A Paradigm to Identify Biomarkers with Tissue Specificity and Disease Causality.

The journey of a biomarker from analytical and clinical validation to clinical and public health utility is laden with a host of challenges. This opinion piece and innovation analysis presents an approach to biomarker discovery and development with a focus on tissue specificity and disease causality, using the case of hepatic disease.

EMT-Related Markers in Serum Exosomes are Potential Diagnostic Biomarkers for Invasive Pituitary Adenomas.

Purpose: Assessing the invasiveness of pituitary adenomas (PAs) is critical to making the best surgical and treatment plan. However, it is difficult to determine the invasiveness of pituitary adenomas based on current clinical methods, such as imaging and histological methods. The present article aims to investigate noninvasive methods to discover viable biomarkers for invasive pituitary adenomas and provide a basis for early intervention of pituitary adenomas.

A rapid procedure for bacterial identification and antimicrobial susceptibility testing directly from positive blood cultures.

There is an urgent need to develop a rapid procedure that can rapidly identify and obtain antimicrobial susceptibility testing (AST) results directly from positive blood cultures. Here, we report a semi-automatic bacterial diagnosis procedure, which includes (1) a bacterial concentration process to isolate bacteria from a positive blood culture bottle (PBCB), (2) an identification process using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), and (3) a rapid AST process based on stimulated Raman scattering imaging of deuterium oxide (DO) incorporation in bacteria. A total of 105 samples were tested for bacterial identification, and a bacterial identification accuracy of 92.

Enhancing the Screening Efficiency of Breast Cancer by Combining Conventional Medical Imaging Examinations With Circulating Tumor Cells.

Purpose: Ultrasound (US) and mammogram (MMG) are the two most common breast cancer (BC) screening tools. This study aimed to assess how the combination of circulating tumor cells (CTC) with US and MMG would improve the diagnostic performance.

Methods: CTC detection and imaging examinations, US and MMG, were performed in 238 treatment-naive BC patients, 217 patients with benign breast diseases (BBD), and 20 healthy females.

Soluble cytotoxic T-lymphocyte-associated antigen 4 (sCTLA-4) as a potential biomarker for diagnosis and evaluation of the prognosis in Glioma.

Background: The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is widely considered as a pivotal immune checkpoint molecule to suppress antitumor immunity. However, the significance of soluble CTLA-4 (sCTLA-4) remains unclear in the patients with brain glioma. Here we aimed to investigate the significance of serum sCTLA-4 levels as a noninvasive biomarker for diagnosis and evaluation of the prognosis in glioma patients.

Soluble programmed death-1 (sPD-1) and programmed death ligand 1 (sPD-L1) as potential biomarkers for the diagnosis and prognosis of glioma patients.

Background: This study aimed at investigating the feasibility of testing for soluble programmed death-1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in serum samples of glioma patients and to evaluate the diagnostic and prognostic value of these two soluble molecules.

Methods: Serum samples collected from 70 glioma patients before surgery were designated as the pre-operative (Pre) group, samples obtained from 90 post-surgery glioblastoma patients were designated as the Post group, and samples from 20 healthy volunteers were used as controls. Peripheral blood sPD-1 and sPD-L1 levels were detected by using ELISA kits and compared among the groups.

Rapid Detection of and Genes by Loop-Mediated Isothermal Amplification in a Microfluidic System for Discrimination of Different Staphylococcal Species and Prediction of Methicillin Resistance.

Staphylococcal infection is one of the most pressing problems in modern medicine due to the increasing antibiotic resistance with the overuse of antibiotics. Conventional methods for identification and antimicrobial susceptibility testing (AST) generally take 3-7 days and require skilled technicians. In this study, a microfluidic device based on loop-mediated isothermal amplification (LAMP) was developed, which could discriminate , , , and and predict their methicillin resistance by targeting the and genes within 70 min including the hands-on time.

Inhibitory Effect of Tetramerized Single-Chain Variable Fragment of Anti-Cyclic Citrullinated Peptide Antibodies on the Proliferation, Activation, and Secretion of Cytokines of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis In Vitro Co-Culture System.

Tetramerized single-chain variable fragment (ScFv) of anti-cyclic citrullinated peptide (TeAb-CCP) is a constructed tetramerized ScFv of anti-cyclic citrullinated peptide (CCP) antibodies with p53 tetrameric domain, aim to investigate its effect on fibroblast-like synoviocytes (FLSs) proliferation, migration, invasion, and production of inflammatory mediators in the in vitro co-culture system of peripheral mononuclear cells (PBMCs) and FLSs. TeAb-CCP was constructed by modifying a monovalent ScFv antibody to CCP with p53 tetrameric domain to improve its affinity. FLSs were isolated and cultured from rheumatoid arthritis (RA) patients and control subjects.

Effect of Toll-like receptor 4 deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in a murine model of experimental autoimmune neuritis.

Introduction: The aim was to observe the effect of Toll-like receptor 4 (TLR4) deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in experimental autoimmune neuritis (EAN).

Material And Methods: We selected C57BL/10 wild type (WT) mice and TLR4 knockout (KO) mice with the C57BL/10 background for induction of the EAN model by immunizing mice twice (days 0 and 8) via subcutaneous injection of 180 μg P0 peptide 180-199 emulsion in 25 μl of PBS and 0.5 mg (Difco, USA) in 25 μl of Freund's incomplete adjuvant into the back of mice.

A pilot study of cdc6 as a biomarker for circulating tumor cells in patients with lung cancer.

Background: Cell division cycle 6 (cdc6) is a key factor of DNA replication initiation license system and a proto-oncogene. It has been detected in some tumor tissues to aid cancer diagnosis in many research projects. However, it remains unclear that if cdc6 could be detected in the peripheral blood, just like liquid biopsy, in solid tumor patients.

The Clinical Significance of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Patients With Gliomas.

Soluble PD-L1 (sPD-L1) in the circulation has been documented to activate global immunosuppression and is considered a predictor of negative clinical outcomes in several malignances. However, the clinical significance of sPD-L1 in the peripheral blood and cerebrospinal fluid (CSF) of patients with glioma remains unclear. The aim of this study was to detect the correlations of sPD-L1 with clinical features in brain tumors and assess the diagnostic value of this protein in gliomas.

Evaluation of a micro/nanofluidic chip platform for diagnosis of central nervous system infections: a multi-center prospective study.

Central nervous system infection (CNSI) is a significant type of infection that plagues the fields of neurology and neurosurgical science. Prompt and accurate diagnosis of CNSI is a major challenge in clinical and laboratory assessments; however, developing new methods may help improve diagnostic protocols. This study evaluated the second-generation micro/nanofluidic chip platform (MNCP-II), which overcomes the difficulties of diagnosing bacterial and fungal infections in the CNS.

Risk Factors of Recurrent Ischemic Events after Acute Noncardiogenic Ischemic Stroke.

Background: A considerable proportion of acute noncardiogenic ischemic stroke patients continue to experience recurrent ischemic events after standard therapy.

Aim: We aimed to identify risk factors for recurrent ischemic event prediction at an early stage.

Methods: 286 non-cardioembolic ischemic stroke patients with the onset of symptoms within 24 hours were enrolled.

Association of SLCO1B1 and ABCB1 Genetic Variants with Atorvastatin-induced Myopathy in Patients with Acute Ischemic Stroke.

Background: Certain patients experience muscle-related adverse effects after taking atorvastatin. Genetic factors play an important role in the occurrence of statin-induced myopathy.

Aim: We aimed to identify genetic variants associated with statin-induced myotoxicity.

Influence of the -202A/C Gene Polymorphism on Clinical Features and Surgery Outcome in Acromegalic Patients.

Excess growth hormone (GH) secretion in acromegaly patients results in increased levels of IGF-1 expression, which causes the clinical manifestations of acromegaly. IGF-1 levels are attenuated by IGFBP3, and a polymorphism in the promoter of IGFBP3 is known to affect the circulating level of IGFBP3 protein. The aim of the study was to evaluate the association of the gene polymorphism with clinical features and surgery outcomes in acromegaly.

Association between acromegaly and a single nucleotide polymorphism (rs2854744) in the IGFBP3 gene.

Background: It has been reported that the single nucleotide polymorphism (SNP) rs2854744 at the - 202 locus of insulin-like growth factor binding protein-3 (IGFBP3) is associated with serum levels and a number of malignancies. However, the effect of IGFBP3 gene polymorphism on acromegaly is less clear. Therefore, in the current study, we aimed to investigate whether the -202A/C polymorphism of IGFBP3 constitutes a risk factor for acromegaly.

The combination of cerebrospinal fluid procalcitonin, lactate, interleukin-8 and interleukin-10 concentrations for the diagnosis of postneurosurgical bacterial meningitis: A prospective study.

Background: The differential diagnosis between postneurosurgical bacterial meningitis and aseptic meningitis remains challenging both for the clinician and the laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival.

Methods: This prospective cohort study included patients with suspected bacterial meningitis after neurosurgery.

Evaluation of a micro/nanofluidic chip platform for the high-throughput detection of bacteria and their antibiotic resistance genes in post-neurosurgical meningitis.

Background: Post-neurosurgical meningitis (PNM) is one of the most severe hospital-acquired infections worldwide, and a large number of pathogens, especially those possessing multi-resistance genes, are related to these infections. Existing methods for detecting bacteria and measuring their response to antibiotics lack sensitivity and stability, and laboratory-based detection methods are inconvenient, requiring at least 24h to complete. Rapid identification of bacteria and the determination of their susceptibility to antibiotics are urgently needed, in order to combat the emergence of multi-resistant bacterial strains.

Association of anti-gangliosides antibodies and anti-CMV antibodies in Guillain-Barré syndrome.

Introduction: Numerous types of infection were closely related to GBS, mainly including , Cytomegalovirus, which may lead to the production of anti-gangliosides antibodies (AGA) Currently, although there are increased studies on the AGA and a few studies of anti-CMV antibodies in GBS, the association between them remains poorly documented. Therefore, our research aims to analyze the correlation of anti-CMV antibodies and AGA in GBS.

Methods: A total of 29 patients with GBS were enrolled in this study.

DHX32 expression is an indicator of poor breast cancer prognosis.

Emerging evidence suggests that DEAH-box polypeptide 32 (DHX32) serves an important role in the progression and metastasis of cancer. However, the role of DHX32 in breast cancer remains to be completely elucidated. The aim of the present study was to evaluate the expression and clinical significance of DHX32 in breast cancer.

Identification and functional characterization of lncRNAs acting as ceRNA involved in the malignant progression of glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common brain malignancy. Long non-coding RNAs (lncRNAs) are aber-rantly expressed in many cancers and involved in pathogenesis, progression and metastasis of tumors. In particular, lncRNAs can function as competing endogenous RNAs (ceRNAs).

High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma.

Ubiquitin-conjugating enzyme E2C (UBE2C) is a key regulator of cell cycle progression and is involved in the tumorigenesis of a variety of cancers. Previous studies have demonstrated that UBE2C is an important factor in the malignant progression of astrocytic tumors. However, the association between UBE2C expression and clinical prognosis of glioma patients has not been defined.

Toll-like receptor 2 and -4 are involved in the pathogenesis of the Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system characterized by weakness in the limbs. To date, numerous hypotheses have been suggested to explain the pathogenesis of GBS; however, the pathogenesis of GBS remains to be elucidated. The aim of the present study was to investigate the association between Toll-like receptor (TLR) 2, TLR4 and GBS.

The diagnostic value of cerebrospinal fluids procalcitonin and lactate for the differential diagnosis of post-neurosurgical bacterial meningitis and aseptic meningitis.

Objectives: Distinguishing between post-neurosurgical bacterial meningitis (PNBM) and aseptic meningitis is difficult. This study aims to evaluate the combined diagnostic value of CSF procalcitonin and lactate as novel PNBM markers in hospitalized post-neurosurgery patients.

Design And Methods: This study was performed using CSF samples, collected by lumbar puncture, from 178 PNBM-suspected patients enrolled in a retrospective clinical study.

Integrated microcapillary for sample-to-answer nucleic acid pretreatment, amplification, and detection.

This work develops an integrated microcapillary-based loop-mediated isothermal amplification (icLAMP) containing preloaded reagents and DNA extraction card, allowing for sample-to-answer screening of single nucleotide polymorphisms (SNPs) typing of the CYP2C19 gene from untreated blood samples with minimal user operation. With all reagents and the DNA extraction card preloaded inside the capillary, this icLAMP system can achieve on-site pretreatment, extraction, amplification, and detection of nucleic acids within 150 min, without the requirement for advanced instruments. As icLAMP technology carries many advantages such as disposability, easy operation, low cost, and reduced cross contamination and biohazard risks, we expect this system to have a great impact on point-of-care (POC) nucleic acid detection.