Molecular mechanisms of oxidative stress-related neonatal jaundice

Oxidative stress is a pathological condition characterized by an overload of oxidant products, named free radicals, which are not well counteracted by antioxidant systems. Free radicals induce oxidative damage to many body organs and systems. In neonatal red blood cells, free-radical mediated-oxidative stress leads to eryptosis, a suicidal death process of erythrocytes consequent to alteration of cell integrity. Neonatal red blood cells are targets and at the same time generators of free radicals through the Fenton and Haber-Weiss reactions. Enhanced eryptosis in case of oxidative stress damage may cause anemia if the increased loss of erythrocytes is not enough compensated by enhanced new erythrocytes synthesis. The oxidative disruption of the red cells may cause unconjugated idiopathic hyperbilirubinemia in neonates. High levels of bilirubin are recognized to be dangerous for the central nervous system in newborns, however, many studies have highlighted the antioxidant function of bilirubin. Recently, it has been suggested that physiologic concentration of bilirubin correlates with higher antioxidant status while high pathological bilirubin levels are associated with pro-oxidants effects. The aim of this educational review is to provide an updated understanding of the molecular mechanisms underlying erythrocyte oxidant injury and its reversal in neonatal idiopathic hyperbilirubinemia.     

The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist

The optimisation of two series of 4-hydroxybenzothiazolone derived β₂-adrenoceptor agonists, bearing α-substituted cyclopentyl and β-phenethyl amino-substituents, as inhaled long-acting bronchodilators is described. Analogues were selected for synthesis using a lipophilicity based hypothesis to achieve the targeted rapid onset of action in combination with a long duration of action. The profiling of the two series led to identification of the α-substituted cyclopentyl analogue 2 as the optimal compound with a comparable profile to the inhaled once-daily long-acting β₂-adrenoceptor agonist indacaterol. On the basis of these data 2 was promoted as the backup development candidate to indacaterol from the Novartis LABA project.     

Gastrodin relieves inflammation injury induced by lipopolysaccharides in MRC‐5 cells by up‐regulation of miR‐103

The beneficial function of gastrodin towards many inflammatory diseases has been identified. This study designed to see the influence of gastrodin in a cell model of chronic obstructive pulmonary disease (COPD). MRC‐5 cells were treated by LPS, before which gastrodin was administrated. The effects of gastrodin were evaluated by conducting CCK‐8, FITC‐PI double staining, Western blot, qRT‐PCR and ELISA. Besides this, the downstream effector and signalling were studied to decode how gastrodin exerted its function. And dual‐luciferase assay was used to detect the targeting link between miR‐103 and lipoprotein receptor‐related protein 1 (LRP1). LPS induced apoptosis and the release of MCP‐1, IL‐6 and TNF‐α in MRC‐5 cells. Pre‐treating MRC‐5 cells with gastrodin attenuated LPS‐induced cell damage. Meanwhile, p38/JNK and NF‐κB pathways induced by LPS were repressed by gastrodin. miR‐103 expression was elevated by gastrodin. Further, the protective functions of gastrodin were attenuated by miR‐103 silencing. And LRP1 was a target of miR‐103 and negatively regulated by miR‐103. The in vitro data illustrated the protective function of gastrodin in LPS‐injured MRC‐5 cells. Gastrodin exerted its function possibly by up‐regulating miR‐103 and modulating p38/JNK and NF‐κB pathways.     

Identification of dynamic signatures associated with smoking‐related squamous cell lung cancer and chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a risk factor for the development of lung cancer. The aim of this study was to identify early diagnosis biomarkers for lung squamous cell carcinoma (SQCC) in COPD patients and to determine the potential pathogenetic mechanisms. The GSE12472 data set was downloaded from the Gene Expression Omnibus database. Differentially co‐expressed links (DLs) and differentially expressed genes (DEGs) in both COPD and normal tissues, or in both SQCC + COPD and COPD samples were used to construct a dynamic network associated with high‐risk genes for the SQCC pathogenetic process. Enrichment analysis was performed based on Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis. We used the gene expression data and the clinical information to identify the co‐expression modules based on weighted gene co‐expression network analysis (WGCNA). In total, 205 dynamic DEGs, 5034 DLs and one pathway including CDKN1A, TP53, RB1 and MYC were found to have correlations with the pathogenetic progress. The pathogenetic mechanisms shared by both SQCC and COPD are closely related to oxidative stress, the immune response and infection. WGCNA identified 11 co‐expression modules, where magenta and black were correlated with the “time to distant metastasis.” And the “surgery due to” was closely related to the brown and blue modules. In conclusion, a pathway that includes TP53, CDKN1A, RB1 and MYC may play a vital role in driving COPD towards SQCC. Inflammatory processes and the immune response participate in COPD‐related carcinogenesis.     

白蛋白静脉滴注联合茵栀黄颗粒治疗新生儿黄疸血清 AKP、TBA、 FFA、γ-GT、HS-CRP的影响

目的:研究白蛋白静脉滴注联合茵栀黄颗粒对新生儿黄疸血清碱性磷酸酶(alkaline phosphatase,AKP)、总胆汁酸(totalbileacids,TBA)、游离脂肪酸(free fatty acid,FFA)、γ-谷氨酰基转移酶(γ-glutamyltransferase,γ-GT)、超敏C-反应蛋白(hypersensitive C-reactive protein, HS-CRP)的影响。方法:选择2016年1月～2019年1月我院收治的95例新生儿病理性黄疸患儿,随机分为两组。对照组服用茵栀黄颗粒治疗,观察组在服用茵栀黄的基础上静脉滴注白蛋白治疗。检测两组的血清间接胆红素(indirectreacting bilirubin,,IBIL)、总胆红素(total bilirubin,TBIL)和AKP、TBA、FFA、y-GT、HS-CRP水平。结果:观察组的有效率明显高于对照组(P0.05);两组治疗后的血清IBIL、TBIL水平明显降低(P0.05),观察组的IBIL、TBIL水平明显低于对照组(P0.05);两组治疗后的血清AKP、TBA、FFA、γ-GT、HS-CRP水平明显降低(P0.05),观察组的血清AKP、TBA、FFA、γ-GT、HS-CRP水平明显低于对照组(P0.05)。结论:白蛋白静脉滴注联合茵栀黄颗粒对新生儿黄疸的治疗效果良好,有助于促进血清胆红素和其他血清学相关指标恢复正常,且安全性好。     

布地奈德福莫特罗联合噻托溴铵吸入剂治疗慢阻肺疗效及对CRP、SaO2、PH水平影响

摘要 目的：探究布地奈德福莫特罗联合噻托溴铵吸入剂对慢阻肺治疗效果及对患者C-反应蛋白（C reaction protein,CRP）、血氧饱和度（arterial oxygen saturation,SaO₂）以及肺动脉高压（pulmonary Hypertension,PH）的影响。方法：选择2016年至2019年于我院接受治疗的82例慢性阻塞性肺病患者,按照随机数字表法将其均分为两组（各41例）,对照组单纯接受布地奈德福莫特罗治疗,研究组在对照组基础上加用噻托溴铵吸入剂施治,对比两组治疗有效率,治疗前后的第1秒用力呼气容积（forced expiratory volume in one second,FEV₁）、用力肺活量（forced vital capacity,FVC）、第1秒用力呼气容积占预计值百分比（Percentage of FEV₁ in the predicted value,FEV₁%）、二氧化碳分压（carbon dioxide partial pressure,PaCO₂）、SaO₂、PH值、CRP。结果：（1）研究组治疗有效率明显高于对照组（P<0.05）;（2）治疗前两组FEV₁、FVC、FEV₁%对比无差异（P>0.05）,治疗后研究组上述指标均高于对照组（P<0.05）;（3）治疗前两组SaO₂、PaCO₂、PH值对比无差异（P>0.05）,治疗后研究组SaO₂、PH值均高于对照组,PaCO₂低于对照组（P<0.05）;（4）治疗前两组CRP水平无差异（P>0.05）,治疗后研究组上述因子水平均低于对照组（P<0.05）。结论：布地奈德福莫特罗联合噻托溴铵吸入剂对慢阻肺具有较好的治疗效果,能够显著改善患者肺功能及血气指标,同时还能够缓解患者炎性状态。     

微生态制剂联合莫西沙星序贯疗法对老年慢性阻塞性肺疾病合并下呼吸道感染患者肠道菌群及免疫功能的影响

目的探究微生态制剂联合莫西沙星序贯疗法对老年慢性阻塞性肺疾病(COPD)合并下呼吸道感染患者肠道菌群及免疫功能的影响。方法选取2016年2月到2019年2月我院收治的98例老年COPD合并下呼吸道感染患者为研究对象,按照随机数字表法分为观察组和对照组各49例。对照组患者采用莫西沙星序贯法进行治疗。观察组患者采用微生态制剂联合莫西沙星治疗。检测两组患者下呼吸道感染病原菌及肠道微生物变化,T淋巴细胞亚群(CD4⁺细胞,CD8⁺细胞,CD4⁺/CD8⁺)水平,并评价患者临床效果和并发症情况。结果治疗后两组患者CAT评分(8.23±3.64、10.41±4.08)和mMRC评分(1.35±0.82、1.77±0.61)均低于治疗前(23.01±4.47、22.87±5.26、2.79±0.54、3.04±0.74),且观察组下降幅度大于对照组,差异具有统计学意义(均P<0.05)。治疗后两组患者下呼吸道感染主要病原菌中肺炎克雷伯菌、大肠埃希菌、铜绿假单胞菌、肺炎链球菌检出率均低于治疗前,但组间比较差异无统计学意义(均P>0.05)。治疗后两组患者肠道双歧杆菌、嗜酸乳杆菌、粪肠球菌数量均高于治疗前,大肠埃希菌数量均低于治疗前,且观察组改善情况优于对照组,差异有统计学意义(均P<0.05)。治疗后两组患者CD4⁺细胞、CD4⁺/CD8⁺均高于治疗前,且观察组高于对照组,差异有统计学意义(均P<0.05)。CD8⁺细胞数量治疗前后及组间比较差异无统计学意义(均P>0.05)。治疗后观察组患者腹胀(18.4%)、胃潴留(20.4%)发生率均低于对照组(36.7%、38.8%),差异有统计学意义(均P<0.05)。两组患者应激性溃疡发生率(20.4%、24.5%)差异无统计学意义(P>0.05)。结论微生态制剂联合莫西沙星序贯疗法治疗老年COPD合并下呼吸道感染能促进患者肠道微生态平衡,调节免疫功能,进而改善患者病情。     

老年慢性阻塞性肺疾病患者和坠积性肺炎患者肺内病原菌比较及感染影响因素分析

目的对比老年慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者和坠积性肺炎患者肺内一般病原菌和多重耐药菌的分布,同时分析COPD患者和坠积性肺炎患者多重耐药菌感染的影响因素。方法对入选COPD患者和坠积性肺炎患者下呼吸道痰标本进行培养和鉴定,对比两组患者病原菌以及多重耐药菌的检出率,同时比较两组患者性别、年龄、住院时间、糖尿病病史、有创机械通气治疗和留置尿管等因素对多重耐药菌感染的影响。结果 COPD患者革兰阴性菌的检出率(48.39%)显著低于坠积性肺炎患者(66.13%),COPD患者真菌的检出率(11.06%)显著高于坠积性肺炎患者(2.42%)。两组患者检出的多重耐药菌均以产超广谱β-内酰胺酶肠杆菌科细菌、耐甲氧西林金黄色葡萄球菌和多重耐药/泛耐药铜绿假单胞菌为主。COPD患者中感染多重耐药菌患者的年龄和住院时间显著高于非感染患者;坠积性肺炎患者中感染多重耐药菌患者的住院时间、机械通气治疗率和留置尿管使用率显著高于非感染患者。结论影响老年COPD患者和坠积性肺炎患者多重耐药菌感染的因素有区别,应有针对性地应用抗生素以减少多重耐药菌的感染。