A novel alpha1-antitrypsin null variant (PiQ0_(Milano))

Alpha1-antitrypsin deficiency is an autosomal recessive disease characterized by reduced serum levels of alpha1-antitrypsin(AAT)due to mutations in the SERPINA1 gene causing early onset pulmonary emphysema and,occasionally,chronic liver disease.We report an incidental finding of a novel null AAT allele,Q0Milano,consisting of a 17 nucleotides deletion in exon 3 of SERPINA1 gene,in an Italian child with persistently increased liver enzymes,a mild decrease in circulating AAT levels and without any pulmonary disease.Q0Milano variant results in an unfunctional protein lacking of AAT active site,as the resultant protein is truncated near PiS locus involved in AAT protein stability.

DETECTION OF ALPHA-1 ANTICHYMOTRYPSIN IN HEPATOCELLULAR CARCINOMA TISSUE

One hundred and fifty-three consecutive cases of HCC and 25 controls from autopsy material were studied by immunohistochemical method in this paper. A review of the histopathology and demonstration of AFP, alpha- 1-antichymotrypsin (AACT), alpha 1-antitrypsin (AAT) and CEA were made.Among the tumor markers. AACT yielded the highest positive rate, 109 cases (71%) out of 153 HCC. CEA was the next, 95 cases (62%) .AFP and AAT gave the same result, 72 cases (47%) . AACT, AAT and CEA were not found in the controls. AFP was present in a few hepatocytes in 1 of 25 controls. The results were in keeping with serum tests so far as the highest positive rate being AACT was concerned. Therefore, combined determination of AACT and AFP would seem a better screening method than by that of AFP alone for survey of HCC.

血清HB-EGF、HIF-1α水平与狼疮性肾炎患儿预后的相关性

【目的】探讨狼疮性肾炎患儿血清肝素结合性表皮生长因子(HB-EGF)、缺氧诱导因子-1α(HIF-1α)水平与患儿预后的相关性。【方法】选取2016年7月至2018年7月榆林市第一医院收治的70例狼疮性肾炎患儿(观察组),对其进行随访观察,随访时间18~36个月。根据随访终止时患儿是否发生复合肾脏终点事件将其分为预后良好组(n=55)和预后不良组(n=15)。选择同期于本院体检的50例健康儿童为对照组,测定入院时不同组别受试者血清HB-EGF、HIF-1α水平,应用受试者工作特征曲线(ROC曲线)及曲线下面积(AUC)评估二者表达水平对狼疮性肾炎患儿预后的预测价值,并对影响患儿预后的相关因素进行Logistic回归分析。【结果】观察组患儿血清HB-EGF、HIF-1α水平均显著高于对照组,差异有统计学意义(P<0.05)。预后不良组患儿血肌酐、血尿素氮及血清HB-EGF、HIF-1α水平均高于预后良好组,差异有统计学意义(P<0.05)。血清HB-EGF、HIF-1α表达水平的曲线下面积(AUC)分别为0.869、0.822,截断值分别为39.692pg/mL、97.448ng/L,敏感度分别为86.70%、66.70%,特异度分别为76.40%、92.70%;二者联合的AUC为0.937,敏感度和特异性为80.00%、96.40%。Logistic分析结果显示:高血清HB-EGF、HIF-1α水平均是影响狼疮性肾炎患儿预后的独立危险因素。【结论】狼疮性肾炎患儿血清HB-EGF、HIF-1α水平明显升高,且其表达水平对患儿预后具有一定的预测价值,二者水平升高是影响狼疮性肾炎患儿预后的危险因素。

Alpha 1-antitrypsin and alpha 1-acid glycoprotein reduce the sensitivity of human dermal fibroblast to endotoxin

Objective: To test the hypothesis that acute phase reactants, such as alpha 1-antitrypsin and alpha 1-acid glycoprotein, could protect mammalian cells from further damage. Methods: Human dermal fibroblasts (5×10 4) were cultured with DMEM plus 10% FBS at 37℃ in a 5% CO 2 incubator. Different doses of LPS (lipopolysaccharide) and/or acute phase reactants were added. After 24 hours, the cultured supernatant was aspirated, the cells were washed, fixed and stained by methylene blue. The unbound stain was washed off. The stained cells were solubilized in 0.1 ml of 1% Triton X-100. The absorbance of each well was measured using an ELISA spectrophotometer. The concentration of LPS which decreased the absorbance to 70% of the control (LPS-free) cultures was defined as LD 30. Results: In order to achieve LD 30 in the presence of acute phase proteins, it was necessary to alter the LPS concentrations. The LD 30 of LPS treated with 0, 0.5, 2, 10 mg/ml antitrypsin and 0, 0.5, 2, 10 mg/ml glycoprotein was 5.4, 6.5, 7.6, 14.2 mg/ml and 5.2, 5.9, 6.9, 10.5 mg/ml, respectively. Statistically, with the treatment of more than 2 mg/ml antitrypsin or glycoprotein, LD 30 increased significantly. Conclusions: Our data show that fibroblasts are susceptible to the direct toxicity of LPS. Alpha 1-antitrypsin and alpha 1-acid glycoprotein can reduce the toxicity and/or increase the tolerance of mammalian cells to LPS.

不同程度膝骨性关节炎患者血清组织蛋白酶D、α1抗胰蛋白酶活性变化及其意义

目的探讨不同程度膝骨性关节炎患者血清组织蛋白酶D（ cathepsin D ，CATD）、α1抗胰蛋白酶（alpha‐1 antitrypsin ，AAT）活性变化及其意义。方法分别收集健康人血清标本（对照组）及Ⅰ～Ⅳ期膝关节炎患者血清标本（观察组）各20份。运用酶联免疫吸附法（ELISA）测定每个标本的CATD、AAT活性，分析不同程度骨性关节炎患者血清CATD、AAT 的活性变化，并与正常对照组进行比较。结果与对照组比较，Ⅰ～Ⅱ期膝关节炎患者血清中CATD酶活性增高（ P ＜0．05），且Ⅱ期高于Ⅰ期（ P ＜0．05）；而Ⅲ～Ⅳ期则活性降低（P ＜0．05），且Ⅳ期比Ⅲ期下降更明显（P ＜0．05）。与对照组比较，Ⅰ～Ⅱ期膝关节炎患者血清中AAT活性增高，且Ⅱ期比Ⅰ期活性高（ P ＜0．05），而Ⅲ～Ⅳ期与对照组比较无统计差异（ P ＞0．05）。结论不同期膝骨性关节炎患者血清中伴随着CATD、AAT两种酶活性改变，测定这两种血清酶活性有利于判断骨性关节炎软骨退变程度。

镇静治疗对危重烧伤患者炎症因子释放的影响

[目的]观察危重烧伤后镇静治疗对促炎/抑炎细胞因子平衡的影响.[方法]46例烧伤Ⅱ度以上,创面总面积＞30％患者随机分为两组,每组23例.对照组按常规补液复苏,观察组在对照组的基础上应用丙泊酚微量持续静脉镇静治疗.分别在镇静前（T0）、镇静后3 h（T1）、镇静后6 h（T2）、镇静后48 h（T3）抽血用ELISA方法检测患者血清中白介素-1（IL-1）、肿瘤坏死因子-α（TNF-α）、IL-10的含量.[结果]与伤前比较,严重烧伤后血清TNF-α、IL-1、IL-10均升高（P＜0.05）,镇静治疗可降低其升高幅度（P＜0.05）.[结论]应用镇静治疗可抑制大面积烧伤患者主要炎症介质的释放,调节促炎/抑炎细胞因子平衡,减轻应激,有利于机体功能的恢复.

Hereditary hemochromatosis:Temporal trends,sociodemographic characteristics,and independent risk factor of hepatocellular cancer–nationwide population-based study

BACKGROUND Hereditary hemochromatosis(HH)has an increased risk of hepatocellular cancer(HCC)both due to genetic risks and iron overload as iron overload can be carcinogenic;HH impacts the increasing risk of HCC,not only through the development of cirrhosis but concerning hepatic iron deposition,which has been studied further recently.AIM To evaluate HH yearly trends,patient demographics,symptoms,comorbidities,and hospital outcomes.The secondary aim sheds light on the risk of iron overload for developing HCC in HH patients,independent of liver cirrhosis complications.The study investigated HH(without cirrhosis)as an independent risk factor for HCC.METHODS We analyzed data from National Inpatient Sample(NIS)Database,the largest national inpatient data collection in the United States,and selected HH and HCC cohorts.HH was first defined in 2011 International Classification of Disease-9th edition(ICD-9)as a separate diagnosis;the HH cohort is extracted from January 2011 to December 2019 using 275.01(ICD-9)and E83.110(ICD-10)diagnosis codes of HH.Patients were excluded from the HH cohort if they had a primary or secondary diagnostic code of cirrhosis(alcoholic,non-alcoholic,and biliary),viralhepatitis,alcoholic liver disease,non-alcoholic fatty liver disease(NAFLD),and non-alcoholic steatohepatitis(NASH).We removed these patients from the HH cohort to rule out bias or ICD-10 diagnostic errors.The HCC cohort is selected from January 2011 to December 2019 using the ICD-9 and ICD-10 codes of HCC.We selected a non-HCC cohort with the 1:1 fixed ratio nearest neighbor(greedy)propensity score method using the patients'age,gender,and race.We performed multivariate analysis for the risk factors of HCC in the HCC and non-HCC matched cohort.We further analyzed HH without cirrhosis(removing HH patients with a diagnosis of cirrhosis)as an independent risk factor of HCC after adjusting all known risk factors of HCC in the multivariate model.RESULTS During the 2011-2019 period,a total of 18031 hospitalizations with a primary or secondary diagnosis of HH(excluding liver diseases)were recorded in the NIS database.We analyzed different patients’characteristics,and we found increments in inpatient population trend with a Ptrend<0.001 and total hospital cost of care trend from$42957 in 2011 to$66152 in 2019 with a Ptrend<0.001 despite no change in Length of Stay over the last decade.The multivariate analyses showed that HH without cirrhosis(aOR,28.8;95%CI,10.4–80.1;P<0.0001),biliary cirrhosis(aOR,19.3;95%CI,13.4–27.6;P<0.0001),non-alcoholic cirrhosis(aOR,17.4;95%CI,16.5–18.4;P<0.0001),alcoholic cirrhosis(aOR,16.9;95%CI,15.9–17.9;P<0.0001),hepatitis B(aOR,12.1;95%CI,10.85–13.60;P<0.0001),hepatitis C(aOR,8.58;95%CI,8.20–8.98;P<0.0001),Wilson disease(aOR,4.27;95%CI,1.18–15.41;P<0.0001),NAFLD or NASH(aOR,2.96;95%CI,2.73–3.20;P<0.0001),alpha1-antitrypsin deficiency(aOR,2.10;95%CI,1.21–3.64;P<0.0001),diabetes mellitus without chronic complications(aOR,1.17;95%CI,1.13–1.21;P<0.0001),and blood transfusion(aOR,1.80;95%CI,1.69–1.92;P<0.0001)are independent risk factor for liver cancer.CONCLUSION Our study showed an increasing trend of in-hospital admissions of HH patients in the last decade.These trends were likely related to advances in diagnostic approach,which can lead to increased hospital utilization and cost increments.Still,the length of stay remained the same,likely due to a big part of management being done in outpatient settings.Another vital part of our study is the significant result that HH without cirrhosis is an independent risk factor for HCC with adjusting all known risk factors.More prospective and retrospective large studies are needed to re-evaluate the HH independent risk in developing HCC.