One of the most important aspects of interventional pulmonology is to obtain tissue or liquid samples of the chest to diagnose a respiratory disease;however,it is still possible to obtain insufficient tissue or cytolo...One of the most important aspects of interventional pulmonology is to obtain tissue or liquid samples of the chest to diagnose a respiratory disease;however,it is still possible to obtain insufficient tissue or cytologic specimens.Indeed,methylation detection is an effective method by which to establish a diagnosis.This review focuses on the clinical application of short stature homeobox 2 and RAS-associated domain family 1 subtype A DNA methylation detection in interventional pulmonology,including bronchoscopic fluid biopsy,transbronchial needle aspiration,and pleural effusion.展开更多
AIM:To assess diagnostic accuracy of Ras association domain family 1A(RASSF1A)promoter methylation in body fluids(serum,plasma and whole blood)for hepatocellular carcinoma(HCC).METHODS:Relative information about study...AIM:To assess diagnostic accuracy of Ras association domain family 1A(RASSF1A)promoter methylation in body fluids(serum,plasma and whole blood)for hepatocellular carcinoma(HCC).METHODS:Relative information about study characteristics and incidence of RASSF1A methylation was collected.Quality of all included studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies-2.Sensitivity and specificity were pooled using a randomeffect model,and a summary receiver operating characteristic curve was used to demonstrate the overall diagnostic performance.Positive likelihood ratio(PLR),negative likelihood ratio(NLR),and diagnostic odds ratio(DOR)with 95%CI were also calculated.Meta-regression was applied to analyze observed heterogeneity,and Deeks’test was performed to detect publication bias.RESULTS:After a systematic literature review,seven studies with a total of 302 cases of HCC and 250 cases of chronic liver diseases were included in the analysis.The pooled sensitivity and specificity were 0.70(95%CI:0.49-0.85)and 0.72(95%CI:0.54-0.85),respectively.The PLR was 2.51(95%CI:1.64-3.86),NLR was 0.41(95%CI:0.25-0.68),and DOR was 6.13(95%CI:3.17-11.84).Theχ2values of sensitivity,specificity,PLR,NLR and DOR were 59.41(P<0.001),50.50(P<0.001),17.40(P=0.010),31.24(P<0.001)and80.51(P<0.001),respectively.The area under the curve was 0.77(95%CI:0.73-0.81).Three factors were analyzed by univariate meta-regression and none was significant to interpret the observed heterogeneity(P>0.05).No significant publication bias was detected by Deeks’test(P=0.346).CONCLUSION:We showed the potential diagnostic value of RASSF1A methylation in body fluids in HCC patients and it may improve diagnostic accuracy combined with theα-fetoprotein test.展开更多
BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(X...BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(XIST)expression has been reported to be elevated in the serum of DN patients.AIM To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell(RTEC)pyroptosis in DN.METHODS A DN rat model was established through streptozotocin injection,and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST.Renal metabolic and biochemical indices were detected,and pathological changes in the renal tissue were assessed.The expression of indicators related to inflammation and pyroptosis was also detected.High glucose(HG)was used to treat HK2 cells,and cell viability and lactate dehydrogenase(LDH)activity were detected after silencing XIST.The subcellular localization and downstream mechanism of XIST were investigated.Finally,a rescue experiment was carried out to verify that XIST regulates NLR family pyrin domain containing 3(NLRP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p(miR-15b-5p)/Toll-like receptor 4(TLR4)axis.RESULTS XIST was highly expressed in the DN models.XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury.The expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells;cell viability was decreased and LDH activity was increased after HGtreatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting NLRP3/caspase-1. Mechanistically,XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promotingmiR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect ofsilencing XIST on HG-induced RTEC pyroptosis.CONCLUSIONSilencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury inDN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.展开更多
BACKGROUND The interleukin-17(IL-17)mediated aberrant immune-inflammatory response plays a paramount role in ulcerative colitis(UC).γδT17 cells are one of the critical sources of IL-17,but the role they play in UC r...BACKGROUND The interleukin-17(IL-17)mediated aberrant immune-inflammatory response plays a paramount role in ulcerative colitis(UC).γδT17 cells are one of the critical sources of IL-17,but the role they play in UC remains under debate.AIM To clarify the role ofγδT17 cells in patients with mild-to-moderate UC.METHODS A single-centre observational pragmatic study was conducted on patients with UC who attended the outpatient and inpatient departments of Xiyuan Hospital of the China Academy of Traditional Chinese Medicine from September 2020 to December 2022.The research population consisted of two groups of adult patients.The first group consisted of healthy volunteers with no significant abnormalities on colonoscopy,and the other group consisted of patients with mild-to-moderate ulcerative colitis.Serum samples from healthy volunteers and patients with UC were collected for the detection of relevant inflammatory factors.Moreover,five colon mucosa samples were randomly selected from each group for testing and analyses.RESULTS An increased number ofγδT17 cells and hyperactivation of the NLR family pyrin domain containing 3/IL-1βsignaling pathway were observed in colonic mucosal tissues from patients with UC.CONCLUSION Hyperactivation of the NLR family pyrin domain containing 3/IL-1βsignaling pathway promotes the activation ofγδT17 cells in colonic mucosal tissues of patients with UC.展开更多
C1q is the first subcomponent of classical pathway in the complement system and a major link between innate and acquired immunities. The globular （gC1q） domain similar with C1q was also found in many non-complement ...C1q is the first subcomponent of classical pathway in the complement system and a major link between innate and acquired immunities. The globular （gC1q） domain similar with C1q was also found in many non-complement C1q-domain-containing （C1qDC） proteins which have similar crystal structure to that of the multifunctional tumor necrosis factor （TNF） ligand family, and also have diverse functions. In this study, we identified a total of 52 independent gene sequences encoding C1q-domain-containing proteins through comprehensive searches of zebrafish genome, cDNA and EST databases. In comparison to 31 orthologous genes in human and different numbers in other species, a significant selective pressure was suggested during vertebrate evolution. Domain organization of C1q-domain-containing （C1qDC） proteins mainly includes a leading signal peptide, a collagen-like region of variable length, and a C-terminal C1q domain. There are 11 highly conserved residues within the C1q domain, among which 2 are invariant within the zebrafish gene set. A more extensive database searches also revealed homologous C1qDC proteins in other vertebrates, invertebrates and even bacterium, but no homologous sequences for encoding C1qDC proteins were found in many species that have a more recent evolutionary history with zebrafish. Therefore, further studies on C1q-domain-containing genes among different species will help us understand evolutionary mechanism of innate and acquired immunities.展开更多
SWI 1 is a member of a new class of tumor DNA-binding proteins named as the AT-rich in- teraction domain family （ARID）, and considered to bind with AT base pairs specifically. Genomic and functional data support ARI...SWI 1 is a member of a new class of tumor DNA-binding proteins named as the AT-rich in- teraction domain family （ARID）, and considered to bind with AT base pairs specifically. Genomic and functional data support ARID1A as a tumor suppressor because AR1D1A/BAF250a （SWI1） subunit of the SWI/SNF chromatin-remodeling complex has emerged as recurrently mutated in a broad array of tumor types. But the crystal structure of SWI1 has not been solved as yet. Using docking and molecular dynamics, we predicted the DNA interaction pattern of human SWI1 ARID and made comparisons with the other two representative ARID family members, human Mrf-2 ARID and Drosophila Dri ARID. Dynamic results revealed that the N-terminal and loop L1 of SWI1 ARID bound with the DNA major groove, while the loop L2 and helix H6 bound with the minor groove. Moreover, it was found that SWI1 ARID bound with DNA apparently in a sequence-nonspecific manner. It was concluded that SWI1 ARID can form stable complex with sequence-nonspecific DNA segment comparing to Mrf-2 ARID/DNA and Dri ARID/DNA sequence-specific complexes.展开更多
目的探讨急性缺血性卒中(acute ischemic stroke,AIS)合并糖尿病(diabetes mellitus,DM)患者氧化三甲胺(trimetlylamine N-oxide,TMAO)、视锥蛋白样蛋白-1(recombinant visinin like protein 1,VILIP-1)、NLR家族含CARD结构蛋白4(NLR fa...目的探讨急性缺血性卒中(acute ischemic stroke,AIS)合并糖尿病(diabetes mellitus,DM)患者氧化三甲胺(trimetlylamine N-oxide,TMAO)、视锥蛋白样蛋白-1(recombinant visinin like protein 1,VILIP-1)、NLR家族含CARD结构蛋白4(NLR family CARD domain containing 4,NLRC4)与神经功能恶化(neurological deterioration,ND)的关系。方法选取2021年1月至2023年10月保山市人民医院AIS合并DM患者290例,根据是否发生ND分为ND组(n=63)和非ND组(n=227)。采用Pearson相关性分析AIS合并DM患者血清TMAO、VILIP-1、NLRC4与入院时美国国立卫生研究院卒中量表(National Institutes of Health stroke scale,NIHSS)评分的相关性。采用多因素logistic回归分析AIS合并DM患者发生ND的影响因素。结果290例患者中,男165例、女125例,年龄50~78岁,平均(65.8±5.4)岁;ND发生率为21.72%。Pearson相关性分析结果显示,TMAO、VILIP-1、NLRC4与入院时NIHSS评分均呈正相关(P<0.05)。多因素logistic回归分析结果显示,入院时NIHSS评分越高(OR=3.972,95%CI:2.259~6.986,P=0.000)、TMAO越高(OR=2.210,95%CI:1.505~3.245,P=0.000)、VILIP-1越高(OR=3.046,95%CI:1.917~4.838,P=0.000)、NLRC4越高(OR=1.036,95%CI:1.017~1.055,P=0.000)的AIS合并DM患者更容易发生ND。结论AIS合并DM患者血清TMAO、VILIP-1、NLRC4水平较高,与入院时NIHSS评分呈正相关,入院时NIHSS评分、TMAO、VILIP-1、NLRC4是AIS合并DM患者发生ND的影响因素。展开更多
文摘One of the most important aspects of interventional pulmonology is to obtain tissue or liquid samples of the chest to diagnose a respiratory disease;however,it is still possible to obtain insufficient tissue or cytologic specimens.Indeed,methylation detection is an effective method by which to establish a diagnosis.This review focuses on the clinical application of short stature homeobox 2 and RAS-associated domain family 1 subtype A DNA methylation detection in interventional pulmonology,including bronchoscopic fluid biopsy,transbronchial needle aspiration,and pleural effusion.
基金Supported by Key Project of Chinese Ministry of Science and Technology,No.2012ZX10002007 and No.2013ZX10002001National Natural Science Foundation of China,No.81171579and No.81201287Natural Science Foundation of Shandong Province,China,No.ZR2010HM070 and No.ZR2010HQ040
文摘AIM:To assess diagnostic accuracy of Ras association domain family 1A(RASSF1A)promoter methylation in body fluids(serum,plasma and whole blood)for hepatocellular carcinoma(HCC).METHODS:Relative information about study characteristics and incidence of RASSF1A methylation was collected.Quality of all included studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies-2.Sensitivity and specificity were pooled using a randomeffect model,and a summary receiver operating characteristic curve was used to demonstrate the overall diagnostic performance.Positive likelihood ratio(PLR),negative likelihood ratio(NLR),and diagnostic odds ratio(DOR)with 95%CI were also calculated.Meta-regression was applied to analyze observed heterogeneity,and Deeks’test was performed to detect publication bias.RESULTS:After a systematic literature review,seven studies with a total of 302 cases of HCC and 250 cases of chronic liver diseases were included in the analysis.The pooled sensitivity and specificity were 0.70(95%CI:0.49-0.85)and 0.72(95%CI:0.54-0.85),respectively.The PLR was 2.51(95%CI:1.64-3.86),NLR was 0.41(95%CI:0.25-0.68),and DOR was 6.13(95%CI:3.17-11.84).Theχ2values of sensitivity,specificity,PLR,NLR and DOR were 59.41(P<0.001),50.50(P<0.001),17.40(P=0.010),31.24(P<0.001)and80.51(P<0.001),respectively.The area under the curve was 0.77(95%CI:0.73-0.81).Three factors were analyzed by univariate meta-regression and none was significant to interpret the observed heterogeneity(P>0.05).No significant publication bias was detected by Deeks’test(P=0.346).CONCLUSION:We showed the potential diagnostic value of RASSF1A methylation in body fluids in HCC patients and it may improve diagnostic accuracy combined with theα-fetoprotein test.
基金Supported by Natural Science Foundation of Shenzhen University General Hospital (SUGH2020QD011)
文摘BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(XIST)expression has been reported to be elevated in the serum of DN patients.AIM To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell(RTEC)pyroptosis in DN.METHODS A DN rat model was established through streptozotocin injection,and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST.Renal metabolic and biochemical indices were detected,and pathological changes in the renal tissue were assessed.The expression of indicators related to inflammation and pyroptosis was also detected.High glucose(HG)was used to treat HK2 cells,and cell viability and lactate dehydrogenase(LDH)activity were detected after silencing XIST.The subcellular localization and downstream mechanism of XIST were investigated.Finally,a rescue experiment was carried out to verify that XIST regulates NLR family pyrin domain containing 3(NLRP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p(miR-15b-5p)/Toll-like receptor 4(TLR4)axis.RESULTS XIST was highly expressed in the DN models.XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury.The expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells;cell viability was decreased and LDH activity was increased after HGtreatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting NLRP3/caspase-1. Mechanistically,XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promotingmiR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect ofsilencing XIST on HG-induced RTEC pyroptosis.CONCLUSIONSilencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury inDN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.
基金Supported by China Academy of Chinese Medical Sciences Outstanding Young Talents(Innovative)Cultivation Project,No.ZZ17-YQ-007Special Project of the National Natural Science Foundation of China,No.82341233.
文摘BACKGROUND The interleukin-17(IL-17)mediated aberrant immune-inflammatory response plays a paramount role in ulcerative colitis(UC).γδT17 cells are one of the critical sources of IL-17,but the role they play in UC remains under debate.AIM To clarify the role ofγδT17 cells in patients with mild-to-moderate UC.METHODS A single-centre observational pragmatic study was conducted on patients with UC who attended the outpatient and inpatient departments of Xiyuan Hospital of the China Academy of Traditional Chinese Medicine from September 2020 to December 2022.The research population consisted of two groups of adult patients.The first group consisted of healthy volunteers with no significant abnormalities on colonoscopy,and the other group consisted of patients with mild-to-moderate ulcerative colitis.Serum samples from healthy volunteers and patients with UC were collected for the detection of relevant inflammatory factors.Moreover,five colon mucosa samples were randomly selected from each group for testing and analyses.RESULTS An increased number ofγδT17 cells and hyperactivation of the NLR family pyrin domain containing 3/IL-1βsignaling pathway were observed in colonic mucosal tissues from patients with UC.CONCLUSION Hyperactivation of the NLR family pyrin domain containing 3/IL-1βsignaling pathway promotes the activation ofγδT17 cells in colonic mucosal tissues of patients with UC.
基金Acknowledgements This work was supported by the National Major Basic Research Program （No. 2004CB117401）；by the National Natural Science Foundation of China （No. 90408013）.
文摘C1q is the first subcomponent of classical pathway in the complement system and a major link between innate and acquired immunities. The globular （gC1q） domain similar with C1q was also found in many non-complement C1q-domain-containing （C1qDC） proteins which have similar crystal structure to that of the multifunctional tumor necrosis factor （TNF） ligand family, and also have diverse functions. In this study, we identified a total of 52 independent gene sequences encoding C1q-domain-containing proteins through comprehensive searches of zebrafish genome, cDNA and EST databases. In comparison to 31 orthologous genes in human and different numbers in other species, a significant selective pressure was suggested during vertebrate evolution. Domain organization of C1q-domain-containing （C1qDC） proteins mainly includes a leading signal peptide, a collagen-like region of variable length, and a C-terminal C1q domain. There are 11 highly conserved residues within the C1q domain, among which 2 are invariant within the zebrafish gene set. A more extensive database searches also revealed homologous C1qDC proteins in other vertebrates, invertebrates and even bacterium, but no homologous sequences for encoding C1qDC proteins were found in many species that have a more recent evolutionary history with zebrafish. Therefore, further studies on C1q-domain-containing genes among different species will help us understand evolutionary mechanism of innate and acquired immunities.
基金supported by the College Scientific and Technological Innovation Project of Huazhong University of Science and Technology(No.15A263)
文摘SWI 1 is a member of a new class of tumor DNA-binding proteins named as the AT-rich in- teraction domain family （ARID）, and considered to bind with AT base pairs specifically. Genomic and functional data support ARID1A as a tumor suppressor because AR1D1A/BAF250a （SWI1） subunit of the SWI/SNF chromatin-remodeling complex has emerged as recurrently mutated in a broad array of tumor types. But the crystal structure of SWI1 has not been solved as yet. Using docking and molecular dynamics, we predicted the DNA interaction pattern of human SWI1 ARID and made comparisons with the other two representative ARID family members, human Mrf-2 ARID and Drosophila Dri ARID. Dynamic results revealed that the N-terminal and loop L1 of SWI1 ARID bound with the DNA major groove, while the loop L2 and helix H6 bound with the minor groove. Moreover, it was found that SWI1 ARID bound with DNA apparently in a sequence-nonspecific manner. It was concluded that SWI1 ARID can form stable complex with sequence-nonspecific DNA segment comparing to Mrf-2 ARID/DNA and Dri ARID/DNA sequence-specific complexes.
文摘目的探讨急性缺血性卒中(acute ischemic stroke,AIS)合并糖尿病(diabetes mellitus,DM)患者氧化三甲胺(trimetlylamine N-oxide,TMAO)、视锥蛋白样蛋白-1(recombinant visinin like protein 1,VILIP-1)、NLR家族含CARD结构蛋白4(NLR family CARD domain containing 4,NLRC4)与神经功能恶化(neurological deterioration,ND)的关系。方法选取2021年1月至2023年10月保山市人民医院AIS合并DM患者290例,根据是否发生ND分为ND组(n=63)和非ND组(n=227)。采用Pearson相关性分析AIS合并DM患者血清TMAO、VILIP-1、NLRC4与入院时美国国立卫生研究院卒中量表(National Institutes of Health stroke scale,NIHSS)评分的相关性。采用多因素logistic回归分析AIS合并DM患者发生ND的影响因素。结果290例患者中,男165例、女125例,年龄50~78岁,平均(65.8±5.4)岁;ND发生率为21.72%。Pearson相关性分析结果显示,TMAO、VILIP-1、NLRC4与入院时NIHSS评分均呈正相关(P<0.05)。多因素logistic回归分析结果显示,入院时NIHSS评分越高(OR=3.972,95%CI:2.259~6.986,P=0.000)、TMAO越高(OR=2.210,95%CI:1.505~3.245,P=0.000)、VILIP-1越高(OR=3.046,95%CI:1.917~4.838,P=0.000)、NLRC4越高(OR=1.036,95%CI:1.017~1.055,P=0.000)的AIS合并DM患者更容易发生ND。结论AIS合并DM患者血清TMAO、VILIP-1、NLRC4水平较高,与入院时NIHSS评分呈正相关,入院时NIHSS评分、TMAO、VILIP-1、NLRC4是AIS合并DM患者发生ND的影响因素。
