摘要信息：方案名称：西维来司他钠预防脓毒症患者发生ARDS的作用 研究目的：明确西维来司他钠预防脓毒症患者发生ARDS的作用 研究设计：一项多中心、随机、双盲、安慰剂对照试验 样本量：238例 研究方案： 疗程：7天 给药方案：持续静脉泵入 治疗期： (1)试验组：西维来司他钠0.2mg/kg.h (2)对照组：同等量仅含西维来司他钠辅料的生理盐水 纳入标准： (1)年龄≥18岁并且≤75岁，性别不限； (2)入院24h内满足sepsis 3.0诊断标准； (3)患者或家属对本次试验目的和意义有充分了解，自愿参加本次临床试验，并签署知情同意书。 排除标准： (1)入组时已明确存在ARDS的患者； (2)明确拒绝机械通气的患者； (3)合并3个及以上肺外器官损伤、器官功能衰竭（单个器官SOFA评分≥3分）的患者； (4)家庭氧疗及机械通气（通过气管切开或无创通气，但不包括CPAP/BIPAP仅用于睡眠呼吸暂停的患者）； (5)预计生存期＜48h的患者； (6)孕妇、哺乳期女性； (7)经研究者判定不适合入选的其它情况。 观察指标及评价时间点： 终点指标 主要终点指标：入组后7天内发生ARDS（柏林标准） 次要终点指标：入组第1、3、7天氧合指数或SpO2/FIO2及炎症因子水平、中性粒细胞弹性蛋白酶含量、血小板计数、超敏C反应蛋白，肝肾功能、凝血功能；SOFA评分、APACHE II评分；28天无呼吸机天数、住院时间和病死率；90天生存率。 安全性指标 (1)生命体征：心率、血压（SBP/DBP/MAP）、呼吸频率、SpO2和（同时记录吸入氧浓度）体温； (2)实验室检查：血常规、肝肾功能、凝血功能、肌钙蛋白I、血气分析、血乳酸、超敏C反应蛋白、PCT、炎症因子及中性粒细胞弹性蛋白酶，育龄期女性妊娠试验（血妊娠或尿妊娠） (3)心电图、胸片或胸部CT检查； (4)不良事件。

摘要信息：研究题目：西维来司他钠治疗脓毒症合并轻中度ARDS患者安全性及有效性的一项前瞻性、多中心、双盲、随机对照试验 研究目的： (1)观察西维来司他钠治疗脓毒症相关ARDS的临床安全性和有效性； (2)了解经西维来司他钠治疗后，患者氧合指数、机械通气时间（非机通时间）、肺功能指标、肺部影像学改变情况、炎症指标。 研究设计 本研究为前瞻性、多中心、双盲、随机对照临床研究。在不中止原本治疗方案基础上，对加用西维来司他钠治疗（试验组）或安慰剂治疗（对照组）的脓毒症合并ARDS的患者进行相关观察及指标记录。 样本量 本研究计划按照试验组：对照组= 1:1抽样，计划纳入试验组（注射用西维来司他钠）71例受试者，对照组（安慰剂）71例受试者，共计142例。 入组标准 (1)男女不限，年龄在18-75周岁之间； (2)依据sepsis3.0诊断为脓毒症的患者（附录一）； (3)依据柏林ARDS诊断标准诊断为ARDS的患者（附录二）； (4)能够在入ICU诊断为ARDS患者48小时内给药的患者（附录五）； (5)能够理解和遵守协议要求，自愿参加本研究； 排除标准 (1)参与其他临床研究的患者； (2)诊疗资料缺失严重的患者； (3)妊娠期、哺乳期女性或可能处于妊娠中的女性； (4)经研究者判断，认为不适合本研究组的患者（如原发严重肝肾功能损伤、慢性肺气肿、呼吸衰竭等慢性疾病器官、移植术后、DIC患者、终末期肿瘤患者、患精神疾病的患者等）; (5)氧合指数PaO2/FiO2 < 100 mmHg的患者（PaO2须在机械通气参数PEEP值不小于5 cm H2O的条件下测得，附录二）； (6)诊断为中性粒细胞减少症（中性粒细胞绝对计数 < 2 ⨉109 / L）的患者； (7)接受化疗药及其他免疫调节药物（如重组人粒细胞集落刺激因子、胸腺法新、乌司他丁、血必净等）或接受大剂量激素（>80mg/天）治疗超过5天的患者; (8)医师认为不适宜本实验对象的患者; (9)不能对原发病进行有效治疗的患者; 研究终点 主要终点指标： 接受西维来司他钠或安慰剂治疗后患者第5天的氧合指数（PaO2/FiO2）改善有效率 接受西维来司他钠或安慰剂治疗后患者第3、5、7、14天的氧合指数（PaO2/FiO2） 次要终点指标： 炎症指标：接受西维来司他钠或安慰剂治疗后患者第0、3、5、7天的血中CRP、PCT、IL-6、IL-8、IL-10、TNF-⍺，NE含量及浓度；及支气管肺泡灌洗液中的IL-6、IL-8、IL-10、TNF-⍺，BUN及蛋白含量和NE的含量及浓度 呼吸支持方式：（有创、无创或者高流量湿化氧疗）和时间 肺功能指标：接受西维来司他钠或安慰剂治疗后患者第3、5、7、14天的肺顺应性、呼吸机PEEP值； ARDS总体转归：ICU 28天生存率。

摘要信息：研究目的： 明确西维来司他钠治疗伴有SIRS的轻中度ARDS的有效性及安全性。 研究内容 本研究通过计算机随机，将伴有SIRS的轻中度ARDS患者随机分为安慰剂组和西维来司他钠组, 观察两组患者入组时(D0), 第1(D1)，3(D3)，5(D5)天氧合指数(PaO2/FiO2)，呼吸频率，28天内有创机械通气率、无机械通气时间、住ICU时间、住院时间、ICU获得性感染发生率、28天全因病死率、ICU病死率等，以评价西维来司他钠治疗伴有SIRS的轻中度ARDS患者肺损伤的效果，以期改善轻中度ARDS患者氧合、增加无机械通气时间、降低ARDS病死率。 纳入标准： (1)18岁≤年龄≤75岁成年病人，其种族、国籍、性别不限； (2)研究符合赫尔辛基宣言及中国临床试验研究法规，病人或其家属知情并同意参加试验； (3)入住ICU依据2012柏林标准诊断ARDS 72 h以内，且氧合指数介于150-300mmHg, 并伴有全身炎症反应综合征(SIRS)患者 (ARDS柏林标准和SIRS诊断标准见附录)； 排除标准： (1)慢性呼吸疾病的病史； (2)单纯的心源性肺水肿； (3)APACH2评分≥21分； (4)合并终末期疾病，或者临床主管医生判断近期患者预后不良； (5)ARDS病程>3天； (6)粒细胞缺乏或者接收免疫抑制剂或大剂量激素(甲强龙>40 mg)患者； (7)怀孕或哺乳； (8)曾经参与过本项研究； (9)不同意参加本试验； 主要观察指标： 1) 72 h氧合改善率[(D3氧合指数-D0氧合指数)/D0氧合指数]； 2) 28天无机械通气时间； 次要观察指标: 1) 28天有创机械通气率； 2) 28天住ICU时间； 3) 28天住院时间； 4) 28天全因病死率； 5) ICU病死率； 6)28天获得性感染发生率(定义为：实验室核酸或培养确诊的继发感染)； 7)血浆中NE及炎症因子IL-6、IL-10、CRP水平变化； 8)28天严重不良事件频率； 9) D1和D5氧合改善率；

摘要信息：摘 要 目的:探讨西维来司他钠对老年轻度阻塞性通气功能障碍患者胸腔镜手术后肺部并发症的影响。方法:选取择期行胸腔镜肺癌根治术的老年患者 180例，随机分成西维来司他钠组(S组)和乌司他丁组(U组)，每组90例。S组静脉泵注西维来司他钠，U组静脉泵注乌司他丁。比较两组至出院前的术后肺部并发症(PPCs)发生情况，麻醉诱导前 10 min (T)、切皮时(T,)、术毕即刻(T,)、术后 24h(T;)及72h(T)时的肺泡-动脉血氧分压差(P DO,)肺泡氧合指数(OI)和呼吸指数(RI);术前和术后2d时的第1秒用力呼气容积占预计值的百分比(FEV,%)、用力肺活量占预计值的百分比(FVC%)和FEV,FVC;术后气管导管拔管时间、麻醉后恢复室(PACU)入住时间及术后住院时间。结果:S组PACU停留时间短于U组;低氧血症、新出现肺部啰音和支气管痉挛发生率均低于U组;T~4时,PDO,和RI水平低于U组，0I水平高于U组:FEV,%、FVC%和FEV,FVC水平高于U组(P<0.05)。结论:西维来司他钠对老年轻度肺功能障碍患者行胸腔镜手术时具有一定的肺保护作用，可降低 PPCs 的发生。

摘要信息：目的 观察西维来司他钠在重症急性胰腺炎(SAP)合并肺损伤患者中的应用效果。方法 按随机数字表法将 2021年1月至 2023 年12月进行治疗的 84例SAP合并肺损伤患者分为对照组和观察组,各 42例。对照组采用鸟司他丁治疗,观察组于对照组的基础上加用注射用西维来司他钠治疗。比较两组炎症介质水平、肺郚超声评分([US)、血清淀粉酶(AMY)、尿淀粉酶(AMY),呼吸功能、肺损伤程度、病情严重程度、脏器功能、症状消失时间及不良反应发生情况。结果 观察组治疗后白细胞介素 -6(Ⅱ-6)、降钙素原(PCT)及C反应蛋白(CRP)水平均低于对照组,LUS 评分、AMY 和 UAMY 水平均低于对照组,氧合指数(PaO,Fi0,)与动脉血氧分压(PaO,)均高于对照组Muray 肺损伤量表(MLIS)评分、急性生理学和慢性健康状况Ⅱ(APACHEII)评分及序贯器官衰竭评分系统(SOFA)评分均低于对照组,呼吸困难、恶心呕吐及腹痛消失时间均短于对照组,差异有统计学意义(P<0.05):两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论 SAP合并肺损伤患者采用注射用西维来司他钠与鸟司他丁联合治疗可减轻炎症反应,改善呼吸功能,保护脏器功能,减轻肺损伤,控制患者病情,且不良反应并未增加。

摘要信息：1、炎症介质 NE、TNF-α、I-6 的过多激活参与 SAP 的进程及相关肾损害，肾组织NF-xB 激活在其中起重要作用;2、SS 发挥肾器官保护的可能活性机理:影响血清中炎症介质 NE、TNF-α、Ⅱ-6 水平是主要环节，减少其释放;其次抑制肾组织 NF-KB 活化，减轻炎性因子对肾组织细胞造成损伤有关。

摘要信息：目的 探讨注射用西维来司他钠治疗急性胰腺炎引发的全身炎症反应综合征(SIRS)及急性肺损伤的疗效。方法，对一例急性胰腺炎引发SIRS及急性肺损伤的患者采取注射用西维来司他钠治疗，通过动态监测血淀粉酶、血脂肪酶、白细胞计数、血小板计数、总胆红素、肌酐、转氨酶、氧合指数、胸部CT变化等，对患者进行效果评价。结果，在常规治疗的基础上采取注射用西维来司他钠治疗7d后，患者SIRS表现得到改善，血淀粉酶、脂肪酶及白细胞计数较入院时下降:与初入重症医学科相比，患者氧合指数明显改善，双肺弥漫性浸润改变及双侧胸腔积液好转;用药期间患者未出现肝肾功能损伤、血小板减少等不良反应。结论，注射用西维来司他钠治疗急性胰腺炎引发的SIRS及急性肺损伤是安全有效的。

摘要信息：Background:In Asia, Hanta virus (HTNV) results in severe hemorrhagic fever with renal syndrome (HFRS). The efficacy of sivelestat in treating children with HTNV-induced HFRS remains unclear. Methods:An ambispective cohort study was performed on children diagnosed with HFRS and hospitalized at the Children's Hospital Affiliated to Xi'an Jiaotong University from August 2018 to 2023. Patients who received neutrophil elastin-inhibitor infusion between August 2019 and August 2023 were assigned to the sivelestat group, while patients who did not were assigned to the control group. The independent sample t test was used for inter-group analysis. The Chi-square test and Fisher's exact probability test were used for categorical variables. Spearman correlation test was used to evaluate the correlation between two sets of continuous variables. Kaplan-Meier survival curve and Log -Rank test was used to evaluate the difference in cumulative probability of survival between the two groups. Results:No significant differences were observed between the two groups in gender, age, contact history, body mass index, HFRS severity, clinical indexes at admission. Compared to the control group, the sivelestat group exhibited a significant decrease in the interleukin-8 level at 48 h (28.5±3 vs 34.5±3.5) and 72 h (21.3±4.5 vs 31.5±5.6) (P<0.05), as well as the ICAM-1 level at 48 h (553±122 vs 784±187) and 72 h (452±130 vs 623±85) (P<0.05). The concentration of VCAM-1 in the sivelestat group exhibited a consistent downward trend. Moreover, the level of VCAM-1 was significantly lower than that in the control group at 24 h (1760±289 vs 2180±445), 48 h (1450±441 vs 1890±267), and 72 h (1149±338 vs 1500±396) (P<0.05). Kaplan-Meier curve analysis revealed a statistically significant difference in the cumulative probability of survival between two groups (P = 0.041). In the secondary outcomes, the sivelestat group demonstrated a decrease in the utilization rate of mechanical ventilation and continuous renal replacement therapy (CRRT). Conclusion:Sivelestat may suppress neutrophil-mediated inflammatory response to reduce endothelial and organ damage, and improve clinical outcomes in children with severe hemorrhagic fever and renal syndrome.

摘要信息：Background:Sivelestat, a neutrophil elastase inhibitor, is a selective and targeted therapy for acute respiratory distress syndrome (ARDS) in adults; and it is also reported to apply to children with ARDS. However, there is little evidence of its efficacy in children. Methods:This study recruited 212 patients ranging in age from 28 days to 18 years old, and who met the diagnostic criteria for pediatric ARDS (PARDS) while hospitalized in the Intensive Care Department of the Affiliated Children's Hospital of Xi'an Jiaotong University. A total of 125 patients (case group) received sivelestat treatment, and 87 were assigned to the control group. There were no significant differences in gender (P=0.445) or age (P=0.521). Control group data were collected from the Electronic Case Information System for pediatric patients diagnosed with ARDS between March 2017 to January 2020. Data for the case group were collected from the Electronic Case Information System between February 2020 to February 2022. Demographic data, clinically relevant indicators, respiratory parameters were recorded. The 28-day mortality was the primary endpoint; the Kaplan-Meier and log-rank tests were used to evaluate cumulative survival rate. Results:For general demographic and clinical characteristics, no significant differences were observed between the two groups. Compared to the control group, the case group displayed significant improvements in PaO2/FiO2at 48 h (141±45 vs. 115±21, P<0.001) and 72 h (169±61 vs. 139±40, P<0.001) post-admission, and plateau pressure was lower than that in the control group at 24 h (24±3 vs. 28±7, P<0.001), 48 h (21±4 vs. 26±7, P<0.001), and 72 h (20±2 vs. 25±6, P<0.001) post-admission. Interleukin-8 levels were lower in the case group at 48 and 72 h post-admission. Overall, 28-day mortality was 25.47% (54/212). Twenty-five children died in the sivelestat group, 29 children died in the control group. Survival analysis revealed that cumulative survival in the case group was higher than that in the control group (P=0.028). Conclusions:ARDS is expected to have high morbidity and mortality in critical care medicine, and precise targeted drugs are lacking. Our study showed that sivelestat improved prognosis and reduces mortality in children with ARDS.

摘要信息：Background:Pulmonary hypertension associated with congenital heart disease increases the risk of surgery using cardiopulmonary bypass. Sivelestat is a neutrophil elastase inhibitor thought to have a prophylactic effect against lung injury after surgery using bypass. We elucidated that Sivelestat had the protective effect on lung in patients with congenital heart disease and pulmonary hypertension who underwent surgery using bypass. Methods:This study was a controlled prospective randomized trial and enrolled 13 neonates or infants with ventricular septal defect and pulmonary hypertension. The patients were assigned to either sivelestat with the dose of 0.2 mg/kg per hour (sivelestat group, n = 7) or saline (placebo group, n = 6) from the start of bypass until 6 hours after bypass. Proinflammatory cytokines and adhesion molecules on leukocytes were measured at 10 time points during the above period. Pulmonary function was assessed perioperatively. Results:Compared with the placebo group, the sivelestat group had significantly lower values of alveolar-arterial oxygen tension gradient at 24 hours (p = 0.038) and at 48 hours (p = 0.028) after bypass, and significantly better balance of hydration at 48 hours after bypass (p = 0.012). The sivelestat group also showed significantly lower plasma levels of interleukin-8 immediately after bypass (p = 0.041) and interleukin-10 at 15 minutes after removal of the aortic cross-clamp (p = 0.048), and immediately after bypass (p = 0.037). Conclusions:Administration of sivelestat during bypass prevented pulmonary damage and activities of proinflammatory cytokines at the cardiac operation in neonates or infants. Our results show that sivelestat may be considered to protect pulmonary function against the injury by bypass. Keywords: 20; ANOVA; Aa-Do(2); CK-MB; CPB; ELAM-1; ICAM-1; ICU; IL; PH; PMN; PaO2/FiO2; Pp/Ps; Qp/Qs; Rp/Rs; VSD; alveolar-arterial oxygen tension gradient; analysis of variance; cardiopulmonary bypass; creatine kinase-myocardial band; endothelial leukocyte adhesion molecule-1; intensive care unit; intercellular adhesion molecule-1; interleukin; polymorphonuclear; pulmonary hypertension; ratio of pulmonary to systemic arterial blood flow; ratio of pulmonary to systemic arterial systolic pressure; ratio of pulmonary to systemic vascular resistance; ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen; ventricular septal defect.