The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

Metabolite acetyl-L-carnitine participates in Bifidobacterium animalis F1-7 to ameliorate atherosclerotic inflammation by downregulating theTLR4/NF-κB pathway

This study aimed to explore the effect of Bifidobacterium animalis F1-7 on the improvement of atherosclerotic inflammation.Arteriosclerosis model ApoE^(-/-)mice were orally administered with B.animalis F1-7 for 12 weeks.The probiotic intervention reduced the plaque areas in aorta and the accumulation of macrophages,and downregulated the expression of toll-like receptor 4(TLR4)/nuclear factorκB(NF-κB)pathway to reduce the levels of inflammatory factors.The widely-targeted metabolomics analysis showed that acetyl-L-carnitine(ALC)in the intestine of atherosclerotic mice was significantly increased after B.animalis F1-7 intervention.Correlation analysis proved that ALC was associated with atherosclerotic inflammatory response.By using oxidized low density lipoprotein induced macrophage foam cells,we further verified that ALC could reduce lipid accumulation and inflammatory response in foam cells by downregulating the TLR4/NF-κB pathway.Finally,our results revealed that B.animalis F1-7 upregulated the metabolite ALC to downregulate the inflammatory responses,leading to the reduction of plaque accumulation of atherosclerosis.

Biological function of miRNA-145-5p in angiotensin II induced renal inflammation

Objective:Chronic kidney disease(CKD)is a progressive disorder characterized by intricate structural and functional alterations in the kidneys,attributable to diverse causative factors.Notably,the therapeutic promise of miR-145-5p in addressing renal pathologies has been discerned.This investigation seeks to elucidate the functional role of miR-145-5p in injured kidneys by subjecting human glomerular mesangial cells(HGMCs)to stimulation with Angiotensin II(AngII).Materials and Methods:Cellular viability and the levels of inflammatory mediators were evaluated utilizing Cell Counting Kit-8(CCK-8),quantitative real-time polymerase chain reaction(qRT-PCR),and western blot methodologies,both in the presence of AngII incubation and in scenarios of miR-145p overexpression and downregulation.Furthermore,the cell cycle dynamics were elucidated through Fluorescence-activated Cell Sorting(FACS)analysis.Results:AngII incubation induced an upregulation of miR-145-5p and inflammatory factors including Intercellular Adhesion Molecule 1(ICAM-1),Interleukin 6(IL-6),Interleukin 8(IL-8),and Interleukin 1β(IL-1β).Additionally,it elevated the expression of Cyclin A2,Cyclin D1,and the G2/M cell cycle ratio.Conversely,inhibition of miR-145-5p heightened the levels of inflammatory factors and cell cycle regulators induced by AngII incubation.Reduced expression of miR-145-5p correlated with a downregulation of Interleukin 10(IL-10)expression,concurrently promoting HGMC proliferation under AngII stimulation.Moreover,ectopic miR-145-5p expression demonstrated a reduction in inflammatory factors,cell cyclin regulators,G2/M cell cycle ratio,and overall proliferation.Conclusion:MiR-145-5p exhibited inhibitory effects on the inflammatory response and proliferation induced by Angiotensin II in HGMCs,showcasing its potential as a therapeutic avenue for the treatment of kidney injury.

High fat diet dysregulates microRNA-17-5p and triggers retinal inflammation:Role of endoplasmic-reticulum-stress

AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid(PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin(BSA)(400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, mi R-17-5p m RNA, as well as nucleotide-binding oligomerization domain-like receptor protein(NLRP3) and IL1β protein was determined.RESULTS High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers(P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased mi R-17-5p expression, whichwere restored by inhibiting endoplasmic reticulumstress with PBA(P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced mi R-17-5p and induced thioredoxin interacting protein m RNA in retinal Müller glial cell line(P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β.CONCLUSION Our work suggests that targeting endoplasmic reticulumstress or thioredoxin interacting protein are potential therapeutic strategies for early intervention of obesityinduced retinal inflammation.

Potential role of chitinase 3-like-1 in inflammation-associated carcinogenic changes of epithelial cells

The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, insects and parasitic nematodes, but is completely absent in mammals. Exposure to antigens containing chitin- or chitin-like structures sometimes induces strong T helper type-I responses in mammals, which may be associated with the induction of mammalian chitinases. Chitinase 3-like-1 （CHI3L1）, a member of the mammalian chitinase family, is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease, hepatitis and asthma. In addition, CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma, colon cancer, breast cancer and malignant melanoma. Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown, CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix. CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways. Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3Ll-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells.

COVID-19 vaccine related hypermetabolic lymph nodes on PET/CT:Implications of inflammatory findings in cancer imaging

We observed several patients presenting 2-[^(18)F]FDG uptake in the reactive axillary lymph node at PET/CT imaging,ipsilateral to the site of the COVID-19 vaccine injection.Analog finding was documented at[^(18)F]Choline PET/CT.The aim of our study was to describe this source of false positive cases.All patients examined by PET/CT were included in the study.Data concerning patient anamnesis,laterality,and time interval from recent COVID-19 vaccination were recorded.SUVmax was measured in all lymph nodes expressing tracer uptake after vaccination.Among 712 PET/CT scans with 2-[^(18)F]FDG,104 were submitted to vaccination;89/104 patients(85%)presented axillary and/or deltoid tracer uptake,related to recent COVID-19 vaccine administration(median from injection:11 days).The mean SUVmax of these findings was 2.1(range 1.6–3.3).Among 89 patients with false positive axillary uptake,36 subjects had received chemotherapy due to lymph node metastases from somatic cancer or lymphomas,prior to the scan:6/36 patients with lymph node metastases showed no response to therapy or progression disease.The mean SUVmax value of lymph nodal localizations of somatic cancers/lymphomas after chemotherapy was 7.8.Only 1/31 prostate cancer patients examined by[^(18)F]Choline PET/CT showed post-vaccine axillary lymph node uptake.These findings were not recorded at PET/CT scans with[^(18)F]-6-FDOPA,[^(68)Ga]Ga-DOTATOC,and[^(18)F]-fluoride.Following COVID-19 mass vaccination,a significant percentage of patients examined by 2-[^(18)F]FDG PET/CT presents axillary,reactive lymph node uptake.Anamnesis,low-dose CT,and ultrasonography facilitated correct diagnosis.Semi-quantitative assessment supported the visual analysis of PET/CT data;SUVmax values of metastatic lymph nodes were considerably higher than post-vaccine lymph nodes.[^(18)F]Choline uptake in reactive lymph node after vaccination was confirmed.After the COVID-19 pandemic,nuclear physicians need to take these potential false positive cases into account in daily clinical practice.

LncRNA HAGLR靶向miR-625-5p对脂多糖诱导的视网膜色素上皮细胞凋亡和炎症因子表达的影响

目的 探讨长链非编码RNA HAGLR(LncRNA HAGLR)是否可通过靶向调控微小RNA-625-5p(miR-625-5p)表达而影响脂多糖(LPS)诱导的视网膜色素上皮(RPE)细胞凋亡、炎症因子表达,为揭示视网膜病变机制奠定实验基础。方法 将LPS诱导人视网膜色素上皮细胞(ARPE-19)设为LPS组,正常培养的ARPE-19细胞设为Con组。实时荧光定量聚合酶链反应(qRT-PCR)检测LncRNA HAGLR、miR-625-5p表达水平。根据转染物不同分为LPS+sh-NC组、LPS+sh-HAGLR组、LPS+miR-NC组、LPS+miR-625-5p组、LPS+sh-HAGLR+anti-miR-NC组、LPS+sh-HAGLR+anti-miR-625-5p组。采用流式细胞术检测细胞凋亡率;ELISA法检测白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)水平;验证LncRNA HAGLR、miR-625-5p靶向关系;Western blot检测活化的半胱氨酸天冬氨酸特异性蛋白酶3(cleaved-Caspase 3)、cleaved-Caspase 9蛋白水平。结果 与Con组比较,LPS组LncRNA HAGLR表达水平升高,miR-625-5p表达水平降低(均为P<0.05),细胞凋亡率,cleaved-Caspase 3、cleaved-Caspase 9蛋白水平,IL-6、IL-1β水平均升高(均为P<0.05)。与LPS+sh-NC组比较,LPS+sh-HAGLR组细胞凋亡率,cleaved-Caspase 3、cleaved-Caspase 9蛋白水平,IL-6、IL-1β水平均降低(均为P<0.05);LncRNA HAGLR可负向调控miR-625-5p表达水平(P<0.05)。与LPS+miR-NC组比较,LPS+miR-625-5p组miR-625-5p表达水平升高,细胞凋亡率,cleaved-Caspase 3、cleaved-Caspase 9蛋白水平,IL-6、IL-1β水平均降低(均为P<0.05)。与LPS+sh-HAGLR+anti-miR-NC组比较,LPS+sh-HAGLR+anti-miR-625-5p组miR-625-5p表达水平降低,细胞凋亡率,cleaved-Caspase 3、cleaved-Caspase 9蛋白水平,IL-6、IL-1β水平均升高(均为P<0.05)。结论 干扰LncRNA HAGLR表达可通过靶向调控miR-625-5p表达抑制细胞凋亡、炎症因子表达,以减轻LPS诱导的ARPE-19细胞损伤。

miR-210、miR-143在支气管哮喘患儿血清中的表达及与气道炎性反应的关系

目的分析miR-210、miR-143在支气管哮喘患儿血清中的表达及与气道炎性反应的关系。方法选取2020年1月—2022年7月廊坊市人民医院儿科收治的支气管哮喘患儿186例为支气管哮喘组,另收集同期体检健康儿童100例为健康对照组,qRT-PCR法检测血清miR-210、miR-143水平,Pearson法分析支气管哮喘患儿miR-210、miR-143水平与TNF-α、IL-4、IL-6、EOS、FeNO、IL-10、IL-12、IgE、IFN-γ间相关性;Logistic回归分析儿童发生支气管哮喘的影响因素。结果支气管哮喘患儿血清miR-210水平显著高于健康儿童,miR-143水平显著低于健康儿童(t=8.317,9.545,P均<0.001),轻度、中度、重度哮喘患儿血清miR-210水平依次升高,miR-143水平依次降低(F=7.566,19.914,P均<0.001)。支气管哮喘患儿FVC、FEV_1、VE、PEF、IL-10、IL-12、IgE、IFN-γ水平显著低于健康儿童,Raw、IL-4、IL-6、TNF-α、EOS、FeNO水平显著高于健康儿童(P<0.05)。Pearson法分析表明,血清miR-210与miR-143水平呈负相关(r=-0.362,P<0.001),血清miR-210水平与TNF-α、IL-4、IL-6、EOS、FeNO呈正相关(r=0.326、0.359、0.315、0.334、0.312,P均<0.001),与IL-10、IL-12、IgE、IFN-γ呈负相关(r=-0.406、-0.303、-0.317、-0.453,P均<0.001);miR-143水平与TNF-α、IL-4、IL-6、EOS、FeNO呈负相关(r=-0.336、-0.324,-0.323、-0.424、-0.397,P均<0.001),与IL-10、IL-12、IgE、IFN-γ呈正相关(0.338、0.338、0.327、0.467,P均<0.001);Logistic回归分析结果表明,miR-210、TNF-α、IL-4、IL-6、EOS、FeNO升高均为儿童发生支气管哮喘的危险因素[OR(95%CI)=1.025(1.015~1.035)、1.034(1.020~1.048)、1.136(1.059~1.219)、1.243(1.147~1.347)、1.349(1.151~1.581)、1.408(1.178~1.683)],而miR-143、IL-10、IL-12、IgE、IFN-γ升高均为其保护因素[OR(95%CI)=0.857(0.788~0.932)、0.932(0.900~0.965)、0.473(0.312~0.718)、0.671(0.549~0.820)、0.583(0.437~0.778)]。结论支气管哮喘患儿血清miR-210水平升高,miR-143水平降低,与患儿气道炎性反应的进展具有密切关系。

miR-146a-5p affects inflammation response of trophoblast by inhibiting TRAF6/NF-кB signaling pathway

Objective:To investigate the association of Micro-rna(miR)-146a-5p expression with preeclampsia,and further explore the potential mechanism involved.Methods:Compared with the blank control group,the expressions of miR-146a-5p and TRAF6 were detected in lipopolysaccharide(LPS)-induced JEG-3 cells.Chorionic carcinoma cell JEG-3 in vitro culture are divided into control,miR-146a-5p mimic+lipopolysaccharide(lps),miR-146a-5p mimic and miR-146a-5p inhibitor groups.qRT-PCR analysis were used to detect the mRNA of miR-146a-5p,IL-1β,IL-6,IL-8 and TNF-α.Western blot assays were carried out to determine the protein expression of TRAF6/NF-кB pathway related proteins.Results:1.miR-146a expression in miR-146a mimic group were significantly higher than the other three groups(P<0.05).2.Compared with the control group,the expression level of miR-146a-5p in JEG-3 cells induced by LPS was significantly increased,and the expression level of TRAF6 was significantly reduced(P<0.05).3.Compared with the control group,the mRNA expression levels of IL-1β,IL-6,IL-8,and TNF-αdecreased significantly after using miR-146a mimic(P<0.05).After adding miR-146a inhibitor,the mRNA expression levels of IL-1β,IL-6,IL-8,and TNF-αwere significantly increased(P<0.05).However,compared with the mimic+LPS group,the difference was not statistically significant(all P>0.05).The results of Western Blot showed that the expression of TRAF6 and NF-κB protein in JEG-3 cells decreased significantly after adding miR-146a mimic and increased after adding miR-146a inhibitor.Conclusion:MiR-146-5p can affect the inflammation response of Maternal-fetal interface by inhibiting TRAF6/NF-кB signaling pathway in preeclampsia.

川芎嗪活血化瘀与微血管血液动力学变化——Micro-VTR方法应用之一

用改良Rosata方法造成家兔实验性腹腔淤血症。用显微电视录像反复再生静画步进法测量川芎嗪对淤血前后肠系膜10μm以下毛细血管血液动力学的影响。结果表明:川芎嗪可使血淤后毛细血管血流速度加快,血流量增多,开放毛细血管数增多;可抑制白细胞游出。

5-羟色胺转运蛋白显像剂^(11)C-DASB的自动化合成及Micro PET/CT显像

目的:自动化合成5-羟色胺转运蛋白显像剂11 C-DASB并进行大鼠Micro PET/CT显像;方法:通过改变甲基化试剂、溶解前体溶剂及反应条件,得到优化的标记条件作为碳-11多功能合成模块的输入参数,进行自动化合成11 C-DASB,大鼠静脉注射11 C-DASB 45 min后进行显像;结果:采用11 C-CH3-Triflate作为甲基化试剂,通入新配制的含1mg去甲基DASB前体的500μL DMSO溶液内,80℃下加热2min,标准率为63.7%,大鼠显像表明,11 C-DASB特异性的浓聚于SERT富集区域;结论:经优化,11 C-DASB自动化合成可得到较高产率,大鼠显像表明,其特异性浓聚于SERT富集区域,有望作为5-羟色胺转运蛋白显像剂。

^(18)F-氟赤硝基咪唑micro PET/CT评价裸鼠乳腺癌早期放疗疗效实验研究

目的探讨^(18)F-氟赤硝基咪唑micro PET/CT评价裸鼠MDA-MB231乳腺癌早期放疗疗效的价值。方法建立16只裸鼠MDA-MB231乳腺癌模型,将其按照随机对照原则分为两组:对照组(A组)、放疗组(B组),每组8只。每组裸鼠行micro PET/CT显像,测定每只裸鼠肿瘤SUVmax值。完成显像后,常规HE染色观察每组肿瘤组织形态学特征,免疫组化方法测定每组肿瘤细胞乏氧诱导因子-1α(HIF-1α)的表达情况。结果放疗前,对照组与放疗组SUVmax值差异无统计学意义(t=0. 375,P> 0. 05)。放疗组放疗后48 h裸鼠肿瘤组织SUVmax值较放疗前(t=9. 958,P <0. 05)、放疗后24 h(t=16. 506,P <0. 05)明显降低,差异有统计学意义(F=58. 860,P <0. 05)。放疗后24 h SUVmax值也低于放疗前24 h(t=5. 405,P <0. 05),差异有统计学意义。HE染色结果显示放疗组肿瘤细胞坏死较对照组更加明显。免疫组化结果显示放疗组放疗后HIF-1α表达阳性率明显低于放疗前(t=14. 802,P <0. 05),差异具有统计学意义。相关性分析结果显示肿瘤SUVmax与HIF-1α的表达呈明显正相关性(r=0. 865,P <0. 05)。结论^(18)F-氟赤硝基咪唑micro PET/CT可以监测肿瘤内部的乏氧状态,并且可以评价裸鼠MDA-MB231乳腺癌的早期放疗疗效。

Comparative proteomes change and possible role in different pathways of micro RNA-21a-5p in a mouse model of spinal cord injury

Our previous study found that microRNA-21 a-5 p(miR-21 a-5 p)knockdown could improve the recovery of motor function after spinal cord injury in a mouse model,but the precise molecular mechanism remains poorly understood.In this study,a modified Allen's weight drop was used to establish a mouse model of spinal cord injury.A proteomics approach was used to understand the role of differential protein expression with miR-21 a-5 p knockdown,using a mouse model of spinal cord injury without gene knockout as a negative control group.We found that after introducing miR-21 a-5 p knockdown,proteins that played an essential role in the regulation of inflammatory processes,cell protection against oxidative stress,cell redox homeostasis,and cell maintenance were upregulated compared with the negative control group.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified enriched pathways in both groups,such as the oxidative phosphorylation pathway,which is relevant to Parkinson's disease,Huntington's disease,Alzheimer's disease,and cardiac muscle contraction.We also found that miR-21 a-5 p could be a potential biomarker for amyotrophic lateral sclerosis,as miR-21 a-5 p becomes deregulated in this pathway.These results indicate successful detection of some important proteins that play potential roles in spinal cord injury.Elucidating the relationship between these proteins and the recovery of spinal cord injury will provide a reference for future research of spinal cord injury biomarkers.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Shandong University of China on March 5,2014.

Effect of Surface Roughness in Micro-nano Scale on Slotted Waveguide Arrays in Ku-band

Modeling of the roughness in micro-nano scale and its influence have not been fully investigated, however the roughness will cause amplitude and phase errors of the radiating slot, and decrease the precision and efficiency of the SWA in Ku-band. Firstly, the roughness is simulated using the electromechanical coupled（EC） model. The relationship between roughness and the antenna＇s radiation properties is obtained. For verification, an antenna proto- type is manufactured and tested, and the simulation method is introduced. According to the prototype, a contrasting experiment dealing with the flatness of the radiating plane is conducted to test the simulation method. The advantage of the EC model is validated by comparisons of the EC model and two classical roughness models （sine wave and fractal function）, which shows that the EC model gives a more accurate description model for roughness, the maxi- mum error is 13%. The existence of roughness strongly broadens the beamwidth and raises the side-lobe level of SWA, which is 1.2 times greater than the ideal antenna. In addition, effect of the EC model＇s evaluation indices is investigated, the most affected scale of the roughness is found, which is 1/10 of the working wavelength. The proposed research provides the instruction for antenna designing and manufacturing.

Pseudogene HMGN2P46 as a microRNA sponge to regulate HMGN2 expression via competing for miR-590-3p in severe acute pancreatitis

HMGN2 have functions in inflammatory response.However,the role of HMGN2 in severe acute pancreatitis(SAP)remains unclear.Here,our study was to discuss the role and regulatory mechanism ofHMGN2 in SAP.In this study,the SAP cell model of AR42J was used to study the function and mechanism of HMGN2 in SAP.The protein expression in cells and serums were examined by western blot and ELISA assay.qPCR was used to test the transcriptional RNA level.Cell viability were examined by MTT assay.Luciferase assay was used to evaluate the interaction between gene and gene.Our results showed that HMGN2 was significantly upregulated in SAP patients.The database predicted and luciferase assay data indicated the HMGN2 was directly binding with miR-590-3p.ELISA,MTT and western blot experiments showed that the HMGN2 were promoted the cell proliferation,reduced the inflammation,and repressed the cell autophagy.Mechanism studies showed that the pseudogene HMGN2P46 level was positively correlated with HMGN2 and upregulated HMGN2 expression by competing for miR-590-3p in SAP.Taken together,all over these results showed upregulation of HMGN2 alleviates SAP,this process was regulated by HMGN2P46 competitively binding with miR-590-3p,which may provide a new insight for the treatment and intervention in SAP.Pseudogene HMGN2P46 was a miRNA sponge to regulate HMGN2 level by competing for miR-590-3p to alleviate the process of SAP.It provided a novel strategy for the diagnosis and treatment of severe acute pancreatitis.

血清lncRNA PVT1和miR-181-5p表达与支气管哮喘患儿气道炎症及肺功能的相关性分析

目的探讨长链非编码RNA浆细胞瘤变异易位基因1(lncRNA PVT1),微小RNA-181-5p(miR-181-5p)在支气管哮喘患儿中的表达及与气道炎症及肺功能的相关性。方法选取2021年1月至2022年6月本院收治的118例支气管哮喘患儿为研究对象,其中急性发作期组71例,缓解期组47例。同期选取年龄、性别相匹配的50例健康体检者为对照组。收集一般资料,使用实时荧光定量PCR(qRT-PCR)法检测患儿血清lncRNA PVT1、miR-181-5p水平。Pearson法分析lncRNA PVT1、miR-181-5p与气道炎症及肺功能指标的相关性,采用ROC曲线分析血清lncRNA PVT1、miR-181-5p对支气管哮喘患儿的诊断价值。结果急性发作期患儿血清中lncRNA PVT1表达水平高于缓解期患儿及对照组,miR-181-5p表达水平低于缓解期患儿及对照组,差异有统计学意义(P<0.05);急性发作期患儿血清中hs-CRP、TNF-β、IFN-γ、IL-6、IL-17、IgE、EOS水平均高于缓解期患儿及对照组,FEV1、FEV1%、PEF水平低于缓解期患儿及对照组,差异有统计学意义(P<0.05);Pearson法分析结果显示,支气管哮喘患儿血清中lncRNA PVT1与miR-181-5p表达呈负相关(r=-0.528,P<0.05);支气管哮喘患儿血清lncRNA PVT1水平与hs-CRP、TNF-β、IFN-γ、IL-6、IL-17、IgE、EOS表达呈正相关(P<0.05),与FEV1、FEV1%、PEF呈负相关(P<0.05);血清miR-181-5p水平与hs-CRP、TNF-β、IFN-γ、IL-6、IL-17、IgE、EOS表达呈负相关(P<0.05),与FEV1、FEV1%、PEF正相关(P<0.05);ROC曲线结果显示,血清lncRNA PVT1、miR-181-5p水平诊断支气管哮喘患儿的AUC分别为0.885、0.896,二者联合诊断的AUC为0.947,高于单一指标检测,差异具有统计学意义(Z=2.264,P=0.024,Z=2.413,P=0.016)。结论lncRNA PVT1在支气管哮喘患儿血清中呈高表达,miR-181-5p呈低表达,二者与患儿气道炎症及肺功能密切相关。

Transcriptome Analysis Reveals the Regulation Role of miR-144-5p in Intestinal Immunity of Japanese Flounder(Paralichthys olivaceus)

MicroRNAs(miRNAs),22-nucleotide-long micromanagers that guide the post-transcriptional regulation of a wide range of target genes,can theoretically be used as a diagnostic or therapeutic target for inflammatory reaction.In fish,miR-144-5p expression varies dramatically in response to the different bacterial infections and can regulate immunity-related genes to reduce the occurrence of inflammation.In this research,the regulation function of miR-144-5p to the intestinal innate immunity was udied in flounder Paralichthys olivaceus.The flounders were interfered by 2μg g^(-1) miR-144-5p antagomir and their tissues(intestine,liver and spleen)were harvested from the fish at 12 h post-injection.More than 60 million high-quality reads were collected.At 24 hours after miR-144-5p or miR-NC interference,a total of 2704 and 1823 different-expresion genes(DEGs)were identified in comparison with control group,respectively.The DEGs were enriched in a variety of immunity-related signaling pathways,including NOD-like receptor,Wnt and Toll-like receptor signaling pathways,according to GO and KEGG analyses.A total of 503 highly interacting DEGs engaged in 33 immunity-related signaling pathways were discovered using KEGG analyses.Additionally,5 hub genes were found by protein-protein interaction networks,which formed an intricate immune regulation network.Meanwhile,these hub genes were mostly involved in focal adhesion,Wnt signaling pathway,as well as the Intestinal Immune Network for IgT(IgA)Production Pathway.In conclusion,the loss of miR-144-5p can affect immunity-related genes and downstream signaling pathways.Our findings suggest that miR-144-5p is a modulator of gene networks and signaling pathways associated with intestinal innate immunity.

复方α-酮酸联合左旋肉碱对维持性血液透析患者微炎症及营养状态的影响

目的研究复方α-酮酸联合左旋肉碱在维持性血液透析患者中的应用,分析两者联合治疗对机体的微炎症及营养状态的影响。方法参与本次研究的维持性血液透析的终末期肾病的患者共86人,依据随机数表法随机划分为观察组和对照组,每组各43人。其中对照组的患者以常规碳酸氢盐透析液血液透析治疗;观察组的患者在对照组的基础上联合复方α-酮酸、左旋肉碱治疗。对比观察两组患者微炎症指标、营养指标、血浆左旋肉毒碱水平。结果治疗后观察组患者的血清hs-CRP、TNF-α及IL-6水平较对照组均明显下降(P<0.01);治疗后观察组患者的MIS评分、ALB、Hb、TRF指标改善均显著优于对照组(P<0.01);治疗后观察组患者的血浆左旋肉毒碱水平较对照组明显升高(P<0.01)。结论复方α-酮酸联合左旋肉碱可以降低维持性血液透析患者血清hs-CRP、TNF-α及IL-6微炎症水平,提高患者的营养状态、左旋肉毒碱水平,有临床推广的意义。

达格列净联合阿托伐他汀治疗糖尿病肾病的效果及对患者胰岛功能和机体微炎症状态的影响

目的探究达格列净联合阿托伐他汀治疗糖尿病肾病(DN)的效果及对患者胰岛功能和机体微炎症状态的影响。方法选取2021年2月至2022年2月海南省海口市人民医院收治的DN患者116例,按随机数字表法分为对照组和观察组,各58例。对照组采用阿托伐他汀钙片治疗,观察组在对照组基础上联合达格列净片治疗,2组均治疗3个月。比较治疗总有效率,治疗前后肾功能、胰岛功能指标和炎症因子水平。结果观察组总有效率显著高于对照组[93.1%(54/58)比77.6%(45/58)],差异有统计学意义(χ^(2)=5.583,P=0.018)。治疗后2组血尿素氮、血肌酐、24 h尿蛋白定量均明显低于治疗前,且观察组均低于对照组,差异均有统计学意义(均P<0.001)。治疗后2组稳态模型胰岛素抵抗指数均显著低于治疗前且观察组低于对照组[(2.43±0.28)比(2.67±0.31)],稳态模型胰岛β细胞功能指数均显著高于治疗前且观察组高于对照组[(13.4±3.8)比(10.5±3.3)],差异均有统计学意义(均P<0.05)。治疗后2组白细胞介素6、肿瘤坏死因子α、高敏C反应蛋白水平均显著低于治疗前且观察组低于对照组,差异均有统计学意义(均P<0.05)。结论达格列净联合阿托伐他汀治疗DN临床效果较好,可以有效改善患者胰岛功能,减轻机体的微炎症状态。

健脾益肾降浊方治疗糖尿病肾病的临床疗效及对患者微炎症状态的影响

目的观察健脾益肾降浊方治疗糖尿病肾病(DKD)的临床疗效及对患者微炎症状态的影响。方法选取2020年1月至2021年3月收治的80例DKD患者为研究对象,按照随机数字表法分为2组,对照组40例予西医常规治疗,治疗组40例在对照组基础上联合健脾益肾降浊方治疗。2组均治疗12周后统计疗效,比较2组患者治疗前后血糖指标[包括空腹血糖(FPG)、餐后2 h血糖(2 hPG)及糖化血红蛋白(HbA_(1)c)]、炎症指标[包括超敏C反应蛋白(hs-CRP)、白细胞介素8(IL-8)、IL-6及肿瘤坏死因子α(TNF-α)]、肾功能指标[包括血肌酐(SCr)、尿素氮(BUN)及尿白蛋白排泄率(UAER)]及中医症状评分变化情况。结果与本组治疗前比较,2组治疗后血糖指标FPG、2 hPG及HbA_(1)c水平均下降(P<0.05),但2组治疗后FPG、2 hPG及HbA_(1)c组间比较差异无统计学意义(P>0.05)。与本组治疗前比较,2组治疗后炎症指标hs-CRP、IL-8、IL-6及TNF-α水平均降低(P<0.05),且治疗组治疗后hs-CRP、IL-8、IL-6及TNF-α水平均低于对照组(P<0.05)。与本组治疗前比较,2组治疗后肾功能指标SCr、BUN及UAER水平均降低(P<0.05),且治疗组治疗后肾功能指标SCr、BUN及UAER水平均低于对照组(P<0.05)。与本组治疗前比较,2组治疗后中医症状评分均降低(P<0.05),且治疗组治疗后中医症状评分低于对照组(P<0.05)。治疗组总有效率87.5%(35/40),对照组总有效率62.5%(25/40),治疗组总有效率高于对照组(P<0.05)。结论健脾益肾降浊方治疗DKD临床疗效确切,可有效改善患者微炎症状态,提高肾功能,改善中医症状,从而减慢疾病进展,安全可靠。