Identification of Cytochrome b‐245, beta‐chain gene mutations,and clinical presentations in Iranian patients with X‐linked chronic granulomatous disease

BackgroundX‐linked chronic granulomatous disease (X‐CGD) is an immunodeficiency disorder caused by defects in the gp91^phox subunit that leads to life‐threatening infections. We aimed to identify CYBB gene mutations and study clinical phenotypes in Iranian patients with probable X‐CGD.MethodsWe studied four unrelated Iranian patients with probable X‐CGD and their families recruited in several years. We isolated genomic DNA from whole blood and performed Sanger sequencing in the CYBB gene''s coding and flanking regions. We also performed pathogenicity predictions using in silico tools.ResultsWe detected four different mutations, including a novel insertion mutation in exon 5 (p.Ile117AsnfsX6), in the patient. Bioinformatics analysis confirmed the pathogenic effect of this mutation. We predicted protein modeling and demonstrated lost functional domains. The patient with the insertion mutation presented pneumonia and acute sinusitis during his life. We also detected three other known nonsense mutations (p.Arg157Ter, p.Arg226Ter, and p.Trp424Ter) in the CYBB gene. The patient with p.Arg157Ter developed lymphadenitis and pneumonia. Moreover, the patient with inflammatory bowel disease showed p.Arg226Ter and the patient with tuberculosis presented p.Trp424Ter. We detected different clinical features in the patients compared to other Iranian patients with the same mutations.ConclusionOur results expand the genetic database of patients with X‐CGD from Iran and make it much easier and faster to identify patients with X‐CGD. Our results also help to detect carriers and enable prenatal diagnosis in high‐risk families as a cost‐effective strategy.     

Novel splicing‐site mutation in DCAF17 gene causing Woodhouse‐Sakati syndrome in a large consanguineous family

BackgroundWoodhouse‐Sakati syndrome is a rare autosomal recessive disease with endocrine and neuroectodermal aberrations with heterogeneous phenotypes and disease course. The most common phenotypes of the disease are progressive sensorineural hearing loss and alopecia, mild‐to‐moderate mental retardation and hypogonadism. The disease results from mutations in the DCAF17 gene.MethodHere, we reported a large consanguineous pedigree with multiple affected individuals with Woodhouse‐Sakati syndrome phenotypes. Laboratory tests confirmed the endocrine perturbance in affected individuals. To find out the underlying genetic change, whole‐exome sequencing was carried out.ResultAnalysis of the exome data identified a splicing‐site deletion {"type":"entrez-nucleotide","attrs":{"text":"NM_025000.3","term_id":"259906387","term_text":"NM_025000.3"}}NM_025000.3:c.1423‐1_1425delGACA in DCAF17 gene. Sanger sequencing confirmed the co‐segregation of the variant with the disease phenotypes in the family.ConclusionThe variant is predicted to cause aberrant splicing, i.e., exon skipping, resulting in the translation of a truncated functionless protein which results in appearance of typical phenotypic features and clinical laboratory findings of Woodhouse‐Sakati syndrome in affected members of the family.     

Th17 cell‐derived miR‐155‐5p modulates interleukin‐17 and suppressor of cytokines signaling 1 expression during the progression of systemic sclerosis

Background miR‐155‐5p is associated with autoimmune diseases. T helper 17 (Th17) cells, interleukin (IL)‐17, and suppressor of cytokines signaling 1 (SOCS1) have important roles in the pathogenesis of systemic sclerosis (SSc). The purpose of this study was to explore the role of miR‐155‐5p in the regulation of IL‐17 and SOCS1 expression in Th17 cells and the subsequent effect on SSc disease progression.MethodsTh17 cells were isolated from peripheral blood mononuclear cells of SSc patients and healthy controls (HCs). RT‐qPCR and western blotting were used to examine the expression patterns of miR‐155‐5p, IL‐17, and SOCS1. Luciferase reporter assays were performed to confirm SOCS1 as a target of miR‐155‐5p. RNA pull‐down assays were performed to detect the interaction of IL‐17 and SOCS1 with miR‐155‐5p. In situ hybridization was performed to analyze the co‐expression pattern of miR‐155‐5p and IL17A in Th17 cells.ResultsThe levels of Th17 cell‐derived miR‐155‐5p were significantly up‐regulated in SSc patients compared with HCs, and its levels were negatively correlated with SOCS1 levels. Meanwhile, miR‐155‐5p positively regulated IL‐17 expression levels in Th17 cells isolated from SSc patients as the disease progressed. Using pmirGLO vectors, SOCS1 was confirmed as a target of miR‐155‐5p. The binding status of IL‐17 and SOCS1 to miR‐155‐5p was related to SSc progression. An increase in the co‐localization of miR‐155‐5p and IL‐17 was associated with greater SSc progression.ConclusionsIL‐17 and SOCS1 expression modulated by Th17 cell‐derived miR‐155‐5p are critical for SSc progression, which may provide novel insights into the pathogenesis of SSc.     

COVID‐19 in HIV‐positive patients: A systematic review of case reports and case series

IntroductionCoronavirus disease 2019 (COVID‐19) and acquired immune deficiency syndrome (AIDS) are two viral diseases for which there are currently no definitive treatments. Nowadays, because of the health system''s focus on the COVID‐19 epidemic, the control of human immunodeficiency virus (HIV) has received less attention. In this review, we will discuss the characteristics of COVID‐19 in HIV‐positive patients.Material and MethodsUsing the PRISMA guideline, the databases of Scopus, PubMed, and Web of Science were searched systematically from January 1, 2019 to February 24, 2021. The following keywords were used: “Human Immunodeficiency Virus,” “acquired immune deficiency syndrome,” “HIV,” “AIDS,” “COVID‐19,” “severe acute respiratory syndrome coronavirus 2,” “novel coronavirus,” “SARS‐CoV‐2,” “nCoV disease,” “SARS2,” and “2019‐nCoV disease.”ResultsTwenty‐one percent of studies were conducted in the USA (n = 13), 16% in China (n = 10), and 13% in Italy (n = 8), respectively. The majority of the patients were men (74.3%). Tenofovir disoproxil fumarate was used in 47.4% of patients, emtricitabine in 58.4%, and lamivudine in 34.8% to treat HIV. Symptoms of HIV patients with COVID‐19 included coughing (81.3%), fever (62.8%), and dyspnea (60%). Hydroxychloroquine (39.34%) and azithromycin (36.58%) were the common treatment options for COVID‐19. The total death rate in HIV‐positive patients with COVID‐19 was about 9%.ConclusionIn the current systematic review, we demonstrated that HIV‐positive patients co‐infected with COVID‐19 have high comorbidity of hypertension and diabetes mellitus. HIV/COVID‐19 co‐infection might have negatively influenced the HIV treatment and diagnosis, which indicates the need to regularly screen HIV patients in the COVID‐19 pandemic.     

Predictive value of lymphocyte‐to‐monocyte ratio in critically Ill patients with atrial fibrillation: A propensity score matching analysis

BackgroundInflammation plays a key role in the initiation and progression of atrial fibrillation (AF). Lymphocyte‐to‐monocyte ratio (LMR) has been proved to be a reliable predictor of many inflammation‐associated diseases, but little data are available on the relationship between LMR and AF. We aimed to evaluate the predictive value of LMR in predicting all‐cause mortality among AF patients.MethodsData of patients diagnosed with AF were retrieved from the Medical Information Mart for Intensive Care‐III (MIMIC‐III) database. X‐tile analysis was used to calculate the optimal cutoff value for LMR. The Cox regression model was used to assess the association of LMR and 28‐day, 90‐day, and 1‐year mortality. Additionally, a propensity score matching (PSM) method was performed to minimize the impact of potential confounders.ResultsA total of 3567 patients hospitalized with AF were enrolled in this study. The X‐tile software indicated that the optimal cutoff value of LMR was 2.67. A total of 1127 pairs were generated, and all the covariates were well balanced after PSM. The Cox proportional‐hazards model showed that patients with the low LMR (≤2.67) had a higher 1‐year all‐cause mortality than those with the high LMR (>2.67) in the study cohort before PSM (HR = 1.640, 95% CI: 1.437–1.872, p < 0.001) and after PSM (HR = 1.279, 95% CI: 1.094–1.495, p = 0.002). The multivariable Cox regression analysis for 28‐day and 90‐day mortality yielded similar results.ConclusionsThe lower LMR (≤2.67) was associated with a higher risk of 28‐day, 90‐day, and 1‐year all‐cause mortality, which might serve as an independent predictor in AF patients.     

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.     

Co‐infection of Klebsiella pneumonia,Cytomegalovirus, Aspergillus and Zygomycete in a patient with SARS‐CoV‐2

Co‐infection between severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and other pathogens has become a serious threat. There are the reports of fungal, bacterial, and viral co‐infections with SARS‐CoV‐2. We report the unusual case of concomitant aspergillosis, mucormycosis, cytomegalovirus pneumonia, and also klebsiella pneumoniae empyema as the complication of SARS‐CoV‐2.     

Establishment of an in‐house real‐time RT‐PCR assay for the detection of severe acute respiratory syndrome coronavirus 2 using the first World Health Organization international standard in a resource‐limited country

BackgroundThe COVID‐19 pandemic caused by SARS‐CoV‐2 remains public health burdens and many unresolved issues worldwide. Molecular assays based on real‐time RT‐PCR are critical for the detection of SARS‐CoV‐2 in clinical specimens from patients suspected of COVID‐19.ObjectiveWe aimed to establish and validate an in‐house real‐time RT‐PCR for the detection of SARS‐CoV‐2.MethodologyPrimers and probes sets in our in‐house real‐time RT‐PCR assay were designed in conserved regions of the N and E target genes. Optimized multiplex real‐time RT‐PCR assay was validated using the first WHO International Standard (NIBSC code: 20/146) and evaluated clinical performance.ResultsThe limit of detection validated using the first WHO International Standard was 159 IU/ml for both E and N target genes. The evaluation of clinical performance on 170 clinical samples showed a positive percent agreement of 100% and the negative percent agreement of 99.08% for both target genes. The Kappa value of 0.99 was an excellent agreement, the strong correlation of C _t values observed between two tests with r ² = 0.84 for the E gene and 0.87 for the N gene. Notably, we assessed on 60 paired saliva and nasopharyngeal samples. The overall agreement was 91.66%, and Kappa value of 0.74 showed a high agreement between two types of samples. When using nasopharyngeal swabs as the reference standard, positive percent agreement, and negative percent agreement were 91.83% and 90.90%, respectively.ConclusionIn the present study, we established and validated an in‐house real‐time RT‐PCR for molecular detection of SARS‐CoV‐2 in a resource‐limited country.     

IL‐23/IL‐17 axis and soluble receptors isoforms sIL‐23R and sIL‐17RA in patients with rheumatoid arthritis‐presenting periodontitis

BackgroundRheumatoid arthritis (RA) and periodontitis (P) are chronic inflammatory diseases characterized by joint and radiographic bone loss, respectively. IL‐23 and IL‐17 have an essential role in the immunopathogenesis of RA, and P. IL‐23 stimulates Th17 cells through which produces IL‐17, IL‐21, and RANKL. IL‐17 stimulates fibroblasts to produce RANKL, which initiates bone loss in the joints in RA and the periodontal tissue in periodontitis. The aim of this study was to determine the expression pattern of IL‐23/IL‐17 axis and soluble receptors isoforms sIL‐23R and sIL‐17RA of patients with RA presenting P (RAP).Material and methodsHealthy subjects (HS) (n = 42), patients with P (n = 40), RA (n = 20), and patients with RAP (n = 40) were included. Plasma samples were obtained to evaluate the IL‐23, IL‐17A, sIL‐23R, and sIL‐17RA by ELISA technique. A nonparametric Mann‐Whitney U test was used to compare the differences between groups. A Chi‐square was used to compare gender, grade and stage of periodontitis, and DAS28‐ESR between the groups. Spearman''s rank correlation coefficient was used to study the association between the molecules and clinical parameters.ResultsIL‐23 levels were increased in the RAP group, and lower sIL‐23R levels were found in the RAP groups. However, IL‐17A was lower in the P and RAP group but not in RA patients. RAP group showed a decrease IL‐17A levels in advanced stages of the periodontal disease.ConclusionThese results suggest that IL‐23 and IL‐17A tend to downregulate their expression patterns when patients present both rheumatoid arthritis and periodontitis.     

Combined fibrinogen‐to‐pre‐albumin ratio and carbohydrate antigen 19–9 score is a promising metric to predict progression of metastatic colorectal mucinous adenocarcinoma

BackgroundChronic inflammation is a hallmark of colorectal mucinous adenocarcinoma (CMA). Albumin‐to‐fibrinogen ratio (AFR) and fibrinogen‐to‐pre‐albumin ratio (FPR) were independent prognostic factors for many kinds of solid malignancies. However, the association between the inflammatory scores and progression of metastatic CMA remains unknown.MethodsPeripheral blood neutrophil count and circulating fibrinogen, albumin, and pre‐albumin levels were detected, and neutrophil‐to‐albumin ratio (NAR), neutrophil‐to‐pre‐albumin ratio(NPAR), AFR, and FPR were calculated in 42 metastatic MCA patients. Kaplan‐Meier curve, Cox regression, time‐dependent receiver operating characteristic curve (tdROC) were selected to investigate the prognostic utility of them in the patients.ResultsMetastatic CMA patients commonly occurred in middle‐younger patients (80.95%). NPAR (adjusted hazard ratio (HR)=2.405, 95% confidence interval (CI)=1.195–4.842) and FPR (p _log‐rank=0.007, adjusted HR=2.364, 95% CI=1.203–4.645) were significantly associated with poor progression‐free survival in these patients. The prognostic prediction area under tdROC (AUROC) of FPR was significantly higher than that of NPAR(0.703 versus 0.537). Moreover, the patients with a high CA19‐9‐FPR score showed worse outcomes than those with the low score (p _log‐rank<0.001, adjusted HR=7.273, 95% CI=2.721–19.435 for the score 1 versus 0). The prediction AUROC, sensitivity, and specificity of the score were 0.892 (0.788–0.996), 76.32%, and 100.00%, respectively, and its predicted efficacy was better than that of the single biomarkers.ConclusionThe combined CA19‐9‐FPR score is an economical, simple, effective, and independent prognostic factor for metastatic MCA.     

MiR‐221‐3p and miR‐92a‐3p enhances smoking‐induced inflammation in COPD

BackgroundSmoking is likely to facilitate airway inflammation and finally contributes to chronic obstructive pulmonary disease (COPD). This investigation was intended to elucidate miRNAs that were involved in smoking‐induced COPD.MethodsAltogether 155 COPD patients and 77 healthy volunteers were recruited, and their serum levels of miR‐221‐3p and miR‐92a‐3p were determined. Besides, human bronchial epithelial cells (16HBECs) were purchased, and they were treated by varying concentrations of cigarette smoke extract (CSE). The 16HBECs were, additionally, transfected by miR‐221‐3p mimic, miR‐92a‐3p mimic, miR‐221‐3p inhibitor or miR‐92a‐3p inhibitor, and cytokines released by them, including TNF‐α, IL‐8, IL‐1β, and TGF‐β1, were monitored using enzyme linked immunosorbent assay (ELISA) kits.ResultsChronic obstructive pulmonary disease patients possessed higher serum levels of miR‐221‐3p and miR‐92a‐3p than healthy volunteers (p < 0.05), and both miR‐221‐3p and miR‐92a‐3p were effective biomarkers in diagnosing stable COPD from acute exacerbation COPD. Moreover, viability of 16HBECs was undermined by CSE treatment (p < 0.05), and exposure to CSE facilitated 16HBECs’ release of TNF‐α, IL‐8, IL‐1β, and TGF‐β1 (p < 0.05). Furthermore, miR‐221‐3p/miR‐92a‐3p expression in 16HBECs was significantly suppressed after transfection of miR‐221‐3p/miR‐92a‐3p inhibitor (p < 0.05), which abated CSE‐triggered increase in cytokine production and decline in viability of 16HBECs (p < 0.05).ConclusionMiR‐221‐3p and miR‐92a‐3p were involved in CSE‐induced hyperinflammation of COPD, suggesting that they were favorable alternatives in diagnosing COPD patients with smoking history.     

Dysregulation of vitamin D synthesis pathway genes in colorectal cancer: A case‐control study

BackgroundThe cytochromes P450 are a superfamily of enzymes that control the synthesis of the biologically active form of vitamin D, 1,25‐dihydroxyvitamin D3. These enzymes contribute to the formation of 1,25‐dihydroxyvitamin D3, which starts with a 25‐hydroxylation by CYP2R1 and CYP27A1 and a subsequent 1α‐hydroxylation via CYP27B1.MethodsBy using quantitative real‐time polymerase chain reaction (qRT‐PCR), we analyzed the expression ratio of CYP2R1, CYP27A1 and CYP27B1 genes within the vitamin D metabolic pathway in a total of 75 colorectal cancer (CRC) tissues compared to the adjacent tissues. Furthermore, we evaluated the association of CYP27B1 rs4646536 and CYP2R1 rs12794714 and rs10766196 polymorphisms with CRC risk in a total of 490 subjects, including 245 CRC patients and 245 non‐cancer controls. The genotyping was performed using tetra‐primer amplification refractory mutation system polymerase chain reaction (TP‐ARMS–PCR) method.ResultsThe results indicated 2.3 and 2.7 upregulation of CYP2R1 and CYP27B1 genes in colorectal cancer tissues compared to the adjacent tissues, respectively. Rs12794714 AG genotype increased the risk of CRC (P = .03). Furthermore, a significant association was observed under the dominant inheritance model (P = .039).Conclusion CYP2R1 and CYP27B1 genes were over‐expressed in CRC samples compared to the adjacent control tissues. Furthermore, CYP2R1 rs12794714 variant was associated with the risk of CRC in the studied samples. CYP2R1 rs10766196 and CYP27B1 rs4646536 are not responsible for CYP2R1 and CYP27B1 genes expression alteration, respectively, but CYP2R1 rs12794714 polymorphism may be the reason of CYP2R1 upregulation and increased the risk of CRC.     

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.     

In‐hospital mortality in SARS‐CoV‐2 stratified by gamma‐glutamyl transferase levels

BackgroundThis study investigates in‐hospital mortality amongst patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and its relation to serum levels of gamma‐glutamyl transferase (GGT).MethodsPatients were stratified according to serum levels of gamma‐glutamyl transferase (GGT) (GGT<50 IU/L or GGT≥50 IU/L).ResultsA total of 802 participants were considered, amongst whom 486 had GGT<50 IU/L and a mean age of 48.1 (16.5) years, whilst 316 had GGT≥50 IU/L and a mean age of 53.8 (14.7) years. The chief sources of SARS‐CoV‐2 transmission were contact (366, 45.7%) and community (320, 40%). Most patients with GGT≥50 IU/L had either pneumonia (247, 78.2%) or acute respiratory distress syndrome (ARDS) (85, 26.9%), whilst those with GGT<50 IU/L had hypertension (141, 29%) or diabetes mellitus (DM) (147, 30.2%). Mortality was higher amongst patients with GGT≥50 IU/L (54, 17.1%) than amongst those with GGT<50 IU/L (29, 5.9%). More patients with GGT≥50 required high (83, 27.6%) or low (104, 34.6%) levels of oxygen, whereas most of those with GGT<50 had no requirement of oxygen (306, 71.2%). Multivariable logistic regression analysis indicated that GGT≥50 IU/L (odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.20–3.45, p=0.009), age (OR: 1.05, 95% CI: 1.03–1.07, p<0.001), hypertension (OR: 2.06, 95% CI: 1.19–3.63, p=0.011), methylprednisolone (OR: 2.96, 95% CI: 1.74–5.01, p<0.001) and fever (OR: 2.03, 95% CI: 1.15–3.68, p=0.016) were significant predictors of all‐cause cumulative mortality. A Cox proportional hazards regression model (B = −0.68, SE =0.24, HR =0.51, p = 0.004) showed that patients with GGT<50 IU/L had a 0.51‐times lower risk of all‐cause cumulative mortality than patients with GGT≥50 IU/L.ConclusionHigher levels of serum GGT were found to be an independent predictor of in‐hospital mortality.     

Predictive significance of neutrophil‐to‐lymphocyte and platelet‐to‐lymphocyte for cytomegalovirus infection in infants less than 3 months: A retrospective study

BackgroundThe aim of this study was to evaluate the predictive value of the hematological parameters in the identification of human cytomegalovirus (CMV) infection in infants less than 3 months.MethodsA single‐center, observational study of infants with CMV infection was conducted retrospectively. Routine blood parameters were analyzed in CMV‐infected infants and controls with no differences of birthweight, sex, gestational age at birth, and date of admission. Furthermore, receiver‐operating curve was used to assess the predictive value of the hematological parameters for CMV infection.ResultsOne hundred ninety cases with CMV infection were studied retrospectively. Compared with the control group, there were significant differences in the white blood cell count, neutrophil count, lymphocyte count, platelet count, hemoglobin, neutrophil‐to‐lymphocyte (NLR), platelet‐to‐lymphocyte (PLR), and lymphocyte‐to‐monocyte (LMR) for the patients with CMV infection (all p < 0.001). The best predicted values for CMV infection based on the area under the curve (AUC) were NLR and PLR with the optimal cut‐off value of 0.28 and 65.36. NLR‐PLR score of 0, 1, or 2 based on an elevated NLR (>0.28), an elevated PLR (>65.36), or both. NLR‐PLR score for CMV infection prediction yielded higher AUC values than NLR or PLR alone (0.760 vs. 0.689, 0.689; p < 0.001).ConclusionsThe NLR combined with PLR is potentially useful as a predictor of CMV infection in infants less than 3 months.     

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.     

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.     

Downregulation of Talin‐1 is associated with the increased expression of miR‐182‐5p and miR‐9‐5p in coronary artery disease

BackgroundEvidence indicates that the dysregulation of extracellular matrix (ECM) components can lead to cardiovascular diseases. The Talin‐1 (TLN1) gene is a major component of the ECM, and it mediates integrin adhesion to the ECM. In this study, we aimed to determine microRNAs (miRs) that regulate the expression of TLN1 and determine expression alterations in TLN1 and its targeting miRs in coronary artery disease (CAD).MethodsData sets of CAD and normal samples of blood exosomes were downloaded, and TLN1 was chosen as one of the genes with differential expressions in an in silico analysis. Next, miR‐182‐5p and miR‐9‐5p, which have a binding site on 3´‐UTR of TLN1, were selected using bioinformatics tools. Then, the miR target site was cloned in the psiCHECK‐2 vector, and direct interaction between the miR target site and the TLN1 3′‐UTR putative target site was investigated by luciferase assay. The expression of miR‐182‐5p, miR‐9‐5p, and TLN1 in the serum samples of CAD and non‐CAD individuals was assessed via a real‐time quantitative polymerase chain reaction.ResultsOur data revealed that miR‐182‐5p directly regulated the expression of TLN1. Moreover, miR‐182‐5p and miR‐9‐5p were significantly upregulated in the CAD group. Hence, both bioinformatics and experimental analyses determined the downregulated expression of TLN1 in the CAD samples.ConclusionsOur findings demonstrated that miR‐182‐5p and miR‐9‐5p could play significant roles in TLN1 regulation and participate in CAD development by targeting TLN1. These findings introduce novel biomarkers with a potential role in CAD pathogenesis.     

Clinical and biochemical indexes of 11 COVID‐19 patients and the genome sequence analysis of the tested SARS‐CoV‐2

BackgroundAt present, SARS‐CoV‐2 epidemic in the world rapidly spread. It is a serious global public health emergency.MethodsIn this study, we described the clinical characteristics of 11 COVID‐19 patients hospitalized in the Meizhou People''s Hospital, and viral genome sequences of SARS‐CoV‐2 from these patients were analyzed.ResultsOf the 11 patients, six cases developed fever, 9 cases developed a cough, and two cases developed headache and chills. Four patients (36.4%) had underlying diseases. Pneumonia is the most common complication. The laboratory test results showed that there were no adult patients with increased lymphocyte/lymphocyte percentage (LYM/LYM%). Most patients had normal total protein (TP) and albumin (ALB), but only two patients had decreased. Most patients had increased or normal levels of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), activated partial thromboplastin time (APTT), fibrinogen (FIB), creatine kinase isoenzymes (CK‐MB), and lactate dehydrogenase (LDH). Neutrophil (NEU) (r = 0.664, p = 0.026), CK‐MB (r = 0.655, p = 0.029) and blood urea nitrogen (BUN) (r = 0.682, p = 0.021) were significantly associated with SARS‐CoV‐2 virus cycle threshold (Ct) value. Multiple sequence alignment (MSA) shows that two different SNPs were identified at positions 8781 and 28144, and have a complete linkage genetic form of 8781C‐28144T and 8781T‐28144C.ConclusionsThe reports of the 11 COVID‐19 patients in our hospital will provide useful information for the diagnosis, treatment, and drug development of SARS‐CoV‐2.