修回日期: 2024-07-02
接受日期: 2024-07-19
在线出版日期: 2024-08-28
外周血C肽、白细胞介素-6(interleutin-6, IL-6)及肝素结合蛋白(heparin-binding protein, HBP)可能与肺损伤发生有关, 对预测高脂血症性胰腺炎(hyperlipidemia acute pancreatitis, HLAP)患者肺损伤可能具有重要价值.
探究HLAP患者外周血C肽、IL-6、HBP与肺损伤的相关性.
选取2019-04/2023-03舟山市第三人民医院150例HLAP患者, 根据患者住院期间是否发生肺损伤分为肺损伤组(n = 56)与非肺损伤组(n = 94). 比较两组基线资料、外周血C肽、IL-6及HBP水平, Pearson相关性分析外周血C肽、IL-6及HBP水平与病情评分的相关性; Logistic回归分析HLAP患者肺损伤的影响因素; 受试者工作特征(receiver operating characteristic, ROC)曲线评价外周血C肽、IL-6及HBP水平对HLAP患者肺损伤的预测价值.
肺损伤组年龄、胸腔积液所占比例、甘油三酯、慢性健康评价系统Ⅱ(Acute Physiological and Chronic Health Evaluation System Ⅱ, APACHEⅡ)评分、BMI、改良CT严重指数(Modified CT Severity Index, MCTSI)评分及序贯器官衰竭评估(Sequential Organ Failure Assessment, SOFA)评分高于非肺损伤组(P<0.05); 肺损伤组外周血C肽水平低于非肺损伤组, IL-6、HBP水平高于非肺损伤组(P<0.05); Pearson相关性分析可知, 外周血C肽水平与急性生理与APACHEⅡ、MCTSI评分、SOFA呈负相关(P<0.05), IL-6、HBP水平与APACHEⅡ评分、MCTSI评分、SOFA评分呈正相关(P<0.05); Logistic回归显示, BMI、三酰甘油、外周血C肽、IL-6及HBP水平均为HLAP患者肺损伤的独立影响因素(P<0.05); ROC曲线显示, 外周血C肽、IL-6及HBP水平联合预测HLAP患者肺损伤的曲线下面积值为0.906, 明显高于各指标单独预测, 且敏感度、特异度分别为89.29%、81.91%, 提示联合预测效能优于各指标单独预测效能.
HLAP患者外周血C肽、IL-6及HBP水平与肺损伤发生有关, 临床检测三者水平, 可为HLAP患者肺损伤预测提供参考依据.
核心提要: 高脂血症性胰腺炎(hyperlipidemia acute pancreatitis, HLAP)患者外周血C肽、白细胞介素-6及肝素结合蛋白水平与肺损伤发生有关, 临床检测三者水平, 可实现HLAP患者肺损伤早期预测, 从而能指导临床治疗.
引文著录: 陈园, 汤武亨, 曹春宇, 徐乾超. 高脂血症性胰腺炎患者外周血C肽、IL-6及HBP与肺损伤的相关性探讨. 世界华人消化杂志 2024; 32(8): 584-590
Revised: July 2, 2024
Accepted: July 19, 2024
Published online: August 28, 2024
Peripheral blood C-peptide, interleutin-6 (IL-6), and heparin-binding protein (HBP) may be related to the occurrence of lung injury and are of great value in predicting lung damage in patients with hyperlipidemia acute pancreatitis (HLAP).
To investigate the correlation of peripheral blood C-peptide, IL-6, and HBP with lung injury in patients with HLAP.
A total of 150 patients with HLAP hospitalized in our hospital from April 2019 to March 2023 were selected and divided into either a lung injury group (n = 56) or a non-lung injury group (n = 94) according to whether they had lung injury during hospitalization. Baseline data and peripheral blood C-peptide, IL-6, and HBP levels were compared between the two groups, and the correlation of peripheral blood C-peptide, IL-6, and HBP levels with disease score was assessed by Pearson correlation analysis. Logistic regression analysis was performed to identify the influencing factors of lung injury in HLAP patients. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive value of peripheral blood C-peptide, IL-6, and HBP levels for lung injury in patients with HLAP.
Age, body mass index (BMI), amount of pleural effusion, Acute Physiological and Chronic Health Evaluation System Ⅱ (APACHE Ⅱ) score, modified CT Severity Index (MCTSI) score, and Sequential Organ Failure Assessment (SOFA) score were significantly higher in the lung injury group than in the non-lung injury group, and the time from onset to hospital admission was longer in the lung injury group than in the non-lung injury group (P < 0.05). The levels of C-peptide in peripheral blood were lower in the lung injury group than in the non-lung injury group, while the levels of IL-6 and HBP were higher in the lung injury group than in the non-lung injury group (P < 0.05). Pearson correlation analysis showed that peripheral blood C-peptide levels were negatively correlated with APACHE Ⅱ, MCTSI, and SOFA scores (P < 0.05). IL-6 and HBP levels were positively correlated with APACHE Ⅱ, MCTSI, and SOFA scores (P < 0.05). Logistic regression analysis showed that BMI, triglycerides, and peripheral blood C-peptide, IL-6, and HBP levels were all independent influencing factors for lung injury in HLAP patients (P < 0.05). ROC curve analysis showed that the AUC value of the combined peripheral blood C-peptide, IL-6, and HBP levels in predicting lung injury in HLAP patients was 0.906, which was significantly higher than that of each index alone, with a sensitivity and specificity of 89.29% and 81.91%, respectively, suggesting that the prediction efficacy of combining the three indexes was better than that of each index alone.
The levels of C-peptide, IL-6, and HBP in peripheral blood of patients with HLAP are related to the occurrence of lung injury. Clinical detection of these indexes can provide a reference for the prediction of lung injury in patients with HLAP.
- Citation: Chen Y, Tang WH, Cao CY, Xu QC. Correlation of peripheral blood C-peptide, interleutin-6, and heparin-binding protein with lung injury in patients with hyperlipidemic pancreatitis. Shijie Huaren Xiaohua Zazhi 2024; 32(8): 584-590
- URL: https://www.wjgnet.com/1009-3079/full/v32/i8/584.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v32.i8.584
急性胰腺炎为临床常见急腹症, 在我国年发病率高达5/10万-30/10万人次, 且发病率呈明显增长趋势[1,2]. 高脂血症性胰腺炎(hyperlipidemia acute pancreatitis, HLAP)为急性胰腺炎的一种类型, 发病率约占所有急性胰腺炎的12%-38%, 其主要是因血脂升高致使胰腺血供障碍, 继而造成胰腺水肿、出血、坏死的急性胰腺炎[3-5]. 既往文献指出, 在急性胰腺炎病因中, HLAP危重症患者所占比例更高, 此类患者病情进展迅速, 可导致全身多器官功能障碍, 病死率较高[6]. 研究表明[7], 以肺水肿为主要表现的肺损伤为HLAP最常见并发症, 也是导致HLAP患者死亡的主要原因. 因此, 探讨可准确预测HLAP患者肺损伤的生物学指标尤为关键. HLAP发病后可激活单核细胞、巨噬细胞, 大量释放炎症介质, 如白细胞介素-6(interleutin-6, IL-6)、肝素结合蛋白(heparin-binding protein, HBP)等, 并经炎症级联反应引起全身性炎症反应综合征, 增加器官损伤风险[8,9]. 此外, 急性胰腺炎患者胰腺受损严重, 胰岛素功能障碍, C肽合成减少, 且与患者疾病转归有关[10]. 然而现阶段关于HLAP患者外周血C肽、IL-6及HBP与肺损伤的相关性的研究并不常见, 因此, 本研究观察HLAP患者外周血C肽、IL-6及HBP水平, 探讨其与肺损伤的关系, 旨在为临床防治工作提供参考.
选取2019-04/2023-03舟山市第三人民医院医院150例HLAP患者, 纳入标准: (1)均符合HLAP诊断标准[11]; (2)首次发病, 发病24 h内入院; (3)自愿签署研究同意书, 具有详细完整的临床资料. 排除标准: (1)胆石症、酒精等病因引起的急性胰腺炎者; (2)合并胰腺肿瘤或其他部位恶性肿瘤者; (3)伴有原发性循环、呼吸系统疾病者; (4)合并肝肾功能障碍者; (5)伴有其他感染性疾病者; (6)伴有其他消化系统疾病者, 如急性肠梗阻、消化性溃疡急性穿孔等; (7)合并原发性血液或免疫系统疾病者; (8)妊娠期、哺乳期女性.
住院期间, 根据《急性肺损伤/急性呼吸窘迫综合征诊断和治疗指南(2006)》中肺损伤标准[12], 判定HLAP患者是否发生肺损伤, 并据此分为肺损伤组(n = 56)与非肺损伤组(n = 94). 本研究经医学伦理委员会审核批准.
基线资料收集: 由经过专业培训的临床医师通过病历资料查阅等方式收集150例HLAP患者性别、年龄、吸烟史、BMI、发病至入院时间、胸腔积液、甘油三酯水平、基础疾病、饮酒史、急性生理与慢性健康评价系统Ⅱ(acute physiology and chronic health evaluation system Ⅱ, APACHEⅡ)、改良CT严重指数(modified CT severity index, MCTSI)评分、序贯器官衰竭评估(sequential organ faliure assessment, SOFA)等.
外周血C肽、IL-6及HBP检测: 150例HLAP患者均于入院时收集5 mL, 低温离心处理(2500 r/min, 4 ℃, 10 min), 提取血清储存于-80 ℃环境下备用; 以美国雅培公司提供放射免疫分析试剂盒测定C肽及IL-6水平; 上海西塘生物科技提供酶联免疫吸附试剂盒测定HBP水平, 仪器采用日本Hitachi全自动生化分析仪.
统计学处理 SPSS 28.0统计分析数据, 计量资料用(mean±SD)表示, t检验, 计数资料用n(%)表示, 卡方检验; Pearson相关性分析外周血C肽、IL-6及HBP水平与病情评分的相关性; Logistic回归分析HLAP患者肺损伤的影响因素; 受试者工作特征(receiver operating characteristic, ROC)曲线评价外周血C肽、IL-6及HBP水平对HLAP患者肺损伤的预测价值. 行双侧检验, 检验水准α = 0.05.
肺损伤组在吸烟史、饮酒史、基础疾病所占比例方面与非肺损伤组比较, 差异无统计学意义; 肺损伤组年龄、BMI、胸腔积液所占比例、甘油三酯、APACHEⅡ评分、MCTSI评分及SOFA评分高于非肺损伤组(P<0.05). 见表1.
| 基线资料 | 肺损伤组(n = 56) | 非肺损伤组(n = 94) | t/χ2值 | P值 |
| 性别 | ||||
| 男 | 31(55.36) | 49(52.13) | 0.147 | 0.701 |
| 女 | 25(44.64) | 45(47.87) | ||
| 年龄(岁) | 52.69±12.33 | 44.87±10.96b | 4.032 | <0.001 |
| BMI(kg/m2) | 24.24±2.89 | 21.87±2.05b | 5.858 | <0.001 |
| 发病至入院时间(h) | 12.57±2.31 | 11.84±3.02 | 1.557 | 0.122 |
| 吸烟史 | 17(30.36) | 24(25.53) | 0.411 | 0.521 |
| 饮酒史 | 20(35.71) | 31(32.98) | 0.117 | 0.732 |
| 基础疾病 | ||||
| 糖尿病 | 19(33.93) | 28(29.79) | 0.280 | 0.597 |
| 冠心病 | 10(17.86) | 15(15.96) | 0.091 | 0.763 |
| 高血压 | 15(26.79) | 22(23.40) | 0.216 | 0.642 |
| 胸腔积液 | ||||
| 有 | 17(30.36) | 13(13.83)a | 5.991 | 0.014 |
| 无 | 39(69.64) | 81(86.17) | ||
| 甘油三酯(mmol/L) | 6.17±1.68 | 4.93±1.45b | 4.772 | <0.001 |
| 病情评分(分) | ||||
| APACHEⅡ评分 | 24.82±2.27 | 19.82±3.04b | 10.659 | <0.001 |
| MCTSI评分 | 6.98±0.25 | 6.57±0.14b | 12.883 | <0.001 |
| SOFA评分 | 3.52±1.15 | 2.01±0.45b | 11.372 | <0.001 |
肺损伤组外周血C肽水平低于非肺损伤组, IL-6、HBP水平高于非肺损伤组(P<0.05). 见表2.
Pearson相关性分析可知, 外周血C肽水平与APACHEⅡ评分、MCTSI评分、SOFA评分呈负相关(P<0.05), IL-6、HBP水平与APACHEⅡ评分、MCTSI评分、SOFA评分呈正相关(P<0.05). 见表3.
| 指标 | APACHEⅡ评分 | MCTSI评分 | SOFA评分 | |||
| r值 | P值 | r值 | P值 | r值 | P值 | |
| C肽 | -0.574 | <0.001 | -0.592 | <0.001 | -0.589 | <0.001 |
| IL-6 | 0.602 | <0.001 | 0.614 | <0.001 | 0.607 | <0.001 |
| HBP | 0.599 | <0.001 | 0.602 | <0.001 | 0.605 | <0.001 |
以HLAP患者肺损伤为因变量, 表2和3中差异有统计学意义的因素作为自变量, 对自变量进行多重共线性检验结果显示, 年龄、胸腔积液、APACHEⅡ评分、MCTSI评分、SOFA评分的VIF均>10, 提示存在明显多重共线性问题, 予以手动剔除后, 进行Logistic回归分析, 最终得到, BMI、三酰甘油、外周血C肽、IL-6及HBP水平均为HLAP患者肺损伤的独立影响因素(P<0.05). 见表4.
| 变量 | β | S.E. | Wald χ2 | OR | 95%CI | P |
| BMI | 0.471 | 0.180 | 6.849 | 1.602 | 1.257-2.041 | <0.001 |
| 三酰甘油 | 0.583 | 0.211 | 7.633 | 1.791 | 1.332-2.409 | <0.001 |
| C肽 | -0.100 | 0.042 | 5.646 | 0.905 | 0.824-0.994 | <0.001 |
| IL-6 | 0.460 | 0.178 | 6.672 | 1.584 | 1.246-2.013 | <0.001 |
| HBP | 0.510 | 0.193 | 6.986 | 1.665 | 1.309-2.119 | <0.001 |
ROC曲线显示, 外周血C肽、IL-6及HBP水平预测HLAP患者肺损伤的曲线下面积(area under the curve, AUC)值分别为0.792、0.794、0.727, 三者联合预测AUC值为0.906, 明显高于各指标单独预测, 且敏感度、特异度分别为89.29%、81.91%, 提示联合预测效能优于各指标单独预测效能. 见表5.
| 指标 | AUC(95%CI) | Z统计 | 截断值 | 敏感度 | 特异度 | P值 |
| C肽(ng/mL) | 0.792(0.718-0.854) | 8.146 | 0.88 | 75.00% | 73.40% | <0.001 |
| IL-6(ng/L) | 0.794(0.721-0.856) | 7.239 | 37.36 | 66.07% | 85.11% | <0.001 |
| HBP(ng/mL) | 0.727(0.649-0.797) | 5.197 | 254.75 | 66.07% | 73.40% | <0.001 |
| 联合预测 | 0.906(0.847-0.947) | 17.417 | - | 89.29% | 81.91% | <0.001 |
HLAP发病机制为血清脂肪微粒栓塞胰腺毛细血管, 胰腺腺泡急性脂肪浸润及胰脂肪酶诱导游离脂肪酸产生, 刺激毛细血管, 致使胰腺血供障碍而发生急性炎症[13,14]. 急性胰腺炎患者伴有不同程度肺损伤, 尤其是HLAP最常见并发症即为肺损伤[15,16], 既往通常采用APACHEⅡ评分、MCTSI评分、SOFA评分系统性评价急性胰腺炎病情变化, 但其主观性较强, 预测器官损伤效能较差, 因此, 探索更为有效的客观指标预测HLAP患者肺损伤风险具有重要意义.
C肽作为胰岛β细胞分泌物, 其与胰岛素有一个共同前体-胰岛素原, 胰岛素原裂解产生的C肽与胰岛素具有等分子关系[17], 因此, 测定C肽浓度可反映胰岛素浓度, 判断胰岛β细胞功能. 由于急性胰腺炎患者胰腺受损严重, 胰岛β细胞功能障碍, 胰岛素原合成减少, C肽及胰岛素生成同步减少[18]. 本研究中, 外周血C肽水平与APACHEⅡ评分、MCTSI评分、SOFA评分呈负相关(P<0.05), 充分说明HLAP患者外周血C肽水平与病情程度有关, 提示外周血C肽水平越低, 胰岛素原合成越少, 病情越严重. 此外, 本研究中肺损伤组外周血C肽水平低于非肺损伤组, 且外周血C肽为HLAP患者肺损伤发生独立影响因素. 过少的C肽水平与胰腺受损有关, 其水平越低, 胰腺受损越严重, 进而激活机体炎症级联反应, 诱发全身炎症反应综合征, 增加肺损伤在内的多器官功能障碍风险. ROC曲线显示, 在HLAP患者肺损伤预测中, 外周血C肽表现出较良好预测效能, 有助于指导临床防治工作的顺利开展.
肺水肿为HLAP患者肺损伤的主要病理特征之一, 主要是因肺损伤过程中机体多种炎症细胞及因子参与肺部炎症反应, 严重损伤肺部毛细血管内皮, 致使血管内液体外漏至肺间质或肺泡引发[19-21], 因此, 炎症细胞因子研究是HLAP患者肺损伤发病机制的重要研究方向之一. IL-6作为单核巨噬细胞、淋巴细胞、中性粒细胞等分泌的细胞因子, 是炎症反应细胞分泌最常见因子之一, 生物学功能较为多样, 目前已有大量研究指出, IL-6可作为炎症反应早期因子, 诱导其炎症因子的合成、分泌, 放大炎症反应[22,23]; HBP是一种主要由成熟中性粒细胞分泌的多功能炎症介质, 具有调节单核巨噬及血管内皮细胞功能, 可促进机体炎症反应, 影响血管内皮通透性改变, 诱导组织水肿及血管渗漏[24,25]. 既往已有研究表明[26,27], 急性胰腺炎患者外周血IL-6、HBP水平与炎症反应、病情程度有关. 本研究中IL-6、HBP水平与APACHEⅡ评分、MCTSI评分、SOFA评分呈正相关(P<0.05)这一结果与之相符, 证实IL-6、HBP水平可评价HLAP患者病情程度. 有研究指出, 15%-60%的重症急性胰腺炎患者伴有不同程度肺损伤[28], 由此说明, 病情程度与急性胰腺炎患者肺损伤发生密切相关. 因此, 本研究推测IL-6、HBP水平不仅与HLAP患者病情程度有关, 同时可能参与该病患者肺损伤发生. Logistic回归分析显示, 外周血IL-6及HBP水平均为HLAP患者肺损伤影响因素, 可作为肺损伤的独立预测因素, ROC曲线显示, IL-6、HBP水平预测HLAP患者肺损伤的AUC值均在0.7以上, 证实二者在HLAP患者肺损伤预测中均具有良好的预测效能.
此外, 本研究进一步采用外周血C肽、IL-6及HBP水平联合预测HLAP患者肺损伤, 结果发现三者联合预测HLAP患者肺损伤的AUC值高达0.906, 明显高于各指标单独预测, 敏感度、特异度分别为89.29%、81.91%, 提示外周血C肽、IL-6及HBP水平联合预测在保证了特异度的同时, 进一步提高预测敏感度, 预测效能良好, 临床同时检测三者水平可为HLAP患者肺损伤风险预测提供有力支持.
综上所述, HLAP患者外周血C肽、IL-6及HBP水平与肺损伤发生有关, 临床检测三者水平, 可为HLAP患者肺损伤预测提供参考依据. 但本研究存在一定局限性: (1)单中心小样本研究; (2)外周血指标检测时间点单一, 一定程度上限制了研究结果的泛化, 有待临床进一步完善.
高脂血症性胰腺炎(hyperlipidemia acute pancreatitis, HLAP)能够造成多器官的损伤, 肺损伤为最常见并发症. 因此, 及时有效发现肺损伤, 采取积极有效的及早治疗尤为关键.
外周血C肽、白细胞介素-6(interleutin-6, IL-6)及肝素结合蛋白(heparin-binding protein, HBP)作为HLAP中常见的炎性因子在肺损伤中也会发生一定的变化, 血清水平的变化为肺损伤的早期发现具有重要临床意义.
观察探讨HLAP患者中外周血C肽、IL-6和HBP在血液中的水平与肺损伤的相关性, 以期为HLAP并发肺损伤患者早发现、早确诊、早治疗, 减少HLAP患者并发肺损伤造成的痛苦.
通过对比2组有无肺损伤患者血清中的外周血C肽、IL-6及HBP含量, Pearson相关性分析外周血C肽、IL-6及HBP水平与病情评分的相关性, Logistic回归分析HLAP患者肺损伤的影响因素.
外周血C肽、IL-6、HBP水平与慢性健康评价系统Ⅱ评分、改良CT严重指数评分、序贯器官衰竭评估评分均相关. BMI、三酰甘油、外周血C肽、IL-6及HBP水平均为HLAP患者肺损伤的独立影响因素. 三者联合预测的敏感度、特异度明显高于各指标单独预测.
HLAP患者外周血C肽、IL-6及HBP水平与肺损伤发生有一定的相关性, 三者联合预测患者肺损伤的灵敏性和准确性更高.
外周血C肽、IL-6及HBP水平对于HLAP患者肺损伤的监测具有重要的临床价值, 但是, 本研究仍具有样本量以单中心为主, 外周血指标检测时间点单一等问题, 接下来研究将进一步扩充样本来源, 增加对不同程度患者进行多点检测等.
学科分类: 胃肠病学和肝病学
手稿来源地: 浙江省
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科学编辑:张砚梁 制作编辑:张砚梁
| 1. | Lei Y, Tang L, Liu S, Hu S, Wu L, Liu Y, Yang M, Huang S, Tang X, Tang T, Zhao X, Vlodavsky I, Zeng S, Tang B, Yang S. Parabacteroides produces acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration. Microbiome. 2021;9:115. [PubMed] [DOI] |
| 3. | Wang L, Xu T, Wang R, Wang X, Wu D. Hypertriglyceridemia Acute Pancreatitis: Animal Experiment Research. Dig Dis Sci. 2022;67:761-772. [PubMed] [DOI] |
| 4. | Yu X. High-Fat Diet, Hypertriglyceridemia, Hyperlipidemic Acute Pancreatitis: Don't Forget Novel Coronavirus-Induced Acute Pancreatitis. Nutr Clin Pract. 2021;36:497. [PubMed] [DOI] |
| 5. | Wu Z, Wang X, Jiang X. Study on the Mechanism of Probucol Nanosuspension on Hyperlipidemic Pancreatitis and Regulation of Blood Lipid Function. J Nanosci Nanotechnol. 2021;21:1286-1292. [PubMed] [DOI] |
| 7. | 陈 飞, 林 小吉, 杨 鲸蓉, 李 毅鸣, 赵 文龙, 廖 达林. 脂蛋白脂肪酶基因敲除对急性高脂血症性胰腺炎所致肺损伤的影响及其机制研究. 现代生物医学进展. 2022;22:2841-2845. [DOI] |
| 8. | Molnár G, Gyarmathy VA, Zádori N, Hegyi P, Kanizsai P. Severe Hypertriglyceridemia-Induced Acute Pancreatitis. Case Rep Gastroenterol. 2021;15:218-224. [PubMed] [DOI] |
| 9. | Dai J, Jiang M, Hu Y, Xiao J, Hu B, Xu J, Han X, Shen S, Li B, Wu Z, He Y, Ren Y, Wen L, Wang X, Hu G. Dysregulated SREBP1c/miR-153 signaling induced by hypertriglyceridemia worsens acute pancreatitis and delays tissue repair. JCI Insight. 2021;6. [PubMed] [DOI] |
| 13. | Park H, Kim MS, Kim J, Lee SM, Cho SY, Yoo EG, Jin DK. Hypertriglyceridemia with acute pancreatitis in a 14-year-old girl with diabetic ketoacidosis. Ann Pediatr Endocrinol Metab. 2022;27:73-77. [PubMed] [DOI] |
| 14. | Thong VD, Mong Trinh NT, Phat HT. Factors associated with the severity of hypertriglyceridemia induced acute pancreatitis. Medicine (Baltimore). 2021;100:e25983. [PubMed] [DOI] |
| 17. | Carr ALJ, Inshaw JRJ, Flaxman CS, Leete P, Wyatt RC, Russell LA, Palmer M, Prasolov D, Worthington T, Hull B, Wicker LS, Dunger DB, Oram RA, Morgan NG, Todd JA, Richardson SJ, Besser REJ. Circulating C-Peptide Levels in Living Children and Young People and Pancreatic β-Cell Loss in Pancreas Donors Across Type 1 Diabetes Disease Duration. Diabetes. 2022;71:1591-1596. [PubMed] [DOI] |
| 18. | Marić N, Mačković M, Bakula M, Mucić K, Udiljak N, Marušić M. Hypertriglyceridemia-induced pancreatitis treated with continuous insulin infusion-Case series. Clin Endocrinol (Oxf). 2022;96:139-143. [PubMed] [DOI] |
| 19. | Zhang XX, Wang HY, Yang XF, Lin ZQ, Shi N, Chen CJ, Yao LB, Yang XM, Guo J, Xia Q, Xue P. Alleviation of acute pancreatitis-associated lung injury by inhibiting the p38 mitogen-activated protein kinase pathway in pulmonary microvascular endothelial cells. World J Gastroenterol. 2021;27:2141-2159. [PubMed] [DOI] |
| 20. | Tang Y, Kong J, Zhou B, Wang X, Liu X, Wang Y, Zhu S. Mesenteric Lymph Duct Ligation Alleviates Acute Lung Injury Caused by Severe Acute Pancreatitis Through Inhibition of High Mobility Group Box 1-Induced Inflammation in Rats. Dig Dis Sci. 2021;66:4344-4353. [PubMed] [DOI] |
| 21. | Xu C, Luo Y, Ntim M, Quan W, Li Z, Xu Q, Jiang L, Zhang J, Shang D, Li L, Zhang G, Chen H. Effect of emodin on long non-coding RNA-mRNA networks in rats with severe acute pancreatitis-induced acute lung injury. J Cell Mol Med. 2021;25:1851-1866. [PubMed] [DOI] |
| 22. | Piao X, Zou Y, Sui X, Liu B, Meng F, Li S, Zhang Q, Ma C, Wu T. Hydrostatin-SN10 Ameliorates Pancreatitis-Induced Lung Injury by Affecting IL-6-Induced JAK2/STAT3-Associated Inflammation and Oxidative Stress. Oxid Med Cell Longev. 2019;2019:9659757. [PubMed] [DOI] |
| 23. | 周 斌, 万 少兵, 王 瑛, 余 平, 典 万康, 周 莹, 周 琴. IL-6通过调控JAK2/STAT3信号通路减轻急性肺损伤的机制研究. 浙江医学. 2024;46:131-138. [DOI] |