1.New insights into translational research in Alzheimer's disease guided by artificial intelligence, computational and systems biology.
Shulan JIANG ; Zixi TIAN ; Yuchen YANG ; Xiang LI ; Feiyan ZHOU ; Jianhua CHENG ; Jihui LYU ; Tingting GAO ; Ping ZHANG ; Hongbin HAN ; Zhiqian TONG
Acta Pharmaceutica Sinica B 2025;15(10):5099-5126
Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.
2.Dynamic distribution and clearance of 99mTc-DTPA in brain extracellular space
Jing ZOU ; Tianzi GAO ; Yang WANG ; Mengmeng REN ; Dongyang LIU ; Ren LONG ; Yumeng CHENG ; Meng LIU ; Zhengren XU ; Zhaoheng XIE ; Pengyu LV ; Lan YUAN ; Hongbin HAN
Journal of Peking University(Health Sciences) 2025;57(3):562-568
Objective:To explore the distribution and clearance of 99mTc labeled diethylenetriamine pentaacetic acid(99mTc-DTPA)in different brain regions of adult rats after administration through brain extracellular space(ECS)pathway.Methods:After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq(100 μCi)of 99mTc-DTPA into the caudate nucleus and thalamus of SD rats through stereotactic positioning of rat brain,the single photon emission computed tomography/computed tomography(SPECT/CT)for small animals was used for imaging at different time points,and the dyna-mic distribution and clearance of the tracer in the whole body were observed continuously.The SD rats were injected with 99mTc-DTPA into thalamus and caudate nucleus respectively for biological distribution in vivo.They were put to death 4 h later.Their blood and urine were collected.The brain,cerebellum,heart,liver,spleen,lung,and kidney were taken and weighed by γ counter to measure its radioactivity.Results:SPECT/CT imaging results showed that after 99mTc-DTPA was administered through brain ECS,the radioactivity was concentrated in the brain,kidney and bladder.The tracer administered to the left caudate nucleus was preferentially drained to the right cerebellum,while the tracer administered to the right caudate nucleus was preferentially drained to the left cerebellum.There was a phenomenon of"con-tralateral cerebellar dominant drainage"in the caudate nucleus.The thalamic area preferentially drained to the ipsilateral cerebellum after administration.Four hours after administration via ECS,high radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.Conclusion:Intracerebral ECS administration is a promising method of administration,but there are significant differences in distribution and clearance in different brain regions.This study further ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.
3.To explore the curative effect of tangerine peel compound on chicken Eimeria tenella disease
Junze CHENG ; Chenchen WANG ; Qi ZHANG ; Huixin LIU ; Qiyuan ZHAO ; Ting ZHANG ; Zong-gu XIE ; Hongbin SI
Chinese Journal of Veterinary Science 2025;45(10):2264-2272,2281
The study explored the therapeutic effect and mechanism of the compound composed of tangerine peel,plum,agrimony and hawthorn on Eimeria tenella in chicks.In the experiment,144 chicks were divided into six groups:the blank group,the model group,the diclazuril group,and the high-dose,medium-dose and low-dose traditional Chinese medicine compound groups.The 14-day-old chickens were infected,the body weight and mortality were recorded,and the samples were dis-sected at 21 days of age.The anticoccidial effect of Chenpi compound at different doses was evalua-ted by calculating anticoccidial index,feed conversion rate and detecting serum cytokine levels and related mRNA expression levels.The results showed that the anticoccidial index of the middle dose group was 172.86,and the anticoccidial index of the low dose group was 158.98.In the middle and low dose groups,the levels of IL-1β,IL-6 and MDA in serum decreased significantly,while the levels of IL-4,IL10,T-AOC,SOD,CAT and GSH-Px increased significantly,and the mRNA ex-pression levels of related inflammation and antioxidant pathways changed.Further studies found that the medium-dose compound can regulate the ChTLR15/ChMyD88/ChNF-κB/ChNLRP3/Caspase-1 inflammatory signaling pathway,activate the Nrf2/Keap1/HO-1 antioxidant signaling pathway,and enhance the body's anti-inflammatory and antioxidant capacity;at the same time,it can increase the expression of intestinal tight junction ZO-1 and Occludin,repair the damaged in-testinal barrier,and play an anticoccidial role.The results showed that the middle dose of tangerine peel compound had a good effect in the treatment of coccidiosis,and its mechanism involved the regulation of anti-inflammatory and antioxidant pathways.
4.To explore the curative effect of tangerine peel compound on chicken Eimeria tenella disease
Junze CHENG ; Chenchen WANG ; Qi ZHANG ; Huixin LIU ; Qiyuan ZHAO ; Ting ZHANG ; Zong-gu XIE ; Hongbin SI
Chinese Journal of Veterinary Science 2025;45(10):2264-2272,2281
The study explored the therapeutic effect and mechanism of the compound composed of tangerine peel,plum,agrimony and hawthorn on Eimeria tenella in chicks.In the experiment,144 chicks were divided into six groups:the blank group,the model group,the diclazuril group,and the high-dose,medium-dose and low-dose traditional Chinese medicine compound groups.The 14-day-old chickens were infected,the body weight and mortality were recorded,and the samples were dis-sected at 21 days of age.The anticoccidial effect of Chenpi compound at different doses was evalua-ted by calculating anticoccidial index,feed conversion rate and detecting serum cytokine levels and related mRNA expression levels.The results showed that the anticoccidial index of the middle dose group was 172.86,and the anticoccidial index of the low dose group was 158.98.In the middle and low dose groups,the levels of IL-1β,IL-6 and MDA in serum decreased significantly,while the levels of IL-4,IL10,T-AOC,SOD,CAT and GSH-Px increased significantly,and the mRNA ex-pression levels of related inflammation and antioxidant pathways changed.Further studies found that the medium-dose compound can regulate the ChTLR15/ChMyD88/ChNF-κB/ChNLRP3/Caspase-1 inflammatory signaling pathway,activate the Nrf2/Keap1/HO-1 antioxidant signaling pathway,and enhance the body's anti-inflammatory and antioxidant capacity;at the same time,it can increase the expression of intestinal tight junction ZO-1 and Occludin,repair the damaged in-testinal barrier,and play an anticoccidial role.The results showed that the middle dose of tangerine peel compound had a good effect in the treatment of coccidiosis,and its mechanism involved the regulation of anti-inflammatory and antioxidant pathways.
5.Dynamic distribution and clearance of 99mTc-DTPA in brain extracellular space
Jing ZOU ; Tianzi GAO ; Yang WANG ; Mengmeng REN ; Dongyang LIU ; Ren LONG ; Yumeng CHENG ; Meng LIU ; Zhengren XU ; Zhaoheng XIE ; Pengyu LV ; Lan YUAN ; Hongbin HAN
Journal of Peking University(Health Sciences) 2025;57(3):562-568
Objective:To explore the distribution and clearance of 99mTc labeled diethylenetriamine pentaacetic acid(99mTc-DTPA)in different brain regions of adult rats after administration through brain extracellular space(ECS)pathway.Methods:After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq(100 μCi)of 99mTc-DTPA into the caudate nucleus and thalamus of SD rats through stereotactic positioning of rat brain,the single photon emission computed tomography/computed tomography(SPECT/CT)for small animals was used for imaging at different time points,and the dyna-mic distribution and clearance of the tracer in the whole body were observed continuously.The SD rats were injected with 99mTc-DTPA into thalamus and caudate nucleus respectively for biological distribution in vivo.They were put to death 4 h later.Their blood and urine were collected.The brain,cerebellum,heart,liver,spleen,lung,and kidney were taken and weighed by γ counter to measure its radioactivity.Results:SPECT/CT imaging results showed that after 99mTc-DTPA was administered through brain ECS,the radioactivity was concentrated in the brain,kidney and bladder.The tracer administered to the left caudate nucleus was preferentially drained to the right cerebellum,while the tracer administered to the right caudate nucleus was preferentially drained to the left cerebellum.There was a phenomenon of"con-tralateral cerebellar dominant drainage"in the caudate nucleus.The thalamic area preferentially drained to the ipsilateral cerebellum after administration.Four hours after administration via ECS,high radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.Conclusion:Intracerebral ECS administration is a promising method of administration,but there are significant differences in distribution and clearance in different brain regions.This study further ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.
6.Deferasirox inhibits lipid peroxidation and ferroptosis in human retinal endothelial cells
Yan LI ; Zixuan CHENG ; Ting LUO ; Hongbin LYU
Chinese Journal of Ocular Fundus Diseases 2024;40(12):947-953
Objective:To observe and preliminarily explore the effects of Deferasirox (DFX) on lipid peroxidation and ferroptosis in human retinal endothelial cells (HREC).Methods:A cell experimental study. Divided the in vitro cultured HREC into normal glucose (NG) group, high glucose (HG) group, NG+DFX group, HG+DFX group, NG+DFX+ferric ammonium citrate (FAC) group, and HG+DFX+FAC group. Light microscope was used to observe the morphology of the cells; cell proliferation was detected by Cell Counting Kit-8 assay, and Calcein-AM staining was used to detect the unstable iron pool (LIP) content; enzyme-linked immunosorbent assay reader was used to detect the reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG); Western blot was used to detect the relative protein expression of Glutathione Peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11 (SLC7A11). Two-tailed Student t test was used for comparison between the two groups; one-way ANOVA was used for comparison between multiple groups. Results:Compared with the HG group and the HG+DFX+FAC group, the cell proliferation rate and the contents of GSH and the relative protein expression of GPX4, and SLC7A11 in the HG+DFX group were significantly increased, and the differences were statistically significant ( F=150.70, 21.02, 26.09, 52.62; P<0.001). The contents of LIP, ROS, MDA, and GSSG were significantly decreased, and the differences were statistically significant ( F=807.20, 16.94, 31.62, 19.21; P<0.001). Conclusions:High glucose significantly induces an increase in LIP, lipid peroxidation, and ferroptosis in HREC. Deferasirox inhibits lipid peroxidation and ferroptosis in HREC by downregulating LIP levels.
7.Fluorescence and MR dual-mode imaging for displaying drainage pathways of interstitial fluid and substance clearance pattern in rat brain
Tianzi GAO ; Lan YUAN ; Yang WANG ; Hanbo TAN ; Ziyi WEI ; Jiayu WANG ; Yajuan GAO ; Dongyang LIU ; Cheng CUI ; Jianfei SUN ; Zhaoheng XIE ; Hongbin HAN
Chinese Journal of Medical Imaging Technology 2024;40(5):705-711
Objective To observe the drainage pathways of interstitial fluid(ISF)and substance clearance pattern in rat brain with fluorescence tracing imaging and treacer-based MRI.Methods Thirty-three male SD rats were randomly divided into fluorescence tracing group(F group,n=18)and treacer-based MRI group(MRI group,n=15),then further divided into thalamic,hippocampal and caudate nucleus subgroups,respectively.Evans blue was injected to rats in F group,and cardiac perfusion was performed after injection,then brain tissue was harvested,and frozen sections were made to observe the drainage pathways of IFS in different subgroups.MRI was performed on rats in MRI group before and after injection of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)to observe signal intensity in ROI of brain regions in different subgroups,the signal unit ratio was calculated,and the changing trend was explored.Results ISF in thalamus,hippocampus and caudate nucleus had different dominant drainage pathways,and the time of tracer reached to adjacent brain regions and whole brain in F group were different.In MRI group,within 4 h after injection of Gd-DTPA,there were differences in direction and clearance rate among tracer in thalamus,hippocampus and caudate nucleus,mainly manifesting as the tracer in thalamus and hippocampus drained to the ipsilateral cortex and lateral ventricle,while the tracer in the caudate nucleus diffused to the cortex and midbrain,and there were differences of the peak time of tracer signal among adjacent drainage brain regions.Conclusion Fluorescence and MR dual-mode imaging showed that there were differences in the dominant drainage pathways of IFS and clearance rates of small molecule substances among hypothalamus,hippocampus and caudate nucleus of rats.
8.Finite element simulation and experimental test of normal coracoclavicular ligament and flexible reconstruction
Guizhu JI ; Qiu ZHENG ; Wuxiang WANG ; Guan WANG ; Wen LI ; Xiaobo LU ; Ke DUAN ; Zhong LI ; Hongbin YANG ; Cheng LIANG
Chinese Journal of Tissue Engineering Research 2024;28(5):706-711
BACKGROUND:For dislocation of acromioclavicular joint induced by coracoclavicular ligament fracture,single EndoButton Plate reconstruction and double EndoButton Plates reconstruction are common repair methods.Further study on the stress distribution and fracture risk of the two repair methods is of great significance. OBJECTIVE:To study the biomechanical properties of the coracoclavicular ligament,and compare the fixation effect,stress distribution and failure mode of single and double EndoButton Plates reconstruction. METHODS:(1)Finite element simulation analysis:Mimics,Wrap and SolidWorks were used to establish normal coracoclavicular ligament,single EndoButton Plate reconstruction and double EndoButton Plates reconstruction.Ansys software was used to analyze the stress and deformation of the scapula and clavicle of each model under vertical load.(2)Sample experiment:Fifteen intact scapular-clavicle specimens were randomly grouped into five groups,with three specimens in each group.In group A,the acromioclavicular ligament was severed and the coracoclavicular ligament remained intact.In group B,acromioclavicular ligaments and trapeoid ligaments were severed,leaving intact conical ligaments.In group C,acromioclavicular ligaments and conical ligaments were cut off,and the intact traprex ligaments were retained.In group D,acromioclavicular and coracoclavicular ligaments were severed,and coracoclavicular ligaments were repaired by single EndoButton Plate reconstruction.In group E,acromioclavicular and coracoclavicular ligaments were severed,and the coracoclavicular ligaments were repaired by double EndoButton Plates reconstruction.The mechanical experiment was carried out by a mechanical testing machine to analyze the biomechanical status,stress distribution and failure patterns of the scapular-clavicle and clavicle. RESULTS AND CONCLUSION:(1)Finite element simulation analysis:The average stress of coracoclavicular ligament attached specimens was the lowest,and the risk of coracoclavicular fracture was less than that of single and double EndoButton Plates reconstruction.The mean stress of the coracoid process was similar in single and double EndoButton Plates reconstruction,and the fracture risk was similar.(2)Sample experiment:In groups A,B,C,D and E,the stiffness of specimens was(26.4±3.5),(19.8±2.8),(21.3±3.2),(57.7±4.1),and(46.2±2.8)N/mm,respectively;the ultimate loads were(545.5±53.7),(360.1±42.1),(250.9±44.4),(643.5±39.1),and(511.9±31.7)N,respectively;global stiffness in groups D and E was higher than that in group A(P=0.000 06,0.000 3);ultimate load in group D was higher than that in group A(P<0.05);the ultimate load was not significantly different between the group E and group A(P>0.05).Ligament fracture was observed in groups A,B and C and coracoid process fracture was found in groups D and E.(3)These results suggest that from the biomechanical analysis,Single EndoButton Plate reconstruction and double EndoButton Plates reconstruction are effective treatment techniques for coracoclavicular ligament fracture in acromioclavicular joint dislocation,but increase the risk of fracture.The double EndoButton Plates reconstruction dispersed the stress of the steel plate and reduced the contact force between the steel plate and bone,but slightly reduced the ultimate bearing capacity.Single and double EndoButton Plates reconstruction should be selected according to the actual clinical situation.
9.Development and clinical application of automatic recording system for resection of soft tissue tumor based on dense video descriptions
Xiaohe WANG ; Haomin LIU ; Debin CHENG ; Jingyi DANG ; Ruimin LI ; Shuiping GOU ; Jun FU ; Hongbin FAN
Chinese Journal of Orthopaedic Trauma 2024;26(1):43-49
Objective:To explore the feasibility and application value of an automated method for generation of surgical records for resection of benign soft tissue tumor based on dense video descriptions.Methods:The Transformer deep learning model was used to establish an automated surgical record generation system to analyze the surgical videos of 30 patients with benign soft tissue tumor who had been admitted to Department of Orthopedics, Xijing Hospital, Air Force Military Medical University from September 2021 to August 2023. The patient data were randomly divided into training sets, validation sets, and test sets in a ratio of 8∶1∶1. In the test sets, 7 evaluation indexes, BLEU-1, BLEU-2, BLEU-3, BLEU-4, Meteor, Rouge, and CIDEr, were used to evaluate the text quality of surgical records generated by the model. The text of surgical records was compared with the classical algorithm, dense video captioning with paralled decoding (PDVC) in the field of video-intensive description.Results:The automated surgical record generation system running in the test sets showed the following: BLEU-1, BLEU-2, BLEU-3, BLEU-4, Rouge, Meteor, and CIDEr were 16.80, 15.23, 13.01, 11.68, 16.01, 12.67 and 62.30, respectively. The operation of the classical algorithm PDVC showed the following: BLEU-1, BLEU-2, BLEU-3, BLEU-4, Rouge, Meteor, and CIDEr were 15.63, 14.17, 11.90, 10.45, 12.97, 11.99 and 53.64, respectively. The automated surgical record generation system resulted in significant improvements compared with PDVC in all evaluation indexes. The BLEU-4, Rouge, Meteor, and CIDEr were improved by 1.23, 3.04, 0.68 and 8.66, respectively, demonstrating that the system proposed can better capture the key data in the video to help generate more effective text records.Conclusion:As the automated surgical record generation system shows good performance in generating surgical records for resection of benign soft tissue tumor based on intensive video descriptions, it can be applied in clinical practice.
10.Deferasirox inhibits lipid peroxidation and ferroptosis in human retinal endothelial cells
Yan LI ; Zixuan CHENG ; Ting LUO ; Hongbin LYU
Chinese Journal of Ocular Fundus Diseases 2024;40(12):947-953
Objective:To observe and preliminarily explore the effects of Deferasirox (DFX) on lipid peroxidation and ferroptosis in human retinal endothelial cells (HREC).Methods:A cell experimental study. Divided the in vitro cultured HREC into normal glucose (NG) group, high glucose (HG) group, NG+DFX group, HG+DFX group, NG+DFX+ferric ammonium citrate (FAC) group, and HG+DFX+FAC group. Light microscope was used to observe the morphology of the cells; cell proliferation was detected by Cell Counting Kit-8 assay, and Calcein-AM staining was used to detect the unstable iron pool (LIP) content; enzyme-linked immunosorbent assay reader was used to detect the reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG); Western blot was used to detect the relative protein expression of Glutathione Peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11 (SLC7A11). Two-tailed Student t test was used for comparison between the two groups; one-way ANOVA was used for comparison between multiple groups. Results:Compared with the HG group and the HG+DFX+FAC group, the cell proliferation rate and the contents of GSH and the relative protein expression of GPX4, and SLC7A11 in the HG+DFX group were significantly increased, and the differences were statistically significant ( F=150.70, 21.02, 26.09, 52.62; P<0.001). The contents of LIP, ROS, MDA, and GSSG were significantly decreased, and the differences were statistically significant ( F=807.20, 16.94, 31.62, 19.21; P<0.001). Conclusions:High glucose significantly induces an increase in LIP, lipid peroxidation, and ferroptosis in HREC. Deferasirox inhibits lipid peroxidation and ferroptosis in HREC by downregulating LIP levels.

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