This study reported a portable point-of-care testing (POCT) system based on a solution-gated graphene transistor (SGGT) for highly sensitive detection of tumorderived exosomal miRNAs. The system demonstrated excellent portability, operational simplicity, and high detection sensitivity, achieving a limit of detection as low as $10^{-20} \mathrm{M}$. It also exhibited remarkable specificity, and each measurement only took approximately 400 seconds. The detection results for exosomal miRNA samples were consistent with those obtained by the gold standard qRTPCR method. With high visualization capability, userfriendly portability, and superior sensitivity, the system provided a novel strategy for tumor diagnosis.
Exosomal miRNAs are promising tumor biomarkers and are closely associated with clinical factors such as patient prognosis and chemotherapy sensitivity. However, their short sequences, low abundance, and dependence on bulky, non-portable instruments limit their application in rapid early screening. Thus, we developed a portable solution-gated graphene transistor (SGGT)-based detection system for tumor-derived exosomal miRNAs, specifically designed for point-of-care testing (POCT). The system integrates weak-signal excitation and acquisition modules and supports dual-mode operation, including transfer characteristic analysis and real-time current monitoring. The device is compact, portable, and enables direct result visualization, while the sensors support batch fabrication and facile functionalization with ssDNA probes on the SGGT gate. Leveraging the electric double-layer gating effect, this system achieved an ultra-low detection limit of 6.17 x 10-1 9 M, enabled miRNA-21 detection within 400 s, and effectively discriminated single-base mismatched sequences. It successfully distinguished exosomal miRNA-21 derived from tumor cells (H1975) and normal cells (HUVECs), consistent with the quantitative reverse transcription polymerase chain reaction(qRT-PCR) results and further differentiated samples from lung cancer patients and healthy individuals. Overall, the POCT system demonstrated rapid response, high sensitivity, and reliable performance, providing a practical platform for portable tumor biomarker detection and clinical diagnostics.
BACKGROUND:ABO blood types have important clinical significance in medicine. In this paper, our primary objective is to evaluate the association between ABO blood types and coronary heart disease (CHD) in the Chinese population. The secondary objective is to explore whether blood lipids may serve as a potential influencing factor in the relationship between blood types and CHD. METHODS:We collected data from 5188 CHD patients to assess the distribution of blood types between CHD patients and blood donors, and performed binary logistic regression analysis to explore the correlation between blood types and CHD. Subgroup analyses and interactions were conducted to verify the robustness of the findings. Serum biological markers of CHD across different blood types were compared to explore potential underlying mechanisms. RESULTS:The proportion of Type A was higher (p = 0.012), and Type O was lower (p = 0.047) in CHD. Logistic regression modeling analyses showed that Type A had a significantly increased risk of CHD by 24% compared with non-A (OR [95% CI] 1.24: 1.05-1.45, p = 0.009). Blood Type A had a consistent effect on the risk of CHD across all subgroups, with no significant interaction observed (p for interaction > 0.1). Further, serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were found to be significantly higher in individuals with Type A CHD compared with those with non-A blood types (p = 0.02, p = 0.045, p = 0.019). CONCLUSIONS:Type A is an independent risk factor for CHD, and CHD patients with Type A exhibit higher blood lipid levels, suggesting that blood type antigens may be involved in the occurrence of CHD through the lipid pathway.
BACKGROUND:Gastric cancer (GC) remains a significant global burden of cancer-related mortality, with current biomarkers exhibiting insufficient sensitivity and specificity for GC detection. This study investigated the potential of transfer RNA-derived small RNAs (tsRNAs) as novel diagnostic biomarkers for GC. METHODS:The candidate biomarker 5'-tRFGly, initially identified through database screening, underwent rigorous validation procedures: including real-time quantitative PCR (RT-qPCR) for expression level detection, sequencing confirmation of sequence consistency, secondary structure computer modeling, and evaluation of its GC diagnostic efficacy based on discriminative power and electrophoresis experiments. RESULTS:The study found that 5'-tRFGly was significantly overexpressed in GC tissues, cells, and serum. Compared with healthy donors and gastritis patients, serum levels of 5'-tRFGly were significantly elevated in GC patients and markedly decreased postoperatively. Furthermore, high expression of 5'-tRFGly was associated with neural/lymphovascular invasion, high-grade histology, regional lymph node metastasis, and advanced TNM stage (all P < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated that 5'-tRFGly exhibited superior diagnostic accuracy for GC compared to existing clinical biomarkers such as carcinoembryonic antigen (CEA), carbohydrate antigen 724 (CA724), and carbohydrate antigen 199 (CA199), with significantly larger area under the curve (AUC) values. CONCLUSIONS:5'-tRFGly is a promising biomarker for gastric cancer, with elevated serum levels reflecting tumor presence and aggressiveness. Its decrease after surgery and superior diagnostic accuracy over conventional markers support its potential use in non-invasive detection, postoperative monitoring, and risk stratification.
AIM:The objective of this study was to investigate the prognostic significance of the preoperative serum albumin-bilirubin (ALBI) score in patients with colorectal cancer (CRC). METHODS:Preoperative ALBI data from 1506 CRC patients were categorized into high-value and low-value groups, and the clinicopathological characteristics of these groups were compared. A Cox proportional hazards regression model was employed to investigate the risk factors associated with distant metastasis. The Kaplan-Meier method and log-rank test were utilized to analyze the relationship between ALBI scores and 5-year distant metastasis-free survival (DMFS). RESULTS:The incidence of distant metastasis in group B (ALBI ≥ -2.4) was significantly higher at 28.81% compared to group A (ALBI < -2.4), which had an incidence of 23.36% (p = 0.018). ALBI score ≥ -2.4 was identified as an independent risk factor for postoperative distant metastasis of CRC (HR = 1.251, 95%CI: 1.021-1.533, p = 0.031). The incidence of 5-year DMFS was significantly lower in the ALBI ≥ -2.4 group compared to that observed in the ALBI < -2.4 group (χ2 = 5.97, p = 0.015, log-rank test). CONCLUSION:The ALBI score of ≥ -2.4 emerges as an independent risk factor for the occurrence of distant metastases following CRC surgery.
Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. In this study, our objective was to identify a specific tRNA-derived small RNA (tsRNA) as a biomarker for GC. We developed and validated a methodology to detect the expression level of tRF-30-RRJ89O9NF5W8 in the serum of GC patients. The results showed that the expression of tRF-30-RRJ89O9NF5W8 was significantly downregulated in the serum of GC patients and increased after radical surgery. Clinicopathological correlation analysis revealed that its expression level was closely associated with TNM stage, T stage, and neural/vascular invasion. Compared with existing GC diagnostic markers, tRF-30-RRJ89O9NF5W8 demonstrated superior diagnostic performance, effectively distinguishing GC patients from those with gastritis and healthy controls. These findings suggest that tRF-30-RRJ89O9NF5W8 may serve as a promising candidate diagnostic biomarker for GC and provide theoretical support for its potential as a therapeutic target.
Tumors are associated with the highest mortality rates worldwide. For more than a decade, research has focused on the genetic involvement of proteins in cancer; however, a complete class of molecular non‑coding (nc)RNAs have been discovered in recent years, and these are considered to be associated with cancer. Notably, ncRNAs are highly conserved and multifunctional. These interact with multiple signaling pathways, influencing cell cycle progression and various physiological processes. Therefore, the present review aimed to investigate ncRNA, microRNA, transfer RNA‑derived small RNA, PIWI‑interacting RNA and long non‑coding RNA to further understand the associated generation processes, functional mechanisms and therapeutic roles in tumors. The present review demonstrated the critical role of ncRNAs in tumors, and may provide a novel theoretical basis for the role of ncRNAs as biomarkers or therapeutic tools in the treatment of cancer.
BACKGROUND:Molecular biology and molecular genetics play an extremely important role in identifying ABO sub-groups. METHODS:Blood group was detected by conventional serological method, and ABO gene was amplified and sequenced by PCR method. RESULTS:The proband's red cell grouping results were AwB or B(A) subgroup and the serum grouping was B group. ABO blood group genotype of the proband and her parents were ABO*BA.02/ABO*O.01.01, ABO*B.01/ ABO*O.01.01 and ABO*BA.02/ABO*B.01, respectively. CONCLUSIONS:Blood group serology and molecular diagnostic techniques can accurately identify the rare B (A) 02 subgroup, pedigree analysis showed that the proband's BA.02 allele mutation came from her mother. Its allele was a point mutation of c.700C>G on the basis of ABO*B.01.
The impact of lipid metabolism on the development and prognosis of bone metastasis from breast cancer (BRCA) is currently unknown. Sequencing data of BRCA samples in this study were obtained from the University of California, Santa Cruz (UCSC) Xena database. The differentially expressed genes (DEGs1) between the BRCA group and the control group, the differentially expressed genes (DEGs2) between the bone metastasis group and the non-bone metastasis group, and the lipid metabolism score-related genes (LMSRGs) were intersected to obtain LMSRGs (DE-LMSRGs). Biomarkers were obtained using univariate logistic regression analysis, support vector machine recursive feature elimination (SVM-RFE) and multivariate logistic regression analysis for Correlation Analysis, Gene Set Enrichment Analysis, Immunohistochemistry, Co-creation of Networks, and Drug Prediction, and then analyses were performed using Immunohistochemistry, Western blot analyses to validate the samples. We identified two biomarkers (Regulator of G-protein Signaling 9 Binding Protein (RGS9BP) and suppressor of cytokine signaling 3 (SOCS3)). There were nine immune cells that were markedly differential between bone metastasis and non-bone metastasis groups, such as activated dendritic cell, neutrophil, plasmacytoid dendritic cell, etc. Then, the lncRNA-miRNA-mRNA network was created, including the regulated relationship pairs HLX-AS1-hsa-mir-541-SOCS3, ZNF337-AS1-hsa-mir-541-SOCS3. Molecular docking analyses have demonstrated that the complexes formed by SOCS3 alongside folic acid, estradiol, and S-Adenosylmethionine exhibit heightened stability. Similarly, the pairing of RGS9BP with benzopyrene showcases a notable degree of stability. Finally, the biomarkers were associated with angiogenesis scores and most angiogenesis related genes (ARGs). Our study identified two potential biomarkers (RGS9BP and SOCS3) for prognostic evaluation of bone metastasis patients with BRCA. These findings provided a scientific reference for further research on bone metastasis in BRCA patients.
Background:The early diagnostic rate of gastric cancer (GC) is relatively low. Transfer RNA-derived fragments (tRFs), as a class of non-coding RNAs with tumor-specific expression and stability in body fluids, have emerged as highly promising diagnostic candidate biomarkers. However, their application value in GC still requires systematic validation. Therefore, this study aims to systematically evaluate the value of specific tsRNA molecules as novel diagnostic biomarkers for GC by identifying and validating them. Methods:After identifying differentially expressed tsRNAs through the OncotRF database, the expression levels of tRF-28-P4R8YP9LOND5 were measured in serum samples from 117 GC patients, 89 healthy controls, and 51 gastritis patients using reverse transcription quantitative polymerase chain reaction (RT-qPCR) technology. The study evaluated the correlation between this biomarker and clinicopathological features, and the diagnostic efficacy of the single biomarker as well as its combination with carcinoembryonic antigen (CEA), cancer antigen 199 (CA199), and CA724 was analyzed using receiver operating characteristic (ROC) curves. Bioinformatics methods were employed to predict potential target genes and enriched signaling pathways. Results:tRF-28-P4R8YP9LOND5, a 5' tRNA-derived fragment originating from tRNA-Gly-GCC, was significantly upregulated in GC sera (P<0.001), with expression levels positively correlated with tumor invasion depth (T3-T4 stage), advanced tumor, node, and metastasis staging (III-IV), and neurovascular invasion (all P<0.05). The single-biomarker ROC analysis yielded an area under the curve (AUC) of 0.737, while combination with CEA and CA199 improved AUC to 0.821 (GC vs. healthy controls) and 0.883 (GC vs. gastritis patients), with optimal sensitivity of 80.3%. Bioinformatics revealed that several target genes were enriched in key pathways, such as cancer pathways and p53 signaling, which are critical to GC progression. Specifically, genes involved in cell migration, such as claudin-1, and p53 signaling-related genes like TP53 and MDM2, are known to play pivotal roles in GC pathogenesis. These genes have been implicated in the regulation of tumor invasion, metastasis, and response to DNA damage, which are central to the malignant behavior of GC cells. Conclusions:This study reveals that tRF-28-P4R8YP9LOND5 has the potential to serve as a novel serum diagnostic marker for GC. It demonstrates significant promise in distinguishing GC from benign conditions such as gastritis and provides a new strategy for early detection. Further studies are needed to explore its biological functions and its potential for therapeutic applications.
Sensitive real-time monitoring of hydrogen peroxide (H2O2) in the tumor microenvironment is crucial for comprehending its dual biological effects and enhancing therapeutic strategies. Existing techniques for real-time detection of H2O2 in tumor cells often suffer from limitations such as low sensitivity, poor selectivity, and difficult achievement of non-invasive dynamic monitoring. In this study, a high-performance electrochemical biosensor was developed based on metal-organic frameworks (MOFs) for non-invasive, real-time detection of H2O2 released by tumor cells. The sensor, featuring an integrated thin-film electrode constructed via microelectromechanical system (MEMS) technology, combined a biosensing interface film of AuNPs/ZIF-8@ZIF-67 and XC-72 carbon black with a poly(dimethylsiloxane) cell culture chamber, enabling real-time monitoring of H2O2 during cell culture. The sensor exhibited a wide linear detection range (1-350 μM), a low detection limit (0.908 μM), high stability (RSD = 4.57 %), and strong anti-interference (under 15 %). Compared to a system with discrete large-area electrodes, this integrated platform not only retained the detection performance but also effectively overcame the limitations associated with in situ cell culture.The system was successfully applied to monitor oxidative stress in various tumor cells under ascorbic acid stimulation. It effectively distinguished differences in H2O2 levels between tumor cells and normal cells, thereby underscoring its potential in tumor research and drug screening.This study provides an efficient and reliable platform for investigating tumor-related oxidative stress and assessing therapeutic responses.
Point-of-care testing (PoCT) method is suitable for rapid detection and daily monitoring of various acute diseases, which can effectively improve patients' survival rates. Current lateral flow assay (LFA)-based PoCT systems, with insufficient sensitivity, cannot meet the simultaneous detection requirements of rare multiple biomarkers. Therefore, we developed an electrochemiluminescence (ECL) microchip-based PoCT system, realizing rapid and highly sensitive detection of multiple biomarkers. This microchip incorporated specific aptamer probes assembled working electrode (WE) array and a shared counting electrode; thus forming a two-electrode-based detection unit for initiating Ru(bpy)(3)(2+) tripropylamine (TPrA)-based ECL reaction. Integrated with photomultiplier tube (PMT) and a constant transient potential (TP) model, the PoCT system was capable of sensitively detecting three acute myocardial infarction (AMI) biomarkers-cardiac troponin I (cTnI), myoglobin (Myo), and creatine kinase MB (CK-MB)-on a single microchip within just 20 min. The system exhibited an excellent detection limit of 0.25, 0.05, and 5 pg/mL for cTnI, Myo, and CK-MB, in a wide linear range of 1- 1 mu g/mL, 0.1-10 ng/mL, and 10- 1 mu g/mL, respectively. Furthermore, the analysis of AMI biomarkers in mixture and serum samples was conducted with high sensitivity and specificity, as well as low crosstalk. The platform synergized high sensitivity of ECL with the multiplexing of microchip, thereby holding tremendous potential for application in PoCT.
BACKGROUND:The purpose of clinical microbiology testing is to provide important information for clinical diagnosis and treatment. The correct collection, processing, and transportation of specimens are the key to the success of clinical microbiological examination. METHODS:Retrospective analysis was done on the composition and causes of unqualified microbial samples submitted by clinical departments from 2019 to 2020 at the Affiliated Hospital of Nantong University. The solutions were proposed from the perspective of nursing management. RESULTS:In 2019, the hospital received 64,244 clinical microbial specimens. The unqualified rate of samples was 8.96%, of which the unqualified sputum accounted for 84.74%. After strengthening the communication with the medical laboratory, increasing publicity and training, and improving the information system and other auxiliary monitoring functions, the unqualified rate of clinical microbial specimens was reduced to 6.05% in 2020. CONCLUSIONS:Continuously improving the theoretical and practical abilities of nurses can reduce the unqualified rate of samples.
Respiratory pathogens pose significant challenges to public health, demanding efficient diagnostic methods. This study presents an integrated microfluidic chip for the simultaneous detection of multiple respiratory pathogens. The chip integrates magnetic bead-based nucleic acid extraction and purification, acoustic streaming-driven mixing, liquid equalization, and multiplex PCR amplification with in situ fluorescence detection. Nucleic acid extraction takes only 12 min, yielding results comparable to commercial kits. Efficient mixing of magnetic beads is achieved through a combination of designed micropillars and bubble-trapping array structures. The micropillars maintain the aqueous phase in the mixing chamber, while the bubble-trapping arrays enable stable formation of bubbles, serving as a micromixer under the acoustic field. To prevent cross-contamination, an oil-encapsulated water droplet system is incorporated throughout nucleic acid extraction and PCR amplification. This assay displays remarkable multiplex analysis capability on a single chip, enabling the simultaneous detection of 12 common respiratory pathogens with a low detection limit of 10 copies/μL. Moreover, this method demonstrates excellent practical applicability in clinical nasal samples. Compared to many microfluidic chip-based molecular biology methods, the assay exhibits comparable or superior multipathogen analysis capability, sensitivity, and speed, completing the sample-to-answer process in approximately 70 min. This integrated microfluidic device offers a promising multiplex molecular diagnosis platform for on-site simultaneous detection of multiple pathogens.
The aim of this study was to examine the relationship between levels of non-high-density lipoprotein cholesterol (non-HDL-C) and postoperative distant metastasis for stages I to III colorectal cancer (CRC). Demographic, clinicopathological, and lipid data were collected from 588 patients, who were subsequently grouped according to their non-HDL-C levels. The primary endpoint was distant metastasis, survival without distant metastasis-free survival (DMFS). The association between non-HDL-C and pathological features, as well as postoperative distant metastasis, was assessed using a chi-square test, Mann-Whitney U test, and Cox proportional hazard regression model. The correlation between DMFS and non-HDL-C levels was analyzed employing the Kaplan-Meier method and log-rank test. The incidence of postoperative distant metastasis was significantly higher in the high non-HDL-C group (34.8%) compared to the low non-HDL-C group (18.2%) (P < .001). Non-HDL-C levels were significantly higher in the metastasis group than in the nonmetastasis group (P = .001). Multivariate Cox proportional hazards identified non-HDL-C >= 4.1mmol/L(HR: 2.604; 95% CI: 1.584-4.282; P = .001) as independent risk factors for postoperative distant metastasis. The high non-HDL-C group exhibited a higher rate of distant metastasis and a shorter duration of DMFS (HR: 2.133; 95% CI: 1.404-3.240; P < .001). Our study suggests that high levels of non-HDL-C (>= 4.1 mmol/L) may potentially serve as predictors for postoperative distant metastasis in stages I to III CRC.
BACKGROUND:The global incidence and mortality rate of gastric carcinoma (GC) persists at elevated levels, often manifesting no overt symptoms in its early stages. Hsa_circ_0002762 has been identified as an important modulator in cervical cancer. This study aims to explore its role in the context of GC.METHODS:A quantitative real-time polymerase chain reaction (qPCR) was implemented to assess the expression level of hsa_circ_0002762. The over-expression was confirmed through an examination of 28 cases of gastric cancer and their corresponding adjacent tissues. In addition, plasma samples from 78 healthy individuals, from 45 benign gastritis patients, and from 106 gastric cancer patients were collected, and the diagnostic efficacy was assessed by analyzing the receiver operating characteristic (ROC) curve. Simultaneously, postoperative specimens from 36 GC cases were collected, and a Kaplan-Meier survival analysis curve was used to evaluate the prognosis of GC.RESULTS:The study revealed an up-regulation in the expression of hsa_circ_0002762 in gastric cancer plasma and tissues. The area under the receiver operating characteristic (ROC) curve for serum hsa_circ_0002762 was 0.784 (95% CI: 0.719 - 0.851), indicating a higher diagnostic efficiency compared to CEA (0.687, 95% CI: 0.611 - 0.763) and CA199 (0.699, 95% CI: 0.625 - 0.744). Combining these three biomarkers demonstrated an increased sensitivity in the diagnostic effectiveness. Finally, postoperative dynamic monitoring revealed a practical utility in predicting the clinical prognosis using serum has_circ_0002762.CONCLUSIONS:The findings from our study suggest that hsa_circ_0002762 holds promise as a novel diagnostic and prognostic marker for individuals with GC.
Background: Colorectal cancer (CRC) has always been one of the most common malignant tumors in the world. Whether the factors related to the diagnosis and risk of CRC can be found from the existing peripheral blood routine indicators. Methods: The relevant data of patients with colorectal diseases in our hospital of about ten years were collected, the differences among the biomarkers in serum were analyzed, the risk factors were analyzed by logistic regression, the ROC was drawn, and the diagnostic efficacy was evaluated. Results: Colorectal malignancies and benign diseases in AST, GGT, LDH, D-BIL, ALB, ALP, AchE, CR, TP, PA, RDW, LMR, NMR, TC, TG, HDL-C, CA19-9, CEA, Cyfra21-1, and Fer have statistical differences (p < 0.05). ALB, PLR, CEA, Fer, NLR, TP, GGT, and Cyfra21-1 in different malignant tumor types have statistical differences (p < 0.05). When CEA increased by 1, the risk of colorectal cancer increased by 45.7%. When AchE and HDL-C increased by 1, the risk of colorectal cancer decreased by 32% and 66.8%. Compared with other blood groups, blood group AB colorectal cancer patients had a shallower tumor invasion (p = 0.047). HDL-C were significantly weakly-correlated with tumor size (p < 0.05, |r| < 0.4). CEA, AchE, and HDL-C were combined diagnosed; the sensitivity, PPV, and accuracy were 94.35%, 95.43%, 90.77%, respectively. Conclusions: The occurrence and development of colorectal cancer is the result of multi-factors, and the combined detection of multi-indicators has positive significance for the diagnosis, pathological stage, and prevention of CRC.
BACKGROUND:This study aims to explore the observable distribution of serum uric acid levels in healthy adults residing in China's coastal areas and to assess the suitability of current reference intervals. METHODS:The study incorporated 20,786 participants. The overall uric acid level displayed a skewed distribution, leading to the division of subjects into six groups based on gender and age. The analysis was conducted to comprehend the distribution of UA in various groups and seasons, establish and validate the reference intervals for the surface healthy population in this region, and analyze the abnormality rates using different reference intervals. RESULTS:Statistically significant differences were observed between the uric acid levels of males and females across all age groups (ALL p < 0.05). Furthermore, there were statistical differences in uric acid levels among different age groups for both genders (H = 69.593 and 326.348, all p < 0.001). The overall reference interval was determined as 238 - 488 µmol/L for males and 155 - 364 µmol/L for females, based on the 95% confidence interval (P2.5 - P97.5). The established reference intervals, grounded on gender and age group, were validated, showing statistically significant disparities in UA levels among groups. The abnormality rate in males decreased by 56.90% following the adjustment of the reference interval. CONCLUSIONS:The study revealed that UA levels at all ages exhibited varying degrees of "right shift". Additionally, the low-value population should not be overlooked in the clinical evaluation of UA test results. Setting a reasonable reference interval and clinical decision level is crucial for clinical diagnosis and treatment.