1.Transcriptional regulatory network analysis of microglia in multiple sclerosis
Qiangwei CAI ; Feng SUN ; Wenyu WU ; Fuming SHAO ; Zhengliang GAO ; Shengkai JIN
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(1):29-41
Objective·To investigate the differential gene expression of microglia in the gray and white matter of multiple sclerosis(MS)using single-nucleus transcriptomic analysis,aiming to explore their roles in disease progression,and identify key transcriptional regulatory networks associated with the disease.Methods·snRNA-seq data of frozen human brain tissue samples from MS patients and control individuals were obtained from the Gene Expression Omnibus(GEO)database.R language,along with R packages such as Seurat,was employed to identify cell types based on specific cell markers.Microglia were extracted from the identified cell populations and classified based on their anatomical origin,either gray matter or white matter.Dimensionality reduction and clustering techniques were utilized to identify distinct microglial subpopulations with differential characteristics.Differentially expressed genes(DEGs)between the MS and control groups at the subpopulation level were analyzed by using the Seurat package.Gene set enrichment analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was conducted on the DEGs to further explore the biological significance of these differences.Monocle3 was used for pseudotime analysis to study dynamic changes in microglia subpopulations during disease progression.Single cell regulatory network inference and clustering(SCENIC)method was applied to analyze transcription factor(TF)regulatory networks,aiming to identify key transcription factors potentially involved in MS regulation.Results·After quality control,a total of 149 062 nuclei were retained for analysis.Following dimensional reduction and clustering,12 238 microglia were identified by using key markers,including DOCK8,CSF1R,P2RY12,and CD74.The results of GO and KEGG pathway analysis showed that in gray matter microglia,functions such as endocytosis,ion homeostasis,and lipid localization were downregulated during disease progression,while in white matter microglia,functions such as protein folding,cytoplasmic translation,and response to thermal stimuli were upregulated.SCENIC analysis revealed that the expression of transcription factors such as FLI1,MITF,and FOXP1 was upregulated in MS.Conclusion·Microglia play a critical role in MS,with white matter microglia being more significantly impacted by MS than their gray matter counterparts.Transcription factors such as FLI1,MITF,and FOXP1 are identified as key regulators involved in disease modulation,with their associated transcriptional regulatory networks playing a central role in disease modulation.
2.Transcriptional regulatory network analysis of microglia in multiple sclerosis
Qiangwei CAI ; Feng SUN ; Wenyu WU ; Fuming SHAO ; Zhengliang GAO ; Shengkai JIN
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(1):29-41
Objective·To investigate the differential gene expression of microglia in the gray and white matter of multiple sclerosis(MS)using single-nucleus transcriptomic analysis,aiming to explore their roles in disease progression,and identify key transcriptional regulatory networks associated with the disease.Methods·snRNA-seq data of frozen human brain tissue samples from MS patients and control individuals were obtained from the Gene Expression Omnibus(GEO)database.R language,along with R packages such as Seurat,was employed to identify cell types based on specific cell markers.Microglia were extracted from the identified cell populations and classified based on their anatomical origin,either gray matter or white matter.Dimensionality reduction and clustering techniques were utilized to identify distinct microglial subpopulations with differential characteristics.Differentially expressed genes(DEGs)between the MS and control groups at the subpopulation level were analyzed by using the Seurat package.Gene set enrichment analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was conducted on the DEGs to further explore the biological significance of these differences.Monocle3 was used for pseudotime analysis to study dynamic changes in microglia subpopulations during disease progression.Single cell regulatory network inference and clustering(SCENIC)method was applied to analyze transcription factor(TF)regulatory networks,aiming to identify key transcription factors potentially involved in MS regulation.Results·After quality control,a total of 149 062 nuclei were retained for analysis.Following dimensional reduction and clustering,12 238 microglia were identified by using key markers,including DOCK8,CSF1R,P2RY12,and CD74.The results of GO and KEGG pathway analysis showed that in gray matter microglia,functions such as endocytosis,ion homeostasis,and lipid localization were downregulated during disease progression,while in white matter microglia,functions such as protein folding,cytoplasmic translation,and response to thermal stimuli were upregulated.SCENIC analysis revealed that the expression of transcription factors such as FLI1,MITF,and FOXP1 was upregulated in MS.Conclusion·Microglia play a critical role in MS,with white matter microglia being more significantly impacted by MS than their gray matter counterparts.Transcription factors such as FLI1,MITF,and FOXP1 are identified as key regulators involved in disease modulation,with their associated transcriptional regulatory networks playing a central role in disease modulation.
3.3D printed guide plate assisted and C-arm X-ray fluoroscopic positioning for femoral tunnel reconstruction of medial patellofemoral ligament in treating recurrent patellofemoral dislocation: a comparison of efficacies
Xianguang YANG ; Yan ZHANG ; Yanlin LI ; Guofeng CAI ; Yang YU ; Zhengliang SHI ; Guoliang WANG
Chinese Journal of Trauma 2023;39(7):583-592
Objective:To compare the efficacies of 3D printed guide plate assisted positioning and C-arm X-ray machine fluoroscopic positioning for femoral tunnel reconstruction of medial patellofemoral ligament in treating recurrent patellofemoral dislocation.Methods:A retrospective cohort study was performed on the clinical data of 60 patients with recurrent patellar dislocation admitted to the First Affiliated Hospital of Kunming Medical University from January 2018 to December 2022. The patients included 29 males and 31 females, with age range of 14-40 years [(28.6±7.6)years]. The 3D printed guide plate was used to locate the femoral tunnel in 30 patients for medial patellofemoral ligament reconstruction (3D guide group), and C-arm X-ray machine was used for another 30 patients (conventional group). (1) CT data of the knee joint were collected before surgery and at 7 days after surgery. Mimics 19.0 software was introduced to measure the distance between the center of femoral tunnel and Sch?ttle point after surgery. (2) Knee Lysholm score and Kujala score were used to evaluate the knee function before and at 3, 6, 9 and 12 months after surgery. (3) At the same time points, Opti-Knee TM 3D knee kinematics analysis system was used to collect the forward and backward displacement, up and down displacement, internal and external displacement, internal and external flipping angle, internal and external rotation angle, and flexion and extension angle of the affected knee joint. The range of each freedom degree was calculated and 6 freedom degree items of 30 healthy people were subjected to knee kinematics analysis. Results:All patients were followed up for 12-15 months [(12.3±0.7)months]. (1) The distance between the center of femoral tunnel and Sch?ttle point in the 3D guide group was (5.5±2.3)mm, smaller than that in the conventional group [(7.6±2.5)mm] ( P<0.01). (2) The Lysholm score and Kujala score of the 3D guide group and conventional gruop gradually increased after surgery (all P<0.01). There were no significant differences in the Lysholm score or Kujala score between the 3D guide group and conventional gruop before surgery and at 12 months after surgery (all P>0.05). At 3, 6 and 9 months after surgery, the Lysholm score of the 3D guide group [(70.4±4.5)points, (86.4±3.1)points, (91.2±3.2)points] and Kujala score [(74.2±5.3)points, (80.9±3.5)points, (85.2±3.2)points] were higher than those of the conventional group [Lysholm score: (67.3±5.2)points, (81.8±2.5)points, (86.2±1.9)points; Kujala score: (69.8±5.2)points, (77.6±2.1)points, (82.7±2.6)points] ( P<0.05 or 0.01). (3) Before surgery, the forward and backward displacement in the 3D guide group and conventional group [(0.6±0.1)cm, (0.6±0.2)cm], up and down displacement [(0.5±0.1)cm, (0.6±0.0)cm], internal and external displacement [(0.7±0.1)cm, (0.6±0.2)cm], and flexion and extension angle [(50.6±10.3)°, (51.6±8.5)°] were less than those in the healthy controls [(1.6±0.3)cm, (1.7±0.5)cm, (1.0±0.4)cm, (63.2±5.1)°] (all P<0.05), while the internal and external flipping angle [(17.5±4.0)°, (17.1±3.8)°] and internal and external rotation angle [(17.9±1.9)°, (17.5±1.5)°] were greater than those in the healthy controls [(11.8±3.6)°, (15.8±4.9)°] (all P<0.05). At other time points, the results of front and back displacement, up and down displacement, internal and external displacement, internal and external rotation angle in the 3D guide group and conventional group were not significantly different compared with the healthy controls (all P>0.05). The flexion and extension angle in the 3D guide group and conventional gruop were smaller than those in the healthy controls at 3 months after surgery (all P<0.05). At 6 and 9 months after surgery, the flexion and extension angle in the conventional group [(55.0±3.7)°, (57.7±4.8)°] were smaller than those in the healthy controls [(63.2±5.1)°, (63.2±5.1)°] (all P<0.05), but no significant difference was found between the 3D guide group [(61.0±4.8)°, (61.8±4.9)°] and the healthy controls (all P>0.05). The flexion and extension angle in the 3D guide group and conventional gruop was similar with that in the healthy controls at 12 months after surgery (all P>0.05). Conclusions:Compared with the C-arm X-ray machine, the 3D printed guide plate assisted positioning of femoral tunnel is more simple and accurate for the medial patellofemoral ligament reconstruction in treating recurrent patellofemoral dislocation, together with better early knee function recovery, better satisfaction of the patients, and better and faster restoration of the flexion and extension angle of knee joint kinematic function.
4.Survey on natural language processing in medical image analysis.
Zhengliang LIU ; Mengshen HE ; Zuowei JIANG ; Zihao WU ; Haixing DAI ; Lian ZHANG ; Siyi LUO ; Tianle HAN ; Xiang LI ; Xi JIANG ; Dajiang ZHU ; Xiaoyan CAI ; Bao GE ; Wei LIU ; Jun LIU ; Dinggang SHEN ; Tianming LIU
Journal of Central South University(Medical Sciences) 2022;47(8):981-993
Recent advancement in natural language processing (NLP) and medical imaging empowers the wide applicability of deep learning models. These developments have increased not only data understanding, but also knowledge of state-of-the-art architectures and their real-world potentials. Medical imaging researchers have recognized the limitations of only targeting images, as well as the importance of integrating multimodal inputs into medical image analysis. The lack of comprehensive surveys of the current literature, however, impedes the progress of this domain. Existing research perspectives, as well as the architectures, tasks, datasets, and performance measures examined in the present literature, are reviewed in this work, and we also provide a brief description of possible future directions in the field, aiming to provide researchers and healthcare professionals with a detailed summary of existing academic research and to provide rational insights to facilitate future research.
Humans
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Natural Language Processing
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Surveys and Questionnaires
5.Analysis on detection situation of motor cognitive risk syndrome and risk factor
Lang PENG ; Honghan LIU ; Jingling CAI ; Shichao ZHAO ; Yuhang CHENG ; Zhengliang QI ; Qingwei XIANG
Chinese Journal of Geriatrics 2022;41(3):261-265
Objective:To investigate the detection rate of motoric cognitive risk(MCR)syndrome and explore the possible risk factors at different age groups.Methods:A total of 561 patients from geriatric outpatient clinic of Hubei Provincial Hospital of Traditional Chinese Medicine from November 2018 to December 2019 were divided into two age groups under 70 years old(n=241)and 70 years old and above(n=320). The general information, Pittsburgh Sleep Quality Index, Geriatric Depression Scale-15(GDS-15), 4-meter walking test, Mini-Mental State Examination and Morse Fall Scale were collected.Patients with MCR were screened out according to the MCR diagnostic criteria.Logistic multiple regression analysis was used to analyze the associated risk factors.Results:7 cases(7/241, 2.9%)met the MCR diagnostic criteria in age<70 years group, and 34 cases(34/320, 10.7%)in age ≥ 70 years group.The proportion of hearing impairment complaints and GDS-15 scores of MCR patients were higher than those of the non-MCR group in age<70 years group, and the Morse Fall Scale of MCR patients was higher than that of the non-MCR group in age ≥70 years old group( P<0.05). After adjusting for associated confounding factors, multiple logistic regression analysis showed that hearing impairment complaints( OR=26.394, P<0.05)and GDS-15( OR=1.385, P<0.05)were independent risk factors for MCR in age<70 years group.And female( OR=0.445, P<0.05)was a protective factor for MCR in age ≥70 years old group. Conclusions:Motoric cognitive risk syndrome has different risk factors in different age groups, which may indicate that the causes and predictive significance of MCR in these two different age groups are different.
6.Synthesis and LAR inhibition of 7-alkoxy analogues of illudalic acid.
Qing LING ; Yueyang ZHOU ; Zhengliang CAI ; Yahui ZHANG ; Bing XIONG ; Lanping MA ; Xin WANG ; Xin LI ; Jia LI ; Jingkang SHEN
Acta Pharmaceutica Sinica 2010;45(11):1385-97
To obtain higher potency and specificity, a series of 7-alkoxy analogues of illudalic acid was synthesized on the base of structure-activity relationship (SAR). All of these compounds exhibited submicromolar inhibition of the enzyme when tested against human leukocyte common antigen-related phosphatase (LAR) (for example, for 15e, IC50 = 180 nmol x L(-1)). They represent the most potent small-molecule inhibitors of LAR so far. These analogues also display excellent selectivity for LAR over other protein tyrosine phosphatases (PTPs) except for the highly homologous PTPsigma. The compound 15f is of 120-fold selectivity for LAR versus PTP-1B inhibition. The development of potent enzyme-specific inhibitors is so important that they may serve both as tools to study the role of LAR and as therapeutic agents for treatment of type II diabetes.
7.Investigation and Analysis of the Blood Lipid Status of Teaching Staff over 40 Years Old in Some Certain University
Lianzhen SU ; Chunling DONG ; Zhengliang QUAN ; Xiangyuan LI ; Lenong CAI
Chinese Medical Ethics 1995;0(03):-
Objective:To investigate the blood lipid status and its variation regularity of a population of teaching staff in order to provide evidence for preventing hyperlipidemia.Method:Lipid indexes such as TC,Triglyceride(TG),LDL-C and HDL-C are inspected of a group of teaching staff over 40 years old in some certain university,and data statistics and analysis are conducted.Conclusion:Main behaviors of male and female teaching staff's hyperlipidemia are high TG and high LDL-C.Special focus should be put on blood lipid's variation level of middle aged males around 40 years old,periodical clinical monitoring should be done for female teaching staff over 50 years old.Medical information instruction on the prevention and control of high blood lipid should be strengthened in order to realize the unity of self control and social control.

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