1.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
2.Adolescent Smoking Addiction Diagnosis Based on TI-GNN
Xu-Wen WANG ; Da-Hua YU ; Ting XUE ; Xiao-Jiao LI ; Zhen-Zhen MAI ; Fang DONG ; Yu-Xin MA ; Juan WANG ; Kai YUAN
Progress in Biochemistry and Biophysics 2025;52(9):2393-2405
ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.
3.Evaluation of the safety and efficacy of mitomycin C-perfluorooctyl bromide liposome nanoparticles in the treatment of human pterygium fibroblasts
Tao LI ; Lingshan LIAO ; Shenglan ZHU ; Juan TANG ; Xiaoli WU ; Qilin FANG ; Ying LI ; Biao LI ; Qin TIAN ; Junmei WAN ; Yi YANG ; Yueyue TAN ; Jiaqian LI ; Juan DU ; Yan ZHOU ; Dan ZHANG ; Xingde LIU
Recent Advances in Ophthalmology 2024;44(2):100-105
Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)%and(34.27±2.04)%,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)%in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)%]was significantly higher than that in the MMC group[(51.62±3.28)%].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P<0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.
4.Evaluation of the correlation between diabetic retinopathy and diabetic ne-phropathy by emission computed tomography and clinical testing data via convolutional neural network
Juan TANG ; Qinghua LI ; Xiuying DENG ; Ting LU ; Guoqiang TANG ; Zhiwu LIN ; Xingde LIU ; Xiaoli WU ; Qilin FANG ; Ying LI ; Xiao WANG ; Yan ZHOU ; Biao LI ; Chuanqiang DAI ; Tao LI
Recent Advances in Ophthalmology 2024;44(2):127-132
Objective To evaluate the relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM)based on imaging and clinical testing data.Methods Totally 600 T2DM patients who visited the First People's Hospital of Ziyang from March 2021 to December 2022 were included.The fundus photography and fundus fluorescein angiography were performed on all these patients and their age,gender,T2DM duration,cardiovascular diseases,cerebrovascular disease,hypertension,smoking history,drinking history,body mass in-dex,systolic blood pressure,diastolic blood pressure and other clinical data were collected.The levels of fasting blood glu-cose(FPG),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipo-protein cholesterol(LDL-C),glycosylated hemoglobin(HbA1c),24 h urinary albumin(UAlb),urinary albumin to creati-nine ratio(ACR),serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.Logistic regression was used to analyze the risk factors associated with DR.DR staging was performed according to fundus images,and the convolutional neural network(CNN)algorithm was used as an image analysis method to explore the correlation between DR and DN based on emission computed tomography(ECT)and clinical testing data.Results The average lesion area rates of DR and DN detected by the CNN in the non-DR,mild-non-proliferative DR(NPDR),moderate-NPDR,severe-NPDR and pro-liferative DR(PDR)groups were higher than those obtained by the traditional algorithm(TCM).As DR worsened,the Scr,BUN,24 h UAlb and ACR gradually increased.Besides,the incidence of DN in the non-DR,mild-NPDR,moderate-NPDR,severe-NPDR and PDR groups was 1.67%,8.83%,16.16%,22.16%and 30.83%,respectively.Logistic regression analysis showed that the duration of T2DM,smoking history,HbA1c,TC,TG,HDL-C,LDL-C,24 h UAlb,Scr,BUN,ACR and glomerular filtration rate(GFR)were independent risk factors for DR.Renal dynamic ECT analysis demonstrated that with the aggravation of DR,renal blood flow perfusion gradually decreased,resulting in diminished renal filtration.Conclusion The application of CCN in the early stage DR and DN image analysis of T2DM patients will improve the diag-nosis accuracy of DR and DN lesion area.The DN is worsening as the aggravation of DR.
5.The role of comprehensive intervention measures in improving the patho-gen detection rate of hospitalized patients before antimicrobial therapy
Yue-Li LI ; Jin-Lan CUI ; Lan-Juan MEI ; Qiu-Chun LIU ; Ju-Fang TIAN
Chinese Journal of Infection Control 2024;23(3):370-376
Objective To understand the pathogen detection of hospitalized patients before antimicrobial therapy in a hospital through implementation of comprehensive intervention measures,and provide reference basis for the de-velopment of targeted measures.Methods Hospitalized patients who received therapeutic antimicrobial agents in this hospital were selected as the research subjects.Patients who were hospitalized from January to May 2022 were selected as the pre-intervention group,comprehensive intervention measures were taken from June to October 2022,and those who were hospitalized from November 2022 to March 2023 were selected as the post-intervention group.The pathogen detection rate before antimicrobial therapy,sterile specimen detection rate,antimicrobial use rate,de-tection rate of key multidrug-resistant organisms of patients before and after the intervention were analyzed.Results Compared to before intervention,the proportion of pathogen detection rate before antimicrobial therapy(62.09%vs 74.04%),detection rate of healthcare-associated infection diagnosis-related pathogens(62.82%vs 92.73%),and sterile specimen detection rate(35.17%vs 41.06%)of hospitalized patients after intervention all increased signifi-cantly,with statistically significant differences(all P<0.05).After intervention,pathogen detection rate before the combination use of key antimicrobial agents was not statistically different from before intervention(93.33%vs 90.48%,P>0.05),while antimicrobial use rate was lower than before intervention(39.93%vs 44.95%,P<0.05).There was no statistically significant difference in the detection rate of key multidrug-resistant organisms be-fore and after intervention(all P>0.05).Conclusion Adopting scientific and rational intervention measures can improve the pathogen detection rate,provide a reference basis for the rational use of antimicrobial agents.There was no significant improvement in the pathogen detection rate before the combination use of key antimicrobial agents and the detection rate of key multidrug-resistant organisms,indicating that relevant measures still need to be further optimized.
6.Research on Governance of Medical Service Price Coordination in the Yangtze River Delta Region from the Perspective of Social Network Analysis
Juan LI ; Liang FANG ; Haiyin WANG ; Chunlin JIN
Chinese Health Economics 2024;43(6):75-78
Objective:To explore the structural characteristics of the medical service price network in the Yangtze River Delta,and provide a new management perspective for the collaborative governance of medical service prices in the Yangtze River Delta.Methods:Taking the related medical security bureaus of some core cities in the Yangtze River Delta as samples,based on the social network analysis method,the structural characteristics of price linkage network are analyzed from the perspectives of network density and correlation,individual centrality and block model analysis.Results:Firstly,the price network is not tight and has poor stability;secondly,the price network is unbalanced,with the Municipal Medical Insurance Bureau playing different roles;thirdly,the price network has obvious spatial aggregation and spatial spillover.Conclusion:The overall situation of the medical service price linkage network is not optimistic,and the network advantages should be fully integrated to promote the coordinated development of medical service prices in the Yangtze River Delta Region.
7.Clinical characteristics and transfusion strategies of delayed serological transfusion reactions caused by platelet transfusion in tumor patients
Min LIU ; Tao PENG ; Jingjing YU ; Ruijuan ZHAO ; Weiwei FANG ; Juan CAI ; Simeng CHEN ; Xiying LI
Chinese Journal of Blood Transfusion 2024;37(5):491-494,500
Objective To analyze the clinical manifestations of delayed serological transfusion reactions(DSTR)after platelet transfusion in tumor patients,and to explore the transfusion strategy.Methods Clinical data and laboratory test re-sults of patients with positive antibody screening were analyzed after platelet transfusion in our hospital from January 1,2015 to June 30,2023,and the incidence rate,clinical characteristics and transfusion strategy of patients with DSTR were ana-lyzed.Results A total of 2 553 patients with 6 057 platelet transfusions were reviewed.Eight patients developed DSTR and received a total of 21 therapeutic amounts of platelets,and 5 patients were subsequently transfused with red blood cells.Rh system antibodies were detected in 7 cases(4 anti-E,1 anti-c/E,1 anti-C and 1 anti-c)and Kell system antibodies in 1 case.Conclusion Tumor patients may also develop DSTR after platelet transfusion.It is necessary to pay close attention to the antibody situation and perform matched transfusion when transfusing blood again.
8.Ibandronate alleviates inflammatory damage in diabetic osteoporosis rats by activating Nrf2/HO-1 signaling pathway
Xiao-Li LIU ; Qin-Fang ZHU ; Jin-Juan LI ; Li-Xin YANG
The Chinese Journal of Clinical Pharmacology 2024;40(2):230-233
Objective To investigate the potential mechanism of ibandronate sodium(IB)in alleviating inflammatory damage in diabetic osteoporosis rats by activating the nuclear transcription factor erythro 2-associated factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods Intraperitoneal injection of streptozotocin at several low doess was used to induce rat model of diabetes mellitus,then bilateral oophorectomy were used to establish type 2 diabetic osteoporosis(T2DOP)rat model.T2DOP model rats were divided into model group,control group,combined group and experimental-L,-M,-H groups,with 8 rats in each group;another 8 diabetic rats were selected as blank group.Model group was treated with normal saline.Control group was given the same volume of solvent.Experimental-L,-M,-H groups were given 2,10 and 50 mg·kg-1 IB.Combined group was treated with 50 mg·kg-1 IB and 50 mg·kg-1 ML385.Seven groups were administered intraperitoneally once a day for 12 weeks.After 12 weeks of treatment,the bone morphologic parameters were detected by calxanthoprotein double labeling method,the expression levels of Nrf2 and HO-1 pathway protein were detected by Western blot.Results The bone morphologic parameters of experimental-M,-H groups,combined group,control group,model group and blank group were 1.74±0.32,2.94±0.58,0.98±0.32,1.01±0.24,0.98±0.42 and 2.92±0.42;the relative expression levels of Nrf2 protein were 0.99±0.09,1.47±0.12,0.51±0.06,0.52±0.06,0.52±0.05 and 1.48±0.12;the relative expression levels of HO-1 protein were 1.02±0.11,1.33±0.14,0.61±0.05,0.59±0.06,0.62±0.06 and 1.29±0.13,respectively.The above indexes in the control group were statistically different with those in the experimental-M,-H groups(all P<0.05).Conclusion IB repairs bone microstructure and alleviates inflammation in diabetic osteoporosis rats by activating the Nrf2/HO-1 signaling pathway.
9.Mechanism of ginsenoside Rg1 inhibiting the proliferation and metastasis of tongue squamous cell carcinoma
Xue LI ; Sha-Fei ZHAI ; Xin-Yang MA ; Dan-Yang WANG ; Juan CHAI ; Fang ZHOU ; Jia ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(13):1888-1892
Objective To investigate the inhibitory effect of Ginsenosides Rg1(GS-Rg1)on the proliferation and metastasis of tongue squamous cell carcinoma(TSCC),and its related mechanisms of action.Methods TSCC cells were treated with GS-Rg1 at concentrations of 1.25,2.5,5.0 and 10.0 μmol·L-1 for 48 hours.The proliferation ability of cells at different concentrations was measured by cell counting kit-8(CCK-8)experiment,and the IC5ovalue of GS-Rg1 at CAL-27 for 48 hours was calculated.TSCC cells CAL-27 were divided into control group and GS-Rg1 group.The control group and GS-Rg1 group were treated with 0.9%NaCl and IC50concentration of GS-Rg1 for 48 hours,respectively.The cell cycle distribution of each group was detected by flow cytometry,and the cell metastasis ability of each group was detected by Transwell experiment.Construct TOP/FOP Flash plasmid,transfect control group and GS-Rg1 group,and detect the effect of GS-Rg1 effect on wnt/β-catenin signaling pathway activity in TSCC cell CAL-27 using luciferase assay.Using wnt/β-catenin pathway inhibitor XAV939 treated GS-Rg1 group cells(XAV939+GS-Rg1 group),and wnt/β-catenin pathway activator HLY78 was used to treat GS-Rg1 group cells(HLY78+GS-Rg1 group)and detect changes of wnt/β-catenin signaling pathway activity,the cell proliferation ability,cell cycle distribution,and metastasis ability in XAV939+GS-Rg1 group,HLY78+GS-Rg1 group and GS-Rg1 group.The expression of wnt/β-catenin signaling pathway related proteins β-catenin,and its downstream cell cycle related proteins cellular myelocytomatosis oncogene(cMYC),Cyclin dependent kinase 4(CDK4),andcyclinD1,as well as metastasis related proteins E-cadherin,N-cadherin and matrix metalloproteinase 2(MMP-2)were detected by Western blotting in each group of cells.Results GS-Rg1 significantly inhibited the proliferation ability of TSCC cells CAL-27(P<0.05),and the IC50value of GS-Rg1 on CAL-27 was(5.46±1.58)μmol·L-1.The ratio of GO/G1 phase cells in the control group and GS-Rg1 group were(60.65±2.16)%and(71.20±2.38)%,respectively;the number of cell transmembrane penetration were 87.33±7.51 and 50.67±3.21,respectively;the luciferase activity were 1.00±0.02 and 0.35±0.06,respectively.Compared with the control group,the GS-Rg1 group showed cell cycle arrest in GO/G1 phase,decreased cell metastasis ability,and the activity of wnt/β-catenin signaling pathway decreased(P<0.05,P<0.01).Compared with the GS-Rg1 group,the activity of the wnt/β-catenin signaling pathway was decreased,cell proliferation ability and metastasis ability was decreased(P<0.05),while the number of GO/G1 phase cells was increased(P<0.05),the expression of β-catenin,cMYC,CDK4,cyclinD1,E-cadherin and MMP-2 proteins were decreased(P<0.05),while the expression of N-cadherin protein increased in XAV939+GS-Rg1 group cells.However,the result were opposite in the HLY78+GS-Rg1 group of cells.Conclusion GS-Rg1 downregulates wnt/β-catenin signaling pathway inhibits the proliferation and metastasis ability of TSCC cells.
10.Research on Governance of Medical Service Price Coordination in the Yangtze River Delta Region from the Perspective of Social Network Analysis
Juan LI ; Liang FANG ; Haiyin WANG ; Chunlin JIN
Chinese Health Economics 2024;43(6):75-78
Objective:To explore the structural characteristics of the medical service price network in the Yangtze River Delta,and provide a new management perspective for the collaborative governance of medical service prices in the Yangtze River Delta.Methods:Taking the related medical security bureaus of some core cities in the Yangtze River Delta as samples,based on the social network analysis method,the structural characteristics of price linkage network are analyzed from the perspectives of network density and correlation,individual centrality and block model analysis.Results:Firstly,the price network is not tight and has poor stability;secondly,the price network is unbalanced,with the Municipal Medical Insurance Bureau playing different roles;thirdly,the price network has obvious spatial aggregation and spatial spillover.Conclusion:The overall situation of the medical service price linkage network is not optimistic,and the network advantages should be fully integrated to promote the coordinated development of medical service prices in the Yangtze River Delta Region.

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