目的 探究玉屏风散合人参五味子汤与常规西医治疗稳定期慢性阻塞性肺疾病的效果.方法 选取2020年3月至2022年8月郑州大学第五附属医院收治的稳定期慢性阻塞性肺疾病患者92例,随机数表法分为观察组、对照组,各46例.对照组行常规西医治疗,观察组在常规西医基础上加行玉屏风散合人参五味子汤治疗,两组均持续治疗12周.比较两组中医证候评分、呼吸力学状态[总呼吸道黏性阻力(R5)、共振频率(Fres)、肺顺应性(CL)、总顺应性(CT)].结果 ①治疗过程观察组脱落1例、对照组脱落2例,最终观察组45例、对照组44例纳入本研究.②治疗6周、12周,两组患者R5、Fres呈降低趋势(P＜0.05),Cl、Ct提高(P＜0.05);且观察组患者治疗6周、12周的R5、Fres低于对照组,Cl、Ct高于对照组,差异有统计学意义(P＜0.05).结论 常规西医基础上加行玉屏风散合人参五味子汤治疗稳定期慢性阻塞性肺疾病可明显改善患者中医证候及肺功能,调节呼吸力学状态,提高临床疗效.

Given that currently used classical chemotherapeutic drugs lack the ideal therapeutic effect and produce severe side effects, platinum nanomaterials (Pt-NMs) have gradually gained attention, and their antitumor effect has been initially explored. However, the specific mechanisms underlying the action of Pt-NMs in non-small cell lung cancer (NSCLC) cells remain unclear. Moreover, the interaction between Pt-NMs and autophagy in inducing apoptosis of NSCLC cells remains unexplored. In this study, we explored the anti-NSCLC effect of amine-caged Pt nanoclusters (Nano-Pt) using cell cycle, migration, proliferation, apoptosis, and autophagy assays. We found that Nano-Pt significantly inhibited cell viability, reduced migration ability, caused DNA damage, induced S phase (period of DNA synthesis in the cell cycle) arrest, and promoted apoptosis in NSCLC cells. Nano-Pt also reduced mitochondrial membrane potential (MMP), increased permeability transition, and promoted apoptosis by upregulating Bax and PARP expression. Nano-Pt-induced apoptosis was accompanied by protective autophagy, which could be enhanced by autophagy inhibitors. Our findings on the biological behavior and the interaction between autophagy and apoptosis can provide the clear anti-NSCLC molecular mechanism of Nano-Pt, which have a promising potential for the development of novel Pt-based antitumor chemotherapy drugs with excellent curative efficacy and fewer side effects.

Lung cancer remains the most common fatal malignant disease, and the 5-year survival rate of patients with metastasis is merely 6%. In this research, the platinum nanocluster (short for nano-Pt) was used for optical imaging without the help of other fluorescent probes and possess targeted antitumor activity as well as low systemic toxicity. The endocytic pathway and distribution of nano-Pt in non-small cell lung cancer NSCLC H1299 cells was explored by the means of quantitative and qualitative tests. Furthermore, the targeting capability and antitumor efficiency of nano-Pt was detected by intravital imaging experiment and antitumor experiment. The research implies that nano-Pt entered H1299 cells dominatingly through macropinocytosis and clathrin-dependent endocytosis pathway, and has significant antitumor efficiency, targeting properties and reliable safety for mouse tumor, indicating this nano-Pt has great potential for clinical diagnosis and therapy of NSCLC H1299 cells.

Objective:To investigate the drug resistance of carbapenem-resistant Acinetobacter baumannii (CRAb), and to analyze the drug resistance genes of the isolated strains.Methods:A total of 339 CRAb strains isolated from clinical specimens in the Fifth Affiliated Hospital of Zhengzhou University from January 2018 to December 2021 were collected. The resistance of CRAb to commonly used antibiotics was detected by drug sensitivity test. The drug resistance genes of isolated strains were detected by ploymerase chain reaction (PCR) amplification method.Results:The 339 CRAb strains had the highest resistance to amoxicillin/sulbactam, aztreonam, cefepime, gentamicin and piperacillin, but had the highest sensitivity to tigecycline and polymyxin B. Results of PCR amplification found that OXA-23 (83.14%), OXA-51 (77.01%), ADC (73.56%) and VIM (15.71%) were main drug resistance genes. One to seven kinds of drug resistance genes were detected in each strain, and strains with 5 kinds of drug resistance genes were the majority (81 strains, 31.03%).Conclusions:There are some characteristics in drug resistance of CRAb strains. OXA-23, OXA-51, ADC and VIM are main drug resistance genes. Prevention and control measures for nosocomial infection should be strengthened in clinical.

Objective Immune checkpoint inhibitors (ICI) has achieved remarkable clinical benefit in advanced lung adenocarcinoma (LUAD). However, effective clinical use of ICI agents is encumbered by the high rate of innate resistance. The aim of our research is to identify significant gene mutations which can predict clinical benefit of immune checkpoint inhibitors in LUAD. Methods The mafComapre function of MafTools package was used to screen the differentially mutated genes between durable clinical benefit (DCB) group and no durable clinical benefit (NDB) group based on the somatic mutation data from NSCLc_PD1_mSK_2018. Machine learning was performed to select significantly mutated genes to accurately classify patients into DCB group and NDB group. A nomogram model was constructed based on the significantly mutated genes to predict the susceptibility of patients to ICI. Finally, we explored the correlation between two classifications of immune cell infiltration, PD-1 and PD-L1 expression, tumor mutational burden (TMB) and prognosis. Results Through utilize machine learning, 6 significantly mutated genes were obtained from 8 differentially mutated genes and used to accurately classify patients into DCB group and NDB group. The DCA curve and clinical impact curve revealed that the patients can benefit from the decisions made based on the nomogram model. Patients highly sensitive to ICI have elevated immune activity, higher expression of PD-1 and PD-L1, increased TMB, and well prognosis if they accept ICI treatment. Conclusions Our research selected 6 significantly mutated genes that can predict clinical benefit of ICI in LUAD patients.

In recent years, multifunctional platinum nanoclusters (Pt-NCs) as new Pt-based anti-cancer drugs exhibit a promising therapeutic efficiency for several cancer diseases, especially for human pulmonary carcinoma. However, the endocytosis behaviors (like uptake pathway, etc.) and induced apoptosis mechanism of Pt-NCs for drug-resistant non-small cell lung cancer (NSCLC), are still inconclusive. In this research, we explored the endocytic pathway of Pt-NCs in both typical NSCLC A549 cells and cisplatin-resistant A549/Cis cells through qualitative confocal laser scanning microscope (CLSM) measurement and quantitative flow cytometry (FCM) and inductive coupled plasma-optical emission spectroscopy (ICP-OES) analysis, by the means of introducing the specific inhibitors which impede the classical ways of endocytosis. It was found that Pt-NCs dominatingly entered A549 cells via caveolin-mediated endocytosis as well as A549/Cis cells through micropinocytosis approach. Pt-NCs possessed an excellent inhibitory effect on the cell proliferation, migration and invasion, which the cell activity of A549 cells reduced to 14% and that of A549/Cis cells went down about four fifths. Moreover, Pt-NCs treatment increased caspase-3 protein levels and downregulated the expression of c-Myc and Bcl-2, proving the Pt-NCs-induced apoptosis of NSCLC cells was related to c-Myc/p53 and Bcl-2/caspase-3 signal pathways. These results demonstrate the explicit uptake pathway and apoptotic signaling pathway of Pt-NCs for NSCLC, which provides an in-depth and reasonable theoretical basis for the development of new Pt-NCs-based chemotherapeutics in future clinical practice.

目的 探讨血清中内皮细胞特异性分子-1(endocan)、C反应蛋白(CRP)、降钙素原(PCT)表达水平对慢性阻塞性肺疾病急性加重(AECOPD)诊断和病情评估的临床价值.方法 选择呼吸内科收治的AECOPD患者85例,按病情严重程度从轻度至重度依次分为A、B、C、D四组,经治疗后以上受试者病情恢复到稳定状态为稳定期组,选择30例健康人作为对照组,测定所有研究对象血清endocan、CRP、PCT水平.分析AECOPD各组患者endocan、CRP、PCT水平变化及AECOPD组、COPD稳定期组与健康对照组endocan、CRP、PCT水平变化意义;使用受试者工作特征曲线(ROC)分析endocan、CRP、PCT分别对AECOPD诊断价值.结果 AECOPD患者endocan各组间差异均有统计学意义(P＜0.05);CRP水平除A组与B组、C组与D组组间差异均无统计学意义(P＞0.05)外,余组间差异均有统计学意义(P＜0.05);PCT水平除A组与B组组间差异无统计学意义(P＞0.05)外,余组间差异均有统计学意义(P＜0.05).稳定期endocan、CRP、PCT水平均高于健康组,各组间差异有统计学意义(P＜0.05).AECOPD组endocan、CRP、PCT水平均高于稳定期组,各组间差异有统计学意义(P＜0.05).应用endocan、CRP、PCT诊断AECOPD的AUC为0.900、0.823、0.819;endocan 最佳临界值为1.315μg/L时诊断AECOPD的敏感度为83.5%,特异度为84.3%;CRP 最佳临界值为13.565mg/L 时诊断AECOPD的敏感度为61.2%,特异度为93%;PCT 最佳临界值为0.235μg/L 时诊断AECOPD的敏感度为54.1%,特异度为98.3%.结论 endocan、CRP、PCT升高均可提示AECOPD.endocan对AECOPD具有较好的诊断价值,其对AECOPD诊断敏感度高于PCT、CRP.

[This corrects the article DOI: 10.3892/ol.2019.10834.].

目的 探讨替米沙坦激活的过氧化物酶体增殖物激活受体 γ(PPARγ)对大鼠肺动脉高压的影响及其机制.方法 皮下注射野百合碱复制大鼠肺动脉高压模型,将大鼠分为模型组、治疗组、干预组及对照组.治疗组每天给予替米沙坦10 mg/kg灌胃处理,模型组不予治疗,干预组在治疗组基础上给予GW96625 mg/kg腹腔注射.3周后取材,测量各组大鼠右心室收缩压(RVSP),肺动脉平均压(mPAP),计算右心室肥大指数(RVHI),苏木精-伊红染色观察肺动脉炎症反应情况,酶联免疫吸附试验检测肺组织匀浆中TNF-α、IL-6、单核细胞趋化蛋白-1(MCP-1)水平,Western blotting检测PPARγ 表达差异.结果 4组mPAP、RVSP及RVHI比较,差异有统计学意义(P<0.05),模型组较对照组高(P<0.05),治疗组、干预组较模型组低(P<0.05),干预组RVHI高于治疗组(P<0.05).模型组和干预组PPARγ 相对表达量较对照组降低(P<0.05),治疗组较模型组升高(P<0.05).模型组、治疗组、干预组MCP-1、IL-6及TNF-α 水平较对照组升高(P<0.05),治疗组、干预组较模型组降低(P<0.05),干预组较治疗组升高(P<0.05).结论 替米沙坦对野百合碱诱导的大鼠肺动脉高压有预防作用,可能与其激活PPARγ,抑制炎症反应有关.

The present study aimed to investigate the association between microRNA-152 and cisplatin resistance in non-small cell lung cancer. A549 and cisplatin-resistant A549 cells (A549/cis) were maintained in vitro. Reverse transcription-quantitative PCR (RT-qPCR) was performed to analyze differences in microRNA-152 levels between A549 and A549/cis cells, and changes in Bcl-2 and NF-κB expression levels were analyzed via RT-qPCR and western blot analyses. MicroRNA-152 was overexpressed in A549/cis cells via transfection of a microRNA-152 mimic. Upon treating transfected or untransfected A549/cis cells with 2 µg/l cisplatin for 24 h, a Cell Counting Kit-8 assay, morphological analysis and flow cytometry analysis were performed to evaluate the effect of microRNA-152 on the inhibition of cell proliferation and induction of apoptosis. Furthermore, changes in Bcl-2 and NF-κB expression levels in microRNA-152-overexpressing A549/cis cells were also analyzed. MicroRNA-152 was significantly downregulated and Bcl-2 and NF-κB were significantly upregulated in A549/cis cells (P<0.05). MicroRNA-152 upregulation enhanced the inhibitory effect of cisplatin on A549/cis cells. These results suggest that microRNA-152 downregulates Bcl-2 and NF-κB. MicroRNA-152 downregulation may induce cisplatin resistance in non-small cell lung cancer cells, whereas microRNA-152 upregulation may improve cisplatin sensitivity among A549/cis cells via downregulation of Bcl-2 and NF-κB.

Objective To investigate the changes of hypoxia-inducible factor (HIF-1α, HIF-2α) expression level in lung cancer A-549 cells under normoxic conditions, different hypoxia durations, and different oxygen concentrations. Methods A549 cells were divided into normoxic group, time control group, and oxygen concentration control group. Western blot was used to detect the expression of HIF-1α and HIF-2α in A-549 cells.Results The expression of HIF-1α and HIF-2α protein were lower under normoxia and significantly increased under hypoxic conditions. The difference was statistically significant. The lower the oxygen concentration, the more HIF-1α and HIF-2α protein expression levels were. The differences between high and high were statistically significant. The expression of HIF-1α protein increased at 2 h after hypoxia, peaked at 8 h, appeared plateau at 8 to 16 h, and decreased at 32 h, with a statistically significant difference. HIF-2α proteins gradually increased with prolonged hypoxia. Conclusions Under hypoxic conditions, the expression of HIF-1α and HIF-2α are increased, and the expression of HIF-2α has a time-dependent pattern, which may have more important biological significance.

目的:探讨肺康复联合音乐疗法干预前后对慢性阻塞肺性疾病(COPD)继发焦虑抑郁患者的外周血TOLL样受体4(TLR4)、白细胞介素-6(IL-6)和肿瘤坏死因子(TNF-α)的变化及临床意义.方法:纳入2017年3-12月稳定期COPD继发焦虑抑郁的患者90例,随机分为A组30例(肺康复治疗组),B组30例(肺康复联合音乐疗法组),C组30例(对照组),3组患者均给予常规治疗,随访12周.观察治疗前后医院焦虑抑郁量表(HADS)、外周血TOLL样受体4(TLR4),白细胞介素-6(IL-6)和肿瘤坏死因子(TNF-α)水平.结果:A组(t=2.81,P＜0.01)、B组(t=5.90,P＜0.01)治疗后的HADS评分均较前降低,对照组HADS评分(P＞0.05)较前无明显变化;A组、B组的血TLR4 (A组:t=18.52,P＜0.01;B组:t=31.13,P＜0.01)、IL-6(A组:t=15.45,P＜0.01;B组:t=14.29,P＜0.01)、TNF-α(A组:t=13.17,P＜0.01;B组:t=29.83,P＜0.01)水平较前降低,对照组较前无明显变化(P＞0.05);B组HADS评分较A组降低,B组的血TLR4、IL-6、TNF-α水平较A组降低,差异有统计学意义(P＜0.01).HADS评分与TLR4(r =0.51,P＜0.01)、TNF-α(r =0.64,P＜0.01)、IL-6(r =0.66,P＜0.01)水平呈正相关.结论:肺康复联合音乐疗法可以降低稳定期COPD继发焦虑抑郁患者的外周血TLR4、TNF-α、IL-6水平,TLR4、TNF-α、IL-6参与了焦虑抑郁疾病的发生发展.

Objective To investigate the clinical application of energy expenditure measurement in severe pneumonia patients with mechanical ventilation.Methods The resting energy expenditure (REE) measured by the indirect calorimety metabolic cart and the basal energy expenditure (BEE) calculated by the formula H-B were analyzed and compared,and the time dependent REE/BEE was calculated to estimate the stress coefficient.Results REE/BEE keeps in 1.07 to 1.11 without significant change during the period of mechanical ventilation in severe pneumonia patients with mechanical ventilation.Both sequential organ failure assessment score (SOFA) and blood concentrations of C-reactive protein (CRP) were decreased over time.Respiratory quotient (RQ) on the last intubation day was greater than that on the first day.Conclusions The REE of patients with severe pneumonia in resting state measured by indirect calorimetry is 1.1 times as high as that of BEE.The ratio of REE/BEE was steady without significant change during treatment,it may be due to the concomitant increase of energy intake and improvement in general condition.

目的 探讨布地奈德、福莫特罗联合治疗慢性阻塞性肺疾病(COPD)对患者肺功能的影响.方法 选取我院2016年8月~2017年6月收治的COPD患者60例作研究对象,并进行随机分组:对照组(n=30)单纯应用福莫特罗治疗,研究组(n=30)应用布地奈德、福莫特罗联合治疗,就两组患者的肺功能变化以及不良反应发生率进行统计学分析.结果 ①治疗前,研究组和对照组患者的FVC、FEV1/FVC指标对比,差异无统计学意义(P>0.05);治疗后,研究组患者的FVC、FEV1/FVC水平均高于对照组,差异有统计学意义(P<0.05);②研究组患者不良反应发生率是10.00%,同对照组不良反应发生率6.67%相比无统计学差异;差异无统计学意义(P>0.05).结论 布地奈德、福莫特罗联合治疗COPD患者,可有效改善其肺功能,且不良反应发生率较低.

目的 吸烟可诱发并加重睡眠呼吸暂停综合征(OSAHS),但其对OSAHS患者胰岛素抵抗(IR)影响却鲜有报道.文中探讨吸烟对男性OSAHS患者IR的影响.方法 回顾性分析2016年4月至2017年3月期间于郑州大学第五附属医院睡眠呼吸障碍诊疗中心就诊的141例男性OSAHS患者临床资料,根据有无吸烟史分为吸烟组(n=104)与非吸烟组(n=37);根据吸烟指数将吸烟组分为吸烟指数≥600支/年者和吸烟指数<600支/年者.所有患者行多导睡眠图(PSG)监测并取得夜间睡眠资料.检测所有患者空腹胰岛素(FINS)、空腹血糖(FBG)、C反应蛋白(CRP)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、血清过氧化脂质(LPO)含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-PX)活性.通过稳态模型胰岛素抵抗指数(HOMA-IR)与FINS评价IR.结果 相比于非吸烟组患者,吸烟组患者缺氧时间更长、血氧饱和度更低,且CRP、TNF-α、IL-6、LPO含量升高,SOD、GSH-PX活性降低,差异均有统计学意义(P<0.05).吸烟指数≥600支/年者和吸烟指数<600支/年者FBG[(5.85±1.23)mmol/L vs(4.85±0.69)mmol/L]、FINS[(11.17±2.98)mU/L vs(9.76±3.15)mU/L]、HOMA-IR[(2.65±0.94)vs(2.21±0.92)]及胰岛素(28.7％vs 23.1％)抵抗发生率间差异均有统计学意义(P<0.05);且均高于非吸烟组,差异均有统计学意义(P<0.05).结论 吸烟可能是导致男性OSAHS患者胰岛素抵抗的重要因素之一;氧化应激、炎症和低氧可能是其影响因素.