小剂量阿奇霉素联合吸入布地奈德和N-乙酰半胱氨酸治疗特发性肺纤维化的临床疗效分析

目的:观察小剂量阿奇霉素联合吸入布地奈德和N-乙酰半胱氨酸对特发性肺纤维化(IPF)患者肺功能及支气管肺泡灌洗液炎症因子表达的影响。方法:随机将56例确诊为IPF的住院患者分为对照组和治疗组,对照组给予常规治疗,吸氧,戒烟,吸入布地奈德及乙酰半胱氨酸;治疗组在常规治疗基础上加服小剂量阿奇霉素片。动态观察两组患者治疗3、6个月的疗效及肺功能的改善情况;完成2个疗程(6个月)治疗后,检测和比较两组支气管肺泡灌洗液相关炎症因子水平的变化。结果:治疗3个月时,两组患者的动脉血氧分压(PO2)、肺活量(VC)、1秒钟用力呼气容积占预计值百分比(FEV1%pred)、最大通气量占预计值百分比(MVV%pred)、单位肺泡容积的一氧化碳弥散量占预计值百分比(DLCO/VA%pred)均较治疗前显著增加(P0.05);治疗6个月时,治疗组的有效率(20/26,76.9%)明显高于对照组(14/30,46.7%),且PO2、VC、FEV1%pred、MVV%pred及DLCO/VA%pred等肺功能指标均显著高于对照组(P0.05);对照组支气管肺泡灌洗液TNF-α、IL-8浓度均较治疗前降低(P0.05),IL-4、IL-10、IFN-γ浓度较治疗前无明显变化;而治疗组支气管肺泡灌洗液TNF-α、IL-8、IL-4、IL-10浓度均较治疗前降低,IFN-γ浓度较治疗前明显增加(P0.05)。结论:阿奇霉素联合吸入布地奈德和N-乙酰半胱氨酸可能通过改变支气管肺泡灌洗液IFN-γ等炎症因子浓度有效改善IPF患者的肺功能。     

布地奈德福莫特罗治疗支气管哮喘患者的临床疗效及对患者血清炎性因子水平的影响

目的:探讨布地奈德福莫特罗吸入治疗对慢性支气管哮喘患者的临床疗效及其对患者血清炎性因子水平、肺功能和生活质量的影响。方法:选择2014年2月至2016年2月于我院呼吸内科就诊并确诊为慢性支气管哮喘患者123例,根据随机数字表法分为观察组65例和对照组58例。比较两组患者治疗前后血清白介素17(IL-17)、白介素33(IL-33)、基质金属蛋白酶9(MMP-9)、肺功能、生活质量评分的变化、临床疗效有效率及不良反应的发生情况。结果:观察组的总有效率为92.3%(60/65),显著高于对照组(81.03%,P0.05)。治疗后,两组患者的血清IL-17、IL-33水平与治疗前相比均显著降低(P0.05),且观察组显著低于对照组(P0.05);两组血清MMP-9水平与治疗前相比差异均无统计学意义(P0.05);观察组患者的第一秒用力呼吸容积(FEV1)、峰值呼气流速(PEF)与第一秒用力呼气容积与用力肺活量比值(FEV1/FVC)水平均明显增加,且观察组上述指标明显高于对照组(P0.05);圣.乔治呼吸问卷(SGRQ)评分结果显示观察组患者的生活质量显著高于对照组患者。结论:布地奈德福莫特罗吸入治疗对慢性支气管哮喘临床效果显著,可显著控制炎症反应,改善肺功能,显著提升患者生活质量。     

大容量全肺灌洗术对尘肺患者肺功能、血气指标及炎症因子的影响

目的:探讨大容量全肺灌洗术(WLL)对尘肺患者肺功能、血气指标及炎症因子的影响。方法:选取2016年10月到2019年10月在我院接受治疗的尘肺患者48例作为本次研究对象,根据随机数字表法将患者分为WLL组和常规组各24例,给予常规组患者汉防己甲素、乙酰半胱氨酸泡腾片等常规药物治疗,在常规组的基础上给予WLL组患者联用双侧同期WLL治疗。分别于治疗前3天和治疗后2周检测并对比两组患者白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平、血氧分压(PaO_2)、动脉血二氧化碳分压(PaCO_2)、肺泡动脉氧分压差(PA-aO_2)、用力肺活量(FVC)、一秒用力呼气容积与用力肺活量的比值(FEV1/FVC%)及最大通气量与预计值的比值(MVV%)。结果:两组治疗前肺功能指标、血气指标、炎症因子水平比较差异均无统计学意义(P0.05),两组治疗后PA-aO_2较治疗前水平明显降低,FVC、FEV_1/FVC%、MVV%、PaO_2、PaCO_2均较治疗前显著上升,IL-6、TNF-α水平与治疗前比较均明显降低(P0.05);治疗后两组PA-aO_2比较差异无统计学意义(P0.05),治疗后WLL组的FVC、FEV_1/FVC%、MVV%、PaO_2、PaCO_2均高于常规组,IL-6、TNF-α水平均低于常规组,差异均有统计学意义(P0.05)。结论:WLL可明显改善尘肺患者肺功能和血气指标,降低患者血清内IL-6、TNF-α的水平,减轻炎症反应,临床疗效确切,值得临床推广应用。     

重症支气管哮喘患者肺泡灌洗液病原菌分布及血清CRP和TNF-α水平

目的研究重症支气管哮喘患者肺泡灌洗液中病原菌分布及血清C反应蛋白(CRP)、肿瘤坏死因子(TNF-α)水平,为该病的治疗提供参考。方法选取2017年5月至2019年5月我院收治的支气管哮喘患者为研究对象,按照病情严重程度分为重度组(n=85)和轻度组(n=80)。收集两组患者肺泡灌洗液并进行细菌培养,同时抽取两组患者静脉血检测血清CRP、TNF-α水平。采用Spearman相关系数分析法分析血清CRP、TNF-α水平与哮喘程度的关系。结果重度组患者肺泡灌洗液中检出革兰阳性菌23株,占36.51%;革兰阴性菌38株,占60.32%;真菌2株,占3.17%。革兰阳性菌中肺炎链球菌占47.83%,金黄色葡萄球菌占30.43%;革兰阴性菌中大肠埃希菌占23.68%,流感嗜血杆菌占26.32%。重度组患者肺泡灌洗液中革兰阴性菌比例及血清CRP与TNF-α水平均显著高于轻度组(均P<0.05)。支气管哮喘严重程度与血清CRP和TNF-α水平均呈正相关(均P<0.05)。结论重度支气管哮喘患者肺泡灌洗液中革兰阴性菌占比较高,同时其血清CRP、TNF-α水平也较高。CRP、TNF-α水平与哮喘严重程度成正比。     

鼻窦功能性手术治疗慢性鼻窦炎合并支气管哮喘的远期疗效评估

目的:评价鼻窦功能性手术(FESS)治疗慢性鼻窦炎合并支气管哮喘的远期疗效。方法:选择自2011年1月至2013年1月我院收治的慢性鼻窦炎患者65例,行FESS治疗。根据是否合并患有支气管哮喘将患者分为观察组(慢性鼻窦炎合并支气管哮喘)和对照组(慢性鼻窦炎),选择同期健康志愿者作为正常组。采用酶联免疫吸附测定测定白细胞介素4(IL-4)、干扰素-γ(IFN-γ)水平、可溶性白细胞介素2受体(sIL-2R)和可溶性Ig E低亲和力受体(sCD23)的水平,并术后随访2年观察对比慢性鼻窦炎和支气管哮喘改善情况。结果:对照组和观察组患者手术后的IL-4、sIL-2R及sCD23水平降低,IFN-γ水平升高,且与手术前的差异均有统计学意义(P0.05);两组患者术后2年的慢性鼻窦炎治愈率均高于术后1年;观察组患者术后1年和术后2年的哮喘完全控制率明显高于术前,且差异具有统计学意义(P0.05),且术后2年哮喘完全控制率显著高于术后1年之间(P0.05);观察组患者术后1年、2年哮喘平均发作率显著低于术前,且术后2年的哮喘平均发作率明显低于术后1年(P0.05)。结论:FESS用于治疗慢性鼻窦炎合并支气管哮喘具有良好的临床疗效,能够显著改善患者的IL-4、IFN-γ、sIL-2R及sCD23水平,且随着时间的延长,其远期疗效较满意。     

细菌溶解产物联合沙美特罗替卡松在支气管哮喘患儿中的应用效果

目的探讨细菌溶解产物胶囊联合沙美特罗替卡松粉吸入剂对支气管哮喘患儿血清CD4~+/CD8~+水平的影响。方法选取我院2016年2月至2017年12月收治的84例支气管哮喘患儿为研究对象,采用随机数字表将患者分为对照组(n=42)和研究组(n=42)。对照组患儿在常规治疗基础上采取沙美特罗替卡松粉吸入剂进行治疗,研究组患者采用沙美特罗替卡松气雾剂+细菌溶解产物胶囊(泛福舒)进行治疗,两组患者均治疗3个月。记录两组患者临床疗效,治疗前及治疗后血清学指标[干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)]水平,肺功能[呼气流速峰值(PEF)、第一秒用力呼气量(FEV_1)]和免疫功能(NK细胞、CD4~+/CD8~+)水平。结果研究组患者治疗总有效率(95.24%)高于对照组(78.57%)。两组患者治疗后IL-4水平低于治疗前,IFN-γ水平高于治疗前,且研究组变化情况优于对照组(均P0.05)。两组患者治疗结束后FEV_1、PEF较治疗前增高,且研究组高于对照组(均P0.05)。治疗后两组患者NK细胞、CD4~+/CD8~+水平较治疗前增高,且研究组高于对照组(均P0.05)。结论沙美特罗替卡松粉吸入剂联合细菌溶解产物胶囊可有效改善支气管哮喘患儿肺功能,降低其血清IFN-γ、IL-4水平,调节机体免疫功能,提高治疗效果。     

Nrf2/Bach1调控γ-谷氨酰半胱氨酸合成酶在支气管哮喘患者痰中炎症细胞内的表达

目的:探讨红系衍生核因子相关因子-2(Nrf2)/BTB-CNC异体同源体1(Bach1)调控γ-谷氨酰半胱氨酸合成酶(γ-GCS)在支气管哮喘患者痰中炎症细胞内的表达。方法:健康对照组、哮喘患者治疗前、治疗后均行肺功能检测。检测三组血浆丙二醛浓度;检测各组痰中炎症细胞内Nrf2、Bach1、γ-GCS蛋白质和mRNA的表达。结果:哮喘患者治疗前血浆丙二醛浓度高于健康对照组和治疗后组(P均0.01);哮喘患者治疗前痰中炎症细胞内γ-GCSmRNA、蛋白表达及Nrf2蛋白质细胞核内表达治疗后高于治疗前(P均0.05);痰中炎症细胞内γ-GCSmRNA表达与Nrf2核内表达呈正相关(P均0.01),与Bach1核内表达呈负相关(P均0.01)。结论:γ-GCS的表达由细胞核内Nrf2和Bach1蛋白水平调控;抗炎治疗增加哮喘患者抗氧化能力可能与调控Nrf2/Bach1核转位而增加γ-GCS表达有关。     

支气管扩张合并支气管哮喘患者支气管肺泡灌洗液病原菌培养及药敏状况研究

目的:对支气管扩张合并支气管哮喘患者支气管肺泡灌洗液病原菌培养及药敏状况展开分析,实现多药耐药医院感染的有效预防与控制。方法:随机选取2010年9月~2013年8月期间收治的50例支气管扩张症合并支气管哮喘患者,对50例患者支气管肺泡灌洗液标本进行病原学检测及药敏试验,并对临床感染资料及病原菌耐药性进行统计学分析。结果:50例支气管扩张症合并支气管哮喘患者支气管肺泡灌洗液培养阳性率为30例,60.0%,共分离出48株细菌。其中,革兰阳性球菌5株,占分离菌的10.4%;革兰阴性杆菌41株,占分离菌的85.4%;真菌2株,占分离菌的4.2%。41株革兰阴性杆菌对抗菌药物的耐药性分别为:复方新诺明73.1%,阿米卡星22.0%,环丙沙星14.6%,头孢曲松48.8%,头孢噻肟41.5%,头孢哌酮19.5%,头孢他啶20.7%,头孢他啶/舒巴坦12.1%,头孢吡肟22.0%,庆大霉素17.1%,阿莫西林/克拉维酸41.5%,哌拉西林/他唑巴坦19.5%。结论:铜绿假单胞菌是支气管扩张合并哮喘患者感染中的常见病原菌,医务人员要结合病原菌高耐药率、高分离阳性率的特征,合理运用抗菌药物控制传播。     

肺力咳合剂辅助布地奈德和复方异丙托溴铵对支气管哮喘患儿肺功能、炎症介质和免疫功能的影响

摘要 目的：探讨肺力咳合剂辅助布地奈德和复方异丙托溴铵对支气管哮喘患儿肺功能、炎症介质和免疫功能的影响。方法：选择2021年2月~2022年3月期间我院小儿内科接收的76例支气管哮喘患儿。根据信封抽签法将患儿分为对照组（n=38,布地奈德和复方异丙托溴铵治疗）和研究组（n=38,肺力咳合剂辅助布地奈德和复方异丙托溴铵治疗）。对比两组患儿疗效、肺功能、炎症介质和免疫功能,同时记录两组治疗期间的用药安全性状况。结果：研究组的临床总有效率较对照组明显升高（P<0.05）。治疗2周后,研究组第1秒用力呼气容积（FEV₁）、用力呼气流量（PEF）、用力肺活量（FVC）高于对照组同期（P<0.05）。治疗2周后,研究组白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）低于对照组,干扰素-γ（IFN-γ）高于对照组（P<0.05）。治疗2周后,研究组CD8⁺低于对照组,CD3⁺、CD4⁺、CD4⁺/CD8⁺较对照组高（P<0.05）。不良反应发生率组间对比无差异（P>0.05）。结论：肺力咳合剂辅助布地奈德和复方异丙托溴铵治疗支气管哮喘患儿,可有效改善患儿的肺功能和免疫功能,降低炎症介质水平,疗效可靠。     

支气管哮喘患者血清趋化因子CXCL12水平的表达及其与炎症因子和肺功能的相关性研究

目的:探讨支气管哮喘患者血清趋化因子CXCL12水平与炎症因子和肺功能的关系。方法:选择2017年10月至2019年10月我院收治的支气管哮喘患者共106例,其中急性发作期67例(急性发作组)、慢性持续期39例(慢性持续组),另选择50例体检的健康志愿者为对照组,均进行血清CXCL12检测,分析CXCL12与炎症因子、肺功能、嗜酸性粒细胞(EOS)、免疫球蛋白E(IgE)、呼出气一氧化氮(FeNo)的相关性。结果:急性发作期组血清CXCL12、白介素-4(IL-4)、白介素-17A(IL-17A)、白介素-13(IL-13)、EOS、Ig E、FeNO水平高于慢性持续期组和对照组(P0.05),慢性持续期组血清CXCL12、IL-4、IL-17A、IL-13、EOS、Ig E、FeNO水平高于对照组(P0.05);急性发作期组第1秒用力呼气容积(FEV_1)、第1秒用力呼气容积与用力肺活量比值(FEV_1/FVC)、第1秒用力呼气容积占预计值百分数(FEV_1%pred)低于慢性持续期组和对照组(P0.05),慢性持续期组FEV_1、FEV_1/FVC、FEV_1%pred低于对照组(P0.05)。多元线性回归分析结果显示血清CXCL12与支气管哮喘患者FEV_1、FEV_1/FVC呈负相关(P0.05),与EOS、Ig E、IL-4、IL-17A、IL-13呈正相关(P0.05)。结论:CXCL12在支气管哮喘进程中可能发挥促炎作用,血清CXCL12水平可反映患者病情严重程度和肺通气功能。     

Anthropology and genetics of the caucasus peoples and the problem of the origin of the caucasoids

The electrophoretical polymorphisms of some blood proteins were studied in the Talysh population of Pirasora situated in South-East Azerbaidjan. We calculated the gene frequencies of these polymorphisms and determined the genetic distances between the Talyshes and some Iranian populations of North, Central and South Iran, Afghans, and three populations of Azerbaijan. The Talyshes are very close to Iranians of Shiraz, whereas they are distant from the Azerbaijanians. Anthropological investigations showed that the Caucasoids and Mongoloids lived in the Aragvi Basin since the Eneolithic period. This was stated by Alexeev (1974), who emphasized the mixture of the Caucasus populations from ancient times on. We calculated the genetic distances between the Caucasus populations and numerous populations of other geographic regions, considering 28 alleles of 12 loci of blood group, serum protein and red cell enzyme polymorphisms and constructed the dendrogram of these populations. The position of the Caucasus populations in the dendrogram corresponds on principle to the earlier anthropological observations. The clustering of the Caucasoid populations corresponds completely with anthropological and historical data, and supports our earlier hypothesis (Nazarova 1999) concerning the differentiation of Caucasoids, Northern Mongoloids and Amerinds from the populations, which inhabitated Asia in palaeolithic times.     

人类基因组及后基因组研究进展及其应用与开发研究现状

人类对自身基因组的研究,随着人类基因组工作草图的绘制完成和对基因功能研究的深入已加快进入了实质性、关键性的开发利用阶段。本文概述了人类基因组及后基因组的研究进展及依此开展基因治疗及基因（组）药物研制等应用开发研究的现状。     

Serology and systematics of the Ebenales and the Theales

The systematic position ofthe Ebenaceae, Sapotaceae, Styracaceae, Ochnaceae, Stachyuraceae, Dipterocarpaceae, Clusiaceae and Hypericaceae has been investigated using serological comparisons of sets of antigenic determinants. The results show that the Sytracaceae and Sapotaceae are undoubtedly more closely associated with the Actinidiaeceae and Theaceae, respectively, than with each other. We found no corresponding determinants betnween antigen systems from the Ebenaceae and systems from any other family whose relations to this family have been proposed. As discovered previously, investigations of antigen systems from the Ochnaceae, Dipterocarpaceae, Stachyuraceae, Clusiaceae and Hypericaceae are against the idea of a natural order “Theales” in which these families, or at least some of them, are combined with the Theaceae and Actinidiaceae. This paper completes our previous investigations which largely support a superorder Ericanae sensu Ehrendorfer and Takhtajan. We propose to include the Actinidiaceae and Theaceae in this superorder, assigning them a central position laong with the Sapotaceae and Sytracaeae on one side and the Primulales and Ericales on the other. Another most interesting finding is that there are corresponding determinants between antigen systems from the members of the Ericanae and representatives of the Polemoniaceae and Loasaceae.     

Kinematics and dynamics of the temporomandibular joint and of the movements of the mandible

In order to analyze the complicated movements of the mandible as the open-closing movement and the protrusio are, it is useful to evaluate the basic kinematic principles and reduce them to simple technical constructions. Both the open-closing movement and the protrusio could be reduced to 4-bar links, which were used to simulate the movements with help of a computer. Besides, the polodes and the curves of points in the muscular attachments could be constructed. The 2 entirely different 4-bar links have 3 things in common: The resting system - cranium, the moving system - mandibula, and 1 of the 2 arms connecting these 2 systems - the ligamentum laterale. As this ligament is taut during movements it can be considered a "guiding ligament" representing 1 of the 3 determining components of the mandibular movements. The other of the 2 arms has no anatomical equivalent; this arm, however, is "replaced" by the 2 other determining components of the mandibular movements: the joint and the muscles. The curves, which the Caput mandibulae describes, are practically identical for the open-closing movement and the protrusio despite of the different 4-bar links and these curves exactly correspond to the Discus articularis, taut by the upper part of the M. pterygoideus lateralis. The muscles do not only just move the mandibula, but they are also the component, which can choose between the different mandibular movements. By means of the curves, which points in the muscular attachments describe, the function of the masticatory muscles could be analyzed exactly.     

On the structure and dynamics of the complex of the nucleosome and the linker histone

Several different models of the linker histone (LH)–nucleosome complex have been proposed, but none of them has unambiguously revealed the position and binding sites of the LH on the nucleosome. Using Brownian dynamics-based docking together with normal mode analysis of the nucleosome to account for the flexibility of two flanking 10 bp long linker DNAs (L-DNA), we identified binding modes of the H5-LH globular domain (GH5) to the nucleosome. For a wide range of nucleosomal conformations with the L-DNA ends less than 65 Å apart, one dominant binding mode was identified for GH5 and found to be consistent with fluorescence recovery after photobleaching (FRAP) experiments. GH5 binds asymmetrically with respect to the nucleosomal dyad axis, fitting between the nucleosomal DNA and one of the L-DNAs. For greater distances between L-DNA ends, docking of GH5 to the L-DNA that is more restrained and less open becomes favored. These results suggest a selection mechanism by which GH5 preferentially binds one of the L-DNAs and thereby affects DNA dynamics and accessibility and contributes to formation of a particular chromatin fiber structure. The two binding modes identified would, respectively, favor a tight zigzag chromatin structure or a loose solenoid chromatin fiber.     

Biophysics and Structure of the Patch and the Gigaseal

Interpreting channel behavior in patches requires an understanding of patch structure and dynamics, especially in studies of mechanosensitive channels. High resolution optical studies show that patch formation occurs via blebbing that disrupts normal membrane structure and redistributes in situ components including ion channels. There is a 1-2 μm region of the seal below the patch where proteins are excluded and this may consist of extracted lipids that form the gigaseal. Patch domes often have complex geometries with inhomogeneous stresses due to the membrane-glass adhesion energy (E_a), cytoskeletal forces, and possible lipid subdomains. The resting tension in the patch dome ranges from 1-4 mN/m, a significant fraction of the lytic tension of a bilayer (∼10 mN/m). Thus, all patch experiments are conducted under substantial, and uneven, resting tension that may alter the kinetics of many channels. E_a seems dominated by van der Waals attraction overlaid with a normally repulsive Coulombic force. High ionic strength pipette saline increased E_a and, surprisingly, increased cytoskeletal rigidity in cell-attached patches. Low pH pipette saline also increased E_a and reduced the seal selectivity for cations, presumably by neutralizing the membrane surface charge. The seal is a negatively charged, cation selective, space with a resistance of ∼7 gigohm/μm in 100 mM KCl, and the high resistivity of the space may result from the presence of high viscosity glycoproteins. Patches creep up the pipette over time with voltage independent and voltage dependent components. Voltage-independent creep is expected from the capillary attraction of E_a and the flow of fresh lipids from the cell. Voltage-dependent creep seems to arise from electroosmosis in the seal. Neutralization of negative charges on the seal membrane with low pH decreased the creep rate and reversed the direction of creep at positive pipette potentials.     

Comparison of the Effects of Flexion and Extension of the Thumb and Fingers on the Position and Cross-Sectional Area of the Median Nerve

Objective

To assess the separate effects of thumb and finger extension/flexion on median nerve position and cross-sectional area.

Methods

Ultrasonography was used to assess median nerve transverse position and cross-sectional area within the carpal tunnel at rest and its movement during volitional flexion of the individual digits of the hand. Both wrists of 165 normal subjects (11 men, 4 women, mean age, 28.6, range, 22 to 38) were studied.

Results

Thumb flexion resulted in transverse movement of the median nerve in radial direction (1.2±0.6 mm), whereas flexion of the fingers produced transverse movement in ulnar direction, which was most pronounced during flexion of the index and middle fingers (3.2±0.9 and 3.1±1.0 mm, respectively). Lesser but still statistically significant movements were noted with flexion of the ring finger (2.0±0.8 mm) and little finger (1.2±0.5 mm). Flexion of the thumb or individual fingers did not change median nerve cross-sectional area (8.5±1.1 mm²).

Conclusions

Volitional flexion of the thumb and individual fingers, particularly the index and middle fingers, produced significant transverse movement of the median nerve within the carpal tunnel but did not alter the cross-sectional area of the nerve. The importance of these findings on the understanding of the pathogenesis of the carpal tunnel syndrome and its treatment remains to be investigated.