharyngeal carcinoma cell lines C666-1, CNE2, TW03-EBV and TW03 were selected. The cell lines C666-1 and CNE2 were divided into the siR-NC group (transfected with small interfering RNA negative control sequence) and siR-ESRRA group (transfected with small interfering RNA against ESRRA gene). The relative expression levels of ESRRA were detected by Western blotting and immunohistochemical assay. EdU assay was used to detect the proliferation ability of C666-1 and CNE2 cells, and Transwell assay was used to detect the migration ability. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of ESRRA and perilipin 3 (PLIN3) mRNA. The formation of lipophagy in C666-1 and CNE2 cells was observed by transmission electron microscopy. The co-localization of LC3, PLIN3 and LAMP2 with lipid droplets labeling with Bodipy was detected by immunofluorescence assay. Dual-luciferase reporter gene assay was used to verify the targeting relationship between ESRRA and PLIN3.Results:The relative expression level of ESRRA in nasopharyngeal carcinoma tissues was higher than that in normal nasopharyngeal mucosa tissues(1.15±0.75 vs. 0.32±0.21, t = 3.02, P = 0.009). The relative expression level of ESRRA in nasopharyngeal carcinoma cell lines C666-1 (1.539±0.044), CNE2 (1.420±0.030), TW03-EBV (2.867±0.044), and TW03 (1.323±0.022) were higher than that in normal nasopharyngeal epithelial cell line NP69 (0.094±0.002), and the difference was statistically significant ( F = 34.08, P < 0.001).The results of EdU assay showed that the proportions of EdU labeled positive cells in CNE2 cells of siR-NC group and siR-ESRRA group were (70.44±4.06)% and (51.51±0.92)% ( t = 7.88, P = 0.001), and the proportions in C666-1 cells were (62.25±3.89)% and (54.91±0.27)% ( t = 3.26, P = 0.031). The results of Transwell assay showed that the number of migrating cells in CNE2 and C666-1 cells was less than that in siR-NC group [CNE2 cells: (181±7) cells vs. (261±21) cells; C666-1 cells: (201±16) cells vs. (256±7) cells], and the differences were statistically significant ( t = 6.30, P = 0.003; t = 5.43, P = 0.006). According to qRT-PCR results, the relative expression level of PLIN3 mRNA in the siR-ESRRA group was higher than that in the siR-NC group (CNE2 cells: 1.58±0.16 vs. 0.83±0.17, t = 5.59, P = 0.005; C666-1 cells: 1.37±0.12 vs. 1.06±0.06, t = 3.86, P = 0.018). The dual-luciferase reporter gene assay results indicated a targeted binding interaction between PLIN3 and ESRRA. Transmission electron microscopy observation showed that the lipid droplets in nasopharyngeal carcinoma cells increased and the binding to autophagosomes decreased after knockdown of ESRRA. The results of immunofluorescence assay demonstrated that, in contrast to the siR-NC group, there was a decrease in the co-localization of LC3 and LAMP2 and an increase in the co-localization of lipid droplets with PLIN3. Conclusions:ESRRA is highly expressed in nasopharyngeal carcinoma tissues and cells. As a transcription repressor, ESRRA may work to prevent PLIN3 from being transcribed, decrease lipid droplet stability, mediate lipophagy, and promote proliferation and migration of nasopharyngeal carcinoma cells.
7.Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis:Possible through SIRT3-AMPK axis
Han XIN ; Ning YAN ; Dou XINYUE ; Wang YIWEN ; Shan QIYUAN ; Shi KAO ; Wang ZEPING ; Ding CHUAN ; Hao MIN ; Wang KUILONG ; Peng MENGYUN ; Kuang HAODAN ; Yang QIAO ; Sang XIANAN ; Cao GANG
Journal of Pharmaceutical Analysis 2024;14(5):758-771
Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.
8.Research of SIRT1 on promoting the proliferation, migration and lipid metabolism of nasopharyngeal carcinoma
Haimeng YIN ; Xin HE ; Ying SHAN ; Hongxiang ZHAI ; Kaiwen ZHANG ; Tian XIA ; Siyu ZHANG ; Wenhui CHEN ; Yiwen YOU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2020;55(10):934-943
Objective:To analyze the differential expression of silent information regulator transcript-1 (SIRT1) in tissues and cells of nasopharyngeal carcinoma (NPC), to explore the effects of SIRT1 on the proliferation and migration of NPC cells, as well as the effects on and mechanisms of lipid metabolism in NPC cells.Methods:Experimental subjects: In this study, tissue specimens were obtained from patients who visited the Department of Otolaryngology and performed nasopharyngeal tissue biopsy in the Affiliated Hospital of Nantong University from 2019 to 2020. Among them, 6 cases were male, 6 cases were female, age range: 27-72 years old, including 7 cases of NPC diagnosed by pathology and 5 cases of normal nasopharyngeal mucosa. Experimental methods and outcome measures: Western Blot and quantitative real time polymerase chain reaction (qRT-PCR) were used to detect the protein and mRNA levels of SIRT1. CNE2 cell line was selected for subsequent experiments. Cell viability and migratory ability were evaluated by CCK8, wound healing and Transwell assays respectively. Animal xenograft tumor model was used to explore the role of SIRT1 inhibitor Ex527 on tumor growth in nude mice. Oil red and Bodipy were used to stain intracellular lipids. For the mechanical investigation, the interactions between SIRT1 and hypoxia inducible factor-1α (HIF-1α) were analyzed by immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP). Finally, statistical analysis was performed by SPSS 26.0 software, P<0.05 was considered statistically significant. Results:The levels of SIRT1 protein (1.005±0.168) and mRNA (5.829±2.395) in NPC tissues were higher than those in normal nasopharyngeal mucosa (0.181±0.042,1.995±1.605). Differences were statistically significant ( t values were 6.438 and 2.759, both P<0.05). The mRNA and protein levels of CNE1, CNE2, 5-8F and 6-10B cell lines were also higher than those in normal nasopharynx epithelial cell line NP69. Besides, overexpression of SIRT1 correlated with the proliferation and migration of NPC cells. The tumorigenesis ability of nude mice in the Ex527 group was lower than that in the control group. The low SIRT1 expression reduced the protein level of the key enzymes of liposynthesis in NPC cells, improved the expression of lipolysis enzymes, while HIF-1α overexpression promoted lipid synthesis enzymes in NPC cells. SIRT1 inhibited HIF-1α transcription by enhancing deacetylation levels. The binding ability of HIF-1α to SIRT1 promoter regions decreased when NPC cells were hypoxic. Conclusions:SIRT1 promotes the proliferation, migration and lipid metabolism of nasopharyngeal carcinoma cells, which might be expected to provide new theoretical basis for prognosis judgment and gene therapy.
9.Comprehensive Comparative Analysis of Sepsis Animal Models and Characteristics of Clinical Syndromes in Integrated Traditional Chinese and Western Medicine
Shan LI ; Chao LI ; Yiwen WU ; Jingwen XUE ; Qingqing CHEN ; Tengxiao LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):212-218
This study, anchored in the traditional Chinese medicine (TCM) syndrome differentiation and treatment principles alongside the clinical characteristics of sepsis in Western medicine, extensively gathers and meticulously dissects the latest research findings on sepsis animal models from both Chinese and international sources. Adhering strictly to TCM syndrome diagnostic criteria for sepsis, the study conducts a thorough evaluation of various animal models across multiple dimensions, including clinical manifestations, pathological changes, and biomarker expressions, so as to reflect the degree of resemblance these models have to human sepsis TCM syndromes. The results reveal that the colon stent implantation model exhibits a higher degree of congruence with both TCM and Western medicine standards, particularly aligning with the diagnosis of the "Fu-Qi obstruction syndrome". Conversely, the extraperitoneal sepsis model shows a higher degree of congruence with TCM, fitting more closely with the diagnosis of "acute deficiency syndrome" and emphasizing the core pathogenesis of Qi deficiency in sepsis. These findings not only augment the diversity of sepsis animal models but also highlight the necessity and potential of integrated TCM and western medicine research. Current sepsis animal models predominantly focus on western pathophysiological mechanisms, with limited direct incorporation of TCM syndrome differentiation elements. This underscores the need, in future study designs, to actively explore integrating TCM syndrome classification and intervention principles into model development. This could be achieved by manipulating model-inducing factors and observing more TCM-specific symptoms and signs among other strategies, so as to establish sepsis models that more closely resemble clinical reality and incorporate both TCM and western medical perspectives.