Diagnosis value of miR‐181, miR‐652, and CA72‐4 for gastric cancer

PurposeTo find a useful disease marker for early diagnosis of gastric cancer, we tried to explore the expression of serum miR‐181, miR‐652, and carbohydrate antigen 72‐4 (CA72‐4).Patients and MethodsAccording to clinical pathologic stages, 112 patients with gastric cancer were divided into early gastric cancer group (n = 60) and advanced gastric cancer group (n = 52), stage I‐II (n = 65), and stage III‐IV (n = 47). Another 50 cases of gastric benign lesions and 40 healthy controls were also selected. Real‐time quantitative PCR together with chemiluminescence were applied to detect expression levels. ROC curve was applied to judge their diagnostic efficiency. Pearson''s correlation analysis was put into use to investigate the relevance of three indicators.ResultsCompared with benign lesions group and control group, significantly higher expression levels were found in patients of gastric cancer (all p < 0.001). Similarly, compared with early gastric cancer group, significantly higher expression levels were found in advanced gastric cancer group (all p < 0.001). The same result was also found in stage III‐IV (all p < 0.001). The best cutoff values were 0.93, 2.38, and 16.94 U/ml, respectively. The area under the curve (0.917, 95%CI: 0.856–0.975) of the three combined diagnosis of early gastric cancer was the largest, and its sensitivity and specificity were 92.5% and 86.8%. And miR‐181 and miR‐652 were positively correlated with CA72‐4 (r = 0.772, p < 0.001, r = 0.853, p < 0.001).ConclusionSerum miR‐181, miR‐652, and CA72‐4 are closely linked to the occurrence and development of gastric cancer. Combination of three indicators has diagnostic value for early gastric cancer.     

Distribution and reference interval establishment of neutral‐to‐lymphocyte ratio (NLR), lymphocyte‐to‐monocyte ratio (LMR), and platelet‐to‐lymphocyte ratio (PLR) in Chinese healthy adults

BackgroundNeutral‐to‐lymphocyte ratio (NLR), lymphocyte‐to‐monocyte ratio (LMR), and platelet‐to‐lymphocyte ratio (PLR) are associated with coronavirus disease 2019 (COVID‐19) and many diseases, but there are few data about the reference interval (RI) of NLR, LMR, and PLR.MethodsThe neutrophil count, lymphocyte count, monocyte count, and platelet count of 404,272 Chinese healthy adults (>18 years old) were measured by Sysmex XE‐2100 automatic hematology analyzer, and NLR, LMR, and PLR were calculated. According to CLSI C28‐A3, the nonparametric 95% percentile interval is defined as the reference interval.ResultsThe results of Mann‐Whitney U test showed that NLR (p < .001) in male was significantly higher than that in female; LMR (p < .001) and PLR (p < .001) in male were significantly lower than that in female. Kruskal‐Wallis H test showed that there were significant differences in NLR, LMR, and PLR among different genders and age groups (p < .001). The linear graph showed that the reference upper limit of NLR and PLR increased with age and the reference upper limit of LMR decreases with age in male population. In female population, the reference upper limit of NLR in 50–59 group, LMR in >80 group, and PLR in 70–79 group appeared a trough; the reference upper limit of NLR in >80 group, LMR in 50–59 group, and PLR in 40–49 group appeared peak.ConclusionThe establishment of RI for NLR, LMR, and PLR in Chinese healthy adults according to gender and age will promote the standardization of clinical application.     

Urinary N‐acetyl‐β‐d‐glucosaminidase‐creatine ratio is a valuable predictor for advanced diabetic kidney disease

BackgroundMany biomarkers show high diagnostic values for diabetic kidney disease (DKD), but fewer studies focus on the predictive assessment of DKD progression by blood and urinary biomarkers.AimThis study aims to find powerful risk predictors and identifying biomarkers in blood and urine for DKD progression.MethodsA total of 117 patients with type 2 DKD including early and advanced stages and their laboratory parameters were statistically assessed. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the significance of discriminating between early and advanced DKD, and the predictive power for advanced DKD was analyzed by regression analysis and trisector grouping.ResultsN‐acetyl‐β‐d‐glucosaminidase‐creatine (NAG/CR) level in advanced DKD was statistically higher than that in early DKD (p < 0.05), and there was a higher incidence of advanced DKD (72% vs. 56%) and high odds ratio (OR: 3.917, 95% CI: 1.579–10.011) of NAG/CR with ≥2.79 U/mmol compared with <2.79 U/mmol (p < 0.05). NAG/CR ratio also showed a higher area under the ROC curve of 0.727 (95% CI: 0.616–0.828, p = 0.010) with a high sensitivity (0.75) and a moderate specificity (0.66) when 1.93 U/mmol was set as the optimal cutoff value. The adjusted‐multivariable analysis revealed that NAG/CR had an OR of 1.021 (95% CI: 1.024–1.038) and 2.223 (95% CI: 1.231–4.463) based on a continuous and categorical variable, respectively, for risk of advanced DKD. Moreover, the prevalence of advanced DKD exhibited an increasing tendency by an increment of the trisector of NAG/CR.ConclusionsThis study suggests that NAG/CR ratio is an independent predictor for advanced DKD, and it also can be used as a powerful identifying marker between early and advanced DKD.     

Red blood cell distribution width‐to‐albumin ratio is associated with all‐cause mortality in cancer patients

BackgroundCancer causes a serious health burden on patients worldwide. Chronic low‐level inflammation plays a key role in tumorigenesis and prognosis. However, the role of the red blood cell distribution width (RDW)‐to‐albumin (RA) ratio in cancer mortality remains unclear.MethodsIn this retrospective cohort study, we collected clinical information from cancer patients from the Medical Information Mart for Intensive Care III (MIMIC‐III) version 1.4 database and then calculated RA by dividing RDW by albumin concentration. The primary outcome was 30 days mortality, while secondary outcomes were 90 days and 1 year mortality. Next, we adopted Cox regression models to calculate hazard ratios (HR) together with 95% confidence intervals (CI) for all‐cause mortalities associated with the RA ratio.ResultsFor 30 days mortality, the HR (95% CI) for the high RA ratio (≥5.51) was 2.17 [95CI% (1.87–2.51); p = <0.0001], compared with the low RA ratio (<5.51). In Model 2, we adjusted sex and age and obtained HR (95% CI) of 2.17 [95CI% (1.87–2.52); p = <0.0001] for the high RA ratio (≥5.51) group, compared to that in the low RA ratio (<5.51). In Model 3, adjusting for age, sex, anion gap, hematocrit, white blood cell count, congestive heart failure, SOFA, liver disease, and renal failure resulted in HR (95% CI) of 1.74 [95CI% (1.48–2.04); p = <0.0001] for the high RA ratio (≥5.51) relative to the low RA ratio (<5.51). We also analyzed common diseases in cancer patients but found no significant association.ConclusionTo the best of our knowledge, this is the first study demonstrating that increased RA ratio is independently associated with increased all‐cause mortality in cancer patients.     

Association between alanine aminotransferase and all‐cause mortality rate: Findings from a study on Japanese community‐dwelling individuals

BackgroundThis study examined the relationship between survival prognosis and alanine aminotransferase (ALT), a critical factor contributing to aging‐related health and mortality. The research is based on a follow‐up study with 6‐ and 10‐year intervals.MethodsThe participants included 1,610 males (63 ± 14 years old) and 2,074 females (65 ± 12 years old) who were part of the Nomura cohort study conducted in 2002 (first cohort) and 2014 (second cohort). The multivariable‐adjusted hazard ratios (HRs) of death between the baseline health checkup and the end of the follow‐up periods were estimated using a Cox proportional hazards model, controlling for potential confounding factors.ResultsThe follow‐up survey revealed 180 male deaths (11.2% of male participants) and 146 female deaths (7.0% of female participants). The univariate Cox regression analysis showed a significant increase in the HRs of all‐cause mortality with decreasing ALT levels (p < 0.001). Furthermore, compared with individuals with ALT levels of 20–29 IU/L, the multivariable‐adjusted HRs (95% confidence interval) for all‐cause mortality were 2.73 (1.59–4.70) for those with ALT levels <10 IU/L, 1.45 (1.05–2.00) for those with ALT levels of 10–19 IU/L, and 1.63 (1.05–2.53) for those with ALT levels ≥30 IU/L.ConclusionsOur findings show that abnormally low ALT levels and high within the normal range were related to all‐cause mortality in Japan''s community‐dwelling individuals. Especially, ALT activity may be an important biomarker for predicting the long‐term survival of older adults.     

Neutrophil percentage‐to‐albumin ratio and monocyte‐to‐lymphocyte ratio as predictors of free‐wall rupture in patients with acute myocardial infarction

BackgroundsFree‐wall rupture (FWR) has a high mortality rate. We aimed to find sensitive predictive indicators to identify high‐risk FWR patients by exploring the predictive values of neutrophil percentage‐to‐albumin ratio (NPAR) and monocyte‐to‐lymphocyte ratio (MLR) on patients with acute myocardial infarction (AMI).Methods76 FWR patients with AMI were collected, and then 228 non‐CR patients with AMI were randomly selected (1:3 ratio) in this retrospective study. The independent influencing factors of FWR were evaluated by univariate and multivariate logistic regression analysis. The receiver‐operating characteristic (ROC) curve analysis was applied to evaluate the predictive value of NPAR and MLR for FWR.ResultsAccording to the results of multivariate logistic regression analysis, emergency percutaneous coronary intervention (PCI) (OR = 0.27, 95% CI: 0.094–0.751, p = 0.012), angiotensin‐converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) treatment (OR = 0.17, 95% CI: 0.044–0.659, p = 0.010), NPAR (OR = 2.69, 95% CI: 1.031–7.044, p = 0.043), and MLR (OR = 5.99, 95% CI: 2.09–17.168, p = 0.001) were the influencing factors of the FWR patients with AMI, independently. Additionally, the NPAR and MLR were the predictors of FWR patients, with AUC of 0.811 and 0.778, respectively (both p < 0.001).ConclusionsIn summary, the emergency PCI and ACEI/ARB treatment were independent protective factors for FWR patients with AMI, while the increase of MLR and NPAR were independent risk factors. What''s more, NPAR and MLR are good indicators for predicting FWR.     

Analysis of anti‐apoptotic PVT1 oncogene and apoptosis‐related proteins (p53, Bcl2, PD‐1, and PD‐L1) expression in thyroid carcinoma

BackgroundAn aberrant expression of long non‐coding RNA PVT1 has been associated with apoptosis in various cancer types. We aimed to explore the PVT1 and four apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) signature in thyroid cancer (TC).MethodsThe PVT1 expression level was measured in 64 FFPE TC paired samples by real‐time quantitative PCR. Overall and stratified analyses by different clinicopathological features were done. The apoptotic proteins were evaluated by immunohistochemistry staining.ResultsOverall analysis showed significant PVT1upregulation in TC tissues (p < 0.001). Similarly, subgroup analysis by BRAF ^V600E mutation showed consistent results. Lower expression of p53 was associated with mortality (p = 0.001). Bcl2 overexpression was associated with greater tumor size (p = 0.005). At the same time, HCV‐positive cases were associated with repressed Bcl2 expression levels (54.3% in HCV‐negative vs. 6.9% in HCV‐positive cases, p = 0.011). PD‐1 expression was associated with lymph node metastasis (p = 0.004). Enhanced PD‐L1 expression in the tumor was associated with a higher tumor stage, lymphovascular invasion, and mortality risk. Kaplan–Meier curves for overall survival showed that low p53 and high PD‐L1 expressions were associated with lower survival time. The p53‐positive staining is associated with a 90% decreased mortality risk (HR = 0.10, 95%CI = 0.02–0.47, p = 0.001), while patients with high PD‐L1 were five times more likely to die (HR = 4.74, 95%CI = 1.2–18.7, p = 0.027).ConclusionOur results confirm the upregulation of PVT1 in TC. The apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) showed different prognostic utility in TC patients; in particular, low p53 and high PD‐L1 expressions associated with low survival times. Further large‐scale and mechanistic studies are warranted.     

Platelet‐Lymphocyte ratio is a predictor for the development of no‐reflow phenomenon in patients with ST‐segment elevation myocardial infarction after thrombus aspiration

BackroundWe aimed to evaluate the utility of the preprocedural platelet–lymphocyte ratio (PLR) for predicting the no‐reflow phenomenon after thrombus aspiration during percutaneous coronary intervention (PCI) in patients with ST‐segment elevation myocardial infarction (STEMI).MethodWe retrospectively analyzed postprocedural thrombolysis in myocardial infarction (TIMI) flow grades and myocardial blush grades (MBG) of 247 patients who underwent a PCI procedure with thrombus aspiration.We divided these patients into two groups according to whether they had no‐reflow (TIMI < 3, MBG < 2) or not (TIMI 3, MBG ≥ 2).ResultsNo‐reflow developed in 43 (17%) patients.Preprocedural PLR was significantly higher in the no‐reflow group (183.76 ± 56.65 vs 118.32 ± 50.42 p < 0.001).Independent predictors of no‐reflow were as follows: higher preprocedural platelet‐lymphocyte ratio (PLR) (OR = 1.018; 95% CI = 1.004, 1.033; p = 0.013),mean corpuscular volume (MCV) (OR = 1.118; 95% CI = 1.024, 1.220; p = 0.012) and SYNTAX Score‐2 (OR = 1.073; 95% CI = 1.005, 1.146; p = 0.036). PLR of 144 had 79% sensitivity and 75% specificity for the prediction of no‐reflow.ConclusionPLR is a reliable predictor for no‐reflow in STEMI patients undergoing thrombus aspiration.     

Association of B‐cell lymphoma 2/microRNA‐497 gene expression ratio score with metastasis in patients with colorectal cancer: A propensity‐matched cohort analysis

BackgroundDeregulated microRNAs (miRs) significantly impact cancer development and progression. Our in silico analysis revealed that miR‐497 and its target gene B‐cell lymphoma‐2 (BCL2) could be related to poor cancer outcomes.PurposeTo investigate the BCL2/miRNA‐497 expression ratio in colorectal cancer (CRC) and explore its association with the clinicopathological characteristics and CRC prognosis.MethodsArchived samples from 106 CRC patients were enrolled. MiR‐497 and BCL2 gene expressions were detected by Taq‐Man Real‐Time quantitative polymerase chain reaction in propensity‐matched metastatic and nonmetastatic cohorts after elimination of confounder bias.ResultsB‐cell lymphoma‐2 gene was upregulated in metastatic samples (median = 1.16, 95%CI = 1.09–1.60) compared to nonmetastatic (median = 1.02, 95%CI = 0.89–1.25, p < 0.001). In contrast, lower levels of miR‐495 were detected in specimens with distant metastasis (median = 0.05, 95%CI = 0.04–0.20) than nonmetastatic samples (median = 0.54, 95%CI = 0.47–0.58, p < 0.001). Estimated BCL2/miR‐497 ratio yielded a significant differential expression between the two cohort groups. Higher scores were observed in metastasis group (median = 1.39, 95%CI = 0.9–1.51) than nonmetastatic patients (median = 0.29, 95%CI = 0.19–0.39, p < 0.001). Receiver operating characteristic curve analysis showed BCL2/miR‐497 ratio score to have the highest predictive accuracy for metastasis at presentation. The area under the curve was 0.90 (95%CI = 0.839–0.964, p < 0.001) at cut‐off of >0.525, with high sensitivity 81.1% (95%CI = 68.6%–89.4%) and specificity 92.5% (95%CI = 82.1%–97.0%). Also, the ratio score was negatively correlated with disease‐free survival (r = −0.676, p < 0.001) and overall survival times (r = −0.650, p < 0.001). Kaplan–Meier curves showed lower survival rates in cohorts with high‐score compared to low‐score patients.ConclusionThe BCL2/miR497 expression ratio is associated with poor CRC prognosis in terms of metastasis and short survival.     

Colchicine,COVID‐19 and hematological parameters: A meta‐analysis

IntroductionColchicine has the potential in reducing patient morbidity and mortality in COVID‐19 infection owing to its anti‐inflammatory properties. This study aims to determine the efficacy of colchicine in optimizing inflammatory hematological biomarker levels among COVID‐19 patients.MethodsIn accordance to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 statement guidelines, a systematic search was conducted using the following keywords: Colchicine, covid*, SARS‐CoV‐2, anti‐inflammatory, trials, clinical, hematological, laboratory. Databases were searched from December 2019 until August 26, 2021: MEDLINE/PubMed, Web of Science, Cochrane, Scopus, and EMBASE. Other sources were located through ClinicalTrials.Gov, manually searching SAGE, Science Direct, Elsevier, and Google Scholar. The meta‐analysis was conducted using Review Manager 5.4.ResultsIn total, six studies were included, of which four reported c‐reactive protein (CRP) standardized mean reductions in the colchicine group (N = 165) as opposed to the control (N = 252; SMD = −0.49, p < 0.001). On noting lactate dehydrogenase (LDH) values post treatment, the colchicine group (N = 204) showed significant reductions at the end of treatment compared to control (N = 290; SMD = −0.85, p < 0.001). Finally, the D‐dimer values in colchicine groups (N = 129) compared to control (N = 216) also documented a negative effect size (SMD = −0.9, p < 0.001).ConclusionColchicine has efficacy in reducing inflammatory biomarkers observed in moderate‐to‐severe COVID‐19 patients. It may be worthwhile to consider monitoring the clinical and laboratory parameters of patients in further trials to consider colchicine as a strong candidate for an adjunct to COVID‐19 treatment.     

JNK pathway‐associated phosphatase illustrates low expression and negative correlations with inflammation,disease activity,and T‐helper 17 cells in inflammatory bowel disease children

BackgroundC‐Jun N‐terminal kinase pathway‐associated phosphatase (JKAP) modulates the T cell receptor and mitogen‐activated protein kinase pathway‐mediated autoimmunity, thus participating in the pathogenesis of autoimmune diseases. This study aimed to explore the clinical implication of JKAP in inflammatory bowel disease (IBD) children.MethodsC‐Jun N‐terminal kinase pathway‐associated phosphatase, tumor necrosis factor‐α (TNF‐α), interleukin‐23, interferon‐γ (T‐helper 1 secreted cytokine), and interleukin‐17A (T‐helper 17 secreted cytokine) in serum samples from 140 IBD children (including 60 Crohn''s disease (CD) children and 80 ulcerative colitis (UC) children) were detected by ELISA. Meanwhile, JKAP from serum samples of 10 healthy controls (HCs) was also detected by ELISA.ResultsC‐Jun N‐terminal kinase pathway‐associated phosphatase was reduced in CD children (median (interquartile range (IQR)): 51.6 (36.8–69.5) pg/ml) and UC children (median (IQR): 57.5 (43.4–78.5) pg/ml) compared with HCs (median (IQR): 101.8 (70.0–143.2) pg/ml) (both p < 0.05). In CD children, JKAP was negatively correlated with C‐reactive protein (CRP) (p = 0.016) and erythrocyte sedimentation rate (ESR) (p = 0.029); while in UC children, JKAP was also negatively correlated with CRP (p = 0.006) and ESR (p = 0.022). Regarding the correlation of JKAP with disease activity, it presented negative correlations with PCDAI (p = 0.001) and PUCAI (p = 0.002). Besides, JKAP was negatively related to TNF‐α (both p < 0.05) but not interleukin‐23 (both p>0.05) in CD and UC children. Additionally, JKAP was not correlated with interferon‐γ in CD or UC children (both p>0.05), while negatively correlated with interleukin‐17A in CD and UC children (both p < 0.05).ConclusionC‐Jun N‐terminal kinase pathway‐associated phosphatase shows low expression and negative correlations with inflammation, disease activity, and T‐helper 17 cells in IBD children.     

Evaluation of automated molecular tests for the detection of SARS‐CoV‐2 in pooled nasopharyngeal and saliva specimens

BackgroundPooling of samples for SARS‐CoV‐2 testing in low‐prevalence settings has been used as an effective strategy to expand testing capacity and mitigate challenges with the shortage of supplies. We evaluated two automated molecular test systems for the detection of SARS‐CoV‐2 RNA in pooled specimens.MethodsPooled nasopharyngeal and saliva specimens were tested by Qiagen QIAstat‐Dx Respiratory SARS‐CoV‐2 Panel (QIAstat) or Cepheid Xpert Xpress SARS‐CoV‐2 (Xpert), and the results were compared to that of standard RT‐qPCR tests without pooling.ResultsIn nasopharyngeal specimens, the sensitivity/specificity of the pool testing approach, with 5 and 10 specimens per pool, were 77%/100% (n = 105) and 74.1%/100% (n = 260) by QIAstat, and 97.1%/100% (n = 250) and 100%/99.5% (n = 200) by Xpert, respectively. Pool testing of saliva (10 specimens per pool; n = 150) by Xpert resulted in 87.5% sensitivity and 99.3% specificity compared to individual tests. Pool size of 5 or 10 specimens did not significantly affect the difference of RT‐qPCR cycle threshold (C_T) from standard testing. RT‐qPCR C_T values obtained with pool testing by both QIAstat and Xpert were positively correlated with that of individual testing (Pearson''s correlation coefficient r = 0.85 to 0.99, p < 0.05). However, the C_T values from Xpert were significantly stronger (p < 0.01, paired t test) than that of QIAstat in a subset of SARS‐CoV‐2 positive specimens, with mean differences of −4.3 ± 2.43 and −4.6 ± 2 for individual and pooled tests, respectively.ConclusionOur results suggest that Xpert SARS‐CoV‐2 can be utilized for pooled sample testing for COVID‐19 screening in low‐prevalence settings providing significant cost savings and improving throughput without affecting test quality.     

Association of alpha‐thalassemia and Glucose‐6‐Phosphate Dehydrogenase deficiency with transcranial Doppler ultrasonography in Nigerian children with sickle cell anemia

BackgroundStroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler Ultrasonography (TCD). The evidence on the role of alpha‐thalassemia and glucose‐6‐phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is conflicting. Thus, this study investigated the association of alpha‐thalassemia and G6PD(A⁻) variant with abnormal TCD velocities among Nigerian children with SCA.MethodsOne hundred and forty‐one children with SCA were recruited: 72 children presented with normal TCD (defined as the time‐averaged mean of the maximum velocity: < 170 cm/s) and 69 children with abnormal TCD (TAMMV ≥ 200 cm/s). Alpha‐thalassemia (the α‐3.7 globin gene deletion) was determined by multiplex gap‐PCR, while G6PD polymorphisms (202G > A and 376A > G) were genotyped using restriction fragment length polymorphism—polymerase chain reaction.ResultsThe frequency of α‐thalassemia trait in the children with normal TCD was higher than those with abnormal TCD: 38/72 (52.8%) [α‐/ α α: 41.7%, α ‐/ α ‐: 11.1%] versus 21/69 (30.4%) [α‐/ α α: 27.5%, α ‐/ α ‐: 2.9%], and the odds of abnormal TCD were reduced in the presence of the α‐thalassemia trait [Odds Ratio: 0.39, 95% confidence interval: 0.20–0.78, p = 0.007]. However, the frequencies of G6PDA⁻ variant in children with abnormal and normal TCD were similar (11.6% vs. 15.3%, p = 0.522).ConclusionOur study reveals the protective role of α‐thalassemia against the risk of abnormal TCD in Nigerian children with SCA.     

Distribution of urinary N‐acetyl‐beta‐D‐glucosaminidase and the establishment of reference intervals in healthy adults

BackgroundUrinary N‐acetyl‐beta‐D‐glucosaminidase (NAG) plays an important role in the early diagnosis and progression of diseases related to renal tubular injury. We detected the urinary NAG concentration, assessed the preliminary statistics of its distribution, and established reference intervals for healthy adults in China using the rate method.MethodsA total of 1,095 reference individuals (aged 20 to 79 years) met the requirements for inclusion in this study. Urinary NAG concentrations were detected using an AU5800 automatic biochemical analyzer with its matched reagents. The Kolmogorov‐Smirnov test was used to analyze the normality of the data. According to the guidelines of C28‐A3 and WS/T 402‐2012, the reference intervals of urinary NAG were established using the nonparametric percentile method (unilateral 95th percentile).ResultsThe urinary NAG data showed a non‐normal distribution. The distribution of urinary NAG was significantly different by sex and age. Therefore, the reference intervals of urinary NAG were established using the rate method: males (aged 20–59 years) <19.4 U/L (90% CI: 18.0–20.3 U/L); males (aged 60–79 years) <22.3 U/L (90% CI: 20.2–22.6 U/L); females (aged 20–59 years) <15.7 U/L (90% CI: 15.2–16.5 U/L); and females (aged 60–79 years) <21.4 U/L (90% CI: 20.3–22.3 U/L).ConclusionsWe established preliminary reference intervals of urinary NAG for healthy adults in China to provide guidance for health screening, auxiliary diagnosis, and treatment monitoring of renal tubule‐related diseases.     

Association of plasma bone morphogenetic protein‐4 levels with arterial stiffness in hypertensive patients

BackgroundArterial stiffness interacts with hypertension, becoming an early marker of hypertension‐mediated target organ damage. This study aimed to assess the association between plasma concentrations of bone morphogenetic protein‐4 (BMP‐4) and arterial stiffness during hypertension.MethodsUsing cardio‐ankle vascular index (CAVI) to determine arterial stiffness status, 204 individuals with essential hypertension were classified into two groups, high CAVI (abnormal) group (n = 94) and low (normal) CAVI group (n = 110). Data were collected including clinical characteristics and laboratory measurements. Plasma levels of BMP‐4 were tested by using ELISA analysis.ResultsPlasma levels of BMP‐4 were substantially greater in high CAVI group than that in low CAVI group [38.51 (31.79–50.83) pg/mL vs. 31.15 (29.38–32.37) pg/mL; p < 0.001]. As shown by spearman correlation analysis, BMP‐4 concentrations were correlated with CAVI values in hypertensive individuals (r = 0.406, p < 0.001). After adjustment for potential confounders, elevated BMP‐4 levels were related with high CAVI (OR, 1.070; 95% CI, 1.003–1.108; p < 0.001). The best BMP‐4 cutoff value for identifying high CAVI, as determined by ROC curve analysis, was 33.34 pg/mL (AUC, 0.751; 95% CI, 0.683–0.818; p < 0.001).ConclusionPlasma levels of BMP‐4 are increased in hypertensive individuals with high CAVI. Elevated BMP‐4 levels are strongly correlated with higher CAVI values, implying a predictive value of BMP‐4 in arterial stiffness during hypertension.     

Cautions on the laboratory indicators of COVID‐19 patients on and during admission

BackgroundDifferent disease severities of COVID‐19 patients could be reflected on clinical laboratory findings.MethodsIn this single‐centered retrospective study, demographic, clinical, and laboratory indicators on and during admission were compared among 74 participants with mild, moderate, critical severe, or severe classification. Risk factors associated with disease severity were analyzed by multivariate analyses. The AUC and 95% CI of the ROC curve were calculated.ResultsThe most common manifestations of these patients were fever and cough. Critical severe or severe group owned the longest length of stay (23 (19,31), p < 0.001). After multivariate logistic regression, independent influence factors on admission for severity of disease were CK‐MB (OR 0.674; 95% CI 0.489–0.928; p = 0.016), LDH (OR 1.111 or 1.107; 95% CI 1.026–1.204 or 1.022–1.199; p = 0.009 or 0.013), normal T‐BIL (OR 4.58 × 10⁻⁸; 95% CI 3.05 × 10⁻⁹–6.88 × 10⁻⁷; p < 0.001), LYM% (OR 0.008; 95% CI 0–0.602; p = 0.029), and normal ESR (OR 0.016; 95% CI 0–0.498; p = 0.019). Factors during hospitalization were normal T‐BIL (OR 8.56 × 10⁻⁹; 95% CI 8.30 × 10⁻¹⁰–8.83 × 10⁻⁸; p < 0.001), LYM (OR 0.068; 95% CI 0.005–0.934; p = 0.044), albumin (OR 0.565; 95% CI 0.327–0.977; p = 0.041), and normal NEU% (OR 0.013; 95% CI 0.000–0.967; p = 0.048). Combined indicators of AUC were 0.860 (LYM, LDH, and normal ESR on admission, p < 0.001) and 0.750 (CK‐MB, LDH, and normal T‐BIL during hospitalization, p = 0.020) when predicting for severe or critical severe patients.ConclusionTo pay close attention to the progression of COVID‐19 and take measures promptly, we should be cautious of the laboratory indicators when patients on admission especially CK‐MB, LDH, LYM%, T‐BIL as well as ESR; and T‐BIL, LYM, albumin, NEU% with the process of disease.     

Real‐life effectiveness of biological therapies on symptoms in severe asthma with comorbid CRSwNP

BackgroundWe aimed to evaluate the effectiveness of different antibody therapies on nasal polyp symptoms in patients treated for severe asthma.MethodsWe performed a retrospective analysis of patients with severe asthma and comorbid CRSwNP who were treated with anti‐IgE, anti‐IL‐5/R or anti‐IL‐4R. CRSwNP symptom burden was evaluated before and after 6 months of therapy.ResultsFifty patients were included hereof treated with anti‐IgE: 9, anti‐IL‐5/R: 26 and anti‐IL‐4R: 15 patients. At baseline median SNOT‐20 was similar among groups (anti‐IgE: 55, anti‐IL‐5/R: 52 and anti‐IL‐4R: 56, p = 0.76), median visual analogue scale (VAS) for nasal symptoms was 4, 7 and 8 (p = 0.14) and VAS for total symptoms was higher in the anti‐IL‐4R group (4, 5 and 8, p = 0.002). After 6 months SNOT‐20 improved significantly in all patient groups with median improvement of anti‐IgE: −8 (p < 0.01), anti‐IL‐5/R: −13 (p < 0.001) and anti‐IL‐4R: −18 (p < 0.001), with larger improvement in the anti‐IL‐4R group than in anti‐IgE (p < 0.001) and anti‐IL‐5/R (p < 0.001) groups. VAS nasal symptoms improved by median anti‐IgE: 0 (n.s.), anti‐IL‐5/R: −1 (p < 0.01) and anti‐IL‐4R: −3 (p < 0.001), VAS total symptoms by anti‐IgE: −1 (n.s.), anti‐IL‐5/R: −2 (p < 0.001) and anti‐IL‐4R: −2 (p < 0.001).ConclusionsTreatment by all antibodies showed effectiveness in reducing symptoms of CRSwNP in patients with severe asthma, with the largest reduction observed in anti‐IL‐4R‐treated patients.     

Clinical value of YKL‐40 in patients with polymyositis/dermatomyositis: A cross‐sectional study and a systematic review

IntroductionWe performed a cross‐sectional study to investigate the clinical usefulness of YKL‐40 in patients with dermatomyositis (DM) and conducted a systematic review to summarize the clinical value of YKL‐40 in patients with polymyositis (PM)/DM.Materials and methodsA cross‐sectional study and a systematic review were performed to study the clinical value of YKL‐40 in patients with PM/DM. Serum YKL‐40 level was detected using enzyme‐linked immunosorbent assay, and its association with clinical and laboratory parameters was analyzed. In the systematic review, electronic databases of OVID Embase, OVID Medline, and web of science were searched to collect studies that reported clinical use of YKL‐40 in patients with PM/DM.ResultsIn the cross‐sectional study, serum YKL‐40 level was higher in patients with DM than in healthy controls (median [interquartile range]: 84.09 [52.72–176.4] ng/ml versus 27.37 [12.30–53.58] ng/ml, p < 0.0001). Serum levels of YKL‐40 were associated with the course of DM (r = −0.469, p < 0.001), CRP (r = 0.303, p = 0.043), CK (r = 0.263, p = 0.037), and global disease activity (r = 0.628, p < 0.001). The area under the ROC curve was 0.835 (95% confidence interval 0.751–0.920). In the systematic review, a total of four studies were included with moderate to high quality. Serum level of YKL‐40 has the possibility for diagnosing PM/DM, identifying PM/DM patients with interstitial lung disease (ILD) or rapid progress ILD, and predicting death.ConclusionSerum YKL‐40 level is a possible useful biomarker for PM/DM diagnosis and may be used to predict prognosis.     

Dynamic changes of IgM and IgG antibodies in asymptomatic patients as an effective way to detect SARS‐CoV‐2 infection

BackgroundCOVID‐19 has become a global pandemic, and close contacts and asymptomatic patients are worthy of attention.MethodsA total of 1844 people in close contacts with 76 COVID‐19 patients were investigated, and nasopharyngeal swabs and venous blood were collected for centralized medical quarantine observation. Real‐time fluorescence was used to detect SARS‐CoV‐2 nucleic acid in nasopharyngeal swabs of all close contacts, and the colloidal gold method was used to detect serum‐specific antibodies. Levels of IgM‐ and IgG‐specific antibodies were detected quantitatively through chemiluminescence from the first nucleic acid turned negative date (0 week) and on weekly intervals of ≤1 week, 1–2 weeks, 2–3 weeks, 3–4 weeks, 4–5 weeks, 5–6 weeks, and 6–7 weeks.ResultsThe total positive rate of the colloidal gold method (88.5%, 23/26) was significantly higher (χ² = 59.182, p < 0.001) than that of the healthy control group (2.0%, 1/50). There was significant difference in IgG concentration at different time points (0–7 weeks) after negative nucleic acid conversion (χ² = 14.034, p = 0.029). Serum IgG levels were significantly higher at weekly time points of 4–5 weeks (Z = −2.399, p = 0.016), 5–6 weeks (Z = −2.049, p = 0.040), and 6–7 weeks (Z = −2.197, p = 0.028) compared with 1–2 weeks after negative nucleic acid conversion. However, there was no significant difference (χ² = 4.936, p = 0.552) in IgM concentration between time points tested (0–7 weeks) after negative nucleic acid conversion. The positive rates of IgM and IgG in asymptomatic patients (χ² = 84.660, p < 0.001) were significantly higher than those in the healthy control group (χ² = 9.201, p = 0.002) within 7 weeks of negative nucleic acid conversion.ConclusionsThe IgG concentration in asymptomatic cases remained at a high level after nucleic acid turned negative. Nucleic acid detection combined with IgM and IgG antibody detection is an effective way to screen asymptomatic infections.