Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and hea...Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and healthy individuals using bioinformatics approaches,and to verify the function of key transcription factors,with the goal of providing new insights into the pathogenesis of PCOS.Methods:Differentially expressed genes(DEGs)and differentially expressed transcription factors(DETFs)between PCOS patients and controls were identified from the RNA sequencing dataset GSE168404 using bioinformatics methods.Functional enrichment analysis was performed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The expression and function of core transcription factors were further validated in ovarian tissues of PCOS model mice and control mice using Western blotting and reverse transcription quantitative polymerase chain reaction(RTqPCR).Results:A total of 332 DEGs were identified between PCOS patients and controls,including 259 upregulated and 73 downregulated genes in the PCOS group.19 DETFs were further screened,of which 16 were upregulated and 3 were downregulated in PCOS.The upregulated DETFs(including TFCP2L1,DACH1,ESR2,AFF3,SMAD9,ZNF331,HOPX,ATOH8,HIF3α,DPF3,HOXC4,HES1,ID1,JDP2,SOX4,and ID3)were primarily associated with lipid metabolism,development,and cell adhesion.Protein and mRNA expression analysis in PCOS model mice revealed significantly decreased levels of hypoxia-inducible factor(HIF)1αand HIF2α,and significantly increased expression of HIF3αcompared to control mice(all P<0.001).Conclusion:Significant differences in gene and TF expression exist between PCOS patients and healthy individuals.HIF-3αmay play a crucial role in PCOS and could serve as a novel biomarker for diagnosis and a potential therapeutic target.展开更多
Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the inju...Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the injury and pathophysiological mechanisms underlying PCAS remain unclear.Experimental animal models are valuable tools for exploring the etiology,pathogenesis,and potential interventions for CA and PCAS.Current CA animal models include electrical induction of ventricular fibrillation(VF),myocardial infarction,high potassium,asphyxia,and hemorrhagic shock.Although these models do not fully replicate the complexity of clinical CA,the mechanistic insights they provide remain highly relevant,including post-CA brain injury(PCABI),post-CA myocardial dysfunction(PAMD),systemic ischaemia/reperfusion injury(IRI),and the persistent precipitating pathology.Summarizing the methods of establishing CA models,the challenges encountered in the modeling process,and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.展开更多
Endoscop c manometry of sphincter of Oddi(SO)and serumlevels of gastrin,glucagon,and somatostatin were measured in patients withpostcholecystectomy syndrome(n=12),asymptomatic cholecystectomised pa-tients(n=6),and con...Endoscop c manometry of sphincter of Oddi(SO)and serumlevels of gastrin,glucagon,and somatostatin were measured in patients withpostcholecystectomy syndrome(n=12),asymptomatic cholecystectomised pa-tients(n=6),and controlled subjects(n=14).Pentagastrin-stimulated gastricacid secretion test was also performed in part of patients who had symptoms orno symptoms after gallbladder resection.The results showed that the patientsof symptomatic group had hypertonic dyskinesia of SO as shown by deep andwide waves superimposed on high basal pressure plateau of SO.The symptoma-tic group also had a higher serum level of gastrin and a greater BAO than tho-se of other two groups.No difference of serum levels of glucagon and soma-tostatin was found among these three groups.The hypertonic dyskinesia of SOand hypergastrinemia are considered as possibly important factors in the patho-genesis of postcholecystectomy syndrome.展开更多
OBJECTIVE To investigate the compatibility of the prescription Rhodiolarosea,Cordycepsmilitaris,and Rhubarb root.METHODS The DIO mice accompanying with insulin resistance,hypercholesterolemia and obesity were induced ...OBJECTIVE To investigate the compatibility of the prescription Rhodiolarosea,Cordycepsmilitaris,and Rhubarb root.METHODS The DIO mice accompanying with insulin resistance,hypercholesterolemia and obesity were induced by high fat diet(HFD)in C57BL/6mice.For evaluating the insulin sensitivity in vivo,the values of serum insulin,HOMA-IR,and the glucose infuse rate(GIR)in hyperinsulinemiceuglycemic clamp test were determined;the time-dependent blood glucose changes were measured after insulin loading in insulin tolerance test(ITT),or after glucose loading in glucose tolerance test(GTT),respectively.Recombinant human protein tyrosine phosphatase 1B(PTP1B)was overexpressed by hGST-PTP1BBL21 E.coli and purified by GST affinity chromatography.The activities of PTP1 Band glutamine:fructose 6-phosphate amidotransferase(GFAT)were measured by the pNPP and GDH method,respectively.The activity ofα-glucosidase was determined with the substrates of p-nitrophenyl-alpha-D-glucopyranoside(pNPG).The IC50 value was calculated using the software GraphPad Prism 5.RESULTS 1st,the standard for the raw materials and for the extraction process of Rhodiolarosea,Cordycepsmilitaris,and Rhubarbroot are formulated according to the inhibition on PTP1 B,α-glucosidase,and GFAT in vitro,and the improvement on impaired glucose tolerance(IGT),hypercholesterolemia,and obesity in vivo,respectively.2nd,the composition was determined by the synergistic effects of Rhodiolarosea,Cordycepsmilitaris,and Rhubarb root on insulin resistance in DIO mice.3rd,in accordance with the IC50 values from the L9(34)and L8(27)orthogonal experiments targeting on PTP1 B and α-glucosidase,respectively,the best rate of Rhodiolarosea∶Cordycepsmilitaris∶Rhubarbroot was selected.4th,the effective dose for the treatment of metabolic syndrome was assessed based on the effects on IGT,hypercholesterolemia,obesity,insulin resistance,respectively,in DIO mice.CONCLUSION The prescription compatibility of Rhodiolarosea,Cordycepsmilitaris,and Rhubarbroot with the rate of 20∶1∶1was formed to treat the metabolic syndrome,such as IGT,hypercholesterolemia,and obesity,with the effective dose of 200 mg·kg-1 by the major mechanism of the improvement on insulin sensitivity.Monarch drug,Rhodiola,can clear away the lung-heat,tonify Qi,resolve stasis and nourish the heart.Adjuvant drug,Cordycepsmilitaris,can tonify the lung Qi and the kidney essence,strong waist and knee,compatibility with Rhodiola to enhance the function of invigorating lung and kidney.Assistant drug,Rhubarb,can clear heat,detoxify,remove blood stasis.These three herbal are compatible to show the effects of tonifying Qi,nourishing essence,cleaning heat,reducing phlegm and resolving masses for the treatment of metabolic syndrome.展开更多
Acute compartment syndrome （ACS） usually occurs after an injury to a limb or other adjacent organ, when there is insufficient blood supply to muscles and nerves due to swelling and increased pressure within a body c...Acute compartment syndrome （ACS） usually occurs after an injury to a limb or other adjacent organ, when there is insufficient blood supply to muscles and nerves due to swelling and increased pressure within a body compartment. Classically, there are six symptoms and signs associated with ACS, all of which have an initial letter ＇P＇： pain, paresthesia, pallor, paralysis, pulselessness and poik- ilothermia The complexities of the clinical diag- nosis and management of ACS remain a challeng- ing oroblem for orthooedic surgeons.展开更多
Patients developing hemoptysis or pulmonary infiltrates together with glomerulonephritis, particu- larly the rapidly progressive cases, are considered to be pulmonary renal syndrome （PRS）. The occur- rence of PRS, a...Patients developing hemoptysis or pulmonary infiltrates together with glomerulonephritis, particu- larly the rapidly progressive cases, are considered to be pulmonary renal syndrome （PRS）. The occur- rence of PRS, an etiologically rare heterogeneous group of diseases, constitutes a medical emergency associated with a high risk of fatal outcome.展开更多
OBJECTIVE Dysregulation of circadian rhythms is associated with metabolic dysfunction,yet it is unclear whether enhancing clock function by small molecules can ameliorate metabolic disorders.METHODS We used an unbiase...OBJECTIVE Dysregulation of circadian rhythms is associated with metabolic dysfunction,yet it is unclear whether enhancing clock function by small molecules can ameliorate metabolic disorders.METHODS We used an unbiased chemical screen in fibroblasts expressing PER2::Luc to identify the Clock amplitude-Enhancing Small Mole⁃cule.In diet-induced obese mice and DB/DB mutant mice,we evaluated the effects of the Clock amplitude-Enhancing small Molecule on metabolic syndrome and locomotor activity.RESULTS We identified Nobiletin(NOB),a natural poly⁃methoxylated flavone,as a Clock amplitude-Enhancing Small Molecule by an unbiased chemical screen.In diet-induced obese mice,NOB strongly improved metabolic syndrome and enhanced locomotor activity in a Clock gene-dependent manner.Moreover,the clock is also required for the beneficial effects of NOB on metabolic disorders in DB/DB mutant mice.Notably,NOB enhanced clock protein levels and reprogramed metabolic gene expressions in the liver.Finally,we revealed retinoid acid receptor-related orphan receptors(RORα/γ)as direct targets of NOB.CONCLUSION Altogether,our results demonstrate that a pharmacological intervention that enhances circadian rhythms by small molecule may be as a novel strategy for combating metabolic disease.展开更多
Fragile X syndrome(FXS)is the most prevalent inherited intellectual disability,resulting from a loss of fragile X mental retardation protein(FMRP).Patients with FXS suffer lifelong cognitive disabilities,but the funct...Fragile X syndrome(FXS)is the most prevalent inherited intellectual disability,resulting from a loss of fragile X mental retardation protein(FMRP).Patients with FXS suffer lifelong cognitive disabilities,but the function of FMRP in the adult brain and the mechanism underlying age-related cognitive decline in FXS is not fully understood.Here,we report that a loss of FMRP results in increased protein synthesis of histone acetyltransferase EP300 and ubiquitinationmediated degradation of histone deacetylase HDAC1 in adult hippocampal neural stem cells(NSCs).Consequently,FMRPdeficient NSCs exhibit elevated histone acetylation and age-related NSC depletion,leading to cognitive impairment in mature adult mice.Reducing histone acetylation rescues both neurogenesis and cognitive deficits in mature adult FMRPdeficient mice.Our work reveals a role for FMRP and histone acetylation in cognition and presents a potential novel ther⁃apeutic strategy for treating adult FXS patients.展开更多
OBJECTIVE To study the therapeutic effects of TGP on SS both in C57BL/6J mice immunized by immu⁃nological induction(SS mice)and NOD/ShiltJNju(NOD)mice.METHODS TGP(180,360,720 mg·kg^-1)was intragastri⁃cally admini...OBJECTIVE To study the therapeutic effects of TGP on SS both in C57BL/6J mice immunized by immu⁃nological induction(SS mice)and NOD/ShiltJNju(NOD)mice.METHODS TGP(180,360,720 mg·kg^-1)was intragastri⁃cally administered for 6 or 16 weeks for SS mice and NOD mice,respectively.Weekly food and water intake,saliva flow,submandibular gland(SMG)and spleen index,and SMG pathology were measured.ELISA was used to evaluate serum interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and autoantigens(SSA/Ro,SSB/La,andα-fodrin).Real-time PCR and Luminex liquid suspension chip assay were applied to analyze SMG inflammatory cytokines mRNA TNF-α,IL-17A,CXCL9,CXCL13,and B-cell activating factor(BAFF)and protein(IL-1β,IL-6,TNF-α,and IFN-γ)expres⁃sion.RESULTS Compared with SS mice,TGP(720 mg·kg^-1)treatment increased saliva flow,reduced organ indexes,and decreased serum IL-6 and IFN-γ concentration.TGP(360 mg·kg^-1)treatment decreased serum IFN-γ concentra⁃tion.TGP(180,360,720 mg·kg^-1)treatment improved SMG pathological damage.Compared with NOD mice,the saliva flowincreased from 9 to 15 weeks of administration.After 2 weeks of administration,TGP(720 mg·kg^-1)treatment decreased serum SSA/Ro,SSB/La and a-fodrin concentration,increased SMG index,inhibited SMG IFN-γ concentra⁃tion,and down-regulated SMG TNF-α,IL-17A,CXCL9,CXCL13 and BAFF mRNA expression.TGP(360 mg·kg^-1)treat⁃ment decreased serum SSB/La and a-fodrin,and SMG TNF-α and IFN-γ concentration,and down-regulated SMG TNF-α,IL-17A,CXCL9 and BAFF mRNA expression.TGP(180 mg·kg^-1)treatment decreased serum SSB/La,a-fodrin,and SMG IL-1β concentration,and down-regulated SMG TNF-α,IL-17A and BAFF mRNA expression.After 8 weeks of administration,TGP(180,360,720 mg·kg^-1)treatment increased SMG index,and decreased serum a-fodrin concentra⁃tion.TGP(720 mg·kg^-1)treatment down-regulated mRNA expression of SMG TNF-α,IL-17A,CXCL9,CXCL13,and BAFF.TGP(360 mg·kg^-1)treatment reduced mRNA expression of TNF-α,CXCL9,CXCL13 and BAFF,and concentra⁃tion of IL-6 and TNF-α.TGP(180 mg·kg^-1)treatment down-regulated mRNA expression of TNF-α,CXCL9,and CXCL13,and decreased IL-6 and TNF-αconcentration in SMG.After 16 weeks of administration,TGP(180,360,720 mg·kg^-1)treatment reduced serum SSA/Ro and a-fodrin concentration,increased SMG index,and decreased SMG CXCL13 and BAFF mRNA expression.TGP(360,720 mg·kg^-1)treatment decreased serum SSB/Laconcentration and SMG TNF-α,IL-17A and CXCL9 mRNA expression.Besides,TGP(180,360,720 mg·kg^-1)treatment alleviated the pathological damage of SMG after 2 and 16 weeks of administration.CONCLUSION TGP has a certain therapeutic effect onmice through inhibiting inflammatory responses.展开更多
Objective causing mutation in a Marfan syndrome(MFS)family with a proband,and to establish genotype-phenotype correlations.Methods Genomic DNA from peripheral blood leukocytes of a Chinese Marfan syndrome familial wer...Objective causing mutation in a Marfan syndrome(MFS)family with a proband,and to establish genotype-phenotype correlations.Methods Genomic DNA from peripheral blood leukocytes of a Chinese Marfan syndrome familial were isolated and screened for fibrillin-1(FBN1)mutations by direct sequencing,and a genotypephenotype study was carried out following a review of the literature on mutations in the searched area.展开更多
Porcine reproductive and respiratory syndrome virus(PRRSV)GP4 protein was prokaryotically expressed,and used as an antigen to immunize six-week-old BALB/c female mice.With conventional cell fusion method,an anti-PRRSV...Porcine reproductive and respiratory syndrome virus(PRRSV)GP4 protein was prokaryotically expressed,and used as an antigen to immunize six-week-old BALB/c female mice.With conventional cell fusion method,an anti-PRRSV GP4 protein monoclonal antibody(Mab)5F12 was successfully prepared.It was identified as IgG2b subclass and had better stability and specificity,which not only responded with recombinant PRRSV GP4 protein,but also with PRRSV.Phage display technique had varieties of applications,in particular,the identification of key antigen epitopes for the development of therapeutic and diagnostic reagents and vaccines.In this study,Mab-5F12 was used as the target for biopanning a 12-mer phage random peptide library.After four rounds of biopanning,two phage-displayed peptides,named P-A and P-G(AKFEVCSPVVLG and GVNQENMLHFSF)were identified that recognized Mab-5F12 specifically.Sequence analysis showed that one or more of the peptides exhibited partial sequence similarity to the native GP4 protein sequence,which corresponded to 69-80 and 84-95 aa segments of the HP-PRRSV GP4 protein.Furthermore,real-time quantitative RT-PCR and indirect immunofluorescence assay indicated consistently the abilities of P-A and P-G to block viral infection in Marc-145 cells and they could function as antiviral agents for PRRSV.展开更多
Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmat...Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmatory evidence of the diagnosis of Liddle syndrome.Methods DNA samples from the proband with early-onset,treatment-resistant hypertension and hypokalemia and 31 additional relatives were all sequenced for mutations in exon 13 of theβ-ENaC andγ-ENaC genes,using amplification by polymerase chain reaction and direct DNA sequencing.展开更多
Objective To report the clinical features and the screening Results of the pathogenic gene in type 2 Marfan syndrome patients,and the relationship between the transmembrane domain of TGFBR2 gene and the clinical pheno...Objective To report the clinical features and the screening Results of the pathogenic gene in type 2 Marfan syndrome patients,and the relationship between the transmembrane domain of TGFBR2 gene and the clinical phenotype.Methods The FBN1 and TGFBR2 genes were sequenced in the genomic DNA by Sanger sequence of type 2 Marfan syndrome pedigrees,and the protein structure prediction and genotype phenotypic analysis of the TGFBR2 gene transmembrane domain termination mutation were carried out.展开更多
Background and Objective Marfan syndrome,a variable and heritable disorder of fibrous connective tissue,characterized by affecting skeletal,ocular and cardiovascular systems.With the research advancement of genetic me...Background and Objective Marfan syndrome,a variable and heritable disorder of fibrous connective tissue,characterized by affecting skeletal,ocular and cardiovascular systems.With the research advancement of genetic mechanism,the diagnosis of Marfan syndrome,based on clinical manifestations and genetic evidence,is more accurate.The aim of this study is identification of genetic pathogenesis in a Chinese family.展开更多
Background and Objective The white blood cell count to mean platelet volume ratio(WMR)has recently been described as a predictor of cardiovascular events in patients who undergo percutaneous coronary intervention(PCI)...Background and Objective The white blood cell count to mean platelet volume ratio(WMR)has recently been described as a predictor of cardiovascular events in patients who undergo percutaneous coronary intervention(PCI).The aim of this study was to investigate the usefulness of admission WMR in predicting outcomes in patients with acute coronary syndrome(ACS).展开更多
OBJECTIVE To investigate whether Renqing Changjue has a protective effect on acute respiratory distress syndrome(ARDS)induced by endotoxin lipopolysaccharide(LPS)in rabbits.METHODS Thirty-six healthy male New Zealand ...OBJECTIVE To investigate whether Renqing Changjue has a protective effect on acute respiratory distress syndrome(ARDS)induced by endotoxin lipopolysaccharide(LPS)in rabbits.METHODS Thirty-six healthy male New Zealand white rabbits were randomly divided into six groups:normal control group,model group,dexamethasone group,Renqing Changjue high,middle and low dose group,with six rabbits in each group.LPS was used to replicate the ARDS model after five consecutive days of gavage.Arterial pressure,respiratory rate and anal temperature blood were recorded for arterial blood gas analysis at 0,0.5,1,2 and 4 h,respectively.At the end of the four-hour experiment,rabbits were killed by bloodletting,and the lung tissue was quickly removed to determine the cytokines,SOD,MDA and pathological examination of rabbit lung.RESULTS Renqing Changjue can significantly reduce the pathological changes of lung in ARDS model group.The expression of AQP1 and MPO in rabbit lung was significantly decreased by immunohistochemistry(P<0.05),reduce the lung wet/dry weight ratio,increase the ratio of PaO_(2)/FiO_(2),inhibit the release of inflammatory factors and scavenge free radicals and antioxidant effects.CONCLUSION Renqing Changjue can effectively protect rabbits with acute respiratory distress syndrome induced by LPS,and may protect the lung by inhibiting the release of cytokines and anti-oxidation.展开更多
基金supported by the Natural Science Foundation of Hunan Province,China(2022JJ30886).
文摘Objective:Polycystic ovary syndrome(PCOS)is a common endocrine disorder that affects women’s health.This study aims to investigate gene and transcription factor(TF)expression differences between PCOS patients and healthy individuals using bioinformatics approaches,and to verify the function of key transcription factors,with the goal of providing new insights into the pathogenesis of PCOS.Methods:Differentially expressed genes(DEGs)and differentially expressed transcription factors(DETFs)between PCOS patients and controls were identified from the RNA sequencing dataset GSE168404 using bioinformatics methods.Functional enrichment analysis was performed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The expression and function of core transcription factors were further validated in ovarian tissues of PCOS model mice and control mice using Western blotting and reverse transcription quantitative polymerase chain reaction(RTqPCR).Results:A total of 332 DEGs were identified between PCOS patients and controls,including 259 upregulated and 73 downregulated genes in the PCOS group.19 DETFs were further screened,of which 16 were upregulated and 3 were downregulated in PCOS.The upregulated DETFs(including TFCP2L1,DACH1,ESR2,AFF3,SMAD9,ZNF331,HOPX,ATOH8,HIF3α,DPF3,HOXC4,HES1,ID1,JDP2,SOX4,and ID3)were primarily associated with lipid metabolism,development,and cell adhesion.Protein and mRNA expression analysis in PCOS model mice revealed significantly decreased levels of hypoxia-inducible factor(HIF)1αand HIF2α,and significantly increased expression of HIF3αcompared to control mice(all P<0.001).Conclusion:Significant differences in gene and TF expression exist between PCOS patients and healthy individuals.HIF-3αmay play a crucial role in PCOS and could serve as a novel biomarker for diagnosis and a potential therapeutic target.
基金supported by the National Key Research and Development Program(2021YFC3002205)the Postgraduate Research and Innovation Program of Tianjin Municipal Education Commission(2022BKY113),China.
文摘Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the injury and pathophysiological mechanisms underlying PCAS remain unclear.Experimental animal models are valuable tools for exploring the etiology,pathogenesis,and potential interventions for CA and PCAS.Current CA animal models include electrical induction of ventricular fibrillation(VF),myocardial infarction,high potassium,asphyxia,and hemorrhagic shock.Although these models do not fully replicate the complexity of clinical CA,the mechanistic insights they provide remain highly relevant,including post-CA brain injury(PCABI),post-CA myocardial dysfunction(PAMD),systemic ischaemia/reperfusion injury(IRI),and the persistent precipitating pathology.Summarizing the methods of establishing CA models,the challenges encountered in the modeling process,and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
文摘Endoscop c manometry of sphincter of Oddi(SO)and serumlevels of gastrin,glucagon,and somatostatin were measured in patients withpostcholecystectomy syndrome(n=12),asymptomatic cholecystectomised pa-tients(n=6),and controlled subjects(n=14).Pentagastrin-stimulated gastricacid secretion test was also performed in part of patients who had symptoms orno symptoms after gallbladder resection.The results showed that the patientsof symptomatic group had hypertonic dyskinesia of SO as shown by deep andwide waves superimposed on high basal pressure plateau of SO.The symptoma-tic group also had a higher serum level of gastrin and a greater BAO than tho-se of other two groups.No difference of serum levels of glucagon and soma-tostatin was found among these three groups.The hypertonic dyskinesia of SOand hypergastrinemia are considered as possibly important factors in the patho-genesis of postcholecystectomy syndrome.
基金The project supported by National Major Special Project on New Drug Innovation of China(2009ZX09103-4322012ZX09103-101-063+1 种基金2012ZX09301002-004)We also appreciate the support of Novo Nordisk Union Diabetes Research Talent Fund
文摘OBJECTIVE To investigate the compatibility of the prescription Rhodiolarosea,Cordycepsmilitaris,and Rhubarb root.METHODS The DIO mice accompanying with insulin resistance,hypercholesterolemia and obesity were induced by high fat diet(HFD)in C57BL/6mice.For evaluating the insulin sensitivity in vivo,the values of serum insulin,HOMA-IR,and the glucose infuse rate(GIR)in hyperinsulinemiceuglycemic clamp test were determined;the time-dependent blood glucose changes were measured after insulin loading in insulin tolerance test(ITT),or after glucose loading in glucose tolerance test(GTT),respectively.Recombinant human protein tyrosine phosphatase 1B(PTP1B)was overexpressed by hGST-PTP1BBL21 E.coli and purified by GST affinity chromatography.The activities of PTP1 Band glutamine:fructose 6-phosphate amidotransferase(GFAT)were measured by the pNPP and GDH method,respectively.The activity ofα-glucosidase was determined with the substrates of p-nitrophenyl-alpha-D-glucopyranoside(pNPG).The IC50 value was calculated using the software GraphPad Prism 5.RESULTS 1st,the standard for the raw materials and for the extraction process of Rhodiolarosea,Cordycepsmilitaris,and Rhubarbroot are formulated according to the inhibition on PTP1 B,α-glucosidase,and GFAT in vitro,and the improvement on impaired glucose tolerance(IGT),hypercholesterolemia,and obesity in vivo,respectively.2nd,the composition was determined by the synergistic effects of Rhodiolarosea,Cordycepsmilitaris,and Rhubarb root on insulin resistance in DIO mice.3rd,in accordance with the IC50 values from the L9(34)and L8(27)orthogonal experiments targeting on PTP1 B and α-glucosidase,respectively,the best rate of Rhodiolarosea∶Cordycepsmilitaris∶Rhubarbroot was selected.4th,the effective dose for the treatment of metabolic syndrome was assessed based on the effects on IGT,hypercholesterolemia,obesity,insulin resistance,respectively,in DIO mice.CONCLUSION The prescription compatibility of Rhodiolarosea,Cordycepsmilitaris,and Rhubarbroot with the rate of 20∶1∶1was formed to treat the metabolic syndrome,such as IGT,hypercholesterolemia,and obesity,with the effective dose of 200 mg·kg-1 by the major mechanism of the improvement on insulin sensitivity.Monarch drug,Rhodiola,can clear away the lung-heat,tonify Qi,resolve stasis and nourish the heart.Adjuvant drug,Cordycepsmilitaris,can tonify the lung Qi and the kidney essence,strong waist and knee,compatibility with Rhodiola to enhance the function of invigorating lung and kidney.Assistant drug,Rhubarb,can clear heat,detoxify,remove blood stasis.These three herbal are compatible to show the effects of tonifying Qi,nourishing essence,cleaning heat,reducing phlegm and resolving masses for the treatment of metabolic syndrome.
文摘Acute compartment syndrome （ACS） usually occurs after an injury to a limb or other adjacent organ, when there is insufficient blood supply to muscles and nerves due to swelling and increased pressure within a body compartment. Classically, there are six symptoms and signs associated with ACS, all of which have an initial letter ＇P＇： pain, paresthesia, pallor, paralysis, pulselessness and poik- ilothermia The complexities of the clinical diag- nosis and management of ACS remain a challeng- ing oroblem for orthooedic surgeons.
文摘Patients developing hemoptysis or pulmonary infiltrates together with glomerulonephritis, particu- larly the rapidly progressive cases, are considered to be pulmonary renal syndrome （PRS）. The occur- rence of PRS, an etiologically rare heterogeneous group of diseases, constitutes a medical emergency associated with a high risk of fatal outcome.
文摘OBJECTIVE Dysregulation of circadian rhythms is associated with metabolic dysfunction,yet it is unclear whether enhancing clock function by small molecules can ameliorate metabolic disorders.METHODS We used an unbiased chemical screen in fibroblasts expressing PER2::Luc to identify the Clock amplitude-Enhancing Small Mole⁃cule.In diet-induced obese mice and DB/DB mutant mice,we evaluated the effects of the Clock amplitude-Enhancing small Molecule on metabolic syndrome and locomotor activity.RESULTS We identified Nobiletin(NOB),a natural poly⁃methoxylated flavone,as a Clock amplitude-Enhancing Small Molecule by an unbiased chemical screen.In diet-induced obese mice,NOB strongly improved metabolic syndrome and enhanced locomotor activity in a Clock gene-dependent manner.Moreover,the clock is also required for the beneficial effects of NOB on metabolic disorders in DB/DB mutant mice.Notably,NOB enhanced clock protein levels and reprogramed metabolic gene expressions in the liver.Finally,we revealed retinoid acid receptor-related orphan receptors(RORα/γ)as direct targets of NOB.CONCLUSION Altogether,our results demonstrate that a pharmacological intervention that enhances circadian rhythms by small molecule may be as a novel strategy for combating metabolic disease.
文摘Fragile X syndrome(FXS)is the most prevalent inherited intellectual disability,resulting from a loss of fragile X mental retardation protein(FMRP).Patients with FXS suffer lifelong cognitive disabilities,but the function of FMRP in the adult brain and the mechanism underlying age-related cognitive decline in FXS is not fully understood.Here,we report that a loss of FMRP results in increased protein synthesis of histone acetyltransferase EP300 and ubiquitinationmediated degradation of histone deacetylase HDAC1 in adult hippocampal neural stem cells(NSCs).Consequently,FMRPdeficient NSCs exhibit elevated histone acetylation and age-related NSC depletion,leading to cognitive impairment in mature adult mice.Reducing histone acetylation rescues both neurogenesis and cognitive deficits in mature adult FMRPdeficient mice.Our work reveals a role for FMRP and histone acetylation in cognition and presents a potential novel ther⁃apeutic strategy for treating adult FXS patients.
文摘OBJECTIVE To study the therapeutic effects of TGP on SS both in C57BL/6J mice immunized by immu⁃nological induction(SS mice)and NOD/ShiltJNju(NOD)mice.METHODS TGP(180,360,720 mg·kg^-1)was intragastri⁃cally administered for 6 or 16 weeks for SS mice and NOD mice,respectively.Weekly food and water intake,saliva flow,submandibular gland(SMG)and spleen index,and SMG pathology were measured.ELISA was used to evaluate serum interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and autoantigens(SSA/Ro,SSB/La,andα-fodrin).Real-time PCR and Luminex liquid suspension chip assay were applied to analyze SMG inflammatory cytokines mRNA TNF-α,IL-17A,CXCL9,CXCL13,and B-cell activating factor(BAFF)and protein(IL-1β,IL-6,TNF-α,and IFN-γ)expres⁃sion.RESULTS Compared with SS mice,TGP(720 mg·kg^-1)treatment increased saliva flow,reduced organ indexes,and decreased serum IL-6 and IFN-γ concentration.TGP(360 mg·kg^-1)treatment decreased serum IFN-γ concentra⁃tion.TGP(180,360,720 mg·kg^-1)treatment improved SMG pathological damage.Compared with NOD mice,the saliva flowincreased from 9 to 15 weeks of administration.After 2 weeks of administration,TGP(720 mg·kg^-1)treatment decreased serum SSA/Ro,SSB/La and a-fodrin concentration,increased SMG index,inhibited SMG IFN-γ concentra⁃tion,and down-regulated SMG TNF-α,IL-17A,CXCL9,CXCL13 and BAFF mRNA expression.TGP(360 mg·kg^-1)treat⁃ment decreased serum SSB/La and a-fodrin,and SMG TNF-α and IFN-γ concentration,and down-regulated SMG TNF-α,IL-17A,CXCL9 and BAFF mRNA expression.TGP(180 mg·kg^-1)treatment decreased serum SSB/La,a-fodrin,and SMG IL-1β concentration,and down-regulated SMG TNF-α,IL-17A and BAFF mRNA expression.After 8 weeks of administration,TGP(180,360,720 mg·kg^-1)treatment increased SMG index,and decreased serum a-fodrin concentra⁃tion.TGP(720 mg·kg^-1)treatment down-regulated mRNA expression of SMG TNF-α,IL-17A,CXCL9,CXCL13,and BAFF.TGP(360 mg·kg^-1)treatment reduced mRNA expression of TNF-α,CXCL9,CXCL13 and BAFF,and concentra⁃tion of IL-6 and TNF-α.TGP(180 mg·kg^-1)treatment down-regulated mRNA expression of TNF-α,CXCL9,and CXCL13,and decreased IL-6 and TNF-αconcentration in SMG.After 16 weeks of administration,TGP(180,360,720 mg·kg^-1)treatment reduced serum SSA/Ro and a-fodrin concentration,increased SMG index,and decreased SMG CXCL13 and BAFF mRNA expression.TGP(360,720 mg·kg^-1)treatment decreased serum SSB/Laconcentration and SMG TNF-α,IL-17A and CXCL9 mRNA expression.Besides,TGP(180,360,720 mg·kg^-1)treatment alleviated the pathological damage of SMG after 2 and 16 weeks of administration.CONCLUSION TGP has a certain therapeutic effect onmice through inhibiting inflammatory responses.
文摘Objective causing mutation in a Marfan syndrome(MFS)family with a proband,and to establish genotype-phenotype correlations.Methods Genomic DNA from peripheral blood leukocytes of a Chinese Marfan syndrome familial were isolated and screened for fibrillin-1(FBN1)mutations by direct sequencing,and a genotypephenotype study was carried out following a review of the literature on mutations in the searched area.
基金Supported by the National Natural Science Foundation of China(31372438,31200122)
文摘Porcine reproductive and respiratory syndrome virus(PRRSV)GP4 protein was prokaryotically expressed,and used as an antigen to immunize six-week-old BALB/c female mice.With conventional cell fusion method,an anti-PRRSV GP4 protein monoclonal antibody(Mab)5F12 was successfully prepared.It was identified as IgG2b subclass and had better stability and specificity,which not only responded with recombinant PRRSV GP4 protein,but also with PRRSV.Phage display technique had varieties of applications,in particular,the identification of key antigen epitopes for the development of therapeutic and diagnostic reagents and vaccines.In this study,Mab-5F12 was used as the target for biopanning a 12-mer phage random peptide library.After four rounds of biopanning,two phage-displayed peptides,named P-A and P-G(AKFEVCSPVVLG and GVNQENMLHFSF)were identified that recognized Mab-5F12 specifically.Sequence analysis showed that one or more of the peptides exhibited partial sequence similarity to the native GP4 protein sequence,which corresponded to 69-80 and 84-95 aa segments of the HP-PRRSV GP4 protein.Furthermore,real-time quantitative RT-PCR and indirect immunofluorescence assay indicated consistently the abilities of P-A and P-G to block viral infection in Marc-145 cells and they could function as antiviral agents for PRRSV.
文摘Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmatory evidence of the diagnosis of Liddle syndrome.Methods DNA samples from the proband with early-onset,treatment-resistant hypertension and hypokalemia and 31 additional relatives were all sequenced for mutations in exon 13 of theβ-ENaC andγ-ENaC genes,using amplification by polymerase chain reaction and direct DNA sequencing.
文摘Objective To report the clinical features and the screening Results of the pathogenic gene in type 2 Marfan syndrome patients,and the relationship between the transmembrane domain of TGFBR2 gene and the clinical phenotype.Methods The FBN1 and TGFBR2 genes were sequenced in the genomic DNA by Sanger sequence of type 2 Marfan syndrome pedigrees,and the protein structure prediction and genotype phenotypic analysis of the TGFBR2 gene transmembrane domain termination mutation were carried out.
文摘Background and Objective Marfan syndrome,a variable and heritable disorder of fibrous connective tissue,characterized by affecting skeletal,ocular and cardiovascular systems.With the research advancement of genetic mechanism,the diagnosis of Marfan syndrome,based on clinical manifestations and genetic evidence,is more accurate.The aim of this study is identification of genetic pathogenesis in a Chinese family.
文摘Background and Objective The white blood cell count to mean platelet volume ratio(WMR)has recently been described as a predictor of cardiovascular events in patients who undergo percutaneous coronary intervention(PCI).The aim of this study was to investigate the usefulness of admission WMR in predicting outcomes in patients with acute coronary syndrome(ACS).
基金2020 Project of Tibetan Medicine Administration of Tibet Autonomous Region(JJKT202004)and 2020 Reform and Development Special Project(324042000101)。
文摘OBJECTIVE To investigate whether Renqing Changjue has a protective effect on acute respiratory distress syndrome(ARDS)induced by endotoxin lipopolysaccharide(LPS)in rabbits.METHODS Thirty-six healthy male New Zealand white rabbits were randomly divided into six groups:normal control group,model group,dexamethasone group,Renqing Changjue high,middle and low dose group,with six rabbits in each group.LPS was used to replicate the ARDS model after five consecutive days of gavage.Arterial pressure,respiratory rate and anal temperature blood were recorded for arterial blood gas analysis at 0,0.5,1,2 and 4 h,respectively.At the end of the four-hour experiment,rabbits were killed by bloodletting,and the lung tissue was quickly removed to determine the cytokines,SOD,MDA and pathological examination of rabbit lung.RESULTS Renqing Changjue can significantly reduce the pathological changes of lung in ARDS model group.The expression of AQP1 and MPO in rabbit lung was significantly decreased by immunohistochemistry(P<0.05),reduce the lung wet/dry weight ratio,increase the ratio of PaO_(2)/FiO_(2),inhibit the release of inflammatory factors and scavenge free radicals and antioxidant effects.CONCLUSION Renqing Changjue can effectively protect rabbits with acute respiratory distress syndrome induced by LPS,and may protect the lung by inhibiting the release of cytokines and anti-oxidation.
