目的优化点分辨波谱(PRESS)的回波时间(TE),以检测胶质瘤中的胱硫醚,并评估PRESS波谱在识别1p/19q共缺失分子分型方面的诊断准确性。方法通过计算机模拟激发和模体实验优化PRESS的TE,以更好地区分胱硫醚和重叠的天冬氨酸多重峰。随后,...目的优化点分辨波谱(PRESS)的回波时间(TE),以检测胶质瘤中的胱硫醚,并评估PRESS波谱在识别1p/19q共缺失分子分型方面的诊断准确性。方法通过计算机模拟激发和模体实验优化PRESS的TE,以更好地区分胱硫醚和重叠的天冬氨酸多重峰。随后,将优化后的PRESS序列和97 ms TE PRESS序列应用于前瞻性纳入的84例疑似胶质瘤或胶质瘤复发的患者。通过拟合包含和不包含天冬氨酸的基组集来研究天冬氨酸对胱硫醚量化的影响,并评估PRESS对1p/19q共缺失胶质瘤的诊断表现。结果PRESS的TE优化为TE=45 ms,胱硫醚和天冬氨酸的谱峰模式在模拟激发和模体实验中一致。在临床实验中,97 ms TE PRESS中不包含天冬氨酸拟合得到的胱硫醚平均浓度显著高于使用完整基组集拟合的浓度[(1.97±2.01)mM vs.(1.55±1.95)mM,P<0.01],而45 ms TE PRESS方法则无显著差异[(0.801±1.217)mM vs.(0.796±1.217)mM,P=0.494]。45 ms方法的胱硫醚浓度与编辑MRS的相关性优于97 ms方法(r=0.68 vs.0.49,P<0.01)。在鉴别1p/19q共缺失胶质瘤方面,45 ms TE PRESS的敏感度和特异度分别为66.7%和73.7%,97 ms TE PRESS的敏感度和特异度分别为44.4%和52.5%。结论45 ms TE PRESS较97 ms方法提供了更精确的胱硫醚检测,将有助于1p/19q共缺失胶质瘤的无创诊断和患者的治疗反应监测。PRESS在1p/19q共缺失胶质瘤中表现出中等诊断性能,表明需要进一步研究。展开更多
Myocardial fibrosis is a major pathogenic factor contributing to cardiac remodeling and heart failure. Recent research has indicated that micro RNAs play a crucial role in the progression of cardiac fibrosis. Bone mor...Myocardial fibrosis is a major pathogenic factor contributing to cardiac remodeling and heart failure. Recent research has indicated that micro RNAs play a crucial role in the progression of cardiac fibrosis. Bone morphogenetic protein and activin membrane-bound inhibitor(BAMBI) have been shown to alleviate myocardial fibrosis by inhibiting the transforming growth factor β1(TGF-β1) signaling pathway. Therefore, the current study aimed to elucidate the post-transcriptional regulation of BAMBI by miR-19a-3p and its role in TGF-β1-induced cardiac fibroblast activation. We found that transverse aortic constriction induced both myocardial interstitial and perivascular collagen deposition. Quantitative reverse transcription-PCR(q RT-PCR) analysis showed that the expression level of miR-19a-3p was increased in the myocardial tissues of cardiac fibrosis, and TGF-β1 induced an upregulation in miR-19a-3p expression in cardiac fibroblasts. The dual-luciferase reporter assay and q RT-PCR verified that miR-19a-3p directly bound to the 3 ′ untranslated regions of BAMBI m RNA, thereby reducing BAMBI expression and diminishing its ability to inhibit the TGF-β1 signaling pathway. Furthermore,overexpression of miR-19a-3p mimic increased the activation of TGF-β1/SMAD2/3 pathway signaling,promoting cardiac fibroblast activation. However, this activation was blocked by BAMBI overexpression. These findings imply that miR-19a-3p enhances the activation of TGF-β1/SMAD2/3 by inhibiting BAMBI, further boosting the activation of cardiac fibroblasts and contributing to myocardial fibrosis.展开更多
Background:As a major histopathological subtype of gastric cancer(GC),stomach adenocarcinoma(STAD)is an important malignant tumor in the digestive system.Increasing evidence also indicates that endoplasmic reticulum(E...Background:As a major histopathological subtype of gastric cancer(GC),stomach adenocarcinoma(STAD)is an important malignant tumor in the digestive system.Increasing evidence also indicates that endoplasmic reticulum(ER)stress plays a pivotal role in the pathogenesis and progression of GC.Therefore,this study aims to screen and identify vital ER stress-related genes that could contribute to the malignant development and poor prognosis for STAD.Methods:A novel ER stress-related risk score signature was developed employingmachine learning techniques.Then,a prognostic prediction nomogram was also built based on the clinicopathological characteristics and the risk score signature.The tumor immune microenvironment characteristics and pathway enrichment analysis in different risk groups were also explored.Furthermore,through the single-cell RNA sequencing(scRNA-seq)analysis,the study highlightedCytochrome P450 Family 19 SubfamilyAMember 1(CYP19A1)as the pivotal research target and detected its effect on cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide(MTT)and the expression of ER stress-related genes by RT-qPCR in STAD.Results:Based on the evaluation of five screened key ER stressrelated genes(AKR1B1,SERPINE1,ADCYAP1,MATN3,CYP19A1),our ER stress-related risk score signature offers a novel approach for assessing STAD prognosis hazards.The novel prognostic prediction nomogram based on the signature also accurately predicted the survival outcomes of patients with STAD.Furthermore,the expression of CYP19A1 is significantly higher in STAD tissues than in normal tissues.High expression of CYP19A1 was related to a poor survival outcome for patients with STAD.Besides,compared to normal gastric epithelial cells,the expression of CYP19A1 was significantly higher in STAD cell lines.Silencing the expression of CYP19A1 significantly inhibited the cell proliferation ability and decreased the expression of ER stress-related genes,including ATF4,DDIT3 and XBP1 in STAD.Conclusions:In conclusion,our study developed a novel prognosis prediction signature and identified the novel diagnostic and therapeutic target CYP19A1 for patients with STAD.展开更多
目的:研究19号染色体短臂微卫星不稳定性(microsatellite instability,MSI)及杂合性缺失(loss of heterozygosity,LOH)与胃癌临床病理特征之间的关系,探讨19号染色体短臂微卫星MSI和LOH的主要临床意义。方法:采用PCR-SSLP-银染方法扩增7...目的:研究19号染色体短臂微卫星不稳定性(microsatellite instability,MSI)及杂合性缺失(loss of heterozygosity,LOH)与胃癌临床病理特征之间的关系,探讨19号染色体短臂微卫星MSI和LOH的主要临床意义。方法:采用PCR-SSLP-银染方法扩增79例原发性胃癌及正常组织标本中19号染色体短臂不同位置的7个点,PCR产物经聚丙烯酰胺凝胶电泳分离,运用Genescan软件和Genotyper软件分析MSI和LOH,然后进一步分析微卫星LOH与原发性胃癌的临床关系。结果:79例胃癌患者中,至少有1种微卫星发生LOH,其频率为31.18%(27/79),在所有微卫星中,D19S591和D19S565的LOH发生率分别为60.32%(38/63)和48.15%(26/54),高于其他微卫星的LOH。LOH高频率与原发性胃癌的临床分期及远处转移相关,且随着恶性程度增加LOH频率也增加(P<0.05),而MSI与胃癌临床病理之间相关性不大。结论:19p高频率的LOH与原发性胃癌的临床分期和远处转移相关,且LOH高频率提示在该区域可能存在肿瘤抑癌基因,其与胃癌的发生及进展相关。展开更多
文摘目的优化点分辨波谱(PRESS)的回波时间(TE),以检测胶质瘤中的胱硫醚,并评估PRESS波谱在识别1p/19q共缺失分子分型方面的诊断准确性。方法通过计算机模拟激发和模体实验优化PRESS的TE,以更好地区分胱硫醚和重叠的天冬氨酸多重峰。随后,将优化后的PRESS序列和97 ms TE PRESS序列应用于前瞻性纳入的84例疑似胶质瘤或胶质瘤复发的患者。通过拟合包含和不包含天冬氨酸的基组集来研究天冬氨酸对胱硫醚量化的影响,并评估PRESS对1p/19q共缺失胶质瘤的诊断表现。结果PRESS的TE优化为TE=45 ms,胱硫醚和天冬氨酸的谱峰模式在模拟激发和模体实验中一致。在临床实验中,97 ms TE PRESS中不包含天冬氨酸拟合得到的胱硫醚平均浓度显著高于使用完整基组集拟合的浓度[(1.97±2.01)mM vs.(1.55±1.95)mM,P<0.01],而45 ms TE PRESS方法则无显著差异[(0.801±1.217)mM vs.(0.796±1.217)mM,P=0.494]。45 ms方法的胱硫醚浓度与编辑MRS的相关性优于97 ms方法(r=0.68 vs.0.49,P<0.01)。在鉴别1p/19q共缺失胶质瘤方面,45 ms TE PRESS的敏感度和特异度分别为66.7%和73.7%,97 ms TE PRESS的敏感度和特异度分别为44.4%和52.5%。结论45 ms TE PRESS较97 ms方法提供了更精确的胱硫醚检测,将有助于1p/19q共缺失胶质瘤的无创诊断和患者的治疗反应监测。PRESS在1p/19q共缺失胶质瘤中表现出中等诊断性能,表明需要进一步研究。
基金National Natural Science Foundation of China (Grant Nos. 82070234 and 82100254)。
文摘Myocardial fibrosis is a major pathogenic factor contributing to cardiac remodeling and heart failure. Recent research has indicated that micro RNAs play a crucial role in the progression of cardiac fibrosis. Bone morphogenetic protein and activin membrane-bound inhibitor(BAMBI) have been shown to alleviate myocardial fibrosis by inhibiting the transforming growth factor β1(TGF-β1) signaling pathway. Therefore, the current study aimed to elucidate the post-transcriptional regulation of BAMBI by miR-19a-3p and its role in TGF-β1-induced cardiac fibroblast activation. We found that transverse aortic constriction induced both myocardial interstitial and perivascular collagen deposition. Quantitative reverse transcription-PCR(q RT-PCR) analysis showed that the expression level of miR-19a-3p was increased in the myocardial tissues of cardiac fibrosis, and TGF-β1 induced an upregulation in miR-19a-3p expression in cardiac fibroblasts. The dual-luciferase reporter assay and q RT-PCR verified that miR-19a-3p directly bound to the 3 ′ untranslated regions of BAMBI m RNA, thereby reducing BAMBI expression and diminishing its ability to inhibit the TGF-β1 signaling pathway. Furthermore,overexpression of miR-19a-3p mimic increased the activation of TGF-β1/SMAD2/3 pathway signaling,promoting cardiac fibroblast activation. However, this activation was blocked by BAMBI overexpression. These findings imply that miR-19a-3p enhances the activation of TGF-β1/SMAD2/3 by inhibiting BAMBI, further boosting the activation of cardiac fibroblasts and contributing to myocardial fibrosis.
基金Natural Science Foundation of Liaoning Province(2022-MS-083)Application Basic Research Plan of Liaoning Province(2023JH2/101300084).
文摘Background:As a major histopathological subtype of gastric cancer(GC),stomach adenocarcinoma(STAD)is an important malignant tumor in the digestive system.Increasing evidence also indicates that endoplasmic reticulum(ER)stress plays a pivotal role in the pathogenesis and progression of GC.Therefore,this study aims to screen and identify vital ER stress-related genes that could contribute to the malignant development and poor prognosis for STAD.Methods:A novel ER stress-related risk score signature was developed employingmachine learning techniques.Then,a prognostic prediction nomogram was also built based on the clinicopathological characteristics and the risk score signature.The tumor immune microenvironment characteristics and pathway enrichment analysis in different risk groups were also explored.Furthermore,through the single-cell RNA sequencing(scRNA-seq)analysis,the study highlightedCytochrome P450 Family 19 SubfamilyAMember 1(CYP19A1)as the pivotal research target and detected its effect on cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide(MTT)and the expression of ER stress-related genes by RT-qPCR in STAD.Results:Based on the evaluation of five screened key ER stressrelated genes(AKR1B1,SERPINE1,ADCYAP1,MATN3,CYP19A1),our ER stress-related risk score signature offers a novel approach for assessing STAD prognosis hazards.The novel prognostic prediction nomogram based on the signature also accurately predicted the survival outcomes of patients with STAD.Furthermore,the expression of CYP19A1 is significantly higher in STAD tissues than in normal tissues.High expression of CYP19A1 was related to a poor survival outcome for patients with STAD.Besides,compared to normal gastric epithelial cells,the expression of CYP19A1 was significantly higher in STAD cell lines.Silencing the expression of CYP19A1 significantly inhibited the cell proliferation ability and decreased the expression of ER stress-related genes,including ATF4,DDIT3 and XBP1 in STAD.Conclusions:In conclusion,our study developed a novel prognosis prediction signature and identified the novel diagnostic and therapeutic target CYP19A1 for patients with STAD.
文摘目的:研究19号染色体短臂微卫星不稳定性(microsatellite instability,MSI)及杂合性缺失(loss of heterozygosity,LOH)与胃癌临床病理特征之间的关系,探讨19号染色体短臂微卫星MSI和LOH的主要临床意义。方法:采用PCR-SSLP-银染方法扩增79例原发性胃癌及正常组织标本中19号染色体短臂不同位置的7个点,PCR产物经聚丙烯酰胺凝胶电泳分离,运用Genescan软件和Genotyper软件分析MSI和LOH,然后进一步分析微卫星LOH与原发性胃癌的临床关系。结果:79例胃癌患者中,至少有1种微卫星发生LOH,其频率为31.18%(27/79),在所有微卫星中,D19S591和D19S565的LOH发生率分别为60.32%(38/63)和48.15%(26/54),高于其他微卫星的LOH。LOH高频率与原发性胃癌的临床分期及远处转移相关,且随着恶性程度增加LOH频率也增加(P<0.05),而MSI与胃癌临床病理之间相关性不大。结论:19p高频率的LOH与原发性胃癌的临床分期和远处转移相关,且LOH高频率提示在该区域可能存在肿瘤抑癌基因,其与胃癌的发生及进展相关。
