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Machine learning applications in stroke medicine:advancements,challenges,and future prospectives

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Neural Regeneration Research 2024年第4期19卷 769-773页

作者： Mario Daidone Sergio Ferrantelli Antonino Tuttolomondo Internal medicine and Stroke Care Ward Department of Health PromotionMother and Child CareInternal Medicine and Medical SpecialtiesUniversity of Palermo Molecular and clinical medicine PhD program University of Palermo

Stroke is a leading cause of disability and mortality worldwide,necessitating the development of advanced technologies to improve its diagnosis,treatment,and patient outcomes.In recent years,machine learning techniques have emerged as promising tools in stroke medicine,enabling efficient analysis of large-scale datasets and facilitating personalized and precision medicine approaches.This abstract provides a comprehensive overview of machine learning’s applications,challenges,and future directions in stroke medicine.Recently introduced machine learning algorithms have been extensively employed in all the fields of stroke medicine.Machine learning models have demonstrated remarkable accuracy in imaging analysis,diagnosing stroke subtypes,risk stratifications,guiding medical treatment,and predicting patient prognosis.Despite the tremendous potential of machine learning in stroke medicine,several challenges must be addressed.These include the need for standardized and interoperable data collection,robust model validation and generalization,and the ethical considerations surrounding privacy and bias.In addition,integrating machine learning models into clinical workflows and establishing regulatory frameworks are critical for ensuring their widespread adoption and impact in routine stroke care.Machine learning promises to revolutionize stroke medicine by enabling precise diagnosis,tailored treatment selection,and improved prognostication.Continued research and collaboration among clinicians,researchers,and technologists are essential for overcoming challenges and realizing the full potential of machine learning in stroke care,ultimately leading to enhanced patient outcomes and quality of life.This review aims to summarize all the current implications of machine learning in stroke diagnosis,treatment,and prognostic evaluation.At the same time,another purpose of this paper is to explore all the future perspectives these techniques can provide in combating this disabling disease.

关键词： cerebrovascular disease deep learning machine learning reinforcement learning stroke stroke therapy supervised learning unsupervised learning

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Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1344-1362页

作者： Zi-Ling Hu Yu-Xuan Wang Zi-Yue Lin Wen-Shuo Ren Bo Liu Hui Zhao Qiong Qin Five year program of Ophthalmology and Optometry 2019 Beijing Tong Ren HospitalCapital Medical UniversityBeijing 100054China Four year program of Traditional Chinese Pharmacy 2020 School of Traditional Chinese MedicineCapital Medical UniversityBeijing 100069China School of Traditional Chinese medicine Capital Medical UniversityBeijing 100069China Beijing Key Laboratory of TCM Collateral Disease Theory Research Beijing 100069China Five year program of Ophthalmology and Optometry 2021 School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Biochemistry&Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Age-related macular degeneration(AMD)is a complicated disease that causes irreversible visual impairment.Increasing evidences pointed retinal pigment epithelia(RPE)cells as the decisive cell involved in the progress of AMD,and the function of anti-oxidant capacity of PRE plays a fundamental physiological role.Nuclear factor erythroid 2 related factor 2(Nrf2)is a significant transcription factor in the cellular anti-oxidant system as it regulates the expression of multiple anti-oxidative genes.Its functions of protecting RPE cells against oxidative stress(OS)and ensuing physiological changes,including inflammation,mitochondrial damage and autophagy dysregulation,have already been elucidated.Understanding the roles of upstream regulators of Nrf2 could provide further insight to the OS-mediated AMD pathogenesis.For the first time,this review summarized the reported upstream regulators of Nrf2 in AMD pathogenesis,including proteins and miRNAs,and their underlying molecular mechanisms,which may help to find potential targets via regulating the Nrf2 pathway in the future research and further discuss the existing Nrf2 regulators proved to be beneficial in preventing AMD.

关键词： Nrf2 upstream regulators retinal pigment epithelia age-related macular degeneration oxidative stress

Icariin attenuates vascular endothelial dysfunction by inhibiting inflammation through GPER/Sirt1/HMGB1 signaling pathway in type 1 diabetic rats

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Chinese Journal of Natural medicines 2024年第4期22卷 293-306页

作者： YAO Wenhui TAO Rongpin WANG Kai DING Xuansheng School of Basic medicine and clinical Pharmacy China Pharmaceutical UniversityNanjing211198China

Icariin, a flavonoid glycoside, is extracted from Epimedium. This study aimed to investigate the vascular protective effects of icariin in type 1 diabetic rats by inhibiting high-mobility group box 1 (HMGB1)-related inflammation and exploring its potential mechanisms. The impact of icariin on vascular dysfunction was assessed in streptozotocin (STZ)-induced diabetic rats through vascular reactivity studies. Western blotting and immunofluorescence assays were performed to measure the expressions of target proteins. The release of HMGB1 and pro-inflammation cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results revealed that icariin administration enhanced acetylcholine-induced vasodilation in the aortas of diabetic rats. It also notably reduced the release of pro-inflammatory cytokines, including interleukin-8 (IL-8), IL-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) in diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). The results also unveiled that the pro-inflammatory cytokines in the culture medium of HUVECs could be increased by rHMGB1. The increased release of HMGB1 and upregulated expressions of HMGB1-related inflammatory factors, including advanced glycation end products (RAGE), Toll-like receptor 4 (TLR4), and phosphorylated p65 (p-p65) in diabetic rats and HG-induced HUVECs, were remarkably suppressed by icariin. Notably, HMGB1 translocation from the nucleus to the cytoplasm in HUVECs under HG was inhibited by icariin. Meanwhile, icariin could activate G protein-coupled estrogen receptor (GPER) and sirt1. To explore the role of GPER and Sirt1 in the inhibitory effect of icariin on HMGB1 release and HMGB-induced inflammation, GPER inhibitor and Sirt1 inhibitor were used in this study. These inhibitors diminished the effects of icariin on HMGB1 release and HMGB1-induced inflammation. Specifically, the GPER inhibitor also negated the activation of Sirt1 by icariin. These findings suggest that icariin activates GPER and increases the exp

关键词： Icariin Diabetes Inflammation Vascular endothelial dysfunction GPER HMGB1

Investigation of the active ingredients and mechanism of Shuangling extract in dextran sulfate sodium salt induced ulcerative colitis mice based on network pharmacology and experimental verification

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Journal of Traditional Chinese medicine 2024年第3期44卷 478-488页

作者： CHU Mengzhen WANG Yu LIN Zhijian Lyu Jintao ZHANG Xiaomeng ZHANG Bing Department of clinical Chinese Pharmacy School of Chinese Materia MedicaBeijing University of Chinese Medicine

OBJECTIVE: To explore the pharmacodynamic effects and potential mechanisms of Shuangling extract against ulcerative colitis(UC). METHODS: The bioinformatics method was used to predict the active ingredients and action targets of Shuangling extract against UC in mice. And the biological experiments such as serum biochemical indexes and histopathological staining were used to verify the pharmacological effect and mechanism of Shuangling extract against UC in mice. RESULTS: The Shuangling extract reduced the levels of seruminterleukin-1β(IL-1β), tumor necrosis factor-α(TNF-N), interleukin-6(IL-6) and other inflammatory factors in UC mice and inhibited the inflammatory response. AKT Serine/threonine Kinase 1 and IL-6 may be the main targets of the anti-UC action of Shuangling extract, and the TNF signaling pathway, Forkhead box O signaling pathway and T-cell receptor signaling pathway may be the main signaling pathways. CONCLUSION: The Shuangling extract could inhibit the inflammatory response induced by UC and regulate intestinal immune function through multiple targets and multiple channels, which provided a new option and theoretical basis for anti-UC.

关键词： Shuangling extract colitis, ulcerative molecular docking simulation network pharmacology pharmacodynamic study

Optimized new Shengmai powder(优化新生脉散方) inhibits myocardial fibrosis in heart failure by regulating the rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway

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Journal of Traditional Chinese medicine 2024年第3期44卷 448-457页

作者： ZHANG Zeyu JIA Zhuangzhuang SONG Yuwei ZHANG Xuan WANG Ci WANG Shuai ZHANG Peipei REN Qiuan WANG Xianliang MAO Jingyuan Department of Cardiovascular the First Teaching Hospital of Tianjin University of Traditional Chinese MedicineNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion

OBJECTIVE: Exploring the effect of Optimized New Shengmai powder(优化新生脉散方, ONSMP) on myocardial fibrosis in heart failure(HF) based on rat sarcoma(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase kinase(MEK)/extracellular regulated protein kinases(ERK) signaling pathway. METHODS: Randomized 70 Sprague-Dawley rats into sham(n = 10) and operation(n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low(L), medium(M), and high(H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat's body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen(COL) Ⅰ and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the m RNA levels of COL Ⅰ, COL Ⅲ, α-smooth muscle actin(α-SMA), and c-Fos proto-oncogene(c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor(p-ELK1), p-c-Fos, α-SMA, COL Ⅰ, and COL Ⅲ by Western blot. RESULTS: ONSMP can effectively improve HF rat's cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL Ⅰ/Ⅲ content, down-regulate the m RNA of COL Ⅰ/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA. CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

关键词： extracellular regulated protein kinases heart failure mitogen-activated protein kinases myocardial fibrosis optimized new Shengmai powder rapidly accelerated fibrosarcoma sarcoma

Chronic infectious unilateral giant thyroid cyst related to diabetes mellitus:A case report

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World Journal of clinical Cases 2024年第8期12卷 1497-1503页

作者： Jiang-Bo Liu Shi-Lei Zhang Wen-Long Jiang Hai-Kuan Sun Hao-Chen Yang Department of Thyroid and Breast Surgery The First Affiliated HospitalCollege of Clinical MedicineHenan University of Science and TechnologyLuoyang 471000Henan ProvinceChina clinical medicine School The First Clinical CollegeChongqing Medical UniversityChongqing 400016China

BACKGROUND Patients rarely develop complicated infections in thyroid cysts.Here,we describe a patient with chronic infected unilateral giant thyroid cyst related to diabetes mellitus(DM).CASE SUMMARY A 66-year-old male was admitted due to an evident neck lump for 5 d after approximately 40 years of gradually progressive neck mass and 7 years of DM.Doppler ultrasound and computed tomography scan showed a giant lump in the left thyroid gland lobe.He was diagnosed with a large thyroid nodule complicated by tracheal dislocation and had surgical indications.Surgical exploration revealed evident inflammatory edema and exudation between the left anterior neck muscles,the nodule and glandular tissue.Fortunately,inflammatory lesions did not affect major neck vessels.Finally,a left partial thyroidectomy was performed.Macroscopic observation showed that the cystic thyroid mass consisted of extensive cystic wall calcification and was rich in massive rough sand-like calculi content and purulent matter.Postoperative pathology confirmed benign thyroid cyst with chronic infection.CONCLUSION The progression of this chronic infectious unilateral giant thyroid cyst may have been related to DM,and identifying blood vessels involvement can prevent serious complications during operation.

关键词： Thyroid nodule Infection Diabetes mellitus Surgery Case report

Efficacy and safety of Yangxinshi tablet for chronic heart failure:A systematic review and meta-analysis

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World Journal of clinical Cases 2024年第13期12卷 2218-2230页

作者： Sheng-Hua Lu Yun-Feng Yu Si-Si Dai Ya-Qi Hu Jian-He Liu The First clinical College of Chinese medicine Hunan University of Chinese MedicineChangsha 410007Hunan ProvinceChina Branch of National clinical Research Center for Chinese medicine Cardiology The First Hospital of Hunan University of Chinese MedicineChangsha 410007Hunan ProvinceChina

BACKGROUND The specific benefits of Yangxinshi tablet(YXST)in the treating chronic heart failure(CHF)remain uncertain.AIM To systematically evaluate the efficacy and safety of YXST in the treatment of CHF.METHODS Randomized controlled trials(RCTs)investigating YXST for CHF treatment were retrieved from eight public databases up to November 2023.Meta-analyses of the included clinical studies were conducted using Review Manager 5.3.RESULTS Twenty RCTs and 1845 patients were included.The meta-analysis results showed that the YXST combination group,compared to the conventional drug group,significantly increased the clinical efficacy rate by 23%[relative risk(RR)=1.23,95%CI:1.17-1.29],(Pclinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile,suggesting its potential as a therapeutic strategy for CHF.

关键词： Yangxinshi tablet Chronic heart failure Cardiac function Systematic evaluation Meta-analysis

Yanggan Jiangmei Formula alleviates hepatic inflammation and lipid accumulation in non-alcoholic steatohepatitis by inhibiting the NF-κB/NLRP3 signaling pathway

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Chinese Journal of Natural medicines 2024年第3期22卷 224-234页

作者： WU Yuanyuan ZHOU Jingwen ZUO Xinchen KUANG Yufeng SUN Lixia ZHANG Xiaolong The First clinical Medical College Nanjing University of Chinese MedicineNanjing 210023China The Affiliated Hospital of Nanjing University of Chinese medicine Jiangsu Province Hospital of Chinese MedicineNanjing 210029China

The role of NF-κB and the NLRP3 inflammasome in the chronic inflammatory microenvironment of non-alcoholic steatohepatitis(NASH)has been posited as crucial.The Yanggan Jiangmei Formula(YGJMF)has shown promise in ameliorating hepatic steatosis in NASH patients,yet its pharmacological mechanisms remain largely unexplored.This study was conducted to investigate the efficacy of YGJMF in NASH and to elucidate its pharmacological underpinnings.To simulate NASH both in vivo and in vitro,high-fat-diet(HFD)rats and HepG2 cells stimulated with free fatty acids(FFAs)were utilized.The severity of liver injury and lipid deposition was assessed using serum indicators,histopathological staining,micro-magnetic resonance imaging(MRI),and the liver-tomuscle signal intensity ratio(SIRL/M).Furthermore,a combination of enzyme-linked immunosorbent assay(ELISA),immunohistochemistry(IHC),immunofluorescence,real-time quantitative polymerase chain reaction(RT-qPCR),and Western blotting analyses was employed to investigate the NF-κB/NLRP3 signaling pathway and associated cytokine levels.The results from liver pathology,MRI assessments,and biochemical tests in rat models demonstrated YGJMF’s significant effectiveness in reducing liver damage and lipid accumulation.Additionally,YGJMF markedly reduced hepatocyte inflammation by downregulating inflammatory cytokines in both liver tissue and serum.Furthermore,YGJMF was found to disrupt NF-κB activation,consequently inhibiting the assembly of the NLRP3 inflammasome in both the in vitro and in vivo models.The preliminary findings of this study suggest that YGJMF may alleviate hepatic steatosis and inhibit the NF-κB/NLRP3 signaling pathway,thereby exerting anti-inflammatory effects in NASH.

关键词： Non-alcoholic steatohepatitis Nuclear factor kappa B NLRP3 inflammasome Yanggan Jiangmei Formula

A novel mechanism of PHB2-mediated mitophagy participating in the development of Parkinson's disease

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Neural Regeneration Research 2024年第8期19卷 1828-1834页

作者： Yongjiang Zhang Shiyi Yin Run Song Xiaoyi Lai Mengmeng Shen Jiannan Wu Junqiang Yan Key Laboratory of Neuromolecular Biology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains unclear.Protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum stress.Parkin is regulated by PERK and is a target of the unfolded protein response.It is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh Parkin.In this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s disease.We used adeno-associated virus to knockdown PHB2 expression.Our res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s disease.Ove rexpression of PHB2 inhibited these abnormalities.We also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s disease.We found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted mitophagy.In addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of PERK.These findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.

关键词： endoplasmic reticulum dopaminergic neuron microtubule-associated protein 1 light chain 3 mitophagy oxidative stress Parkin Parkinson’s disease PKR-like endoplasmic reticulum kinase reactive oxygen species prohibitin-2

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