Application of a six sigma model to evaluate the analytical performance of urinary biochemical analytes and design a risk‐based statistical quality control strategy for these assays: A multicenter study

BackgroundThe six sigma model has been widely used in clinical laboratory quality management. In this study, we first applied the six sigma model to (a) evaluate the analytical performance of urinary biochemical analytes across five laboratories, (b) design risk‐based statistical quality control (SQC) strategies, and (c) formulate improvement measures for each of the analytes when needed.MethodsInternal quality control (IQC) and external quality assessment (EQA) data for urinary biochemical analytes were collected from five laboratories, and the sigma value of each analyte was calculated based on coefficients of variation, bias, and total allowable error (TEa). Normalized sigma method decision charts for these urinary biochemical analytes were then generated. Risk‐based SQC strategies and improvement measures were formulated for each laboratory according to the flowchart of Westgard sigma rules, including run sizes and the quality goal index (QGI).ResultsSigma values of urinary biochemical analytes were significantly different at different quality control levels. Although identical detection platforms with matching reagents were used, differences in these analytes were also observed between laboratories. Risk‐based SQC strategies for urinary biochemical analytes were formulated based on the flowchart of Westgard sigma rules, including run size and analytical performance. Appropriate improvement measures were implemented for urinary biochemical analytes with analytical performance lower than six sigma according to the QGI calculation.ConclusionsIn multilocation laboratory systems, a six sigma model is an excellent quality management tool and can quantitatively evaluate analytical performance and guide risk‐based SQC strategy development and improvement measure implementation.     

Establishment of age‐ and sex‐specific reference intervals for serum liver function tests in pediatric population aged 1–<18 years: A prospective study

BackgroundThe diagnosis, treatment, and prognosis of pediatric diseases rely on the accurate establishment of the reference interval (RI). This study aimed to establish pediatric RIs for liver function tests and evaluated the correlation of the analytes.MethodsPediatric population (aged 1–<18 years) was prospectively recruited in Jilin Province, China. Analytes detected by Ortho VITORS 5600 automatic biochemical analyzer. All strata were divided using the regression tree and Harris and Boyd''s method. The dynamic changes of RI were evaluated by the lambda‐mu‐sigma method.ResultsReference individuals were comprised of 6,322 children and adolescents. Age and sex differences were present in all analytes except serum total protein. The serum albumin, total protein, γ‐glutamyl transferase, total bilirubin, and unconjugated bilirubin levels increased with age while serum aspartate aminotransferase was opposite. The serum alanine aminotransferase level reached a trough at the age of 5 and later steadily in males but slowly decreased in females. The serum alkaline phosphatase level dropped rapidly after reaching a peak at 9 years old in females and 12 years old in males. RIs were divided into 11 partitions at most and 5 partitions at least. The strongest correlation between analytes was total bilirubin and unconjugated bilirubin (r = 0.788), followed by total bilirubin and albumin (r = 0.511).ConclusionsAnalytes show unique dynamic changes in pediatric population. The correlations among liver function tests can inform future studies of particular variables. Age‐ and sex‐special pediatric RIs should be established to help an accurate diagnosis of disease.     

Evaluation of the analytical performance of endocrine analytes using sigma metrics

Background(a) To evaluate the clinical performance of endocrine analytes using the sigma metrics (σ) model. (b) To redesign quality control strategies for performance improvement.MethodsThe sigma values of the analytes were initially evaluated based on the allowable total error (TEa), bias, and coefficient of variation (CV) at QC materials level 1 and 2 in March 2018. And then, the normalized QC performance decision charts, personalized QC rules, quality goal index (QGI) analysis, and root causes analysis (RCA) were performed based on the sigma values of the analytes. Finally, the sigma values were re‐evaluated in September 2018 after a series of targeted corrective actions.ResultsBased on the initial sigma values, two analytes (FT3 and TSH) with σ > 6, only needed one QC rule (1_3S) with N2 and R500 for QC management. On the other hand, seven analytes (FT4, TT4, CROT, E2, PRL, TESTO, and INS) with σ < 4 at one QC material level or both needed multiple rules (1_3S/2_2S/R_4S/4_1S/10_X) with N6 and R10‐500 depending on different sigma values for QC management. Subsequently, detailed and comprehensive RCA and timely corrective actions were performed on all the analytes base on the QGI analysis. Compared with the initial sigma values, the re‐evaluated sigma metrics of all the analytes increased significantly.ConclusionsIt was demonstrated that the combination of sigma metrics, QGI analysis, and RCA provided a useful evaluation system for the analytical performance of endocrine analytes.     

Hematological changes associated with COVID‐19 infection

BackgroundThe unresolved COVID‐19 pandemic considerably impacts the health services in Iraq and worldwide. Consecutive waves of mutated virus increased virus spread and further constrained health systems. Although molecular identification of the virus by polymerase chain reaction is the only recommended method in diagnosing COVID‐19 infection, radiological, biochemical, and hematological studies are substantially important in risk stratification, patient follow‐up, and outcome prediction.AimThis narrative review summarized the hematological changes including the blood indices, coagulative indicators, and other associated biochemical laboratory markers in different stages of COVID‐19 infection, highlighting the diagnostic and prognostic significance.MethodsLiterature search was conducted for multiple combinations of different hematological tests and manifestations with novel COVID‐19 using the following key words: “hematological,” “complete blood count,” “lymphopenia,” “blood indices,” “markers” "platelet" OR "thrombocytopenia" AND "COVID‐19," "coronavirus2019," "2019‐nCoV," OR "SARS‐CoV‐2." Articles written in the English language and conducted on human samples between December 2019 and January 2021 were included.ResultsHematological changes are not reported in asymptomatic or presymptomatic COVID‐19 patients. In nonsevere cases, hematological changes are subtle, included mainly lymphocytopenia (80.4%). In severe, critically ill patients and those with cytokine storm, neutrophilia, lymphocytopenia, elevated D‐dimer, prolonged PT, and reduced fibrinogen are predictors of disease progression and adverse outcome.ConclusionMonitoring hematological changes in patients with COVID‐19 can predict patients needing additional care and stratify the risk for severe course of the disease. More studies are required in Iraq to reflect the hematological changes in COVID‐19 as compared to global data.     

Clinical and laboratory characteristics of severe and non‐severe patients with COVID‐19: A retrospective cohort study in China

BackgroundPatients diagnosed with the novel coronavirus disease (COVID‐19) who develop severe symptoms need to be determined in advance so that appropriate treatment strategies are in place.MethodsTo determine the clinic features of patients diagnosed definitely with COVID‐19 and evaluate risk factors for severe outcome, the medical records of hospitalized patients were reviewed retrospectively by us and data were compiled. Laboratory data from 90 cases were analyzed, and COVID‐19 patients were classified into two groups (severe and non‐severe) based on the severity.ResultsSevere COVID‐19 cases on admission had higher leukocyte and neutrophil counts, neutrophil‐to‐lymphocyte ratio (NLR), D‐dimer, fibrinogen, C‐reactive protein levels, and lower lymphocyte counts compared with those of non‐severe cases (p < 0.05). The area under the curve (AUC) for leukocyte counts, neutrophil counts, and levels of C‐reactive protein was 0.778, 0.831, and 0.800, respectively. The thresholds were 7.70 × 10⁹/L for leukocyte counts, 5.93 × 10⁹/L for neutrophil counts, and 75.07 mg/L for C‐reactive protein, respectively. Logistic regression analyses indicated that higher white blood cell (WBC) counts (OR, 1.34; 95% CI, 1.05–1.71), neutrophil counts (OR, 1.35; 95% CI, 1.06–1.73), and C‐reactive protein levels (OR, 1.02; 95% CI, 1.0–1.04) were several predictive factors for severe outcome. Severe COVID‐19 patients had a reduction in WBC counts, D‐dimer, C‐reactive protein, and fibrinogen upon discharge from hospital, while lymphocyte counts increased (p < 0.05).ConclusionCounts of WBC, neutrophil, and lymphocyte, NLR, and levels of C‐reactive protein, D‐dimer, and fibrinogen are helpful for prediction of the deterioration trend in patients diagnosed with COVID‐19.     

Does initiation of an ambulance pre‐alert call reduce the door to needle time in acute myocardial infarct?

Objectives

To assess the effect an ambulance pre‐alert call for patients with suspected acute myocardial infarction (AMI) would have on door to needle (DTN) times.

Methods

We carried out back to back audits of DTN times following the initiation of the pre‐alert calls.

Participants

All patients thrombolysed within the emergency department between July 2003 and April 2004 (inclusive).

Statistical analysis

Mean DTN times and time to ECG pre‐change and post‐change were compared using the Two sample t test. The Fisher''s exact test was used to compare pre‐change and post‐change proportions of patients seen within guideline times.

Results

In total, 73 patients were thrombolysed with 40 of these arriving by ambulance. Eighteen of these 40 were pre‐change and 22 were post‐change. Four patients were excluded. Fifty per cent of the pre‐change group had a DTN time of <30 minutes compared with 91% of the post‐change group (p = 0.005, Fisher''s exact test). The phase one mean DTN time was found to be significantly greater than that for phase two (Two sample t test, p = 0.016; 95% CI 1.6 to 14.6).

Conclusions

There was a significant reduction in DTN times after the introduction of the pre‐alert call.     

Simultaneous quantitation of four androgens and 17-hydroxyprogesterone in polycystic ovarian syndrome patients by LC-MS/MS

BackgroundDue to the low concentration of androgens in women and the limitation of immunoassays, it remains a challenge to accurately determine the levels of serum androgens in polycystic ovary syndrome (PCOS) patients for clinical laboratories. In this report, a liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method was developed and validated for simultaneous quantitation of testosterone (T), androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone (DHT), and 17‐hydroxyprogesterone (17‐OHP) that are associated with PCOS.MethodsThe serum samples were processed by protein precipitation and solid phase extraction before analysis with the in‐house developed LC‐MS/MS. The chromatographic separation was achieved with a C18 column, using a linear gradient elution with two mobile phases: 0.02% formic acid in water (phase A) and 0.1% formic acid in methanol (phase B). The separated analytes were detected by positive or negative electrospray ionization mode under multiple reaction monitoring (MRM).ResultsThe assay for all the five analytes was linear, stable, with imprecision less than 9% and recoveries within ±10%. The lower limits of quantification were 0.05, 0.05, 5, 0.025, and 0.025 ng/mL for T, A4, DHEAS, DHT, and 17‐OHP, respectively. In the receiver operating characteristic curve (ROC) analyses with the PCOS (n = 63) and healthy (n = 161) subjects, the AUC of the four‐androgen combined was greater than that of any single androgen tested in PCOS diagnosis.ConclusionsThe LC‐MS/MS method for the four androgens and 17‐OHP showed good performance for clinical implementation. More importantly, simultaneous quantitation of the four androgens provided better diagnostic power for PCOS.     

Establishing pediatric reference intervals for 13 biochemical analytes derived from normal subjects in a pediatric endocrinology clinic in Korea

ObjectivesDefining pediatric reference intervals is one of the most difficult tasks for laboratory physicians. The continuously changing physiology of growing children makes their laboratory values moving targets. In addition, ethnic and behavioral differences might also cause variations. The aim of this study was to establish age- and sex-specific partitioned reference intervals for 13 serum biochemical analytes in Korean children.Design and methodsA total of 2474 patients, girls aged 2–14 years and boys aged 2–16 years, who underwent a short stature workup but were diagnosed as normal at the Pediatric Endocrinology Clinic of Severance Hospital (Seoul, Korea) between September 2010 and June 2012 were included in this study. The levels of serum calcium, inorganic phosphorus, blood urea nitrogen, creatinine, uric acid, glucose, total cholesterol, total protein, albumin, alkaline phosphatase, aspartic aminotransferase, alanine aminotransferase, and total bilirubin were measured using a Hitachi 7600 analyzer (Hitachi High-Technologies Corporation, Tokyo, Japan). Reference intervals were partitioned according to sex or age subgroups using the Harris and Boyd method.ResultsMost analytes except calcium and albumin required partitioning either by sex or age. Age-specific partitioned reference intervals for alkaline phosphatase, creatinine, and total bilirubin were established for both males and females after being partitioned by sex. Additional age-specific partitioning of aspartic aminotransferase in females and total protein and uric acid in males was also required. Inorganic phosphorus, total cholesterol, alanine aminotransferase, blood urea nitrogen, and glucose were partitioned only by sex.ConclusionsThis study provided updated age- and sex-specific pediatric reference intervals for 13 basic serum chemistry analytes from a sufficient number of healthy children by using a modern analytical chemistry platform.     

Cardiac injury is associated with inflammation in geriatric COVID‐19 patients

BackgroundGeriatric patients with coronavirus disease (COVID‐19) are at high risk of developing cardiac injury. Identifying the factors that affect high‐sensitivity cardiac troponin I may indicate the cause of cardiac injury in elderly patients, and this could hopefully assist in protecting heart function in this patient population.MethodsOne hundred and eighty inpatients who were admitted for COVID‐19 were screened. Patients older than 60 years were included in this study, and the clinical characteristics and laboratory results of the cohort were analyzed. The correlation between cardiac injury and clinical/laboratory variables was statistically analyzed, and further logistic regression was performed to determine how these variables influence cardiac injury in geriatric patients.ResultsAge (p < 0.001) significantly correlated with cardiac injury, whereas sex (p = 0.372) and coexisting diseases did not. Rising procalcitonin (p = 0.001), interleukin‐2 receptor (p < 0.001), interleukin 6 (p = 0.001), interleukin 10 (p < 0.001), tumor necrosis factor α (p = 0.001), high‐sensitivity C‐reactive protein (p = 0.001), D‐dimer (p < 0.001), white blood cells (p < 0.001), neutrophils (p = 0.001), declining lymphocytes (p < 0.001), and natural killer cells (p = 0.005) were associated with cardiac injury and showed predictive ability in the multivariate logistic regression.ConclusionOur results suggest that age and inflammatory factors influence cardiac injury in elderly patients. Interfering with inflammation in this patient population may potentially confer cardiac protection.     

Exploratory assessment of serological tests to determine antibody titer against SARS‐CoV‐2: Appropriateness and limits

BackgroundSerological tests can be used to detect antibodies in the serum of subject''s after SARS‐CoV‐2 infection and vaccination. Currently, variability in antibody titers and the availability of a multiplicity of serological tests have made it necessary to highlight their appropriateness and limitations in various diagnostic settings.MethodsThis study is part of Covidiagnostix, a multicenter project aimed at the assessment of the health technology used in SARS‐CoV‐2 serological tests. Based on data gained from the analysis of over 5000 subjects, a selected number of serum samples, representative of different diagnostic settings, were analyzed first by qualitative immunoassays (IgA, M, and G MILLIPLEX^® SARS‐CoV‐2 tests based on Luminex^®) to define the immunoglobulins serum composition and subsequently by four serological diagnostic tests (Elecsys Anti‐SARS‐CoV‐2 and Elecsys Anti‐SARS‐CoV‐2 S by Roche, SARS‐CoV‐2 IgG by Siemens Healthcare, and CHORUS SARS‐CoV‐2 “NEUTRALIZING” Ab by DIESSE). The first WHO International Standard for SARS‐CoV‐2 was also analyzed using the same methods.ResultsThis study evaluated the antibody content and titer of the WHO Standard and serum of subjects with/without previous infection and before/after vaccination for SARS‐CoV‐2.ConclusionThe definition of antibodies in the WHO standard and the analysis of serum samples allowed for the identification of the appropriateness of serological tests in each diagnostic setting, increasing the effectiveness of the resulting laboratory data. Furthermore, we found that it would be optimal to produce new international standards against the S1 domain and RBD of the SARS‐CoV‐2 spike protein for a more effective serological monitoring of vaccination.     

The utility of SARS‐CoV‐2 nucleocapsid protein in laboratory diagnosis

BackgroundThe Coronavirus Disease 2019 (COVID‐19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which has now become a global pandemic owing to its high transmissibility. The SARS‐CoV‐2 nucleocapsid protein tests are playing an important role in screening and diagnosing patients with COVID‐19, and studies about the utility of SARS‐CoV‐2 nucleocapsid protein tests are increasing now.MethodsIn this review, all the relevant original studies were assessed by searching in electronic databases including Scopus, Pubmed, Embase, and Web of Science. “SARS‐CoV‐2”, “COVID‐19”, “nucleocapsid protein”, and “antigen detection” were used as keywords.ResultsIn this review, we summarized the utility of SARS‐CoV‐2 nucleocapsid protein in laboratory diagnosis. Among the representative researches, this review analyzed, the sensitivity of SARS‐CoV‐2 nucleocapsid protein detection varies from 13% to 87.9%, while the specificity could almost reach 100% in most studies. As a matter of fact, the sensitivity is around 50% and could be higher or lower due to the influential factors.ConclusionIt is well suggested that SARS‐CoV‐2 nucleocapsid protein is a convenient method with a short turnaround time of about half an hour, and the presence of N antigen is positively related to viral transmissibility, indicating that SARS‐CoV‐2 N protein immunoassays contribute to finding out those infected people rapidly and segregating them from the uninfected people.     

Association between aldehyde dehydrogenase 2 gene rs671 G>A polymorphism and alcoholic liver cirrhosis in southern Chinese Hakka population

BackgroundAlcoholic liver cirrhosis (ALC) endangering people''s health. The association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and ALC is not clear. To analyze the relationship between ALDH2 and ALC among Hakka population in southern China.MethodsA total of 292 ALC patients and 278 controls were included in the study. The ALDH2 gene rs671 polymorphism was analyzed by polymerase chain reaction (PCR)‐gene chip. Relevant information and medical records of these participants were collected.ResultsThe ALC patients had higher percentage of smoking, lower prevalence of hypertension, higher level of alanine aminotransferase (ALT), aspertate aminotransferase (AST), alkaline phosphatase (ALP), gamma‐glutamyltransferase (GGT), total bile acid (TBA), total bilirubin (Tbil), and direct bilirubin (Dbil), lower level of total cholesterol (TC), high‐density lipoprotein‐cholesterol (HDL‐C), and low‐density lipoprotein‐cholesterol (LDL‐C) than controls. The proportions of the G/A genotype (p = 0.017), G/A plus A/A genotype (p = 0.023) and A allele (p = 0.031) were significantly higher in ALC patients than that of controls. ALC patients with G/A genotype had higher TC, HDL‐C, and Apo‐A1 than those with G/G genotype, while with A allele had higher HDL‐C, and Apo‐A1 than those with G allele. Logistic regression analysis indicated that ALDH2 SNP rs671 G/A plus A/A genotypes (A allele carriers) (OR 2.030, 95% CI 1.109–3.715, p = 0.022) in the dominant model was the risk factor for ALC.Conclusions ALDH2 A allele (G/A + A/A genotypes) increased the risk of developing ALC among Hakka people in southern China. The results should enrich the relevant data and provide valuable information for the future related research.     

Analysis of serum gastrin-17 and Helicobacter pylori antibody in healthy Chinese population

BackgroundGastrin‐17 (G‐17) and Helicobacter pylori (H pylori) antibody are widely used in the screening of gastric diseases, especially in gastric cancer. In this study, we aimed to evaluate the value of G‐17 and H pylori antibody in gastric disease screening.MethodsHealthy males and females (1368 and 1212, respectively) aged between 21‐80 years were recruited for the study. Serum G‐17 value was measured using ELISA, and H pylori antibodies were measured using Western blotting. Statistical analyses were performed using the chi‐square, Mann‐Whitney U, and Kruskal‐Wallis H tests.ResultsSerum G‐17 level was higher in the H pylori‐positive group than in the negative group. Serum G‐17 level was higher in the type 1 H pylori‐positive group than in the type 2 H pylori‐positive group. Further, serum G‐17 level was higher in females than in males and showed significant differences among different age‐groups, with changes in trend proportional to the age. The positive rate of H pylori infection in all the subjects was 58.29% and did not show a significant difference between males and females. However, it showed significant differences among different age‐groups, with the changing trend proportional to the age.ConclusionAnalysis of serum G‐17 level and H pylori antibody typing is valuable in gastric disease screening. Every laboratory should establish its own reference interval for G‐17 level.     

The Estimation of Lidocaine and Prilocaine in Biological Material by gas Chromatography

Abstract

Objectives. To determine the hemolysis interference on biochemical tests and immunoassays performed on Roche Diagnostics analyzers, according to different maximum allowable limits. Design and methods. Heparinized plasma and serum pools, free of interferences, were overloaded by increasing amounts of a hemoglobin-titrated hemolysate. This interference was evaluated for 45 analytes using Modular^® and Cobas^® analyzers. For each parameter, the hemolysis index (HI) corresponding to the traditional ± 10% change of concentrations from baseline (± 10%Δ) was determined, as well as those corresponding to the analytical change limit (ACL), and to the reference change value (RCV). Then, the relative frequencies distribution (% RFD) of hemolyzed tests performed in a hospital laboratory over a 25-day period were established for each HI as allowable limit. Results. Considering the ± 10%Δ, the analyte concentrations enhanced by hemolysis were: Lactate dehydrogenase (LDH), aspartate aminotransferase (AST), folate, potassium, creatine kinase, phosphorus, iron, alanine aminotransferase, lipase, magnesium and triglycerides, decreasingly. The analyte concentrations decreased by hemolysis were: Haptoglobin, high-sensitive troponin T and alkaline phosphatase. Over the 25-day period, the % RFD of tests impacted more than 10%Δ by hemolysis were < 7% for LDH; < 5% for AST, folates and iron; and < 1% for the other analytes. Considering the ACL, HI were lower, giving % RFD substantially increased for many analytes, whereas only four analytes remain sensitive to hemolysis when considering RCV. Conclusion. This study proposes new HI based on different allowable limits, and can therefore serve as a starting point for future harmonization of hemolysis interference evaluation needed in routine laboratory practice.     

Clinical significance of the serum IgM and IgG to SARS‐CoV‐2 in coronavirus disease‐2019

ObjectiveTo explore the clinical value of serum IgM and IgG to SARS‐CoV‐2 in COVID‐19.Methods105 COVID‐19 patients were enrolled as the disease group. 197 non‐COVID‐19 patients served as the control group. Magnetic chemiluminescent immunoassay (MCLIA) was used to detect the IgM and IgG.ResultsThe peak of positive rates of SARS‐CoV‐2 IgM was about 1 week earlier than that of IgG. It reached to peak within 15–21 days and then began a slowly decline. The positive rates of IgG were increased with the disease course and reached the peak between 22 and 39 days. The differences in sensitivity of the three detection modes (IgM, IgG, and IgM + IgG) were statistically significant. The largest group of test cases (illness onset 15–21 days) showed that the positive rate of IgG was higher than IgM. Also, the sensitivity of IgM combined with IgG was higher than IgM or IgG. IgM and IgG were monitored dynamically for 16 patients with COVID‐19, the results showed that serological transformation of IgM was carried out simultaneously with IgG in seven patients, which was earlier than IgG in four patients and later than IgG in five patients.ConclusionThe detection of SARS‐CoV‐2 IgM and IgG is very important to determine the course of COVID‐19. Nucleic acid detection combined with serum antibody of SARS‐CoV‐2 may be the best laboratory indicator for the diagnosis of SARS‐CoV‐2 infection and the phrase and predication for prognosis of COVID‐19.     

Comparison of antifungal and cytotoxicity activities of titanium dioxide and zinc oxide nanoparticles with amphotericin B against different Candida species: In vitro evaluation

Background Candida species are known to cause serious fungal infections that produce cutaneous, mucosal, and systemic infections. Nowadays, mortality and morbidity candidiasis in immunocompromised patients have increased. Nanotechnology is a new world‐known technology and includes particles ranging from about 1 to 100 nanometers. The purpose of this study was to evaluate the antifungal and cytotoxicity activities of titanium dioxide nanoparticles (TiO2‐NPs) and zinc oxide nanoparticles (ZnO‐NPs) compared to amphotericin B (AmB) on different Candida spp in in vitro conditions.MethodsIn the present study, susceptibility of different Candida species to TiO2‐NPs and ZnO‐NPs compared to AmB was determined by broth microdilution (BMD) and agar well diffusion methods. Cytotoxicity of TiO2‐NPs and ZnO‐NPs and amphotericin B was measured by MTT (3‐(4, 5‐Dimethylthiazol‐2‐yl)‐2, 5‐Diphenyltetrazolium Bromide) assay.ResultsThe results indicated that the TiO2‐NPs and ZnO‐NPs showed antifungal activities against pathogenic Candida spp. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of TiO2‐NP ranges against Candida spp. were 128‐256 µg/mL and 256‐512 µg/mL, respectively. The MIC and MFC values of ZnO‐NPs were 64‐128 µg/mL and 256‐512 µg/mL, respectively. However, MICs and MFCs of AmB were 8‐16 µg/mL and 16‐32 µg/mL, respectively. The MTT assay results showed that the CC50% belonged to ZnO‐NPs 706.2 μg/mL, for TiO2‐NPs 862.1 μg/mL, and for AmB 70.19 μg/mL, respectively.ConclusionOur findings showed that TiO2‐NPs and ZnO‐NPs had antifungal effects against all Candida species, yet the antifungal properties of TiO2‐NPs and ZnO‐NPs were significantly less than those of AmB. The CC50% of AmB was significantly lower than ZnO‐NPs and TiO2‐NPs.     

Increased FURIN expression in rheumatoid arthritis patients and its anti-inflammatory effect

BackgroundFURIN belongs to the proprotein convertase family that processes proproteins and is involved in many diseases. However, the role of FURIN in rheumatoid arthritis (RA) remains unknown. In this study, we investigated the association between circulating FURIN and disease activity in patients with RA and the effect of FURIN in THP‐1‐derived macrophages.MethodsA total of 108 RA patients and 39 healthy controls participants were included in this study. RA patients were divided into four disease activity groups determined by the Disease Activity Score of 28 joints (DAS28). FURIN expression in peripheral blood mononuclear cells (PBMCs) and serum was detected by using quantitative real‐time polymerase chain reaction (qRT‐PCR) and enzyme‐linked immunosorbent assay (ELISA), respectively. Western blotting and qRT‐PCR were used to detect cytokines level after interfering FURIN expressed in THP‐1‐derived macrophages.ResultsBoth FURIN mRNA and protein levels were significantly higher in RA patients than in healthy controls participants (P < .001). No significant difference in FURIN expression was observed among the four RA groups (P > .05). Spearman correlation revealed that FURIN positively correlated with transforming growth factor‐β1(TGF‐β1), rheumatoid factor (RF), and anti‐cyclic citrullinated peptide (anti‐CCP). Moreover, the inhibition of FURIN in THP‐1‐derived macrophages promoted the caspase‐1 and IL‐1β expression (P < .05).ConclusionFURIN levels were significantly increased in the peripheral blood of RA patients and were not associated with disease activity. The inhibition of FURIN in THP‐1‐derived macrophages with elevated IL‐1β levels shows that FURIN may have an anti‐inflammatory effect.     

Analysis of microRNA processing machinery gene (DROSHA,DICER1, RAN,and XPO5) variants association with end-stage renal disease

BackgroundMicroRNA (miRNA) processing machinery gene variant was associated with several diseases. We aimed to explore for the first time the association of machinery gene (DROSHA rs10719A/G; DICER1 rs3742330A/G; RAN rs14035C/T; and XPO5 rs11077T/G) variants with the susceptibility and phenotype of end‐stage renal disease (ESRD).MethodA total of 281 participants (98 ESRD patients and 183 healthy volunteers) were enrolled. Real‐Time TaqMan allelic discrimination assay was applied for the genotyping of the specified variants. Multiple logistic regression models, univariate, multivariate, and principal component analyses were carried out.ResultsCarrying one DICER1 rs3742330*G allele conferred protection against developing ESRD [heterozygote comparison: OR = 0.30, 95% CI = 0.15‐0.62, dominant model: OR = 0.35, 95% CI = 0.17‐0.70]. Similarly, for XPO5 rs11077T/G, homozygote and heterozygote carriers of G variant were less likely to develop ESRD [homozygote comparison: adjusted OR = 0.23, 95% CI = 0.11‐0.50, and heterozygote comparison: OR = 0.50, 95% CI = 0.22‐0.92, and allelic model: OR = 0.46, 95% CI = 0.34‐0.70]. RAN rs14035*TT subjects were 5 times more likely to develop ESRD while being heterozygote (CT) have twice the risk [homozygote comparison: 5.18, 95% CI = 2.28‐11.8, heterozygote comparison: OR = 2.12, 95% CI = 1.10‐409]. Subgroup analysis also detected DICER1 rs3742330*A, XPO5 rs11077*T, and RAN rs14035*T as genetic risk determinants for ESRD development in both sex and age categories. Two genotype combinations of DROSHA/DICER1/XPO5/RAN were associated with increased susceptibility to ESRD [A‐A‐T‐T: OR = 9.49, 95%CI = 2.48‐36.31 (P = .001) and G‐A‐T‐T: OR = 5.92, 95%CI = 1.77‐19.83 (P = .004), respectively].ConclusionVariants and combined genotypes of DICER1 rs3742330, XPO5 rs11077, and RAN rs14035 might be associated with ESRD development in the study population. Integrating molecular analysis in ESRD risk stratification is warranted.     

Extreme diet without calcium may lead to hyperoxaluria and kidney stone recurrence—A case study

BackgroundThe aim of the study was to present a case study of a 56‐year‐old woman with hyperoxaluria induced by calcium‐free diet that resulted in kidney stone recurrence.MethodsA 24‐hour urine collection and serum tests for kidney stone risk factors identification were performed. The monitoring of urine risk factors was done by untimed urine samples and 24‐hour urine collections. Polarized light microscopy was performed for kidney stone analysis.ResultsThe results of urine collection showed hyperoxaluria of 0.551 mmoL per 24 hours. After adding calcium‐containing products to the diet the oxaluria decreased to reference range value of 0.352 mmoL/24 hours and all untimed oxalate to creatinine ratios returned to reference ranges. Polarized light microscopy revealed 100% calcium oxalate kidney stone composition (It was 50% Weddellite and 50% Whewellite).ConclusionsThe case study shows the importance of calcium intake in the prevention of calcium oxalate kidney stone recurrence. Particularly, unsuitable diet without calcium can induce kidney stone recurrence. Knowledge of diet habits is important for interpretation of kidney stone risk factors and their inhibitors excreted in urine.