Journal of Clinical Laboratory Analysis

Background and Objectives From a preventive medicine perspective, this study aims to clarify the role of screening data in aging and health problems by estimating age from screening data and verifying the number of data items required in widely used screening tests. Materials and Methods A random forest model was applied to 11554 men and women (3043 and 8511, respectively) aged 0–95 years who underwent screening tests (60 blood tests, 8 urine tests and 2 saliva tests) between February 2020 and August 2023. All analyses were conducted in Python 3.10.12. Results Using all 71 items including gender, a high accuracy of R² = 0.7010 was achieved with 9243 training datasets (80% of total). R² decreased slightly to 0.6937 when data items were reduced to 15 by removing less important variables. When datasets numbered fewer than 800 or data items fewer than 7, R² fell below 0.6. Notably, postmenopausal women tended to have higher estimated ages compared to premenopausal women. Conclusions Age estimation from blood data using the random forest model (blood age) is sufficiently precise for assessing physical aging state. Blood age, as well as other biological ages estimated from various omics estimators, was shown to be a very promising method for exploring the problems of aging such as metabolic syndrome and frail syndrome.

Background Sequence alternations in mitochondrial genomes, especially in mitochondrial tRNA (mt‐tRNA), are closely related to type 2 diabetes mellitus (T2DM); however, the detailed molecular mechanism is still largely undetermined. Methods Herein, we reported a T2DM Chinese family by using molecular and biochemical analyses. The mtDNA mutations in this pedigree were detected by PCR and Sanger sequencing. Moreover, phylogenetic analysis was used to assess the pathogenic mitochondrial DNA (mtDNA) mutation. We further evaluated mt‐tRNA stability levels and mitochondrial functions in cybrids with and without the m.14687A>G mutation. Results Members of this family expressed variable clinical phenotypes. Screening for the entire mitochondrial genomes revealed the occurrence of a novel m.14687A>G mutation, which was located at position 60 in the TψC loop of tRNAGlu, and that position was important for tRNA structure and function. By establishing cybrids derived from three diabetic patients carrying the m.14687A>G mutation and three healthy individuals without this mutation, we noticed that this mutation caused approximately 52% reduction in tRNAGlu stability level (p < 0.0001). The 14687G cybrid showed more severely impaired mitochondrial functions than the 14687A cybrid: mtDNA content, ATP, and mitochondrial membrane potential (MMP) and OXPHOS enzyme activities were markedly decreased. But the levels of reactive oxygen species (ROS) were significantly increased. Conclusion Our finding revealed that the novel m.14687A>G mutation resulted in aberrant mt‐tRNA metabolism and mitochondrial dysfunctions, which should be regarded as a pathogenic mutation for T2DM.

Objective This study was to investigate the correlation between plasma nerve growth factor (NGF) and postoperative range of motion (ROM) in patients with rotator cuff tears (RCT). Methods From January 2022 to March 2024, a total of 135 patients with degenerative RCT were included. The patients were divided into Stiff group (n = 42) and Non‐Stiff group (n = 93) accordingly. The receiver operating characteristic curve (ROC) and area under the curve (AUC) were drawn to evaluate the predictive value of plasma NGF for postoperative joint stiffness. The Spearman test was used to analyze the relationship between plasma NGF and joint motion, VAS score, and joint function scores (UCLA score and Constant score). The relationship between plasma NGF and postoperative ROM and risk of joint stiffness was evaluated by restricted cubic spline (RCS) analysis of independent variables. Results In the preoperative and postoperative comparison, the two groups improved in joint flexion, VAS pain score, and joint function, except that the external rotation of the Stiff group did not change before and after surgery. After surgery, the ROM of the Stiff group was still significantly limited, and the ROM and joint function scores were lower than those of the Non‐Stiff group (p < 0.01). Conclusion This study suggests that reduced plasma NGF in patients with degenerative RCT may be associated with early shoulder stiffness, showing a negative non‐linear dose–response relationship. On a clinical basis, plasma NGF is beneficial to quantify the risk of early shoulder stiffness after RCT.

Background This study tested HIV‐1 antibodies in saliva samples (sHIV‐1 Ab) collected by the Self‐Lollisponge device. Methods Blood and saliva from confirmed persons with HIV and HIV‐negative controls were analyzed for HIV‐1/2 antibodies using the blood‐based First Response HIV 1‐2.O Card Test. The sampling device containing sHIV‐1 Ab was stored at 6°C for 60 days, with intermittent testing on days 2, 5, 10, 20, 30, and 60. Regression analysis was done to assess the relationship between the presence of sHIV‐1 Ab and independent variables. Results The sensitivity and the specificity of detecting sHIV‐1 Ab were 72.9% (95% CI: 63.92%–80.65%) and 100% (95% CI: 92.89%–100.00%), respectively. The presence of opportunistic infections (AOR = 13.1, p < 0.001), having stomatorrhagia (AOR = 4.56, p = 0.0022), and hyperviremia (> 201 copies/mL) (AOR = 4.91, p = 0.0225) heightened sHIV‐1 Ab detection. Furthermore, fatigue (AOR = 12.1, p = 0.0024), fever (AOR = 3.5, p = 0.0144), and weight loss (AOR = 10.9, p = 0.0318) increased the odds of having sHIV‐1 Ab in persons living with HIV (PLWHIV). sHIV‐1 Ab was identified in over 90% of PLWHIV with opportunistic infections (OIs) and stomatorrhagia, OIs and hyperviremia, and stomatorrhagia and hyperviremia. Upon storage for 60 days, the sHIV‐1 Ab was detected in all the samples. Conclusion Saliva could be an alternative to blood for diagnosing HIV. In addition, the Self‐Lollisponge device was found to be user‐friendly, acquiescent to all settings, and cheap, and can preserve sHIV‐1 Ab for at least 60 days.

Objective This study enrolled 119 elderly patients with severe lower respiratory tract infections (LRTIs) and used machine learning (ML) to evaluate the predictive value of unconventional T lymphocytes (uT cells) in sepsis and 90‐day prognosis. Methods We used random forest (RF) and LASSO analyses to screen model uT cells (identified by RF‐LASSO overlapping). The ML models, including LR, LDA, RandomForest, XGBoost, KNN, QDA, NaiveBayes, and ANN, were developed. These models were evaluated and compared based on accuracy, precision, recall, F1 score, sensitivity, specificity, area under the ROC curve (AUROC), and Brier score. Results Two T cells were identified as factors of sepsis diagnosis: CD3⁺ and CD4⁺CD25⁺CD127dim. The LDA model demonstrated superior performance, achieving an accuracy of 0.806, AUROC of 0.771, F1 score of 0.720, and a low Brier score of 0.182. Four T cells were identified for predicting the 90‐day prognosis: CD3⁺, CD3⁺CD4⁺, CD4⁺CD28⁺, and CD4⁺CD25⁺CD127dim. For the 90‐day prognosis, the LDA model again performed best, with an accuracy of 0.972, F1 score of 0.952, AUROC of 0.935, and a low Brier score of 0.059. Conclusions The LDA model is optimal for both diagnosing sepsis and predicting the 90‐day prognosis in elderly patients with severe LRTIs. Key T‐cell markers identified for sepsis include CD3⁺ and CD4⁺CD25⁺CD127dim, while the 90‐day prognosis model includes CD3⁺, CD3⁺CD4⁺, CD4⁺CD28⁺, and CD4⁺CD25⁺CD127dim T cells. These markers should be prioritized for clinical testing. Trial Registration: Not applicable

Background Severe aplastic anemia (SAA) is a life‐threatening hematologic disorder characterized by bone marrow failure and impaired immunity. Purpose Investigating the role of Toll‐like receptor 4 (TLR4) highly expressing macrophages in the immunopathogenesis of SAA. Methods Macrophage TLR4 expression levels were detected by reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and western blotting (WB). Knocked down or inhibited macrophage TLR4 expression, detected the pyroptosis (IL‐1β, IL‐18, NLRP3, caspase‐1, gasdermin D) levels by RT‐qPCR and WB. Using RNA sequencing to find differential genes and pathways. Co‐cultured CD8+ T cells with macrophages that knocked down or inhibited TLR4, and the levels of perforin and granzyme B expression in CD8+ T cells were detected by flow cytometry. CD8+ T cells were further co‐cultured with K562, and the apoptosis rate of K562 was detected. Results The TLR4 in the bone marrow macrophages of patients with untreated SAA were significantly higher than those in the remission and control groups, and were negatively correlated with clinical indicators. RNA sequencing of macrophages with TLR4 knockdown showed that differentially expressed genes were enriched in the innate immune and inflammatory chemotaxis signaling pathways. After TLR4 knockout or TLR4 inhibitor addition in bone marrow macrophages of patients with untreated SAA, the mRNA and protein expression levels of pyroptosis markers interleukin (IL)‐1β, IL‐18, NLRP3, caspase‐1, and gasdermin D were significantly lower than those in the control group. When CD8+ T cells were co‐cultured with TLR4‐knocked‐down or inhibitor‐added macrophages, the expression of perforin and granzyme B in CD8+ T cells was significantly reduced, and CD8+ T cell cytotoxicity decreased. Conclusions Inhibition of macrophage TLR4 expression in SAA patients could alleviate the over‐activated cellular immune response in SAA patients by decreasing the level of pyroptosis.

Objective This study evaluated the diagnostic performance of the FilmArray GI Panel multiplex polymerase chain reaction (PCR) compared to conventional stool culture (CSC) and microscopic stool analysis in children with bacterial acute infectious gastroenteritis (AIG) in the emergency department (ED). It also assessed the impact of PCR use on clinical decision‐making, antibiotic stewardship, and ED workflow. Methods A retrospective analysis was conducted in a tertiary pediatric ED. Children diagnosed with AIG who underwent CSC, microscopy, and multiplex PCR were included. Data on demographics, clinical findings, diagnostic results, antibiotic prescriptions, and patient outcomes were collected. Diagnostic performance metrics—sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)—were compared. Results Among 257 pediatric patients, enteropathogens were detected in 31.9% via CSC and 39.3% via multiplex PCR. PCR showed superior sensitivity (96.2%) and NPV (97.4%) compared to CSC. The median turnaround time for PCR (7.9 h) was significantly shorter than for CSC (47.5 h, p < 0.001). Antibiotic use was significantly lower in PCR‐negative cases (p < 0.001), and ED length of stay was also reduced. Conclusion The FilmArray GI Panel offers improved sensitivity and faster results than conventional methods, enhancing diagnostic accuracy and reducing unnecessary antibiotic use. Its integration in ED protocols can support antimicrobial stewardship and streamline care.

Purpose Active surveillance (AS) strategy aims to avoid unnecessary or excessive early treatment in patients at a low risk for prostate cancer (PCa). However, a biomarker that can predict the need for early curative treatment in patients under AS has not been identified to date. In this study, we aimed to investigate the potential of inflammatory biomarkers in predicting the requirement of curative treatment in the early period in patients under AS. Materials and Methods This study included a total of 83 patients with the diagnosis of PCa and under AS. Patient age, prostate‐specific antigen (PSA) level, prostate volume (PV), PSA density (PSAD), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immune‐inflammation index (SII) and follow‐up period were compared between the groups. Results There was a significant difference between the two groups in terms of PSAD, NLR, PLR and SII (p = 0.037, p = 0.046, p = 0.008, p = 0.004 and p = 0.005, respectively). The cut‐off value determined by performing ROC analysis to evaluate the levels that predict the need for curative treatment before AS was 0.125 for PSAD (sensitivity: 61.8%, specificity: 61.2%), 2.01 for NLR (sensitivity: 67.6%, specificity: 55.1%), 115.49 for PLR (sensitivity: 73.5%, specificity: 59.2%) and 465.40 for SII (sensitivity: 70.6%, specificity: 59.2%). Conclusions The analysis of PSAD, NLR, PLR and SII before making the decision to conduct AS can guide clinicians regarding curative treatment in the early period.

Background COVID‐19 can affect hematological and biochemical parameters, potentially altering platelet function. This study aimed to evaluate the long‐term effects of COVID‐19 on the quality of platelet concentrates (PCs) collected from donors with a history of infection. Materials and Methods Twenty PCs were selected from male donors who had recovered from COVID‐19. Donors were divided into two groups: control (recovered more than 6 months ago) and case (recovered between 1 and 3 months ago). Research variables, including metabolic and oxidative parameters, were evaluated. Platelet aggregation was also measured at various time points during PC storage. Results Both groups showed significant decreases in glucose and pH, and increases in lactate, LDH activity, and ROS during storage (p < 0.001). Collagen‐induced platelet aggregation declined over time in both groups without a significant difference between them (interaction p = 0.8). In contrast, arachidonate‐induced aggregation showed a significant group‐by‐time interaction (p = 0.003), with a significant decrease over time in the case group but not in controls. Other parameters did not differ significantly between groups (p > 0.05). Conclusion PC from donors recently recovered from COVID‐19 exhibited a decline in aggregation in response to both collagen and arachidonic acid; however, the reduction in arachidonic acid‐induced aggregation was particularly significant, indicating a selective impairment in platelet function following infection. Biochemical markers did not show significant differences between groups. Further studies with larger cohorts and clinical efficacy assessments are essential to comprehensively evaluate the safety and effectiveness of transfusing PC from donors recently recovered from COVID‐19.

Background Various factors, including virulence determinants, biofilm formation, and antimicrobial resistance, contribute to the severity of infections caused by Enterococcus spp. Methods Enterococcus isolates were obtained from hospitalized patients in Yazd, Iran, and identified using microbiological and molecular tests. High‐level resistance, biofilm formation, and the genes encoding virulence factors and resistance were investigated following standard methods. Results Enterococcus faecalis was the most prevalent species (60.7%), followed by Enterococcus faecium (30.4%). Linezolid was highly effective, with 94.6% of isolates being susceptible. However, more than 76% of isolates exhibited resistance to rifampin, erythromycin, tetracycline, and ciprofloxacin, and 94.6% were multidrug‐resistant (MDR). Additionally, 39.3% of the isolates were vancomycin‐resistant enterococci (VRE) with a MIC > 32 μg/mL, and the vanA gene was detected in 35.7% of the isolates. High‐level resistance to gentamicin and streptomycin was seen in 60.7% and 50% of the isolates, respectively. The most prevalent aminoglycoside resistance gene was aph(3′)‐IIIa (62.5%) followed by ant(6′)‐Ia (58.9%), and aac(6′)‐Ie‐aph(2″)‐Ia (50%). The ant(3″)‐Ia was found in only one isolate. Most of the isolates (87.5%) were biofilm producers, and the distribution of virulence‐encoding genes was as follows: gelE (66.1%), efaA (57.1%), asa1 (51.8%), esp (25%), cylA (19.6%), and hyl (8.9%). Furthermore, the ace gene was present in 79.4% of E. faecalis isolates, while the fnm and acm genes were found in 76.5% and 23.5% of E. faecium isolates, respectively. Conclusion The study highlights the significant role of notable drug resistance and the widespread presence of virulence traits in the development of enterococcal infections.

Background Recent studies from various countries, including those in Africa, have highlighted the importance of region‐specific data in assessing hematological health. However, no study has established hematological reference intervals (RIs) in Northern Sudan. We aimed to investigate the normal hematological values among apparently healthy adults in Northern Sudan. Methods A cross‐sectional study was conducted in Northern Sudan. Standardized procedures measured participants' weight, height, and hematological parameters. The Mann–Whitney U test was used to compare the parameters between males and females. Mean, median, and RIs (2.5th–97.5th percentiles) were computed for the adults. Results Two hundred fifty‐three adults were enrolled (141 [55.7%] males and 112 [44.3%] females). The median (interquartile [IQR]) of the enrolled adults' age was 40.0 (29.7–50.0) years. The RIs for both genders, hemoglobin 9.71–16.10 g/dL, red blood cells (RBC) 3.66–5.79 × 10⁶/mm³, hematocrit (HCT) 28.02%–46.75%, mean corpuscular volume (MCV) 64.02–95.65 fL, mean corpuscular hemoglobin (MCH) 21.57–33.80 pg, mean corpuscular hemoglobin concentration (MCHC) 31.60–36.56 g/dL, platelet count 155.35–454.30 × 10³/mm³, and total white blood cells (WBCs) 2.90–10.76 × 10³/mm³. Significantly higher median values were observed in males compared to females for hemoglobin, RBC, HCT, MCH, MCHC, and platelet distribution width. In contrast, females demonstrated significantly higher red cell distribution width‐coefficient of variation, WBC, platelet, mean platelet volume, and plateletcrit than males. MCV showed no significant difference between genders. Conclusion The study's findings underscore the importance of establishing RIs for each region and specific gender population. RIs should also be established in other regions of Sudan to enhance clinical relevance and accuracy.

Background We investigated the association of two novel indices, the athero‐inflammatory (AI) index and athero‐inflammatory glucose (AIG) index, with coronary artery stenosis (CAS). Methods In this case–control study, the cases were grouped as angiography (+) and angiography (−) according to the angiographic results. The control group comprised subjects who attended clinics for routine check‐ups or pre‐employment medical assessments. The AI index and AIG index were compared between the groups using ANOVA. Binary logistic regression (LR) was performed to find the association of the indices with angiography (+). Receiver operating characteristic (ROC) curve analysis was used to establish the cut‐off values in differentiating angiography (+) from angiography (−) and healthy subjects. p < 0.05 were considered statistically significant. Results Among a total of 2326 participants (761 angiography (+), 406 angiography (−), and 1159 controls), the AI index and AIG index were significantly different between the groups (p < 0.001). In LR analysis, after adjustment for potential confounders, the AI index and AIG index were independently associated with angiography (+). ROC curve analysis showed that the AI index (AUC: 0.895; 95% CI: 0.880, 0.908; p < 0.0001) and AIG index (AUC: 0.918; 95% CI: 0.905, 0.930; p < 0.0001) performed better diagnostic performance in differentiating angiography (+) from healthy subjects. Conclusion AI index demonstrated higher AUC compared to other biomarkers in differentiating angiography (+) from angiography (−) and healthy subjects. If it combines with fasting glucose (AIG index), it is a promising indicator for the identification of the CAS particularly from a healthy population, with a promising AUC.

Background Augmented renal clearance (ARC) refers to a phenomenon in critically ill patients characterized by increased creatinine clearance. Neurological patients seem to be at higher risk compared with other groups. The epidemiology study of ARC reported in critically ill neurological patients varies substantially with the definitions used and the population evaluated. Objective We aimed to describe the prevalence of ARC and to explore risk factors in critically ill neurological patients. Methods A retrospective observational study was conducted in a university‐affiliated neurocritical care unit (NCCU). Study participants had a serum creatinine concentration (Scr) < 120 μmol/L. Kidney function was assessed by the 24‐h creatinine clearance (CLcr); ARC was defined as CLcr ≥ 120 mL/min/1.73m² in women and ≥ 130 mL/min/1.73m² in men. The prevalence and clinical characteristics of ARC were evaluated. Multivariate logistic regression analysis was used to assess variables associated with ARC occurrence. Results Of the 137 patients, 56.2% were male, and the mean age was 50.2 (17.4) years. ARC was present in 55.5% of the NCCU patients, ranging from 50% in intracranial infection to 75% in patients with spinal lesions. ARC patients have a mean CLcr159.3 (IQR:139.6–185.2) ml/min/1.73m². Age was the only factor independently associated with ARC (OR 0.996, 95% CI: 0.934–0.999, p = 0.043) in multivariable logistic analysis. Scr (Pearson correlation = −0.477) and cystatin C (Pearson correlation = −0.336) were found to have a negative correlation with ARC with statistically significant effects. Conclusion ARC is prevalent in critically neurological patients. Age is likely to significantly influence renal clearance in this population, especially as patients with low Scr and cystatin C levels should be given more attention.

Objectives Nanopore sequencing shows advantages in detecting single nucleotide variations (SNVs), deletions, and complex structural variants as a single test in thalassemia. However, the performance evaluation or verification of this method remains unestablished, which is essential before clinical utility and panel registration. Here, we developed a classification method for thalassemia mutations, enabling automated interpretation, visual representation, and identification of diverse mutation types. Methods We used a total of 36 samples, comprising 32 reference materials and four clinical samples to assess the performance of nanopore sequencing in identifying variants in terms of concordance, precision, and the lower limits of detection. Results Our analysis successfully identified 19 SNVs, six deletions, and two triplications using nanopore sequencing across all samples. Notably, these variants showed complete concordance of 100% with the genotypes of the reference materials and known results. The precision of nanopore sequencing for detecting thalassemia variants was consistently high, with neither false positive nor false negative observed. Furthermore, the lower limits of detection achieved in our study were 3 ng/μL. Conclusions Overall, our study proved that the reference materials can be used to evaluate the performance of nanopore sequencing in identifying thalassemia mutations, and it is necessary to incorporate triplications when utilizing reference materials for performance evaluation of long‐read sequencing. The consistent and robust performance of nanopore sequencing in this study demonstrates its potential as a reliable method for comprehensive variant detection in thalassemia and other genetic diseases diagnosis.

Background Adrenomedullin (ADM) is a potent hormone‐like peptide rapidly induced by hypoxia and inflammatory cytokines in the early stages of sepsis. For this reason, the dosage of its more stable precursor fragment called mid‐regional (MR)‐proADM is currently recommended to assist in triaging patients in the emergency department. Since MR‐proADM dosage is currently only approved for use in plasma, we validated its dosage in cerebrospinal fluid (CSF) samples to improve the diagnosis of central nervous system (CNS) diseases. Methods MR‐proADM concentrations were measured in samples using a fully automated platform (Brahms Kryptor Gold Analyzer, Thermo Scientific, Germany), applying the same analytical conditions in plasma and CSF samples, to finally set up an accurate laboratory protocol to validate its dosage in CSF. Results MR‐proADM is highly stable in CSF samples stored at room temperature for up to 48 h, allowing it to be measured with confidence also in CSF samples that may be left on the bench for several hours. In addition, the repeatability and within‐laboratory precision of the MR‐proADM assay using CSF samples appeared equal to or better than those obtained by the manufacturer using plasma samples, allowing the use of this assay, with high precision, also for CSF samples. Conclusion The reliable measure of MR‐proADM in CSF and the role of this molecule in CNS will allow its introduction in the diagnostic process of infectious, inflammatory, and degenerative neurological diseases.

Aim This study aimed to determine the important features and cut‐off values after demonstrating the detectability of cirrhosis using routine laboratory test results of chronic hepatitis C (CHC) patients in machine learning (ML) algorithms. Methods This retrospective multicenter (37 referral centers) study included the data obtained from the Hepatitis C Turkey registry of 1164 patients with biopsy‐proven CHC. Three different ML algorithms were used to classify the presence/absence of cirrhosis with the determined features. Results The highest performance in the prediction of cirrhosis (Accuracy = 0.89, AUC = 0.87) was obtained from the Random Forest (RF) method. The five most important features that contributed to the classification were platelet, αlpha‐feto protein (AFP), age, gamma‐glutamyl transferase (GGT), and prothrombin time (PT). The cut‐off values of these features were obtained as platelet < 182.000/mm³, AFP > 5.49 ng/mL, age > 52 years, GGT > 39.9 U/L, and PT > 12.35 s. Using cut‐off values, the risk coefficients were AOR = 4.82 for platelet, AOR = 3.49 for AFP, AOR = 4.32 for age, AOR = 3.04 for GGT, and AOR = 2.20 for PT. Conclusion These findings indicated that the RF‐based ML algorithm could classify cirrhosis with high accuracy. Thus, crucial features and cut‐off values for physicians in the detection of cirrhosis were determined. In addition, although AFP is not included in non‐invasive indexes, it had a remarkable contribution in predicting cirrhosis. Trial Registration Clinicaltrials.gov identifier: NCT03145844

Background Colorectal cancer (CRC) is a worldwide burden. Circular RNAs are promising biomarkers for diagnosing and prognosis of CRC. Objective To investigate the possible association of sera levels of CircFUNDC1 and CircUHRF1 expression with predisposition and clinicopathological findings in CRC, ulcerative colitis (UC), and Crohn's disease (CD) in Egyptian patients. Methods The serum levels of CircFUNDC1 and CircUHRF1 were evaluated in 113 Egyptian subjects divided into four groups; CRC (31), UC (26), and CD (25) and compared to healthy controls (31) using quantitative polymerase chain reaction. Results The median values of log2 serum fold change (FC) of CircFUNDC1 in CRC, UC, and CD patients were 9.11, 6.58, and 6.17, respectively. It was upregulated in all case groups. CRC, UC, and CD patients had significantly higher serum CircFUNDC1 levels than controls (p < 0.001). However, there were no significant differences among patient groups (CRC, UC, and CD). The medians of log 2 of serum FC CircUHRF1 in patients with CRC, UC, and CD were −2.00, 3.33, and 3.12, respectively. The CircUHRF1 serum level was lower in the CRC group of patients, with no significant difference between the CRC group and the controls. Serum CircUHRF1 was significantly overexpressed in patients with UC and CD compared to the CRC groups or controls (p < 0.001). By Roc curve analysis, both genes can differentiate CRC patients from inflammatory bowel disease (IBD) patients or healthy controls with p < 0.05. Conclusion Serum CircFUNDC1 is a biomarker for CRC, while CircUHRF1 is a biomarker of IBD.

Background Rheumatoid arthritis (RA) is a persistent autoimmune disorder that impacts the joints, leading to a reduction in physical function and a decline in overall well‐being. UCMA is a vitamin K‐dependent protein that plays a role in some human diseases, including osteoarthritis and cardiovascular disorders. Nevertheless, the possible role of UCMA in the pathogenesis of RA remains unclear. Therefore, we aimed to investigate the expression of UCMA in serum samples of patients with RA, its relationship with disease activity and some blood markers. Methods The current study included 98 RA patients and 24 healthy individuals. Serum UCMA, COMP, TNF‐α, and IL‐6 levels were measured using enzyme‐linked immunosorbent assay. Results Serum UCMA, COMP, TNF‐α, and IL‐6 expressions were significantly increased in RA patients compared to healthy controls (p < 0.05). The ROC curve analysis demonstrated that blood UCMA, COMP, TNF‐α, and IL‐6 levels had the capability to differentiate between patients with RA and healthy controls (p < 0.05). UCMA was positively correlated with certain laboratory indicators, such as COMP, TNF‐α, IL‐6, CRP, and CCP. Conclusion Here, we report for the first time that UCMA may reflect cartilage degeneration and inflammatory changes in RA patients. Furthermore, UCMA could be employed as a predictive or diagnostic marker in the clinical practice of RA.

Background Non‐Hodgkin lymphoma (NHL) is one of the most prevalent disorders worldwide, with a variety range of etiology from environmental to genetic factors. H19 is a non‐coding RNA that codes no protein while playing regulatory roles and is hypothesized to be involved in susceptibility to NHL. Methods 209 NHL patients and 259 healthy subjects were studied. The salting out method was used for genomic DNA extraction, followed by the Refractory fragment length polymorphism polymerase chain reaction (RFLP‐PCR) technique for genotyping. SPSS package V.22 software was used for statistical analysis. Several in silico tools were used to predict the probable consequences of studied H19 genetic variants on the different aspects of non‐coding RNAs. Results The results revealed that statistically, both rs3741219T>C and rs217727C>T variants increased the susceptibility to NHL. The T allele of rs3741219T>C in the codominant model caused the most enhancement in the incidence of NHL (OR = 2.33, 95% CI = 1.28–4.25, p = 0.005). Moreover, The CC genotype of rs217727C>T compared to TT had the sharpest impact on the susceptibility to NHL (OR = 2.27, 95% CI = 1.21–4.23, p = 0.009). In silico predictions revealed that the studied variants seem to alter the binding sites of miRNAs on the H19 long non‐coding RNA and change its targets. Furthermore, nucleotide substitution in both rs3741219T>C and rs217727C>T may prepare a new binding site for a transcription factor called Y‐Box‐binding protein‐1 (YB‐1). Conclusions The rs217727C>T and rs3714219T>C were responsible for elevating the likelihood of NHL in our population. These substitutions alter the RNA folding of H19 and alter the miRNA binding sites on the H19 transcript.

Background Sexually transmitted infections (STIs) are a major threat to global health, and the emergence of antibiotic‐resistant strains has made therapeutic strategies more complex. Antimicrobial peptides (AMPs) are a ubiquitous class of natural compounds that are expected to be an alternative to conventional antibiotics due to their broad spectrum of activity and lower propensity for resistance, promising alternatives to conventional antibiotics. Objective To emphasize the importance of antimicrobial peptides in the fight against STIs and to review recent advances in AMPs for the treatment and prevention of STIs. Methods This article focuses on reviewing the progress of research on AMPs in the treatment and prognosis of STIs such as gonorrhea, HIV, HPV, and chlamydia, and discusses the challenges and future directions of the field. Results AMPs have great potential in the prevention and treatment of STIs. However, AMPs for the treatment of STIs face challenges such as enzymatic degradation, safety and high cost, while nanotechnology and peptide modification are expected to enhance the stability and bioavailability of AMPs. Conclusion AMPs have the potential to become an important tool for the treatment of STIs with further research and technological innovation.

Background Shrimp and crab allergies have garnered increasing attention in recent years. Unlike many other food allergies, they are less likely to be outgrown by children and tend to trigger more severe allergic symptoms. The underlying mechanisms that lead to these phenomena have not yet been fully elucidated. Methods We used proteomics iTRAQ technology to identify differentially expressed proteins in shrimp and crab allergic patients and normal controls. Results Ninety differentially expressed proteins, including 82 upregulated proteins and 8 downregulated proteins, were identified. Furthermore, MRC2 was validated to be upregulated in shrimp and crab allergic patients by ELISA. Conclusion These findings have established a comprehensive proteomics map of shrimp and crab allergies, laying the foundation for further analysis of the pathogenesis and regulatory network of shrimp and crab allergies.

Background In clinical practice, acute‐phase reactive proteins (APRPs) are frequently measured at random times. However, it is unclear whether the use of fasting or nonfasting samples affects results. This study aims to investigate the variations of APRPs between fasting and nonfasting conditions. Methods This study was conducted based on the oral glucose tolerance test (OGTT) experiment due to standard energy intake and strict time flow. Fifty subjects were enrolled and underwent a 12‐h fasting period before the experiment. Blood samples were collected the following day at baseline (fasting, T0) and 30 (T1), 60 (T2), 120 (T3), 180 (T4) minutes postglucose intake. A total of 250 blood samples were obtained. To quantify clinical fluctuations, percentage bias was calculated, and Bland–Altman plots were employed. Results Our observational study demonstrated significant postprandial variations for APRPs. For CRP, 17 (34%) of 50 subjects at T1, 21 (42%) at T2, 23 (46%) at T3, and 16 (32%) at T4 exhibited levels exceeding the maximum allowable error in medical laboratory testing, indicating clinically unacceptable bias. For IL‐6, thirty subjects (60%) at T1, 27 (54%) at T2, 28 (56%) at T3, and 32 (64%) at T4 displayed clinically unacceptable fluctuations. Among other APRPs, the maximum number of subjects exceeding acceptable bias thresholds was 28% (14/50) for procalcitonin, 38% (19/50) for transferrin, 34% (17/50) for prealbumin, and 24% (12/50) for ceruloplasmin. Conclusion Clinical fluctuations were observed in the levels of APRPs between fasting and nonfasting states. Clinicians should pay attention to the effects of dietary factors on test results.

Background Preeclampsia (PE), as a pathological pregnancy process, is still unclear in its precise pathophysiology. The current consensus on PE pathogenesis is that it is an immune‐inflammatory response due to placental dysfunction leading to multiorgan involvement in the mother. Macrophages can polarize into different phenotypes under the influence of distinct microenvironments, secreting various cytokines or chemokines with distinct functions. These phenotypes play roles in either promoting inflammation or facilitating tissue repair. Studies have observed the increase in M1 polarization of decidual macrophages during the occurrence of PE, with this polarization imbalance contributing to the immuno‐inflammatory response involved in placental formation. Therefore, understanding the polarization characteristics of macrophages provides a valuable direction for research related to the prevention and treatment of PE. Methods Authors searched for related literature on PubMed using the professional terms “preeclampsia” and “macrophage polarization”. The obtained literature was categorized according to its research. Similar articles are summarized in the same sections, which are divided into different small sections according to their specific contents. Results Different studies have explored the metabolic characteristics, surface markers, secretions, signaling pathways, and functions of different macrophage polarization types, highlighting the critical role of polarization imbalance and excessive inflammatory responses in the development of PE. Intervening in inflammatory responses at the maternal‐fetal interface holds significant value for the prevention and treatment of PE. Conclusion Understanding the metabolic characteristics of different macrophage polarization types, combined with their polarization imbalance during the development of PE, can facilitate targeted prevention of PE.

Background Pulmonary lophomoniasis is an emerging disease caused by the protozoan pathogen Lophomonas spp. Recently, a conventional polymerase chain reaction (PCR) method has been developed. However, its sensitivity and specificity remain to be fully established. Therefore, this study aimed to develop in‐house conventional and multiplex PCR for the detection and identification of Lophomonas infections. Additionally, we attempted to compare the diagnostic performance of these novel PCR tests with the current microscopic examination method using BAL samples. Methods We studied 120 bronchoalveolar lavage (BAL) specimens of the patients clinically suspected of having lophomoniasis. The specimens were examined using three methods: microscopic examination (Giemsa staining), in‐house conventional PCR, and multiplex‐PCR. Moreover, multiplex‐PCR was used for the simultaneous identification of two species of Lophomonas. Results Out of the 120 BAL specimens tested, 30 (25%) tested positive through microscopic wet mount examination. Among the three techniques, multiplex‐PCR was the most sensitive (100%, 95% CI, 88.3–100), while Giemsa staining had the lowest sensitivity (86.2%, 95% CI, 69.4–94.5). The data reveal a strong agreement between multiplex‐PCR and conventional PCR (κ = 0.96), while the lowest agreement was found between multiplex‐PCR and microscopy methods (κ = 0.16). The study also confirmed the presence of L. blattarum species in all samples using multiplex‐PCR. Conclusions This study demonstrates that the in‐house multiplex‐PCR is a robust and accurate diagnostic test for the detection and identification of Lophomonas species. Therefore, our findings suggest that this method may be a powerful tool to overcome some diagnostic pitfalls for lophomoniasis.