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Objective To investigate the effects of tryptophan-2,3-dioxygenase(TDO2) on collagen-induced arthritis, the expression of CIA in mice and the specific mechanism by which prostaglandin E2(PGE2) inhibits the expression and activity of TDO2 and thus regulates the function of macrophages. Methods Type Ⅱ collagen induced the CIA model in DBA/1J mice. The ankle joint injury of CIA mice was detected by X-ray. The expression of TDO2 in ankle joint and spleen was detected by immunohistochemistry. Changes of TDO2 expression in peritoneal macrophages(PMs) were detected by qPCR and immunofluorescence. TDO2 expression was detected by small interference in RAW264.7 cells, TDO2 inhibitor 680C91, PGE2 stimulation with different concentrations(0.1, 1, 10 μmol/L) and EP4 receptor agonist CAY10598. qPCR and Western blot were used to detect TDO2 expression. The phagocytosis and polarization of macrophages were detected by flow cytometry. The activity of TDO2 was detected by colorimetry. Results Compared with normal mice, CIA mice had larger soft tissue swelling in ankle, and increased TDO2 expression in synovium, spleen and PMs. In RAW264.7 cells, TDO2 expression was significantly inhibited after small interference, TDO2 inhibitor 680C91, PGE2 stimulation, and EP4 receptor agonist CAY10598, macrophage phagocytosis decreased, and M1/M2 ratio decreased(P<0.05). Colorimetric results showed that the activity of TDO2 was inhibited after stimulation of PGE2 and EP4 agonist CAY10598 in RAW264.7 cells(P<0.05). Conclusion The increased expression of TDO2 in macrophages may promote synovial injury in CIA mice, and PGE2 regulates the function of macrophages by inhibiting the expression and activity of TDO2 by activating EP4 receptor.

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Objective To investigate the effects of linoleic acid(LA) on the diversity and structure of intestinal flora in mice. Methods Twelve SPF grade male C57BL/6J mice at 7 weeks were randomly divided into control group(CTRL group) and linoleic acid group(LA group).One day before the linoleic acid diet was supplemented, the normal food was removed from the LA group and the mice in the LA group were fasted for one night, so that the LA diet was more acceptable to the mice in the LA group, and LA was given on the day of the experiment recording, and the feed was updated at any time to ensure that the mice could eat freely until the end of modeling.After 12 weeks of modeling, mouse feces were collected, and mixed samples were collected for every two mice feces, and then 16sRNA high-throughput sequencing was performed to analyze intestinal flora structure, Alpha and Beta diversity. Results 16sRNA high-throughput sequencing showed that LA intervention damaged the richness and diversity of intestinal flora.The results of principal component analysis showed that the composition of flora in CTRL group was different from that in LA group.At gate level, the relative abundance ofActinobacteriain LA group increased(P<0.01).At the genus level, the relative abundance ofL.Duchenneiin the LA group decreased(P<0.05),but the relative abundance ofBifidobacterium,FaecalibaculumandErysipelotrichaceaein the LA group increased(allP<0.01). Conclusion LA intervention could reduce the richness and diversity of intestinal flora in mice, and adjust the structure of intestinal flora.There were significant differences between beneficial bacteria and pathogenic bacteria in intestinal flora after LA intervention, which provided certain basis for the treatment of bioactive compounds of linoleic acid and the therapeutic adjustment of intestinal microorganisms as targets.

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Objective To observe the role of the renin-angiotensin system in myocardial injury induced by experimental vascular dementia. Methods Eighteen adult male rats were categorized into a normal group, sham group, and modified 2-vessel occlusion group(model).To assess the myocardial injury caused by experimental vascular dementia, immunostaining was conducted to evaluate the interstitial collagen fraction and myocyte cross-sectional area.The concentrations of angiotensin Ⅱ(Ang Ⅱ) and angiotensin 1-7(Ang1-7) in the serum, as well as the expression levels of angiotensin converting enzyme(ACE),angiotensin converting enzyme 2(ACE2),Ang Ⅱ,Ang1-7,angiotensin type 1(AT1) receptor, and Mas receptor in the myocardium, were assessed. Results Modified 2-vessel occlusion led to pronounced cognitive dysfunction(P<0.01) and myocardial injury(P<0.000 1) when compared to the sham and normal groups.Additionally, modified 2-vessel occlusion induced significant upregulation of the ACE/Ang Ⅱ/AT1 receptor axis(P<0.01) and downregulation of the ACE2/Ang1-7/Mas axis(P<0.05) of the renin-angiotensin system in the myocardium. Conclusion Myocardial injury in rats with experimental vascular dementia may be related to dysregulation of the renin-angiotensin system.

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Objective To investigate testicular damage in traumatic brain injury(TBI) rats and to analyze the interventional effects of cannabidiol(CBD) on TBI-induced testicular damage. Methods 18 Sprague Dawley(SD) rats were randomly divided into three groups: the sham operation group(Sham group),model group(TBI group) and treatment group(TBI+CBD group).HE staining was used to observe the testicular histopathological changes in the rat testis.ELISA was used to detect testosterone level in rat serum.TUNEL staining was utilized to observe apoptosis, while immunofluorescence staining, Western blot and RT-qPCR were employed to evaluate Bax, Bcl-2,Cleaved Caspase-3 and TNF-α protein and mRNA expression. Results HE staining showed pathological changes in the testes of TBI rats compared with those in the Sham group.ELISA assay showed a decrease in testosterone levels in the TBI group compared to the Sham group, but there was no significant difference(P>0.05).Immunofluorescence results showed that the intensity of Bax fluorescence expression increased in the TBI group compared with the Sham group(P<0.01),whereas the intensity of Bax fluorescence decreased and the intensity of Bcl-2 fluorescence increased in the rats after the CBD intervention(P<0.01).Western Blot results showed that CBD treatment in rats decreased the protein levels of testicular apoptosis-related proteins(Bax and Cleaved Caspase-3,allP<0.05) and inflammation-related proteins(TNF-α,P<0.01),and increased the protein level of the anti-apoptotic protein, Bcl-2(P<0.05).The trend of RT-qPCR results was similar, with mRNA expression of Bax(P<0.05) and TNF-α(P<0.01) decreased and mRNA expression of Bcl-2 increased after CBD intervention compared with the TBI group(P<0.05). Conclusion TBI induces testis injury, and CBD treatment effectively repairs apoptosis and inflammatory in testicular tissue of TBI rats.

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Objective To explore the mechanism of Prunella vulgaris and Scutellaria barbata herb pair against breast cancer based on network pharmacology and in vitro cell experiments. Methods The effective components and targets of Prunella vulgaris and Scutellaria barbata herb pair were screened.GeneCards and OMIM databases were used to find breast cancer targets, and then drug-active ingredient-key target network and protein-protein interaction(PPI) were constructed.R language was used to perform GO function and KEGG pathway enrichment analysis and survival analysis.Then the screened active components and core targets were verified by molecular docking.Cell viability was detected by CCK-8 assay.EdU and flow cytometry were used to detect cell proliferation and apoptosis.The protein expression levels of p-AKT1,AKT1,β-catenin and c-MYC were detected by Western blot. Results Through databases analysis, a total of 36 active components and 105 intersection targets were screened out, the core components were quercetin, luteolin, kaempferol, wogonin and baicalein.Through PPI and survival analysis, the key targets were AKT1,ESR1,CASP3 and MYC.GO analysis contained 4 303 enrichment results, KEGG analysis contained 232 pathways.Molecular docking showed that the core components had strong binding ability with the key targets.Cell experiments showed that the core active ingredient quercetin could inhibit the proliferation of breast cancer cells and promote their apoptosis(P<0.05),and down-regulate the expression levels of p-AKT1,β-catenin and c-MYC proteins(P<0.05). Conclusion The active components quercetin in Prunella vulgaris and Scutellaria barbata herb pair may play a role through AKT1/β-catenin signaling pathway, which provides a scientific reference for the study of its mechanism of action in the treatment of breast cancer.

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Objective To evaluate the effects and mechanisms of frozen-thawed platelet-rich plasma(PRP) stored at-80 ℃ on wound healing-related cells.Furthermore, to explore the feasibility and effectiveness of using cryopreserved PRP at low temperatures for promoting wound healing.Methods Using non-activated fresh PRP,calcium-activated fresh PRP,and post-thawed PRP,co-cultured with macrophages, fibroblasts, and vascular endothelial cells, the study measured and compared the expression of polarization and inflammatory factors associated with macrophages, as well as cell migration and proliferation rates, among other indicators, to analyze the effects of PRP on macrophage polarization, inflammation, and cell proliferation.Results Compared with the control group, post-cryopreserved PRP at ultra-low temperatures resulted in decreased expression of M1-like polarized macrophage gene iNOS( P<0. 000 1),reduced NO secretion( P<0. 001),increased urea content( P<0. 000 1),decreased M1-related inflammatory factor tumor necrosis factor-alpha( TNF-α)( P<0. 001),and decreased secretion of white blood cell interleukin( IL)-1( P<0. 001); M2-related anti-inflammatory factor IL-10 secretion levels increased( P<0. 01),and IL-12 secretion increased( P<0. 05) Furthermore,co-culturing with frozen-thawed PRP significantly promoted cell migration and enhanced vascular formation efficiency,surpassing the effects of fresh PRP and being comparable to activated PRP( P<0. 01). Cell viability assays and CCK-8 proliferation experiments also showed a significant increase in the proliferation rates of L929 and HUVEC co-cultured with frozen-thawed PRP( P<0. 01). Conclusion After being cryopreserved at-80 ℃,PRP has been proven to significantly enhance cell migration,differentiation,and proliferation capabilities,while inhibiting the production of inflammatory factors and promoting M2 polarization of macrophages. Therefore,low-temperature cryopreservation can be considered as an effective method for PRP preservation.

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Objective To explore the effect of 2-aminoethoxy-diphenyl borate(2-APB) on H2O2-induced chondrocyte apoptosis and its mechanism. Methods The experiment was divided into control group, H2O2group, 2-APB group and H2O2+2-APB group.CCK-8 method was used to detect the cell viability of each group; The effect of 2-APB on the morphological changes of chondrocytes induced by H2O2was observed under microscopy; TUNEL method and flow cytometry were used to detect chondrocyte apoptosis; Flow cytometry was used to detect Lipid reactive oxygen species(ROS);Western blot was used to detect the protein expressions of Cleaved-PARP,p-PKCα and HIF-1α in H2O2-induced cells by 2-APB;Immunofluorescence was used to detect the fluorescent expression of HIF-1α in cells induced by H2O2by PKCα inhibitor BIM-1. Results 2-APB inhibited H2O2-induced apoptosis in chondrocytes, and the inhibitory effect was the most significant when the concentration of 2-APB was 100 μmol/L(F=235.80,P<0.01);22-APB could inhibit the positive rate of H2O2-induced apoptosis of chondrocytes(F=114.80,P<0.01) and the level of ROS(F=52.99,P<0.01).and inhibited the expression of Cleaved-PARP(F=10.10,P<0.05),p-PKCα(F=24.56,P<0.05) and HIF-1α proteins(F=6.85,P<0.05).The PKCα inhibitor BIM-Ⅰ could inhibit the increase in HIF-1α fluorescence intensity caused by H2O2. Conclusion 2-APB can inhibit chondrocytes apoptosis induced by H2O2through the PKCα/HIF-1α pathway and thus protect chondrocytes.

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Objective To clarify the impact of GATA2 overexpression on transcriptional expression in chicken preadipocytes. Methods Chicken preadipocytes ICP1 were cultivated, pCMV-myc-GATA2 or pCMV-myc plasmid was transfected, Western blot was used to verify the overexpression of GATA2 in cells, RNA-seq was used to study the changes in cell transcriptome expression caused by overexpression of GATA2,ChIP-seq was used to study the binding of GATA2 in the genome, Real time PCR was used to verify some differentially expressed genes, ChIP-PCR was used to verify the collection of GATA2 to TAF3 genes. Results Transfection of pCMV-myc-GATA2 allowed overexpression of GATA2 protein in ICP1 cells; overexpression of GATA2 resulted in up-regulation of 942 genes and down-regulation of 840 genes in ICP1 cells(P<0.05),and enrichment analysis showed that differentially expressed genes were associated with ribosome and mitochondrial structure and function(P<0.01);GESA analysis showed that the expression of GATA2-overexpressing ICP1 cells showed up-regulation of RNA polymerase Ⅱ transcription initiation complex, ribosome biogenesis, propionate metabolism, and oxidative phosphorylation-related gene sets, and down-regulation of histone lysine N-methyltransferase, nuclear transcription repression complex formation, adipokines, and calcium ions signaling pathway-related gene sets.ChIP-seq in ICP1 cells identified 2833 GATA2-binding genomic peaks involving 2018 genes.motif analysis revealed GATA2-binding(T/A) GATA motifs; enrichment analysis showed that these genes are involved in embryonic development, signaling, cellular metabolism, and cell-cell interactions.Differently expressed genes and GATA2-binding genes were taken to intersect to obtain 105 genes, and enrichment analysis showed that these genes were associated with transcription, post-transcriptional regulation, cell-cell interactions, signaling, and cell cycle(P<0.001). Conclusion GATA2 can at least bind to the genome of chicken preadipocytes to regulate their transcriptome expression patterns.

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Objective To explore the impact of high glucose(HG) intervention on immune escape of pancreatic cancer cells and its molecular mechanisms. Methods PANC-1 cells were treated with different concentrations of glucose(0,7.5,15,30 mmol/L) for 24 h to establish high glucose intervention PANC-1 cells.miR-429 mimics and its negative control(mimics NC) were transfected into PANC-1 cells, which were divided into control group, HG group, HG+mimics NC group, HG+mimics group, HG+mimics+oe-NC group, and HG+mimics+oe-ZEB1 group.Flow cytometry was utilized to measure the expression level of cell surface molecule PD-L1;qRT-PCR was used to detect the expression levels of miR-429 and ZEB1 mRNA in cells; Western blot was used to detect the expression level of ZEB1 protein in cells.The above-mentioned PANC-1 cells from each group were co-cultured with CD8+T cells to establish a co-culture system, and CCK-8 was used to assess cell proliferation activity; apoptosis levels of cells were measured using flow cytometry; lactate dehydrogenase(LDH) release assay was used to detect the killing effect of CD8+T cells on PANC-1 cells; dual-luciferase reporter system was used to validate the target-regulatory relationship between miR-429 and ZEB1. Results HG could promote the expression of cell surface molecules PD-L1 and ZEB1 in PANC-1 cells(P<0.05),inhibit the expression of miR-429,and exhibit concentration dependence.Overexpression of miR-429 could significantly suppress the expression of cell surface molecule PD-L1 induced by HG in PANC-1 cells, while overexpression of ZEB1 could reverse the inhibitory effect of miR-429 overexpression on the expression of cell surface molecule PD-L1 induced by HG.After establishing a co-culture system with CD8+T cells, compared with the control group, the proliferation activity of PANC-1 cells in the HG group significantly increased, and the apoptosis rate and cytotoxicity significantly decreased(P<0.05).Compared with the HG+mimics NC group, the proliferation activity of PANC-1 cells in the HG+mimics group significantly decreased, and the apoptosis level and cytotoxicity significantly increased(P<0.05).Compared with the HG+mimics group, the proliferation activity of PANC-1 cells in the HG+mimics+oe-ZEB1 group significantly increased, and the apoptosis rate and cytotoxicity significantly decreased(P<0.05).Dual luciferase reporter gene assay confirmed that miR-429 negatively regulated ZEB1. Conclusion High glucose promotes immune escape of PANC-1 cells by downregulating the expression level of miR-429,negatively regulating the expression of ZEB1 mRNA,and increasing the expression level of cell surface molecule PD-L1 in PANC-1 cells.

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Objective To construct Csf1r-CreERT2R26REYFPreporter gene mice and assess the efficacy of Csf1r-CreERT2-mediated enhancement of CSF1R in CD45+cells labeled with yellow fluorescein protein EYFP. Methods Csf1r-CreERT2mice were crossbred with R26REYFPhomozygous mice, and Csf1r-CreERT2R26REYFPmice were identified through PCR and Western Blot analyses.Flow cytometry was employed to evaluate CSF1R tag-efficiency in CD45+cells across different mouse tissues following tamoxifen induction. Results Csf1r-CreERT2R26REYFPreporter gene mice were acquired.In addition, it was found that Csf1r-CreERT2-mediated EYFP could effectively mark CSF1R in various tissues of mice and CD45+cells in different locations.Compared to the R26REYFPgroup, the highest labeling efficiency was observed in the brain tissue(P<0.001), the lowest in the thymus tissue(P<0.05), and no significant difference was observed in the spleen tissue. Conclusion Adult Csf1r-CreERT2mice and R26REYFPmice are effective ways to obtain Csf1r-CreERT2R26REYFPinduced conditional fluorescence mice.Csf1r-CreERT2can mediate EYFP to effectively trace CSF1R in CD45+cells in different parts of mice.

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Objective To investigate the regulatory role of ubiquitin-specific protease 10(USP10) on the protein expression of Krüppel-like factor 4(KLF4) and its impact on the proliferation and invasion ability of hepatocellular carcinoma(HCC) cells. Methods The protein expression differences of USP10 and KLF4 in normal liver cell line L02 and HCC cell lines, including HepG2,HUH7,HCCLM3 were detected by immunoblotting(Western blot) methods.HCCLM3 and HUH7 cells were selected, and lentiviral particles overexpressing or silencing USP10(oe-USP10 or sh-USP10) was transfected into the cells, and they were designated as the oe-USP10 group and oe-NC group, respectively.Immunoprecipitation(Co-IP) experiments were conducted to examine whether USP10 could directly interact with KLF4 in HCCLM3 or HUH7 cells.The Co-IP assay was repeated in HCC cells transfected with oe-USP10 or sh-USP10,with the addition of the proteasome inhibitor MG132,which used to detect the ubiquitination level of KLF4 protein in the transfected HCC cells.The pcDNA3.1 vector containing overexpressed KLF4 or its negative control plasmid(pc-KLF4 or pc-NC) was co-transfected into cells of the sh-USP10 group or sh-NC group.These cells were designated as the sh-NC+pc-NC group, sh-USP10+pc-NC group, sh-NC+pc-KLF4 group, and sh-USP10+pc-KLF4 group.The cell proliferation activity of each group was measured using the CCK-8 assay, and the cell invasion ability was assessed using the Transwell assay. Results Compared to L02 cells, the protein expression of USP10 and KLF4 significantly decreased in HepG2,HUH7,HCCLM3,and other cells(P<0.05).In HCCLM3 and HUH7 cells, USP10 protein directly interacted with KLF4.Furthermore, treatment with MG132 resulted in a time-dependent increase in KLF4 protein expression in HCCLM3 and HUH7 cells.Silencing USP10 increased the ubiquitination of KLF4 in HCCLM3 or HUH7 cells, while overexpressing USP10 decreased the ubiquitination level of KLF4 in cells.Compared to the sh-NC+pc-NC group, both the proliferation activity and invasion ability of HCCLM3 and HUH7 cells significantly increased in the sh-USP10+pc-NC group(P<0.01),while they significantly decreased in the sh-NC+pc-KLF4 group and sh-USP10+pc-KLF4 group(P<0.05).Compared to the sh-USP10+pc-NC group, the proliferation activity and invasion ability of cells significantly decreased in the sh-USP10+pc-KLF4 group(P<0.05). Conclusion USP10 can promote the stability of KLF4 protein through deubiquitination in HCC cell lines, thereby inhibiting the proliferation and invasion of tumor cells.

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Objective To investigate the role of G protein signal regulator 2(RGS2) in regulating the formation of angiotensin Ⅱ(AngⅡ)-induced aortic dissection. Methods C57BL/6 mice were divided into 3 groups: control group(n=10),AngⅡ group(n=20),AngⅡ+sh-RGS2 group(n=20).The AngⅡ group and AngⅡ+sh-RGS2 group established an aortic dissection model.The incidence of aortic dissection was evaluatedin vivo,and the phenotypic transformation of VSMC was evaluatedin vitroandin vivo. Results Knockdown of RGS2 largely counteracted AngⅡ-induced inhibition of αSMA,ACTA2 and MYH11,and suppressed AngⅡ-induced SPP1 and Vimentin in VSMC.The incidence of aortic dissection in AngⅡ group and AngⅡ+sh-RGS2 group were 45%(9/20) and 10%(2/20),respectively.Fewer elastic lamina thickening, aortic rupture, and aortic wall collagen fiber content were observed in AngⅡ+sh-RGS2 group compared to AngⅡ group.In addition, compared with the AngⅡ group, the maximum diameter of the aorta in the AngⅡ+sh-RGS2 group was significantly reduced(P<0.05).In addition, the ACTA2 and MYH11 proteins in the aorta of the AngⅡ+sh-RGS2 group were significantly higher than those in the AngⅡ group(P<0.01),while the RGS2,SPP1,and Vimentin proteins significantly decreased(P<0.01). Conclusion Knockdown of RGS2 inhibits the transformation of AngⅡ-induced VSMC from a contractile phenotype to a synthetic phenotype, thereby reducing the incidence of aortic dissection formation.

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Objective To explore the effect of miRNA-222-3p in endothelial progenitor cell-derived exosomes(EPCs-Exo) on skin wound healing in diabetic mice. Methods Endothelial progenitor cell(EPCs) derived from C57BL/6 mouse bone marrow were identified by fluorescence staining.Subsequently, EPCs-Exo isolated from the media of EPCs were identified, and high-throughput sequencing of EPCs-Exo miRNA was completed.The skin injury model of diabetic mice was established.According to different groups, the wounds were treated with externally applied phosphate buffer solution(PBS) and EPCs-Exo; Subcutaneous injection of PBS,agomiR-222-3p, and antagomiR-222-3p at the edge of the wound was performed continuously for 14 days, and the wound healing rate was observed.Meanwhile, immunofluorescence methods were used to investigate the changes in the expression levels of ROS,CD31,and VEGF in the wound margin tissue before and after treatment. Results EPCs-Exo significantly accelerated skin wound healing in diabetic mice, reduced the level of ROS,and increased the expression level of VEGF and CD31 in the wound margin tissue(P<0.05). High-throughput sequencing showed that miRNA-222-3p was highly expressed in EPCs-Exo.Local subcutaneous injection of miRNA-222-3p into wound margin tissue significantly promoted the skin wound healing of diabetic mice, reduced the level of ROS,and increased the expression level of VEGF and CD31 in the wound margin tissue(P<0.05). Conclusion MiRNA-222-3p promotes wound healing in diabetic mice and plays an important role in EPCs-Exo promoting wound healing.

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Objective To study the protective effect of polydatin on lipopolysaccharide-induced injury of human umbilical vein vascular endothelial cells(HUVECs) through the protein Janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3) signaling pathway. Methods HUVECs were culturedin vitro,and 500 ng/ml LPS induced their injury and set as a model group; based on the model group, endothelial cells were intervened with different concentrations(10,20,and 40 μmol/L) of polydatin for 24 h, and set as polydatin lowconcentration group, polydatin medium concentration group, and polydatin high concentration group, respectively; a control group was set as another group.CCK-8,monocyte-endothelial cell adhesion, scratch and Transwell assays were used to detect cell viability, adhesion, migration and invasive ability; ELISA was used to detect interleukin-6(IL-6) and tumor necrosis factor-alpha(TNF-α) levels in the cell supernatant; Western blot was used to detect the expression of proteins related to the JAK2/STAT3 signaling pathway levels of JAK2/STAT3 signaling pathway related proteins. Results Compared with the control group, the model group showed decreased cell survival(P<0.01),increased cell adhesion, migration and invasion(P<0.001,P<0.05,P<0.01),increased levels of IL-6 and TNF-α in the cell supernatant(P<0.001),and increased levels of phosphorylation of JAK2 and STAT3 proteins in the cells(P<0.05).Compared with the model group, LPS damage to cells was attenuated after polydatin intervention, cell survival was increased in polydatin low-,medium-and high-concentration groups(P<0.05),cell adhesion, migration, and invasion decreased(P<0.05,P<0.05,P<0.001),IL-6 and TNF-α levels in cell supernatants decreased(P<0.05),and the levels of cellular JAK2 and STAT3 protein phosphorylation levels decreased(P<0.05). Conclusion Polydatin seems to reduce the inflammatory injury of human umbilical vein endothelial cells induced by LPS,reducing the secretion of inflammatory factors, and inhibiting the ability of cell adhesion, migration and invasion, which may be related to the down-regulation of JAK2/STAT3 signal pathway by polydatin.

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Objective To investigate the role and mechanism of urate in chronic kidney disease complicated with renal interstitial fibrosis(CKD-RIF). Methods Mice were continuously fed with a diet containing 0.2% adenine for a duration of 9 weeks to establish mice models with CKD-RIF.By the end of the 9-week experimental periods, collected blood samples from the posterior orbital venous plexus of mice to measure renal functions and serum urate concentrations prior to euthanizing the mice.Hematoxylin-eosin(HE) staining and periodic acid-Schiff staining(PAS) were used to investigate the pathological alternations in kidney tissues.Masson′s trichrome staining was used to observe the extent of renal fibrosis.Urate staining was used to detect urate deposition in renal tissues.Western blot and immunohistochemistry were used to detect the expression of target molecules.Scratch tests were used to examine the migration abilities of cells treated with different concentrations of uric acid. Results The kidney function analysis showed that a significant increase in the levels of serum urea nitrogen(P=0.006 4),creatinine(P=0.008 0) and urate(P=0.000 7) in the CKD-RIF mice compared with the normal control group.The results of HE staining and PAS staining showed a significance of renal tubule injury and infiltration of inflammatory cells in the model group.Masson′s trichrome staining showed that a marked increase in collagen deposition in the model group.The results of urate staining showed a significant presence of urate crystals in kidney tissue of the model group when compared to the control group.Animal tissue immunoblotting and immunohistochemistry analysis showed a significant increase in the expression levels of vimentin, α-SMA and TGF-β1 in the model group in comparison to the control group.Conversely, in the model group, E-cadherin levels exhibited a dramatic reduction compared to the control group.The findings from the scratching tests showed that uric acid significantly enhanced cell migration.Western blot analysis showed a dramatic increase in the expression levels of vimentin and α-SMA,while E-cadherin exhibited significant decrease in the cells subjected to uric acid treatment. Conclusion Urate stimulates the secretion of TGF-β1 by renal tubule epithelial cells and induces epithelial-mesenchymal transdifferentiation, thereby exacerbating renal interstitial fibrosis in CKD.

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Objective To prepare and identify CS-PLGA microspheres carrying bilayer antigen protein.Methods Porous microspheres were prepared by emulsion polymerization combined with solvent evaporation.The antigen was loaded in a water bath at 4 ℃,and the antigen was promoted to enter the microspheres by physical diffusion mediated by antigen concentration gradient and combined with the outer surface of the microspheres by electrostatic action, forming an inner and outer double-layer antigen carrier.Then, according to the glass transition temperature of PLGA material, the pores on the surface of porous microspheres were promoted to heal at 48 ℃ to form a closed microsphere preparation, and then the obtained microsphere preparation was suspended with chitosan solution for cationic modification to reverse the negative potential on the surface of microspheres. In this study,the morphology,particle size distribution and potential changes of microspheres were detected by scanning electron microscope and dynamic light scattering particle size analyzer. In addition,sodium dodecyl sulfate polyacrylamide gel electrophoresis( SDS-PAGE) was used to identify whether the antigen was loaded into the microsphere preparation. The fluorescent labeled BSA and fluorescent labeled PLGA materials were used to observe the distribution of the antigen after loading by laser confocal microscope. The encapsulation efficiency and drug loading rate of the microsphere preparation were detected by BCA method. Results The results of scanning electron microscope and optical microscope showed that the porous microspheres had good pore formation,the particle size was( 73. 94 ± 0. 81) nm,and the Polydispersity index was 0. 038 ± 0. 004. Zeta potential changed from negative to positive,which indicated that chitosan had been successfully coated on the surface of microspheres. SDS-PAGE,laser confocal microscope and other detection methods confirmed that BSA had been successfully carried. The encapsulation rate of porous microspheres was( 3. 01 ± 0. 04) % and the drug loading rate was( 1. 50 ± 0. 02) % after detection by micro BCA kit. Conclusion CS-PLGA preparation carrying bilayer antigen was successfully prepared,which provided a new idea for the subsequent study of sustained and controlled release preparations.

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Objective To study the mechanism of the treatment of metabolism associated steatohepatitis(MASH) in rats with Xiaoyao Wan. Methods Twenty-four SD male rats were randomly divided into control group(CON group,n=8) and model group(n=8). The model group was given high-fat diet, carbon tetrachloride(CCl4) subcutaneous injection, hunger and satiety disorder and tail clamping for four weeks to establish the MASH model, and the rats were randomly divided into the MOD group and the Xiaoyao Wan group(XYW group), with 8 rats in each group. The rats of the XYW group were given Xiaoyao Wan, the other two groups were given normal saline. Four weeks after administration, the serum biochemical indexes and oxidative stress indexes of rats in different groups were detected. The pathological sections of rat liver tissue were observed by hematoxylin-eosin(HE) staining and oil red O staining. The expression of cytochrome P450 2E1(CYP2E1), factor-related apoptosis ligand(FasL), tumor necrosis factor-α(TNF-α) and tumor growth factor-β1(TGF-β1) in rat liver were detected by Western blot method. The relative contents of CYP2E1, FasL, TNF-α and TGF-β1 mRNA in liver tissue were detected by RT-qPCR. Results The general condition of rats in the XYW group was significantly improved compared with the MOD group; the level of hepatic index was significant decrease compared with the MOD group(P<0.01) and the level of body mass index was significant increase compared with the MOD group(P<0.01); the serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, aspartate aminotransferase, alanine aminotransferase, malondialdehyde, monocyte chemotactic protein-1, TNF-α, and interleukin(IL)-18 were significantly reduced compared with the MOD group(allP<0.05), and the levels of high-density lipoprotein cholesterol, superoxide dismutase, and IL-10 were significantly elevated compared with the MOD group(allP<0.05); the content of lipid droplets in hepatocytes of rats was significantly reduced compared with the MOD group under light microscope; the protein levels of CYP2E1, FasL, TNF-α and TGF-β1 in liver tissues were significantly reduced compared with the MOD group(allP<0.05), and the relative contents of CYP2E1, FasL, TNF-α and TGF-β1 mRNA were significantly reduced compared with the MOD group(allP<0.05). Conclusion Xiaoyao Wan can regulate the expression of CYP2E1, FasL, TNF-α and TGF-β1 in the liver tissue of MASH rats by reducing the accumulation of fat in the liver, so as to achieve the purpose of treating MASH.

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Objective To examine the impact and partial mechanism of bupivacaine sustained-release drug(code PB21) in combination with low-dose dexamethasone(Dex) on the analgesic time of rats with knee osteoarthritis(KOA). Methods Using the techniques of anterior cruciate ligament transection and meniscus instability, a rat KOA model was created.After eight weeks, SD mice were split into three groups at random: a group for the model, one for Dex(50 μg),one for PB21(1.5 mg),and one for combined administration(1.5 mg PB21/50 μg Dex),with a control group that received a sham operation.The pain thresholds of KOA rats were measured using a Pressure Application Measurement(PAM) at different intervals before to delivery and 4,24,36,and 48 hours following administration; to gauge changes in discomfort, a CatWalk was used to assess the rats′ average foot strength and maximum contact area before, four, twenty-four, and forty-eight hours after treatment.A portion of the rats were put to sleep at four, twenty-four, and forty-eight hours following the injection, and the joint synovium was removed for paraffin sectioning.Immunohistochemistry was used to identify the expression of GAP43 in the synovium, whereas immunofluorescence was used to identify the expression of CGRP in the same tissue. Results The average strength and maximum contact area of the foot and claw decreased(P<0.01), and the pain threshold decreased(P<0.01) in the model group compared to the sham operation group. The PB21+Dex group experienced a delayed pain threshold lowering time delay when compared to the PB21 and Dex treatment groups alone. Up to 48 hours later, the combination administration group′s average strength and maximum contact area of the foot paw remained elevated, and there was a statistically significant difference(P<0.05) between the combined administration group and PB21 and Dex alone. GAP43 and CGRP expression levels in synovial tissue were detected. The results indicated that PB21 and Dex alone could lower protein expression levels at 4 and 24 h at the two time points, and that the PB21+Dex group could still significantly lower GAP43 and CGRP expression levels at 48 h. At the 48 h time point, the PB21+Dex group was statistically significant when compared to the PB21 and Dex alone administration group(P<0.05). Conclusion In summary low dose dexamethasone can prolong the analgesic effect of PB21 on KOA rats, which is connected to reducing the expression of pain related proteins CGRP and GAP43.

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Objective To study the effect of leucine rich repeat kinase 2(LRRK2) on pain sensitivity in neuropathic pain(NP) rats and explore its possible mechanism.Methods 48 SD rats were randomly divided into four groups: sham surgery(Sham),model, LRRK2 inhibitor(MLi-2),and LRRK2 inhibitor+p38 mitogen activated protein kinase(MAPK) agonist(MLi-2+Anisomycin),with 12 rats in each group.The NP rat model was induced by chronic constriction injury(CCI) of the sciatic nerve.Intrathecal injection of MLi-2(1 mg/kg, 10 μl) or Anisomycin(20 μmol/L,10 μl) was started from the 8 th day after surgery, once a day for 7 consecutive days.Pain sensitivity tests were conducted before surgery(day 0) and on postoperative days 7 and 14,respectively.The changes in mechanical withdrawal threshold(MWT) and paw withdraw thermal latency(PWTL) were analyzed in each group of rats.ELISA was used to detect the levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α) in the dorsal horn of the rat spinal cord.Nissl staining was used to observe the pathological changes of neurons in rat spinal cord tissue.Immunofluorescence staining was used to observe the expression levels of ionized calcium-binding adapter molecule-1(Iba-1),a marker of microglia in the spinal cord of rats.Western blot was used to detect the protein expression levels of LRRK2,p-p38 mitogen activated protein kinase( MAPK),p38 MAPK,and Iba-1 in the dorsal horn of the rat spinal cord. Results Compared with the sham group,the model group showed a significant decrease in MWT and PWTL in the right hind limb of rats( P<0. 01). The levels of IL-1,IL-6,and TNF in the spinal dorsal horn tissue,as well as the expression levels of LRRK2,Iba-1 proteins and p-p38 MAPK/p38 MAPK protein ratio significantly increased( P<0. 01). The proportion of Iba-1 positive cells in the spinal cord tissue significantly increased( P<0. 01),while Nissl bodies were significantly reduced( P<0. 01). Compared with the model group,the MLi-2 group showed a significant increase in MWT and PWTL in the right hind limb of rats( P<0. 01),a significant increase in Nissl bodies( P<0. 01),a significant decrease in the proportion of Iba-1 positive cells in the spinal cord tissue( P<0. 01),and a significant decrease in the levels of IL-1,IL-6,and TNF and the expression levels of LRRK2,Iba-1 proteins and p-p38 MAPK/p38 MAPK protein ratio( P<0. 01). However,Anisomychin intervention could activate the p38 MAPK signaling pathway and partially reverse the beneficial effects of MLi-2 on pain sensitivity and neuroinflammation in rats with neuropathic pain. Conclusion Inhibiting the expression of LRRK2 can alleviate pain sensitivity in NP rats induced by microglia activation mediated neuroinflammation,and its mechanism of action may be related to regulating the p38 MAPK signaling pathway.

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Objective To investigate the molecular mechanisms by which SOX7 regulates the SHP-2/Wnt/β-catenin/ROS pathway, affecting the proliferation, invasion, and migration of colorectal cancer cells. Methods Twenty nude mice with subcutaneously transplanted tumor models were randomly divided into four groups: SOX7 NC(n=5),SOX mimic(n=5),SOX7 NC+PHPS1(n=5),and SOX7 mimic+PHPS1(n=5) to observe tumor growth.Human colorectal cancer cell line SW480 cells were transfected via lipofection and divided into six groups: SOX7 NC,SOX7 mimic, SOX7 NC+H2O2,SOX7 mimic+H2O2,SOX7 NC+PHPS1,and SOX7 mimic+PHPS1.The expression of SHP-2/Wnt/β-catenin/ROS pathway-related proteins in SW480 cells of each group was detected by Western blot.The invasion and migration capabilities of SW480 cells were assessed through scratch and Transwell invasion assays, while cell proliferation was evaluated using CCK-8. Results In vivoexperiments demonstrated that tumors in the SOX7 mimic group were significantly smaller than those in the SOX7 NC group(P<0.01).Tumors treated with PHPS1 intervention exhibited a significant increase in volume.There was no statistical significance in the difference in tumor volume between the SOX7 mimic+PHPS1 group and the SOX7 NC+PHPS1 group.In vitroexperiments revealed that SOX7 mimic inhibited the expression of Wnt, β-catenin, NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P<0.01),and promoted the expression of p-SHP-2 protein(P<0.01).The addition of hydrogen peroxide and SHP-2 inhibitor reversed the effects of SOX7 on SW480 cells(P<0.05),and significantly promoted the expression levels of Wnt, β-catenin, NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins, with no significant difference, while significantly reducing the expression levels of SHP-2,p-SHP-2 proteins, with no significant difference.PHPS1 inhibited the expression of SHP-2,p-SHP-2 proteins(P<0.05) and upregulated the expression of Wnt, β-catenin, NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P<0.05).Scratch, Transwell invasion and migration assays, and CCK-8 experiments indicated that SOX7 suppressed the migration, invasion, and proliferation of SW480 cells through oxidative stress and the SHP-2 pathway(P<0.01),while H2O2and PHPS1 intervention promoted the migration, invasion, and proliferation of SW480 cells(P<0.05). Conclusion SOX7 can suppress the proliferation, invasion, and migration of colorectal cancer by targeting the SHP-2/Wnt/β-catenin/ROS pathway.

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Objective To investigate the neurobehavioral development of young children aged 24 to 60 months in Shunde and explore the factors influencing the development of young children and provide reference for the intervention of neurobehavioral development delays in young children. Methods A retrospective cohort study was used to enroll the young children who were initially screened by the Pediatric Neuropsychological Developmental Scale(Pediatric Heart Scale) with a score of ≤85 was included in the study.With a score of ≤85,the young children might be at risk of developmental delays, and needed to be further diagnosed by the GESELL Developmental Diagnostic Scale, the basic information of the young children and their mothers at the time of birth were investigated, as well as basic information about the young children at the time of completing the GESELL Developmental Diagnostic Scale was collected. Results A total of 271 young children were included, 196 males and 75 females.Young children had the lowest developmental quotient(DQ) in the language domain among the five domains(P<0.001).Multiple linear regression models showed: compared with girls, the language domain DQ of boys decreased by 5.321 points(P=0.049,95%CI:-10.620--0.021),and the personal-social domain DQ decreased by 4.474 points(P=0.023,95%CI:-8.316--0.631).Compared with young childrenvianatural vaginal delivery(NVD),the gross motor domain DQ of young childrenviacaesarean section(CS) decreased by 4.890 points(P=0.008,95%CI:-8.499--1.281),the fine motor domain DQ decreased by 3.373 points(P=0.037,95%CI:-6.532--0.213),the language domain DQ decreased by 7.621 points(P=0.004,95%CI:-12.826--2.416),personal-social domain DQ decreased by 6.232 points(P=0.001,95%CI:-10.006--2.457).The results of binary logistic regression models showed, compared with young childrenviaNVD,the risk of gross motor domain retardation in young children increased(OR=1.763,95%CI:1.003-3.100),the risk of fine motor domain retardation increased(OR=2.217,95%CI:1.235-3.980),the risk of language domain retardation increased(OR=3.306,95%CI:1.080-10.124). Conclusion Young children with suspected neurobehavioral delays were more likely to have delayed development in language domain than in other domains, boys had lower DQ in language domain and personal-social domain than girls, and the development of young childrenviaCS was slower than thatviaNVD.Focus should be on the language development of young children especially on the language and personal-social development of boys.Carefully chose delivery way.Focus should be placed on assessment of young children′s comprehensive neurobehavioral development in early time.

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Objective To explore the causal relationship between rheumatoid arthritis(RA) and iron deficiency anemia(IDA) in European population by two-sample Mendelian randomization analysis. Methods The single nucleotide polymorphisms(SNPs) of RA and IDA were analyzed using public genome-wide association studies(GWAS).The inverse variance weighting method(IVW) was used as the main analysis method to evaluate the causal effect of RA on IDA.MR-Egger method, weighted median method(WM),weighted model method and simple model method were used as regression supplements to evaluate the robustness of sensitivity analysis results.The heterogeneity function was used to calculate theP-value to test the heterogeneity, and the intercept term intercept was used to test the level pleiotropy. Results In the FINNGEN database at the genome-wide level, strong-related SNPs that removed linkage disequilibrium and met theP<5.0×10-8by Mendelian randomization analysis were selected.After integrating exposure and outcome data, 31 SNPs were obtained as the final effective instrumental variables.IVW showed that RA was a risk factor for IDA(the risk of IDA in RA patients was 1.064 times higher than that in non-RA patients,OR=1.064,95%CI:1.028-1.103).The weighted median method and MR-Egger method results supported the positive correlation between RA and IDA.The intercept value was close to 0,indicating that there was no horizontal pleiotropy between exposure and outcome.The heterogeneity function′sP<0.05 indicated that there was heterogeneity between exposure and outcome, but the random effect model test showedP<0.05,indicating that even if there was heterogeneity in causality, the overall trend was stable. Conclusion RA is a risk factor for IDA,and there is a positive correlation between RA and IDA.

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Objective To investigate the relationship between the single nucleotide polymorphism of PPARG rs2290449 and the efficacy of combination therapy in sepsis patients with MODS. Methods 382 cases of sepsis with MODS were selected and divided into the effective group and the ineffective group, and a case-control study was conducted. PCR-RFLP and Sequenom MassARRAY were used to detect the genotype and allele frequencies of the loci. Unconditional Logistic regression was used to calculate odds ratio(OR) and 95% confidence interval(CI) to evaluate the efficacy of combination therapy for sepsis with MODS in patients with different genotypes. Results There were G and A alleles in PPARG rs2290449 locus, GG、GA and AA genotype. Non-conditional Logistic regression analysis showed that compared with the GG genotype group, the GA genotype group had a significant correlation with the efficacy of combination therapy for sepsis with MODS(OR=0.449,95%CI=0.280-0.722,P=0.001). In the dominant model, there was a significant correlation between the GA+AA genotype and the efficacy of combination therapy compared with the GG genotype(OR=2.104,95%CI=1.332-3.321,P=0.001).After adjusting for confounding factors, unconditional Logistic regression analysis showed that compared with the GG genotype, the GA+AA genotype was significantly correlated with the efficacy of combination therapy in sepsis patients with MODS(OR=2.307,95%CI=1.438-3.701,P=0.001). Stratified analysis showed that compared with the population carrying GG genotype, the population carrying GA+AA genotype was significantly correlated with the efficacy of combination therapy in sepsis with MODS in the stratified analysis of age, gender and ethnicity. Conclusion PPARG rs2290449 single nucleotide polymorphism is significantly correlated with the efficacy of combination therapy in sepsis patients with MODS in Yanbian area.

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Objective To observe the effects of brain-computer interface-controlled pedal training system on balance function and serum interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) levels in ischemic stroke patients. Methods Forty patients with ischemic stroke who were hospitalized from September 2022 to September 2023 were selected as observation subjects.The patients were equally divided into stroke control group and stroke experimental group according to the random number table method.At the same time, 20 healthy subjects with similar gender and age were recruited as the healthy control group to collect relevant plantar pressure data.Patients in the stroke control group received conventional rehabilitation training including the upper and lower extremity active and passive motor training system, and the stroke experimental group replaced the upper and lower extremity active and passive motor training system in the stroke control group with the brain-computer interface-controlled pedal training system for rehabilitation treatment, and other things remained unchanged.Bilateral plantar pressure symmetry index(SI) and center of body pressure(COP) swing area were collected from both groups of stroke patients with eyes open and closed using the plantar pressure assessment system before and after 4 weeks of treatment.Fugl-meyer lower extremity motor function score(FMA-LE) and berg balance scale(BBS) were used to evaluate the two groups of stroke patients.Serum IL-6 and TNF-α levels were also compared between the two groups before and after treatment. Results (1) The SI value and COP swing area in the eyes open and closed state improved in both groups of stroke patients after treatment compared with that before admission, and the results of the stroke experimental group were better than those of the stroke control group(P<0.05),but there was still a gap with the healthy control group(P<0.05).(2) The BBS and FMA-LE scores of stroke patients in both groups were higher after treatment than before treatment, and the scores of the stroke experimental group were greater than those of the stroke control group, with statistically significant differences(allP<0.05).(3) Serum IL-6 and TNF-α levels decreased in both groups of stroke patients after treatment compared with before, and the degree of decrease in serum IL-6 and TNF-α levels in the stroke experimental group was greater than that in the stroke control group, and the difference was statistically significant(P<0.001,P<0.05). Conclusion Brain-computer interface-controlled pedal training system has a facilitating effect on the recovery of balance function in hemiplegic patients with ischemic stroke, and its mechanism may be related to the reduction of serum IL-6 and TNF-α levels.

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Objective To investigate the correlation between uric acid to high-density lipoprotein cholesterol ratio(UHR) and late recurrence after radiofrequency ablation in patients with non-valvular atrial fibrillation(AF). Methods The clinical data of 586 patients with non-valvular AF underwent catheter radiofrequency ablation for the first time from January 2018 to January 2022 were selected, and the study population was classified into a low-value group(n=196),a medium-value group(n=195),and a high-value group(n=195) according to the trichotomous method based on the UHR value, with late recurrence of AF as the endpoint event of the follow up.The general data and laboratory indexes were compared among the three groups.Survival curves were estimated and plotted using the Kaplan-Meier method.Multivariate COX regression analysis was used to evaluate the independent correlation between UHR and recurrence of AF after ablation, followed by subgroup analysis. Results Late recurrence of AF was documented in a total of 182(31.1%) patients during the follow-up time.The Kaplan-Meier survival curve showed a gradual decrease in the maintenance rate of sinus rhythm across the UHR low-value group, middle-value group, and high-value group(Log-rank test,P<0.001).In the fully-adjusted model, compared with the patients in the low-value group, the medium-value and high-value groups had a post-ablation late recurrence of AF withHR(95%CI,P) were 1.56(0.99-2.42,P=0.057) and 2.03(1.28-3.23,P=0.003),respectively.Subgroup analysis showed that the association between UHR and late recurrence of AF after ablation was remarkable among patients with aged≥60 years, BMI≥25 kg/m2,persistent AF,LAD≥4.3 cm, hypertension, without heart failure and without hyperlipidemia. Conclusion Higher UHR values in patients with non-valvular AF are independently associated with an increased risk of late recurrence of AF after radiofrequency ablation procedures.

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Objective To investigate the expression levels and clinical significance of cold-inducible RNA-binding protein(CIRBP) and triggering receptor expressed on myeloid cells-1(TREM-1) in peripheral blood of patients with chronic obstructive pulmonary disease(COPD).Methods Forty hospitalized COPD patients from October 2022 to June 2023 were selected as the acute exacerbation group.After treatment, they entered the stable phase and were included in the stable phase group.During the same period, 40 healthy individuals underwent physical examinations as the control group.General information from each group was collected, peripheral blood was collected, and the levels of CIRBP and TREM-1 in plasma were measured using enzyme-linked immunosorbent assay(ELISA).The relative expression levels of CIRBP mRNA and TREM-1 mRNA were measured using real-time fluorescence quantitative polymerase chain reaction( qRT-PCR),and lung function was measured in COPD patients and healthy individuals. Results The expression levels of CIRBP and TREM-1 in peripheral blood during the acute exacerbation of COPD were higher than those in the stable phase group,and the differences were statistically significant( all P<0. 001); The expression levels of CIRBP and TREM-1 in peripheral blood during acute exacerbation and stable phases were higher than those in the control group,and the differences were statistically significant( all P<0. 001); In both acute exacerbation and stable phases,CIRBP levels were positively correlated with TREM-1 levels;The levels of CIRBP and TREM-1 during acute exacerbation were positively correlated with white blood cell count,neutrophil percentage,neutrophil to lymphocyte ratio; The stable CIRBP and TREM-1 levels were negatively correlated with the percentage of forced expiratory volume at 1 second to the expected value,and the ratio of forced expiratory volume to forced vital capacity at 1 second. They were positively correlated with white blood cell count,neutrophil percentage,and neutrophil/lymphocyte ratio. Conclusion The expression levels of CIRBP and TREM-1 are elevated in the peripheral blood of COPD patients. The expression of CIRBP is correlated with TREM-1 expression,and is associated with clinical indicators such as lung function,white blood cell count,neutrophil percentage,neutrophil to lymphocyte ratio,monocyte to high-density lipoprotein ratio,etc.,suggesting that CIRBP and TREM-1 may jointly participate in the occurrence and development of COPD.

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Objective To analyze the changes of serum C-type lectin domain family 11 member A(Clec11a) in the progression of diabetic kidney disease(DKD) and evaluate its value in bone metabolism. Methods The clinical data of 184 patients with type 2 diabetes(T2DM) were collected and serum Clec11a levels were detected.According to the UACR,patients were divided into non-albuminuria group of 76 cases, microalbuminuria group of 72 cases and macroalbuminuria group of 36 cases.In the same period, 50 healthy subjects were selected as control group.The general clinic data, bone mineral density and bone metabolism indexes of all groups were measured.The correlation between Clec11a level and bone metabolism indexes of DKD patients was analyzed. Results Levels of Clec11a and eGFR in all T2DM subgroups were significantly lower than those in normal control group(P<0.05).Levels of Clec11a and eGFR in T2DM subgroups significantly decreased with the increasement of UACR(P<0.05).Bone mineral density(BMD) of neck of femur and Clec11a levels in microalbuminuria group were lower than those in non-albuminuria group(P<0.05).The levels of Clec11a and BMD of lumbar vertebra in macroalbuminuria group were lower than those in microalbuminuria group(P<0.05).Bone metabolism indexes such as 25 hydroxyvitamin D[25(OH)D],N-terminal fragment of osteocalcin, amino terminal peptide of type Ⅰ procollagen, parathyroid hormone, and β collagen degradation products were not significantly different between microalbuminuria group and non-albuminuria group.BMD,25(OH)D and Clec11a levels were negatively correlated with UACR levels(P<0.05).Clec11a had the strongest correlation with UACR. Conclusion Serum Clec11a levels in T2DM patients significantly decreased with the increasement of UACR.Compared with other bone metabolism indexes, Clec11a showed a stronger negative correlation with UACR.Regular detection of serum Clec11a levels for DKD patients is conducive to identify bone loss early.