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The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

Neural Regeneration Research 2024年第4期19卷 800-806页

作者： Xinxin Wang Yushu Hu Renshi Xu medical college of Nanchang University Department of Neurology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical College

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory ***,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the *** disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized *** TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral *** review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

关键词： amyotrophic lateral sclerosis axonal transport liquid-liquid phase separation noncellular autonomous functions oxidative stress pathogenesis post-translational modification protein quality control system stress granules TAR DNA-binding protein 43(TDP-43)

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Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients,may mediate immune evasion

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2091-2112页

作者： Ming-Yue Tang Xue Shen Run-Sheng Yuan Hui-Yuan Li Xin-Wei Li Yi-Ming Jing Yue Zhang Hong-Hong Shen Zi-Shu Wang Lei Zhou Yun-Chuan Yang He-Xin Wen Fang Su Department of medical Oncology The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Otolaryngology and Head and Neck Surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Department of Neurology The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Department of Hepatobiliary Surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Department of Gastrointestinal Surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina

BACKGROUND For the first time,we investigated the oncological role of plexin domain-containing 1(PLXDC1),also known as tumor endothelial marker 7(TEM7),in hepatocellular carcinoma(HCC).AIM To investigate the oncological profile of PLXDC1 in *** Based on The Cancer Genome Atlas database,we analyzed the expression of PLXDC1 in *** immunohistochemistry,quantitative real-time polymerase chain reaction(qRT-PCR),and Western blotting,we validated our *** prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features,such as patient survival,methylation level,tumor immune microenvironment features,and immune cell surface checkpoint ***,to assess the immune evasion potential of PLXDC1 in HCC,we used the tumor immune dysfunction and exclusion(TIDE)website and immunohistochemical staining *** Based on immunohistochemistry,qRT-PCR,and Western blot assays,overexpression of PLXDC1 in HCC was associated with poor *** and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic *** HCC patients with high methylation levels,the prognosis was worse than in patients with low methylation *** enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling,and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 *** high-risk group had a significantly lower immune evasion rate as well as a poor prognosis,and PLXDC1-related risk scores were also associated with a poor *** As a result of this study analyzing PLXDC1 from multiple biological perspectives,it was revealed that it is a biomarker of poor prognosis for HCC patients,and that it plays a role in determining immune evasion status.

关键词： Plexin domain-containing 1 Biomarker Immune evasion Prognosis Immunotherapy Hepatocellular carcinoma

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Predictive value of neutrophil-to-lymphocyte ratio in coronary chronic total occlusion patients

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Journal of Geriatric Cardiology 2024年第5期21卷 542-549页

作者： Qian LI Yue YU Ya-Qiong ZHOU Yi ZHAO Jin WU Yuan-Jing WU Bin DU Pei-Jian WANG Tao ZHENG Department of Cardiovascular Medicine the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina Department of Cardiology First Affiliated Hospital of Chengdu Medical CollegeChengduChina Department of Neurology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina

BACKGROUND The neutrophil to lymphocyte ratio(NLR)has been reported as a novel predictor for atherosclerosis and car-diovascular *** study aimed to determine the effects of NLR on long-term clinical outcomes of chronic total occlusion(CTO)*** A total of 670 patients with CTO who met the inclusion criteria were included at the end of the follow-up *** were divided into tertiles according to their baseline NLR levels at admission:low(n=223),intermediate(n=223),and high(n=224).The incidence of major adverse cardiac events(MACEs)during the follow-up period,including all-cause death,nonfatal myocardial infarction(MI),or ischemia-driven revascularization,were compared among the three *** Major adverse cardiac events were observed in 27 patients(12.1%)in the low tertile,40(17.9%)in the intermediate tertile,and 61(27.2%)in the high NLR tertile(P<0.001).Kaplan-Meier analysis demonstrated a significantly higher incidence of MACE,ischemia-driven coronary revascularization,non-fatal MI,and mortality in patients within the high tertile than those in the low and intermediate groups(all P<0.001).Multivariable COX regression analysis showed that the high tertile of baseline NLR level showed a strong association with the risk of MACE(hazard ratio[HR]=2.21;95%confidence interval[CI]:1.21-4.03;P=0.009),ischemia-driven coronary revascularization(HR=3.19;95%CI:1.56-6.52;P=0.001),MI(HR=2.61;95%CI:1.35-5.03;P=0.043)and mortality(HR=3.78;95%CI:1.65-8.77;P=0.001).CONCLUSION Our findings suggest that NLR is an inexpensive and readily available biomarker that can independently pre-dict cardiovascular risk in patients with CTO.

关键词： patients coronary occlusion

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Effect of Tanshinone IIA on High Glucose-induced Apoptosis and Oxidative Stress Damage in Vascular Endothelial Cells

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Chinese Journal of Biomedical Engineering 2024年第2期33卷 62-68页

作者： QIU Shui-lin HUANG Rong HUANG Jian-qing QIU Rong-shui Longyan first affiliated hospital of Fujian medical University Xiamen medical college affiliated Haicang hospital

Objective: The primary cause of microvascular disease in diabetic complications is long-term hyperglycemia, wherein the damage and apoptosis of vascular endothelial cells play a significant role. Sodium tanshinone IIA sulfonate(STS) has been found to have beneficial effects on cardiovascular health. This study aimed to investigate the impact of STS on high glucose-induced apoptosis and oxidative stress damage in vascular endothelial cells, as well as its potential protective mechanisms. Methods:Human umbilical vein endothelial cells(HUVECs) were divided into five groups:low-glucose group, high-glucose group, and three STS groups(STS-a, STS-b, and STS-c). The low-glucose group was incubated with DMEM low-sugar medium containing 5.5 mmol·L-1glucose, while the high-glucose group was treated with 33.3mmol·L-1glucose. The STS groups were exposed to 10, 30, and 50 μg·m L-1of STS,respectively. Each group was cultured for 72 h, and the MTT method was utilized to assess cell proliferation. Additionally, flow cytometry was employed to monitor changes in cell apoptosis and cellular oxidative stress indicators at 24, 48, and 72 h of cell culture in each group. Results: As time went on, the cell proliferation ability and apoptosis rate of each group gradually increased. The high-glucose group exhibited lower proliferation ability compared to the other groups. The STS-c group demonstrated the highest OD value for proliferation ability(24 h: 1.19±0.12; 48 h: 1.20±0.13; 72 h:1.25 ±0.12), but it was still lower than that of the low-sugar group. Notably, the high-glucose group had the highest cell apoptosis rate, while the low-glucose group had the lowest. The apoptosis rate of the STS-c group(24 h: 8.02±0.13; 48 h: 10.10±0.12;72 h: 13.18 ±0.11)% was between that of the low-glucose group and the high-glucose group, and lower than the STS-a and STS-b groups. Furthermore, the high-glucose group exhibited the highest malondialdehyde and nitric oxide synthase activities, as well as super

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Knockdown of RCN1 contributes to the apoptosis of colorectal cancer via regulating IP3R1

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BIOCELL 2024年第5期48卷 835-845页

作者： XUAN SHI YUFEN WANG CHENYU LI WANGSHU FU XINYUE ZHANG AIXIA GONG Department of Gastroenterology The First Affiliated Hospital of Dalian Medical UniversityDalianChina Department of Gastroenterology The First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina The first Clinical college Dalian Medical UniversityDalianChina

Background:The incidence of colorectal cancer(CRC)has been increasing in recent ***,the discovery of factors that can assist in alleviating CRC is urgently ***:To identify a potential factor involved in the development of CRC,we screened the upregulated genes in tumor tissues through four datasets from an online *** expression of reticulocalbin 1(RCN1),a Ca2+-binding protein,was upregulated in the four *** on loss-offunction experiments,the effect of RCN1 on cell viability was assessed by Cell Counting Kit-8(CCK-8)*** regulatory effect of RCN1 on apoptosis was evaluated through Annexin V-fluorescein 5-isothiocyanate(FITC)/propidium iodide(PI)staining assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)assay in RKO and SW480 *** of endoplasmic reticulum(ER)stress signaling pathways was confirmed by estimating the phosphorylation and expression of PRKR-like ER kinase(PERK),inositol-requiring kinase-1(IRE1),transcription factor 6(ACT6),and CCAAT/enhancer-binding protein-homologous protein(CHOP).The intracellular Ca2+homeostasis regulated by RCN1 was determined through the detection of Ca2+concentration and mitochondrial membrane potential(MMP)***,whether inositol 1,4,5-trisphosphate receptor type 1(IP3R1)was involved in the regulation of RCN1 in CRC was verified through the depletion of IP3R1 in RKO ***:Knockdown of RCN1 reduced cell viability and facilitated apoptosis in RKO and SW480 *** of PERK and IRE1,activation of ATF6,and upregulation of CHOP were induced by the absence of RCN1,suggesting that the unfolded protein response(UPR)was activated in CRC *** concentration of Ca2+in mitochondria was increased after RCN1 depletion,followed by reduction in the MMP and release of cytochrome c from mitochondria to the cytoplasm in RKO and SW480 ***,it was demonstrated that IP3R1 mediates the effect of RCN1 on apoptosis i

关键词： Reticulocalbin 1 Unfolded protein response IP3R1 Colorectal cancer

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Analysis of large datasets for identifying molecular targets in intestinal polyps and metabolic disorders

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BIOCELL 2024年第3期48卷 415-429页

作者： SHAN OU YUN XU QINGLAN LIU TIANWEN YANG WEI CHEN XIU YUAN XIN ZUO PENG SHI JIE YAO Department of Gastroenterology The First Affiliated Hospital of Chongqing Medical and Pharmaceutical CollegeChongqingChina

Background:The interrelation between intestinal polyps,metabolic syndrome(MetS),and colorectal cancer(CRC)is a critical area of *** research focuses on pinpointing potential molecular targets to understand the link between intestinal polyp formation,metabolic irregularities,and CRC ***:We examined clinical samples from patients with intestinal polyps coexisting with MetS and compared them with samples from patients with standard intestinal *** sequencing and public database analysis were employed to identify significant pathways and *** targets were then validated through immunohistochemistry(IHC).Following the RNA interference of key target expression,a series of experiments,including the cell counting kit-8 assay,colony formation,wound healing,and Transwell assays,were ***:Comparative analysis revealed 75 up-regulated and 61 down-regulated differentially expressed genes(DEGs)in the MetS polyp group *** *** encyclopedia of genes and genomes(KEGG)pathway enrichment suggested these DEGs were primarily associated with cell cycle and *** with comparative toxicogenomics database(CTD)and the cancer genome atlas(TCGA)databases highlighted 44 key CRC-related *** interaction networks indicated connections of purkinje cell protein 4(PCP4),olfactomedin 1(OLFM1),fibronectin 1(FN1),and transforming growth factor beta 3(TGF-β3)with the mitogen-activated protein kinase(MAPK)*** correlation studies suggested higher risk associations with FN1,PCP4,and TGF-β3,while OLFM1 was identified as a lower risk *** analysis revealed a decrease in OLFM1 in MetS-associated intestinal *** interference with OLFM1 in polyp epithelial cells,there was a significant enhancement in cell proliferation,colony formation,and cell migration and invasion ***:Our study highlights a significant decrease in OLFM1 expression in MetS-associated intestinal

关键词： Colorectal cancer Metabolic syndrome Intestinal polyp OLFM1 Exosome

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NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

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Opto-Electronic Advances 2024年第6期7卷 58-73页

作者： Ziqing Xu Yakun Kang Jie Zhang Jiajia Tang Hanyao Sun Yang Li Doudou He Xuan Sha Yuxia Tang Ziyi Fu Feiyun Wu Shouju Wang Laboratory of Molecular Imaging Department of RadiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Breast Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Women&Children Research Center The First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune *** these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS *** not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor *** in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/*** such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

关键词： photothermal therapy photodynamic therapy nitric oxide reactive nitrogen species triple-negative breast cancer immune response nanoreactor

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One-year results for myopia control of orthokeratology with different back optic zone diameters: a randomized trial using a novel multispectral-based topographer

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 324-330页

作者： Wen-Ting Tang Xiang-Ning Luo Wen-Jing Zhao Jia Liao Xin-Yue Xu Hui-Dan Zhang Li Zhang Department of Ophthalmology the First Affiliated Hospital of Chengdu Medical CollegeChengdu Medical CollegeChengdu 610500Sichuan ProvinceChina

AIM:To present the 1-year results of a prospective cohort study investigating the efficacy,potential mechanism,and safety of orthokeratology(ortho-k)with different back optic zone diameters(BOZD)for myopia control in ***:This randomized clinical study was performed between Dec.2020 and *** were randomly assigned to three groups wearing ortho-k:5 mm BOZD(5-MM group),5.5 mm BOZD(5.5-MM group),and 6 mm BOZD(6-MM group).The 1-year data were recorded,including axial length,relative peripheral refraction(RPR,measured by multispectral refractive topography,MRT),and visual *** contrast sensitivity(CS)was evaluated by CSV-1000 instrument with spatial frequencies of 3,6,12,and 18 cycles/degree(c/d);the corneal higher-order aberrations(HOAs)were measured by iTrace aberration *** one-way ANOVA was performed to assess the differences between the three *** correlation between the change in AL and RPR was calculated by Pearson’s correlation ***:The 1-year results of 20,21,and 21 subjects in the 5-MM,5.5-MM,and 6-MM groups,respectively,were *** were no statistical differences in baseline age,sex,or ocular parameters between the three groups(all P>0.05).At the 1-year visit,the 5-MM group had lower axial elongation than the 6-MM group(0.07±0.09 vs 0.18±0.11 mm,P=0.001).The 5-MM group had more myopic total RPR(TRPR,P=0.014),with RPR in the 15°–30°(RPR 15–30,P=0.015),30°–45°(RPR 30–45,P=0.011),temporal(RPR-T,P=0.008),and nasal area(RPR-N,P<0.001)than the 6-MM *** 15–30 in the 5.5-MM group was more myopic than that in the 6-MM group(P=0.002),and RPR-N in the 5-MM group was more myopic than that in the 5.5-MM group(P<0.001).There were positive correlations between the axial elongation and the change in TRPR(r=0.756,P<0.001),RPR 15–30(r=0.364,P=0.004),RPR 30–45(r=0.306,P=0.016),and RPR-N(r=0.253,P=0.047).The CS decreased at 3 c/d(P<0.001),and the corneal HOAs increased in the 5-MM group(P=0.030).CONCL

关键词： relative peripheral refraction orthokeratology myopia back optic zone diameter axial length multispectral refractive topography

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Musculoskeletal ultrasound to evaluate the efficacy of acupuncture: a review

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Journal of Traditional Chinese Medicine 2024年第3期44卷 629-632页

作者： WANG Dingyue YU Yana WANG Yiyuan ZHANG Zhen Department of Ultrasound the First Affiliated Hospital of China Medical University

Acupuncture is a typical example of Traditional Chinese Medicine and has been used in China for hundreds of years to treat a wide range of illnesses. However, in the clinic, issues and deficiencies were primarily seen in four areas: loss of accuracy in the operation process; difficulty understanding the depth of acupuncture; difficulty using reinforcing and reducing techniques; and lack of a clear dynamic effect of acupuncture points following acupuncture. Musculoskeletal ultrasonography may quantitatively evaluate the acupuncture location and display the distribution of small nerves near and within the fascia of the acupuncture point in real time. The subjects were asked how they felt about receiving Qi when the needle body reached different depths and different tissues. The Qi obtained from an acupuncture point and the connective tissue of the fascia can be further understood by combining the physiological response of the acupuncture point with the anatomical structure,which offers a new method for defining the nature of the acupuncture point and standardizing the acupuncture point.

关键词： acupuncture De Qi dynamic effect musculoskeletal ultrasound visualization

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OSMR is a potential driver of inflammation in amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第11期19卷 2513-2521页

作者： Wenzhi Chen Shishi Jiang Shu Li Cheng Li Renshi Xu Department of Neurology Jiangxi Provincial People’s HospitalXiangya Hospital Jiangxi Hospital of Central South UniversityThe Clinical College of Nanchang Medical CollegeThe First Affiliated Hospital of Nanchang Medical CollegeNanchangJiangxi ProvinceChina

Amyotrophic lateral sclerosis is a neurodegenerative disease,and the molecular mechanism underlying its pathology remains poorly ***,inflammation is known to play an important role in the development of this *** identify driver genes that affect the inflammatory response in amyotrophic lateral sclerosis,as well as potential treatment targets,it is crucial to analyze brain tissue samples from patients with both sporadic amyotrophic lateral sclerosis and C9orf72-related amyotrophic lateral ***,in this study we used a network-driven gene analysis tool,NetBID2.0,which is based on SJARACNe,a scalable algorithm for the reconstruction of accurate cellular networks,to experimentally analyze sequencing data from patients with sporadic amyotrophic lateral *** results showed that the OSMR gene is pathogenic in amyotrophic lateral sclerosis and participates in the progression of amyotrophic lateral sclerosis by mediating the neuroinflammatory ***,there were differences in OSMR activity and expression between patients with sporadic amyotrophic lateral sclerosis and those with C9orf72-related amyotrophic lateral *** findings suggest that OSMR may be a diagnostic and prognostic marker for amyotrophic lateral sclerosis.

关键词： amyotrophic lateral sclerosis driver neuroinflammation OSMR C9ORF72 neurodegenerative disease pathogenesis oxidative stress protein misfolding mitochondrial dysfunction

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