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Nanomedicine integrating the lipidic derivative of 5-fluorouracil,miriplatin and PD-L1 si RNA for enhancing tumor therapy

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Chinese Chemical Letters 2024年第6期35卷 385-391页

作者： An Lu Yuhao Guo Yi Yan Lin Zhai Xiangyu Wang Weiran Cao Zijie Li Zhixia Zhao Yujie Shi Yuanjun Zhu Xiaoyan Liu Huining He Zhiyu Wang Jian-Cheng Wang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Tianjin Key Laboratory on Technologies Enabling development of clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China department of Immuno-oncology The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011China department of Pharmacy Clinical Trial Research CenterChina-Japan Friendship HospitalBeijing 100029China Laboratory of innovative formulations and pharmaceutical excipients Ningbo Institute of Marine MedicinePeking UniversityNingbo 315832China

Immunosuppressive microenvironments present critical problems in clinical *** regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)with chemotherapeutics has been applied *** this study,miriplatin(MiPt),the lipidic derivative of 5-fluorouracil(Fu-OA),as well as the programmed death ligand 1(PD-L1)target si RNA(siPD-L1)were integrated into Lip-Pt/Fu@siPD-L1 nanoparticles(NPs)for *** vitro results showed that Lip-Pt/Fu@siPD-L1 NPs could exhibit effective siRNA gene silencing and promote the phagocytosis of tumor cells by ***,in vivo results revealed that LipPt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of Mi Pt,5-fluorouracil,and Lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor efficiency of Lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of Mi Pt and siPD-L1 based on the inhibition of CD47 expression and the downregulation of PD-L1 in tumor cells,which elicited a robust anti-tumor immune response through the activation of macrophage phagocytosis and immune checkpoint *** Lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.

关键词： Chemo-immunotherapy Immune checkpoint inhibition Gene silencing Miriplatin Macrophage phagocytosis Nanotechnology

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Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

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Neural Regeneration Research 2024年第3期19卷 642-649页

作者： Xiuling Tang Tao Yan Saiying Wang Qingqing Liu Qi Yang Yongqiang Zhang Yujiao Li Yumei Wu Shuibing Liu Yulong Ma Le Yang Precision Pharmacy&Drug development Center Department of PharmacyTangdu HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina department of clinical Pharmacy Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu ProvinceChina department of Pharmacology School of PharmacyAir Force Medical UniversityXi’anShaanxi ProvinceChina department of Anesthesiology The First Medical Center of Chinese PLA General HospitalBeijingChina department of Anatomy Histology and Embryology and K.K.Leung Brain Research CentreAir Force Medical UniversityXi’anShaanxi ProvinceChina

β-Sitosterol is a type of phytosterol that occurs naturally in *** studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic *** we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced *** investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic *** addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its *** conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

关键词： apoptosis blood-brain barrier β-sitosterol cerebral ischemia/reperfusion injury cholesterol overload cholesterol transport endoplasmic reticulum stress ischemic stroke molecular docking NPC1L1

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miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1- containing AMPA receptors in a mouse model of Alzheimer’s disease

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Acta Pharmaceutica Sinica B 2024年第2期14卷 635-652页

作者： Man Luo Yayan Pang Junjie Li Lilin Yi Bin Wu Qiuyun Tian Yan He Maoju Wang Lei Xia Guiqiong He Weihong Song Yehong Du Zhifang Dong Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China department of Anatomy Basic Medical CollegeChongqing Medical UniversityChongqing 400016China Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouver BC V6T 1Z3Canada Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceZhejiang Clinical Research Center for Mental DisordersSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhou 325000China Institute for Brain Science and Disease of Chongqing Medical University Chongqing 400016China

Alzheimer ’s disease(AD) is a leading cause of dementia in the ***-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in ***,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively ***(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA ***,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model *** further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ *** importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

关键词： Alzheimer's disease MKP-1 miR-429-3p AMPAreceptor Learning and memory Long-term potentiation

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Celastrus orbiculatus Extract Inhibits Immune Inflammatory Thrombotic State of B-Lymphoma

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Chinese Journal of Integrative Medicine 2024年第11期30卷 1018-1026页

作者： ZHU Miao SHI Qing-qing NI Jun WU Wei SUN Xing SUN Mei XU Kai-lin LIU Yan-qing GU Jian GU Hao department of Hematology Clinical Medical Col ege Yangzhou University Yangzhou Institute of Hematology department of Hematology The Affiliated Hospital of Xuzhou Medical University department of Oncology The Affiliated Hospital of Yangzhou University Yangzhou University department of Neurology The Affiliated Brain Hospital of Nanjing Medical University

Objective:To investigate the inhibitory effect of Celastrus orbiculatus extracts（COE） on the proliferation of lymphoma cells and the immune regulation ability on inflammation and thrombophilia in ***:The 38B9 lymphoma cells were treated with COE（160μg/mL） and CTX（25 μmol/L）.The apoptosis rate and cell cycle of each group were detected by flow *** secretion of inflammatory factors,including interleukin（IL）-6,IL-10,and tumor necrosis factor α（TNF-α）,in cell supernatant was detected by enzyme-linked immunosorbent assay（ELISA）.In vivo,BALB/c mice were subcutaneously injected with 38B9 lymphoma cells to establish lymphoma ***(3 mg·kg-1·d-1) and CTX(40 mg-kg-1·d-1) were administered to the model mice,*** expression of plasma inflammatory factors（IL-6,IL-10 and TNF-α） and thrombus indexes,including D-dimer（D-D）,von Willebrand factor（vWF） and tissue factor（TF）,were detected by ELISA before tumor bearing（1 d）,after tumor formation（14 d） and after intervention（21 d）.PicoGreen dsDNA was used to detect the level of serum neutrophil extracellular traps（NETs）.Flow cytometry was used to detect the expression of platelet activation marker calcium-dependent lectin-like receptor 2（CLEC-2）.The tumor growth and survival of mice were ***:The 38B9 lymphoma cells were apoptotic after the intervention of COE and *** ratio of G2-M phase cells decreased in COE intervented cells compared with the control cells（P<0.05）,and S phase cells decreased in CTX intervented cells（P<0.05）.Also,the secretion level of IL-6 was significantly reduced after COE or CTX intervention（P<0.05）,and IL-10 was significantly increased（P<0.05）.Furthermore,the tumor mass was reduced,and the median survival time was longer in COE and CTX intervented tumor-bearing mice than in nonintervented *** significantly lower levels of TNF-α,IL-6,NETs,TF,DD and CLEC-2,as well as higher IL-10 were observed in COE and CTX treatment mice in comparision with the control mice（P

关键词： Celastrus orbiculatus extract immune regulation lymphoma murine lymphoma cells proliferation inhibition thrombotic state tumor inflammation

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Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+T Cell-Related Immune Genes

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Biomedical and Environmental Sciences 2024年第6期37卷 581-593页

作者： Nani Li Xiaoting Qiu Jingsong Xue Limu Yi Mulan Chen Zhijian Huang department of Medical Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014FujianChina department of Breast Surgical Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014FujianChina Departmen of Pathology Shenzhen Longhua Maternity and Child Healthcare HospitalShenzhen 518109GuangdongChina

Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment ***8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing *** leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to *** Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC *** the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T ***,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic *** accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)***,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic ***,we investigated the potential underlying biological pathways that contribute to divergent treatment *** We successfully developed a model capable of predicting the prognosis of patients with *** areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,*** this risk model,we stratified the samples into high-and low-risk *** KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine ***,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores,indicating that o

关键词： Breast Cancer Immunotherapy Prognosis CD8+T cells PD-L1

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Coinfection of SARS-CoV-2 Omicron variant and other respiratory pathogens in children

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World Journal of Pediatrics 2024年第1期20卷 92-96页

作者： Wei Li Bing-Han Wang Bao-Hai Chen Yi Sun Lin Li Wen-Qing Xiang Ahmed Faisal Ali Lin-Xuan Su Hai-Yan Mao Hong-Qiang Shen Qiang Shu department of clinical Laboratory Children's HospitalNational Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhouChina School of Public Health Zhejiang University School of MedicineHangzhouChina department of Information Center Children's HospitalZhejiang University School of MedicineHangzhouChina Zhejiang Provincial Center for Disease Control and Prevention HangzhouChina department of Thoracic&Cardiovascular Surgery Children's HospitalNational Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhouChina

Since the outbreak of coronavirus disease 2019(COVID-19),the entire world has been affected by the epidemic[1,2].On November 9,2021,a variant of the novel coronavirus B.1.1.529 was detected for the first time from case samples in South *** Omicron strain spread and mutated significantly *** variant has the characteristics of escape immunity,which can induce relatively extreme disease and reduce the neutralization of antibodies in vaccinators,and is more likely to be reinfected[3,4].The clinical presentation of severe acute respiratory syndrome coronavirus 2(SARSCoV-2)in children has mild symptoms and a lower risk of hospitalization and death.

关键词： respiratory immunity acute

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Electroacupuncture inhibits hippocampal oxidative stress and autophagy in sleep-deprived rats through the protein kinase B and mechanistic target of rapamycin signaling pathway

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Journal of Traditional Chinese Medicine 2024年第5期44卷 974-980页

作者： ZHENG Peng MENG Ying LIU Meijun YU Di LIU Huiying WANG Fuchun XU Xiaohong department of Neurology The Third Affiliated Clinical Hospital of Changchun University of Chinese Medicine Rehabilitation Medicine Academy Changchun University of Chinese Medicine

OBJECTIVE: To investigate the effects of acupuncture on learning and memory impairment, oxidative stress and autophagy induced by sleep depriv ation in rats, and to analyze the related ***: Thirty Wistar rats were randomly divided into a normal group, sleep deprivation group and acupuncture group. The rat model of sleep deprivation was established by a modified multiplatform sleep deprivation *** Baihui(GV20), Shenmen(HT7) and Sanyinjiao(SP6)acupoints of rats were located to give electroacupuncture(density wave, frequency 20 Hz, intensity 1 mA) to maintain the needle feeling, and to keep the needle for 15min and continuous acupuncture for 7 d. The spatial learning and memory abilities of the rats were detected by the water maze test. The content of malondialdehyde(MDA) and the activities of superoxide dismutase(SOD)and glutathione peroxidase(GPX) in the brain were detected by an assay kit, and the autophagy related proteins light chain 3 alpha(LC3A), light chain 3 beta(LC3B) and Beclin 1 and the activation of the protein kinase B(PKB/AKT) and mechanistic target of rapamycin(mTOR) signaling pathway in the rat's brain were detected by Western ***: Compared with the normal group, the time spent in the target quadrant(P < 0.05) and the number of times entering the target quadrant(P < 0.05) in the rats of sleep deprivation group were significantly reduced, and the content of MDA was significantly increased(P < 0.01),while the activities of SOD and GPX(P < 0.01) in the brain were significantly decreased, and LC3A Ⅱ/Ⅰ, LC3B Ⅱ/Ⅰand Beclin 1 increased significantly(P < 0.01), while pAKT(ser473)/AKT, p-mTOR(ser2448)/mTOR and pp70s6K(thr389)/p70S6 decreased significantly(P < 0.01).Compared with the sleep deprivation group, the time spent in the target quadrant and the times of entering the target quadrant(P < 0.05) in the rats of acupuncture group after 7 d of treatment were significantly increased,Additionally, the content of MDA was signific

关键词： acupuncture autophagySupporting information memory and learning tests oxidative stress sleep deprivation

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The association and underlying mechanism of the digit ratio(2D:4D)in hypospadias

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Asian Journal of Andrology 2024年第4期26卷 356-365页

作者： Yu Ding Zu-Quan Chen Wen-Feng Pan Hao-Jie Chen Min Wu Yi-Qing Lyu Hua Xie Yi-Chen Huang Zhong-Zhong Chen Fang Chen department of Urology Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China Urogenital development Research Center Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China clinical Research Center for Hypospadias Pediatric CollegeShanghai Jiao Tong University School of MedicineShanghai 200062China.

The second-to-fourth digit(2D:4D)ratio is thought to be associated with prenatal androgen ***,the relationship between the 2D:4D ratio and hypospadias is poorly understood,and its molecular mechanism is not *** this study,by analyzing the hand digit length of 142 boys with hypospadias(23 distal,68 middle,and 51 proximal)and 196 controls enrolled in Shanghai Children’s Hospital(Shanghai,China)from December 2020 to December 2021,we found that the 2D:4D ratio was significantly increased in boys with hypospadias(Pdevelopment of *** mechanistic explorations revealed that during the androgen-sensitive window,the downregulation of the androgen receptor(AR)caused by low testosterone levels,as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a(Wnt5a),Wnt5b,Smad family member 2(Smad2),and Smad3;mitochondrial function-related genes in cartilage such as AMP-activated protein kinase(AMPK)and nuclear respiratory factor 1(Nrf-1);and vascular development-related genes such as myosin light chain(MLC),notch receptor 3(Notch3),and sphingosine kinase 1(Sphk1),are responsible for the limitation of 4D growth,which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral *** study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism.

关键词： androgen receptor digit ratio(2D:4D) endochondral ossification hypospadias testosterone level

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Early detection of multiple endocrine neoplasia type 1: A case report

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World Journal of Gastroenterology 2024年第26期30卷 3247-3252页

作者： Jie-Hao Yuan Su Luo Ding-Guo Zhang Li-Sheng Wang department of Gastroenterology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan University)Shenzhen 518020Guangdong ProvinceChina

BACKGROUND Multiple endocrine neoplasias(MENs)are a group of hereditary diseases invol-ving multiple endocrine glands,and their prevalence is *** type 1(MEN1)has diverse clinical manifestations,mainly involving the parathyroid glands,gastrointestinal tract,pancreas and pituitary gland,making it easy to miss the clinical *** SUMMARY We present the case of a patient in whom MEN1 was detected early.A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the *** tests at admission revealed hypercalcemia and hypophosphatemia,and emission computed tomography of the parathyroid glands revealed a hy-perfunctioning parathyroid *** findings suggested a duodenal bulge and *** endoscopy revealed a hypoechoic lesion in the duodenal *** blood tests revealed elevated levels of serum *** was performed,and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal *** time from onset to the definitive diagnosis of MEN1 was only approximately 1 *** For patients who present with gastrointestinal symptoms accompanied by hyper-calcemia and hypophosphatemia,clinicians need to be alert to the possibility of MEN1.

关键词： Multiple endocrine neoplasia type 1 Gastrointestinal symptoms Hypercal-cemia Early detection Case report

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Small molecular decoys in Alzheimer's disease

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Neural Regeneration Research 2024年第8期19卷 1658-1659页

作者： Sho Oasa Valentina L.Kouznetsova Igor F.Tsigelny Lars Terenius department of clinical Neuroscience Center for Molecular MedicineKarolinska InstitutetStockholmSweden San Diego Supercomputer Center University of California San DiegoLa JollaCAUSA department of Neurosciences University of California San DiegoLa JollaCAUSA department of clinical Neuroscience Karolinska University HospitalKarolinska InstitutetStockholmSweden

Recent progress in the treatment of Alzheimer’s disease(AD)using antibodies against amyloid sustains amyloid generation as a key process in *** formation starts with two amyloidbeta(Aβ)molecules interacting(dimer formation)followed by an accelerating build-up of socalled protofibrils,which turn into fibrils,which accumulate in the characteristic plaques.

关键词： Alzheimer decoy Aβ

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