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Objective:To analyze the changes of NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasomes in peripheral blood of patients with diabetic nephropathy (DN) and its clinical significance.Methods:208 patients with type 2 diabetes (T2DM) admitted to our hospital from Feb. 2018 to Dec. 2020 were selected and were divided them into 3 groups according to the urine albumin (UA) /urinary creatinine (UC) ratio (UACR) : simple T2DM group (UACR<30 mg/g) 83 cases, microalbuminuria group (UACR 30-300 mg/g) 70 cases, and massive proteinuria group (UACR>300 mg/g) 55 cases; Fifty healthy volunteers were selected as the control group. General data of each group were collected. Western blot was used to detect the level of NLRP3 in peripheral blood, and enzyme-linked immunosorbent assay (ELISA) kit was used to detect the level of serum interleukin (IL) -1β and IL-18. Logistic regression was employed to analyze the occurrence of DN in T2DM patients. Receiver operating characteristic curve (ROC) curve was used to analyze the value of NLRP3, IL-1β, IL-18 in the diagnosis of DN in peripheral blood.Results:Compared with the control group, the course of disease, FBG, LDL-C, TG, TC, SCr, BUN, HbA1c, NLRP3 protein, IL-1β and IL-18 significant increased in the other 3 groups, and HDL-C, ALB, and eGFR were significant decreased, and the difference was statistically significant ( P<0.05) . The order of their level changes was: massive proteinuria group>microalbuminuria group>pure T2DM group; Pearson test found that peripheral blood NLRP3, IL-1β, IL-18 levels were significantly positively correlated with UACR, LDL-C, TG, and TC ( P<0.001) , while they were significantly negatively correlated with HDL-C ( P<0.001) .The results of unconditional Logistic regression analysis showed that the course of disease, FBG, HDL-C, LDL-C, TG, TC, SCr, BUN, ALB, HbA1c, eGFR, NLRP3 protein, IL-1β and IL-18 may all be related to DN-related in patients with T2DM ( P<0.05) . Multivariate analysis found that high levels of BUN, ALB, HbA1c, EGFR, NLRP3 protein and IL-1 were found β and IL-18 are high risk factors for DN in patients with T2DM ( P<0.05) . The ROC curve showed that the combination of peripheral blood NLRP3, IL-1β, and IL-18 predicted the highest AUC, sensitivity, and specificity of DN in patients with T2DM as 0.918, 93.40%, and 90.13%, respectively. Conclusions:Different stages of DN are often accompanied by increased levels of NLRP3, IL-1β, and IL-18 in peripheral blood. Strengthening the monitoring of NLRP3 inflammasome levels can help assess the renal function of patients and provides a theoretical basis for early diagnosis of DN.
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Objective@#To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy.@*Methods@#This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS.@*Results@#There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109).@*Conclusion@#There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.
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<p><b>OBJECTIVE</b>To analyze the clinicopathological characteristics of patients with anaplastic lymphoma kinase (ALK) rearrangements in lung adenocarcinoma, and the clinical therapy and prognosis of the patients.</p><p><b>METHODS</b>Clinicopathological data of 34 cases of ALK-positive patients treated in the Beijing Chest Hospital from 2005 to 2014 were reviewed. The expression of ALK proteins in the resected tumors was detected by immunohistochemistry, and EGFR mutations were examined by polymerase chain reaction and a direct DNA sequencing method.</p><p><b>RESULTS</b>Among the 34 patients, 20 were male and 14 were female, the median age was 49, and 11 were smokers and 23 were never smokers. The clinical stages of the patients were stage IA in 5 patients, IB in one patient, IIA in two patients, IIIA in 16 patients, IIIB in 5 patients, IV in 4 patients, and one patient of unknown stage. ALK-positive tumors showed strong granular staining in cell cytoplasm by immunohistochemistry. Forteen patients were solid predominant subtype with mucin production, 10 of acinar predominant subtype, 6 of papillary predominant subtype, 3 of micropapillary predominant subtype, and one was of colloid variant. There were 18 cases with mucin production, 6 cases had signet-ring cell morphology, and 10 cases showed cribriform pattern. Only one patient had coexistence of ALK rearrangement and EGFR mutation (L858R at exon 21). Of the 34 patients, 24 patients were followed up. The median follow up of the 24 patients was 11.0 months (1.7-48.7 months).</p><p><b>CONCLUSIONS</b>ALK-positive tumors as a molecular subtype of lung adenocarcinoma have distinct clinicopathological features. The histological findings of ALK-positive tumors are characterized by solid predominant subtype with mucin production, acinar predominant subtype, signet-ring cells and cribriform structures. They were rarely co-mutated with EGFR mutation.</p>