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Distribution of Traditional Chinese medicine syndromes in diabetic kidney disease chronic kidney disease 1-5: a correlation study

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Journal of Traditional Chinese medicine 2024年第3期44卷 572-580页

作者： LI Shuang DUAN Shuwei DONG Zheyi QU Yilun LUO Yayong KE Jianghua WANG Conghui PENG Yangzhi ZHOU Xuefeng CHEN Xiangmei Department of Nephrology First Medical Center of Chinese PLA General HospitalNephrology Institute of the Chinese People's Liberation ArmyNational Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijing 100853China School of clinical medicine Guangdong Pharmaceutical Universityjuangzhou510006China Basic Medical College Chengdu University of Traditional Chinese MedicineChengdu610075China

OBJECTIVE: To analyze the distribution of Traditional Chinese medicine(TCM) syndromes in patients with diabetic kidney disease(DKD) and its related ***: We enrolled 435 patients with DKD, who were not undergoing dialysis, admitted to the Department of Nephrology, First Medical center, Chinese PLA General Hospital from April 2020 to August *** of their TCM syndromes and related factors was carried ***: The 435 patients included 109, 117, 86, and 123 chronic kidney disease(CKD) 1-2, CKD3, CKD4, and CKD5 cases, respectively. With the progression of CKD1-5, the proportion of Yin deficiency and dry heat syndrome,and that of Qi and Yin deficiency syndrome showed a downward trend, whereas the proportion of spleen-kidney Yang deficiency, blood deficiency, blood stasis, water stagnation, and phlegm turbidity syndromes showed an upward trend;the differences were statistically significant(P < 0.05). Multivariate logistic regression analysis showed that Yin deficiency and dry heat syndrome was positively correlated with hemoglobin [odds ratio(OR) =1.022, P = 0.005], albumin(OR = 1.058, P = 0.006), and estimated glomerular filtration rate(eGFR)(OR = 1.020,P < 0.001) but negatively correlated with male sex(OR =0.277, P = 0.004). Qi and Yin deficiency syndrome was positively correlated with albumin(OR = 1.056, P < 0.001)and eGFR(OR = 1.008, P = 0.022) but negatively correlated with age(OR = 0.977, P = 0.023). Liver-kidney Yin deficiency syndrome was positively correlated with age(OR = 1.028, P = 0.021) and glycosylated hemoglobin(OR = 1.223, P = 0.007) but negatively correlated with total cholesterol(OR = 0.792, P = 0.006).Spleen-kidney Yang deficiency syndrome was negatively correlated with hemoglobin(OR = 0.977, P < 0.001),albumin(OR = 0.891, P < 0.001), and eGFR(OR = 0.978,P < 0.001) but positively correlated with high density lipoprotein(OR = 3.376, P = 0.001). CONCLUSION: With CKD1-5 progression, TCM syndromes changed from Yin deficiency and dry

关键词： diabetic nephropathies syndrome and complex hemoglobins albumins glomerular filtration rate correlation of data

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Network Pharmacology Based Elucidation of Molecular Mechanisms of Laoke Formula for Treatment of Advanced Non-Small Cell Lung Cancer

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Chinese Journal of Integrative medicine 2024年第11期30卷 984-992页

作者： FENG Yu-yu LIU Jin-feng XUE Yang LIU Dan WU Xiong-zhi Department of Nursing Tangshan Vocational and Technical College School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine Department of Oncology Tianjin Medical University General Hospital Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for China Tianjin Nankai Hospital Tianjin Medical University

Objective: To explore the specific pharmacological molecular mechanisms of Laoke Formula(LK)on treating advanced non-small cell lung cancer(NSCLC) based on clinical application, network pharmacology and experimental validation. Methods: Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of Chinese medicine(CM) treatment in 296 patients with NSCLC in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2015. The compounds of LK were screened using the Traditional Chinese medicine Systems Pharmacology Database and Analysis Platform, and the corresponding targets were performed from Swiss Target prediction. NSCLC-related targets were obtained from Therapeutic Target Database and Comparative Toxicogenomics Database. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction(PPI) network analysis, respectively. Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) enrichment analysis were used to predict the potential signaling pathways involved in the treatment of advanced NSCLC with LK. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, A549 cell proliferation and migration assay were used to evaluate the antitumor activity of LK. Western blot was used to further verify the expression of key target proteins related to the predicted pathways. Results: Kaplan-Meier survival analysis showed that the overall survival of the CM group was longer than that of the non-CM group(36 months vs.26 months), and COX regression analysis showed that LK treatment was an independent favorable prognostic factor(P=0.027). Next, 97 components and 86 potential targets were included in the network pharmacology, KEGG and GO analyses, and the results indicated that LK was associated with proliferation and apoptosis. Moreover,molecular docking revealed a good binding affinity between the key

关键词： Chinese medicine LaoKe Formula anti-tumor network pharmacology non-small cell lung cancer

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Black phosphorus quantum dots induce myocardial inflammatory responses and metabolic disorders in mice

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Journal of Environmental Sciences 2024年第3期137卷 53-64页

作者： Chao Shen Xiaoyan Ding Jinpeng Ruan Fengkai Ruan Weiping Hu Jiyi Huang Chengyong He Yi Yu Zhenghong Zuo Department of Nephrology State Key Laboratory of Cellular Stress BiologySchool of Life SciencesFaculty of Medicine and Life SciencesFujian Clinical Research Center for Chronic Glomerular DiseaseThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China

As an ultrasmall derivative of black phosphorus(BP)sheets,BP quantum dots(BP-QDs)have been effectively used in many ***,information on the cardiotoxicity induced by BP-QDs remains *** aimed to evaluate BP-QD-induced cardiac toxicity in *** examination of heart tissue sections was *** sequencing,real-time quantitative PCR(RT–qPCR),western blotting,and enzyme-linked immunosorbent assay(ELISA)assays were used to detect the m RNA and/or protein expression of proinfammatory cytokines,nuclear factor kappa B(NF-κB),phosphatidylinositol3 kinase-protein kinase B(PI3K-AKT),peroxisome proliferator-activated receptor gamma(PPARγ),and glucose/lipid metabolism pathway-related *** found that heart weight and heart/body weight index(HBI)were significantly reduced in mice after intragastric administration of 0.1 or 1 mg/kg BP-QDs for 28 *** addition,obvious infammatory cell infiltration and increased cardiomyocyte diameter were observed in the BP-QD-treated *** expression of proinfammatory cytokines and genes related to the NF-κB signaling pathway further confirmed that BP-QD exposure induced infammatory *** addition,BP-QD treatment also affected the PI3K-AKT,PPARγ,thermogenesis,oxidative phosphorylation,and cardiac muscle contraction signaling *** expression of genes related to glucose/lipid metabolism signaling pathways was dramatically affected by BP-QD exposure,and the effect was primarily mediated by the PPAR signaling *** study provides new insights into the toxicity of BP-QDs to human health.

关键词： BP-QDs Cardiac toxicity Infammatory responses NF-κB signaling pathway PPARγsignaling pathway Glucose/lipid metabolism

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Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 686-699页

作者： Junfen XU Mengyan TU Department of Gynecologic Oncology Women’s HospitalZhejiang University School of MedicineHangzhou 310006China Zhejiang Provincial clinical research center for Obstetrics and Gynecology Hangzhou 310006China

Objective:The present study used single-cell RNA sequencing(scRNA-seq)to characterize the cellular composition of ovarian carcinosarcoma(OCS)and identify its molecular ***:scRNA-seq was performed in resected primary OCS for an in-depth analysis of tumor cells and the tumor *** staining was used for *** scRNA-seq data of OCS were compared with those of high-grade serous ovarian carcinoma(HGSOC)tumors and other OCS ***:Both malignant epithelial and malignant mesenchymal cells were observed in the OCS patient of this *** identified four epithelial cell subclusters with different biological *** them,epithelial subcluster 4 presented high levels of breast cancer type 1 susceptibility protein homolog(BRCA1)and DNA topoisomerase 2-α(TOP2A)expression and was related to drug resistance and cell *** analyzed the interaction between epithelial and mesenchymal cells and found that fibroblast growth factor(FGF)and pleiotrophin(PTN)signalings were the main pathways contributing to communication between these ***,we compared the malignant epithelial and mesenchymal cells of this OCS tumor with our previous published HGSOC scRNA-seq data and OCS *** the epithelial subclusters in the OCS tumor could be found in the HGSOC ***,the mesenchymal subcluster C14 exhibited specific expression patterns in the OCS tumor,characterized by elevated expression of cytochrome P450 family 24 subfamily A member 1(CYP24A1),collagen type XXIIIα1 chain(COL23A1),cholecystokinin(CCK),bone morphogenetic protein 7(BMP7),PTN,Wnt inhibitory factor 1(WIF1),and insulin-like growth factor 2(IGF2).Moreover,this subcluster showed distinct characteristics when compared with both another previously published OCS tumor and normal ovarian ***:This study provides the single-cell transcriptomics signature of human OCS,which constitutes a new resource for elucidating OCS diversity.

关键词： Ovarian carcinosarcoma Single-cell RNA sequencing(scRNA-seq) Tumor heterogeneity

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Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses

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Genes & Diseases 2024年第4期11卷 327-339页

作者： Li Chen Wenyan Ren Hong Lei Jiayu Wang Haiying Que Dandan Wan Aqu Alu Dandan Peng Minyang Fu Weiqi Hong Yuhe Huang Xiangrong Song Guangwen Lu Xiawei Wei Laboratory of Aging research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants has decreased the efficacy of SARs-CoV-2 vaccines in containing coronavirus disease 2019(CoVID-19)over time,and booster vaccination strategies are urgently necessitated to achieve sufficient *** immunization can improvemucosal immunity,offer-ing protection against the infection and sustaining the spread of *** this study,an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum,nasal lavage fluid,and bronchoal-veolar lavage fluid compared with only two doses of mRNA *** intranasal boosting with the RBD-HR vaccine,the levels of serum neutralizing antibodies against prototype and variant strains of SARS-Cov-2 pseudoviruses weremarkedly higher than those in mice receiving mRNA vaccine alone,and intranasal boosting with the RBD-HR vaccine also inhibited the bind-ing of RBD to hACE2 ***,the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+dendritic cells in the respiratory mucosa,and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs,including mediastinal lymph nodes,inguinal lymph nodes,and ***,these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locallyandsystemically.

关键词： Heterologous immunization Intranasal immunization mRNA vaccine SARS-CoV-2 Subunitprotein vaccine

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Activation of cerebral Ras-related C3 botulinum toxin substrate(Rac) 1 promotes post-ischemic stroke functional recovery in aged mice

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Neural Regeneration research 2024年第4期19卷 881-886页

作者： Fan Bu Jia-Wei Min Md Abdur Razzaque Ahmad El Hamamy Anthony Patrizz Li Qi Akihiko Urayama Jun Li Department of Neurology University of Texas Health Science Center Department of Neurology&Psychology The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine

Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain *** is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following *** evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced *** studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke ***,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic *** found that as mice aged,Rac1 expression declined in the *** overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–*** was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by *** a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial ***,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after *** work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.

关键词： aging angiogenesis brain-derived neurotrophic factor(BDNF) cerebral ischemia cognitive recovery neurite Pak1 Rac1 sensorimotor recovery

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Variations, effectiveness and its associated factors of a nationwide web-based hypertension management training project in China: insights from a government-led campaign for 1.2 million lay health workers

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Journal of Geriatric Cardiology 2024年第7期21卷 733-750页

作者： Wei WANG Hai-Bo ZHANG Jia-Min LIU Yan LI Na TIAN Lei YAN Jin-Xiao SONG Mei-Li LI Yue PENG Jing LI National Primary Health Care Hypertension Management Office National Clinical Research Center for Cardiovascular DiseasesNHC Key Laboratory of Clinical Research for Cardiovascular MedicationsFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

OBJECTIVES To evaluate the effectiveness of a large-scale,web-based,in-service hypertension management training project among lay health workers(LHWs) at primary care health(PHC) settings in China,and to examine the factors contributing to the variations of *** We used data from a web-based national hypertension management training project implemented in 2018,it was designed to facilitate LHWs to learn,understand,and apply the relevant knowledge and skills in hypertension management through providing training courses by use of the web-based platform with unified *** LHWs were required to participate in the exams before and after training to acquire scores for the use of evaluating their performance of hypertension management *** first used descriptive analysis to present the variations of effectiveness in hypertension management knowledge among LHWs by important ***,we used multilevel logistic regression to examine the individual and regional factors contributing to the variations and quantify the magnitude of how these factors affected training *** There were 1,208,610 LHWs who completed training and were ***,the scores of LHWs increased significantly from 62.87 ± 21.14 out of 100 in the pre-test to 88.30 ± 11.31 in the post-test by 25.43(95% confidence interval[CI]:25.40-25.47).Training contents involved in antihypertensive medication showed the lowest score(54.36) in the pre-test and soared the most after training,up to 84.22 by 54.94%.Individual factors associated with disparities in the knowledge of hypertension management decreased substantially after training,which included sex,age,education,practice type,professional level,and hierarchy of working *** variations were shown at the provincial level,with the majority of them being explained by factors at the regional *** Accessible web-based training modality,government efforts,accompa

关键词： hypertension workers nationwide

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clinical prediction of insufficient vaults after implantable collamer lens implantation

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1300-1306页

作者： Jun Zhu Dan Cheng Xue-Ying Zhu Fen-Fen Li Ye Yang Yu-Feng Ye National clinical research center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina

AIM:To determine the factors related to preoperative ocular characters that are predictive of insufficient vault(<250μm)after implantable collamer lens(ICL V4c;STAAR Surgical)***:The participants underwent ICL surger... 详细信息

AIM:To determine the factors related to preoperative ocular characters that are predictive of insufficient vault(preoperative biometric parameters and clinical outcomes were compared between the two *** relationship between the 3-month vault values and preoperative ocular parameters were evaluated by Generalized estimating ***:Sixteen(23 eyes)and 36 patients(63 eyes)were in the low and normal vault groups,*** implantation procedures were uneventful with no cataract formation in the early postoperative *** sulcusto-sulcus lens rise(STSL)and iris ciliary angle(ICA)were correlated with vault at 3mo after *** 0.1 mm increase in STSL was associated with 38.9μm decrease in the postoperative 3-month vault.A rise of 1 degree in ICA is associated with a reduction of 4μm in ***:Eyes with a narrow ciliary sulcus are associated with a higher rate of low vault after ICL implantation,suggesting a need for adjustments to the ICL size in these *** the characteristics of the ciliary sulcus contributes valuable information to predict low vault after surgery.

关键词： insufficient vault implantable collamer lens ciliary body posterior chamber

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GRK2 inhibits Flt-1^(+)macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2024年第1期14卷 241-255页

作者： Xuezhi Yang Yingjie Zhao Qi Wei Xuemin Zhu Luping Wang Wankang Zhang Xiaoyi Liu Jiajie Kuai Fengling Wang Wei Wei Institute of clinical Pharmacology Anhui Medical UniversityKey Laboratory of Anti-Inflammatory and Immune MedicineAnhui Collaborative Innovation Center of Anti-Inflammatory and Immune MedicineMinistry of EducationHefei 230032China Department of clinical Pharmacology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China

Rheumatoid arthritis(RA)is an autoimmune disease with a complex ***-derived macrophages(MDMs)infiltration are associated with RA *** have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor ***,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been ***,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)*** inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)*** experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting *** further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγ***,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 ***,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and ***,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular *** GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.

关键词： GRK2 Monocyte-derived macrophages Rheumatoid arthritis PPARg Flt-1

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Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai Huang Wei-Lin Jin center for clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First Affiliated Hospital of Guizhou University of Traditional Chinese medicine Guiyang 550001PR China School of clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global *** significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic ***,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer *** promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved *** repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety *** light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat *** describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor *** addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug *** also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy *** conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

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