铁死亡参与四氯化碳致肝纤维化发病过程的研究

目的 探讨铁死亡是否参与CCl4致肝纤维化发病过程。方法 小鼠分为对照组和CCl4组。采用腹腔注射法造模,每隔2 d给药1次,共8次,造模完成后隔2 d处死。通过HE、MASSON和天狼星红染色评价CCl4致小鼠肝损伤及纤维化情况;铁离子检测试剂盒检测小鼠肝组织铁离子含量;MDA检测试剂盒检测小鼠肝组织MDA含量;免疫荧光法观察小鼠肝组织中MDA含量;谷胱甘肽/氧化型谷胱甘肽(GSH/GSSG)评价小鼠肝组织脂质过氧化情况;通过Western Blot和RT - qPCR评价谷胱甘肽过氧化物酶4(GPX4)、铁蛋白(Ferritin)的蛋白和mRNA表达水平。结果 通过HE染色、MASSON染色和天狼星红染色发现,CCl4引起小鼠肝细胞排列紊乱,炎症细胞浸润,纤维化隔片形成。而对照组没有显著的病理变化;CCl4组小鼠肝组织铁离子含量(2.83±0.81) μmol/g较对照组小鼠肝组织铁离子含量(1.54±0.19) μmol/g增加(t = 5.415,P＜0.001);CCl4组MDA荧光强度高于对照组;CCl4组MDA含量(0.74±0.13) nmol/mg较对照组MDA含量(0.21±0.06) nmol/mg增加(t = 15.650,P＜0.001);GSH/GSSG在CCl4组(1.29±0.19)较对照组(1.90±0.16)降低(t = 10.580,P＜0.001);在CCl4组GPX4蛋白相对表达水平(0.27±0.07)较对照组(0.42±0.10)降低(t = 3.000,P = 0.013)。CCl4组Ferritin蛋白相对表达水平(0.18±0.06)较对照组(0.30±0.06)降低(t = 3.571,P = 0.005);CCl4组Ferritin mRNA相对表达水平(1.83±0.60)较对照组(0.84±0.30)降低(t = 4.420,P＜0.001)。CCl4组GPX4 mRNA相对表达水平(1.10±0.45)较对照组(3.54±0.87)降低(t = 7.385,P＜0.001)。结论 铁死亡参与了四氯化碳致肝纤维化的发病过程。     

使用多肿瘤标志物蛋白质芯片诊断系统(C-12)检测胃癌的临床价值

目的研究多肿瘤标志物蛋白芯片诊断系统用于胃癌的诊断价值。方法用多肿瘤标志物蛋白芯片诊断系统检测50例正常人,70例胃良性疾病及80例胃癌患者血清中十二种常见的肿瘤标志物:甲胎蛋白(AFP),癌胚抗原(CEA),神经元特异性烯醇化酶(NSE),糖原125(CA125),糖原153(CA153),糖原242(CA242),糖原199(CA199),前列腺特异性抗原(PSA),游离前列腺特异性抗原(f-PSA),铁蛋白(FER),β-人绒毛膜促性腺激素(β-HCG),人生长激素(HGH)的水平并进行统计学分析。结果80例胃癌患者血清有74例血清肿瘤标志物为阳性(阳性率为92.75%),70例良性胃疾病中10例肿瘤标志物为阳性(阳性率为14.28%),50份正常对照血清有1例血清肿瘤标志物为阳性(特异性为98%)。试验还发现部分胃癌患者血清中出现NSE,HGH,PSA,f-PSA。结论多肿瘤蛋白芯片的应用,对胃癌患者的术前肿瘤良恶性的判定有一定的临床应用价值。     

Association between Body Iron Status and Leukocyte Telomere Length,a Biomarker of Biological Aging,in a Nationally Representative Sample of US Adults

Background

Excess iron levels can induce oxidative stress and could therefore affect telomere attrition. However, little is known about the impact of body iron status on telomere length.

The Prognostic Significance of Elevated Levels of Serum Ferritin Before Chemotherapy in Patients With Non-Hodgkin Lymphoma

BackgroundElevated levels of serum ferritin have been documented to be an adverse prognostic factor in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation. The purpose of this study was to estimate the correlation between elevated levels of serum ferritin and survival outcomes in patients with non-Hodgkin lymphoma (NHL).Patients and MethodsA total of 267 patients who were newly diagnosed with NHL and who received chemotherapy between September 1999 and April 2012 were retrospectively analyzed.ResultsIn multivariate analysis, other chemotherapy regimens excluding CHOP-like chemotherapy regimens (cyclophosphamide, adriamycin, vincristine, prednisolone) and RCHOP (rituximab plus CHOP), a high level of β2-microglobulin, a high-intermediate/high risk according to the international prognostic index (IPI), and elevated levels of serum ferritin were all significant independent prognostic factors for 5-year progression-free survival rates. RCHOP and other chemotherapy regimens, a high level of β2-microglobulin, a high-intermediate/high IPI risk, and high levels of serum ferritin were significant independent prognostic factors for 5-year overall survival rates.ConclusionElevated levels of serum ferritin of 500 ng/mL or more as well as the use of chemotherapy regimens besides CHOP-like or RCHOP, a high-intermediate/high risk IPI, and a high level of beta2-microglobulin in NHL may be an important marker for predicting poor survival outcomes.     

Hyperferritinemia in neonatal and infantile human parechovirus-3 infection in comparison with other infectious diseases

Human parechovirus-3 (HPeV-3) has been associated with severe clinical manifestations in neonates and infants in the form of sepsis or hemophagocytic lymphohistiocytosis (HLH)-like illness. To clarify the clinical features of HPeV-3 infection, we compared clinical signs and laboratory findings among enteroviruses (EVs), HPeV-3, and other infections. Participants were 26 febrile infants in whom EVs (n = 20) or HPeV-3 (n = 6) were isolated from throat swab or fecal specimens. Clinical and laboratory data were compared among EVs, HPeV-3, respiratory syncytial virus (RSV) infection (n = 15), and bacterial meningitis (n = 8) groups. Apnea was frequently seen in the HPeV-3 group although there were no significant differences in other clinical symptoms. Leukocyte count was significantly lower in the HPeV-3 group than in the EV and RSV group. Platelet count was significantly lower in the HPeV-3 group than in the RSV group. Serum ferritin levels in the HPeV-3 group (mean, 2437 ng/ml) and EV group (mean, 552 ng/ml) were significantly higher than in the RSV group (mean 237 ng/ml; P = 0.008 and P = 0.002, respectively). The frequency of patients with clearly high ferritin levels ≥1000 ng/ml was comparatively higher in the HPeV-3 group (4/6) than the EV group (3/20) (P = 0.03). In the HPeV-3 group, ferritin levels were high on Days 4–5. Elevated ferritin levels, decreased leukocyte and platelet counts could offer diagnostic clues to HPeV-3 infection in infant. These laboratory findings might be associated with aberrant immune response to HPeV-3, which could contribute to the development of sepsis or HLH-like illness in neonates.     

恩替卡韦治疗乙型肝炎患者血清铁蛋白的检测与临床意义

目的:检测慢性乙型肝炎患者血清铁蛋白(SF)的水平及恩替卡韦抗病毒治疗前后的变化。方法:采用化学发光法检测102例慢性乙型肝炎患者SF水平,并检测ALT、HBV DNA、基因型等指标。结果:轻度、中度至重度患者SF水平依次递增,均高于健康对照组,SF与ALT水平呈正相关,不同基因型之间SF水平差异无统计学意义(P>0.05)。抗病毒治疗48周后,ALT复常组及HBV DNA阴性组患者SF水平均明显下降。结论:检测SF水平可以在一定程度上反映肝脏炎性反应程度。定期监测SF的变化,对判断恩替卡韦抗病毒疗效及疾病预后有一定意义。     

Ferritin in bone marrow and serum in iron deficiency and iron overload

Summary Nonheme iron and ferritin in the bone marrow and serum ferritin was investigated in patients with iron deficiency anaemia or iron overload. As controls served patients without any disturbance of the iron metabolism.There is a precise correlation between the nonheme iron and ferritin in the bone marrow of patients with and without disturbance of iron metabolism. A correlation was also found between the ferritin in the bone marrow and the serum. Nonheme iron and ferritin in the bone marrow and serum ferritin was decreased in patients with iron deficiency anaemia. Conversely, the same parameters were increased in patients with iron overload.     

Increase in Glycosylated and Nonglycosylated Serum Ferritin in Chronic Alcoholism and Their Evolution during Alcohol Withdrawal

Increase in serum ferritin, which occurs in 40 to 70% of chronic alcoholics, remains poorly understood. We tested the hypothesis which links hyperferritinemia in chronic alcoholism not only to ferritin release from damaged liver cells, but also to increased ferritin secretion. Fifty-eight chronic alcoholic patients hospitalized for alcohol withdrawal were subdivided into three groups according to liver damage. Their serum levels of ferritin and ferritin bound to concanavalin A (ferritin Con A, which represents glycosylated, i.e., secreted ferritin) were measured serially on days 1, 7, and 11 of withdrawal and compared with a control group. The results were: (1) Total serum ferritin increased in alcoholics. Both free and Con A ferritins increased in equal proportions, the ferritin Con A to total ferritin ratio remaining unchanged. The increase was dependent on liver disease, as both free and Con A ferritins increased significantly with the severity of liver illness. Serum ferritin levels were related to iron status: it correlated with hepatic iron concentration (obtained in 19 patients); however, high ferritin values were not related to the degree of iron overload, which remained low. Finally, there was no correlation between serum ferritin and the average of alcohol consumption. (2) Both free and Con A ferritin decreased by about 40% during alcohol withdrawal. In conclusion, we have demonstrated that (1) total serum ferritin is increased in chronic alcoholism and (2) that this ferritin increase is due in part to an increase in ferritin Con A, proof of the induction of ferritin secretion by alcohol in humans.     

Biochemistry tests in hospitalized COVID-19 patients: Experience from a Canadian tertiary care centre

BackgroundCoronavirus Disease 2019 (COVID-19) has variable clinical presentation, from asymptomatic to severe disease leading to death. Biochemical markers may help with management and prognostication of COVID-19 patients; however, their utility is still under investigation.MethodsA retrospective study was conducted to evaluate alanine aminotransferase, C-reactive protein (CRP), ferritin, lactate, and high sensitivity troponin T (TnT) levels in 67 patients who were admitted to a Canadian tertiary care centre for management of COVID-19. Logistic, cause-specific Cox proportional-hazards, and accelerated failure time regression modelling were performed to assess the associations of initial analyte concentrations with in-hospital death and length of stay in hospital; joint modelling was performed to assess the associations of the concentrations over the course of the hospital stay with in-hospital death.ResultsInitial TnT and CRP concentrations were associated with length of stay in hospital. Eighteen patients died (27%), and the median initial TnT concentration was higher in patients who died (55 ng/L) than those who lived (16 ng/L; P < 0.0001). There were no survivors with an initial TnT concentration > 64 ng/L. While the initial TnT concentration was predictive of death, later measurements were not. Only CRP had prognostic value with both the initial and subsequent measurements: a 20% increase in the initial CRP concentration was associated with a 14% (95% confidence interval (CI): 1–29%) increase in the odds of death, and the hazard of death increased 14% (95% CI: 5–25%) for each 20% increase in the current CRP value. While the initial lactate concentration was not predictive of death, subsequent measurements were.ConclusionCRP, lactate and TnT were associated with poorer outcomes and appear to be useful biochemical markers for monitoring COVID-19 patients.