Interplay of serum biomarkers bilirubin andγ-glutamyltranspeptidase in predicting cardiovascular complications in type-2 diabetes mellitus

This editorial synthesizes insights from a series of studies examining the interplay between metabolic and oxidative stress biomarkers in cardiovascular disease(CVD),focusing particularly on type-2 diabetes mellitus(T2DM)and acute coronary syndrome(ACS).The central piece of this synthesis is a study that investigates the balance between oxidative stress and antioxidant systems in the body through the analysis of serum bilirubin andγ-glutamyltranspeptidase(γ-GGT)levels in T2DM patients with ACS.This study highlights serum bilirubin as a protective antioxidant factor,while elevatedγ-GGT levels indicate increased oxidative stress and correlate with major adverse cardiovascular events.Complementary to this,other research contributions revealγ-GGT’s role as a risk factor in ACS,its association with cardiovascular mortality in broader populations,and its link to metabolic syndrome,further elucidating the metabolic dysregulation in CVDs.The collective findings from these studies underscore the critical roles ofγ-GGT and serum bilirubin in cardiovascular health,especially in the context of T2DM and ACS.By providing a balanced view of the body’s oxidative and antioxidative mechanisms,these insights suggest potential pathways for targeted interventions and improved prognostic assessments in patients with T2DM and ACS.This synthesis not only corroborates the pivotal role ofγ-GGT in cardiovascular pathology but also introduces the protective potential of antioxidants like bilirubin,illuminating the complex interplay between T2DM and heart disease.These studies collectively underscore the critical roles of serum bilirubin andγ-GGT as biomarkers in cardiovascular health,particularly in T2DM and ACS contexts,offering insights into the body’s oxidative and antioxidative mechanisms.This synthesis of research supports the potential of these biomarkers in guiding therapeutic strategies and improving prognostic assessments for patients with T2DM and some CVD.

Association of total bilirubin with depression risk in adults with diabetes:A cross-sectional study

BACKGROUND Individuals with diabetes mellitus are more likely to experience depression,although most patients remain undiagnosed.The relation between total bilirubin and depression has been increasingly discussed,but limited studies have examined the association of total bilirubin with depression risk in adults with diabetes,which warrants attention.AIM To investigate the association between total bilirubin levels and the risk of depression in adults with diabetes.METHODS The study included adults with diabetes from the National Health and Nutrition Examination Survey 2007-2018.Depression was determined using the Patient Health Questionnaire-9.Multivariable logistic regression,propensity scorematched analysis and restricted cubic spline models were utilized to investigate the association between total bilirubin levels and depression risk in adults with diabetes.RESULTS The study included 4758 adults with diabetes,of whom 602(12.7%)were diagnosed with depression.After adjusting for covariates,we found that diabetic adults with lower total bilirubin levels had a higher risk of depression(OR=1.230,95%CI:1.006-1.503,P=0.043).This association was further confirmed after propensity score matching(OR=1.303,95%CI:1.034-1.641,P=0.025).Subgroup analyses showed no significant dependence of age,body mass index,sex,race or hypertension on this association.Restricted cubic spline models displayed an inverted U-shaped association of total bilirubin levels with depression risk within the lower range of total bilirubin levels.The depression risk heightened with the increasing levels of total bilirubin,reaching the highest risk at 6.81μmol/L and decreasing thereafter.CONCLUSION In adults with diabetes,those with lower levels of total bilirubin were more likely to have depressive symptoms.Serum total bilirubin levels may be used as an additional indicator to assess depression risk in adults with diabetes.

Predictive value of bilirubin and serum γ-glutamyltranspeptidase levels in type-2 diabetes mellitus patients with acute coronary syndrome

BACKGROUND Cardiovascular disease is a major complication of diabetes mellitus(DM).Type-2 DM(T2DM)is associated with an increased risk of cardiovascular events and mortality,while serum biomarkers may facilitate the prediction of these outcomes.Early differential diagnosis of T2DM complicated with acute coronary syndrome(ACS)plays an important role in controlling disease progression and improving safety.AIM To investigate the correlation of serum bilirubin andγ-glutamyltranspeptidase(γ-GGT)with major adverse cardiovascular events(MACEs)in T2DM patients with ACS.METHODS The clinical data of inpatients from January 2022 to December 2022 were analyzed retrospectively.According to different conditions,they were divided into the T2DM complicated with ACS group(T2DM+ACS,n=96),simple T2DM group(T2DM,n=85),and simple ACS group(ACS,n=90).The clinical data and laboratory indices were compared among the three groups,and the correlations of serum total bilirubin(TBIL)levels and serumγ-GGT levels with other indices were discussed.T2DM+ACS patients received a 90-day follow-up after discharge and were divided into event(n=15)and nonevent(n=81)groups according to the occurrence of MACEs;Univariate and multivariate analyses were further used to screen the independent influencing factors of MACEs in patients.RESULTS The T2DM+ACS group showed higherγ-GGT,total cholesterol,low-density lipoprotein cholesterol(LDL-C)and glycosylated hemoglobin(HbA1c)and lower TBIL and high-density lipoprotein cholesterol levels than the T2DM and ACS groups(P<0.05).Based on univariate analysis,the event and nonevent groups were significantly different in age(t=3.3612,P=0.0011),TBIL level(t=3.0742,P=0.0028),γ-GGT level(t=2.6887,P=0.0085),LDL-C level(t=2.0816,P=0.0401),HbA1c level(t=2.7862,P=0.0065)and left ventricular ejection fraction(LEVF)levels(t=3.2047,P=0.0018).Multivariate logistic regression analysis further identified that TBIL level and LEVF level were protective factor for MACEs,and age andγ-GGT level were risk factors(P<0.05).CONCLUSION Serum TBIL levels are decreased andγ-GGT levels are increased in T2DM+ACS patients,and the two indices are significantly negatively correlated.TBIL andγ-GGT are independent influencing factors for MACEs in such patients.

Better performance of PIVKA-II for detecting hepatocellular carcinoma in patients with chronic liver disease with normal total bilirubin

BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.

Predictive value of preoperative albumin-bilirubin score and other risk factors for short-term outcomes after open pancreatoduodenectomy

BACKGROUND Pancreatoduodenectomy represents a complex procedure involving extensive organ resection and multiple alimentary reconstructions.It is still associated with high morbidity,even in high-volume centres.Prediction tools including preoperative patient-related factors to preoperatively identify patients at high risk for postoperative complications could enable tailored perioperative management and improve patient outcomes.AIM To evaluate the clinical significance of preoperative albumin-bilirubin score and other risk factors in relation to short-term postoperative outcomes in patients after open pancreatoduodenectomy.METHODS This retrospective study included all patients who underwent open pancreatic head resection(pylorus-preserving pancreatoduodenectomy or Whipple resection)for various pathologies during a five-year period(2017-2021)in a tertiary care setting at University Medical Centre Ljubljana,Slovenia and Cattinara Hospital,Trieste,Italy.Short-term postoperative outcomes,namely,postoperative complications,postoperative pancreatic fistula,reoperation,and mortality,were evaluated in association with albumin-bilirubin score and other risk factors.Multiple logistic regression models were built to identify risk factors associated with these short-term postoperative outcomes.RESULTS Data from 347 patients were collected.Postoperative complications,major postoperative complications,postoperative pancreatic fistula,reoperation,and mortality were observed in 52.7%,22.2%,23.9%,21.3%,and 5.2%of patients,respectively.There was no statistically significant association between the albumin-bilirubin score and any of these short-term postoperative complications based on univariate analysis.When controlling for other predictor variables in a logistic regression model,soft pancreatic texture was statistically significantly associated with postoperative complications[odds ratio(OR):2.09;95%confidence interval(95%CI):1.19-3.67];male gender(OR:2.12;95%CI:1.15-3.93),soft pancreatic texture(OR:3.06;95%CI:1.56-5.97),and blood loss(OR:1.07;95%CI:1.00-1.14)were statistically significantly associated with major postoperative complications;soft pancreatic texture was statistically significantly associated with the development of postoperative pancreatic fistula(OR:5.11;95%CI:2.38-10.95);male gender(OR:1.97;95%CI:1.01-3.83),soft pancreatic texture(OR:2.95;95%CI:1.42-6.11),blood loss(OR:1.08;95%CI:1.01-1.16),and resection due to duodenal carcinoma(OR:6.58;95%CI:1.20-36.15)were statistically significantly associated with reoperation.CONCLUSION The albumin-bilirubin score failed to predict short-term postoperative outcomes in patients undergoing pancreatoduodenectomy.However,other risk factors seem to influence postoperative outcomes,including male sex,soft pancreatic texture,blood loss,and resection due to duodenal carcinoma.

Correlation between pre-treatment serum total blood bilirubin andunconjugated bilirubin and prognosis in patients with colorectalcancer

BACKGROUND Epidemiological studies have found that unconjugated bilirubin(UCB)levels are positively correlated with the incidence of colorectal cancer(CRC).Therefore,bilirubin may also play an important role in the prognosis of CRC.AIM To investigate the predictive value of total bilirubin(TBIL)and UCB in the prognosis of patients with CRC.METHODS A total of 142 CRC patients were selected as the research subjects in Jingxian Hospital,from October 2014 to May 2021.General and tumour-related clinical data at admission and the overall survival at 3 years after surgery were collected.The optimal cut-off values of TBIL and UCB were determined by receiver operating characteristic curve analysis.Univariate and multivariate Cox regression were used to analyse the effect of bilirubin level on the survival of CRC patients.The Kaplan–Meier method was used to assess the survival time.RESULTS The 3-year overall survival rate of CRC patients was significantly higher in the high TBIL(>13.45μmol/L)group than in the low TBIL(≤13.45μmol/L)group(76.4%vs 37.1%;P<0.05).The 3-year overall survival rate of CRC patients in the high UCB(>10.75μmol/L)group was significantly higher than that in the low UCB(≤10.75μmol/L)group(83.3%vs 34.2%;P<0.05).Multivariate Cox regression analysis showed that higher TBIL levels were an independent predictor of better prognosis in CRC patients(hazard ratio=0.360,95%confidence interval:0.159-0.812,P=0.014).CONCLUSION TBIL levels can be used as a prognostic indicator for CRC patients.

新生儿外周血检出胆红素结晶1例报道

胆红素结晶临床可见于阻塞性黄疸、急性肝坏死等疾病个体,出现在胸腹水、关节液中有报道,而外周血检出胆红素结晶罕见。本文报道1例出生4 d男性患儿,诊断为新生儿呼吸窘迫综合征、高胆红素血症。外周血涂片镜检于部分中性粒细胞、单核细胞内见金黄色、折光性强,呈针状、菱形、矩形、斜方体形或长方体形胆红素结晶。根据临床经验,显著高胆红素血症的新生儿外周血偶见胆红素结晶,可造成血清胆红素测定结果偏低。提示血常规结果的审核,需在审核各项检测数值的同时,务必注意观察散点图和报警信息,并结合血清胆红素水平及临床表现,镜检时仔细观察细胞形态,以便及时发现仅仅依靠检测数值发现不了的对临床诊疗有意义的形态学异常结果。

DBIL/TBIL表达与超声引导下射频消融治疗原发性肝癌患者复发的关系

目的分析血清直接胆红素(DBIL)/总胆红素(TBIL)比值与超声引导下射频消融治疗原发性肝癌(PLC)患者复发的关系。方法入选2018年3月至2021年2月124例拟行射频消融治疗的PLC患者作为研究对象,根据研究目的,在射频消融治疗前常规检测相关指标,包括血清DBIL、TBIL、肿瘤标志物及患者一般临床资料。以射频消融治疗达到完全消融视为消融成功,将消融治疗成功后2 a内复发视为随访终点,采用Cox回归,分析血清DBIL/TBIL与超声引导下射频消融治疗PLC患者复发的关系。结果2018年3月至2021年2月共收录124例PLC患者,一次消融成功率为92.06%(116/126),复发率为21.55%(25/116),射频消融治疗后复发患者肿瘤数目、肿瘤直径大于未复发患者,血清TBIL、DBIL低于未复发患者,甲胎蛋白、DBIL/TBIL比值高于未复发患者(P<0.05)。构建Cox回归分析显示,肿瘤数量≥3、瘤体直径、血清TBIL表达下调,DBIL/TBIL比值升高导致PLC患者射频消融治疗后复发风险增加(P<0.05)。绘制受试者工作特征曲线,血清DBIL/TBIL比值预测PLC患者射频消融治疗后复发的曲线下面积为0.776,当DBIL/TBIL截断值达到0.50时,可以获得最高敏感度(0.920)和特异度(0.495)。结论血清DBIL/TBIL比值升高导致PLC患者射频消融治疗后2 a内复发风险增加,消融治疗前计算DBIL/TBIL比值有助于预测复发风险。

血清Hcy、TBIL联合SUA检测对首发缺血性脑卒中及不良预后的预测价值

目的探讨血清同型半胱氨酸(Hcy)、总胆红素(TBIL)联合血尿酸(SUA)水平检测对首发缺血性脑卒中(FIS)及不良预后的预测价值。方法该研究为回顾性分析,选择2020年1月至2021年7月在该院神经内科住院治疗的210例FIS患者作为观察组,另匹配同期体检健康者210例作为对照组。比较两组血清Hcy、TBIL和SUA水平。统计FIS患者出院后1个月时的脑卒中致残、复发情况并使用改良Rankin量表(mRS)评估出院3个月时的预后情况,采用多因素Logistic回归分析FIS及其不良预后事件的危险因素。采用受试者工作特征(ROC)曲线评价血清Hcy、TBIL和SUA联合检测对FIS及复发、致残、mRS评分≥3分等不良预后事件的预测价值。结果与对照组相比,FIS患者的血清Hcy和SUA水平均显著升高,血清TBIL水平显著降低,差异有统计学意义(P<0.01)。出现复发、致残和mRS评分≥3分等不良预后事件的患者群体血清Hcy和SUA水平显著升高,血清TBIL水平显著降低,差异有统计学意义(P<0.01)。多因素Logistic回归分析结果显示,血清Hcy、TBIL和SUA不仅是FIS的影响因素(P<0.01),也是FIS患者疾病复发、致残和mRS评分≥3分等不良预后事件的影响因素(P<0.01)。ROC曲线分析结果显示,血清Hcy、TBIL和SUA 3项指标联合诊断FIS的曲线下面积(AUC)为0.835(95%CI:0.789~0.875),3项指标联合诊断FIS的效能显著优于单指标检测(P<0.01)。3项指标联合检测对致残(AUC=0.859,95%CI:0.804~0.903)、复发(AUC=0.807,95%CI:0.747~0.858)、mRS≥3分(AUC=0.847,95%CI:0.791~0.893)等不良预后事件也具备一定的预测效能,且预测效能显著优于单指标检测(P<0.05)。结论血清Hcy、TBIL和SUA水平与FIS发生及预后密切相关,血清Hcy、TBIL和SUA联合检测在FIS的诊断和预后评估中具有较高的临床价值。

高产胆盐水解酶乳杆菌的筛选及对新生大鼠黄疸的防治作用

为筛选高产胆盐水解酶的乳杆菌,探究其对新生儿黄疸的防治作用。采用添加了25 U/mL制霉菌素的LBS选择性培养基,从健康新生儿粪便和母乳中筛选乳杆菌并鉴定种类;以鼠李糖乳杆菌LGG为阳性对照,体外评估菌株的益生菌特性;利用盐酸苯肼诱导新生SD大鼠黄疸模型,通过分析血清胆红素水平和肝脏组织的损伤情况,以及肝脏炎症因子、核转录因子的相对表达水平,探究高产胆盐水解酶乳杆菌对新生大鼠黄疸的防治作用及机制。结果表明,来自婴儿粪便的格氏乳杆菌FWJL-5在体外具良好的益生特性,并且产胆盐水解酶能力优于LGG,能够显著缓解新生大鼠胆红素水平升高、肝脏组织肿胀和溶血症状,减少肝脏损伤中肝酶的释放,抑制促炎因子的分泌,促进UGt1A1和上游核转录因子孕烷X受体(pregnane X receptor,pXR)、法尼醇X受体(farnesol X receptor,FXR)的表达。综上所述,婴儿粪便来源的格氏乳杆菌FWJL-5可通过上调核受体FXR/pXR促进UGt1A1表达以调节肝脏胆红素代谢,从而减轻新生大鼠黄疸症状,本研究可为格氏乳杆菌防治新生儿黄疸提供新思路。

胆红素总量/白蛋白比值、听力筛查及MRI-T_(1)WI影像对新生儿急性胆红素脑病的诊断价值

目的:探究胆红素总量/白蛋白比值(B/A)、听力筛查及磁共振成像-T_(1)加权成像(MRI-T_(1)WI)对新生儿急性胆红素脑病(ABE)的诊断价值。方法:选取2013年6月—2023年6月于太仓市第一人民医院接受治疗的136例新生儿高胆红素血症(NHB)患儿作为研究对象,根据是否并发ABE分为并发组(n=42)和对照组(n=94)。对比两组的临床资料、B/A水平、听力筛查结果、苍白球T_(1)WI信号强度,对单因素分析有意义的指标进行多因素logistic回归分析,采用ROC曲线分析其对新生儿ABE的诊断价值。结果:并发组总血清胆红素(TSB)峰值、B/A水平均高于对照组,差异有统计学意义(P<0.05)。并发组初筛听力异常率为38.10%,复筛听力异常率为35.71%,均高于对照组的18.09%、8.51%,差异有统计学意义(P<0.05)。并发组苍白球与额叶脑皮质T_(1)WI信号强度比值(G/Gr)水平高于对照组,差异有统计学意义(P<0.05)。logistic回归分析显示,B/A、听力异常和G/Gr水平表达均为影响NHB患儿并发ABE的独立危险因素,差异有统计学意义(P<0.05)。ROC曲线分析显示,B/A、G/Gr、听力异常及三者联合检测NHB患儿并发ABE的AUC值分别为0.773、0.652、0.754、0.863,有较高诊断价值,且联合诊断价值最高(P<0.05)。结论:ABE患儿中B/A、听力异常和G/Gr表达水平明显升高,三者单独和联合检测NHB患儿并发ABE均有较高诊断价值,其中三者联合诊断效果最佳。

不同甲基泼尼松龙治疗方案对胆道闭锁患儿的疗效

目的比较不同甲基泼尼松龙治疗方案对胆道闭锁患儿血清胆红素水平及术后胆管炎预防效果的影响。方法选取我院收治的胆道闭锁患儿114例,均接受改良Kassi术治疗,依照甲基泼尼松龙应用剂量分为小剂量组和大剂量组,每组57例。小剂量组给予小剂量甲基泼尼松龙维持治疗,大剂量组给予大剂量甲基泼尼松龙冲击治疗,对比两组患儿血清胆红素水平、黄疸消退情况、激素相关并发症情况及术后6个月的胆管炎发生情况。结果两组术后3个月总胆红素、直接胆红素水平较术前降低,且大剂量组低于小剂量组(P<0.05)。大剂量组黄疸消退情况优于小剂量组(P<0.05)。大剂量组并发症发生率与小剂量组比较,P>0.05;大剂量组术后胆管炎发生率与小剂量组比较,P>0.05。结论大剂量甲基泼尼松龙治疗可改善胆道闭锁患儿血清胆红素水平,促进黄疸消退,安全性良好。

双重血浆分子吸附联合低剂量血浆置换治疗肝衰竭高胆红素患者的疗效研究

目的探究双重血浆分子吸附(Double Plasma Molecular Absorb System,DPMAS)联合低剂量血浆置换(Plasma Exchange,PE)治疗肝衰竭高胆红素患者的疗效。方法简单随机选取2021年3月—2023年3月潮州市中心医院收治的50例肝衰竭高胆红素患者作为研究对象,采用简单随机化法将其分为DPMAS+PE组(n=25)和PE组(n=25)。观察两组疗效、肝功能、血常规指标与凝血功能。结果DPMAS+PE组总有效率(96.00%)高于PE组(72.00%),差异有统计学意义(P<0.05);DPMAS+PE组谷草转氨酶、总胆红素以及谷丙转氨酶低于PE组,差异有统计学意义(P均<0.05);DPMAS+PE组活化部分凝血酶原时间、凝血酶原活动度优于PE组,差异有统计学意义(P均<0.05)。治疗后两组血红蛋白、血小板计数、白细胞比较,差异无统计学意义(P均>0.05)。结论DPMAS+PE可有效提高在肝衰竭高胆红素患者中的疗效,改善患者的肝功能及凝血功能指标。

T2DM患者不同亚型血清胆红素水平与糖尿病肾病的相关性研究

目的探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者不同亚型血清胆红素水平与糖尿病肾病(diabetic nephropathy,DN)的相关性。方法回顾性分析湖北医药学院附属随州市中心医院2019年1月至2023年5月住院的494例T2DM患者的临床资料,按是否为DN将其分为DN组(175例)和非DN组(319例)。分析血清总胆红素(total bilirubin,TBil)、直接胆红素(direct bilirubin,DBil)、间接胆红素(indirect bilirubin,IBil)水平与DN发生的相关性。结果两组患者的年龄、糖尿病病程、高血压、冠心病、吸烟、饮酒、TBil、DBil、IBil、丙氨酸转氨酶(alanine aminotransferase,ALT)、血尿素氮(blood urea nitrogen,BUN)、血肌酐(serum creatinine,SCr)、尿酸(uric acid,UA)、总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、低密度脂蛋白(low density lipoprotein,LDL)、高密度脂蛋白(high density lipoprotein,HDL)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、体质量指数(body mass index,BMI)、收缩压、空腹血糖(fasting plasma glucose,FPG)、估算的肾小球滤过率比较差异均有统计学意义(P<0.05)。年龄、糖尿病病程、高血压、冠心病、TBil、DBil、IBil、ALT、BUN、SCr、UA、TC、TG、HDL、LDL、HbA1c、BMI和FPG是女性T2DM患者发生DN的影响因素(P<0.05),年龄、糖尿病病程、高血压、冠心病、吸烟、饮酒、TBil、DBil、IBil、ALT、BUN、SCr、UA、TC、TG、HDL、LDL、HbA1c、BMI和FPG是男性T2DM患者发生DN的影响因素(P<0.05)。T2DM患者中,TBil、DBil、IBil与DN发生显著相关(P<0.001),随着TBil(1~15μmol/L)、IBil(1~10μmol/L)、DBil(1~4μmol/L)范围内升高,DN发生风险逐渐降低,但在TBil>15μmol/L、IBil>10μmol/L、DBil>4μmol/L后,TBil、DBil、IBil水平增高不再降低DN发病风险。结论T2DM患者的TBil、DBil、IBil水平均与DN患病风险存在非线性关联,一定水平范围内TBil、DBil、IBil是DN发生的独立保护因素,达到一定水平不再降低DN的发生风险;不同性别下不同亚型血清胆红素与DN的患病风险无明显差异。

分子伴侣介导的自噬对胆红素诱导的小鼠小胶质细胞损伤的影响

目的探讨分子伴侣介导的自噬(chaperone-mediated autophagy,CMA)对未结合胆红素(unconjugated bilirubin,UCB)诱导的小鼠小胶质细胞BV2损伤的影响。方法BV2细胞实验分为两部分。(1)CMA激活实验分为:对照组(等体积二甲基亚砜处理)、QX77组(20μmol/L QX77处理24 h)、UCB组(40μmol/L UCB处理24 h)、UCB+QX77组(20μmol/L QX77和40μmol/L UCB共处理24 h)。(2)细胞转染实验分为:LAMP2A沉默对照组(等体积二甲基亚砜处理)、LAMP2A沉默对照+UCB组(40μmol/L UCB处理24 h)、LAMP2A沉默组(等体积二甲基亚砜处理)、LAMP2A沉默+UCB组(40μmol/L UCB处理24 h)。采用改良MTT法检测细胞存活率,蛋白免疫印迹法检测p65、核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)、半胱氨酸天冬氨酸蛋白水解酶-1(cysteinyl aspartate specific proteinase-1,caspase-1)蛋白表达水平,实时荧光定量聚合酶链反应法检测炎症因子白细胞介素(interleukin,IL)-1β、IL-6、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)mRNA相对表达量,ELISA法检测细胞培养上清液中炎症因子IL-6和TNF-α水平,免疫荧光法检测细胞内p65、NLRP3与热休克同源蛋白70的荧光共定位。结果与UCB组相比,UCB+QX77组细胞存活率升高,炎症相关蛋白p65、NLRP3、caspase-1表达水平降低,炎症因子IL-1β、IL-6、TNF-αmRNA相对表达量降低以及IL-6、TNF-α水平降低(P<0.05)。与对照组相比,UCB组和UCB+QX77组热休克同源蛋白70与p65、NLRP3存在共定位。沉默LAMP2A基因后,与LAMP2A沉默对照+UCB组相比,LAMP2A沉默+UCB组炎症相关蛋白p65、NLRP3、caspase-1蛋白表达水平升高,炎症因子IL-1β、IL-6、TNF-αmRNA相对表达量升高以及IL-6、TNF-α水平升高(P<0.05)。结论CMA在UCB诱导的BV2细胞损伤中被抑制,激活CMA可能通过降低p65和NLRP3蛋白水平,抑制炎症反应,拮抗胆红素神经毒性。

白蛋白-胆红素评分联合肝功能指标及CEA对结直肠癌肝转移的预测价值

目的 探讨白蛋白-胆红素(albumin-bilirubin,ALBI)评分联合肝功能指标及癌胚抗原(carcinoembryonic antigen,CEA)对结直肠癌肝转移的预测价值。方法 回顾性分析2016年1月至2021年7月于兰州大学第二医院接受手术治疗且随访满24个月的结直肠癌患者临床资料,依据随访结果将入组患者分为肝转移组和非肝转移组,并按2∶1比例随机分为建模组与验证组。分析结直肠癌患者发生肝转移的风险因素,采用Lasso-Logistic回归构建预测模型,采用Bootstrap法进行内部验证,应用受试者工作特征曲线、校准曲线和临床决策曲线评价预测模型的可靠性,最后绘制列线图展示预测结果。结果 共入选符合纳入和排除标准的结直肠癌患者195例,其中建模组130例,验证组65例;Lasso回归变量筛选及Logistic回归分析结果显示,ALBI评分(OR=8.062,95%CI:2.545~25.540)、丙氨酸氨基转移酶(alanine transaminase,ALT)(OR=1.037,95%CI:1.004~1.071)与CEA(OR=1.025,95%CI:1.008~1.043)是结直肠癌发生肝转移的独立预测因素;建模组三者联合预测结直肠癌发生肝转移的曲线下面积(area under the curve,AUC)为0.921,灵敏度为78.0%,特异度为95.0%,C-index为0.921,H-L拟合度曲线χ~2=0.851,P=0.654,校准曲线斜率接近1,提示该模型准确度较高,临床决策曲线显示该模型具有良好的临床应用价值。对建模组数据采用Bootstrap法进行1000次重抽样的内部验证,准确度为0.869,Kappa一致性为0.709,AUC为0.913;应用ALBI评分、ALT与CEA单独诊断结直肠癌肝转移时,CEA的AUC最大(0.897),三者联合诊断结直肠癌肝转移的效能最高。验证组三者联合预测结直肠癌发生肝转移的AUC为0.918,灵敏度为85.0%,特异度为95.6%,C-index为0.918,H-L拟合度曲线χ~2=0.586,P=0.746。结论 ALBI评分、ALT与CEA对结直肠癌肝转移具有一定预测价值,三者联合预测结直肠癌肝转移的效能较高,通过其构建的风险预测模型具有良好的临床应用前景。

基于DECT的碘斜率无创评估肝硬化患者肝功能的相关研究

目的:探究碘斜率无创评估肝硬化患者肝功能分级的相关研究,确定碘斜率在肝硬化患者中的应用价值。方法:前瞻性收集包头市中心医院2022年5月至2023年6月期间行腹部双能量CT(DECT)患者,筛选经临床/病理诊断为肝硬化患者59例(ALBI 1、2、3级分别27例、23例、9例),同时选取健康对照患者15例,收集所有入组对象基线资料。通过DECT扫描的动脉期、门脉期、延时期获取碘值以及各期相间隔时间计算碘斜率,采用白蛋白-胆红素评分(ALBI)进行肝功能分级。使用Spearman相关系数分析碘斜率与ALBI之间的相关性;使用单因素方差分析及非参数K-W检验比较组间碘斜率的差异性;使用受试者操作特征(ROC)曲线评估碘斜率鉴别不同肝功能分组的诊断效能,并计算其截断值、敏感度、特异度以及ROC曲线下面积(AUC)。结果:λ1、λ2与ALBI分级(r=-0.82,P<0.01;r=-0.66,P<0.01)间均存在显著负相关;λ1在对照组、肝硬化组ALBI分级各组间差异均有统计学意义(P<0.001),λ2在对照组和肝硬化组间差异具有统计学意义(P<0.001);λ1鉴别对照组vs. ALBI 1级、ALBI 1级vs. ALBI 2级、ALBI 2级vs. ALBI 3级的AUC为0.80、0.86、0.96;λ2鉴别对照组vs. ALBI 1级、ALBI 1级vs. ALBI 2级、ALBI 2级vs. ALBI 3级的AUC为0.64、0.78、0.76。结论:基于DECT的碘斜率与ALBI有显著相关性,能够作为评估肝硬化患者肝功能的可靠指标,且随着肝硬化的加重,评估效能也逐渐提高,具有一定的临床应用价值。

药物相关性胆管消失综合征患者胆红素水平与预后的相关性

目的:观察药物相关性胆管消失综合征(D-VBDS)患者胆红素升高与否与病理形态特点及预后转归之间的相关性。方法:回顾性分析经肝穿刺组织病理检查明确诊断为D-VBDS的患者45例,根据病程中是否出现胆红素升高分为胆红素正常组和高胆红素组,观察两组患者的临床资料、用药史、生化指标、病理形态学特点及预后情况等数据,并对比分析两组患者胆红素升高与否与病理形态特点及预后之间的相关性。结果:胆红素正常组和高胆红素组患者在平均发病年龄、性别构成及病程等方面差异均无统计学意义(P>0.05),中药或中成药用药在两组均占比最高(39.3%vs 40.0%)。除皮肤巩膜黄染外,两组患者其他症状及体征差异均无统计学意义(P>0.05);高胆红素组TBil、DBil、ALP、GGT、TBA及CHOL明显高于胆红素正常组(P<0.05);高胆红素组患者胆色素沉积、毛细胆管胆栓、泡沫样细胞评分均高于胆红素正常组,其他病理形态评分差异均无统计学意义(P>0.05)。细胆管增生、汇管区炎症、纤维化、慢性胆盐淤积是与预后相关的病理形态改变,两组患者预后情况差异无统计学意义(P>0.05)。结论:病程中是否出现胆红素升高不是影响D-VBDS患者预后的主要因素。

胆红素水平与缺血性卒中病人溶栓后出血转化相关性

目的探讨血清胆红素水平与大动脉粥样硬化(LAA)型急性缺血性卒中(AIS)病人静脉溶栓(IVT)治疗后出血转化(HT)的关系。方法LAA型AIS行IVT后的病人473例,根据是否发生HT分成HT组和非HT(NHT)组。采用多因素logistic回归分析总胆红素、直接胆红素和间接胆红素水平与HT之间的关系。结果与NHT组比较,HT组的发病到静脉溶栓时间缩短、入院到静脉溶栓时间延长、美国国立卫生研究院卒中量表评分增加(t=5.27~18.00,P<0.05),总胆红素、间接胆红素和尿酸水平降低(t=2.00~2.28,P<0.05)。血清总胆红素(OR=0.951,95%CI=0.915~0.988)、间接胆红素(OR=0.923,95%CI=0.874~0.974)水平与HT呈负相关。结论血清总胆红素和间接胆红素水平升高能降低LAA型AIS行IVT后病人的HT风险。

新生儿急性胆红素脑病相关危险因素的meta分析

目的:通过meta分析探讨新生儿急性胆红素脑病(ABE)的危险因素,为尽早识别和治疗ABE患儿提供理论依据。方法;检索万方数据库、中国知网、维普、PubmMed、Web of Science、Embase、Cochrane Library建库至2023年8月1日。按照纳入和排除标准筛选文献并提取相关数据,采用RevMan 5.3软件进行meta分析。结果:最终纳入30个临床研究,涉及12965名研究对象,共提取15个相关危险因素。meta分析显示,总胆红素峰值(OR=1.27,95%CI 1.21~1.34)、总胆红素/白蛋白比值(OR=1.47,95%CI 1.21~1.79)、24小时内黄疸(OR=6.03,95%CI 2.73~13.32)、ABO或Rh溶血(OR=3.31,95%CI 2.57~4.26)、血红蛋白水平高(OR=1.05,95%CI 1.01~1.11)、葡萄糖-6-磷酸脱氢酶缺乏(OR=3.82,95%CI 1.98~7.37)、围生期缺氧(OR=12.20,95%CI 1.95~76.27)、新生儿败血症(OR=3.13,95%CI 1.98~4.95)、感染(OR=4.99,95%CI 3.58~6.97)、代谢性酸中毒(OR=2.84,95%CI 1.64~4.91)、颅脑血肿(OR=4.17,95%CI 2.39~7.27)、出生体质量低(OR=3.31,95%CI:1.97~5.55)、出生后体质量下降(OR=1.08,95%CI:1.03~1.13)、母乳缺乏(OR=3.90,95%CI:1.97~7.74)、非医院出生(OR=2.59,95%CI 1.93~3.45)是新生儿ABE危险因素。结论:经文献分析分析出15个新生儿ABE危险因素,但仍需更多大样本、多中心、精确性的前瞻性研究进一步验证。