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Improved stability and oral bioavailability of Ganneng dropping pills following transforming lignans of herpeto- spermum caudigerum into nanosuspensions

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Chinese Journal of Natural Medicines 2018年第1期16卷 70-80页

作者： LI Juan-Juan cheng Ling shen Gang QIU Ling shen cheng-ying ZHENG Juan XU Rong YUAN Hai-Long Department of Pharmacy Air Force General Hospital of PLA Beijing 100142 China Department of Pharmacy Guangyuan Central Hospital Guanyuan 628000 China Department of Pharmacy Shuangliu District Maternal and Child Health Hospital Chengdu 610075 China chengdu Institute of Chinese Herbal Medicine Chengdu 610045 China

The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills(GNDP) by transforming lignans of Herpetospermum caudigerum(HL) composed of herpetrione(HPE) and herpetin(HPN) into nanosuspension(HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles(HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015 J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy(PCS), zeta potential measurement, and scanning electron microscopy(SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC0–t, Cmax and decrease in Tmax when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.

关键词： Ganneng dropping pills Lignans Herpetospermum caudigerum Nanosuspensions Stability Oral bioavailability

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Nanostructured lipid carrier based topical gel of Ganoderma Triterpenoids for frostbite treatment

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Chinese Journal of Natural Medicines 2015年第6期13卷 454-460页

作者： shen cheng-ying DAI Ling shen Bao-De ZHOU Xu BAI Jin-Xia XU He LV Qing-Yuan HAN Jin YUAN Hai-Long Department of Pharmacy 302 Military Hospital College of Pharmacy Chengdu University of Traditional Chinese Medicine

The objective of this study was to prepare nanostructured lipid carrier(NLC)-based topical gel of Ganoderma Triterpenoids(GTs) and evaluate their effects on frostbite treatment. GT-NLCs was prepared by the high pressure homogenization method and then characterized by morphology and analyses of particle size, zeta potential, entrapment efficiency(EE), and drug loading(DL). The NLCs was suitably gelled for skin permeation studies in vitro and pharmacodynamic evaluation in vivo, compared with the GT emulgel. The GT-NLC remained within the colloidal range and was uniformly dispersed after suitably gelled by carbopol preparation. Transmission electron microscopy(TEM) study showed GT-NLCs was spherical in shape. The EE(%) and DL(%) could reach up to(81.84 ± 0.60)% and(2.13 ± 0.12)%, respectively. The result of X-ray diffractograms(XRD) showed that GTs were in an amorphous state in the NLC-gel. In vitro permeation studies through rat skin indicated that the amount of GTs permeated through skin of GT-NLCs after 24 h was higher than that of GT emulsion, and GT-NLCs increased the accumulative amounts of GTs in epidermis 7.76 times greater than GT emulsion. GT-NLC-gel was found to possess superior therapeutic effect for frostbite, compared with the GT emulgel. The NLC based topical gel of GTs could improve-their therapeutic effect for frostbite.

关键词： Nanostructured lipid carriers High pressure homogenization Topical gel Ganoderma Triterpenes Frostbite

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Theoretical insights of the pharmaceutical compound fluoxetine in water:Role in direct photolysis and indirect photolysis by free radicals

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Journal of Environmental Sciences 2024年第8期142卷 269-278页

作者： ying Lu Se Wang Yifan shen School of Environmental Science and Engineering Collaborative Innovation Center of Atmospheric Environment and Equipment TechnologyJiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution ControlNanjing University of Information Science and TechnologyNanjing 210044China

The frequent detection of pharmaceutical compounds in the environment has led to a growing awareness,which may pose a major threat to the aquatic environment.In this study,photodegradation(direct and indirect photolysis)of two different dissociation states of fluoxetine(FLU)was investigated in water,mainly including the determination of photolytic transition states and products,and the mechanisms of indirect photodegradation with·OH,CO_(3)^(*-)and NO_(3)^(*).The main direct photolysis pathways are defluorination and C–C bond cleavage.In addition,the indirect photodegradation of FLU in water is mainly through the reactions with·OH and NO_(3)^(*),and the photodegradation reaction with CO_(3)^(*-)is relatively difficult to occur in the water environment.Our results provide a theoretical basis for understanding the phototransformation process of FLU in the water environment and assessing its potential risk.

关键词： Fluoxetine Photochemical mechanism Direct photolysis Free radical reaction DFT

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Incidence,Risk Factors,and Prognosis of Patients with Hepatocellular Carcinoma and Brain Metastases

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Current Medical Science 2024年第1期44卷 180-186页

作者： Jin-cheng FENG ying HE Georgios Polychronidis Jian XIN shen YOU Jun XIONG Department of Liver Transplantation Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Key Laboratory of Transplant Engineering and Immunology Laboratory of Liver TransplantationFrontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China Department of General Visceral and Transplant SurgeryUniversity of HeidelbergIm Neuenheimer Feld 110Heidelberg 69120Germany Department of Hepatobiliary and Pancreatic Surgery Fujian Provincial HospitalFuzhou 350001China

Objective Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma(HCC).This study aimed to examine the age-related incidence,demographics,and survival of patients with HCC and brain metastases.Methods Data of HCC patients from 2010 to 2015 in the Surveillance,Epidemiology,and End Results(SEER)Registry were screened for the presence of brain metastases.They were stratified by age and ethnicity.Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival(OS)and liver cancer-specific survival(CSS),respectively.Results A total of 141 HCC patients presenting with brain metastases were identified,accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease.Among all HCC patients,the incidence rate was the highest among patients aged 30-49 years old(0.47%).Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis.However,African-American patients presented with a significantly lower disease-specific survival[median time:1 month;interquartile range(IQR):0-3.0 months].Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases[odds ratio(OR):12.62,95% confidence interval(CI):8.40-18.97]but was not associated with a worse OS or CSS among those with brain metastases.Conclusion This study identified the age-related incidence and risk factors of brain metastases in HCC patients.These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases,and influence the counseling of this patient population regarding their prognosis.

关键词： brain metastases hepatocellular carcinoma age-related incidence cancer-specific survival overall survival

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Bioinspired 3D flexible devices and functional systems

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National Science Review 2024年第3期11卷 271-295页

作者： Xu cheng Zhangming shen Yihui Zhang Applied Mechanics Laboratory Department of Engineering Mechanics Tsinghua University Laboratory of Flexible Electronics Technology Tsinghua University

Flexible devices and functional systems with elaborated three-dimensional(3D) architectures can endow better mechanical/electrical performances, more design freedom, and unique functionalities, when compared to their two-dimensional(2D) counterparts. Such 3D flexible devices/systems are rapidly evolving in three primary directions, including the miniaturization, the increasingly merged physical/artificial intelligence and the enhanced adaptability and capabilities of heterogeneous integration.Intractable challenges exist in this emerging research area, such as relatively poor controllability in the locomotion of soft robotic systems, mismatch of bioelectronic interfaces, and signal coupling in multi-parameter sensing. By virtue of long-time–optimized materials, structures and processes, natural organisms provide rich sources of inspiration to address these challenges, enabling the design and manufacture of many bioinspired 3D flexible devices/systems. In this Review, we focus on bioinspired 3D flexible devices and functional systems, and summarize their representative design concepts, manufacturing methods, principles of structure-function relationship and broad-ranging applications. Discussions on existing challenges, potential solutions and future opportunities are also provided to usher in further research efforts toward realizing bioinspired 3D flexible devices/systems with precisely programmed shapes,enhanced mechanical/electrical performances, and high-level physical/artificial intelligence.

关键词： bioinspired designs biomimetic 3D structures 3D flexible electronics 3D functional systems direct 3D manufacture 2D-to-3D assembly

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Analytical computation of magnetic field in coil-dominated superconducting quadrupole magnets based on racetrack coils

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Nuclear Science and Techniques 2024年第4期35卷 119-135页

作者： Chuang shen ying-Shun Zhu Fu-San Chen China Spallation Neutron Source Institute of High Energy PhysicsChinese Academy of Sciences1 Zhongziyuan RoadDongguan 523000China Institute of High Energy Physics Chinese Academy of Sciences19B Yuquan RoadBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China

Currently,three types of superconducting quadrupole magnets are used in particle accelerators:cos 2θ,CCT,and serpentine.However,all three coil configurations have complex spatial geometries,which make magnet manufacturing and strain-sensitive superconductor applications difficult.Compared with the three existing quadrupole coils,the racetrack quadrupole coil has a simple shape and manufacturing process,but there have been few theoretical studies.In this paper,the two-dimensional and three-dimensional analytical expressions for the magnetic field in coil-dominated racetrack superconducting quadrupole magnets are presented.The analytical expressions of the field harmonics and gradient are fully resolved and depend only on the geometric parameters of the coil and current density.Then,a genetic algorithm is applied to obtain a solution for the coil geometry parameters with field harmonics on the order of 10^(-4).Finally,considering the practical engineering needs of the accelerator interaction region,electromagnetic design examples of racetrack quadrupole magnets with high gradients,large apertures,and small apertures are described,and the application prospects of racetrack quadrupole coils are analyzed.

关键词： Superconducting quadrupole magnet Racetrack coil Multipole field Genetic algorithm Magnetic design

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Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第8期30卷 901-918页

作者： Yi-ying Wang Mei-Mei shen Jian Gao Department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Department of Gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of M

关键词： Metadherin Hepatocellular carcinoma Cancer stem cells Immune infiltration

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A Synchronization Acquisition Algorithm Based on the Frequency Hopping Pulses Combining

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China Communications 2024年第4期21卷 74-87页

作者： She Honghan cheng Yufan Zhang Wenzihan Zhang Yaohui Zhao Yuheng shen Haoran Mou ying National Key Laboratory of Wireless Communications UESTCChengdu 611731China

As modern electromagnetic environments are more and more complex,the anti-interference performance of the synchronization acquisition is becoming vital in wireless communications.With the rapid development of the digital signal processing technologies,some synchronization acquisition algorithms for hybrid direct-sequence(DS)/frequency hopping(FH)spread spectrum communications have been proposed.However,these algorithms do not focus on the analysis and the design of the synchronization acquisition under typical interferences.In this paper,a synchronization acquisition algorithm based on the frequency hopping pulses combining(FHPC)is proposed.Specifically,the proposed algorithm is composed of two modules:an adaptive interference suppression(IS)module and an adaptive combining decision module.The adaptive IS module mitigates the effect of the interfered samples in the time-domain or the frequencydomain,and the adaptive combining decision module can utilize each frequency hopping pulse to construct an anti-interference decision metric and generate an adaptive acquisition decision threshold to complete the acquisition.Theory and simulation demonstrate that the proposed algorithm significantly enhances the antiinterference and anti-noise performances of the synchronization acquisition for hybrid DS/FH communications.

关键词： adaptive anti-interference frequency hopping synchronization acquisition

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Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第6期30卷 515-524页

作者： CAO Liu-jing LIU Li-ya CHEN You-qin HAN Yu-ying WEI Li-hui YAO Meng-ying FANG Yi WU Mei-zhu cheng ying Thomas J.Sferra LIU Hui-xin LI Li PENG Jun shen A-ling Clinical Research Institute the Second Affiliated Hospital&Academy of Integrative MedicineFujian University of Traditional Chinese MedicineFuzhou350122China Fujian Key Laboratory of Integrative Medicine in Geriatrics Fujian University of Traditional Chinese MedicineFuzhou350122China Department of Pediatrics Case Western Reserve University School of MedicineUH Rainbow Babies and Children’s HospitalClevelandOH44106USA Innovation and Transformation Center Fujian University of Traditional Chinese MedicineFuzhou350122China Department of Health Management Fujian Provincial HospitalShengli Clinical College of Fujian Medical UniversityFuzhou000000China

ObjectiveTo explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it’s down-stream mediators in colorectal cancer (CRC) cells.MethodsQuantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues.ResultsPZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05).ConclusionThe mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

关键词： colorectal cancer Pien Tze Huang Chinese medicine partner of NOB1 proliferation p53/p21 pathway

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Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interferewith 5-HT Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第2期30卷 152-162页

作者： YANG ying QU Jin-yu GUO Hua ZHOU Hai-ying RUAN Xia PENG ying-chun shen Xue-fang XIONG Jin WANG Yi-li School of Clinical Medicine Chengdu Medical CollegeChengdu(610500)China Department of Rehabilitation Medicine the First Affliated Hospital of Chengdu Medical CollegeChengdu(610500)China Department of Rehabilitation Medicine West China HospitalSichuan University/West China School of NursingSichuan UniversityChengdu(610041)China Department of Neurology the First Affiliated Hospital of Chengdu Medical CollegeChengdu(610500)China

Objective:To investigate whether electroacupuncture(EA) at sensitized acupoints could reduce sympathetic-sensory coupling(SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine(5-HT)ergic neural pathways to relieve colitis and somatic referred pain,and explore the underlying mechanisms.Methods:Rats were treated with 5% dextran sodium sulfate(DSS) solution for 7 days to establish a colitis model.Twelve rats were randomly divided into the control and model groups according to a random number table(n=6).According to the Research on Rat Acupoint Atlas",sensitized acupoints and non-sensitized acupoints were determined.Rats were randomly divided into the control,model,Zusanli-EA(ST 36),Dachangshu-EA(BL 25),and Xinshu(BL 15) groups(n=6),as well as the control,model,EA,and EA+GR113808(a 5-HT inhibitor)groups(n=6).The rats in the control group received no treatment.Acupuncture was administered on 2 days after modeling using the stimulation pavameters:1 mA,2 Hz,for 30 min,with sparse and dense waves,for 14 consecutive days.GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days.Mechanical sensitivity was assessed with von Frey filaments.Body weight and disease activity index(DAI) scores of rats were determined.Hematoxylin and eosin staining was performed to observe colon histopathology.SSC was analyzed by immunofluorescence staining.Immunohistochemical staining was performed to detect 5-HT and substance P(SP) expressions.The calcitonin gene-related peptide(CGRP) in skin tissue and tyrosine hydroxylase(TH) protein levels in DRG were detected by Western blot.The levels of hyaluronic acid(HA),bradykinin(BK),prostaglandin I2(PGI2) in skin tissue,5-HT,tryptophan hydroxylase 1(TPH1),serotonin transporters(SERT),5-HT 3 receptor(5-HT3R),and 5-HT 4 receptor(5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay(ELISA).Results:BL 25 and ST 36 acupoints were determined as sensitized acupoints,and BL 15 acupoint was used as a non-sensitized acupoint

关键词： electroacupuncture sensitized acupoints sympathetic-sensory coupling 5-hydroxytryptamine neurogenic inflammation somaticreferredpain

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