SWI/SNF染色质重塑复合体参与调控多种基因转录,发挥抑癌基因作用,其多个亚基高频突变与肿瘤发生密切相关,SMARCA4 亚基突变为最常见类型[1]. SMARCA4 基因位于 19 号染色体短臂,编码BGR1 蛋白,在非小细胞肺癌中突变率约 6％ [2].

睾丸核蛋白( nuclear protein in testis,NUT)癌是一种罕见,具有高度侵袭性的低分化癌,以15 q14染色体基因重排引起NUT与含溴结构域蛋白 4 ( bro-modomain-containing protein 4 , BRD4 ) 融合形成NUT-BRD4为特征[1].

目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)SMARCA4突变患者临床特征及预后,并应用生物信息学方法探究其临床意义.方法:回顾性分析35例SMARCA4基因突变NSCLC患者临床资料,根据伴随基因突变类型分组,采用Kaplan-Meier法行生存分析.应用TIMER数据库、GEPIA数据库分析SMARCA4基因在NSCLC及正常肺组织中的表达差异.cBioPortal数据库分析SMARCA4基因突变情况及与预后的相关性.STRING数据库构建SMARCA4相互作用蛋白网络.结果:SMARCA4突变NSCLC患者以老年男性为主,主要病理类型为腺癌;主要伴随突变基因有EGFR(14例)、TP53(11例)、KRAS(4例)、ERBB2(4例)等.生存分析发现伴随EGFR突变患者预后较野生型好,而伴随KRAS突变患者预后较野生型差.生物信息学分析发现8%的NSCLC患者携带SMARCA4基因突变,突变类型包括错义突变、剪接突变、删除突变等;含SMARCA4突变的肺腺癌患者预后较野生型差.结论:SMARCA4突变影响NSCLC患者预后,且伴随基因种类对患者预后产生不同影响,这为肺癌的精准化治疗提供更多依据.

目的:通过比较慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)相关性肺动脉高压(pulmonary hy-pertension,PH)患者及COPD无PH患者在心肺运动试验(cardiopulmonary exercise testing,CPET)中气体交换及运动耐量的差异,探索CPET在COPD相关性PH无创评估中的作用.方法:94例稳定期COPD患者根据右心导管平均肺动脉压分为COPD-nonPH组、COPD-PH组、COPD-严重PH组,分别进行常规肺功能及CPET检查.结果:相较于COPD-nonPH,在发生PH后一氧化碳弥散量明显下降[(46.5±21.8)％ vs.(64.6±34.0)％,P＜ 0.05].COPD-PH组峰值功率、峰值摄氧量占预计值百分比、峰值公斤摄氧量、峰值氧脉搏及摄氧效率斜率均低于COPD-nonPH组,且随PH严重程度进一步降低,差异均有统计学意义(P＜0.05).COPD-PH组通气效率最低点高于COPD-nonPH组,且随PH严重程度明显升高(49.0±24.6 vs.38.6±11.4 vs.35.6±9.6,P＜ 0.05).峰值心率、呼吸交换率、摄氧效率平台、潮气末二氧化碳分压在各组间差异无统计学意义(P＞0.05).结论:相较于COPD-nonPH患者,COPD-PH患者气体交换和运动耐量显著下降,且随PH严重程度进一步加重,CPET可以作为COPD相关性PH病情严重程度无创评估的有效工具.

Objectives:To systematically evaluate effectiveness and safety of early warning and prevention of hospital-acquired venous thromboembolism (HAT) .Methods:Computers were used to search PubMed, Embase, Web of Science, CINAHL, Cochrane Central Register of Controlled Trials, China Biology Medicine disc, CNKI and Wanfang Database. RCTs of early warning and prevention HAT at home and abroad was searched systematically and the retrieval time was from the establishment of databases to June 1, 2020. Two researchers independently screened the literature according to the literature inclusion and exclusion criteria, extracted data and evaluated the risk of bias in the study. RevMan 5.3 software was used to conduct Meta-analysis of the incidences of HAT, pulmonary thromboembolism (PTE) , deep vein thrombosis (DVT) , bleeding and prevention rate of HAT.Results:A total of 8 articles were included. Results of Meta-analysis showed that the incidence of PTE in the early-warning group ( RR=0.69, 95% CI 0.53-0.91, P=0.009) and the prevention rate of HAT ( RR=1.45, 95% CI 1.14-1.84, P < 0.001) were statistically significantly different from those in the non-warning group. However, the incidences of HAT ( RR=0.89, 95% CI 0.68-1.16, P=0.380) , DVT ( RR=0.99, 95% CI 0.76-1.29, P=0.970) and bleeding ( RR=0.95, 95% CI 0.81-1.11, P=0.500) had no statistically significant difference between the two groups. HAT prevention was defined as a subgroup of appropriate prevention. There was no statistically significant difference in the HAT prevention rate of patients between the two groups ( RR=1.01, 95% CI 0.95-1.07, P=0.810) . In the subgroup that did not describe in detail whether prevention was appropriate, the HAT prevention rate in the early-warning group was higher than that in the non-early warning group, and the difference was statistically significant ( RR=2.28, 95% CI 2.09-2.49, P<0.001) . Conclusions:Early warning can reduce the incidence of PTE by increasing the prevention rate of HAT without increasing the incidence of bleeding, but it has no significant effect on the incidences of HAT and DVT. Limited by the quantity and quality of the included studies, the above conclusions need to be verified by more high-quality studies.

目的:探讨降钙素原(PCT),白介素17(IL-17)与C反应蛋白(CRP)在慢性阻塞性肺疾病急性加重期(AECOPD)合并肺动脉高压患者外周血中的表达水平,探究联合检测的诊断价值.方法:收集2015年8月至2017年2月我院收治的AECOPD患者120例,纳入研究患者根据是否合并肺动脉高压分为分为单纯AECOPD组60例及AECOPD合并肺动脉高压(AECOPD+PH)组60例,另选取20例健康志愿者作为对照组.采用化学发光法检测PCT水平,双抗夹心酶联免疫吸附试验法(ELISA)检测IL-17水平及生化分析仪检测CRP水平,采用受试者工作特征曲线(ROC)评估PCT,IL-17与CRP对AECOPD合并肺动脉高压的诊断价值.结果:AECOPD+PH组及AECOPD组的PCT,IL-17,CRP水平较健康对照组均明显升高,而AECOPD+PH组的各指标水平也均高于单纯AECOPD组,差异均有统计学意义(P＜0.05).通过Pearson相关性分析发现,AECOPD合并肺动脉高压的PCT与IL-17之间存在表达正相关性(r=0.733,P＜0.05),PCT与CRP表达存在正相关性(r=0.817,P＜0.05).此外,针对AECOPD合并肺动脉高压的诊断中PCT的ROC曲线下面积为0.83,IL-17为0.71,CRP为0.77,联合三者的ROC曲线下面积为0.94.结论:PCT、IL-17和CRP可能与AECOPD患者肺动脉高压的形成有关,各指标存在一定的相关性,联合以上三项生物学指标对诊断AECOPD合并肺动脉高压患者具有一定的临床参考价值.

目的:探讨CT引导下经皮肺穿刺活检对机化性肺炎患者的诊断价值,并总结机化性肺炎的临床诊治经验.方法:回顾性分析2015年7月-2017年9月在南京医科大学附属常州第二人民医院住院行CT引导下经皮肺穿刺活检取得肺部病灶组织确诊为机化性肺炎的14例患者,所有患者行CT引导下经皮肺穿刺活检,总结机化性肺炎患者的临床诊治经验.结果:14例机化性肺炎患者平均年龄为59岁,平均起病时间为21天.主要临床症状以发热、咳嗽、咳痰为主.6例肺部听诊可闻及湿啰音.影像学检查主要表现为肺部斑片状不均匀密度增高影.所有患者初次就诊时均未首先诊断考虑机化性肺炎.所有患者入院后均行CT引导下经皮肺穿刺活检术,术后病理均确诊为机化性肺炎,术中3例出现少量气胸,4例出现少量出血,予吸氧止血等对症处理后好转.14例患者予糖皮质激素治疗后,主要临床症状改善,影像学检查均较前吸收好转.结论:对于持续性干咳、呼吸困难、发热病人,抗生素疗效差,影像学显示片状或块状影病灶,特别是游走性斑片阴影,需要高度警惕机化性肺炎.CT引导下经皮肺穿刺活检可作为明确机化性肺炎诊断的首选方法.机化性肺炎对糖皮质激素治疗敏感,可出现可逆性的好转,一旦确诊,建议及早使用糖皮质激素治疗.

Objective To investigate the clinical characteristics of spontaneous pneumothorax secondary to systemic lupus erythematosus (SLE).Methods A case of spontaneous pneumothorax secondary to SLE was reported and related literatures were reviewed.Results A female patient,26 years old,complaining of repeated fever for 3 months,chest tightness and shortness of breath more than 10 days,was hospitalized in December 2016.After admission,the patient was diagnosed as acute lupus pneumonia and received glucocorticoid,cyclophosphamide and plasma exchange therapy.Sudden right chest pain happened during hospitalization.Bedside chest CT showed right pneumothorax.After closed thoracic drainage,the syndrome of the patient was improved.A total of 14 patients were reviewd but 2 patients were excluded because of incomplete data.The left patients included 9 females and 3 males.The mean age was (28.0± 11.9)years.Clinical manifestations of spontaneous pneumothorax secondary to SLE were sudden chest tightness and shortness of breath accompanied by subpleural lung cavity and vesicular changes.The majority of patients could be cured with drainage.Conclusions Pneumothorax secondary to SLE is rare which is associated with the rupture of cavity and cyst in pulmonary secondary to SLE.Majority of patients with pneumothorax could be cured after closed thoracic drainage.

Objective:To investigate the therapeutics effect and the potential mechanism of paeoniflorin on the bleomycin-induced pulmonary fibrosis in mice.Methods:Sixty adult male SPF C57BL/6 mice were randomly divided into four groups:the control group (Sham operation,SH),the control+paeoniflorin group (SH+PA),the bleomycin group (BLM) and the bleomycin+paeoniflorin group (BLM+PA).From the day of operation,the mice of the SH+PA and BLM+PA groups were treated with paeoniflorin intragastrically (50 mg/kg,daily) while the mice of the SH and BLM groups were given the same volume of normal saline.The model of pulmonary fibrosis was established through intratracheally instillation with bleomycin (2 mg/kg) except for the control group,in which normal saline was used.All the samples were sacrificed on the day 14 after operation,and the change of body weight and mortality rates of each group were analyzed.The pathological section of lung tissues were harvested for hemotoxylin and eosin stain.Collagen deposition in the lung was determined by measuring the total hydroxyproline content.ELISA was pertbrmed to analyze the level of IL-18 and IL-1β in the lung homogenates.The levels of NLRP3 and TGF-β1 in the lung were detected by Western blotting.Results:Paeoniflorin significantly increased the survival rate and attenuated the collagen deposition in the bleomycin-induced pulmonary fibrosis mouse model compared with the control group (P＜0.05).The IL-18 and IL-1β in the lung homogenates were decreased notably after administration of paeoniflorin,when compared to the control group (P＜0.05).The expression of NLRP3 and TGF-β1 were down regulated significantly (P＜0.05).Conclusion:Paeoniflorin may attenuate bleomycin-induced pulmonary fibrosis in mice by suppressing NLRP3 inflammsome formation.

目的 波生坦及其联合用药治疗肺动脉高压(PAH )患者的临床观察.方法 PA H患者23例 ,给予波生坦62. 5 mg ,每日2次 ,治疗4周后改为125 mg ,每日2次.随访期间根据病情 ,必要时联合磷酸二酯酶-5抑制剂、前列环素类、内皮素受体拮抗剂药物.监测肝功能、氨基端脑利钠肽原(NT-proBNP)变化 ,评估WHO 心功能分级 ,测量6 min步行距离(6MWD) ,二维超声心动图测量肺动脉收缩压变化.结果 波生坦治疗时间为(21 ± 4 )个月 ,波生坦单药治疗至需要联合或更换药物治疗时间为(17 ± 4)个月.波生坦及其联合用药能有效改善PAH病情 ,总体生存率达95.7% .治疗后患者的WHO心功能分级、6 MWD和肺动脉收缩压(P<0 .01或P<0 .05);NT-proBNP呈下降趋势 ,但差异无统计学意义(P>0 .05).结论 波生坦及其联合用药可以长期用于PAH治疗 ,能够改善心功能 ,提高患者的运动能力 ,降低肺动脉压力 ,治疗PA H安全有效.

Objective To investigate the role of the percentage of the total cross-sectional area of small pulmonary vessels for the lung area (%CSA) from multi-slice CT (MSCT) in evaluating the severity of chronic obstructive pulmonary disease (COPD). Methods One hundred and sixty-six COPD patients and 166 normal subjects underwent chest MSCT scans and all data were analyzed retrospectively. COPD patients underwent pulmonary function tests (PFT), including forced expiratory volume in one second (FEV1%) and FEV1/forced vital capacity (FEV1/FVC), and were classified into mild (n=32), moderate (n=65), severe (n=69) groups according to pulmonary function results, respectively. The%CSA less than 5 mm2 and 5—10 mm2 for the lung area (%CSA<5 and %CSA5-10) of small pulmonary vessels were measured with Image J image-processing program. Comparison of%CSA<5 and%CSA5-10 between the COPD and control groups was perfomred using t test, and the comparison between the 3 COPD subgroups and control group were carried out using ANOVA test. The correlation between %CSA and PFT was evaluated by the Spearman rank correlation test. The sensitivity and specificity of %CSA to diagnose COPD and the best cutoff were calculated from areas under the ROC curves. Results %CSA<5 of COPD patients and control group were (0.56 ± 0.19)%and (0.82 ± 0.15)%(t=12.80, P<0.001), respectively.%CSA5-10 of the two groups were (0.19 ± 0.09)%and (0.33 ± 0.16)%(t=8.93,P<0.001), respectively. The AUC values of%CSA<5 and%CSA5-10 were 0.866 and 0.790, respectively. When the cut-off values of%CSA<5 and%CSA5-10 were 0.65%and 0.24%, the sensitivities and specificities were 88%and 71%, 76%and 81%, respectively. The mean values of%CSA<5 in mild, moderate and severe groups were (0.67±0.20)%, (0.61±0.16)%and (0.44±0.14)%, respectively (P<0.05). The mean values of %CSA5-10 in the three groups were (0.19 ± 0.06)%, (0.19 ± 0.10)% and (0.20 ± 0.08)%, respectively.%CSA5-10 in the three groups were of no significant difference (P>0.05). FEV1%and FEV1/FVC in COPD patients were (60.38±15.52)%and 57.95±22.27.%CSA<5 in COPD patients correlated positively with both FEV1%and FEV1/FVC (r=0.609 and 0.721, P<0.01, respectively).%CSA5-10 in COPD patients correlated positively with both FEV1%and FEV1/FVC (r=0.271 and 0.288, P<0.01, respectively). Conclusion The measurement of%CSA<5 and%CSA5-10 in MSCT images correlated with PFTs and%CSA<5, which may play an important role in evaluating the severity of COPD.

Interferon gamma induced GTPase (IGTP) (also named Irgm3) and interferon gamma inducible protein 47 (IRG-47) (also named Irgd) are interferon (IFN)-inducible p47 GTPases that have been shown to regulate host resistance to intracellular pathogens. Little knowledge has been known about the role of p47 GTPases in host responses against extracellular pathogens. To investigate possible roles of IGTP and IRG-47 in the course of Schistosoma japonicum infection, IGTP and IRG-47 knockout and wild-type (WT) mice were challenged with cercariae of S. japonicum, and host responses were analyzed. At the acute stage of S. japonicum infection, mice that lacked IGTP displayed similar parasite burden and pathological damage to WT mice. Importantly, S. japonicum-infected IRG-47-deficient mice, in contrast to IGTP-deficient mice and WT mice, showed significantly reduced worms and lower egg-burden, but intense granulomatous reaction evoked by schistosome eggs in peripheral parts of liver lobes. In addition, upregulation of inflammation-related gene expression was observed in the spleen of IRG-47-deficient mice using oligonucleotide microarrays, in which multiple pathways of cytokine–cytokine receptor interaction, T-cell receptor signaling, complement, coagulation cascades and cell adhesion molecules were highlighted. Taken together, these data suggest that IGTP and IRG-47 might have distinct features that were differentially required for resistance to S. japonicum.

Objective To investigate the effects of p47 GTPase deficiency on the maturation and function of macrophages in the IGTP and IRG-47 deficient mice model infected with Schistosoma japonicum. Methods Measured the mRNA levels of igtp, irg47 and lrg47 with IGTP and IRG-47 deficient macrophages by real-time quantitative PCR, the expression of surface molecule markers on IGTP and IRG-47 deficient macrophages in different infection stages by FACS, and the inflammatory response by the measurement of NO in the culture supernatant of macrophages stimulated with or without LPS. Results Macrophage mRNA expression levels of igtp, irg47 and lrg47 were quickly up-regulated after 3 weeks of infection, while after 6 weeks of infection they displayed differentiation such that the expression of igtp and lrg47 was significantly up-regulated in IRG-47-/-mice. There was no significance in the expression of MHC class Ⅱ (I-A), CD16/32, CD40 and CD80 on the surface of IGTP and IRG-47 deficient macrophages at 6 weeks after infection. Groups produced equivalent levels of NO after stimulation by LPS. Conclusion IGTP or IRG-47 deficiency does not influence macrophage maturation and the potential for secreting NO, suggesting that p47 GTPase may function in a unique NO-independent manner.

Objective To observe the therapeutic effect of artesunate on Schisitosoma japonicum infected mice,the dynamic changes of schistosome-specific IgG antibodies in sera,explore the relationship between sera antibody and the killing effect on schistosomulae in vitro.Methods S.japonicum infected C57/BL6 mice were orally administered with artesunate at 300 mg/kg on 8th,15th,22nd,29th day respectively after infection.Meanwhile,control group mice were treated with 1% sodium carboxymethycellulose.All the mice were sacrificed 7 days after the last administration,and the numbers of worms and eggs were counted.The S.japonicum-specific IgG antibody levels in sera were detected by indirect ELISA.To observe the cooperative killing effect,schistosomulae were cultured with sera of mice administered with artesunate and macrophages in vitro.Results No worm and egg was found in artesunate-treated mice.The anti-SCA-specific IgG antibody peaked at 21 days post-infection,then declined,and the anti-SWAP-specific IgG antibody showed a rising trend in experimental group,there was no significant difference on these two compared with control group.The anti-SEA-specific IgG antibody in artesunate-treated mice remained at a low level,much less than that in control group.The sera from artesunate-treated mice and control mice all had preferable schitosomulae killing effect in vitro.Conclusion The therapeutic efficacy of artesunate on S.japonicum infection was prominent.The sera and macrophages had cooperative killing effect on schistosomulae in vitro.

Objective To explore the best condition isolating the peripheral blood mononuclear cells(PBMC)from pig's blood in order to provide an effective method for parasite immunology.MethodsPBMCs from pig's blood were isolated with pig's lymphocyte separation medium(LSM)at different rotation speeds for different periods,the thickness of cloudlike PBMC layer was observed and the yield of obtained PBMC and their activity were caculated.Simultaneously,PBMCs from pig's blood were isolated with human LSM under the conditions reported by previous papers(1500 r/min,30 min)and the isolating efficiency was compared with that of pig's LSM.ResultsThe best result was got with pig's LSM(density:1.110 ng/L)by first centrifuging the samples at 1500 r/min(radius:15 cm)for 30 minutes at room temperature(20-25 ℃),followed by washing the cell pellets twice with D-Hank's medium at 1500 r/min for 10 minutes at 4 ℃.PBMC that were isolated with human LSM from pig's blood under the same condition were impure and mixed with other cells such as red cells and other cell debris,and both the yield of obtained PBMC and their activity were low.ConclusionThis study offered a method to get a large quantity of active PBMC.