The long non-coding RNA,Negative Regulator of Antiviral Response(NRAV)has been identified as a participant in both respiratory virus replication and immune checkpoints,however,its involvement in pan-cancer immune regu...The long non-coding RNA,Negative Regulator of Antiviral Response(NRAV)has been identified as a participant in both respiratory virus replication and immune checkpoints,however,its involvement in pan-cancer immune regulation and prognosis,particularly those of hepatocellular carcinoma(HCC),remains unclear.To address this knowledge gap,we analyzed expression profiles obtained from The Cancer Genome Atlas(TCGA)database,comparing normal and malignant tumor tissues.We found that NRAV expression is significantly upregulated in tumor tissues compared to adjacent nontumor tissues.Kaplan-Meier(K-M)analysis revealed the prognostic power of NRAV,wherein overexpression was significantly linked to reduced overall survival in a diverse range of tumor patients.Furthermore,noteworthy associations were observed between NRAV,immune checkpoints,immune cell infiltration,genes related to autophagy,epithelial-mesenchymal transition(EMT),pyroptosis,tumor mutational burden(TMB),and microsatellite instability(MSI)across different cancer types,including HCC.Moreover,NRAV upregulation expression was associated with multiple pathological stages by clinical observations.Furthermore,our investigation revealed a substantial elevation in the expression of NRAV in both HCC tumor tissues and cells compared to normal tissues and cells.The inhibition of NRAV resulted in the inhibition of cell proliferation,migration,and invasion in HCC cells,while also influencing the expression of CD274(PD-L1)and CD44,along with various biomarkers associated with EMT,autophagy,and pyroptosis.The aforementioned results propose NRAV as a promising prognostic biomarker for HCC.展开更多
T lymphocytes,the main participants of cellular immunity,can express a variety of surface molecules and form different lymphocyte subsets under the induction of different factors to play the functions of immune regula...T lymphocytes,the main participants of cellular immunity,can express a variety of surface molecules and form different lymphocyte subsets under the induction of different factors to play the functions of immune regulation and immune killing.Studies have shown that platelets play a crucial role in maintaining the stable differentiation of lymphocytes and the balance in immunomodulation.Therefore,it is necessary to study the effect of platelets on lymphocytes in vitro to better understand the role of platelets in the immune system and broaden the application of adoptive immunotherapy.Methods:Cell counting and microscopic observation were used to detect the effect of activated platelets on lymphocyte proliferation in vitro;Flow cytometry was used to detect whether changes in platelet activity affect the proportion of lymphocyte subpopulations in vitro,and to detect differences in the expression of granzyme B;lactate dehydrogenase assay(LDH)was used to determine the difference in lymphocyte killing activity caused by platelet activity in vitro.Results:This was the first to promote lymphocyte proliferation through the expression or release of certain molecules in vitro,demonstrating that platelet activation is one of the key factors.Secondly,activated platelets or inactivated platelets promoted lymphocyte subset differentiation by enhancing the proportion of CD3+CD8+T lymphocytes(CTL cells)but had a slight effect on the proportion of CD3+CD4+T(Th cells)and CD4+CD25+T lymphocytes(Treg cells).Then,it was found that either activated platelets or inactivated platelets down-regulated the proportion of natural killer(NK)T lymphocytes,while activated platelets significantly enhance the proportion of NK lymphocytes.Therefore,by further detecting the killing activity of PBMCs treated with platelets,it was found that activated platelets promoted the extensive anti-tumor activity of lymphocytes and significantly increased the expression of granzyme B.Conclusion:Our results suggest that activated platelets promote lymphocyte proliferation,optimize lymphocyte subpopulation ratio,and promote cytotoxic effect of lymphocytes in vitro,which may provide a new strategy for optimizing the adoptive immunotherapy culture system and improving its efficacy.展开更多
Objective To investigate the molecular characteristics and intracellular growth ability of Legionella pneumophila(L. pneumophila) strains from 1989 to 2016 in Sichuan Province, China. Methods Seventy-nine isolates of ...Objective To investigate the molecular characteristics and intracellular growth ability of Legionella pneumophila(L. pneumophila) strains from 1989 to 2016 in Sichuan Province, China. Methods Seventy-nine isolates of L. pneumophila were collected from environmental and clinical sources, including cooling towers, hot springs, bath water, fountains, and patients, and identified with 16 S rRNA gene analysis and serum agglutination assay. The isolates were then typed by Sequence-Based Typing(SBT), and Genotyping of forty-two LP1 strains were analyzed by means of multiple-locus VNTR analysis with 8 loci(MLVA-8). All strains were further analyzed for two virulence genes: Legionella vir homologue(lvh) and repeats in structural toxin(rtx A). The intracellular growth ability of 33 selected isolates was determined by examining their interaction with J774 cells. Results All isolates were identified to L. pneumophila including 11 serogroups, among which the main serogroup were LP1, accounting for 54.43%. Thirty-three different sequence types(STs) from five main clonal groups and five singletons were identified, along with 8 different MLVA patterns. Both the lvh and rtx A loci were found in all 79 strains. Thirty isolates showed high intracellular growth ability in J774 cells. Conclusion L. pneumophila is a potential threat to public health, and effective control and prevention strategies are urgently needed.展开更多
OBJECTIVE Oxyresveratrol(OXY)has many biological activities including anti-inflammation,anti-oxida⁃tive stress,anti-cancer and immunomodulation.However,the mechanisms underlying its effects against hepatocellular carc...OBJECTIVE Oxyresveratrol(OXY)has many biological activities including anti-inflammation,anti-oxida⁃tive stress,anti-cancer and immunomodulation.However,the mechanisms underlying its effects against hepatocellular carcinoma(HCC)remain poorly understood.METHODS Two HCC cell lines,HepG2 and SMMC-7721 cells,were employed.Their proliferation was determined by CCK8 assay.The migration and invasion of cells were examined by wound healing and transwell assay.Metastasis of HCC was detected by in vivo experiment.Meanwhile,transcriptome analysis was applied to explore the mechanisms of OXY.The results of transcriptome analysis were validated by in vitro experiment.Further⁃more,western blot was used to measure the expression of LC3 and p62 protein.RESULTS OXY significantly inhibited the proliferation,migration and invasion of HCC cells in vitro.OXY suppressed the metastasis of HCC in Balb/c mice with attenuated side effects compared to Doxorubicin.Transcription profiling analysis revealed that OXY may affect autophagy related signaling pathway of HepG2 cells.Western blotting showed that OXY significantly inhibite autophagy by downregulating LC3 and upregulating p62 genes expression.CONCLUSION Our study demonstrated that OXY inhibits the metastasis of HCC by inhibiting autophagy,which suggested OXY to be a candidate for HCC metastasis.展开更多
To dissect which subset of bone marrow monocyte is the major precursor of osteoclast,3-month-old rat bone marrow was obtained for single-cell RNA sequencing.A total of 6091 cells were acquired for detailed analysis,wi...To dissect which subset of bone marrow monocyte is the major precursor of osteoclast,3-month-old rat bone marrow was obtained for single-cell RNA sequencing.A total of 6091 cells were acquired for detailed analysis,with a median number of 1206 genes detected per cell and 17,959 genes detected in total.A total of 19 cell clusters were recognized,with the main lineages identified as B cells,Granulocytes,Monocytes,T cells,Erythrocytes and Macrophages.Monocytes were further divided into classical monocytes and non-classical monocytes.Compared with non-classical monocytes,classical monocytes highly expressed osteoclast differentiation related genes Mitf,Spi1,Fos and Csf1r.Additionally,biological processes of classical monocytes were related to osteoclast differentiation.qPCR revealed differentially expressed genes of classical monocytes played a role in osteoclast differentiation.In conclusion,classical monocytes were identified as the main precursors of osteoclasts in rats,and may contribute to osteoclast differentiation by regulating S100a4,S100a6,S100a10,Fn1,Vcan and Bcl2a1.The results of this study contribute to the understanding of the origin of osteoclasts and may provide potential biomarkers for early diagnosis of bone metabolic diseases,as well as molecular and cellular targets for clinical intervention in bone metabolic diseases.展开更多
Objective: To explore the correlation between muscle strength, muscle mass and bone mineral density (BMD) in Zhuang female population, body composition analysis and grip strength, and to analyze the possible influenci...Objective: To explore the correlation between muscle strength, muscle mass and bone mineral density (BMD) in Zhuang female population, body composition analysis and grip strength, and to analyze the possible influencing factors of BMD. Methods: 182 postmenopausal women were selected from Guangxi Province of China. Broadband ultrasound attenuation (BUA) was used to evaluate BMD. Grip dynamometer to assess muscle strength. Height, weight and muscle mass of each part were measured by body composition measuring instrument. Body mass index (BMI), skeletal muscle mass index (SMI) and limb skeletal muscle mass (SM) were calculated according to the measurement results. Results: BUA, grip strength and SMI in postmenopausal women of Zhuang nationality showed a decreasing trend with age (p p p r = 0.305, p Conclusion: With the increase of age, the decline rate of muscle strength of postmenopausal Zhuang women in Guangxi is slower than that of BMD and muscle mass. SM can better reflect the BMD level of the body than SMI, and the LSM is the main influencing factor of BMD.展开更多
Pharmacodynamics material basis and effective mechanisms are the two main issues to decipher the mechnisms of action of Traditional Chinese medicines(TCMs)for the treatment of diseases.TCMs,in“multi-component,multi-t...Pharmacodynamics material basis and effective mechanisms are the two main issues to decipher the mechnisms of action of Traditional Chinese medicines(TCMs)for the treatment of diseases.TCMs,in“multi-component,multi-target,multi-pathway”paradigm,show satisfactory clinical results in complex diseases.New ideas and methods are urgently needed to explain the complex interactions between TCMs and diseases.Network pharmacology(NP)provides a novel paradigm to uncover and visualize the underlying interaction networks of TCMs against multifactorial diseases.The development and application of NP has promoted the safety,efficacy,and mechanism investigations of TCMs,which then reinforces the credibility and popularity of TCMs.The current organcentricity of medicine and the“one disease-one target-one drug”dogma obstruct the understanding of complex diseases and the development of effective drugs.Therefore,more attentions should be paid to shift from“phenotype and symptom”to“endotype and cause”in understanding and redefining current diseases.In the past two decades,with the advent of advanced and intelligent technologies(such as metabolomics,proteomics,transcriptomics,single-cell omics,and artificial intelligence),NP has been improved and deeply implemented,and presented its great value and potential as the next drug-discovery paradigm.NP is developed to cure causal mechanisms instead of treating symptoms.This review briefly summarizes the recent research progress on NP application in TCMs for efficacy research,mechanism elucidation,target prediction,safety evaluation,drug repurposing,and drug design.展开更多
Fibrosis is the end-stage change of damaged tissues in various human diseases,which can lead to permanent scarring or organ malfunction.Hypoxia leads to oxidative stress,mitochondrial dysfunction,and inflammation in d...Fibrosis is the end-stage change of damaged tissues in various human diseases,which can lead to permanent scarring or organ malfunction.Hypoxia leads to oxidative stress,mitochondrial dysfunction,and inflammation in dysfunctional organs and tissues.Oxidative stress resulting from the overproduction of reactive oxygen species plays a central role in the fibrosis of injured organs.This review addresses the updated knowledge of the relationship between hypoxia and tissue fibrosis mediated by the reactive oxygen species pathway.Moreover,novel anti-fibrotic strategies are discussed,which may suppress reactive oxygen species and organ fibrosis.展开更多
More than 90%of surgical patients develop postoper-ative adhesions,and the incidence of hospital re-admissions can be as high as 20%.Current adhesion barriers present limited efficacy due to difficulties in applicatio...More than 90%of surgical patients develop postoper-ative adhesions,and the incidence of hospital re-admissions can be as high as 20%.Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions.To solve thisclinical limitation,we developed an injectable and sprayable shear-thinning hydrogel barrier(STHB)composed of silicate nanoplatelets and poly(ethylene oxide).We optimized this technology to recover mechanical integrity after stress,enabling its delivery though inject-able and sprayable methods.We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro.The STHB was then tested in a rodent model of peritoneal injury to determine its e cacy preventing the formation of postoperative adhesions.After two weeks,the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions,and STHB formulations presented superior e cacy compared to a commercially available adhesion barrier.Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations.Our technology demonstrated increased e cacy,ease of use in complex anatomies,and compatibility with di erent delivery methods,providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.展开更多
Background Toxoplasma gondii is an obligate intracellular apicomplexan parasite and is responsible for zoonotic toxoplasmosis.It is essential to develop an effective anti-T.gondii vaccine for the control of toxoplasmo...Background Toxoplasma gondii is an obligate intracellular apicomplexan parasite and is responsible for zoonotic toxoplasmosis.It is essential to develop an effective anti-T.gondii vaccine for the control of toxoplasmosis,and this study is to explore the immunoprotective effects of a live attenuated vaccine in mice and cats.Methods First,theompdc anduprt genes of T.gondii were deleted through the CRISPR-Cas9 system.Then,the intracellular proliferation and virulence of this mutant strain were evaluated.Subsequently,the immune responses induced by this mutant in mice and cats were detected,including antibody titers,cytokine levels,and subsets of T lymphocytes.Finally,the immunoprotective effects were evaluated by challenge with tachyzoites of different strains in mice or cysts of the ME49 strain in cats.Furthermore,to discover the effective immune element against toxoplasmosis,passive immunizations were carried out.GraphPad Prism software was used to conduct the log-rank(Mantel–Cox)test,Student’st test and one-way ANOVA.Results The RHΔompdcΔuprt were constructed by the CRISPR-Cas9 system.Compared with the wild-type strain,the mutant notably reduced proliferation(P<0.05).In addition,the mutant exhibited virulence attenuation in both murine(BALB/c and BALB/c-nu)and cat models.Notably,limited pathological changes were found in tissues from RHΔompdcΔuprt-injected mice.Furthermore,compared with nonimmunized group,high levels of IgG(IgG1 and IgG2a)antibodies and cytokines(IFN-γ,IL-4,IL-10,IL-2 and IL-12)in mice were detected by the mutant(P<0.05).Remarkably,all RHΔompdcΔuprt-vaccinated mice survived a lethal challenge with RHΔku80 and ME49 and WH6 strains.The immunized sera and splenocytes,especially CD8^(+)T cells,could significantly extend(P<0.05)the survival time of mice challenged with the RHΔku80 strain compared with naïve mice.In addition,compared with nonimmunized cats,cats immunized with the mutant produced high levels of antibodies and cytokines(P<0.05),and notably decreased the shedding numbers of oocysts in feces(95.3%).Conclusions The avirulent RHΔompdcΔuprt strain can provide strong anti-T.gondii immune responses,and is a promising candidate for developing a safe and effective live attenuated vaccine.展开更多
Accumulating studies reveal that mesenchymal stem cells(MSCs)promote skin wound healing mainly through the paracrine effects.Exosomes,one of the crucial paracrine mediators in wound healing,are cell-derived nanosized ...Accumulating studies reveal that mesenchymal stem cells(MSCs)promote skin wound healing mainly through the paracrine effects.Exosomes,one of the crucial paracrine mediators in wound healing,are cell-derived nanosized membranous vesicles containing diverse bioactive cargoes.With the potent ability of modulating skin cell behaviors,MSC-derived exosomes(MSC-Exos)are regarded as a promising nanomaterial for regenerative wound therapy.Under hostile conditions,MSC-Exos are efficient in protecting skin cells from severe damage and restoring their function.According to recent studies,MSC-Exos possess remarkable pro-healing effects in a variety of skin wounds,typically resulting in increased wound closure,inhibited scar tissue formation,and better restoration of skin function.To further enhance the therapeutic potential of MSC-Exos,the development of applicable pretreatment strategies and the optimization of exosome delivery are under intensive investigation.Herein,we summarize current research progress of MSC-Exos for skin wound treatment,with an emphasis on the biological effects of these nanovesicles,the repair mechanisms,and future challenges in clinical translation.展开更多
Inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases,which continuously pose one of the most serious threats to human health,attributed to factors such as ...Inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases,which continuously pose one of the most serious threats to human health,attributed to factors such as the emergence of new pathogens,increasing drug resistance,changes in living environments and lifestyles,and the aging population.Despite rapid advancements in mechanistic research and drug development for these diseases,current treatments often have limited efficacy and notable side effects,necessitating the development of more effective and targeted anti-inflammatory therapies.In recent years,the rapid development of nanotechnology has provided crucial technological support for the prevention,treatment,and detection of inflammation-associated diseases.Various types of nanoparticles(NPs)play significant roles,serving as vaccine vehicles to enhance immunogenicity and as drug carriers to improve targeting and bioavailability.NPs can also directly combat pathogens and inflammation.In addition,nanotechnology has facilitated the development of biosensors for pathogen detection and imaging techniques for inflammatory diseases.This review categorizes and characterizes different types of NPs,summarizes their applications in the prevention,treatment,and detection of infectious and inflammatory diseases.It also discusses the challenges associated with clinical translation in this field and explores the latest developments and prospects.In conclusion,nanotechnology opens up new possibilities for the comprehensive management of infectious and inflammatory diseases.展开更多
Drug resistance is one of the most serious issues in epilepsy.Despite using various appropriate anti-epileptic drugs(AEDs),30%of epilepsy patients are still drugresistant.The percentage of resistance in temporal lobe ...Drug resistance is one of the most serious issues in epilepsy.Despite using various appropriate anti-epileptic drugs(AEDs),30%of epilepsy patients are still drugresistant.The percentage of resistance in temporal lobe epilepsy(TLE)is even higher[1].Although epilepsy surgery and deep brain stimulation are emerging as alternative therapeutic strategies,the curative outcome is still unsatisfactory.展开更多
Heavy alcohol drinking is a major public health problem,causing a large disease,social and economic burden in societies.Subjective response (SR) to alcohol is an intermediate characteristic of heavy drinking.A variety...Heavy alcohol drinking is a major public health problem,causing a large disease,social and economic burden in societies.Subjective response (SR) to alcohol is an intermediate characteristic of heavy drinking.A variety of candidate genes have been reported to be associated with SR to alcohol.In this study,we investigated nine single nucleotide polymorphisms (SNPs) related to SR to alcohol in healthy individuals from five Chinese ethnic groups,the Han,Hui,Tibetan,Mongolian and Uygur populations,and a total of 584 bloodstain samples were collected.The nine SNPs included four SNPs in alcohol-metabolizing genes (ADH1B,ADH1C,ALDH2 and CYP2E1*5B) and five SNPs in genes of neurobiological pathways (GABRA2,OPRM1,CHRNA3,HYKK and SLC6A4).A SNaPshot analysis method was developed to type these SNPs simultaneously,and all samples were typed successfully.Statistical analyses of the allele frequencies indicated that the frequencies of all SNPs,except for ADH1C,showed varying degrees of difference in the five studied ethnic groups.Tibetans showed the highest frequencies of risk alleles for heavy drinking at most loci.The genetic polymorphic differences found in this study revealed the variation in genetic susceptibility to heavy drinking in the studied populations.展开更多
Resistance to cancer therapy is a major barrier to cancer management.Conventional views have proposed that acquisition of resistance may result from genetic mutations.However,accumulating evidence implicates a key rol...Resistance to cancer therapy is a major barrier to cancer management.Conventional views have proposed that acquisition of resistance may result from genetic mutations.However,accumulating evidence implicates a key role of non-mutational resistance mechanisms underlying drug tolerance,the latter of which is the focus that will be discussed here.Such non-mutational processes are largely driven by tumor cell plasticity,which renders tumor cells insusceptible to the drug-targeted pathway,thereby facilitating the tumor cell survival and growth.The concept of tumor cell plasticity highlights the significance of re-activation of developmental programs that are closely correlated with epithelial–mesenchymal transition,acquisition properties of cancer stem cells,and transdifferentiation potential during drug exposure.From observations in various cancers,this concept provides an opportunity for investigating the nature of anticancer drug resistance.Over the years,our understanding of the emerging role of phenotype switching in modifying therapeutic response has considerably increased.This expanded knowledge of tumor cell plasticity contributes to developing novel therapeutic strategies or combination therapy regimens using available anticancer drugs,which are likely to improve patient outcomes in clinical practice.展开更多
OBJECTIVE:To investigate the anti-bacterial and anti-viral effects of Fengreqing oral liquid(风热清口服液,FRQ)in vitro and in vivo.METHODS:The minimum inhibitory concentrations of Fengreqing Oral Liquid against six gr...OBJECTIVE:To investigate the anti-bacterial and anti-viral effects of Fengreqing oral liquid(风热清口服液,FRQ)in vitro and in vivo.METHODS:The minimum inhibitory concentrations of Fengreqing Oral Liquid against six gram-positive bacteria(Staphylococcus aureus,Streptococcus mutans,Peptostreptococcus anaerobius,Hemolytic streptococcus,Streptococcus pneumoniae,Klebsiella pneumoniae),seven gram-negative bacteria(Escherichia coli,Actinobacillus actinomycetemcomitans,Porphyromonas gingivalis,Haemophilus influenzae,Helicobacter pylori,Pseudomonas aeruginosa,Gardnerella vaginalis)and Candida albicans were detected by the paper disc diffusion method.The inhibition rate of A/Puerto Rico/8/34(H1N1)(PR8)influenza virus in different concentrations of Fengreqing oral solution was detected by chicken embryo method.CCK8 method was used to detect the half-cell infection of RSV,VSV and CVB3.The effect of FRQ on the survival curve of mice was detected by using co-infection model of Streptococcus pneumoniae and influenza virus.RESULTS:In vitro,FRQ can inhibit Actinobacillus actinomycetemcomitans,Helicobacter pylori,Gardnerella vaginalis,Staphylococcus aureus,Streptococcus mutans and Streptococcus pneumoniae and has an antiviral effect on the envelope virus H1N1.In vivo,Fengreqing oral solution had therapeutic effect on influenza-Streptococcus pneumoniae co-infection in mice,significantly improving the survival rate of mice.The medium dose and low dose FRQ significantly prolonged the survival time of mice.CONCLUSION:FRQ has good anti-bacterial and anti-viral effects in vivo and in vitro.展开更多
Drug-facilitated sexual assault(DFSA)is a sexual act in which the victim is unable to give or rescind consent due to alcohol or drug intoxication,which involved the abuse of benzodiazepines around the world.Convention...Drug-facilitated sexual assault(DFSA)is a sexual act in which the victim is unable to give or rescind consent due to alcohol or drug intoxication,which involved the abuse of benzodiazepines around the world.Conventional techniques used for the analysis of benzodiazepines have the limitation of short detection time window due to the rapid metabolism of these drugs in body.This study aimed to investigate the characteristic changes of metabolites in the blood of rats after ingesting diazepam/clonazepam through a gas chromatography-mass spectrometry-based metabolomics method,allowing the indirect reveal of the rats ingested diazepam/clonazepam.First,we found that diazepam and clonazepam in the blood of rats could not be detected by liquid chromatography-tandem mass spectrometry after 48 h of ingestion.Then,orthogonal partial least squares discrimination analysis regression models were,respectively,constructed to determine whether the rats ingested diazepam/clonazepam after 48 h.The results showed that 5 metabolites were found to be associated with diazepam exposure,and 7 metabolites were found to be associated with clonazepam exposure,which may be characterization for the evaluation of digestion of diazepam and clonazepam in rat.展开更多
The aim of this study was to develop a gas chromatography‑mass spectrometry(GC‑MS)‑based metabolomics method to distinguish different kinds of poisons in the blood.We examined the changes in blood metabolites using GC...The aim of this study was to develop a gas chromatography‑mass spectrometry(GC‑MS)‑based metabolomics method to distinguish different kinds of poisons in the blood.We examined the changes in blood metabolites using GC‑MS following administration of four different poisons(paraquat,dichlorvos,aconitine,and sodium nitrite).The data were analyzed with orthogonal partial least squares.Then,total and single differential metabolite profiles were evaluated with support vector machine(SVM)models.The results showed that various metabolites(5‑ketone proline,1,5‑anhydrohexitol,lactic acid,glycine 2,2‑furoic acid,and 3‑hydroxybutyric acid)were differential between the experimental groups and the control groups.The accuracy rates of the SVM models established using total and single differential metabolites were 80%and 100%,respectively.In conclusion,we successfully developed a poison screening method.The established SVM models can distinguish four kinds of poisons and could be used to establish a complete poison metabonomic information database.Furthermore,some of the metabolites could be biomarkers of these poisons.Finally,both the models and potential biomarkers may reduce the time required for poison detection and provide direction for solving cases and auxiliary diagnosis.展开更多
A simple,rapid and sensitive liquid chromatography with tandem mass spectrometry method for the determination of periplocymarin in human blood and urine was developed.The digoxin‑d3 was used as an internal standard.Pe...A simple,rapid and sensitive liquid chromatography with tandem mass spectrometry method for the determination of periplocymarin in human blood and urine was developed.The digoxin‑d3 was used as an internal standard.Periplocymarin and digoxin‑d3(IS)were processed with ethyl acetate by liquid–liquid extraction.The chromatographic separation was performed on a Shim‑pack XR‑ODSIII C18 column with a 7 min gradient elution using methanol‑ammonium formate(5 mmol/L)as mobile phase at a flow rate of 0.3 mL/min(65:35,v/v).The detection was performed on a triple quadrupole tandem mass spectrometer using positive‑ion mode electrospray ionization in selected reaction monitoring mode.The periplocymarin was well separated from the internal standard.Two calibration curves were linear within the concentration range 0.01–1µg/mL.The limit of detection and quantification of blood and urine samples were both estimated at 0.005 and 0.01µg/mL.The interday and intraday precisions,accuracy,and recovery were assessed to verify this method.The results showed that the method was suitable for the determination of periplocymarin in forensic toxicological analysis and clinical diagnosis.展开更多
Chlorpyrifos is an organophosphate pesticide used to kill pests such as insects and worms.Wide use of chlorpyrifos has led to serious safety concerns worldwide.Research on the mechanism of action of chlorpyrifos poiso...Chlorpyrifos is an organophosphate pesticide used to kill pests such as insects and worms.Wide use of chlorpyrifos has led to serious safety concerns worldwide.Research on the mechanism of action of chlorpyrifos poisoning is continuing.We investigated changes in the small‑molecular metabolites in the brain and blood of rats upon exposure to chlorpyrifos at an acute‑poisoning dose.Rats were given twice the lowest dose of chlorpyrifos that is lethal for 100%of exposed animals(2×LD_(100))and then killed after 2 h.After treatment,gas chromatography‑mass spectrometry was used to analyze the metabolomic changes in the brain and blood samples of rats.An increase in blood levels of creatinine and uric acid were noted,along with a decrease in levels of various amino acids.These changes suggested that chlorpyrifos exposure may damage kidney function and cause disorders in amino‑acid metabolism of rats.Decreased concentrations of gamma‑aminobutyric acid and niacinamide in the brain and increased concentrations of 3‑hydroxybutyric acid in rats with acute poisoning by chlorpyrifos were observed,which may suggest oxidative damage in the body.展开更多
基金funded by China National Natural Youth Science Foundation(81802078)Zhejiang Province Public Welfare Research Foundation(GF20H200021)Zhejiang Provincial Department of Medicine and Health Foundation(2019RC315).
文摘The long non-coding RNA,Negative Regulator of Antiviral Response(NRAV)has been identified as a participant in both respiratory virus replication and immune checkpoints,however,its involvement in pan-cancer immune regulation and prognosis,particularly those of hepatocellular carcinoma(HCC),remains unclear.To address this knowledge gap,we analyzed expression profiles obtained from The Cancer Genome Atlas(TCGA)database,comparing normal and malignant tumor tissues.We found that NRAV expression is significantly upregulated in tumor tissues compared to adjacent nontumor tissues.Kaplan-Meier(K-M)analysis revealed the prognostic power of NRAV,wherein overexpression was significantly linked to reduced overall survival in a diverse range of tumor patients.Furthermore,noteworthy associations were observed between NRAV,immune checkpoints,immune cell infiltration,genes related to autophagy,epithelial-mesenchymal transition(EMT),pyroptosis,tumor mutational burden(TMB),and microsatellite instability(MSI)across different cancer types,including HCC.Moreover,NRAV upregulation expression was associated with multiple pathological stages by clinical observations.Furthermore,our investigation revealed a substantial elevation in the expression of NRAV in both HCC tumor tissues and cells compared to normal tissues and cells.The inhibition of NRAV resulted in the inhibition of cell proliferation,migration,and invasion in HCC cells,while also influencing the expression of CD274(PD-L1)and CD44,along with various biomarkers associated with EMT,autophagy,and pyroptosis.The aforementioned results propose NRAV as a promising prognostic biomarker for HCC.
文摘T lymphocytes,the main participants of cellular immunity,can express a variety of surface molecules and form different lymphocyte subsets under the induction of different factors to play the functions of immune regulation and immune killing.Studies have shown that platelets play a crucial role in maintaining the stable differentiation of lymphocytes and the balance in immunomodulation.Therefore,it is necessary to study the effect of platelets on lymphocytes in vitro to better understand the role of platelets in the immune system and broaden the application of adoptive immunotherapy.Methods:Cell counting and microscopic observation were used to detect the effect of activated platelets on lymphocyte proliferation in vitro;Flow cytometry was used to detect whether changes in platelet activity affect the proportion of lymphocyte subpopulations in vitro,and to detect differences in the expression of granzyme B;lactate dehydrogenase assay(LDH)was used to determine the difference in lymphocyte killing activity caused by platelet activity in vitro.Results:This was the first to promote lymphocyte proliferation through the expression or release of certain molecules in vitro,demonstrating that platelet activation is one of the key factors.Secondly,activated platelets or inactivated platelets promoted lymphocyte subset differentiation by enhancing the proportion of CD3+CD8+T lymphocytes(CTL cells)but had a slight effect on the proportion of CD3+CD4+T(Th cells)and CD4+CD25+T lymphocytes(Treg cells).Then,it was found that either activated platelets or inactivated platelets down-regulated the proportion of natural killer(NK)T lymphocytes,while activated platelets significantly enhance the proportion of NK lymphocytes.Therefore,by further detecting the killing activity of PBMCs treated with platelets,it was found that activated platelets promoted the extensive anti-tumor activity of lymphocytes and significantly increased the expression of granzyme B.Conclusion:Our results suggest that activated platelets promote lymphocyte proliferation,optimize lymphocyte subpopulation ratio,and promote cytotoxic effect of lymphocytes in vitro,which may provide a new strategy for optimizing the adoptive immunotherapy culture system and improving its efficacy.
基金supported by grants from the National Natural Science Foundation of China [81672048]the Youth Innovation Project of Sichuan Medical Association Foundation [Q15081]the Priority Project on Infectious Disease Control and Prevention [2018ZX10714002]
文摘Objective To investigate the molecular characteristics and intracellular growth ability of Legionella pneumophila(L. pneumophila) strains from 1989 to 2016 in Sichuan Province, China. Methods Seventy-nine isolates of L. pneumophila were collected from environmental and clinical sources, including cooling towers, hot springs, bath water, fountains, and patients, and identified with 16 S rRNA gene analysis and serum agglutination assay. The isolates were then typed by Sequence-Based Typing(SBT), and Genotyping of forty-two LP1 strains were analyzed by means of multiple-locus VNTR analysis with 8 loci(MLVA-8). All strains were further analyzed for two virulence genes: Legionella vir homologue(lvh) and repeats in structural toxin(rtx A). The intracellular growth ability of 33 selected isolates was determined by examining their interaction with J774 cells. Results All isolates were identified to L. pneumophila including 11 serogroups, among which the main serogroup were LP1, accounting for 54.43%. Thirty-three different sequence types(STs) from five main clonal groups and five singletons were identified, along with 8 different MLVA patterns. Both the lvh and rtx A loci were found in all 79 strains. Thirty isolates showed high intracellular growth ability in J774 cells. Conclusion L. pneumophila is a potential threat to public health, and effective control and prevention strategies are urgently needed.
文摘OBJECTIVE Oxyresveratrol(OXY)has many biological activities including anti-inflammation,anti-oxida⁃tive stress,anti-cancer and immunomodulation.However,the mechanisms underlying its effects against hepatocellular carcinoma(HCC)remain poorly understood.METHODS Two HCC cell lines,HepG2 and SMMC-7721 cells,were employed.Their proliferation was determined by CCK8 assay.The migration and invasion of cells were examined by wound healing and transwell assay.Metastasis of HCC was detected by in vivo experiment.Meanwhile,transcriptome analysis was applied to explore the mechanisms of OXY.The results of transcriptome analysis were validated by in vitro experiment.Further⁃more,western blot was used to measure the expression of LC3 and p62 protein.RESULTS OXY significantly inhibited the proliferation,migration and invasion of HCC cells in vitro.OXY suppressed the metastasis of HCC in Balb/c mice with attenuated side effects compared to Doxorubicin.Transcription profiling analysis revealed that OXY may affect autophagy related signaling pathway of HepG2 cells.Western blotting showed that OXY significantly inhibite autophagy by downregulating LC3 and upregulating p62 genes expression.CONCLUSION Our study demonstrated that OXY inhibits the metastasis of HCC by inhibiting autophagy,which suggested OXY to be a candidate for HCC metastasis.
基金supported by the National Natural Science Foundation of China(Nos.11572209,11872260)National Natural Science Foundation of China(Key Program,No.11932014).
文摘To dissect which subset of bone marrow monocyte is the major precursor of osteoclast,3-month-old rat bone marrow was obtained for single-cell RNA sequencing.A total of 6091 cells were acquired for detailed analysis,with a median number of 1206 genes detected per cell and 17,959 genes detected in total.A total of 19 cell clusters were recognized,with the main lineages identified as B cells,Granulocytes,Monocytes,T cells,Erythrocytes and Macrophages.Monocytes were further divided into classical monocytes and non-classical monocytes.Compared with non-classical monocytes,classical monocytes highly expressed osteoclast differentiation related genes Mitf,Spi1,Fos and Csf1r.Additionally,biological processes of classical monocytes were related to osteoclast differentiation.qPCR revealed differentially expressed genes of classical monocytes played a role in osteoclast differentiation.In conclusion,classical monocytes were identified as the main precursors of osteoclasts in rats,and may contribute to osteoclast differentiation by regulating S100a4,S100a6,S100a10,Fn1,Vcan and Bcl2a1.The results of this study contribute to the understanding of the origin of osteoclasts and may provide potential biomarkers for early diagnosis of bone metabolic diseases,as well as molecular and cellular targets for clinical intervention in bone metabolic diseases.
文摘Objective: To explore the correlation between muscle strength, muscle mass and bone mineral density (BMD) in Zhuang female population, body composition analysis and grip strength, and to analyze the possible influencing factors of BMD. Methods: 182 postmenopausal women were selected from Guangxi Province of China. Broadband ultrasound attenuation (BUA) was used to evaluate BMD. Grip dynamometer to assess muscle strength. Height, weight and muscle mass of each part were measured by body composition measuring instrument. Body mass index (BMI), skeletal muscle mass index (SMI) and limb skeletal muscle mass (SM) were calculated according to the measurement results. Results: BUA, grip strength and SMI in postmenopausal women of Zhuang nationality showed a decreasing trend with age (p p p r = 0.305, p Conclusion: With the increase of age, the decline rate of muscle strength of postmenopausal Zhuang women in Guangxi is slower than that of BMD and muscle mass. SM can better reflect the BMD level of the body than SMI, and the LSM is the main influencing factor of BMD.
基金the Natural Science Foundation of Zhejiang Province(No.LZ20H290002)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202002)+2 种基金the Fundamental Research Funds for the Central Universities(No.226-2022-00226)the Science and Technological Innovation Project for College Students in Zhejiang Province(Xinmiao Talent Plan 2022R424A005)Zhejiang Provincial Administration of Traditional Chinese Medicine(Nos.2022ZQ022,2023ZF083).
文摘Pharmacodynamics material basis and effective mechanisms are the two main issues to decipher the mechnisms of action of Traditional Chinese medicines(TCMs)for the treatment of diseases.TCMs,in“multi-component,multi-target,multi-pathway”paradigm,show satisfactory clinical results in complex diseases.New ideas and methods are urgently needed to explain the complex interactions between TCMs and diseases.Network pharmacology(NP)provides a novel paradigm to uncover and visualize the underlying interaction networks of TCMs against multifactorial diseases.The development and application of NP has promoted the safety,efficacy,and mechanism investigations of TCMs,which then reinforces the credibility and popularity of TCMs.The current organcentricity of medicine and the“one disease-one target-one drug”dogma obstruct the understanding of complex diseases and the development of effective drugs.Therefore,more attentions should be paid to shift from“phenotype and symptom”to“endotype and cause”in understanding and redefining current diseases.In the past two decades,with the advent of advanced and intelligent technologies(such as metabolomics,proteomics,transcriptomics,single-cell omics,and artificial intelligence),NP has been improved and deeply implemented,and presented its great value and potential as the next drug-discovery paradigm.NP is developed to cure causal mechanisms instead of treating symptoms.This review briefly summarizes the recent research progress on NP application in TCMs for efficacy research,mechanism elucidation,target prediction,safety evaluation,drug repurposing,and drug design.
基金supported by the Science and Technology Department of Sichuan Province(No.2021YFS0182)Science and Technology Department of Tibet(No.XZ202201ZY0033G)Sichuan Provincial Administration of Traditional Chinese Medicine(No.2021MS088).
文摘Fibrosis is the end-stage change of damaged tissues in various human diseases,which can lead to permanent scarring or organ malfunction.Hypoxia leads to oxidative stress,mitochondrial dysfunction,and inflammation in dysfunctional organs and tissues.Oxidative stress resulting from the overproduction of reactive oxygen species plays a central role in the fibrosis of injured organs.This review addresses the updated knowledge of the relationship between hypoxia and tissue fibrosis mediated by the reactive oxygen species pathway.Moreover,novel anti-fibrotic strategies are discussed,which may suppress reactive oxygen species and organ fibrosis.
基金funding from the National Institutes of Health(1R01EB023052,1R01HL140618,1R01HL137193,1R01GM126831)the financial support from the Canadian Institutes of Health Research(CIHR)through a postdoctoral fellowshipthe startup fund from the Pennsylvania State University。
文摘More than 90%of surgical patients develop postoper-ative adhesions,and the incidence of hospital re-admissions can be as high as 20%.Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions.To solve thisclinical limitation,we developed an injectable and sprayable shear-thinning hydrogel barrier(STHB)composed of silicate nanoplatelets and poly(ethylene oxide).We optimized this technology to recover mechanical integrity after stress,enabling its delivery though inject-able and sprayable methods.We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro.The STHB was then tested in a rodent model of peritoneal injury to determine its e cacy preventing the formation of postoperative adhesions.After two weeks,the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions,and STHB formulations presented superior e cacy compared to a commercially available adhesion barrier.Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations.Our technology demonstrated increased e cacy,ease of use in complex anatomies,and compatibility with di erent delivery methods,providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.
基金supported by the National Natural Science Foundation of China(No.81871684,No.81802037)the Provincial Key R&D program of Zhejiang Department of Science and Technology(No.2019C03057)+3 种基金the Zhejiang Provincial Natural Science Foundation of China(No.LY22H190003)the Zhejiang Medical and Health Science and Technology Plan(WKJ-ZJ-2203)the Central Leading Local Science and Technology Development Fund Project(2023ZY1019)the Key Discipline of Zhejiang Province in Public Health and Preventive Medicine(First Class,Category A),Hangzhou Medical College.
文摘Background Toxoplasma gondii is an obligate intracellular apicomplexan parasite and is responsible for zoonotic toxoplasmosis.It is essential to develop an effective anti-T.gondii vaccine for the control of toxoplasmosis,and this study is to explore the immunoprotective effects of a live attenuated vaccine in mice and cats.Methods First,theompdc anduprt genes of T.gondii were deleted through the CRISPR-Cas9 system.Then,the intracellular proliferation and virulence of this mutant strain were evaluated.Subsequently,the immune responses induced by this mutant in mice and cats were detected,including antibody titers,cytokine levels,and subsets of T lymphocytes.Finally,the immunoprotective effects were evaluated by challenge with tachyzoites of different strains in mice or cysts of the ME49 strain in cats.Furthermore,to discover the effective immune element against toxoplasmosis,passive immunizations were carried out.GraphPad Prism software was used to conduct the log-rank(Mantel–Cox)test,Student’st test and one-way ANOVA.Results The RHΔompdcΔuprt were constructed by the CRISPR-Cas9 system.Compared with the wild-type strain,the mutant notably reduced proliferation(P<0.05).In addition,the mutant exhibited virulence attenuation in both murine(BALB/c and BALB/c-nu)and cat models.Notably,limited pathological changes were found in tissues from RHΔompdcΔuprt-injected mice.Furthermore,compared with nonimmunized group,high levels of IgG(IgG1 and IgG2a)antibodies and cytokines(IFN-γ,IL-4,IL-10,IL-2 and IL-12)in mice were detected by the mutant(P<0.05).Remarkably,all RHΔompdcΔuprt-vaccinated mice survived a lethal challenge with RHΔku80 and ME49 and WH6 strains.The immunized sera and splenocytes,especially CD8^(+)T cells,could significantly extend(P<0.05)the survival time of mice challenged with the RHΔku80 strain compared with naïve mice.In addition,compared with nonimmunized cats,cats immunized with the mutant produced high levels of antibodies and cytokines(P<0.05),and notably decreased the shedding numbers of oocysts in feces(95.3%).Conclusions The avirulent RHΔompdcΔuprt strain can provide strong anti-T.gondii immune responses,and is a promising candidate for developing a safe and effective live attenuated vaccine.
基金supported by the National Natural Science Foundation of China(Nos.32071331 and 31600792)Post-Doctor Research Project,West China Hospital,Sichuan University(No.2018HXBH053).
文摘Accumulating studies reveal that mesenchymal stem cells(MSCs)promote skin wound healing mainly through the paracrine effects.Exosomes,one of the crucial paracrine mediators in wound healing,are cell-derived nanosized membranous vesicles containing diverse bioactive cargoes.With the potent ability of modulating skin cell behaviors,MSC-derived exosomes(MSC-Exos)are regarded as a promising nanomaterial for regenerative wound therapy.Under hostile conditions,MSC-Exos are efficient in protecting skin cells from severe damage and restoring their function.According to recent studies,MSC-Exos possess remarkable pro-healing effects in a variety of skin wounds,typically resulting in increased wound closure,inhibited scar tissue formation,and better restoration of skin function.To further enhance the therapeutic potential of MSC-Exos,the development of applicable pretreatment strategies and the optimization of exosome delivery are under intensive investigation.Herein,we summarize current research progress of MSC-Exos for skin wound treatment,with an emphasis on the biological effects of these nanovesicles,the repair mechanisms,and future challenges in clinical translation.
基金supported by grants from the National Key R&D Program of China(2020YFA0509400)Guangdong Basic and Applied Basic Research Foundation(2019B030302012)+4 种基金National Natural Science Foundation of China(81821002,82130082,82341004)1•3•5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD22007,ZYJC21004)Sichuan Science and Technology Program(2021YFH0002,2023NSFSC1878)the 1•3•5 Project of Excellent Development of Discipline of West China Hospital of Sichuan University(No.ZYYC21001)BioRender was used to create the figures.
文摘Inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases,which continuously pose one of the most serious threats to human health,attributed to factors such as the emergence of new pathogens,increasing drug resistance,changes in living environments and lifestyles,and the aging population.Despite rapid advancements in mechanistic research and drug development for these diseases,current treatments often have limited efficacy and notable side effects,necessitating the development of more effective and targeted anti-inflammatory therapies.In recent years,the rapid development of nanotechnology has provided crucial technological support for the prevention,treatment,and detection of inflammation-associated diseases.Various types of nanoparticles(NPs)play significant roles,serving as vaccine vehicles to enhance immunogenicity and as drug carriers to improve targeting and bioavailability.NPs can also directly combat pathogens and inflammation.In addition,nanotechnology has facilitated the development of biosensors for pathogen detection and imaging techniques for inflammatory diseases.This review categorizes and characterizes different types of NPs,summarizes their applications in the prevention,treatment,and detection of infectious and inflammatory diseases.It also discusses the challenges associated with clinical translation in this field and explores the latest developments and prospects.In conclusion,nanotechnology opens up new possibilities for the comprehensive management of infectious and inflammatory diseases.
文摘Drug resistance is one of the most serious issues in epilepsy.Despite using various appropriate anti-epileptic drugs(AEDs),30%of epilepsy patients are still drugresistant.The percentage of resistance in temporal lobe epilepsy(TLE)is even higher[1].Although epilepsy surgery and deep brain stimulation are emerging as alternative therapeutic strategies,the curative outcome is still unsatisfactory.
基金Ethical approval was given by the medical ethics committee of Sichuan University with the following reference number:2012-001-1.
文摘Heavy alcohol drinking is a major public health problem,causing a large disease,social and economic burden in societies.Subjective response (SR) to alcohol is an intermediate characteristic of heavy drinking.A variety of candidate genes have been reported to be associated with SR to alcohol.In this study,we investigated nine single nucleotide polymorphisms (SNPs) related to SR to alcohol in healthy individuals from five Chinese ethnic groups,the Han,Hui,Tibetan,Mongolian and Uygur populations,and a total of 584 bloodstain samples were collected.The nine SNPs included four SNPs in alcohol-metabolizing genes (ADH1B,ADH1C,ALDH2 and CYP2E1*5B) and five SNPs in genes of neurobiological pathways (GABRA2,OPRM1,CHRNA3,HYKK and SLC6A4).A SNaPshot analysis method was developed to type these SNPs simultaneously,and all samples were typed successfully.Statistical analyses of the allele frequencies indicated that the frequencies of all SNPs,except for ADH1C,showed varying degrees of difference in the five studied ethnic groups.Tibetans showed the highest frequencies of risk alleles for heavy drinking at most loci.The genetic polymorphic differences found in this study revealed the variation in genetic susceptibility to heavy drinking in the studied populations.
基金supported by project of the State Key Laboratory of Trauma,Burn and Combined Injury,Third Military Medical University(SKLJYJF20).
文摘Resistance to cancer therapy is a major barrier to cancer management.Conventional views have proposed that acquisition of resistance may result from genetic mutations.However,accumulating evidence implicates a key role of non-mutational resistance mechanisms underlying drug tolerance,the latter of which is the focus that will be discussed here.Such non-mutational processes are largely driven by tumor cell plasticity,which renders tumor cells insusceptible to the drug-targeted pathway,thereby facilitating the tumor cell survival and growth.The concept of tumor cell plasticity highlights the significance of re-activation of developmental programs that are closely correlated with epithelial–mesenchymal transition,acquisition properties of cancer stem cells,and transdifferentiation potential during drug exposure.From observations in various cancers,this concept provides an opportunity for investigating the nature of anticancer drug resistance.Over the years,our understanding of the emerging role of phenotype switching in modifying therapeutic response has considerably increased.This expanded knowledge of tumor cell plasticity contributes to developing novel therapeutic strategies or combination therapy regimens using available anticancer drugs,which are likely to improve patient outcomes in clinical practice.
基金Supported by Sichuan Youth Science and Technology Innovation Research Team of Experimental Formulology(No.2020JDTD0022)Chengdu University of Traditional Chinese Medicine"Xinglin Scholar"Scientific Research Promotion Program for Talents(No.XSGG2019006)Youth Talent Promotion Project of China Association for Science and Technology(No.CACM-2020-QNRC1-01)。
文摘OBJECTIVE:To investigate the anti-bacterial and anti-viral effects of Fengreqing oral liquid(风热清口服液,FRQ)in vitro and in vivo.METHODS:The minimum inhibitory concentrations of Fengreqing Oral Liquid against six gram-positive bacteria(Staphylococcus aureus,Streptococcus mutans,Peptostreptococcus anaerobius,Hemolytic streptococcus,Streptococcus pneumoniae,Klebsiella pneumoniae),seven gram-negative bacteria(Escherichia coli,Actinobacillus actinomycetemcomitans,Porphyromonas gingivalis,Haemophilus influenzae,Helicobacter pylori,Pseudomonas aeruginosa,Gardnerella vaginalis)and Candida albicans were detected by the paper disc diffusion method.The inhibition rate of A/Puerto Rico/8/34(H1N1)(PR8)influenza virus in different concentrations of Fengreqing oral solution was detected by chicken embryo method.CCK8 method was used to detect the half-cell infection of RSV,VSV and CVB3.The effect of FRQ on the survival curve of mice was detected by using co-infection model of Streptococcus pneumoniae and influenza virus.RESULTS:In vitro,FRQ can inhibit Actinobacillus actinomycetemcomitans,Helicobacter pylori,Gardnerella vaginalis,Staphylococcus aureus,Streptococcus mutans and Streptococcus pneumoniae and has an antiviral effect on the envelope virus H1N1.In vivo,Fengreqing oral solution had therapeutic effect on influenza-Streptococcus pneumoniae co-infection in mice,significantly improving the survival rate of mice.The medium dose and low dose FRQ significantly prolonged the survival time of mice.CONCLUSION:FRQ has good anti-bacterial and anti-viral effects in vivo and in vitro.
基金The study was financially supported by the Project of the National Natural Sciences Foundation of China(81373239)The Innovation and Business Starting-oriented training program of College Students in Sichuan Province(C2020113713).
文摘Drug-facilitated sexual assault(DFSA)is a sexual act in which the victim is unable to give or rescind consent due to alcohol or drug intoxication,which involved the abuse of benzodiazepines around the world.Conventional techniques used for the analysis of benzodiazepines have the limitation of short detection time window due to the rapid metabolism of these drugs in body.This study aimed to investigate the characteristic changes of metabolites in the blood of rats after ingesting diazepam/clonazepam through a gas chromatography-mass spectrometry-based metabolomics method,allowing the indirect reveal of the rats ingested diazepam/clonazepam.First,we found that diazepam and clonazepam in the blood of rats could not be detected by liquid chromatography-tandem mass spectrometry after 48 h of ingestion.Then,orthogonal partial least squares discrimination analysis regression models were,respectively,constructed to determine whether the rats ingested diazepam/clonazepam after 48 h.The results showed that 5 metabolites were found to be associated with diazepam exposure,and 7 metabolites were found to be associated with clonazepam exposure,which may be characterization for the evaluation of digestion of diazepam and clonazepam in rat.
基金This work was financially supported by the project of the National Natural Sciences Foundation of China(No.81373239).
文摘The aim of this study was to develop a gas chromatography‑mass spectrometry(GC‑MS)‑based metabolomics method to distinguish different kinds of poisons in the blood.We examined the changes in blood metabolites using GC‑MS following administration of four different poisons(paraquat,dichlorvos,aconitine,and sodium nitrite).The data were analyzed with orthogonal partial least squares.Then,total and single differential metabolite profiles were evaluated with support vector machine(SVM)models.The results showed that various metabolites(5‑ketone proline,1,5‑anhydrohexitol,lactic acid,glycine 2,2‑furoic acid,and 3‑hydroxybutyric acid)were differential between the experimental groups and the control groups.The accuracy rates of the SVM models established using total and single differential metabolites were 80%and 100%,respectively.In conclusion,we successfully developed a poison screening method.The established SVM models can distinguish four kinds of poisons and could be used to establish a complete poison metabonomic information database.Furthermore,some of the metabolites could be biomarkers of these poisons.Finally,both the models and potential biomarkers may reduce the time required for poison detection and provide direction for solving cases and auxiliary diagnosis.
基金supported by the Project of the National Natural Sciences Foundation of China(81373239).
文摘A simple,rapid and sensitive liquid chromatography with tandem mass spectrometry method for the determination of periplocymarin in human blood and urine was developed.The digoxin‑d3 was used as an internal standard.Periplocymarin and digoxin‑d3(IS)were processed with ethyl acetate by liquid–liquid extraction.The chromatographic separation was performed on a Shim‑pack XR‑ODSIII C18 column with a 7 min gradient elution using methanol‑ammonium formate(5 mmol/L)as mobile phase at a flow rate of 0.3 mL/min(65:35,v/v).The detection was performed on a triple quadrupole tandem mass spectrometer using positive‑ion mode electrospray ionization in selected reaction monitoring mode.The periplocymarin was well separated from the internal standard.Two calibration curves were linear within the concentration range 0.01–1µg/mL.The limit of detection and quantification of blood and urine samples were both estimated at 0.005 and 0.01µg/mL.The interday and intraday precisions,accuracy,and recovery were assessed to verify this method.The results showed that the method was suitable for the determination of periplocymarin in forensic toxicological analysis and clinical diagnosis.
基金The study was financially supported by the Project of the National Natural Sciences Foundation of China(81373239).
文摘Chlorpyrifos is an organophosphate pesticide used to kill pests such as insects and worms.Wide use of chlorpyrifos has led to serious safety concerns worldwide.Research on the mechanism of action of chlorpyrifos poisoning is continuing.We investigated changes in the small‑molecular metabolites in the brain and blood of rats upon exposure to chlorpyrifos at an acute‑poisoning dose.Rats were given twice the lowest dose of chlorpyrifos that is lethal for 100%of exposed animals(2×LD_(100))and then killed after 2 h.After treatment,gas chromatography‑mass spectrometry was used to analyze the metabolomic changes in the brain and blood samples of rats.An increase in blood levels of creatinine and uric acid were noted,along with a decrease in levels of various amino acids.These changes suggested that chlorpyrifos exposure may damage kidney function and cause disorders in amino‑acid metabolism of rats.Decreased concentrations of gamma‑aminobutyric acid and niacinamide in the brain and increased concentrations of 3‑hydroxybutyric acid in rats with acute poisoning by chlorpyrifos were observed,which may suggest oxidative damage in the body.
