吡非尼酮联合乙酰半胱氨酸治疗IPF患者的疗效及机制分析

目的:探讨吡非尼酮联合乙酰半胱氨酸治疗特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)患者的疗效及可能机制。方法:选择2018年1月至2020年1月我院收治的78例IPF患者,根据随机数字表法将其分为观察组(38例)及对照组(40例)。对照组患者给予吡非尼酮,观察组给予吡非尼酮联合乙酰半胱氨酸,对比两组患者的治疗效果、治疗前及治疗后1 d的肺功能指标、血清肺纤维化指标、肿瘤坏死因子、转移生长因子β-1水平的变化及不良反应的发生情况。结果:治疗后,与对照组相比,观察组治疗有效率明显升高(P<0.05)。治疗后,两组弥散量、用力肺活量、第一秒用力呼气容积均较治疗前明显升高,且观察组以上指标均明显高于对照组高(P<0.05)。治疗后,两组的透明质酸、层粘蛋白、Ⅲ型胶原、Ⅲ型前胶原、尿素氮、血清肿瘤坏死因子、转移生长因子β-1及基质金属蛋白酶-9水平均较治疗前明显降低,观察组以上指标均明显低于对照组低(P<0.05)。观察组不良反应发生率为26.32%,对照组为30.00%,组间对比差异无统计学意义(P>0.05)。结论:与单独应用吡非尼酮相比,吡非尼酮联合乙酰半胱氨酸可提高IPF患者的治疗效果,可能与其可改善患者的炎症因子水平有关。     

过敏性紫癜患者银杏达莫注射液治疗前后血管内皮功能、凝血功能的变化及相关性研究

摘要 目的：探讨过敏性紫癜（HSP）患者银杏达莫注射液治疗前后血管内皮功能、凝血功能的变化,并分析HSP患者血管内皮功能与凝血功能的相关性。方法：选择2018年2月至2020年2月期间我院收治的HSP患者93例,按照随机数字表法将患者分为对照组（n=46）和观察组（n=47）,其中对照组给予糖皮质激素治疗,观察组给予银杏达莫注射液治疗,对比两组疗效、血管内皮功能、凝血功能的变化及紫癜性肾炎的发生率,并分析HSP患者血管内皮功能与凝血功能的相关性。结果：观察组治疗2周后的总有效率95.74%（45/47）,较对照组的76.09%（35/46）升高（P<0.05）。两组患者治疗2周后血清血管内皮生长因子（VEGF）、内皮素-1（ET-1）水平均降低,且观察组低于对照组（P<0.05）。两组患者治疗2周后纤维蛋白原（FIB）、D-二聚体（D-D）、血小板计数（PLT）均降低,且观察组低于对照组（P<0.05）,凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）均升高,且观察组高于对照组（P<0.05）。两组紫癜性肾炎发生率对比无统计学差异（P>0.05）。观察组患者中VEGF、ET-1均与FIB、D-D、PLT呈正相关,而与PT、APPT、TT呈负相关（P<0.05）。结论：HSP的发病过程中存在血管内皮细胞损伤及血液高凝状态,采用银杏达莫注射液治疗HSP患者,疗效显著,可有效改善患者血管内皮功能、凝血功能,且血管内皮功能与凝血功能存在一定的相关性。     

过敏性紫癜并肺炎支原体感染患儿免疫球蛋白和补体的研究

【摘 要】 目的 检测过敏性紫癜（HSP）合并肺炎支原体(MP) 感染的患儿血清免疫球蛋白及补体的水平,探讨MP感染与HSP的体液免疫学关系。方法 研究对象为55例HSP患儿,检测MP-IgM抗体,分为MP-IgM阳性组20例、MP-IgM阴性组35例,并以20名正常儿童作为对照组。采用全自动生化分析仪检测血清免疫球蛋白IgA、IgM、IgG、IgE及补体C3、C4。结果 HSP患儿MP感染阳性率达36.36%,合并MP感染的患儿临床症状更严重。与正常对照组相比,MP-IgM阴性组IgA、IgE明显增高（P<0.01）,C3水平降低（P<0.05）,同时IgE明显高于MP-IgM阳性组（P<0.01）,IgG、IgM、C4无明显变化。MP-IgM阳性组与正常对照组相比,IgA增高,IgM、C3、C4水平降低,且其中IgM、C3低于MP-IgM阴性组,差异均有统计学意义（P<0.05）,而IgG、IgE水平无明显改变。结论 在HSP儿童中有较高MP感染率,所有HSP患儿存在血清IgA增高及C3水平降低,说明体液免疫参与HSP的发病。伴MP感染的HSP患儿体液免疫功能更加紊乱,表现在C4水平下降,IgM、C3明显低于MP-IgM阴性组,IgE增高仅见于MP-IgM阴性组,提示MP感染的HSP患儿可能更多伴有低补体血症的自身免疫紊乱参与,说明MP感染引起的免疫紊乱可能在HSP发生、发展中具有重要作用。     

重组人生长激素治疗特发性矮小患儿的疗效及生长速率预测模型的建立

摘要 目的：探讨重组人生长激素（rhGH）对特发性矮小（ISS）患儿的治疗效果,并建立rhGH治疗后生长速率（GV）的预测模型。方法：回顾性分析确诊为 ISS并应用rhGH治疗1年的130例患儿的疗效,以治疗12个月后的GV为因变量,采用多元逐步回归方法建立ISS患儿疗效的预测模型。结果：rhGH治疗6个月、12个月的身高、身高标准差分值（HtSDS）均逐渐升高（P<0.05）,治疗12个月的身高增长（△Ht）、GV 低于治疗 6个月（P<0.05）。治疗6个月、治疗12个月的GV 均与初始治疗时的生活年龄（CA）、骨龄（BA）、身高、体重及垂体高度呈负相关（P<0.05）。将治疗12个月GV 作为因变量,治疗前初始身高（X1）、治疗6个月GV（X2）被纳入方程建立预测模型：Y=7.631-0.035X1+0.567X2,R²=0.791,并通过内外部验证。结论：rhGH治疗对ISS患儿的身高增长具有良好效果,前6个月的效果更好。rhGH治疗后ISS患儿的GV与治疗前CA、BA、身高、体重及垂体高度呈负相关。治疗前的身高、治疗6个月的GV能够较好地预测治疗12个月的GV。     

Alveolar epithelial cells undergo epithelial-to-mesenchymal transition in response to endoplasmic reticulum stress

Expression of mutant surfactant protein C (SFTPC) results in endoplasmic reticulum (ER) stress in type II alveolar epithelial cells (AECs). AECs have been implicated as a source of lung fibroblasts via epithelial-to-mesenchymal transition (EMT); therefore, we investigated whether ER stress contributes to EMT as a possible mechanism for fibrotic remodeling. ER stress was induced by tunicamyin administration or stable expression of mutant (L188Q) SFTPC in type II AEC lines. Both tunicamycin treatment and mutant SFTPC expression induced ER stress and the unfolded protein response. With tunicamycin or mutant SFTPC expression, phase contrast imaging revealed a change to a fibroblast-like appearance. During ER stress, expression of epithelial markers E-cadherin and Zonula occludens-1 decreased while expression of mesenchymal markers S100A4 and α-smooth muscle actin increased. Following induction of ER stress, we found activation of a number of pathways, including MAPK, Smad, β-catenin, and Src kinase. Using specific inhibitors, the combination of a Smad2/3 inhibitor (SB431542) and a Src kinase inhibitor (PP2) blocked EMT with maintenance of epithelial appearance and epithelial marker expression. Similar results were noted with siRNA targeting Smad2 and Src kinase. Together, these studies reveal that induction of ER stress leads to EMT in lung epithelial cells, suggesting possible cross-talk between Smad and Src kinase pathways. Dissecting pathways involved in ER stress-induced EMT may lead to new treatment strategies to limit fibrosis.     

Crystal structure of the Marasmius oreades mushroom lectin in complex with a xenotransplantation epitope

MOA, a lectin from the mushroom Marasmius oreades, is one of the few reagents that specifically agglutinate blood group B erythrocytes. Further, it is the only lectin known to have exclusive specificity for Galalpha(1,3)Gal-containing sugar epitopes, which are antigens that pose a severe barrier to animal-to-human organ transplantation. We describe here the structure of MOA at 2.4 A resolution, in complex with the linear trisaccharide Galalpha(1,3)Galbeta(1,4)GlcNAc. The structure is dimeric, with two distinct domains per protomer: the N-terminal lectin module adopts a ricinB/beta-trefoil fold and contains three putative carbohydrate-binding sites, while the C-terminal domain serves as a dimerization interface. This latter domain, which has an unknown function, reveals a novel fold with intriguing conservation of an active site cleft. A number of indications suggest that MOA may have an enzymatic function in addition to the sugar-binding properties.     

儿童过敏性紫癜发病的危险因素研究

为了探讨儿童过敏性紫癜发病的危险因素,本研究选取了2015年7月至2017年6月在本院治疗的过敏性紫癜患儿118例作为观察组研究对象,同时选取健康正常儿童120例作为对照组,调查分析两组微生物感染、食物过敏、药物过敏史等资料,同时观察治疗疗效。研究显示,观察组的幽门螺杆菌(Hp)、肺炎支原体、链球菌感染率和螨虫阳性率分别为61.02%、16.10%、10.17%和13.56%,明显高于对照组(p<0.05);观察组对牛奶、鸡蛋、虾过敏的比例分别为9.32%、11.02%和8.47%,明显高于对照组(p<0.05);观察组有药物过敏史、家中饲养猫、狗等动物、家中近3个月装修的比例为22.88%、45.76%和17.80%,明显高于对照组(p<0.05);Logistic回归分析显示,Hp感染是发生过敏性紫癜的危险因素(OR=1.613, p<0.05);Hp感染和无Hp感染患者治疗疗效差异比较无统计学意义(p>0.05)。本研究表明,Hp感染可能是儿童过敏性紫癜发生的影响因素,但Hp感染对治疗疗效无明显影响。     

Increased constitutive αSMA and Smad2/3 expression in idiopathic pulmonary fibrosis myofibroblasts is KCa3.1-dependent

Background

Idiopathic pulmonary fibrosis is a common and invariably fatal disease with limited therapeutic options. Ca²⁺-activated K_Ca3.1 potassium channels play a key role in promoting TGFβ1 and bFGF-dependent profibrotic responses in human lung myofibroblasts (HLMFs). We hypothesised that K_Ca3.1 channel-dependent cell processes regulate HLMF αSMA expression via Smad2/3 signalling pathways.

Methods

In this study we have compared the phenotype of HLMFs derived from non-fibrotic healthy control lungs (NFC) with cells derived from IPF lungs. HLMFs grown in vitro were examined for αSMA expression by immunofluorescence (IF), RT-PCR and flow cytommetry. Basal Smad2/3 signalling was examined by RT-PCR, western blot and immunofluorescence. Two specific and distinct K_Ca3.1 blockers (TRAM-34 200 nM and ICA-17043 [Senicapoc] 100 nM) were used to determine their effects on HLMF differentiation and the Smad2/3 signalling pathways.

Results

IPF-derived HLMFs demonstrated increased constitutive expression of both α-smooth muscle actin (αSMA) and actin stress fibres, indicative of greater myofibroblast differentiation. This was associated with increased constitutive Smad2/3 mRNA and protein expression, and increased Smad2/3 nuclear localisation. The increased Smad2/3 nuclear localisation was inhibited by removing extracellular Ca²⁺ or blocking K_Ca3.1 ion channels with selective K_Ca3.1 blockers (TRAM-34, ICA-17043). This was accompanied by de-differentiation of IPF-derived HLMFs towards a quiescent fibroblast phenotype as demonstrated by reduced αSMA expression and reduced actin stress fibre formation.

Conclusions

Taken together, these data suggest that Ca²⁺- and K_Ca3.1-dependent processes facilitate “constitutive” Smad2/3 signalling in IPF-derived fibroblasts, and thus promote fibroblast to myofibroblast differentiation. Importantly, inhibiting K_Ca3.1 channels reverses this process. Targeting K_Ca3.1 may therefore provide a novel and effective approach for the treatment of IPF and there is the potential for the rapid translation of K_Ca3.1-directed therapy to the clinic.     

星状神经节阻滞联合针刺治疗特发性面神经麻痹临床观察

目的:观察星状神经节阻滞联合针刺治疗对特发性面神经麻痹的临床疗效。方法:将62例特发性面神经麻痹患者分为两组,对照组30例采用药物治疗+针灸理疗等常规治疗,治疗组32例采用常规治疗+星状神经节阻滞(SGB)疗法,疗程30天。采用House-Brackmann面神经功能分级评定及临床疗效指标判定。结果:治疗前两组H-B面神经功能分级具有可比性。治疗后,两组H-B评分比较差异有统计学意义(P<0.05);临床疗效指标比较显示两组总有效率分别为:治疗组96.9%,对照组80.00%,治疗组优于对照组,两组差异有统计学意义(P<0.05)。结论:星状神经节阻滞联合针刺治疗对急性特发性面神经麻痹有效。     

特发性腹膜后纤维化误诊为输尿管癌1 例报告并文献复习

目的:分析并掌握腹膜后纤维化的诊疗特点,避免对该病的误诊误治。方法:回顾性分析1例腹膜后纤维化患者分别因两侧肾积水先后两次住院并最终确诊的诊疗过程中的临床资料,包括临床表现、影像特点、病理结果、治疗方法及预后等,并结合相关文献进行复习。结果:患者因右肾积水首次入院诊断为右输尿管癌而行右侧肾输尿管切除术,后患者因左肾积水来我院住院诊断为腹膜后纤维化,行腹腔镜输尿管松解+腹腔内置术,术后长期随访疗效满意。结论:腹膜后纤维化作为一种少见病,缺乏对其认识极易导致误诊误治,掌握该疾病的临床特点及选择适宜的治疗方案,对本病的诊疗具有重要意义。