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Integration of network pharmacology and bone marrow mesenchymal stem cells experimental research to reveal the molecular mechanisms for Hai Honghua medicinal liquor against osteoporosis

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Integrative Medicine Discovery

Integrative Medicine Discovery 2024年第3期8卷 1-11页

作者： Die Qian Chi Xu Cheng-Xun He Mei-Yan Li juan guo Hong Zhang School of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China Department of Orthopedics Longquan Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610017China Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicineShanghai 201203China

Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to promote fracture healing.However,the underlying mechanisms of HHML in the treatment of osteoporosis(OP)are still unclear.Methods:Firstly,Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to screen the targets of the active compounds of HHML.At the same time,OP targets were identified through GeneCards,Online Mendelian Inheritance in Man,DisGeNET,Therapeutic Target Database,Comparative Toxicogenomics Database and Human Phenotype Ontology databases.Next,protein-protein interaction and pathway networks were constructed for compound-disease common targets,and core targets and compounds were screened for molecular docking.Furthermore,rat bone marrow mesenchymal stem cells were extracted as model cells,and the osteogenic effects of HHML were verified via in vitro experiments.Results:Total of 343 common targets of HHML-OP and the top 10 target proteins in the protein-protein interaction network are TP53,AKT1,STAT3,HSP90AA1,ESR1,TNF,IL6,MAPK1,MAPK3 and MAPK8.Enrichment analysis yielded that the key molecular pathway was the PI3K/Akt signaling pathway.Molecular docking analysis showed that baicalein,erysodienone and naringenin docked with the target proteins AKT1,STAT3 and TP53,respectively,with low binding energy and high affinity.In addition,In vitro experiments demonstrated that HHML promoted the proliferation of bone marrow mesenchymal stem cells;compared with the control group,HHML-treated cells showed enhanced alkaline phosphatase staining,promoted the expression of OCN,RUNX2,BSP,and COL1 mRNAs as well as the expression of PI3K and AKT phosphorylated proteins.Secondly,the expression of target proteins revealed that HHML promoted the phosphorylation of STAT3 protein and inhibited the expression of P53.Conclusions

关键词： Hai Honghua medicinal liquor osteoporosis network pharmacology molecular docking PI3K/AKT signal pathway

Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 687-698页

作者： juan Lin Zhu-Feng Chen guo-Dong guo Xin Chen Shengli Clinical Medical College Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina Department of Pathology Fujian Provincial HospitalFuzhou 350001Fujian ProvinceChina Department of Internal Medicine Fujian Provincial HospitalFuzhou 350001Fujian ProvinceChina

BACKGROUND The Alcian blue(AB)and periodic acid Schiff(PAS)stains are representative mucus markers in gastric signet ring cell carcinoma(SRCC).They are low-cost special staining methods used to detect acidic mucus and neutral mucus,respectively.However,the clinical importance of the special combined AB and PAS stain is unclear.AIM To investigate AB expression,PAS expression and the AB-to-PAS(A/P)ratio in gastric SRCC patients and to assess patient prognosis.METHODS Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS,and signet ring cell positivity was assessed quantitatively.Immuno-histochemical staining for Ki67,protein 53(P53)and human epidermal growth factor receptor 2(HER2)was performed simultaneously.The cancer-specific survival(CSS)rate was estimated via Kaplan-Meier analysis.Cox proportional hazards models were used for univariate and multivariate survival analyses.RESULTS Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup(P0.5 group(P=0.042).Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter,lymph node metastasis,vessel carcinoma embolus,tumor stage,the A/P ratio and the expression of Ki67,P53 and the PAS.Cox multivariate regression analysis confirmed that low PAS expression[hazard ratio(HR)=3.809,95%confidence interval(CI):1.563-9.283,P=0.003]and large tumor diameter(HR=2.761,95%CI:1.086-7.020,P=0.033)were independent risk factors for poor prognosis.CONCLUSION A/P>0.5 is potentially a risk factor for prognosis,and low PAS expression is an independent risk factor in the prognosis of gastric SRCC.PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.

关键词： Alcian blue Periodic acid-Schiff Prognosis Gastric Signet ring cell carcinoma

C2-phenyl-substituted benzimidazolium-based covalent organic framework as efficient catalyst for CO_(2) conversion without solvents,metals,and cocatalysts

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Science China Chemistry 2024年第2期67卷 551-557页

作者： Zhenzhen Wu Jing Wang Lili Liu Shang guo juan Li Xianming Zhang Shanxi Institute for Functional Food Shanxi Agricultural UniversityTaiyuan030031China Institute of Crystalline Materials Shanxi UniversityTaiyuan030006China Key Laboratory of Interface Science and Engineering in Advanced Materials College of ChemistryTaiyuan University of TechnologyTaiyuan030024China

Covalent organic frameworks(COFs) are a potential platform for carbon dioxide(CO_(2)) conversion owing to their periodic permanent porosity,adjustable structure,and chemical stability.For good catalytic performance in CO_(2) conversion,collaborative multifunctions should be strategically integrated into the catalytic system design and construction.In this study,a four-in-one high-efficiency catalyst was synthesized and tested for CO_(2) cycloaddition to form cyclic carbonate.The obtained Tp-MPB-BrCOF had a high nitrogen content,which enhanced its CO_(2) affinity through substantial Lewis acid-base or dipole-quadrupole interactions;moreover,the acid(protons transferring from oxygen(–OH) to nitrogen(–NH)),hydrogen bond donor(hydroxyl group),and Br-(nucleophile group) served as three active sites,further improving the catalyst activity.These results provide a basis for designing efficient and stable CO_(2)-conversion catalysts.

关键词： covalent organic framework C2-phenyl-substituted benzimidazolium CO_(2)conversion four-in-one catalyst

Simultaneous removal of 1,2-dichlorobenzene and furan over Mn-Ce-Fe oxide catalyst:Catalytic activity and product analysis

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Journal of Rare Earths 2024年第5期42卷 972-979,I0006页

作者： juan Qiu Minghui Tang Yaqi Peng Xuanhao guo Shengyong Lu Jianhua Yan Taizhou Institute of Zhejiang University Taizhou 318000China State Key Laboratory for Clean Energy Utilization Institute for Thermal Power EngineeringZhejiang UniversityHangzhou 310027China

The Mn-Ce-Fe mixed oxide(MCFe)was prepared by co-precipitation and the catalytic performance was tested by using 1,2-dichlorobenzene(1,2-DCB)and furan as model molecules of PCDD/F.The effect of O_(2)concentration,SO_(2) and NO on the catalytic activity was studied.At 270℃,the MCFe oxide catalyst presents significant simultaneous removal efficiency of 75.25%and 100%for 1,2-DCB and furan,respectively.Brunauer-Emmett-Teller(BET)method(BET),X-ray diffraction(XRD),scanning electron microscopy(SEM),X-ray photoelectron spectroscopy(XPS),Fourier transform infrared spectroscopy(FTIR),H_2-temperature programmed reduction(H_(2)-TPR),NH_(3)-temperature programmed desorption(NH_3-TPD)and O_(2)-TPD were used to characterize the catalysts before and after the reaction.Competition tests suggest that the oxidation behavior of furan occurred prior to that of 1,2-DCB.According to the intermediate products detected by gas chromatography-mass spectrometry(GC-MS),the by-products include chlorinated hydrocarbons,long-chain hydrocarbons,ketone,etc.Possible catalytic oxidation reaction paths are proposed.

关键词： 1 2-dichlorobenzene Furan Catalytic oxidation Product analysis Rare earths

Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

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World Journal of Stem Cells 2024年第4期16卷 444-458页

作者： Cheng-Jin Ai Ling-juan Chen Li-Xuan guo Ya-Ping Wang Zi-Yi Zhao Department of Laboratory Medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Department of Ophthalmology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Central Laboratory Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Traditional Chinese Medicine Regulating Metabolic Diseases Key Laboratory of Sichuan Province Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

关键词： Leukemia stem cells Gossypol acetic acid Reactive oxygen species Mitochondrial dysfunction Interleukin 6/janus kinase 1/signal transducer and activator of transcription 3 signaling

Effects of ulinastatin combined with dexmedetomidine on cognitive dysfunction and emergence agitation in elderly patients who underwent total hip arthroplasty

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World Journal of Psychiatry 2024年第1期14卷 26-35页

作者： Qi-Fan Huo Li-juan Zhu Jian-Wei guo Yan-An Jiang Jing Zhao Department of Anesthesiology Shaanxi Provincial People’s HospitalXi’an 710068Shaanxi ProvinceChina

BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture increases.Hip fracture is a common type of fracture in older people.Total hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint function.AIM To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent THA.METHODS A total of 397 patients who underwent THA from February 2019 to August 2022.We conducted a three-year retrospective cohort study in Shaanxi Provincial People’s Hospital.Comprehensive demographic data were obtained from the electronic medical record system.We collected preoperative,intraoperative,and postoperative data.One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group.One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group.One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin group.The patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were evaluated.RESULTS There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(P<0.05).Compared with the Dex and ulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all P<0.05).Compared with those in the Dex and ulinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of the alertness/sedation score and Ramsay score of t

关键词： Ulinastatin Dexmedetomidine Postoperative cognitive dysfunction Inflammatory cytokines Total hip arthroplasty

Clinical Analysis and Mental Health Survey of Hemophilia Carriers:a Cross-sectional Study

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Current Medical Science 2024年第2期44卷 435-440页

作者： Wen WANG Li-juan JIANG Dong-yan CUI Ai ZHANG Xiong WANG Ai-guo LIU Qun HU Department of Pediatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Laboratory Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Hemophilia carriers(HCs),who are heterozygous for mutations in the clotting factor VIII/clotting factor IX gene(F8 or F9),may have a wide range of clotting factor levels,from very low,similar to afflicted males,to the upper limit of normal,and may experience mental health issues.The purpose of this study was to provide genetic information on mothers of hemophilia patients and to understand the clotting factor activity and phenotype of HCs.Additionally,we aimed to investigate the mental health status of HCs in China.Methods:A total of 127 hemophilia mothers,including 93 hemophilia A(HA)mothers and 34 hemophilia B(HB)mothers,were enrolled in this study.Long distance PCR,multiplex PCR,and Sanger sequencing were used to analyze mutations in F8 or F9.Coagulation factor activity was detected by a one-stage clotting assay.The Symptom Checklist 90(SCL-90,China/Mandarin version)was given to HCs at the same time to assess their mental health.Results:A total of 90.6%of hemophilia mothers were diagnosed genetically as carriers,with inversion in intron 22 and missense mutations being the most common mutation types in HA and HB carriers,respectively.The median clotting factor level in carriers was 0.74 IU/mL(ranging from 0.09 to 1.74 IU/mL)compared with 1.49 IU/mL(ranging from 0.93 to 1.89 IU/mL)in noncarriers,of which 14.3%of HCs had clotting factor levels of 0.40 IU/mL or below.A total of 53.8%(7/13)of HA carriers with low clotting factor levels(less than 0.50 IU/mL)had a history of bleeding,while none of the HB carriers displayed a bleeding phenotype.The total mean score and the global severity index of the SCL-90 for surveyed HCs were 171.00(±60.37)and 1.78(±0.59),respectively.A total of 67.7%of the respondents had psychological symptoms,with obsessive-compulsive disorder being the most prevalent and severe.The pooled estimates of all nine factors were significantly higher than those in the general population(P<0.05).Conclusions:The detection rate of gene mutations in hemophilia mothers was 90.6%,with a median cl

关键词： hemophilia A hemophilia B mutation carrier mental health

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

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Zoological Research 2024年第3期45卷 617-632页

作者： Jing-Hang Jiang Yi-Fu Wang Jie Zheng Yi-Ming Lei Zhong-Yuan Chen Yi guo Ya-Jie guo Bing-Qian guo Yu-Fang Lv Hong-Hong Wang juan-juan Xie Yi-Xuan Liu Ting-Wei Jin Bi-Qi Li Xiao-Shu Zhu Yong-Hua Jiang Zeng-Nan Mo Center for Genomic and Personalized Medicine Guangxi Collaborative Innovation Center for Genomic and Personalized MedicineGuangxi Key Laboratory for Genomic and Personalized MedicineGuangxi Medical UniversityNanningGuangxi 530021China Department of Urology First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530021China Reproductive Medicine Center Jingmen People’s HospitalJingChu University of Technology Affiliated Central HospitalJingmenHubei 448000China School of Computer Science and Engineering Yulin Normal UniversityYulinGuangxi 537000China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanningGuangxi 530021China Department of Pathology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China Department of Obstetrics and Gynecology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://***:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

关键词： Tree shrew Adrenal gland Dehydroepiandrosterone Genome-wide association studies Disease model

Interface optimization of graphene paper-Cu composite prepared by electrodeposition

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Journal of Iron and Steel Research(International) 2024年第1期31卷 64-73页

作者： Jing guo Hai-jing Wang Shuang-juan Liu Peng Zhang Jing-yu Tang Wei-yang Zhang Han-jie guo Peng-cheng Wang Cai Meng School of Metallurgical and Ecological Engineering University of Science and Technology BeijingBeijing100083China Institute of High Energy Physics Chinese Academy of SciencesBeijing100049China Advanced Technology and Materials Co. Ltd.Beijing100083China School of Nuclear Science and Technology University of Science and Technology of ChinaHefei230027AnhuiChina

A room-temperature electrodeposition method with an organic electrolyte was developed to fabricate a HNO3-pretreated graphene paper Cu(GP'-Cu)composite.To improve the interfacial bonding of GP'-Cu composite,magnetron sputtering technology was used to create a"sandwich"structural gradient GP'-Cu composite.The selection of the intermediate transition layer metal was based on two-dimensional disregistry.Scanning electron microscopy,X-ray photoelectron spectroscopy,and other analytical methods confirmed that the addition of an intermediate transition metal(Cr,Ni)layer reduced the gap distance and enhanced the interfacial bonding of the GP'and Cu deposited layers.The GP'-Ni-Cu composite exhibited the largest increase in tensile strength and conductivity.In addition,it had the highest thermal diffusivity and elongation at break among the GP'-Cu,GP'-Cr-Cu and GP'-Ni-Cu composites.

关键词： Graphene paper Two-dimensional disregistry Magnetron sputtering Metal composite