迪利单抗对肺癌患者嗜酸性气道炎症的研究

目的 探讨信迪利单抗对肺癌患者嗜酸性气道炎症的影响。方法 选取2019年4月—2020年4月于徐州医科大学附属宿迁医院就诊的60例IV期非鳞非小细胞肺癌患者,随机分为对照组(单纯化疗组)和试验组(信迪利单抗联合化疗组);对照组给予培美曲塞500 mg/m2联合顺铂75 mg/m2静脉注射;试验组在对照组治疗方案基础上联合免疫检查点抑制剂信迪利单抗200 mg静脉注射,均21天为1个周期。6个周期治疗后检测两组患者呼出气一氧化氮(Fractional exhaled nitric oxide,FeNO)、外周血嗜酸性粒细胞计数、肺功能及动脉血气;分析信迪利单抗治疗组严重不良事件(SAE)及免疫相关性肺炎(CIP)的发生率。结果 ⑴试验组在第2、4、6周期治疗后FeNO水平、外周血嗜酸性粒细胞计数相较于基线水平出现升高趋势,但差异无统计学意义(PFeNO=0.536; PEos=0.762)。⑵两组患者经6个周期治疗后,第1秒用力呼吸容积(FEV1)、用力肺活量(FVC)、FEV1/FVC、一氧化碳弥散量占预计值百分比(DLco%)较治疗前均无明显变化(PFEV1=0.615; PFVC=0.473; PFEV1/FVC=0.637; PDLco%=0.598);动脉血气分析中PH、PaO2、PaCO2水平较治疗前均无明显变化(PPH=0.457; PPaCO2=0.242; PPaO2=0.631)。⑶试验组免疫相关SAE发生率和CIP的发生率均为0。结论 6周期治疗后信迪利单抗对肺癌患者的嗜酸性气道炎症、肺功能、动脉血气分析无明显影响,未出现免疫相关SAE及CIP。     

人体呼吸道的二级及三级支气管内吸气流动的数值研究

呼吸系统的主要生理机能是在大气和血液之间交换氧气和二氧化碳，其生理过程与呼吸道内的气体流动和输送有密切关系。本文利用数值模拟方法对呼吸道内二级及三级支气管模型内的吸气过程进行数值研究，研究表明：二级支气管的计算结果与现有的实验值吻合很好；在三级支气管内。当人体处于正常吸气流量下，支气管内未发生任何分离现象。但流道几何形状的弯曲和分岔使支气管内出现强烈的二次流现象，主流速度出现倾斜分布及m-型分布特征。从而加大了分岔管内侧壁面及前后侧壁面上的切应力；在三级支气管的末级管内，流量分流不均匀。在计算条件下，中部支气管内的流量与侧部支气管内的流量之比为1．2。     

Bronchoconstriction of the asthmatic airway by inhaled and ingested propranolol

Summary Responsiveness to inhaled histamine and DL propranolol hydrochloride was measured in 31 adult asthmatics and compared with bronchoconstriction provoked by acute oral propranolol dosing (max 160 mg).Twelve asthmatics developed 15% reduction in the forced expired volume in 1 s (FEV₁), 2 h after 100 mg oral propranolol; cardiac -adrenoceptor blockade was confirmed by cycle exercise tests in the 19 without airway response. The provocative inhaled dose of each aerosol causing a 20% fall in FEV₁ (PC₂₀) was lower, histamine 0.43 mg·ml^–1, propranolol 3.12 mg·ml^–1, in the 12 with a positive oral test compared with the 19 with a negative test, PC₂₀ histamine 1.65 mg·ml^–1, PC₂₀ propranolol 16.2 mg·ml^–1 (P < 0.001 for both aerosols). A correlation was demonstrated between the PC₂₀ values for asthmatics with a negative oral test (r=0.72, P < 0.001, n=19) but not for the remainder (r=0.14, P > 0.05, n=12).Plasma propranolol concentrations (CL, ng·ml^–1) after the final oral dose did not correlate with the % FEV₁(26.3) (r=-0.28) when an airway response was provoked or with the reduction in exercise tachycardia (25.9%) (r=0.31) when no bronchoconstriction occurred. CL exceeded the limit of detection after the final inhaled propranolol dose (7.5 ng·ml^–1) and was weakly related to the PC₂₀ propranolol value (r=0.53, P=0.01, n=27). The prevalence of a positive oral challenge was low in this group (39%). APC₂₀ propranolol value which was 100% sensitive as a predictor of a positive oral test had low specificity (58%) and a low predictive value (60%).This study has not found that nonspecific bronchial responsiveness to histamine or specific responsiveness to inhaled propranolol can be employed to predict bronchoconstriction in asthmatics following acute oral propranolol dosing.     

Intratracheal administration of recombinant adenovirus containing IL-18 gene in treatment of experimental metastatic lung carcinoma

Objective: To study the treatment of experimental metastatic lung carcinoma by intratracheal injection of IL-18 gene recombinant adenovirus. Methods: (1)The mouse IL-18 mRNA was detected by RT-PCR, and the concentration of 1L-18 and associated cytokines in lung lavages and blood were determined by ELISA at different time points after intratracheal injection of IL-18 recombinant adenovirus. (2)The lung metastasis nodes, mouse survival periods and survival rates were evaluated. NK activity and CTL activity were determined by 51Cr 4 h release method. Results: (1)IL-18 mRNA was detectable in lung tissue 6 h after intratracheal use of IL-18 recombinant adenovirus, and the concentration of IL-18 in lung lavage was higher than that in peripheral blood. Neither IL-18 mRNA nor IL-18 was detectable in control group. (2) Intmtmcheal use of IL-18 recombinant adenovirus resulted in increased CTL and NK activity, longer survival time and higher survival rates compared with the control group, showing significant therapeutic effect on experimental lung metastasis. Conclusion: Intratracheal use of adenovirus vector containing IL-18 gene has therapeutic effect on the lung metastasis, denoting that gene therapy of lung diseases could be applied through airway directly with recombinant adenovirus.     

原癌基因表达在哮喘气道重塑中的作用

目的观察原癌基因表达在哮喘气道重逆中的作用。方法卵蛋白致敏豚鼠 建立哮喘模型。Dot-blot,North-ern-blot分子杂交及免疫组织化学技术观察豚鼠气道上皮,肺组织中原癌基因c-fos,c-myc,c-jun和c-sis的表达及其与气道重塑的关系。结果：正常豚鼠气道及肺组织中c-fos和c-myc mRNA无或很少表达,哮喘发作后,豚鼠气道上皮及肺组织c-fos和c-mycmRNA的表达明显增加;免疫组织化学染色显示Fos,Myc,Jun及Sis在政党豚鼠低水平表达,4种原癌基因产物表达增,国,阳性反应细胞主要分布于气道上皮细胞胞质、气道及细支气的上皮细胞胞核及浸润的炎症细胞中,病理结果显示气道粘膜及小鼠气管平滑肌周围淋巴细胞、嗜酸性粒细胞及中性粒细胞浸润,气道平滑肌显著增生,结论原部达在气道重逆过程中有重要作用。     

白细胞介素-4对哮喘患者血清IgE的影响

目的：探讨白细胞介素－４（ＩＬ－４）在过敏性支气管哮喘发病机制中对ＩｇＥ的作用。方法：试验采用双盲、交叉、随机、安慰剂对照的设计方法,给予８例过敏性哮患者吸入２０μｇ人重组ＩＬ－４或载体溶液,并分别于吸入前、吸入后２,２４,４８ｈ测定患者血清ＩｇＥ水平。结果：吸入载体溶液与吸入ＩＬ－４前的血清总ＩｇＥ基础值无显著差异（ｐ〉０．０５）,吸入后各时点血清总ＩｇＥ亦无明显变化（ｐ〉０．０５）。结论：吸入     

诱导型一氧化氮合酶在哮喘大鼠肺组织的表达

目的　观察哮喘大鼠肺组织中诱导型一氧化氮合酶 (i NOS)活性的表达 ,探讨一氧化氮在哮喘大鼠气道炎症中的作用。方法　用卵白蛋白作为致敏原制备哮喘大鼠模型 ,用 SP免疫组化染色方法检测肺组织 i NOS的表达并观察 i NOS在气道组织分布的改变。结果　哮喘大鼠肺组织 i NOS的表达阳性率 (90 % )明显高于正常对照组 (2 0 % ) (P<0 .0 0 1)。哮喘大鼠气道组织 i NOS表达阳性细胞主要位于气道上皮细胞、气道平滑肌细胞、血管内皮和平滑肌细胞、浸润的中性粒细胞和巨噬细胞 ,而淋巴细胞表达不明显。用甲基强的松龙处理后哮喘大鼠肺组织i NOS表达阳性率 (30 % )明显降低。结论　以上结果提示一氧化氮在哮喘气道炎症中起重要作用 ,用甲基强的松龙治疗哮喘可以使哮喘大鼠肺组织中 i NOS表达阳性率降低 ,提示哮喘时产生过多的一氧化氮可能有加重气道炎症的作用     

Associated anomalies in Pierre Robin sequence

Pierre Robin sequence (PRS) is frequently co-occurring with other non-PRS congenital anomalies. The types and the prevalence of anomalies co-occurring with PRS vary in the reported studies. The aims of this report was to study the types and the prevalence of the anomalies co-occurring with PRS in a well-studied population northeastern France. The types and the prevalence of anomalies co-occurring in cases with PRS were ascertained in all terminations of pregnancy, stillbirths and live births in 387,067 births occurring consecutively during the period 1979–2007 in the area covered by our registry of congenital anomalies which is population-based, 89 cases of PRS were registered during the study period with a prevalence of 2.29 per 10,000 births, 69.7% of the cases had associated non-PRS anomalies. Chromosomal abnormalities were present in 10 (11.2%) cases including three 22 q11.2 deletion. Non-chromosomal recognizable conditions were diagnosed in 27 cases (30.3%) including 10 Stickler syndrome, 8 Treacher Collins syndrome, 3 cases with short stature and 6 other syndromes. Multiple congenital anomalies (MCA) were present in 25 cases (28.1%). The most frequent MCA were in the ear, face and neck (35 out of 98 anomalies, 35.7%), cardiovascular (18 anomalies, 18.4%), musculoskeletal (11 anomalies, 11.2%), central nervous (7 anomalies, 7.1%), urinary (6 anomalies, 6.1%), and eye (6 anomalies, 6.1%) system. The high prevalence of associated anomalies justifies a thorough screening for other congenital anomalies in cases with PRS.     

Role of Ca2+-activated K+ channel in epithelium-dependent relaxation of human bronchial smooth muscle

1. To elucidate whether K⁺ channels play a role in the action of epithelium-dependent bronchodilatation, we studied responses in human bronchial strips in the presence of indomethacin and N^G-nitro-L-arginine methylester under isometric conditions, in vitro.
2. Mechanical removal of the epithelium increased the contractile responses to acetylcholine; the pD₂ values increased from 5.0±0.2 to 5.9±0.3 (P<0.001). This potentiation was abolished by iberiotoxin but not by apamin or glibenclamide.
3. In cascade bioassay, application of the bathing medium from dispersed, bronchial epithelial cells to epithelium-denuded bronchial strips decreased acetylcholine-induced contraction by 44±6%. This effect was reduced to 10±3% (P<0.01) when the epithelial cells were pretreated with iberiotoxin, and to 4±1% (P<0.001) when the epithelial cells were incubated with Ca²⁺-free medium containing [1,2-bis (2) aminophenoxy] ethane N,N,N′,N′-tetraacetic acid-acetomethoxy ester.
4. In contrast, the bronchodilator effect of the medium bathing epithelial cells was not altered by the direct addition of iberiotoxin to epithelium-denuded tissues.
5. These results suggest that the Ca²⁺-activated K⁺ channel may play a role in the synthesis and/or release of smooth muscle relaxing factor, which is neither nitric oxide nor a cyclo-oxygenase product, from airway epithelial cells.