Inhibitors of the programmed death receptor 1 (PD-1) or its ligand PD-L1 are widely used in cancer treatment. Despite their efficacy, these immunotherapies can induce adverse effects, particularly dermatitis and pneumonitis. However, the prognosis of these conditions is infrequently reported. The present study discusses a case of a patient with non-small-cell lung cancer (NSCLC) who developed severe dermatitis and grade 4 pneumonitis following treatment with pembrolizumab. Initially, the patient was administered methylprednisolone at a dosage of 4 mg/kg/day. Reducing the dosage to 1 mg/kg/day exacerbated the pneumonitis, following which the patient was administered mycophenolate mofetil (MMF), which notably ameliorated both conditions. The methylprednisolone dosage was then gradually reduced to 4 mg daily. The present case represents a rare instance of simultaneous severe dermatitis and grade 4 pneumonitis in a patient with NSCLC following immunotherapy. The conditions were successfully managed with a combination of MMF with methylprednisolone, resolving the steroid-dependent dermatitis and pneumonitis. The patient maintained a partial remission, with a tumor size of >30% smaller compared with the initial tumor size, for >3 years following the cessation of immunotherapy.

tRNA衍生的小RNA(transfer RNA-derived small RNA,tsRNA)是一种在人体组织中稳定表达的新型非编码RNA.目前已知两种tsRNA亚型:tRNA半分子和tRNA衍生片段.高通量测序技术的发展和应用为肿瘤中tsRNA的失调提供了越来越多的证据.tsRNA在肿瘤组织中的异常表达已经被发现与肿瘤的增殖、侵袭和进展有关.这些新发现的tsRNA有很大的潜力作为新的生物标志物和肿瘤治疗的靶点.综述就tsRNA在肿瘤中的最新研究进展进行论述并讨论其潜在临床价值.

OBJECTIVES:Chronic obstructive pulmonary disease (COPD) patients have higher laryngopharyngeal reflux (LPR)-related symptom incidence. But LPR treatment is empirical. We aimed to determine the frequency of LPR, diagnosed by 24-hour Dx-pH monitoring, among acute exacerbations of COPD (AECOPD) patients with Reflux Symptom Index (RSI) ≥13 and investigate proton pump inhibitor (PPI) treatment effect on LPR, COPD symptoms, and pulmonary function.METHODS:From January 2016 to September 2017, 102 AECOPD patients with RSI ≥13 were enrolled. COPD assessment test (CAT), mMRC dyspnea scale, pulmonary function tests, and 24-hour Dx-pH monitoring were performed. The Ryan score was evaluated by using the Dx-pH DataView Lite software, which identifies patients with abnormal pharyngeal pH environments. Associations among RSI, pulmonary function test results, and Ryan score parameters were evaluated. The abovementioned assessments were reperformed after treatment, and pre- and posttreatment data were compared.RESULTS:Of the 102 eligible patients, 49 (48.04%) were diagnosed with LPR based on Ryan score. Percentage of the forced expiratory volume at 1 second (FEV1%) was significantly worse in Ryan-positive than in Ryan-negative AECOPD patients. There were significant negative correlations between FEV1% and Ryan score (r = -0.394, P < 0.001), FEV1% and % time below pH threshold (r = -0.371, P < 0.001) in upright position but not in supine position. There was no significant correlation between RSI and Ryan score parameters. There were significant improvements in RSI, mMRC, CAT, and FEV1% in Ryan-positive AECOPD patients after PPI and basic treatments.CONCLUSION:Study results indicate unreliability of RSI threshold for LPR diagnosis. Combination of symptoms, endoscopic findings, and 24-hour Dx-pH monitoring is recommended for LPR diagnosis and PPI treatment decisions, especially in difficult-to-control or severe COPD patients.

1 病历摘要 患者女,54岁,因"发热3天"于2019年2月7日就诊我院.入院前3天患者无明显诱因出现发热,体温最高达38.3℃,具体热型不详,伴畏寒,无寒战,少许阵发性咳嗽咳痰,痰量少,不易咳出,伴乏力、食欲缺乏明显,不思饮食,休息时即感胸闷,至当地卫生院就诊,予退热药物(具体不详)处理后病情无好转.

目的 探讨CT引导下经皮125I放射性粒子植入术后肺癌针道种植转移的危险因素.方法 回顾性选取2015年1月至2020年4月在我院呼吸与危重症医学科接受CT引导下经皮125I放射性粒子植入术治疗的156例肺癌患者作为研究对象,收集并分析其临床资料.术后随访,统计所有发生针道种植转移的病例,计算针道种植转移的发生率,计算每例患者的平均穿刺深度,记录首次发现肿瘤针道种植转移的时间.通过病例对照研究,分别将位于胸膜下的肿瘤、低分化的肿瘤、平均穿刺深度、肿瘤直径作为暴露因素,探讨其与肿瘤针道种植转移的关系.结果 34例患者病灶紧贴胸膜,34例患者病理示低分化癌,所有患者平均穿刺深度为(12.138±4.913)cm,其中63例患者平均穿刺深度<10 cm,28例患者病灶直径<2 cm.2例患者发生针道种植转移,病灶直径均>2 cm;病理结果显示2例均为低分化癌,发现针道种植转移的平均时间为(154.500±19.091)d;平均穿刺深度为(9.849±1.228)cm.125I粒子植入术后发生肿瘤针道种植转移患者与未发生转移患者肿瘤是否位于胸膜下、是否为低分化肿瘤、平均穿刺深度、肿瘤直径比较,差异无统计学意义(P>0.05).结论 经皮125I放射性粒子植入治疗后可能发生肿瘤针道种植转移,但发生率低,经过积极治疗后,不会成为患者的致死因素.

目的 探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)与夜间咽喉反流(LPR)的相关性.方法 选择2016年1月～2017年12月在我院接受治疗的52例OSAHS患者作为研究对象,监测患者整夜睡眠呼吸情况、行24 h咽喉pH值以及高分辨食管动力检查,探讨OSAHS与LPR的相关性.结果 52例患者中有13例存在LPR,LPR患者OSAHS严重程度与患者咽喉pH平均值呈现出明显的负相关(P＜0.05);LPR患者上食道括约肌(UES)静息压及下食管括约肌(LES)静息压分别为(71.13±9.25)mmHg、(27.39±11.14)mmHg,均显著低于非LPR患者,差异有统计学意义(P＜0.05).结论 阻塞性睡眠呼吸暂停低通气综合征患者病情程度与夜间咽喉反流密切相关,其夜间容易诱发胃食管反流,伴随咽喉部pH值下降,需给予高度临床关注.

Overexpression of RING finger protein 187 (RNF187) was recently revealed to be a driver of several cancers. However, the expression and function of RNF187 in non-small-cell lung cancer (NSCLC) are still unknown. Here, we uncovered that RNF187 expression was significantly higher in NSCLC samples than in matched normal lung samples at both the messenger RNA (3.55 ± 0.79 vs. 1.74 ± 0.63) and protein (2.85 ± 0.14 vs. 1.24 ± 0.02) levels. By downregulating or upregulating RNF187 expression in NSCLC cells, we showed that elevated RNF187 expression distinctly enhanced the migration, invasion, and colony formation of NSCLC cells. Moreover, we revealed that high level of RNF187 promoted NSCLC progression by inducing cell epithelial to mesenchymal transition (EMT) and apoptosis resistance mainly via activating the mitogen-activated protein kinase and PI3K signaling. Clinically, we demonstrated that RNF187 expression was positively associated with advanced TNM stage (p = 1.29 × 10 -6 ), lymph node metastasis ( p = 2.69 × 10 -9 ), and large tumor size ( p = 0.002). Importantly, NSCLC patients with elevated RNF187 expression related to the short overall survival rate( p = 1.29, E-7) and could serve as an independent prognostic factor in NSCLC patients. Thus, elevated RNF187 expression promotes NSCLC development by inducing cell EMT and apoptosis resistance, and RNF187 may be a novel prognostic indicator for NSCLC patients after curative resection.

目的:探究铝碳酸镁联合质子泵抑制剂(PPI)治疗慢性阻塞性肺疾病(COPD)合并咽喉反流的疗效及对慢性阻塞性肺疾病急性加重(AECOPD)的预防作用.方法:选取2015年6月到2017年6月于本院就诊的98例COPD合并咽喉反流患者,随机数字表法分为研究组和对照组,各49例.两组患者均给予常规COPD药物治疗,对照组患者给予PPI治疗,研究组在此基础上给予铝碳酸镁联合治疗,院外随访12个月.比较两组患者临床疗效、治疗前后咽喉部24 h连续pH监测情况、肺功能和咽喉反流指标,应用Kaplan-Meier法绘制生存曲线,分析两组患者AECOPD发作和死亡风险间的差异.结果:两组患者临床疗效存在差异(Z=-1.976,P=0.048),且研究组治疗有效率显著高于对照组(97.96％ 和79.59％,χ2=8.295,P=0.004);治疗后两组患者酸反流次数、Ryan指数和酸反流总时间均显著减少,且研究组显著低于对照组,差异具有统计学意义(P<0.05);治疗后,两组患者第1秒用力呼气容积占预计值百分比(FEV1％)和第1秒用力呼气容积/用力肺活量(FEV1/FVC)均显著升高,自我评估测试(CAT)、反流症状指数评分量表(RSI)和反流体征评分量表(RFS)评分均显著降低,且研究组FEV1％和FEV1/FVC均显著高于对照组,CAT、RSI和RFS评分均显著低于对照组,差异具有统计学意义(P<0.05);对照组和研究组在出院后12个月内的急性发作率分别为69.39％(34/49)和46.94％(23/49),研究组的急性发作风险显著低于对照组(HR=0.513,95％CI[0.318,0.904],P=0.015);对照组和研究组在出院后12个月内分别有2例和1例死亡病例,研究组和对照组的死亡风险间无明显差异(HR=0.489,95％CI[0.050,4.709],P=0.551).结论:铝碳酸镁联合PPI治疗COPD合并咽喉反流能显著提高临床疗效,有效改善患者肺功能和咽喉反流症状,明显降低COPD急性发作发生风险,值得临床推广.

慢性咳嗽是指成年人持续8周、儿童持续4周以上的咳嗽.引起慢性咳嗽的病因众多,根据胸部X线检查有无异常可分为两类:一类是X线显示存在明确病变者如肺炎、结核、支气管肺癌等;另一类是胸部X线检查无明显异常者,仅咳嗽为唯一症状.对于无明显原因的慢性咳嗽患者,研究表明[1],咽喉反流性疾病(laryngopharyngeal reflux disease,LPRD)是引起慢性咳嗽的一大原因.国外研究报道[2],LPRD在40岁以上人群发病率达35％左右,在西方国家,咽喉反流性咳嗽约占慢性咳嗽病因的21％～41％,但在我国慢性咳嗽患者中LPRD的发生率尚无确切报道.本研究旨在观察我院收治的慢性咳嗽患者中LPRD的发生率并分析其治疗结果,为临床治疗LPRD引起的慢性咳嗽提供客观参考.

目的 探讨老年重症肺炎患者细胞炎症因子、凝血功能和肺功能的变化及影响其预后的危险因素.方法 选择50例老年重症肺炎为研究组;另选择普通肺炎患者50例作为对照组;采用酶联免疫吸附试验(ELISA)测定两组血浆白细胞介素(IL)-10、IL-18和肿瘤坏死因子(TNF)-α含量;采用全自动血凝分析仪测定纤维蛋白原(Fib)、凝血酶原时间(PT)、凝血酶时间(TT)、活化部分凝血活酶时间(APTT)和D-二聚体含量,严格依据试剂盒说明书标准测定;采用肺功能仪测定第1秒最大呼吸容积(FEV1)、最高呼气流速(PEF)和用力肺活量(FVC).结果 研究组血浆IL-10、IL-18和TNF-α水平明显高于对照组(P<0.05).研究组Fib、PT、TT、APTT和D-二聚体水平明显高于对照组(P<0.05).研究组FEV1、PEF和FVC明显低于对照组(P<0.05).根据患者临床转归,研究组分为存活组(21例)及死亡组(29例)两亚组.经单因素分析表明,两亚组性别、合并基础疾病、白蛋白和白细胞(WBC)比较差异无统计学意义(P>0.05);两亚组年龄、急性生理与慢性健康评分表(APACHE)Ⅱ评分、多器官功能障碍综合征(MODS)评分、累及器官、机械通气和长期卧床比较差异有统计学意义(P<0.05).多因素Logistic回归分析,年龄、APACHEⅡ评分、MODS评分、累及器官和长期卧床为影响老年重症肺炎独立危险因素.结论 老年重症肺炎患者存在明显炎症反应、凝血功能异常及肺功能下降,年龄、APACHEⅡ评分、MODS评分、累及器官和长期卧床为影响老年重症肺炎独立危险因素.

Objective To assess the diagnosis value of traditional culture method and the real-time fluorescent quantitative PCR(RT-qPCR) method in identification of bacterial pathogens in lower respiratory tract.Methods 65 bronchiectasis patients associated with infection in Yinzhou People's Hospital have been enrolled.Both traditional culture and RT-qPCR methods were performed for the samples of bronchoalveolar lavage fluid (BALF) and protected specimen brush (PSB) obtained by bronchoscope,and the results were analyzed.Results The negative rate of traditional culture detection in PSB samples was 36.9％,which was significantly higher than the negative rate in BALF samples (23.1％),with the differences statistically significant(P ＜ 0.01).The total positive rate of fluorescence quantitative PCR analysis in PSB samples was 7.7％.And the positive rate of RT-qPCR in each strain was significantly higher than that of traditional culture detection,with the differences statistically significant(P ＜ 0.01).Klebsiella pneumonia and Pseudomonas aeruginosa had higher copies than the other four stains,with the differences statistically significant(P ＜ 0.05).Conclusion In patients with bronchiectasis complicated with infection,the detection specificity of PSB was higher;fluorescence quantitative PCR is rapider and more sensitive,which has important guiding significance for the early application of antibiotics.

目的 比较血清及支气管肺泡灌洗液(BALF)两种不同标本的GM试验在侵袭性肺曲霉病(IPA)早期诊断中的价值.方法 收集拟诊为IPA的26例患者为病例组,普通细菌感染性肺炎患者15例为对照组.观察两种标本GM试验I值的差异,并比较在不同诊断阈值下,血清及BALF GM试验诊断IPA的价值.通过ROC曲线分析确定血清及BALF两种标本的不同诊断阈值.结果 两组组内血清和BALF这两种不同的标本,GM试验I值存在显著性差异(均P＜0.05).在不同诊断阈值下,BALF GM试验诊断IPA的敏感度、特异度、阳性预测值、阴性预测值均优于血清.ROC曲线分析显示血清和BALF标本GM试验的诊断阈值分别为0.68、0.8,曲线下面积分别为0.809及0.894.结论 血清和BALF标本GM试验在IPA的早期诊断中都有重要的价值,但在非粒细胞缺乏的IPA患者中,BALF GM试验诊断价值可能高于血清,并且血清及BALF使用同一诊断阈值可能存在一定的不足.

OBJECTIVE To investigate L‐mycobacterium tuberculosis infection in patients with primary lung cancer and drug resistance ,so as to provide basis for clinical treatment .METHODS A total of 224 tissue specimens of pa‐tients with primary lung cancer were selected from the hospital from May 2012 to Aug 2015 ,and L‐mycobacterium tuberculosis infection was detected by in situ hybridization and given drug sensitivity test to have its drug resist‐ance rate .RESULTS From the total of 224 cases of lung cancer patients ,87 cases of lung tissue analysis showed positive after the surgery ,and the positive rate was 38 .84% ;after the isolation of pathogenic bacteria from patho‐genic organization ,a total of 117 strains of L‐mycobacterium tuberculosis were isolated ;and the drug resistance rate to first‐line and second‐line antituberculosis drugs were 52 .99% and 47 .01% ;the drug resistance analysis of L‐mycobacterium tuberculosis to multidrug‐resistant(MDR) and extensive drug resistance(XDR)showed that the drug resistant rate of MDR was 35 .04% ,which was significantly higher than 16 .24% of XDR (P< 0 .05) . CONCLUSION L‐mycobacterium tuberculosis has a high drug resistance in clinic ,and the analysis of its drug re‐sistance can guide clinical treatment to L‐mycobacterium tuberculosis .

OBJECTIVE To investigate the Th17 cell and Treg cell levels in patients with sarcoidosis, and their relation to disease activation and glucocorticoids treatment. METHODS Twenty-three sarcoidosis patients admitted in Yinzhou People's Hospital from January 2009 to December 2013 and 25 healthy subjects (controls) were included in this study. The blood samples and bronchoalveolar lavage fluid (BALF) samples were collected in all patients before and after glucocorticoids treatment. The serum angiotensin converting enzyme (SACE) levels were detected. The percentages of Th17 cells and Treg cells in peripheral blood and BALF were determined by flow cytometry, the concentrations of cytokines in serum and supernatants of BALF were measured by enzyme-linked immunosorbent assay (ELISA). The levels of ROR-γt and Foxp3 mRNA transcripts in peripheral blood mononuclear cells (PBMC) were determined by real-time quantitative PCR. The potential correlation between the percentages of Th17 or Treg cells and SACE levels was evaluated. RESULTS Compared with healthy controls, significantly higher frequencies of Th17 cells (4.34%±0.89% vs 1.60% ± 0.42%), lower frequencies of Treg cells (1.28% ± 0.37% vs 3.39% ± 0.50%) in peripheral blood were observed. Higher level of ROR-γt mRNA (21.31 ± 3.55 vs 3.63 ± 1.00) and lower level of Foxp3 mRNA (1.60 ± 0.24 vs 3.12 ± 0.76) in peripheral blood were detected in sarcoidosis patients in active stage (before glucocorticoids treatment) (all P<0.01). After the treatment of glucocorticoids, these index in peripheral blood were significantly improved (Th17 cells 2.16% ± 0.68%，Treg cells 2.21% ± 0.42%, ROR-γt mRNA 10.15 ± 1.93, Foxp3 mRNA 2.44 ± 0.38) ( all P<0.05). The changing trends of Th17 and Treg cell cytokines levels in serum were consistent with two type cells. Meanwhile, the changing trends of above index in BALF of patients treated by glucocorticoids were consistent with those in sarcoidosis patients in active stage. The increased ratios of Th17 cells to Treg cells were positively correlated with the level of serum SACE (r= 0.781). CONCLUSION The imbalance of Th17 cells and Treg cells in peripheral blood and airway may be involved in the pathogenesis of sarcoidosis, which was associated with the activity of disease, and the treatment of glucocorticoids may achieve a therapeutic effect by correcting the immune imbalance.

BACKGROUND:Bacterial infection of the lower respiratory tract is believed to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and acute exacerbations of COPD (AECOPD). This study investigates the potential relationship between AECOPD and the load of six common bacterial pathogens in the lower respiratory tract using real-time quantitative PCR (RT-qPCR) in COPD patients.METHODS:Protected specimen brush (PSB) and bronchoalveolar lavage fluid (BALF) samples from the lower respiratory tract of 66 COPD patients and 33 healthy subjects were collected by bronchoscopy. The load of Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonos aeruginosa, Haemophilus influenzeae, and Moraxella catarrhalis were detected by RT-qPCR.RESULTS:High Klebsiella pneumoniae, Pseudomonos aeruginosa, Haemophilus influenzeae and Moraxella catarrhalis burden were detected by RT-qPCR in both PSB and BALF samples obtained from stable COPD and AECOPD patients compared with healthy subjects. The load of the above four pathogenic strains in PSB and BALF samples obtained from AECOPD patients were significantly higher compared with stable COPD patients. Finally, positive correlations between bacterial loads and inflammatory mediators such as neutrophil count and cytokine levels of IL-1β, IL-6 and IL-8, as well as negative correlations between bacterial loads and the forced expiratory volume in one second (FEV1) % predicted, forced vital capacity (FVC) % predicted, and FEV1/FVC ratio, were detected.CONCLUSIONS:These findings suggest that increased bacterial loads mediated inflammatory response in the lower respiratory tract and were associated with AECOPD. In addition, these results provide guidance for antibiotic therapy of AECOPD patients.

骨化性气管支气管病（TO）是指气管、支气管黏膜下多发性骨质或软骨组织结节状增生并突向管腔的良性病变。目前原因不明，发病率低，国内外文献阐述较少，其临床症状无特异性，常被误诊或漏诊。我院近年来诊治3例骨化性气管支气管病患者，均曾误诊为支气管哮喘。

BACKGROUND:MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood.METHODS:We detected miR-27a expression in two lung adenocarcinoma cell lines, A549 and A549/CDDP, and then investigated the effects of miR-27a on the metastasis and the chemosensitivity of cancer cells, using both gain- and loss-of-function studies. The correlation between miR-27a level and chemoresistance was further investigated in clinical lung adenocarcinoma specimens.RESULTS:miR-27a was significantly up-regulated in cisplatin-resistant lung adenocarcinoma A549/CDDP cells compared with parental A549 cells. miR-27a regulates epithelial-mesenchymal transition (EMT) and cisplatin resistance in vitro and modulates response of lung adenocarcinoma cells to cisplatin in vivo. Further studies identified Raf Kinase Inhibitory Protein (RKIP) as a direct and functional target of miR-27a. Small interfering RNA-mediated RKIP knockdown revealed similar effects as that of ectopic miR-27a expression, while overexpression of RKIP attenuated the function of miR-27a in lung adenocarcinoma cells. Increased miR-27a expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with cisplatin-based chemotherapy and was proved to be correlated with low expression of RKIP, decreased sensitivity to cisplatin, and poor prognosis.CONCLUSION:Our results suggest that up-regulation of miR-27a could suppress RKIP expression and in turn contribute to chemoresistance of lung adenocarcinoma cells to cisplatin.

Objective To investigate the values of fluticasone salmeterol in the treatment of early COPD.Methods One hundred and sixty patients with early COPD from January 2006 to February 2010 in our hospital were selected and randomly divided into treatment group(fluticasone salmeterol inhaler therapy) and control group(conventional therapy),the lung function before and after 1 year treatment,FEV1 decline rate,FEV1/FVC,quality of life assessment(St.George's questionnaire) and acute exacerbation were compared between the two groups.Results After 1 year treatment,the total FEV1 decline rate in the observation group was significantly lower than that of the control group(P 0.05);the FEV1/FVC had more improvement than the pre-treatment in the two groups(P 0.05),and the acute exacerbation situation and life quality score in the observation group were significantly better than those of the control group(P 0.05).Conclusion Early application of fluticasone salmeterol can delay the development of COPD,reduce acute exacerbation and acute exacerbation.

目的探讨慢性阻塞性肺疾病(COPD)合并侵袭性肺曲霉菌病(IPA)的临床特点。方法回顾性分析30例COPD合并IPA患者的临床资料。结果 COPD合并IPA临床表现、影像表现等均缺乏特异性,曲霉菌培养阳性率低,早期诊断困难,死亡率高。结论对于COPD具有危险因素者,治疗中出现病情恶化,需警惕IPA可能,应积极病原学培养、胸部CT检查及半乳甘露聚糖检测,对于诊断困难的重症患者应尽早进行经验性抗真菌治疗,以改善预后。

Recent studies have implied that miRNAs act as crucial modulators for epithelial‐to‐mesenchymal transition (EMT). We found that miR‐134 expression correlated with invasive potential and EMT phenotype of NSCLC cells. Functional assays demonstrated that miR‐134 inhibited EMT in NSCLC cells. In addition, we showed that Forkhead Box M1 (FOXM1) is a direct target of miR‐134. Knockdown of FOXM1 reversed EMT resembling that of miR‐134 overexpression. We further found that FOXM1 was involved in TGF‐β1‐induced EMT in A549 cells. These findings suggest that miR‐134 acts as a novel EMT suppressor in NSCLC cells.