1.Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions.
Fang REN ; Jing WEI ; Qingxin CHEN ; Mengling HU ; Lu YU ; Jianing MI ; Xiaogang ZHOU ; Dalian QIN ; Jianming WU ; Anguo WU
Acta Pharmaceutica Sinica B 2025;15(9):4327-4385
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, with few effective treatments currently available. The multifactorial nature of AD, shaped by genetic, environmental, and biological factors, complicates both research and clinical management. Recent advances in artificial intelligence (AI) and multi-omics technologies provide new opportunities to elucidate the molecular mechanisms of AD and identify early biomarkers for diagnosis and prognosis. AI-driven approaches such as machine learning, deep learning, and network-based models have enabled the integration of large-scale genomic, transcriptomic, proteomic, metabolomic, and microbiomic datasets. These efforts have facilitated the discovery of novel molecular signatures and therapeutic targets. Methods including deep belief networks and joint deep semi-non-negative matrix factorization have contributed to improvements in disease classification and patient stratification. However, ongoing challenges remain. These include data heterogeneity, limited interpretability of complex models, a lack of large and diverse datasets, and insufficient clinical validation. The absence of standardized multi-omics data processing methods further restricts progress. This review systematically summarizes recent advances in AI-driven multi-omics research in AD, highlighting achievements in early diagnosis and biomarker discovery while discussing limitations and future directions needed to advance these approaches toward clinical application.
2.A CYP80B enzyme from Stephania tetrandra enables the 3'-hydroxylation of N-methylcoclaurine and coclaurine in the biosynthesis of benzylisoquinoline alkaloids.
Yaoting LI ; Yuhan FENG ; Wan GUO ; Yu GAO ; Jiatao ZHANG ; Lu YANG ; Chun LEI ; Yun KANG ; Yaqin WANG ; Xudong QU ; Jianming HUANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(5):630-640
Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry*
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Benzylisoquinolines/chemistry*
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Hydroxylation
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Plant Proteins/chemistry*
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Alkaloids/metabolism*
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Stephania tetrandra/genetics*
3.Pathogenic investigation of human respiratory syncytial virus infection in kindergarten children in Tongzhou District, Beijing City in 2023
Lin ZOU ; Chong ZHANG ; Ling TONG ; Xiao LIU ; Jing MA ; Jianguo WANG ; Fang WANG ; Xiang GAO ; Lu XI ; Jianming ZHANG
Chinese Journal of Preventive Medicine 2024;58(8):1150-1153
The study focused on individuals with influenza-like symptoms (fever, cough, sore throat, runny nose, and other respiratory symptoms) in three kindergartens in Tongzhou District, Beijing City, in April 2023. Nasopharyngeal swab specimens were collected, and real-time fluorescent quantitative PCR was used to detect common respiratory pathogens in the collected specimens. Positive specimens were subjected to sequencing analysis of the highly variable region of human respiratory syncytial virus (HRSV) G protein, homology analysis and phylogenetic tree analysis. A total of 25 fever cases were collected from 3 kindergartens, aged 3-8 years old, with an age M ( Q1, Q3) of 4 (3.5, 5) years old. Ten confirmed cases of HRSV positive were screened and detected using the fluorescent quantitative PCR method, with a total detection rate of 40% (10/25). Typing identification and sequencing analysis confirmed that the main epidemic type was HRSV subtype B, which was highly homologous and closely related to previous epidemic strains in the region. Through pathogen investigation and analysis, it was preliminarily determined that this epidemic was dominated by HRSV subtype B.
4.Pathogenic investigation of human respiratory syncytial virus infection in kindergarten children in Tongzhou District, Beijing City in 2023
Lin ZOU ; Chong ZHANG ; Ling TONG ; Xiao LIU ; Jing MA ; Jianguo WANG ; Fang WANG ; Xiang GAO ; Lu XI ; Jianming ZHANG
Chinese Journal of Preventive Medicine 2024;58(8):1150-1153
The study focused on individuals with influenza-like symptoms (fever, cough, sore throat, runny nose, and other respiratory symptoms) in three kindergartens in Tongzhou District, Beijing City, in April 2023. Nasopharyngeal swab specimens were collected, and real-time fluorescent quantitative PCR was used to detect common respiratory pathogens in the collected specimens. Positive specimens were subjected to sequencing analysis of the highly variable region of human respiratory syncytial virus (HRSV) G protein, homology analysis and phylogenetic tree analysis. A total of 25 fever cases were collected from 3 kindergartens, aged 3-8 years old, with an age M ( Q1, Q3) of 4 (3.5, 5) years old. Ten confirmed cases of HRSV positive were screened and detected using the fluorescent quantitative PCR method, with a total detection rate of 40% (10/25). Typing identification and sequencing analysis confirmed that the main epidemic type was HRSV subtype B, which was highly homologous and closely related to previous epidemic strains in the region. Through pathogen investigation and analysis, it was preliminarily determined that this epidemic was dominated by HRSV subtype B.
5.Effect of respiratory training based on core stability training on feedforward control in patients with chronic non-specific low back pain
Linghui CHEN ; Qi ZHENG ; Yan LI ; Jianming FU ; Ming ZENG ; Xin JIN ; Jingjing LU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(6):737-744
Objective To investigate the effect of respiratory training based on core stability training on feedforward control in pa-tients with chronic nonspecific low back pain(CNLBP). Methods A total of 60 patients with CNLBP in Jiaxing Second Hospital from January,2022 to March,2023 were ran-domly divided into control group(n=30)and experimental group(n=30).Both groups received health educa-tion,physical factor therapy and core stability training,while the experimental group received respiratory training in addition,for four weeks.Visual Analogue Scale(VAS)score,Japanese Orthopaedic Association low back pain(JOA)score and Oswestry Dysfunction Index(ODI)were compared between two groups before and after treat-ment,while surface electromyography was used to detect the root mean square(RMS)and integrated electromy-ography(iEMG)of transversus abdominis,multifidus and triceps(movement muscles),and the activation se-quence and relative activation time of transversus abdominis,multifidus and triceps were calculated. Results After treatment,the scores of VAS,JOA and ODI improved significantly in both groups(|t|>8.515,P<0.001),and the scores were better in the experimental group than in the control group(|t|>2.089,P<0.05).RMS and iEMG of transversus abdominis and multifidus improved significantly after treatment in both groups(|t|>18.831,P<0.001),and were significantly better in the experimental group(|t|>3.481,P<0.05).The transversus abdominis and multifidus in both groups were activated before the movement muscles,and the relative activation time of transversus abdominis and multifidus increased in negative(|t|>48.115,P<0.001),the experimental group being better(|t|>3.229,P<0.05). Conclusion Combination of core stability training and respiratory training is beneficial in reducing the pain of patients with CNLBP,reducing the lumbar dysfunction,improving the order of muscle activation,and strengthening feed-forward control.
6.Analysis of inflammatory factors and BDNF expression in the brain hippocampus of Alzheimer's disease-like mice caused by Aβ25-35
Wen LU ; Jinye REN ; Xiangwei HE ; Liang TANG ; Jianming LI
Chongqing Medicine 2024;53(5):657-663
Objective To investigate the expression of inflammatory factors and brain-derived neurotro-phic factor(BDNF)in the brain hippocampus of Alzheimer's disease(AD)-like mice caused by amyloid β-protein 25-35(Aβ25-35).Methods A total of 40 six-week-old male Kunming mice were taken to construct an AD-like mouse model using bilateral ventricular injection of Aβ25-35,and were divided into the 0 d,7 d,14 d,and 28 d groups for observation,with 10 mice in each group.The Y-maze and new object recognition assay were used to test the learning and memory functions of the mice.The hematoxylin-eosin(HE)staining was used to observe the neuronal damage in the hippocampal region.Immunohistochemical staining was used to detect the expression levels of phosphorylated-tau(p-tau),CD11b and BDNF in hippocampus.ELISA was used to detect the expression levels of inflammatory factors in hippocampus,including interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF)-α,and real-time quantitative reverse transcription PCR(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of BDNF.Results Aβ25-35 could impair memory and cognitive function in the mice.Compared with the 0 d group,the neuron number in the hippocampal tissue of mice in the 14 d and 28 d groups was significantly reduced(P<0.05),and the optical density values of p-Tau and CD11b,and expression levels of IL-1β and TNF-α in the hippocampal region of mice in the 14 d and 28 d groups were significantly increased(P<0.05).In addition,compared with the 0 d group,the relative expression levels of BDNF mRNA and protein in the hippocampal tissue of mice were sig-nificantly increased in the 7 d group(P<0.05),while the relative expression levels of BDNF mRNA and pro-tein were significantly decreased in the 14 d and 28 d groups(P<0.05).Conclusion Aβ25-35 may increase the expression of TNF-α,IL-1β and p-tau in hippocampal tissue by activating microglia,which in turn impaired the memory and cognitive functions of mice,and the expression level of BDNF in hippocampal tissue showed a first increase and then a decrease in the injury period.
7.Analysis of three-dimensional visualization imaging of severe portal vein stenosis after liver transplantation and clinical efficacy of portal vein stent implantation
Hongqiang ZHAO ; Ying LIU ; Jianming MA ; Ang LI ; Lihan YU ; Xuan TONG ; Guangdong WU ; Qian LU ; Yuewei ZHANG ; Rui TANG
Organ Transplantation 2024;15(1):82-89
Objective To analyze three-dimensional imaging characteristics and advantages for severe portal vein stenosis after liver transplantation, and to evaluate clinical efficacy of portal vein stent implantation. Methods Clinical data of 10 patients who received portal vein stent implantation for severe portal vein stenosis after liver transplantation were retrospectively analyzed. Imaging characteristics of severe portal vein stenosis, and advantages of three-dimensional reconstruction imaging and interventional treatment efficacy for severe portal vein stenosis were analyzed. Results Among 10 patients, 3 cases were diagnosed with centripetal stenosis, tortuosity angulation-induced stenosis in 2 cases, compression-induced stenosis in 2 cases, long-segment stenosis and/or vascular occlusion in 3 cases. Three-dimensional reconstruction images possessed advantages in accurate identification of stenosis, identification of stenosis types and measurement of stenosis length. All patients were successfully implanted with portal vein stents. After stent implantation, the diameter of the minimum diameter of portal vein was increased [(6.2±0.9) mm vs. (2.6±1.7) mm, P<0.05], the flow velocity at anastomotic site was decreased [(57±19) cm/s vs. (128±27) cm/s, P<0.05], and the flow velocity at the portal vein adjacent to the liver was increased [(41±6) cm/s vs. (18±6) cm/s, P<0.05]. One patient suffered from intrahepatic hematoma caused by interventional puncture, which was mitigated after conservative observation and treatment. The remaining patients did not experience relevant complications. Conclusions Three-dimensional visualization technique may visually display the location, characteristics and severity of stenosis, which is beneficial for clinicians to make treatment decisions and assist interventional procedures. Timely implantation of portal vein stent may effectively reverse pathological process and improve portal vein blood flow.
8.Analysis of the mechanism of fibrauretine alleviating Alzheimer's disease based on transcriptomics and proteomics
Lu HAN ; Weijia CHEN ; Ying ZONG ; Yan ZHAO ; Jianming LI ; Zhongmei HE ; Rui DU
The Korean Journal of Physiology and Pharmacology 2024;28(4):361-377
The dried rattan stem of the Fibraurea Recisa Pierre plant contains the active ingredient known as fibrauretine (FN). Although it greatly affects Alzheimer's disease (AD), the mechanism of their effects still remains unclear. Proteomics and transcriptomics analysis methods were used in this study to determine the mechanism of FN in the treatment of AD. AD model is used through bilateral hippocampal injection of Aβ1-40. After successful modeling, FN was given for 30 days. The results showed that FN could improve the cognitive dysfunction of AD model rats, reduce the expression of Aβ and P-Tau, increase the content of acetylcholine and reduce the activity of acetylcholinesterase. The Kyoto Encyclopedia of Genes and Genomes enriched differentially expressed genes and proteins are involved in signaling pathways including metabolic pathway, AD, pathway in cancer, PI3K-AKT signaling pathway, and cAMP signaling pathway. Transcriptomics and proteomics sequencing resulted in 19 differentially expressed genes and proteins. Finally, in contrast to the model group, after FN treatment, the protein expressions and genes associated with the PI3K-AKT pathway were significantly improved in RT-qPCR and Western blot and assays. This is consistent with the findings of transcriptomic and proteomic analyses. Our study found that, FN may improve some symptoms of AD model rats through PI3K-AKT signaling pathway.
9.Relationship between myocardial viability and early application of intra-aortic balloon pump after coronary artery bypass grafting
Lu ZHANG ; Yijin HU ; Jianming LI ; Jiao WANG ; Hongwu WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(03):396-402
Objective To explore the relationship between myocardial viability in patients with coronary artery disease who underwent elective coronary artery bypass grafting (CABG) and early application of intra-aortic balloon pump (IABP) after coronary revascularization, and to provide relevant clinical reference for the pre-implantation of 16G single-lumen catheter in the femoral artery of high-risk patients to facilitate the addition of IABP after operation. Methods This retrospective study included 521 patients (414 males and 107 females, aged 62.50±8.82 years) who underwent positron emission tomography (PET)-computed tomography (CT) perfusion-metabolism imaging prior to CABG surgery in our institution from December 2015 to August 2020. The myocardial viability information and left ventricular functional parameters were measured, including the proportion of non-viable myocardium (perfusion-metabolic imaging match), hibernating myocardium (perfusion-metabolic imaging mismatch) and dysfunctional myocardium (non-viable+viable myocardium), left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume (LVESV). The patients were divided into an IABP group and a non-IABP group according to whether they received IABP treatment after revascularization. The clinical data were reviewed and compared to explore significant impact factors between the two groups. And the multivariate logistic regression analysis was performed to investigate the correlation between preoperative myocardial viability and early use of IABP after CABG. Results In multivariate logistic regression analysis, the amount of non-viable, dysfunctional myocardium and LVESV value were identified as the independent predictors for the probability of IABP use in the initial postoperative period. Receiver operating characteristic analysis showed that 9.5% non-viable myocardium, 19.5% dysfunctional myocardium, and LVESV of 114.5 mL were the optimal cutoff for predicting early IABP implantation during CABG. Conclusion The myocardial survival status displayed by preoperative PET-CT myocardial perfusion-metabolism imaging can predict the possibility of applying IABP in CABG perioperative period. In addition to routine pre-anesthesia assessment, anesthesiologists can conduct risk stratification assessment for patients with CABG according to the results of preoperative myocardial viability imaging, which is of great significance to ensure the perioperative safety of high-risk patients with CABG.
10.Effect of robot-assisted bilateral task-oriented upper limb training on upper limb function of patients with stroke
Ya SUN ; Yan LI ; Jianming FU ; Jingjing LU ; Xin JIN ; Zailong LIN
Chinese Journal of Rehabilitation Theory and Practice 2023;29(10):1195-1200
ObjectiveTo investigate the effect of robot-assisted bilateral task-oriented upper limb training on upper limb function of patients with stroke. MethodsFrom January, 2021 to June, 2022, 52 patients with stroke in the Second Hospital of Jiaxing were enrolled and randomized into control group (n = 26) and experimental group (n = 26). Both groups received routine treatment. The control group added conventional bilateral upper limb training, while the experimental group added robot-assisted bilateral task-oriented upper limb training, for six weeks. Before and after treatment, the upper limb motor function and activities of daily living were assessed with Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and modified Barthel Index (MBI). The upper limb proprioception test system was used to measure the average trace error (ATE) and test execution time of the upper limb. ResultsBefore treatment, there was no significant difference in the scores of FMA-UE and MBI, and ATE and test execution time between two groups (P > 0.05). After treatment, all the indexes improved significantly in both groups (|t| > 5.400, P < 0.001), and were better in the experimental group than in the control group (|t| > 2.123, P < 0.05). ConclusionRobot-assisted bilateral task-oriented upper limb training could facilitate to improve the upper limb motor function and activities of daily living of stroke patients.

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