抗白细胞介素靶向治疗支气管哮喘临床应用研究进展

支气管哮喘的经典病理、生理学研究认为,引起哮喘的主要病理学改变主要是由于支气管的平滑肌发生痉挛及肥大。世界卫生组织（WHO）在关于哮喘病的免疫脱敏治疗中明确指导并指出：免疫脱敏治疗是根治过敏性疾病的唯一治疗方法。本文研究分析利用细胞因子中白细胞介素（IL-1、IL-2、IL-4、IL-5、IL-13、IL-33等）作为靶点进行靶向治疗支气管哮喘的临床应用及其进展。     

哮喘患者单核细胞功能学变化与糖皮质激素受体的表达

目的探讨细胞因子及其相互作用对哮喘患者单核细胞(PBMCs)功能的影响,及其与糖皮质激素治疗作用的关系.方法分离受试者PBMCs培养24、48 h,给予TNF-α、IL-2、DXM、IFN-α等因素干预,用免疫细胞化学和放免分析检测细胞中糖皮质激素受体(hGR)亚单位和培养液中IL-6表达.结果哮喘组PBMCs在基础水平和单一细胞因子刺激时均较正常组生成更多IL-6;随细胞因子刺激时间延长,哮喘组生成IL-6增多;IFN-α对TNF-α介导的炎性反应有体外拮抗作用;IL-6水平与细胞的hGRα表达负相关;在该实验条件下,未发现hGRβ表达.结论多种细胞因子以其复杂的交互作用参与哮喘发病过程;糖皮质激素受体亚单位表达的不同直接参与和影响哮喘治疗效果.     

重症哮喘患者血清MIP-1α和IL-13水平动态变化及其预后评估价值

目的：分析重症哮喘患者血清巨噬细胞炎症蛋白1α（MIP-1α）和白细胞介素13（IL-13）水平的动态变化,评估其判断患者短期预后的临床价值。方法：102例哮喘患者按病情严重程度分为重症哮喘组（42例重症哮喘患者）和轻症哮喘组（60例轻中度哮喘患者）,选择同时期健康体检者50人作为对照组。随访1年后根据是否发生未控制哮喘发作将重症哮喘组分为控制亚组与再发亚组。在治疗前与治疗后第1、3、7天分别测定3组研究对象血清IL-13、MIP-1α、白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）水平,记录3组研究对象用力肺活量（FVC）、第1秒用力呼气容积（FEV1）、FEV1/FVC、最大呼气中段流量（MMEF）和呼气峰流速（PEF）等肺功能指标,采用Pearson相关分析评估治疗第7天重症哮喘患者血清IL-13、MIP-1α与FEV1、MMEF及PEF的相关性,比较重症哮喘组中控制亚组与再发亚组患者治疗第7天时血清IL-13及MIP-1α水平,应用多元Logistic回归分析上述各临床指标与患者随访1年再发率的相关性,绘制受试者工作特征（ROC）曲线评估患者血清IL-13和MIP-1α水平对重症哮喘患者再发作的判断价值。结果：随治疗时间延长,重症哮喘组和轻症哮喘组患者血清IL-6、IL-13、TNF-α和MIP-1α水平逐渐降低（P<0.05）,而FEV1、FEV1/FVC、MMEF和PEF逐渐增加（P<0.05）;同一时间点重症哮喘组患者血清IL-6、IL-13、TNF-α和MIP-1α水平高于轻症哮喘组（P<0.05）和对照组（P<0.05）,而重症哮喘组患者FEV1、FEV1/FVC、MMEF和PEF低于轻症哮喘组（P<0.05）和对照组（P<0.05）。Pearson相关分析,重症哮喘患者血清IL-13及MIP-1α与FEV1、MMEF及PEF呈负相关关系（P<0.05）。随访1年,重症哮喘组控制亚组患者血清IL-13及MIP-1α水平低于再发亚组（P<0.01）。多元Logistic回归分析,治疗前后重症哮喘患者血清IL-13及MIP-1α水平差值为再发作危险性因素（OR=2.867,P=0.023; OR=2.135,P=0.033）。结论：重症哮喘患者治疗过程中血清IL-13和MIP-1α水平降低程度能较好评估患者的肺功能及随访1年后再发作情况。     

血清MIP-1α、IL-13、IL-6、TNF-α水平变化与重症哮喘患者肺功能的相关性及其临床意义

目的 分析血清巨噬细胞炎症蛋白1α(MIP-1α)、白细胞介素-13(IL-13)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平变化与重症哮喘患者肺功能的相关性。方法 选取兰考第一医院2019年6月至2021年5月收治的101例重症哮喘患者，另选取同期95例健康体检者作为研究对象。采用酶联免疫检测法检测血清MIP-1α、IL-13、IL-6、TNF-α水平；采用肺功能检测仪检测呼气峰流速(PEF)、最大呼气中段流量(MMEF)、第1秒用力呼气容积(FEV₁)。比较治疗前及治疗后1、3、7 d重症哮喘患者血清MIP-1α、IL-13、IL-6、TNF-α水平与PEF、MMEF、FEV₁水平，并分析其相关性。结果 治疗后1、3、7 d,重症哮喘患者血清MIP-1α、IL-13、IL-6、TNF-α水平低于治疗前，且呈下降趋势(P<0.05);治疗前及治疗后1、3、7 d,重症哮喘患者血清MIP-1α、IL-13、IL-6、TNF-α水平高于健康体检者(P<0.05);治疗后1、3、7 d,重症哮喘患者PEF、MMEF...     

孟鲁斯特对哮喘患者诱导痰中炎症细胞及细胞因子的影响

目的 观察孟鲁斯特对哮喘患者诱导痰中炎症细胞及细胞因子的影响.方法 73例哮喘患者被随机分配到对照组和试验组,其中:对照组(n=37),使用吸入糖皮质激素,长效β2受体激动剂等常规治疗.试验组(n=36),常规治疗加每日口服孟鲁斯特10mg;观察治疗前后,患者诱导痰中的细胞分类情况,以及IL-2,TNF-α的变化情况.结果 治疗后试验组和对照组诱导痰中的细胞总数及中性.嗜酸性粒细胞分类比例,IL-2及TNF-α浓度均较治疗前明显降低(P<0.05),其中试验组嗜酸性粒细胞分类比例、IL-2、TNF-α浓度的降低较对照组更加显著(P<0.05).结论 口服孟鲁斯特可降低哮喘患者诱导痰中的嗜酸性粒细胞分类比例、IL-2、TNF-α浓度.     

Th17和IL-17在中性粒细胞性哮喘发生发展中作用的研究进展Progress research in effects of Th17 and IL-17 in occurrence and development of neutrophilic asthma

中性粒细胞性哮喘对于哮喘常规治疗方案反应不佳,已成为临床关注的焦点。辅助性T淋巴细胞17（Th17）主要通过分泌白细胞介素17（IL-17）来发挥其生物学作用,可诱导气道中性粒细胞性炎症、杯状细胞增生、黏液高分泌、肌纤维母细胞分化和气道平滑肌增生肥大,在该疾病的病理生理过程中扮演着重要角色。现总结分析Th17/IL-17在中性粒细胞性哮喘气道炎症、激素抵抗和气道重塑中的作用机制,以进一步认识Th17/IL-17在中性粒细胞性哮喘发生发展过程中所发挥的重要作用,并阐述以其为靶点治疗中性粒细胞性哮喘的可行性及最新进展,以便系统深入地探讨国内外相关研究的现状和不足,为中性粒细胞性哮喘的进一步研究提供新的方向,为其治疗提供新的思路和策略。     

白细胞介素4受体和哮喘

Th1/Th2亚群的失衡可能是哮喘发病的主要机制。本文主要对在哮喘发病过程中起主要作用的Th2型细胞因子IL-4及其受体的生物学作用及其与哮喘的关系作一综述。对IL-4及其受体的研究，不仅使我们深入了解过敏性疾病。自身免疫性疾病和感染性疾病的发病机制，而且为治疗这类疾病提供了一个新的思路。     

儿童哮喘与TNF-α及sTNFR的研究进展

肿瘤坏死因子α（TNF-α）是一种多功能的促炎因子,参与多种慢性炎症反应性疾病的发病,近年来研究显示,TNF-α参与哮喘发病的整个病理生理过程,与哮喘有着密切的关系,TNF-α通过膜受体（TNFR）来实现对靶细胞的多种效应,而可溶性肿瘤坏死因子受体（sTNFR）则通过与TNFR竞争性地结合TNF-α来抑制TNF-α对靶细胞的作用,研究TNF-α及其相关受体与哮喘的关系,有助于探索哮喘的发病机制,判断其预后,并为哮喘的靶向治疗提供新的思路。     

诱导痰中炎性细胞及细胞因子在哮喘患者发病中的作用

目的:探讨白细胞介素13(IL-13)、肿瘤坏死因子α(TNF-α)在哮喘中的发病机制以及诊疗意义。方法:采用酶联免疫吸附法(ELASE)测定33例哮喘患者诱导痰的上清液及血清中IL-13、TNF-α,同时用肺功能仪测定FEV1%pre及计数痰涂片中嗜酸粒细胞,与20例健康对照者的结果进行比较,同时分析IL-13、TNF-α与痰炎症细胞及FEV1%pre的关系。结果:1哮喘组痰LogIL-13的浓度2.09±0.25pg/ml、嗜酸粒细胞/白细胞%(EOS/Leu%)15.8±5.7%、痰TNF-α浓度58.38±13.28pg/ml高于对照组的LogIL-13的浓度1.71±0.19pg/ml、EOS/Leu%1.6±0.4%和TNF-α浓度15.20±4.99pg/ml,有显著性差异;2哮喘组痰IL-13浓度与痰内EOS/Leu%呈正相关(r=0.823,P=0.000),与FEV1%pre呈负相关(r=-0.752,P=0.000)。结论:哮喘发作时IL-13、TNF-α浓度及嗜酸粒细胞明显增高,提示IL-13可能通过对嗜酸粒细胞的调节从而参与哮喘的发病过程,同时IL-13参与哮喘呼吸道炎症及其呼吸道高反应性的发生机制。     

中性粒细胞在哮喘中的地位和作用

支气管哮喘是由多种细胞包括气道的炎性细胞和结构细胞及细胞组分参与的气道慢性炎症性疾病,其特征为气道炎症、气道高反应性、可逆性气道阻塞和气道重塑。以往哮喘被认为主要由2型炎症因子驱动,Th2细胞分泌IL-4、IL-5和IL-13,引起气道嗜酸性粒细胞炎症。随着研究的深入,发现中性粒细胞与哮喘炎症过程也存在密切关系。哮喘患者气道中的中性粒细胞在趋化增加的同时凋亡下降,从而导致中性粒细胞数量增多。中性粒细胞比嗜酸性粒细胞更早到达,通过产生弹性蛋白酶、髓过氧化物酶、中性粒细胞胞外诱捕网、趋化因子和细胞因子等,参与哮喘的发生及发展过程。针对这些效应分子的拮抗剂如抗IL-8受体抗体、抗IL-17抗体,DNA酶显示出对中性粒细胞哮喘的治疗作用,但应用于临床还需要更多的实验数据支持。本文主要就中性粒细胞在哮喘中的地位和作用作一综述。     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

Development on Adjustable Calibration Marker for Shock Wave Focus

Shock wave lithotripsy （SWL） is a treatment of choice for upper urinary stones. However, this procedure is inappropriate for obese patients because the focus is often unable to reach the target owing to the limited focal distance in shock wave source. Although treating such patients in a blast path may increase the application length of shock wave source, it＇s difficult to find this path on the lithotripter monitor. For this reason, we invented an adjustable calibration marker in order to set an effective focus in the shock wave hath.     

Study on the TCM Pathogenesis of Angiopathic Complications of Type II Diabetes

Excess production of reactive oxygen species(ROS)of mitochondrion mediated by hyperglycemia is the common pathogenesis of angiopathic complications of diabetes.TCM holds that the damp from the dysfunction of spleen.kidney and liver is the causative factor of complications of diabetes.This is similar to the mechanism of Ros resulting in angiopathic complications of diabetes.When the angiopathic complications of type II diabetes mellitus(T2DM)are difierentiated as caused by turbid damp in TCM can be explained as ROS.Since the obstruction of pathogenic damp in channels and collaterals is said to be the main pathogenesis,the treating principle should be dissolving the damp to remove the obstruction.     

Leptin, Ghrelin and TNF-α before and after Hypo-caloric Traditional Chinese Diet and Auricular Acupuncture

INTRODUCTION Obesity is a complex emergent problem, which can be possibly solved not only by the diet but also by the life style and promotion of a constant physical exercise. 1, 2 No doubt careful attentions must be given to the nutritional condition of obese people, the dietary habits, the somatic build (i.e. distribution of fat mass) and the organic functions linked to formation of the fat mass. All the parameters should be constantly monitored before, during and after a diet treatment. 3, 4, 5     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

Relationship between Dysglycemia and Carotid Atherosclerosis in Tibetan Population

People with dysglycemia are at high risk for atherosclerotic diseases. This study aims at investigating the atherosclerotic vascular damage in dysglycemia and its metabolic origin in Tibetan population.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.     

Luo Lingjie's Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.