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基于集成机器学习构建胰十二指肠术后胰瘘风险预测模型及其验证

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中华外科杂志 2024年第10期62卷 929-937页

作者：程诗博赵传兵吴遒勾善淼熊炯炘杨明王春友吴河水殷涛华中科技大学同济医学院附属协和医院胰腺外科武汉430022

目的构建并验证预测胰十二指肠切除术后患者发生临床相关术后胰瘘(CR-POPF)的集成机器学习模型。方法本研究为预测模型研究。回顾性收集2020年6月至2023年5月在华中科技大学同济医学院附属协和医院胰腺外科接受胰十二指肠切除术的421例... 详细信息

目的构建并验证预测胰十二指肠切除术后患者发生临床相关术后胰瘘(CR-POPF)的集成机器学习模型。方法本研究为预测模型研究。回顾性收集2020年6月至2023年5月在华中科技大学同济医学院附属协和医院胰腺外科接受胰十二指肠切除术的421例患者的临床资料。其中男性241例(57.2%),女性180例(42.8%),年龄(59.7±11.0)岁(范围:12~85岁)。通过分层随机抽样法将研究对象按照3∶1的比例分为训练集(315例)和测试集(106例)。使用递归特征消除算法对特征进行筛选,运用9种机器学习算法分别建模,挑选拟合能力较优的三组模型,通过Stacking算法进行模型融合构建集成模型。通过多种指标评估模型性能,并使用Shapley Additive Explanations(SHAP)方法对最优模型进行可解释性分析。根据替代胰瘘风险评分系统(a-FRS)的预测概率(P)将测试集患者分为不同风险组,对a-FRS评分进行验证并比较其与所建模型的预测效能。结果421例患者中,发生CR-POPF 84例(20.0%)。在测试集中,Stacking集成模型表现最佳,其受试者工作特征曲线的曲线下面积(AUC)为0.823,准确率为0.83,F1分数为0.63,Brier得分为0.097。SHAP总结图显示,影响胰十二指肠切除术后发生CR-POPF的前9位因素依次为胰管直径、CT值比值、术后血清淀粉酶、IL-6水平、体重指数、手术时间、术前术后白蛋白差值、降钙素原及IL-10。各个因素对胰十二指肠切除术后CR-POPF发生的影响均呈现出复杂的非线性关系。当胰管直径150 U/L、IL-6水平>280 ng/L、手术时间>350 min、白蛋白降低超过10 g/L时,发生CR-POPF的风险增加。a-FRS在测试集中的AUC为0.668,预测效能低于Stacking集成机器学习模型。结论本研究构建的Stacking集成机器学习模型能够预测胰十二指肠切除术后CR-POPF的发生,有潜力成为胰十二指肠切除术后个性化诊疗的有效工具。

关键词：胰十二指肠切除术手术后并发症临床相关胰瘘预测模型机器学习集成学习

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胰腺囊性肿瘤的诊治策略

临床外科杂志 2024年第7期32卷 680-682页

作者：朱志华刘志强吴河水九江学院附属医院普外科江西九江332000 华中科技大学同济医学院附属协和医院胰腺外科

胰腺囊性肿瘤(PCN)是一类源于胰腺导管上皮和(或)间质组织的囊性肿瘤性病变,主要包括浆液性囊腺瘤(SCN)、黏液性囊性肿瘤(MCN)、导管内乳头状黏液性瘤(IPMN)、实性假乳头状瘤(SPN)和囊性神经内分泌肿瘤(cNET)[1]。PCN的生物学行为各不... 详细信息

胰腺囊性肿瘤(PCN)是一类源于胰腺导管上皮和(或)间质组织的囊性肿瘤性病变,主要包括浆液性囊腺瘤(SCN)、黏液性囊性肿瘤(MCN)、导管内乳头状黏液性瘤(IPMN)、实性假乳头状瘤(SPN)和囊性神经内分泌肿瘤(cNET)[1]。PCN的生物学行为各不相同。

关键词：胰腺囊性肿瘤胰腺导管内乳头状黏液性瘤黏液性囊性肿瘤浆液性囊腺瘤实性假乳头状瘤

Protective effect of N-acetylcysteine against lipopolysaccharide injury in hepatocytes of neonatal mice

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Frontiers of Medicine 2008年第2期2卷 182-185页

作者： Lin WANG Jianbo XU Yuan TIAN heshui wu Yalan LIU Department of Pediatrics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of General Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

The present study provides supportive evid-ence for the effective prevention and treatment of lipopo-lysaccharide(LPS)-induced hepatocyte injury in neonatal mice by N-acetylcysteine(NAC).Hepatocytes of neonatal mice were obtained through collagenase digestion of the *** hepatocytes were treated either with LPS(10 mg/mL)alone or with NAC(5 mmol/L)for 1 h before the addition of LPS(10 mg/mL).After LPS treatment,12 wells of the cultured hepatocytes and supernatants were harvested at 0,6,and 12 h,*** of alanine aminotransferase(ALT)and nitric oxide(NO)in the supernatant were biochemically quantified and reverse transcription-polymerase chain reaction(RT-PCR)was performed to detect the expression of inducible nitric oxide synthase(iNOS)mRNA after different *** 0 h following the treatment of primary cultured hepa-tocytes with LPS,the levels of ALT,NO and iNOS mRNA in the supernatant were(21.1±4.78)u/L,(1.6±0.31)mmol/L and 0.17±0.023,respectively;at 6 h,(59.8±8.59)u/L,(6.6±0.81)mmol/L,and 0.71±0.091;and at 12 h,(89.6±15.30)u/L,(7.8±1.01)mmol/L,and 0.71±*** levels of ALT,NO and iNOS mRNA at 6 and 12 h increased significantly,compared to those at 0 h(P<0.01).In contrast to LPS treatment alone,pre-treatment with NAC before LPS addition significantly reduced the levels of ALT,NO and iNOS mRNA in the supernatant at 6 h to(40.8±7.30)u/L,(3.2±0.71)mmol/L,and 0.41±0.060;and at 12 h to(55.4±5.48)u/L,(4.0±0.71)mmol/L,and 0.40¡0.067,respectively(P<0.01).However,the levels of ALT,NO and iNOS mRNA at 0 h did not change significantly with both treat-ment *** has protective effects in hepato-cytes of neonatal mice against LPS-induced injury as shown by the reduced levels of ALT,NO and iNOS mRNA when primary hepatocytes were treated with NAC prior to LPS *** postulate that NAC exhibits its protective function by inhibiting LPS-induced transcription of iNOS,resulting in decreased levels of NO.

关键词： N-acetylcysteine endotoxin hepatocytes nitric oxide inducible nitric oxide synthase

The expression of toll-like receptor 2, 4 of livers in mice with systemic inflammatory response syndrome

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Hepatobiliary & Pancreatic Diseases International 2006年第1期5卷 143-146页

作者： Jing Xiong ZhongHua Zhu JianShe Liu Yang Wang heshui wu Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China.

BACKGROUND: The complicated pathogenesis of systemic inflammatory response syndrome (SIRS) is a hot topic in critical care medicine. In this study we explored the expression of toll-like receptor (TLR) 2, 4 of livers in SIRS mice and evaluated the role of TLR2, 4 in the pathogenesis of SIRS. METHODS: Forty BABL/C mice were randomly divided into 2 groups: control (n=20) and SIRS (n=20). SIRS model was induced by severe acute pancreatitis. Blood routine, blood amylase, glutamic pyruvic transaminase and temperature were measured. Histological changes of pancreases and livers were observed microscopically. The mRNA expressions of TLR2, 4 were detected by real-time polymerase chain reaction (PCR). The protein expressions of TLR2, 4 were examined by Western blot. RESULTS: Marked edema, inflammatory cell infiltration, hemorrhage, and necrosis were observed in the pancreases and livers of SIRS mice. The concentrations of amylase and glutamic pyruvic transaminase were increased significantly. Body temperature and white blood cell count were decreased. The mRNA and protein expressions of TLR2, 4 increased markedly in SIRS mice. Significant difference was observed between SIRS and control mice (P<0.01). CONCLUSION: The expressions of TLR2, 4 of livers were increased markedly in SIRS mice, indicating that TLR might play an important role in the pathogenesis of SIRS.

关键词： toll-like receptor systemic inflammatory response syndrome severe acute pancreatitis

Expression of Toll-like Receptor 2/4 on Alveolar Macrophage in the Model of Total Hepatic Ischemia/Reperfusion Injury in Mice

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The Chinese-German Journal of Clinical Oncology 2006年第4期5卷 298-300页

作者： GU Yuanting wu heshui XU Jianbo WANG Lin TIAN Yuan WANG Chunyou Department of General Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China Department of Surgery the First Affiliated Hospital Zhengzhou University Zhengzhou 450052 China Department of Pediatrics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

Objective： To explore the expression and meaning of Toll-like receptor 2/4 in alveolar macrophage during the process of total hepatic ischemia in mice. Methods： BALB/c mice were used in a model of total hepatic ischemia/reperfusion. Alveolar Macrophage were collected at the time point of lh, 6h and 12h by the means of bronchoalveolar lavage （BAL）, and its TLR2/4 mRNA and protein were detected with Flow Cytometry and Real-time PCR. The level of TNF in BAL fluid were measured. The concentration of MPO, the ratio of wet/dry and lung histological scores were used to assess the degrees of lung injuries. Results： At the three time points of hepatic ischemia reperfusion, the expression of TLR2/4 protein of and mRNA were up-regulated and the level of TLR2 was on the rise continually. TLR4 at the time of 6 h reached the peak value （P〈0.01）. The level of TNF-2 in BAL fluid reached the highest point at the time of 6 h （P〈0.01）. The ratio of wet/dry rose continually during hepatic ischemia reperfusion. After 1 h, the level of MPO increased rapidly. Then it reached the peak value during the period of 6 h to 12 h. Conclusion： TLR2/4 on the mice of alveolar macrophage were activated in the process of hepatic ischemia/reperfusion and involved in the injury of lung.

关键词： Toll-like receptors liver hepatic ischemia reperfusion injury of lungs, alveolar macrophage

The relationship between activation of TLR4 and partial hepatic ischemia/reperfusion injury in mice

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Hepatobiliary & Pancreatic Diseases International 2006年第1期5卷 101-104页

作者： Lin Wang JianBo Xu heshui wu JinXiang Zhang JinHui Zhang Yuan Tian ChunYou Wang Department of Pediatrics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China. whs1898@***

BACKGROUND: Toil-like receptors (TLRs) are a group of evolutionarily conserved pattern recognition receptors involved in the activation of the immune system in response to various pathogens. In this study, we elucidated the relationship between activation of TLR4 and liver injury in partial hepatic ischemia/reperfusion (I/R) injury in mice. METHODS: BALB/c mice were used in a model of partial hepatic I/R injury, and the changes of TLR4 gene expression in ischemic liver lobes were detected with real-time polymerase chain reaction (RT-PCR). The levels of plasma ALT and endotoxin in the portal vein were measured. TLR4-deficient mice (C3H/Hej) and wild type mice (C3H/Heouj) were used in a model of I/R injury; liver function impairment and the level of serum TNF-α were observed. RESULTS: After one hour ischemia, the expression of TLR4 mRNA increased at the 1st, 3rd hour of reperfusion, indicating the value of △Ct(1st hour: 1.21±0.87vs. 5.85±1.07, t=13.72, P<0.01; 3rd hour: 0.85±0.92vs. 6.11±1.24, t=16.33, P<0.01). No endotoxemia developed in every group of mice. At the 3rd hour of reperfusion, the level of serum TNF-α was significantly higher than that of sham group (Hej: 152±43 pg/ml vs. 18±10pg/ml, t=5.26, P<0.01; Heouj: 249±52pg/ml vs. 25±13 pg/ml, t=7.24, P<0.01). At the 1st, 3rd hour reperfusion, the level of plasmid ALT in Hej mice was lower than that in Heouj mice (1st hour 662±106 U/Lvs. 1216±174 U/L, t=4.21, P<0.01; 3rd hour 1145±132U/L vs. 29584±187 U/L, t=13.72, P<0.01). The level of serum TNF-αwas lower than that in Heouj mice (1524.43 U/L vs. 2494±52 U/L, t=3.94, P<0.01) at the 3rd hour reperfusion. CONCLUSION: TLR4 activation causes partial hepatic I/R injury through release of TNF-α.

关键词： liver reperfusion injury toll-like receptor endotoxin

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胰腺癌新辅助治疗的适应证的选择与疗效评估

中华医学杂志 2021年第10期101卷 716-721页

作者：勾善淼吴河水华中科技大学同济医学院附属协和医院胰腺外科武汉430022

胰腺癌恶性程度较高、预后较差。虽然手术切除仍是目前唯一能够治愈胰腺癌的方法,但伴随着胰腺癌辅助治疗的进展,其治疗模式已由“手术优先”向“多学科协作”转变。新辅助治疗已被证实可提高交界性可切除和局部进展期胰腺癌的R0切除率... 详细信息

胰腺癌恶性程度较高、预后较差。虽然手术切除仍是目前唯一能够治愈胰腺癌的方法,但伴随着胰腺癌辅助治疗的进展,其治疗模式已由“手术优先”向“多学科协作”转变。新辅助治疗已被证实可提高交界性可切除和局部进展期胰腺癌的R0切除率并改善患者预后,这些患者应给予新辅助治疗已成共识,但胰腺癌新辅助化疗方案的选择、放射治疗的地位、新辅助治疗后影像学与病理学评估等方面仍存较大争议。

关键词：胰腺肿瘤新辅助治疗放射治疗影像学评估病理学评估

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胰腺癌免疫治疗的现状及前景

肿瘤防治研究 2020年第3期47卷 154-158页

作者：金鑫吴河水华中科技大学同济医学院附属协和医院胰腺外科武汉430030

胰腺癌(胰腺导管腺癌)是一种恶性程度较高,诊断和治疗都较困难的消化系统恶性肿瘤。近年来,肿瘤免疫治疗在多种肿瘤中如黑色素瘤、膀胱癌、乳腺癌、非小细胞肺癌和肾癌等均取得了令人振奋的治疗效果,但是胰腺癌的免疫治疗策略尚在不断... 详细信息

胰腺癌(胰腺导管腺癌)是一种恶性程度较高,诊断和治疗都较困难的消化系统恶性肿瘤。近年来,肿瘤免疫治疗在多种肿瘤中如黑色素瘤、膀胱癌、乳腺癌、非小细胞肺癌和肾癌等均取得了令人振奋的治疗效果,但是胰腺癌的免疫治疗策略尚在不断探索中。目前针对胰腺癌独特的肿瘤微环境设计了多种免疫治疗策略,包括强化/提高自身免疫反应(免疫调节剂、单克隆抗体、肿瘤疫苗和细胞治疗)以及抑制肿瘤免疫逃逸(免疫检查点抑制剂和肿瘤微环境)等。本文就胰腺癌免疫治疗的研究进展进行综述,着重探讨PD-1/PD-L1抑制剂在胰腺癌中的应用,并分析免疫治疗联合其他方式治疗胰腺癌的前景。

关键词：胰腺癌免疫治疗 PD-1/PD-L1 强化免疫机制免疫逃逸

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胰腺癌靶向治疗的研究现状和展望

中华实验外科杂志 2023年第1期40卷 5-7页

作者：孙岩吴河水华中科技大学同济医学院附属协和医院胰腺外科武汉430022

胰腺癌是侵袭性和致命性均极高的消化系统恶性肿瘤,近年来,吉西他滨联合白蛋白紫杉醇是不可切除胰腺癌治疗的主要方案,但其改善预后的效果并不显著,因此需要探索新的治疗方案来提升患者的生存率。研究表明,基因突变和细胞信号传导通路... 详细信息

胰腺癌是侵袭性和致命性均极高的消化系统恶性肿瘤,近年来,吉西他滨联合白蛋白紫杉醇是不可切除胰腺癌治疗的主要方案,但其改善预后的效果并不显著,因此需要探索新的治疗方案来提升患者的生存率。研究表明,基因突变和细胞信号传导通路异常是驱动胰腺癌发生发展的重要因素,如果能够识别这些异常的靶点并针对这些靶点设计药物,对于改善胰腺癌预后具有重要意义。同时,不同的胰腺癌患者可能有其特定的基因改变,这为患者的个性化治疗提供了理论基础,有希望进一步延长患者的生存时间。本文阐述了胰腺癌靶向治疗的研究现状,并展望其临床应用前景。

关键词：胰腺癌基因突变细胞信号传导通路靶向治疗耐药