Clinical Significance In Early Diagnosis Research Articles

Identifying Key Genes to the Early Diagnosis of Inflammatory Bowel Disease by Integrating Analysis at the Blood and Tissue Levels.

Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC), is challenging to diagnose, and frequently relapses, significantly affecting patients' quality of life. Despite extensive efforts, the pathogenesis of IBD remains unclear. In this study, we integrated bioinformatics analysis and animal disease model to investigate IBD from two dimensions to identify potential diagnostic biomarkers and explore the pathogenesis of distinct conditions at tissue-specific levels. Firstly, we identified dysferlin (DYSF) and C-X-C motif chemokine ligand 2 (CXCL2) as crucial biomarkers for IBD, with 11 and 13 putative biomarkers for CD and UC, respectively, identified by peripheral blood testing only. CXCL8 and S100 calcium-binding protein A8 (S100A8) were determined to be critical hub genes and validated by real-time polymerase chain reaction (RT-PCR). Secondly, in CD, the differentially expressed genes (DEGs) were mainly associated with immunity based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, while the metabolism of multiple substances and substance transport activity were dominant in UC. Thirdly, essential genes in the pathological progression of CD and UC were identified through protein-protein interaction networks and molecular complex detection (MCODE) analysis. Finally, pathological examination and quantitative analysis of IBD models confirmed the above results. Our findings could contribute to understanding the molecular mechanism of IBD, hold clinical significance for early diagnosis and prevention, and provide effective targets for treating IBD.

HCFC1 variants in the proteolysis domain are associated with X-linked idiopathic partial epilepsy: Exploring the underlying mechanism.

HCFC1 encodes transcriptional co-regulator HCF-1, which undergoes an unusual proteolytic maturation at a centrally located proteolysis domain. HCFC1 variants were associated with X-linked cobalamin metabolism disorders and mental retardation-3. This study aimed to explore the role of HCFC1 variants in common epilepsy and the mechanism underlying phenotype heterogeneity. Whole-exome sequencing was performed in a cohort of 313 patients with idiopathic partial (focal) epilepsy. Functional studies determined the effects of the variants on the proteolytic maturation of HCF-1, cell proliferation and MMACHC expression. The role of HCFC1 variants in partial epilepsy was validated in another cohort from multiple centers. We identified seven hemizygous HCFC1 variants in 11 cases and confirmed the finding in the validation cohort with additional 13 cases and six more hemizygous variants. All patients showed partial epilepsies with favorable outcome. None of them had cobalamin disorders. Functional studies demonstrated that the variants in the proteolysis domain impaired the maturation by disrupting the cleavage process with loss of inhibition of cell growth but did not affect MMACHC expression that was associated with cobalamin disorder. The degree of functional impairment was correlated with the severity of phenotype. Further analysis demonstrated that variants within the proteolysis domain were associated with common and mild partial epilepsy, whereas those in the kelch domain were associated with cobalamin disorder featured by severe and even fatal epileptic encephalopathy, and those in the basic and acidic domains were associated with mainly intellectual disability. HCFC1 is potentially a candidate gene for common partial epilepsy with distinct underlying mechanism of proteolysis dysfunction. The HCF-1 domains played distinct functional roles and were associated with different clinical phenotypes, suggesting a sub-molecular effect. The distinct difference between cobalamin disorders and idiopathic partial epilepsy in phenotype and pathogenic mechanism, implied a clinical significance in early diagnosis and management.

Neuroimaging in Alzheimer's Disease for Early Diagnosis: A Comprehensive Review.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting roughly half of those over the age of 85. Webriefly discussed the risk factors, epidemiology, and treatment options for AD. The development of therapeutic therapies operating very early in the disease cascade has been spurred by the realization that the disease process begins at least a decade or more before the manifestation of symptoms. Thus, the clinical significance of early diagnosis was emphasized.Using various keywords, a literature search was carried out using PubMed and other databases. For inclusion, pertinent articles were chosen and reviewed. This article has reviewed different neuroimaging techniques that are considered advanced tools to aid in establishing a diagnosis and highlighted the advantages as well as disadvantages of those techniques. Besides, the prevalence of several in vivo biomarkers aided in discriminating affected individuals from healthy controls in the early stages of the disease.Each imaging method has its advantages and disadvantages, hence no single imaging approach can be the optimum modality for diagnosis. This article also commented on a better approach to using these techniques to increase the likelihood of an early diagnosis.

Molecularly imprinted miniature electrochemical biosensor for SARS-CoV-2 spike protein based on Au nanoparticles and reduced graphene oxide modified acupuncture needle

Accurate detection of SARS-CoV-2 spike (SARS-CoV-2-S) protein is of clinical significance for early diagnosis and timely treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, a surface molecularly imprinted miniature biosensor was fabricated. Au nanoparticles (AuNPs), reduced graphene oxide (rGO), poly(methylene blue)/poly(ionic liquids) and poly(ionic liquids) were successively electrodeposited onto the pinpoint of an acupuncture needle (AN). The molecularly imprinted miniature biosensor was obtained after the template of SARS-CoV-2-S protein was removed, which could be used for sensitive detection of SARS-CoV-2-S protein. The linear range and limit of detection (LOD) were 0.1 ∼ 1000 ng mL−1 and 38 pg mL−1, respectively, which were superior to other molecularly imprinted biosensors previously reported. The developed miniature biosensor also exhibited high specificity and stability. The reliability of the biosensor was evaluated by the detection of SARS-CoV-2-S protein in clinical serum samples.

Dual-template molecularly imprinted electrochemical biosensor for IgG-IgM combined assay based on a dual-signal strategy

Detection of immunoglobulins (Igs) is of clinical significance for early diagnosis and timely treatment of diseases. Herein, a dual-template molecularly imprinted (DTMI) electrochemical biosensor was developed for IgG-IgM combined assay. In this DTMI electrochemical biosensor, Prussian blue (PB) and thionine (TH) decorated on graphene oxide (GO) and multi-walled carbon nanotubes (MWCNTs), respectively, were utilized as the dual-signal probes, and Au nanoparticles (AuNPs) were used for Igs anchoring and signal amplification. Polypyrrole (PPy) was electrodeposited on the biosensor surface and acted as the molecularly imprinted polymers (MIPs). After the removal of the IgG and IgM templates, the resultant DTMI electrochemical biosensor was used for IgG-IgM combined assay, and the concentrations of IgG and IgM could be indicated by the changes in the peak currents of PB (ΔIPB) and TH (ΔITH), respectively. The DTMI electrochemical biosensor displayed a wide linear range and a low limit of detection (LOD) for both IgG (28.80 pg mL−1) and IgM (0.58 pg mL−1). Finally, the developed DTMI biosensor was used for IgG-IgM combined assay in clinical serum samples, and the results were comparable to those obtained by conventional immunoturbidimetry, implying its great potential in clinical diagnosis.

Hyperbranched Tetraphenylethylene Derivatives with Low Non-specific Aggregation-Induced Emission for Fluorescence Recognition of Proteins with Hydrophobic Pockets.

Proteins play an important role in the physiological process of many organisms, and their abnormal level often indicates the occurrence of some diseases. Therefore, protein analysis has important reference value and clinical significance for early diagnosis and therapy of disease. Using human serum albumin (HSA) as a model protein, a series of super-branched tetraphenylethylene (TPE) derivatives with different branching structures and terminal groups are reported herein for highly sensitive and specific recognition of proteins with hydrophobic cages. Benefiting from the hyperbranched structures, these probes showed much higher critical micelle concentrations (CMCs) than most linear TPE-based amphiphilic molecules since the hyperbranched structure not only improved their solubility but also amplified the steric hindrance effect and electrostatic repulsive force to prevent their aggregation. Dynamic light scattering experiments proved that these probes formed dense aggregates at CMC, and such aggregate structures would lead to a higher background fluorescence noise. Hence, a higher CMC is more conducive to the detection of the target with low backgrounds. Among them, P3-COOH with -COOH as the terminal unit and a relatively longer branch showed the highest CMC and the best signal to background ratio (S/N). Mechanism studies showed that P3-COOH was bound to HSA mainly through a hydrophobic force, resulting in a limited P3-COOH molecular movement and less attack from quenchers in solutions, thus leading to greatly enhanced fluorescence intensity. In addition, P3-COOH was also applied to the determination of HSA content in actual human serum samples.

C Reactive Protein and Procalcitonine as Diagnostic Markers in Critically Ill Patients with Suspected Sepsis

Abstract The primary aim of this retrospective study was to estimate significance of determining C-reactive protein and procalcitonine for a diagnosis of sepsis in adult patients in early triage. Also, the aim of this study was to measure the sensitivity of the SIRS criteria, PCT and CRP levels and sepsis definitions to identify the most serious sepsis cases in the prehospital setting and at the Emergency Department (ED) triage. All patients were divided into two groups according to specific criteria for defining sepsis. First group (SIRS+ group) of patients were patients with clinically and/or laboratory confirmed sepsis (or systemic inflammatory response syndrome (SIRS) to bacterial infection with different localization). For confirmation of the SIRS we consider positive two or more clinical criteria (≥2 clinical criteria). The SIRS criteria use the clinical criteria of the Surviving Sepsis Campaign (SSC) for the SIRS, comprising at least two of the following criteria: HR > 90/min, RR > 20/min and temperature < 36° or ≥ 38.3°C and the next laboratory parameters such as leucocytosis > 15x109/L, leucopenia < 4x109/L, > 10% immature leucocytes. Second group of patients were patients with the SIRS negative criteria as a diagnostic tool (SIRS- group). We have founded that the CRP showed high sensitivity but no specificity in patients with sepsis, but on the other side, the PCT as a diagnostic marker showed a high sensitivity and high specificity in these patients. Also, the PCT is in positive correlation with the SIRS criteria, which could be of a clinical significance in early diagnosis of septic infections.

Experimental study on the expression and diagnostic significance of I-FABP in acute intestinal ischemia

Objective: To detect the expression and distribution of I-FABP in intestinal tissue and the changes of serum concentrations at different time of acute intestinal ischemia, and explore the significance and mechanism of I-FABP in early diagnosis of acute ischemic bowel disease. Methods: The selected 96 healthy adult SD rats were randomly divided into the experimental group and control group; 48 in each group. Each group was randomly subdivided into 6 groups with 8 rats in each group. The superior mesenteric artery was ligated in the experimental group and the peritoneal switch operation was performed in the control group. The venous blood samples were extracted from each group rats’ right ventricle at 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h after the operation and the concentration of I-FABP was tested respectively. Then the rats were killed, and the diseased intestinal tubes were cut out for paraffin sections. The I-FABP in intestinal tissue was stained by routine HE staining and direct immunofluorescence staining. Results: The I-FABP was mainly expressed in the epithelial villi of intestinal mucosa, and there was a small amount of expression in the intestinal submucosa and even the muscularis. Within 1 hour of intestinal ischemia, the number of I-FABP positive granules in the intestine and intestinal cavity increased gradually, and then gradually decreased after 1 hour. The difference has statistically significant between the experimental group and the control group (P < 0.05). The serum I-FABP: In the experimental group, the serum I-FABP concentration began to increase at 0.5 h, and reached a peak at 1 h (290. 24 ± 156.69) μg·L–1, then gradually decreased. Compared with the control group, the difference was statistically significant (P < 0.05). Conclusion: I-FABP usually mainly exists in the epithelial cells of intestinal mucosa. When acute intestinal ischemia occurs, the epithelial cells of intestinal mucosa permeability changes; I-FABP expression rapidly releases to intestinal tissue and intestinal cavity, and is absorbed into the blood. Therefore, I-FABP has certain clinical significance in early diagnosis and treatment of acute intestinal ischemia.

Bioinformatics Analysis Identifies Molecular Markers Regulating Development and Progression of Endometriosis and Potential Therapeutic Drugs.

Endometriosis, a common disease that presents as polymorphism, invasiveness, and extensiveness, with clinical manifestations including dysmenorrhea, infertility, and menstrual abnormalities, seriously affects quality of life in women. To date, its underlying etiological mechanism of action and the associated regulatory genes remain unclear. This study aimed to identify molecular markers and elucidate mechanisms underlying the development and progression of endometriosis. Specifically, we downloaded five microarray expression datasets, namely, GSE11691, GSE23339, GSE25628, GSE7305, and GSE105764, from the Gene Expression Omnibus (GEO) database. These datasets, obtained from endometriosis tissues, alongside normal controls, were subjected to in-depth bioinformatics analysis for identification of differentially expressed genes (DEGs), followed by analysis of their function and pathways via gene ontology (GO) and KEGG pathway enrichment analyses. Moreover, we constructed a protein–protein interaction (PPI) network to explore the hub genes and modules, and then applied machine learning algorithms support vector machine-recursive feature elimination and least absolute shrinkage and selection operator (LASSO) analysis to identify key genes. Furthermore, we adopted the CIBERSORTx algorithm to estimate levels of immune cell infiltration while the connective map (CMAP) database was used to identify potential therapeutic drugs in endometriosis. As a result, a total of 423 DEGs, namely, 233 and 190 upregulated and downregulated, were identified. On the other hand, a total of 1,733 PPIs were obtained from the PPI network. The DEGs were mainly enriched in immune-related mechanisms. Furthermore, machine learning and LASSO algorithms identified three key genes, namely, apelin receptor (APLNR), C–C motif chemokine ligand 21 (CCL21), and Fc fragment of IgG receptor IIa (FCGR2A). Furthermore, 16 small molecular compounds associated with endometriosis treatment were identified, and their mechanism of action was also revealed. Taken together, the findings of this study provide new insights into the molecular factors regulating occurrence and progression of endometriosis and its underlying mechanism of action. The identified therapeutic drugs and molecular markers may have clinical significance in early diagnosis of endometriosis.

Potential value of MicroRNA-21 as a biomarker for predicting the prognosis of patients with breast cancer: A protocol for meta-analysis and bioinformatics analysis.

Background:The latest global cancer data from 2020 shows that breast cancer has replaced lung cancer as the number one cancer in the world. Searching for new biomarkers of breast cancer has important clinical significance for early diagnosis, prediction of prognosis, and targeted therapy. MicroRNA-21 (miRNA-21) can be used as a new molecular marker for early diagnosis, prognosis, and treatment of tumors. However, the expression of miRNA-21 in breast cancer and its prognosis are not clear. Therefore, this study conducted a meta-analysis to further clarify the relationship between the expression of miRNA-21 in breast cancer and prognosis. At the same time, we carried out bioinformatics analysis to further analyze the possible molecular mechanism of miRNA-21, so as to provide potential clinical indicators for the diagnosis, treatment, and prognosis of patients.Methods:PubMed, Medline, Embase, Web of Science, Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and other databases were used to retrieve the published relevant literatures. Include the eligible research, extract the survival data hazard ratios and 95% confidence intervals and other information. STATA16.0 software was used for meta-analysis. Download the miRNA data of breast cancer through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. The data extracted for independent sample t test and ROC curve was drawn. OncomiR plotted the survival curve of miRNA-21 on the prognosis of breast cancer. The target genes of miRNA-21 were predicted, and the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were analyzed. STRING database and Cytoscape construct protein-protein interaction (PPI) network to obtain Hub gene. The correlation between the expression level of Hub gene in breast cancer and the abundance of immune cell infiltration was analyzed by TIMER database and verified by Kaplan–Meien plotter database.Results:The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion:In this study, meta-analysis and bioinformatics analysis were used to further explore the prognosis, mechanism, and related pathways of miRNA-21 in breast cancer.Ethics and dissemination:The private information from individuals will not be published. This systematic review also should not damage participants’ rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.OSF REGISTRATION NUMBER:DOI 10.17605/OSF.IO/R32A9.

The Diagnostic Value of Plasma miRNA-497, cTnI, FABP3 and GPBB in Pediatric Sepsis Complicated with Myocardial Injury.

ObjectiveTo investigate the diagnostic value of plasma miRNA-497, cardiac troponin I (cTnI), fatty acid binding protein 3 (FABP3), glycogen phosphorylase isoenzyme BB (GPBB) in pediatric sepsis complicated with myocardial injury.MethodsFrom August 2018 to February 2020, 82 children with sepsis admitted to our hospital and 50 health children who came for physical examination (defined as control group) were enrolled in this study. Children with sepsis and myocardial injury were enrolled in the combined group (n=35), and those without myocardial injury were enrolled in the sepsis group (n=47). General data of three groups were collected, and the levels of miRNA-497, FABP3, GPBB, creatine kinase isoenzyme MB (CK-MB), procalcitonin (PCT), C-reactive protein (CRP), cTnI and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were detected and the cardiac function was measured. The diagnostic value of plasma miRNA-497, cTnI, FABP3 and GPBB in pediatric sepsis complicated with myocardial injury was analyzed.ResultsThe infection site of the combined group was not significantly different from that of the sepsis group. The levels of miRNA-497, FABP3, GPBB, CK-MB, PCT, CRP, cTnI, NT-proBNP in the combined group were all higher than those in the sepsis group and the control group (P<0.05), and the left ventricular ejection fraction (LVEF) in the combined group was significantly lower than that in the other two group (P<0.05). The area under the curve (AUC) of the combination of miRNA-497, FABP3, GPBB, and cTnI in the diagnosis of sepsis complicated with myocardial injury was significantly higher than that of CK-MB, PCT, CRP, NT-proBNP alone (P<0.05), but there was no significant difference when compared with miRNA-497, FABP3, GPBB and cTnI alone (P>0.05). When the optimal thresholds of miRNA-497, FABP3, GPBB, and cTnI were set to 2.03, 6.23ng/mL, 4.01ng/mL, 1.23ng/mL, respectively, the sensitivity was 95.65%, 88.89%, 82.61%, 87.50%, respectively; the specificity was 83.33%, 94.12%, 83.33%, 90.91%, respectively; and the accuracy was 91.43%, 91.43%, 82.86%, 88.57%, respectively. Pearson correlation analysis indicating that miRNA-497 was positively correlated with the levels of FABP3, GPBB, and cTnI in the combined group (r=0.821, 0.621, 0.782, P<0.05).ConclusionPlasma miRNA-497, cTnI, FABP3, and GPBB levels were increased in pediatric sepsis complicated with myocardial injury, and their combination had high diagnostic value, which was of great clinical significance for early diagnosis and early treatment of pediatric sepsis complicated with myocardial injury.

Different characteristics of infants diagnosed with congenital choledochal malformation prenatally or postnatally

The general condition, clinical and pathological characteristics, and treatment regimens of patients prenatally and postnatally diagnosed with congenital choledochal malformation (CM) were analyzed in order to investigate the clinical significance of early diagnosis, treatment, and intervention in CM. We retrospectively analyzed 33 children who were admitted to the Children’s Hospital of Soochow University between 1 March 2010 and 31 May 2019, and their diagnosis of CM was confirmed by radiological, surgical and pathological findings. All the patients were under 36 months of age. The patients were divided into prenatally diagnosed and postnatally diagnosed groups. There were 16 and 17 CM patients in the prenatally and postnatally diagnosed groups, respectively, with a preponderance of females in both groups. Compared with the prenatally diagnosed group, the postnatally diagnosed group had a higher incidence of abdominal pain and vomiting (p < 0.05) and higher AST, GGT, and TB levels (p < 0.05). Although postoperative histopathological examination showed inflammation in both groups, congestion in the cyst walls and fibrous tissue hyperplasia were more significant in the postnatally diagnosed group (p < 0.05). In addition, operation time, length of time required to resume a normal diet after surgery, and total length of hospitalization differed between the 2 groups (p < 0.05), with the prenatally diagnosed group having a relatively longer operation time and taking longer to resume a normal diet after surgery. However, the total length of hospitalization in the prenatally diagnosed group was shorter than that in the postnatally diagnosed group. Compared with prenatally diagnosed CM patients, more symptoms, greater severity of symptoms, and more time to recovery after surgery were observed in postnatally diagnosed CM patients.

Analysis of Clinical Related Factors of Neonatal Hand-Foot-Mouth Disease Complicated With Encephalitis.

Objective: To explore the clinical related factors of neonatal hand-foot-mouth disease (HFMD) complicated with encephalitis.Method: The neonatal HFMD complicated with encephalitis treated in our hospital from July 2015 to July 2020 was taken as the object of study. According to the NBNA score at discharge, the patients were divided into normal group and abnormal group. The clinical symptoms, auxiliary examination and prognosis of the two groups were compared.Result: (1) General condition: there was no significant difference in sex, age, duration of fever, treatment time and etiological test between the two groups (P > 0.05). (2) Clinical symptoms and signs: there was significant difference in abnormal consciousness between the two groups (P < 0.05). However, there was no significant difference in skin rash, respiratory system symptoms, digestive system symptoms, signs of high intracranial pressure, increased muscle tone and weakening of primitive reflex (P > 0.05). (3) Auxiliary examination: the number of white blood cells and the level of cytokines (CK-BB, UCH-L1) in cerebrospinal fluid (CSF) in the group with abnormal NBNA score were significantly higher than those in the group with normal NBNA score (P < 0.05). The serum IgM level in the abnormal NBNA score group was higher than that in the normal NBNA score group, and the serum IgG level in the abnormal NBNA score group was lower than that in the normal NBNA score group, and the difference was statistically significant (P < 0.05). The abnormal rate of Craniocerebral MRI in abnormal NBNA score group was higher than that in normal NBNA score group, and there was significant difference between the two groups (P < 0.05). There was no significant difference in the levels of protein, sugar, chloride, lactate dehydrogenase, and MMP-9 in CSF and the abnormal rate of amplitude integrated EEG (aEEG) between the two groups (P > 0.05). (4) The prognoses of patients with normal and abnormal NBNA score are good, and there are not significantly differences in the prognosis between the two groups (P > 0.05).Conclusion: (1) Neonatal HFMD complicated with encephalitis occurs more than 10 days after birth, there is no obvious abnormality in male and female, the vast majority of newborns have febrile symptoms, rash is not its specific manifestation, and most of them are atypical. (2) The positive rate of HFMD-related virus detected in CSF of neonatal HFMD is high. For newborns with abnormal consciousness, CSF examination should be accomplished in time, which has certain clinical significance for early diagnosis and treatment of severe newborns. (3) The increase of white blood cell count and cytokines (CK-BB, UCH-L1) in CSF of neonatal HFMD complicated with encephalitis has a certain clinical reference value for early diagnosis and identification of severe newborns. (4) There is a certain humoral immune disorder in newborns with HFMD complicated with encephalitis, but the overall prognosis is better due to the protective effect of maternal IgG.

A Reliable BioFET Immunosensor for Detection of p53 Tumour Suppressor in Physiological-Like Environment.

The concentration of wild-type tumour suppressor p53wt in cells and blood has a clinical significance for early diagnosis of some types of cancer. We developed a disposable, label-free, field-effect transistor-based immunosensor (BioFET), able to detect p53wt in physiological buffer solutions, over a wide concentration range. Microfabricated, high-purity gold electrodes were used as single-use extended gates (EG), which avoid direct interaction between the transistor gate and the biological solution. Debye screening, which normally hampers target charge effect on the FET gate potential and, consequently, on the registered FET drain-source current, at physiological ionic strength, was overcome by incorporating a biomolecule-permeable polymer layer on the EG electrode surface. Determination of an unknown p53wt concentration was obtained by calibrating the variation of the FET threshold voltage versus the target molecule concentration in buffer solution, with a sensitivity of 1.5 ± 0.2 mV/decade. The BioFET specificity was assessed by control experiments with proteins that may unspecifically bind at the EG surface, while 100pM p53wt concentration was established as limit of detection. This work paves the way for fast and highly sensitive tools for p53wt detection in physiological fluids, which deserve much interest in early cancer diagnosis and prognosis.

Multiprobe Assay for Clinical SEPT9 Methylation Based on the Carbon Dot-Modified Liquid-Exfoliated Graphene Field Effect Transistor with a Potential to Present a Methylation Panorama.

The hypermethylation in the promoter region of the SEPT9 gene is associated with the development of colorectal cancer (CRC). Although its clinical significance for early diagnosis and screening of CRC has been demonstrated, the tedious operations in the conventional DNA methylation (DNAm) detection hinder its wide application. Herein, an electronic method for determining SEPT9 methylation in CRC patients is proposed by using the carbon dot-modified liquid exfoliated graphene field effect transistor (CDs-LEG-FET) as the DNAm sensor, the specifically designed probes to capture the SEPT9 gene and the immunologic recognition to recognize 5-methylcytosine (5mC) positions on the anchored sequences. The identification and nanomorphology of the as-prepared materials and devices are executed first by the characterizations of UV–vis, Raman, atomic force microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and electronic measurements. Then, the role of CDs in enhancing DNAm sensitivity of CD-LEG-FET is manifested by comparing it with that of CD-free LEG-FET. Third, the captured SEPT9 genes on CD-LEG-FETs by different probes are evaluated, and the optimized temperature for hybridizing the target ssDNA sequences is determined to be 48 °C. Furthermore, the detection sensitivity for the low-quantity of DNA samples is demonstrated to be as low as 2 ng. Finally, the methylation degree of the tumor and corresponding noncancerous tissue DNA samples were examined by the proposed electric method and methylight assay in parallel. The diagnostic value of the electrical assay is confirmed by using the receiver operating characteristic curves; meanwhile, the superiority of the CD-LEG-FET platform is found to present a methylation panorama of the target gene.

Pattern of haemoglobin phenotypes in newborn infants at the national hospital abuja using high performance liquid chromatography

Haemoglobin (Hb) disorders are among the most common blood genetic disorders worldwide, and they constitute an important cause of morbidity and mortality, especially in Nigeria. Despite the clinical significance of early diagnosis, newborn screening for these conditions is not routinely done in Nigeria. This study was undertaken to document the pattern of Hb phenotypes of newborn babies at the National Hospital Abuja and highlight the relevance of neonatal screening for early diagnosis of abnormal Hb phenotypes in Nigeria. A prospective study of eligible newborn babies delivered in the hospital at the study site was undertaken following parental informed consent. Venous blood was collected from the babies into an ethylenediaminetetraacetic acid sample bottles. The samples were analysed using high-performance liquid chromatography (HPLC) techniques, and the Hb phenotypes obtained were documented. Data were analysed using the Statistical Package for Social Sciences (SPSS) version 20 (IBM-SPSS, Armonk, NY, USA). Three hundred and eleven newborns (male = 173, female = 138) aged 0-28 days were recruited. Two hundred and thirty-six (75.9%) babies had Hb AA (FA) phenotype, 63 (20.3%) Hb AS (FAS), 6 (1.9%) Hb SS (FS), 4 (1.3%) Hb AC (FAC) and 2 (0.6%) had abnormal HbA variants. The overall prevalence of abnormal Hb phenotype was 24.1%. The results showed a significant association of sex (P = 0.003) and ethnicity (P = 0.047) with Hb phenotype. There is a wide spectrum of abnormal Hb phenotypes in Nigeria, and these phenotypes can easily be detected at birth using HPLC. We, therefore, recommend routine neonatal screening for sickle cell disease by HPLC in Nigeria.

Identification of differentially expressed genes and signaling pathways involved in endometriosis by integrated bioinformatics analysis.

Endometriosis is a common gynecological disease characterized by the presence and growth of endometrial tissue outside the uterus, including the pelvis and abdominal cavity. This condition causes various clinical symptoms, such as non-menstrual pelvic pain, dysmenorrhea and infertility, seriously affecting the health and quality of life of women. To date, the specific mechanism and the key molecules of endometriosis remain uncertain. The purpose of the present study was to elucidate the mechanisms involved in the development and persistence of the disease. A number of mRNA expression profile datasets (namely GSE11691, GSE23339, GSE25628 and GSE78851) were downloaded from the Gene Expression Omnibus (GEO) database. These gene expression profiles were normalized, and the differentially expressed genes (DEGs) were identified by integrated bioinformatics analysis. A total of 103 DEGs were screened upon excluding the genes that exhibited inconsistency of expression (P<0.05). Furthermore, the Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and construction of protein-protein interaction networks of DEGs were performed using online software. The results revealed that the DEGs were closely associated with cell migration, adherens junction and hypoxia-inducible factor signaling. In addition, immunohistochemical assay results were found to be consistent with the bioinformatics results. The present study may help us understand underlying molecular mechanisms and the development of endometriosis, which has a great clinical significance for early diagnosis of the disease.

"Honeycomb" pattern of gallbladder wall thickening - A forward step in early diagnosis of "Severe Dengue Fever".

Aims and Objectives:To study “Honeycomb” pattern of gallbladder wall thickening (GBWT) in dengue fever (DF) and to assess its clinical significance in early diagnosis of severe DF.Materials and Methods:A total 244 patients of DF were studied, 84 patients were classified as severe DF, 61 patients as DF with warning signs, and 99 patients as DF without warning signs. Abdominal ultrasound was performed for assessment of GBWT patterns, hepatomegaly, splenomegaly, pancreatic enlargement, ascites, pleural effusion, and other additional findings were recorded in severe DF cases. Statistical comparison between “Honeycomb” pattern of GBWT and clinically severe DF was done using Pearson correlation test.Results:Out of 244 patients, 145 patients were males and 99 patients were females, belonging to various age groups ranging from 1 to 81 years and 14.34% (35 patients) among them included in pediatric group. In total, 65.57% (160 patients) were non-severe DF cases and 34.42% (84 patients) were severe DF cases. A total of 84 patients of severe DF, 92.85% patients showed GBWT, and out of which, 71.42% patients had “Honeycomb” pattern, whereas a total of 160 patients of non-severe DF patients, 45% patients had GBWT and out of which, only 5.6% patients showed “Honeycomb” pattern. “Honeycomb” pattern of GBWT shows sensitivity of 71.4%, 94.37%, Positive predictive value of 86.95%, and Negative predictive value of 86.28% in severe DF.Conclusion:“Honeycomb” pattern of GBWT is significant finding in severe DF. Its sensitivity and specificity are high in severe DF with significant statistical correlation. It can aid in early diagnosis of severe DF.

Diagnosis and treatment of bacterial infection in patients with end-stage liver disease

Patients with end-stage liver disease have an increased risk of developing bacterial infections, resulting in an increase in the number of hospitalizations and medical expenses, a decline in the quality of life of patients, and an increased fatality rate. Bacterial infections in patients with end-stage liver disease is mainly due to the falling off the body's immune response causing respiratory infections, spontaneous bacterial peritonitis, urinary tract infections and gastrointestinal infections. The diagnosis of bacterial infection is more challenging because the occurrence of infection shows no typical symptoms and signs. The examination of some biological markers has important clinical significance for early diagnosis. The clinical prognosis is entirely marked on the patient conditions, the effective control of infection, appropriate broad-spectrum antibiotics, and empiric therapy. Antibiotics are the choice, but also need to be alert against drug-induced liver damage.

The application of high-field magnetic resonance perfusion imaging in the diagnosis of pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer death in the world. It is a disease of insidious progression and high lethality. The present study was to investigate the diagnostic value of high-filed magnetic resonance (MR) perfusion imaging in pancreatic cancer. Thirty-three patients with suspected pancreatic cancer were recruited in our study and underwent routine MR imaging. When compared with para-tumoral and normal tissue, the pancreatic lesions showed significant lower slope, peak enhancement (PE), and signal enhancement ratio (SER) as well as higher time to peak (TTP). Para-tumoral tissue was found to have significantly lower slope and PE, slightly higher TTP than normal tissue. MR perfusion imaging displays hemodynamic alterations in both pancreatic cancer and surrounding pancreatic tissue, and provides indirect assessment of tumor vascularity. In conclusion, high field MR perfusion imaging has important clinical significance in early diagnosis of pancreatic cancer.